BRCA 1/BRCA 2 Pathogenic/Likely Pathogenic Variant Patients with Breast, Ovarian, and Other Cancers.

The demographic and clinical characteristics of patients who have BRCA 1/BRCA 2 pathogenic/likely pathogenic variants may differ from their relatives who had BRCA-related cancer. In this study, we aimed to demonstrate the clinical and demographic findings of patients who had BRCA-related cancer and to assess the differences comparing their relatives who had BRCA-related cancer with breast, genital tract, prostate, and pancreas cancers as well. The results of sequencing analysis of 200 cancer patients (190 women, 10 men) who have been directed to genetic counseling with an indication of BRCA1/BRCA2 testing from different regions across 9 medical oncology centers were retrospectively analyzed. A total of 200 consecutive cancer patients who harbored the BRCA1/BRCA2 pathogenic/likely pathogenic variant (130 (65%) patients harbored BRCA 1 pathogenic/likely pathogenic variant, and 70 harbored BRCA 2 pathogenic/likely pathogenic variant) were included. Of these, 64.0% had breast cancer (43.8% of them had the triple-negative disease, and about 2.3% had only the HER-2 mutant), 31.5% had genital cancers (92.1% of them had ovarian cancer, 3.2% had endometrium, and 1.6% had peritoneum cancer as the primary site and mostly serous adenocarcinoma was the most common histopathology and 14.3% of the patients had endometrioid adenocarcinoma), 3.5% had prostate (median time from metastasis to castration-resistant status was 28 months) and 1.0% had pancreas cancer. Newly diagnosed cancer (breast and ovary) patients who had BRCA 1/BRCA 2 pathogenic/ likely pathogenic variant were younger than their previous cancer diagnosed (breast, ovary, and pancreas) parents who harbored BRCA pathogenic/likely pathogenic variant. We suggest that the genetic screening of BRCA 1/ BRCA 2 pathogenic/likely pathogenic variant is needed as a routine screening for those with a personal or family history of breast, ovarian, tubal, or peritoneal cancer. In addition, once BRCA 1 or BRCA 2 germline pathogenic variant has been identified in a family, testing of at-risk next-generation relatives earlier can identify those family members who also have the familial pathogenic variant, and thus need increased surveillance.

Association of body mass index and weight gain patterns with albumin excretion in pregnancy.

AIM: We examined body mass index (BMI) and gestational weight gain (GWG) patterns of pregnant women and investigated the impact of these factors on the urinary albumin-creatinine ratio (ACR) during pregnancy. METHODS: The data of 163 women whose basal BMI and ACR were measured during the first trimester were used in this study. Body weight alone between 12-16 weeks and body weight together with ACR after 37 weeks of gestation were measured. RESULTS: Overall, 46% of women were overweight or obese, 60.7% had excessive weight gain and 16.6% had inadequate weight gain. Only 22.7% of women gained weight within the recommended range. There was no difference in weight gain patterns with respect to BMI. ACR during the third trimester was significantly higher than during the first trimester (7.08 [0.00-1180.90] mg/g vs 4.73 [0.00-275.00] mg/g, respectively; P = 0.001). The ACR of obese women was higher than in normal weight subjects during the third trimester (16.79 mg/g [0.01-1180.90] vs 8.07 mg/g [0.10-402.14] respectively; adjusted P = 0.015). Both ACR change and third trimester ACR were weakly but significantly correlated with basal BMI (r: 0.228 P: 0.003 and r: 0.301 P < 0.001, respectively) but not with GWG or GWG rate. Basal BMI was not associated with first-trimester ACR. CONCLUSION: Obesity is associated with an increase in urinary albumin excretion during the course of pregnancy. Distinction of this relationship during pregnancy offers an opportunity for further research on pathophysiological mechanisms. The alarmingly high rate of non-compliance with IOM guidelines in pregnant women is a concern. Prompt measures for counseling of women before and during pregnancy in order to maintain healthy weight are needed.

