The potential role of hypoxia inducible factor 1alpha in tumor progression after hypoxia and chemotherapy in hepatocellular carcinoma.

Abstract:

:This study investigates the possible molecular basis leading to failure in a treatment that is composed of hypoxia and chemotherapy in a rat orthotopic hepatoma model. Hypoxia was induced by hepatic artery ligation, whereas chemotherapeutic effect was achieved by intraportal injection of cisplatin. High-dose sodium salicylate was administered to achieve transcriptional blockade. Significant prolongation of animal survival was observed in the groups receiving hepatic artery ligation with cisplatin or sodium salicylate. Massive tumor cell necrosis and apoptosis were found in the ligation and all of the combined treatment groups. Up-regulation of hypoxia inducible factor 1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) at both mRNA and protein levels were detected in the groups receiving ligation and ligation with cisplatin, whereas a decreased level of von Hippel-Lindau tumor suppressor protein was identified in the group receiving ligation with cisplatin. Sodium salicylate enhanced expression of von Hippel-Lindau tumor suppressor protein but down-regulated HIF-1alpha and VEGF levels after ligation with or without cisplatin. An increased number of activated hepatic stellate cells in the tumors were observed in the ligation and ligation with cisplatin groups, whereas they were greatly reduced by sodium salicylate. In vitro study revealed that under hypoxic condition, both cisplatin and sodium salicylate could remarkably augment P53 and caspase 3 levels. Cisplatin stimulated HIF-1alpha up-regulation, whereas sodium salicylate suppressed HIF-1alpha expression. In conclusion, tumor progression after hypoxia and chemotherapy might be related to up-regulation of HIF-1alpha and subsequent VEGF production, and transcriptional blockade by sodium salicylate could enhance the therapeutic efficacy of hypoxia and chemotherapy.

journal_name

Cancer Res

journal_title

Cancer research

authors

Yang ZF,Poon RT,To J,Ho DW,Fan ST

doi

10.1158/0008-5472.CAN-03-3311

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

5496-503

issue

15

eissn

0008-5472

issn

1538-7445

pii

64/15/5496

journal_volume

64

pub_type

杂志文章,收录出版
  • Erythropoietin-induced polycythemia in athymic mice following transplantation of a human renal carcinoma cell line.

    abstract::An established cloned human renal carcinoma line RC-1, which has been continuously maintained in culture for several years and which produces erythropoietin, was injected s.c. into BALB/c athymic mice and produced tumors. Tumorigenicity was directly correlated with the number of RC-1 cells inoculated. Tumor cell histo...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Shouval D,Anton M,Galun E,Sherwood JB

    更新日期:1988-06-15 00:00:00

  • Production of human hematopoietic survival and growth factor by a myeloid leukemia cell line (KPB-M15) and placenta as detected by a monoclonal antibody.

    abstract::Fifty-five hematopoietic cell lines, including 19 T-, 16 B-, 5 pre-B-, 5 non-T non-B-, 1 erythroid, and 9 myeloid-monocytoid cells, were screened for production of human hematopoietic survival and stem cell growth factor (SCGF) by enzyme immunoassay using anti-SCGF monoclonal antibody. The KPB-M15 myeloid cell line co...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Hiraoka A,Ohkubo T,Fukuda M

    更新日期:1987-10-01 00:00:00

  • Human cutaneous fatty acid-binding protein induces metastasis by up-regulating the expression of vascular endothelial growth factor gene in rat Rama 37 model cells.

    abstract::Human cutaneous fatty acid-binding protein (C-FABP) gene is capable of inducing the metastatic phenotype when overexpressed in nonmetastatic rat Rama 37 cells. However, the mechanism of how it induces metastasis is not clear. Northern and slot blot analyses revealed that expression of the endogenous vascular endotheli...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Jing C,Beesley C,Foster CS,Chen H,Rudland PS,West DC,Fujii H,Smith PH,Ke Y

