The efficacy and safety of niraparib for ovarian cancer: a single-center observational study from China.

BACKGROUND: Niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for first/second-line maintenance treatment of ovarian cancer patients with complete or partial response to platinum-based chemotherapy, and multi-line monotherapy in BRCAmt patients or platinum-sensitive recurrence patients with homologous recombination deficiency (HRD). We present real-world experience from a single center of China. METHODS: Patients treated with niraparib in Jiangsu Cancer Hospital between June 2019 to July 2020 were recruited. The initial dose was given according to individualization. Response and adverse events (AEs) were analyzed by Response Evaluation Criteria in Solid Tumors v1.1. and National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, respectively. HRD testing (AmoyDx®) was detected in most patients. Treatment was given until unequivocal progression or intolerable toxicity. RESULTS: Twenty-two patients all received niraparib at a bolus of 200 mg/d. Fifty percent of patients with high-grade serous ovarian cancer are HRD-positive. Six patients underwent first-line maintenance therapy. Sixteen patients received exploratory therapy. Ultimately image evaluation revealed that two patients achieved partial response (PR) and one patient achieved stable disease (SD), yielding objective response rate (ORR) of 33.3% (95%CI = 0.060-0.759) and disease control rate (DCR) of 50% (95%CI = 0.140-0.861) in the exploratory multi-line monotherapy group. The most common AEs were nausea, thrombocytopenia, and anemia. Grade 3-4 thrombocytopenia were managed by dose reduction and interruption. Leg swelling was observed as a new adverse event. CONCLUSION: It is feasible that patients receiving a bolus of 200 mg/d in patients from Chinese population can acquire promising efficacy and tolerance. This is the first real-world data about niraparib in ovarian cancer patients with available HRD status from China.

Anlotinib as Exploratory Therapy for Platinum-Resistant Ovarian Cancer: A Retrospective Study on Efficacy and Safety.

PURPOSE: Survival of platinum-resistant ovarian cancer (PROC) patients is significantly shortened to around 12 months. Anlotinib is a new multi-target tyrosine kinase inhibitor. The goal of this study is to evaluate the efficacy and safety of anlotinib in PROC patients. PATIENTS AND METHODS: PROC patients treated with anlotinib in Jiangsu Cancer Hospital between June 2018 to September 2019 were recruited. Most patients received an initial bolus of 12mg orally once daily on days 1-14 of a 21-day cycle (except one received a dose of 10mg and another one received a dose of 8mg orally once a day). The adverse events (AEs) and efficacy were analyzed by CTCAE 4.0 and RECIST 1.1. RESULTS: Of all 15 enrolled patients, 12 patients received anlotinib as multi-line therapy and 3 patients received it as maintenance therapy. In the multi-line therapy group, eight patients received anlotinib monotherapy and four patients received anlotinib combined with chemotherapy. Ultimately, evaluation showed that one patient achieved partial response (PR), five patients achieved stable disease (SD) and one patient had progressive disease (PD) with monotherapy, yielding objective response rate (ORR) of 14.3% (95% CI=0.01-0.58) and disease control rate (DCR) of 85.7% (95% CI=0.42-0.99). One patient achieved PR, two patients achieved SD with combination therapy, yielding ORR of 33.3% (95% CI=0.02-0.87) and DCR of 100% (95% CI=0.31-1.00). Three patients with maintenance therapy were followed up for 5, 8, and 11 months, respectively. The most grade 1-2 AEs were hand-foot syndrome, nausea, and hypertension. Serious AEs (SAEs) (Grade 3-4) were observed in one patient with oral ulcer and another patient with hand-foot syndrome that were managed by dose reduction. CONCLUSION: Anlotinib was of promising efficacy and well tolerated in PROC patients. This is the first retrospective study about exploratory therapy for ovarian cancer patients with anlotinib.

MicroRNA-218 regulates the chemo-sensitivity of cervical cancer cells through targeting survivin.

