Oteseconazole versus fluconazole for the treatment of severe vulvovaginal candidiasis: a multicenter, randomized, double-blinded, phase 3 trial.

Vulvovaginal candidiasis (VVC) is a common condition among women. Fluconazole remains the dominant treatment option for VVC. Oteseconazole is a highly selective inhibitor of fungal CYP51. This randomized, double-blinded, phase 3 trial was conducted to evaluate the efficacy and safety of oteseconazole compared with fluconazole in treating severe VVC. Female subjects presenting with vulvovaginal signs and symptoms score of ≥7 and positive Candida infection determined by potassium hydroxide test or Gram staining were randomly assigned to receive oteseconazole (600 mg on D1 and 450 mg on D2) or fluconazole (150 mg on D1 and D4) in a 1:1 ratio. The primary endpoint was the proportion of subjects achieving therapeutic cure [defined as achieving both clinical cure (absence of signs and symptoms of VVC) and mycological cure (negative culture of Candida species)] at D28. A total of 322 subjects were randomized and 321 subjects were treated. At D28, a statistically significantly higher proportion of subjects achieved therapeutic cure in the oteseconazole group than in the fluconazole group (66.88% vs 45.91%; P = 0.0002). Oteseconazole treatment resulted in an increased proportion of subjects achieving mycological cure (82.50% vs 59.12%; P < 0.0001) and clinical cure (71.25% vs 55.97%; P = 0.0046) compared with fluconazole. The incidence of treatment-emergent adverse events was similar between the two groups. No subjects discontinued study treatment or withdrew study due to adverse events. Oteseconazole showed statistically significant and clinically meaningful superiority over fluconazole for the treatment of severe VVC and was generally tolerated.

Preparation and Characterization Evaluation of Poly(L-Glutamic Acid)-g-Methoxy Poly(Ethylene Glycol)/Combretastatin A4/BLZ945 Nanoparticles for Cervical Cancer Therapy.

Purpose: Cervical cancer (CC) is a highly vascularized tumor with abundant abnormal blood vessel, which could be targeted by therapeutic strategies. Poly(L-glutamic acid)-g-methoxy poly(ethylene glycol)/combretastatin A4 (CA4)/BLZ945 nanoparticles (CB-NPs) have shown great potential as nano vascular disrupting agents (VDAs) in the realm of synergistic cancer therapy. Methods: In this study, we investigated the nanocharacteristics of CB-NPs, focusing on active pharmaceutical ingredients (API), as well as lyophilized samples combining API with protective agents (PAs). The in vivo efficacy of final sample (API + PAs) was evaluated. Results: The assembled sphere of API with complex core and thin-shell structure was confirmed. PAs were found to significantly influence in vivo efficacy. Collaborative efforts between API and PAs, namely mannitol and lactose, resulted in the most promising lyophilized sample, ie, the final sample (FS2) for CC therapy. Impressively, FS2 demonstrated an exceptional 100% cure rate on the CC U14-bearing mice model. Conclusion: FS2 has provided significant insights for cervical cancer therapy. It is also crucial to develop a comprehensive evaluation strategy for the formulation of nanomedicine, which has the potential to serve as a guideline for future clinical trials.

HGF-modified human umbilical cord mesenchymal stem cells rescue impaired ovarian reserve function in chemotherapy-induced POI rats by improving angiogenesis while decreasing apoptosis and fibrosis in the ovary.

Complications caused by Primary ovarian insufficiency (POI), including infertility, osteoporosis, cardiovascular diseases and depression, severely affect the life quality of female patients. Although hormone replacement therapy (HRT) can alleviate some long-term complications, there is still no standard treatment for the restoration of ovarian reserve function. Currently, human umbilical cord mesenchymal stem cells (HUCMSC) transplantation showed considerable treatment effect for POI in both rat model and clinic. To improve the effectiveness of naïve HUCMSC (HUCMSC-Null) treatments on POI, an exogenous gene hepatocyte growth factor (HGF) which promotes follicular angiogenesis in POI ovaries was used to modify HUCMSC. Subsequently, HGF-overexpressed HUCMSC (HUCMSC-HGF) was transplanted into the ovaries of chemotherapy-induced POI Sprague-Dawley (SD) rats to observe the effectiveness on POI improvement and its related mechanisms. Our results showed that when compared with POI and HUCMSC-Null treatment group, HUCMSC-HGF significantly improved ovarian reserve function in POI group, which might be attributed to the decrease of ovarian tissue fibrosis and granulosa cells (GCs) apoptosis, and the increase of ovarian angiogenesis mediated by HGF over-expression. The findings suggest that HGF-modified HUCMSC may present a more superior capacity than HUCMSC alone for the rescue of ovarian reserve function in POI.

