| 41. |
- Hagman, Zandra, et al.
(författare)
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The tumour suppressor miR-34c targets MET in prostate cancer cells.
- 2013
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 109:5, s. 1271-1278
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Tidskriftsartikel (refereegranskat)abstract
- Background:The microRNA, miR-34c, is a well-established regulator of tumour suppression. It is downregulated in most forms of cancers and inhibits malignant growth by repressing genes involved in processes such as proliferation, anti-apoptosis, stemness, and migration. We have previously reported downregulation and tumour suppressive properties for miR-34c in prostate cancer (PCa).Methods:In this study, we set out to further characterize the mechanisms by which miR-34c deregulation contributes to PCa progression. The genes regulated by miR-34c in the PCa cell line PC3 were identified by microarray analyses and were found to be enriched in cell death, cell cycle, cellular growth, and cellular movement pathways. One of the identified targets was MET, a receptor tyrosine kinase activated by hepatocyte growth factor, that is crucial for metastatic progression.Results:We confirmed the inhibitory effect of miR-34c on both MET transcript and protein levels. The binding of miR-34c to two binding sites in the 3'-UTR of MET was validated using luciferase reporter assays and target site blockers. The effect of this regulation on the miR-34c inhibition of the migratory phenotype was also confirmed. In addition, a significant inverse correlation between miR-34c expression levels and MET immunostaining was found in PCa patients.Conclusion:These findings provide a novel molecular mechanism of MET regulation in PCa and contribute to the increasing evidence that miR-34c has a key tumour suppressive role in PCa.British Journal of Cancer advance online publication, 6 August 2013; doi:10.1038/bjc.2013.449 www.bjcancer.com.
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| 42. |
- Hall, P, et al.
(författare)
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Breast cancer screening: time to target women at risk
- 2013
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 108:11, s. 2202-2204
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 43. |
- Hansen, T. F., et al.
(författare)
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MicroRNA-126 and epidermal growth factor-like domain 7-an angiogenic couple of importance in metastatic colorectal cancer. Results from the Nordic ACT trial
- 2013
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 109:5, s. 1243-1251
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study investigated the clinical importance of linked angiogenetic biomarkers to chemotherapy, combined with the anti-vascular endothelial growth factor A (anti-VEGF-A), as a first-line treatment in patients with metastatic colorectal cancer (mCRC). Methods: A total of 230 patients from a randomised phase III study were included. The primary microRNA-126 (pri-miRNA-126) A24G single-nucleotide polymorphism and the mature miRNA-126 were analysed by PCR using genomic DNA (full blood) and formalin-fixed paraffin-embedded tissue sections, respectively. The epidermal growth factor-like domain 7 (EGFL7) protein was visualised and quantified using immunohistochemistry. Results: High tumour expression of miRNA-126 was significantly related to a longer progression-free survival. The independent prognostic value of miRNA-126 was confirmed using a Cox regression analysis (hazard ratio = 0.49, 95% confidence interval = 0.29-0.84, P = 0.009). Although not significant, a relationship between EGFL7 expression and response rates is suggested, with EGFL7 expression at the invasive front being lower in responding patients than in the non-responders (P = 0.063). Conclusion: The results validate the previous findings on the prognostic value of miRNA-126 in mCRC and may suggest a relationship between treatment efficacy and EGFL7 expression. As miRNA-126 may target VEGF-A as well as EGFL7, the results may provide predictive information in relation to next-generation anti-angiogenetics.
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| 44. |
- Harlid, Sophia, 1978-, et al.
(författare)
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Combined effect of low-penetrant SNPs on breast cancer risk
- 2012
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Ingår i: British Journal of Cancer. - London : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 106:2, s. 389-396
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although many low-penetrant genetic risk factors for breast cancer have been discovered, knowledge about the effect of multiple risk alleles is limited, especially in women <50 years. We therefore investigated the association between multiple risk alleles and breast cancer risk as well as individual effects according to age-approximated pre- and post-menopausal status.METHODS: Ten previously described breast cancer-associated single-nucleotide polymorphisms (SNPs) were analysed in a joint European biobank-based study comprising 3584 breast cancer cases and 5063 cancer-free controls. Genotyping was performed using MALDI-TOF mass spectrometry, and odds ratios were estimated using logistic regression.RESULTS: Significant associations with breast cancer were confirmed for 7 of the 10 SNPs. Analysis of the joint effect of the original 10 as well as the statistically significant 7 SNPs (rs2981582, rs3803662, rs889312, rs13387042, rs13281615, rs3817198 and rs981782) found a highly significant trend for increasing breast cancer risk with increasing number of risk alleles (P-trend 5.6 x 10(-20) and 1.5 x 10(-25), respectively). Odds ratio for breast cancer of 1.84 (95% confidence interval (CI): 1.59-2.14; 10 SNPs) and 2.12 (95% CI: 1.80-2.50; 7 SNPs) was seen for the maximum vs the minimum number of risk alleles. Additionally, one of the examined SNPs (rs981782 in HCN1) had a protective effect that was significantly stronger in premenopausal women (P-value: 7.9 x 10(-4)).CONCLUSION: The strongly increasing risk seen when combining many low-penetrant risk alleles supports the polygenic inheritance model of breast cancer. British Journal of Cancer (2012) 106, 389-396. doi:10.1038/bjc.2011.461 www.bjcancer.com Published online 1 November 2011 (C) 2012 Cancer Research UK
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| 45. |
- Harris, H. R., et al.
