Abstract:
:gamma-L-glutaminyl-4-hydroxy-3-iodobenzene (I-GHB), a novel iodinated analog of gamma-L-glutaminyl-4-hydroxybenzene (GHB), demonstrates greater anti-tumor activity in human and in murine melanoma cell lines. These phenolic amides are substrates for gamma-glutamyltranspeptidase (GGTP; E.C. 2.3.2.2), a cell-membrane-associated ecto-enzyme which is elevated in a number of tumor systems. We now present data to show that the growth-inhibitory activity of I-GHB and GHB may be mediated via GGTP-catalyzed reactions. The growth-inhibitory activity of I-GHB and GHB in pigmented B16-BL6 melanoma cells was blocked significantly by rabbit anti-rat GGTP polyclonal antibodies. The combination of L-serine and sodium borate, a specific transition-state inhibitor of GGTP, as well as acivicin, a glutamine antagonist and irreversible GGTP inhibitor, inhibited the killing of BL6 cells by GHB and I-GHB. To further define the role of GGTP expression in the regulation of phenolic amide cytotoxicity, GGTP-negative Chinese hamster ovary cells (CHO-K1) were transfected with a functional rat renal cDNA representing the full-length GGTP transcript. I-GHB and GHB were significantly more cytotoxic in GGTP cDNA transfected Chinese hamster ovary (CHO-K1-GGTP) cells than in non-transfected CHO-K1 cells. The combination of L-serine and sodium borate blocked the cytotoxic activity of these pro-drugs and also inhibited GGTP-catalyzed formation of polymerized products from these phenolic amides in intact BL6 melanoma and CHO-K1-GGTP cells. Furthermore, melanin formation from GHB was not observed in non-transfected CHO-K1 cells lacking GGTP expression. The combined data strongly suggest that GGTP-catalyzed hydrolysis of the anti-tumor pro-drugs I-GHB and GHB to 4-aminophenols mediates the expression of antitumor activity.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Prezioso JA,Hughey RP,Wang N,Damodaran KM,Bloomer WDdoi
10.1002/ijc.2910560620subject
Has Abstractpub_date
1994-03-15 00:00:00pages
874-9issue
6eissn
0020-7136issn
1097-0215journal_volume
56pub_type
杂志文章abstract::A case-control study involving interviews with 1,244 patients (758 males and 486 females) with cancer of the esophagus or gastric cardia and 1,314 population-based controls (789 males, 525 females) was carried out in Linxian, a rural county in North Central China with one of the world's highest mortality rates for the...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910430502
更新日期:1989-05-15 00:00:00
abstract::alpha beta+ TCR T cells recognize peptide fragments displayed by MHC-class I or -class II molecules. Recently, additional mechanisms of antigen recognition by T cells have been identified, including CD1-mediated presentation of nonpeptide antigens. Only a limited number of CD1 antigens is retained in the mouse, i.e., ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.10141
更新日期:2002-03-20 00:00:00
abstract::The role of transcript variants of cyclin D1 in cancer biology is unclear. Most tumors with high levels of cyclin D1 express 2 transcripts due to alternative splicing: one full-length transcript of 4.4 kb and one short transcript of approximately 1.7 kb. The short transcript lacks part of the 3'UTR region regulating m...
journal_title:International journal of cancer
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doi:10.1002/ijc.21166
更新日期:2005-11-10 00:00:00
abstract::Previous studies have shown that the in vitro-selected adriamycin-resistant human small-cell lung-carcinoma cell line GLC4-ADR150 displays multidrug resistance as the result of 3-fold decreased DNA-topoisomerase II (topo II) activity and a 6-fold reduction in adriamycin accumulation. Not the MDR1 gene, but the MRP gen...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910610317
更新日期:1995-05-04 00:00:00
abstract::Both retinoids and anti-estrogens inhibit breast cancer cell proliferation with accumulation of cells in the G1 phase of the cell cycle, but the effect of retinoids is delayed compared to that of anti-estrogens. To determine whether this temporal difference is due to a simple delay in the action of retinoids on a comm...
journal_title:International journal of cancer
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更新日期:1997-01-27 00:00:00
abstract::We have studied the production and release of cholecystokinin (CCK) forms by rat medullary thyroid cancer (MTC) in vivo. MTC cells were inoculated s.c. into 8 Wag-Rij rats. One month later, after i.v. injection of calcium plasma levels of CCK, calcitonin and tissue contents of gastrin and calcitonin were determined by...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910480510
更新日期:1991-07-09 00:00:00
abstract::Folate receptor-alpha (FR-alpha) is generally over-expressed in non-mucinous human ovarian carcinomas. The meaning of FR-alpha over-expression and its role in the 5-methyltetrahydrofolic acid (N5-CH3-H4PteGlu) transport in such tumors is not clear, especially compared with the reduced folate carrier (RFC), the other k...
