Pathology Commons^™

The Humoral Theory Of Transplantation: Epitope Analysis And The Pathogenicity Of Hla Antibodies., Edward J Filippone, John Farber

Department of Medicine Faculty Papers

Central to the humoral theory of transplantation is production of antibodies by the recipient against mismatched HLA antigens in the donor organ. Not all mismatches result in antibody production, however, and not all antibodies are pathogenic. Serologic HLA matching has been the standard for solid organ allocation algorithms in current use. Antibodies do not recognize whole HLA molecules but rather polymorphic residues on the surface, called epitopes, which may be shared by multiple serologic HLA antigens. Data are accumulating that epitope analysis may be a better way to determine organ compatibility as well as the potential immunogenicity of given HLA …

A Novel Comparative Pattern Analysis Approach Identifies Chronic Alcohol Mediated Dysregulation Of Transcriptomic Dynamics During Liver Regeneration., Lakshmi Kuttippurathu, Egle Juskeviciute, Rachael P Dippold, Jan B. Hoek, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Liver regeneration is inhibited by chronic ethanol consumption and this impaired repair response may contribute to the risk for alcoholic liver disease. We developed and applied a novel data analysis approach to assess the effect of chronic ethanol intake in the mechanisms responsible for liver regeneration. We performed a time series transcriptomic profiling study of the regeneration response after 2/3(rd) partial hepatectomy (PHx) in ethanol-fed and isocaloric control rats.

RESULTS: We developed a novel data analysis approach focusing on comparative pattern counts (COMPACT) to exhaustively identify the dominant and subtle differential expression patterns. Approximately 6500 genes were differentially regulated …

Multiplatform Molecular Profiling Identifies Potentially Targetable Biomarkers In Malignant Phyllodes Tumors Of The Breast., Zoran Gatalica, Semir Vranic, Anatole Ghazalpour, Joanne Xiu, Idris Tolgay Ocal, John Mcgill, Ryan P Bender, Erin Discianno, Aaron Schlum, Souzan Sanati, Juan P. Palazzo, Sandeep Reddy, Barbara Pockaj

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Malignant phyllodes tumor is a rare breast malignancy with sarcomatous overgrowth and with limited effective treatment options for recurrent and metastatic cases. Recent clinical trials indicated a potential for anti-angiogenic, anti-EGFR and immunotherapeutic approaches for patients with sarcomas, which led us to investigate these and other targetable pathways in malignant phyllodes tumor of the breast. Thirty-six malignant phyllodes tumors (including 8 metastatic tumors with two cases having matched primary and metastatic tumors) were profiled using gene sequencing, gene copy number analysis, whole genome expression, and protein expression. Whole genome expression analysis demonstrated consistent over-expression of genes involved in angiogenesis including …

Intraventricular Sialidase Administration Enhances Gm1 Ganglioside Expression And Is Partially Neuroprotective In A Mouse Model Of Parkinson's Disease., Jay S Schneider, Thomas N Seyfried, Hyo-S Choi, Sarah Kidd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Preclinical and clinical studies have previously shown that systemic administration of GM1 ganglioside has neuroprotective and neurorestorative properties in Parkinson's disease (PD) models and in PD patients. However, the clinical development of GM1 for PD has been hampered by its animal origin (GM1 used in previous studies was extracted from bovine brains), limited bioavailability, and limited blood brain barrier penetrance following systemic administration.

OBJECTIVE: To assess an alternative therapeutic approach to systemic administration of brain-derived GM1 to enhance GM1 levels in the brain via enzymatic conversion of polysialogangliosides into GM1 and to assess the neuroprotective potential of this approach. …

Slit2/Robo1-Mir-218-1-Ret/Plag1: A New Disease Pathway Involved In Hirschsprung's Disease., Weibing Tang, Junwei Tang, Jun He, Zhigang Zhou, Yufeng Qin, Jingjing Qin, Bo Li, Xiaoqun Xu, Qiming Geng, Weiwei Jiang, Wei Wu, Xinru Wang, Yankai Xia

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Hirschsprung's disease (HSCR) is a rare congenital disease caused by impaired proliferation and migration of neural crest cells. We investigated changes in expression of microRNAs (miRNAs) and the genes they regulate in tissues of patients with HSCR. Quantitative real-time PCR and immunoblot analyses were used to measure levels of miRNA, mRNAs, and proteins in colon tissues from 69 patients with HSCR and 49 individuals without HSCR (controls). Direct interactions between miRNAs and specific mRNAs were indentified in vitro, while the function role of miR-218-1 was investigated by using miR-218 transgenic mice. An increased level of miR-218-1 correlated with increased levels …

Bordetella Petrii Recovered From Chronic Pansinusitis In An Adult With Cystic Fibrosis, Laura Biederman, Marc Rosen Md, Brent S. Bobik, Amity L. Roberts, Phd, D(Abmm)

