| 211. |
- Obon-Santacana, Mireia, et al.
(författare)
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Dietary Intake of Acrylamide and Epithelial Ovarian Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort
- 2015
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 24:1, s. 291-297
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Tidskriftsartikel (refereegranskat)abstract
- Acrylamide, classified in 1994 by the International Agency for Research on Cancer (IARC) as "probably carcinogenic" to humans, was discovered in 2002 in some heat-treated, carbohydrate-rich foods. The association between dietary acrylamide intake and epithelial ovarian cancer risk (EOC) has been previously studied in one case-control and three prospective cohort studies which obtained inconsistent results and could not further examine histologic subtypes other than serous EOC. The present study was carried out in the European Prospective Investigation into Cancer and Nutrition (EPIC) subcohort of women (n = 325,006). Multivariate Cox proportional hazards models were used to assess the association between questionnaire-based acrylamide intake and EOC risk. Acrylamide was energy-adjusted using the residual method and was evaluated both as a continuous variable (per 10 mu g/d) and in quintiles; when subgroups by histologic EOC subtypes were analyzed, acrylamide intake was evaluated in quartiles. During a mean follow-up of 11 years, 1,191 incident EOC cases were diagnosed. At baseline, the median acrylamide intake in EPIC was 21.3 mu g/d. No associations and no evidence for a dose-response were observed between energy-adjusted acrylamide intake and EOC risk (HR10 mu(g/d), 1.02; 95% CI, 0.96-1.09; HRQ5vsQ1, 0.97; 95% CI, 0.76-1.23). No differences were seen when invasive EOC subtypes (582 serous, 118 endometrioid, and 79 mucinous tumors) were analyzed separately. This study did not provide evidence that acrylamide intake, based on food intake questionnaires, was associated with risk for EOC in EPIC. Additional studies with more reliable estimates of exposure based on biomarkers may be needed.
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| 212. |
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| 213. |
- Oda, Husam, 1975-
(författare)
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Leucine-rich repeats and immunoglobulin-like domain (LRIG) proteins : possible prognostic markers in vulvar squamous cell carcinoma, endometrial carcinoma, and oropharymgeal squamous cell carcinoma
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The human leucine-rich repeats and immunoglobulin-like domain (LRIG) gene family comprises three genes, LRIG1, LRIG2 and LRIG3, which encode the LRIG1, LRIG2 and LRIG3 proteins, respectively. Previous stidies have revealed the different prognostic roles of these proteins in different cancers, and it has been shown that LRIG1 functions as a tumour suppressor in certain cancers via its negative regulation of several receptor tyrosine kinases. Much less is known about the functionof LRIG2 and LRIG3. The expression of all three LRIG genes has been studied with human papillomavirus (HPV). In particular, expression of LRIG1 has been associated with improved survival in cervical, vaginal, and oropharyngeal cancers. Since LRIG1 has been shown to predict sensitivity to paltinum-based chemotherapy when studied in different cell lines, the possible role of LRIG protein expression in HPV-associated and other cancers may be interesting to investigate furthur.The overall aim of this thesis was to evaluate the immunoreactivity of LRIGs in vulvar squamous cell carcinoma (VSCC), endometrial carcinoma (EC) and oropharyngeal squamous cell carcinoma (OPSCC) and to investigate the potential prognostic value of LRIG proteins in association with HPV and p16 status in VSCC and OPSCC and to investigate the possible prognostic value of LMO7 and other prognostic markers of interest. Expression of the LRIG proteins and other markers was evaluated with immunohistochemistry, and HPV status was determined by PCR.In VSCC, high immunoreactivity of LRIG2 and LMO7 was associated with good survival. LRIG1 was not a significant prognostic factor in VSCC. We also conducted a pilot study to evaluate the immunoreactivity of LRIG proteins in 75 women with EC. Most of the patients in this cohort had very high positivity for LRIG proteins. High expression of LRIG3 was associated with better survival. LRIG1 and LRIG2 expression in tumours had no impact on prognosis in this study, but this should be interpreted with great caution due to the limited size of the cohort. Finally, high expression of LMO7 was associated with improved survival in OPSCC. In this cohort of 143 patients, LRIG1 expression was associated with worse survival in HPV-driven tumours. This is in contrast to previous published work where high LRIG1 expression has been associated with good survival. Notably, in both the VSCC and OPSCC cohort, a new polyclonal LRIG1 antibody was used in contrast to that in a previous study of OPSCC.In conclusion, we report additional data on the prognosticvalue of LRIG proteins in smaller cohort of VSCC, EC and OPSCC and suggest that these molecular markers need to be investigated furthur to elucidate possible clinical implications. In addition, a new monoclonal antibody against LRIG1 needs to be developed to ensure the reproducibility of the data.
