Change search
Refine search result
1234 51 - 100 of 159
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 51.
    Frödin, Ulla
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    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 Diagnostics, Department of Clinical Pharmacology.
    Fomichov, Victoria
    Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Juliusson, G.
    Lund University, Sweden; Lund University, Sweden.
    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.
    Frequent and long-term follow-up of health-related quality of life following allogeneic haematopoietic stem cell transplantation2015In: European Journal of Cancer Care, ISSN 0961-5423, E-ISSN 1365-2354, Vol. 24, no 6, p. 898-910Article in journal (Refereed)
    Abstract [en]

    Health-related quality of life (HRQL) was evaluated in 94 patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) after myeloablative (MAC, n=18) or reduced intensity conditioning (RIC, n=76). HRQL was assessed with the EORTC QLQ C-30 during the inpatient period as well as during the following 3years, i.e. at baseline and 12 times thereafter. Functional status and global quality of life decreased from baseline to weeks 2 and 3, especially role and social functions. Symptoms increased significantly during the first 3weeks, particularly appetite loss, nausea and vomiting, diarrhoea and fatigue. It took at least 1year for HRQL to return to the baseline level. The only function that improved significantly 3years after HSCT was role function. Patients treated with MAC experienced significantly worse HRQL at baseline than patients treated with RIC, as well as more pain, sleep disturbance and appetite loss in weeks 3 and 4. Patients with extensive chronic graft-versus-host disease experienced reduced HRQL. These results provide a clinically useful overview of patients HRQL during and after HSCT and indicate when they require increased support. The results demonstrate the importance of close follow-ups during the first year after HSCT to improve preventive or supportive interventions.

  • 52.
    Fuglsang, Katrine
    et al.
    Aarhus Univ Hosp, Denmark.
    Haldorsen, Ingfrid S.
    Haukeland Hosp, Norway.
    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.
    Lindahl, Gabriel
    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.
    Roed, Henrik
    Univ Hosp, Denmark.
    Woie, Kathrine
    Haukeland Hosp, Norway.
    Pakarinen, Paivi
    Univ Helsinki, Finland.
    Thoroddsen, Asgeir
    Reykjavik Univ Hosp, Iceland.
    Anttila, Maarit
    Kuopio Univ Hosp, Finland.
    Blaakaer, Jan
    Odense Univ Hosp, Denmark.
    Cervical cancer staging, pretreatment planning, and surgical treatment in the Nordic countriesSurvey from the Surgical Subcommittee of the Nordic Society of Gynecological Oncology2018In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 97, no 10, p. 1178-1184Article in journal (Refereed)
    Abstract [en]

    IntroductionWomen with cervical cancer in the Nordic countries are increasingly undergoing pretreatment imaging by ultrasound, magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT) or computed tomography, or sentinel lymph node procedure. The present survey reports the influence of pretreatment imaging findings on the recorded clinical International Federation of Gynecology and Obstetrics (FIGO) stage in Nordic countries and its impact on treatment planning and preferred surgical approach in cervical cancer. Material and methodsThe Nordic Society of Gynecological Oncology Surgical Subcommittee developed a questionnaire-based survey that was conducted from 1 January to 31 March 2017. All the 22 Nordic Gynecological Oncology Centers (Denmark 5, Finland 5, Iceland 1, Norway 4, and Sweden 7) were invited to participate. ResultsThe questionnaires were returned by 19 of 22 (86.3%) centers. The median number (range) of women with cervical cancer treated at each center annually was 32 (15-120). In 58% (11/19) of the centers, imaging findings were reported to influence the clinical staging. MRI in combination with PET-CT was the preferred imaging method and the results influenced treatment planning. Robotic-assisted radical hysterectomy was the preferred surgical method in 72% (13/18) of the centers. Sentinel lymph node procedure was not routinely implemented in the majority of the Nordic centers. ConclusionMore than half of the Nordic Gynecological Oncology Centers already report a clinical FIGO stage influenced by pretreatment imaging findings. The trend in preferred treatment is robotic-assisted radical hysterectomy and the sentinel lymph node procedure is gradually being introduced.

  • 53.
    Gabrielson, Marike
    et al.
    University of Örebro, Sweden; Karolinska Institute, Sweden.
    Reizer, Edwin
    University of Örebro, 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.
    Tina, Elisabet
    University of Örebro, Sweden.
    Mitochondrial regulation of cell cycle progression through SLC25A432016In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 469, no 4, p. 1090-1096Article in journal (Refereed)
    Abstract [en]

    An increasing body of evidence is pointing towards mitochondrial regulation of the cell cycle. In a previous study of HER2-positive tumours we could demonstrate a common loss in the gene encoding for the mitochondrial transporter SLC25A43 and also a significant relation between SLC25A43 protein expression and S-phase fraction. Here, we investigated the consequence of suppressed SLC25A43 expression on cell cycle progression and proliferation in breast epithelial cells. In the present study, we suppressed SLC25A43 using siRNA in immortalised non-cancerous breast epithelial MCF10A cells and HER2-positive breast cancer cells BT-474. Viability, apoptosis, cell proliferation rate, cell cycle phase distribution, and nuclear Ki-67 and p21, were assessed by flow cytometry. Cell cycle related gene expressions were analysed using real-time PCR. We found that SLC25A43 knockdown in MCF10A cells significantly inhibited cell cycle progression during G(1)-to-S transition, thus significantly reducing the proliferation rate and fraction of Ki-67 positive MCF10A cells. In contrast, suppressed SLC25A43 expression in BT-474 cells resulted in a significantly increased proliferation rate together with an enhanced G(1)-to-S transition. This was reflected by an increased fraction of Ki-67 positive cells and reduced level of nuclear p21. In line with our previous results, we show a role for SLC25A43 as a regulator of cell cycle progression and proliferation through a putative mitochondrial checkpoint. These novel data further strengthen the connection between mitochondrial function and the cell cycle, both in non-malignant and in cancer cells. (C) 2015 Elsevier Inc. All rights reserved.

  • 54.
    Gnosa, Sebastian
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Capodanno, Alessandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Dahl Ejby 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.
    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.
    AEG-1 knockdown in colon cancer cell lines inhibits radiation-enhanced migration and invasion in vitro and in a novel in vivo zebrafish model2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 49, p. 81634-81644Article in journal (Refereed)
    Abstract [en]

    Background Radiotherapy is a well-established anti-cancer treatment. Although radiotherapy has been shown to significantly decrease the local relapse in rectal cancer patients, the rate of distant metastasis is still very high. Several studies have shown that radiation enhances migration and invasion both in vitro and in vivo. The aim of this study was to evaluate whether AEG-1 is involved in radiation-enhanced migration and invasion in vitro and in a novel in vivo zebrafish model.

    Materials and Methods We evaluated the involvement of AEG-1 in migration and invasion and radiation-enhanced migration and invasion by Boyden chamber assay in three colon cancer cell lines and respective AEG-1 knockdown cell lines. Furthermore, we injected the cells in zebrafish embryos and evaluated the amount of disseminated cells into the tail.

    Results Migration and invasion was decreased in all the AEG-1 knockdown cell lines. Furthermore, radiation enhanced migration and invasion, while AEG-1 knockdown could abolish this effect. The results from the zebrafish model confirmed the results obtained in vitro. MMP-9 secretion and expression were decreased in AEG-1 knockdown cells.

    Conclusion Our results demonstrate that AEG-1 knockdown inhibits migration and invasion, as well as radiation-enhanced migration and invasion. We speculate that this is done via the downregulation of the intrinsic or radiation-enhanced MMP-9 expression. The zebrafish model can be used to study early events in radiation-enhanced invasion.

  • 55.
    Gnosa, Sebastian
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ticha, Ivana
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Institute of Pathology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
    Haapaniemi, Staffan
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    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.
    MTDH genetic variants in colorectal cancer patients2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6Article in journal (Refereed)
    Abstract [en]

    Colorectal cancer (CRC) is the second most common cancer worldwide and accounts for around 8.5% of all cancer related death. The colorectal carcinogenesis is a complex process of genetic alterations. For better prognosis it is very important to understand the composition of genetic alterations in a tumor. Astrocyte elevated gene-1 (AEG-1) has been shown to be overexpressed in CRC and had prognostic significance. The aim of this study was to determine the frequency and the spectrum of MTDH variants, and their relationship to clinicopathological variables in CRC patients. The study included tumors from 356 unselected CRC patients. Mutation analysis of the MTDH gene, including coding region and adjacent intronic sequences, was performed by direct DNA sequencing. We detected 42 intronic variants, whereby 25 were novel. Furthermore, we found eight exonic variants of which four, one missense (c.977C>G) and three frameshift mutations (c.533delA, c.1731delA, c.1340dupA), were novel. In silico prediction analyses revealed that four variants c.232G>T, c.533delA, c.1340dupA and c.1731delA were deleterious. There were no correlations between the MTDH variants and tumor stage, differentiation or patient survival. The detection of pathogenic mutations and alterations in functional protein domains suggest their involvement in tumorigenesis, although none of the variants had prognostic potential.

  • 56.
    Gopinath, Madhumala
    et al.
    Department of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai-603103, India.
    Di Liddo, Rosa
    Department of Pharmacology and Pharmaceutical Sciences, University of Padova, Padova, Italy.
    Marotta, Francesco
    ReGenera RandD International for Aging Intervention, Milano-Beijing, Italy-China, VCC Preventive Medical Promotion Foundation, Beijing, China.
    Murugesan, Ramachandran
    Department of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai-603103, India.
    Banerjee, Antara
    Department of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai-603103, India.
    Sriramulu, Sushmitha
    Department of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai-603103, India.
    Jothimani, Ganesan
    Department of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai-603103, India.
    Subramaniam, Vimala Devi
    Department of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai-603103, India.
    Narasimhan, Srinivasan
    Department of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai-603103, India.
    Priya K, Swarna
    Department of Gynecology and Pediatrics, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai-603103, 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.
    Pathak, Surajit
    Department of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai-603103, India.
    Role of Hippo Pathway Effector Tafazzin Protein in Maintaining Stemness of Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSC)2018In: International Journal of Hematology-Oncology and Stem Cell Research, ISSN 2008-3009, E-ISSN 2008-2207, Vol. 12, no 2, p. 153-165Article, review/survey (Refereed)
    Abstract [en]

    Tafazzin (TAZ) protein has been upregulated in various types of human cancers, although the basis for elevation is uncertain, it has been made definite that the effect of mutation in the hippo pathway, particularly when it is switched off, considerably activates tafazzin transcriptionally and thus this results in tissue or tumor overgrowth. Recent perceptions into the activity of tafazzin, have ascribed to it, a role as stem cell factor in mouse mesenchymal and as well as in neural stem cells. Being a downstream molecule in Hippo signalling, phosphorylation or dephosphorylation of tafazzin gene regulates its transcriptional activity and the stemness of mesenchymal stem cells. Commonly, extracellular matrix controls the stem cell fate commitment and perhaps tafazzin controls stemness through altering the extra cellular matrix. Extracellular matrix is generally made up of prime proteoglycans and the fate stabilization of the resulting lineages is surveilled by engineering these glycans. Tafazzin degradation and addition of proteoglycans affect physical attributes of the extracellular matrix that drives cell differentiation into various lineages. Thus, tafazzin along with major glycans present in the extracellular matrix is involved in imparting stemness. However, there are incoherent molecular events, wherein both tafazzin and the extracellular matrix components, together either activate or inhibit differentiation of stem cells. This review discusses about the role of tafazzin oncoprotein as a stemness factor.

  • 57.
    Gothlin Eremo, Anna
    et al.
    University of Örebro, Sweden.
    Tina, Elisabet
    Örebro University Hospital, Sweden.
    Wegman, Pia
    Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    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.
    Fransen, Karin
    University of Örebro, Sweden.
    Fornander, Tommy
    Karolinska University Hospital, Sweden; Regional Cancer Centre Stockholm Gotland, Sweden.
    Wingren, Sten
    University of Örebro, Sweden.
    HER4 tumor expression in breast cancer patients randomized to treatment with or without tamoxifen2015In: International Journal of Oncology, ISSN 1019-6439, Vol. 47, no 4, p. 1311-1320Article in journal (Refereed)
    Abstract [en]

    The human epidermal growth factor receptor (HER) 4 is a relative of HER2 and has been associated to endocrine breast cancer and prediction of tamoxifen response. In addition to PI3K/Akt and MAPK pathway activation, ligand binding to HER4 triggers proteolytic cleavage and release of an intracellular receptor domain (4ICD) with signaling properties. The aim of the present study was to analyze HER4 protein expression and intracellular localization in breast cancer tissue from patients randomized to treatment with or without adjuvant tamoxifen. To investigate HER4 expression and localization in response to estradiol (E2) and 4-hydroxytamoxifen (4-OHT) exposure, we also performed in vitro studies. Cytoplasmic, nuclear and membrane expression of HER4 protein was evaluated by immunohistochemical staining in tumor tissue from 912 breast cancer patients. Three different breast epithelia cancer cell lines were exposed to E2 and 4-OHT and mRNA expression was analyzed using qPCR. Further, nuclear and cytoplasmic proteins were separated and analyzed with western blotting. We found an association between nuclear HER4 protein expression and ER-positivity (P=0.004). Furthermore, significant association was found between cytoplasmic HER4 and ER-negativity (Pless than0.0005), PgR-negativity (Pless than0.0005), tumor size greater than20 mm (P=0.001) and HER2-negativity (P=0.008). However, no overall significance of HER4 on recurrence-free survival was found. After E2 exposure, HER4 mRNA and protein expression had decreased in two cell lines in vitro yet no changes in nuclear or cytoplasmic protein fractions were seen. In conclusion, nuclear HER4 seem to be co-located with ER, however, we did not find support for overall HER4 expression in independently predicting response of tamoxifen treatment. The possible influence of separate isoforms was not tested and future studies may further evaluate HER4 significance.