MCM10: An effective treatment target and a prognostic biomarker in patients with uterine corpus endometrial carcinoma.

Molecular profiling has been applied for uterine corpus endometrial carcinoma (UCEC) management for many years. The aim of this study was to explore the role of MCM10 in UCEC and construct its overall survival (OS) prediction models. Data from TCGA, GEO, cbioPotal and COSMIC databases and the methods, such as GO, KEGG, GSEA, ssGSEA and PPI, were employed to bioinformatically detect the effects of MCM10 on UCEC. RT-PCR, Western blot and immunohistochemistry were used to validate the effects of MCM10 on UCEC. Based on Cox regression analysis using the data from TCGA and our clinical data, two OS prediction models for UCEC were established. Finally, the effects of MCM10 on UCEC were detected in vitro. Our study revealed that MCM10 was variated and overexpressed in UCEC tissue and involved in DNA replication, cell cycle, DNA repair and immune microenvironment in UCEC. Moreover, silencing MCM10 significantly inhibited the proliferation of UCEC cells in vitro. Importantly, based on MCM10 expression and clinical features, the OS prediction models were constructed with good accuracy. MCM10 could be an effective treatment target and a prognostic biomarker for UCEC patients. The OS prediction models might help establish the strategies of follow-up and treatment for UCEC patients.

UBP43 promotes epithelial ovarian carcinogenesis via activation of ß-catenin signaling pathway.

Dysregulation of the deubiquitinating protease, UBP43, has been implicated in many human diseases, including cancer. Here, we evaluated the functional significance and mechanism of action of UBP43 in epithelial ovarian cancer. We found that UBP43 was significantly upregulated in the tumor tissues of patients with epithelial ovarian cancer. Similar results were observed in OVCAR-3, Caov-3, TOV-112D, A2780, and SK-OV-3 cells. Furthermore, in vitro functional assays of A2780 and TOV-112D cells demonstrated that UBP43 overexpression promoted cell proliferation, migration, and invasion. Upregulation of UBP43 might result in epithelial-mesenchymal transition by inducing the nuclear transport of ß-catenin, which was accompanied by enhanced N-cadherin but decreased E-cadherin expression. These malignant phenotypes were reversed by UBP43 silencing. Further investigation revealed that the knockdown of UBP43 inhibited cell proliferation by inducing a cell cycle arrest at the G2/M phase. The oncogenic characteristics of UBP43 were validated in a subcutaneous xenograft mouse model. In vivo, tumor growth was delayed in the UBP43-silenced group but accelerated after UBP43 overexpression. Finally, we demonstrated that ß-catenin is a key protein in the UBP43-mediated malignant development of epithelial ovarian cancer. Specifically, overexpression of UBP43 decreased the ubiquitination degradation of ß-catenin and enhanced its protein stability. Also, we observed that the downstream genes of beta-catenin such as cyclin D1, MMP2, and MMP9 were upregulated due to UBP43 overexpression. Thus, we concluded that UBP43 promoted epithelial ovarian cancer tumorigenesis and metastasis through activation of the ß-catenin pathway, suggesting that UBP43 may be a potential therapeutic target for this intractable disease.

CAR-T Cells in the Treatment of Ovarian Cancer: A Promising Cell Therapy.

Ovarian cancer (OC) is among the most common gynecologic malignancies with a poor prognosis and a high mortality rate. Most patients are diagnosed at an advanced stage (stage III or IV), with 5-year survival rates ranging from 25% to 47% worldwide. Surgical resection and first-line chemotherapy are the main treatment modalities for OC. However, patients usually relapse within a few years of initial treatment due to resistance to chemotherapy. Cell-based therapies, particularly adoptive T-cell therapy and chimeric antigen receptor T (CAR-T) cell therapy, represent an alternative immunotherapy approach with great potential for hematologic malignancies. However, the use of CAR-T-cell therapy for the treatment of OC is still associated with several difficulties. In this review, we comprehensively discuss recent innovations in CAR-T-cell engineering to improve clinical efficacy, as well as strategies to overcome the limitations of CAR-T-cell therapy in OC.

