Dietary Folate, Alcohol Consumption, and Risk of Ovarian Cancer in an Italian Case-Control Study

An increasing number of studies are focusing on the potential association between dietary folate intake and risk of various cancers (1), particularly of the colorectum and breast (2, 3). A low folate status can induce misincorporation of uracil into DNA, leading to chromosome breaks in humans and hence increasing cancer risk (4). Alcohol may increase folate requirements in the body and cause relative folate deficiencies (2). Although several findings on the relation between folate intake and ovarian cancer risk are inconsistent (5-9), recent results from two prospective studies, including 266 and 147 incident cases of epithelial ovarian cancer, have suggested an interaction of folate and alcohol in ovarian carcinogenesis [i.e., folate would be inversely related to ovarian cancer risk in alcohol drinkers (5, 6), and alcohol in those with high folate intake (7)]. With the aim to provide further data on the issue, we assessed the relation between dietary folate, alcohol consumption, and ovarian cancer risk in a multicentric case-control study conducted in Italy (10)

Benign ovarian cysts and breast cancer risk

Benign ovarian cysts have been suggested to influence breast cancer risk. To provide a comprehensive picture of the relation between ovarian cysts and breast cancer, we analyzed the data of 3 case-control studies conducted in northern Italy and the Swiss Canton of Vaud between 1983 and 2001. These studies included 6,315 incident, histologically confirmed breast cancer cases and 6,038 hospital-based controls. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models, including terms for sociodemographic, menstrual and reproductive factors. Overall, 4.9% of breast cancer cases and 6.6% of controls reported a history of ovarian cysts, with a multivariate OR of 0.72 (95% CI 0.62-0.85). The inverse association between ovarian cysts and breast cancer was consistent in separate strata of age at menarche, parity, age at menopause status and family history of breast cancer. No meaningful differences were also found across strata of menstrual cycle length, oral contraceptive use, history of oophorectomy and body mass index. Thus, the inverse relation between ovarian cysts and breast cancer risk was not accounted for by earlier menopause, or by any difference in reproductive and menstrual characteristics. Although some hormonal correlates of ovarian cysts may have a role on breast cancer risk, a biological explanation of this inverse association is still unclear. [Ed.]]]> Breast Neoplasms; Ovarian Cysts eng oai:serval.unil.ch:BIB_60E7401120E0 2022-05-07T01:19:00Z openaire documents urnserval <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_60E7401120E0 Peroxisome proliferator-activated receptor beta regulates acyl-CoA synthetase 2 in reaggregated rat brain cell cultures. info:doi:10.1074/jbc.274.50.35881 info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.274.50.35881 info:eu-repo/semantics/altIdentifier/pmid/10585473 Basu-Modak, S. Braissant, O. Escher, P. Desvergne, B. Honegger, P. Wahli, W. info:eu-repo/semantics/article article 1999 Journal of Biological Chemistry, vol. 274, no. 50, pp. 35881-35888 info:eu-repo/semantics/altIdentifier/pissn/0021-9258[print], 0021-9258[linking] <![CDATA[Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that regulate the expression of many genes involved in lipid metabolism. The biological roles of PPARalpha and PPARgamma are relatively well understood, but little is known about the function of PPARbeta. To address this question, and because PPARbeta is expressed to a high level in the developing brain, we used reaggregated brain cell cultures prepared from dissociated fetal rat telencephalon as experimental model. In these primary cultures, the fetal cells initially form random aggregates, which progressively acquire a tissue-specific pattern resembling that of the brain. PPARs are differentially expressed in these aggregates, with PPARbeta being the prevalent isotype. PPARalpha is present at a very low level, and PPARgamma is absent. Cell type-specific expression analyses revealed that PPARbeta is ubiquitous and most abundant in some neurons, whereas PPARalpha is predominantly astrocytic. We chose acyl-CoA synthetases (ACSs) 1, 2, and 3 as potential target genes of PPARbeta and first analyzed their temporal and cell type-specific pattern. This analysis indicated that ACS2 and PPARbeta mRNAs have overlapping expression patterns, thus designating the ACS2 gene as a putative target of PPARbeta. Using a selective PPARbeta activator, we found that the ACS2 gene is transcriptionally regulated by PPARbeta, demonstrating a role for PPARbeta in brain lipid metabolism

Bosentan and macitentan prevent the endothelial-to-mesenchymal transition (EndoMT) in systemic sclerosis: in vitro study.

