Pathology Commons^™

Mammographic Breast Density And Breast Cancer Molecular Subtypes: The Kenyan-African Aspect, Asim Jamal, Maeve Mullooly, Shahin Sayed, Rose Ndumia, Innocent Abayo, James Orwa, Ronald Wasike, Zahir Moloo, Gretchen L. Gierach

Internal Medicine, East Africa

Introduction: Data examiningmammographic breast density (MBD) among patients in Sub-Saharan Africa are sparse.We evaluated how MBD relates to breast cancer characteristics in Kenyan women undergoing diagnostic mammography.

Methods: This crosssectional study included women with pathologically confirmed breast cancers (𝑛 = 123). Pretreatment mammograms of the unaffectedbreast were assessed to estimate absolute dense area (cm2), nondense area (cm2), and percent density (PD). Relationships between density measurements and clinical characteristics were evaluated using analysis of covariance.

Results: Median PD and dense area were 24.9% and 85.3 cm2. Higher PD and dense area were observed in younger women (𝑃 < 0.01). Higher dense and nondense areas were observed in obese women (𝑃-trend < 0.01). Estrogen receptor (ER) positive patients (73%) had higher PD and dense area than ER-negative patients (𝑃 ≤ 0.02). Triple negative breast cancer (TNBC) patients (17%) had lower PD and dense area (𝑃 ≤ 0.01) compared with non-TNBCs. No associations were observed between MBD and tumor size and grade.

Conclusions: Our findings show …

Tissue Specific Origin, Development, And Pathological Perspectives Of Pericytes., Tomoko Yamazaki, Yoh-Suke Mukouyama

Articles, Abstracts, and Reports

Pericytes are mural cells surrounding blood vessels, adjacent to endothelial cells. Pericytes play critical roles in maturation and maintenance of vascular branching morphogenesis. In the central nervous system (CNS), pericytes are necessary for the formation and regulation of the blood-brain barrier (BBB) and pericyte deficiency accompanies CNS diseases including multiple sclerosis, diabetic retinopathy, neonatal intraventricular hemorrhage, and neurodegenerative disorders. Despite the importance of pericytes, their developmental origins and phenotypic diversity remain incompletely understood. Pericytes express multiple markers and the origin of pericytes differs by tissue, which may cause difficulty for the identification and understanding of the ontogeny of pericytes. Also, …

Overexpression Of Egfr In Oral Premalignant Lesions And Oscc And Its Impact On Survival And Recurrence, Yumna Mirza, Syed Adnan Ali, Mohammad Sohail Awan, Romana Idress, Sana Naeem, Nida Zahid, Urooj Qadeer

Department of Surgery Docs

Introduction: Oral squamous cell carcinoma (OSCC) the sixth leading cancer worldwide ranks as the most common cancer in males, and the third most common in females in Pakistan. It is influenced by risk factors which are widely consumed in our population. The epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor that is imperative for cell signalling, growth and differentiation. It is mutated and overexpressed in a variety of cancers, while in OSCC it has been linked to poor patient survival; premalignant to malignant transformation and recurrence. This study investigates the use of EGFR as a prognostic factor …

Immune Checkpoint Inhibitors In Neuroendocrine Tumors: A Single Institution Experience With Review Of Literature, Aman Chauhan, Millicent Horn, Gray Magee, Kurt Hodges, B. Mark Evers, Susanne Arnold, Lowell B. Anthony

Markey Cancer Center Faculty Publications

This unique case series and review of literature suggests that immune checkpoint inhibitors may have clinical activity in neuroendocrine tumors.

Objective: Summarize advances of immuno-oncology in neuroendocrine tumors with the help of a case series.

Design: Case series and review of literature.

Intervention or Exposure: The patients were treated with immune checkpoint inhibitors (pembrolizumab or nivolumab).

Main Outcome(s) and Measures(s): Life expectancy, quality of life, disease progression.

Results: Maximum durable response of 16 months in one of the patients so far. All patients showed improvement in quality of life before disease progression. Two out of four are still on therapy. …

Hematopoietic Stem Cell Transplantation In Pakistan – Country Report, Parvez Ahmed, Tahir Sultan Shamsi, Salman Adil, Tariq Mahmood Satti, Qamar Un Nisa Chaudhry, Tahir Sultan Shamsi, Syed Kamran Mahmood, Saqib Ansari, Natasha Bahadur Ali, Tariq Ghafoor

Department of Pathology and Laboratory Medicine

No abstract provided.

