SLC5A3 is important for cervical cancer cell growth.

Novel molecular targets for cervical cancer must be identified. This study examined the role of SLC5A3, a myo-inositol transporter, in the pathogenesis of cervical cancer. Through boinformatics analysis, we showed that the SLC5A3 mRNA levels were upregulated in cervical cancer tissues. The upregulated SLC5A3 mRNA levels were negatively correlated with survival and progression-free interval. Genes co-expressed with SLC5A3 were enriched in multiple signaling cascades involved in cancer progression. In primary/established cervical cancer cells, SLC5A3 shRNA/knockout (KO) exerted growth-inhibitory effects and promoted cell death/apoptosis. Furthermore, SLC5A3 knockdown or KO downregulated myo-inositol levels, induced oxidative injury, and decreased Akt-mTOR activation in cervical cancer cells. In contrast, supplementation of myo-inositol or n-acetyl-L-cysteine or transduction of a constitutively active Akt1 construct mitigated SLC5A3 KO-induced cytotoxicity in cervical cancer cells. Lentiviral SLC5A3 overexpression construct transduction upregulated the cellular myo-inositol level and promoted Akt-mTOR activation, enhancing cervical cancer cell proliferation and migration. The binding of TonEBP to the SLC5A3 promoter was upregulated in cervical cancer. In vivo studies showed that intratumoral injection of SLC5A3 shRNA-expressing virus arrested cervical cancer xenograft growth in mice. SLC5A3 KO also inhibited pCCa-1 cervical cancer xenograft growth. The SLC5A3-depleted xenograft tissues exhibited myo-inositol downregulation, Akt-mTOR inactivation, and oxidative injury. Transduction of sh-TonEBP AAV construct downregulated SLC5A3 expression and inhibited pCCa-1 cervical cancer xenograft growth. Together, overexpressed SLC5A3 promotes growth of cervical cancer cells, representing as a novel therapeutic oncotarget for the devastating disease.

Function, quality-of-life and complications after sacrospinous ligament fixation using an antegrade reusable suturing device (ARSD-Ney) at 6 and 12 months: a retrospective cohort study.

Background: Pelvic organ prolapse (POP) is a common pathology in the female population. Sacrospinous ligament fixation (SSLF) is one of the traditional transvaginal procedures for POP and high sacrospinous ligament fixation (h-SSLF) optimizes it using an antegrade reusable suturing device (ARSD-Ney). Previous studies on h-SSLF have focused on the correction of anatomical positions, with less assessment of patients' function, quality of life and complications. In this study, we evaluated post-operative complications, function, and quality-of-life after h-SSLF to confirm the safety and effectiveness of it. Methods: This was a retrospective cohort study that included 71 patients between 2018 and 2021: 50 patients for h-SSLF and 21 patients for laparoscopic sacrocolpopexy (LSC) according to patient age and background, POP-Q stage, patient preference, and so on. A clinical evaluation took place before surgery and was repeated at 6 and 12 months postoperatively. Intra- and post-operative complications and anatomical results were recorded. Patients completed self-administered questionnaires for functional pelvic problems [Pelvic Floor Disability Index-20 (PFDI-20)], quality of life [Pelvic Floor Impact Questionnaire-7 (PFIQ-7)], and sexual function [Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 (PISQ-12)] at each medical visit. Results: Patients in both h-SSLF and LSC groups were similar in terms of demographic characteristics except for surgery time (86.04±28.70 vs. 153.19±54.88, P<0.05), postoperative indwelling catheter time (3.88±1.65 vs. 4.90±1.84, P<0.05), and hospital stay (8.94±2.38 vs. 10.57±2.06, P<0.05). There were no statistically significant differences between the 2 groups in scores of PFDI-20, PFIQ-7, and PISQ-12 at pre- and post-operative 6 and 12 months (P>0.05). Functional pelvic problems (PFDI-20 scores) and their impact on patients' quality of life (PFIQ-7 scores) significantly improved at 6 and 12 months postoperatively (P<0.05). Improvements in sexual activity were noted at 6 and 12 months postoperatively (P<0.05). Conclusions: This retrospective cohort study confirmed the positive results of h-SSLF in terms of improvement in function and quality of life following treatment for pelvic organ prolapse.

Hyperthermia enhances the efficacy of chemotherapeutic drugs in heat-sensitive cells through interfering with DNA damage repair.

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be clinically effective, but the mechanisms by which hyperthermia enhances the sensitivity of cells to chemotherapeutic drugs has not yet been elucidated. Methods: To identify the key molecules involved in thermochemotherapy, this study used mass spectrometry (MS)-based quantitative proteomics technology to analyze the effects of thermochemotherapy on the heat-sensitive ovarian cancer cell line A2780. We divided the A2780 cell line into four groups, one group served as blank control, and the other three groups were stimulated by oxaliplatin, stimulated by hyperthermia at 42 ℃, and stimulated by hyperthermia combined with oxaliplatin. Samples were then collected for tandem mass tag (TMT) labeling, high-performance liquid chromatography fractionation, and MS-based quantitative proteomics for analysis The differentially expressed proteins were quantitatively compared and identified, and Gene Ontology (GO) assessment and cluster analyses were performed. Finally, the above MS results were verified again by Western blotting experiments. Results: A total of 349 differentially expressed proteins were identified between cells treated with chemotherapy alone (group B) and cells treated with a combination of chemotherapy and hyperthermia (group D). There were 145 upregulated proteins and 204 downregulated proteins. Among the top 20 proteins with significantly different expression levels, nearly two-thirds were involved in DNA damage repair. These proteins were subsequently verified by Western blot analysis. Indeed, consistent with MS data, the expression of the RBL1 protein was significantly upregulated in cells treated with thermochemotherapy (group D) compared to cells treated with chemotherapy alone (group B). Conclusions: In heat-sensitive ovarian cancer cells, the damage repair of tumor cell DNA is disturbed by hyperthermia, making it unable to fully repair when damaged by chemotherapeutic drugs. As a result, hyperthermia enhances the efficacy of chemotherapeutic drugs. RBL1, as a tumor suppressor gene, may be associated with the repair of DNA damage, and thus it may be a key target for hyperthermia to enhance the sensitivity of thermosensitive cells to chemotherapeutic drugs.