  • 58.
    Green, Henrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Division of Gene Technology, Royal Institute of Technology, Solna, Sweden/ Royal Institute Technology, Sweden; National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Hasmats, Johanna
    Royal Institute Technology, Sweden.
    Kupershmidt, Ilya
    Royal Institute Technology, Sweden; NextBio, CA USA.
    Edsgard, Daniel
    Royal Institute Technology, Sweden.
    de Petris, Luigi
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Lewensohn, Rolf
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Blackhall, Fiona
    Christie Hospital, England; University of Manchester, England.
    Vikingsson, Svante
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Besse, Benjamin
    University of Paris 11, France.
    Lindgren, Andrea
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Branden, Eva
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Koyi, Hirsh
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    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.
    Lundeberg, Joakim
    Royal Institute Technology, Sweden.
    Using Whole-Exome Sequencing to Identify Genetic Markers for Carboplatin and Gemcitabine-Induced Toxicities2016In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 22, no 2, p. 366-373Article in journal (Refereed)
    Abstract [en]

    Purpose: Chemotherapies are associated with significant interindividual variability in therapeutic effect and adverse drug reactions. In lung cancer, the use of gemcitabine and carboplatin induces grade 3 or 4 myelosuppression in about a quarter of the patients, while an equal fraction of patients is basically unaffected in terms of myelosuppressive side effects. We therefore set out to identify genetic markers for gemcitabine/carboplatin-induced myelosuppression. Experimental Design: We exome sequenced 32 patients that suffered extremely high neutropenia and thrombocytopenia (grade 3 or 4 after first chemotherapy cycle) or were virtually unaffected (grade 0 or 1). The genetic differences/polymorphism between the groups were compared using six different bioinformatics strategies: (i) whole-exome nonsynonymous single-nucleotide variants association analysis, (ii) deviation from Hardy-Weinberg equilibrium, (iii) analysis of genes selected by a priori biologic knowledge, (iv) analysis of genes selected from gene expression meta-analysis of toxicity datasets, (v) Ingenuity Pathway Analysis, and (vi) FunCoup network enrichment analysis. Results: A total of 53 genetic variants that differed among these groups were validated in an additional 291 patients and were correlated to the patients myelosuppression. In the validation, we identified rs1453542 in OR4D6 (P = 0.0008; OR, 5.2; 95% CI, 1.8-18) as a marker for gemcitabine/carboplatin-induced neutropenia and rs5925720 in DDX53 (P = 0.0015; OR, 0.36; 95% CI, 0.17-0.71) as a marker for thrombocytopenia. Patients homozygous for the minor allele of rs1453542 had a higher risk of neutropenia, and for rs5925720 the minor allele was associated with a lower risk for thrombocytopenia. Conclusions: We have identified two new genetic markers with the potential to predict myelosuppression induced by gemcitabine/ carboplatin chemotherapy. (C)2015 AACR.

  • 59.
    Gregers, Jannie
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. University of Copenhagen Hospital, Denmark.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. KTH Royal Institute Technology, Sweden; National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    Christensen, I. J.
    Rigshosp, Denmark.
    Dalhoff, K.
    Bispebjerg Hospital, Denmark.
    Schroeder, H.
    University Hospital Skejby, Denmark.
    Carlsen, N.
    Odense University Hospital, Denmark.
    Rosthoej, S.
    University Hospital Aalborg, Denmark.
    Lausen, B.
    University of Copenhagen, Denmark.
    Schmiegelow, K.
    University of Copenhagen, Denmark; University of Copenhagen, Denmark.
    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.
    Polymorphisms in the ABCB1 gene and effect on outcome and toxicity in childhood acute lymphoblastic leukemia2015In: The Pharmacogenomics Journal, ISSN 1470-269X, E-ISSN 1473-1150, Vol. 15, no 4, p. 372-379Article in journal (Refereed)
    Abstract [en]

    The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences the pharmacokinetics of anti-cancer drugs. We hypothesized that variants of ABCB1 affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL). We studied 522 Danish children with ALL, 93% of all those eligible. Risk of relapse was increased 2.9-fold for patients with the 1199GA variant versus 1199GG (P = 0.001), and reduced 61% and 40%, respectively, for patients with the 3435CT or 3435TT variants versus 3435CC (overall P = 0.02). The degree of bone marrow toxicity during doxorubicin, vincristine and prednisolone induction therapy was more prominent in patients with 3435TT variant versus 3435CT/3435CC (P = 0.01/P less than 0.0001). We observed more liver toxicity after high-dose methotrexate in patients with 3435CC variant versus 3435CT/TT ( P = 0.03). In conclusion, there is a statistically significant association between ABCB1 polymorphisms, efficacy and toxicity in the treatment of ALL, and ABCB1 1199G greater than A may be a new possible predictive marker for outcome in childhood ALL.

  • 60.
    Hagman, H.
    et al.
    County Hospital Ryhov, Sweden.
    Frodin, J. -E.
    Karolinska University Hospital, Sweden.
    Berglund, A.
    University of Uppsala Hospital, Sweden.
    Sundberg, J.
    Skåne University Hospital, Sweden.
    Vestermark, L. W.
    Odense University Hospital, Denmark.
    Albertsson, Maria
    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.
    Fernebro, E.
    Vaxjo Hospital, Sweden.
    Johnsson, A.
    Skåne University Hospital, Sweden.
    A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer: the Nordic ACT2 trial2016In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 27, no 1, p. 140-147Article in journal (Refereed)
    Abstract [en]

    Maintenance treatment (mt) with bevacizumab (bev) +/- erlotinib (erlo) has modest effect after induction chemotherapy in metastatic colorectal cancer (mCRC). We hypothesized the efficacy of erlo to be dependent on KRAS mutational status and investigated this by exploring mt strategies with bev +/- erlo and low-dose capecitabine (cap). Included patients had mCRC scheduled for first-line therapy, Eastern Cooperative Oncology Group (ECOG) 0-1 and no major comorbidities. Treatment with XELOX/FOLFOX or XELIRI/FOLFIRI + bev was given for 18 weeks. After induction, patients without progression were eligible for randomization to mt; KRAS wild-type (wt) patients were randomized to bev +/- erlo (arms wt-BE, N = 36 versus wt-B, N = 35), KRAS mutated (mut) patients were randomized to bev or metronomic cap (arms mut-B, N = 34 versus mut-C, N = 33). Primary end point was progression-free survival (PFS) rate (PFSr) at 3 months after start of mt. A pooled analysis of KRAS wt patients from the previous ACT study was performed. We included 233 patients. Median age was 64 years, 62% male, 68% ECOG 0, 52% with primary tumor in situ. A total of 138 patients started mt after randomization. PFSr was 64.7% versus 63.6% in wt-B versus wt-BE, P = 1.000; and 75% versus 66.7% in mut-B versus mut-C, P = 0.579, with no significant difference in median PFS and overall survival (OS). In the pooled cohort, median PFS was 3.7 months in wt-B (N = 64) and 5.7 months in wt-BE (N = 62) (hazard ratios 1.03, 95% confidence interval 0.70-1.50, P = 0.867). The frequency of any grade 3/4 toxicities during mt was: 28%/58%/18%/15% (wt-B/wt-BE/mut-B/mut-C). Addition of erlo to bev as mt in KRAS wt mCRC did not significantly improve PFS or OS, but it did increase toxicity. KRAS status does not seem to influence the outcome of treatment with erlotinib. Metronomic cap warrants further investigation in mt strategies, given our explorative results. NCT01229813.

  • 61.
    Hall, Kirsten Sundby
    et al.
    Oslo Univ Hosp, Norway.
    Bruland, Oyvind S.
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Bjerkehagen, Bodil
    Oslo Univ Hosp, Norway.
    Zaikova, Olga
    Oslo Univ Hosp, Norway.
    Engellau, Jacob
    Oslo Univ Hosp, Norway.
    Hagberg, Oskar
    Reg Canc Ctr South, Sweden.
    Hansson, Lina
    Sahlgrens Univ Hosp, Sweden.
    Hagberg, Hans
    Uppsala Univ Hosp, Sweden.
    Ahlstrom, Marie
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Knobel, Heidi
    St Olavs Univ Hosp, Norway.
    Papworth, Karin
    Norrlands Univ Hosp, Sweden.
    Zemmler, Maja
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Goplen, Dorota
    Haukeland Hosp, Norway.
    Bauer, Henrik C. F.
    Karolinska Inst, Sweden.
    Eriksson, Mikael
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Adjuvant chemotherapy and postoperative radiotherapy in high-risk soft tissue sarcoma patients defined by biological risk factors-A Scandinavian Sarcoma Group study (SSG XX)2018In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 99, p. 78-85Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the outcome following adjuvant doxorubicin and ifosfamide in a prospective non-randomised study based on a soft tissue sarcoma (STS) patient subgroup defined by specific morphological characteristics previously shown to be at a high-risk of metastatic relapse. The expected 5-year cumulative incidence of metastases in patients with this risk profile has previously been reported to be about 50% without adjuvant chemotherapy. Methods: High-risk STS was defined as high-grade morphology (according to the Federation Nationale des Centres de Lutte Contre le Cancer [FNCLCC] grade II-III) and either vascular invasion or at least two of the following criteria: tumour size amp;gt;= 8.0 cm, infiltrative growth and necrosis. Six cycles of doxorubicin (60 mg/m(2)) and ifosfamide (6 g/m(2)) were given. Postoperative accelerated radiotherapy was applied and scheduled between cycles 3 and 4. Results: For the 150 eligible patients, median follow-up time for metastases-free survival was 3.9 years (range 0.2-8.7). Five-year metastases-free survival (MFS) was 70.4% (95% confidence interval [CI]: 63.1-78.4) with a local recurrence rate of 14.0% (95% CI: 7.8-20.2). For overall survival (OS), the median follow-up time was 4.4 years (range: 0.2-8.7). The five-year OS was 76.1% (95% CI: 68.8-84.2). Tumour size, deep location and reduced dose intensity (amp;lt;80%) had a negative impact on survival. Toxicity was moderate with no treatment-related death. Conclusions: A benefit of adjuvant chemotherapy, compared to similar historical control groups, was demonstrated in STS patients with defined poor prognostic factors. Vascular invasion, tumour size, growth pattern and necrosis may identify patients in need of adjuvant chemotherapy. (C) 2018 Elsevier Ltd. All rights reserved.

  • 62.
    Hedin, Christina
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Sjödahl, Rune
    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 Surgery in Linköping.
    Aldman, Åke
    Västerviks sjukhus, Västervik, Sweden.
    Davidson, Thomas
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Kammerlind, Ann-Sofie
    Region Jönköpings län, Jönköping, Sweden.
    Nodbrant, Per
    Onkologiska kliniken, Länssjukhuset Ryhov, Jönköping, Sweden.
    Agrup, Måns
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Intraoperativ strålbehandling vid primar operation for bröstcancer: TARGIT-A-studien ej konklusiv2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115, article id EWFFArticle, review/survey (Refereed)
    Abstract [sv]

    The TARGIT-A (TARGeted Intraoperative radioTherapy) multicentre study of early breast cancer compared intraoperative radiotherapy with external radiotherapy. While the intraoperative radiotherapy was standardised, the external postoperative comparison treatment followed established routines in the participating treatment centres resulting in substantial variations in dosages and treatment durations. The uncertainties in the interpretation of the study results created by the design of the TARGIT-A study constitute substantial obstacles to the possible introduction of intraoperative radiotherapy for early breast cancer.

