TRIM47 inhibits cisplatin chemosensitivity and endoplasmic reticulum stress-induced apoptosis of ovarian cancer cells.

Ovarian cancer (OC) is the fifth most common cause of death in women worldwide. Chemoresistance is a key reason for treatment failure, causing high mortality. As a member of the tripartite motif-containing (TRIM) protein family, tripartite motif 47 (TRIM47) plays a vital role in the carcinogenesis and drug resistance of various cancers. This study investigated the impact and mechanisms of TRIM47 on cisplatin (DDP) chemosensitivity and apoptosis in OC. OC cell viability was assessed with a cell counting kit-8 assay and OC cell apoptosis was assessed using flow cytometry, caspase-3 and caspase-9 activity, and Bax and Bcl-2 expression assays while gene and protein expression were assessed using qRT-PCR and Western blot assays. The expression of TRIM47 was significantly increased in both DDP-resistant tissues from patients with OC tissues and in cancer cell lines compared with that in normal tissue or parental cell lines. The increased level of TRIM47 correlated with poor prognosis in patients with OC. Functional assays demonstrated that TRIM47 promoted DDP resistance both in vitro and in vivo. The increased viability and reduced apoptosis of OC cells induced by TRIM47 can be rescued by the endoplasmic reticulum (ER) stress-inducer tunicamycin, suggesting that TRIM47 inhibits OC cell apoptosis by suppressing ER stress. Therefore, TRIM47 may be targeted as a therapeutic strategy for DDP resistance in OC.

Treatment of secondary uterine malignancy following radiotherapy for cervical cancer: a study based on the SEER database.

BACKGROUND: Radiotherapy is one of the main treatments for cervical cancer. Long-term complications of radiation exposure include the emergence of secondary tumors. This is a retrospective study based on an American population. We discuss the optimal treatment modality for patients with radiation-induced secondary uterine malignancy based on the Surveillance, Epidemiology, and End Results database. METHODS: The study included patients with a definitive pathological diagnosis of cervical cancer who were diagnosed with a uterine malignant tumor ≥ 1 year later. Patients in whom cervical cancer was not the first tumor or patients with missing data were excluded. Univariate and multivariate analyses were performed using the COX regression model to screen independent prognostic factors affecting overall survival. Kaplan-Meier survival curves were analyzed using the R software package. RESULTS: We screened 142 patients with a secondary uterine malignancy after cervical cancer treatment, 115 patients with a secondary uterine malignancy after radiotherapy, and 27 patients with a secondary uterine malignancy who did not receive radiotherapy. The average latency period for developing a secondary tumor was 8 years, and 57.04% of the patients had a second tumor at ≥ 60 years of age. In patients with a secondary uterine malignancy after radiotherapy, surgery improved the prognosis [hazard ratio (HR), 0.374; 95% confidence interval (CI), 0.229-0.612], whereas radiotherapy and chemotherapy did not reduce the risk of death. In the subgroup analysis, the surgery plus chemotherapy group had a significantly better survival prognosis than the other groups (HR, 0.251; 95% CI, 0.122-0.515). CONCLUSIONS: The results suggest that the treatment modality in patients with secondary uterine malignancy after radiotherapy for cervical cancer has a significant impact on survival. The survival outcomes of patients receiving surgery combined with chemotherapy are superior to those of patients receiving other treatments.

Deposition and water repelling of temperature-responsive nanopesticides on leaves.

Pesticides are widely used to increase agricultural productivity, however, weak adhesion and deposition lead to low efficient utilization. Herein, we prepare a nanopesticide formulation (tebuconazole nanopesticides) which is leaf-adhesive, and water-dispersed via a rapid nanoparticle precipitation method, flash nanoprecipitation, using temperature-responsive copolymers poly-(2-(dimethylamino)ethylmethylacrylate)-b-poly(ε-caprolactone) as the carrier. Compared with commercial suspensions, the encapsulation by the polymer improves the deposition of TEB, and the contact angle on foliage is lowered by 40.0°. Due to the small size and strong van der Waals interactions, the anti-washing efficiency of TEB NPs is increased by 37% in contrast to commercial ones. Finally, the acute toxicity of TEB NPs to zebrafish shows a more than 25-fold reduction as compared to commercial formulation indicating good biocompatibility of the nanopesticides. This work is expected to enhance pesticide droplet deposition and adhesion, maximize the use of pesticides, tackling one of the application challenges of pesticides.