In Vitro Antifungal Activity of Azoles and Other Antifungal Agents Against Pathogenic Yeasts from Vulvovaginal Candidiasis in China.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a public health issue worldwide. Little is known of the optimal treatment of recurrent VVC (RVVC) has not been established. OBJECTIVE: Through the in vitro antifungal susceptibility profiling of VVC isolates, we hope to foster significant improvements in the control and treatment of this disease. METHODS: Candida isolates from VVC patients were collected from 12 hospitals in 10 cities across China. Species were identified by phenotype analysis and DNA sequencing. Species were identified by phenotype analysis and DNA sequencing. Susceptibilities to 11 drugs were determined by Clinical and Laboratory Standards Institute broth microdilution. RESULTS: 543 strains were isolated from those VVC patients enrolled in this study, of which, 15.7% were from RVVC. The most commonly identified species was C. albicans (460, 84.71%), and the most commonly non-albicans Candida spp. (NAC) was C. glabrata (47, 8.66%). NAC also included C. Krusei, Meyerozyma Guillermondii, Meyerozyma Caribbica, C. Tropicalis, C. Parapsilosis, and C. Nivariensis. Most C. albicans isolates were susceptible to caspofungin (99.8%), followed by fluconazole (92%) and voriconazole (82.6%). The proportion of C. albicans strains with wild type (WT) MICs that were susceptible to amphotericin B and caspofungin were 98%, followed by posaconazole at 95%, itraconazole at 86%, fluconazole at 74% and voriconazole at 54%. The fluconazole MICs for C. albicans were lower than those for NAC (P < 0.05), while the itraconazole MICs showing no significant difference (P > 0.05). The susceptible rate of uncomplicated VVC to fluconazole was 92%. The proportion of WT strains to fluconazole in RVVC was much lower than that in other types of VVC (67 vs. 77%, P < 0.05). However, the proportions of WT strains to itraconazole in RVVC was over 85%, which was much higher than that to fluconazole (87 vs. 67%, P < 0.05). CONCLUSIONS: C. albicans was still the predominant pathogen for VVC in China, while C. glabrata was the main species in NAC. Fluconazole could still be used as an empirical treatment for uncomplicated VVC. However, fluconazole may not be the first choice for the therapy of RVVC. In such cases, itraconazole appears to be the more appropriate treatment. As for VVC caused by NAC, nonfluconazole drugs, such as itraconazole, may be a good choice.

Neoadjuvant chemotherapy for patients with international federation of gynecology and obstetrics stages IB3 and IIA2 cervical cancer: a multicenter prospective trial.

BACKGROUND: Preoperative neoadjuvant chemotherapy (NACT) has been widely used in developing countries for the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB3 and IIA2 cervical cancer. However, the effectiveness of NACT and treatment options for NACT-insensitive patients have been concerning. This study will assess prognostic differences between NACT and primary surgery treatment (PST), determine factors associated with prognosis, and explore better adjuvant treatment modalities for NACT-insensitive patients. METHODS: This study analyzed clinical characteristics, pathological characteristics, treatment options, and follow-up information of 774 patients with FIGO stages IB3 and IIA2 cervical cancer from 28 centers from January 2016 to October 2019 who participated in a multicenter, prospective, randomized controlled trial. RESULTS: For patients undergoing NACT, the 5-year OS and PFS rate was 85.8 and 80.5% respectively. They were similar in the PST group. There was no significant difference in OS and PFS between clinical response (CR)/partial response (PR) groups and stable disease (SD)/progressive disease (PD) groups. Apart from deep cervical invasion (p = 0.046) affecting OS for patients undergoing NACT, no other clinical and pathological factors were associated with OS. 97.8% of NACT-insensitive patients opted for surgery. If these patients did not have intermediate- or high-risk factors, whether they had undergone postoperative adjuvant therapy was irrelevant to their prognosis, whereas for patients with intermediate- or high-risk factors, adjuvant chemotherapy resulted in better PFS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.019) and OS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.002). CONCLUSIONS: NACT could be a choice for patients with FIGO stages IB3 and IIA2 cervical cancer. The main risk factor influencing prognosis in the NACT group is deep cervical invasion. After systematic treatment, insensitivity to NACT does not indicate a poorer prognosis. For NACT-insensitive patients, Chinese prefer surgery. Postoperative adjuvant therapy in patients with no intermediate- or high-risk factors does not improve prognosis, and chemotherapy in patients with intermediate- and high-risk factors is more effective than radiation therapy and other treatments. TRIAL REGISTRATION: The study was prospectively registered on ClinicalTrials.gov (NCT03308591); date of registration: 12/10/2017.

MutL homolog 1 germline mutation c.(453+1_454-1)_(545+1_546-1)del identified in lynch syndrome: A case report and review of literature.

BACKGROUND: Lynch syndrome (LS) is an autosomal dominant hereditary disorder because of germline mutations in DNA mismatch repair genes, such as MutL homolog 1 (MLH1), PMS1 homolog 2, MutS homolog 2, and MutS homolog 6. Gene mutations could make individuals and their families more susceptible to experiencing various malignant tumors. In Chinese, MLH1 germline mutation c.(453+1_454-1)_(545+1_546-1)del-related LS has been infrequently reported. Therefore, we report a rare LS patient with colorectal and endometrioid adenocarcinoma and describe her pedigree characteristics. CASE SUMMARY: A 57-year-old female patient complained of irregular postmenopausal vaginal bleeding for 6 mo. She was diagnosed with LS, colonic malignancy, endometrioid adenocarcinoma, secondary fallopian tube malignancy, and intermyometrial leiomyomas. Then, she was treated by abdominal hysterectomy, bilateral oviduct oophorectomy, and sentinel lymph node resection. Genetic testing was performed using next-generation sequencing technology to detect the causative genetic mutations. Moreover, all her family members were offered a free genetic test, but no one accepted it. CONCLUSION: No tumor relapse or metastasis was found in the patient during the 30-mo follow-up period. The genetic panel sequencing showed a novel pathogenic germline mutation in MLH1, c.(453+1_454-1)_(545+1_546-1)del, for LS. Moreover, cancer genetic counseling and testing are still in the initial development state in China, and maybe face numerous challenges in the further.

Aptamer Nanomaterials for Ovarian Cancer Target Theranostics.

Ovarian cancer is among the leading causes of gynecological cancer-related mortality worldwide. Early and accurate diagnosis and an effective treatment strategy are the two primary means of improving the prognosis of patients with ovarian cancer. The development of targeted nanomaterials provides a potentially efficient strategy for ovarian cancer theranostics. Aptamer nanomaterials have emerged as promising nanoplatforms for accurate ovarian cancer diagnosis by recognizing relevant biomarkers in the serum and/or on the surface of tumor cells, as well as for effective ovarian cancer inhibition via target protein blockade on tumor cells and targeted delivery of various therapeutic agents. In this review, we summarize recent advances in aptamer nanomaterials as targeted theranostic platforms for ovarian cancer and discusses the challenges and opportunities for their clinical application. The information presented in this review represents a valuable reference for creation of a new generation of aptamer nanomaterials for use in the precise detection and treatment of ovarian cancer.

A review of autoimmunity and immune profiles in patients with primary ovarian insufficiency.

Primary ovarian insufficiency (POI) is a complicated clinical syndrome characterized by progressive deterioration of ovarian function. Autoimmunity is one of the main pathogenic factors affecting approximately 10% to 55% of POI cases. This review mainly focuses on the role of autoimmunity in the pathophysiology of POI and the potential therapies for autoimmunity-related POI. This review concluded that various markers of ovarian reserve, principally anti-Müllerian hormone, could be negatively affected by autoimmune diseases. The presence of lymphocytic oophoritis, anti-ovarian autoantibodies, and concurrent autoimmune diseases, are the main characteristics of autoimmune POI. T lymphocytes play the most important role in the immune pathogenesis of POI, followed by disorders of other immune cells and the imbalance between pro-inflammatory and anti-inflammatory cytokines. A comprehensive understanding of immune characteristics of patients with autoimmune POI and the underlying mechanisms is essential for novel approaches of treatment and intervention for autoimmune POI.

[Retracted] Downregulation of matrix metalloproteinase 9 by small interfering RNA inhibits the tumor growth of ovarian epithelial carcinoma in vitro and in vivo.

Following the publication of this paper, the authors contacted the Editorial Office to request that the article be retracted on account of an inability to obtain consistent results after having repeated the experiments portrayed in Figs. 1B and 3B. Independently, it was drawn to the Editor's attention that certain of the western blotting data shown in these figures were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that these other articles were under consideration for publication at the same time as the above article was submitted for publication to Molecular Medicine Reports, the Editor has agreed to the authors' request that this article should be retracted from the Journal. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 12: 753­759, 2015; DOI: 10.3892/mmr.2015.3425].

[Retracted] Effects of cyclooxygenase­2 gene silencing on the biological behavior of SKOV3 ovarian cancer cells.

Following the publication of the above article, the authors have requested that it be retracted. They alerted the Editorial Office to the fact that the same data, albeit with a different view, had been selected to show the 'CON' and 'NC' experiments for the colony­formation assays featured in Fig. 6. The Editor has agreed to the authors' request that the paper be retracted. All the authors agree to this retraction, and apologize for any inconvenience caused. [the original article was published in Molecular Medicine Reports 11: 59­66, 2015; DOI: 10.3892/mmr.2014.2732].

Sentinel Lymph Node Mapping in Endometrial Cancer: A Comprehensive Review.

Endometrial cancer (EC) is known as a common gynecological malignancy. The incidence rate is on the increase annually. Lymph node status plays a crucial role in evaluating the prognosis and selecting adjuvant therapy. Currently, the patients with high-risk (not comply with any of the following: (1) well-differentiated or moderately differentiated, pathological grade G1 or G2; (2) myometrial invasion< 1/2; (3) tumor diameter < 2 cm are commonly recommended for a systematic lymphadenectomy (LAD). However, conventional LAD shows high complication incidence and uncertain survival benefits. Sentinel lymph node (SLN) refers to the first lymph node that is passed by the lymphatic metastasis of the primary malignant tumor through the regional lymphatic drainage pathway and can indicate the involvement of lymph nodes across the drainage area. Mounting evidence has demonstrated a high detection rate (DR), sensitivity, and negative predictive value (NPV) in patients with early-stage lower risk EC using sentinel lymph node mapping (SLNM) with pathologic ultra-staging. Meanwhile, SLNM did not compromise the patient's progression-free survival (PFS) and overall survival (OS) with low operative complications. However, the application of SLNM in early-stage high-risk EC patients remains controversial. As revealed by the recent studies, SLNM may also be feasible, effective, and safe in high-risk patients. This review aims at making a systematic description of the progress made in the application of SLNM in the treatment of EC and the relevant controversies, including the application of SLNM in high-risk patients.

Disseminated ovarian granulosa cell tumor after laparoscopic surgery: Two case reports.

RATIONALE: Granulosa cell tumors (GCT) have an incidence of 0.6 to 0.8/100,000. Short-term relapsed ovarian GCT is extremely rare. Herein, this report aims to present 2 rare cases of disseminated ovarian GCT and analyze the causes of recurrence. PATIENT CONCERNS: The 2 patients presented with abdominal pain. DIAGNOSIS: Both the patients were diagnosed with relapsed ovarian GCT (IIIc stage) in the adult type. INTERVENTIONS: The 2 patients had a medical history of surgery for ovarian GCT by using laparoscopic with power morcellators (LPM). They experienced relapsed ovarian GCT postoperatively. Subsequently, they received a repeated operation through a laparotomy approach. Numerous malignant metastasis neoplasms were detected at the port-sites. Then, tumor resection was performed. OUTCOMES: The postoperative pathologies of both case 1 and case 2 reported ovarian GCT (IIIc stage) in adult type. The 2 patients presented disease-free survival for more than 33 months follow-up period. LESSONS: The application of LPM may be a risk factor of disseminated ovarian GCT. However, laparoscopic surgery is still an optimal treatment strategy for ovarian tumors. Besides, gynecologists should comply with the tumor-free principle during surgery.

FGFR3 phosphorylates EGFR to promote cisplatin-resistance in ovarian cancer.

Ovarian cancer is a deadly gynecologic cancer, and the majority of patients with ovarian cancer experience relapse after traditional treatment. Cisplatin (DDP) is a common chemotherapeutic drug for ovarian cancer, but many patients acquire DDP-resistance after treatment with long-term chemotherapy. The mechanisms of drug-resistance in ovarian cancer are not clear, and we thus aim to investigate novel targets for DDP-resistant ovarian cancer. Differential analysis, KEGG pathway enrichment and protein interaction networks were employed to identify the key genes related to DDP-resistance in ovarian cancer. Subsequently, cell viability, apoptosis and migration were measured to assess the effect of fibroblast growth factor receptor 3 (FGFR3) on DDP-resistance. Further, Pearson correlation analysis and co-expression analysis were used to explore the downstream pathways of FGFR3, and the function of FGFR3 and its downstream targets were further demonstrated by in vitro and nude mice experiments. FGFR3 were expressed at high levels in DDP-resistant ovarian cancer cells. FGFR3 silencing suppressed the activation of PI3K/AKT pathway and impeded the drug-resistance and development of tumor cells. Afterwards, we found that FGFR3 was co-expressed with epidermal growth factor receptor (EGFR). FGFR3 overexpression elevated EGFR phosphorylation and activated PI3K/AKT signaling. Furthermore, in nude mice, silencing FGFR3 and inhibiting EGFR phosphorylation were observed to promote the therapeutic effect of DDP. In conclusion, FGFR3 overexpression enhances DDP-resistance of ovarian cancer by promoting EGFR phosphorylation and further activating PI3K/AKT pathway. This study may offer promising targets for DDP-resistant ovarian cancer.

Pegylated liposomal doxorubicin in patients with epithelial ovarian cancer.

OBJECTIVE: To evaluate the efficacy and safety of PLD in treating of in patients who experience epithelial ovarian, fallopian tubal, and peritoneal cancer progression within 12 months after the first-line platinum-based therapy. METHODS: This was an open-label, single-arm and multicenter clinical trial. The ORR was the interim primary objective, and the DCR, AEs and QOL were the secondary objectives. The impact of factors on efficacy outcomes, the change trend of CA125 and the artificial platinum-free interval were exploratory endpoints. RESULTS: Totally, 115 patients were enrolled in this study and included in the ITT population. Moreover, 101 patients were included in the safety population. The median follow-up time was 4 months (IQR 2-6). In the ITT population, the confirmed ORR was 37.4% (95% CI, 28.4-46.4%), and the DCR was 65.2% (95% CI, 56.4-74.1%). The previous response status to platinum-based chemotherapy and baseline CA125 levels were significantly correlated with the ORR. The ORR was significantly higher in patients with a CA125 decrease after the first cycle than in the patients with a CA125 increase. The most common grade 3 or higher AE was hand-foot syndrome (3 [3.0%] of 101 patients). No statistically significant differences existed between the baseline and the postbaseline questionnaires. CONCLUSIONS: For patients who experience platinum-resistant and platinum-refractory relapse, the use of PLD may be acceptable because of the associated satisfactory efficacy, low frequency of AEs and high patient QOL. Moreover, a low CA125 level at baseline and a reduction in CA125 after the first cycle are predictive factors for satisfactory efficacy.

MicroRNA-101 inhibits growth and metastasis of human ovarian cancer cells by targeting PI3K/AKT.

INTRODUCTION: Ovarian cancer is the most frequent cause of gynecological cancer related mortality in woman. This study was designed to investigate the role and therapeutic potential of miRNA-101 in ovarian cancer. MATERIAL AND METHODS: Expression analysis was carried out by real-time quantitative polymerase chain reaction. Transfections were performed with the help of Lipofectamine 2000 reagent. AO/EB and annexin V/PI staining was used to detect apoptosis and flow cytometry was used for cell cycle analysis. Western blotting was employed for cell cycle analysis. RESULTS: It was found that miRNA-101 was significantly down-regulated in ovarian cancer cells. The over-expression of miRNA-101 causes a significant decrease in the viability of ovarian cancer cells via the initiation of apoptosis and sub-G1 arrest of OVACAR-3 cells. It was indicated that PTEN was the potential target of miRNA-101 in OVACAR-3 cells. There was 4.5-fold up-regulation of PTEN expression in ovarian cancer cell lines and the over-expression of miRNA-101 in OVACAR-3 cells resulted in the down-regulation of PTEN expression. The inhibition of PTEN in the OVACAR-3 cells arrested the proliferation of these cells. The over-expression of miRNA-101 causes significant down-regulation in PI3K and AKT expression of OVACAR-3 cells. CONCLUSIONS: It can be concluded that miRNA-101 acts as a tumor suppressor which may be beneficial in the treatment of ovarian cancer.

cGAS-STING signaling in cancer immunity and immunotherapy.

Recent studies have shown that the innate immune cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway may play an important role in antitumor immunity. Additionally, the cGAS-STING pathway promotes the senescence of cancer cells, induces apoptosis of cancer cells, and increases the protective effect of cytotoxic T cells and natural killer cell-mediated cytotoxicity. We believe that the combination of the cGAS-STING signaling pathway with other therapeutic methods provides a new perspective from which to overcome obstacles in the application of this review. Further, we highlight the antitumor mechanism of the cGAS-STING signaling pathway and the latest advances in monotherapy and combination therapy with related agonists.