  • 63.
    Hilborn, Erik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Gacic, Jelena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Fornander, Tommy
    Karolinska Institute, 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.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Jansson, Agneta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Androgen receptor expression predicts beneficial tamoxifen response in oestrogen receptor-alpha-negative breast cancer2016In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 114, no 3, p. 248-255Article in journal (Refereed)
    Abstract [en]

    Background: Although the androgen receptor (AR) is frequently expressed in breast cancer, its relevance in the disease is not fully understood. In addition, the relevance of AR in determining tamoxifen treatment efficiency requires evaluation. Purpose: To investigate the tamoxifen predictive relevance of the AR protein expression in breast cancer. Methods Patients were randomised to tamoxifen 40 mg daily for 2 or 5 years or to no endocrine treatment. Mean follow-up was 15 years. Hazard ratios were calculated with recurrence-free survival as end point. Results: In patients with oestrogen receptor (ER)-negative tumours, expression of AR predicted decreased recurrence rate with tamoxifen (hazard ratio (HR) = 0.34; 95% confidence interval (CI) = 0.14-0.81; P = 0.015), whereas the opposite was seen in the AR- group (HR = 2.92; 95% CI = 1.16-7.31; P = 0.022). Interaction test was significant P < 0.001. Patients with triple-negative and AR+ tumours benefitted from tamoxifen treatment (HR = 0.12; 95% CI = 0.014-0.95 P = 0.044), whereas patients with AR- tumours had worse outcome when treated with tamoxifen (HR = 3.98; 95% CI = 1.32-12.03; P = 0.014). Interaction test was significant P = 0.003. Patients with ER+ tumours showed benefit from tamoxifen treatment regardless of AR expression. Conclusions: AR can predict tamoxifen treatment benefit in patients with ER- tumours and triple-negative breast cancer.

  • 64.
    Hilborn, Erik
    et al.
    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.
    Alexeyenko, Andrey
    Karolinska Institute, Sweden; National Bioinformat Infrastruct Sweden, Sweden.
    Jansson, Agneta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    The regulation of hydroxysteroid 17 beta-dehydrogenase type 1 and 2 gene expression in breast cancer cell lines by estradiol, dihydrotestosterone, microRNAs, and genes related to breast cancer2017In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 37, p. 62183-62194Article in journal (Refereed)
    Abstract [en]

    Aim. To investigate the influence of estrogen, androgen, microRNAs, and genes implicated in breast cancer on the expression of HSD17B1 and HSD17B2. Materials. Breast cancer cell lines ZR-75-1, MCF7, T47D, SK-BR-3, and the immortalized epithelial cell line MCF10A were used. Cells were treated either with estradiol or dihydrotestosterone for 6, 24, 48 hours, or 7 days or treated with miRNAs or siRNAs predicted to influence HSD17B expression Results and discussion. Estradiol treatment decreased HSD17B1 expression and had a time-dependent effect on HSD17B2 expression. This effect was lost in estrogen receptor-alpha down-regulated or negative cell lines. Dihydrotestosterone treatment increased HSD17B2 expression, with limited effect on HSD17B1 expression. No effect was seen in cells without AR or in combination with the AR inhibitor hydroxyflutamide. The miRNA-17 up-regulated HSD17B1, while miRNA-210 and miRNA-7-5p had up- and down-regulatory effect and miRNA-1304-3p reduced HSD17B1 expression. The miRNA-204-5p, 498, 205-3p and 579-3p reduced HSD17B2 expression. Downregulation of CX3CL1, EPHB6, and TP63 increased HSD17B1 and HSD17B2 expression, while GREB1 downregulation suppressed HSD17B1 and promoted HSD17B2 expression. Conclusion. We show that HSD17B1 and HSD17B2 are controlled by estradiol, dihydrotestosterone, and miRNAs, as well as modulated by several breast cancer-related genes, which could have future clinical applications.

  • 65.
    Hilborn, Erik
    et al.
    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.
    Jansson, Agneta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Estrogen and androgen-converting enzymes 17 beta-hydroxysteroid dehydrogenase and their involvement in cancer: with a special focus on 17 beta-hydroxysteroid dehydrogenase type 1, 2, and breast cancer2017In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 18, p. 30552-30562Article, review/survey (Refereed)
    Abstract [en]

    Sex steroid hormones such as estrogens and androgens are involved in the development and differentiation of the breast tissue. The activity and concentration of sex steroids is determined by the availability from the circulation, and on local conversion. This conversion is primarily mediated by aromatase, steroid sulfatase, and 17 beta-hydroxysteroid dehydrogenases. In postmenopausal women, this is the primary source of estrogens in the breast. Up to 70-80% of all breast cancers express the estrogen receptor-a, responsible for promoting the growth of the tissue. Further, 60-80% express the androgen receptor, which has been shown to have tissue protective effects in estrogen receptor positive breast cancer, and a more ambiguous response in estrogen receptor negative breast cancers. In this review, we summarize the function and clinical relevance in cancer for 17 beta-hydroxysteroid dehydrogenases 1, which facilitates the reduction of estrone to estradiol, dehydroepiandrosterone to androstendiol and dihydrotestosterone to 3 alpha- and 3 beta-diol as well as 17 beta-hydroxysteroid dehydrogenases 2 which mediates the oxidation of estradiol to estrone, testosterone to androstenedione and androstendiol to dehydroepiandrosterone. The expression of 17 beta-hydroxysteroid dehydrogenases 1 and 2 alone and in combination has been shown to predict patient outcome, and inhibition of 17 beta-hydroxysteroid dehydrogenases 1 has been proposed to be a prime candidate for inhibition in patients who develop aromatase inhibitor resistance or in combination with aromatase inhibitors as a first line treatment. Here we review the status of inhibitors against 17 beta-hydroxysteroid dehydrogenases 1. In addition, we review the involvement of 17 beta-hydroxysteroid dehydrogenases 4, 5, 7, and 14 in breast cancer.

  • 66.
    Hjerpe, Elisabet
    et al.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Staf, Christian
    Sahlgrens Univ Hosp, Sweden.
    Dahm-Kahler, Pernilla
    Sahlgrens Univ Hosp, Sweden.
    Stalberg, Karin
    Uppsala Univ, Sweden.
    Bjurberg, Maria
    Skåne Univ Hosp, Sweden; Lund Univ, Sweden.
    Holmberg, Erik
    Sahlgrens Univ Hosp, Sweden; Sahlgrens Acad, Sweden.
    Borgfeldt, Christer
    Skåne Univ Hosp, Sweden; Lund Univ, Sweden.
    Tholander, Bengt
    Uppsala Univ Hosp, Sweden.
    Hellman, Kristina
    Karolinska Univ Hosp, Sweden; Karolinska Inst, 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.
    Högberg, Thomas
    Lund Univ, Sweden.
    Rosenberg, Per
    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.
    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 Inst, Sweden.
    Lymph node metastases as only qualifier for stage IV serous ovarian cancer confers longer survival than other sites of distant disease - a Swedish Gynecologic Cancer Group (SweGCG) study2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 3, p. 331-337Article in journal (Refereed)
    Abstract [en]

    Background: The International Federation of Gynecology and Obstetrics (FIGO) ovarian cancer staging system includes no sub-stage for lymph nodes (LN) as only distant disease manifestation. We explore the prognostic implication of LN as only stage IV classifier in serous ovarian cancer.Method: This is a nation-wide, population-based study on 551 women with serous stage IV cancers diagnosed between 2009-2014. We compare overall survival (OS) in women with LN as only distant metastatic site to those with pleural metastases only and to patients with other/multiple stage IV manifestations. Cox regression models were used for uni- and multivariable estimations.Results: Of 551stage IV cases, distant metastatic site was registered in 433. Median OS for women with LN (n=51) was 41.4 months, compared to 25.2 and 26.8 months for patients with pleural (n=195) or other/multiple (n=187) distant metastases (p=.0007). The corresponding five-year survival rates were 32, 11 and 22%, respectively. Multivariable analyzes confirmed shorter survival for women with pleural (HR 2.99, p=.001) or other/multiple distant sites (HR 2.67, p=.007), as compared to LN cases. LN only patients lived 9.1 months longer after primary than after interval surgery, but this difference was not significant (p=.245).Conclusion: Women with stage IV serous ovarian cancer having lymph nodes as only distant metastatic site live longer than other stage IV patients.

  • 67.
    Hu, Wenjun
    et al.
    Sichuan Univ, Peoples R China.
    Lei, Linping
    Sichuan Univ, Peoples R China.
    Xie, Xuqin
    Sichuan Univ, Peoples R China.
    Huang, Libin
    Sichuan Univ, Peoples R China.
    Cui, Qian
    Univ Elect Sci and Technol China, Peoples R China.
    Dang, Tang
    Huazhong Univ Sci and Technol, Peoples R China.
    Liu, Gang Logan
    Huazhong Univ Sci and Technol, Peoples R China.
    Li, Yuan
    Sichuan Univ, 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.
    Zhou, Zongguang
    Sichuan Univ, Peoples R China.
    Heterogeneous nuclear ribonucleoprotein L facilitates recruitment of 53BP1 and BRCA1 at the DNA break sites induced by oxaliplatin in colorectal cancer2019In: Cell Death and Disease, ISSN 2041-4889, E-ISSN 2041-4889, Vol. 10, article id 550Article in journal (Refereed)
    Abstract [en]

    Although oxaliplatin is an effective chemotherapeutic drug for treatment of colorectal cancer (CRC), tumor cells can develop mechanisms to evade oxaliplatin-induced cell death and show high tolerance and acquired resistance to this drug. Heterogeneous nuclear ribonucleoprotein L (hnRNP L) has been proved to play a critical role in DNA repair during IgH class switch recombination (CSR) in B lymphocytes, while, its role in CRC and chemotherapeutic resistance remain unknown. Our study aims to uncover an unidentified mechanism of regulating DNA double-strand breaks (DSBs) by hnRNP L in CRC cells treated by oxaliplatin. In present study, we observed that knockdown of hnRNP L enhanced the level of DNA breakage and sensitivity of CRC cells to oxaliplatin. The expression of key DNA repair factors (BRCA1, 53BP1, and ATM) was unaffected by hnRNP L knockdown, thereby excluding the likelihood of hnRNP L mediation via mRNA regulation. Moreover, we observed that phosphorylation level of ATM changed oppositely to 53BP1 and BRCA1 in the CRC cells (SW620 and HCT116) which exhibit synergistic effect by oxaliplatin plus hnRNP L impairment. And similar phenomenon was observed in the foci formation of these critical repair factors. We also found that hnRNP L binds directly with these DNA repair factors through its RNA-recognition motifs (RRMs). Analysis of cell death indicated that the RRMs of hnRNP L are required for cell survival under incubation with oxaliplatin. In conclusion, hnRNP L is critical for the recruitment of the DNA repair factors in oxaliplatin-induced DSBs. Targeting hnRNP L is a promising new clinical approach that could enhance the effectiveness of current chemotherapeutic treatment in patients with resistance to oxaliplatin.

  • 68.
    Högberg, Thomas
    et al.
    Avdelningen för cancerepidemiologi, Skånes universitetssjukhus, Lund.
    Bergfeldt, Kjell
    Regionalt cancercentrum Stockholm–Gotland, Stockholm.
    Borgfeldt, Christer
    Kvinnokliniken, Skånes universitetssjukhus, Lund.
    Holmberg, Erik
    Regionalt cancercentrum Väst, Göteborg.
    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.
    Hopp om förbättring av överlevnad i ovarialcancer2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, no 50, p. 2281-3Article in journal (Refereed)
    Abstract [en]

    Ovarian cancer is the most common cause of death from a gynecologic cancer. Every year around 700 women contracts ovarian cancer in Sweden. The overall survival is among the highest in Europe, but still long term relative survival is only 46%. It is a long-held myth that ovarian cancer is a disease without symptoms. Almost 90% of women have symptoms, even in the early stages. Symptoms that should arise suspicion of ovarian cancer and initiate diagnostic work-up are continuous abdominal extension, early feeling of satiety, pelvic or abdominal pain, urinary urge and postmenopausal bleeding. Women's awareness of symptoms and willingness to seek medical advice and the organization of the health care system are important factors determining cancer survival. Ovarian cancer is a heterogeneous group of diseases with different tumor traits and prognosis. Personalized medicine and preventive measures recognizing recent knowledge about tumor biology will positively affect survival.

  • 69.
    Högström, G.
    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. Lund Univ, Sweden.
    Ohlsson, H.
    Lund Univ, Sweden.
    Crump, C.
    Lund Univ, Sweden; Icahn Sch Med Mt Sinai, NY 10029 USA.
    Sundquist, J.
    Lund Univ, Sweden.
    Sundquist, K.
    Lund Univ, Sweden.
    Aerobic fitness in late adolescence and the risk of cancer and cancer-associated mortality in adulthood: A prospective nationwide study of 1.2 million Swedish men2019In: Cancer Epidemiology, ISSN 1877-7821, E-ISSN 1877-783X, Vol. 59, p. 58-63Article in journal (Refereed)
    Abstract [en]

    Background: The incidence of cancer has steadily risen. It is important to identify modifiable predictors in early life that may decrease cancer risks and mortality. The present study aims to investigate the relationship between aerobic fitness in adolescence and the subsequent risk of cancer and cancer-associated mortality. Methods: The study included 1 185 439 Swedish men born between 1950 and 1980 that participated in the military conscription (mean age = 18 years). The results from the aerobic fitness test (W-max) was linked to the risk of cancer and cancer-associated mortality during a 40-years follow-up using Cox proportional hazards models. A co-sibling design was employed to take familial factors into account. Results: During a mean follow-up of 27 years 15 093 cases of cancer and 4900 cancer-associated mortalities were registered. Higher W-max (per additional 1 SD) was associated with a decreased risk of cancer at 40 years of follow-up (HR 0.93; 95% CI 0.91-0.96 for cancer and HR 0.82 95% CI 0.76-0.87 for cancer-associated mortality) but not at 5 years of follow-up (HR 1.03; 95% CI 0.99-1.07; and HR 1.04; 95% CI 0.97-1.12). In the co-sibling model the protective effects of high W-max were increased at 40 years of follow-up for cancer (HR 0.91; 95% CI 0.85-0.98) and cancer-associated mortality (HR 0.78; 95% CI 0.68-0.89). Conclusions: These findings identify in late adolescence a potentially modifiable predictor of cancer, with higher aerobic fitness associated with a decreased risk of cancer incidence and mortality later in life.

