Neoadjuvant Chemotherapy Alters Neuropilin-1, PlGF, and SNAI1 Expression Levels and Predicts Breast Cancer Patients Response.

Circulating proteins hold a potential benefit as biomarkers for precision medicine. Previously, we showed that systemic levels of neuropilin-1 (NRP-1) and its associated molecules correlated with poor-prognosis breast cancer. To further identify the role of NRP-1 and its interacting molecules in correspondence with patients' response to neoadjuvant chemotherapy (NAC), we conducted a comparative study on blood and tissue samples collected from a cohort of locally advanced breast cancer patients, before and after neoadjuvant chemotherapy (NAC). From a panel of tested proteins and genes, we found that the levels of plasma NRP-1, placenta growth factor (PlGF) and immune cell expression of the transcription factor SNAI1 before and after NAC were significantly different. Paired t-test analysis of 22 locally advanced breast cancer patients showed that plasma NRP-1 levels were increased significantly (p = 0.018) post-NAC in patients with pathological partial response (pPR). Kaplan-Meier analysis indicated that patients who received NAC cycles and their excised tumors remained with high levels of NRP-1 had a lower overall survival compared with patients whose tissue NRP-1 decreased post-NAC (log-rank p = 0.049). In vitro validation of the former result showed an increase in the secreted and cellular NRP-1 levels in resistant MDA-MB-231 cells to the most common NAC regimen Adriyamicin/cyclophosphamide+Paclitaxel (AC+PAC). In addition, NRP-1 knockdown in MDA-MB-231 cells sensitized the cells to AC and more profoundly to PAC treatment and the cells sensitivity was proportional to the expressed levels of NRP-1. Unlike NRP-1, circulating PlGF was significantly increased (p = 0.014) in patients with a pathological complete response (pCR). SNAI1 expression in immune cells showed a significant increase (p = 0.018) in patients with pCR, consistent with its posited protective role. We conclude that increased plasma and tissue NRP-1 post-NAC correlate with pPR and shorter overall survival, respectively. These observations support the need to consider anti-NRP-1 as a potential targeted therapy for breast cancer patients who are identified with high NRP-1 levels. Meanwhile, the increase in both PlGF and SNAI1 in pCR patients potentially suggests their antitumorigenic role in breast cancer that paves the way for further mechanistic investigation to validate their role as potential predictive markers for pCR in breast cancer.

Neuropilin-1 Associated Molecules in the Blood Distinguish Poor Prognosis Breast Cancer: A Cross-Sectional Study.

Circulating plasma and peripheral blood mononuclear (PBMCs) cells provide an informative snapshot of the systemic physiological state. Moreover, they provide a non-invasively accessible compartment to identify biomarkers for personalized medicine in advanced breast cancer. The role of Neuropilin-1 (NRP-1) and its interacting molecules in breast tumor tissue was correlated with cancer progression; however, the clinical impact of their systemic levels was not extensively evaluated. In this cross-sectional study, we found that circulating and tumor tissue expression of NRP-1 and circulating placental growth factor (PlGF) increase in advanced nodal and metastatic breast cancer compared with locally advanced disease. Tumor tissue expression of NRP-1 and PlGF is also upregulated in triple negative breast cancer (TNBC) compared to other subtypes. Conversely, in PBMCs, NRP-1 and its interacting molecules SEMA4A and SNAI1 are significantly downregulated in breast cancer patients compared to healthy controls, indicating a protective role. Moreover, we report differential PBMC expression profiles that correlate inversely with disease stage (SEMA4A, SNAI1, PLXNA1 and VEGFR3) and can differentiate between the TNBC and non-TNBC tumor subtypes (VEGFR3 and PLXNA1). This work supports the importance of NRP-1-associated molecules in circulation to characterize poor prognosis breast cancer and emphasizes on their role as favorable drug targets.

Advanced Maternal Age and Risks for Adverse Pregnancy Outcomes: A Population-Based Study in Oman.

To test the hypothesis that advanced maternal age (AMA) of 35 years and above is associated with increased risk of adverse pregnancy outcomes, we performed a population-based retrospective study using data from the 2000 National Health Survey in Oman. The last pregnancy outcomes of mothers aged ≥35 years were compared with adult mothers aged 20-34 years using bivariate and multivariate statistical techniques. Significantly increased risks of spontaneous abortion, gestational diabetes, preeclampsia, prolonged labor, and cesarean section delivery have been observed for advanced maternal age. Our findings may contribute to cross-cultural understanding of the risks associated with AMA and will facilitate evidence-based counseling of older expectant mothers.

The reproductive cycle of the male house gecko, Hemidactylus flaviviridis, in relation to plasma steroid concentrations, progesterone receptors, and steroidogenic ultrastructural features, in Oman.

The annual testicular cycle of the house gecko Hemidactylus flaviviridis in Oman was studied. Plasma testosterone (T), estradiol (E2) and progesterone (P) concentrations were measured using a sensitive HPLC-MS/MS detection technique. The ultrastructural steroidogenic features in Sertoli and Leydig cells, which were the major source of steriodogenesis, were examined, using transmission electron microscopy (TEM). In addition, progesterone receptors (PR) were examined throughout the testicular cycle, using an immunohistochemical technique. The steroidogenic ultrastructural features were characterized by the presence of smooth endoplasmic reticulum (SER) in the form of cisternal whorls and tubular cisternae, presence of swollen vesiculated mitochondria, and association between SER, mitochondria and lipid droplets. The rise in plasma steroid concentrations was closely associated with the development of the ultrastructural features and PR expression in Leydig and Sertoli cells. During the active phase (November-May), there was a significant rise in plasma steroid concentrations (P<0.05) related to well developed steroidogenic features and strongly expressed PR. During the quiescent phase (June-August) there was a significant decline in plasma steroid concentrations, undeveloped steroiodogenic features and weakly expressed PR. The Renal Sexual Segment (RSS) was fully developed during the active phase. The data provides strong evidence that these ultrastructural steroidogenic features were related to the plasma sex steroid concentrations during the testicular cycle.

Biodegradation of crude oil and n-alkanes by fungi isolated from Oman.

Ten fungal species isolated from tar balls collected from the beaches of Oman were tested for their abilities to grow and degrade n-alkanes and crude oil. The abilities of Aspergillus niger, A. ochraceus and Penicillium chrysogenum to degrade n-alkanes (C13-C18), crude oil were compared and their mycelial biomass was measured. Significant differences were found in the utilization of C15, C16, C17 and C18 by the three fungi. Similarly, significant differences we found in the amount of biomass produced by the three fungi growing on C13, C17, C18 and crude oil. The correlation coefficient of biomass and oil utilization was not statistically significant for Aspergillus niger, significant for Aspergillus terreus and highly significant for P. chrysogenum.

A study of fertility patterns of ever married women in oman.

OBJECTIVE: To examine the relation between age, education, residence and fertility rate and change in fertility rate between 1994/95 and 1999/2000. METHODS: The data for the study was extracted from the Oman National Health Survey, 2000. The birth histories data was used to extract data on woman years and births in the periods 1990 to 1994 and 1995 to 2000. RESULTS: The marital fertility rate in 1999/2000 was 7.12 births. The rates for rural and urban dwellers were 8.07 and 6.75 respectively in 1999/2000. Corresponding rates in 1994/95 (8.65, 8.30 and 9.69 respectively) were significantly higher than those in 1999/2000 for all categories, indicating a reduction in rates. In both periods the higher the education level of the mother the lower her fertility. CONCLUSION: Education was a strong determinant of fertility. This study confirms that the higher the education of the woman the lower her fertility and that fertility is on the decline in Oman.

Fungi and aflatoxins associated with spices in the Sultanate of Oman.

One hundred and five samples of seven spices (cumin, cinnamon, clove, black pepper, cardamom, ginger, and coriander) were purchased from five popular companies in the Sultanate of Oman. The spices were surveyed for the mycoflora and aflatoxins. Twenty fungal species were isolated in which Aspergillus flavus, A. niger. Penicillium, Rhizopus, and Syncephalastrum racemosum were the most dominant. When colony forming units per gm (cfu/gm) of fungi were compared, significant differences were found among spices and companies. Of the seven spices studied, clove was found to be the least contaminated, while cumin was the most contaminated. None of the 15 selected samples of the spices contaminated by A. flavus were found to contain aflatoxins. Nevertheless, nine isolates (45%) of the twenty A. flavus strains screened for aflatoxins were aflatoxigenic. The moisture content of most of the spices was below the maximum standard limit. The results showed that the spices were contaminated by some fungi that might constitute health hazards for humans.