CDK1 promotes the phosphorylation of KIFC1 to regulate the tumorgenicity of endometrial carcinoma.

OBJECTIVE: This study aims to clarify the mechanical action of cyclin-dependent protein kinase 1 (CDK1) in the development of endometrial carcinoma (EMCA), which may be associated with the phosphorylation of kinesin family member C1 (KIFC1) and further activate the PI3K/AKT pathway. METHODS: The protein and gene expression of CDK1 in EMCA tissues and tumor cell lines were evaluated by western blot, quantitative polymerase chain reaction, and immunohistochemistry staining. Next, Cell Counting Kit-8 and colony formation assay detected cell survival and proliferation. Cell migration and invasion were measured by Transwell assay. Cell apoptosis and cell cycle were tested by flow cytometry. Immunofluorescence staining of γH2AX was used to evaluate DNA damage, respectively. Subsequently, a co-immunoprecipitation assay was used to detect the interaction between CDK1 and KIFC1. The phosphorylated protein of KIFC1 and PI3K/AKT was detected by western blot. Finally, the effect of CDK1 on the tumor formation of EMCA was evaluated in a nude mouse xenograft model. RESULTS: CDK1 was highly expressed in EMCA tumor cell lines and tissues, which contributed to cell survival, proliferation, invasion, and migration, inhibited cell apoptosis, and induced DNA damage of EMCA cells dependent on the phosphorylation of KIFC1. Moreover, the CDK1-KIFC1 axis further activated PI3K/AKT pathway. Finally, CDK1 knockdown repressed tumor formation of EMCA in vivo. CONCLUSION: We report that increased CDK1 promotes tumor progression and identified it as a potential prognostic marker and therapeutic target of EMCA.

Application of single-port procedure and ERAS management in the laparoscopic myomectomy.

OBJECTIVE: Advances in surgical techniques and perioperative management are the two major contributing factors to improved surgical outcomes. The purpose of the current study was to compare the efficacy of single-port surgery and perioperative enhanced recovery after surgery (ERAS) management in laparoscopic myomectomy. METHODS: The present study included 120 patients undergoing laparoscopic myomectomy in the Gynecological Ward of Quzhou Affiliated Hospital of Wenzhou Medical University. According to the traditional perioperative management mode and ERAS management, multi-port and single-port procedures, all patients were assigned to the Conventional-SPLS (Single-Port Laparoscopic Surgery with conventional perioperative care) group (n = 34), Conventional-Multi (multi-port laparoscopic surgery with conventional perioperative care) group (n = 47), and ERAS (multi-port laparoscopic surgery with ERAS perioperative care) group (n = 39). The surgical outcomes of the three groups were compared operation time, intraoperative blood loss, variations in postoperative hemoglobin, postoperative walking time, postoperative flatus expelling time, postoperative hospital stay, and visual analog scale (VAS) scores at 6 and 12 h following surgery. RESULTS: The ERAS group recovered the quickest in terms of postoperative walking time and flatus expelling duration. The ERAS group also recovered the shortest postoperative hospital stay (3.85 ± 1.14 days), which differed significantly from that in the Conventional-Multi group, but not significantly from that in the Conventional-SPLS group. In terms of VAS scores at 6 and 12 h after surgery, the ERAS group had the lowest pain intensity, which differed significantly from that of the other two groups. The effect of surgical procedures or postoperative care on hospital stay was assessed using multiple regression analysis. The results demonstrated that ERAS was an important independent contributor to reducing postoperative hospital stay (ß = 0.270, p = 0.002), while single-port surgery did not affect this index (ß = 0.107, p = 0.278). CONCLUSION: In laparoscopic myomectomy, perioperative ERAS management could control postoperative pain and shorten hospital stay. Single-port surgery could speed up the recovery of gastrointestinal function and postoperative walking time, but it did not affect postoperative pain management or the length of hospital stay. Thus, the most effective approach to improving postoperative outcomes in laparoscopic myomectomy was the application of perioperative ERAS management.

Effect of Mifepristone vs Placebo for Treatment of Adenomyosis With Pain Symptoms: A Randomized Clinical Trial.

Importance: Adenomyosis is a common chronic gynecological disorder, and its treatment is an unmet need. New therapies need to be developed. Mifepristone is being tested for adenomyosis treatment. Objective: To determine whether mifepristone is effective and safe for adenomyosis treatment. Design, Setting, and Participants: This multicenter, placebo-controlled, double-blind randomized clinical trial was conducted in 10 hospitals in China. In total, 134 patients with adenomyosis pain symptoms were enrolled. Trial enrollment began in May 2018 and was completed in April 2019, and analyses were conducted from October 2019 to February 2020. Interventions: Participants were randomized 1:1 to receive mifepristone 10 mg or placebo orally once a day for 12 weeks. Main Outcomes and Measures: The primary end point was the change in adenomyosis-associated dysmenorrhea intensity, evaluated by the visual analog scale (VAS) after 12 weeks of treatment. Secondary end points included the change in menstrual blood loss, increased level of hemoglobin in patients with anemia, CA125 level, platelet count, and uterine volume after 12 weeks of treatment. Safety was assessed according to adverse events, vital signs, gynecological examinations, and laboratory evaluations. Results: In total, 134 patients with adenomyosis and dysmenorrhea were randomly assigned, and 126 patients were included in the efficacy analysis, including 61 patients (mean [SD] age, 40.2 [4.6] years) randomized to receive mifepristone and 65 patients (mean [SD] age, 41.7 [5.0] years) randomized to received the placebo. The characteristics of the included patients at baseline were similar between groups. The mean (SD) change in VAS score was -6.63 (1.92) in the mifepristone group and -0.95 (1.75) in the placebo group (P < .001). The total remission rates for dysmenorrhea in the mifepristone group were significantly better than those in the placebo group (effective remission: 56 patients [91.8%] vs 15 patients [23.1%]; complete remission: 54 patients [88.5%] vs 4 patients [6.2%]). All the secondary end points showed significant improvements after mifepristone treatment for menstrual blood loss, hemoglobin (mean [SD] change from baseline: 2.13 [1.38] g/dL vs 0.48 [0.97] g/dL; P < .001), CA125 (mean [SD] change from baseline: -62.23 [76.99] U/mL vs 26.89 [118.70] U/mL; P < .001), platelet count (mean [SD] change from baseline: -28.87 [54.30]×103/µL vs 2.06 [41.78]×103/µL; P < .001), and uterine volume (mean [SD] change from baseline: -29.32 [39.34] cm3 vs 18.39 [66.46] cm3; P < .001). Safety analysis revealed no significant difference between groups, and no serious adverse events were reported. Conclusions and Relevance: This randomized clinical trial showed that mifepristone could be a new option for treating patients with adenomyosis, based on its efficacy and acceptable tolerability. Trial Registration: ClinicalTrials.gov Identifier: NCT03520439.

Modified laparoscopic high uterosacral ligament suspension for treatment of apical prolapse: A feasibility study.

OBJECTIVES: The purpose of this study was to evaluate the feasibility of modified laparoscopic high uterosacral ligament suspension (LHUS) in women with apical prolapse who require uterine preservation. METHODS: This retrospective feasibility study analyzed the demographic characteristics, procedure, and 3-year follow-up data of 23 women who underwent modified LHUS at our institution. Outcome measures included clinical and anatomical cure. Patient satisfaction was measured by the Patient Global Impression of Improvement (PGI-I). The improvement on quality of life was evaluated by pelvic floor distress inventory-short form 20 (PFDI-20). RESULTS: The operation time was 50 ± 17 min, the blood loss was 100 ml (50-300 ml), and the postoperative hospital stay was 3.5 days (3-6 days). At a median follow-up time of 4.3 years (3-6 years), the clinical cure rate was 91.6% and the anatomical cure rate was 87.0%. The values of Aa, Ba, C, and D points were significantly higher than those observed before operation (p < 0.05). According to PGI-I, 20 patients were satisfied, and the overall subjective satisfaction rate was 87%. The scores of PFDI-20 after operation were significantly lower than those recorded before operation (p < 0.05). CONCLUSION: Modified LHUS has the advantages of short operation time, fast postoperative recovery, low 3-year recurrence rate, and high patient satisfaction in women with apical prolapse who require uterine preservation, which is worthy of clinical promotion.

KIFC1 promotes aerobic glycolysis in endometrial cancer cells by regulating the c-myc pathway.

Endometrial cancer (EC) is a common gynecological malignant tumor worldwide. It is imperative to study pathogenesis and therapeutic targets for improving the prognosis of EC. The present study aimed to explore the function and mechanism of kinesin family member C1 (KIFC1) in EC. EC tumor and adjacent normal tissues were collected from 68 pairs of patients. The expression of KIFC1 in tissues and EC cells was analyzed by immunohistochemistry, qRT-PCR or western blot. MTT assay was used to test the cell viability. Flow cytometry was used to determine apoptosis and the cell cycle. Glucose uptake, lactate production, ATP contents and lactate dehydrogenase (LDH) activity were evaluated by a glucose metabolism kit. The expression of HMGA1, c-myc and glycolytic genes was assessed using western blot or qRT-PCR. A mouse xenograft model was established in BALB/c mice to detect tumor growth in vivo. KIFC1 was significantly upregulated in EC tumor tissues compared to adjacent normal control tissues. The upregulated expression of KIFC1 was correlated with poor prognosis in patients. Lentiviral-mediated overexpression of KIFC1 observably enhanced cell viability and reduced the apoptotic rate of Ishikawa and HEC-1B cells. Cell cycle progression was also expedited in the KIFC1 vector group. Moreover, overexpression of KIFC1 elevated glucose uptake, lactate production, ATP contents and LDH activity. However, knockdown of KIFC1 by short hairpin RNA (shRNA) showed the reverse effect on cellular functions. In addition, the expression of c-myc, GLUT1, LDHA and HK2 was increased by the KIFC1 vector. Moreover, HMGA1 regulated the expression of c-myc and glycolytic genes. Upregulated HMGA1 could rescue the effect of KIFC1 knockdown on cellular functions and the expression of glycolytic genes. Finally, KIFC1 knockdown inhibits tumor growth in vivo. The upregulation of KIFC1 was correlated with poor prognosis in EC. KIFC1 promoted aerobic glycolysis in endometrial cancer cells by regulating the HMGA1/c-myc pathway. KIFC1 may be a potential target for the diagnosis and therapy of EC.

Kinesin Family Member C1 (KIFC1) Accelerates Proliferation and Invasion of Endometrial Cancer Cells Through Modulating the PI3K/AKT Signaling Pathway.

Endometrial cancer (EC) is one of the most common cancers among women worldwide. Kinesin family member C1 (KIFC1) has been demonstrated to play crucial roles in various tumors. However, the function of KIFC1 in EC remains to be revealed. In this study, upregulation of KIFC1 expression in human EC tissues was found from analysis on data from The Cancer Genome Atlas (TCGA), and positively correlated with short survival outcome of EC patients. In addition, the mRNA and protein levels of KIFC1 were confirmed to be up-regulated in EC cells (Ishikawa, HEC-1B, HEC-1A and KLE) compared to human normal endometrial stromal cells (hESCs) by quantitative real time PCR and western blot. In vitro functional experiments showed that overexpression of KIFC1 promoted proliferation, migration and invasion of EC cells, while KIFC1 depletion showed the opposite results. Moreover, KIFC1 knockdown suppressed tumor growth in mice. Further mechanism analysis showed that KIFC1 participated in the regulation of EC progression through regulating the PI3K/AKT signaling pathway. Collectively, KIFC1 promoted proliferation and invasion through modulating PI3K/AKT signaling pathway in EC, implying that KIFC1 might provide a promising therapeutic target for the therapy of EC.