The American Journal of Pathology

article

Loss of Heterozygosity on Chromosome 11p15 during Histological Progression in Microdissected Ductal Carcinoma of the Breast

Jack H. Lichy, Maryam Zavar, Mark M. Tsai, Timothy J. O'Leary, more

The American Journal of Pathology > 1998 > 153 > 1 > 271-278

Microdissection of histologically identifiable components from formalin-fixed, paraffin-embedded tissue sections allows molecular genetic analyses to be correlated directly with pathological findings. In this study, we have characterized loss of heterozygosity (LOH) at chromosome 11p15 at different stages of progression in microdissected tumor components from 115 ductal carcinomas of the breast. Microdissected...

article

Up-Regulation of Vascular Endothelial Growth Factor in Stromal Cells of Hemangioblastomas Is Correlated with Up-Regulation of the Transcription Factor HRF/HIF-2α

Ingo Flamme, Marion Krieg, Karl H. Plate

The American Journal of Pathology > 1998 > 153 > 1 > 25-29

Hemangioblastomas, the most frequent manifestation of the hereditary von Hippel-Lindau disease (VHL), are highly vascularized tumors of the central nervous system. In previous studies, the endothelial-specific mitogen vascular endothelial growth factor (VEGF) was shown to be up-regulated in the stromal cells, the putative neoplastic cells in hemangioblastomas. Therefore, it was suggested that secretion...

article

Histopathological and Molecular Genetic Analysis

Irina A. Lubensky, Svetlana Pack, David Ault, Alexander O. Vortmeyer, more

The American Journal of Pathology > 1998 > 153 > 1 > 223-231

Although pancreatic neuroendocrine tumors (NETs) in von Hippel-Lindau (VHL) disease have been reported, their pathological features have not been characterized. In addition, it is unknown whether alterations of the VHL gene are responsible for pancreatic NET development. To evaluate NETs in VHL patients, we performed histopathological analysis of 30 pancreatic tumors in 14 patients. In addition, DNA...

article

Activation of the Urokinase Plasminogen Activator/Urokinase Plasminogen Activator Receptor System and Redistribution of E-Cadherin Are Associated with Hepatocyte Growth Factor-Induced Motility of Pancreas Tumor Cells Overexpressing Met

Rosanna Paciucci, Maya R. Vilá, Teresa Adell, Víctor M. Díaz, more

The American Journal of Pathology > 1998 > 153 > 1 > 201-212

Because hepatocyte growth factor (HGF) is a potent mitogen for normal human exocrine pancreas cells (NPCs) in vitro, we have analyzed the expression of HGF and its receptor, Met, in NPC and pancreas cancer cells and studied its effects in vitro. Using immunohistochemistry, Northern blotting, and reverse transcription-polymerase chain reaction, we examined the expression of HGF and Met in normal pancreas...

article

Origin of Inflammatory and Vascular Wall Cells

Satoru Hasegawa, Gerold Becker, Hiroaki Nagano, Peter Libby, more

The American Journal of Pathology > 1998 > 153 > 1 > 69-79

In solid-tissue allografts, donor vascular cells as well as recipient inflammatory cells can express MHC class II molecules. However, it is uncertain how much residual donor endothelium persists and to what extent donor versus recipient MHC class II expression can contribute to the ongoing immune response, especially in long-term grafts. To establish the origin of class-II-expressing cells in the...

article

Association of v-Ha-ras Transgene Expression with Development of Erythroleukemia in Tg.AC Transgenic Mice

Carol S. Trempus, Sandra Ward, Georgia Farris, David Malarkey, more

The American Journal of Pathology > 1998 > 153 > 1 > 247-254

A transgenic mouse line (Tg.AC) carrying an activated v-Ha-ras oncogene fused to the embryonic ζ-globin promoter develops an array of spontaneous epithelial and mesenchymal neoplasms. In this report we describe the morphological, immunophenotypic, and molecular features of a unique hematopoietic neoplasm in these mice. The cardinal lesion of this disease is marked hepatomegaly due to leukemic proliferation...

