102 results match your criteria: "Institute For Cancer Prevention[Affiliation]"

There are many functional assays of oxidative damage to DNA, protein, and lipids but few reliable markers of chronic oxidative stress. The glutathiolation of proteins at key Cys residues is considered an important redox-sensitive, posttranslational signaling mechanism in the regulation of critical cellular functions. To determine whether protein bound glutathione (GSSP) is a sensitive indicator of oxidative stress, red blood cell and plasma concentrations were measured and compared between smokers and nonsmokers.

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NSAIDs and chemoprevention.

Curr Cancer Drug Targets

February 2004

Chemoprevention Program, Institute For Cancer Prevention, American Health Foundation-Cancer Center, 1 Dana Road, Valhalla, NY 10595, USA.

Several epidemiological, clinical and experimental studies established nonsteroidal anti-inflammatory drugs (NSAIDs) as promising cancer chemopreventive agents. Long-term use of aspirin and other NSAIDs has been shown to reduce the risk of cancer of the colon and other gastrointestinal organs as well as of cancer of the breast, prostate, lung, and skin. Understanding the action of NSAIDs provides substantial insights into the mechanisms by which these unique agents regulate tumor cell growth and enable better strategies for prevention and treatment.

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Apoptosis is a critical cellular event in cancer chemoprevention and chemotherapy by selenium compounds.

Curr Cancer Drug Targets

February 2004

Division of Cancer Etiology and Prevention, American Health Foundation Cancer Center, Institute for Cancer Prevention, 1 Dana Road, Valhalla, NY 10595, USA.

Epidemiological studies, preclinical investigations and clinical intervention trials support the role of selenium compounds as potent cancer chemopreventive agents; the dose and the form of selenium are critical factors in cancer prevention. Induction of apoptosis and inhibition of cell proliferation are considered important cellular events that can account for the cancer preventive effects of selenium. Toxicity should always be considered a determining factor in the selection of potential chemopreventive agents.

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Genotoxic carcinogens exert their tumorigenic effects in part by inducing genomic instability. We recently showed that loss of heterozygosity (LOH) on chromosome 12 associates significantly with the induction of chromosome instability (CIN) by the likely human lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and vinyl carbamate (VC) during mouse lung carcinogenesis. Here, we demonstrate the carcinogen specificity of this event and its effect on lung tumor evolution.

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The chemopreventive effect of nitric oxide-releasing aspirin (NO-ASA) against gastrointestinal tumorigenesis was evaluated in Min (APC(Min/+)) mice. NO-ASA consists of a traditional ASA that bears covalently attached to it an NO-releasing moiety. Four groups (N=10) of six-week-old female C57BL/6J APC(Min/+) and the corresponding C57BL/6J(+/+) wild type mice were treated either with vehicle or NO-ASA 100 mg/kg/day intrarectally for 21 days.

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Several studies have measured the association between blood or adipose concentrations of organochlorinated compounds (OCs), such as pesticides and polychlorinated biphenyls (PCBs), and breast cancer. The estrogenic effects of OCs might adversely affect breast cancer recurrence. The participants were 224 women with nonmetastatic breast cancer enrolled in a New York-based case-control study.

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Epidemiological studies, clinical intervention trials (including the trial with selenium-enriched yeast by Clark et al. JAMA 276, 1957, 1996) and assays in laboratory animals provide evidence for a protective role of selenium against the development of several cancers, including lung cancer. We have demonstrated that selenium in the form of 1,4-phenylenebis(methylene)selenocyanate (p-XSC) is a promising chemopreventive agent in the A/J mouse lung tumor model induced with the carcinogenic tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK); under identical conditions, selenomethionine (SM), a component of selenium-enriched yeast, had no effect.

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Do irradiated foods cause or promote colon cancer?

Nutr Cancer

May 2004

Division of Nutritional Carcinogenesis, Institute for Cancer Prevention, American Health Foundation Cancer Center, Valhalla, NY 10595, USA.