Background: Systemic sclerosis (SSc) is characterized by early vascular abnormalities and subsequent fibroblast activation to myofibroblasts, leading to fibrosis. Recently, endothelial-to-mesenchymal transition (EndoMT), a complex biological process in which endothelial cells lose their specific markers and acquire a mesenchymal or myofibroblastic phenotype, has been reported in SSc. In the present study, we evaluated the ability of endothelin-1 (ET-1) dual receptor antagonists bosentan (BOS) and macitentan (MAC) to antagonize EndoMT in vitro. Methods: Ten women with limited SSc were enrolled. They underwent double skin biopsy (affected and nonaffected skin). Fibroblasts and microvascular endothelial cells (MVECs) were isolated from biopsies. We performed mono- or coculture of MVECs (isolated from nonaffected skin) with fibroblasts (isolated from affected skin and stimulated with ET-1 and transforming growth factor beta [TGF-\u3b2]). In cocultures, the MVEC layer was left undisturbed or was preincubated with BOS or MAC. After 48 h of coculture, MVECs were analyzed for their tube formation ability and for messenger RNA and protein expression of different vascular (CD31, vascular endothelial growth factor-A [VEGF-A], VEGF-A165b) and profibrotic (alpha-smooth muscle actin [\u3b1-SMA], collagen type I [Col I], TGF-\u3b2) molecules. Results: After 48 h, MVECs showed a reduced tube formation ability when cocultured with SSc fibroblasts. CD31 and VEGF-A resulted in downregulation, while VEGF-A165b, the antiangiogenic isoform, resulted in upregulation. At the same time, mesenchymal markers \u3b1-SMA, Col I, and TGF-\u3b2 resulted in overexpression in MVECs. Tube formation ability was restored when MVECs were preincubated with BOS or MAC, also reducing the expression of mesenchymal markers and restoring CD31 expression and the imbalance between VEGF-A and VEGF-A165b. Conclusions: With this innovative EndoMT in vitro model realized by coculturing nonaffected MVECs with affected SSc fibroblasts, we show that the presence of a myofibroblast phenotype in the fibroblast layer, coupled with an ET-1-TGF-\u3b2 synergic effect, is responsible for EndoMT. BOS and MAC seem able to antagonize this phenomenon in vitro, confirming previous evidence of endothelium-derived fibrosis in SSc and possible pharmacological interferenc

Molecular profiles of screen detected vs. symptomatic breast cancer and their impact on survival: results from a clinical series

Stage shift is widely considered a major determinant of the survival benefit conferred by breast cancer screening. However, factors and mechanisms underlying such a prognostic advantage need further clarification. We sought to compare the molecular characteristics of screen detected vs. symptomatic breast cancers and assess whether differences in tumour biology might translate into survival benefit

HISTOPATHOLOGICAL FINDINGS IN SYSTEMIC SCLEROSIS-RELATED MYOPATHY: FIBROSIS AND MICROANGIOPATHY

Objectives: The objective of this study was to identify specific histopathological features of skeletal muscle involvement in systemic sclerosis (SSc) patients. Methods: A total of 35 out of 112 SSc-patients (32%, including 81% female and 68% diffuse scleroderma) presenting clinical, biological and electromyographic (EMG) features of muscle weakness, were included. Patients underwent vastus lateralis biopsy, assessed for individual pathologic features including fibrosis [type I collagen (Coll-I), transforming growth factor β (TGF-β)], microangiopathy [cluster of differentiation 31 (CD31), pro-angiogenic vascular endothelial growth factor A (VEGF-A), anti-angiogenic VEGF-A165b], immune/ inflammatory response [CD4, CD8, CD20, human leucocyte antigens ABC (HLA-ABC)], and membranolytic attack complex (MAC). SSc biopsies were compared with biopsies of (n = 35) idiopathic inflammatory myopathies (IIMs) and to (n = 35) noninflammatory myopathies (NIMs). Ultrastructural abnormalities of SSc myopathy were also analyzed by transmission electron microscopy (TEM). Results: Fibrosis in SSc myopathy (81%) is higher compared with IIM (32%, p &lt; 0.05) and with NIM (18%, p &lt; 0.05). Vascular involvement is dominant in SSc muscle (92%), and in IIM (78%) compared with NIM (21%, p &lt; 0.05). In particular, CD31 shows loss of endomysial vessels in SSc myopathy compared with IIM (p &lt; 0.05) and with NIM (p &lt; 0.01). VEGF-A is downregulated in SSc myopathy compared with IIM (p &lt; 0.05) and NIM (p &lt; 0.05). Conversely, VEGF-A165b is upregulated in SSc myopathy. The SSc immune/inflammatory response suggested humoral process with majority (85%) HLA-ABC fibral neoexpression and complement deposits on endomysial capillaries MAC, compared with IIM (p &lt; 0.05), characterized by CD4+/CD8+/B-cell infiltrate, and NIM (p &lt; 0.05). TEM analysis showed SSc vascular alterations consisting of thickening and lamination of basement membrane and endothelial cell ‘swelling’ coupled to endomysial/perimysial fibrosis. Conclusions: Fibrosis, microangiopathy and humoral immunity are predominant in SSc myopathy, even if it is difficult to identify specific histopathological hallmarks of muscle involvement in SSc, since they could be present also in other (IIM/NIM) myopathies. © 2016, © The Author(s), 2016

