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Full-Text Articles in Medicine and Health Sciences

The Pathogenesis Of Natural Killer/T Cell Lymphoma, Bei Jiang Aug 2016

The Pathogenesis Of Natural Killer/T Cell Lymphoma, Bei Jiang

Theses & Dissertations

Extranodal natural killer/T-cell lymphomas (NKTCL) are uncommon lymphomas with poor prognosis. In order to gain a better understanding of the molecular pathogenesis of NKTCL, we obtained and compared the global gene expression profile, global somatic mutation profile, and global methylation profile of normal NK cells, malignant NK cell lines, and NKTCL patient samples. We showed that the JAK-STAT pathway was constitutively activated in NKTCL through the cooperation between activation of signal transducer and activator of transcription proteins (STATs) via activating mutations and inactivation of STAT suppressor protein suppressor of cytokine signaling 6 (SOCS6) through promoter hypermethylation. Activating STAT3 and STAT5B …


Nrp2 Transcriptionally Regulates Its Downstream Effector Wdfy1., Samikshan Dutta, Sohini Roy, Navatha S. Polavaram, Gustavo B. Baretton, Michael H. Muders, Surinder K. Batra, K Datta Mar 2016

Nrp2 Transcriptionally Regulates Its Downstream Effector Wdfy1., Samikshan Dutta, Sohini Roy, Navatha S. Polavaram, Gustavo B. Baretton, Michael H. Muders, Surinder K. Batra, K Datta

Journal Articles: Biochemistry & Molecular Biology

Neuropilins (NRPs) are cell surface glycoproteins that often act as co-receptors for plexins and VEGF family receptors. Neuropilin-2 (NRP2), a family member of NRPs, was shown to regulate autophagy and endocytic trafficking in cancer cells, a function distinctly different from its role as a co-receptor. WD Repeat and FYVE domain containing 1 (WDFY1)-protein acts downstream of NRP2 for this function. Our results indicated that NRP2 maintains an optimum concentration of WDFY1 by negatively regulating its expression. Since increased expression of WDFY1 reduces the endocytic activity, maintenance of WDFY1 level is crucial in metastatic cancer cells to sustain high endocytic activity, …


Ceramide Induces Human Hepcidin Gene Transcription Through Jak/Stat3 Pathway., Sizhao Lu, Sathish Kumar Natarajan, Justin L. Mott, Kusum K. Kharbanda, Duygu Dee Harrison-Findik Jan 2016

Ceramide Induces Human Hepcidin Gene Transcription Through Jak/Stat3 Pathway., Sizhao Lu, Sathish Kumar Natarajan, Justin L. Mott, Kusum K. Kharbanda, Duygu Dee Harrison-Findik

Journal Articles: Biochemistry & Molecular Biology

Changes in lipid metabolism and iron content are observed in the livers of patients with fatty liver disease. The expression of hepcidin, an iron-regulatory and acute phase protein synthesized by the liver, is also modulated. The potential interaction of lipid and iron metabolism is largely unknown. We investigated the role of lipid intermediate, ceramide in the regulation of human hepcidin gene, HAMP. Human hepatoma HepG2 cells were treated with cell-permeable ceramide analogs. Ceramide induced significant up-regulation of HAMP mRNA expression in HepG2 cells. The effect of ceramide on HAMP expression was mediated through transcriptional mechanisms because it was completely blocked …


Ceramide Induces Human Hepcidin Gene Transcription Through Jak/Stat3 Pathway., Sizhao Lu, Sathish Kumar Natarajan, Justin L. Mott, Kusum K. Kharbanda, Duygu Dee Harrison-Findik Jan 2016

Ceramide Induces Human Hepcidin Gene Transcription Through Jak/Stat3 Pathway., Sizhao Lu, Sathish Kumar Natarajan, Justin L. Mott, Kusum K. Kharbanda, Duygu Dee Harrison-Findik

Journal Articles: Biochemistry & Molecular Biology

Changes in lipid metabolism and iron content are observed in the livers of patients with fatty liver disease. The expression of hepcidin, an iron-regulatory and acute phase protein synthesized by the liver, is also modulated. The potential interaction of lipid and iron metabolism is largely unknown. We investigated the role of lipid intermediate, ceramide in the regulation of human hepcidin gene, HAMP. Human hepatoma HepG2 cells were treated with cell-permeable ceramide analogs. Ceramide induced significant up-regulation of HAMP mRNA expression in HepG2 cells. The effect of ceramide on HAMP expression was mediated through transcriptional mechanisms because it was completely blocked …


Overexpression Of Pd2 Leads To Increased Tumorigenicity And Metastasis In Pancreatic Ductal Adenocarcinoma., Arokia Priyanka Vaz, Shonali Deb, Satyanarayana Rachagani, Parama Dey, Sakthivel Muniyan, Imayavaramban Lakshmanan, Saswati Karmakar, Lynette M. Smith, Sonny L. Johansson, Subodh M. Lele, M Ouellette, Moorthy P. Ponnusamy, Surinder K. Batra Jan 2016

Overexpression Of Pd2 Leads To Increased Tumorigenicity And Metastasis In Pancreatic Ductal Adenocarcinoma., Arokia Priyanka Vaz, Shonali Deb, Satyanarayana Rachagani, Parama Dey, Sakthivel Muniyan, Imayavaramban Lakshmanan, Saswati Karmakar, Lynette M. Smith, Sonny L. Johansson, Subodh M. Lele, M Ouellette, Moorthy P. Ponnusamy, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Pancreatic differentiation 2 (PD2), an important subunit of the human PAF complex, was identified after differential screening analysis of 19q13 amplicon, and its overexpression induces oncogenic transformation of NIH3T3 cells, hence raising the possibility of a role for PD2 in tumorigenesis and metastasis. To test this hypothesis, we analyzed here the functional role and clinical significance of PD2 in pancreatic ductal adenocarcinoma (PDAC) and its pathogenesis. Using immunohistochemical analysis, we found that PD2 is detected in the acini but not in the ducts in the normal pancreas. In human PDAC specimens, PD2 was instead primarily detected in the ducts (12/48 …