Pathology Commons^™

Promoter Hypermethylation Of Tumor Suppressor Genes Correlates With Tumor Grade And Invasiveness In Patients With Urothelial Bladder Cancer, Shumaila M. Bilgrami, Sohail A. Qureshi, Shahid Pervez, Farhat Abbas

Section of Urology

Purpose: To investigate the promoter methylation status at selected loci which encode for key proteins involved in apoptosis, DNA repair, cell cycle control and progression in urothelial cell carcinoma of bladder and compare the findings from tissue samples with that of plasma.
Methods: Total genomic DNA was isolated from 43 non-muscle invasive (low grade) and 33 muscle invasive (high grade) urothelial bladder cancer samples along with 10 control cases of normal bladder mucosa. Promoter methylation status was investigated for RASSF1A, APC, MGMT, CDKN2A and CDKN2B genes using real-time methylation-specific PCR with SYBR® green. Plasma samples from 16 patients with muscle …

Response To Imatinib Mesylate In Patients With Early Chronic Phase Chronic Myeloid Leukemia And Derivative Chromosome 9 Deletion Or Clonal Evolution, Mohammad Usman Shaikh, Tariq Moatter, Naveen Naz Syed, Natasha Bahadur Ali, Salman Adil

Department of Pathology and Laboratory Medicine

Objectives: The significance of clonal evolution and derivative chromosome 9 in Philadelphia-positive CML is not fully characterized and studies have yielded conflicting results. After working on emergence of clonal evolution from our region, we continued to find out the response of Imatinib Mesylate on such cases of CML treated in our center.
Materials and methods: We conducted a cross sectional, prospective analysis on response of Imatinib Mesylate on patients with Philadelphia positive chronic myeloid leukemia with clonal evolution treated from period of September 2007 till 2010. Patients were grouped on basis of cytogenetic analysis performed by conventional cytogenetic and fluorescence …

Evidence For Aberrant Astrocyte Hemichannel Activity In Juvenile Neuronal Ceroid Lipofuscinosis (Jncl)., Maria Burkovetskaya, Nikolay Karpuk, Juan Xiong, Megan Bosch, Michael D. Boska, Hideyuki Takeuchi, Akio Suzumura, Tammy Kielian

Journal Articles: Pathology and Microbiology

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a lysosomal storage disease caused by an autosomal recessive mutation in CLN3 that leads to vision loss, progressive cognitive and motor decline, and premature death. Morphological evidence of astrocyte activation occurs early in the disease process and coincides with regions where neuronal loss eventually ensues. However, the consequences of CLN3 mutation on astrocyte function remain relatively ill-defined. Astrocytes play a critical role in CNS homeostasis, in part, by their ability to regulate the extracellular milieu via the formation of extensive syncytial networks coupled by gap junction (GJ) channels. In contrast, unopposed hemichannels (HCs) have …

Labrad : Vol 40, Issue 1 - April 2014, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Provocative Testing for Growth Hormone Disorders
• Serum Procalcitonin for Early Sepsis Diagnosis
• Monoclonal Gammopathy of Undetermined Significance (MGUS)
• Understanding Six Sigma Methodology
• Blood Collection for Culture
• Molecular Analysis of Alpha Thalassaemia by Multiple Ligation Probe Assay
• Prognostification of Acute Myeloid Leukemia with FLT 3 Mutation
• Interferon Gamma Release Assay (IGRA) for Detection of Mycobacterium Tuberculosis Infection in the Host
• Meeting Report: The 37th Annual Conference of the Pakistan Association of Pathologists

Functional Proteomic Analysis Reveals The Involvement Of Kiaa1199 In Breast Cancer Growth, Motility And Invasiveness., Mohammad-Saeid Jami, Jinxuan Hou, Miao Liu, M L. Varney, Hesham Hassan, Jixin Dong, Liying Geng, J. Wang, Fang Yu, Xin Huang, Hong Peng, Kai Fu, Yan Li, Rakesh Singh, Shi-Jian Ding

Journal Articles: Pathology and Microbiology

BACKGROUND: KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness.

METHODS: We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to …

Carp-1 Functional Mimetics Are A Novel Class Of Small Molecule Inhibitors Of Malignant Pleural Mesothelioma Cells, Shazia Jamal, Vino T. Cheriyan, Magesh Muthu, Sara Munie, Edi Levi, Abdelkader E. Ashour, Harvey I. Pass, Anil Wali, Mandip Singh, Arun K. Rishi

Oncology Faculty Publications

Malignant pleural mesothelioma (MPM) is an asbestos-related thoracic malignancy that is characterized by late metastases, and resistance to therapeutic modalities. The toxic side-effects of MPM therapies often limit their clinical effectiveness, thus necessitating development of new agents to effectively treat and manage this disease in clinic. CARP-1 functional mimetics (CFMs) are a novel class of compounds that inhibit growth of diverse cancer cell types. Here we investigated MPM cell growth suppression by the CFMs and the molecular mechanisms involved. CFM-1, -4, and -5 inhibited MPM cell growth, in vitro, in part by stimulating apoptosis. Apoptosis by CFM-4 involved activation of …

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 …

Natural History Of Untreated Prostate Specific Antigen Radiorecurrent Prostate Cancer In Men With Favorable Prognostic Indicators, Andrew Renshaw

All Publications

No abstract provided.