Non-Hodgkin And Hodgkin Lymphomas Select For Overexpression Of Bclw., Clare M. Adams, Ramkrishna Mitra, Jerald Z. Gong, Md, Christine M. Eischen

Department of Cancer Biology Faculty Papers

Purpose: B-cell lymphomas must acquire resistance to apoptosis during their development. We recently discovered BCLW, an antiapoptotic BCL2 family member thought only to contribute to spermatogenesis, was overexpressed in diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. To gain insight into the contribution of BCLW to B-cell lymphomas and its potential to confer resistance to BCL2 inhibitors, we investigated the expression of BCLW and the other antiapoptotic BCL2 family members in six different B-cell lymphomas. Experimental Design: We performed a large-scale gene expression analysis of datasets comprising approximately 2,300 lymphoma patient samples, including non-Hodgkin and Hodgkin lymphomas as well as …

Characteristics Associated With Requests By Pathologists For Second Opinions On Breast Biopsies., Berta M Geller, Heidi D Nelson, Donald L Weaver, Paul D Frederick, Kimberly H Allison, Tracy Onega, Patricia A Carney, Anna N A Tosteson, Joann G Elmore

Articles, Abstracts, and Reports

AIMS: Second opinions in pathology improve patient safety by reducing diagnostic errors, leading to more appropriate clinical treatment decisions. Little objective data are available regarding the factors triggering a request for second opinion despite second opinion consultations being part of the diagnostic system of pathology. Therefore we sought to assess breast biopsy cases and interpreting pathologists characteristics associated with second opinion requests.

METHODS: Collected pathologist surveys and their interpretations of 60 test set cases were used to explore the relationships between case characteristics, pathologist characteristics and case perceptions, and requests for second opinions. Data were evaluated by logistic regression and …

Bk Polyomavirus Virus Hemorrhagic Cystitis Following Allogeneic Bone Marrow Transplant With Haploidentical Related Donor: Case Reports From Two Patients, Danish Shakeel, Natasha Bahadur Ali, Mohammad Usman Shaikh, Salman Adil

Section of Haematology/Oncology

BK virus is well known to be associated with allograft failure in renal transplant recipients due to polyomavirus-associated nephropathy (PVAN). BK viruses are increasingly recognized an important cause of hemorrhagic cystitis during hematopoietic stem cell transplantation (HSCT). Here we describe two patients with acute lymphoblastic leukemia who received a haplo identical match related donor hematopoietic stem cell transplant after myeloablative conditioning and post-transplant cyclophosphamide. They developed cytology proven BK Virus cystitis. Both were treated with Leflunomide. Treatment was effective in alleviating the symptoms temporarily but eventually the symptoms progressed and resulted in mortality of both patients.

Iron Overload Assessment In Beta Thalassemia Major - Is T2* Magnetic Resonance Imaging The Answer?, Natasha Ali

Department of Pathology and Laboratory Medicine

No abstract provided.

Posttranscriptional Upregulation Of Idh1 By Hur Establishes A Powerful Survival Phenotype In Pancreatic Cancer Cells., Mahsa Zarei, Shruti Lal, Seth J. Parker, Avinoam Nevler, Ali Vaziri-Gohar, Katerina Dukleska, Nicole C. Mambelli-Lisboa, Cynthia Moffat, Fernando F Blanco, Saswati N. Chand, Masaya Jimbo, Joseph A. Cozzitorto, Wei Jiang, Charles J. Yeo, Eric R. Londin, Erin L. Seifert, Christian M. Metallo, Jonathan R. Brody, Jordan M. Winter

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Cancer aggressiveness may result from the selective pressure of a harsh nutrient-deprived microenvironment. Here we illustrate how such conditions promote chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Glucose or glutamine withdrawal resulted in a 5- to 10-fold protective effect with chemotherapy treatment. PDAC xenografts were less sensitive to gemcitabine in hypoglycemic mice compared with hyperglycemic mice. Consistent with this observation, patients receiving adjuvant gemcitabine (n = 107) with elevated serum glucose levels (HgbA1C > 6.5%) exhibited improved survival. We identified enhanced antioxidant defense as a driver of chemoresistance in this setting. ROS levels were doubled in vitro by either nutrient withdrawal …

