the biological function of non-thermal atmospheric pressure plasma has been widely accepted in several types of cancer. We previously developed plasma-activated medium (pAM) for clinical use, and demonstrated that PAM exhibits a metastasis-inhibitory effect on ovarian cancer through reduced MMP-9 secretion. However, the anti-tumor effects of PAM on endometrial cancer remain unknown. In this study, we investigated the inhibitory effect of PAM on endometrial cancer cell viability in vitro.Our results demonstrated that AMEC and HEC50 cell viabilities were reduced by PAM at a certain PAM ratio, and PAM treatment effectively increased autophagic cell death in a concentration dependent manner. in addition, we evaluated the molecular mechanism of pAM activity and found that the mtoR pathway was inactivated by pAM. Moreover, our results demonstrated that the autophagy inhibitor MHY1485 partially inhibited the autophagic cell death induced by PAM treatment. These findings indicate that pAM decreases the viability of endometrial cancer cells along with alteration of the mtoR pathway, which is critical for cancer cell viability. collectively, our data suggest that pAM inhibits cell viability while inducing autophagic cell death in endometrial cancer cells, representing a potential novel treatment for endometrial cancer.Endometrial cancer is the most common gynecologic malignancy in Japan, with an estimated 13,600 new cases diagnosed in 2015 1 . The incidence of new cases is believed to have increased over the last few decades due to increased levels of obesity, hypertension, and diabetes mellitus, particularly in South Africa and several Asian countries including Japan 1,2 . Although the majority of endometrial cancer patients are diagnosed in the early stage and outcomes are generally favorable because of the typical symptom of irregular vaginal bleeding in women of menopausal age, the prognoses of patients in advanced stages not amenable to localized therapies remain poor 1 . Indeed, a frequent pattern of progression and recurrence is peritoneal metastasis, which is often resistant to systemic chemotherapy 3 . In addition, cytotoxic agents for endometrial cancer are relatively limited compared with other gynecologic malignancies. Thus, there is an increasing demand for novel approaches to peritoneal dissemination.For the past decade, nonequilibrium atmospheric pressure plasma (NEAPP) has been studied for its clinical applications such as sterilization, wound healing, and cancer therapy 4-6 . NEAPP represents a partially ionized gas with energy mainly accumulated as free electrons 7 . Recent studies have revealed that in addition to the direct irradiation of NEAPP to bacteria or tissues, indirect plasma treatment with plasma-activated medium (PAM) and plasma-activated lactate (PAL), which are activated by NEAPP, exhibit anti-tumor activity in several types of cancer, including ovarian, pancreatic, colorectal and gastric cancers 4,8-13 . The molecular mechanism of the anti-tumor effects triggered by PAM have been investigat...

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ObjectivesThere is increasing evidence that systemic inflammatory response (SIR) markers are prognostic factors for various types of cancers. This is the first study to evaluate the usefulness of SIR markers for the prognosis of early-stage ovarian clear-cell carcinoma (OCCC).MethodsWe retrospectively investigated 83 patients diagnosed with stage I–II OCCC who underwent surgery between 2005 and 2017. Initially, receiver operating characteristic curve analysis for overall survival (OS) was used to determine optimal cut-off values for neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Patients were stratified into 2 groups by the cut-off values (NLR=3.26, PLR=160). Univariate and multivariate analyses were performed to elucidate the significance of SIR markers as prognostic factors.ResultsIn the median follow-up period of 64.1 months, 16 patients experienced recurrence, and nine patients died. The Kaplan-Meier curve showed that OS of the NLR-low group was significantly longer than the NLR-high group (p=0.021). There was no significant difference in progression-free survival between the 2 groups (p=0.668), but the post-recurrence survival of the NLR-low group was significantly longer than the NLR-high group (p=0.019). Furthermore, multivariate analysis showed that increase in NLR is a significant independent prognostic factor for poor prognosis (hazard ratio=7.437, p=0.017). There was no significant difference between PLR-low and PLR-high group.ConclusionResults suggest that NLR can be a significant independent prognostic factor for early-stage OCCC.

Abstract. The aim of the present study was to estimate the post-recurrence survival (PRS) of patients with relapsed uterine cervical cancer (RUCC). In addition, clinicopathological indicators that influenced PRS were investigated. Between 1998 and 2014, of 740 patients with cervical cancer, 165 patients experienced recurrence (recurrence rate, 22.3%), and 83 patients succumbed to the disease within a median follow-up of 34.3 months. A total of 151 stage Ib-IV patients who experienced recurrence after initial treatment for cervical cancer at our institute were analyzed. Uni-and multivariate analyses were performed using the Kaplan Meier method, and Cox regression model. The median age was 55 years (range, 20-88 years). In all, 80 patients succumbed to the disease. The median PRS time of all the patients was 28.4 months. The 1-, 3-, and 5-year PRS rates of patients were 75.1, 41.9, and 32.1%, respectively. In addition, the median survival period in patients who had received surgery as an initial treatment was significantly longer compared with that in patients who had not previously undergone surgery (36.7 vs. 23.3 months, respectively; P=0.0338). Following the univariate analysis, the median PRS in patients with in-and out-field recurrence was 12.6, and 45.9 months, respectively (P<0.0001). Furthermore, in the multivariable analysis, the recurrence site was a significant prognostic indicator of PRS [(In-field vs. Out-field); hazard ratio, 2.848; 95% confidence interval, 1.707-4.738; P<0.0001]. The long-term clinical outcome of patients with RUCC was poor. In particular, the in-field recurrence was identified to be associated with poor post-recurrence oncological outcome in patients with RUCC.

MicroRNAs (miRNAs) regulate the expression of their target genes post-transcriptionally; thus, they are deeply involved in fundamental biological processes. miRNA clusters contain two or more miRNA-encoding genes, and these miRNAs are usually coexpressed due to common expression mechanisms. Therefore, miRNA clusters are effective modulators of biological pathways by the members coordinately regulating their multiple target genes, and an miRNA cluster located on the X chromosome q27.3 region has received much attention in cancer research recently. In this review, we discuss the novel findings of the chrXq27.3 miRNA cluster in various types of cancer.The chrXq27.3 miRNA cluster contains 30 mature miRNAs synthesized from 22 miRNA-encoding genes in an ~ 1.3-Mb region. The expressions of these miRNAs are usually negligible in many normal tissues, with the male reproductive system being an exception. In cancer tissues, each miRNA is dysregulated, compared with in adjacent normal tissues. The miRNA-encoding genes are not uniformly distributed in the region, and they are further divided into two groups (the miR-506-514 and miR-888-892 groups) according to their location on the genome. Most of the miRNAs in the former group are tumor-suppressive miRNAs that are further downregulated in various cancers compared with normal tissues. miR-506-3p in particular is the most well-known miRNA in this cluster, and it has various tumor-suppressive functions associated with the epithelial–mesenchymal transition, proliferation, and drug resistance. Moreover, other miRNAs, such as miR-508-3p and miR-509-3p, have similar tumor-suppressive effects. Hence, the expression of these miRNAs is clinically favorable as prognostic factors in various cancers. However, the functions of the latter group are less understood. In the latter group, miR-888-5p displays oncogenic functions, whereas miR-892b is tumor suppressive. Therefore, the functions of the miR-888–892 group are considered to be cell type- or tissue-specific.In conclusion, the chrXq27.3 miRNA cluster is a critical regulator of cancer progression, and the miRNAs themselves, their regulatory mechanisms, and their target genes might be promising therapeutic targets.