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Articles 601 - 616 of 616

Full-Text Articles in Neoplasms

Transgenic Cyclin E Triggers Dysplasia And Multiple Pulmonary Adenocarcinomas, Yan Ma, Steven Fiering, Candice Black, Xi Liu, Ziqiang Yuan, Vincent A. Memoli, David J. Robbins, Heather A. Bentley, Gregory J. Tsongalis, Eugene Demidenko, Sarah J. Freemantle, Ethan Dmitrovsky Mar 2007

Transgenic Cyclin E Triggers Dysplasia And Multiple Pulmonary Adenocarcinomas, Yan Ma, Steven Fiering, Candice Black, Xi Liu, Ziqiang Yuan, Vincent A. Memoli, David J. Robbins, Heather A. Bentley, Gregory J. Tsongalis, Eugene Demidenko, Sarah J. Freemantle, Ethan Dmitrovsky

Dartmouth Scholarship

Cyclin E is a critical G(1)-S cell cycle regulator aberrantly expressed in bronchial premalignancy and lung cancer. Cyclin E expression negatively affects lung cancer prognosis. Its role in lung carcinogenesis was explored. Retroviral cyclin E transduction promoted pulmonary epithelial cell growth, and small interfering RNA targeting of cyclin E repressed this growth. Murine transgenic lines were engineered to mimic aberrant cyclin E expression in the lung. Wild-type and proteasome degradation-resistant human cyclin E transgenic lines were independently driven by the human surfactant C (SP-C) promoter. Chromosome instability (CIN), pulmonary dysplasia, sonic hedgehog (Shh) pathway activation, adenocarcinomas, and metastases occurred. Notably, …


Cdx4 Dysregulates Hox Gene Expression And Generates Acute Myeloid Leukemia Alone And In Cooperation With Meis1a In A Murine Model, Dimple Bansal, Claudia Scholl, Stefan Frohling, Elizabeth Mcdowell, Benjamin H. Lee, Konstanze Döhner, Patricia Ernst Nov 2006

Cdx4 Dysregulates Hox Gene Expression And Generates Acute Myeloid Leukemia Alone And In Cooperation With Meis1a In A Murine Model, Dimple Bansal, Claudia Scholl, Stefan Frohling, Elizabeth Mcdowell, Benjamin H. Lee, Konstanze Döhner, Patricia Ernst

Dartmouth Scholarship

HOX genes have emerged as critical effectors of leukemogenesis, but the mechanisms that regulate their expression in leukemia are not well understood. Recent data suggest that the caudal homeobox transcription factors CDX1, CDX2, and CDX4, developmental regulators of HOX gene expression, may contribute to HOX gene dysregulation in leukemia. We report here that CDX4 is expressed normally in early hematopoietic progenitors and is expressed aberrantly in approximately 25% of acute myeloid leukemia (AML) patient samples. Cdx4 regulates Hox gene expression in the adult murine hematopoietic system and dysregulates Hox genes that are implicated in leukemogenesis. Furthermore, bone marrow progenitors that …


Growth Factor–Induced Shedding Of Syndecan-1 Confers Glypican-1 Dependence On Mitogenic Responses Of Cancer Cells, Kan Ding, Martha Lopez-Burks, José A. Sánchez-Duran, Murray Korc, Arthur D. Lander Nov 2005

Growth Factor–Induced Shedding Of Syndecan-1 Confers Glypican-1 Dependence On Mitogenic Responses Of Cancer Cells, Kan Ding, Martha Lopez-Burks, José A. Sánchez-Duran, Murray Korc, Arthur D. Lander

Dartmouth Scholarship

The cell surface heparan sulfate proteoglycan (HSPG) glypican-1 is up-regulated by pancreatic and breast cancer cells, and its removal renders such cells insensitive to many growth factors. We sought to explain why the cell surface HSPG syndecan-1, which is also up-regulated by these cells and is a known growth factor coreceptor, does not compensate for glypican-1 loss. We show that the initial responses of these cells to the growth factor FGF2 are not glypican dependent, but they become so over time as FGF2 induces shedding of syndecan-1. Manipulations that retain syndecan-1 on the cell surface make long-term FGF2 responses glypican …


Ionizing Radiation And Endostatin Gene Therapy Against Lung Tumor, Xian Luo Jun 2004

Ionizing Radiation And Endostatin Gene Therapy Against Lung Tumor, Xian Luo

Loma Linda University Electronic Theses, Dissertations & Projects

Although many advances have been made in radiotherapy, tumor radioresistance and normal tissue damage continue to always be important issues for radiation oncologists. Numerous reports have also documented that radiation exposure increases the risk for malignancy and suppresses immune mechanisms. However, increasing evidence has suggested that anti-angiogenic therapy that targets tumor blood supply may alter abnormal tumor vasculature, thus synergizing radiotherapy. The governing hypothesis of the present study was that modification of tumor vasculature by antiangiogenic gene therapy can increase the efficacy of radiotherapy and that radiation can also improve DNA transfection efficiency by increasing expression of the administered gene. …