journal_title:International journal of cancer
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doi:10.1002/(sici)1097-0215(19980105)75:1<125::aid-ijc
更新日期:1998-01-05 00:00:00
abstract::Alcohol consumption is associated with a modest increased risk of colon cancer, but its relationship with colon cancer survival has not been elucidated. Using data from a phase III randomized adjuvant trial, we assessed the association of alcohol consumption with colon cancer outcomes. Patients completed a risk factor...
journal_title:International journal of cancer
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abstract::Polyisoprenylated benzophenones derived from Garcinia xanthochymus have cytotoxic activity in vitro and antitumor activity in rodent models, but the mechanism is unknown. The purpose of our study was to examine in parallel molecular pathways that are targeted by 3 Garcinia-derived benzophenones-xanthochymol (X), gutti...
journal_title:International journal of cancer
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doi:10.1002/ijc.23515
更新日期:2008-08-01 00:00:00
abstract::Sprague-Dawley rats were given combinations of aminopyrine or oxytetracycline and sodium nitrite in drinking water. Of 30 animals receiving 0.1% (1,000 ppm) of aminopyrine and sodium nitrite for 30 weeks, 29 died with hemangioendothelial sarcomas of the liver. The same tumor caused death in 26 of 30 animals that recei...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910160203
更新日期:1975-08-15 00:00:00
abstract::Reverse-transcriptase polymerase chain reaction has been used to analyze the expression of 2 latent genes (EBNA-1 and LMP-1) and one replicative gene (BZLF-1) of Epstein-Barr virus in mononuclear cells from bone marrow and peripheral blood of healthy donors. EBV-gene transcription was detected in 8 out of 15 bone-marr...
journal_title:International journal of cancer
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doi:10.1002/(sici)1097-0215(19970304)70:5<524::aid-ijc
更新日期:1997-03-04 00:00:00
abstract::Organochlorine insecticides have been studied extensively in relation to breast cancer incidence, and results from two meta-analyses have been null for late-life residues, possibly due to measurement error. Whether these compounds influence survival remains to be fully explored. We examined associations between organo...
journal_title:International journal of cancer
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doi:10.1002/ijc.29806
更新日期:2016-02-01 00:00:00
abstract::The intrauterine environment appears to play a role in the development of adult diseases, including several prominent cancers. Our study aims to characterize the relationship between birth weight, a measure of the intrauterine environment, and adult obesity. A population-based sample of women aged 50-79, living in the...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.10886
更新日期:2003-03-01 00:00:00
abstract::Phosphorylation/activation of c-jun NH2-terminal kinase (JNK) has an ambivalent role, pro-proliferation or antiproliferation, in human cancers, which is determined by different cell types and by its crosstalk with other kinases. So far, the role of phosphorylated JNK (p-JNK) in breast cancer is mostly undefined. In th...
journal_title:International journal of cancer
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doi:10.1002/ijc.21707
更新日期:2006-06-01 00:00:00
abstract::There is limited information present to explain temporal improvements in colon cancer survival. This nationwide study investigates the temporal changes in survival over a 35-year period (1970-2004) in Iceland and uses incidence, mortality, surgery rate, stage distribution, lymph node yield, tumor location and histolog...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.30766
更新日期:2017-08-01 00:00:00
abstract::TDE2, a gene with sequence similarity to the mouse testicular tumor-differentially-expressed (Tde1/MUSTETU) gene, was identified by serial analysis of gene expression (SAGE) in nonsmall cell lung cancers (NSCLC). Here we characterized the TDE2 gene and determined its transcript levels in a panel of lung tumors, adjace...
journal_title:International journal of cancer
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doi:10.1002/ijc.11391
更新日期:2003-11-01 00:00:00
abstract::Stem cell-like cells have recently been identified in melanoma cell lines, but their relevance for melanoma pathogenesis is controversial. To characterize the stem cell signature of melanoma, expression of stem cell markers BMI-1 and nestin was studied in 64 cutaneous melanomas, 165 melanoma metastases as well as 53 m...