Environment and bladder cancer: molecular analysis by interaction networks

Bladder cancer (BC) is the 9th most common cancer worldwide, and the 6th most common cancer in men. Its development is linked to chronic inflammation, genetic susceptibility, smoking, occupational exposures and environmental pollutants. Aim of this work was to identify a sub-network of genes/proteins modulated by environmental or arsenic exposure in BC by computational network approaches. Our studies evidenced the presence of HUB nodes both in “BC and environment” and “BC and arsenicals” networks. These HUB nodes resulted to be correlated to circadian genes and targeted by some miRNAs already reported as involved in BC, thus suggesting how they play an important role in BC development due to environmental or arsenic exposure. Through data-mining analysis related to putative effect of the identified HUB nodes on survival we identified genes/proteins and their mutations on which it will be useful to focus further experimental studies related to the evaluation of their expression in biological matrices and to their utility as biomarkers of BC developmen

Mediterranean Diet and Breast Cancer Risk

Abstract: The Mediterranean diet has been related to a reduced risk of several common cancers but its role on breast cancer has not been quantified yet. We investigated the association between adherence to the Mediterranean diet and breast cancer risk by means of a hospital-based case-control study conducted in Italy and Switzerland. 3034 breast cancer cases and 3392 controls admitted to the same network of hospitals for acute, non-neoplastic and non-gynaecologic diseases were studied. Adherence to the Mediterranean diet was quantitatively measured through a Mediterranean Diet Score (MDS), summarizing the major characteristics of the Mediterranean dietary pattern and ranging from 0 (lowest adherence) to 9 (highest adherence). We estimated the odds ratios (ORs) of breast cancer for the MDS using multiple logistic regression models, adjusting for several covariates. Compared to a MDS of 0–3, the ORs for breast cancer were 0.86 (95% confidence interval, CI, 0.76–0.98) for a MDS of 4–5 and 0.82 (95% CI, 0.71–0.95) for a MDS of 6–9 (p for trend = 0.008). The exclusion of the ethanol component from the MDS did not materially modify the ORs (e.g., OR = 0.81, 95% CI, 0.70–0.95, for MDS ≥ 6). Results were similar in pre- and post-menopausal women. Adherence to the Mediterranean diet was associated with a reduced breast cancer risk

Computational identification of microRNAs associated to both epithelial to mesenchymal transition and NGAL/MMP-9 pathways in bladder cancer

Bladder cancer is one of the leading cancer of the urinary tract. It is often diagnosed at advanced stage of the disease. To date, no specific and effective early detection biomarkers are available. Cancer development and progression are associated with the involvement of both epithelial-mesenchymal transition (EMT) and tumor microenvironment of which NGAL/MMP-9 complex represents the main player in bladder cancer. It is known that change in microRNAs (miRNAs) expression may result in gene modulation. Therefore, the identification of specific miRNAs associated with EMT pathway and NGAL/MMP-9 complex may be useful to detect the development of bladder cancer at early stages. On this ground, the expression levels of miRNAs in public available datasets of bladder cancer containing data of non-coding RNA profiling was evaluated. This analysis revealed a group of 16 miRNAs differentially expressed between bladder cancer patients and related healthy controls. By miRNA prediction tool (mirDIP), the relationship between the identified miRNAs and the EMT genes was established. Using the DIANA-mirPath (v.2) software, miRNAs, able to modulate the expression of NGAL and MMP-9 genes, were recognized. The results of this study provide evidence that the downregulated hsa-miR-145-5p and hsa-miR-214-3p may modulate the expression of both EMT and NGAL/MMP-9 pathways. Therefore, further validation analyses may confirm the usefulness of these selected miRNAs for predicting the development of bladder cancer at the early stage of the disease