Efficacy and impact of PARPi monotherapy to subsequent platinum-based chemotherapy in BRCA1/2 mutant ovarian cancer patients with secondary platinum-sensitive relapse / 부인종양

Objective@#The therapeutic effect of poly(ADP-ribose) polymerase inhibitors (PARPi) monotherapy compared with platinum-based chemotherapy, and the impact to subsequent platinum-based chemotherapy after PARPi resistance were inconclusive. @*Methods@#BRCA1/2 mutant ovarian cancer patients with secondary platinum-sensitive relapse were included. The patients did not receive any maintenance regimen after first- and second-line platinum therapy, and the secondary platinum-free interval (PFI) was more than 6 months. Patients in study group were treated with PARPi monotherapy until disease progression, and patients in control group were treated with platinum-based chemotherapy. @*Results@#A total of 64 patients were retrospectively analyzed, including 31 (48.4%) in study group and 33 (51.6%) in control group. The objective response rate (77.4% vs. 84.0%; p=0.538) and median progression-free survival (8.6 vs. 11.1 months; p=0.679) were comparable. PARPi monotherapy significantly prolonged post-recurrent survival (PRS) (hazard ratio [HR]=0.35; p=0.024), and was the independent factor associated with PRS (HR=0.33; p=0.038) in multivariate analysis. The median time from treatment to first subsequent therapy or death (mTFST) of patients with platinum-based chemotherapy after PARPi progression and patients in control group with PFI ≥6 months after third-line platinum-based chemotherapy was comparable (mTFST: 7.5 vs. 7.1 months; p=0.800). Further survival analysis showed that PRS of patients with PARPi monotherapy were similar to patients with PFI ≥6 months after third-line platinum chemotherapy (HR=0.66; p=0.503), and superior to patients with PFI <6 months after third-line platinum chemotherapy (HR=0.15; p=0.009). @*Conclusion@#PARPi monotherapy was equivalent to platinum-based chemotherapy for BRCA1/2-mutated ovarian cancer patients with secondary platinum-sensitive recurrence, and could improve prognosis.

Serum bilirubin is negatively associated with white blood cell count

OBJECTIVE: Bilirubin is considered an important antioxidant, anti-inflammatory factor and immunomodulator. The current investigation aimed to explore the association between bilirubin and white blood cell (WBC) count in a large Chinese cohort. METHODS: A total of 61091 participants (29259 males, 31832 females) were recruited from a Chinese tertiary hospital. Data were sorted by sex, and the association between bilirubin and WBC count was analyzed after dividing bilirubin levels into quartiles. RESULTS: Most parameters (including age, body mass index, systolic blood pressure, diastolic blood pressure, alanine aminotransferase, total bilirubin, blood urea nitrogen, creatinine, uric acid, triglycerides and WBC count) were significantly higher in men than in women. Bilirubin displayed significant negative relationships with most other measured variables. Linear logistic regression analysis further indicated their negative relationships. Females showed a significantly higher frequency of leucopenia than males. Significant associations of leucopenia with high bilirubin quartiles were shown in binary logistic regression models for both sexes, with a much closer association in men than in women. For instance, for men with bilirubin levels in quartile 4, the adjusted likelihood of leucopenia was 1.600-times higher than that of men with values in quartile 1. For women with bilirubin levels in quartile 4, the adjusted likelihood of leucopenia was 1.135-times higher than that of women with values in quartile 1. CONCLUSION: Bilirubin is negatively related to WBC count. Significant associations exist between leucopenia and high bilirubin quartiles, and these associations are more obvious in men than in women.

Effect and Underlying Mechanism of Bu-Shen-An-Tai Recipe on Ovarian Apoptosis in Mice with Controlled Ovarian Hyperstimulation Implantation Dysfunction / 华中科技大学学报（医学）（英德文版）

The effect and underlying mechanism of Bu-Shen-An-Tai recipe on ovarian apoptosis in mice with controlled ovarian hyperstimulation (COH) implantation dysfunction were studied.The COH implantation dysfunction model in mice was established by intraperitoneal injection of 7.5 IU pregnant mare's serum gonadotrophin (PMSG),followed by 7.5 IU human chorionic gonadotrophin (HCG) 48 h later.Then the female mice were mated with male at a ratio of 2:l in the same cage at 6:00 p.m.The female mice from normal group were injected intraperitoneally with normal saline and mated at the corresponding time.Day 1 of pregnancy was recorded by examining its vaginal smears at 8:00 a.m.of the next day.Fifty successfully pregnant mice were equally randomly divided into 5 groups:normal control pregnant group (NC),COH implantation dysfunction model group (COH),low dosage of Bu-Shen-An-Tai recipe group (LOW),middle dosage of Bu-Shen-An-Tai recipe group (MID) and high dosage of Bu-Shen-An-Tai recipe group (HIGH).Then from day 1,the mice in different groups were respectively intragastrically given corresponding treatments at 9:00 a.m.for 5 consecutive days.The concentrations of 17β-estradiol (E2) and progesterone (P4) were determined by radioimmunoassay (RIA).The ultrastructural changes of ovarian tissues were observed by transmission electron microscope (TEM).The histopathological changes of ovarian tissues were observed by HE staining.The number of atretic follicles and pregnant corpus luteum were also recorded.TUNEL was applied to measure apoptotic cells of ovarian tissues.Western blotting was used to detect the protein expression of apoptosis-related factors like Bax,Bcl-2 and cleaved-caspase-3 in ovarian tissue of mice.The results showed that ovarian weight,the concentrations of E2 and P4,the number of atretic follicles and pregnant corpus luteum,as well as the apoptosis of granulosa cells were significantly increased in the COH group.The ultrastructures of ovarian tissues in the COH group showed that chromatin in granulosa cells was increased,agglutinated,aggregated or crescent-shaped.The focal cavitation and the typical apoptotic bodies could be seen in granulosa cells in the late stage of apoptosis.After the treatment with different doses of Bu-Shen-An-Tai recipe,the ultrastructural changes of ovarian granulosa cells apoptosis were dramatically improved and even disappeared under TEM.Visible mitochondria and mitochondrial cristae were increased and vacuoles were significantly reduced.The lipid dropltes were shown in a circluar or oval shape.The protein expression levels of Bax and cleaved-caspase-3 were decreased,and the expression of Bcl-2 protein was increased after treatment.It was concluded that Bu-Shen-An-Tai recipe can inhibit the apoptosis of ovarian granulosa cells,probably by up-regulating the protein expression of Bcl-2 and down-regulating Bax and cleaved-caspase-3,which contributes to the formation and maintenance of ovarian corpus luteum.It's helpful to promote the embryonic implantation,to reduce embryo loss and ultimately to improve the success rate of pregnancy.