The biological and therapeutic importance of gastrin gene expression in pancreatic adenocarcinomas.

Abstract:

:The gastrin gene is expressed widely in pancreatic adenocarcinomas and the study aimed to assess its role in both the resistance of cancer cells to apoptosis and the sensitivity of cells to chemotherapeutic agents. Two human pancreatic cell lines, PAN1 and BXPC3, expressed gastrin at both the RNA and protein levels and are shown to be representative of human pancreatic adenocarcinomas in terms of gastrin expression. Inhibition of endogenous gastrin production by tumor cells was achieved with neutralizing gastrin antiserum and transfection with a gastrin antisense plasmid. Gastrin antiserum synergized with both taxotere and gemcitabine in inhibiting the in vitro growth of the PAN1 cell line with the inhibitory effect of the antiserum increasing from 12.7% to 70.2% with taxotere (P < 0.05) and 28.6% with gemcitabine (P < 0.01) after controlling for the effects of the cytotoxics. Synergy was only achieved with taxotere in BXPC3 cells with the inhibitory effect of gastrin antiserum increasing from 22.9% to 50.0% (P < 0.005). Cells transfected with gastrin antisense had reduced in vitro growth in low serum conditions and were poorly tumorigenic in nude mice at an orthotopic site. Gastrin antisense-transfected PAN1 cells had increased sensitivity to the antiproliferative effects of both gemcitabine (IC50 of > 100 microg/ml reduced to 0.1 microg/ml) and taxotere (IC50 of 20 microg/ml reduced to < 0.01 microg/ml) when compared with vector controls. The increased sensitivity of PAN1 antisense coincided with increased caspase-3 activity and reduced protein kinase B/Akt phosphorylation in response to both gemcitabine and taxotere. Gastrin gene circumvention may be an optimal adjunct to chemotherapeutic agents, such as taxotere and gemcitabine, in pancreatic adenocarcinoma.

journal_name

Cancer Res

journal_title

Cancer research

authors

Harris JC,Gilliam AD,McKenzie AJ,Evans SA,Grabowska AM,Clarke PA,McWilliams DF,Watson SA

doi

10.1158/0008-5472.CAN-04-0106

subject

Has Abstract

pub_date

2004-08-15 00:00:00

pages

5624-31

issue

16

eissn

0008-5472

issn

1538-7445

pii

64/16/5624

journal_volume

64

pub_type

杂志文章
  • Effect of dietary cellulose on cell proliferation and progression of 1,2-dimethylhydrazine-induced colon carcinogenesis in rats.

    abstract::The effects of different levels of dietary cellulose on colonic crypt mitotic activity and colon carcinogenesis were studied in 190 male Sprague-Dawley rats. Rats were divided into groups and fed a basal fiber-free diet supplemented with either 0, 5, or 15% pure cellulose (w/w), for periods of 10 weeks (initiation sta...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Heitman DW,Ord VA,Hunter KE,Cameron IL

    更新日期:1989-10-15 00:00:00

  • Src stimulates fibroblast growth factor receptor-2 shedding by an ADAM15 splice variant linked to breast cancer.

    abstract::ADAMs (a disintegrin and metalloproteinase) have important roles in development and diseases such as cancer. Previously, an ADAM15 splice variant (ADAM15B), which contains an inserted cytoplasmic Src-binding site, was linked to clinical aggressiveness in breast cancer, yet little was known about how this splice varian...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-4766

    authors: Maretzky T,Le Gall SM,Worpenberg-Pietruk S,Eder J,Overall CM,Huang XY,Poghosyan Z,Edwards DR,Blobel CP

    更新日期:2009-06-01 00:00:00

  • Glycosylation of Recombinant Anticancer Therapeutics in Different Expression Systems with Emerging Technologies.

    abstract::Glycosylation, a posttranslational modification, has a major role in recombinant anticancer therapeutic proteins, as most of the approved recombinant therapeutics are glycoproteins. The constant amino acid sequence of therapeutics determines the enzymatic activity, while the presence of glycans influences their pharma...

    journal_title:Cancer research

    pub_type: 杂志文章,评审

    doi:10.1158/0008-5472.CAN-18-0032

    authors: Nadeem T,Khan MA,Ijaz B,Ahmed N,Rahman ZU,Latif MS,Ali Q,Rana MA

    更新日期:2018-06-01 00:00:00

  • Characterization by molecular hybridization of two viral populations derived from a radiation leukemia virus.

