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  • 101.
    Mi, Yushuai
    et al.
    Shanghai Jiao Tong University, Peoples R China.
    Zhao, Senlin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Shanghai Jiao Tong University, Peoples R China.
    Zhang, Weihao
    Shanghai Jiao Tong University, Peoples R China.
    Zhang, Dongyuan
    Shanghai Jiao Tong University, Peoples R China.
    Weng, Junyong
    Shanghai Jiao Tong University, Peoples R China.
    Huang, Kejian
    Shanghai Jiao Tong University, Peoples R China.
    Sun, Huimin
    Shanghai Jiao Tong University, Peoples R China.
    Tang, Huamei
    Shanghai Jiao Tong University, Peoples R China.
    Zhang, Xin
    Zhejiang Prov Peoples Hospital, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Peng, Zhihai
    Shanghai Jiao Tong University, Peoples R China.
    Wen, Yugang
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Shanghai Jiao Tong University, Peoples R China.
    Down-regulation of Barx2 predicts poor survival in colorectal cancer2016In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 478, no 1, p. 67-73Article in journal (Refereed)
    Abstract [en]

    Human BarH-like homeobox 2 (Barx2), a homeodomain factor of the Bar family, has an important role in controlling the expression of cell adhesion molecules and has been reported in an increasing array of tumor types except colorectal cancer (CRC). The purpose of the current study was to characterize the expression of Barx2 and assess the clinical significance of Barx2 in CRC. First, we analyzed the expression of Barx2 in two independent public datasets from Oncomine. Subsequently, we evaluated Barx2 mRNA and protein expression by quantitative real-time PCR and western blotting, respectively. It was determined that Barx2 expression was lower in tumor tissues than in adjacent non-tumorous colorectal tissues of CRC patients, consistent with results from the public datasets. Subsequently, a tissue microarray containing 196 CRC specimens was evaluated for Barx2 expression by immunohistochemical staining. It was found that low expression of Barx2 significantly correlated with TNM stage, AJCC stage, differentiation, and relapse in patients with CRC. Patients with lower levels of Barx2 expression showed reduced disease-free survival and overall survival. Furthermore, a trend toward shorter overall survival in the patient group with Barx2-negative tumors independent of advanced AJCC stage and poor differentiation was determined by Kaplan-Meier survival analysis. Based on univariate and multivariate analyses, Barx2 expression was an independent prognostic factor for determining CRC prognosis. Taken together, low Barx2 expression was associated with the progression of CRC and could serve as a potential independent prognostic biomarker for patients with CRC. (C) 2016 The Authors. Published by Elsevier Inc.

  • 102.
    Mi, Yushuai
    et al.
    Shanghai Jiao Tong University, Peoples R China.
    Zhao, Senlin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Shanghai Jiao Tong University, Peoples R China.
    Zhou, Chongzhi
    Shanghai Jiao Tong University, Peoples R China.
    Weng, Junyong
    Shanghai Jiao Tong University, Peoples R China.
    Li, Jikun
    Shanghai Jiao Tong University, Peoples R China.
    Wang, Zhanshan
    Shanghai Jiao Tong University, Peoples R China.
    Sun, Huimin
    Shanghai Jiao Tong University, Peoples R China.
    Tang, Huamei
    Shanghai Jiao Tong University, Peoples R China.
    Zhang, Xin
    Zhejiang Prov Peoples Hospital, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Peng, Zhihai
    Shanghai Jiao Tong University, Peoples R China.
    Wen, Yugang
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Shanghai Jiao Tong University, Peoples R China.
    Downregulation of homeobox gene Barx2 increases gastric cancer proliferation and metastasis and predicts poor patient outcomes2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 37, p. 60593-60608Article in journal (Refereed)
    Abstract [en]

    Barx2 is a Bar family homeodomain transcription factor shown to play a critical role in cell adhesion and cytoskeleton remodeling, key processes in carcinogenesis and metastasis. Using quantitative real-time PCR, Western blotting, and immunohistochemistry, we found that Barx2 is expressed at lower levels in human gastric cancer (GC) tissues than in adjacent normal mucosa. In a multivariate analysis, Barx2 expression emerged as an independent prognostic factor for disease-free and overall survival. Kaplan-Meier survival analysis showed a trend toward even shorter overall survival in the patient group with Barx2-negative tumors, independent of advanced UICC stage and tumor relapse. Using in vitro and in vivo assays, we demonstrated that under normal conditions Barx2 inhibited GC cell proliferation and invasiveness through inhibition of the Wnt/beta-catenin signaling pathway. These findings indicate that reduction or loss of Barx2 dis-inhibits GC cell proliferation and invasion, and that reduction in Barx2 could serve as an independent prognostic biomarker for poor outcome in GC patients.

  • 103.
    Mirza, M. R.
    et al.
    Nordic Soc Gynecol Oncol, Denmark; Copenhagen University Hospital, Denmark.
    Monk, B. J.
    University of Arizona, AZ USA; Creighton University of Phoenix, AZ USA; Arizona Oncology Associates, AZ USA.
    Herrstedt, J.
    University of Southern Denmark, Denmark.
    Oza, A. M.
    University of Toronto, Canada.
    Mahner, S.
    Arbeitsgemeinschaft Gynakol Onkol, Germany; University of Munich, Germany.
    Redondo, A.
    GEICO, Spain; Hospital University of La Paz, Spain.
    Fabbro, M.
    French Investigator Grp Ovarian and Breast Cancer GIN, France; Institute Cancer Montpellier, France.
    Ledermann, J. A.
    UCL, England; UCL, England.
    Lorusso, D.
    Ist Nazl Tumori, Italy.
    Vergote, I.
    Luxembourg Gynecol Oncology Grp, Belgium; University of Leuven, Belgium.
    Ben-Baruch, N. E.
    Kaplan Medical Centre, Israel.
    Marth, C.
    AGO Austria, Austria; Medical University of Innsbruck, Austria.
    Madry, R.
    Central and Eastern European Gynecol Oncology Grp, Poland; Uniwersytet Medical Poznaniu, Poland.
    Christensen, R. D.
    University of Southern Denmark, Denmark.
    Berek, J. S.
    Stanford Comprehens Cancer Institute, CA USA.
    Dorum, A.
    Oslo University Hospital, Norway.
    Tinker, A. V.
    British Columbia Cancer Agency, Canada.
    du Bois, A.
    Kliniken Essen Mitte, Germany.
    Gonzalez-Martin, A.
    GEICO, Spain; MD Anderson Cancer Centre Madrid, Spain.
    Follana, P.
    GINECO, France; Centre Antoine Lacassagne, France.
    Benigno, B.
    Northside Hospital, GA USA.
    Rosenberg, Per
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Gilbert, L.
    McGill University, Canada.
    Rimel, B. J.
    Cedars Sinai Medical Centre, CA USA.
    Buscema, J.
    Arizona Oncology Associates, AZ USA.
    Balser, J. P.
    Veristat, MA USA.
    Agarwal, S.
    Tesaro, MA USA.
    Matulonis, U. A.
    Dana Farber Cancer Institute, MA 02115 USA.
    Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer2016In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 375, no 22, p. 2154-2164Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer. METHODS In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2: 1 ratio to receive niraparib (300 mg) or placebo once daily. The primary end point was progression-free survival. RESULTS Of 553 enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234 assigned to niraparib and 116 to placebo). Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval [CI], 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61; P amp;lt; 0.001 for all three comparisons). The most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications. CONCLUSIONS Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274.)

  • 104.
    Mishra, Ameet K.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Abrahamsson, Annelie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Fulvestrant inhibits growth of triple negative breast cancer and synergizes with tamoxifen in ER alpha positive breast cancer by up-regulation of ER beta2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 35, p. 56876-56888Article in journal (Refereed)
    Abstract [en]

    The estrogen receptor-alpha (ER alpha) is used as a predictive marker for antiestrogen therapy in breast cancer patients. In addition to aromatase inhibitors, ER alpha can be targeted at the receptor level using the receptor modulator tamoxifen or by the pure anti-estrogen fulvestrant. The role of the second ER, ER-beta (ER beta), as a therapeutic target or prognostic marker in breast cancer is still elusive. Hitherto, it is not known if ER alpha+/ER beta+ breast cancers would benefit from a treatment strategy combining tamoxifen and fulvestrant or if fulvestrant exert any therapeutic effects in ER alpha-/ER beta+ breast cancer. Here, we report that fulvestrant up-regulated ER beta in ER alpha+/ER beta+ breast cancer and in triple negative ER beta+ breast cancers (ER alpha-/ER beta+). In ER alpha+/ER beta+ breast cancer, a combination therapy of tamoxifen and fulvestrant significantly reduced tumor growth compared to either treatment alone both in vivo and in vitro. In ER alpha-/ER beta+ breast cancer fulvestrant had potent effects on cancer growth, in vivo as well as in vitro, and this effect was dependent on intrinsically expressed levels of ER beta. The role of ER beta was further confirmed in cells where ER beta was knocked-in or knocked-down. Inhibition of DNA methyltransferase (DNMT) increased the levels of ER beta and fulvestrant exerted similar potency on DNMT activity as the DNMT inhibitor decitabine. We conclude that fulvestrant may have therapeutic potential in additional groups of breast cancer patients; i) in ER alpha+/ER beta+ breast cancer where fulvestrant synergizes with tamoxifen and ii) in triple negative/ER beta+ breast cancer patients, a subgroup of breast cancer patients with poor prognosis.

  • 105.
    Morad, Vivian
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Abrahamsson, Annelie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Adipokines and Vascular Endothelial Growth Factor in Normal Human Breast Tissue in Vivo - Correlations and Attenuation by Dietary Flaxseed2016In: Journal of mammary gland biology and neoplasia, ISSN 1083-3021, E-ISSN 1573-7039, Vol. 21, no 1-2, p. 69-76Article in journal (Refereed)
    Abstract [en]

    Exposure to sex steroids increases the risk of breast cancer but the exact mechanisms are yet to be elucidated. Events in the microenvironment are important for carcinogenesis. Diet containing phytoestrogens can affect the breast microenvironment and alter the risk of breast cancer. It has previously been shown that estrogen regulates extracellular levels of leptin, adiponectin, and VEGF in normal breast tissue in vivo. Whether these proteins correlate in breast tissue in vivo or if diet addition of flaxseed, a major source of phytoestrogens in Western diets, alters adipokine levels in breast tissue are unknown. We used microdialysis to sample proteins of normal human breast tissue and abdominal subcutaneous fat in situ in 34 pre-and postmenopausal women. In vitro, co-culture of breast cancer cells and primary human adipocytes was used. In vivo, in normal breast tissue, a significant positive correlation between VEGF and leptin was detected. No correlations were found in fat tissue. Co-culture of adipocytes and breast cancer cells per se increased the secretion of VEGF and leptin and enhanced the effects of estradiol compared to culture of either cell type alone. In vitro, inhibition of VEGF diminished the release of leptin while inhibition of leptin had no influence on VEGF secretion. The levels of leptin decreased and adiponectin increased after a dietary addition of 25 g of flaxseed/day for one menstrual cycle. We conclude that VEGF and leptin correlate significantly in normal human breast tissue in vivo and that dietary addition of flaxseed affect adipokine levels in the breast.

  • 106.
    Mosrati, Mohamed Ali
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Malmström, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Lysiak, Malgorzata
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Krysztofiak, Adam
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Milos, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery. Linköping University, Faculty of Medicine and Health Sciences.
    Hallbeck, Anna-Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Bratthall, Charlotte
    Dist Hospital, Sweden.
    Strandeus, Michael
    Ryhov Hospital, Sweden.
    Stenmark Askmalm, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    TERT promoter mutations and polymorphisms as prognostic factors in primary glioblastoma2015In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, no 18, p. 16663-16673Article in journal (Refereed)
    Abstract [en]

    Telomerase reverse transcriptase (TERT) activity is up-regulated in several types of tumors including glioblastoma (GBM). In the present study, 128 primary glioblastoma patients were examined for single nucleotide polymorphisms of TERT in blood and in 92 cases for TERT promoter mutations in tumors. TERT promoter mutations were observed in 86% of the tumors and of these, C228T (-124 bp upstream start codon) was detected in 75% and C250T (-146 bp) in 25% of cases. TERT promoter mutations were associated with shorter overall survival (11 vs. 20 months p = 0.002 and 12 vs. 20, p = 0.04 for C228T and C250T, respectively). The minor alleles of rs2736100 and rs10069690 SNPs, located in intron 2 and the promotor regions, respectively, were associated with an increased risk of developing GBM (p = 0.004 and 0.001). GBM patients having both TERT promoter mutations and being homozygous carriers of the rs2853669 C-allele displayed significantly shorter overall survival than those with the wild type allele. The rs2853669 SNP is located in a putative Ets2 binding site in the promoter (-246 bp upstream start codon) close to the C228T and C250T mutation hot spots. Interleukin-6 (IL-6) expression regulated by TERT promoter status and polymorphism, what leads us to think that TERT and IL-6 plays a significant role in GBM, where specific SNPs increase the risk of developing GBM while the rs2853669 SNP and specific mutations in the TERT promoter of the tumor lead to shorter survival.

  • 107.
    Nordenskjold, A. E.
    et al.
    Southern Alvsborg Hospital, Sweden; Sahlgrens University Hospital, Sweden.
    Fohlin, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden. Linköping University, Faculty of Medicine and Health Sciences. Regional Cancer Centre South East Sweden, Linkoping, Sweden.
    Albertsson, P.
    Sahlgrens University Hospital, Sweden.
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Chamalidou, C.
    Southern Alvsborg Hospital, Sweden; Sahlgrens University Hospital, Sweden.
    Einbeigi, Z.
    Sahlgrens University Hospital, Sweden.
    Holmberg, E.
    Regional Cancer Centre, Sweden.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Karlsson, P.
    Sahlgrens University Hospital, Sweden.
    No clear effect of postoperative radiotherapy on survival of breast cancer patients with one to three positive nodes: a population-based study2015In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 26, no 6, p. 1149-1154Article in journal (Refereed)
    Abstract [en]

    Background: In published radiotherapy trials, the failure rate in the control arm among patients with one to three positive nodes is high compared with that seen with modern adjuvant treatments. Therefore, the generalizability of the results has been questioned. The aim of the present study was to compare relative survival in breast cancer patients between two Swedish regions with screening mammography programs and adjuvant treatment guidelines similar with the exception of the indication of radiotherapy for patients with one to three positive nodes. Patients and methods: Between 1989 and 2006, breast cancer patients were managed very similarly in the west and southeast regions, except for indication for postoperative radiotherapy. In patients with one to three positive nodes, post-mastectomy radiotherapy was generally given in the southeast region (89% of all cases) and generally not given in the west region (15% of all cases). For patients with one to three positive nodes who underwent breast-conserving surgery, patients in the west region had breast radiotherapy only, while patients in the southeast region had both breast and lymph nodes irradiated. Results: The 10-year relative survival for patients with one to three positive lymph nodes was 78% in the west region and 77% in the southeast region (P = 0.12). Separate analyses depending on type of surgery, as well as number of examined nodes, also revealed similar relative survival. Conclusion: Locoregional postoperative radiotherapy has well-known side-effects, but in this population-based study, there was little or no influence of this type of radiotherapy on survival when one to three lymph nodes were involved.