The Tumor Suppressor Lkb1 Kinase Directly Activates Amp-Activated Kinase And Regulates Apoptosis In Response To Energy Stress, Reuben J. Shaw, Monica Kosmatka, Nabeel Bardeesy, Rebecca L. Hurley, Lee A. Witters, Ronald A. Depinho, Lewis C. Cantley Mar 2004

The Tumor Suppressor Lkb1 Kinase Directly Activates Amp-Activated Kinase And Regulates Apoptosis In Response To Energy Stress, Reuben J. Shaw, Monica Kosmatka, Nabeel Bardeesy, Rebecca L. Hurley, Lee A. Witters, Ronald A. Depinho, Lewis C. Cantley

Dartmouth Scholarship

AMP-activated protein kinase (AMPK) is a highly conserved sensor of cellular energy status found in all eukaryotic cells. AMPK is activated by stimuli that increase the cellular AMP/ATP ratio. Essential to activation of AMPK is its phosphorylation at Thr-172 by an upstream kinase, AMPKK, whose identity in mammalian cells has remained elusive. Here we present biochemical and genetic evidence indicating that the LKB1 serine/threonine kinase, the gene inactivated in the Peutz-Jeghers familial cancer syndrome, is the dominant regulator of AMPK activation in several mammalian cell types. We show that LKB1 directly phosphorylates Thr-172 of AMPKalpha in vitro and activates its …


Ube1l Is A Retinoid Target That Triggers Pml/Rarα Degradation And Apoptosis In Acute Promyelocytic Leukemia, Sutisak Kitareewan, Ian Pitha-Rowe, David Sekula, Christopher H. Lowrey, Michael J. Nemeth, Todd R. Golub, Sarah J. Freemantle, Ethan Dmitrovsky Mar 2002

Ube1l Is A Retinoid Target That Triggers Pml/Rarα Degradation And Apoptosis In Acute Promyelocytic Leukemia, Sutisak Kitareewan, Ian Pitha-Rowe, David Sekula, Christopher H. Lowrey, Michael J. Nemeth, Todd R. Golub, Sarah J. Freemantle, Ethan Dmitrovsky

Dartmouth Scholarship

All-trans-retinoic acid (RA) treatment induces remissions in acute promyelocytic leukemia (APL) cases expressing the t(15;17) product, promyelocytic leukemia (PML)/RA receptor α (RARα). Microarray analyses previously revealed induction of UBE1L (ubiquitin-activating enzyme E1-like) after RA treatment of NB4 APL cells. We report here that this occurs within 3 h in RA-sensitive but not RA-resistant APL cells, implicating UBE1L as a direct retinoid target. A 1.3-kb fragment of the UBE1L promoter was capable of mediating transcriptional response to RA in a retinoid receptor-selective manner. PML/RARα, a repressor of RA target genes, abolished this UBE1L promoter activity. A hallmark of …


Epstein-Barr Virus Serology In The Diagnosis Of Nasopharyngeal Carcinoma From Sarawak, Madeline Wong Mei Fong Jan 2001

Epstein-Barr Virus Serology In The Diagnosis Of Nasopharyngeal Carcinoma From Sarawak, Madeline Wong Mei Fong

Student Works (2000-2009)

The Epstein-Barr virus (EBV) is closely associated with nasopharyngcal carcinoma (NPC). The role(s) of EBV in NPC remains unclear but antibodies to two EBV proteins namely the viral capsid antigen (VCA) and early antigen (EA), are clinically useful diagnostic markers of NPC. The NPC scenario in Malaysia has been based on studies done on West Malaysian patients but not much has been described for NPC in Sarawak, East Malaysia. In this study, 164 NPC sera from newly histologically confirmed NPC patients were collected from the Radiotherapy Unit of Kuching General Hospital, Sarawak prior to radiotherapy. One hundred and forty seven …


Naturally Occurring Tap-Dependent Specific T-Cell Tolerance For A Variant Of An Immunodominant Retroviral Cytotoxic T-Lymphocyte Epitope, Victor Kim, Jonathan W. Yewdell, William R. Green Jan 2000

Naturally Occurring Tap-Dependent Specific T-Cell Tolerance For A Variant Of An Immunodominant Retroviral Cytotoxic T-Lymphocyte Epitope, Victor Kim, Jonathan W. Yewdell, William R. Green

