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Biomedical subjects

Jan Geliebter

Publications and source records attributed to Jan Geliebter.

10 recordsLinked to original sources
PubMed2005

3,3'-Diindolylmethane, a cruciferous vegetable derived synthetic anti-proliferative compound in thyroid disease.

Considerable epidemiological evidence exists to link thyroid disease with differing patterns of dietary consumption, in particular, cruciferous vegetables. We have been studying the anti-thyroid cancer (TCa) activity of indole-3-carbinol (I3C) found in cruciferous vegetables and its acid catalyzed dimer, 3,3'-diindolylmethane (DIM). There are no studies as yet to elucidate the effect of these compounds on the altered proliferative patterns in goiter or thyroid neoplasia. In this study, we tested the anti-proliferative effects of I3C and DIM on four different thyroid cancer cell lines representative of papillary (B-CPAP and 8505-C) and follicular carcinoma of the thyroid (CGTH-W-1 and ML-1), and primary human goiter cells. Cell survival and IC50 values for I3C and DIM were calculated by the XTT assay and cell cycle distribution analysis was done by flow cytometry. DIM was found to be a better anti-proliferative agent than I3C in both papillary and follicular TCa resulting in a greater cytotoxic effect at a concentration over three fold lower than predicted by the molar ratio of DIM and I3C. The anti-proliferative activity of DIM in follicular TCa was mediated by a G1 arrest followed by induction of apoptosis. DIM also inhibited the growth of primary goiter cells by 70% compared to untreated controls. Contrary to traditional belief that cruciferous vegetables are "goitrogenic", DIM has anti-proliferative effects in glandular thyroid proliferative disease. Our preclinical studies provide a strong rationale for the clinical exploration of DIM as an adjuvant to surgery in thyroid proliferative disease.

Anticarcinogenic Agents↗
PubMed2005

Aging-associated changes in gene expression in the ACI rat prostate: Implications for carcinogenesis.

BACKGROUND: Prostate cancer is the most frequently diagnosed neoplasm and the second leading cause of cancer-related mortality in men. Although the incidence of prostate cancer increases with age, the link between aging and prostate cancer is poorly understood. METHODS: Affymetrix oligonucleotide microarrays were used to analyze the mRNA expression levels in the dorsolateral prostates from 6- and 18-month-old ACI rats. Real-time RT-PCR and immunohistochemistry was performed to validate microarray data in a select set of genes. RESULTS: Microarray analysis revealed changes in gene expression associated with inflammation, oxidative stress, tissue remodeling, and energy metabolism. Most of these changes have been related to increased proliferative status of the prostate, anti-apoptosis, activated stroma, and alteration of the energy metabolism. CONCLUSIONS: Age-associated alterations in the gene expression profile may put the aging prostate in risk for the initiation, promotion, and progression of neoplastic transformation in both our animal model and humans.

Aging↗
PubMed2005

Gene therapy in cancer: the missing point.

Over the last century cancer research has produced data leading to a composite picture where gene mutations and epigenetic phenomena strictly relate and overlap. This complexity has repercussions on the anti-cancer therapeutical strategies. The therapeutic pathway paved by the kochian one-cause/one disease principle fails in front of a multigenic multiphenomena disease like cancer. We still do not know what target(s) to hit/modify in order to prevent/stop the carcinogenic progression. On the light of cancer statistics 2005, we discuss the need of exactly defining the cancer targets in order to exploit the high potential of gene therapy.

Chromosome Aberrations↗
PubMed2004

Interaction of a Mycobacterium tuberculosis repetitive DNA sequence with eukaryotic proteins.

Mycobacterium tuberculosis infects one-third of the world's population and causes two million deaths annually. Its intracellular residence raises the possibility that bacterial nucleic acids might interact with key host proteins and contribute to the pathophysiology of infection. To test this hypothesis, we searched for motifs closely resembling eukaryotic transcription factor binding sites in the M. tuberculosis H37Rv genome and found activator protein-2 and zinc finger protein-5 binding motifs in a 36-nucleotide repetitive mycobacterial DNA sequence (RPT1). RPT1 bound specifically to nuclear extract proteins from U937, A549, and HeLa cells in electrophoretic mobility shift assays but not to activator protein-2. Several nuclear and cytosolic proteins showing at least partial binding specificity for RPT1 were isolated from U937 and A549 cells by pull-down assays, including Ku70 (DNA-dependent protein kinase subunit) and poly(ADP-ribose) polymerase-1. RPT1 also specifically activated DNA-dependent protein phosphorylation. These results suggest that mycobacterial nucleic acid fragments may interact specifically with eukaryotic regulatory proteins which might contribute to bacterial life-cycle maintenance.