  • 108.
    Nordenskjold, Anna
    et al.
    Sahlgrens Acad, Sweden; Southern Alvsborg Hospital, Sweden.
    Fohlin, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Fornander, Tommy
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden; Regional Cancer Centre Stockholm Gotland, Sweden.
    Lofdahl, Britta
    St Göran Hospital, Sweden.
    Skoog, Lambert
    Karolinska University Hospital, Sweden.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Progesterone receptor positivity is a predictor of long-term benefit from adjuvant tamoxifen treatment of estrogen receptor positive breast cancer2016In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 160, no 2, p. 313-322Article in journal (Refereed)
    Abstract [en]

    The independent predictive information from progesterone receptor (PgR) positivity for breast cancer treated with tamoxifen has been questioned after an overview by the Early Breast Cancer Trialists Collaborative Group (EBCTCG). However, the studies in the overview were to a large content performed before modern PgR immunohistochemistry (IHC) was developed. We therefore investigated the predictive value of PgR determined with IHC in estrogen receptor (ER)-positive tumors from patients participating in the Stockholm trial of adjuvant tamoxifen therapy. The Stockholm Breast Cancer Study Group conducted a randomized trial during 1976 through 1990 comparing adjuvant tamoxifen versus control. The patients were stratified according to tumor size and lymph node status in high-risk and low-risk groups. In this study, we evaluated 618 patients with ER-positive "low-risk" breast cancer (size aecurrency sign 30 mm, lymph node-negative) for whom PgR was determined by IHC at one pathology laboratory. The median time of follow-up was 21 years. Patients with ER-positive tumors that were also PgR-positive by IHC did benefit from tamoxifen, while we could not show any long-term benefit for those with tumors positive for ER only (recurrence rate ratio 0.43, 95 % CI 0.29-0.62 and 0.87, 95 % CI 0.52-1.46, respectively). We further investigated the influence of different levels of PgR positivity on recurrence risk. The results show that at all receptor levels with aeyen10 % stained PgR-positive cells, the patients did benefit from tamoxifen. There was no clear linear trend in benefit with increasing proportion of stained cells. PgR positivity determined by IHC is a marker indicating long-term benefit from adjuvant tamoxifen in patients with ER-positive tumors.

  • 109.
    Nyholm, Tufve
    et al.
    Umeå University, Sweden; Uppsala University, Sweden.
    Olsson, Caroline
    Gothenburg University, Sweden; Western Sweden Healthcare Reg, Sweden.
    Agrup, Måns
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Bjork, Peter
    Mälar Hospital, Sweden.
    Bjork-Eriksson, Thomas
    Sahlgrenska University Hospital, Sweden.
    Gagliardi, Giovanna
    Karolinska University Hospital, Sweden.
    Grinaker, Hanne
    Swedish Radiation Safety Authority, Sweden.
    Gunnlaugsson, Adalsteinn
    Lund University, Sweden.
    Gustafsson, Anders
    Cureos AB, Sweden.
    Gustafsson, Magnus
    Sahlgrenska University Hospital, Sweden.
    Johansson, Bengt
    Örebro University Hospital, Sweden; University of Örebro, Sweden.
    Johnsson, Stefan
    Kalmar County Hospital, Sweden.
    Karlsson, Magnus
    Umeå University, Sweden.
    Kristensen, Ingrid
    Lund University, Sweden.
    Nilsson, Per
    Lund University, Sweden.
    Nystrom, Leif
    Umeå University, Sweden.
    Onjukka, Eva
    Karolinska University Hospital, Sweden.
    Reizenstein, Johan
    University of Örebro, Sweden.
    Skonevik, Johan
    Umeå University, Sweden; Örebro University Hospital, Sweden.
    Soderstrom, Karin
    Umeå University, Sweden.
    Valdman, Alexander
    Karolinska University Hospital, Sweden.
    Zackrisson, Bjorn
    Umeå University, Sweden.
    Montelius, Anders
    Uppsala University, Sweden.
    A national approach for automated collection of standardized and population-based radiation therapy data in Sweden2016In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 119, no 2, p. 344-350Article in journal (Refereed)
    Abstract [en]

    Purpose: To develop an infrastructure for structured and automated collection of interoperable radiation therapy (RT) data into a national clinical quality registry. Materials and methods: The present study was initiated in 2012 with the participation of seven of the 15 hospital departments delivering RT in Sweden. A national RT nomenclature and a database for structured unified storage of RT data at each site (Medical Information Quality Archive, MIQA) have been developed. Aggregated data from the MIQA databases are sent to a national RT registry located on the same IT platform (INCA) as the national clinical cancer registries. Results: The suggested naming convention has to date been integrated into the clinical workflow at 12 of 15 sites, and MIQA is installed at six of these. Involvement of the remaining 3/15 RT departments is ongoing, and they are expected to be part of the infrastructure by 2016. RT data collection from ARIA (R), Mosaiq (R), Eclipse (TM), and Oncentra (R) is supported. Manual curation of RT-structure information is needed for approximately 10% of target volumes, but rarely for normal tissue structures, demonstrating a good compliance to the RT nomenclature. Aggregated dose/volume descriptors are calculated based on the information in MIQA and sent to INCA using a dedicated service (MIQA2INCA). Correct linkage of data for each patient to the clinical cancer registries on the INCA platform is assured by the unique Swedish personal identity number. Conclusions: An infrastructure for structured and automated prospective collection of syntactically inter operable RT data into a national clinical quality registry for RT data is under implementation. Future developments include adapting MIQA to other treatment modalities (e.g. proton therapy and brachytherapy) and finding strategies to harmonize structure delineations. How the RT registry should comply with domain-specific ontologies such as the Radiation Oncology Ontology (ROO) is under discussion. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 110.
    Paramita, Pragyan
    et al.
    Chettinad Acad Res and Educ, India.
    Subramaniam, Vimala Devi
    Chettinad Acad Res and Educ, India.
    Murugesan, Ramachandran
    Chettinad Acad Res and Educ, India.
    Gopinath, Madhumala
    Chettinad Acad Res and Educ, India.
    Ramachandran, Ilangovan
    Univ Madras, India.
    Ramalingam, Satish
    Chettinad Acad Res and Educ, India; SRM Inst Sci and Technol, India.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Banerjee, Antara
    Chettinad Acad Res and Educ, India.
    Marotta, Francesco
    ReGenera RandD Int Aging Intervent, Italy; ReGenera RandD Int Aging Intervent, Peoples R China; VCC Prevent Med Promot Fdn, Peoples R China.
    Pathak, Surajit
    Chettinad Acad Res and Educ, India.
    Evaluation of potential anti-cancer activity of cationic liposomal nanoformulated Lycopodium clavatum in colon cancer cells2018In: IET Nanobiotechnology, ISSN 1751-8741, E-ISSN 1751-875X, Vol. 12, no 6, p. 727-732Article in journal (Refereed)
    Abstract [en]

    Research dealing with early diagnosis and efficient treatment in colon cancer to improve patients survival is still under investigation. Chemotherapeutic agent result in high systemic toxicity due to their non-specific actions on DNA repair and/or cell replication. Traditional medicine such as Lycopodium clavatum (LC) has been claimed to have therapeutic potentials against cancer. The present study focuses on targeted drug delivery of cationic liposomal nanoformulated LC (CL-LC) in colon cancer cells (HCT15) and comparing the efficacy with an anti-colon cancer drug, 7-ethyl-10-hydroxy-camptothecin (SN38) along with its nanoformulated form (CL-SN38). The colloidal suspension of LC was made using thin film hydration method. The drugs were characterised using ultraviolet, dynamic light scattering, scanning electron microscopy, energy, dispersive X-ray spectroscopy. Invitro drug release showed kinetics of 49 and 89% of SN38 and LC, whereas CL-SN38 and CL-LC showed 73 and 74% of sustained drug release, respectively. Studies on morphological changes, cell viability, cytotoxicity, apoptosis, cancer-associated gene expression analysis of Bcl-2, Bax, p53 by real-time polymerase chain reaction and western blot analysis of Bad and p53 protein were performed. Nanoformulated LC significantly inhibited growth and increased the apoptosis of colon cancer cells indicating its potential anti-cancer activity against colon cancer cells.

  • 111.
    Pathak, Surajit
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. CARE, India.
    Banerjee, Antara
    CARE, India.
    Meng, Wen-Jian
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Department of Gastrointestinal Surgery , West China Hospital, Sichuan University , Chengdu , China.
    Nandy, Suman Kumar
    Univ Kalyani, India; North Eastern Hill Univ, India.
    Gopinath, Madhumala
    CARE, India.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Significant expression of tafazzin (TAZ) protein in colon cancer cells and its downregulation by radiation2018In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 94, no 1, p. 79-87Article in journal (Refereed)
    Abstract [en]

    Aim: To demonstrate the radiation responses of tafazzin (TAZ) protein in colon cancer. Methods: TAZ expression was examined in colon cancer cell lines SW480, KM12C, SW620 and KM12L4a. KM12C and KM12L4a cell lines were used for this experiment with exposure to X- and UV rays (mW/cm(2)). HCT15 cell line was used to test the expression of TAZ by using an anti-TAZ drug, namely 9-fluorenone, which is a Hippo-YAP/TAZ signaling inhibitor. The experimentation also involved exposing HCT15 cell line, to UV radiation. Cell proliferation and apoptosis studies were carried out. TAZ interactions with oncoproteins were screened and the oncoproteins Livin, MAC30 and FXYD-3 were considered for in silico protein-protein interaction studies. Results: TAZ protein was significantly downregulated after 2Gy radiations. 9-Fluorenone inhibited the expression of TAZ. Action of 9-fluorenone along with radiation, decreased the percentage of proliferation and increased apoptosis. Computational studies predicted that TAZ interacts with the oncoproteins Livin, MAC30 and FXYD-3. Conclusions: Our results suggest that TAZ plays a significant role in non-metastatic KM12C cells and is predominantly seen in the colon cancer cells isolated from primary stages of cancer. Thus, use of TAZ protein as a biomarker will be an efficient way to detect tumors in the early stages and treatment may be modulated with radiation before surgery/therapy.

  • 112.
    Pathak, Surajit
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Meng, Wen-Jian
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Sichuan University, Peoples R China.
    Kumar Nandy, Suman
    University of Kalyani, India.
    Ping, Jie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Bisgin, Atil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Helmfors, Linda
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Waldmann, Patrik
    Linköping University, Department of Computer and Information Science, Statistics. Linköping University, Faculty of Arts and Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Radiation and SN38 treatments modulate the expression of microRNAs, cytokines and chemokines in colon cancer cells in a p53-directed manner2015In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, no 42, p. 44758-44780Article in journal (Refereed)
    Abstract [en]

    Aberrant expression of miRNAs, cytokines and chemokines are involved in pathogenesis of colon cancer. However, the expression of p53 mediated miRNAs, cyto- and chemokines after radiation and SN38 treatment in colon cancer remains elusive. Here, human colon cancer cells, HCT116 with wild-type, heterozygous and a functionally null p53, were treated by radiation and SN38. The expression of 384 miRNAs was determined by using the TaqMan (R) miRNA array, and the expression of cyto- and chemokines was analyzed by Meso-Scale-Discovery instrument. Up- or down-regulations of miRNAs after radiation and SN38 treatments were largely dependent on p53 status of the cells. Cytokines, IL-6, TNF-alpha, IL-1 beta, Il-4, IL-10, VEGF, and chemokines, IL-8, MIP-1 alpha were increased, and IFN-gamma expression was decreased after radiation, whereas, IL-6, IFN-gamma, TNF-alpha, IL-1 beta, Il-4, IL-10, IL-8 were decreased, and VEGF and MIP-1 alpha were increased after SN38 treatment. Bioinformatic analysis pointed out that the highly up-regulated miRNAs, let-7f-5p, miR-455-3p, miR-98, miR-155-5p and the down-regulated miRNAs, miR-1, miR-127-5p, miR-142-5p, miR-202-5p were associated with colon cancer pathways and correlated with cyto- or chemokine expression. These miRNAs have the potential for use in colon cancer therapy as they are related to p53, pro- or anti-inflammatory cyto- or chemokines after the radiation and SN38 treatment.

  • 113.
    Pathak, Surajit
    et al.
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    S, Sushmitha
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    Banerjee, Antara
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    Marotta, Francesco
    ReGenera Research Group for Aging-Intervention, Milano, Italy and San Babila Clinic, Healthy Aging Unit by Genomics and Biotechnology, Milano, Italy.
    Gopinath, Madhumala
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    Murugesan, Ramachandran
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    Zhang, Hong
    School of Medicine, Orebro University, Örebro, Sweden.
    B, Bhavani
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    Girigoswami, Agnishwar
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    Sollano, Jose
    Gastroenterology Department, University of Santo Tomas, Manila, The Philippines.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Review on comparative efficacy of bevacizumab, panitumumab and cetuximab antibody therapy with combination of FOLFOX-4 in KRAS-mutated colorectal cancer patients2018In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 9, no 7, p. 7739-7748Article, review/survey (Refereed)
    Abstract [en]

    Colorectal cancer, fourth leading form of cancer worldwide and is increasing in alarming rate in the developing countries. Treating colorectal cancer has become a big challenge worldwide and several antibody therapies such as bevacizumab, panitumumab and cetuximab are being used with limited success. Moreover, mutation in KRAS gene which is linked with the colorectal cancer initiation and progression further interferes with the antibody therapies. Considering median progression free survival and overall survival in account, this review focuses to identify the most efficient antibody therapy in combination with chemotherapy (FOLFOX-4) in KRAS mutated colorectal cancer patients. The bevacizumab plus FOLFOX-4 therapy shows about 9.3 months and 8.7 months of progression free survival for KRAS wild and mutant type, respectively. The overall survival is about 34.8 months for wild type whereas for the mutant it is inconclusive for the same therapy. In comparison, panitumumab results in better progression-free survival which is about (9.6 months) and overall survival is about (23.9 months) for the wild type KRAS and the overall survival is about 15.5 months for the mutant KRAS. Cetuximab plus FOLFOX-4 therapy shows about 7.7 months and 5.5 months of progression-free survival for wild type KRAS and mutant type, respectively. Thus, panitumumab shows significant improvement in overall survival rate for wild type KRAS, validating as a cost effective therapeutic for colorectal cancer therapy. This review depicts that panitumumab along with FOLFOX-4 has a higher response in colorectal cancer patients than the either of the two monoclonal antibodies plus FOLFOX-4.