Background: Cervical cancer is one of the most lethal malignancies among women in the world. Every year about 311,365 women die because of cervical cancer. Chemo-resistance is the main reason of the lethal malignancies, and the mechanism of chemo-resistance in cervical cancer still remains largely elusive. Purpose: Previous studies reported that microRNAs played important biological roles in the chemo-resistance in many types of cancers, in the present study we tried to investigate the biological roles of microRNA-218 in chemo-resistance in cervical cancer cells. Results: Real-time PCR results indicated microRNA-218 was downregulated in cisplatin-resistant HeLa/DDP and SiHa/DDP cells compared with the mock HeLa and SiHa cells. CCK-8 assay results showed upregulation of microRNA-218 enhanced the cisplatin sensitivity of cervical cancer cells; while downregulation of microRNA-218 decreased the cisplatin sensitivity of cervical cancer cells. Dual-luciferase assay indicated survivin was a direct target of microRNA-218. Western blotting and PCR results indicated the expression of survivin in HeLa/DDP and SiHa/DDP cells was significantly increased compared with HeLa and SiHa cells. Further study indicated induction of microRNA-218 decreased the expression of survivin while inhibition of microRNA-218 increased the expression of survivin in cervical cancer cells. Cell apoptosis results indicated induction of microRNA-218 induced the cell apoptosis in cervical cancer cells. Conclusion: Our data revealed microRNA-218 enhanced the cisplatin sensitivity in cervical cancer cells through regulation of cell growth and cell apoptosis, which could potentially benefit to the cervical cancer treatment in the future.

Video Endoscopic Inguinal Lymphadenectomy via 3-Incision Lateral Approach for Vulvar Cancers: Our Preliminary Outcome of 37 Cases.

OBJECTIVE: The purpose of this study was to build a video endoscopic inguinal lymphadenectomy (VEIL) via the 3-incision superolateral inguinal approach and explore the feasibility and significance of this method for vulvar cancer. METHODS: Thirty-seven patients with vulvar cancer who underwent VEIL via the 3-incision superolateral inguinal approach were enrolled and followed up. The number of excised lymph nodes, intraoperative complications, inguinal wound healing, and the prognosis were retrospectively analyzed. RESULTS: The average number of excised lymph nodes per side is 8.8 ± 3.7 (4-18) among the 37 patients and after the new method was more mature, is 9.6 ± 3.6 among the 34 patients treated. Primary healing was found in 36 cases, whereas delayed healing occurred in 1 case complicated with diabetes. The lymph node-positive patients (6 cases) were supplemented with postoperative radiochemotherapy (RCT). All patients survived during the follow-up. Of the 2 recurrent patients, one patient who received surgery again and RCT survived without tumor. The other patient undergoing RCT survived with tumor. CONCLUSIONS: Compared with open lymphadenectomy, VEIL via the 3-incision lateral approach provides a feasible, but more cosmetic, and promising minimally invasive modality in clinic for treating patients with vulvar cancer.

Quantitative proteomic analysis of mitochondria from human ovarian cancer cells and their paclitaxel-resistant sublines.

Paclitaxel resistance is a major obstacle for the treatment of ovarian cancer. The chemoresistance mechanisms are partly related to the mitochondria. Identification of the relevant proteins in mitochondria will help in clarifying the possible mechanisms and in selecting effective chemotherapy for patients with paclitaxel resistance. In the present study, mitochondria from two paclitaxel-sensitive human ovarian cancer cell lines (SKOV3 and A2780) and their corresponding resistant cell lines (SKOV3-TR and A2780-TR) were isolated. Guanidine-modified acetyl-stable isotope labeling and liquid chromatography-hybrid linear ion trap Fourier-transform ion cyclotron resonance mass spectrometry (LC-FTICR MS) were performed to find the expressed differential proteins. Comparative proteomic analysis revealed eight differentially expressed proteins in the ovarian cancer cells and their paclitaxel-resistant sublines. Among them, mimitin and 14-3-3 ζ/δ were selected for further research. The effects of mimitin and 14-3-3 ζ/δ were explored using specific siRNA interference in ovarian cancer cell lines and immunohistochemistry in human tissue specimens. The downregulation of mimitin and 14-3-3 ζ/δ using specific siRNA in paclitaxel-resistant ovarian cancer cells led to an increase in the resistance index to paclitaxel. Multivariate analyses demonstrated that lower expression levels of the mimitin and 14-3-3 ζ/δ proteins were positively associated with shorter progression-free survival (PFS) and overall survival (OS) in patients with primary ovarian cancer (mimitin: PFS: P = 0.041, OS: P = 0.003; 14-3-3 ζ/δ: PFS: P = 0.031, OS: P = 0.011). Mimitin and 14-3-3 protein ζ/δ are potential markers of paclitaxel resistance and prognostic factors in ovarian cancer.