Knowledge, Attitude And Perceptions Of Muslim Cancer Patients Regarding Cancer Treatment During Ramadan: Results From A Tertiary Care Hospital Karachi, Afshan Asghar Rasheed, Yasmin Abdul Rashid, Farah Tahir Pirzada, Fawad Haroon, Adnan Jabbar, Ahmed Raheem Buksh

Department of Radiation Oncology

Objective: To assess the knowledge and attitude of Muslim cancer patients regarding cancer treatment during Ramadan.
Methods: This cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, from July to August 2015, and comprised cancer patients. .Adult Muslim cancer patients receiving active oncological treatment or on surveillance were included. Patients on only supportive treatment were excluded. SPSS 19 was used for data analysis.
Results: Of the 265 patients, 87(32.8%) were males and 178(67.2%) were females. The overall mean age was 49±13.87 years. Besides, 184(70.9%) patients belonged to the middle class. Breast cancer was the most common cancer 106(40.6%). …

Multiparametric Immune Profiling In Hpv- Oral Squamous Cell Cancer., Zipei Feng, Daniel Bethmann, Matthias Kappler, Carmen Ballesteros-Merino, Alexander Eckert, R Bryan Bell, Allen Cheng, Tuan Bui, Rom Leidner, Walter Urba, Kent Johnson, Clifford Hoyt, Carlo Bifulco, Juergen Bukur, Claudia Wickenhauser, Barbara Seliger, Bernard A Fox

Articles, Abstracts, and Reports

Evaluation of T lymphocyte frequency provides prognostic information for patients with oral squamous cell cancer (OSCC). However, the effect of simultaneously evaluating T cell frequency and assessing suppressive elements and defects in antigen-processing machinery (APM) has not been clarified. Simultaneous characterization of CD3+, CD8+, FoxP3+, CD163+, and PD-L1+ cells using multispectral imaging was performed on sections from 119 patients with HPV- OSCC. Expression of β2-microglobulin, MHC class I heavy chain, and large multifunctional peptidase 10 was quantified, and all data were correlated with patient outcome. We found that, consistent with previous reports, high numbers of CD8+ T cells at the …

Macrophage Type 2 Differentiation In A Patient With Laryngeal Squamous Cell Carcinoma And Metastatic Prostate Adenocarcinoma To The Cervical Lymph Nodes., Michael C. Topf, Madalina Tuluc, Larry A. Harshyne, Adam J. Luginbuhl

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

BACKGROUND: The tumor microenvironment often polarizes infiltrating macrophages towards a type 2, or M2 phenotype, that is characterized by expression of various cysteine-rich, scavenger receptors, including CD163. The primary function of M2 macrophages is to facilitate wound healing. As such, they are capable of providing metabolic support to a growing tumor, neovascularization, as well as protection from cytotoxic T cells. The tumor microenvironment contains a milieu of secreted factors and vesicles, which in certain circumstances can gain access to lymphatic vessels that drain to local lymph nodes.

CASE PRESENTATION: We report a 59-year-old male with recurrent T4 squamous cell carcinoma …

Cyclin D1 Restrains Oncogene-Induced Autophagy By Regulating The Ampk-Lkb1 Signaling Axis., Mathew C. Casimiro, Gabriele Disante, Agnese Di Rocco, Emanuele Loro, Claudia Pupo, Timothy G. Pestell, Sara Bisetto, Marco A. Velasco-Velázquez, Xuanmao Jiao, Zhiping Li, Christine M. Kusminski, Erin L. Seifert, Chenguang Wang, Daniel Ly, Bin Zheng, Che-Hung Shen, Philipp E. Scherer, Richard Pestell

Department of Cancer Biology Faculty Papers

Autophagy activated after DNA damage or other stresses mitigates cellular damage by removing damaged proteins, lipids, and organelles. Activation of the master metabolic kinase AMPK enhances autophagy. Here we report that cyclin D1 restrains autophagy by modulating the activation of AMPK. In cell models of human breast cancer or in a cyclin D1-deficient model, we observed a cyclin D1-mediated reduction in AMPK activation. Mechanistic investigations showed that cyclin D1 inhibited mitochondrial function, promoted glycolysis, and reduced activation of AMPK (pT172), possibly through a mechanism that involves cyclin D1-Cdk4/Cdk6 phosphorylation of LKB1. Our findings suggest how AMPK activation by cyclin D1 …

Pathologists' Diagnosis Of Invasive Melanoma And Melanocytic Proliferations: Observer Accuracy And Reproducibility Study., Joann G Elmore, Raymond L Barnhill, David E Elder, Gary M Longton, Margaret S Pepe, Lisa M Reisch, Patricia A Carney, Linda J Titus, Heidi D Nelson, Tracy Onega, Anna N A Tosteson, Martin A Weinstock, Stevan R Knezevich, Michael W Piepkorn

Articles, Abstracts, and Reports

No abstract provided.

