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Prediction Analysis (prediction + analysis)
Selected AbstractsGene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrationsINTERNATIONAL JOURNAL OF CANCER, Issue 7 2006Balazs Györffy Abstract Cancer patients with tumors of similar grading, staging and histogenesis can have markedly different treatment responses to different chemotherapy agents. So far, individual markers have failed to correctly predict resistance against anticancer agents. We tested 30 cancer cell lines for sensitivity to 5-fluorouracil, cisplatin, cyclophosphamide, doxorubicin, etoposide, methotrexate, mitomycin C, mitoxantrone, paclitaxel, topotecan and vinblastine at drug concentrations that can be systemically achieved in patients. The resistance index was determined to designate the cell lines as sensitive or resistant, and then, the subset of resistant vs. sensitive cell lines for each drug was compared. Gene expression signatures for all cell lines were obtained by interrogating Affymetrix U133A arrays. Prediction Analysis of Microarrays was applied for feature selection. An individual prediction profile for the resistance against each chemotherapy agent was constructed, containing 42,297 genes. The overall accuracy of the predictions in a leave-one-out cross validation was 86%. A list of the top 67 multidrug resistance candidate genes that were associated with the resistance against at least 4 anticancer agents was identified. Moreover, the differential expressions of 46 selected genes were also measured by quantitative RT-PCR using a TaqMan micro fluidic card system. As a single gene can be correlated with resistance against several agents, associations with resistance were detected all together for 76 genes and resistance phenotypes, respectively. This study focuses on the resistance at the in vivo concentrations, making future clinical cancer response prediction feasible. The TaqMan-validated gene expression patterns provide new gene candidates for multidrug resistance. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat. © 2005 Wiley-Liss, Inc. [source] A novel CD4+ T-helper lymphocyte epitope in the VP3 protein of hepatitis A virusJOURNAL OF MEDICAL VIROLOGY, Issue 4 2004Glòria Sánchez Abstract Prediction analysis of TH -cell epitopes in the VP3 capsid protein of the hepatitis A virus (HAV) revealed the occurrence of a putative TH epitope in the 102,121 region complying with all the algorithms tested. To confirm these predictions, spleen T lymphocytes obtained from BALB/c mice previously immunised with HAV, were stimulated in vitro with different concentrations of synthetic peptides 102,121 and 110,121 of VP3. The ability of these peptides to stimulate CD4+ T-helper lymphocytes proliferation was evaluated by an immunological flow cytometry detection of bromodeoxyuridine incorporation. Using this method, it is concluded that the amino terminal part of the VP3 102,121 sequence contains a T cell epitope. J. Med. Virol. 72:525,532, 2004. © 2004 Wiley-Liss, Inc. [source] Biogenesis of Yersinia pestis PsaA in recombinant attenuated Salmonella Typhimurium vaccine (RASV) strainFEMS MICROBIOLOGY LETTERS, Issue 2 2010Ascención Torres-Escobar Abstract Yersinia pestis PsaA is an adhesin important for the establishment of bacterial infection. PsaA synthesis requires the products of the psaEFABC genes. Here, by prediction analysis, we identified a PsaA signal sequence with two signal peptidase (SPase) cleavage sites, type-I and type-II (SPase-I and SPase-II). By Edman degradation and site-directed mutagenesis, the precise site for one of these Spase-I PsaA cleavage sites was located between alanine and serine at positions 31 and 32, respectively. Yersinia pestis psaA expression and the role of the PsaB and PsaC proteins were evaluated in recombinant attenuated Salmonella Typhimurium vaccine strains. PsaA was detected in total extracts as a major 15-kDa (mature) and 18-kDa (unprocessed) protein bands. PsaA synthesis was not altered by a ,A31,,S32 double-deletion mutation. In contrast, the synthesis of PsaA (,A31,,S32) in Y. pestis and delivery to the supernatant was decreased. Otherwise, substitution of the amino acid cysteine at position 26 by valine involved in the SPase-II cleavage site did not show any effect on the secretion of PsaA in Salmonella and Yersinia. These results help clarify the secretion pathway of PsaA for the possible development of vaccines against Y. pestis. [source] Whole genome analysis for liver metastasis gene signatures in colorectal cancerINTERNATIONAL JOURNAL OF CANCER, Issue 9 2007Dong Hyuk Ki Abstract Liver metastasis is one of the major causes of death in colorectal cancer (CRC) patients. To understand this process, we investigated whether the gene expression profiling of matched colorectal carcinomas and liver metastases could reveal key molecular events involved in tumor progression and metastasis. We performed experiments using a cDNA microarray containing 17,104 genes with the following tissue samples: paired tissues of 25 normal colorectal mucosa, 27 primary colorectal tumors, 13 normal liver and 27 liver metastasis, and 20 primary colorectal tumors without liver metastasis. To remove the effect of normal cell contamination, we selected 4,583 organ-specific genes with a false discovery rate (FDR) of 0.0067% by comparing normal colon and liver tissues using significant analysis of microarray, and these genes were excluded from further analysis. We then identified and validated 46 liver metastasis-specific genes with an accuracy of 83.3% by comparing the expression of paired primary colorectal tumors and liver metastases using prediction analysis of microarray. The 46 selected genes contained several known oncogenes and 2 ESTs. To confirm that the results correlated with the microarray expression patterns, we performed RT-PCR with WNT5A and carbonic anhydrase II. Additionally, we observed that 21 of the 46 genes were differentially expressed (FDR = 2.27%) in primary tumors with synchronous liver metastasis compared with primary tumors without liver metastasis. We scanned the human genome using a cDNA microarray and identified 46 genes that may play an important role in the progression of liver metastasis in CRC. © 2007 Wiley-Liss, Inc. [source] | ||||||||||