  • 114.
    Paulsson, Janna
    et al.
    Department of Oncology-Pathology Cancer Center Karolinska, Karolinska Institutet Stockholm, Sweden.
    Rydén, Lisa
    Division of Surgery, Department of Clinical Sciences Lund UniversityLundSweden; Department of Surgery Skåne University Hospital Lund, Sweden.
    Strell, Carina
    Department of Oncology-Pathology Cancer Center Karolinska, Karolinska Institutet Stockholm, Sweden.
    Frings, Oliver
    Department of Oncology-Pathology Cancer Center Karolinska, Karolinska Institutet Stockholm, Sweden.
    Tobin, Nicholas P
    Department of Oncology-Pathology Cancer Center Karolinska, Karolinska Institutet Stockholm, Sweden.
    Fornander, Tommy
    Department of Oncology-Pathology Cancer Center Karolinska, Karolinska Institutet Stockholm, Sweden.
    Bergh, Jonas
    Department of Oncology-PathologyCancer Center Karolinska, Karolinska InstitutetStockholmSweden; Radiumhemmet, Karolinska University Hospital Stockholm, Sweden.
    Landberg, Göran
    Department of Pathology Sahlgrenska Cancer Centre, University of Gothenburg Gothenburg, Sweden.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Östman, Arne
    Department of Oncology-Pathology Cancer Center Karolinska, Karolinska Institutet Stockholm, Sweden.
    High expression of stromal PDGFRß is associated with reduced benefit of tamoxifen in breast cancer2017In: The journal of pathology. Clinical research, ISSN 2056-4538, Vol. 3, no 1, p. 38-43Article in journal (Refereed)
    Abstract [en]

    Cancer-associated fibroblasts (CAFs) regulate tumour growth, metastasis and response to treatment. Recent studies indicate the existence of functionally distinct CAF subsets. Suggested mechanisms whereby CAFs can impact on treatment response include paracrine signalling affecting cancer cell drug sensitivity and effects on tumour drug uptake. PDGFRß is an important regulator of fibroblasts. Experimental studies have linked PDGFRß-positive fibroblasts to metastasis and also to reduced tumour drug uptake. This study has investigated the potential role of PDGFRß-positive fibroblasts in response to adjuvant tamoxifen treatment of breast cancer. Analyses of two breast cancer collections from randomised studies analysing adjuvant tamoxifen treatment in early breast cancer demonstrated significant benefit of tamoxifen in the group with low stromal PDGFRß, which was not observed in the group with high stromal PDGFRß. In general terms these findings provide novel evidence, derived from analyses of randomised clinical studies, of response-predictive capacity of a marker-defined subset of CAFs and, more specifically, identify stromal PDGFRß as a marker related to tamoxifen benefit in early breast cancer.

  • 115.
    Pihl Lesnovska, Katarina
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Börjeson, Sussanne
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Hollman Frisman, Gunilla
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping.
    Hjortswang, Henrik
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science.
    Wenemark, Marika
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Business support and Development, Department of Health and Care Development.
    The quality of care questionnaire: development of a valid measure for persons with inflammatory bowel disease2018In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, no 9, p. 1043-1050Article in journal (Refereed)
    Abstract [en]

    Background and aims: Quality of care is important in lifelong illnesses such as inflammatory bowel disease (IBD). Valid, reliable and short questionnaires to measure quality of care among persons with IBD are needed. The aim of this study was to develop a patient-derived questionnaire measuring quality of care in persons with IBD.Methods and results: The development of the questionnaire The Quality of Care -Questionnaire (QoC-Q) was based on a literature review of studies measuring quality of care, and the results of two qualitative studies aiming to identify the knowledge need and perception of health care among persons with IBD. Further development and evaluation was done by focus groups, individual testing and cognitive interviews with persons with IBD, as well as evaluation by a group of professionals. After the development, the questionnaire was tested for validity and test-retest reliability in 294 persons with IBD.Conclusions: The QoC-Q is showing promising validity and reliability for measuring the subjective perception of quality of care. Further testing in clinical practice is suggested to assess if the QoC-Q can be used to evaluate care and areas of improvement in health care for persons living with IBD.

  • 116.
    Pihl Lesnovska, Katarina
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Department of Medical and Health Sciences, Division of Nursing Science.
    Hollman Frisman, Gunilla
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping.
    Hjortswang, Henrik
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Börjeson, Sussanne
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Critical situations in daily life as experienced by patients with inflammatory bowel disease2016In: Gastroenterology Nursing, ISSN 1042-895X, Vol. 39, no 3, p. 195-203Article in journal (Refereed)
    Abstract [en]

    Crohn disease and ulcerative colitis, collectively known as inflammatory bowel disease (IBD), are chronic and have a fluctuating clinical course that impacts daily life. Daily life with a chronic disease involves thinking and worrying about the limitations that chronic disease causes. Knowledge about how patients who suffer from IBD manage critical incidents in daily life is lacking. The aim of the study was to describe how patients living with IBD experience critical incidents in daily life in relation to their disease and symptoms. Thirty adult patients were interviewed focusing on critical incidents in daily life. Data were analyzed using the critical incident technique. The study comprised 224 critical incidents and was grouped into 21 subcategories and 5 categories: losing bowel control, having a body that smells, being unable to meet own and others' expectations, not being believed or seen, and experiencing frustration due to side effects and ineffective treatment. These categories formed one main area describing the overall result "The bowels rule life." The uncertain nature of IBD created critical incidents in which the bowel ruled life, causing patients to avoid social interaction. It also placed considerable demands on the family and sometimes had a negative effect on the afflicted person's career.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

  • 117.
    Pihl Lesnovska, Katarina
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Hollman Frisman, Gunilla
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Hjortswang, Henrik
    Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hjelm, Katarina
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Börjeson, Sussanne
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Healthcare as perceived by persons with inflammatory bowel disease – a focus group study2017In: Journal of Clinical Nursing, ISSN 0962-1067, Vol. 26, no 21-22, p. 3677-3687Article in journal (Refereed)
    Abstract [en]

    Background: The quality of care plays an important role in the life of persons with a chronic disease. In order to define what persons with inflammatory bowel disease perceive as high quality care, greater focus must be placed on the individual’s own perspective of living with the condition. Design: A qualitative exploratory study was conducted based on focus groups. Methods: Five focus groups were conducted with adult persons living with inflammatory bowel disease, fourteen men and twelve women aged 19-76 years. The interviews were performed between January and June 2014. Results: The perceptions of healthcare from the perspective of persons living with inflammatory bowel disease were summarized in two categories: “Professional attitudes of healthcare staff” and “Structure of the healthcare organization”. Persons with Inflammatory bowel disease want to be encountered with respect, experience trust and obtain information at the right time. They also expect shared decision-making, communication and to encounter competent healthcare professionals. Furthermore, the expectations on and perceptions of the structure of the healthcare organization comprises access to care, accommodation, continuity of care, as well as the pros and cons of specialized care. Conclusion: The findings show the importance of establishing a respectful and trusting relationship, facilitating healthcare staff and persons with inflammatory bowel disease to work as a team in fulfilling individual care needs – but there is room for improvement in terms of quality of care. Relevance to clinical practice: A person-centred approach, which place the individual and her/his family at the centre, considering them experts on their own health and enabling them to collaborate with healthcare staff, seems important to reach a high quality healthcare organization for patients with IBD.

  • 118.
    Roncolato, Felicia T
    et al.
    NHMRC Clinical Trials Centre, University of Sydney, Australia; Macarthur Cancer Therapy Centre, NSW, Australia; Australia New Zealand Gynaecological Oncology Group (ANZGOG), Australia.
    Berton-Rigaud, Dominique
    ICO Centre René Gauducheau, Saint Herblain, France.
    O'Connell, Rachel
    NHMRC Clinical Trials Centre, University of Sydney, Australia.
    Lanceley, Anne
    University College London, United Kingdom.
    Sehouli, Jalid
    Charite Berlin, Germany.
    Buizen, Luke
    NHMRC Clinical Trials Centre, University of Sydney, Australia.
    Okamoto, Aikou
    Jikei University School of Medicine, Japan.
    Aotani, Eriko
    Kitasato Academic Research Organization, Japan.
    Lorusso, Domenica
    MITO, Rome, Italy.
    Donnellan, Paul
    Galway University Hospital, Ireland; All-Ireland Oncology Research Group (ICORG), Ireland.
    Oza, Amit
    Princess Margaret Hospital, Canada.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Karolinska Institutet, Stockholm, Sweden.
    Berek, Jonathan
    Stanford Women's Cancer Center, USA.
    Hilpert, Felix
    Klinik fur Gynakologie und Geburtshilfe, UKSH, Germany.
    Ledermann, Jonathan A
    CRUK and UCL Cancer Trials Centre, NCRI UK, United Kingdom.
    Kaminsky, Marie Christine
    ICL Institut de Cancérologie de Lorraine, Vandoeuvre-Les-Nancy, France.
    Stockler, Martin R
    NHMRC Clinical Trials Centre, University of Sydney, Australia.
    King, Madeleine T
    Psycho-oncology Research Group (PoCoG), School of Psychology, Central Clinical School, Sydney Medical School, University of Sydney, Australia.
    Friedlander, Michael
    Australia New Zealand Gynaecological Oncology Group (ANZGOG), Australia; Prince of Wales Hospital, Sydney, Australia.
    Validation of the modified Glasgow Prognostic Score (mGPS) in recurrent ovarian cancer (ROC): Analysis of patients enrolled in the GCIG Symptom Benefit Study (SBS)2018In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 148, no 1, p. 36-41, article id S0090-8258(17)31422-1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Modified Glasgow Prognostic Score (mGPS) is predictive of survival in many advanced cancers, but has not been evaluated in recurrent ovarian cancer (ROC). The aim was to determine validity of mGPS in ROC, investigate its associations with health related quality of life (HRQL) and ECOG performance status (PS).

    METHODS: mGPS is based on serum C reactive protein (CRP) and albumin, with scores ranging from 0 (least) to 2 (most). HRQL was measured with EORTC QLQ C-30 and OV-28. χ2 tests for trend were used to examine the relationship between HRQL, PS and mGPS. Cox proportional hazards regression was used to assess associations between mGPS, HRQL, clinicopathological factors, and overall survival (OS).

    RESULTS: Inflammatory markers were available in 516 of 948 patients in GCIG SBS. 200(39%) had potentially platinum sensitive ROC with ≥3 lines of chemotherapy, 316(61%) had platinum resistant ROC. 282(55%), 123(24%), 111(22%) had mGPS of 0, 1, 2, respectively. Median OS (months) was 18.1, 9.6, and 6.6 for mGPS 0, 1, and 2 respectively. mGPS was an independent predictor of OS after adjusting for PS and platinum sensitivity (p<0.001). mGPS remained a predictor of OS after adjusting for physical function, role function, global health status, abdominal/GI symptoms, and multiple clinicopathologic factors (p=0.02). Worse PS and higher mGPS were associated with poorer HRQL (p<0.001). Higher mGPS was associated with worse HRQL, independent of PS.

    CONCLUSION: The mGPS is an independent predictor of OS in ROC after adjusting for HRQL and clinicopathological factors. Higher mGPS is associated with worse HRQL independent of PS. mGPS is simple, inexpensive and may be suitable for clinical practice, clinical trial patient selection and stratification.

  • 119.
    Roncolato, Felicia T.
    et al.
    University of Sydney, Australia; ANZGOG, Australia; Macarthur Cancer Therapy Centre, Australia.
    Joly, Florence
    Centre Francois Baclesse, France.
    OConnell, Rachel
    University of Sydney, Australia.
    Lanceley, Anne
    UCL, England.
    Hilpert, Felix
    UKSH, Germany.
    Buizen, Luke
    University of Sydney, Australia.
    Okamoto, Aikou
    Jikei University, Japan.
    Aotani, Eriko
    Kitasato Academic Research Org, Japan.
    Pignata, Sandro
    IRCCS, Italy.
    Donnellan, Paul
    Galway University Hospital, Ireland.
    Oza, Amit
    University of Toronto, Canada.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Karolinska Institute, Sweden.
    Berek, Jonathan S.
    Stanford Comprehens Cancer Institute, CA USA.
    Heitz, Florian
    KEM, Germany; KEM, Germany.
    Feeney, Amanda
    Cancer Research UK, England; UCL Cancer Trials Centre, England.
    Berton-Rigaud, Dominique
    ICO Centre Rene Gauducheau, France.
    Stockler, Martin R.
    University of Sydney, Australia; ANZGOG, Australia.
    King, Madeleine
    ANZGOG, Australia; University of Sydney, Australia.
    Friedlander, Michael
    ANZGOG, Australia; Prince Wales Hospital, Australia.
    Reducing Uncertainty: Predictors of Stopping Chemotherapy Early and Shortened Survival Time in Platinum Resistant/Refractory Ovarian Cancer-The GCIG Symptom Benefit Study2017In: The Oncologist, ISSN 1083-7159, E-ISSN 1549-490X, Vol. 22, no 9, p. 1117-1124Article in journal (Refereed)
    Abstract [en]

    Background. Clinicians and patients often overestimate the benefits of chemotherapy, and overall survival (OS), in platinum resistant/refractory ovarian cancer (PRROC). This study sought to determine aspects of health-related quality of life and clinicopathological characteristics before starting chemotherapy that were associated with stopping chemotherapy early, shortened survival, and death within 30 days of chemotherapy. Materials and Methods. This study enrolled women with PRROC before starting palliative chemotherapy. Health-related quality of life was measured with EORTC QLQ-C30/QLQ-OV28. Chemotherapy stopped within 8 weeks of starting was defined as stopping early. Logistic regression was used to assess univariable and multivariable associations with stopping chemotherapy early and death within 30 days of chemotherapy; Cox proportional hazards regression was used to assess associations with progression-free and OS. Results. Low baseline global health status (GHS), role function (RF), physical function (PF), and high abdominal/gastrointestinal symptom (AGIS) were associated with stopping chemotherapy early (all pamp;lt;.007); low PF and RF remained significant after adjusting for clinicopathological factors (both pamp;lt;.0401). Most who stopped chemotherapy early had Eastern Cooperative Oncology Group Performance Score 0-1 at baseline (79%); PF, RF, and GHS remained independently significant predictors of stopping chemotherapy early in this subgroup. Death within 30 days of chemotherapy occurred in 14%. Low-GHS, RF, and PF remained significantly associated with death within 30 days of chemotherapy after adjusting for clinicopathological factors (all pamp;lt;.012). Conclusion. Women with low GHS, RF, or PF before starting chemotherapy were more likely to stop chemotherapy early, with short OS. Self-ratings of GHS, RF, and PF could improve patient-clinician communication regarding prognosis and help decision-making in women considering chemotherapy for PRROC.