    abstract::Two leukemogenic viral populations were derived from a radiation leukemia virus of the C57BL mouse. One (FB), in which only B-tropic virus could be detected, was obtained in vivo by serial passage of cell-free extract in newborn rats. The second (3C), a complex containing at least B-tropic and xenotropic viruses, was ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Janowski M,Astier T,Guillemain B,Baugnet-Mahieu L,Duplan JF,Maisin JR

    更新日期:1978-10-01 00:00:00

  • Integrin beta3 overexpression suppresses tumor growth in a human model of gliomagenesis: implications for the role of beta3 overexpression in glioblastoma multiforme.

    abstract::alphaVbeta3 integrin complexes are overexpressed in the growing, invading margins of human glioblastoma multiforme (GBM) and in the GBM vasculature, suggesting a key role for alphaVbeta3 in GBM growth and invasion. The function of alphaVbeta3 complexes in tumor formation, however, has been challenged by studies showin...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.can-03-3354

    authors: Kanamori M,Vanden Berg SR,Bergers G,Berger MS,Pieper RO

    更新日期:2004-04-15 00:00:00

  • Bcl-2/adenovirus E1B 19 kDa interacting protein-3 knockdown enables growth of breast cancer metastases in the lung, liver, and bone.

    abstract::The mouse breast cancer cell lines 4T1, 4T07, and 67NR are highly tumorigenic but vary in metastatic potential: 4T1 widely disseminates, resulting in secondary tumors in the lung, liver, bone, and brain; 4T07 spreads to the lung and liver but is unable to establish metastatic nodules; 67NR is unable to metastasize. Th...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-3091

    authors: Manka D,Spicer Z,Millhorn DE

    更新日期:2005-12-15 00:00:00

  • Sustained small interfering RNA delivery by mesoporous silicon particles.

    abstract::RNA interference (RNAi) is a powerful approach for silencing genes associated with a variety of pathologic conditions; however, in vivo RNAi delivery has remained a major challenge due to lack of safe, efficient, and sustained systemic delivery. Here, we report on a novel approach to overcome these limitations using a...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-09-3931

    authors: Tanaka T,Mangala LS,Vivas-Mejia PE,Nieves-Alicea R,Mann AP,Mora E,Han HD,Shahzad MM,Liu X,Bhavane R,Gu J,Fakhoury JR,Chiappini C,Lu C,Matsuo K,Godin B,Stone RL,Nick AM,Lopez-Berestein G,Sood AK,Ferrari M

    更新日期:2010-05-01 00:00:00

  • Disrupting Hypoxia-Induced Bicarbonate Transport Acidifies Tumor Cells and Suppresses Tumor Growth.

    abstract::Tumor hypoxia is associated clinically with therapeutic resistance and poor patient outcomes. One feature of tumor hypoxia is activated expression of carbonic anhydrase IX (CA9), a regulator of pH and tumor growth. In this study, we investigated the hypothesis that impeding the reuptake of bicarbonate produced extrace...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-15-1862

    authors: McIntyre A,Hulikova A,Ledaki I,Snell C,Singleton D,Steers G,Seden P,Jones D,Bridges E,Wigfield S,Li JL,Russell A,Swietach P,Harris AL

    更新日期:2016-07-01 00:00:00

  • Transcriptional profiling of melanoma sentinel nodes identify patients with poor outcome and reveal an association of CD30(+) T lymphocytes with progression.

    abstract::Sentinel lymph nodes set the stance of the immune system to a localized tumor and are often the first site to be colonized by neoplastic cells that metastasize. To investigate how the presence of neoplastic cells in sentinel lymph nodes may trigger pathways associated with metastatic progression, we analyzed the trans...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-13-1672

    authors: Vallacchi V,Vergani E,Camisaschi C,Deho P,Cabras AD,Sensi M,De Cecco L,Bassani N,Ambrogi F,Carbone A,Crippa F,Vergani B,Frati P,Arienti F,Patuzzo R,Villa A,Biganzoli E,Canevari S,Santinami M,Castelli C,Rivoltini L

    更新日期:2014-01-01 00:00:00

  • Phase I clinical study of N-[(4-chlorophenyl)amino]carbonyl-2,3-dihydro-1H-indene-5-sulfonamide (LY186641).

