Masseyluna3851

The insulin-like growth factor 1 receptor (IGF-1R) governs several signaling pathways for cell proliferation, survival, and anti-apoptosis. Thus, targeting IGF-1R appears as a reasonable rationale for tumor treatment. However, clinical studies showed that inhibition of IGF-1R has very limited efficacy due to the development of resistance to IGF-1R blockade in tumor cells. Here, we discovered that prolonged treatment of colon cancer cells with IGF-1R inhibitors (BMS-754807 and GSK1838705A) stimulates p70 KDa ribosomal protein S6 kinase 1 (p70S6K1) activation, a well-known kinase signaling for cell survival. We also found that p70S6K1 activation by IGF-1R inhibition is independent of K-Ras and PIK3CA mutations that frequently occur in colon cancer. Besides the increased p70S6K1 phosphorylation, the phosphorylation of mitogen-activated protein kinase kinase 1 and 2 (MEK1/2) was elevated in the cells treated with BMS-754807. Interestingly, the increases in MEK1/2 and p70S6K1 phosphorylation were also observed when cells were subjected to the treatment of AKT inhibitor or genetic knockdown of AKT2 but not AKT1, suggesting that AKT2 inhibition stimulates MEK1/2 phosphorylation to activate p70S6K1. Conversely, inhibition of MEK1/2 by MEK1/2 inhibitor (U0126) or knockdown of MEK1 and MEK2 by corresponding mek1 and mek2 siRNA enhanced AKT phosphorylation, indicating mutual inhibition between AKT and MEK. Furthermore, the combination of BMS-754807 and U0126 efficiently decreased the cell viability and increased cleaved caspase 3 and apoptosis in vitro and in vivo. Our data suggest that the treatment of colon tumor cells with IGF-1R inhibitors stimulates p70S6K1 activity via MEK1/2 to promote survival, providing a new strategy for colorectal cancer therapeutics.Nonnoble metal catalysts are low-cost alternatives to Pt for the oxygen reduction reactions (ORRs), which have been studied for various applications in electrocatalytic systems. Among them, transition metal complexes, characterized by a redox-active single-metal-atom with biomimetic ligands, such as pyrolyzed cobalt-nitrogen-carbon (Co-Nx/C), have attracted considerable attention. Therefore, we reported the ORR mechanism of pyrolyzed Vitamin B12 using operando X-ray absorption spectroscopy coupled with electrochemical impedance spectroscopy, which enables operando monitoring of the oxygen binding site on the metal center. Our results revealed the preferential adsorption of oxygen at the Co2+ center, with end-on coordination forming a Co2+-oxo species. Furthermore, the charge transfer mechanism between the catalyst and reactant enables further Co-O species formation. These experimental findings, corroborated with first-principle calculations, provide insight into metal active-site geometry and structural evolution during ORR, which could be used for developing material design strategies for high-performance electrocatalysts for fuel cell applications.BACKGROUND Colorectal cancer (CRC) cell-derived extracellular vesicles (EVs) contribute to tumor progression. Differentially expressed long non-coding (lnc)RNAs may serve as biomarkers for CRC diagnosis. This study aimed to discuss the diagnostic value of serum EV-derived lncRNA X inactive-specific transcript (XIST) in CRC. MATERIAL AND METHODS Serum EVs were extracted and identified. Microarray analysis was performed to screen out the differentially expressed lncRNAs in serum EVs. The expression and diagnostic efficacy of the most differentially expressed lncRNA were measured. Kaplan-Meier survival analysis was performed to evaluate the association between survival time and XIST expression in EVs. The expression profile of serum EV-carried XIST in 94 CRC patients with different tumor-node-metastasis stages, lymph node metastasis, and differentiation was assessed. The serum contents of CEA, CA242, CA199, and CA153 were measured. RESULTS XIST in serum EVs in CRC patients was upregulated, with greatest diagnostic value. CRC patients with higher expression of XIST in serum EVs had worse 5-year survival rates and shorter life cycles, lower differentiation, higher lymph node metastasis, and tumor-node-metastasis than patients with lower XIST expression. XIST expression in serum EVs was positively correlated with CRC marker contents. CONCLUSIONS XIST upregulation in serum EVs is related to CRC progression, which may be helpful to the clinical diagnosis and prognosis of CRC.BACKGROUND Chromosome 22q11.2 deletion syndrome (22q11.2 DS) currently includes DiGeorge syndrome, conotruncal anomaly face syndrome, and velocardiofacial syndrome. We present the case of a male infant with 22q11.2 DS exhibiting generalized skin rash and dermatopathic lymphadenitis. CASE REPORT The patient was born at 40 weeks of gestation with interruption of aortic arch, ventricular septal defect, and thymic defect. Fluorescence in situ hybridization method performed on buccal smears detected the deletion of 22q11.2. On day of life 33, diffuse erythema appeared on the entire body. A skin biopsy detected vacuolar interface dermatitis with superficial perivascular infiltration. Laboratory examinations revealed eosinophilia and hypocalcemia. Clinically, cutaneous inflammation was correlated with the abnormal immune response in 22q11.2 DS. On day of life 210, the patient died due to sepsis caused by Pseudomonas aeruginosa. An autopsy revealed lymph nodes swellings in the bilateral axillar and subclavicular areas and around the bilateral iliac arteries. Histology of the lymph nodes demonstrated sparse distribution of atrophic germinal centers surrounded by wide zones of proliferating spindle