SP1-Regulated Non-Coding RNA SNHG22 Promotes Ovarian Cancer Growth and Glycolysis.

OBJECTIVES: Long non-coding RNAs (lncRNAs) play a crucial part in cancer progression. However, in epithelial ovarian carcinoma (EOC), the role of SNHG22 needs to be further explained. METHODS: Quantitative real-time PCR was used to detect the expression of SNHG22. EOC cells were stably transfected with lentivirus approach and cell proliferation, glycolysis and cell apoptosis, as well as tumorigenesis in animal were performed to assess the effects of SNHG22 in EOC. Chromatin immunoprecipitation (ChIP) and luciferase reporter assay were conducted to confirm the relationship between SP1 and SNHG22. RESULTS: Higher expressed SNHG22 was associated with a poor prognosis in EOC tissues. SNHG22 facilitated glycolysis and proliferation. Mechanistically, LDHA deficiency and glycolysis inhibitor (2-DG, 3-BG) partly rescued proliferation. SP1 mediated SNHG22 expression at the transcriptional level and the SNHG22 promoter region (-900~ -600) was necessary for SP1 binding. Hypoxia and HIF-1α also upregulated SNHG22 expression. CONCLUSION: SNHG22 is an independent prognostic biomarker for EOC. SNHG22 promotes EOC progression and is a prospective therapeutic target.

TRIM59, amplified in ovarian cancer, promotes tumorigenesis through the MKP3/ERK pathway.

Tripartite motif containing 59 (TRIM59) functions as an oncoprotein in various human cancers including ovarian cancer. In this study, we found that TRIM59 gene amplification was prevalent in ovarian cancer tissues, and its amplification was significantly correlated with poorer overall survival. Moreover, knockdown of TRIM59 in SKOV3 and OVCAR3 cells, which had relatively high level of TRIM59, suppressed glucose uptake and lactate production. TRIM59 knockdown also decreased the expression of c-Myc and lactate dehydrogenase A, and the phosphorylation of extracellular signal-regulated kinase (ERK). TRIM59 overexpression in A2780 cells, which expressed low level of TRIM59, showed reverse effects. Notably, treatment with an ERK inhibitor (PD98059) completely abolished the oncogenic effects of TRIM59 overexpression. Interestingly, TRIM59 increased the ubiquitination of MAP kinase phosphatase 3 (MKP3), which may dephosphorylate and inactivate ERK. Ectopic expression of MKP3 inhibited the promoting effects of TRIM59 on glycolysis and the phosphorylation of ERK. TRIM59 protein expression was negatively correlated with MKP3 protein expression in ovarian cancer tissues. Finally, TRIM59 amplification potently affected the anticancer effect of 3-bromopyruvate, an inhibitor of glycolysis, in ovarian cancer cells and patient-derived xenograft. In conclusion, these results suggest that TRIM59 may regulate glycolysis in ovarian cancer via the MKP3/ERK pathway.

Expression levels of MRP1, GST-π, and GSK3ß in ovarian cancer and the relationship with drug resistance and prognosis of patients.

Expression levels of multidrug resistance-associated protein 1 (MRP1), glutathione S-transferase π (GST-π) and glycogen synthase kinase-3ß (GSK3ß) were investigated in ovarian epithelial cancer and the relationship with the primary drug resistance of patients with ovarian cancer to chemotherapy. One hundred and twenty-one ovarian cancer tissue samples from patients who underwent ovarian cancer resection from January 2013 to June 2015 in Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University were enrolled in the Experimental group, while 58 ovarian tissue samples from patients with fallopian tube obstruction but with no ovarian cancer who received surgical treatment for blocked fallopian tube were included in the Control group. After the detection of the expression levels of MRP1, GST-π, and GSK3ß mRNA by RT-PCR and the analysis of related clinical pathological factors, patients in the Experimental group were divided into the Chemotherapy-sensitive and Chemotherapy-resistant groups according to the chemotherapy efficacy. Additionally, with the mean expression levels of MRP1, GST-π, and GSK3ß in ovarian cancer tissues as the boundaries, the expression levels of the three genes in the Experimental group were classified into high expression and low expression. Ovarian cancer tissues had much higher expression levels of MRP1, GST-π, and GSK3ß mRNA than normal ovarian tissues (P<0.05). The expression levels of MRP1, GST-π, and GSK3ß mRNA in the Chemotherapy-sensitive group were significantly lower than those in the Chemotherapy-resistant group (P<0.05). Patients with high expression of MRP1, GST-π, and GSK3ß mRNA had a much lower 3-year survival rate than patients with low expression of the genes (P<0.05). Highly expressed in patients with ovarian cancer, MRP1, GST-π, and GSK3ß mRNA play an important role in the development and drug resistance of ovarian cancer, which ensures this study is of positive clinical guiding significance in developing proper treatment for ovarian cancer and evaluating the efficacy of chemotherapy.

Growth inhibition of human ovarian cancer cells by blocking STAT3 activation with small interfering RNA.

OBJECTIVE: Signal transducer and activator of transcription 3 (STAT3) are constitutively activated in a variety of cancers and it is a common feature of ovarian cancer. Thus, STAT3 represents a promising molecular target for tumor therapy. We applied a DNA vector-based STAT3-specific RNA interference approach which specifically blocks over-activated STAT3, to treat human ovarian cancer cells, and evaluated the cellular proliferation ability and investigated the molecular mechanisms in vitro. STUDY DESIGN: A DNA vector-based RNA interference approach was used to knockdown STAT3 expression in human ovarian cancer cells in vitro. RESULTS: The STAT3 siRNA down-regulated the expression of cyclin D1, survivin, and VEGF in ovarian cancer cells both at transcription and translation levels. Inhibition of STAT3 and its related genes was accompanied by growth suppression and induction of apoptosis in cancer cells in vitro. CONCLUSIONS: These data indicate that STAT3 signaling is a promising molecular target for ovarian cancer therapy.

Prognostic factors of patients with ovarian yolk sac tumors: a study in Chinese patients.

BACKGROUND: The aim of this study was to investigate the prognostic factors of ovarian yolk sac tumors (YST) and the survival rates in Chinese patients. PATIENTS AND METHODS: We retrospectively reviewed 76 patients with ovarian YST from the Department of Obstetrics and Gynecology, Liaoning Cancer Hospital & Institute, China, between 1984 and 2007. RESULTS: Five-year overall survival rates in stages I, II, III, and IV were 91.8, 88.9, 39.5, and 25.0%, respectively. Age, histologic type, preoperative serum alpha-fetoprotein level, fertility-sparing surgery, tumor size and lymphadenectomy did not affect the prognosis of YST in our study. Multivariate analysis confirmed cisplatin-based chemotherapy (hazard ratio (HR) = 4.945), chemotherapy courses > 3 (HR = 2.954), residual tumor < or = 2 cm (HR = 0.224) and ascites volume < or = 100 ml (HR = 0.389) as independent predictors for overall survival. CONCLUSIONS: Our study demonstrated that the 5-year overall survival rate of YST was 53.9% for the Liaoning Cancer Hospital & Institute, China. Cisplatin-based chemotherapy, chemotherapy courses, residual tumor size and ascites volume were independent prognosis factors.

Isolation of human mesenchymal stem cells from third-trimester amniotic fluid.

OBJECTIVE: To determine whether mesenchymal stem cells (MSCs) can be isolated in third-trimester amniotic fluid (AF) and their differentiation induced. METHOD: Sufficient numbers of MSCs were isolated from the AF of 15 healthy women undergoing cesarean delivery in the third trimester to be cultured and induced to differentiate into osteocytes. RESULTS: Reverse-transcriptase polymerase chain reaction showed the MSCs to express the pluripotency marker gene OCT4, and flow cytometry showed these cells to be positive for CD29, CD73, CD90, and CD105 and negative for CD31, CD45, and CD61. The MSCs were also determined to be nontumorigenic. CONCLUSION: Multipotent MSCs can be obtained from AF in the third trimester, which may be less dangerous than the second trimester to women and their fetuses.