Perivascular Epithelioid Cell Tumor (PEComa) of Abdominal Cavity from Falciform Ligament: A Case Report

We present a case of perivascular epithelioid cell tumors (PEComas) in the abdominal cavity at the falciform ligament. A 30-yr-old Korean man visited to hospital for the evaluation of a growing, palpable abdominal mass. He had felt the mass growing over 6 months. There was no family or personal history of tuberous sclerosis. The resected specimen showed a mass of 8.0×7.0×5.5 cm in size. Histological examination showed sheets of spindle-to-epithelioid cells with clear-to-eosinophilic cytoplasm. Immunohistochemically, tumor cells were positive for HMB-4 (gp100) and smooth muscle actin. They were also positive for the S-100, which is a marker of neurogenic and melanocytic tumors. Patient was treated with radical resection of tumor without any adjuvant therapy. He is well and on follow-up visits without tumor recurrence

Downregulation of Protein Kinase CK2 Activity Facilitates Tumor Necrosis Factor-α-Mediated Chondrocyte Death through Apoptosis and Autophagy

Despite the numerous studies of protein kinase CK2, little progress has been made in understanding its function in chondrocyte death. Our previous study first demonstrated that CK2 is involved in apoptosis of rat articular chondrocytes. Recent studies have suggested that CK2 downregulation is associated with aging. Thus examining the involvement of CK2 downregulation in chondrocyte death is an urgently required task. We undertook this study to examine whether CK2 downregulation modulates chondrocyte death. We first measured CK2 activity in articular chondrocytes of 6-, 21- and 30-month-old rats. Noticeably, CK2 activity was downregulated in chondrocytes with advancing age. To build an in vitro experimental system for simulating tumor necrosis factor (TNF)-α-induced cell death in aged chondrocytes with decreased CK2 activity, chondrocytes were co-treated with CK2 inhibitors and TNF-α. Viability assay demonstrated that CK2 inhibitors facilitated TNF-α-mediated chondrocyte death. Pulsed-field gel electrophoresis, nuclear staining, flow cytometry, TUNEL staining, confocal microscopy, western blot and transmission electron microscopy were conducted to assess cell death modes. The results of multiple assays showed that this cell death was mediated by apoptosis. Importantly, autophagy was also involved in this process, as supported by the appearance of a punctuate LC3 pattern and autophagic vacuoles. The inhibition of autophagy by silencing of autophage-related genes 5 and 7 as well as by 3-methyladenine treatment protected chondrocytes against cell death and caspase activation, indicating that autophagy led to the induction of apoptosis. Autophagic cells were observed in cartilage obtained from osteoarthritis (OA) model rats and human OA patients. Our findings indicate that CK2 down regulation facilitates TNF-α-mediated chondrocyte death through apoptosis and autophagy. It should be clarified in the future if autophagy observed is a consequence versus a cause of the degeneration in vivo

Ion-selective and chemical-protective elastic block copolymer interphase for durable zinc metal anode

Aqueous rechargeable batteries based on zinc anodes are among the most promising systems to replace conventional lithium-ion batteries owing to their intrinsic safety, high ionic conductivity, and economic benefits. However, inferior reversibility of zinc anode resulting from zinc dendrites and surface side reactions limits the practical realization of zinc-ion batteries. Herein, we develop a thin but robust polymeric artificial interphase to enhance reversibility of zinc anode. The grafted maleic anhydride groups in the polymer structure restrain the detrimental reactions through selective zinc-ion penetration and homogenize ion distribution, leading to a smooth electrode surface after plating-stripping processes. Consequently, the coated zinc anode shows excellent stability with a long-term symmetric cell lifespan (>3,000 h at 3 mA??cm???2) and maintains capacity retention of 80% after 2,500 cycles, paired with a manganese oxide cathode. This study provides a facile fabrication process and accessible analysis methods to rationalize the development of high-performance zinc-ion batteries

Hyperprogressive Disease during Anti-PD-1 (PDCD1) / PD-L1 (CD274) Therapy: A Systematic Review and Meta-Analysis

Hyperprogressive disease (HPD) is a recently acknowledged pattern of rapid tumor progression after the initiation of immune checkpoint inhibitors. HPD has been observed across various types of tumors and has been associated with poor survival. We performed a meta-analysis to identify baseline (i.e., prior to programmed cell death 1 [PD-1, PDCD1] / programmed cell death 1 ligand 1 [PD-L1, CD274] inhibitor therapy) patient factors associated with risks of developing HPD during PD-1/PD-L1 inhibitor therapy. We searched eight databases until 6 June 2019. We calculated the summary odds ratio (OR) and its 95% confidence interval (CI) using the random-effects model and explored between-study heterogeneity and small-study effects. A total of nine articles was eligible (217 HPD cases, 1519 cancer patients) for meta-analysis. There was no standard definition of HPD, and the incidence of HPD ranged from 1 to 30%. We identified twenty-three baseline patient factors, of which five factors were statistically significantly associated with HPD. These were serum lactate dehydrogenase (LDH) above the upper normal limit (OR = 1.89, 95% CI = 1.02-3.49, p = 0.043), more than two metastatic sites (OR = 1.86, 1.34-2.57, p < 0.001), liver metastases (OR = 3.33, 2.07-5.34, p < 0.001), Royal Marsden Hospital prognostic score of 2 or above (OR = 3.33, 1.96-5.66, p < 0.001), and positive PD-L1 expression status that was inversely correlated with HPD (OR = 0.60, 0.36-0.99, p = 0.044). Between-study heterogeneity was low. Evidence of small-study effect was found in one association (PD-L1 expression). Subset analyses of patients with non-small cell lung cancer showed similar results. Future studies are warranted to identify underlying molecular mechanisms and to test their roles as predictive biomarkers of HPD

Empirical assessment of biases in cerebrospinal fluid biomarkers of Alzheimer's disease: an umbrella review and re-analysis of data from meta-analyses

OBJECTIVE: Alzheimer’s disease (AD) is a leading cause of years lived with disability in older age, and several cerebrospinal fluid (CSF) markers have been proposed in individual meta-analyses to be associated with AD but field-wide evaluation and scrutiny of the literature is not available. MATERIALS AND METHODS: We performed an umbrella review for the reported associations between CSF biomarkers and AD. Data from available meta-analyses were reanalyzed using both random and fixed effects models. We also estimated between-study heterogeneity, small-study effects, excess significance, and prediction interval. RESULTS: A total of 38 meta-analyses on CSF markers from 11 eligible articles were identified and reanalyzed. In 14 (36%) of the meta-analyses, the summary estimate and the results of the largest study showed non-concordant results in terms of statistical significance. Large heterogeneity (I2≥75%) was observed in 73% and small-study effects under Egger’s test were shown in 28% of CSF biomarkers. CONCLUSIONS: Our results suggest that there is an excess of statistically significant results and significant biases in the literature of CSF biomarkers for AD. Therefore, the results of CSF biomarkers should be interpreted with caution