Journal: BMC cancer
Research on a possible causal association between alcohol consumption and risk of prostate cancer is inconclusive. Recent studies on associations between alcohol consumption and other health outcomes suggest these are influenced by drinker misclassification errors and other study quality characteristics. The influence of these factors on estimates of the relationship between alcohol consumption and prostate cancer has not been previously investigated.
As with many anti-cancer drugs, the topoisomerase II inhibitor etoposide is considered safe for administration to women in the second and third trimesters of pregnancy, but assessment of effects on the developing fetus have been limited. The purpose of this research was to examine the effect of etoposide on germ cells in the developing ovary. Mouse ovary tissue culture was used as the experimental model, thus allowing us to examine effects of etoposide on all stages of germ cell development in the same way, in vitro.
Abnormal NF-κB2 activation has been implicated in the pathogenesis of multiple myeloma, a cancer of plasma cells. However, a causal role for aberrant NF-κB2 signaling in the development of plasma cell tumors has not been established. Also unclear is the molecular mechanism that drives the tumorigenic process. We investigated these questions by using a transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma-associated NF-κB2 mutant, and human multiple myeloma cell lines.
BACKGROUND: To evaluated the prognostic significance of the pre-operative C-reactive protein (CRP) serum level in patients with renal cell cancer (RCC). METHODS: We evaluated 1,161 RCC patients with complete patient and tumour specific characteristics as well as information about their pre-operative CRP-level, who had undergone either radical nephrectomy or nephron-sparing surgery at two German high-volume centres (University Hospitals of Hannover and Ulm). The mean follow-up was 54 months. RESULTS: The CRP-level, stratified to three subgroups (CRP <= 4, 4--10, and >10 mg/l), correlated significantly with tumour stage (p < 0.001), the risk of presenting nodal disease (2.1, 3.1, and 16.4%) and distant metastasis (2.9, 8.6, and 30.0%; p < 0.001). The Kaplan-Meier 5-year cancer specific survival (CSS) rates were 89.4, 77.9, and 49.5%, respectively (p < 0.001). Multivariate analysis identified CRP as an independent prognosticator for CSS as well as overall survival (p < 0.001). Patients with a CRP of 4--10 and >10 mg/l had a 1.67 and 2.48 fold higher risk of dying due to their RCC compared to those with a pre-operative CRP <=4 mg/l, respectively. CONCLUSIONS: A high preoperative serum CRP level is an independent predictor of poor survival in patients with RCC. Its routine use could allow better risk stratification and risk-adjusted follow-up of RCC patients.
BACKGROUND: Temozolomide (TMZ) is the most widely used drug to treat glioblastoma (GBM), which is the most common and aggressive primary tumor of Central Nervous System and one of the hardest challenges in oncotherapy. TMZ is an alkylating agent that induces autophagy, apoptosis and senescence in GBM cells. However, therapy with TMZ increases survival after diagnosis only from 12 to 14.4 months, making the development of combined therapies to treat GBM fundamental. One candidate to GBM therapy is Resveratrol (Rsv), which has additive toxicity with TMZ in several glioma cells in vitro and in vivo. However, the mechanism of Rsv and TMZ additive toxicity, which is the aim of the present work, is not clear, especially concerning cell cycle dynamics and long term effects. METHODS: Glioma cell lines were treated with Rsv and TMZ, alone or in combinations, and the induction and the role of autophagy, apoptosis, cell cycle dynamics and protein expression and phosphorylation status were measured. We further evaluate senescence induction and clonogenic capacity at long term. RESULTS: As expected, temozolomide caused a G2 cell cycle arrest and extensive DNA damage response. Rsv did not reduced this response, even increasing pATM, pChk2 and gammaH2Ax levels, but abrogated the temozolomide-induced G2 arrest, increasing levels of cyclin B and pRb(S807/811) and reducing levels of pWee1(S642) and pCdk1(Y15). This suggests a cellular state of forced passage through G2 checkpoint despite large DNA damage, a scenario that may produce mitotic catastrophe. Indeed, the proportion of cells with high nuclear irregularity increased from 6 to 26% in 48 h after cotreatment. At a long term, a reduction in clonogenic capacity was observed, accompanied by a large induction of senescence. CONCLUSION: The presence of Rsv forces cells treated with TMZ through mitosis leading to mitotic catastrophe and senescence, fully reducing the clonogenic capacity of glioma cells and increasing the chronic effects of temozolomide.