Hiding In Plain Sight: Interplay Between Staphylococcal Biofilms And Host Immunity., Tyler D. Scherr, Cortney E. Heim, John M. Morrison, Tammy Kielian

Journal Articles: Pathology and Microbiology

Staphylococcus aureus and Staphylococcus epidermidis are notable for their propensity to form biofilms on implanted medical devices. Staphylococcal biofilm infections are typified by their recalcitrance to antibiotics and ability to circumvent host immune-mediated clearance, resulting in the establishment of chronic infections that are often recurrent in nature. Indeed, the immunomodulatory lifestyle of biofilms seemingly shapes the host immune response to ensure biofilm engraftment and persistence in an immune competent host. Here, we provide a brief review of the mechanisms whereby S. aureus and S. epidermidis biofilms manipulate host-pathogen interactions and discuss the concept of microenvironment maintenance in infectious outcomes, as …

Expression Of Mir-15/107 Family Micrornas In Human Tissues And Cultured Rat Brain Cells, Wang-Xia Wang, Robert J. Danaher, Craig S. Miller, Joseph R. Berger, Vega G. Nubia, Bernard R. Wilfred, Janna H. Neltner, Christopher M. Norris, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

The miR-15/107 family comprises a group of 10 paralogous microRNAs (miRNAs), sharing a 5' AGCAGC sequence. These miRNAs have overlapping targets. In order to characterize the expression of miR-15/107 family miRNAs, we employed customized TaqMan Low-Density micro-fluid PCR-array to investigate the expression of miR-15/107 family members, and other selected miRNAs, in 11 human tissues obtained at autopsy including the cerebral cortex, frontal cortex, primary visual cortex, thalamus, heart, lung, liver, kidney, spleen, stomach and skeletal muscle. miR-103, miR-195 and miR-497 were expressed at similar levels across various tissues, whereas miR-107 is enriched in brain samples. We also examined the expression …

Targeting Fibroblast Activation Protein In Tumor Stroma With Chimeric Antigen Receptor T Cells Can Inhibit Tumor Growth And Augment Host Immunity Without Severe Toxicity., Liang-Chuan S. Wang, Albert Lo, John Scholler, Jing Sun, Rajrupa S. Majumdar, Veena Kapoor, Michael Antzis, Cody E. Cotner, Laura A. Johnson, Amy C. Durham, Charalambos C. Solomides, Md, Carl H. June, Ellen Puré, Steven M. Albelda

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The majority of chimeric antigen receptor (CAR) T-cell research has focused on attacking cancer cells. Here, we show that targeting the tumor-promoting, nontransformed stromal cells using CAR T cells may offer several advantages. We developed a retroviral CAR construct specific for the mouse fibroblast activation protein (FAP), comprising a single-chain Fv FAP [monoclonal antibody (mAb) 73.3] with the CD8α hinge and transmembrane regions, and the human CD3ζ and 4-1BB activation domains. The transduced muFAP-CAR mouse T cells secreted IFN-γ and killed FAP-expressing 3T3 target cells specifically. Adoptively transferred 73.3-FAP-CAR mouse T cells selectively reduced FAP(hi) stromal cells and inhibited the …

Response Of An Aggressive Periosteal Aneurysmal Bone Cyst (Abc) Of The Radius To Denosumab Therapy., Chantal Pauli, Bruno Fuchs, Christian Pfirrmann, Julia A. Bridge, Silvia Hofer, Beata Bode

Journal Articles: Pathology and Microbiology

Aneurysmal bone cyst (ABC), once considered a reactive lesion, has been proven to be a neoplasia characterized by rearrangements of the USP6-gene. Aggressive local growth and recurrences are common and therapeutic options may be limited due to the vicinity of crucial structures. We describe a case of a locally aggressive, multinucleated giant cell-containing lesion of the forearm of a 21-year old woman, treated with denosumab for recurrent, surgically uncontrollable disease. Under the influence of this RANKL inhibitor, the tumor showed a marked reduction of the content of the osteoclastic giant cells and an extensive metaplastic osteoid production leading to the …

Steady Increment Of Immature Platelet Fraction Is Suppressed By Irradiation In Single-Donor Platelet Components During Storage, Hong Hong, Wenbin Xiao, Robert W. Maitta

Faculty Scholarship

Circulating immature platelet fraction (IPF) reflects real-time thrombopoiesis and correlates with platelet recovery from thrombocytopenic presentations. To understand the dynamics of IPF in platelet transfusions, we quantified the %-IPF in single-donor platelet components (SDP) during prolonged storage. %-IPF significantly increased from baseline by day 5 post-donation. Absolute IPF counts (A-IPC) had similar significant increments. However, gamma-irradiation suppressed the increments of %-IPF and A-IPC by >50%. Ultrastructural analysis of SDP units at day 10 showed well preserved morphology of immature platelets. Our findings suggest that IPF might actively expand ex-vivo and may have a longer shelf life than their mature counterparts. …