Secondary cytoreduction surgery improves prognosis in platinum-sensitive recurrent ovarian cancer.

BACKGROUND: There is no consensus regarding the secondary cytoreduction surgery (CRS) in recurrent ovarian cancer patients. The present study aims to determine the value of secondary CRS and the eligible subgroup for this procedure. METHODS: 96 platinum-sensitive recurrent ovarian cancer patients were recruited from Jiangsu Institute of Cancer Research between 1992 and 2011. Follow-up was conducted based on the surveillance protocol of MD Anderson Cancer Center. Cox proportional hazards model and log-rank test were used to assess the associations between the survival durations and covariates. Logistic regression analysis was used to explore optimal secondary CRS related factors. RESULTS: Optimal secondary CRS was associated with time to progression (TTP) and overall survival (OS) in patients (p < 0.01 both). Optimal secondary CRS and asymptomatic recurrent were similarly associated with longer OS (median: 79.2 vs. 53.9 and 76.1 vs. 56.0 months with p = 0.02 and p = 0.04, respectively) and TTP (median: 13.9 vs. 10.5 and 19.3 vs. 9.0 months with p = 0.02 and p = 0.03, respectively) than counterparts. Optimal initial CRS (p = 0.01), asymptomatic recurrent (p = 0.02) and longer progression-free survival duration (p = 0.02) were the independent indicators of optimal secondary CRS. CONCLUSIONS: Optimal secondary CRS had survival benefit for platinum-sensitive epithelial ovarian cancer. Asymptomatic recurrent was one of the recruited factors for this procedure.

Mitochondrial comparative proteomics of human ovarian cancer cells and their platinum-resistant sublines.

Resistance to platinum-based chemotherapy is the major obstacle to successful treatment of ovarian cancer. It is evident that mitochondrial defects and the dysfunctions of oxidative phosphorylation and energy production in ovarian cancer cells were directly related to their resistance to platinum drugs. Using 2-D DIGE, we compared mitochondrial proteins from two platinum-sensitive human ovarian cancer cell lines (SKOV3 and A2780) with that of four platinum-resistant sublines (SKOV3/CDDP, SKOV3/CBP, A2780/CDDP, and A2780/CBP). Among the 236 differentially expressed spots, five mitochondrial proteins (ATP-α, PRDX3, PHB, ETF, and ALDH) that participate in the electron transport respiratory chain were identified through mass spectrometry. All of them are downregulated in one or two of the platinum-resistant cell lines. Three proteins (ATP-α, PRDX3, and PHB) were validated by using western blot and immunohistochemistry. There is a significant decrease of PHB in tumor tissues from ovarian cancer patients who were resistant to platinum-based chemotherapies. This is the first direct mitochondrial proteomic comparison between platinum-sensitive and resistant ovarian cancer cells. These studies demonstrated that 2-D DIGE-based proteomic analysis could be a powerful tool to investigate limited mitochondrial proteins, and the association of PHB expression with platinum resistance indicates that mitochondria defects may contribute to platinum resistance in ovarian cancer cells.

Clinical characteristics of endometrial stromal sarcoma from an academic medical hospital in China.

