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Aspects on Head and neck Cancer with special reference to Salivary Gland Tumours and Single Nucleotide Polymorphism
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. (Magnus Lindskog)
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

A thesis on Head and neck cancer focusing on dose planning, salivary gland carcinoma and Single nucleotide polymorphism.

For dose planning PET/CT (Positron emissions tomography/computed tomography) with tracer gave more precise information in comparison dose planning with CT. More primary tumours and metastases were found with the acetate tracer than with glucose tracer. Acetate PET/CT also showed larger volume of tumours attributed to lipid metabolism.

In a retrospective study salivary gland cancer 5-year overall survival (OS) was 53 %. Salivary gland carcinoma consists of many histopathological groups, the two largest groups being mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ASCC). For ACC, having the best 5-year OS, it was 70 percent. Facial palsy, advanced stage disease, lymph node metastases worsened prognosis. ACC and polymorphous low grade carcinoma (PLGA) expressed c-myc and cyclin D1 to a larger extent than MEC.

In squamous cell carcinoma of the head and neck we examined the occurrence of Single Nucleotide polymorphism, SNP. We found that the SNPs in male and female patients differed from each other. In male patients the SNPs were associated with immune response while in female patients the association was to SNPs concerning inflammation. This means that different pathways were engaged in cancer development for men and women. We also found that the SNPs in patients were different from those expressed in the healthy controls.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. , p. 47
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1390
Keyword [en]
salivary gland carcinoma, adenoid cystic, mucoepidermoid, polymorphous low-grade carinoma, c-myc, cyclin D1, perineural
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-332192ISBN: 978-91-513-0130-3 (print)OAI: oai:DiVA.org:uu-332192DiVA, id: diva2:1152459
Public defence
2017-12-14, Skoogsalen, ingång 78/79 pl 1, Akademiska sjukhuset, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2017-11-20 Created: 2017-10-25 Last updated: 2018-03-07
List of papers
1. Cancer of the parotid gland; long-term follow-up: A single centre experience on recurrence and survival
Open this publication in new window or tab >>Cancer of the parotid gland; long-term follow-up: A single centre experience on recurrence and survival
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2009 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 48, no 4, p. 549-555Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

The aim of the study was to investigate the results of treatment of malignant parotid gland tumours at a single centre during a 56 year period, focusing on tumour control and survival.

PATIENTS AND METHODS:

At Uppsala University Hospital, Sweden, 144 patients (73 male and 71 female) with parotid cancer were treated between 1948 and 2004. The mean and median ages were 62 and 65 years, respectively (range 16-89 years). Surgery was the primary treatment in 113 (78%) patients followed by radiotherapy in 81. Postoperative radiotherapy in doses of 64-66 Gy, where the intention was curative and delivered with either split course or not, was administered to a majority of patients after 1970. The split-course mode was practised between 1970 and 1989. The median follow-up time was 8.3 years for patients still alive. There were 57 (40%) relapses, of which 40 were local recurrences with 26 inside the treatment volume.

RESULTS:

The overall 5-year survival was 53%. The majority of tumour-related deaths appeared in the first 3-5 years after diagnosis. Age, co-morbidity, the presence of lymph node metastases, adenoid cystic carcinoma and extent of disease were important for outcome; gender, however, was not. We found no difference in the survival between patients following split course therapy versus continuous fractionation. No difference could be seen in the survival of patients treated in the 1970s versus the 1990s.

CONCLUSIONS:

Age, nodal engagement, a higher T-stage, adenoid cystic carcinoma histopathology, facial palsy and intercurrent disease worsen the outcome of patients, whereas gender does not. Treatment principles at our hospital have been surgery followed by radiotherapy since the early 1970s even though a split course technique was practised during a part of this period. Survival has not improved markedly. Thus, there is scope for improvement for this group of patients.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-105426 (URN)10.1080/02841860802680419 (DOI)000265272900009 ()19140053 (PubMedID)
Available from: 2009-06-03 Created: 2009-06-03 Last updated: 2017-12-13Bibliographically approved
2. The Combined Effects of Single-Nucleotide Polymorphisms, Tobacco Products, and Ethanol on Normal Resting Blood Mononuclear Cells
Open this publication in new window or tab >>The Combined Effects of Single-Nucleotide Polymorphisms, Tobacco Products, and Ethanol on Normal Resting Blood Mononuclear Cells
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2013 (English)In: Nicotine & tobacco research, ISSN 1462-2203, E-ISSN 1469-994X, Vol. 15, no 5, p. 890-895Article in journal (Refereed) Published
Abstract [en]