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We determined the mutant fractions (MF) and mutational specificities in the cII gene in histologically confirmed normal, non-involved and tumor mammary tissues of female transgenic (Big Blue F344 x Sprague-Dawley)F1 rats treated with the environmental pollutant 6-nitrochrysene (6-NC). At 30 days of age, three groups were set up for oral treatment with 6-NC dissolved in trioctanoin, or trioctanoin alone once a week for 8 weeks. Two dose levels of 6-NC (100 and 200 micromol/rat) were selected on the basis of our previous carcinogenicity bioassays with CD rats.

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The cyclic 1,N(2)-propanodeoxyguanosine adducts, derived from alpha,beta-unsaturated aldehydes or enals, including acrolein (Acr), crotonaldehyde (Cro), and trans-4-hydroxy-2-nonenal (HNE), have been detected as endogenous DNA lesions in rodent and human tissues. Collective evidence has indicated that the oxidative metabolism of polyunsaturated fatty acids (PUFAs) is an important pathway for endogenous formation of these adducts. In a recent study, we examined the specific role of different types of fatty acids, omega-3 and omega-6 PUFAs, in the formation of cyclic adducts of Acr, Cro, and HNE.

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Evidence of alterations in base excision repair of oxidative DNA damage during spontaneous hepatocarcinogenesis in Long Evans Cinnamon rats.

Cancer Res

November 2003

DNA Repair Laboratory, Mechanism of Carcinogenesis Program, American Health Foundation Cancer Center, Institute For Cancer Prevention, 1 Dana Road, Valhalla, NY 10595, USA.

The Long-Evans Cinnamon (LEC) rat, an animal model for Wilson's disease, is an inbred mutant strain, which because of the genetic copper metabolism disorder develops hepatitis approximately 4 months after birth, followed by chronic hepatitis later in life, and eventually all of the surviving animals from liver injury and hepatitis develop spontaneous hepatocellular carcinomas. This animal model also shows that the generation of reactive oxygen species and the accumulation of oxidative damage in the liver DNA has significantly increased over the lifetime of LEC versus the wild-type Long-Evans Agouti (LEA) rats. Thus, the LEC rats having this genetically induced oxidative condition are proved to be very useful model for the study of endogenous DNA lesions and their relation to spontaneous carcinogenesis.

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Nitric oxide (NO)-releasing aspirin (ASA), consisting of a traditional ASA molecule to which a NO-donating moiety is covalently bound, is a promising colon cancer chemopreventive agent. NO-ASA inhibits colon cancer cell growth more potently than ASA by inhibiting cell proliferation and enhancing cell killing. We examined in cultured human colon cancer cells the effect of NO-ASA on the beta-catenin/T-cell factor signaling pathway, nuclear factor-kappaB, and NO synthase 2 and on cyclooxygenase (COX) expression, all presumed to participate in colon carcinogenesis.

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O(6)-Alkylguanine-DNA alkyltransferase (AGT) repairs O(6)-methylguanine (O(6)mG) by transferring the methyl group from the DNA to a cysteine residue on the protein. The kinetics of this reaction was examined by reacting an excess of AGT (0-300 nM) with [5'-(32)P]-labeled oligodeoxynucleotides (0.5 nM) of the sequence 5'-CGT GGC GCT YZA GGC GTG AGC-3' in which Y or Z was G or O(6)mG, annealed to its complementary strand.

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1,4-phenylenebis(methylene)selenocyanate (p-XSC) inhibits 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis and DMBA-DNA binding in the rat mammary gland. Tetraselenocyclophane (TSC) was identified in rat feces as a metabolite of p-XSC. This led us to postulate the metabolic pathway: p-XSC-->glutathione conjugate (p-XSeSG)-->aromatic selenol (p-XSeH)-->TSC.

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In vitro and in vivo dimerization of human endonuclease III stimulates its activity.

J Biol Chem

December 2003

DNA Repair Laboratory, Mechanism of Carcinogenesis Program, American Health Foundation Cancer Center, Institute for Cancer Prevention, Valhalla, New York 10595, USA.

Human endonuclease III (hNTH1), a DNA glycosylase with associated abasic lyase activity, repairs various mutagenic and toxic-oxidized DNA lesions, including thymine glycol. We demonstrate for the first time that the full-length hNTH1 positively cooperates in product formation as a function of enzyme concentration. The protein concentrations that caused cooperativity in turnover also exhibited dimerization, independent of DNA binding.