OBJECTIVES: The purpose of this study was to evaluate the clinical features, treatments, and outcomes of endometrial stromal sarcoma (ESS) in China. METHODS: Seventy consecutive ESS patients were treated at Peking Union Medical College Hospital from 1983 to 2005, and 51 of them completed the treatment and follow-up. The demographic, clinicopathologic, treatment, and survival information was retrospectively reviewed. Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression. RESULTS: In all, the mean age of the patients was 43.5 years. Irregular vaginal bleeding and uterine enlargement were presented in 71.0% and 65.7% of the cases, respectively. Uterine cavity lesions were found in 17 patients (24.3%). Twenty-six cases (37.2%) were diagnosed preoperatively through diagnostic curettage. Among 51 patients who completed the treatment and follow-up in Peking Union Medical College Hospital, 37 were diagnosed as having low-grade ESS (LGESS) and 14 high-grade ESS, which is now classified as undifferentiated endometrial sarcoma (UES). The median overall survival time was 334 months, and the 5-year survival rate was 87.8%. Twenty-six of 51 patients, including 14 with LGESS and 12 with UES, developed disease recurrence. The tumor's classification, initial surgery, and adjuvant therapy were the factors related to the disease-free survival, whereas only the tumor's classification was associated with the overall survival. CONCLUSIONS: Endometrial stromal sarcoma is a rare kind of uterine malignancy; the possibilities of preoperative diagnosis may be improved by diagnostic curettage. Low-grade ESS and UES represent 2 distinct clinical entities and should be treated as such. The tumor's classification may be the most important prognostic factor.

[Evaluation of the follow up results of patients with cervical intraepithelial neoplasia III after surgical treatment].

OBJECTIVE: To evaluate the follow-up results of patients with cervical intraepithelial neoplasia III (CIN III) after surgical treatment. METHODS: A retrospective analysis of consecutive patients with CIN III after surgical treatment between Jan 1st, 1999 and Jun 30th, 2004 was performed. The follow-ups of the patients after surgical treatment were assessed. RESULTS: In the follow-up of patients with CIN III after surgical treatment, the rate of abnormal cytology was 9.3%. The rate of follow-up was higher in patients with cervical conization than in patients with initial hysterectomy and in patients of the oncological group than of the non-oncological group. The rate of follow-up was lower in patients over 40 years old. There was no difference in the residential areas of the patients. CONCLUSIONS: Cytological follow-up of patients with CIN III after operation is varied. The rate of follow-up is lower in patients over 40 years old, in patients having initial hysterectomy and in patients of the non-oncological group. The rate of follow-up is associated with the knowledge about CIN of both surgeons and patients.

[Study of bone mineral density in complete androgen insensitivity syndrome patients].

OBJECTIVE: To explore the characteristics and treatment of bone mineral density (BMD) change in complete androgen insensitivity syndrome (CAIS) of Chinese patients. METHODS: Fourteen cases of CAIS were studied retrospectively through analyzing and comparing BMD of pre- and post-orchidectomy with normal Chinese men and women. BMD at the lumbar spine and the femur were measured by dual energy X-ray absorptiometry (DXA). RESULTS: Ten cases of CAIS had pre-orchidectomy DXA, in which 6 cases had very significantly reduced L(2-4) BMD (0.92 +/- 0.08) g/cm(2) compared with normal men and women (P < 0.01). Five cases had significantly reduced femur neck BMD (0.89 +/- 0.12) g/cm(2) compared with normal male (P < 0.05). Seven cases had 12 post-orchidectomy DXA, in which all L(2-4) BMD (0.95 +/- 0.06) g/cm(2) were very significantly reduced compared with normal male and female (P < 0.01), femur neck BMD (0.91 +/- 0.08) g/cm(2) was also significantly reduced compared with normal male (P < 0.01) and normal female (P < 0.05). CONCLUSIONS: There are different degrees of osteopenia in patients of CAIS, especially in lumbar vertebra. This suggests that estrogen and androgen play important roles in the acquirement and maintenance of bone mass.