Urinary estrogen metabolites and prostate cancer : a case-control study and meta-analysis

Objective: To investigate prostate cancer (Pca) risk in relation to estrogen metabolism, expressed as urinary 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1) and 2-OHE1 to 16α-OHE1 ratio. Methods: We conducted a case-control study within the Western New York Health Cohort Study (WNYHCS) from 1996 to 2001. From January 2003 through September 2004, we completed the re-call and follow-up of 1092 cohort participants. Cases (n = 26) and controls (n = 110) were matched on age, race and recruitment period according to a 1:4 ratio. We used the unconditional logistic regression to compute crude and adjusted odds ratios (OR) and 95% confident interval (CI) of Pca in relation to 2-OHE1, 16αOHE1 and 2-OHE1 to 16α-OHE1 by tertiles of urine concentrations (stored in a biorepository for an average of 4 years). We identified age, race, education and body mass index as covariates. We also conducted a systematic review of the literature which revealed no additional studies, but we pooled the results from this study with those from a previously conducted case-control study using the DerSimonian-Laird random effects method. Results: We observed a non-significant risk reduction in the highest tertile of 2-OHE1 (OR 0.72, 95% CI 0.25-2.10). Conversely, the odds in the highest tertile of 16α-OHE1 showed a non-significant risk increase (OR 1.76 95% CI 0.62-4.98). There was a suggestion of reduced Pca risk for men in the highest tertile of 2-OHE1 to 16α-OHE1 ratio (OR 0.56, 95% CI 0.19-1.68). The pooled estimates confirmed the association between an increased Pca risk and higher urinary levels of 16α-OHE1 (third vs. first tertile: OR 1.82, 95% CI 1.09-3.05) and the protective effect of a higher 2-OHE 1 to 16α-OHE1 ratio (third vs. first tertile: OR 0.53, 95% CI 0.31-0.90). Conclusion: Our study and the pooled results provide evidence for a differential role of the estrogen hydroxylation pathway in Pca development and encourage further study

Malignancies and Biosensors: A Focus on Oral Cancer Detection through Salivary Biomarkers

Oral cancer is among the deadliest types of malignancy due to the late stage at which it is usually diagnosed, leaving the patient with an average five-year survival rate of less than 50%. The booming field of biosensing and point of care diagnostics can, in this regard, play a major role in the early detection of oral cancer. Saliva is gaining interest as an alternative biofluid for non-invasive diagnostics, and many salivary biomarkers of oral cancer have been proposed. While these findings are promising for the application of salivaomics tools in routine practice, studies on larger cohorts are still needed for clinical validation. This review aims to summarize the most recent development in the field of biosensing related to the detection of salivary biomarkers commonly associated with oral cancer. An introduction to oral cancer diagnosis, prognosis and treatment is given to define the clinical problem clearly, then saliva as an alternative biofluid is presented, along with its advantages, disadvantages, and collection procedures. Finally, a brief paragraph on the most promising salivary biomarkers introduces the sensing technologies commonly exploited to detect oral cancer markers in saliva. Hence this review provides a comprehensive overview of both the clinical and technological advantages and challenges associated with oral cancer detection through salivary biomarkers

Effectiveness and tolerability of Poliprotect, a natural mucosal protective agent for gastroesophageal reflux disease and dyspepsia: Surveys from patients, physicians, and pharmacists

Background: Gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) are very common in the general population. GERD prevalence is considerably high in pregnant women, and it increases at a young age, alongside obesity. Mucosal protective agents (MPAs) are over-the-counter (OTC) treatments for FD and GERD commonly used alone or as add-on therapy to proton pump inhibitors (PPIs). Real-world data through surveys allow a clinical evaluation of marketed products that also complies with the new regulation on substance-based medical devices (SBMDs).Aim: The study aimed to evaluate perceived effectiveness, safety, and pattern of usage among patients, physicians, and pharmacists of the natural MPA Poliprotect, as assessed by a validated survey methodology.Methods: Questionnaire repeatability was first assessed, resulting in the intraclass correlation coefficient agreement level >0.9 in the three validation cohorts of physicians, pharmacists, and patients. All questions were closed multiple-choice, allowing measuring variations in frequency, quality, or magnitude of effect on a 5-point Likert-like verbal scale.Results: Three different surveys were performed in Italy and Spain on a total of 3,471 physicians, including 77 gastroenterologists, 848 patients, and 146 pharmacists who had an experience with Poliprotect in the previous year. Over 90% of general practitioners (GPs) rated Poliprotect effectiveness as good/excellent in controlling pyrosis, 80% for epigastric pain, and approximately 70% for digestion difficulties. GPs reported Poliprotect as very or extremely useful as an alternative to PPIs (73%) and for pregnancy-associated GERD symptoms (61%), almost unanimously (99.5%) reporting an excellent to good tolerability; 79% of the gastroenterologists answered to be extremely or very satisfied with the improvement of typical GERD symptoms, whereas improvement of dyspepsia and pregnancy- and breast-feeding-associated GERD symptoms was rated as highly satisfactory for 69, 52, and 62%, respectively, among GI specialists. Its use because of painful dyspeptic symptoms was reported by over 80% of patients, who rated symptom relief as excellent/good, and reported a marked quality-of-life improvement in 73% and in 65% of their answers, respectively. The product was used as monotherapy by 63% of patients. Conclusion: Large-scale, validated surveys support the safety and effectiveness of Poliprotect in the treatment of common functional upper GI disorders

Magnitude of benefit of the addition of bevacizumab to first-line chemotherapy for metastatic colorectal cancer: meta-analysis of randomized clinical trials

<p>Abstract</p> <p>Background</p> <p>Although the addition of bevacizumab to 1^stline chemotherapy provides a significant survival benefit for advanced colorectal cancer, the magnitudes of both advantages and toxicities have not been extensively investigated.</p> <p>Methods</p> <p>A literature-based meta-analysis was conducted; Hazard Ratios were extracted from randomized trials for primary end-points (Progression Free Survival, PFS, Overall Survival OS). The log of event-based risk ratio were derived for secondary endpoints (objective/partial response rate, ORR/PR; severe hypertension, bleeding and proteinuria). Absolute differences and the number needed to treat/harm (NNT/NNH) were calculated. A meta-regression analysis with clinical predictors and a sensitivity analysis according to the trial phase-design were conducted as well.</p> <p>Results</p> <p>Five trials (2,728 pts) were selected. The addition of bevacizumab to 1^stline chemotherapy significantly increased both PFS (although with significant heterogeneity) and OS over exclusive chemotherapy by 17.1% and 8.6% (NNT 6 and 12), regardless of the study setting (non significant interaction between phase II and III). The chance to improve PR was significantly increased by 6.5% (NNT 15), with a trend for ORR. The risk of hypertension was significantly increased by 6.2% (NNH 16). According to the meta-regression analysis, female gender and rectal primary site were significant predictors for PFS benefit.</p> <p>Conclusions</p> <p>Notwithstanding all the concerns related to costs and the significant HTN risk, the significant outcome improvement provided by bevacizumab in first-line treatment for unselected advanced colorectal cancer patients, should be considered when choosing the appropriate up-front therapy.</p

Publication of the International Union Against Cancer

Because of large intra-individual variation in hormone levels, few studies have investigated the relation of serum sex hormones to breast cancer (BC) in premenopausal women. We prospectively studied this relation, adjusting for timing of blood sampling within menstrual cycle. Premenopausal women (5,963), recruited to the Hormones and Diet in the Etiology of Breast Tumors (ORDET) cohort study, provided a blood sample in the 20 -24th day of their menstrual cycle. The hypothesis that breast cancer (BC) is related to ovarian function dates back over a century. 1 Epidemiological, in vitro and in vivo studies conducted in the second half of the last century made it clear that steroid sex hormones regulate cell proliferation and play a major role in promoting BC. 2,3 Several mechanistic hypotheses for the development of BC have been proposed, 2,4 but until recently, hormone measurements by epidemiological studies have failed to corroborate any of them. Over the last decade, however, several prospective cohort studies in postmenopausal women have shown that BC development is preceded by alterations in levels of circulating sex hormones. 5 High serum levels of free and total estradiol, total testosterone and other estrogens and androgens, as well as low serum levels of sex hormone-binding globulin (SHBG), have been found to be implicated in the risk of BC. 5 Our own study also indicated that high serum levels of free testosterone are associated with the risk of BC. 6 These prospective investigations were carried out with the help of thousands of healthy women who provided blood samples for storage and future nested-in-the-cohort case-control analyses. Compared to case control studies in clinical settings, the strengths of prospective studies are that control subjects belong to the same cohort that generates the incident disease cases and that blood is collected before the diagnosis of cancer thereby excluding abnormal values that may be due to overt illness. Hormone measurements in premenopausal women are difficult to interpret because serum levels change with the menstrual cycle and because cycle length varies inter-and intra-individually. Only a few prospective investigations have addressed the role of sex hormone levels in BC before the menopause; 7-10 all considered small numbers of case women and did not produce clear results. The endocrine basis of BC in premenopause is therefore the subject of several disparate hypotheses. These include the hypothesis of Grattarola, advanced in the 1960s, 11-12 that hyperandrogenism with luteal inadequacy plays a role in the induction of BC, and of Henderson et al. The present prospective study was designed to investigate whether luteal inadequacy and hyperandrogenism increase the risk of BC in premenopausal women. We collected blood samples from premenopausal women participating in the study on Hormones and Diet in the Etiology of Breast Tumors (ORDET). 6,14 Samples were taken between the 20th and 24th day of the cycle (theoretically during the mid luteal phase). The first day of menstrual bleeding subsequent to sampling was also recorded to provide an additional data point for correctly locating the sampling day within the cycle. In these women, we analyzed the relationship between BC and serum levels of the androgens dehydroepiandrosterone sulfate (DHEAS), total testosterone, free testosterone, androstenedione and androstanediol-glucoronide (Adiol-G), and also progesterone, 17-OH-progesterone, SHBG, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Estradiol was not considered in the present analysis because of its extraordinary intra-individual variation in premenopausal women

MALAT1-dependent hsa_circ_0076611 regulates translation rate in triple-negative breast cancer

Vascular Endothelial Growth Factor A (VEGFA) is the most commonly expressed angiogenic growth factor in solid tumors and is generated as multiple isoforms through alternative mRNA splicing. Here, we show that lncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) and ID4 (inhibitor of DNA-binding 4) protein, previously referred to as regulators of linear isoforms of VEGFA, induce back-splicing of VEGFA exon 7, producing circular RNA circ_0076611. Circ_0076611 is detectable in triple-negative breast cancer (TNBC) cells and tissues, in exosomes released from TNBC cells and in the serum of breast cancer patients. Circ_0076611 interacts with a variety of proliferation-related transcripts, included MYC and VEGFA mRNAs, and increases cell proliferation and migration of TNBC cells. Mechanistically, circ_0076611 favors the expression of its target mRNAs by facilitating their interaction with components of the translation initiation machinery. These results add further complexity to the multiple VEGFA isoforms expressed in cancer cells and highlight the relevance of post-transcriptional regulation of VEGFA expression in TNBC cells

Circulating soluble Fas levels and risk of ovarian cancer

BACKGROUND: Dysregulation of apoptosis, specifically overexpression of soluble Fas (sFas), has been proposed to play a role in the development of ovarian cancer. The main objective of the present study was to evaluate serum sFas as a potential biomarker of ovarian cancer risk. METHODS: The association between serum sFas levels and the risk of ovarian cancer was examined in a case-control study nested within three prospective cohorts in New York (USA), Umeå (Sweden), and Milan (Italy). Case subjects were 138 women with primary invasive epithelial ovarian cancer diagnosed between 2 months and 13.2 years after the initial blood donation. Control subjects were 263 women who were free of cancer, and matched the case on cohort, menopausal status, age, and enrollment date. Serum sFas levels were determined using a quantitative sandwich enzyme immunoassay. RESULTS: Serum sFas levels were similar in women subsequently diagnosed with ovarian cancer (median, 6.5 ng/mL; range, 4.4 – 10.2) and in controls (median, 6.8 ng/mL; range, 4.5 – 10.1). Statistically significant trends of increasing serum sFas with age were observed among cases (r = 0.39, p < 0.0001) and controls (r = 0.42, p < 0.0001). Compared to women in the lowest third, women in the highest third of serum sFas were not at increased risk of ovarian cancer after adjustment for potential confounders (odd ratio (OR), 0.87; 95% confidence interval (CI), 0.42 – 1.82). CONCLUSION: The results suggest that serum sFas may not be a suitable marker for identification of women at increased risk of ovarian cancer

An evaluation of the integration of non-traditional learning tools into a community based breast and cervical cancer education program: The witness project of Buffalo

BACKGROUND: Breast and cervical cancer continue to represent major health challenges for African American women. among Caucasian women. The underlying reasons for this disparity are multifactorial and include lack of education and awareness of screening and early detection. Traditional educational methods have enjoyed varied success in the African American community and spawned development of novel educational approaches. Community based education programs employing a variety of educational models have been introduced. Successful programs must train and provide lay community members with the tools necessary to deliver strong educational programs. METHODS: The Witness Project is a theory-based, breast and cervical cancer educational program, delivered by African American women, that stresses the importance of early detection and screening to improve survival and teaches women how to perform breast self examination. Implementing this program in the Buffalo Witness Project of Buffalo required several modifications in the curriculum, integration of non-traditional learning tools and focused training in clinical study participation. The educational approaches utilized included repetition, modeling, building comprehension, reinforcement, hands on learning, a social story on breast health for African American women, and role play conversations about breast and cervical health and support. RESULTS: Incorporating non-traditional educational approaches into the Witness Project training resulted in a 79% improvement in the number of women who mastered the didactic information. A seventy-two percent study participation rate was achieved by educating the community organizations that hosted Witness Project programs about the informed consent process and study participation. CONCLUSION: Incorporating non-traditional educational approaches into community outreach programs increases training success as well as community participation