journal_title:International journal of cancer
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doi:10.1002/ijc.22891
更新日期:2007-10-15 00:00:00
abstract::Although adult obesity is known to increase endometrial cancer risk, evidence for childhood obesity is limited. We prospectively examined the association between body fatness throughout life and endometrial cancer risk. 47,289 participants in the Nurses' Health Study (NHS) and 105,386 of the Nurses' Health Study II (N...
journal_title:International journal of cancer
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更新日期:2015-08-01 00:00:00
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journal_title:International journal of cancer
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abstract::Infection with erbB-2 (E) of Ha-ras (H) oncogene-transfected cells has been previously shown to cooperatively induce anchorage-independent growth of the MCF10A human mammary epithelial cell line in vitro, but not to induce nude mouse tumorigenicity. Here we show that oncogene-transformed MCF10A are able to halt in the...
journal_title:International journal of cancer
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doi:10.1002/ijc.2910630612
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abstract::The incidence of breast cancer among women in Shanghai, a traditionally low-risk population, has increased substantially over the past 20 years. To evaluate the association of menstrual and reproductive factors with breast cancer risk and the influence of these factors on the temporal trend of breast cancer incidence,...
journal_title:International journal of cancer
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abstract::Epidermal growth factor receptor (EGFR) plays an important role in essential cellular processes such as proliferation, survival and migration. Aberrant activation of EGFR is frequently found in human cancers of various origins and has been implicated in cancer pathogenesis. The therapeutic antibody cetuximab (Erbitux)...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.28585
更新日期:2014-06-01 00:00:00
abstract::The ability of endogenously synthesized protoporphyrin IX (PpIX) to damage Chinese hamster lung fibroblasts of the line V79 by exposure to light was examined. This treatment induced reduction of cellular ATP, GTP, of the NADH/NAD+ ratio and of oxygen consumption. The present results indicate a close relationship betwe...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0215(19960917)67:6<791::AID-IJC
更新日期:1996-09-17 00:00:00
abstract::A human revertant cell line, derived from non-producer human osteosarcoma cells (NP/KHOS) induced by Kirsten murine sarcoma virus, was treated in vitro with various levels of polycyclic aromatic hydrocarbons (3-methylcholanthrene, 7,12-dimethylbenz(alpha)anthracene, and benzo(alpha)pyrene [BP] or dimethyl sulfoxide (c...
journal_title:International journal of cancer
pub_type: 杂志文章
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更新日期:1978-01-15 00:00:00
abstract::The knowledge that cervical neoplasia are caused by human papillomavirus (HPV) infection has led to the evaluation of its role in screening. We evaluated the accuracy of HPV testing by Hybrid capture II (HC II) method in detecting cervical intraepithelial neoplasia grade 2 and 3 (CIN 2 and 3) lesions in 4 cross-sectio...
journal_title:International journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1002/ijc.20396
更新日期:2004-11-01 00:00:00
abstract::We previously reported that exosomal nanoparticles secreted by human pancreatic tumoral cell lines decrease tumoral cell proliferation through the mitochondria-dependent apoptotic pathway, because of activation of pro-apoptotic phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and of glucose synthase kina...
journal_title:International journal of cancer
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更新日期:2009-09-01 00:00:00
abstract::Dietary patterns reflect combinations of dietary exposures, and here we examine these in relation to prostate cancer risk. In a case-control study, 80 incident primary prostate cancer cases and 334 urology clinic controls were enrolled from 1997 through 1999 in Kingston, Ontario, Canada. Food-frequency questionnaires ...
journal_title:International journal of cancer
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doi:10.1002/ijc.21112
更新日期:2005-09-10 00:00:00
abstract::Heme oxygenase (HO)-1 catalyzes the degradation of cytotoxic heme into biliverdin and blocks antitumor immune responses, thus protecting cancer against host defense. Whether this scenario also applies to neuroblastoma (NB), the most common extracranial solid childhood tumor, is not known. Here, we demonstrate for the ...
journal_title:International journal of cancer
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doi:10.1002/ijc.29933
更新日期:2016-04-15 00:00:00
abstract::The results of a survey of a population with a high incidence of oral and oesophageal cancer are presented. The population under study appears to have several epidemiologic characteristics, some of which may be associated with a high incidence of oral and oesophageal cancer. A remarkably high proportion (41%) of the m...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910360205
更新日期:1985-08-15 00:00:00
abstract::Dietary information from a case-control study of pancreatic cancer conducted in Metropolitan Toronto between 1983 and 1986 is reported. A total of 249 cases and 505 population-based controls completed quantitative diet histories from which total caloric intake and the intake of a number of nutrients were estimated. A ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910450405
更新日期:1990-04-15 00:00:00