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| 214. |
- Ose, Jennifer, et al.
(författare)
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Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:2, s. 399-410
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Tidskriftsartikel (refereegranskat)abstract
- The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2=0.79, 95% confidence interval [CI]=[0.64-0.97]). Moreover, associations differed for low-grade and high-grade carcinomas, with positive associations for low-grade and inverse associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2=1.99 [0.98-4.06]; high grade: ORlog2=0.75 [0.61-0.93], p(het)0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed. What's new? There appear to be several types of epithelial invasive ovarian cancer (EOC), and hormone-related risk factors are poorly understood. In this study, the authors found that the impact of endogenous androgens on the risk of developing EOC differed depending upon tumor characteristics. Androgen concentrations were positively associated with the risk of low-grade and type-I carcinomas, but the study found an inverse association for high-grade tumors. These findings support a possible role for androgens in ovarian carcinogenesis, and emphasize the need for additional research.
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| 215. |
- Ose, J., et al.
(författare)
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Insulin-like growth factor I and risk of epithelial invasive ovarian cancer by tumour characteristics: results from the EPIC cohort
- 2015
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 112:1, s. 162-166
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prospective studies on insulin-like growth factor I (IGF-I) and epithelial ovarian cancer (EOC) risk are inconclusive. Data suggest risk associations vary by tumour characteristics. Methods: We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate IGF-I concentrations and EOC risk by tumour characteristics (n = 565 cases). Multivariable conditional logistic regression models were used to estimate associations. Results: We observed no association between IGF-I and EOC overall or by tumour characteristics. Conclusions: In the largest prospective study to date was no association between IGF-I and EOC risk. Pre-diagnostic serum IGF-I concentrations may not influence EOC risk.
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| 216. |
- Palma, Marzia, et al.
(författare)
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Ibrutinib induces rapid down-regulation of inflammatory markers and altered transcription of chronic lymphocytic leukaemia-related genes in blood and lymph nodes
- 2018
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Ingår i: British Journal of Haematology. - : WILEY. - 0007-1048 .- 1365-2141. ; 183:2, s. 212-224
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Tidskriftsartikel (refereegranskat)abstract
- In chronic lymphocytic leukaemia (CLL) patients, treatment with the Bruton tyrosine kinase inhibitor ibrutinib induces a rapid shift of tumour cells from lymph nodes (LN) to peripheral blood (PB). Here, we characterized in depth the dynamics of ibrutinib-induced inflammatory, transcriptional and cellular changes in different compartments immediately after treatment initiation in seven relapsed/refractory CLL patients. Serial PB and LN samples were taken before start and during the first 29 days of treatment. Changes in plasma inflammation-related biomarkers, CLL cell RNA expression, B-cell activation and migration markers expression, and PB mononuclear cell populations were assessed. A significant reduction of 10 plasma inflammation markers, the majority of which were chemokines and not CLL-derived, was observed within hours, and was paralleled by very early increase of CD19(+) circulating cells. At the RNA level, significant and continuous changes in transcription factors and signalling molecules linked to B-cell receptor signalling and CLL biology was observed in both PB and LN CLL cells already after 2 days of treatment. In conclusion, ibrutinib seems to instantly shut off an ongoing inflammatory response and interfere with diverse sensitive pathways in the LN.
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| 217. |
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| 218. |
- Patthey, Annika, et al.
