Chloride channel 3 (CIC-3) predicts the tumor size in hepatocarcinoma

Chloride channel 3 (CIC-3) has been suggested to be implicated in the carcinogenesis though; it still remains ill understood in hepatocarcinoma, especially in terms of clinicopathological meaning of its expression. Given this, herein, to understand the clinicopathological significance of CIC-3 expression in hepatocarcinoma, Immunohistochemistry was performed to examine the level of CIC-3, followed by statistical analysis of the correlation between expression versus clinicopathological variables, including gender, age, TNM classifications, tumor size, lymph node metastasis and overall prognosis. It was shown that positive staining of CIC-3 can be present in both hepatocarcinoma and its paired normal controls; and that CIC-3 was significantly over-expressed in hepatcarcioma on the whole relative to paired normal controls. Moreover, up-regulation of CIC-3 markedly correlated with tumor size and overall prognosis, suggesting that CIC-3 expression could predict both tumor size and overall prognosis in hepatocarcinoma.     

Working with gender-expansive clients in psychotherapy

Gender expansive individuals of all ages are at an elevated risk for mental and physical health problems compared not only to the general population, but also to lesbian, gay, and bisexual individuals. Yet mental healthcare providers tend to be underprepared to provide services to this population, which is due in part to the dearth of scholarship on how to provide competent care to gender-expansive people. The present article introduces themes and terminology crucial to working with this population, as well as three case studies—two individuals and one family—highlighting the nuances inherent in workng with gender expansive clients. We conclude by offering ways to conceptualize each case, and by highlighting certain areas that we believe deserve specific considerations from care providers.     

ARL4C stabilized by AKT/mTOR pathway promotes the invasion of PTEN-deficient primary human glioblastoma

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) deficiency in primary human glioblastoma (GBM) is associated with increased invasiveness and poor prognosis with unknown mechanisms. Therefore, how loss of PTEN promotes GBM progression remains to be elucidated. Herein, we identified that ADP-ribosylation factor like-4C (ARL4C) was highly expressed in PTEN-deficient human GBM cells and tissues. Mechanistically, loss of PTEN stabilized ARL4C protein due to AKT/mTOR pathway-mediated inhibition of ARL4C ubiquitination. Functionally, ARL4C enhanced the progression of GBM cells in vitro and in vivo. Moreover, microarray profiling and GST pull-down assay identified that ARL4C accelerated tumor progression via RAC1-mediated filopodium formation. Importantly, targeting PTEN potently inhibited GBM tumor progression in vitro and in vivo, whereas overexpression of ARL4C reversed the tumor progression impaired by PTEN overexpression. Clinically, analyses with patients' specimens validated a negative correlation between PTEN and ARL4C expression. Elevated ARL4C expression but PTEN deficiency in tumor was associated with poorer disease-free survival and overall survival of GBM patients. Taken together, ARL4C is critical for PTEN-deficient GBM progression and acts as a novel prognostic biomarker and a potential therapeutic candidate. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Relationships of varicella zoster virus (VZV)-specific cell-mediated immunity and persistence of VZV DNA in saliva and the development of postherpetic neuralgia in patients with herpes zoster

There are no surrogate markers for the development of postherpetic neuralgia (PHN) in patients with herpes zoster (HZ). All patients with HZ were prospectively enrolled to evaluate the associations of saliva varicella zoster virus (VZV) DNA persistence and VZV-specific cell-mediated immunity (CMI) with the development of PHN. Slow clearers were defined if salivary VZV DNA persisted after day 15. Salivary VZV was detected in 60 (85.7%) of a total of 70 patients with HZ on initial presentation. Of 38 patients for whom follow-up saliva samples were available, 26 (68.4%) were classified as rapid clearers and 12 (31.6%) as slow cleares. Initial VZV-specific CMI was lower in slow clearers than rapid clearers (median 45 vs 158 spot forming cells/10 ⁶ cells, P = .02). Of the 70 patients with HZ, 22 (31.4%) eventually developed PHN. Multivariate analysis showed that slow clearers (OR, 15.7, P = .01) and lower initial VZV-specific CMI (OR, 13.8, P = .04) were independent predictors of the development of PHN, after adjustment for age and immunocompromised status. Initial low VZV CMI response and persistence of VZV DNA in saliva may be associated with the development of PHN.     

Immunobiology of chimeric antigen receptor T cells and novel designs

Advances in the development of immunotherapies have offered exciting new options for the treatment of malignant diseases that are refractory to conventional cytotoxic chemotherapies. The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) has demonstrated dramatic results in clinical trials and highlights the promise of novel immune‐based approaches to the treatment of cancer. As experience with CAR T cells has expanded with longer follow‐up and to a broader range of diseases, new obstacles have been identified which limit the potential lifelong benefits of CAR T cell therapy. These obstacles highlight not only the gaps in knowledge of the optimal clinical application of this “living drug”, but also gaps in our understanding of the fundamental biology of CAR T cells themselves. In this review, we discuss the obstacles facing CAR T cell therapy, how these relate to our current understanding of CAR T cell biology and approaches to enhance the clinical efficacy of this therapy.     

Molecular characterization of Coxsackievirus A16 strains isolated from children with severe hand,foot, and mouth disease in Yunnan,Southwest China,during 2009-2015

Coxsackievirus A16 (CV-A16) commonly causes mild symptoms, but severe diseases, such as aseptic meningitis, encephalitis, and even fatal cases, have been reported. Thirteen CV-A16 strains were isolated from patients with severe hand, foot, and mouth disease in Yunnan, Southwest China, from 2009 to 2015. Subgenotype B1a and B1b of CV-A16 were predominantly circulating the region with B1b the predominant strain in recent years. The mean rate of nucleotide substitution based on the VP1 gene sequence was 4.545 × 10 ⁻³ substitution per site per year from 2009 to 2015. These results may help in understanding the genetic diversity of CV-A16 and develop a CV-A16 vaccine.