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The role of tea in protection against cancer has been supported by ample evidence from studies in cell culture and animal models. However, epidemiological studies have generated inconsistent results, some of which associated tea with reduced risk of cancer, whereas others found that tea lacks protective activity against certain human cancers. These results raise questions about the actual role of tea in human cancer that needs to be addressed.

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Inactivation of the p53 tumor suppressor gene usually involves somatic mutation or binding of viral oncoproteins to the p53 protein. However, several types of malignant and premalignant tissues harbor a genetically wild-type, but transcriptionally inactive, form of p53, often localized in the cytoplasm. Electrophilic prostaglandins (PGs) are known to sequester and inactivate p53 in the cytoplasm, an effect that is likely to occur when cyclooxygenase (COX)-2 levels become elevated during colon carcinogenesis.

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Oral cytology and morphometric staining is used to identify malignant keratinocytes in oral premalignant or malignant lesions. To detect and to begin to assess changes in oral keratinocytes exposed to tobacco-derived carcinogens, which are at risk for malignant transformation, a novel method is required. The approach uses oral cytology harvested oral keratinocytes analyzed using flow cytometry (FC) for changes in DNA content, damage, cell cycle and apoptosis.

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BRCA1 in cancer, cell cycle and genomic stability.

Front Biosci

September 2003

Institute for Cancer Prevention, American Health Foundation Cancer Prevention Center, Valhalla, New York 10595, USA.

The BRCA1 gene was isolated in 1994; germline mutations of this gene are known to confer susceptibility to breast and ovarian cancer in high-risk families. Since its discovery, several mutations have been identified in this gene; these are scattered throughout the gene, and include insertion and deletion frameshifts, base substitutions, and inferred regulatory mutations. It role in the pathogenesis of breast cancer, which accounts for almost 95%, although unproven to date, cannot be ruled out.

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Objective: To investigate breast cancer outcomes in a group of African American and white patients offered the same access to mammography screening in a health maintenance organization located in suburban Philadelphia, Pennsylvania.

Methods: We used medical chart reviews and retrospective tumor tissue studies to investigate disparities in the mode of diagnosis and breast cancer outcomes among African American and white patients in a health maintenance organization.

Results: African American women were more likely to have detected their breast cancers accidentally and to have breast tumors larger than 2 cm than were whites.

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We employed cDNA microarray analysis to identify, in mammary adenocarcinomas induced by 7,12-dimethylbenz[a] anthracene (DMBA) in the rat, target genes as potential biomarkers for cancer chemoprevention by 1,4-phenylenebis(methylene)selenocyanate (p-XSC). Confirmation of selected genes was conducted by reverse transcription polymerase chain reactions (RT-PCR). The glutathione conjugate, p-XSeSG, a putative metabolite of p-XSC was also employed to test our hypothesis that p-XSeSG is a more effective cancer chemopreventive agent in the mammary cancer model than p-XSC.

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Breast cancer and obesity: an update.

Nutr Cancer

December 2003

Institute for Cancer Prevention, American Health Foundation Cancer Center, One Dana Road, Valhalla, NY 10595, USA.

Obesity has a complicated relationship to both breast cancer risk and the clinical behavior of the established disease. In postmenopausal women, particularly the elderly, various measures of obesity have been positively associated with risk. However, before menopause increased body weight is inversely related to breast cancer risk.

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Histone deacetylase (HDAC) inhibitors, such as suberoylanilide hydroxamic acid (SAHA), represent a promising new class of chemopreventive agents. We have synthesized SAHA by an improved method and examined its efficacy as a dietary supplement at 450 ppm against lung tumor development in female A/J mice induced by the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). We observed significant inhibition (80%, p < 0.

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Benzo[c]chrysene (BcC), an environmental pollutant, is a unique polycyclic aromatic hydrocarbon that possesses both a bay region and a fjord region in the same molecule. We previously demonstrated that both bay region and fjord region terminal rings are involved in the in vitro metabolism of BcC. In the present investigation, we prepared [14-(3)H]BcC and tested the hypothesis that BcC can be activated to both bay region and fjord region diol epoxides in female CD rats.

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