(författare)
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Alcohol intake and mortality among women with invasive breast cancer
- 2012
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 106:3, s. 592-595
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Alcohol intake has consistently been associated with increased breast cancer incidence in epidemiological studies. However, the relation between alcohol and survival after breast cancer diagnosis is less clear.METHODS: We investigated whether alcohol intake was associated with survival among 3146 women diagnosed with invasive breast cancer in the Swedish Mammography Cohort. Alcohol consumption was estimated using a food frequency questionnaire. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs).RESULTS: From 1987 to 2008 there were 385 breast cancer-specific deaths and 860 total deaths. No significant association was observed between alcohol intake and breast cancer-specific survival. Women who consumed 10 g per day (corresponding to approximately 0.75 to 1 drinks) or more of alcohol had an adjusted HR (95% CI) of breast cancer-specific death of 1.36 (0.82-2.26; p(trend) = 0.47) compared with non-drinkers. A significant inverse association was observed between alcohol and non-breast cancer deaths. Those who consumed 3.4-9.9 g per day of alcohol had a 33% lower risk of death compared with non-drinkers (95% CI 0.50-0.90; p(trend) = 0.04).CONCLUSION: Our findings suggest that alcohol intake up to approximately one small drink per day does not negatively impact breast cancer-specific survival and a half drink per day is associated with a decreased risk of mortality from other causes.
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| 46. |
- Harris, H R, et al.
(författare)
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Coffee and black tea consumption and breast cancer mortality in a cohort of Swedish women
- 2012
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 107:5, s. 874-878
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Tidskriftsartikel (refereegranskat)abstract
- Background:Coffee and black tea contain a mixture of compounds that have the potential to influence breast cancer risk and survival. However, epidemiologic data on the relation between coffee and black tea consumption and breast cancer survival are sparse.Methods:We investigated the association between coffee and black tea consumption and survival among 3243 women with invasive breast cancer in the Swedish Mammography Cohort. Intake was estimated using a food frequency questionnaire. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs).Results:From 1987 to 2010 there were 394 breast cancer-specific deaths and 973 total deaths. Coffee and black tea were not associated with breast cancer-specific or overall mortality. Women consuming 4+ cups of coffee per day had a covariate and clinical characteristics-adjusted HR (95% CI) of death from breast cancer of 1.14 (0.71-1.83; ptrend=0.81) compared with those consuming <1 cup per day. Women consuming 2+ cups of black tea per day had a covariate and clinical characteristics-adjusted HR (95% CI) of death from breast cancer of 1.02 (0.67-1.55; ptrend=0.94) compared with non-tea drinkers. Caffeine was also not associated with breast cancer-specific (HR for top to bottom quartile=1.06; 95% CI=0.79-1.44; ptrend=0.71) or overall mortality.Conclusion:Our findings suggest that coffee, black tea, and caffeine consumption before breast cancer diagnosis do not influence breast cancer-specific and overall survival.
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| 47. |
- Harris, H. R., et al.
(författare)
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Vitamin C intake and breast cancer mortality in a cohort of Swedish women
- 2013
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 109:1, s. 257-264
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vitamin C may influence cancer progression through its antioxidant properties. However, the evidence from observational epidemiologic studies on vitamin C intake and survival following breast cancer diagnosis is not consistent, and the safety of vitamin C supplements following breast cancer diagnosis has not been extensively studied. Methods: Using a food-frequency questionnaire we investigated whether vitamin C intake was associated with survival among 3405 women diagnosed with invasive breast cancer in the Swedish Mammography Cohort. Results: From 1987-2010, there were 1055 total deaths with 416 deaths from breast cancer. Women in the highest quartile of pre-diagnosis vitamin C intake had an adjusted HR (95% CI) of breast cancer death of 0.75 (0.57-0.99) compared with those in the lowest quartile (P-trend=0.03). There was a borderline significant association between vitamin C intake and total mortality (HR 0.84; 95% CI 0.71-1.00; P-trend=0.08). Among 717 breast cancer cases for whom post-diagnosis supplement use was available, there was no association between vitamin C supplement use (approximate to 1000 mg) and breast cancer-specific mortality (HR=1.06; 95% CI=0.52-2.17). Conclusion: Our findings suggest that dietary vitamin C intake before breast cancer diagnosis may be associated with breast cancer survival. In addition, post-diagnosis vitamin C supplementation at the level observed in our population was not associated with survival.