Intratumoral Heterogeneity Analysis Reveals Hidden Associations Between Protein Expression Losses And Patient Survival In Clear Cell Renal Cell Carcinoma., Wei Jiang, Essel Dulaimi, Karthik Devarajan, Theodore Parsons, Qiong Wang, Raymond O'Neill, Charalambos C. Solomides, Stephen C. Peiper, Joseph R. Testa, Robert Uzzo, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Intratumoral heterogeneity (ITH) is a prominent feature of kidney cancer. It is not known whether it has utility in finding associations between protein expression and clinical parameters. We used ITH that is detected by immunohistochemistry (IHC) to aid the association analysis between the loss of SWI/SNF components and clinical parameters.160 ccRCC tumors (40 per tumor stage) were used to generate tissue microarray (TMA). Four foci from different regions of each tumor were selected. IHC was performed against PBRM1, ARID1A, SETD2, SMARCA4, and SMARCA2. Statistical analyses were performed to correlate biomarker losses with patho-clinical parameters. Categorical variables were compared between groups …

Mct1 In Invasive Ductal Carcinoma: Monocarboxylate Metabolism And Aggressive Breast Cancer., Jennifer M. Johnson, Paolo Cotzia, Roberto Fratamico, Lekha Mikkilineni, Jason Chen, Daniele Colombo, Mehri Mollaee, Diana Whitaker-Menezes, Marina Domingo-Vidal, Zhao Lin, Tingting Zhan, Madalina Tuluc, Juan P. Palazzo, Ruth C. Birbe, Ubaldo E. Martinez-Outshoorn

Department of Medical Oncology Faculty Papers

Introduction: Monocarboxylate transporter 1 (MCT1) is an importer of monocarboxylates such as lactate and pyruvate and a marker of mitochondrial metabolism. MCT1 is highly expressed in a subgroup of cancer cells to allow for catabolite uptake from the tumor microenvironment to support mitochondrial metabolism. We studied the protein expression of MCT1 in a broad group of breast invasive ductal carcinoma specimens to determine its association with breast cancer subtypes and outcomes. Methods: MCT1 expression was evaluated by immunohistochemistry on tissue micro-arrays (TMA) obtained through our tumor bank. Two hundred and fifty-seven cases were analyzed: 180 cases were estrogen receptor and/or …

Camp Signaling Enhances Hiv-1 Long Terminal Repeat (Ltr)-Directed Transcription And Viral Replication In Bone Marrow Progenitor Cells., Anupam Banerjee, Luna Li, Vanessa Pirrone, Fred C. Krebs, Brian Wigdahl, Michael R. Nonnemacher

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

CD34⁺ hematopoietic progenitor cells have been shown to be susceptible to HIV-1 infection, possibly due to a low-level expression of CXCR4, a coreceptor for HIV-1 entry. Given these observations, we have explored the impact of forskolin on cell surface expression of CXCR4 in a cell line model (TF-1). The elevation of intracellular cyclic adenosine monophosphate (cAMP) by forskolin through adenylyl cyclase (AC) resulted in transcriptional upregulation of CXCR4 with a concomitant increase in replication of the CXCR4-utilizing HIV-1 strain IIIB. Transient expression analyses also demonstrated an increase in CXCR4-, CCR5-, and CXCR4-/CCR5-utilizing HIV-1 (LAI, YU2, and 89.6, respectively) promoter …

Rmdo-2, Olig-2 And Synaptophysin Expression Is A Frequent Event In Malignant Melanoma: Diagnostic Pitfalls In Glial Tumor, Taliya Farooq, Esther C. Yoon, Anas Mashlah, Sina Zomorrodian, George M. Kleinman

NYMC Faculty Posters

No abstract provided.