    abstract::Between February 1987 and July 1988, 45 patients with advanced refractory cancer were treated with LY186641, a diarylsulfonylurea that has shown a broad spectrum of activity in preclinical testing. Patients received a weekly p.o. dose of LY186641 for 6 consecutive weeks; responding and stable patients continued weekly...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Hainsworth JD,Hande KR,Satterlee WG,Kuttesch J,Johnson DH,Grindey G,Jackson LE,Greco FA

    更新日期:1989-09-15 00:00:00

  • Prostaglandin E2 stimulates human lung carcinoma cell growth through induction of integrin-linked kinase: the involvement of EP4 and Sp1.

    abstract::Cyclooxygenase-2-derived prostaglandin E(2) (PGE(2)) stimulates tumor cell growth and progression. However, the mechanisms by which PGE(2) increases tumor growth remain incompletely understood. In studies performed in non-small cell lung carcinoma (NSCLC) cells, we found that PGE(2) stimulates the expression of integr...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-2677

    authors: Zheng Y,Ritzenthaler JD,Sun X,Roman J,Han S

    更新日期:2009-02-01 00:00:00

  • Genetic variants in oxidative stress-related genes predict chemoresistance in primary breast cancer: a prospective observational study and validation.

    abstract::Chemotherapy response in patients with primary breast cancer is difficult to predict and the role of host genetic factors has not been thoroughly investigated. We hypothesized that polymorphisms in oxidative stress (OS)-related genes, including estrogen-quinone metabolizing enzymes NQO2 and GSTM1-5, may influence dise...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-11-2998

    authors: Yu KD,Huang AJ,Fan L,Li WF,Shao ZM

    更新日期:2012-01-15 00:00:00

  • MFF Regulation of Mitochondrial Cell Death Is a Therapeutic Target in Cancer.

    abstract::The regulators of mitochondrial cell death in cancer have remained elusive, hampering the development of new therapies. Here, we showed that protein isoforms of mitochondrial fission factor (MFF1 and MFF2), a molecule that controls mitochondrial size and shape, that is, mitochondrial dynamics, were overexpressed in pa...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-19-1982

    authors: Seo JH,Chae YC,Kossenkov AV,Lee YG,Tang HY,Agarwal E,Gabrilovich DI,Languino LR,Speicher DW,Shastrula PK,Storaci AM,Ferrero S,Gaudioso G,Caroli M,Tosi D,Giroda M,Vaira V,Rebecca VW,Herlyn M,Xiao M,Fingerman D,Ma

    更新日期:2019-12-15 00:00:00

  • Repair of DNA following incorporation of 1-beta-D-arabinofuranosylcytosine into herpes simplex virus type 1.

    abstract::The nucleoside analogue 1-beta-D-arabinofuranosylcytosine (ara-C) is incorporated into herpes simplex virus type 1 (HSV-1) DNA, and this correlates with inhibition of virus replication. The technique of Weigle-type reactivation (WR) was used to compare the ability of induced cellular DNA repair pathways to recognize o...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Bubley GJ,Crumpacker CS,Schnipper LE

    更新日期:1984-05-01 00:00:00

  • ANCCA/ATAD2 overexpression identifies breast cancer patients with poor prognosis, acting to drive proliferation and survival of triple-negative cells through control of B-Myb and EZH2.

    abstract::Chromatin coregulators are important factors in tumorigenesis and cancer progression. ANCCA is an AAA+ ATPase and a bromodomain-containing nuclear coactivator for the estrogen and androgen receptors that is crucial for assembly of chromatin-modifying complexes and proliferation of hormone-responsive cancer cells. In t...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-10-1199

    authors: Kalashnikova EV,Revenko AS,Gemo AT,Andrews NP,Tepper CG,Zou JX,Cardiff RD,Borowsky AD,Chen HW

    更新日期:2010-11-15 00:00:00

  • Reduction of O6-alkylguanine-DNA alkyltransferase activity in HeLa cells treated with O6-alkylguanines.

    abstract::Exposure of HeLa cells to 0.2 mM O6-methylguanine for 4 h or longer led to a 70-80% loss in the activity of the DNA-repair protein, O6-alkylguanine-DNA alkyltransferase. The decline in alkyltransferase activity brought about by O6-methylguanine was reversible on removing the base but at least 48 h were required for co...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Dolan ME,Morimoto K,Pegg AE