  • 70.
    Jakola, Asgeir Store
    et al.
    Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Neurosurgery, St. Olavs Hospital, Trondheim, Norway; Institute of Neuroscience and Physiology, Department of Clinical Neuroscience, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden.
    Werlenius, Katja
    Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Clinical Sciences, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden.
    Mudaisi, Munila
    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.
    Hylin, Sofia
    Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Kinhult, Sara
    Department of Oncology, Skåne University Hospital, Lund, Sweden.
    Bartek, Jiri
    Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Salvesen, Øyvind
    Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway.
    Carlsen, Sven Magnus
    Department of Cancer Research and Molecular medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Endocrinology, St. Olavs Hospital, Trondheim, Norway.
    Strandéus, Michael
    Department of Oncology, County Hospital Ryhov, Jönköping, Sweden.
    Lindskog, Magnus
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Section of Oncology, Akademiska University Hospital, Uppsala, Sweden.
    Löfgren, David
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Rydenhag, Bertil
    Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Neuroscience and Physiology, Department of Clinical Neuroscience, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden.
    Carstam, Louise
    Department of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Neuroscience and Physiology, Department of Clinical Neuroscience, University of Gothenburg, Sahlgrenska Academy, Gothenburg, Sweden.
    Gulati, Sasha
    Department of Neurosurgery, St. Olavs Hospital, Trondheim, Norway; Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
    Solheim, Ole
    Department of Neurosurgery, St. Olavs Hospital, Trondheim, Norway; Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
    Bartek, Jiri
    Department of Medical Biochemistry and Biophysics, Division of Genome Biology, Science for Life Laboratory,, Karolinska Institute, Stockholm, Sweden; Research Center, Danish Cancer Society, Copenhagen, Denmark.
    Solheim, Tora
    European Palliative Care Research Centre (PRC), Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Cancer Clinic, St. Olavs Hospital, Trondheim, Norway.
    Disulfiram repurposing combined with nutritional copper supplement as add-on to chemotherapy in recurrent glioblastoma (DIRECT): Study protocol for a randomized controlled trial2018In: F1000 Research, E-ISSN 2046-1402, Vol. 7, article id 1797Article in journal (Refereed)
    Abstract [en]

    Background: Disulfiram (DSF) is a well-tolerated, inexpensive, generic drug that has been in use to treat alcoholism since the 1950s. There is now independent preclinical data that supports DSF as an anticancer agent, and experimental data suggest that copper may increase its anti-neoplastic properties. There is also some clinical evidence that DSF is a promising anticancer agent in extracranial cancers. In glioblastoma, DSF induced O 6-methylguanine methyltransferase (MGMT) inhibition may increase response to alkylating chemotherapy. A recent phase I study demonstrated the safety of DSF in glioblastoma patients when DSF was administered at doses below 500 mg/day together with chemotherapy. We plan to assess the effects of DSF combined with nutritional copper supplement (DSF-Cu) as an adjuvant to alkylating chemotherapy in glioblastoma treatment. Methods: In an academic, industry independent, multicenter, open label randomized controlled phase II/III trial with parallel group design (1:1) we will assess the efficacy and safety of DSF-Cu in glioblastoma treatment. The study will include 142 patients at the time of first recurrence of glioblastoma where salvage therapy with alkylating chemotherapy is planned. Patients will be randomized to treatment with or without DSF-Cu. Primary end-point is survival at 6 months. Secondary end-points are overall survival, progression free survival, quality of life, contrast enhancing tumor volume and safety. Discussion: There is a need to improve the treatment of recurrent glioblastoma. Results from this randomized controlled trial with DSF-Cu in glioblastoma will serve as preliminary evidence of the future role of DSF-Cu in glioblastoma treatment and a basis for design and power estimations of future studies. In this publication we provide rationale for our choices and discuss methodological issues. Trial registration: The study underwent registration in EudraCT 2016-000167-16 (Date: 30.03.2016,) and Clinicaltrials.gov NCT02678975 (Date: 31.01.2016) before initiating the study.

  • 71. Johnson, Christina
    et al.
    Wilhelmsson, Susan
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. 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.
    Lindberg, Malou
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care. Linköping University, Faculty of Medicine and Health Sciences.
    Improvement of communication and interpersonal competence in telenursing - development of a self-assessment tool2015In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 24, no 11-12, p. 1489-1501Article in journal (Refereed)
    Abstract [en]

    Aims and objectivesThe aim of this study was to develop a self-assessment tool aiming to raise telenurses awareness of their communication and interpersonal competence, and highlight areas in need of improvement. BackgroundSeveral studies have revealed the need for development of communication competence in telenursing. Structured analyses of conversations with patients/callers, is one way to increase telenurses awareness of their unique communication and interpersonal competence. DesignInstrument development, Validation assessment using the method Content Validity Index. MethodThe process to determine content validity was done in two stages; the development stage and the assessment stage. The development stage started with a literature search. The assessment stage was separated into two phases, assessment by an expert group and assessment and test by telenurses. The telenurses also participated in consensus discussions. ResultsA telenursing self-assessment tool with 58 items was developed. The items were sorted into five sections according to the nursing process. ConclusionThis study describes the thorough development process of the telenursing self-assessment tool to be used by telenurses in order to become aware of their unique communication and interpersonal competence when analysing their own conversations with patients/callers. As a formative tool it is meant to provide self-direction, feedback and coaching, and create learning opportunities. Relevance to clinical practiceThe self-assessment tool helps the telenurse to follow the nursing process, to be patient-centred, and it is meant to provide self-direction, feedback, and coaching, as well as create learning opportunities. The tool can contribute to the development of communication and interpersonal competence in telephone advice nursing. Further development of the tool may provide an objective scoring instrument for evaluating communication training and education in the field.

  • 72.
    Jothimani, Ganesan
    et al.
    CARE, India.
    Sriramulu, Sushmitha
    CARE, India.
    Chabria, Yashna
    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.
    Banerjee, Antara
    CARE, India.
    Pathak, Surajit
    CARE, India.
    A Review on Theragnostic Applications of microRNAs and Long Non-Coding RNAs in Colorectal Cancer2018In: Current Topics in Medicinal Chemistry, ISSN 1568-0266, E-ISSN 1873-4294, Vol. 18, no 30, p. 2614-2629Article, review/survey (Refereed)
    Abstract [en]

    Colorectal cancer (CRC) is a heterogeneous malignancy leading to increased mortality and poor prognosis due to the lack of efficient early diagnostics. Metastasis of the tumor being the most common cause of mortality is accountable for almost 90% of CRC associated deaths. Intensified screening procedures and molecular target identification has inflated the median survival rate of in CRC patients. microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have come forward as potential targets for developing a novel approach in CRC theragnostics. Non-coding RNA (ncRNAs) sequences are abundantly present and thereby play a vital role in several biological processes such as cellular organization, cell fate determination, proliferation, apoptosis, tissue homeostasis maintenance as well as pathological conditions such as cancer by acting as post transcriptional regulators of gene expression. Several studies have highlighted the involvement of these ncRNAs in CRC development. However, the molecular mechanism involved in regulating CRC has not been clearly elucidated. This review, throws light upon the several non-coding RNAs involved in CRC with a focus on novel mechanisms of action, recent advances in the regulatory mechanisms that control the gene expression related to carcinogenesis. Furthermore, the potential role of ncRNAs as diagnostic as well as therapeutic targets has been reviewed.

  • 73.
    Karlsson, Elin
    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.
    Magic, Ivana
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Bostner, Josefine
    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.
    Dyrager, Christine
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Lysholm, Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, Faculty of Science & Engineering.
    Hallbeck, Anna-Lotta
    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.
    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.
    Lundström, Patrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Revealing Different Roles of the mTOR-Targets S6K1 and S6K2 in Breast Cancer by Expression Profiling and Structural Analysis2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 12, p. e0145013-Article in journal (Refereed)
    Abstract [en]

    Background

    The AKT/mTORC1/S6K pathway is frequently overstimulated in breast cancer, constituting a promising therapeutic target. The benefit from mTOR inhibitors varies, likely as a consequence of tumour heterogeneity, and upregulation of several compensatory feed-back mechanisms. The mTORC1 downstream effectors S6K1, S6K2, and 4EBP1 are amplified and overexpressed in breast cancer, associated with a poor outcome and divergent endocrine treatment benefit. S6K1 and S6K2 share high sequence homology, but evidence of partly distinct biological functions is emerging. The aim of this work was to explore possible different roles and treatment target potentials of S6K1 and S6K2 in breast cancer.

    Materials and methods

    Whole-genome expression profiles were compared for breast tumours expressing high levels of S6K1, S6K2 or 4EBP1, using public datasets, as well as after in vitro siRNA downregulation of S6K1 and/or S6K2 in ZR751 breast cancer cells. In silico homology modelling of the S6K2 kinase domain was used to evaluate its possible structural divergences to S6K1.

    Results

    Genome expression profiles were highly different in S6K1 and S6K2 high tumours, whereas S6K2 and 4EBP1 profiles showed significant overlaps, both correlated to genes involved in cell cycle progression, among these the master regulator E2F1. S6K2 and 4EBP1 were inversely associated with IGF1 levels, and their prognostic value was shown to be restricted to tumours positive for IGFR and/or HER2. In vitro, S6K1 and S6K2 silencing resulted in upregulation of genes in the mTORC1 and mTORC2 complexes. Isoform-specific silencing also showed distinct patterns, e.g. S6K2 downregulation lead to upregulation of several cell cycle associated genes. Structural analyses of the S6K2 kinase domain showed unique structure patterns, deviating from those of S6K1, facilitating the development of isoform-specific inhibitors. Our data support emerging proposals of distinct biological features of S6K1 and S6K2, suggesting their importance as separate oncogenes and clinical markers, where specific targeting in different breast cancer subtypes could facilitate further individualised therapies.

  • 74.
    Karlsson, Elin
    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.
    Veenstra, Cynthia
    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.
    Emin, Shad
    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.
    Dutta, Chhanda
    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.
    Perez-Tenorio, Gizeh
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    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. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Loss of protein tyrosine phosphatase, non-receptor type 2 is associated with activation of AKT and tamoxifen resistance in breast cancer2015In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 153, no 1, p. 31-40Article in journal (Refereed)
    Abstract [en]

    Breast cancer is a heterogeneous disease and new clinical markers are needed to individualise disease management and therapy further. Alterations in the PI3K/AKT pathway, mainly PIK3CA mutations, have been shown frequently especially in the luminal breast cancer subtypes, suggesting a cross-talk between ER and PI3K/AKT. Aberrant PI3K/AKT signalling has been connected to poor response to anti-oestrogen therapies. In vitro studies have shown protein tyrosine phosphatase, non-receptor type 2 (PTPN2) as a previously unknown negative regulator of the PI3K/AKT pathway. Here, we evaluate possible genomic alterations in the PTPN2 gene and its potential as a new prognostic and treatment predictive marker for endocrine therapy benefit in breast cancer. PTPN2 gene copy number was assessed by real-time PCR in 215 tumour samples from a treatment randomised study consisting of postmenopausal patients diagnosed with stage II breast cancer 1976-1990. Corresponding mRNA expression levels of PTPN2 were evaluated in 86 available samples by the same methodology. Gene copy loss of PTPN2 was detected in 16 % (34/215) of the tumours and this was significantly correlated with lower levels of PTPN2 mRNA. PTPN2 gene loss and lower mRNA levels were associated with activation of AKT and a poor prognosis. Furthermore, PTPN2 gene loss was a significant predictive marker of poor benefit from tamoxifen treatment. In conclusion, genomic loss of PTPN2 may be a previously unknown mechanism of PI3K/AKT upregulation in breast cancer. PTPN2 status is a potential new clinical marker of endocrine treatment benefit which could guide further individualised therapies in breast cancer.

