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We tested if METCAM/MUC18 overexpression also plays a suppressor role in another human ovarian cancer cell line, BG-1, in addition to the SK-OV3 cell line.

Human ovarian cancer BG-1 cells were transfected with METCAM/MUC18 cDNA and G418-resistant clones expressing different levels of METCAM/MUC18 were isolated. These clones were used to test the effects of enforced expression of METCAM/MUC18 on in vitro motility, invasiveness, and anchorage-independent colony formation (in vitro tumorigenesis), and in vivo tumorigenesis after SC injection and after IP injection in female athymic nude mice.

Overexpression of METCAM/MUC18 reduced in vitro motility and invasiveness of BG-1 cells and anchorage-independent colony formation (in vitro tumor formation). Higher expression of METCAM/MUC18 in BG-1 cells significantly reduced in vivo tumor proliferation of the BG-1 cells after IP injection (orthotopic route) of the clones in female nude mice, though it did not significantly affect in vivo tumor proliferation after SC injection (non-orthotopic route).

Similar to SK-OV3 cells, METCAM/MUC18 also plays a suppressor role in the progression of BG-1 cells in a xenograft mouse model.

Similar to SK-OV3 cells, METCAM/MUC18 also plays a suppressor role in the progression of BG-1 cells in a xenograft mouse model.Ovarian cancer remains the leading cause of death from gynecologic malignancy in the Western world. Tumors are comprised of heterogeneous populations of various cancer, immune, and stromal cells; it is hypothesized that rare cancer stem cells within these subpopulations lead to disease recurrence and treatment resistance. Technological advances now allow for the analysis of tumor genomes and transcriptomes at the single-cell level, which provides the resolution to potentially identify these rare cancer stem cells within the larger tumor.In this chapter, we review the evolution of next-generation RNA sequencing techniques, the methodology of single-cell isolation and sequencing, sequencing data analysis, and the potential applications in ovarian cancer. We also summarize the current published work using single-cell sequencing in ovarian cancer.By utilizing this novel technique to characterize the gene expression of rare subpopulations, new targets and treatment pathways may be identified in ovarian cancer to change treatment paradigms.Ovarian Cancer is one of the most lethal and widespread gynecological malignancies. It is the seventh leading cause of all cancer deaths worldwide. High-Grade Serous Cancer (HGSC), the most commonly occurring subtype, alone contributes to 70% of all ovarian cancer deaths. This is mainly attributed to the complete lack of symptoms during the early stages of the disease and absence of an early diagnostic marker.PAX8 is emerging as an important histological marker for most of the epithelial ovarian cancers, as it is expressed in about 90% of malignant ovarian cancers, specifically in HGSC. PAX8 is a member of the Paired-Box gene family (PAX1-9) of transcription factors whose expression is tightly controlled temporally and spatially. The PAX genes are well known for their role in embryonic development and their expression continues to persist in some adult tissues. PAX8 is required for the normal development of Müllerian duct that includes Fallopian tube, uterus, cervix, and upper part of vagina. In adults, it is expressed in the Fallopian tube and uterine epithelium and not in the ovarian epithelium. Considering the recent studies that predict the events preceding the tumorigenesis of HGSC from the Fallopian tube, PAX8 appears to have an important role in the development of ovarian cancer.In this chapter, we review some of the published findings to highlight the significance of PAX8 as an important marker and an emerging player in the pathogenesis of ovarian cancer. We also discuss regarding the future perspectives of PAX8 wherein it could contribute to the betterment of ovarian cancer diagnosis and treatment.The majority of ovarian cancer patients present clinically with wide-spread metastases throughout the peritoneal cavity, metastasizing to the mesothelium-lined peritoneum and visceral adipose depots within the abdomen. This unique metastatic tumor microenvironment is comprised of multiple cell types, including mesothelial cells, fibroblasts, adipocytes, macrophages, neutrophils, and T lymphocytes. Modeling advancements, including complex 3D systems and organoids, coupled with 2D cocultures, in vivo mouse models, and ex vivo human tissue cultures have greatly enhanced our understanding of the tumor-stroma interactions that are required for successful metastasis of ovarian cancer cells. However, advanced multifaceted model systems that incorporate frequency and spatial distribution of all cell types present in the tumor microenvironment of ovarian cancer are needed to enhance our knowledge of ovarian cancer biology in order to identify methods for preventing and treating metastatic disease. This review highlights the utility of recently developed modeling approaches, summarizes some of the resulting progress using these techniques, and suggests how these strategies may be implemented to elucidate signaling processes among cell types of the tumor microenvironment that promote ovarian cancer metastasis.Ovarian cancer, one of the three leading malignancies in women, has high incidence and mortality worldwide. It is hard to diagnose until very late stages and the 5-year survival rate is very low, due mostly to its distant metastasis. Chemotherapy is currently the most common treatment to inhibit cancer growth, but long-term use could result in resistance and tumor recurrence in addition to damages to normal tissues and functions of the patients. In order to achieve safe and curative effects against cancers, many investigators have focused their attention on traditional Chinese herbal medicines. Paclitaxel, a natural antitumor agent, has significant effects on advanced malignancies including ovarian cancer and is in the standard front-line treatment. Additional natural anticancer substances have continually been discovered for their high effectiveness and low side-effects in ovarian cancer prevention and therapy. In this chapter, we summarize recent work on a selected group of natural components, including lignans, ellagic acid, luteolin, mangiferin, and Acanthopanax senticosus, which have all been demonstrated to reduce the progress of epithelial ovarian cancer in a dose-depend manner, by both in vitro and in vivo experiments. The mechanisms of the anticancer activities by these natural components involve expression suppression of MMP2 and MMP9.Ovarian cancer generally escapes diagnosis until the advanced stages. High-grade serous ovarian cancer (HGSOC) is the most frequently occurring form of this malaise and is a disease which has the highest mortality rate of gynecologic cancers. Over recent years it has been revealed that the course of such cancers can be significantly influenced by the nature of immune cells in tumors at the time of diagnosis and by immune cells induced by therapy. Numerous investigators have since focused on disease biology to identify biomarkers or therapeutic targets. Yet, while over the past decade there have been significant improvements in state-of-the-art surgery for ovarian cancer as frontline therapy, there have been limited advancements in the development of novel curative or management drugs for this disease. This chapter discusses the major elements of immune suppression in HGSOC from a biological viewpoint, mechanisms of overcoming resistance to therapies, and recent therapy aimed at improving patient care and survival.Epithelial ovarian cancer is a lethal gynecological cancer. It is related to high mortality because the majority of the patients present in advanced stage and because of the high recurrence rates of the disease. Selleck Chidamide Recurrent ovarian cancer is classified according to the time interval between the last platinum-based chemotherapy and the occurrence of recurrence, to platinum-sensitive and platinum-resistant. Many theories tried to explain development of resistance to platinum-based therapy. "Cancer stem cells" is one of these theories and is being currently under investigation by many groups. This chapter will demonstrate the suggested contribution of cancer stem cells to the development of recurrent ovarian cancer.Ovarian cancer (OC) is the most lethal gynecological malignancy among women worldwide. In most cases, it is diagnosed late at an advanced stage and does not respond well to existing therapies leading to its poor prognosis. In addition, other factors including epidemiological, complex histological diversity, multiple molecular alterations, and overlapping signaling pathways are also important contributors to poor disease outcome. Efforts have continued to develop a deeper understanding of the molecular pathogenesis and altered signaling nodes that provide hope for better clinical management through the development of novel approaches for early diagnosis, disease subtyping, prognosis, and therapy. In this chapter, we provide a detailed overview of OC and its histological subtypes and discuss prevalent molecular aberrations and active signaling pathways that drive OC progression. We also summarize various diagnostic and prognostic markers and therapeutic approaches currently being employed and discuss emerging findings that hold the potential to change the future course of OC management.

Whether the sensitivity of the BinaxNOW Streptococcus pneumoniae urinary antigen test kit (BinaxNOW), adjusted by some variables including vital signs, laboratory examinations and pneumonia severity, has been decreasing is unknown. The aim of the present study was to investigate whether BinaxNOW sensitivity has decreased recently and to identify the predictors of the BinaxNOW result, including the time trend.

This prospective cohort study enrolled consecutive patients with pneumococcal community-acquired pneumonia who were hospitalised at Kurashiki Central Hospital from January 2001 to December 2015. Pneumococcal community-acquired pneumonia was defined as positive blood or pleural effusion or sputum culture results. To evaluate the effect of the time trend for the sensitivity of BinaxNOW, time series regression analysis was performed. In addition, predictors of the BinaxNOW result were examined by multivariable analysis using variables such as sex, vital signs, blood tests such as C-reactive protein, albumin, blood urea nitrogen, creatinine, white blood cell count, haematocrit and platelets, antibiotic pre-treatment, bacteraemia, and pneumonia severity, in addition to time trend and seasonality.

A total of 446 patients were included. BinaxNOW sensitivity showed a significant, gradual decrease from 2001 (81.3%) to 2015 (48.7%). On multivariable analysis [odds ratio (95% confidence interval)], bacteraemia [2.516 (1.387-4.561), P = 0.002] was a predictor of a positive BinaxNOW result, whereas male sex [0.467 (0.296-0.736), P = 0.001], white blood cell count [0.959 (0.930-0.989), P = 0.008] and the time trend per year [0.900 (0.859-0.943), P < 0.001] were predictors of a negative BinaxNOW result.

The sensitivity of BinaxNOW decreased over a 15-year period. We should be careful when interpreting BinaxNOW results in daily clinical practice, and the development of a new kit with good sensitivity is anticipated.

UMIN000004353.

UMIN000004353.

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