cells, as well as macrophages, Langerhans cells, and interdigitating dendritic cells. Fontana-Masson staining revealed abundant melanin particles in the macrophages. Accordingly, we diagnosed this case as dermatopathic lymphadenitis. Interestingly, CD123 and CD56 double-positive spindle cells also proliferated around the germinal center. CONCLUSIONS This case had an unusual histological feature of dermatopathic lymphadenitis. Considering the wide variety of unusual immune conditions in 22q11.2 DS, the lymph nodes in the systemic skin inflammation may exhibit an extraordinary histology of spindle cells proliferation.BACKGROUND Gliomas are the most common primary tumors of the brain and spinal cord. The tumor microenvironment (TME) is the cellular environment in which tumors exist. This study aimed to identify the role of the TME and the effects of genes involved in the TME of malignant glioma. MATERIAL AND METHODS The ESTIMATE algorithms in the R package were used to calculate the immune and stromal scores of samples in the TCGA and GSE4290 datasets. The associations of stromal and immune scores with clinicopathological characteristics and overall survival of malignant glioma patients were assessed by analysis of variance and Kaplan-Meier analysis. Differentially expressed genes (DEGs) were obtained through the median immune and stromal score using the R package "limma". Functional enrichment analysis and the PPI network MCODE were used to analyze DEGs. RESULTS Increased immune and stromal scores were closely related with advanced glioma grade and poor prognosis (all P less then 0.01). In total, 558 DEGs were found and most were related to tumor prognosis. Functional enrichment analysis showed that DEGs were associated with cell-matrix regulation and immune response. Four hub modules related to tumor angiogenesis, collagen formation, and immune response were found and analyzed. Previously overlooked microenvironment-related genes such as LAMB1, FN1, ACTN1, TRIM, SERPINH1, CYBA, LAIR1, and LILRB2 showed prognostic values in malignant glioma patients. CONCLUSIONS The glioma stromal/immune scores are closely related to glioma grade, histology, and survival time. Some glioma microenvironment-related genes including LAMB1, FN1, ACTN1, TRIM6, SERPINH1, CYBA, LAIR1, and LILRB2 show prognostic values in malignant gliomas and serve as potential biomarkers.Gallbladder agenesis is a rare condition. Patients with gallbladder agenesis can present with biliary type symptoms and rarely pancreatitis. We present the case of a 35-year-old gentleman who was admitted and treated for recurrent pancreatitis on a background of gallbladder agenesis, ansa pancreatica and Santorinicoele. He has had several admissions with pancreatitis and has had multiple imaging modalities during these admissions which we delineate. We discuss this rare anatomical variant and describe the course and management of his illness leading up to his eventual diagnosis of intraductal papillary neoplasia (IPMN).Resection of the whole distal common bile duct (CBD) with in situ re-implantation of the main pancreatic duct can be a surgical option to avoid pancreaticoduodenectomy. in this study, we present two cases of cholangiocarcinomas with diffuse involvement of the extrahepatic CBD that was resected through a retroduodenal approach and re-implantation of the main pancreatic duct. The first case was a 70-year-old male patient with intraductal papillary neoplasm with invasive cholangiocarcinoma. He underwent retroduodenal resection of the whole CBD and in situ re-implantation of the main pancreatic duct. He was disease-free for 8 years, but tumor recurrence occurred at the hepaticojejunostomy site. This patient is currently undergoing chemoradiation therapy for treatment of recurrent lesions. The second case was a 71-year-old male patient with diffuse cholangiocarcinoma involving the whole extrahepatic CBD. He underwent medial sectionectomy, retroduodenal resection of the whole CBD and in situ re-implantation of the main pancreatic duct. He received postoperative chemoradiation therapy. He was disease-free for 3 years, but tumor recurrence occurred at the hepaticojejunostomy site. He passed away 4 years and 6 months after surgery. In conclusion, complete resection of the extrahepatic CBD through a retroduodenal approach with in situ re-implantation of the main pancreatic duct is feasible and less invasive than PD. Therefore, the proposed less-invasive approach can be an alternative procedure in selected patients requiring complete resection of the distal CBD.Complete resection of Todani type IV choledochal cyst (CC) is not possible, because the intrahepatic portion is not resectable. We present a case of intrahepatic cholangiocarcinoma that arose from the remnant CC portion that was located within the liver 10 years after resection. A 59-year-old female patient had undergone resection of type IV CC 10 years ago, leaving large remnant portions of CC at the liver and pancreas. Two and four years after resection of the extrahepatic CC, cholangitis with intrahepatic stones developed hence these episodes were treated with percutaneous transhepatic cholangioscopy. Ten years after the first operation, intrahepatic stones and a new mass were identified in follow-up imaging studies. Because the mass was identified as adenocarcinoma on biopsy, we performed left hepatectomy with redo hepaticojejunostomy. Pathologic examination showed a 4.5-cm-sized moderately differentiated adenocarcinoma arising from the remnant CC with lymph node metastasis. The patient recovered uneventfully and is currently undergoing adjuvant chemotherapy.