Tumor-and osteoclast-derived NRP2 in prostate cancer bone metastases

INTRODUCTION Bone is the most common metastatic site for castration-resistant prostate cancer.1 Nearly 70％–80％ of the patients with advanced-stage prostate canc...     

Local Proliferation of Fibroblast-Like Synoviocytes Contributes to Synovial Hyperplasia

Objective. To test the hypothesis that local proliferation contributes significantly to the hyperplasia of rheumatoid synovium. Methods. Immunohistologic and chemical staining was used to identify 3 markers of cell proliferation: proliferating cell nuclear antigen, c-myc proto-oncogene, and nucleolar organizer regions. Synovium from 21 patients with rheumatoid arthritis, 34 with degenerative joint disease, and 7 with joint trauma was examined. Results. All 3 markers indicated substantial, active proliferation of synovial lining cells in synovium with hyperplasia. Proliferating cells showed type I procollagen immunoreactivity but were negative for CD68, a monocyte/macrophage marker. Proliferation was greater in rheumatoid arthritis than in the other conditions evaluated. Conclusion. In situ proliferation of fibroblast-like synoviocytes in the synovium lining contributes considerably to the increase in cell numbers in rheumatoid synovium.     

Genetic variation in alcohol dehydrogenase is associated with neurocognition in men with HIV and history of alcohol use disorder: preliminary findings

The co-occurrence of HIV and alcohol use disorder (AUD) amplifies risk for neural injury and neurocognitive deficits. However, the substantial neurocognitive heterogeneity across HIV+/AUD+ individuals suggests inter-individual differences in vulnerability to the neurotoxicity of comorbid HIV/AUD. Genetic variation in alcohol dehydrogenase (ADH), which metabolizes ethanol, may contribute to inter-individual neurocognitive variability. We evaluated associations between five ADH single-nucleotide polymorphisms (SNPs) and neurocognition in men stratified by HIV and lifetime AUD status. Neurobehavioral assessments were administered to 153 men. Three-way ANOVAs examined the interaction of HIV, AUD, and ADH SNPs on global and domain-specific demographically corrected T scores. Follow-up ANCOVAs adjusted for age, estimated verbal IQ, depression, and remote non-alcohol substance use disorders. HIV/AUD groups differed globally and for verbal fluency, working memory, executive function, and processing speed T scores specifically, with HIV+/AUD+ exhibiting the poorest performance. ADH4 (rs1126671) was associated with large effects on working memory (d?=???1.16, p?=?.001) and executive function (d?=???0.77, p?=?.028) selectively in HIV+/AUD+, which remained significant in ANCOVA models. ADH1A (rs3819197) moderated the deleterious effects of HIV+/AUD+ on processing speed such that HIV+/AUD+ related to slower information processing in A allele carriers but not GG homozygotes (ps?<?0.03). Preliminary findings suggest genetic variation in the ADH pathway moderates the deleterious neurocognitive effects of comorbid HIV/AUD. Differential metabolism of heavy ethanol exposure may compromise neurocognition under conditions of neurobiological stress, such as in HIV infection. The functional effects on ethanol metabolism of ADH SNPs examined in this study remain poorly understood, warranting further examination of pharmacokinetic mechanisms mediating ADH gene-neurobehavior relationships in HIV.

     

Loss of mitochondrial ClpP,Lonp1, and Tfam triggers transcriptional induction of Rnf213, a susceptibility factor for moyamoya disease

neurogenetics - Human RNF213, which encodes the protein mysterin, is a known susceptibility gene for moyamoya disease (MMD), a cerebrovascular condition with occlusive lesions and compensatory...     

Antiviral therapy for recurrent hepatitis C reduces recurrence of hepatocellular carcinoma following liver transplantation

Recurrence of hepatocellular carcinoma (HCC) is one of the major concerns following liver transplantation (LT). With the potential antitumor properties of interferon (IFN), their role in prevention of HCC recurrence is to be defined. We retrospectively reviewed 46 patients who underwent LT for hepatitis C virus (HCV)‐related HCC between January 2004 and December 2008. Twenty‐four (52.2%) patients with biopsy‐proven HCV recurrence received antiviral therapy (IFN group); their outcomes were compared with 22 patients (control group). There was no significant difference for tumor size, number, and type of neo‐adjuvant therapy between the two groups. The 1‐ and 3‐year overall patient survival (100% vs. 90.9% and 87.3% vs. 71.8%; P = 0.150) and tumor‐free survival (100% vs. 72.7% and 83.1% vs. 67.5%; P = 0.214) between IFN and control group were comparable. HCC recurrence was the most common cause of death (n = 6 of 12, 50%), all in the control group. During follow‐up, seven (15.2%) patients developed HCC recurrence: one (4.1%) in the IFN group and six (27.3%) in the control group (P < 0.05). In conclusions, HCC recurrence rate and related deaths were significantly lower in patients that received post‐transplant antiviral therapy for recurrent HCV.