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Gilbert S Omenn

Publications and source records attributed to Gilbert S Omenn.

46 records · Page 3Linked to original sources
PubMed2003

Profiling of pathway-specific changes in gene expression following growth of human cancer cell lines transplanted into mice.

BACKGROUND: Tumor cells cultured in vitro are widely used to investigate the molecular biology of cancers and to evaluate responses to drugs and other agents. The full extent to which gene expression in cancer cells is modulated by extrinsic factors and by the microenvironment in which the cancer cells reside remains to be determined. Two cancer cell lines (A549 lung adenocarcinoma and U118 glioblastoma) were transplanted subcutaneously into immunodeficient mice to form tumors. Global gene-expression profiles of the tumors were determined, based on analysis of expression of human genes, and compared with expression profiles of the cell lines grown in culture. RESULTS: A bioinformatics approach associated genes that showed changes in their expression levels with functional classes as defined by either the GO gene annotations or MeSH terms in the literature. The classes of genes expressed at higher levels in cells grown in vitro indicated increased cell division and metabolism, reflecting the more favorable environment for cell proliferation. In contrast, in vivo tumor growth resulted in upregulation of a significant number of genes involved in the extracellular matrix (ECM), cell adhesion, cytokine and metalloendopeptidase activity, and neovascularization. When placed in comparable tissue environments, the U118 cells and the A549 cells expressed different sets of ECM and cell adhesion-related genes, suggesting different mechanisms of extracellular interaction at work in the different cancers. CONCLUSIONS: Studies of this type allow us to examine the specific contribution of cancer cells to gene expression patterns within an in vivo tumor mixed with non-cancerous tissue.

Animals↗
PubMed2003

Microarrays of tumor cell derived proteins uncover a distinct pattern of prostate cancer serum immunoreactivity.

The broad characterization of the immune responses elicited by tumors has valuable applications in diagnostics and basic research. We present here the use of microarrays of tumor-derived proteins to profile the antibody repertoire in the sera of prostate cancer patients and controls. Two-dimensional liquid chromatography was used to separate proteins from the prostate cancer cell line LNCaP into 1760 fractions. These fractions were spotted in microarrays on coated microscope slides, and the microarrays were incubated individually with serum samples from 25 men with prostate cancer and 25 male controls. The amount of immunoglobulin bound to each fraction by each serum sample was quantified. Statistical analysis revealed that 38 of the fractions had significantly higher levels of immunoglobulin binding in the prostate cancer samples compared to the controls. Two fractions showed higher binding in the control samples. The significantly higher immunoglobulin reactivity from the prostate cancer samples may reflect a strong immune response to the tumors in the prostate cancer patients. We used multivariate analysis to classify the samples as either prostate cancer or control. In a cross-validation study, recursive partitioning classified the samples with 84% accuracy. A decision tree with two levels of partitioning classified the samples with 98% accuracy. Additional studies will allow further characterization of tumor antigens in prostate cancer and their significance for diagnosis. These results suggest that microarrays of fractionated proteins could be a powerful tool for tumor antigen discovery and cancer diagnosis.

Antibodies, Neoplasm↗
PubMed2003

Fruits and vegetables are associated with lower lung cancer risk only in the placebo arm of the beta-carotene and retinol efficacy trial (CARET).