  • 120.
    Rosell, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Business support and Development, Regional Cancer Center.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Bengtsson, Nils-Olof
    Umeå University Hospital, Sweden.
    Fornander, Tommy
    Karolinska University Hospital, Sweden.
    Hatschek, Thomas
    Karolinska University Hospital, Sweden.
    Lindman, Henrik
    Uppsala University Hospital, Sweden.
    Malmstrom, Per-Olof
    Skåne University Hospital, Sweden.
    Wallgren, Arne
    Sahlgrens University Hospital, Sweden.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Long-term effects on the incidence of second primary cancers in a randomized trial of two and five years of adjuvant tamoxifen2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 4, p. 614-617Article in journal (Refereed)
    Abstract [en]

    Background: Tamoxifen is a well established treatment for breast cancer, but its long-term effects on the incidence of secondary cancers are not fully evaluated.Material and methods: We have studied 4128 postmenopausal patients with early stage breast cancer who were alive and free of breast cancer recurrence after two years of tamoxifen, and who were randomized to receive totally two or five years of therapy.Results: Compared to patients randomized to two years of tamoxifen the incidence of contralateral breast cancer [hazard ratio (HR) 0.73; 95% CI 0.56-0.96] and of lung cancer (HR 0.45; 95% CI 0.27-0.77), especially squamous cell and small cell lung cancer, were reduced in the five-year group, and similar results were seen when restricting the analysis to the 10-year period after treatment stopped. An increased incidence of endometrial cancer was observed in the five-year group, but the excess risk decreased over time.Conclusion: Further studies of the effects of tamoxifen on the risk of different histological types of lung cancer are needed.

  • 121.
    Rosenberg, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Staf, Christian
    Reg Canc Ctr, Sweden; Sahlgrens Univ Hosp, Sweden.
    Bjurberg, Maria
    Skane Univ Hosp, Sweden.
    Borgfeldt, Christer
    Lund Univ, Sweden.
    Dahm-Kahler, Pernilla
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Hellman, Kristina
    Karolinska Inst, Sweden.
    Hjerpe, Elisabet
    Karolinska Inst, Sweden.
    Holmberg, Erik
    Reg Canc Ctr, Sweden; Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Stalberg, Karin
    Uppsala Univ, Sweden.
    Tholander, Bengt
    Uppsala Univ, Sweden.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Hogberg, Thomas
    Lund Univ, Sweden.
    Data quality in the Swedish Quality Register of Gynecologic Cancer - a Swedish Gynecologic Cancer Group (SweGCG) study2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 3, p. 346-353Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study is to evaluate the quality of data on endometrial (EC) and ovarian, fallopian tube, peritoneal, abdominal or pelvic cancers (OC) registered in the Swedish Quality Register of Gynecologic Cancer (SQRGC).Method: A random sample of 500 patients was identified in the SQRGC and their medical charts were reviewed for re-abstraction of 31 selected core variables by an independent validator. The data in the SQRGC and the re-abstracted data were compared. The data were collected from 25 hospitals evenly distributed throughout Sweden. The main outcomes were comparability, timeliness, completeness and validity. Coverage was compared with the National Cancer Register (NCR). Timeliness was defined as the speed of registration i.e. when patients were registered in the SQRGC relative to date of diagnosis. Internationally accepted coding systems for stage, grading and histologic type were used ensuring a high degree of comparability. Correlations were estimated using Pearsons correlation coefficient and Cohens kappa coefficient.Results: The completeness was 95%. The timeliness was 88-91% within 12 months of diagnosis. The median degree of agreement between re-abstracted data and data in the SQRGC was 82.1%, with a median kappa value of 0.73 for ordinate variables and a median Pearsons correlation coefficient of 0.96. The agreements for the type of surgery were 76% (95% CI 70-81%; kappa 0.49) and type of primary treatment 90% (95% CI 87-94%; kappa 0.85) in OC and in EC 88% (95% CI 84-93%; kappa 0.84). The agreements for the FIGO stage were in OC and EC 74% (95% CI 68-80%; kappa 0.69) and 87% (95% CI 82-91%; kappa 0.79), respectively.Conclusions: The data in the Swedish Quality Register for Gynecologic Cancer are of adequate quality in order to be used as a basis for research and to evaluate possible differences in treatment, lead times and treatment results.

  • 122.
    Salehi, Sahar
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Brandberg, Yvonne
    Karolinska Inst, Sweden.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Suzuki, Chikako
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Johansson, Hemming
    Karolinska Inst, Sweden.
    Legerstam, Berit
    Karolinska Inst, Sweden.
    Falconer, Henrik
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Long-term quality of life after comprehensive surgical staging of high-risk endometrial cancer - results from the RASHEC trial2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 12, p. 1671-1676Article in journal (Refereed)
    Abstract [en]

    Purpose: The health-related quality of life (HRQoL) outcomes after comprehensive surgical staging including infrarenal paraaortic lymphadenectomy in women with high-risk endometrial cancer (EC) are unknown. Our aim was to investigate the long-term HRQoL between robot-assisted laparoscopic surgery (RALS) and laparotomy (LT). Patients and Methods: A total of 120 women with high-risk stage I-II EC were randomised to RALS or LT for hysterectomy, bilateral salpingoophorectomy, pelvic and infrarenal paraaortic lymphadenectomy in the previously reported Robot-Assisted Surgery for High-Risk Endometrial Cancer trial. The HRQoL was measured with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-30) and its supplementary questionnaire module for endometrial cancer (QLQ-EN24) questionnaire. Women were assessed before and 12 months after surgery. In addition, the EuroQol Eq5D non-disease specific questionnaire was used for descriptive analysis. Results: There was no difference in the functional scales (including global health status) in the intention to treat analysis, though LT conferred a small clinically important difference (CID) over RALS in cognitive functioning albeit not statistically significant -6 (95% CI-14 to 0, p = .06). LT conferred a significantly better outcome for the nausea and vomiting item though it did not reach a CID, 4 (95% CI 1 to 7, p = .01). In the EORTC-QLQ/QLQ-EN24, no significant differences were observed. Eq5D-3L questionnaire demonstrated a higher proportion of women reporting any extent of mobility impairment 12 months after surgery in the LT arm (p = .03). Conclusion: Overall, laparotomy and robot-assisted surgery conferred similar HRQoL 12 months after comprehensive staging for high-risk EC.

  • 123.
    Salehi, Sahar
    et al.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Karolinska Institute, Sweden.
    Legerstam, Berit
    Karolinska University Hospital, Sweden.
    Carlson, Joseph W.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Falconer, Henrik
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Robot-assisted laparoscopy versus laparotomy for infrarenal paraaortic lymphadenectomy in women with high-risk endometrial cancer: A randomised controlled trial2017In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 79, p. 81-89Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate if robot-assisted laparoscopic surgery (RALS) was non-inferior to laparotomy (LT) in harvesting infrarenal paraaortic lymph nodes in patients with presumed stage IeII high-risk endometrial cancer. Patients and methods: Patients with histologically proven endometrial cancer, presumed stage IeII with high-risk tumour features, were randomised to hysterectomy, bilateral salpingo-oophorectomy, pelvic and paraaortic lymphadenectomy by either RALS or LT. Primary outcome was paraaortic lymph node count. Secondary outcomes were perioperative events, postoperative complications and total health care cost. Results: Overall 120 patients were randomised and 96 patients were included in the per protocol analysis. Demographic, clinical and tumour characteristics were evenly distributed between groups. Mean (+/- SD) paraaortic lymph node count was 20.9 (+/- 9.6) for RALS and 22 (+/- 11, p = 0.45) for LT. The difference of means was within the non-inferiority margin (-1.6, 95% CI -5.78, 2.57). Mean pelvic node count was lower after RALS (28 +/- 10 versus 22 +/- 8, p amp;lt; 0.001). There was no difference in perioperative complications or readmissions between the groups. Operation time was longer (p amp;lt; 0.001) but total blood loss less (amp;lt;0.001) and hospital stay shorter (amp;lt;0.001) in RALS group than LT group. Health care costs for RALS was significantly lower (mean difference $1568 USD/(sic)1225 Euro, p amp;lt; 0.05). Conclusion: Our results demonstrate non-inferiority in paraaortic lymph node count, comparable complication rates, shorter hospital length and lower total cost for RALS over laparotomy. Generalisability of the latter finding requires a high-volume setting and high surgical proficiency. In women with high-risk endometrial cancer confined to the uterus, RALS is a valid treatment modality. Clinical trials registrations: ClinicalTrials.gov NCT01847703. (C) 2017 Elsevier Ltd. All rights reserved.

  • 124.
    Schroeder, Brock
    et al.
    Biotheranostics, Inc., San Diego, CA USA.
    Zhang, Yi
    Biotheranostics, Inc., San Diego, CA USA.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Fornander, Tommy
    Karolinska Institute, Stockholm, Sweden.
    Brufsky, Adam
    University of Pittsburgh School of Medicine, Pittsburgh, PA USA.
    Sgroi, Dennis C
    Massachusetts General Hospital, Boston, MA USA.
    Schnabel, Catherine A.
    Biotheranostics, Inc., San Diego, CA USA.
    Risk stratification with Breast Cancer Index for late distant recurrence in patients with clinically low-risk (T1N0) estrogen receptor-positive breast cancer2017In: NPJ breast cancer, ISSN 2374-4677, Vol. 3Article in journal (Refereed)
    Abstract [en]

    Patients with early-stage, hormone receptor-positive breast cancer with favorable clinicopathologic features are often not recommended for extended endocrine therapy. However, even patients with T1N0 disease remain at significant risk of distant recurrence up to 15 years following 5 years of endocrine therapy, highlighting the need for further stratification based on individualized risk to select patients for extended endocrine therapy. In this study, the incremental utility of genomic classification to stratify clinically low-risk patients for late distant recurrence was evaluated using the Breast Cancer Index. In 547 T1N0 patients from two cohorts that were disease-free at 5 years post-diagnosis, Breast Cancer Index categorized 32 and 36% from each cohort, respectively, with high risk of late distant recurrence that was associated with significantly reduced distant recurrence-free survival (86.7 and 89.6%) between years 5-15 and 5-10 compared to Breast Cancer Index low risk (95.4%; P?=?0.0263 and 98.4%; P?=?0.008). Findings support consideration of genomic classification in clinically low-risk hormone receptor-positive patients to identify candidates for extended endocrine therapy.

  • 125.
    Seoud, Muhieddine
    et al.
    Amer University of Beirut, Lebanon.
    Åvall Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Fujiwara, Keiichi
    Saitama Medical University, Japan.
    Targeted therapy in gynecologic cancers: Ready for prime time?2015In: International Journal of Gynecology & Obstetrics, ISSN 0020-7292, E-ISSN 1879-3479, Vol. 131, p. S150-S152Article in journal (Refereed)
    Abstract [en]

    n/a

  • 126.
    Skoglund, Karin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Richter, Johan
    Skåne University Hospital, Sweden.
    Olsson-Stromberg, Ulla
    Uppsala University, Sweden.
    Bergquist, Jonas
    Uppsala University, Sweden.
    Aluthgedara, Warunika
    Uppsala University, Sweden.
    Ubhayasekera, S. J. Kumari A.
    Uppsala University, Sweden.
    Vikingsson, Svante
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    Svedberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Söderlund, Stina
    Uppsala University, Sweden.
    Sandstedt, Anna
    Linköping University, Department of Social and Welfare Studies. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Johnsson, Anders
    Region Östergötland, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Aagesen, Jesper
    Ryhov County Hospital, Sweden.
    Alsenhed, Jonas
    Vastervik Hosp, Dept Internal Med, Västervik, Sweden.
    Hägg, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Lotfi, Kourosh
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    In Vivo Cytochrome P450 3A Isoenzyme Activity and Pharmacokinetics of Imatinib in Relation to Therapeutic Outcome in Patients With Chronic Myeloid Leukemia2016In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 38, no 2, p. 230-238Article in journal (Refereed)
    Abstract [en]

    Background: Cytochrome P450 3A (CYP3A) isoenzyme metabolic activity varies between individuals and is therefore a possible candidate of influence on the therapeutic outcome of the tyrosine kinase inhibitor imatinib in patients with chronic myeloid leukemia (CML). The aim of this study was to investigate the influence of CYP3A metabolic activity on the plasma concentration and outcome of imatinib in patients with CML. Methods: Forty-three patients with CML were phenotyped for CYP3A activity using quinine as a probe drug and evaluated for clinical response parameters. Plasma concentrations of imatinib and its main metabolite, CGP74588, were determined using liquid chromatography-mass spectrometry. Results: Patients with optimal response to imatinib after 12 months of therapy did not differ in CYP3A activity compared to nonoptimal responders (quinine metabolic ratio of 14.69 and 14.70, respectively; P = 0.966). Neither the imatinib plasma concentration nor the CGP74588/imatinib ratio was significantly associated with CYP3A activity. Conclusions: The CYP3A activity does not influence imatinib plasma concentrations or the therapeutic outcome. These results indicate that although imatinib is metabolized by CYP3A enzymes, this activity is not the rate-limiting step in imatinib metabolism and excretion. Future studies should focus on other pharmacokinetic processes so as to identify the major contributor to patient variability in imatinib plasma concentrations.