Early postpartum lactation effects of cesarean and vaginal birth.

OBJECTIVES: Breastfeeding has positive effects for both, the mother and the infant. The purpose of the study was to ex-amine how cesarean delivery and vaginal delivery influenced subsequent breastfeeding. The study was conducted at the Kirikkale University Medical School. MATERIAL AND METHODS: Breastfeeding outcomes after an elective cesarean delivery and after a planned vaginal delivery were compared. The study included 169 consenting mothers who gave birth to healthy infants (86 cesarean deliveries and 83 vaginal deliveries) between March and September 2001. All cesarean deliveries were performed under regional anesthesia. RESULTS: Elective cesarean delivery was performed at a significantly earlier gestational age as compared to vaginal delivery (p = 0.001). Maternal age in the planned vaginal delivery group was significantly lower (p = 0.003). As for the change in prolactin levels, the results were similar but not statistically significant (p = 0.21). The frequency of breastfeeding per day did not differ significantly between the groups (p = 0.20). However, women after cesarean delivery tended to breastfeed more often than after vaginal delivery (p = 0.003). Mean number of points recorded at the first breastfeeding session, according to the LATCH charting system, was lower in the group after cesarean delivery as compared to vaginal labor. The difference between the average point scores of vaginal delivery and cesarean delivery mothers was found to be meaningful in favor of the women after vaginal delivery (p = 0.05). CONCLUSIONS: Elective cesarean section has negative effects on breastfeeding. Our results indicate that cesarean section constitutes a risk factor for delayed lactogenesis.

Synthesis and colloidal polymerization of ferromagnetic Au-Co nanoparticles into Au-Co3O4 nanowires.

The preparation of cobalt oxide nanowires with gold nanoparticle (AuNP) inclusions (Au-Co(3)O(4) nanowires) via colloidal polymerization of dipolar core-shell NPs is reported. Polystyrene-coated ferromagnetic NPs composed of a dipolar metallic cobalt shell and a gold NP core (PS-AuCoNPs) were synthesized by thermolysis of octacarbonyldicobalt [Co(2)(CO)(8)] in the presence of AuNP seeds and polymeric ligands. The colloidal polymerization process of these dipolar PS-AuCoNPs comprises dipolar nanoparticle assembly and solution oxidation of preorganized NPs to form interconnected cobalt oxide nanowires via the nanoscale Kirkendall effect, with AuNP inclusions in every repeating unit of the one-dimensional mesostructure. Calcination of the polymer-coated nanowires afforded polycrystalline Au-Co(3)O(4) nanowires that were determined to be electroactive. Nanocomposite materials were characterized by transmission electron microscopy, field-emission scanning electron microscopy, X-ray diffraction, vibrating sample magnetometry, and cyclic voltammetry. We demonstrate that the optical and electrochemical properties of Au-Co(3)O(4) nanowires are significantly enhanced in comparison with hollow Co(3)O(4) nanowires prepared via colloidal polymerization.

Predictive Gene Signature for Pyrazolopyrimidine Derivative c-Src Inhibitor 10a Sensitivity in Melanoma Cells.

Melanoma is a highly aggressive cancer with poor prognosis. Although more than 80% of melanomas harbor an activating mutation in genes within the MAPK pathway, which are mutually exclusive, usefulness of therapies targeting MAPK pathway are impeded by innate and/or acquired resistance in most patients. In this study, using melanoma cells, we report the efficacy of a recently developed pyrazolo[3,4-d]pyrimidine derived c-Src inhibitor 10a and identify a molecular signature which is predictive of 10a chemosensitivity. We show that the expression of TMED7, PLOD2, XRCC5, and NSUN5 are candidate biomarkers for 10a sensitivity. Although an undifferentiated/mesenchymal/invasive status of melanoma cells is associated with resistance to 10a, we show here for the first time that melanoma cells can be sensitized to 10a via treatment with valproic acid, a histone deacetylase inhibitor.

