KIF5A upregulation in hepatocellular carcinoma: A novel prognostic biomarker associated with unique tumor microenvironment status.

Liver hepatocellular carcinoma (LIHC) is one of the most common liver malignancies with high mortality and morbidity. Thus, it is crucial to identify potential biomarker that is capable of accurately predicting the prognosis and therapeutic response of LIHC. Kinesin family member 5A (KIF5A) is a microtubule-based motor protein involved in the transport of macromolecules such as organelle proteins in cells. Recent studies have illustrated that the high expression of KIF5A was related to poor prognosis of solid tumors, including bladder cancer, prostate cancer, and breast cancer. However, little is currently known concerning the clinical significance of KIF5A expression in LIHC. Herein, by adopting multi-omics bioinformatics analysis, we comprehensively uncovered the potential function and the predictive value of KIF5A in stratifying clinical features among patients with LIHC, for which a high KIF5A level predicted an unfavorable clinical outcome. Results from KIF5A-related network and enrichment analyses illustrated that KIF5A might involve in microtubule-based process, antigen processing and presentation of exogenous peptide antigen via MHC class II. Furthermore, immune infiltration and immune function analyses revealed upregulated KIF5A could predict a unique tumor microenvironment with more CD8+T cells and a higher level of anti-tumor immune response. Evidence provided by immunohistochemistry staining (IHC) further validated our findings at the protein level. Taken together, KIF5A might serve as a novel prognostic biomarker for predicting immunotherapy response and could be a potential target for anti-cancer strategies for LIHC.

Ultrasound-guided percutaneous microwave ablation for adenomyosis: efficacy of treatment and effect on ovarian function.

A total of 142 premenopausal women with symptomatic adenomyosis underwent ultrasound (US)-guided percutaneous microwave ablation (PMWA) at the Chinese PLA General Hospital. This study aimed to evaluate changes in serum pituitary, gonadal hormone and cancer antigen 125 (CA125) levels after US-guided PMWA. Therefore, estradiol (E2), follicle-stimulating hormone (FSH), prolactin (PRL) and CA125 levels were evaluated before ablation and at 3, 6, 9 and 12 months after ablation. No significant differences were observed in the E2 and FSH levels pre-ablation and during follow-up (E2: p=0.933, p=0.987, p=0.106, p=0.936; FSH: p=0.552, p=0.295, p=0.414, p=0.760). The mean absolute values of serum CA125 and PRL were significantly decreased at 3, 6, 9 and 12 months after ablation (CA125: p<0.001, p<0.001, p<0.001, p=0.003; PRL: p<0.001, p<0.001, p<0.001, p<0.001). A significant correlation between changes in CA125 levels and uterine volume was found (p<0.001). No evidence of a decline in ovarian function was observed after US-guided PMWA.

Association between TP53 Arg72Pro polymorphism and hepatocellular carcinoma risk: a meta-analysis.

BACKGROUND: Previous studies on the association between the TP53 Arg72Pro polymorphism and hepatocellular carcinoma (HCC) risk obtained controversial findings. This study aimed to quantify the strength of the association by meta-analysis. METHODS: We searched PubMed and Wangfang databases for published studies on the association between the TP53 Arg72Pro polymorphism and HCC risk, using the pooled odds ratio (OR) with its 95% confidence intervals (95% CI) for assessment. RESULTS: 10 studies with a total of 2,026 cases and 2,733 controls were finally included into this meta-analysis. Overall, the TP53 Arg72Pro polymorphism was not associated with HCC risk (all P values greaterth HCC risk in Caucasians in three genetic models (For Pro versus Arg, OR = 1.20, 95%CI 1.03-1.41; For ProPro versus ArgArg, OR = 1.74, 95%CI 1.23-2.47; For ProPro versus ArgPro/ArgArg, OR = 1.85, 95%CI 1.33-2.57). However, there was no significant association between the TP53 Arg72Pro polymorphism and HCC risk in East Asians (all P values greater than 0.10). No evidence of publication bias was observed. CONCLUSION: Meta-analyses of available data suggest an obvious association between the TP53 Arg72Pro and HCC risk in Caucasians. However, the TP53 Arg72Pro polymorphism may have a race-specific effect on HCC risk and further studies are needed to elucidate this possible effect.

Percutaneous radiofrequency ablation guided by contrast-enhanced ultrasound in treatment of metastatic hepatocellular carcinoma after liver transplantation.

This study evaluated the advantages and applications of contrast-enhanced ultrasound (CEUS)-supported percutaneous radiofrequency ablation (RFA) in the treatment of metastatic hepatocellular carcinoma after liver transplantation, based on clinical details. CEUS-supported percutaneous RFA was adopted to treat 12 patients with hepatic metastatic carcinomas after liver transplantation. The diameters of the metastatic carcinomas varied from 1 cm to 5 cm, and the foci were discovered after 3 months to 12 months. Each focus was diagnosed and localised by CEUS for RFA once or twice. Curative effects were evaluated by CEUS or contrast-enhanced CT after the treatment. The re-examination results at 2 weeks post-treatment showed that the foci of 11 patients were ablated completely, whereas one patient with the largest focus required retreatment by RFA because of a partial residue. No local recurrence was found one month later in the re-examination. CEUS-supported percutaneous RFA in the treatment of hepatic metastatic carcinoma after liver transplantation has the advantages of accurate localisation, good efficacy, easy operation, and minimal invasion without any complications. Therefore, it can be recommended as the preferred therapy for hepatic metastatic carcinoma after liver transplantation.

High mobility group box-1 protein regulate immunosuppression of regulatory T cells through toll-like receptor 4.

INTRODUCTION: High mobility group box-1 protein (HMGB1), a recently recognized mediator of immune response might contribute to immune suppression when released extracellularly. The present study was performed to clarify effects of HMGB1 on regulatory T cells (Tregs) and the involvement of toll-like receptor (TLR) 4 signaling. METHODS: CD4(+)CD25(+)Tregs, isolated from spleens of normal mice and treated with HMGB1 in vitro, and those isolated from HMGB1-treated C3H/HeN (wild type) or C3H/HeJ (TLR4 mutant type) mice, were analyzed for expressions of cytotoxic T lymphocyte-associated antigen (CTLA)4, forkhead/winged helix transcription factor p3 (Foxp3) and interleukin (IL)-10 secretion. RESULTS: HMGB1-treatment was found to markedly decrease the expressions of CTLA4 and Foxp3, as well as IL-10 secretion. Administration of TLR4 neutralizing antibody abolished the phenotypic and functional changes in Tregs induced by HMGB1. Tregs from HMGB1-treated normal mice showed lower expression of CTLA4, Foxp3, and IL-10 secretion when compared with non-treated mice. Yet opposite results were observed in that of C3H/HeJ mice. Moreover, HMGB1 stimulation could down-regulate the expression of TLR4 on Tregs. CONCLUSION: Our data suggest that HMGB1 has the ability to directly modulate the suppressive capacity of CD4(+)CD25(+)Tregs, and TLR4 might be a potential receptor essential for the negative effect of HMGB1 on CD4(+)CD25(+)Tregs activity.