Glypican-3 And Cd81 Promote Development Of Hepatocellular Carcinoma And Hepatoblastoma Through Negative Selection., Yuhua Xue, Wendy Mars, William Bowen, Aatur D. Singhi, Sarangarajan Ranganathan, George K. Michalopoulos

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Proteoglycan Neofunctions: Regulation Of Inflammation And Autophagy In Cancer Biology., Liliana Schaefer, Claudia Tredup, Maria A. Gubbiotti, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Inflammation and autophagy have emerged as prominent issues in the context of proteoglycan signaling. In particular, two small, leucine-rich proteoglycans, biglycan and decorin, play pivotal roles in the regulation of these vital cellular pathways and, as such, are intrinsically involved in cancer initiation and progression. In this minireview, we will address novel functions of biglycan and decorin in inflammation and autophagy, and analyze new emerging signaling events triggered by these proteoglycans, which directly or indirectly modulate these processes. We will critically discuss the dual role of proteoglycan-driven inflammation and autophagy in tumor biology, and delineate the potential mechanisms through which …

Yap And The Hippo Pathway In Pediatric Cancer., Atif Ahmed, Abdalla D. Mohamed, Melissa Gener, Weijie Li, Eugenio Taboada

Manuscripts, Articles, Book Chapters and Other Papers

The Hippo pathway is an important signaling pathway that controls cell proliferation and apoptosis. It is evolutionarily conserved in mammals and is stimulated by cell-cell contact, inhibiting cell proliferation in response to increased cell density. During early embryonic development, the Hippo signaling pathway regulates organ development and size, and its functions result in the coordinated balance between proliferation, apoptosis, and differentiation. Its principal effectors, YAP and TAZ, regulate signaling by the embryonic stem cells and determine cell fate and histogenesis. Dysfunction of this pathway contributes to cancer development in adults and children. Emerging studies have shed light on the upregulation …

Pediatric Ovarian Growing Teratoma Syndrome., Rebecca M. Rentea, Aaron Varghese, Atif Ahmed, Alexander Kats, Michelle Manalang, Tazim Dowlut-Mcelroy, Richard J. Hendrickson

Manuscripts, Articles, Book Chapters and Other Papers

Ovarian immature teratoma is a germ cell tumor that comprises less than 1% of ovarian cancers and is treated with surgical debulking and chemotherapy depending on stage. Growing teratoma syndrome (GTS) is the phenomenon of the growth of mature teratoma elements with normal tumor markers during or following chemotherapy for treatment of a malignant germ cell tumor. These tumors are associated with significant morbidity and mortality due to invasive and compressive growth as well as potential for malignant transformation. Current treatment modality is surgical resection. We discuss a 12-year-old female who presented following resection of a pure ovarian immature teratoma …

Stars In Cytoplasm: Pediatric Neuroblastoma, Monazza Chaudhary, Shahzad Sarwar, Natasha Bahadur Ali

Section of Haematology/Oncology

We report a case of a 2-year-old female child who presented with abdominal distention and fever. On examination, there was a palpable mass in the right hypochondrium. Computed tomography of the abdomen revealed a large mass in the right suprarenal area. Biopsy of the mass revealed malignant round blue cell neoplasm. Bone marrow examination showed diffuse infiltration with atypical mononuclear cells and cytogenetic studies showed positivity for NMyc translocation.

Intrahepatic Cholangiocarcinoma Presenting As Li-Rads 5 "Hcc", Raja K. Dhanekula, Md, Donald Mitchell, Md, John Farber, Md, Ashwin R. Sama, Md, Jesse M. Civan, Md

Division of Gastroenterology and Hepatology Posters

Background

• Hepatocellular Carcinoma (HCC), if within Milan Criteria, is an indication for liver transplantation.

• In contrast, intrahepatic cholangiocarcinoma (IHCC) is a contra-indication to liver transplantation due to high rates of recurrence.

• LI-RADS 5 classification (synonymous with OPTN-5) carries a near 100% positive predictive value for HCC, allowing prioritization of patients for liver transplantation without histological confirmation.

• The “LI-RADS M” classification indicates the presence of malignancy not meeting diagnostic criteria for HCC. In theory, IHCC lesions should be identified as LI-RADS M and not LI-RADS 5.

