Prediction of outcome of advanced cervical cancer to thermoradiotherapy according to expression profiles of 35 genes selected by cDNA microarray analysis
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
Authors: Harima, Y; Togashi, A; Horikoshi, K; Imamura, M; Sougawa, M; Sawada, S; Tsunoda, T; Nakamura, Y; Katagiri, T
Abstract
Purpose: To identify a set of genes related to thermoradiosensitivity of cervical carcinoma and to establish a predictive method. Methods and Materials: A total of 19 patients with cervical cancer (1 with Stage IIIA, 11 with Stage IIIB, 5 with Stage IVA, and 2 with Stage IVB) who underwent definitive thermoradiotherapy between May 1995 and August 2001 were included in this study. We compared the expression profiles of 8 thermoradiosensitive and 11 thermoradioresistant tumors obtained by punch biopsy before treatment using a cDNA microarray consisting of 23,040 human genes. Results: We selected 35 genes on the basis of a clustering analysis and confirmed the validity of these genes with a cross-validation test. Some of these genes were already known to be associated with apoptosis (BIK, TEGT, SSI-3), hypoxia-inducible genes (HIF1A, CA12), and tumor cell invasion and metastasis (CTSL, CTSB, PLAU CD44). We developed a "predictive score" system that could clearly separate the thermoradiosensitive group from the thermoradioresistant group. Conclusion: These results from the treatment program between May 1995 and August 2001 showed that by using gene-expression profiles we can predict the outcome of thermoradiotherapy for advanced cervical carcinoma. A "predictive score" system was developed that could clearly separate the thermoradiosensitive group from the thermoradioresistant group. These results may eventually lead to the achievement of "personalized therapy" for this disease. (C) 2004 Elsevier Inc.
Candida albicans CHT3 encodes the functional homolog of the Cts1 chitinase of Saccharomyces cerevisiae
FUNGAL GENETICS AND BIOLOGY
Authors: Dunkler, A; Walther, A; Specht, CA; Wendland, J
Abstract
Chitin synthesis and chitin degradation play an important role in cellular morphogenesis and influence the cell shape of fungal organisms. The Candida albicans genome contains four chitinase genes, CHT1, CHT2, and CHT3, which are homologous to the Saccharomyces cerevisiae CTS1 vene and C. albicans CHT4, Which is homologues to S. cerevisiae CTS2. To determine which of the C albicans CHT genes represents the functional homolog of the S. cerevisiae CTS1 gene we constructed mutants of these genes and characterized the resulting phenotypes using Morphological assays such as in vivo time lapse microscopy and enzymatic assays to determine the chitinase activity. Deletion of CaCHT1 and CaCHT2 provided no phenotypic alterations in liquid Culture but resulted in increased hyphal growth on solid media. Deletion of CaCHT3 generated chains of unseparated cells in the yeast growth phase strongly resembling the ctsl deletion phenotype of S. cerevisiae cells. Expression of CHT3 under control of the regulatable MAL2-promoter in C albicans resulted in the reversion of the cell separation defect when cells were grown in maltose. Cht3, but not Cht2 when expressed in S. cerevisiae was also able to reverse the cell separation defect of the S. cerevisiae c tsl deletion strain. Measurements of chitinase activity from yeast cells of C. albicans showed that Cht2 is bound to cells, consistent with it being GPI-anchored while Cht3 is secreted into growth medium; Cht3 is also the principal, observed activity. (c) 2005 Elsevier Inc. All rights reserved.