Base Sequence↗
PubMed2004

Effect of linoleic acid on proliferation and gene expression in the breast cancer cell line T47D.

Human and animal studies have linked n-6 polyunsaturated fatty acids with mammary carcinogenesis. We investigated the cellular and molecular effects of linoleic acid on the human breast cancer cell line T47D. Linoleic acid had a stimulatory effect on the growth of T47D cells, associated with an increase in the proportion of cells in the S phase of the cell cycle. Microarray, functional group and quantitative PCR analyses indicate that linoleic acid may affect T47D cell growth by modulation of the estrogen receptor (ERalpha), the G13alpha G protein, and p38 MAP kinase gene expression as well genes involved in RNA transcription and cell cycle regulation.

Cell Division↗
PubMed2004

Computational peptide dissection of Melan-a/MART-1 oncoprotein antigenicity.

We have mapped the linear antigenic determinant of a commercial MAb raised in the mouse against the melanoma-associated-antigen Melan-A/MART-1. The B cell epitope on the Melan-A/MART-1 oncoprotein is located in the 15-mer amino acid sequence 101-115 PPAYEKLSAEQSPPP, within residues 102-106. The definition of the antigenic sequence on Melan-A/MART-1 oncoprotein was reached following analyses of MHC II binding potential and similarity level to the mouse proteome, that put into evidence the 15-mer amino acid sequence 101-115 PPAYEKLSAEQSPPP as the top scoring peptide in binding H2-A(d) molecules and the epitopic sequence residues 102-106 (i.e., the peptide sequence PAYEK) as having low-similarity level to the mouse proteome. Dot-blot epitope mapping immunoassay identified proline residue 102 as critical, based on its effect on antibody recognition. The present study adds to previous companion reports in validating the hypothesis that low-similarity to the host's proteome and binding potential to MHC II molecules are essential concurring factors in the modulation of the pool of epitopic sequences.

Amino Acid Sequence↗
PubMed2002

Microarray analysis of diet-induced alterations in gene expression in the ACI rat prostate.

The natural history of prostate cancer is a multistage process that involves the transition from normal tissue to subclinical cancer, with progression to carcinoma in situ and eventually metastatic disease. Evidence suggests that a high-fat diet plays a critical role in the biology and progression of the disease. ACI rats were maintained for two generations on high beef fat or control diets for 18 months. Affymetrix microarrays were used to analyze the mRNA expression levels in the dorsolateral prostates of rats on the different diets. Approximately 4752 genes and expressed sequence tag (EST) were expressed in the prostates of rats on either diet. Twenty-seven genes were upregulated and 28 genes downregulated in the high beef fat diet. Data analysis indicated that a high beef fat diet affects the expression of genes involved in inflammation, glucose and fatty acid metabolism, androgen metabolism, potential tumor suppression and protein kinase activity, as well as intracellular and extracellular matrix molecules, growth factors and androgen responsive genes. Results from these and future studies will lead to a better understanding of the effect of diet on gene expression in the prostate and facilitate the rational design and assessment of potential dietary programs for prostate cancer prevention.

Animals↗
PubMedDate not supplied

Cancer prevention and therapy: strategies and problems.

During the next years, molecular diagnostic science and the pharmaceutical industry will face increasing demand for personalized medicine. Therapeutic treatments should be tailored to the needs of individual patient. Patients will inquire for information about potential tumor detection at an early stage when disease can be more likely to be arrested or cured with specific regimens of drug therapy. To respond to this demand, science and industry need to modulate therapeutic approaches to the continuous development of cancer. Now more than ever, it is necessary to fill the knowledge hiatus between the "beginning" and the "end" of cancer development, i.e we need to critically analyze the extensive multi-step process of cancer development that still remains poorly understood.

Humans↗