    更新日期:2001-06-01 00:00:00

  • Relationship between a tumor promoter-induced decrease in queuine modification of transfer RNA in normal human cells and the expression of an altered cell phenotype.

    abstract::With normal human skin fibroblasts in culture, a transient decrease in queuine modification of tRNA precedes a phorbol ester tumor promoter-induced 5- to 10-fold increase in saturation density. Subsequently, an increase in the queuine content of cellular tRNA (to levels comparable to those in untreated cultures) prece...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Elliott MS,Katze JR,Trewyn RW

    更新日期:1984-08-01 00:00:00

  • miRNA-708 control of CD44(+) prostate cancer-initiating cells.

    abstract::Tumor recurrence in prostate cancer has been attributed to the presence of CD44-expressing tumor-initiating cells. In this study, we report that miR-708 is a key negative regulator of this CD44(+) subpopulation of prostate cancer cells, with important implications for diagnosis and prognosis of this disease. miR-708 w...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-12-0540

    authors: Saini S,Majid S,Shahryari V,Arora S,Yamamura S,Chang I,Zaman MS,Deng G,Tanaka Y,Dahiya R

    更新日期:2012-07-15 00:00:00

  • DNA polymerase beta gene mutation in human prostate cancer.

    abstract::DNA polymerase beta is a nuclear protein essential to DNA repair in mammalian cells. A high frequency of mutations in this gene has been reported in colorectal cancers. To clarify the tumorigenesis steps of human prostate cancers in the molecular basis, we examined the entire coding region of the human DNA polymerase ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Dobashi Y,Shuin T,Tsuruga H,Uemura H,Torigoe S,Kubota Y

    更新日期:1994-06-01 00:00:00

  • Predicting response to radioimmunotherapy from the tumor microenvironment of colorectal carcinomas.

    abstract::Solid tumors have a heterogeneous pathophysiology, which directly affects antibody-targeted therapies. Here, we consider the influence of selected tumor parameters on radioimmunotherapy, by comparing the gross biodistribution, microdistribution, and therapeutic efficacy of either radiolabeled or fluorescently labeled ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-2967

    authors: El Emir E,Qureshi U,Dearling JL,Boxer GM,Clatworthy I,Folarin AA,Robson MP,Nagl S,Konerding MA,Pedley RB

    更新日期:2007-12-15 00:00:00

  • Regulation of PTEN binding to MAGI-2 by two putative phosphorylation sites at threonine 382 and 383.

    abstract::We have reported previously that the PTEN COOH-terminal 33 amino acids play a role in the maintenance of PTEN protein stability (Tolkacheva and Chan, Oncogene, 19: 680-689, 2000). By site-directed mutagenesis, we identified two threonine residues within this COOH-terminal region at codon 382 and 383 that may be target...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Tolkacheva T,Boddapati M,Sanfiz A,Tsuchida K,Kimmelman AC,Chan AM

    更新日期:2001-07-01 00:00:00

  • Immunity to cell surface antigens and immune complex glomerulonephritis in hamsters bearing human epithelial tumors.

    abstract::A glomerulopathy in hamsters bearing human epithelial tumors is described. The tumors resulted from the s.c. implantation of human heteroploid cells (MA160) derived originally from a benign prostatic adenoma. The renal immunomorphological and ultrastructural changes include expansion of mesangial matrix and cellularit...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Richman AV,Alexander RW

    更新日期:1979-02-01 00:00:00

  • Kinetics of senescence-associated changes of gene expression in an epithelial, temperature-sensitive SV40 large T antigen model.

    abstract::Replicative senescence limits the number of times primary cells can divide and is therefore regarded as a potential checkpoint for cancer progression. The majority of studies examining changes of gene expression upon senescence have been made with stationary senescent cells. We wanted to study the transition from norm...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.can-03-1872

    authors: Larsson O,Scheele C,Liang Z,Moll J,Karlsson C,Wahlestedt C

    更新日期:2004-01-15 00:00:00

  • Calcium Promotes Human Gastric Cancer via a Novel Coupling of Calcium-Sensing Receptor and TRPV4 Channel.

