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ObjectiveTo investigate the expression of RNA binding motif single stranded interacting protein 3 （RBMS3） in epithelial ovarian cancer （EOC） tissues and its relationship with the clinicopathological features and prognosis of EOC. MethodsThe study enrolled the paraffin-embedded tissues from 110 EOC cases and 73 benign epithelial ovarian tumor cases pathologically diagnosed in the first affiliated Hospital of Bengbu Medical College from January 2015 to December 2019. By using anti-RBMS3 polyclonal antibody， the immunohistochemical staining was employed to detect RBMS3 expression in the tissues and then its correlation with the clinicopathological parameters and prognosis of EOC was analyzed. ResultsRBMS3 was expressed in both EOC and benign epithelial ovarian tumor tissues. RBMS3 expression in EOC tissues， significantly related with International Federation of Gynecology and Obstetrics （FIGO） stage， histological grade， CEA levels and survival status， was significantly lower than that in benign epithelial ovarian tumor tissues （P<0.05）. Kaplan–Meier survival curve showed that low RBMS3 expression in EOC patients was correlated with decreased progression-free survival （PFS） and overall survival （OS） （P<0.05）. Univariate analysis showed that RBMS3 expression， FIGO stage， residual lesion size， intestinal metastasis and intraperitoneal implantation were associated with OS of EOC patients （P<0.05）； multivariate analysis showed that low RBMS3 expression and intestinal metastasis were independent risk factors for poor prognosis in EOC patients （P<0.05）. ConclusionsRBMS3 is expressed at low levels in EOC tissues， which is closely related to poor prognosis of EOC patients. RBMS3 may function as a tumor suppressor gene in EOC tissues and can be used as an EOC-independent prognostic marker for targeted therapy against EOC.
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Resumen OBJETIVO: Comparar la cirugía radical con la cirugía conservadora de la fertilidad en mujeres con cáncer de ovario epitelial en estadio 1A-C con respecto a la tasa de recurrencia y las tasas de supervivencia. Además, evaluar los desenlaces reproductivos y obstétricos para las mujeres con cáncer de ovario epitelial en estadio I tratadas con una conducta conservadora de la fertilidad. PACIENTES Y MÉTODOS: Estudio prospectivo efectuado en pacientes con cáncer de ovario epitelial, estadio I, con edad ≤ 40 años. A las pacientes del grupo de preservación de la fertilidad se les practicó salpingooforectomía del lado del ovario afectado y una biopsia por incisión o escisión en cuña del ovario contralateral. A las pacientes del grupo de cirugía radical se les practicó la histerectomía total y salpingooforectomía bilateral. Para evaluar los desenlaces reproductivos y oncológicos se dio seguimiento a todas las pacientes durante cinco años. RESULTADOS: Se estudiaron 60 pacientes; las del grupo de cirugía de preservación de la fertilidad eran significativamente más jóvenes (30 ± 4 en comparación con 35 ± 5) (p < 0.001), el tamaño de sus tumores era más pequeño 3.4 ± 1.3 en comparación con 6.0 ± 2,6 (p < 0.001), de menor grado (p < 0.001). = 0.011), estadio más precoz (p < 0.001) y con más histología mucinosa que las pacientes del grupo de cirugía radical. No hubo diferencias estadísticamente significativas entre ambos grupos en cuanto a la recurrencia tumoral o las tasas de supervivencia. De 25 pacientes operadas para preservación de la fertilidad 18 de 25 intentaron quedar embarazadas. Se registraron 15 de 18 embarazos, incluidos 13 nacidos vivos, 1 aborto espontáneo y 1 muerte fetal intrauterina. CONCLUSIÓN: La cirugía conservadora de la fertilidad podría ser una alternativa adecuada a la cirugía radical para mujeres jóvenes con cáncer epitelial de ovario en estadio I.
Abstract OBJECTIVE: In the current study, we aimed to compare between radical surgery and fertility saving surgery in females with stage 1A-C EOC regarding recurrence rate and patients survival rates in addition to evaluating reproductive and obstetric outcomes for stage I EOC females who were managed by fertility saving surgery. PATIENTS AND METHODS: We prospectively identified 60 patients diagnosed with stage I EOC aged ≤ 40 years. Patients in the fertility-preservation group underwent salpingo-oophorectomy on the side of the affected ovary in addition to incisional biopsy or wedge excision of the ovary on the other side. Patients in the radical surgery group underwent total hysterectomy and bilateral salpingo-oophorectomy. We followed up all patients for 5 years to assess their reproductive and oncological outcomes. RESULTS: Patients in the fertility preservation surgery group were significantly younger (30 ± 4 versus 35 ± 5) (p < 0.001), their tumor sizes were smaller 3.4 ± 1.3 versus 6.0 ± 2.6 (p < 0.001), of lower grade (p = 0.011), earlier stage (p < 0.001) and has more mucinous histology than patients in the radical surgery group. There were no statistically significant differences between both groups regarding tumor recurrence or survival rates. Of 25 patients underwent fertility preservation surgery, 18/25 (72%) tried to get pregnant. 15/18 (83%) pregnancies were recorded, including 13 live births, 1 miscarriage, and 1 intrauterine fetal death. CONCLUSION: Fertility sparing surgery could be adequate alternative to radical surgery for young females with stage I EOC.
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Abstract Therapeutically, piracetam has been used for decades as a cognitive enhancer for memory- related neuronal disorders. The present study aimed to investigate the neuroprotective potential of piracetam on lipopolysaccharides (LPS)-induced neuronal deficit using both in-vitro and in-vivo experimental models. For the in-vitro analysis, EOC-20 murine microglial cells were induced with a neuronal toxicity of 100 µg/ml of LPS, and the formation of intracellular reactive oxygen species (ROS) and nitric oxide (NO) productions were determined. For in-vivo neuroprotective analysis, groups of mice were treated orally with two doses of piracetam (200 and 400 mg/kg) for 30 days. Neuronal toxicity was induced by four intraperitoneal injections of LPS (250 µg/kg/day). The malondialdehyde (MDA) level was measured for oxidative stress, and catalase reduced glutathione (GSH), glutathione reductase (GRD), and superoxide dismutase (SOD) levels were determined as the antioxidant parameters. The result of the cell viability study was that pre-treatment with piracetam significantly protected the LPS-induced cell loss, and attenuated the ROS generation and NO production in LPS-induced EOC-20 cells. Moreover, the treatment of piracetam significantly reduced the MDA levels and improved catalase, GSH, GRD, and SOD activities in LPS-induced mice brains. The overall results from this study supported the neuroprotective effects of piracetam against LPS-induced neuronal toxicity.
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Animals , Male , Mice , Piracetam/analysis , Lipopolysaccharides/pharmacology , Neuroprotection/drug effects , Oxidative Stress , Cerebrum/abnormalities , Neuroinflammatory Diseases/chemically induced , Antioxidants/adverse effectsABSTRACT
@# Objective: To explore the action mechanism of miR-139-5p inhibiting proliferation and invasion of epithelial ovarian cancer (EOC) cells by targetedly regulatingNotch1.Methods: A total of 24 pairs of EOC tissues and its corresponding para-cancerous tissues from patients, who underwent surgical resection in the DepartmentofGynecology,Nanyang Central Hospital of Henan Province, were collected for this study; in addition, human ovarian cancer cell lines (SKOV3, ES2, HEY-T30) and human ovarian epithelial cell line IOSE80 were also collected. Real-time quantitative PCR (qPCR) was applied to detectmRNAexpressionofmiR-139-5pandNotch1 in EOC tissues and cell lines. The miR-139-5p over-expression vector and recombinant plasmid pLV-Notch1 were transfected into SKOV3 cells. Blank control group (Ctrl group) and negative control group (NC group) were set up. Dual luciferase reporter gene assay was applied to verify the targeting relationship between miR-139-5p and Notch1 3'-UTR. CCK-8, Transwell and Scratch healing experiments were applied to detect cell proliferationinvasionandmigration, respectively. Western blotting was applied to detect expressions of proliferation and migration related proteins in cells. Results: Compared with para-cancerous tissues and IOSE80 cells, the expression of miR-139-5p was significantly decreased in EOC tissues and cell lines, while the expression of Notch1 mRNA was significantly increased (all P<0.01). The results of Dual luciferase reporter showed that Notch1 was the downstream target gene of miR-139-5p. Compared with NC group, cell proliferation, invasion and migration ability, expression levels of Notch1, NICD, Cyclin D1, Cyclin A1, Snail1, β-catenin and N-cadherin were all significantly decreased on 3 d in miR-139-5p mimic group (all P<0.01), while expression of E-cadherin was significantly increased (P<0.01); meanwhile, over-expression of Notch1 could reverse the inhibitory effect of miR-1395p on proliferation, invasion and migration of SKOV3 cells. Conclusion: miR-139-5p can targetedly regulate Notch1 to inhibit proliferation, invasion and migration of EOC cells, which may be related to its down-regulation of NICD, Cyclin D1, Cyclin A1, Snail1, βcatenin and N-cadherin, and up-regulation of E-cadherin.
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Background & objectives: Advanced epithelial ovarian cancer (EOC) is associated with dismal outcome and progression-free survival (PFS) shortens with each subsequent relapse. For patients with recurrent and platinum refractory disease, therapeutic options are limited. Oral metronomic therapy (OMT) is associated with symptomatic relief and stable response in a significant proportion of patients. We retrospectively evaluated the outcome of patients with EOC treated with OMT at a tertiary care hospital in north India. Methods: Between January 2011 to December 2017, 36 EOC patients received OMT. Patients' median age was 50 yr (range, 38-81 yr) and they had received a median of two lines of prior chemotherapy. OMT regimen included a combination of cyclophosphamide, etoposide (VP-16) and celecoxib with or without pazopanib along with supportive care. Response rates and outcomes were ascertained using the Gynecological Cancer Intergroup Guidelines. The toxicity was graded according to the Common Terminology Criteria for Adverse Events v.4.03. Results: The median CA-125 before initiating OMT was 160 U/ml (range, 42.23-5330 U/ml). The median interval between last chemotherapy and starting OMT regimen was 159 days (range, 1-1211 days). The overall response rate was 50 per cent. The median progression-free survival (PFS) was 8.2 months [95% confidence interval (CI): 5.03-10.33], and the median overall survival was 38 months (95% CI: 25.6-NR). Patients who received two lines of chemotherapy before OMT (P=0.052) and those who received pazopanib-based OMT (P=0.0513) had better PFS. Interpretation & conclusions: For patients with relapse and refractory EOC, OMT could be a reasonable option. A combination of oral etoposide (VP-16) and pazopanib needs further evaluation in a large number of patients in a randomized trial.
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To assess the efficacy and safety of apatinib for patients with epithelial ovarian cancer (EOC) who had failed in second-line chemotherapy. Methods: The clinical data of 46 patients with recurrent EOC who had failed in second-line chemotherapy and were admitted to the Cancer Hospital of Tianjin Medical University from September 2017 to November 2018 were collected. The treatment efficacy of apatinib was evaluated, and treatment-related adverse events (AEs) were recorded to evaluate its safety. Results:A total of 46 eligible patients were enrolled. The median follow-up time was 12 months. The median overall survival (OS) was 6 months (range 2-15 months). The objective response rate (ORR) was 26.1% (12/46 patients), and the disease control rate (DCR) was 86.9% (40/46 patients). AEs occurred in 30 patients (65.2%), and were mainly of grade 1-2. The most common treatment-related AEs were hypertension (39.1%) and hand-foot-skin syndrome (30.4%); only one patient experienced grade 3 treatment-related hyperten-sion. All grade 1-2 AEs could be recovered rapidly and well-tolerated after treatment with medication. Conclusions: Apatinib may be a safe and effective option for patients with advanced EOC who had failed in second-line chemotherapy. Further Studies are warranted in large-scale clinical trials.
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Introduction @#The HER2 (Human epidermal receptor 2) proto-oncogene encodes a transmembrane receptor protein involved in the development and progression of the majority of cancers. Prior studies have shown that HER2 oncogene is overexpressed in approximately 15–30% of ovarian carcinomas. However findings regarding the overexpression and prognosis are still conflicting. @*Goal@#To determine the histomorphological structure of ovarian tumor and perform immunohistochemical analysis of HER2 in tumor tissues @*Materials and Methods@#A total of epithelial ovarian cancer paraffin-embedded tissue blocks 11collected. The hematoxylin and eosin stained histopathology slides of each of the cases were reviewed to confirm the original diagnosis, and to assess the histological grade of the neoplasm. Our study was performed on 11 ovarian epithelial cancer tissues obtained at the time of first surgery. The staining procedure for HER2 overexpression was performed using a monoclonal antibody.@*Results@#The positive expression rate of HER2 in this study was 81.8%. Significant association was not found between HER2 expression International Federation of Gynecologists and Obstetrics (FIGO) stage p-values of 0.196, grading 0.642 and histological subtypes. However, there were more cases of advanced-stage disease (III/IV) with HER-2 expression than early-stage EOC (I/II). HER2 positive tumor were grades 1, 2 and 3 respectively. A higher proportion of serous ovarian neoplasm and adenocarcinoma NOS was also observed to be HER2 positive.@*Conclusion@#HER2 expression was observed to increase with advanced stages of cancer and was more commonly seen in serous rather than in adenocarcinoma NOS.
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Objective:To investigate the impact and mechanisms of TAM to the imbalance of Treg /Th17 in the Eoc microenvi-ronment.Mte hods:Build the in vitro M2 macrophage model ,which was like TAMs .Use flow cytometry to detect the difference of the Treg/Th17 before and after the co-culture of M2 macrophage and CD 4+T cells.Use Western bolt to detect the change of T cell transcription factor and ELISA to detect the IL-10 levels in the supernatant after co-culture.Use crystal violet methods to detect the influence to the ovarian tumor cell proliferation between the different co-culture supernatants and the Transwell to detect the influence to the ovarian tumor cell migration.Thus to analysis the how TAMs influence the imbalance of Treg/Th17 in Eoc microenvironments.R esults:①After coc-ultured with M2 macrophage ,the ratio of Treg/Th17 was( 0.76 ±0.33 ) significant increased compared with control (0.41±0.25) ,M0( 0.40±0.32) and M1(0.31±0.16) (P<0.05).②After co-cultured,the supernatant of M2 group has a significant ability to promote the proliferation of Skov-3 cells.After co-cultured for 1 day, the Skov-3 cell number of M2 group was 14 942.43 ±434.19 , which was significantly higher than the control group ( 12 445.57 ±179.34 ) and CD3/28 group (12 470.32±434.18)(P<0.001).After co-cultured for 2 days,the Skov-3 cell number of M2 group was 30 129.09±520.53 ,which was significantly higher than the control group (25 622.81±897.07) and CD3/28 group(25 721.62±1 808.60) (P<0.05).③After co -cultured with M2 macrophage , the Treg-specific transcription factor Foxp 3 increased ( P=0.047 ) compared with control and M 1 group .④After co-cultured with M2 macrophage for 3 days,the concentration of IL1-0 in the supernatant was(264.04±75.9)pg/ml, which was significantly higher than CD 3/28 group ( 60.89 ±46.54 ) pg/ml,M 0 group ( 44.81 ±32.93 ) pg/ml, M1 group ( 42.71 ± 26.09)pg/ml(P=0.001).Conclusion: M2 macrophage induces the increase of the radio of Treg /Th17 as well as the increase of Treg-specific transcription factor Foxp 3 and the decrease of Th17 -specific transcription factor ROR-γt.Meanwhile , the co-culture supernatant of M2 macrophage and CD4+T cell have the ability to promote the proliferation and migration of ovarian cancer cell ,the mechanism which ,may related to the IL -10 in the supernatant .