Dartmouth Scholarship

Upon immunization and restimulation with tumors induced by the endogenous AKR/Gross murine leukemia virus (MuLV), C57BL/6 mice generate vigorous H-2K(b)-restricted cytotoxic T-lymphocyte (CTL) responses to a determinant (KSPWFTTL) derived from the p15E transmembrane portion of the viral envelope glycoprotein. By contrast, the highly homologous determinant RSPWFTTL, expressed by tumor cells induced by Friend/Moloney/Rauscher (FMR) MuLV, is not immunogenic, even when presented to the immune system as vaccinia virus-encoded cytosolic or endoplasmic reticulum (ER)-targeted minigene products. Such minigene products are usually highly immunogenic since they bypass the need for cells to liberate the peptide or transport the peptide into the ER …


The “Spot 14” Gene Resides On The Telomeric End Of The 11q13 Amplicon And Is Expressed In Lipogenic Breast Cancers: Implications For Control Of Tumor Metabolism, Joel T. Moncur, Jonathan P. Park, Vincent A. Memoli, T. K. Mohandas, William B. Kinlaw Jun 1998

The “Spot 14” Gene Resides On The Telomeric End Of The 11q13 Amplicon And Is Expressed In Lipogenic Breast Cancers: Implications For Control Of Tumor Metabolism, Joel T. Moncur, Jonathan P. Park, Vincent A. Memoli, T. K. Mohandas, William B. Kinlaw

Dartmouth Scholarship

Enhanced long chain fatty acid synthesis may occur in breast cancer, where it is necessary for tumor growth and predicts a poor prognosis. “Spot 14” (S14) is a carbohydrate- and thyroid hormone-inducible nuclear protein specific to liver, adipose, and lactating mammary tissues that functions to activate genes encoding the enzymes of fatty acid synthesis. Amplification of chromosome region 11q13, where the S14 gene (THRSP) resides, also predicts a poor prognosis in breast tumors. We localized the S14 gene between markers D11S906 and D11S937, at the telomeric end of the amplified region at 11q13, and found that it was …


The Amino-Terminal Functions Of The Simian Virus 40 Large T Antigen Are Required To Overcome Wild-Type P53-Mediated Growth Arrest Of Cells., Robin S. Quartin, Charles N. Cole, James M. Pipas, Arnold J. Levine Mar 1994

The Amino-Terminal Functions Of The Simian Virus 40 Large T Antigen Are Required To Overcome Wild-Type P53-Mediated Growth Arrest Of Cells., Robin S. Quartin, Charles N. Cole, James M. Pipas, Arnold J. Levine

Dartmouth Scholarship

High levels of the p53 tumor suppressor protein can block progression through the cell cycle. A model system for the study of the mechanism of action of wild-type p53 is a cell line (T64-7B) derived from rat embryo fibroblasts transformed by activated ras and a temperature-sensitive murine p53 gene. At 37 to 39 degrees C, the murine p53 protein is in a mutant conformation and the cells actively divide, whereas at 32 degrees C, the protein has a wild-type conformation and the cells arrest in the G1 phase of the cell cycle. Wild-type simian virus 40 large T antigen and …


Cytolytic T Lymphocytes Specific For Tumors And Infected Cells From Mice With A Retrovirus-Induced Immunodeficiency Syndrome., Jennifer G. Erbe, Kathy A. Green, Karen M. Crassi, Herbert C. Morse, W R. Green May 1992

Cytolytic T Lymphocytes Specific For Tumors And Infected Cells From Mice With A Retrovirus-Induced Immunodeficiency Syndrome., Jennifer G. Erbe, Kathy A. Green, Karen M. Crassi, Herbert C. Morse, W R. Green

Dartmouth Scholarship

LP-BM5 retrovirus complex-infected C57BL/6 mice develop immunodeficiency, somewhat analogous to AIDS, termed murine AIDS (MAIDS). After secondary stimulation with syngeneic B-cell lymphomas from LP-BM5-infected mice, C57BL/6 mice produced vigorous CD8+ cytotoxic T lymphocytes specific for MAIDS-associated tumors. An anti-LP-BM5 specificity was suggested because spleen and lymph node cells from LP-BM5-infected mice served as target cells in competition assays, and cells from LP-BM5, but not ecotropic, virus-infected mice functioned as secondary in vitro stimulators to generate cytotoxic T lymphocytes to MAIDS tumors.


