No abstract

Whole genome sequencing (WGS) is a powerful tool for postnatal genetic diagnosis, but relevant clinical studies in the field of prenatal diagnosis are limited. The present study aimed to prospectively evaluate the utility of WGS compared with chromosomal microarray (CMA) and whole exome sequencing (WES) in the prenatal diagnosis of fetal structural anomalies. We performed trio WGS (≈40-fold) in parallel with CMA in 111 fetuses with structural or growth anomalies, and sequentially performed WES when CMA was negative (CMA plus WES). In comparison, WGS not only detected all pathogenic genetic variants in 22 diagnosed cases identified by CMA plus WES, yielding a diagnostic rate of 19.8% (22/110), but also provided additional and clinically significant information, including a case of balanced translocations and a case of intrauterine infection, which might not be detectable by CMA or WES. WGS also required less DNA (100 ng) as input and could provide a rapid turnaround time (TAT, 18 ± 6 days) compared with that (31 ± 8 days) of the CMA plus WES. Our results showed that WGS provided more comprehensive and precise genetic information with a rapid TAT and less DNA required than CMA plus WES, which enables it as an alternative prenatal diagnosis test for fetal structural anomalies.

Tamoxifen inhibits estrogen receptor (ER)-positive breast cancer growth while CD36 potentiates cancer metastasis. The effects of CD36 on proliferation/migration of breast cancer cells and tamoxifen-inhibited ER-positive cell growth are unknown. In this study, we correlated the mortality of breast cancer patients to tumor CD36 expression levels. We also found CD36 was higher in ER-rich (MCF-7>T-47D~ZR-75-30) than ER-negative (MDA-MB-231) cells. CD36 siRNA decreased viability and migration of MCF-7 and MDA-MB-231 cells with more potent effects on MCF-7 cells. Inversely, high expressing CD36 enhanced cell growth/migration. Mechanistically, CD36 increased expression of genes responsible for cell proliferation, migration and anti-apoptosis. CD36 also activated ERα and ER-targeted genes for cell cycles, and phosphorylated ERK1/2 (p-ERK1/2). Tamoxifen inhibited CD36 and p-ERK1/2 in ERα-positive but not ERα-negative cells. Reciprocally, inhibition of MCF-7 cell growth by tamoxifen was attenuated by high expressing CD36. CD36, ERα and p-ERK1/2 expression was higher in tamoxifen-resistant MCF-7 (MCF-7/TAMR) cells than normal MCF-7 cells. However, CD36 siRNA restored the capacity of tamoxifen inhibiting MCF-7/TAMR cell growth. CD36 antibody inhibited cell growth and expression of ERα, p-ERK1/2 and CCND1. Therefore, our study unveils a pro-tumorigenic role of CD36 in breast cancer by enhancing proliferation/migration of breast cancer cells while attenuating tamoxifen-inhibited ER-positive cell growth.

Co-treatment with T317 and metformin inhibited the development of atherosclerosis without activation of lipogenesis, suggesting that combined treatment with T317 and metformin may be a novel approach to inhibition of atherosclerosis.