Introduction: Tobacco and ethanol consumption are crucial factors in the development of various diseases including cancer. In this investigation, we evaluated the combined effects of a number of single nucleotide polymorphisms (SNPs), with ethanol and tobacco products on healthy individuals. Methods: Pure nicotine, cigarette smoke extract, and Swedish snuff (snus) extract were used. The effects were examined by means of in vitro cell cycle progression and cell death of peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. Results: After 3 days, in vitro, resting PBMCs entered the S and G2 stage in the presence of 100 mu M nicotine. The PBMCs only proceeded to S stage, in the presence of 0.2% ethanol. The nicotine- and ethanol-induced normal cell cycle progression correlated to a number of SNPs in the IL12RB2, Rad 52, XRCC2, P53, CCND3, and ABCA1 genes. Certain SNPs in Caspases 8, IL12RB2, Rad 52, MMP2, and MDM2 genes appeared to significantly influence the effects of EtOH-, snus-, and snus + EtOH-induced cell death. Importantly, the highest degree of cell death was observed in the presence of smoke + EtOH. The amount of cell death under this treatment condition also correlated to specific SNPs, located in the MDM2, ABCA1, or GASC1 genes. Conclusions: Cigarette smoke in combination with ethanol strongly induced massive cell death. Long-term exposure to smoke and ethanol could provoke chronic inflammation, and this could be the initiation of disease including the development of cancer at various sites.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-200343 (URN)10.1093/ntr/nts207 (DOI)000317796500004 ()
Available from: 2013-05-28 Created: 2013-05-27 Last updated: 2017-12-06Bibliographically approved
3. Expression of Cyclin D1 and c-myc in adenoid cystic carcinoma, mucoepidermoid carcinoma and polymorphous low grade carcinoma
Open this publication in new window or tab >>Expression of Cyclin D1 and c-myc in adenoid cystic carcinoma, mucoepidermoid carcinoma and polymorphous low grade carcinoma
(English)Manuscript (preprint) (Other academic)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-332191 (URN)
Available from: 2017-10-25 Created: 2017-10-25 Last updated: 2017-10-25
4. Single Nucleotide Polymorphism and Cancer Risk, Tumour Recurrence or Survival of Head & Neck Cancer Patients
Open this publication in new window or tab >>Single Nucleotide Polymorphism and Cancer Risk, Tumour Recurrence or Survival of Head & Neck Cancer Patients
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2017 (English)In: OncologyArticle in journal (Refereed) Published
Abstract [en]

OBJECTIVE: This paper aims at studying the influence of single-nucleotide polymorphisms (SNPs) on cancer risk, tumor recurrence, and survival in head and neck (H&N) cancer patients. METHODS: A total of 45 SNPs in 41 genes were investigated. A total of 174 Caucasian H&N cancer patients and 245 healthy blood donors were enrolled in the study. RESULTS: Ten SNPs were associated with H&N cancer risk, but the identified SNPs differed among males and females. Some of the SNPs were related to immune response genes. The immune response gene SNPs were also related to survival. In particular, we noted that the tumor necrosis factor alpha (TNFalpha) rs1800629 could have an influence on cancer risk, tumor recurrence as well as survival. CONCLUSION: Genetic variation of the TNFalpha rs1800629 might be useful as a biomarker in clinical decision-making since it was found to be related to cancer risk, tumor recurrence, and survival of H&N cancer patients.

Place, publisher, year, edition, pages
karger, 2017
Keyword
Tumor recurrenceSurvival timeSingle-nucleotide polymorphismsHead and neck cancer
National Category
Medical and Health Sciences
Research subject
Oncology
Identifiers
urn:nbn:se:uu:diva-331352 (URN)10.1159/000452278 (DOI)
Available from: 2017-10-13 Created: 2017-10-13 Last updated: 2017-10-25
5. 1-[C-11]-acetate PET imaging in head and neck cancer - a comparison with F-18-FDG-PET: implications for staging and radiotherapy planning
Open this publication in new window or tab >>1-[C-11]-acetate PET imaging in head and neck cancer - a comparison with F-18-FDG-PET: implications for staging and radiotherapy planning
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2007 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 34, no 5, p. 651-657Article in journal (Refereed) Published
Abstract [en]

Purpose  The aim of this study was to evaluate the feasibility of using 1-[11C]-acetate positron emission tomography (ACE-PET) to detect and delineate the gross tumour volume of head and neck cancer before radiotherapy, and to compare the results with those obtained using 18F-fluoro-2-deoxy-D-glucose (FDG) PET. Methods  Ten patients with histologically verified squamous cell carcinoma were investigated by FDG-PET and dynamic ACE-PET prior to radiotherapy. The two scans were performed on the same day or on consecutive days, except in one patient in whom they were done 5 days apart. Diagnostic CT or MRI was performed in all patients. The image data sets were analysed both visually and semi-quantitatively. All primary tumours and metastases were delineated automatically by using the 50% threshold of maximum radioactivity corrected for background. The mean standardised uptake value (SUV) and the tumour volumes were evaluated and compared. Results  All ten primary tumours were detected by ACE-PET, while nine primaries were detected by FDG-PET and CT and/or MRI. The ACE SUV tended to be lower than the FDG SUV (5.3±2.7 vs 9.6±7.0, p=0.07). The tumour volumes delineated with ACE were on average 51% larger than the FDG volumes (p<0.05). ACE-PET identified 20/21 lymph node metastases, while only 13/21 lesions were detected by FDG-PET and 16/21 lesions by CT or MRI. Conclusion  ACE-PET appears promising for the staging of head and neck cancer. The biological information provided by both FDG and ACE must be carefully validated before it can be used in clinical routine for radiation treatment planning. More studies are needed to evaluate the differences in volumes and to confirm the clinical potential of both FDG and ACE-PET, especially in radiotherapy.

 

Keyword
11C-acetate, 18F-FDG, PET, Head and neck cancer, SUV
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-14998 (URN)10.1007/s00259-006-0298-9 (DOI)000246095900005 ()17146654 (PubMedID)
Available from: 2008-02-01 Created: 2008-02-01 Last updated: 2017-12-11Bibliographically approved

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