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Richard J Ablin

Publications and source records attributed to Richard J Ablin.

9 recordsLinked to original sources
PubMed2006

Cholecalciferol (vitamin D3) and the retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) are synergistic for chemoprevention of prostate cancer.

Prostate cancer, the most commonly diagnosed cancer among American men, develops slowly over many years. The long latent period of 20 to 30 years, involved in the multistep process of carcinogenesis, provides an important opportunity to block or reverse progression to a malignant state. Vitamin A (retinoids) and vitamin D not only have the ability to block steps in the process of carcinogenesis but they can also modulate or reverse some malignant characteristics of cancer cells. However, at high levels, vitamins A and D have undesirable side effects, thus, limiting effective dose levels and efficacy. Therefore, combination treatment at low doses, to increase efficacy and avoid toxicity, is of special interest. This study examines the effects of the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) in combination with cholecalciferol (vitamin D3) on growth, and on the expression of vimentin, matrix metalloproteinase-2 (MMP-2), and retinoid and vitamin D receptor expression, using the non-tumorigenic, human prostate epithelial cell line RWPE-1. Treatment with 4-HPR and cholecalciferol resulted in synergistic growth inhibition when compared to that caused by each agent alone. A decrease in vimentin expression and MMP-2 activity, and up-regulation of vitamin D receptor (VDR) and some of the retinoid-X (RXRs) and retinoic acid receptor (RARs) subtypes, was observed. These results suggest that combined treatment with 4-HPR and cholecalciferol, at doses lower than what might be effective with single agents, increases their efficacy and suggest that this may serve as an effective strategy for chemoprevention and treatment of prostate cancer.

Anticarcinogenic Agents↗
PubMed2005

A stem cell fusion model of carcinogenesis.

The origin of cancer remains enigmatic. Current models of carcinogenesis based on the gene mutation hypothesis have limitations in explaining many aspects of cancer. We put forward a new model of multistage carcinogenesis and propose that cancer development involves gene mutations and cell fusions. Specifically, cancer can result from a fusion between an "altered" pre-malignant cell and a bone marrow-derived stem cell (BMDSC). "Aneuploidy", which is a hallmark of malignancy, is a direct consequence of this cell fusion. The "stem cell fusion" model explains the remarkable similarities between malignant cells and BMDSC. This model also explains why non-mutagens can be carcinogens, and why non-mutagenic processes, such as wound healing and chronic inflammation, can promote malignant transformation. This model is readily testable. Cancer has been difficult to treat because of tissue heterogeneity and gene instability. However, if the malignant characteristics of cancer cells are derived from BMDSC, new conserved targets such as homing receptors for designing novel therapies may emerge.

Aging↗
PubMed2005

Selection of cell lines with enhanced invasive phenotype from xenografts of the human prostate cancer cell line WPE1-NB26.

Prostate cancer is a leading cause of death from cancer in American men and metastasis the main cause of death. To better understand the disease and accelerate development of new therapies, in vivo models that reflect different disease stages are needed. A family of cell lines that mimics multiple steps in cancer development and tumor progression has been developed in our laboratory from the parent, non-tumorigenic, RWPE-1 cell line by transformation with N-methyl-N-nitrosourea (MNU). The MNU cell lines mimic multiple steps in tumor progression where WPE1-NB26 is the most malignant cell line. WPE1-NB26 cells form metastases in the lungs of athymic, male, nude mice after intravenous injection. Two new cell lines, WPE1-NB26-64 and WPE1-NB26-65, showing more malignant characteristics than the parent WPE1-NB26 cell line, were derived from tumors after subcutaneous injection of WPE1-NB26 cells into nude mice. The WPE1-NB26-64 and WPE1-NB26-65 cell lines show an increase in anchorage-dependent growth and invasive ability as compared to the parent WPE1-NB26 cells. While the parent WPE1-NB26 cells express barely detectable levels, the new cell lines produce high levels of matrix metalloproteinase MMP-2 and detectable levels of MMP-9. By immunostaining, all three cell lines were positive for cytokeratins CK18 and CK5/14. These cell lines, having the same lineage, represent additional steps in the multi-step process of tumor progression and provide novel and useful cell models for studies on tumor progression and for drug development for the treatment of prostate cancer.

Animals↗
PubMed2002

The G-spot.

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Ejaculation↗