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| 48. |
- Hellman, K., et al.
(författare)
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Human papillomavirus, p16(INK4A), and Ki-67 in relation to clinicopathological variables and survival in primary carcinoma of the vagina
- 2014
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 110:6, s. 1561-1570
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study aimed to determine human papillomavirus (HPV) status and to investigate p16(INK4A) and Ki-67 expression and their correlation with clinical parameters and survival in women with primary carcinoma of the vagina (PCV). Methods: The presence of HPV DNA was evaluated by PCR. Genotyping was performed by Luminex in 68 short-term (<= 2 years) and long-term (>= 8 years) PCV survivors. p16(INK4A) and Ki-67 expression was evaluated by immunohistochemistry. Results: Human papillomavirus DNA was detected in 43% of patients, the majority (63%) of whom were HPV16 positive. High p16INK4A expression was significantly correlated with low histopathological grade (P =0.004), HPV positivity (P =0.032), and long-term survival (P =0.045). High Ki-67 expression was negatively correlated with histopathological grade (P < 0.001) and tumour size (P =0.047). There was an association between HPV positivity and low histopathological grade, but not between HPV positivity and survival. Conclusion: High p16(INK4A) expression was associated with long-term survival, but the only independent predictors for survival were tumour size and histopathological grade. Our results indicate that p16(INK4A) and Ki-67 expression might be useful in tumour grading, and that it might be possible to use p16(INK4A) expression as a marker for HPV positivity, but this has to be further elucidated.
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| 49. |
- Hemdan, Tammer, et al.
(författare)
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The prognostic value and therapeutic target role of stathmin-1 in urinary bladder cancer
- 2014
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 111:6, s. 1180-1187
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Tidskriftsartikel (refereegranskat)abstract
- Background:The oncoprotein-18/stathmin 1 (STMN1), involved in cell progression and migration, is associated with clinical outcome in breast cancer. Here we aim to investigate its clinical significance in urinary bladder cancer and its possibilities as a therapeutic target.Methods:Immunohistochemical analyses of STMN1 protein expression were performed in three patient cohorts: cohort I (n=115 Ta, n=115 T1, n=112 T2-4 stages), cohort II, based on randomised controlled trials (n=239 T1-T4), and cohort III of primary tumour/matched metastasis (n=90 T1-T4). The effects of STMN1 on cell proliferation and migration were evaluated in the urinary bladder cancer cell line, T24, by inhibiting STMN1-cellular expression using siRNA.Results:In cohort I, high STMN1 expression correlated to shorter disease-specific survival hazard ratio (HR)=2.04 (95% confidence interval (CI) 1.13-3.68; P=0.02), elevated p53- (P<0.001) and Ki67-protein levels (P<0.001). The survival result was validated in cohort II: HR=1.76 (95% CI 1.04-2.99; P=0.03). In the metastatic bladder cancer material, 70% of the patients were STMN1-positive in both the primary tumour and matched metastases. In vitro, the growth and migration of the T24 cells were significantly reduced (P<0.01, P<0.0001, respectively), when transfecting the cells with STMN1-siRNA.Conclusions:STMN1 protein expression has prognostic significance but is primarily a potential treatment target in urinary bladder cancer.
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| 50. |
- Hemminki, Kari, et al.
(författare)
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Familial risks in nervous system tumours: joint Nordic study.
- 2010
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 102, s. 1786-1790
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Tidskriftsartikel (refereegranskat)abstract
- Background:Familial nervous system cancers are rare and limited data on familial aspects are available particularly on site-specific tumours.Methods:Data from five Nordic countries were used to analyse familial risks of nervous system tumours. Standardised incidence ratios (SIRs) were calculated for offspring of affected relatives compared with offspring of non-affected relatives.Results:The total number of patients with nervous system tumour was 63 307, of whom 32 347 belonged to the offspring generation. Of 851 familial patients (2.6%) in the offspring generation, 42 (4.7%) belonged to the families of a parent and at least two siblings affected. The SIR of brain tumours was 1.7 in offspring of affected parents; it was 2.0 in siblings and 9.4 in families with a parent and sibling affected. For spinal tumours, the SIRs were much higher for offspring of early onset tumours, 14.0 for offspring of affected parents and 22.7 for siblings. The SIRs for peripheral nerve tumours were 16.3 in offspring of affected parents, 27.7 in siblings and 943.9 in multiplex families.Conclusion:The results of this population-based study on medically diagnosed tumours show site-, proband- and age-specific risks for familial tumours, with implications for clinical genetic counselling and identification of the underlying genes.British Journal of Cancer advance online publication, 25 May 2010; doi:10.1038/sj.bjc.6605708 www.bjcancer.com.
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