Despite the unexpected results from the beta-Carotene and Retinol Efficacy Trial (CARET) and similar supplementation trials showing that supplementation with beta-carotene increased, rather than decreased, lung cancer incidence, considerable interest remains in investigating how other compounds in fruits and vegetables may affect lung cancer risk. We used data from 14,120 CARET participants who completed food frequency questionnaires to examine associations of diet with lung cancer risk. After 12 years of follow-up (1989-2001), 742 participants developed lung cancer. We used Cox proportional hazards models to estimate multivariate relative risks (RRs) and 95% confidence intervals (CIs). Analyses were controlled for smoking, asbestos exposure, and other covariates. Analyses of specific botanical groups were also controlled for total fruit and vegetable intake. All models were stratified by CARET treatment arm, and all statistical tests were two-sided. Statistically significant associations of fruit and vegetable intake with lower lung cancer risk were restricted to the CARET placebo arm. The RR for highest versus lowest quintile of total fruit consumption in the placebo arm was 0.56 (95% CI, 0.39-0.81) with a two-sided P for trend = 0.003. Two specific botanical groups were associated with reduced risk of lung cancer. Compared with the lowest quintile of rosaceae fruit consumption, placebo participants in the top quintile had a RR of 0.63 (95% CI, 0.42-0.94; P for trend = 0.02); for cruciferae vegetables, the RR was 0.68 (95% CI, 0.45-1.04; P for trend = 0.01). We did not observe any statistically significant associations of fruit and vegetable intake with lung cancer risk among participants randomized to receive the CARET supplements (30 mg of beta-carotene and 25,000 IU of retinyl palmitate). This report provides evidence that plant foods have an important preventive influence in a population at high risk for lung cancer. However, persons who use beta-carotene supplements do not benefit from the protective compounds in plant foods.

Aged↗
PubMed2003

The association between lung and prostate cancer risk, and serum micronutrients: results and lessons learned from beta-carotene and retinol efficacy trial.

beta-Carotene and Retinol Efficacy Trial is a nationwide chemoprevention trial that recruited 18,314 high-risk individuals to test the effect of supplemental beta-carotene and retinol on lung cancer incidence. In this report, we conducted a prospective nested case-control study of the association between serum carotenoids, retinoids, and tocopherols on both lung and prostate cancer incidence. Prerandomization serum samples were selected from 278 lung cancer cases and 205 prostate cancer cases, and 483 controls matched by high-risk population, study center location, age, sex (lung cancer only), smoking status, and year of randomization. Carotenoids, retinoids, and tocopherols were analyzed by high-performance liquid chromatography. Endpoints were confirmed by pathology review (lung cancer) or review of the pathology report (prostate cancer). In the control-only population, there was a significant association between tobacco use and serum micronutrient concentration. Current smokers compared with former smokers had lower mean levels of all of the micronutrients tested with zeaxanthin, beta-cryptoxanthin, alpha-carotene, alpha-tocopherol, retinol, and retinyl palmitate reaching statistical significance at P = 0.05. In the overall population, the mean serum concentrations of all of the micronutrients except gamma-tocopherol were lower for lung cancer cases than controls. Statistically significant trends across quartiles were observed in lutein (P = 0.02), zeaxanthin (P = 0.02), and alpha-tocopherol (P = 0.03). The carotenoid findings in the overall population were because of the strong inverse association between serum micronutrients and lung cancer in females. Statistically significant odds ratios (ORs) comparing 4(th) to 1st quartiles in the female population were seen in lutein [OR, 0.31; confidence interval (CI), 0.13-0.75], zeaxanthin (OR, 0.31; CI, 0.12-0.77), and beta-cryptoxanthin (OR, 0.34; CI, 0.14-0.81). For prostate cancer, mean serum concentrations were lower in cases for all of the nutrients except alpha-carotene. Only for alpha-tocopherol (P(trend) = 0.04) were the findings statistically significant. There was no statistically significant association between serum carotenoids and prostate cancer. Our findings provide additional support for the association between physiological levels of dietary micronutrients and cancer incidence.

Aged↗
PubMed2002

Streamlining IRB review in multisite trials through single-study IRB Cooperative Agreements: experience of the Beta-Carotene and Retinol Efficacy Trial (CARET).

With their extensive data and specimen repositories, clinical trials are a long-term, valuable resource to health researchers. However, assuring protection of participants' rights can be challenging, particularly when such trials are conducted at multiple sites with multiple Institutional Review Boards (IRBs). One little-used mechanism that can streamline IRB review in multisite trials while maintaining participants' protections is the single-study IRB Cooperative Agreement. This agreement is entirely different from reciprocity agreements between institutions. Beginning in 1996, the Beta-Carotene and Retinol Efficacy Trial established single-study IRB Cooperative Agreements among its performance sites, which reduced the average time to complete IRB approval from over 6 months to 1 month for each of many substudies. We describe our experience and make recommendations for other multisite clinical trials.

