Microtubule-severing protein Fidgetin-like 1 promotes spindle organization during meiosis of mouse oocytes.

Microtubule-severing proteins (MTSPs) play important roles in mitosis and interphase. However, to the best of our knowledge, no previous studies have evaluated the role of MTSPs in female meiosis in mammals. It was found that FIGNL1, a member of MTSPs, was predominantly expressed in mouse oocytes and distributed at the spindle poles during meiosis in the present study. FIGNL1 was co-localized and interacted with γ-tubulin, an important component of the microtubule tissue centre (MTOC). Fignl1 knockdown by specific small interfering RNA caused spindle defects characterized by an abnormal length:width ratio and decreased microtubule density, which consequently led to aberrant chromosome arrangement, oocyte maturation and fertilization obstacles. In conclusion, the present results suggested that FIGNL1 may be an essential factor in oocyte maturation by influencing the meiosis process via the formation of spindles.

Spastin interacts with CRMP5 to promote spindle organization in mouse oocytes by severing microtubules.

Microtubule-severing protein (MTSP) is critical for the survival of both mitotic and postmitotic cells. However, the study of MTSP during meiosis of mammalian oocytes has not been reported. We found that spastin, a member of the MTSP family, was highly expressed in oocytes and aggregated in spindle microtubules. After knocking down spastin by specific siRNA, the spindle microtubule density of meiotic oocytes decreased significantly. When the oocytes were cultured in vitro, the oocytes lacking spastin showed an obvious maturation disorder. Considering the microtubule-severing activity of spastin, we speculate that spastin on spindles may increase the number of microtubule broken ends by severing the microtubules, therefore playing a nucleating role, promoting spindle assembly and ensuring normal meiosis. In addition, we found the colocalization and interaction of collapsin response mediator protein 5 (CRMP5) and spastin in oocytes. CRMP5 can provide structural support and promote microtubule aggregation, creating transportation routes, and can interact with spastin in the microtubule activity of nerve cells (30). Knocking down CRMP5 may lead to spindle abnormalities and developmental disorders in oocytes. Overexpression of spastin may reverse the abnormal phenotype caused by the deletion of CRMP5. In summary, our data support a model in which the interaction between spastin and CRMP5 promotes the assembly of spindle microtubules in oocytes by controlling microtubule dynamics, therefore ensuring normal meiosis.

Surgery in platinum-resistant recurrent epithelial ovarian carcinoma.

BACKGROUND: Ovarian cancer is one of the three most common malignant tumors of the female reproductive tract and ranks first in terms of mortality among gynecological tumors. Epithelial ovarian carcinoma (EOC) is the most common ovarian malignancy, accounting for 90% of all primary ovarian tumors. The clinical value of cytoreductive surgery in patients with platinum-resistant recurrent EOC remains largely unclear. AIM: To evaluate the feasibility of secondary cytoreductive surgery for treating platinum-resistant recurrent EOC. METHODS: This was a retrospective study of the clinical data of patients with platinum-resistant EOC admitted to the Cancer Hospital of the University of Chinese Academy of Sciences between September 2012 and June 2018. Patient baseline data were obtained from clinical records. Routine follow-up of disease progression was performed as follows. CA125 assessment and physical examination were performed every 3 wk during treatment, including gynecological examination. Imaging assessment was carried out every 12 wk by B-mode ultrasound, computed tomography, or magnetic resonance imaging. The primary outcome was progression-free survival (PFS). Secondary outcomes included overall survival (OS), chemotherapy-free interval (CFI), and complications. Follow-up ended on April 15, 2019. RESULTS: A total of 38 patients were included. R0 resection was achieved in 25 (65.8%) patients and R1/2 in 13 (34.2%). Twenty-five (65.8%) patients required organ resection. Nine (23.7%) patients had operative complications, 36 (94.7%) received chemotherapy, and five (13.2%) had targeted therapy. Median PFS and OS were 10 (95%CI: 8.27-11.73) months and 28 (95%CI: 12.75-43.25) months, respectively; median CFI was 9 (95%CI: 8.06-9.94) months. R0 resection and postoperative chemotherapy significantly prolonged PFS and OS (all P < 0.05), and R0 resection also significantly prolonged CFI (P < 0.05). Grade ≥ 3 complications were observed, including rectovaginal fistula (n = 1), intestinal and urinary fistulas (n = 1), and renal failure-associated death (n = 1). Except for the patient who died after surgery, all other patients with complications were successfully managed. Two patients developed intestinal obstruction and showed improvement after conservative treatment. CONCLUSION: Secondary cytoreductive surgery is feasible for treating platinum-resistant recurrent EOC. These findings provide important references for the selection of clinical therapeutic regimens.

[Feasibility of unilateral or bilateral nerve-sparing radical hysterectomy in patients with cervical cancer and evaluation of the post-surgery recovery of the bladder and rectal function].

OBJECTIVE: To investigate the feasibility of unilateral or bilateral nerve-sparing radical hysterectomy and evaluate the recovery of bladder and bowel function postoperatively. METHODS: From August 2008 to October 2009, sixty-one patients with cervical cancer stage Ib1 to IIa underwent radical hysterectomy (33 cases) and nerve-sparing radical hysterectomy (28 cases). Unilateral nerve-sparing radical hysterectomy was performed in 10 patients, and bilateral nerve-sparing radical hysterectomy (BNS) was performed in 18 patients. The data of operation time, blood loss, postoperative hospital stay days, residual urine volume, and postoperative complications were collected. The postoperative recovery of bladder and bowel function was evaluated. RESULTS: There were no significant differences between nerve-sparing radical hysterectomy (NSRH) and radical hysterectomy (RH) groups in operation time [NSRH: (224.5 ± 40.0) min, RH: (176.4 ± 30.0 min)], blood loss [NSRH: (464.3 ± 144.0) ml, RH: (374.2 ± 138.7) ml], postoperative hospital stay days [NSRH: (8.4 ± 2.0) d, RH: (9.2 ± 1.8) d, and residual urine volume [NSRH: (64.8 ± 16.9) ml, RH: (70.6 ± 16.0) ml]. There were also no significant differences between UNSRH and BNSRH groups in operation time [UNSRH: (208.5 ± 28.5) min, BNSRH: (233.3 ± 43.1) min], blood loss [UNSRH: (440.0 ± 104.9) ml, BNSRH: (477.8 ± 162.90) ml], postoperative hospital stay days [UNSRH: 9.1 ± 1.8) d, BNSRH: (8.7 ± 2.1 d], and the residual urine volume [UNSRH: (68.3 ± 12.5) ml, BNSRH: (62.8 ± 20.0) ml]. There was a significant difference in the time of the Foley catheter removal between NSRH [(12.4 ± 5.2) d] and RH [(22.4 ± 9.7) d] groups. There was a significant difference in the time of the Foley catheter removal between UNSRH [(18.2 ± 3.6) d] and BNSRH [(9.1 ± 2.0) d] groups. During the postoperative 3 weeks follow-up, the patients in the NSRH group had a higher rate of satisfaction at urination and defecation (100%, 75%) than the RH group (54.5%, 24.2%). CONCLUSION: UNSRH and BNSRH are safe and feasible techniques for early stage cervical cancer, and may significantly improve the recovery of bladder and rectal function.

[Association between endometrial cancer and metabolic syndrome].

OBJECTIVE: To study the association between endometrioid uterine carcinomas and metabolic syndrome (MS). METHODS: A retrospective study was conducted on 123 patients who were admitted in Department of Gynecology Oncology, Zhejiang Cancer Hospital (study group) and 90 healthy women (control group) with matching age from Jan. 2005 to Mar. 2009. The general conditions [including age, whether menopausal, body mass index (BMI)]; the risk factors for MS [including waist circumference, fasting plasma glucose, triglycerides (TG), high-density lipoprotein (HDL) and systolic and diastolic blood pressure] were analyzed. The clinical stage, histological type, and pathology differentiated degree of study group with or without MS were also analyzed by univariate analysis and Cox proportional hazards models. RESULTS: (1) The univariate survival analysis shown that there were no significant difference with age in two groups [(54.3 +/- 0.6) vs. (54.2 +/- 0.9) years; P > 0.05], while the rate of menopausal, BMI (> or = 25 kg/m(2)), the cases coupled with MS, the size of waist circumference (> 80 cm), the level of fasting plasma glucose (> or = 5.6 mmol/L), TG (> 1.7 mmol/L) and abnormal systolic and diastolic blood pressure in study group were higher than those in control group (67.5% vs. 48.9%, 45.5% vs. 23.3%, 43.9% vs. 18.9%, 50.4% vs. 27.8%, 53.7% vs. 21.1%, 40.7% vs. 21.1% and 40.7% vs. 25.6%, respectively, all P < 0.05). The percentage of HDL (< 1.30 mmol/L) was higher in study group than that in control group (63.4% vs. 32.2%, P < 0.05). (2) There were not significant difference for the clinical stage, pathological type, grades between patients with or without MS in study group (P > 0.05). (3) The Logistic multivariate survival analysis shown that central obesity, higher TG, lower HDL and abnormal plasma glucose were independent risk factors for endometrioid uterine carcinomas coupled with MS (P < 0.05). CONCLUSION: Metabolic syndrome is marginally associated with an increased risk of endometrioid uterine carcinomas, which may be the new point to screen, prevention and treatment endometrioid uterine carcinomas.