BACKGROUND: Diabetic patients have a higher risk of bladder cancer and benign prostatic hyperplasia (BPH). Theoretically, BPH patients may have an increased risk of bladder cancer because residual urine in the bladder surely increases the contact time between urinary excreted carcinogens and the urothelium. However, whether BPH increases bladder cancer risk in patients with type 2 diabetes has not been studied. METHODS: The reimbursement databases of all Taiwanese diabetic patients under oral anti-diabetic agents or insulin from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2006 and a total of 547584 men with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Incidences of bladder cancer for BPH by status and by duration were calculated and adjusted hazard ratios (95 % confidence intervals) were estimated by Cox regression. The effects of diabetes duration and medications used for diabetic control in relation with bladder cancer risk were also evaluated by Cox regression in BPH men. RESULTS: The incidences were 258.77 and 69.34 per 100,000 person-years for patients with and without BPH, respectively, adjusted hazard ratio 1.794 (1.572, 2.047). For BPH patients, those who underwent surgical procedures for BPH had a higher incidence than those who did not (355.45 vs. 250.09 per 100,000 person-years), respective adjusted hazard ratios: 2.459 (1.946, 3.109) and 1.709 (1.492, 1.958). The significantly higher risk could be demonstrated for BPH of any duration: respective adjusted hazard ratios 1.750 (1.430, 1.605), 1.844 (1.543, 2.203), 2.011 (1.680, 2.406) and 1.605 (1.341, 1.921) for BPH <1, 1--3, 3--5 and >=5 years versus patients without BPH. Sensitivity analyses for patients aged >=60 years and after excluding BPH patients with surgical procedures or without surgical procedures, respectively, yielded similar results. In BPH men, diabetes duration was not significantly related with bladder cancer; but metformin was consistently associated with a significantly lower risk, with adjusted hazard ratio of 0.719 (0.590, 0.875) for all ages and 0.742 (0.604, 0.912) for age >=60 years. CONCLUSIONS: BPH is a significant risk factor for bladder cancer in men with type 2 diabetes. Metformin may protect against bladder cancer in BPH men.
BACKGROUND: This pilot study aimed to test the acceptability and short-term effectiveness of a telephone-delivered multiple health behaviour change intervention for relatives of colorectal cancer survivors. METHODS: A community-based sample of 22 first-degree relatives of colorectal cancer survivors were recruited via a media release. Data were collected at baseline and at six weeks (post-intervention). Outcome measures included health behaviours (physical activity, television viewing, diet, alcohol, body mass index, waist circumference and smoking), health-related quality of life (Short Form-36) and perceived colorectal cancer risk. Intervention satisfaction levels were also measured. The intervention included six telephone health coaching sessions, a participant handbook and a pedometer. It focused on behavioural risk factors for colorectal cancer [physical activity, diet (red and processed meat consumption, fruit and vegetable intake), alcohol, weight management and smoking], and colorectal cancer risk. RESULTS: From baseline to six weeks, improvements were observed for minutes moderate-vigorous physical activity (150.7 minutes), processed meat intake (-1.2 serves/week), vegetable intake (1 serve/day), alcohol intake (-0.4 standard drinks/day), body mass index (-1.4 kg/m2), and waist circumference (-5.1 cm). Improvements were also observed for physical (3.3) and mental (4.4) health-related quality of life. Further, compared with baseline, participants were more likely to meet Australian recommendations post-intervention for: moderate-vigorous physical activity (27.3 vs 59.1%);fruit intake (68.2 vs 81.8%); vegetable intake (4.6 vs 18.2%); alcohol consumption (59.1 vs 72.7%); body mass index (31.8 vs 45.5%) and waist circumference (18.2 vs 27.3%). At six weeks participants were more likely to believe a diagnosis of CRC was related to family history, and there was a decrease in their perceived risk of developing CRC in their lifetime following participation in CanPrevent. The intervention retention rate was 100%, participants reported that it was highly acceptable and they would recommend it to others at risk of colorectal cancer. CONCLUSIONS: Positive behaviour change achieved through this intervention approach has the potential to impact on the progression of CRC and other cancers or chronic diseases. A large scale randomised controlled trial is required to confirm the positive results of this acceptability and short-term effectiveness study.Trial RegistrationACTRN12612000516886.
BACKGROUND: Pancreatic cancer, including cancer of the ampulla of Vater and bile duct, is very aggressive and has a poor five year survival rate; improved methods of patient stratification are required. METHODS: We assessed the expression of calpain-1, calpain-2 and calpastatin in two patient cohorts using immunohistochemistry on tissue microarrays. The first cohort was composed of 68 pancreatic adenocarcinomas and the second cohort was composed of 120 cancers of the bile duct and ampulla. RESULTS: In bile duct and ampullary carcinomas an association was observed between cytoplasmic calpastatin expression and patient age (P=0.036), and between nuclear calpastatin expression and increased tumour stage (P=0.026) and the presence of vascular invasion (P=0.043). In pancreatic cancer, high calpain-2 expression was significantly associated with improved overall survival (P=0.036), which remained significant in multivariate Cox-regression analysis (hazard ratio=0.342; 95% confidence interval=0.157-0.741; P=0.007). In cancers of the bile duct and ampulla, low cytoplasmic expression of calpastatin was significantly associated with poor overall survival (P=0.012), which remained significant in multivariate Cox-regression analysis (hazard ratio=0.595; 95% confidence interval=0.365-0.968; P=0.037). CONCLUSION: The results suggest that calpain-2 and calpastatin expression is important in pancreatic cancers, influencing disease progression. The findings of this study warrant a larger follow-up study.
BACKGROUND: Elevated Glasgow Prognostic Score (GPS) has been related to poor prognosis in patients with hepatocellular carcinoma (HCC) undergoing surgical resection or receiving sorafenib. The aim of this study was to investigate the prognostic value of GPS in patients with various stages of the disease and with different liver functional status. METHODS: One hundred and fifty patients with newly diagnosed HCC were prospectively evaluated. Patients were divided according to their GPS scores. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with overall survival; the identified variables were then compared with those of other validated staging systems. RESULTS: Elevated GPS were associated with increased asparate aminotransferase ( P<0.0001), total bilirubin ( P<0.0001), decreased albumin (P<0.0001), alpha-fetoprotein ( P=0.008), larger tumor diameter ( P=0.003), tumor number ( P=0.041), vascular invasion ( P=0.0002), extra hepatic metastasis ( P=0.02), higher Child-Pugh scores (P<0.0001), and higher Cancer Liver Italian Program scores (P<0.0001). On multivariate analysis, the elevated GPS was independently associated with worse overall survival. CONCLUSIONS: Our results demonstrate that the GPS can serve as an independent marker of poor prognosis in patients with HCC in various stages of disease and different liver functional status.
Most cases of colorectal cancer (CRC) are initiated by inactivation mutations in the APC gene, which is a negative regulator of the Wnt-β-catenin pathway. Patients with familial adenomatous polyposis (FAP) inherit a germline mutation in one APC allele, and loss of the second allele leads to the development of polyps that will turn malignant if not removed. It is not fully understood which molecular mechanisms are activated by APC loss and when the loss of the second APC allele occurs.