    更新日期:1985-12-01 00:00:00

  • Tumor Suppressor HIPK2 Regulates Malignant Growth via Phosphorylation of Notch1.

    abstract::The receptor Notch1 plays an important role in malignant progression of many cancers, but its regulation is not fully understood. In this study, we report that the kinase HIPK2 is responsible for facilitating the Fbw7-dependent proteasomal degradation of Notch1 by phosphorylating its intracellular domain (Notch1-IC) w...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-15-3310

    authors: Ann EJ,Kim MY,Yoon JH,Ahn JS,Jo EH,Lee HJ,Lee HW,Kang HG,Choi DW,Chun KH,Lee JS,Choi CY,Ferrando AA,Lee K,Park HS

    更新日期:2016-08-15 00:00:00

  • Genetic ancestry and risk of breast cancer among U.S. Latinas.

    abstract::U.S. Latinas have a lower incidence of breast cancer compared with non-Latina White women. This difference is partially explained by differences in the prevalence of known risk factors. Genetic factors may also contribute to this difference in incidence. Latinas are an admixed population with most of their genetic anc...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-2039

    authors: Fejerman L,John EM,Huntsman S,Beckman K,Choudhry S,Perez-Stable E,Burchard EG,Ziv E

    更新日期:2008-12-01 00:00:00

  • Effect of hepatocarcinogens on the adenine purine nucleotide cycle during the initiation phase of carcinogenesis.

    abstract::Activities of the adenine purine nucleotide cycle enzymes, i.e., adenylosuccinate (SAMP) synthetase, SAMP lyase, and adenosine 5'-monophosphate deaminse, were determined in hepatic tissue of rats fed and/or given injections of 3'-methyl-4-dimethylaminoazobenzene, 4'-methyl-4-dimethylaminoazobenzene, thioacetamide, eth...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Smith LD,Emerson RL,Nixon LK

    更新日期:1979-06-01 00:00:00

  • Chlorozotocin, 2-(3-(2-chloroethyl)-3-nitrosoureido)-D-glucopyranose, an antitumor agent with modified bone marrow toxicity.

    abstract::Chlorozotocin, 2-(3-(2-chloroethyl)-3-nitrosoureido)-D-glucopyranose, is a newly synthesized, water-soluble nitrosourea antitumor agent that is active against L1210 leukemia in mice. A 701% and a 401% increase in life-span were attained with a dose that was lethal to 10% of the animals (15 to 20 mg/kg, i.p.) in mice t...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Anderson T,McMenamin MG,Schein PS

    更新日期:1975-03-01 00:00:00

  • Identification of PDE4D as a proliferation promoting factor in prostate cancer using a Sleeping Beauty transposon-based somatic mutagenesis screen.

    abstract::Retroviral and transposon-based mutagenesis screens in mice have been useful for identifying candidate cancer genes for some tumor types. However, many of the organs that exhibit the highest cancer rates in humans, including the prostate, have not previously been amenable to these approaches. This study shows for the ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-3901

    authors: Rahrmann EP,Collier LS,Knutson TP,Doyal ME,Kuslak SL,Green LE,Malinowski RL,Roethe L,Akagi K,Waknitz M,Huang W,Largaespada DA,Marker PC

    更新日期:2009-05-15 00:00:00

  • Functional analysis of alternative isoforms of the transcription factor PAX3 in melanocytes in vitro.

    abstract::Transcription factor PAX3 has seven isoforms of which PAX3c has been studied extensively whereas the functions of the other isoforms are less well known. Here, we found that PAX3 isoforms in a stable transfection system have different biological functions in mouse melanocytes in vitro. PAX3a and PAX3b had negative eff...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-0947

    authors: Wang Q,Kumar S,Slevin M,Kumar P

    更新日期:2006-09-01 00:00:00

  • Differential inhibition of the epidermal growth factor-, platelet-derived growth factor-, and protein kinase C-mediated signal transduction pathways by the staurosporine derivative CGP 41251.

    abstract::The microbial alkaloid staurosporine is a potent but nonselective inhibitor of protein kinases. The derivative CGP 41251 has been shown to exert a high degree of selectivity for inhibition of protein kinase C activity. Both compounds are powerful inhibitors of proliferation of both normal and transformed cells in vitr...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Andrejauskas-Buchdunger E,Regenass U

    更新日期:1992-10-01 00:00:00

  • Cancer suppression at old age.

    abstract::Increased age is regularly linked with heightened cancer risk, but recent research suggests a flattening around age 80. We report that, independent of cancer site or time period, most incidence rates decrease in the more elderly and drop to or toward zero near the ceiling of human life span. For all major organ sites,...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-1670

    authors: Harding C,Pompei F,Lee EE,Wilson R

    更新日期:2008-06-01 00:00:00

  • Humanized anti-Lewis Y antibodies: in vitro properties and pharmacokinetics in rhesus monkeys.

    abstract::ABL 364 is a murine monoclonal IgG3 antibody directed against the Lewis Y carbohydrate antigen (Le(y)) expressed on the surface of many epithelial cell tumors. The antibody mediates cytotoxicity via activation of human complement or human effector cells, and has been evaluated in several clinical trials including two ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Co MS,Baker J,Bednarik K,Janzek E,Neruda W,Mayer P,Plot R,Stumper B,Vasquez M,Queen C,Loibner H

    更新日期:1996-03-01 00:00:00

  • Simultaneous inhibition of PDK1/AKT and Fms-like tyrosine kinase 3 signaling by a small-molecule KP372-1 induces mitochondrial dysfunction and apoptosis in acute myelogenous leukemia.

    abstract::Phosphoinositol-3-kinase (PI3K)/protein kinase B (AKT) and Fms-like tyrosine kinase 3 (FLT3) signaling are aberrantly activated in acute myelogenous leukemia (AML) cells. Constitutively activated AKT and FLT3 regulate leukemia cell survival and resistance to chemotherapy. In this study, we investigated the effects of ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-1278

    authors: Zeng Z,Samudio IJ,Zhang W,Estrov Z,Pelicano H,Harris D,Frolova O,Hail N Jr,Chen W,Kornblau SM,Huang P,Lu Y,Mills GB,Andreeff M,Konopleva M

    更新日期:2006-04-01 00:00:00

  • Human papillomavirus 16/18 E6 oncoprotein is expressed in lung cancer and related with p53 inactivation.

    abstract::Inactivation of p53 by human papillomavirus 16/18 E6 plays a crucial role in cervical tumorigenesis. To investigate the involvement of HPV16/18 in lung tumorigenesis, the association between HPV16 or HPV18 E6 and p53 protein expression in 122 lung tumors was evaluated by immunohistochemistry, and data showed that HPV1...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-1461

    authors: Cheng YW,Wu MF,Wang J,Yeh KT,Goan YG,Chiou HL,Chen CY,Lee H

    更新日期:2007-11-15 00:00:00

  • Deregulated CDC25A expression promotes mammary tumorigenesis with genomic instability.

    abstract::Checkpoint pathways help cells maintain genomic integrity, delaying cell cycle progression in response to various risks of fidelity, such as genotoxic stresses, compromised DNA replication, and impaired spindle control. Cancer cells frequently exhibit genomic instability, and recent studies showed that checkpoint path...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-3927

    authors: Ray D,Terao Y,Fuhrken PG,Ma ZQ,DeMayo FJ,Christov K,Heerema NA,Franks R,Tsai SY,Papoutsakis ET,Kiyokawa H

    更新日期:2007-02-01 00:00:00

  • Pulmonary radiation injury: identification of risk factors associated with regional hypersensitivity.

    abstract::Effective radiation treatment of thoracic tumors is often limited by radiosensitivity of surrounding tissues. Several experimental studies have suggested variations in radiosensitivity of different pulmonary regions. Mice and rat studies in part contradict each other and urge for a more detailed analysis. This study w...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-3466

    authors: Novakova-Jiresova A,van Luijk P,van Goor H,Kampinga HH,Coppes RP

    更新日期:2005-05-01 00:00:00

  • Topoisomerase II-mediated DNA breaks and cytotoxicity in relation to cell proliferation and the cell cycle in NIH 3T3 fibroblasts and L1210 leukemia cells.

    abstract::The DNA intercalator, 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) and the nonintercalator, etoposide (VP-16) produce topoisomerase II-mediated protein-linked DNA strand breaks. This function of topoisomerase II was investigated in relation to cell proliferation and cell cycle. Mouse fibroblasts NIH 3T3 and...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Markovits J,Pommier Y,Kerrigan D,Covey JM,Tilchen EJ,Kohn KW

    更新日期:1987-04-15 00:00:00