Inhibition of cell proliferation, vascular endothelial growth factor and tumor growth by albendazole.

Vascular endothelial growth factor (VEGF) is the key molecule mediating tumor growth and malignant ascites formation. We recently reported that, in an end stage OVCAR-3 xenograft model, albendazole (ABZ) suppresses ascites formation, but not tumor growth. Hence, in the present study, we assessed the effect of ABZ on in vitro OVCAR-3 cell proliferation plus in vivo tumor growth, however, initiating ABZ treatment at mid stage (3 weeks post cell inoculation) rather than end stage disease. Here, ABZ treatment led to potent inhibition of cell proliferation, VEGF suppression, complete inhibition of ascites formation and most strikingly arrest of tumor growth.

Pharmacokinetics of albendazole in New Zealand white rabbits: oral versus intraperitoneal administration.

BACKGROUND: Recent studies from our group have shown the potent antitumor effects of albendazole (ABZ). It was hypothesized that intraperitoneal (i.p.) administration of ABZ in peritoneal carcinomatosis (PC) could lead to long exposure of tumor cells to high concentration of the drug and possibly to reduced systemic toxicity. MATERIALS AND METHODS: Eight male New Zealand white rabbits were randomized into two groups, all given a single dose of ABZ 150 mg/kg suspended in 0.5% carboxymethylcellulose (CMC), either as i.p. injection, or as oral administration. The concentration of ABZ and its metabolites in plasma were determined using a high performance liquid chromatography method. RESULTS: The parent drug was detected in plasma after oral and i.p. administration. The C(max) of albendazole sulphoxide (ABZ-SO) resulted in a much higher plasma concentration in the oral group (41.86 microg/ml) than in the i.p. group (16.84 microg/ml, p < 0.05). The area under the concentration over time curve of ABZ-SO in the oral group (1010.43 microg/ml/h) was also significantly higher than that of the i.p. group (528.33 microg/ml/h, p < 0.05). Compared to oral administration, the i.p. administration of an ABZ suspension led to significantly lower plasma levels of the major metabolite (ABZ-SO). This could have considerable therapeutic benefits in the regional treatment of PC.

Delta tryptase is expressed in multiple human tissues, and a recombinant form has proteolytic activity.

Tryptases are neutral serine proteases selectively expressed in mast cells and have been implicated in the development of a number of inflammatory diseases including asthma. It has recently been established that the number of genes encoding human mast cell tryptases is much larger than originally believed, but it is not clear how many of these genes are expressed. A recent report suggested that the transcript for at least one of these genes, originally named mMCP-7-like tryptase, is not expressed. To further address this question, we screened tissue-specific RNA samples by RT-PCR, using primers designed to match the putative exonic sequence of this gene. We successfully generated and cloned the correctly sized RT-PCR product from mRNA isolated from the human mast cell-I cell line. Two distinct clones were identified whose nucleotide sequence matched the published sequence of the mMCP-7-like I and mMCP-7-like II genes. Transcripts were detected in a wide variety of human tissues including lung, heart, stomach, spleen, skin, and colon. A polyclonal antipeptide Ab that specifically recognizes the translated product of this transcript was used to demonstrate its expression in mast cells that reside in the colon, lung, and inflamed synovium. A recombinant form of this protein expressed in bacterial cells was able to cleave a synthetic trypsin-sensitive substrate, D-Ile-Phe-Lys pNA. These results suggest that the range of functional tryptases is larger than previously recognized. For simplicity, we suggest that the gene, transcripts, and corresponding protein product be named delta tryptase.