Project description:Renal leiomyosarcomas (LMS) are extremely rare neoplasms with aggressive behaviour and poor survival prognosis. The most frequent somatic events in leiomyosarcomas are mutations in TP53, RB1, ATRX and PTEN genes, chromosomal instability and chromoanagenesis. By using chromosomal microarray analysis we identified monosomy of chromosomes 3 and 11, gain of Xp (ATRX) arm and three chromoanasynthesis regions (6q21-q27, 7p22.3-p12.1 and 12q13.11-q21.2), with MDM2 and CDK4 oncogenes copy number gains, whereas no CNVs or tumor specific SNVs in TP53, RB1 and PTEN genes were observed.
Project description:Glioneuronal tumor (GN) is one type of biphasic central nervous system (CNS) tumor that exhibits both glial and neuronal immunohistological characteristics. We report a case of glioneuronal tumor (GN) with a discovery of novel gene fusion of CLIP2-MET resulting from aberrant chromosome 7 abnormalities. The tumor exhibited typical characteristics on histological examinations. We executed an elaborate genomic study on this case including whole-exome sequencing and RNA sequencing. Genomic analysis of the tumor revealed aberrations in chromosomes 1 and 7 and a CLIP2-MET fusion. Further analysis of the upregulated genes revealed substantial connections with MAPK pathway activation. We concluded that the chromosome 7 abnormalities prompted CLIP2-MET gene fusion which successively leads to MAPK pathway activation. We deliberated that MAPK pathway activation is responsible for the oncogenesis of GN based on our case and other previously reported ones.
Project description:Fine particulate matters less than 2.5 µm (PM2.5) in the ambient atmosphere are strongly associated with adverse health effects. However, it is unlikely that all fine particles are equally toxic in view of their different sizes and chemical components. Toxicity of fine particles produced from various combustion sources (diesel engine, gasoline engine, biomass burning (rice straw and pine stem burning), and coal combustion) and non-combustion sources (road dust including sea spray aerosols, ammonium sulfate, ammonium nitrate, and secondary organic aerosols (SOA)), which are known major sources of PM2.5, was determined. Multiple biological and chemical endpoints were integrated for various source-specific aerosols to derive toxicity scores for particles originating from different sources. The highest toxicity score was obtained for diesel engine exhaust particles, followed by gasoline engine exhaust particles, biomass burning particles, coal combustion particles, and road dust, suggesting that traffic plays the most critical role in enhancing the toxic effects of fine particles. The toxicity ranking of fine particles produced from various sources can be used to better understand the adverse health effects caused by different fine particle types in the ambient atmosphere, and to provide practical management of fine particles beyond what can be achieved only using PM mass which is the current regulation standard.
Project description:People with obesity who do not have the metabolic syndrome or components of the metabolic syndrome have been characterized as having metabolically healthy obesity (MHO). However, the existence of MHO has been questioned because people with MHO are at greater risk of developing diabetes and fatal cardiovascular disease than people who are lean and healthy. A 25 year-old woman with rigorously defined MHO (based on normal oral glucose tolerance, insulin sensitivity (assessed by using the hyperinsulinemic-euglycemic clamp procedure), plasma triglyceride and HDL-cholesterol, intrahepatic triglyceride content and carotid intima-media thickness [CIMT]) was evaluated at baseline (BMI=37.7 kg/m2) and 5 years later, after gaining 30.8 kg (32%) in weight (BMI=49.6 kg/m2). The increase in weight was comprised of an 8.8 kg (20%) increase in FFM, 22.0 kg (42%) increase in total body fat, 8.1 kg (37%) increase in leg fat mass, 57% increase in subcutaneous abdominal fat and a 78% in intra-abdominal fat. Weight gain did not have adverse effects on fasting plasma glucose, oral glucose tolerance, beta-cell function, insulin sensitivity, plasma triglyceride, intrahepatic triglyceride content and CIMT. Adipose tissue expression of genes involved in extracellular matrix formation did not change. Adipose tissue expression of several inflammation-related genes increased by more than 30%, but was not associated with a corresponding increase in plasma cytokine concentrations, with the exception of an increase in plasma IL-6. The present case study demonstrates that some people with obesity are resistant to the adverse cardiometabolic effects of excess adiposity and marked weight gain.
Project description:To understand the persistent inflammation even after 5 years of treatment of dapsone in Rosai-Dorfmann patient, we performed single cell RNA sequencing for persistent nodular lesions.
Project description:IntroductionHistiocytic sarcoma (HS) is a rare and aggressive hematologic malignancy with a poor prognosis. HS can present with either isolated organ involvement or multi-systemic disease. This case series reports on nine patients with diverse clinical presentations and outcomes.MethodsDiagnoses of HS were confirmed using immunohistochemistry, with markers such as CD68 and lysozyme. Treatment primarily involved anthracycline-based chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, and with salvage therapies for resistant or relapsed cases including allogeneic HSCT (allo-HSCT).ResultsDespite intensive treatment, long-term remission was rare. Among the nine patients, three achieved complete remission but relapsed, three had stable disease, two experienced progressive disease, and one is under treatment. No patient maintained complete remission for at least three years, indicating the chemo-resistant nature of HS. Moreover, of three cases in our cohort that achieved complete remission, two declined auto-HSCT owing to the intensity of first-line chemotherapy, and one relapsed shortly after achieving remission. To overcome chemo-resistance, four patients underwent allo-HSCT, and two of them achieved long-term remission.ConclusionThese findings highlight the importance of early diagnosis and suggest potential benefits of either autologous or allogeneic transplantation, while emphasizing the need for further research on treatment protocols.