  • 75.
    Karlsson, Elin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Veenstra, Cynthia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Garsjö, Jon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    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.
    PTPN2 deficiency along with activation of nuclear Akt predict endocrine resistance in breast cancer2019In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 145, no 3, p. 599-607Article in journal (Refereed)
    Abstract [en]

    Purpose The protein tyrosine phosphatase, non-receptor type 2 (PTNP2) regulates receptor tyrosine kinase signalling, preventing downstream activation of intracellular pathways like the PI3K/Akt pathway. The gene encoding the protein is located on chromosome 18p11; the 18p region is commonly deleted in breast cancer. In this study, we aimed to evaluate PTPN2 protein expression in a large breast cancer cohort, its possible associations to PTPN2 gene copy loss, Akt activation, and the potential use as a clinical marker in breast cancer. Methods PTPN2 protein expression was analysed by immunohistochemistry in 664 node-negative breast tumours from patients enrolled in a randomised tamoxifen trial. DNA was available for 146 patients, PTPN2 gene copy number was determined by real-time PCR. Results PTPN2 gene loss was detected in 17.8% of the tumours. Low PTPN2 protein expression was associated with higher levels of nuclear-activated Akt (pAkt-n). Low PTPN2 as well as the combination variable low PTPN2/high pAkt-n could be used as predictive markers of poor tamoxifen response. Conclusion PTPN2 negatively regulates Akt signalling and loss of PTPN2 protein along with increased pAkt-n is a new potential clinical marker of endocrine treatment efficacy, which may allow for further tailored patient therapies.

  • 76.
    Kimbung, Siker
    et al.
    Lund University, Sweden.
    Johansson, Ida
    Lund University, Sweden.
    Danielsson, Anna
    University of Gothenburg, Sweden.
    Veerla, Srinivas
    Lund University, Sweden.
    Egyhazi Brage, Suzanne
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Frostvik Stolt, Marianne
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Skoog, Lambert
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Carlsson, Lena
    Sundsvall Hospital, Sweden.
    Einbeigi, Zakaria
    University of Gothenburg, Sweden.
    Lidbrink, Elisabet
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Linderholm, Barbro
    University of Gothenburg, Sweden.
    Loman, Niklas
    Skåne University Hospital, Sweden.
    Malmstrom, Per-Olof
    Skåne University Hospital, Sweden.
    Soderberg, Martin
    Skåne University Hospital, Sweden.
    Walz, Thomas
    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.
    Ferno, Marten
    Lund University, Sweden.
    Hatschek, Thomas
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Hedenfalk, Ingrid
    Lund University, Sweden; Lund University, Sweden.
    Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis-Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer2016In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 22, no 1, p. 146-157Article in journal (Refereed)
    Abstract [en]

    Purpose: The complete molecular basis of the organ-specificity of metastasis is elusive. This study aimed to provide an independent characterization of the transcriptional landscape of breast cancer metastases with the specific objective to identify liver metastasis-selective genes of prognostic importance following primary tumor diagnosis. Experimental Design: A cohort of 304 women with advanced breast cancer was studied. Associations between the site of recurrence and clinicopathologic features were investigated. Fine-needle aspirates of metastases (n = 91) were subjected to whole-genome transcriptional profiling. Liver metastasis-selective genes were identified by significance analysis of microarray (SAM) analyses and independently validated in external datasets. Finally, the prognostic relevance of the liver metastasis-selective genes in primary breast cancer was tested. Results: Liver relapse was associated with estrogen receptor (ER) expression (P = 0.002), luminal B subtype (P = 0.01), and was prognostic for an inferior postrelapse survival (P = 0.01). The major variation in the transcriptional landscape of metastases was also associated with ER expression and molecular subtype. However, liver metastases displayed unique transcriptional fingerprints, characterized by down-regulation of extracellular matrix (i.e., stromal) genes. Importantly, we identified a 17-gene liver metastasis-selective signature, which was significantly and independently prognostic for shorter relapse-free (P < 0.001) and overall (P = 0.001) survival in ER-positive tumors. Remarkably, this signature remained independently prognostic for shorter relapse-free survival (P = 0.001) among luminal A tumors. Conclusions: Extracellular matrix (stromal) genes can be used to partition breast cancer by site of relapse and may be used to further refine prognostication in ER positive primary breast cancer. (C)2015 AACR.

  • 77.
    King, Madeleine T.
    et al.
    Univ Sydney, Australia; Univ Sydney, Australia.
    Stockler, Martin R.
    ANZGOG, Australia.
    OConnell, Rachel L.
    Univ Sydney, Australia.
    Buizen, Luke
    Univ Sydney, Australia.
    Joly, Florence
    Ctr Francois Baclesse, France.
    Lanceley, Anne
    UCL, England.
    Hilpert, Felix
    Krankenhaus Jerusalem Hamburg, Germany.
    Okamoto, Aikou
    Jikei Univ, Japan.
    Aotani, Eriko
    Kanagawa Acad Sci and Technol, Japan.
    Bryce, Jane
    IRCCS, Italy.
    Donnellan, Paul
    Galway Univ Hosp, Ireland.
    Oza, Amit
    Univ 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 Inst, Sweden.
    Berek, Jonathan S.
    Stanford Comprehens Canc Inst, CA USA.
    Sehouli, Jalid
    AGO Study Grp, Germany.
    Feeney, Amanda
    UCL, England.
    Berton-Rigaud, Dominique
    GINECO, France.
    Costa, Daniel S. J.
    Univ Sydney, Australia.
    Friedlander, Michael L.
    ANZGOG, Australia.
    Measuring what matters MOST: validation of the Measure of Ovarian Symptoms and Treatment, a patient-reported outcome measure of symptom burden and impact of chemotherapy in recurrent ovarian cancer2018In: Quality of Life Research, ISSN 0962-9343, E-ISSN 1573-2649, Vol. 27, no 1, p. 59-74Article in journal (Refereed)
    Abstract [en]

    Gynecologic Cancer Intergroup Symptom Benefit Study (GCIG-SBS) Stage 2 aimed to review, revise, and validate a patient-reported outcome measure (PROM), the Measure of Ovarian Symptoms and Treatment concerns (MOST), developed in GCIG-SBS Stage 1 (MOSTv1, 35 items), and document recurrent ovarian cancer (ROC) symptom burden and benefit. GCIG-SBS Stage 2 recruited patients with platinum-resistant/refractory ROC (PRR-ROC) or potentially platinum-sensitive ROC with aeamp;lt;yenamp;gt; 3 lines of prior chemotherapy (PPS-ROC aeamp;lt;yenamp;gt; 3). Patients completed MOSTv1, QLQ-C30, QLQ-OV28, and FACT-O/FOSI at baseline and before cycle 3 of chemotherapy (pre-C3), and global assessments of change (MOST-Change) pre-C3. Clinicians rated patients cancer-related symptoms, performance status, and adverse events. Convergent and divergent validity (Spearmans correlations), discriminative validity (effect sizes between groups classified by clinician-rated characteristics), and responsiveness (paired t tests in patients expected to experience clinically meaningful change) were assessed. Of 948 recruits, 903 completed PROMs at baseline and 685 pre-C3. Baseline symptom burden was substantial for PRR-ROC and PPS-ROC aeamp;lt;yenamp;gt; 3. MOSTv2 has 24 items and five multi-item scales: abdominal symptoms (MOST-Abdo), disease or treatment-related symptoms (MOST-DorT), chemotherapy-related symptoms (MOST-Chemo), psychological symptoms (MOST-Psych), and MOST-Well-being. Correlations confirmed concurrent and divergent validity. Discriminative validity was confirmed by effect sizes that conformed with a priori hypotheses. MOST-Abdo was responsive to improvements in abdominal symptoms and MOST-Chemo detected the adverse effects of chemotherapy. The MOSTv2 validly quantifies patient-reported symptom burden, adverse effects, and symptom benefit in ROC, and as such is fit-for-purpose for clinical trials of palliative chemotherapy in ROC. Further research is required to assess test-retest reliability.

  • 78.
    Kjölhede, Preben
    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 of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Dahm-Kähler, Pernilla
    Kvinnosjukvården, Sahlgrenska universitetssjukhuset, Göteborg.
    Tholander, Bengt
    Onkologiska kliniken, Akademiska sjukhuset, Uppsala.
    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.
    Individualiserad behandling vid ovarialcancer kan bli möjlig2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, no 50, p. 2281-3Article in journal (Refereed)
    Abstract [en]

    Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy in developed countries. Several promising steps toward individualized therapy have been taken recently due to increased knowledge of molecular biology. Multidisciplinary conferences for treatment planning and the centralization to tertiary surgical centers improve quality of surgery and survival. The primary treatment of EOC is radical surgery followed by adjuvant chemotherapy with carboplatin and paclitaxel. Bevacizumab added to the chemotherapy and used as maintenance treatment is standard in the primary treatment of patients with residual tumor or inoperable patients. The PARP inhibitor olaparib is recommended as maintenance treatment of women with platinum sensitive relapsed BRCA mutated high-grade serous EOC who have responded to platinum-based chemotherapy. BRCA testing should be offered to women with EOC. In platinum-resistant recurrence addition of bevacizumab to chemotherapy should be considered.

  • 79.
    Kotti, Angeliki
    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 Diagnostics, Department of Radiology in Linköping. Linköping University, Department of Medical and Health Sciences.
    Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Albertsson, Maria
    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.
    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.
    Survival benefit of statins in older patients with rectal cancer: A Swedish population-based cohort study2019In: Journal of Geriatric Oncology, ISSN 1879-4068, E-ISSN 1879-4076, Vol. 10, no 5, p. 690-697Article in journal (Refereed)
    Abstract [en]

    Objectives

    Increasing evidence suggests that statins may have antitumor effects but their rolein rectal cancer appears inconclusive. The aim of this study was to investigate whether statins may have an impact on survival of older and younger patients with rectal cancer.

    Materials and Methods

    This study included 238 patients ≥70 years and 227 patients <70 years old, from the Southeast Health Care Region of Sweden, who were diagnosed with rectal adenocarcinoma between 2004 and 2013.

    Results

    In the older group (n = 238), statin use at the time of diagnosis was related to better cancer-specific survival (CSS) and overall survival (OS), compared to non-use (CSS: Hazard Ratio (HR), 0.37; 95% CI, 0.19–0.72; P = .003; OS: HR, 0.62; 95% CI, 0.39–0.96; P = .032). In the older group with stages I-III disease (n = 199), statin use was associated with better disease-free survival (DFS) compared to non use (HR, 0.18; 95% CI, 0.06–0.59; P = .005). The improvement of CSS, OS and DFS remained significant after adjusting for potential confounders. In the older group with stage III disease, statin users had better CSS and DFS compared to non-users (log rank P = .043; log-rank P = .028, respectively). In the older group with short course radiotherapy, statin use was related to better CSS (log-rank P = .032). No such association was present in the younger group.

    Conclusion

    Statin use was related to improved survival in older patients with rectal cancer.

    This observation is important given the low cost and safety of statins as a drug.

  • 80.
    Leandro-Garcia, Luis J.
    et al.
    Spanish National Cancer Research Centre, Spain .
    Inglada-Perez, Lucia
    Spanish National Cancer Research Centre, Spain .
    Pita, Guillermo
    Spanish National Cancer Research Centre, Spain .
    Hjerpe, Elisabet
    Karolinska University Hospital, Sweden .
    Leskelae, Susanna
    Spanish National Cancer Research Centre, Spain .
    Jara, Carlos
    Fdn Hospital Alcorcon, Spain .
    Mielgo, Xabier
    Fdn Hospital Alcorcon, Spain .
    Gonzalez-Neira, Anna
    Spanish National Cancer Research Centre, Spain .
    Robledo, Mercedes
    Spanish National Cancer Research Centre, Spain .
    Åvall-Lundqvist, Elisabeth
    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. Karolinska University Hospital, Sweden .
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Rodriguez-Antona, Cristina
    Spanish National Cancer Research Centre, Spain .
    Genome-wide association study identifies ephrin type A receptors implicated in paclitaxel induced peripheral sensory neuropathy2013In: Journal of Medical Genetics, ISSN 0022-2593, E-ISSN 1468-6244, Vol. 50, no 9, p. 599-605Article in journal (Refereed)
    Abstract [en]

    Background Peripheral neuropathy is the dose limiting toxicity of paclitaxel, a chemotherapeutic drug widely used to treat solid tumours. This toxicity exhibits great inter-individual variability of unknown origin. The present study aimed to identify genetic variants associated with paclitaxel induced neuropathy via a whole genome approach. less thanbrgreater than less thanbrgreater thanMethods A genome-wide association study (GWAS) was performed in 144 white European patients uniformly treated with paclitaxel/carboplatin and for whom detailed data on neuropathy was available. Per allele single nucleotide polymorphism (SNP) associations were assessed by Cox regression, modelling the cumulative dose of paclitaxel up to the development of grade 2 sensory neuropathy. less thanbrgreater than less thanbrgreater thanResults The strongest evidence of association was observed for the ephrin type A receptor 4 (EPHA4) locus (rs17348202, p=1.0x10(-6)), and EPHA6 and EPHA5 were among the top 25 and 50 hits (rs301927, p=3.4x10(-5) and rs1159057, p=6.8x10(-5)), respectively. A meta-analysis of EPHA5-rs7349683, the top marker for paclitaxel induced neuropathy in a previous GWAS (r(2)=0.79 with rs1159057), gave a hazard ratio (HR) estimate of 1.68 (p=1.4x10(-9)). Meta-analysis of the second hit of this GWAS, XKR4-rs4737264, gave a HR of 1.71 (p=3.1x10(-8)). Imputed SNPs at LIMK2 locus were also strongly associated with this toxicity (HR=2.78, p=2.0x10(-7)). less thanbrgreater than less thanbrgreater thanConclusions This study provides independent support of EPHA5-rs7349683 and XKR4-rs4737264 as the first markers of risk of paclitaxel induced neuropathy. In addition, it suggests that other EPHA genes also involved in axonal guidance and repair following neural injury, as well as LIMK2 locus, may play an important role in the development of this toxicity. The identified SNPs could form the basis for individualised paclitaxel chemotherapy.