Metabotropic Glutamate Receptor-1 Contributes To Progression In Triple Negative Breast Cancer, Malathi Banda, Cecilia L. Speyer, Sara N. Semma, Kingsley O. Osuala, Nicole Kounalakis, Keila E. Torres Torres, Nicola J. Barnard, Hyunjin J. Kim, Bonnie F. Sloane, Fred R. Miller, James S. Goydos, David H. Gorski

Department of Surgery

TNBC is an aggressive breast cancer subtype that does not express hormone receptors (estrogen and progesterone receptors, ER and PR) or amplified human epidermal growth factor receptor type 2 (HER2), and there currently exist no targeted therapies effective against it. Consequently, finding new molecular targets in triple negative breast cancer (TNBC) is critical to improving patient outcomes. Previously, we have detected the expression of metabotropic glutamate receptor-1 (gene: GRM1; protein: mGluR1) in TNBC and observed that targeting glutamatergic signaling inhibits TNBC growth both in vitro and in vivo. In this study, we explored how mGluR1 contributes to TNBC …

Gold(Iii)-Dithiocarbamato Peptidomimetics In The Forefront Of The Targeted Anticancer Therapy: Preclinical Studies Against Human Breast Neoplasia, Chiara Nardon, Sara M. Schmitt, Huanjie Yang, Jian Zuo, Delores Fregona, Q. Ping Dou

Oncology Faculty Publications

Since the serendipitous discovery of cisplatin, platinum-based drugs have become well-established antitumor agents, despite the fact that their clinical use is limited by many severe side-effects. In order to both improve the chemotherapeutic index and broaden the therapeutic spectrum of current drugs, our most recent anti-neoplastic agents, Au(III) complexes, were designed as carrier-mediated delivery systems exploiting peptide transporters, which are up-regulated in some cancers. Among all, we focused on two compounds and tested them on human MDA-MB-231 (resistant to cisplatin) breast cancer cell cultures and xenografts, discovering the proteasome as a major target both in vitro and in vivo. …

Can Newly Developed, Rapid Immunochromatographic Antigen Detection Tests Be Reliably Used For The Laboratory Diagnosis Of Influenza Virus Infections?, J. J. Dunn, C. C. Ginocchio

Journal Articles

Five years ago, the Point-Counterpoint series was launched. The initial article asked about the role of rapid immunochromatographic antigen testing in diagnosis of influenza A virus 2009 H1N1 infection (1). Since that article, major changes have been made not only in immunochromatographic antigen detection (IAD) test for the influenza viruses but there also has been rapid development of commercially available nucleic acid amplification tests (NAATs) for influenza virus detection as well. Further, a novel variant of influenza A, H7N9, has emerged in Asia and H5N1 is also re-emergent. In this initial article, the editor of this series, Peter Gilligan, identified …

Sinusoidal Obstruction Syndrome (Hepatic Veno-Occlusive Disease), C. Q. Fan, J. M. Crawford

Journal Articles

Hepatic sinusoidal obstruction syndrome (SOS) is an obliterative venulitis of the terminal hepatic venules, which in its more severe forms imparts a high risk of mortality. SOS, also known as veno-occlusive disease (VOD), occurs as a result of cytoreductive therapy prior to hematopoietic stem cell transplantation (HSCT), following oxaliplatin-containing adjuvant or neoadjuvant chemotherapy for colorectal carcinoma metastatic to the liver and treated by partial hepatectomy, in patients taking pyrrolizidine alkaloid-containing herbal remedies, and in other particular settings such as the autosomal recessive condition of veno-occlusive disease with immunodeficiency (VODI). A central pathogenic event is toxic destruction of hepatic sinusoidal endothelial …

Is Aggressive Digital Papillary Adenocarcinoma Really Aggressive Digital Papillary Adenocarcinoma?, S. Chen, M. Asgari

Journal Articles

No abstract provided.

Papillary Adenocarcinoma In Situ Of The Skin: Report Of Four Cases, S. Chen, M. Asgari

Journal Articles

Although rare isolated cases of adenocarcinoma in situ of skin have been reported in the literature, adenocarcinoma in situ of skin as a concept and as a diagnostic category has not been established in the field of dermatopathology. In this work, four cases of papillary adenocarcinoma in situ of the skin are presented. In addition, the notion that lesions previously reported in the medical literature under the term of "papillary eccrine adenoma" are actually adenocarcinoma in situ is discussed.

Brain Region-Specific Alterations In The Gene Expression Of Cytokines, Immune Cell Markers And Cholinergic System Components During Peripheral Endotoxin-Induced Inflammation, H. A. Silverman, M. Dancho, A. Regnier-Golanov, M. Nasim, M. Ochani, P. S. Olofsson, M. Ahmed, E. J. Miller, S. S. Chavan, E. Golanov, C. Metz, K. J. Tracey, V. A. Pavlov

Journal Articles

Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune - brain communication, including the impact of peripheral inflammation on brain region-specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels) remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum, and thalamus in mice following an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels …