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© 2015 Marisa Shiina and Lilly Y. W. Bourguignon.We determined that human head and neck cancer cells (HSC-3 cell line) contain a subpopulation displaying cancer stem cell (CSC) properties and are very tumorigenic. Specifically, we investigated whether diff

Takashi Takeda,1,2 Masami Shiina1 1Division of Women’s Health, Research Institute of Traditional Asian Medicine, Kindai University, Osaka, Japan; 2Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan Background: Catastrophic disasters such as great earthquakes cause tremendous physical and mental damage. We previously reported that the Great East Japan Earthquake worsened premenstrual symptoms among adolescent girls in the disaster-stricken area. Objectives: We reanalyzed these data to determine the positive effects of education on premenstrual symptoms. Materials and methods: Annual school-based surveys about premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) have been conducted in Sendai since 2009. The Great East Japan Earthquake occurred on March 11, 2011. First-year students in one school had received education on PMS/PMDD before the earthquake, whereas those in another school had not. We reanalyzed data for 1431 girls (November 2010) and 1489 girls (December 2011) aged 15–18 years. Results: The severity of PMS/PMDD in students who had received the education program showed no changes between before and after the earthquake. However, students who had not received education showed worsening of the severity of PMS/PMDD. Conclusion: This study showed education had a possible beneficial effect for the prevention of stress-induced PMS/PMDD. Keywords: premenstrual syndrome, premenstrual dysphoric disorder, Great East Japan Earthquake, adolescents, education

Background: Lymphotropic hepatitis C virus (HCV) infection of B and T cells might play an important role in the pathogenesis of hepatitis C. Recently, we showed that a lymphotropic HCV (SB strain) could infect established T-cell lines and B-cell lines. However, whether HCV replication interferes with cell proliferation and function in primary T lymphocytes is still unclear.Aim: The aim of this study was to analyze whether HCV replication in primary T lymphocytes affected their development, proliferation, and Th1 commitment.Methods: SB strain cell culture supernatant (2 × 10(4) copies/ml HCV) was used to infect several kinds of primary lymphocyte subsets. Mock, UV-irradiated SB-HCV, JFH-1 strain, and JFH-1 NS5B mutant, which could not replicate in T cells, were included as negative controls. Carboxyfluorescein succinimidyl ester (CFSE) and CD45RA double staining was used to evaluate the proliferative activity of CD4(+)CD45RA(+)CD45RO(-) naïve CD4(+) cells. Interferon (IFN)-γ and interleukin (IL)-10 secretion assays magnetic cell sorting (MACS) were carried out.Results: Negative strand HCV RNA was detected in CD4(+), CD14(+), and CD19(+) cells. Among CD4(+) cells, CD4(+)CD45RA(+)RO(-) cells (naïve CD4(+) cells) were most susceptible to replication of the SB strain. The levels of CFSE and CD45RA expression gradually declined during cell division in uninfected cells, while HCV-infected naïve CD4(+) cells expressed higher levels of CFSE and CD45RA than Mock or UV-SB infected naïve CD4(+) cells. Moreover, the production of IFN-γ was significantly suppressed in SB-infected naïve CD4(+) cells.Conclusions: Lymphotropic HCV replication suppressed proliferation and development, including that towards Th1 commitment, in human primary naïve CD4(+) cells. [ABSTRACT FROM AUTHOR]

The ability of oncolytic adenoviruses to replicate in and lyse cancer cells offers a potential therapeutic approach. However, selectivity and efficacy of adenovirus replication need to be improved. In this study, we present that loss of p21WAF1 promotes adenovirus replication and more effective cell killing. To test our hypothesis, we took HCT116 colon cancer cell lines carrying deletions of either p21WAF1 or p53, and infected these cell lines with wild-type adenovirus (WtD) or the oncolytic adenoviruses, ONYX-015 and Delta-24. We found that WtD, ONYX-015 and Delta-24 induced stronger cytopathic effects in HCT116 p21−/− cells compared with HCT116-WT cells. This was accompanied by increased virus production. siRNA-mediated knockdown of p21WAF1, and similarly of p27KIP1, in HCT116-WT cells also enhanced replication of and cell killing by these viruses. Furthermore, we found that TE7, an esophageal carcinoma cell line, also showed a strong cell-killing effect and virus production when p21WAF1 expression was suppressed by RNA interference before adenoviruses infection. Also, H1299 and DU-145 cells transfected with p21WAF1 siRNA showed higher virus production after ONYX-015 and Delta-24 infections. These observations suggest that p21WAF1 plays a role in mediating replication of oncolytic viruses with potential implications for adenoviral therapy of cancer. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to elucidate a method for predicting the intrahepatic arteriovenous shunt rate from computed tomography (CT) images and biochemical data, instead of from arterial perfusion scintigraphy, because adverse exacerbated systemic effects may be induced in cases where a high shunt rate exists. CT and arterial perfusion scintigraphy were performed in patients with liver metastases from gastric or colorectal cancer. Biochemical data and tumor marker levels of 33 enrolled patients were measured. The results were statistically verified by multiple regression analysis. The total metastatic hepatic tumor volume (V(metastasized)), residual hepatic parenchyma volume (V(residual); calculated from CT images), and biochemical data were treated as independent variables; the intrahepatic arteriovenous (IHAV) shunt rate (calculated from scintigraphy) was treated as a dependent variable. The IHAV shunt rate was 15.1 +/- 11.9%. Based on the correlation matrixes, the best correlation coefficient of 0.84 was established between the IHAV shunt rate and V(metastasized) (p < 0.01). In the multiple regression analysis with the IHAV shunt rate as the dependent variable, the coefficient of determination (R (2)) was 0.75, which was significant at the 0.1% level with two significant independent variables (V(metastasized) and V(residual)). The standardized regression coefficients (beta) of V(metastasized) and V(residual) were significant at the 0.1 and 5% levels, respectively. Based on this result, we can obtain a predicted value of IHAV shunt rate (p < 0.001) using CT images. When a high shunt rate was predicted, beneficial and consistent clinical monitoring can be initiated in, for example, hepatic arterial infusion chemotherapy. [ABSTRACT FROM AUTHOR]