article

Long-Term, Near-Total Liver Replacement by Transplantation of Isolated Hepatocytes in Rats Treated with Retrorsine

Ezio Laconi, Ran Oren, Deb K. Mukhopadhyay, Ethel Hurston, more

The American Journal of Pathology > 1998 > 153 > 1 > 319-329

Genetically marked hepatocytes from dipeptidyl peptidase (DPP) IV ⁺ Fischer 344 rats were transplanted into the liver of DPPIV ⁻ mutant Fischer 344 rats after a combined treatment with retrorsine, a pyrrolizidine alkaloid that blocks the hepatocyte cell cycle, and two-thirds partial hepatectomy. In female rats, clusters of proliferated DPPIV ⁺ hepatocytes containing 20 to 50...

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Comparative Phenotypic Studies of Duct Epithelial Cell Lines Derived from Normal Human Pancreas and Pancreatic Carcinoma

Ni Liu, Toru Furukawa, Masao Kobari, Ming-Sound Tsao

The American Journal of Pathology > 1998 > 153 > 1 > 263-269

We have investigated the mRNA/protein expression of several tyrosine kinase receptors, growth factors, and p16 ^INK4A cyclin inhibitor in cell lines derived from normal human pancreatic duct epithelium (HPDE) and compared them with those of five pancreatic ductal carcinoma cell lines. Cultured HPDE cells express low levels of epidermal growth factor receptor (EGFR), erbB2, transforming growth...

article

Effect on Mast Cell Recruitment, Distribution, and Phenotype Expression

Frank Aldenborg, Ralph Peeker, Magnus Fall, Anita Olofsson, more

The American Journal of Pathology > 1998 > 153 > 1 > 149-157

Mucosal mast cells (MCs) are normally found in the connective tissue stroma but are redistributed into the epithelium in conditions associated with immunoglobulin E responses, such as allergic inflammation and nematode infections, as well as in interstitial cystitis, a condition of unknown etiology. The potential role of epithelium-derived factors in this response prompted this inquiry into growth...

article

Genetic Alterations in Hormone-Refractory Recurrent Prostate Carcinomas

Nina N. Nupponen, Laura Kakkola, Pasi Koivisto, Tapio Visakorpi

The American Journal of Pathology > 1998 > 153 > 1 > 141-148

To study the genetic basis of tumor progression, we have screened 37 hormone-refractory prostate carcinomas for genetic changes by comparative genomic hybridization (CGH). All recurrent tumors showed genetic aberrations, with a mean total number of changes per tumor of 11.4 (range, 3 to 23). The most common genetic aberrations were losses of 8p (72.5%), 13q (50%), 1p (50%), 22 (45%), 19 (45%), 10q...

article

Vascular Endothelial Growth Factors VEGF-B and VEGF-C Are Expressed in Human Tumors

Petri Salven, Athina Lymboussaki, Päivi Heikkilä, Hilkka Jääskela-Saari, more

The American Journal of Pathology > 1998 > 153 > 1 > 103-108

The growth of solid tumors is dependent on angiogenesis, the formation of new blood vessels. Vascular endothelial growth factor (VEGF) is a secreted endothelial-cell-specific mitogen. We have recently characterized two novel endothelial growth factors with structural homology to VEGF and named them VEGF-B and VEGF-C. To further define the roles of VEGF-B and VEGF-C, we have studied their expression...

article

Mantle Cell Lymphomas Lack Expression of p27kip1, a Cyclin-Dependent Kinase Inhibitor

Leticia Quintanilla-Martinez, Catherine Thieblemont, Falko Fend, Shimareet Kumar, more