  • 127.
    Smith, Amber R.
    et al.
    University of Kansas, KS 66045 USA.
    Marquez, Rebecca T.
    University of Kansas, KS 66045 USA.
    Tsao, Wei-Chung
    University of Kansas, KS 66045 USA.
    Pathak, Surajit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Roy, Alexandria
    University of Kansas, KS 66045 USA.
    Ping, Jie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Wilkerson, Bailey
    University of Kansas, KS 66045 USA.
    Lan, Lan
    University of Kansas, KS 66045 USA.
    Meng, Wenjian
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Neufeld, Kristi L.
    University of Kansas, KS 66045 USA; University of Kansas, KS 66103 USA.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Xu, Liang
    University of Kansas, KS 66045 USA; University of Kansas, KS 66103 USA.
    Tumor suppressive microRNA-137 negatively regulates Musashi-1 and colorectal cancer progression2015In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, no 14, p. 12558-12573Article in journal (Refereed)
    Abstract [en]

    Stem cell marker, Musashi-1 (MSI1) is over-expressed in many cancer types; however the molecular mechanisms involved in MSI1 over-expression are not well understood. We investigated the microRNA (miRNA) regulation of MSI1 and the implications this regulation plays in colorectal cancer. MicroRNA miR-137 was identified as a MSI1-targeting microRNA by immunoblotting and luciferase reporter assays. MSI1 protein was found to be highly expressed in 79% of primary rectal tumors (n=146), while miR-137 expression was decreased in 84% of the rectal tumor tissues (n=68) compared to paired normal mucosal samples. In addition to reduced MSI1 protein, exogenous expression of miR-137 inhibited cell growth, colony formation, and tumorsphere growth of colon cancer cells. Finally, in vivo studies demonstrated that induction of miR-137 can decrease growth of human colon cancer xenografts. Our results demonstrate that miR-137 acts as a tumor-suppressive miRNA in colorectal cancers and negatively regulates oncogenic MSI1.

  • 128.
    Sonnenblick, Amir
    et al.
    University of Libre Bruxelles, Belgium.
    Francis, Prudence A.
    Peter MacCallum Cancer Centre, Australia; Australia and New Zealand Breast Cancer Trials Grp, Australia; Int Breast Cancer Study Grp, Switzerland.
    Azim, Hatem A. Jr.
    University of Libre Bruxelles, Belgium.
    de Azambuja, Evandro
    University of Libre Bruxelles, Belgium.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Gutierez, Jorge
    Clin Las Condes, Chile.
    Quinaux, Emmanuel
    Int Institute Drug Dev, Belgium.
    Mastropasqua, Mauro G.
    University of Milan, Italy; University of Milan, Italy.
    Ameye, Lieveke
    University of Libre Bruxelles, Belgium.
    Anderson, Michael
    Copenhagen University Hospital, Denmark; Danish Breast Cancer Cooperat Grp, Denmark.
    Lluch, Ana
    University of Valencia, Spain.
    Gnant, Michael
    Medical University of Vienna, Austria; Medical University of Vienna, Austria.
    Goldhirsch, Aron
    European Institute Oncol, Italy; Int Breast Cancer Study Grp, Switzerland.
    Di Leo, Angelo
    Hospital Prato, Italy.
    Barnadas, Agusti
    University of Autonoma Barcelona, Spain.
    Cortes-Funes, Hernan
    University Hospital 12 Octubre, Spain.
    Piccart, Martine
    University of Libre Bruxelles, Belgium.
    Crown, John
    St Vincets University Hospital, Ireland.
    Final 10-year results of the Breast International Group 2-98 phase III trial and the role of Ki67 in predicting benefit of adjuvant docetaxel in patients with oestrogen receptor positive breast cancer2015In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 51, no 12, p. 1481-1489Article in journal (Refereed)
    Abstract [en]

    Aim: Breast International Group (BIG) 2-98 is a randomised phase III trial that tested the effect of adding docetaxel, either in sequence to or in combination with anthracycline-based adjuvant chemotherapy, in women with node-positive breast cancer (BC). Here, we present the 10-year final trial safety and efficacy analyses. We also report an exploratory analysis on the predictive value of Ki67 for docetaxel efficacy, in the BIG 2-98 and using a pooled analysis of three other randomised trials. Patients and methods: 2887 patients were randomly assigned in a 2 x 2 trial design to one of four treatments. The primary objective was to evaluate the overall efficacy of docetaxel on disease free survival (DFS). Secondary objectives included comparisons of sequential docetaxel versus sequential control arm, safety and overall survival (OS). Ki67 expression was centrally evaluated by immunohistochemistry. Results: After a median follow-up of 10.1 years, the addition of docetaxel did not significantly improve DFS or OS (hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.81-1.04; P = 0.16 and HR = 0.88, 95% CI = 0.76-1.03; P = 0.11, respectively). Sequential docetaxel did not improve DFS compared to the sequential control arm (HR = 0.86, 95% CI = 0.721.03; P = 0.10). In oestrogen receptor (ER)-positive tumours with Ki67 greater than= 14%, the addition of docetaxel resulted in 5.4% improvement in 10-year OS (P = 0.03, test for interaction = 0.1). In a multivariate model, there was a trend for improved DFS and OS in ER-positive patients with high Ki67 and treated with docetaxel (HR = 0.79, 95% CI = 0.63-1.01; P = 0.05 and HR = 0.76, 95% CI = 0.57-1.01; P = 0.06, respectively). A pooled analysis of four randomised trials showed a benefit of taxanes in highly proliferative ER-positive disease but not in low proliferating tumours (interaction test P = 0.01). Conclusion: The DFS benefit previously demonstrated with sequential docetaxel is no longer observed at 10 years. However, an exploratory analysis suggested a benefit of docetaxel in patients with highly proliferative ER-positive BC.

  • 129.
    Stalberg, Karin
    et al.
    Uppsala Univ, Sweden.
    Bjurberg, Maria
    Skane Univ Hosp Lund, Sweden; Lund Univ, Sweden.
    Borgfeldt, Christer
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Carlson, Joseph
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Dahm-Kahler, Pernilla
    Gothenburg Univ, Sweden.
    Floter-Radestad, Angelique
    Karolinska Inst, Sweden.
    Hellman, Kristina
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Hjerpe, Elisabet
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Holmberg, Erik
    Sahlgrens Acad, Sweden; Sahlgrens Univ Hosp, Sweden.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Marcickiewicz, Janusz
    Reg Canc Ctr Vast, Sweden; Hallands Hosp Varberg, Sweden.
    Rosenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Tholander, Bengt
    Uppsala Univ, Sweden.
    Åvall Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Hogberg, Thomas
    Lund Univ, Sweden.
    Lymphovascular space invasion as a predictive factor for lymph node metastases and survival in endometrioid endometrial cancer - a Swedish Gynecologic Cancer Group (SweGCG) studyIn: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226XArticle in journal (Refereed)
    Abstract [en]

    Background: The aim of this study is to evaluate the impact of lymphovascular space invasion (LVSI) on the risk of lymph node metastases and survival in endometrioid endometrial adenocarcinoma. Material and methods: As regard the study design, this is a cohort study based on prospectively recorded data. Patients with endometrioid endometrial adenocarcinoma registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2017 with FIGO stages I-III and verified nodal status were identified (n = 1587). LVSI together with established risk factors, namely DNA ploidy, FIGO grade, myometrial invasion and age, were included in multivariable regression analyses with lymph node metastases as the dependent variable. Associations between the risk factors and overall and relative survival were included in multivariable models. Estimates of risk ratios (RR), hazard ratios (HR), excess mortality rate ratios (EMR), and 95% confidence intervals (95% CI) were calculated. Results: The presence of LVSI presented the strongest association with lymph node metastases (RR = 5.46, CI 3.69-8.07, p amp;lt; .001) followed by deep myometrial invasion (RR = 1.64, CI 1.13-2.37). In the multivariable survival analyses, LVSI (EMR = 7.69, CI 2.03-29.10,) and non-diploidy (EMR = 3.23, CI 1.25-8.41) were associated with decreased relative survival. In sub-analyses including only patients with complete para-aortic and pelvic lymphadenectomy and negative lymph nodes (n = 404), only LVSI (HR = 2.50, CI 1.05-5.98) was associated with a worsened overall survival. Conclusion: This large nationwide study identified LVSI as the strongest independent risk factor for lymph node metastases and decreased survival in patients with endometrioid adenocarcinomas. Moreover, decreased overall survival was also seen in patients with LVSI-positive tumors and negative lymph nodes, indicating that hematogenous dissemination might also be important.

  • 130.
    Stinesen Kollberg, Karin
    et al.
    University of Gothenburg, Sweden.
    Waldenstrom, Ann-Charlotte
    University of Gothenburg, Sweden.
    Bergmark, Karin
    University of Gothenburg, Sweden; Karolinska Institute, Sweden.
    Dunberger, Gail
    Karolinska Institute, Sweden; Ersta Skondal University of Coll, Sweden.
    Rossander, Anna
    Hallands Hospital Kungsbacka, Sweden.
    Wilderang, Ulrica
    University of Gothenburg, Sweden.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Karolinska Institute, Sweden.
    Steineck, Gunnar
    University of Gothenburg, Sweden; Karolinska Institute, Sweden.
    Reduced vaginal elasticity, reduced lubrication, and deep and superficial dyspareunia in irradiated gynecological cancer survivors2015In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 5, p. 772-779Article in journal (Refereed)
    Abstract [en]

    Purpose. The purpose of this study was to examine whether or not vaginal elasticity or lack of lubrication is associated with deep or superficial dyspareunia. We investigated gynecological cancer survivors treated with radiation therapy. Methods. In a population-based study with 616 women answering a questionnaire (participation rate 78%) and who were treated with radiotherapy for gynecological cancer, we analyzed information from 243 women (39%) who reported that they had had intercourse during the previous six months. Analyses included log-binomial regression (relative risks) and multiple imputations by chained equations in combination with Bayesian Model Averaging, yielding a posterior probability value. Age range of this cancer recurrent-free group of women was 29-80. Results. Dyspareunia affected 164 of 243 of the women (67%). One hundred thirty-four women (55%) reported superficial pain, 97 women (40%) reported deep pain, and 87 women (36%) reported both types of dyspareunia. The relative risk (RR) of deep dyspareunia was 1.87 (CI 1.41-2.49) with impaired vaginal elasticity compared to normal vaginal elasticity. Age and lower abdominal swelling were separate risk factors for deep dyspareunia. However, effects remain after adjusting for these factors. Conclusion. The relative risk of deep dyspareunia was almost twice as high with impaired vaginal elasticity compared to normal vaginal elasticity. If we wish to treat or even prevent deep dyspareunia in women with gynecological cancer, we may use our knowledge of the pathophysiology of deep dyspareunia and increasingly provide dilators together with instructions on how to use them for stretching exercises in order to retain vaginal elasticity. Results highlight the need for studies with more precise questions distinguishing superficial from deep dyspareunia so that in the future we may be able to primarily try to avoid reduced vaginal elasticity and secondarily reduce the symptoms.

  • 131.
    Stålberg, Karin
    et al.
    Uppsala University, Sweden.
    Kjölhede, Preben
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Bjurberg, M.
    Skånes University of Sjukhus, Sweden; Lund University, Sweden.
    Borgfeldt, C.
    Lund University, Sweden.
    Dahm-Kahler, P.
    University of Gothenburg, Sweden.
    Falconer, H.
    Karolinska Institute, Sweden.
    Holmberg, E.
    Sahlgrens University Hospital, Sweden; Gothenburg University, Sweden.
    Staf, C.
    Sahlgrens University Hospital, Sweden.
    Tholander, B.
    Uppsala University Hospital, Sweden.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Karolinska Institute, Sweden.
    Rosenberg, Per
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences.
    Högberg, T.
    Lund University, Sweden.
    Risk factors for lymph node metastases in women with endometrial cancer: A population-based, nation-wide register studyOn behalf of the Swedish Gynecological Cancer Group2017In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 140, no 12, p. 2693-2700Article in journal (Refereed)
    Abstract [en]

    The role of lymphadenectomy in the management of early endometrial cancer remains controversial. In the recent ESMO-ESGO-ESTRO guidelines, lymphadenectomy is recommended for patients with endometrioid adenocarcinoma Grade 3 with deep myometrial invasion, but complete agreement was not achieved. In Sweden, DNA aneuploidy has been included as a high-risk factor. The aim of our study was to evaluate the impact of tumor histology, FIGO grade, DNA ploidy and myometrial invasion (MI) on occurrence of lymph node metastasis (LNM) in patients with endometrial cancer. The study design is a retrospective cohort study based on prospectively recorded register data. Endometrial cancer patients registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2015 with FIGO Stages I-III and verified nodal status were included. Data on DNA ploidy, histology, FIGO grade and MI were included in multivariable log-binomial regression analyses with LNM as dependent variable. 1,165 cases fulfilled the inclusion criteria. The multivariable analyses revealed increased risk of LNM in patients with tumors with MI50% (risk ratio [RR]=4.1; 95% confidence interval [CI] 3.0-5.6), nonendometrioid compared to endometrioid histology (RR 1.8; CI 1.4-2.4) and FIGO Grade 3 compared to Grade 1-2 tumors (RR 1.5; CI 1.1-2.0). No statistically significant association between DNA ploidy status and LNM was detected. This population-based, nation-wide study in women with endometrial cancer confirms a strong association between MI50%, nonendometrioid histology and FIGO Grade 3, respectively, and LNM. DNA ploidy should not be included in the preoperative decision making of removing nodes or not. Whats new? Whether lymphadenectomy is beneficial for women with endometrial cancer remains uncertain. Moreover, additional studies are needed to explore factors that reliably predict lymph node metastasis (LNM). Here, multiple factors, including tumor histology, grade of differentiation and DNA aneuploidy, were evaluated for associations with LNM risk in women with endometrial cancer and verified lymph node status. Most significantly, deep myometrial invasion in tumors increased LNM risk fourfold, whereas DNA ploidy had essentially no impact on LNM risk. The findings confirm the predictive relevance of myometrial invasion, histology and grade reported in previous single-center and multicenter studies.

  • 132.
    Subramaniam, Vimala Devi
    et al.
    CARE, India.
    Prasad, Suhanya Veronica
    CARE, India.
    Banerjee, Antara
    CARE, India.
    Gopinath, Madhumala
    CARE, India.
    Murugesan, Ramachandran
    CARE, India.
    Marotta, Francesco
    Preventit Med Promot Fdn, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Pathak, Surajit
    CARE, India.
    Health hazards of nanoparticles: understanding the toxicity mechanism of nanosized ZnO in cosmetic products2019In: Drug and chemical toxicology (New York, N.Y. 1978), ISSN 0148-0545, E-ISSN 1525-6014, Vol. 42, no 1, p. 84-93Article, review/survey (Refereed)
    Abstract [en]

    In recent years, nanoparticles are being used extensively in personal healthcare products such as cosmetics, sunscreens, soaps, and shampoos. Particularly, metal oxide nanoparticles are gaining competence as key industrial constituents, progressing toward a remarkable rise in their applications. Zinc oxide and titanium oxide nanoparticles are the most commonly employed metal oxide nanoparticles in sunscreens, ointments, foot care, and over the counter topical products. Dermal exposure to these metal oxides predominantly occurs through explicit use of cosmetic products and airway exposure to nanoparticle dusts is primarily mediated via occupational exposure. There is a compelling need to understand the toxicity effects of nanoparticles which can easily enter the cells and induce oxidative stress. Consequently, these products have become a direct source of pollution in the environment and thereby greatly impact our ecosystem. A complete understanding of the toxicity mechanism of nano-ZnO is intended to resolve whether and to what extent such nanoparticles may pose a threat to the environment and to human beings. In this review article, we have discussed the characteristics of metal oxide nanoparticles and its applications in the cosmetic industry. We have also highlighted about their toxicity effects and their impact on human health.

  • 133.
    Sun, Hui-Min
    et al.
    Shanghai Jiao Tong University, Peoples R China.
    Mi, Yu-Shuai
    Shanghai Jiao Tong University, Peoples R China.
    Yu, Fu-Dong
    Shanghai Jiao Tong University, Peoples R China.
    Han, Yang
    Shanghai Jiao Tong University, Peoples R China.
    Liu, Xi-Sheng
    Shanghai Jiao Tong University, Peoples R China.
    Lu, Su
    Shanghai Jiao Tong University, Peoples R China.
    Zhang, Yu
    Shanghai Jiao Tong University, Peoples R China.
    Zhao, Sen-Lin
    Shanghai Jiao Tong University, Peoples R China.
    Ye, Ling
    Shanghai Jiao Tong University, Peoples R China.
    Liu, Ting-Ting
    Shanghai Jiao Tong University, Peoples R China.
    Yang, Dao-Hua
    Shanghai Jiao Tong University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Qin, Xue-Bin
    Temple University, PA 19122 USA.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China.
    Tang, Hua-Mei
    Shanghai Jiao Tong University, Peoples R China.
    Peng, Zhi-Hai
    Shanghai Jiao Tong University, Peoples R China.
    SERPINA4 is a novel independent prognostic indicator and a potential therapeutic target for colorectal cancer2016In: American Journal of Cancer Research, ISSN 2156-6976, E-ISSN 2156-6976, Vol. 6, no 8, p. 1636-1649Article in journal (Refereed)
    Abstract [en]

    Serpina family A member 4 (SERPINA4), also known as kallistatin, exerts important effects in inhibiting tumor growth and angiogenesis in many malignancies. However, the precise role of SERPINA4 in CRC has not been fully elucidated. The present study aimed to investigate the expression of SERPINA4 and its clinical significance in CRC. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses showed that the mRNA and protein expression of SERPINA4 in colorectal cancer (CRC) specimens was significantly decreased than that in adjacent normal mucosa. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of SERPINA4 by using a tissue microarray (TMA) containing 327 archived paraffin-embedded CRC specimens. Statistical analyses revealed that decreased SERPINA4 expression was significantly associated with invasion depth, nodal involvement, distant metastasis, American Joint Committee on Cancer (AJCC) stage, and tumor differentiation. SERPINA4 was also an independent prognostic indicator of disease-free survival and overall survival in patients with CRC. Furthermore, the impact of altered SERPINA4 expression on CRC cells was analyzed with a series of in vitro and in vivo assays. The results demonstrated that SERPINA4 significantly inhibits malignant tumor progression and serves as a novel prognostic indicator and a potential therapeutic target for CRC.

  • 134.
    Svensson, Susanne
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Abrahamsson, Annelie
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Vazquez Rodriguez, Gabriela
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology.
    Olsson, Anna-Karin
    Uppsala University, Sweden.
    Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Stockholm, Sweden..
    Cao, Yihai
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden; University of Leicester, England; Glenfield Hospital, England.
    Dabrosin, Charlotta
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    CCL2 and CCL5 Are Novel Therapeutic Targets for Estrogen-Dependent Breast Cancer2015In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 21, no 16, p. 3794-3805Article in journal (Refereed)
    Abstract [en]

    Purpose: Novel therapeutic targets of estrogen receptor (ER)-positive breast cancers are urgently needed because current antiestrogen therapy causes severe adverse effects, nearly 50% of patients are intrinsically resistant, and the majority of recurrences have maintained ER expression. We investigated the role of estrogen-dependent chemokine expression and subsequent cancer growth in human tissues and experimental breast cancer models. Experimental Design: For in vivo sampling of human chemokines, microdialysis was used in breast cancers of women or normal human breast tissue before and after tamoxifen therapy. Estrogen exposure and targeted therapies were assessed in immune competent PyMT murine breast cancer, orthotopic human breast cancers in nude mice, cell culture of cancer cells, and freshly isolated human macrophages. Cancer cell dissemination was investigated using zebrafish. Results: ER+ cancers in women produced high levels of extracellular CCL2 and CCL5 in vivo, which was associated with infiltration of tumor-associated macrophages. In experimental breast cancer, estradiol enhanced macrophage influx and angiogenesis through increased release of CCL2, CCL5, and vascular endothelial growth factor. These effects were inhibited by anti-CCL2 or anti-CCL5 therapy, which resulted in potent inhibition of cancer growth. In addition, estradiol induced a protumorigenic activation of the macrophages. In a zebrafish model, macrophages increased cancer cell dissemination via CCL2 and CCL5 in the presence of estradiol, which was inhibited with anti-CCL2 and anti-CCL5 treatment. Conclusions: Our findings shed new light on the mechanisms underlying the progression of ER+ breast cancer and indicate the potential of novel therapies targeting CCL2 and CCL5 pathways. (C)2015 AACR.

  • 135.
    Tandstad, T.
    et al.
    St Olavs University Hospital, Norway.
    Stahl, O.
    Skåne University Hospital, Sweden.
    Dahl, O.
    University of Bergen, Norway; Haukeland Hospital, Norway.
    Haugnes, H. S.
    University of Tromso, Norway; University Hospital North Norway, Norway.
    Håkansson, U.
    Skåne University Hospital, Sweden.
    Karlsdottir, A.
    Haukeland Hospital, Norway.
    Kjellman, A.
    Karolinska University Hospital, Sweden.
    Langberg, C. W.
    Oslo University Hospital, Norway.
    Laurell, A.
    University of Uppsala Hospital, Sweden.
    Oldenburg, J.
    Akershus University Hospital, Norway; University of Oslo, Norway.
    Solberg, A.
    St Olavs University Hospital, Norway.
    Söderström, K.
    Norrland University Hospital, Sweden.
    Stierner, U.
    Sahlgrens University Hospital, Sweden; University of Gothenburg, Sweden.
    Cavallin-Stahl, E.
    Skåne University Hospital, Sweden.
    Wahlqvist, R.
    Oslo University Hospital, Norway.
    Wall, Najme
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Cohn-Cedermark, G.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Treatment of stage I seminoma, with one course of adjuvant carboplatin or surveillance, risk-adapted recommendations implementing patient autonomy: a report from the Swedish and Norwegian Testicular Cancer Group (SWENOTECA)2016In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 27, no 7, p. 1299-1304Article in journal (Refereed)
    Abstract [en]

    A total of 1118 patients with clinical stage I seminoma one course of adjuvant carboplatin or managed by surveillance were included. Stromal invasion of rete testis and tumor size amp;gt; 4 cm are confirmed as risk factors predicting relapse. Relapse rates following one course of adjuvant carboplatin is high and there is need to explore more effective adjuvant treatment options in patients with seminoma.The purpose of the protocol was to reduce the treatment burden in clinical stage I (CSI) seminoma by offering risk-adapted treatment. The protocol aimed to prospectively validate the proposed risk factors for relapse, stromal invasion of the rete testis and tumor diameter amp;gt; 4 cm, and to evaluate the efficacy of one course of adjuvant carboplatin. From 2007 to 2010, 897 patients were included in a prospective, population-based, risk-adapted treatment protocol implementing one course of adjuvant carboplatin AUC7 (amp;gt;n = 469) or surveillance (amp;gt;n = 422). In addition, results from 221 patients receiving carboplatin between 2004 and 2007 are reported. At a median follow-up of 5.6 years, 69 relapses have occurred. Stromal invasion of the rete testis [hazard ratio (HR) 1.9, amp;gt;P = 0.011] and tumor diameter amp;gt; 4 cm (HR 2.7, amp;gt;P amp;lt; 0.001) were identified as risk factors predicting relapse. In patients without risk factors, the relapse rate (RR) was 4.0% for patients managed by surveillance and 2.2% in patients receiving adjuvant carboplatin. In patients with one or two risk factors, the RR was 15.5% in patients managed by surveillance and 9.3% in patients receiving adjuvant carboplatin. We found no increased RR in patients receiving carboplatin amp;lt; 7 x AUC compared with that in patients receiving a parts per thousand yen7 x AUC. Stromal invasion in the rete testis and tumor diameter amp;gt; 4 cm are risk factors for relapse in CSI seminoma. Patients without risk factors have a low RR and adjuvant therapy is not justified in these patients. The efficacy of adjuvant carboplatin is relatively low and there is need to explore more effective adjuvant treatment options in patients with high-risk seminoma. The data do not support the concept of a steep dose response for adjuvant carboplatin.

  • 136.
    Trovik, Clement
    et al.
    Haukeland Hospital, Norway.
    Bauer, Henrik C. F.
    Karolinska Hospital, Sweden.
    Styring, Emelie
    Lund University, Sweden.
    Sundby Hall, Kirsten
    Oslo University Hospital, Norway.
    Vult von Steyern, Fredrik
    Lund University, Sweden.
    Eriksson, Sigvard
    Sahlgrenska Hospital, Sweden.
    Johansson, Ingela
    Norrland University Hospital, Sweden.
    Sampo, Mika
    Helsinki University Hospital, Finland.
    Laitinen, Minna
    Tampere University Hospital, Finland.
    Kalén, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Jonsson, Halldor Jr.
    Landspitalin, Iceland.
    Jebsen, Nina
    Haukeland Hospital, Norway.
    Eriksson, Mikael
    Lund University Hospital, Sweden.
    Tukiainen, Erkki
    Helsinki University Hospital, Finland.
    Wall, Najme
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Zaikova, Olga
    Oslo University Hospital, Norway.
    Sigurdsson, Helgi
    Landspitalin, Iceland.
    Lehtinen, Tuula
    Tampere University Hospital, Finland.
    Bjerkehagen, Bodil
    Oslo University Hospital, Norway.
    Skorpil, Mikael
    Akad Sjukhuset, Sweden; Karolinska Institute, Sweden.
    Egil Eide, Geir
    Haukeland Hospital, Norway; University of Bergen, Norway.
    Johansson, Elisabeth
    Lund University Hospital, Sweden..
    Alvegard, Thor A.
    Lund University Hospital, Sweden..
    The Scandinavian Sarcoma Group Central Register: 6,000 patients after 25 years of monitoring of referral and treatment of extremity and trunk wall soft-tissue sarcoma2017In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 88, no 3, p. 341-347Article in journal (Refereed)
    Abstract [en]

    Purpose - We wanted to examine the potential of the Scandinavian Sarcoma Group (SSG) Central Register, and evaluate referral and treatment practice for soft-tissue sarcomas in the extremities and trunk wall (STS) in the Nordic countries. Background - Based on incidence rates from the literature, 8,150 (7,000-9,300) cases of STS of the extremity and trunk wall should have been diagnosed in Norway, Finland, Iceland, and Sweden from 1987 through 2011. The SSG Register has 6,027 cases registered from this period, with 5,837 having complete registration of key variables. 10 centers have been reporting to the Register. The 5 centers that consistently report treat approximately 90% of the cases in their respective regions. The remaining centers have reported all the patients who were treated during certain time periods, but not for the entire 25-year period. Results - 59% of patients were referred to a sarcoma center untouched, i.e. before any attempt at open biopsy. There was an improvement from 52% during the first 5 years to 70% during the last 5 years. 50% had wide or better margins at surgery. Wide margins are now achieved less often than 20 years ago, in parallel with an increase in the use of radiotherapy. For the centers that consistently report, 97% of surviving patients are followed for more than 4 years. Metastasis-free survival (MFS) increased from 67% to 73% during the 25-year period. Interpretation - The Register is considered to be representative of extremity and trunk wall sarcoma disease in the population of Scandinavia, treated at the reporting centers. There were no clinically significant differences in treatment results at these centers.

  • 137.
    van t Veer, Laura J.
    et al.
    University of Calif San Francisco, CA 94115 USA.
    Yau, Christina
    University of Calif San Francisco, CA 94115 USA; Buck Institute Research Aging, CA 94945 USA.
    Yu, Nancy Y.
    Karolinska Institute, Sweden.
    Benz, Christopher C.
    Buck Institute Research Aging, USA; University of Calif San Francisco,USA.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Fornander, Tommy
    Karolinska Institute, Sweden.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Esserman, Laura J.
    University of Calif San Francisco, CA 94115 USA.
    Sofie Lindstrom, Linda
    Karolinska Institute, Sweden.
    Tamoxifen therapy benefit for patients with 70-gene signature high and low risk2017In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 166, no 2, p. 593-601Article in journal (Refereed)
    Abstract [en]

    Breast cancer molecular prognostic tools that predict recurrence risk have mainly been established on endocrine-treated patients and thus are not optimal for the evaluation of benefit from endocrine therapy. The Stockholm tamoxifen (STO-3) trial which randomized postmenopausal node-negative patients to 2-year tamoxifen (followed by an optional randomization for an additional 3-year tamoxifen vs nil), versus no adjuvant treatment, provides a unique opportunity to evaluate long-term 20-year benefit of endocrine therapy within prognostic risk classes of the 70-gene prognosis signature that was developed on adjuvantly untreated patients. We assessed by Kaplan-Meier analysis 20-year breast cancer-specific survival (BCSS) and 10-year distant metastasis-free survival (DMFS) for 538 estrogen receptor (ER)-positive, STO-3 trial patients with retrospectively ascertained 70-gene prognosis classification. Multivariable analysis of long-term (20 years) BCSS by STO-3 trial arm in the 70-gene high-risk and low-risk subgroups was performed using Cox proportional hazard modeling adjusting for classical patient and tumor characteristics. Tamoxifen-treated, 70-gene low- and high-risk patients had 20-year BCSS of 90 and 83%, as compared to 80 and 65% for untreated patients, respectively (log-rank p amp;lt; 0.0001). Notably, there is equivalent tamoxifen benefit in both high (HR 0.42 (0.21-0.86), p = 0.018) and low (HR 0.46 (0.25-0.85), p = 0.013) 70-gene risk categories even after adjusting for clinico-pathological factors for BCSS. Limited tamoxifen exposure as given in the STO-3 trial provides persistent benefit for 10-15 years after diagnosis in a time-varying analysis. 10-year DMFS was 93 and 85% for low- and high-risk tamoxifen-treated, versus 83 and 70% for low- and high-risk untreated patients, respectively (log-rank p amp;lt; 0.0001). Patients with ER-positive breast cancer, regardless of high or low 70-gene risk classification, receive significant survival benefit lasting over 10 years from adjuvant tamoxifen therapy, even when given for a relatively short duration.