Erythropoietin Promotes Glioblastoma via miR-451 Suppression.

Erythropoietin (EPO) is an erythropoiesis stimulating growth factor and hormone. EPO has been widely used in the treatment of chronic renal failure, cancer, and chemotherapy-related anemia for three decades. However, many clinical trials showed that EPO treatment may be associated with tumorigenesis and cancer progression. EPO is able to cross blood-brain barriers, and this may lead to an increased possibility of central nervous system tumors such as glioblastoma. Indeed, EPO promotes glioblastoma growth and invasion in animal studies. Additionally, EPO increases glioblastoma cell survival, proliferation, migration, invasion, and chemoresistancy in vitro. However, the exact mechanisms of cancer progression induced by EPO treatment are not fully understood. Posttranscriptional gene regulation through microRNAs may contribute to EPO's cellular and biological effects in tumor progression. Here, we aimed to study whether tumor suppressive microRNA, miR-451, counteracts the positive effects of EPO on U87 human glioblastoma cell line. Migration and invasion were evaluated by scratch assay and transwell invasion assay, respectively. We found that EPO decreased basal miR-451 expression and increased cell proliferation, migration, invasion, and cisplatin chemoresistancy in vitro. miR-451 overexpression by transfection of its mimic significantly reversed these effects. Furthermore, ectopic expression of miR-451 inhibited expression of its own target genes, such as metalloproteinases-2 and -9, which are stimulated by EPO treatment and involved in carcinogenesis processes, especially invasion. These findings suggest that miR-451 mimic delivery may be useful as adjuvant therapy in addition to chemotherapy and anemia treatment by EPO and should be tested in experimental glioblastoma models.

Gene expression changes in bioceramic paste-treated human dental pulp cells.

We evaluated the gene expression profiles of human dental pulp cells exposed to iRoot BP using microarray after 24 and 72 h. The results were verified using quantitative reverse transcriptase PCR analysis. Of the 36,000 transcripts arrayed, 21 were up-regulated and 15 were down-regulated by more than two fold. The largest group of up-regulated genes included those involved in nucleobase-containing compound metabolic processes, cell communication, protein metabolic processes, developmental processes, and biological regulation. The largest groups of down-regulated genes were those involved in cell communication, development, and biological regulation processes. In conclusion, iRoot BP affects the expression of genes involved in different biological processes in human dental pulp cells. (J Oral Sci 58, 307-315, 2016).

Effects of lamotrigine and topiramate on brain maturation and cognitive functions in offspring of pregnant rats - preliminary study.

BACKGROUND: Antiepileptic drugs (AED) which are used to treat seizures in pregnant women, infants, and young children may cause cognitive impairment or other uncertain injury. However, the precise mechanisms responsible for the negative effects of new AEDs like lamotrigine (LTG) and topiramate (TPM) in the developing brain are still unclear. OBJECTIVES: To investigate the GFAP, NCAM and S100B levels in the whole brain of newborn rats on postnatal 1 day and in the hippocampus of adult rats to find out the effect of TPM and LTG on cognitive impairment and brain maturation. MATERIAL AND METHODS: Twenty eight pregnant rats were randomly divided into 7 groups with 4 animals in each group. The first group, receiving no drugs, was assigned as the control group. The study groups received intraperitoneal TPM or LTG injections in each trimester. Western blot analysis of the GFAP, NCAM and S100B was performed in the offspring. Behavioral tests were performed at postnatal day 75. RESULTS: The rats in the TPM-I and TPM-III groups had a significant impairment in escape latency on the 5th day as compared to the control rats in a Morris water maze test. In addition, in the expression of astrocyte derived markers, GFAP was upregulated, whereas S100ß and NCAM were downregulated in the whole brain on postnatal day 1, in offspring exposed to LTG and TPM in utero. CONCLUSIONS: The detrimental effects of TPM and LTG appear to be confined particularly to the early stages of brain development. And TPM seems to have a partial role in the cognitive impairment.