The American Journal of Pathology > 1998 > 153 > 1 > 175-182

p27 ^Kip1 is a cyclin-dependent kinase inhibitor that regulates the decision to enter S phase or withdraw from the cell cycle. In resting cells, the level of p27 ^Kip1 provides an inhibitory threshold above which G1 cyclin D/E/cyclin-dependent kinases accumulate before activation; however, in cycling cells, p27 ^Kip1 protein is sequestered by high levels of active cyclin D/cyclin-dependent...

article

Characterization of Keratinocyte Growth Factor and Receptor Expression in Human Pancreatic Cancer

Toshiyuki Ishiwata, Helmut Friess, Markus W. Büchler, Martha E. Lopez, more

The American Journal of Pathology > 1998 > 153 > 1 > 213-222

Keratinocyte growth factor (KGF) is an angiogenic and mitogenic polypeptide that has been implicated in cancer growth and tissue development and repair. Its actions are dependent on its binding to a specific cell-surface KGF receptor (KGFR), which is encoded by the fibroblast growth factor (FGF) receptor type II (FGFR-2) gene. In the present study, we compared the immunohistochemical localization...

article

Collagenase-3 (MMP-13) Expression in Chondrosarcoma Cells and Its Regulation by Basic Fibroblast Growth Factor

José A. Uría, Milagros Balbín, José M. López, Jesús Alvarez, more

The American Journal of Pathology > 1998 > 153 > 1 > 91-101

Human collagenase-3 (MMP-13) is a member of the matrix metalloproteinase family of enzymes that was originally identified in breast carcinomas and subsequently detected during fetal ossification and in arthritic processes. In this work, we have found that collagenase-3 is produced by HCS-2/8 human chondrosarcoma cells. An analysis of the ability of different cytokines and growth factors to induce...

article

The Role of Carbonic Anhydrases in Tumors

Antal Nógrádi

The American Journal of Pathology > 1998 > 153 > 1 > 1-4

article

New Isolation Technique to Study Apoptosis in Human Intestinal Epithelial Cells

Johannes Grossmann, Julie M. Maxson, Cecilia M. Whitacre, David E. Orosz, more

The American Journal of Pathology > 1998 > 153 > 1 > 53-62

Intestinal epithelial cells derive from stem cells at the base of the crypt and migrate along the crypt-lumen axis. Their life is terminated as they reach the luminal surface where they detach and are shed. Intestinal epithelial cells show evidence of apoptosis in the region of shedding, and cell death is thought to resemble a form of apoptosis called detachment-induced cell death, or anoikis. Human...

article

Differentiation-Dependent Peroxisomal Proliferator-Activated Receptor γ (PPARγ) Expression and Reduction of MMP-9 Activity through PPARγ Activation in Mononuclear Phagocytes in Vitro

Nikolaus Marx, Galina Sukhova, Curran Murphy, Peter Libby, more

The American Journal of Pathology > 1998 > 153 > 1 > 17-23

Mononuclear phagocytes play an important role in atherosclerosis and its sequela plaque rupture in part by their secretion of matrix metalloproteinases (MMPs), including MMP-9. Peroxisomal proliferator-activated receptor γ (PPARγ), a transcription factor in the nuclear receptor superfamily, regulates gene expression in response to various activators, including 15-deoxy-Δ ^12,14 -prostaglandin...

article

Immunohistochemical Study of the β-Chemokine Receptors CCR3 and CCR5 and Their Ligands in Normal and Alzheimer's Disease Brains

MengQi Xia, ShiXin Qin, LiJun Wu, Charles R. Mackay, more

The American Journal of Pathology > 1998 > 153 > 1 > 31-37

Chemokines belong to an expanding family of cytokines the primary function of which is recruitment of leukocytes to inflammatory sites. Recent evidence has shown their presence in the central nervous system. Because inflammatory responses have been implicated in the pathogenesis of Alzheimer's disease (AD), we studied the expression of CCR3, CCR5, and their ligands in normal and AD brains by immunohistochemistry...