    abstract::Although dietary calcium intake has long been recommended for disease prevention, the influence of calcium in development of cancer in the upper gastrointestinal tract has not been explored. Here, we assess the roles of calcium and calcium-sensing receptor (CaSR) in gastric cancer development. CaSR expression was enha...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-17-0360

    authors: Xie R,Xu J,Xiao Y,Wu J,Wan H,Tang B,Liu J,Fan Y,Wang S,Wu Y,Dong TX,Zhu MX,Carethers JM,Dong H,Yang S

    更新日期:2017-12-01 00:00:00

  • Dll4 Blockade in Stromal Cells Mediates Antitumor Effects in Preclinical Models of Ovarian Cancer.

    abstract::The Notch ligand delta-like 4 (Dll4) has been identified as a promising target in tumor angiogenesis in preclinical studies, and Dll4 inhibitors have recently entered clinical trials for solid tumors, including ovarian cancers. In this study, we report the development of REGN421 (enoticumab), a fully human IgG1 monocl...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-14-3773

    authors: Kuhnert F,Chen G,Coetzee S,Thambi N,Hickey C,Shan J,Kovalenko P,Noguera-Troise I,Smith E,Fairhurst J,Andreev J,Kirshner JR,Papadopoulos N,Thurston G

    更新日期:2015-10-01 00:00:00

  • Effects of actinomycin D on cell cycle kinetics and the DNA of Chinese hamster and mouse mammary tumor cells cultivated in vitro.

    abstract::Actinomycin D produces changes in the cell cycle kinetics of Chinese hamster (HA1) and mouse mammary tumor cells (EMT6) cultivated in vitro. There was a reduced rate of progression of the cells through S phase and a G2 arrest, the duration and degree of which were drug dose dependent. The lethal effects of the drug on...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Roots R,Smith KC

    更新日期:1976-10-01 00:00:00

  • Hepatocyte growth factor activator inhibitor 2/placental bikunin (HAI-2/PB) gene is frequently hypermethylated in human hepatocellular carcinoma.

    abstract::To identify methylation-mediated silencing of genes in hepatocellular carcinoma (HCC), we surveyed genes induced by treatment with 5-aza-2'-deoxycytidine (5-Aza-CdR) in six human hepatoma cell lines using cDNA microarray analysis and determined the methylation status of 5' CpG islands by bisulfite DNA sequencing or me...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Fukai K,Yokosuka O,Chiba T,Hirasawa Y,Tada M,Imazeki F,Kataoka H,Saisho H

    更新日期:2003-12-15 00:00:00

  • Epidermal growth factor receptor-targeted immunophotodiagnosis and photoimmunotherapy of oral precancer in vivo.

    abstract::Immunophotodiagnosis uses a fluorescence-labeled monoclonal antibody (MAb) that recognizes a tumor-associated antigen to image the fluorescence emitted from the fluorophore-bound MAb that has localized in the tissue. It may be used to diagnose malignant or precancerous lesions, to delineate the margins for tumor resec...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Soukos NS,Hamblin MR,Keel S,Fabian RL,Deutsch TF,Hasan T

    更新日期:2001-06-01 00:00:00

  • Receptor channel TRPC6 is a key mediator of Notch-driven glioblastoma growth and invasiveness.

    abstract::Glioblastoma multiforme (GBM) is the most frequent and incurable type of brain tumor of adults. Hypoxia has been shown to direct GBM toward a more aggressive and malignant state. Here we show that hypoxia increases Notch1 activation, which in turn induces the expression of transient receptor potential 6 (TRPC6) in pri...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-09-2654

    authors: Chigurupati S,Venkataraman R,Barrera D,Naganathan A,Madan M,Paul L,Pattisapu JV,Kyriazis GA,Sugaya K,Bushnev S,Lathia JD,Rich JN,Chan SL

    更新日期:2010-01-01 00:00:00

  • Alternatively spliced RAGEv1 inhibits tumorigenesis through suppression of JNK signaling.

