Polymorphisms in genes involved in T-cell co-stimulation are associated with blood pressure in women.

In recent years, conclusive data have emerged on a relationship between immune system, especially the T-cell, and blood pressure (BP). The objective of the present study was to determine the association between BP and four polymorphisms in CD80, CD86, CD28 and CTLA4 genes that code for key proteins in the T-cell co-stimulation process, in a female cohort. To that end, an association study in a cohort of 934 women over 40 years old from two hospitals was done. Raw data showed a significant association between the SNP rs1129055 of CD86 gene and BP. Analyzing this association against inheritance patterns, higher SBP (p  0.000) and DBP (p = 0.005) values were observed in AA than in GG/GA genoty…

A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

Background Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) varies between 30 and 40% approximately. To provide further insight into the prediction of pCR, we evaluated the role of an epigenetic methylation-based signature. Methods Epigenetic assessment of DNA extracted from biopsy archived samples previous to NAC from TNBC patients was performed. Patients included were categorized according to previous response to NAC in responder (pCR or residual cancer burden, RCB = 0) or non-responder (non-pCR or RCB > 0) patients. A methyloma study was performed in a discovery cohort by the Infinium HumanMethylation450 BeadChip (450K arra…

Additional file 2: of A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

Thirty-five differentially methylated CpGs between responders and non-responders group selected from 450k array (delta value ≥ 0.2) corresponding to 23 genes located in promoter and island/shore (PPT 172 kb)

Additional file 3: of A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

Eleven differentially methylated CpGs, corresponding to 11 genes, showed significant methylation differences between non-responder and responder patients: 6 genes (LOC641518; LEF1; HOXA5; EVC2; CDKL2; TLX3) presented a methylation increase in non-responders group vs responders, and 5 genes (ZFHX4; LOC100192378; FERD3L; CHL1; TRIP10) decreased methylation level in non-responder patients compared to those who responded to NAC treatment (PPT 225 kb)

MicroRNA-33b Suppresses Epithelial-Mesenchymal Transition Repressing the MYC-EZH2 Pathway in HER2+ Breast Carcinoma

Downregulation of miR-33b has been documented in many types of cancers and is being involved in proliferation, migration, and epithelial-mesenchymal transition (EMT). Furthermore, the enhancer of zeste homolog 2-gene (EZH2) is a master regulator of controlling the stem cell differentiation and the cell proliferation processes. We aim to evaluate the implication of miR-33b in the EMT pathway in HER2+ breast cancer (BC) and to analyze the role of EZH2 in this process as well as the interaction between them. miR-33b is downregulated in HER2+ BC cells vs healthy controls, where EZH2 has an opposite expression in vitro and in patients' samples. The upregulation of miR-33b suppressed proliferatio…

Additional file 1: of A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

List of all the biological processes enriched for the 71 differentially methylated genes between responder and non-responder patients according to the Gene Ontology analysis (DOCX 32 kb)

Associations between aromatase CYP19 rs10046 polymorphism and breast cancer risk: from a case-control to a meta-analysis of 20,098 subjects.

Lifetime exposure to estrogen is a factor that plays an important role in the pathogenesis and progression of breast cancer. Genetic variants in genes of the biosynthesis and metabolism of estrogen have been associated with breast cancer risk. Among them, the CYP19 gene encodes for aromatase, the enzyme that catalyzes the conversion of androgens to estrogens. The rs10046 polymorphism on the CYP19 gene has been related to levels of circulating estradiol and to the estradiol/testosterone ratio. To date, epidemiological studies of rs10046 have been performed in different populations with contradictory results. In the present study, we have conducted a case-control analysis (522 cases and 1221 …

The role of miR-26a and miR-30b in HER2+ breast cancer trastuzumab resistance and regulation of the CCNE2 gene

AbstractA subset of HER2+ breast cancer patients manifest clinical resistance to trastuzumab. Recently, miR-26a and miR-30b have been identified as trastuzumab response regulators, and their target gene CCNE2 seems to play an important role in resistance to trastuzumab therapy. Cell viability was evaluated in trastuzumab treated HER2+ BT474 wt (sensitive), BT474r (acquired resistance), HCC1954 (innate resistance), and MDA-MB-231 (HER2−) cell lines, and the expression of miR-26a, miR-30b, and their target genes was measured. BT474 wt cell viability decreased by 60% and miR-26a and miR-30b were significantly overexpressed (~3-fold, p = 0.003 and p = 0.002, respectively) after trastuzumab trea…

Isopropanolic Cimicifuga racemosa is favorable on bone markers but neutral on an osteoblastic cell line

Postmenopausal women treated with an isopropanolic extract of Cimicifuga racemosa underwent a decrease in the urinary concentration of N-telopeptides, a marker of bone resorption, and an increase in alkaline phosphatase, a marker of bone formation, at the third month of therapy. Serum from treated women did not modify the activity of alkaline phosphatase or the expression of three genes, runt-related transcription factor-2 (Runx-2), alkaline phosphatase, and osteocalcin, when added to the MC3T3-E1 osteoblastic cell line.