Clinical Trials as Topic↗
PubMed2002

Homocyst(e)ine and coronary heart disease: pharmacoeconomic support for interventions to lower hyperhomocyst(e)inaemia.

Homocyst(e)ine, a sulphur-containing amino acid, is an intermediate formed during the metabolism of the essential amino acid methionine. Biological and epidemiological evidence suggest that elevated plasma levels of homocyst(e)ine are a risk factor for atherosclerosis and coronary heart disease (CHD). In the general US population, hyperhomocyst(e)inaemia is common and most often due to mild nutritional deficiencies in the B vitamins (folic acid, vitamin B(12) and vitamin B(6)). While high homocyst(e)ine levels can be effectively lowered using folic acid and other B vitamins, it is unknown whether such vitamin therapy will lead to clinical benefits. Given that strategies for homocyst(e)ine-lowering are safe and inexpensive, however, even small reductions in CHD risk will be highly cost effective. Thus, it may be prudent for patients to ensure an adequate daily intake of dietary folic acid and other B vitamins and for physicians to screen high-risk adults such as those with established CHD as we await definitive results from ongoing clinical trials.

Coronary Disease↗
PubMedDate not supplied

Development of natural protein microarrays for diagnosing cancer based on an antibody response to tumor antigens.

The detection of autoantibodies to tumor antigens has potential utility for the early diagnosis of cancers. In previous studies, we have identified tumor antigens based on Western blot analysis of tumor cell lysates that were incubated with subject sera to identify proteins that elicit specific reactivity in sera from patients with the corresponding tumor type. More recently, we have explored the use of microarrays spotted with tumor proteins as an alternative to Western blots. Microarrays provide a high throughput, high sensitivity alternative to the use of Western blots for tumor antigen profiling. In this study, we have assessed the reproducibility of natural protein microarrays and their ability to distinguish between lung cancer sera and controls. Protein lysates from the A549 human lung adenocarcinoma cell line were separated into 1840 fractions that were spotted in duplicate, along with various controls, on nitrocellulose coated slides. Sera from 18 newly diagnosed patients with lung cancer and from 15 healthy controls were each hybridized to an individual microarray. The reactivity of arrayed proteins with Ig was determined by incubation with biotinylated goat-anti-human-Ig followed by phycoerythrin-conjugated streptavidin. The intensity measures of duplicate spots (within-slide) and duplicate slides (between-slides) were highly reproducible, exhibiting correlation values >0.9. A total of 63 of the 1840 arrayed fractions demonstrated increased reactivity in cancer patients relative to controls as measured by a rank-based statistic (p < 0.008). Microarrays of tumor-derived proteins provide the means for uncovering a repertoire of tumor antigens that have induced an antibody response in patients with specific cancers.

Adenocarcinoma↗
PubMedDate not supplied

Genetic advances will influence the practice of medicine: examples from cancer research and care of cancer patients.

Exciting new techniques of genomics, proteomics, and bioinformatics are beginning to influence the practice of medicine, most notably in diagnosis and drug development for patients with various cancers. Examples are drawn from B-cell lymphomas, melanomas, and prostate, lung, and breast cancers. As in all evidence-based clinical practice, physicians will be better prepared if they understand the nature of the tests and the kinds of information from which they and their consultants will make clinical inferences and assist patients in making clinical decisions. Physicians also can help put new technologies in cultural and ethical context.

Breast Neoplasms↗
PubMedDate not supplied

The crucial role of the public health sciences in the postgenomic era.

Genomic sequence information and gene and protein expression patterns must be linked with information about diet and metabolism, lifestyle behaviors, diseases and medications, and microbial, chemical, and physical exposures. These linkages depend upon the public health sciences: epidemiology, biostatistics, environmental health sciences, pathobiology, health sciences research, and clinical prevention trials.

Environmental Health↗