(författare)
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Combination of aneuploidy and high S-phase fraction indicates increased risk of relapse in stage I endometrioid endometrial carcinoma
- 2021
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Ingår i: Acta Oncologica. - : Taylor & Francis Group. - 0284-186X .- 1651-226X. ; 60:9, s. 1218-1224
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Endometrioid endometrial carcinoma is a cancer type with generally excellent prognosis when diagnosed at an early stage, but there is a subset of patients with relapsing disease in spite of early diagnosis and surgical treatment. There is a need to find prognostic markers to identify these patients with increased risk of relapse. Depth of myometrial invasion, histological grade, and presence of lymphovascular invasion are known risk factors. DNA content (ploidy) and proliferation measured as S-phase fraction (SPF) have been discussed as prognostic markers but need additional evaluation.MATERIAL AND METHODS: We evaluated relapse-free survival (RFS) with respect to ploidy and SPF, which was analyzed by flow cytometry on fresh tumor tissue, in a cohort of 1001 women treated for stage I endometrioid endometrial carcinoma in northern Sweden during the period of 1993-2010, with a median follow up time of 12.0 years. Data were obtained from historical records.RESULTS: In simple analysis, both aneuploidy and high SPF were associated to increased risk of relapse with hazard ratios (HR) 2.37 (95% CI 1.52-3.70) and 1.94 (95% CI 1.24-3.02), respectively. Our data also confirmed stage, tumor grade, and ploidy as independent prognostic markers in an age adjusted cox regression multivariable analysis but we did not find SPF to contribute to prognosis. However, the combination of aneuploidy and high SPF identified a group of patients with increased risk of relapse, HR 2.02 (95% CI 1.19-3.44).CONCLUSION: In this study, which is the largest study of ploidy and SPF in stage I endometrioid endometrial carcinoma using fresh frozen tissue, aneuploidy was shown to be an independent prognostic marker. Furthermore, the combination of aneuploidy and high SPF could be used to identify patients with increased risk of relapse.
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| 219. |
- Paus, Elisabeth, et al.
(författare)
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TD-11 workshop report : characterization of monoclonal antibodies to S100 proteins
- 2011
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Ingår i: Tumor Biology. - : Springer Science and Business Media LLC. - 1010-4283 .- 1423-0380. ; 32:1, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Fourteen monoclonal antibodies with specificity against native or recombinant antigens within the S100 family were investigated with regard to immunoreactivity. The specificities of the antibodies were studied using ELISA tests, Western blotting epitope mapping using competitive assays, and QCM technology. The mimotopes of antibodies against S100A4 were determined by random peptide phage display libraries. Antibody specificity was also tested by IHC and pair combinations evaluated for construction of immunoradiometric assays for S100B. Out of the 14 antibodies included in this report eight demonstrated specificity to S100B, namely MAbs 4E3, 4D2, S23, S53, 6G1, S21, S36, and 8B10. This reactivity could be classified into four different epitope groups using competing studies. Several of these MAbs did display minor reactivity to other S100 proteins when they were presented in denatured form. Only one of the antibodies, MAb 3B10, displayed preferential reactivity to S100A1; however, it also showed partial cross-reactivity with S100A10 and S100A13. Three antibodies, MAbs 20.1, 22.3, and S195, were specific for recombinant S100A4 in solution. Western blot revealed that MAb 20.1 and 22.3 recognized linear epitopes of S100A4, while MAb S195 reacted with a conformational dependent epitope. Surprisingly, MAb 14B3 did not demonstrate any reactivity to the panel of antigens used in this study.
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| 220. |
- Petersen, Marsanna, et al.
(författare)
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Clinical experiments for Huntington's disease : Recommendations to medical researchers regarding how to inform potential participants
- 2016
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Huntington's disease (HD) is a severe, genetic brain disorder that causes great suffering and leads to an early death. The medical research team in the project Treatments of the Future at Lund University aims to develop a new molecular gene therapeutic method that will give the possibility to cure the disease. The authors’, social- and cultural scientists, mission is to develop recommendations for how information should be designed to potential research subjects in an experimental gene therapy study regarding HD. More specifically, to find and recommend a model that makes it possible for individuals who are affected by HD to decide if they want to participate as research subjects in the clinical trials within Treatments of the Future.
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