The Ability Of Simian Virus 40 Large T Antigen To Immortalize Primary Mouse Embryo Fibroblasts Cosegregates With Its Ability To Bind To P53., Jiyue Y. Zhu, Marina Abate, Philip W. Rice, Charles N. Cole Dec 1991

The Ability Of Simian Virus 40 Large T Antigen To Immortalize Primary Mouse Embryo Fibroblasts Cosegregates With Its Ability To Bind To P53., Jiyue Y. Zhu, Marina Abate, Philip W. Rice, Charles N. Cole

Dartmouth Scholarship

The large T antigen encoded by simian virus 40 (SV40) plays essential roles in the infection of permissive cells, leading to production of progeny virions, and in the infection of nonpermissive cells, leading to malignant transformation. Primary mouse embryo fibroblasts (MEFs) are nonpermissive for SV40, and infection by wild-type SV40 leads to immortalization and transformation of a small percentage of infected cells. We examined the ability of an extensive set of mutants whose lesions affect SV40 large T antigen to immortalize MEFs. We found that immortalization activity was retained by all mutants whose lesions are located upstream of codon 346. …


Simian Virus 40 Host Range/Helper Function Mutations Cause Multiple Defects In Viral Late Gene Expression., Terryl Stacy, Michele Chamberlain, Charles N. Cole Dec 1989

Simian Virus 40 Host Range/Helper Function Mutations Cause Multiple Defects In Viral Late Gene Expression., Terryl Stacy, Michele Chamberlain, Charles N. Cole

Dartmouth Scholarship

Simian virus 40 (SV40) deletion mutants dlA2459 and dlA2475 express T antigens that lack the normal carboxy terminus. These mutants are called host range/helper function (hr/hf) mutants because they form plaques at 37 degrees C on BSC-1 and Vero monkey kidney cell lines but not on CV-1p monkey kidney cells. Wild-type SV40 can provide a helper function to permit growth of human adenoviruses in monkey kidney cells; the hr/hf mutants cannot. Progeny yields of hr/hf mutants are also cold sensitive in all cell lines tested. Patterns of viral macromolecular synthesis in three cell lines (Vero, BSC-1, and CV-1) at three …


In Vitro Evaluation Of Cancer Patient Immune Responses Following Infusion Of Radiolabeled Murine Monoclonal Antibody, Kelly A. King Jun 1989

In Vitro Evaluation Of Cancer Patient Immune Responses Following Infusion Of Radiolabeled Murine Monoclonal Antibody, Kelly A. King

Loma Linda University Electronic Theses, Dissertations & Projects

Several monoclonal antibody (MAb) types derived from mice have been developed specifically for the use of targeting human tumors. The specificity of these murine MAb’s for their respective tumor antigens is very high making them potentially good immunotherapeutic agents for cancer treatment and diagnosis. A limiting factor in using these murine MAb’s in patients is the development of human anti-mouse antibody (HAMA). The presence of HAMA may reduce the effectiveness of MAb for tumor targeting. If patient sensitization could be quickly detected following the initial infusion of MAb, then future infusion could be altered or terminated to prevent further sensitization. …


Absence Of A Structural Basis For Intracellular Recognition And Differential Localization Of Nuclear And Plasma Membrane-Associated Forms Of Simian Virus 40 Large Tumor Antigen., Donald L. Jarvis, Charles N. Cole, Janet S. Butel Mar 1986

Absence Of A Structural Basis For Intracellular Recognition And Differential Localization Of Nuclear And Plasma Membrane-Associated Forms Of Simian Virus 40 Large Tumor Antigen., Donald L. Jarvis, Charles N. Cole, Janet S. Butel

Dartmouth Scholarship

The simian virus 40 large tumor antigen (T-ag) is found in both the nuclei (nT-ag) and plasma membranes (mT-ag) of simian virus 40-infected or -transformed cells. It is not known how newly synthesized T-ag molecules are recognized, sorted, and transported to their ultimate subcellular destinations. One possibility is that these events depend upon structural differences between nT-ag and mT-ag. To test this possibility, we compared the structures of nT-ag and mT-ag from simian virus 40-infected cells. No differences between the two forms of T-ag were detected by migration in polyacrylamide gels, by Staphylococcus aureus V8 partial proteolytic mapping of methionine- …


Cell Mediated Immunity By Cytotoxicity Assay And The Effect Of Corynebacterium Parvum And Radiation On Mice Bearing Herpes-Induced Tumors, Robert B. Stagg May 1979

Cell Mediated Immunity By Cytotoxicity Assay And The Effect Of Corynebacterium Parvum And Radiation On Mice Bearing Herpes-Induced Tumors, Robert B. Stagg

Loma Linda University Electronic Theses, Dissertations & Projects

Cell mediated immune (CMI) cytotoxic reactivity of Balb/c mice against H238 cells, a Herpes simplex virus (HSV) Type 2 - induced sarcoma, was measured by the 125IUdR release assay. The Balb/c mouse response to the growing HSV-induced tumor, treated with radiation and , was measured by survival rate, tumor growth and immune cytotoxicity of spleen and peritoneal exudate cells (PEC) as determined by 125IUdR release assay. Subcutaneous (s.c.) inoculation of 1 x 106 H238 cells (high dose) produced progressive tumor growth while s.c. inoculation of 1 x 104 H238 cells (low dose) produced no tumors. A …