Aurora kinases in ovarian cancer

Aurora kinases (AURK) are key regulators of the mitotic spindle formation. AURK is frequently overexpressed in ovarian cancer and this overexpression has been frequently associated with prognosis in these tumours. Interestingly, AURK have been shown to interact with DNA repair mechanisms and other cell cycle regulators. These functions have brought light to Aurora family as a potential target for anticancer therapy. In the last years, two clinical trials with different AURK inhibitors have shown activity in epithelial and clear-cell ovarian cancer. Although there is a lack of predictive factors of AURK inhibition activity, recent trials have identified some candidates. This review will focu…

MicroRNA Profile in Response to Doxorubicin Treatment in Breast Cancer

UNLABELLED Chemotherapy treatment is the standard in triple negative breast cancers, a cancer subgroup which lacks a specific target. The mechanisms leading to the response, as well as any markers that allow the differentiation between responder and non-responder groups prior to treatment are unknown. In parallel, miRNAs can act as oncogenes or tumor suppressors and there is evidence of their involvement in promoting resistance to anticancer drugs. Therefore we hypothesized that changes in miRNA expression after doxorubicin treatment may also be relevant in treatment response. OBJECTIVE To study miRNAs that are differentially expressed in response to doxorubicin treatment. METHODS One lumin…

Additional file 5: of A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

Representation of the pathway interaction network of FERD3L and TRIP10 with other genes using Pathway Commons. FERD3L and TRIP10 are able to interact with different genes that have shown to be implicated in cancer drug resistance (PPT 452 kb)

Additional file 4: of A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

CpGs studied by pyrosequencing in the DC and in the VC to validate methylation in the candidate genes identified in the 450k array (Illumina). In bold, CpGs from 450k array. Normal type, consecutive CpGs (PPT 140 kb)

Additional file 6: of A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

Mean differences in methylation levels according to clinicopathological prognostic factors in both cohorts (DC+VC). cT, clinical tumor size; cN, clinical nodule affectation (PPTX 48 kb)

The role of CD40 and CD40L in bone mineral density and in osteoporosis risk: A genetic and functional study.

Compelling data are revealing that the CD40/CD40L system is involved in bone metabolism. Furthermore, we have previously demonstrated that polymorphisms in both genes are associated with bone phenotypes. The aim of this study is to further characterize this association and to identify the causal functional mechanism. We conducted an association study of BMD with 15 SNPs in CD40/CD40L genes in a population of 779 women. In addition, we assessed the functionality of this association through the study of the allele-dependent expression of CD40 and CD40L in peripheral blood leukocytes (PBLs) and in human osteoblasts (OBs) obtained from bone explants by qPCR and by sequencing. When an allelic im…

Estrogen receptor agonists and immune system in ovariectomized mice.

Several data implicate the immune system in bone lost after estrogen deficiency, however, some of the effects on the immune system of estrogen deficiency or of estrogen receptor (ER) modulation are not well established. In this study, the effect of ER agonists on the immune system in ovariectomized mice is analyzed. Mice were ovariectomized and were administered 17β-estradiol (E2), raloxifene (RAL) or genistein (GEN). The effect of a 4-week treatment on bone turnover and on several parameters that reflect the status of the immune system was studied. Results show that ovariectomy provoked both uterine atrophy and thymic hypertrophy. Although RAL corrected thymic hypertrophy, only E2 correct…

Gene expression profile induced by ovariectomy in bone marrow of mice: a functional approach to identify new candidate genes associated to osteoporosis risk in women.

Osteoporosis is a multifactorial skeletal pathology with a main genetic component. To date, however, the majority of genes associated with this pathology remain unknown since genes cataloged to date only explain a part of the heritability of bone phenotypes. In the present study, we have used a genome-wide gene expression approach by means of microarrays to identify new candidate genes involved in the physiopathology of osteoporosis, using as a model the ovariectomized (OVX) mice by comparing global bone marrow gene expression of the OVX mice with those of SHAM operated mice. One hundred and eighty transcripts were found to be differentially expressed between groups. The analysis showed 23 …

No effect of Cimicifuga racemosa extract on serum interleukin-6 levels and prostacyclin production by human endothelial cells

Additional file 8: of A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

Sequence of primers used by pyrosequencing in the validation assay of candidate genes obtained from 450k array (PPT 143 kb)

Alleles and haplotypes of the estrogen receptor alpha gene are associated with an increased risk of spontaneous abortion.

Objective To investigate whether polymorphisms in estrogen receptor alpha (ERα) or beta (ERβ) genes are associated with a risk of miscarriage. Design A retrospectively analyzed, prospectively obtained database of cases and controls. Setting University hospital menopause unit. Patient(s) 177 women with at least one spontaneous abortion and 442 controls with at least one live birth and no history of miscarriage. Intervention(s) None. Main Outcome Measure(s) Genotype frequencies and odd ratios for abortion risk in cases and controls for four single nucleotide polymorphisms (SNPs) located in intron 1 (C>T and A>G), intron 4 (A>T), and exon 8 (T>C) for the ERα gene, and two SNPs located in intro…

Additional file 7: of A two-gene epigenetic signature for the prediction of response to neoadjuvant chemotherapy in triple-negative breast cancer patients

Clinical inclusion and exclusion criteria followed to select TNBC patients for the methylation study (PPT 89 kb)