article

Lack of Association between Enhanced TRPM-2/Clusterin Expression and Increased Apoptotic Activity in Sex-Hormone-Induced Prostatic Dysplasia of the Noble Rat

Shuk-Mei Ho, Irwin Leav, Shibnath Ghatak, Frederick Merk, more

The American Journal of Pathology > 1998 > 153 > 1 > 131-139

Although the functional role of TRPM-2/clusterin in the prostate remains controversial, it has been postulated that transcriptional activation of the gene is an important mechanism in castration-induced prostatic involution and perhaps is a means for prostatic cells to escape apoptotic induction. In the present study, we have measured expression levels of TRPM-2/clusterin and apoptotic activities...

article

CDKN2A Gene Deletions and Loss of p16 Expression Occur in Osteosarcomas That Lack RB Alterations

Gunnlaugur P. Nielsen, Karen L. Burns, Andrew E. Rosenberg, David N. Louis

The American Journal of Pathology > 1998 > 153 > 1 > 159-163

Osteosarcomas often suffer mutations of the RB(retinoblastoma) gene, with resultant inactivation of the pRb protein. pRb is one component in a cell-cycle control pathway that includes the p16 (encoded by the CDKN2A gene) and cyclin-dependent kinase 4 (cdk4, encoded by theCDK4 gene) proteins. We therefore sought to determine whether the CDKN2A and CDK4 genes were altered in those osteosarcomas that...

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The American Journal of Pathology

Loss of Heterozygosity on Chromosome 11p15 during Histological Progression in Microdissected Ductal Carcinoma of the Breast

Up-Regulation of Vascular Endothelial Growth Factor in Stromal Cells of Hemangioblastomas Is Correlated with Up-Regulation of the Transcription Factor HRF/HIF-2α

Histopathological and Molecular Genetic Analysis

Activation of the Urokinase Plasminogen Activator/Urokinase Plasminogen Activator Receptor System and Redistribution of E-Cadherin Are Associated with Hepatocyte Growth Factor-Induced Motility of Pancreas Tumor Cells Overexpressing Met

Origin of Inflammatory and Vascular Wall Cells

Association of v-Ha-ras Transgene Expression with Development of Erythroleukemia in Tg.AC Transgenic Mice

Long-Term, Near-Total Liver Replacement by Transplantation of Isolated Hepatocytes in Rats Treated with Retrorsine

Comparative Phenotypic Studies of Duct Epithelial Cell Lines Derived from Normal Human Pancreas and Pancreatic Carcinoma

Effect on Mast Cell Recruitment, Distribution, and Phenotype Expression

Genetic Alterations in Hormone-Refractory Recurrent Prostate Carcinomas

Vascular Endothelial Growth Factors VEGF-B and VEGF-C Are Expressed in Human Tumors

Mantle Cell Lymphomas Lack Expression of p27kip1, a Cyclin-Dependent Kinase Inhibitor

Characterization of Keratinocyte Growth Factor and Receptor Expression in Human Pancreatic Cancer

Collagenase-3 (MMP-13) Expression in Chondrosarcoma Cells and Its Regulation by Basic Fibroblast Growth Factor

The Role of Carbonic Anhydrases in Tumors

New Isolation Technique to Study Apoptosis in Human Intestinal Epithelial Cells

Differentiation-Dependent Peroxisomal Proliferator-Activated Receptor γ (PPARγ) Expression and Reduction of MMP-9 Activity through PPARγ Activation in Mononuclear Phagocytes in Vitro

Immunohistochemical Study of the β-Chemokine Receptors CCR3 and CCR5 and Their Ligands in Normal and Alzheimer's Disease Brains

Lack of Association between Enhanced TRPM-2/Clusterin Expression and Increased Apoptotic Activity in Sex-Hormone-Induced Prostatic Dysplasia of the Noble Rat

CDKN2A Gene Deletions and Loss of p16 Expression Occur in Osteosarcomas That Lack RB Alterations

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