  • 138.
    Vazquez Rodriguez, Gabriela
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Abrahamsson, Annelie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Jensen, Lasse D
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Adipocytes Promote Early Steps of Breast Cancer Cell Dissemination via Interleukin-82018In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, p. 1-17, article id 1767Article in journal (Refereed)
    Abstract [en]

    Fat is a major tissue component in human breast cancer (BC). Whether breast adipocytes (BAd) affect early stages of BC metastasis is yet unknown. BC progression is dependent on angiogenesis and inflammation, and interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) are key regulators of these events. Here, we show that BAd increased the dissemination of estrogen receptor positive BC cells (BCC) in vivo in the zebrafish model of metastasis, while dissemination of the more aggressive and metastatic BCC such as estrogen receptor negative was unaffected. While anti-VEGF and anti-IL-8 exhibited equal inhibition of angiogenesis at the primary tumor site, anti-IL-8 reduced BCC dissemination whereas anti-VEGF had minor effects on this early metastatic event. Mechanistically, overexpression of cell-adhesion molecules in BCC and neutrophils via IL-8 increased the dissemination of BCC. Importantly, the extracellular in vivo levels of IL-8 were 40-fold higher than those of VEGF in human BC. Our results suggest that IL-8 is a clinical relevant and promising therapeutic target for human BC.

  • 139.
    Vazquez Rodriguez, Gabriela
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Abrahamsson, Annelie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Linköping University, Faculty of Medicine and Health Sciences.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Estradiol promotes breast cancer cell migration via recruitment and activation of neutrophils2017In: Cancer Immunology research, ISSN 2326-6066, Vol. 5, no 3, p. 234-247, article id 28159748Article in journal (Refereed)
    Abstract [en]

    Estradiol (E2) plays a key role in breast cancer progression. Most breast cancer recurrences express the estrogen receptor (ER), but nearly 50% of patients are resistant to antiestrogen therapy. Novel therapeutic targets of ER-positive breast cancers are needed. Protumoral neutrophils expressing the lymphocyte function-associated antigen 1 (LFA-1) integrin may mediate cancer metastasis, and TGFβ1 is the major chemoattractant for neutrophils. The role of E2 in neutrophil–ER+ breast cancer cell interactions is unknown. We studied this in vivo using murine breast cancers in immunocompetent mice and human breast cancers in nude mice. Cell dissemination was evaluated in a zebrafish model, and microdialysis of breast cancer patients was performed. In vitro studies were done with mammosphere cultures of breast cancer cells and human neutrophils. We found that E2 increased the number of LFA-1+ neutrophils recruited to the invasive edge of mouse tumors, increased TGFβ1 secretion and promoted neutrophil infiltration in mammospheres, and induced overexpression of LFA-1 in neutrophils. In zebrafish, in the presence of E2, neutrophils increased dissemination of ER+ breast cancer cells via LFA-1 and TGFβ1, thus causing noninvasive cancer cells to be highly metastatic. Time-lapse imaging in zebrafish revealed close interactions of neutrophils with cancer cells, which drove breast cancer metastasis. We also found that extracellular TGFβ1 was overproduced in human breast cancer tissue compared with adjacent normal breast tissue. Thus, E2 can regulate immune/cancer cell interactions in tumor microenvironments. Our results indicate that extracellular TGFβ1 is a relevant target in human breast cancer.

  • 140.
    Vazquez Rodriguez, Gabriela
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Abrahamsson, Annelie
    Linköping University, Department of Clinical and Experimental Medicine.
    Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology.
    Dabrosin, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Neutrophils Promote Breast Cancer Progression and Metastasis via LFA-1 Integrin2015Conference paper (Other academic)
    Abstract [en]

    Cancer is considered an inflammatory condition where immune cells play an important role in progression and metastasis. Neutrophils may be pro- or antitumorigenic, depending on their phenotype or the number of infiltrating neutrophils in the tumor microenvironment. Massive infiltration of neutrophils in cancer tissue may elicit a cytotoxic effect, leading to tumor regression, whereas a S139 low-grade neutrophil gradient is tumor progressive. Chemokines, cytokines, and growth factors present in the tumor microenvironment, as well as cell-cell interactions mediated by integrins have shown to be determinant steps for cancer cells to break through the endothelial wall and establish metastatic niches. In this work we evaluated the role of lymphocyte functionassociated antigen 1 (LFA-1) integrin in neutrophils-mediated metastasis of estrogen receptor positive breast cancer cells (MCF-7) cells in a tumor xenograft model in zebrafish and in neutrophil infiltration in MCF-7 mammospheres. The metastatic capability of MCF-7 cells was evaluated in presence or absence of human neutrophils and with/without estradiol treatment. Two days old zebrafish embryos were injected into the perivitelline space with labeled MCF-7 cells and human neutrophils, an anti-human LFA-1 antibody (CD11a) was included. We show that estradiol treatment significantly increased the infiltration of neutrophils into MCF-7 mammospheres and this infiltration was significantly reduced by the presence of an anti-human CD11a antibody. Co-injection of MCF-7 cells with neutrophils significantly increased the migration of MCF-7 cells to distant sites in zebrafish and this effect was inhibited by using an anti-human CD11a antibody. We conclude that neutrophils affect the dissemination of breast cancer cells via LFA-1 integrin. Although estradiol increased the number of infiltrating neutrophils into mammospheres exposure to estradiol seemed to have minor effects on the dissemination in the zebrafish.

  • 141.
    Veenstra, Cynthia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Karlsson, Elin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Mirwani, Sanam Mirwani
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Fornander, Tommy
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Perez Tenorio, Gizeh
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    The effects of PTPN2 loss on cell signalling and clinical outcome in relation to breast cancer subtype2019In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 145, no 7, p. 1845-1856Article in journal (Refereed)
    Abstract [en]

    PurposeThe protein tyrosine phosphatase PTPN2 dephosphorylates several tyrosine kinases in cancer-related signalling pathways and is thought to be a tumour suppressor. As PTPN2 is not frequently studied in breast cancer, we aimed to explore the role of PTPN2 and the effects of its loss in breast cancer.MethodsProtein expression and gene copy number of PTPN2 were analysed in a cohort of pre-menopausal breast cancer patients with immunohistochemistry and droplet digital PCR, respectively. PTPN2 was knocked down in three cell lines, representing different breast cancer subtypes, with siRNA transfection. Several proteins related to PTPN2 were analysed with Western blot.ResultsLow PTPN2 protein expression was found in 50.2% of the tumours (110/219), gene copy loss in 15.4% (33/214). Low protein expression was associated with a higher relapse rate in patients with Luminal A and HER2-positive tumours, but not triple-negative tumours. In vitro studies further suggested a subtype-specific role of PTPN2. Knockdown of PTPN2 had no effect on the triple-negative cell line, whilst knockdown in MCF7 inhibited phosphorylation of Met and promoted that of Akt. Knockdown in SKBR3 led to increased Met phosphorylation and decreased Erk phosphorylation as well as EGF-mediated STAT3 activation.ConclusionWe confirm previous studies showing that the PTPN2 protein is lost in half of the breast cancer cases and gene deletion occurs in 15-18% of the cases. Furthermore, the results suggest that the role of PTPN2 is subtype-related and should be further investigated to assess how this could affect breast cancer prognosis and treatment response.

  • 142.
    Veenstra, Cynthia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Perez-Tenorio, Gizeh
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Stelling, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Karlsson, Elin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Mirwani Mirwani, Sanam
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Fornander, Tommy
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Met and its ligand HGF are associated with clinical outcome in breast cancer2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 24, p. 37145-37159Article in journal (Refereed)
    Abstract [en]

    Few biomarkers exist to predict radiotherapy response in breast cancer. In vitro studies suggest a role for Met and its ligand HGF. To study this suggested role, MET and HGF gene copy numbers were determined by droplet digital PCR in tumours from 205 pre-menopausal and 184 post-menopausal patients, both cohorts randomised to receive either chemo-or radiotherapy. MET amplification was found in 8% of the patients in both cohorts and HGF amplification in 7% and 6% of the patients in the pre-and post-menopausal cohort, respectively. Met, phosphorylated Met (pMet), and HGF protein expression was determined by immunohistochemistry in the premenopausal cohort. Met, pMet, and HGF was expressed in 33%, 53%, and 49% of the tumours, respectively. MET amplification was associated with increased risk of distant recurrence for patients receiving chemotherapy. For the pre-menopausal patients, expression of cytoplasmic pMet and HGF significantly predicted benefit from radiotherapy in terms of loco-regional recurrence. Similar trends were seen for MET and HGF copy gain. In the post-menopausal cohort, no significant association of benefit from radiotherapy with neither genes nor proteins was found. The present results do not support that inhibition of Met prior to radiotherapy would be favourable for pre-menopausal breast cancer, as previously suggested.

  • 143.
    Vernmark, Karolina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Björnsson, Bergthor
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Gasslander, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland. Linköping University, Faculty of Medicine and Health Sciences.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    From palliative to curative treatment - stage IV mucinous adenocarcinoma, successfully treated with metronomic capecitabine in combination with Bevacizumab and surgery- a case report2015In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 15, no 884Article in journal (Refereed)
    Abstract [en]

    Background: Mucinous adenocarcinoma (MAC) represents 6-19 % of all colorectal carcinoma. It is associated with poorer response to chemotherapy and chemoradiotherapy. Case presentation: A 27-year-old Swedish woman presented with stomach pain and weight loss, and was diagnosed with locally advanced MAC in the transverse colon as well as 3 liver metastases. Neoadjuvant treatment with fluorouracil, folinic acid and oxaliplatin (FLOX) failed due to several infections, pulmonary embolism and deteriorated performance status. The patient was therefore considered palliative. Palliative treatment with metronomic capecitabine 500 mg x 2 daily and bevacizumab every other week were initiated. After 4 months of treatment the tumors had regressed and the patient was able to undergo radical surgery, thereby changing the treatment intention from palliative to curative. No adjuvant chemotherapy was given. There were no signs of recurrence 9 months later. Conclusions: The role of the combination of metronomic capecitabine and bevacizumab in patients with MAC merits further investigation.

  • 144.
    Wang, Chaojie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Henan Univ, Peoples R China.
    Zhou, Jian-Wei
    Henan Univ, Peoples R China.
    Cheng, Qiao-Mei
    Henan Univ, Peoples R China.
    Zhou, Yun
    Henan Univ, Peoples R China.
    Zhang, Hong
    Orebro Univ, Sweden.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    FBI-1 mRNA in normal mucosa is an independent prognostic factor in colorectal cancer patients2018In: International Journal of Clinical and Experimental Pathology, ISSN 1936-2625, E-ISSN 1936-2625, Vol. 11, no 2, p. 642-649Article in journal (Refereed)
    Abstract [en]

    Although several studies provide evidence that FBI-1 is an important gene regulator in colorectal cancer (CRC), it is noteworthy that, to our knowledge, no analysis of the correlation between FBI-1 expression and prognosis in CRC has been reported. Using real-time RT-PCR, we detected FBI-1 mRNA in 161 CRC patients (primary tumor, along with the corresponding normal mucosa), 36 liver metastases, and analyzed the relationship of its expression with clinicopathological features. Colon cancer cell lines were used to study FBI-1 function. Our study found that FBI-1 was significant up-regulated in tumor tissue (2.621 +/- 0.157) compared with the corresponding normal mucosa (1.620 +/- 0.165, P amp;lt; 0.0001). FBI-1 in normal mucosa was a prognostic factor (P = 0.039, RR 0.431, 95% CI 0.194-0.958), independent of gender, age, stage, and differentiation. High levels of FBI-1 mRNA were related with good survival. Patients with complications had a higher primary tumor FBI-1 expression than those without complications (3.400 +/- 0.332 vs. 2.516 +/- 0.241, P = 0.032). Suppression of FBI-1 in colon cancer cell lines could repress proliferation of cancer cells. In conclusion, FBI-1 mRNA is overexpressed in CRC, and takes part in the development of CRC. FBI-1 mRNA in normal mucosa is an independent prognostic factor. Our findings give further support to the concept of "field cancerization", and hint that when we study a biomarker, we should not only focus on the tumor tissue but also the corresponding normal mucosa.

  • 145.
    Wang, Mojin
    et al.
    Sichuan University, Peoples R China.
    Li, Yuan
    Sichuan University, Peoples R China.
    Wang, Rui
    Sichuan University, Peoples R China.
    Wang, Ziqiang
    Sichuan University, Peoples R China.
    Chen, Keling
    Sichuan University, Peoples R China.
    Zhou, Bin
    Sichuan University, Peoples R China.
    Zhou, Zongguang
    Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    The PKA RI alpha/A-kinase anchoring proteins 10 signaling pathway and the prognosis of colorectal cancer2015In: Journal of Gastroenterology and Hepatology, ISSN 0815-9319, E-ISSN 1440-1746, Vol. 30, no 3, p. 496-503Article in journal (Refereed)
    Abstract [en]

    Background and AimPreviously study showed that the loss of the control of cAMP-dependent protein kinase A RI (PKA RI)/ A-kinase anchoring proteins 10 (AKAP10) signaling pathway initiate dysregulation of cellular healthy physiology leading to tumorigenesis. The aim of this study was to investigate the role of PKA RI/AKAP10 signaling pathway in colorectal cancer (CRC). MethodsThe AKAP10 expression at the mRNA and protein level have been analyzed in colon cancer cell lines, primary CRCs and matched normal mucosa samples, and compared in accordance with specific clinicopathological features of CRC. The correlation between expression of AKAP10 and PKA RI were also analyzed. ResultsCompared with HCT116 and SW480 cells, the AKAP10 was significantly upregulated in the colon cell line KM12C and its metastatic counterparts, KM12SM and KM12L4A. Moreover, the KM12SM and KM12L4A having high metastatic potentials displayed the elevated levels of AKAP10 compared with KM12C having poor metastatic potential. A notably higher level of AKAP10 expression was found in CRC tissues at both mRNA and protein levels. Increased expression of AKAP10 in CRC patients was positively associated with the depth of invasion and the grade of differentiation. Univariate survival analysis showed that the increased expression of AKAP10 was related to poorer survival. Cox multivariate regression analysis confirmed that AKAP10 was an independent predictor of the overall survival of CRC patients. PKA RI mRNA was also expressed at high levels in CRC. The correlation coefficient between mRNA expression of AKAP10 and PKA RI in CRC was 0.417. AKAP10mRNA overexpression was correlated significantly with PKA RI. ConclusionsOur data indicated that PKA RI/AKAP10 signaling pathway is associated with the progression and prognosis of CRC.

  • 146.
    Wang, Mo-Jin
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Sichuan University, Peoples R China.
    Ping, Jie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Li, Yuan
    Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Adell, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Nodin, Bjorn
    Lund University, Sweden.
    Meng, Wen-Jian
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Zhang, Hong
    University of Örebro, Sweden.
    Yu, Yong-Yang
    Sichuan University, Peoples R China.
    Wang, Cun
    Sichuan University, Peoples R China.
    Yang, Lie
    Sichuan University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    The prognostic factors and multiple biomarkers in young patients with colorectal cancer2015In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, no 10645Article in journal (Refereed)
    Abstract [en]

    The incidence of colorectal cancer (CRC) in young patients (less than= 50 years of age) appears to be increasing. However, their clinicopathological characteristics and survival are controversial. Likewise, the biomarkers are unclear. We used the West China (2008-2013, China), Surveillance, Epidemiology, and End Results program (1973-2011, United States) and Linkoping Cancer (1972-2009, Sweden) databases to analyse clinicopathological characteristics, survival and multiple biomarkers of young CRC patients. A total of 509,934 CRC patients were included from the three databases. The young CRC patients tended to have more distal location tumours, fewer tumour numbers, later stage, more mucinous carcinoma and poorer differentiation. The cancer-specific survival (CSS) of young patients was significantly better. The PRL (HR = 12.341, 95% CI = 1.615-94.276, P = 0.010), RBM3 (HR = 0.093, 95% CI = 0.012-0.712, P = 0.018), Wrap53 (HR = 1.952, 95% CI = 0.452-6.342, P = 0.031), p53 (HR = 5.549, 95% CI = 1.176-26.178, P = 0.045) and DNA status (HR = 17.602, 95% CI = 2.551-121.448, P = 0.001) were associated with CSS of the young patients. In conclusion, this study suggests that young CRC patients present advanced tumours and more malignant pathological features, while they have a better prognosis. The PRL, RBM3, Wrap53, p53 and DNA status are potential prognostic biomarkers for the young CRC patients.

  • 147.
    Wang, Mo-Jin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Ping, Jie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Li, Yuan
    Sichuan University, Peoples R China.
    Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Adell, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Zhang, Hong
    University of Örebro, Sweden.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China; .
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Sichuan University, Peoples R China.
    Prognostic Significance and Molecular Features of Colorectal Mucinous Adenocarcinomas: A Strobe-Compliant Study2015In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 94, no 51, p. e2350-Article in journal (Refereed)
    Abstract [en]

    Mucinous adenocarcinoma (MC) is a special histology subtype of colorectal adenocarcinoma. The survival of MC is controversial and the prognostic biomarkers of MC remain unclear. To analyze prognostic significance and molecular features of colorectal MC. This study included 755,682 and 1001 colorectal cancer (CRC) patients from Surveillance, Epidemiology, and End Results program (SEER, 1973 2011), and Linkoping Cancer (LC, 1972-2009) databases. We investigated independently the clinicopathological characteristics, survival, and variety of molecular features from these 2 databases. MC was found in 9.3% and 9.8% patients in SEER and LC, respectively. MC was more frequently localized in the right colon compared with nonmucinous adenocarcinoma (NMC) in both SEER (57.7% vs 37.2%, P &lt; 0.001) and LC (46.9% vs 27.7%, P &lt; 0.001). Colorectal MC patients had significantly worse cancer-specific survival (CSS) than NMC patients (SEER, P &lt; 0.001; LC, P = 0.026), prominently in stage III (SEER, P &lt; 0.001; P=0.023). The multivariate survival analysis showed that MC was independently related to poor prognosis in rectal cancer patients (SEER, hazard ratios [HR], 1.076; 95% confidence intervals [CI], 1.057-1.096; P &lt; 0.001). In LC, the integrated analysis of genetic and epigenetic features showed that that strong expression of PINCH (HR, 3.954; 95% CI, 1.493-10.47; P = 0.013) and weak expression of RAD50 (HR 0.348, 95% CT, 0.106-1.192; P=0.026) were significantly associated with poor CSS of colorectal MC patients. In conclusion, the colorectal MC patients had significantly worse CSS than NMC patients, prominently in stage III. MC was an independent prognostic factor associated with worse survival in rectal cancer patients. The PINCH and RAD50 were prognostic biomarkers for colorectal MC patients.

  • 148.
    Wang, Mo-Jin
    et al.
    Sichuan University, Peoples R China.
    Wang, Zi-Qiang
    Sichuan University, Peoples R China.
    Wang, Rui
    Sichuan University, Peoples R China.
    Ping, Jie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Letter: The elderly patients with colorectal cancer need careful multidisciplinary evaluation and optimizing comprehensive management in INTERNATIONAL JOURNAL OF COLORECTAL DISEASE, vol 30, issue 5, pp 713-7142015In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 30, no 5, p. 713-714Article in journal (Other academic)
    Abstract [en]

    n/a

  • 149.
    Widmark, Anders
    et al.
    Umea Univ, Sweden.
    Gunnlaugsson, Adalsteinn
    Lund Univ, Sweden.
    Beckman, Lars
    Sundsvall Hosp, Sweden.
    Thellenberg-Karlsson, Camilla
    Umea Univ, Sweden.
    Hoyer, Morten
    Aarhus Univ Hosp, Denmark.
    Lagerlund, Magnus
    Kalmar Hosp, Sweden.
    Kindblom, Jon
    Univ Gothenburg, Sweden.
    Ginman, Claes
    Karlstad Cent Hosp, Sweden.
    Johansson, Bengt
    Orebro Univ, Sweden.
    Bjornlinger, Kirsten
    Ryhov Hosp, Sweden.
    Seke, Mihajl
    Cent Lasarettet, Sweden.
    Agrup, Måns
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Fransson, Per
    Umea Univ, Sweden.
    Tavelin, Bjorn
    Umea Univ, Sweden.
    Norman, David
    Umea Univ, Sweden.
    Zackrisson, Bjorn
    Umea Univ, Sweden.
    Anderson, Harald
    Lund Univ, Sweden.
    Kjellen, Elisabeth
    Lund Univ, Sweden.
    Franzen, Lars
    Umea Univ, Sweden.
    Nilsson, Per
    Lund Univ, Sweden.
    Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial2019In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 394, no 10196, p. 385-395Article in journal (Refereed)
    Abstract [en]

    Background Hypofractionated radiotherapy for prostate cancer has gained increased attention due to its proposed high radiation-fraction sensitivity. Recent reports from studies comparing moderately hypofractionated and conventionally fractionated radiotherapy support the clinical use of moderate hypofractionation. To date, there are no published randomised studies on ultra-hypofractionated radiotherapy. Here, we report the outcomes of the Scandinavian HYPO-RTPC phase 3 trial with the aim to show non-inferiority of ultra-hypofractionation compared with conventional fractionation. Methods In this open-label, randomised, phase 3 non-inferiority trial done in 12 centres in Sweden and Denmark, we recruited men up to 75 years of age with intermediate-to-high-risk prostate cancer and a WHO performance status between 0 and 2. Patients were randomly assigned to ultra-hypofractionation (42.7 Gy in seven fractions, 3 days per week for 2.5 weeks) or conventional fractionated radiotherapy (78.0 Gy in 39 fractions, 5 days per week for 8 weeks). No androgen deprivation therapy was allowed. The primary endpoint was time to biochemical or clinical failure, analysed in the per-protocol population. The prespecified non-inferiority margin was 4% at 5 years, corresponding to a critical hazard ratio (HR) limit of 1.338. Physician-recorded toxicity was measured according to the Radiation Therapy Oncology Group (RTOG) morbidity scale and patient-reported outcome measurements with the Prostate Cancer Symptom Scale (PCSS) questionnaire. This trial is registered with the ISRCTN registry, number ISRCTN45905321. Findings Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionation (n=602) or ultra-hypofractionation (n=598), of whom 1180 (591 conventional fractionation and 589 ultra-hypofractionation) constituted the per-protocol population. 1054 (89%) participants were intermediate risk and 126 (11%) were high risk. Median follow-up time was 5.0 years (IQR 3.1-7.0). The estimated failure-free survival at 5 years was 84% (95% CI 80-87) in both treatment groups, with an adjusted HR of 1.002 (95% CI 0.758-1.325; log-rank p=0.99). There was weak evidence of an increased frequency of acute physician-reported RTOG grade 2 or worse urinary toxicity in the ultra-hypofractionation group at end of radiotherapy (158 [28%] of 569 patients vs 132 [23%] of 578 patients; p=0.057). There were no significant differences in grade 2 or worse urinary or bowel late toxicity between the two treatment groups at any point after radiotherapy, except for an increase in urinary toxicity in the ultra-hypofractionation group compared to the conventional fractionation group at 1-year follow-up (32 [6%] of 528 patients vs 13 [2%] of 529 patients; (p=0.0037). We observed no differences between groups in frequencies at 5 years of RTOG grade 2 or worse urinary toxicity (11 [5%] of 243 patients for the ultra-hypofractionation group vs 12 [5%] of 249 for the conventional fractionation group; p=1.00) and bowel toxicity (three [1%] of 244 patients vs nine [4%] of 249 patients; p=0.14). Patient-reported outcomes revealed significantly higher levels of acute urinary and bowel symptoms in the ultra-hypofractionation group compared with the conventional fractionation group but no significant increases in late symptoms were found, except for increased urinary symptoms at 1-year follow-up, consistent with the physician-evaluated toxicity. Interpretation Ultra-hypofractionated radiotherapy is non-inferior to conventionally fractionated radiotherapy for intermediate-to-high risk prostate cancer regarding failure-free survival. Early side-effects are more pronounced with ultra-hypofractionation compared with conventional fractionation whereas late toxicity is similar in both treatment groups. The results support the use of ultra-hypofractionation for radiotherapy of prostate cancer. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

  • 150.
    Zardavas, Dimitrios
    et al.
    Breast Int Grp, Belgium.
    te Marvelde, Luc
    Canc Council, Australia.
    Milne, Roger L.
    Canc Council, Australia; Univ Melbourne, Australia.
    Fumagalli, Debora
    Breast Int Grp, Belgium.
    Fountzilas, George
    Aristotle Univ Thessaloniki, Greece.
    Kotoula, Vassiliki
    Aristotle Univ Thessaloniki, Greece.
    Razis, Evangelia
    Hygeia Hosp, Greece.
    Papaxoinis, George
    Hippokrateion Hosp, Greece.
    Joensuu, Heikki
    Helsinki Univ Hosp, Finland; Univ Helsinki, Finland.
    Moynahan, Mary Ellen
    Mem Sloan Kettering Canc Ctr, NY 10021 USA.
    Hennessy, Bryan T.
    Beaumont Hosp, Ireland; Royal Coll Surg, Ireland.
    Bieche, Ivan
    Curie Inst, France.
    Saal, Lao H.
    Lund Univ, Sweden.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Iacopetta, Barry
    Univ Western Australia, Australia.
    Jensen, Jeanette Dupont
    Univ Southern Denmark, Denmark.
    OToole, Sandra
    Garvan Inst Med Res, Australia.
    Lopez-Knowles, Elena
    Garvan Inst Med Res, Australia; Royal Marsden NHS Trust, England; Inst Canc Res, England.
    Barbaraeschi, Mattia
    Santa Chiara Hosp, Italy.
    Noguchi, Shinzaburo
    Osaka Univ, Japan.
    Azim, Hatem A. Jr.
    Amer Univ Beirut, Lebanon.
    Lerma, Enrique
    Univ Autonoma Barcelona, Spain.
    Bachelot, Thomas
    Ctr Rech Cancerol Lyon, France.
    Wang, Qing
    Not Found:Linkoping Univ, Linkoping, Sweden.
    Perez Tenorio, Gizeh
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    de Velde, Cornelis J. H. Can
    Leiden Univ, Netherlands.
    Rea, Daniel W.
    Univ Birmingham, England.
    Sabine, Vicky
    Univ Guelph, Canada.
    Bartlett, John M. S.
    Ontario Inst Canc Res, Canada.
    Sotiriou, Christos
    Univ Libre Bruxelles, Belgium.
    Michiels, Stefan
    Gustave Roussy, France; Univ Paris Saclay, France.
    Loi, Sherene
    Univ Melbourne, Australia.
    Tumor PIK3CA Genotype and Prognosis in Early-Stage Breast Cancer: A Pooled Analysis of Individual Patient Data2018In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 36, no 10, p. 981-+Article in journal (Refereed)
    Abstract [en]

    PurposePhosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations are frequently observed in primary breast cancer. We evaluated their prognostic relevance by performing a pooled analysis of individual patient data.Patients and MethodsAssociations between PIK3CA status and clinicopathologic characteristics were tested by applying Cox regression models adjusted for age, tumor size, nodes, grade, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, treatment, and study. Invasive disease-free survival (IDFS) was the primary end point; distant disease-free survival (DDFS) and overall survival (OS) were also assessed, overall and by breast cancer subtypes.ResultsData from 10,319 patients from 19 studies were included (median OS follow-up, 6.9 years); 1,787 patients (17%) received chemotherapy, 4,036 (39%) received endocrine monotherapy, 3,583 (35%) received both, and 913 (9%) received none or their treatment was unknown. PIK3CA mutations occurred in 32% of patients, with significant associations with ER positivity, increasing age, lower grade, and smaller size (all P amp;lt; .001). Prevalence of PIK3CA mutations was 18%, 22%, and 37% in the ER-negative/HER2-negative, HER2-positive, and ER-positive/HER2-negative subtypes, respectively. In univariable analysis, PIK3CA mutations were associated with better IDFS (HR, 0.77; 95% CI, 0.71 to 0.84; P amp;lt; .001), with evidence for a stronger effect in the first years of follow-up (0 to 5 years: HR, 0.73; 95% CI, 0.66 to 0.81; P amp;lt; .001; 5 to 10 years: HR, 0.82; 95% CI, 0.68 to 0.99; P = .037); amp;gt; 10 years: (HR, 1.15; 95% CI, 0.84 to 1.58; P = .38; P heterogeneity = .02). In multivariable analysis, PIK3CA genotype remained significant for improved IDFS (P = .043), but not for the DDFS and OS end points.ConclusionIn this large pooled analysis, PIK3CA mutations were significantly associated with a better IDFS, DDFS, and OS, but had a lesser prognostic effect after adjustment for other prognostic factors. (C) 2018 by American Society of Clinical Oncology

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