BIIB021, an orally available and small-molecule inhibitor of HSP90, activates intrinsic apoptotic pathway in human cervical adenocarcinoma cell line (HeLa).

OBJECTIVE: Heat shock protein 90 (HSP90) is a highly conserved ATP-dependent chaperone protein that plays a vital role in tumorigenesis. This study aims to investigate the apoptosis inducer role of BIIB021 (orally available HSP90 inhibitors) compound via inhibition of HSP90 activity in the human cervical cancer cell line (HeLa). PATIENTS AND METHODS: The anticancer potential of BIIB021 was determined by XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)] cell proliferation assay against the human cervical cancer cell line (HeLa). ATPase and luciferase aggregation assays were carried out to detect the HSP90 inhibitor potential of BIIB021. To determine the antiproliferative mechanism of the BIIB021, the expression level of the pro-apoptotic and antiapoptotic markers was determined by reverse transcription polymerase chain reaction (RT-PCR) and ELISA experiments. RESULTS: BIIB021 exhibited a cytotoxic effect on HeLa cell proliferation and the inhibitory concentration (IC)50 dose of BIIB021 was found to be 14.79 nM at 48 h. BIIB021 decreased the ATP hydrolysis rate of HSP90 and blocked the refolding of the desaturated luciferase in the presence of ATP. To understand the antiproliferative mechanism of the BIIB021 in HeLa cells, the mRNA and protein expression levels of the apoptotic markers [BCL-2 associated X (BAX), B-cell lymphoma 2 (BCL-2), cytochrome-c (CYT-c), and caspase-3 (CAS-3)] were determined by RT-PCR and ELISA experiments. The results obtained indicated that BIIB021 decreased BCL-2 levels and increased BAX, CYT-c, and CAS-3 levels in human cervical cancer cells. CONCLUSIONS: These results confirmed that BIIB021 inhibited the chaperone activity of HSP90, resulting in anti-proliferating effects in cervical cancer cells via the induction of the intrinsic apoptotic pathways.

Evaluation of second trimester uterine artery doppler indices in women diagnosed with COVID-19 during the first trimester of their pregnancy.

OBJECTIVE: This study aimed at evaluating the hypothesis that 6-14 months pregnant women diagnosed with COVID-19 may have abnormal placental function detectable by increased uterine artery Doppler indices in the second trimester and whether these women could benefit from treatment. PATIENTS AND METHODS: A total of 63 women were diagnosed with COVID-19 during the first trimester of their pregnancy and 68 healthy women were involved according to the exclusion criteria. In both groups, Doppler measurements were performed for the determination of high-risk pregnancy by increased uterine artery Doppler indices in the second trimester. RESULTS: It was observed that uterine artery Doppler indices (PI and RI) were significantly increased in second trimester women with COVID-19 infection compared to those without COVID-19. Furthermore, the number of women with a PI value exceeding the 95th percentile and the number of patients with early diastolic notch were higher in the COVID group compared to the control group. CONCLUSIONS: Doppler Ultrasound measurement may be a potential method for the management of high-risk pregnancies after asymptomatic/mild COVID-19 infection.

Effects of laparoscopic tubal ligation on ovarian blood flow and steroidogenesis.

Changes in serum ovarian hormone and gonadotrophine levels and ovarian artery blood flow rate by Doppler ultrasonography following laparoscopic tubal sterilization were evaluated. Forty-seven cases of laparoscopic tubal sterilization by electrocoagulation were included in the study. Forty-two women who used nonhormonal contraceptive methods were randomized as a control group. Serum concentrations of estradiol, FSH, LH, progesterone and bilateral ovarian artery pulsatility indexes were measured at baseline and at three, six and 12 months. In the study group, the mean value of midluteal progesterone was significantly decreased three months postoperatively 3. and bilateral ovarian artery pulsatility indexes were increased three and six months postoperatively, compared to their preoperative values. However, there was no statistical difference between bilateral ovarian PI values calculated preoperatively and at 12 months. Laparoscopic tubal ligation by electrocoagulation may temporarily cause reduced bilateral ovarian artery flow and corpus luteum dysfunction proven by low mid-luteal progesterone levels.