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

Mir-143 Acts As A Tumor Suppressor By Targeting N-Ras And Enhances Temozolomide-Induced Apoptosis In Glioma., Lin Wang, Zhu-Mei Shi, Cheng-Fei Jiang, Xue Liu, Qiu-Dan Chen, Xu Qian, Dong-Mei Li, Xin Ge, Xie-Feng Wang, Ling-Zhi Liu, Yong-Ping You, Ning Liu, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Therapeutic applications of microRNAs (miRNAs) in RAS-driven glioma were valuable, but their specific roles and functions have yet to be fully elucidated. Here, we firstly report that miR-143 directly targets the neuroblastoma RAS viral oncogene homolog (N-RAS) and functions as a tumor-suppressor in glioma. Overexpression of miR-143 decreased the expression of N-RAS, inhibited PI3K/AKT, MAPK/ERK signaling, and attenuated the accumulation of p65 in nucleus of glioma cells. In human clinical specimens, miR-143 was downregulated where an adverse with N-RAS expression was observed. Furthermore, overexpression of miR-143 decreased glioma cell migration, invasion, tube formation and slowed tumor growth and angiogenesis in …

Adiponectin Inhibits Tumor Necrosis Factor-Α-Induced Vascular Inflammatory Response Via Caveolin-Mediated Ceramidase Recruitment And Activation., Yajing Wang, Xiaoliang Wang, Wayne Bond Lau, Yuexing Yuan, David Booth, Jing-Jing Li, Rosario Scalia, Kyle Preston, Erhe Gao, Walter Koch, Xin-Liang Ma

Department of Medicine Faculty Papers

RATIONALE: Anti-inflammatory and vascular protective actions of adiponectin are well recognized. However, many fundamental questions remain unanswered.

OBJECTIVE: The current study attempted to identify the adiponectin receptor subtype responsible for adiponectin's vascular protective action and investigate the role of ceramidase activation in adiponectin anti-inflammatory signaling.

METHODS AND RESULTS: Adiponectin significantly reduced tumor necrosis factor (TNF)α-induced intercellular adhesion molecule-1 expression and attenuated TNFα-induced oxidative/nitrative stress in human umbilical vein endothelial cells. These anti-inflammatory actions were virtually abolished by adiponectin receptor 1 (AdipoR1-), but not AdipoR2-, knockdown (KD). Treatment with adiponectin significantly increased neutral ceramidase (nCDase) activity (3.7-fold; P87% of adiponectin-induced nCDase …

Proline-Rich Tyrosine Kinase 2 (Pyk2) Regulates Igf-I-Induced Cell Motility And Invasion Of Urothelial Carcinoma Cells, Marco Genua, Shi-Qiong Xu, Simone Buraschi, Stephen C. Peiper, Leonard G. Gomella, Antonio Belfiore, Renato V. Iozzo, Andrea Morrione

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The insulin-like growth factor receptor I (IGF-IR) plays an essential role in transformation by promoting cell growth and protecting cancer cells from apoptosis. We have recently demonstrated that the IGF-IR is overexpressed in invasive bladder cancer tissues and promotes motility and invasion of urothelial carcinoma cells. These effects require IGF-I-induced Akt- and MAPK-dependent activation of paxillin. The latter co-localizes with focal adhesion kinases (FAK) at dynamic focal adhesions and is critical for promoting motility of urothelial cancer cells. FAK and its homolog Proline-rich tyrosine kinase 2 (Pyk2) modulate paxillin activation; however, their role in regulating IGF-IR-dependent signaling and motility in …

The Variable Presentations Of Anaplastic Spindle Cell Squamous Carcinoma Associated With Tall Cell Variant Of Papillary Thyroid Carcinoma., Pallavi P Gopal, Kathleen T Montone, Zubair Baloch, Madalina Tuluc, Virginia Livolsi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: In 1976, Hawk and Hazard described the tall cell variant (TCV) of papillary thyroid carcinoma (PTC). While the lesions they described had cytologic features of papillary carcinoma, they showed more aggressive behavior with a greater propensity for extrathyroid extension and lymphovascular invasion than classic PTC. In 1991, Bronner and LiVolsi described a series of patients with TCV that progressed to spindle cell squamous carcinoma (SCSC), a unique form of anaplastic thyroid carcinoma. This study describes the variable clinical and pathologic presentations in 31 patients with anaplastic SCSC arising in association with TCV.

METHODS: The surgical pathology archives as well …

One Year Survival With Poorly Differentiated Metastatic Pancreatic Carcinoma Following Chemoembolization With Gemcitabine And Cisplatin., Daniel B Brown, Carin F Gonsalves, Charles J Yeo, Agnes K Witkiewicz, Brian I Carr

Department of Radiology Faculty Papers

While hepatic arterial chemoembolization is efficacious for a number of malignancies, there is scant data regarding treatment of pancreatic adenocarcinoma. We report a complete radiographic response at one year from diagnosis of metastatic pancreatic carcinoma. Gemcitabine/cisplatin based chemoembolization may be of potential benefit for patients with liver-dominant metastases from pancreatic carcinoma. Given the typical survival of 6 months or less in this patient group with standard therapies, further research is warranted.