Studies on the chemopreventive effect of carnitine on tumorigenesis in vivo, using two experimental murine models of colon cancer.

Carnitine is known for its essential role in intermediary metabolism. In vitro studies suggest that its antioxidant and anti-inflammatory properties are potentially beneficial toward cancer prevention. This study tested effects of carnitine on the development of colon cancer in vivo using 2 murine models: azoxymethane (AOM) treatment as a model of carcinogen-induced colon cancer and a genetically induced model using Apc (Min/+) mice.

Matrix metalloproteinase-9 functions as a tumor suppressor in colitis-associated cancer.

There is a well-documented association of matrix metalloproteinase-9 (MMP-9) and receptor Notch-1 overexpression in colon cancer. We recently showed that MMP-9 is also upregulated in colitis, where it modulates tissue damage and goblet cell differentiation via proteolytic cleavage of Notch-1. In this study, we investigated whether MMP-9 is critical for colitis-associated colon cancer (CAC).

Molecular analysis of cell lines from patients with mucolipidosis II and mucolipidosis III.

Mucolipidosis II and III are autosomal recessive disorders due to mutations in the GNPTAB and GNPTG genes encoding the alphabeta- and gamma-subunits of the GlcNAc-1-phosphotransferase, respectively. This protein has a subunit structure of alpha(2)beta(2)gamma(2) and initiates the first step of tagging lysosomal enzymes with mannose-6-phosphate (M6P). In the present study, we screened four MLII and three MLIII cell lines for mutations in GNPTAB and GNPTG.

In vitro studies on the inhibition of colon cancer by butyrate and carnitine.

Objective: Epidemiologic studies support an association between diet and the incidence of colorectal cancer. Butyrate, a short-chain fatty acid present in dietary fiber and dairy products, is a potential anticarcinogenic compound. We previously showed that carnitine can enhance the bioavailability of butyrate in vivo.

PSC 833, an inhibitor of P-glycoprotein inhibits 1,2-dimethylhydrazine-induced colorectal carcinogenesis in male Fischer F344 rats.

Background: The expression of P-glycoprotein (Pgp) is intimately associated with cancer development. In order to explore the therapeutic value of Pgp as a target for chemotherapy, we studied the effect of PSC 833 (PSC), a potent inhibitor of Pgp, on 1,2-dimethylhydrazine (1,2-DMH)-initiated colorectal carcinogenesis in rats.

Materials And Methods: Male Fischer 344 rats, initiated with 1,2-DMH coupled with partial hepatectomy, were exposed to dietary 1% orotic acid for 22 weeks.

Effect of PSC 833, an inhibitor of P-glycoprotein on N-methyl-N-nitrosourea induced mammary carcinogenesis in rats.

Studies in our laboratory on the role of P-glycoprotein (Pgp, coded by mdr1 gene) have led to the hypothesis that over-expression of Pgp is closely associated with the development of cancer. It was conceived therefore that inhibitors of Pgp should inhibit the development of cancer. We have reported that PSC833 (PSC), a potent inhibitor of Pgp, inhibits the development of liver cancer in rats.

Source of a micro-nutrient in a semi-synthetic basal diet as a causative factor in inducing urinary calculi in rats and its inhibition by PSC 833, a potent inhibitor of P-glycoprotein.

We report a serendipitous finding of urinary calculi in rats fed a semi-synthetic basal diet. This observation was made during ongoing studies to evaluate the inhibitory effect of PSC 833, a potent inhibitor of P-glycoprotein, on development of tumors in rodent tumor model systems. A large number of specific-pathogen-free (SPF) female Sprague-Dawley and SPF male Fischer 344 rats being fed the diet were euthanized when it became evident clinically that they were uremic.

Effect of PSC 833, an inhibitor of P-glycoprotein, on 1,2-dimethylhydrazine-induced liver carcinogenesis in rats.

The present study explores the hypothesis that over-expression of P-glycoprotein (Pgp, product of mdr1) is intimately associated with liver cancer development and therefore inhibitors of Pgp should inhibit the development of liver cancer. Accordingly, we determined the effect of PSC833 (PSC), a potent inhibitor of Pgp, on experimental liver carcinogenesis in rats. To study the effects of PSC on liver cancer development, a daily dose of 30 mg PSC/kg body wt (PSC30) was chosen based on an initial dose-response experiment.