The article discusses the study that evaluated the long-term outcome and patient safety for a radical hysterectomy (RH) in pregnant women with invasive cervical cancer. It states that the median treatment period was 17 weeks of gestation and pelvic lymph node metastases were observed in all patients. It adds that radical hysterectomy can be safely performed even during pregnancy and subsequent cesarean section.

Background: The cellular immune response is important in chronic hepatitis C (CHC). To better understand its mechanism, we examined dendritic cells (DCs) and hepatitis C virus (HCV)-specific cytotoxic T cells (CTLs), which are thought to contribute to liver injury and viral clearance.Methods: CHC patients received 24 weeks of interferon-alpha-based antiviral therapy. We analyzed time-sequential frequencies of peripheral DCs, classified as myeloid DCs (mDCs) or plasmacytoid DCs (pDCs), together with peptide major histocompatibility class I tetramers, epitope specific for HCV core 129-137 (t*24/c129) or HCV NS3 1296-1304 (t*24/ns1294), directly ex vivo.Results: The mDC and pDC populations changed in parallel (P < 0.05), showing a significant transient decrease at weeks 12 and 16 during the therapy, and then recovering. However, neither of the tetramer results showed a direct correlation with the kinetics of peripheral DCs.Conclusions: There is an apparent effect of antiviral therapy or a subsequent reduction of HCV on host immunity, but the effect may not include the induction of CTLs in CHC. [ABSTRACT FROM AUTHOR]

Differences in cytotoxic T lymphocyte activity in hepatitis C virus infection may account for the outcome of interferon monotherapy. To investigate this hypothesis, we analysed the response of peripheral CD8+ T cells that recognized epitopes presented by HLA-A*2402. We synthesized HLA/β2-microglobulin/peptide complexes using two epitopes. Production of interferon-γ by CD8+ T cells in response to plastic-bound monomeric HLA/peptide complex was observed frequently in sustained virus responders (SVR) ( n = 13) against all the peptides, NS31296–1304 (the percentage of responding patients, 61·5%) and core 129–137 (53·8%), while no interferon-γ production was observed in non-responders (NR) ( n = 13) for any of the peptides. Tetramer-staining showed the presence of CD8+ T cells specific for all the peptides except NS31296–1304 in two SVR at the end of interferon monotherapy, although hardly any such cells were found in four NR. Specific killing was observed against peptides NS31296–1304 (3/4) and core 129–137 (1/4) in sustained responders but none in non-responders. These results suggest that the responses of cytotoxic T lymphocytes (CTLs) were induced during interferon therapy in these patients and that interferon-γ production by CD8+ T lymphocytes against HCV NS31296–1304 and core 129–137 are well maintained in patients with SVR compared with those with NR. These findings emphasize the importance of the CD8+ T cell response in controlling HCV infection. [ABSTRACT FROM AUTHOR]

Background: Fulminant hepatitis is a clinical syndrome characterized by sudden and severe liver dysfunction. Met hods: We analyzed two patients with a superacute form of fulminant hepatitis B and compared findings with those of four patients with acute self-limited hepatitis B, two patients with acute exacerbation of chronic hepatitis B and four healthy individuals. Results: In fulminant hepatitis, an increased population of human leukocyte antigen (HLA)-DR+ CD8+ lymphocytes was observed in peripheral blood by flow cytometry, which was accompanied by the presence of HLA-DRhi' lymphocytes. The phenotype of CD8+ T lymphocytes from patients with fulminant hepatitis was mostly that of the effector T lymphocytes in peripheral blood, whereas lymphocytes with CD45RA - CCR7 - phenotype dominated in the liver of these patients. A larger population of hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) appeared in peripheral circulation of the fulminant hepatitis patients compared with that in a patient with acute hepatitis. HBV-specific CTLs were highly concentrated in the liver, although epitopes recognized by these CTLs in the peripheral blood and in the liver were similar. Peripheral CTLs were mostly functional as indicated by intracellular perform and interferon-'y. Conclusions: These results suggest the presence of vigorous activation of CD8+ T cells in vivo in fulminant hepatitis and the necessity of extensive therapy in patients with this disease. [ABSTRACT FROM AUTHOR]

A phospholipid antigen that reacted with the serum antibody from a patient with peripheral neuropathy and paraproteinemia with both impaired sensory and motor functions, but not with sera from patients with only impaired sensory functions and healthy controls, was purified from bovine cauda equina as a minor component with a concentration of about 0.6 µg per gram wet-weight tissue. The structure of the phospholipid was characterized as lysophosphatidylinositol by means of thin-layer chromatography, gas–liquid chromatography, and negative-ion fast-atom-bombardment mass spectrometry. The major fatty acid component of this phospholipid was stearic acid (> 81%). Our data suggest the possible involvement of a lysophospholipid antigen in the immunopathogenesis of peripheral neuropathies with severe motor and sensory dysfunctions. There is an intriguing possibility that the difference in immunoreactivity of serum antibodies may underlie the differential clinical manifestations in patients with peripheral neuropathy and paraproteinemia. [ABSTRACT FROM AUTHOR]