Histological And Molecular Analysis Of A Progressive Diffuse Intrinsic Pontine Glioma And Synchronous Metastatic Lesions: A Case Report., Javad Nazarian, Gary E Mason, Cheng Ying Ho, Eshini Panditharatna, Madhuri Kambhampati, Louis Gilbert Vezina, Roger J. Packer, Eugene I Hwang

Genomics and Precision Medicine Faculty Publications

There is no curative treatment for patients with diffuse intrinsic pontine glioma (DIPG). However, with the recent availability of biopsy and autopsy tissue, new data regarding the biologic behavior of this tumor have emerged, allowing greater molecular characterization and leading to investigations which may result in improved therapeutic options. Treatment strategies must address both primary disease sites as well as any metastatic deposits, which may be variably sensitive to a particular approach.In this case report, we present a patient with DIPG treated with irradiation and serial investigational agents. The clinical, pathological and molecular phenotypes of both the progressive primary tumor …

Acute Promyelocytic Leukemia Co-Existing With Jak2 V617f Positive Myeloproliferative Neoplasm: A Case Report, Aleksandra Mamorska-Dyga, Jingjing Wu, Pallavi Khattar, Faisal Ronny, Humayun Islam, Karen Seiter, Delong Liu

NYMC Faculty Publications

The V617F mutation of Janus-associated kinase 2 (JAK2) is commonly seen in myeloproliferative neoplasms (MPN). Transformation of JAK2 positive MPNs to acute leukemia has been reported. We here report a case of acute promyelocytic leukemia which was later confirmed to have a co-existing JAK2 V617F positive MPN. In addition, the patient was found to have FLT3-TKD mutation, which, together with PML/RARa, could play a role in the MPN transformation to APL.

Cd34(+) Therapy-Related Acute Promyelocytic Leukemia In A Patient Previously Treated For Breast Cancer, John Savooji, Fouzia Shakil, Humayun Islam, Delong Liu, Karen Seiter

NYMC Faculty Publications

Therapy-related acute myeloid leukemia (AML) is a long term complication of chemotherapy for a variety of cancers. In most cases, the marrow demonstrates high risk cytogenetics and the prognosis is poor. In a minority of patients "good risk" cytogenetics, including t(15;17)(q22;q12), are seen and the patient's prognosis is similar to those who have de novo disease. Currently we present a patient who developed therapy-related acute promyelocytic leukemia (APL) after chemoradiotherapy for breast cancer. This case was especially atypical because the leukemic cells were CD34(+), which is an unusual immunophenotype for APL. Recognition that this patient had APL, rather than the …

Gene 33/Mig6 Inhibits Hexavalent Chromium-Induced Dna Damage And Cell Transformation In Human Lung Epithelial Cells, Soyoung Park, Cen Li, Hong Zhao, Zbigniew Darzynkiewicz, Dazhong Xu

NYMC Faculty Publications

Hexavalent Chromium [Cr(VI)] compounds are human lung carcinogens and environmental/occupational hazards. The molecular mechanisms of Cr(VI) carcinogenesis appear to be complex and are poorly defined. In this study, we investigated the potential role of Gene 33 (ERRFI1, Mig6), a multifunctional adaptor protein, in Cr(VI)-mediated lung carcinogenesis. We show that the level of Gene 33 protein is suppressed by both acute and chronic Cr(VI) treatments in a dose- and time-dependent fashion in BEAS-2B lung epithelial cells. The inhibition also occurs in A549 lung bronchial carcinoma cells. Cr(VI) suppresses Gene 33 expression mainly through post-transcriptional mechanisms, although the mRNA level of gene …

Activation Of Signal Transduction Pathways During Hepatic Oncogenesis, W Chung, M Kim, S De La Monte, L Longato, R Carlson, B L. Slagle, X Dong, J R. Wands

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Understanding the molecular pathogenesis of hepatocellular carcinoma (HCC) is essential to identify therapeutic targets. A hepatitis B virus (HBV) related double transgenic murine model was developed. METHODS: Liver specific expression of HBV X protein (HBx) and insulin receptor substrate 1 (IRS1) was achieved and transgenic mice were followed from birth to age 21 months. Liver and tumor tissue were assessed for histologic changes as well as activation of signal transduction pathways by qRT-PCR and multiplex ELISA protein assays. RESULTS: Overexpression of HBx and IRS1 stimulates liver cell proliferation in the double transgenic mice. Only the male mice …