  • 81.
    Leandro-Garcia, Luis J
    et al.
    Spanish National Cancer Research Centre, Spain .
    Leskelae, Susanna
    Spanish National Cancer Research Centre, Spain .
    Jara, Carlos
    Fdn Hospital Alcorcon, Spain .
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Åvall-Lundqvist, Elisabeth
    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. Karolinska Institute, Sweden .
    Wheeler, Heather E
    University of Chicago, IL 60637 USA .
    Dolan, M Eileen
    University of Chicago, IL 60637 USA .
    Inglada-Perez, Lucia
    Spanish National Cancer Research Centre, Spain CIBERER, Spain .
    Maliszewska, Agnieszka
    Spanish National Cancer Research Centre, Spain .
    de Cubas, Aguirre A
    Spanish National Cancer Research Centre, Spain .
    Comino-Mendez, Inaki
    Spanish National Cancer Research Centre, Spain .
    Mancikova, Veronika
    Spanish National Cancer Research Centre, Spain .
    Cascon, Alberto
    Spanish National Cancer Research Centre, Spain CIBERER, Spain .
    Robledo, Mercedes
    Spanish National Cancer Research Centre, Spain CIBERER, Spain .
    Rodriguez-Antona, Cristina
    Spanish National Cancer Research Centre, Spain CIBERER, Spain .
    Regulatory Polymorphisms in beta-Tubulin IIa Are Associated with Paclitaxel-Induced Peripheral Neuropathy2012In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 18, no 16, p. 4441-4448Article in journal (Refereed)
    Abstract [en]

    Purpose: Peripheral neuropathy is the dose-limiting toxicity of paclitaxel, a chemotherapeutic drug widely used to treat several solid tumors such as breast, lung, and ovary. The cytotoxic effect of paclitaxel is mediated through beta-tubulin binding in the cellular microtubules. In this study, we investigated the association between paclitaxel neurotoxicity risk and regulatory genetic variants in beta-tubulin genes. less thanbrgreater than less thanbrgreater thanExperimental Design: We measured variation in gene expression of three beta-tubulin isotypes (I, IVb, and IIa) in lymphocytes from 100 healthy volunteers, sequenced the promoter region to identify polymorphisms putatively influencing gene expression and assessed the transcription rate of the identified variants using luciferase assays. To determine whether the identified regulatory polymorphisms were associated with paclitaxel neurotoxicity, we genotyped them in 214 patients treated with paclitaxel. In addition, paclitaxel-induced cytotoxicity in lymphoblastoid cell lines was compared with beta-tubulin expression as measured by Affymetrix exon array. less thanbrgreater than less thanbrgreater thanResults: We found a 63-fold variation in beta-tubulin IIa gene (TUBB2A) mRNA content and three polymorphisms located at -101, -112, and -157 in TUBB2A promoter correlated with increased mRNA levels. The -101 and -112 variants, in total linkage disequilibrium, conferred TUBB2A increased transcription rate. Furthermore, these variants protected from paclitaxel-induced peripheral neuropathy [HR, 0.62; 95% confidence interval (CI), 0.42-0.93; P = 0.021, multivariable analysis]. In addition, an inverse correlation between TUBB2A and paclitaxel-induced apoptosis (P = 0.001) in lymphoblastoid cell lines further supported that higher TUBB2A gene expression conferred lower paclitaxel sensitivity. less thanbrgreater than less thanbrgreater thanConclusions: This is the first study showing that paclitaxel neuropathy risk is influenced by polymorphisms regulating the expression of a beta-tubulin gene.

  • 82.
    Li, Yifei
    et al.
    Hebei Medical University, Peoples R China.
    Zhang, Xia
    Hebei Medical University, Peoples R China.
    Ge, Jing
    Hebei Medical University, Peoples R China.
    Liu, Xiaoli
    Hebei Medical University, Peoples R China.
    Xu, Shuwen
    Hebei Medical University, Peoples R China.
    Zhu, Zhenlong
    Hebei Medical University, Peoples R China.
    Fang, Guiying
    Hebei Medical University, Peoples R China.
    Liu, Jing
    Hebei Medical University, Peoples R China.
    Zhang, Hongzhen
    Hebei Medical 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.
    Can Nup88 expression be associated with atypical endometrial hyperplasia and endometrial cancer? A preliminary study2016In: Pathology, Research and Practice, ISSN 0344-0338, E-ISSN 1618-0631, Vol. 212, no 4, p. 274-278Article in journal (Refereed)
    Abstract [en]

    Background: Nup88 is overexpressed in a number of types of carcinomas and is associated with myometrial invasion, but its exact expression pattern in endometrial cancer and premalignant lesions is unknown. Aims: To evaluate the role of Nup88 in endometrial cancers and atypical endometrial hyperplasia and its clinicopathological significance. Methods: Nup88 expression was examined by immunohistochemistry in samples from 104 endometrial cancers, 21 atypical endometrial hyperplasia lesions, and 40 normal endometria. All samples were from patients who underwent surgery at the First Hospital of Hebei Medical University (Shijiazhuang, China) between April 2006 and December 2009. Nup88 expression was compared between the groups and associations were assessed between Nup88 and clinicopathological characteristics of the subjects. Results: Nup88 expression in cancer (76% of samples) and atypical hyperplasia (91%) was significantly higher compared to normal endometrium (33%, both P &lt; 0.001), but there was no significant difference between endometrial cancer and atypical hyperplasia (P = 0.237). The expression of Nup88 increased significantly with increasing exposure time to estrogen (P = 0.033). Conclusions: Nup88 may be related to the occurrence of endometrial cancers and premalignant lesions. Nup88 might be a useful biomarker for pre-malignant lesions and early-stage endometrial cancer. (C) 2016 Elsevier GmbH. All rights reserved.

  • 83.
    Liest, Lisbeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Omran, Ahmed Shaker
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Mikiver, Rasmus
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Business support and Development, Regional Cancer Center.
    Rosenberg, Per
    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.
    Uppugunduri, Srinivas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    RMI and ROMA are equally effective in discriminating between benign and malignant gynecological tumors: A prospective population-based study2019In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 98, no 1, p. 24-33Article in journal (Refereed)
    Abstract [en]

    Introduction Our primary objective was to test the hypothesis that human epididymal protein 4 (HE4) and risk of ovarian malignancy index outperform the CA 125 and risk of malignancy index tests in categorizing a pelvic mass into high or low risk of malignancy in a Swedish population. Furthermore, cut-off values needed to be defined for HE4 and ROMA in premenopausal and postmenopausal women prior to their introduction to clinical practice. A third objective was to investigate the correlation between HE4 levels in serum and urine. Material and methods Women with a pelvic mass scheduled for surgery were recruited from nine hospitals in south-east Sweden. Preoperative blood samples were taken for analyzing CA125 and HE4 as well as urine samples for analyzing HE4. Results We enrolled a total of 901 women, of whom 784 were evaluable. In the premenopausal and postmenopausal groups, no significant differences were found for sensitivity, positive and negative predictive value, either for RMI vs ROMA or for CA125 vs HE4 using a fixed specificity of 75%. Cut-off values indicating malignancy were established for HE4 and ROMA in premenopausal and postmenopausal women. We found no correlation between HE4 concentration in serum and urine. Conclusions We could not confirm that ROMA had diagnostic superiority over RMI in categorizing women with a pelvic mass into low-risk or high-risk groups for malignancy in a Swedish population. We have defined cut-off values for HE4 and ROMA. The lack of correlation between serum and urine HE4 obviates the introduction of urine HE4 analysis in clinical diagnostics.

  • 84.
    Lindahl, Gabriel
    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.
    Rzepecka, Anna
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    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.
    Increased Extracellular Osteopontin Levels in Normal Human Breast Tissue at High Risk of Developing Cancer and Its Association With Inflammatory Biomarkers in situ2019In: Frontiers in Oncology, ISSN 2234-943X, E-ISSN 2234-943X, Vol. 9, article id 746Article in journal (Refereed)
    Abstract [en]

    Mammographic breast density is a strong independent risk factor for breast cancer (BC), but the molecular mechanisms behind this risk is yet undetermined and prevention strategies for these women are lacking. The anti-estrogen tamoxifen may reduce the risk of BC but this treatment is associated with severe side effects. Thus, other means for BC prevention, such as diet interventions, need to be developed. Osteopontin (OPN) is a major mediator of inflammation which is key in carcinogenesis. OPN may be cleaved by proteases in the tissue and cleaved OPN may in turn induce an inflammatory cascade in the extracellular microenvironment. We aimed to determine if extracellular OPN was altered in BC and in normal breast tissue with different densities and if tamoxifen or a diet of flaxseed could modify OPN levels. The study comprised 103 women; 13 diagnosed with BC, 42 healthy post-menopausal women with different breast densities at their mammography screen, and 34 post-menopausal women who added 25 g of ground flaxseed/day or were treated with tamoxifen 20 mg/day and were investigated before and after 6 weeks of exposure. Additionally, 10 premenopausal women who added flaxseed for one menstrual cycle and four who were investigated in two unexposed consecutive luteal phases of the menstrual cycle. Microdialysis was used to sample extracellular proteins in vivo in breast tissue and proteins were quantified using a multiplex proximity extension assay. We found that, similar to BC, extracellular in vivo OPN levels were significantly increased in dense breast tissue. Additionally, significant correlations were found between OPN and chemokine (C-X-C motif) ligand (CXCL)-1, -8, -9, -10, and - 11, interleukin-6, vascular endothelial growth factor, matrix metalloproteinase (MMP)-1, - 2, -3, 7, and -12 and urokinase-type plasminogen activator whereas no correlations were found with MMP-9, chemokine (C-C motif) ligand (CCL)-2, and -5. Estradiol did not affect OPN levels in breast tissue. None of the interventions altered OPN levels. The pro-tumorigenic protein OPN may indeed be a molecular target for BC prevention in women with increased breast density but other means than tamoxifen or flaxseed i.e., more potent anti-inflammatory approaches, need to be evaluated for this purpose.

  • 85.
    Lindemann, Kristina
    et al.
    Oslo University Hospital, Norway; University of Sydney, Australia; Westmead Hospital, Australia.
    Gibbs, Emma
    University of Sydney, Australia.
    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.
    dePont Christensen, Rene
    University of Southern Denmark, Denmark.
    Woie, Kathrine
    Haukeland Hospital, Norway.
    Kalling, Marten
    Skåne University Hospital, Sweden.
    Auranen, Annika
    Tampere University Hospital, Finland.
    Grenman, Seija
    Turku University Hospital, Finland; University of Turku, Finland.
    Hoegberg, Thomas
    Skåne University Hospital Lund, Sweden.
    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.
    Skeie-Jensen, Tone
    Oslo University Hospital, Norway.
    Hjerpe, Elisabet
    University of Southern Denmark, Denmark.
    Dorum, Anne
    Oslo University Hospital, Norway.
    Gebski, Val
    University of Sydney, Australia.
    Kristensen, Gunnar
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Chemotherapy vs tamoxifen in platinum-resistant ovarian cancer: a phase III, randomised, multicentre trial (Ovaresist)2017In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 116, no 4, p. 455-463Article in journal (Refereed)
    Abstract [en]

    Background: Chemotherapy in platinum-resistant ovarian cancer (PROC) aims for palliation and prolonging of progression-free survival (PFS). This study compares Health-related Quality of Life (HRQoL) and efficacy between single-agent chemotherapy and tamoxifen in PROC. Methods: Patients with PROC were randomised (2 : 1) to chemotherapy (weekly paclitaxel 80 mg m(-2) or four weekly pegylated liposomal doxorubicin 40 mg m(-2)) or tamoxifen 40mg daily. The primary end point was HRQoL. Secondary end points were PFS by RECIST and overall survival (OS). Results: Between March 2002 and December 2007, 156 and 82 patients were randomised to chemotherapy and tamoxifen, respectively. In the chemotherapy arm, a significantly larger proportion of patients experienced a worsening in their social functioning. There was no difference in the proportion of patients experiencing improvement of gastrointestinal symptoms. Median PFS on tamoxifen was 8.3 weeks (95% CI, 8.0-10.4) compared with 12.7 weeks (95% CI, 9.0-16.3) on chemotherapy (HR, 1.54; 95% CI, 1.16-2.05; log-rank P = 0.003). There was no difference in OS between the treatment arms. Conclusions: Patients on chemotherapy had longer PFS but experienced more toxicity and poorer HRQoL compared with tamoxifen. Control over gastrointestinal symptoms was not better on chemotherapy. These data are important for patient counselling and highlight the need to incorporate HRQoL end points in studies of PROC.

  • 86.
    Lindstrom, Linda S.
    et al.
    Karolinska Inst, Sweden.
    Yau, Christina
    Univ Calif San Francisco, CA USA; Buck Inst Res Aging, CA USA.
    Czene, Kamila
    Karolinska Inst, Sweden.
    Thompson, Carlie K.
    Univ Calif San Francisco, CA USA.
    Hoadley, Katherine A.
    Univ North Carolina Chapel Hill, NC USA.
    vant Veer, Laura J.
    Univ Calif San Francisco, CA 94140 USA; Univ Calif San Francisco, CA 94143 USA.
    Balassanian, Ron
    Univ Calif San Francisco, CA 94140 USA.
    Bishop, John W.
    Univ Calif Davis, CA 95616 USA.
    Carpenter, Philip M.
    Univ Southern Calif, CA USA; Univ Calif Irvine, CA USA.
    Chen, Yunn-Yi
    Univ Calif San Francisco, CA 94140 USA.
    Datnow, Brian
    Univ Calif San Diego, CA 92093 USA.
    Hasteh, Farnaz
    Univ Calif San Diego, CA 92093 USA.
    Krings, Gregor
    Univ Calif San Francisco, CA 94140 USA.
    Lin, Fritz
    Univ Calif Irvine, CA USA.
    Zhang, Yanhong
    Univ Calif Davis, CA 95616 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.
    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.
    Benz, Christopher C.
    Univ Calif San Francisco, CA USA; Buck Inst Res Aging, CA USA.
    Fornander, Tommy
    Karolinska Inst, Sweden.
    Borowsky, Alexander D.
    Univ Calif Davis, CA 95616 USA.
    Esserman, Laura J.
    Univ Calif San Francisco, CA USA.
    Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer2018In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 110, no 7, p. 726-733, article id djx270Article in journal (Refereed)
    Abstract [en]

    Background: Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer. Methods: The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Raos quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. Results: A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P amp;lt; .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio (HR] = 1.98, 95% confidence interval (CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI -1.18 to 4.99). Conclusions: Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors.

  • 87.
    Lindström, L.
    et al.
    Karolinska universitetet, Södersjukhuset, Sweden.
    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, T.
    Karolinska universitetet, Södersjukhuset, Sweden.
    Test identifierade patienter med mycket låg risk att dö i bröstcancer2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, no 41Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 88.
    Liu, Na
    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. State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an, China.
    Cox, Thomas R.
    Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
    Cui, Weiyingqi
    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.
    Adell, Gunnar
    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.
    Holmlund, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Ping, Jie
    Shanghai Center for Bioinformation Technology, Shanghai, China.
    Jarlsfelt, Ingvar
    Department of Pathology, Ryhov Hospital, Jönköping, Sweden.
    Erler, Janine T.
    Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
    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.
    Nuclear expression of lysyl oxidase enzyme is an independent prognostic factor in rectal cancer patients.2017In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 36, p. 60015-60024Article in journal (Refereed)
    Abstract [en]

    Emerging evidence has implicated a pivotal role for lysyl oxidase (LOX) in cancer progression and metastasis. Whilst the majority of work has focused on the extracellular matrix cross-linking role of LOX, the exact function of intracellular LOX localisation remains unclear. In this study, we analysed the LOX expression patterns in the nuclei of rectal cancer patient samples and determined the clinical significance of this expression. Nuclear LOX expression was significantly increased in patient lymph node metastases compared to their primary tumours. High nuclear LOX expression in tumours was correlated with a high rate of distant metastasis and increased recurrence. Multivariable analysis showed that high nuclear LOX expression was also correlated with poor overall survival and disease free survival. Furthermore, we are the first to identify LOX enzyme isoforms (50 kDa and 32 kDa) within the nucleus of colon cancer cell lines by confocal microscopy and Western blot. Our results show a powerful link between nuclear LOX expression in tumours and patient survival, and offer a promising prognostic biomarker for rectal cancer patients.

  • 89.
    Liu, Na
    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. Xi An Jiao Tong Univ, Peoples R China.
    Cui, Weiyingqi
    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.
    Jiang, Xia
    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. Hebei Med Univ, Peoples R China.
    Zhang, Zhiyong
    Fourth Mil Med Univ, Peoples R China.
    Gnosa, Sebastian
    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.
    Ali, Zaheer
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Jönsson, Jan-Ingvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Hematopoiesis and Developmental Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Blockhuys, Stephanie
    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.
    Lam, Eric W-F
    Imperial Coll London, England.
    Zhao, Zengren
    Hebei Med Univ, Peoples R China.
    Ping, Jie
    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.
    Xie, Ning
    Xi An Jiao Tong Univ, Peoples R China.
    Kopsida, Maria
    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.
    Wang, Xin
    Fourth Mil Med Univ, 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.
    The Critical Role of Dysregulated RhoB Signaling Pathway in Radioresistance of Colorectal Cancer2019In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 104, no 5, p. 1153-1164Article in journal (Refereed)
    Abstract [en]

    Purpose

    To explore whether the Rho protein is involved in the radioresistance of colorectal cancer and investigate the underlying mechanisms.

    Methods and Materials

    Rho GTPase expression was measured after radiation treatment in colon cancer cells. RhoB knockout cell lines were established using the CRISPR/Cas9 system. In vitro assays and zebrafish embryos were used for analyzing radiosensitivity and invasive ability. Mass cytometry was used to detect RhoB downstream signaling factors. RhoB and Forkhead box M1 (FOXM1) expression were detected by immunohistochemistry in rectal cancer patients who participated in a radiation therapy trial.

    Results

    RhoB expression was related to radiation resistance. Complete depletion of the RhoB protein increased radiosensitivity and impaired radiation-enhanced metastatic potential in vitro and in zebrafish models. Probing signaling using mass cytometry–based single-cell analysis showed that the Akt phosphorylation level was inhibited by RhoB depletion after radiation. FOXM1 was downregulated in RhoB knockout cells, and the inhibition of FOXM1 led to lower survival rates and attenuated migration and invasion abilities of the cells after radiation. In the patients who underwent radiation therapy, RhoB overexpression was related to high FOXM1, late Tumor, Node, Metastasis stage, high distant recurrence, and poor survival independent of other clinical factors.

    Conclusions

    RhoB plays a critical role in radioresistance of colorectal cancer through Akt and FOXM1 pathways.

  • 90.
    Liu, Yong
    et al.
    Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Chen, Xiao-Dong
    Sichuan University, Peoples R China.
    Yu, Jiang
    Sichuan University, Peoples R China.
    Chi, Jun-Lin
    Sichuan University, Peoples R China.
    Long, Fei-Wu
    Sichuan University, Peoples R China.
    Yang, Hong-Wei
    Sichuan University, Peoples R China.
    Chen, Ke-Ling
    Sichuan University, Peoples R China.
    Lv, Zhao-Ying
    Sichuan University, Peoples R China.
    Zhou, Bin
    Sichuan University, Peoples R China.
    Peng, Zhi-Hai
    Shanghai Jiao Tong University, 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. Sichuan University, Peoples R China.
    Li, Yuan
    Sichuan University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China.
    Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-kappa B activity2017In: Cell Death and Disease, ISSN 2041-4889, E-ISSN 2041-4889, Vol. 8, article id e2685Article in journal (Refereed)
    Abstract [en]

    Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of L-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor kappa B (NF-kappa B) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-kappa B activation and less release of TNF-alpha and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that inhibition of XIAP represents a potential therapeutic strategy for the treatment of acute pancreatitis.

  • 91.
    Liu, Yong
    et al.
    Sichuan University, Peoples R China.
    Zhou, Dan
    Sichuan University, Peoples R China.
    Long, Fei-Wu
    Sichuan University, Peoples R China.
    Chen, Ke-Ling
    Sichuan University, Peoples R China.
    Yang, Hong-Wei
    Sichuan University, Peoples R China.
    Lv, Zhao-Yin
    Sichuan University, Peoples R China.
    Zhou, Bin
    Sichuan University, Peoples R China.
    Peng, Zhi-Hai
    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. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Li, Yuan
    Sichuan University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China.
    Resolvin D1 protects against inflammation in experimental acute pancreatitis and associated lung injury2016In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 310, no 5, p. G303-G309Article in journal (Refereed)
    Abstract [en]

    Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure with considerable mortality. Recently, resolvin D1 (RvD1) as an endogenous anti-inflammatory lipid mediator has been confirmed to protect against many inflammatory diseases. This study was designed to investigate the effects of RvD1 in acute pancreatitis and associated lung injury. Acute pancreatitis varying from mild to severe was induced by cerulein or cerulein combined with LPS, respectively. Mice were pretreated with RvD1 at a dose of 300 ng/mouse 30 min before the first injection of cerulein. Severity of AP was assessed by biochemical markers and histology. Serum cytokines and myeloperoxidase (MPO) levels in pancreas and lung were determined for assessing the extent of inflammatory response. NF-kappa B activation was determined by Western blotting. The injection of cerulein or cerulein combined with LPS resulted in local injury in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the cerulein and LPS group. Pretreated RvD1 significantly reduced the degree of amylase, lipase, TNF-alpha, and IL-6 serum levels; the MPO activities in the pancreas and the lungs; the pancreatic NF-kappa B activation; and the severity of pancreatic injury and associated lung injury, especially in the severe acute pancreatitis model. These results suggest that RvD1 is capable of improving injury of pancreas and lung and exerting anti-inflammatory effects through the inhibition of NF-kappa B activation in experimental acute pancreatitis, with more notable protective effect in severe acute pancreatitis. These findings indicate that RvD1 may constitute a novel therapeutic strategy in the management of severe acute pancreatitis.

  • 92.
    Loftås, Per
    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 Surgery in Norrköping.
    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.
    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.
    Edler, David
    Department of Surgery, Karolinska Institute, Stockholm, Sweden.
    Syk, Erik
    Department of Surgery, Ersta Hospital, Stockholm, Sweden.
    Hallböök, Olof
    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.
    FXYD-3 expression in relation to local recurrence of rectal cancer2016In: Radiation Oncology Journal, ISSN 2234-1900, Vol. 34, no 1, p. 52-58Article in journal (Refereed)
    Abstract [en]

    Purpose: In a previous study, the transmembrane protein FXYD-3 was suggested as a biomarker for a lower survival rate and reduced radiosensitivity in rectal cancer patients receiving preoperative radiotherapy. The purpose of preoperative irradiation in rectal cancer is to reduce local recurrence. The aim of this study was to investigate the potential role of FXYD-3 as a biomarker for increased risk for local recurrence of rectal cancer.

    Materials and Methods: FXYD-3 expression was immunohistochemically examined in surgical specimens from a cohort of patients with rectal cancer who developed local recurrence (n = 48). The cohort was compared to a matched control group without recurrence (n = 81).

    Results: Weak FXYD-3 expression was found in 106/129 (82%) of the rectal tumors and strong expression in 23/129 (18%). There was no difference in the expression of FXYD-3 between the patients with local recurrence and the control group. Furthermore there was no difference in FXYD-3 expression and time to diagnosis of local recurrence between patients who received preoperative radiotherapy and those without.

    Conclusion: Previous findings indicated that FXYD-3 expression may be used as a marker of decreased sensitivity to radiotherapy or even overall survival. We were unable to confirm this in a cohort of rectal cancer patients who developed local recurrence.

  • 93.
    Loorents, Vera
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Rosell, Johan
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences.
    Salgado Willner, Helen
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    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.
    Health-related quality of life up to 1 year after radiotherapy in patients with head and neck cancer (HNC)2016In: SpringerPlus, E-ISSN 2193-1801, Vol. 5, no 1, article id 669Article in journal (Refereed)
    Abstract [en]

    Background

    Detailed symptom specific descriptions of health-related quality of life (HRQOL), using validated questionnaires in patients with head and neck cancer (HNC) are sparse. The aim of the present study was to investigate HRQOL in patients with HNC up to 1 year after radiotherapy (RT), using two standardised questionnaires.

    Methods

    The data for the present study was originally collected in a randomised, prospective study. Forty-seven patients from two RT clinics in Sweden were included to investigate the secondary aim: HRQOL. Data was recorded at baseline, completion of RT, and 3, 6, 12 months after completed RT, using the questionnaire EORTC QLQ-C30-version 3 and the disease-specific module EORTC QLQ-H&N35.

    Results

    Most symptoms and functions deteriorated significantly by the end of RT, improved gradually by 3 and 6 months and reached baseline levels at 12 months after completed RT. However, 1 year after completed RT there were remaining significant problems in senses, dry mouth and sticky saliva.

    Conclusions

    Radiation therapy affects health-related quality of life in patients with head and neck cancer, both in the short and long term. Caregivers need management strategies for early detection and treatment of specific problems throughout the treatment period to help in the prevention of long-term symptoms.

  • 94.
    Makitie, A.
    et al.
    Univ Helsinki, Finland; Helsinki Univ Hosp, Finland; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Ruuskanen, M.
    Turku Univ Hosp, Finland.
    Bentzen, J.
    Herlev Univ Hosp, Denmark.
    Brun, E.
    Lund Univ, Sweden.
    Gebre-Medhin, M.
    Lund Univ, Sweden.
    Friesland, S.
    Karolinska Univ Hosp, Sweden.
    Marsk, E.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Hammarstedt-Nordenvall, L.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Gille, E.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Reizenstein, J.
    Örebro Univ Hosp, Sweden.
    Adell, Gunnar
    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.
    Farnebo, Lovisa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Speech language pathology, Audiology and Otorhinolaryngology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Otorhinolaryngology in Linköping.
    Rzepecki, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Haugen, H.
    Sahlgrens Univ Hosp, Sweden.
    Soderstrom, K.
    Umeå Univ, Sweden.
    Zackrisson, B.
    Umea Univ, Sweden.
    Bergstrom, S.
    Gävle Cent Hosp, Sweden.
    Loden, B.
    Karlstad Hosp, Sweden.
    Cederblad, L.
    Uppsala Univ Hosp, Sweden.
    Laurell, G.
    Uppsala Univ Hosp, Sweden.
    Smeland, E.
    Univ Hosp North Norway, Norway.
    Evensen, J. Folkvard
    Oslo Univ Hosp, Norway.
    Lund, J. A.
    Trondheim Reg and Univ Hosp, Norway.
    Tondel, H.
    Trondheim Reg and Univ Hosp, Norway.
    Karlsdottir, A.
    Haukeland Hosp, Norway.
    Johannsson, J.
    Landspitali Univ Hosp, Iceland.
    Johansen, J.
    Odense Univ Hosp, Denmark.
    Kristensen, C. A.
    Rigshosp, Denmark.
    Jensen, K.
    Aarhus Univ Hosp, Denmark.
    Andersen, L. J.
    Aalborg Hosp, Denmark.
    Koivunen, P.
    Oulu Univ Hosp, Finland.
    Korpela, M.
    Oulu Univ Hosp, Finland.
    Voutilainen, L.
    Kuopio Univ Hosp, Finland.
    Wigren, T.
    Tampere Univ Hosp, Finland.
    Minn, H.
    Turku Univ Hosp, Finland.
    Joensuu, H.
    Helsinki Univ Hosp, Finland; Univ Helsinki, Finland.
    Overgaard, J.
    Aarhus Univ Hosp, Denmark.
    Saarilahti, K.
    Helsinki Univ Hosp, Finland; Univ Helsinki, Finland.
    The management and survival outcomes of nasopharyngeal cancer in the Nordic countries2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 4, p. 557-560Article in journal (Other academic)
    Abstract [en]

    n/a

  • 95.
    Malmström, Annika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Skovgaard Poulsen, Hans
    Rigshosp, Denmark.
    Henning Gronberg, Bjorn
    Norwegian University of Science and Technology, Norway; Trondheim Regional and University Hospital, Norway.
    Stragliotto, Giuseppe
    Karolinska University Hospital, Sweden.
    Hansen, Steinbjorn
    University of Southern Denmark, Denmark.
    Asklund, Thomas
    Karolinska University Hospital, Sweden; Umeå University, Sweden.
    Holmlund, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Lysiak, Malgorzata
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Dowsett, Joseph
    University of Southern Denmark, Denmark.
    Winther Kristensen, Bjarne
    University of Southern Denmark, Denmark.
    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.
    Rosell, Johan
    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.
    Henriksson, Roger
    Umeå University, Sweden; Regional Cancer Centre Stockholm Gotland, Sweden.
    Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 12, p. 1776-1785Article in journal (Refereed)
    Abstract [en]

    Introduction: A pilot study of temozolomide (TMZ) given before radiotherapy (RT) for anaplastic astrocytoma (AA) and glioblastoma (GBM) resulted in prolonged survival compared to historical controls receiving RT alone. We therefore investigated neoadjuvant TMZ (NeoTMZ) in a randomized trial. During enrollment, concomitant and adjuvant radio-chemotherapy with TMZ became standard treatment. The trial was amended to include concurrent TMZ.Patients and methods: Patients, after surgery for GBM or AA, age 60 years and performance status (PS) 0-2, were randomized to either 2-3 cycles of TMZ, 200mg/m(2) days 1-5 every 28 days, followed by RT 60Gy in 30 fractions or RT only. Patients without progressive disease after two TMZ cycles, received the third cycle. From March 2005, TMZ 75mg/m(2) was administered daily concomitant with RT. TMZ was recommended first-line treatment at progression. Primary endpoint was overall survival and secondary safety.Results: The study closed prematurely after enrolling 144 patients, 103 with GBM and 41 with AA. Median age was 53 years (range 24-60) and 89 (62%) were male. PS was 0-1 for 133 (92%) patients, 53 (37%) had complete surgical resection and 18 (12%) biopsy. Ninety-two (64%) received TMZ concomitant with RT. Seventy-two (50%) were randomized to neoadjuvant treatment. For the overall study population survival was 20.3 months for RT and 17.7 months for NeoTMZ (p=.76), this not reaching the primary objective. For the preplanned subgroup analysis, we found that NeoTMZ AA patients had a median survival of 95.1 months compared to 35.2 months for RT (p=.022). For patients with GBM, no difference in survival was observed (p=.10). MGMT and IDH status affected outcome.Conclusions: No advantage of NeoTMZ was noted for the overall study population or subgroup of GBM, while NeoTMZ resulted in 5 years longer median survival for patients diagnosed as AA.

  • 96.
    Meng, Wen-Jian
    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. Sichuan University, Peoples R China.
    Pathak, Surajit
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ding, Zhen-Yu
    Sichuan University, Peoples R China.
    Zhang, Hong
    University of Örebro, Sweden.
    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.
    Holmlund, Birgitta
    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.
    Li, Yuan
    Sichuan University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China; 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.
    Special AT-rich sequence binding protein 1 expression correlates with response to preoperative radiotherapy and clinical outcome in rectal cancer2015In: Cancer Biology & Therapy, ISSN 1538-4047, E-ISSN 1555-8576, Vol. 16, no 12, p. 1738-1745Article in journal (Refereed)
    Abstract [en]

    Our recent study showed the important role of special AT-rich sequence binding protein 1 (SATB1) in the progression of human rectal cancer. However, the value of SATB1 in response to radiotherapy (RT) for rectal cancer hasnt been reported so far. Here, SATB1 was determined using immunohistochemistry in normal mucosa, biopsy, primary cancer, and lymph node metastasis from 132 rectal cancer patients: 66 with and 66 without preoperative RT before surgery. The effect of SATB1 knockdown on radiosensitivity was assessed by proliferation-based assay and clonogenic assay. The results showed that SATB1 increased from normal mucosa to primary cancer, whereas it decreased from primary cancer to metastasis in non-RT patients. SATB1 decreased in primary cancers after RT. In RT patients, positive SATB1 was independently associated with decreased response to preoperative RT, early time to metastasis, and worse survival. SATB1 negatively correlated with ataxia telangiectasia mutated (ATM) and pRb2/p130, and positively with Ki-67 and Survivin in RT patients, and their potential interaction through different canonical pathways was identified in network ideogram. Taken together, our findings disclose for the first time that radiation decreases SATB1 expression and sensitizes cancer cells to confer clinical benefit of patients, suggesting that SATB1 is predictive of response to preoperative RT and clinical outcome in rectal cancer.

  • 97.
    Meng, Wen-Jian
    et al.
    Sichuan University, Peoples R China.
    Yang, Lie
    Sichuan University, Peoples R China.
    Ma, Qin
    Sichuan University, Peoples R China.
    Zhang, Hong
    University of Örebro, Sweden.
    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.
    Wang, Zi-Qiang
    Sichuan University, Peoples R China.
    Li, Yuan
    Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China; Sichuan University, Peoples R China; 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.
    MicroRNA Expression Profile Reveals miR-17-92 and miR-143-145 Cluster in Synchronous Colorectal Cancer2015In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 94, no 32Article in journal (Refereed)
    Abstract [en]

    The expression of abnormal microRNA (miRNA, miR) is a ubiquitous feature of colorectal cancer (CRC). The pathological features and clinical behaviors of synchronous CRC have been comprehensively described; however, the expression profile of miRNA and small nucleolar RNA (snoRNA) in synchronous CRC has not been elucidated. In the present study, the expression profile of miRNA and snoRNA in 5 synchronous CRCs, along with the matched normal colorectal tissue was evaluated by microarray. Function and pathway analyses of putative targets, predicted from miRNA-mRNA interaction, were performed. Moreover, we analyzed clinicopathological and molecular characteristics of 22 patients with synchronous CRC and 579 solitary CRCs in a retrospective cohort study. We found a global dysregulation of miRNAs, including an oncogenic miR-17-92 cluster and oncosuppressive miR-143-145 cluster, and snoRNAs in synchronous CRC. Differential miRNA rather than snoRNA expression was robust enough to distinguish synchronous cancer from normal mucosa. Function analysis of putative targets suggested that miRNA clusters may modulate multiple effectors of oncogenic pathways involved in the pathogenesis of synchronous CRC. A comparison of normal mucosa between synchronous and solitary CRC suggested a differential genetic background of synchronous CRC from solitary CRC during carcinogenesis. Compared with solitary cancer patients, synchronous cases exhibited multiple extra-colonic cancers (P=0.012), coexistence of adenoma (P=0.012), microsatellite instability (P=0.024), and less glucose transporter 1 (P=0.037). Aberrant miRNA expression profiles could potentially be used as a diagnostic tool for synchronous CRC. Our findings represent the first comprehensive miRNA and snoRNA expression signatures for synchronous CRC, implicating that the miRNAs and snoRNAs may present therapeutic targets for synchronous CRC.

  • 98.
    Mi, Yushuai
    et al.
    Shanghai Jiao Tong University, Peoples R China.
    Zhang, Dongyuan
    Shanghai Jiao Tong University, Peoples R China.
    Jiang, Weiliang
    Shanghai Jiao Tong University, Peoples R China.
    Weng, Junyong
    Shanghai Jiao Tong University, Peoples R China.
    Zhou, Chongzhi
    Shanghai Jiao Tong University, Peoples R China.
    Huang, Kejian
    Shanghai Jiao Tong University, Peoples R China.
    Tang, Huamei
    Shanghai Jiao Tong University, Peoples R China.
    Yu, Yang
    Shanghai Jiao Tong University, Peoples R China.
    Liu, Xisheng
    Shanghai Jiao Tong University, Peoples R China.
    Cui, Weiyingqi
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Zhang, Meng
    Fudan University, 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.
    Zhou, Zongguang
    Sichuan University, Peoples R China.
    Peng, Zhihai
    Shanghai Jiao Tong University, Peoples R China.
    Zhao, Senlin
    Shanghai Jiao Tong University, Peoples R China.
    Wen, Yugang
    Shanghai Jiao Tong University, Peoples R China.
    miR-181a-5p promotes the progression of gastric cancer via RASSF6-mediated MAPK signalling activation2017In: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 389, p. 11-22Article in journal (Refereed)
    Abstract [en]

    We previously discovered that Ras association domain family member 6 (RASSF6) was downregulated and predicted poor prognosis in GC patients. However, the mechanisms of the down regulation of RASSF6 in GC remained unclear. Increasing evidence indicates that dysregulation of microRNAs promotes the progression of cancer through the repression of tumour suppressors. Here, we identified miR-181a-5p as a novel regulator of RASSF6 in GC. Functionally, ectopic expression or silencing of miR-181a-5p, respectively, promoted or inhibited GC cell proliferation, colony formation and cell cycle transition, as well as enhanced or prevented the invasion, metastasis of GC cells and epithelial to mesenchymal transition of GC cells in vitro and in vivo. Molecularly, miR-181a-5p functioned as an onco-miRNA by activating the RASSF6-regulated MAKP pathway. Overexpression or silencing of RASSF6 could partially reverse the effects of the overexpression or repression of miR-181a-5p on GC progress caused by activation of the MAKP pathway in vitro and in vivo. Clinically, high miR-181a-5p expression predicted poor survival in GC patients, especially combined with low RASSF6 expression. Collectively, we identified miR-181a-5p as an onco-miRNA, which acts by directly repressing RASSF6 in GC. (C) 2017 The Authors. Published by Elsevier Ireland Ltd.

  • 99.
    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.

  • 100.
    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.

1234 51 - 100 of 159
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf