In this study, we describe a novel approach to human cancer therapy that is based upon trans-splicing ribozyme-mediated replacement of cancer-specific RNAs with new transcripts that exert therapeutic activities. We have developed a specific ribozyme that can reprogram human telomerase reverse transcriptase (hTERT) RNA to induce transgene activity selectively in cancer cells that express the RNA. The ribozyme-mediated triggering of the transgene expression was accomplished via a high-fidelity trans-splicing reaction with the targeted residue in the hTERT-expressing cells. The ribozyme also induced cytotoxic activity in various hTERT-expressing cancer cells, hence selectively retarding the growth of those cells. Efficient and specific cell regression was also detected with ganciclovir (GCV) treatment only in hTERT-positive cancer cells, which were established to express stably the specific ribozyme that contains the herpes simplex virus thymidine kinase (HSV-tk) gene. Tissue-specific expression of the ribozyme could further augment the target specificity of the ribozyme. Importantly, we observed efficient regression of tumors with GCV treatment in mice that had been inoculated subcutaneously with hTERT-positive cancer cells that stably expressed the specific ribozyme that contains HSV-tk. These results suggest that the hTERT RNA-targeting trans-splicing ribozyme could be a powerful agent for tumor-targeted specific gene therapy.

Objective: The aim of the present study was to determine the prognostic significances of markers of preoperative systemic inflammatory response (SIR) in patients with ovarian clear cell carcinoma (OCCC).Methods: A total of 109 patients diagnosed with OCCC that underwent primary cytoreductive surgery and adjuvant platinum-based chemotherapy from 2009 to 2012 were enrolled in this retrospective study. SIR markers were calculated from complete blood cell counts determined before surgery. Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values for neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR). Prognostic significances with respect to overall survival (OS) and progression-free survival (PFS) were determined by Kaplan-Meier curve and multivariate Cox regression analysis.Results: The optimized NLR, LMR and PLR cut-off values as determined by ROC curve analysis for PFS and OS were 2.3, 4.2, and 123.6, respectively. When the cohort was divided using these optimized cut-offs, NLR and LMR were found to be significantly associated with clinicopathologic factors, NLR with FIGO stage, the presence of malignant ascites, and platinum response, and LMR with FIGO stage, lymph node metastasis, malignant ascites, and platinum response. Kaplan-Meier analysis revealed a high NLR (> 2.3) was significantly associated with low 5-year PFS and OS rates and that a high LMR was significantly associated with high 5-year PFS and OS rates. Multivariate analysis identified FIGO stage, residual mass, and platinum response as independent prognostic factors of PFS, and FIGO stage, residual mass, platinum response, and LMR as independent prognostic factors of OS.Conclusions: Markers of systemic inflammatory response provide useful prognostic information and lymphocyte-to-monocyte ratio is the most reliable independent prognostic factor of overall survival in patients with ovarian clear cell carcinoma.

We evaluated the effect of red ginseng on toxicity, health-related quality of life (HRQL) and survival after adjuvant chemotherapy in patients with epithelial ovarian cancer (EOC). A total of 30 patients with EOC were randomly assigned to placebo (n = 15) and red ginseng groups (n = 15). All patients took placebo or red ginseng (3000 mg/day) for three months. Then, we compared changes of genotoxicity, HRQL and survival between the two groups. As a result, red ginseng reduced micronuclei yield in comparison with placebo despite no difference of binucleated cells index. Although red ginseng increased serum levels of alanine aminotransferase and aspartate aminotransferase significantly, they were within the normal value. Moreover, there were no differences in adverse events between placebo and red ginseng groups. In terms of HRQL, red ginseng was associated with improved emotional functioning and decreased symptoms of fatigue, nausea and vomiting, and dyspnea, reduced anxiety and interference affecting life and improved daytime somnolence. However, there was no effect of red ginseng on prognosis of EOC. Conclusively, red ginseng may be safe and effective to reduce genotoxicity and improve HRQL despite no benefit of survival in patients with EOC who received chemotherapy.

Background PD-L1 expression levels determined by immunostaining are known to be related to the survival rate and prognosis of patients with various types of cancers, as well as to the therapeutic response to immune checkpoint inhibitors. Recently, the U.S. Food and Drug Administration approved an immune checkpoint inhibitor for the treatment of non-small cell lung cancer along with the clones used for PD-L1 immunostaining to predict the resulting response. In this study, we performed PD-L1 immunostaining of tissue microarrays from ovarian epithelial cancer using SP263, an approved clone, and examined the effect of PD-L1 expression on survival rate and prognosis. Methods Tissue microarrays were constructed from ovarian epithelial cancer tissues of 248 patients and PD-L1 immunostaining was performed using the SP263 clone. PD-L1 expression levels in tumor cells, intraepithelial tumor-infiltrating lymphocytes, and stromal tumor-infiltrating lymphocytes were evaluated, and the effect of PD-L1 expression on survival and prognosis was analyzed. Results PD-L1 was detected in tumor cells as well as intraepithelial tumor-infiltrating lymphocytes and stromal tumor-infiltrating lymphocytes. It was most frequently expressed in stromal tumor-infiltrating lymphocytes. The Kaplan-Meier curve analysis and log rank test showed that only high stromal PD-L1 expression was associated with increased overall survival in ovarian serous carcinoma. Multivariate and univariate Cox regression analyses revealed that stromal PD-L1 expression was an independent prognostic factor, especially in ovarian serous carcinoma. Conclusions PD-L1 immunostaining using SP263 was observed in tumor cells as well as intraepithelial and stromal tumor-infiltrating lymphocytes. PD-L1-expressing stromal tumor-infiltrating lymphocytes were associated with an increased overall survival rate and may serve as a favorable prognostic factor in ovarian cancer, particularly serous carcinoma. Electronic supplementary material The online version of this article (10.1186/s13048-019-0526-0) contains supplementary material, which is available to authorized users.

Tumor angiogenesis is an essential process for growth and metastasis of cancer cells as it supplies tumors with oxygen and nutrients. During tumor angiogenesis, many pro-angiogenic factors are secreted by tumor cells to induce their own vascularization via activation of pre-existing host endothelium. However, accumulating evidence suggests that vasculogenic mimicry (VM) is a key alternative mechanism for tumor vascularization when tumors are faced with insufficient supply of oxygen and nutrients. VM is a tumor vascularization mechanism in which tumors create a blood supply system, in contrast to tumor angiogenesis mechanisms that depend on pre-existing host endothelium. VM is closely associated with tumor progression and poor prognosis in many cancers. Therefore, inhibition of VM may be a promising therapeutic strategy and may overcome the limitations of anti-angiogenesis therapy for cancer patients. In this review, we provide an overview of the current anti-angiogenic therapies for ovarian cancer and the current state of knowledge regarding the links between microRNAs and the VM process, with a focus on the mechanism that regulates associated signaling pathways in ovarian cancer. Moreover, we discuss the potential for VM as a therapeutic strategy against ovarian cancer. [