    abstract::Receptor for advanced glycation end products (RAGE) and its ligands are overexpressed in multiple cancers. RAGE has been implicated in tumorigenesis and metastasis, but little is known of the mechanisms involved. In this study, we define a specific functional role for an alternate splice variant termed RAGE splice var...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-10-0595

    authors: Kalea AZ,See F,Harja E,Arriero M,Schmidt AM,Hudson BI

    更新日期:2010-07-01 00:00:00

  • Mechanisms of Taxol-induced cell death are concentration dependent.

    abstract::Although the ability of Taxol to stabilize cellular microtubules is well accepted, the mechanisms by which Taxol induces growth arrest and cell death remain unclear. Recent evidence indicates that Taxol alters specific intracellular signal transduction events, such as the activation of Raf-1 kinase, that may be essent...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Torres K,Horwitz SB

    更新日期:1998-08-15 00:00:00

  • Enhancement of the activity of immunotoxins by analogues of verapamil.

    abstract::Verapamil has been shown to enhance immunotoxin activity but only at concentrations that are too high for in vivo use. Therefore, four structural analogues of verapamil (D792, D595, D528, and Sz45) were evaluated for their ability to enhance the in vitro activity of immunotoxins made with either ricin A chain or Pseud...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Pirker R,FitzGerald DJ,Raschack M,Frank Z,Willingham MC,Pastan I

    更新日期:1989-09-01 00:00:00

  • Inhibition of RAS-mediated transformation and tumorigenesis by targeting the downstream E3 ubiquitin ligase seven in absentia homologue.

    abstract::Constitutively active RAS small GTPases promote the genesis of human cancers. An important goal in cancer biology is to identify means of countervailing activated RAS signaling to reverse malignant transformation. Oncogenic K-RAS mutations are found in virtually all pancreatic adenocarcinomas, making the RAS pathway a...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-4471

    authors: Schmidt RL,Park CH,Ahmed AU,Gundelach JH,Reed NR,Cheng S,Knudsen BE,Tang AH

    更新日期:2007-12-15 00:00:00

  • Properties of immunotoxins against a glycolipid antigen associated with Burkitt's lymphoma.

    abstract::A monoclonal immunoglobulin M (IgM) antibody (38-13) which recognizes Burkitt's lymphoma (BL) cells, by reacting with the neutral glycolipid Gal alpha 1 leads to 4-Gal beta 1 leads to 4-Glc beta 1 leads to 1-ceramide, was recently characterized. This monoclonal IgM was coupled to either ricin A chain or gelonin. The t...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Wiels J,Junqua S,Dujardin P,Le Pecq JB,Tursz T

    更新日期:1984-01-01 00:00:00

  • IRF8 regulates acid ceramidase expression to mediate apoptosis and suppresses myelogeneous leukemia.

    abstract::IFN regulatory factor 8 (IRF8) is a key transcription factor for myeloid cell differentiation and its expression is frequently lost in hematopoietic cells of human myeloid leukemia patients. IRF8-deficient mice exhibit uncontrolled clonal expansion of undifferentiated myeloid cells that can progress to a fatal blast c...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-10-2493

    authors: Hu X,Yang D,Zimmerman M,Liu F,Yang J,Kannan S,Burchert A,Szulc Z,Bielawska A,Ozato K,Bhalla K,Liu K

    更新日期:2011-04-15 00:00:00

  • Effects of nonionic detergents on P-glycoprotein drug binding and reversal of multidrug resistance.

    abstract::Multidrug-resistant cells are thought to maintain low intracellular cytotoxic drug concentration though the active efflux of drugs across the cell membrane. It is presently believed that P-glycoprotein mediates this energy-dependent drug efflux by interacting directly with various lipophilic compounds. In this report,...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Zordan-Nudo T,Ling V,Liu Z,Georges E

    更新日期:1993-12-15 00:00:00

  • T-lymphocytes and macrophages in primary murine fibrosarcomas at different stages in their progression.

    abstract::The relative contribution of lymphocytes, macrophages, and granulocytes to the cell content of primary 3-methyl-cholanthrene-induced murine fibrosarcomas was determined at different stages in their progression by differential cell analysis on enzyme-derived single-cell suspensions. Furthermore, immunohistological anal...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Wood GW,Gollahon KA

    更新日期:1978-07-01 00:00:00

  • The DNA damage response arouses the immune system.

    abstract::Although there is considerable knowledge of how DNA damage triggers cell cycle arrest, DNA repair, and apoptosis, little was known about its potential role in immune responses. Recently, we showed that genotoxic stress and stalled DNA replication forks induce the expression of ligands for the NKG2D receptor found in n...

    journal_title:Cancer research

    pub_type: 杂志文章,评审

    doi:10.1158/0008-5472.CAN-05-4603

    authors: Gasser S,Raulet DH

    更新日期:2006-04-15 00:00:00

  • Effects of structural modifications of antitumor antibiotics (luzopeptins) on the interactions with deoxyribonucleic acid.

    abstract::Luzopeptins consist of two identical, substituted quinolines linked to a cyclic decadepsipeptide, with a 2-fold symmetry. Luzopeptin A, with two acetylated sites in its peptide ring, is active against several experimental animal tumor systems. Luzopeptin B (one acetylated site) is less active, and luzopeptin C (no ace...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Huang CH,Crooke ST

    更新日期:1985-08-01 00:00:00

  • Unusually high expression of N-acetylglucosaminyltransferase-IVa in human choriocarcinoma cell lines: a possible enzymatic basis of the formation of abnormal biantennary sugar chain.

    abstract::Structural analysis of the sugar chains of human chorionic gonadotropin (hCG) has revealed that abnormal biantennary structures appear specifically on hCG in the urine of choriocarcinoma patients. However, the enzymatic and molecular mechanisms of the biosynthesis of abnormal biantennary sugar chains have not yet been...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Takamatsu S,Oguri S,Minowa MT,Yoshida A,Nakamura K,Takeuchi M,Kobata A

    更新日期:1999-08-15 00:00:00

  • Two antigens recognized by autologous cytolytic T lymphocytes on a melanoma result from a single point mutation in an essential housekeeping gene.

    abstract::We have pursued our analysis of antigens recognized by autologous cytolytic T lymphocytes (CTLs) on the melanoma cells of patient LB33. This patient enjoys an unusually favorable evolution, which is associated with a strong and sustained antitumor CTL response. We reported previously the analysis of two melanoma cell ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Chiari R,Foury F,De Plaen E,Baurain JF,Thonnard J,Coulie PG

    更新日期:1999-11-15 00:00:00

  • Constitutive expression of mature transforming growth factor beta1 in the liver accelerates hepatocarcinogenesis in transgenic mice.

    abstract::Transforming growth factor beta-1 (TGF-beta1) is a potent inhibitor of hepatocyte growth both in vivo and in vitro. In this study, we analyzed the effects of TGF-beta1 on both naturally occurring and diethylnitrosamine-induced hepatocarcinogenesis using single transgenic TGF-beta1 and double transgenic c-myc/TGF-beta1...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Factor VM,Kao CY,Santoni-Rugiu E,Woitach JT,Jensen MR,Thorgeirsson SS

    更新日期:1997-06-01 00:00:00

  • Specific uptake of m-[125I]iodobenzylguanidine in the human neuroblastoma cell line SK-N-SH.

    abstract::The uptake of m-[125I]iodobenzylguanidine (mIBG), a compound structurally analogous to the antihypertensive drug guanethidine, was examined in various human cell lines. Of three neuroblastoma lines, SK-N-LO, IMR-32, and SK-N-SH, only the last showed specific uptake of the compound. In contrast, only a nonspecific upta...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Buck J,Bruchelt G,Girgert R,Treuner J,Niethammer D

    更新日期:1985-12-01 00:00:00