Some new AACR abstracts. Here's a couple that are a bit different from the protein profiling for diagnostics stuff. One for dietary alterations aimed at prevention of prostate cancer, and another for cisplatin resistance.
>>Abstract Number: 6304
Inhibition of prostate carcinogenesis in tramp mice by the administration of antioxidants in the diet: Protein profiling by SELDI mass spectrometry
Vasundara Venkateswaran, Haiyan Xu, Laurence H. Klotz, Neil E. Fleshner. Sunnybrook and Women's College Health Sciences Centre, Toronto, ON, Canada; Princess Margaret Hospital, Toronto, ON, Canada.
INTRODUCTION: We have demonstrated that administration of the antioxidants vitamin E, selenium and lycopene in the diet of TRAMP mice at doses comparable to human supplementation inhibits CaP development dramatically. We have used a proteomics approach based on SELDI-ToF mass spectroscopy to identify novel protein biomarkers functionally expressed following micronutrient administration. These offer the potential to identify patients likely to respond to micronutrients and categorize those at high risk for prostate cancer. MATERIALS AND METHODS: Male transgenic animals (LADY TRAMP, 12T-10)were divided into two groups-Control animals that received standard diet and control animals treated with the additives. Animals were maintained on these diets for about 30 weeks. Crude sera were fractionated by anion exchange chromatography and proteins analyzed by SELDI-ToF mass spectroscopy. RESULTS: There was no evidence of antioxidant related toxicity. Micronutrient treated animals had a dramatic reduction in the incidence of prostate cancer compared to controls. A highly restricted subset of proteins was altered in the sera obtained from additive treated transgenic mice. These putative biomarkers were expressed with a high degree of consistency amongst each group. Mass (Da) of proteins altered: 4397, 9078, 3078, 3240, 4170 CONCLUSION: The addition of vitamin E, selenium and lycopene to the diet reduced the incidence of prostate cancer dramatically. Five putative biomarkers were identified. These may be useful as markers of prostate cancer prevention. <<
>>Abstract Number: 5551
Identification of protein biomarkers of cisplatin resistance in tyrosinase-deficient melanocytes by SELDI
Yaacov Ben-David, Brian J. Pak, Jane S. Lee, Ruth Halaban. Sunnybrook and Women's College Health Sciences Centre, Toronto, ON, Canada; Ciphergen Biosystems, Inc., Fremont, CA; Yale University, New Haven, CT.
Pigmentation in cells of melanocytic lineage results from the enzymatic conversion of L-tyrosine to melanins by the coordinated activities of tyrosinase and tyrosinase-related proteins. These proteins, however, have been reported to function in a variety of other cellular pathways. We have recently described an association between the expression of tyrosinase-related protein 2 (TYRP2), also known as dopachrome tautomerase (dct), and the levels of drug resistance in malignant melanoma cells. Here, we analysed the possible involvement of tyrosinase, the rate-limiting enzyme in melanin synthesis, in this resistance pathway. A comparison of survival following treatment with various doses of the chemotherapeutic agent, cisplatin, showed that normal mouse melanocytes were significantly more resistant to drug treatment than tyrosinase-deficient mutant cells. Taken together with our previous findings, these results suggest an association between decreased melanogenic activity and drug resistance. In an attempt to understand the molecular changes underlying tyrosinase-associated cisplatin resistance, surface enhanced laser desorption ionization time-of-flight (seldi-ToF) mass spectrometry was utilized to compare protein expression between the control and tyrosinase-deficient melanocytes. In the normal state, these two cell lines showed remarkable similarity in protein expression with only a few proteins demonstrating differences in expression. However, their response to acute cisplatin treatment was shown to be significantly different. These differentially expressed proteins may represent potential protein markers of cisplatin resistance and the identification of these proteins may enhance our understanding of drug resistance in melanoma. <<
Cheers, Tuck |
