Biomedical subjects

Balazs Györffy

Publications and source records attributed to Balazs Györffy.

4 recordsLinked to original sources

PubMed2006

A Web-based data warehouse on gene expression in human malignant melanoma.

The identification of melanoma-specific dysregulated genes could identify new molecular markers. By applying bioinformatic tools for screening of biomedical databases, a melanoma-specific gene expression profile "data warehouse" was constructed. Utilizable data sets of global gene expression analyses were available from nine studies that applied different technology platforms. A single study used cell lines, five investigations analyzed cell lines and tissues obtained from patients, two studies used exclusively specimens obtained from patients, and one study analyzed blood cells prepared from patients. The total number of investigated patients was 116. From 815 differential-regulated genes, 772 (95%) were identified merely in a single study, 37 in at least two studies, five (RAB33A, ERBB3, ADRB2, MERTK, SNF1LK, and ITPKB) in at least three studies, and a single gene, RAB33A, in four studies. These data show that the accuracy, reproducibility, and comparability among different gene expression profile studies are low in melanoma. In conclusion, the study demonstrates the high diversity of gene expression profiles associated with melanoma, the necessity to include a sufficient number of samples regarding clinical standards, for the design of standardized sample collecting and preparation, for the development of common standards for microarray data processing, and for developing standardized bioinformatic tools.

Cell Line↗

PubMed2006

Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations.

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.

Antineoplastic Agents↗

PubMed2006

Analysis of gene expression profiles in melanoma cells with acquired resistance against antineoplastic drugs.

Resistance to various antineoplastic agents is common in the clinical management of malignant melanoma. The biological mechanisms conferring these different drug-resistant phenotypes are still unclear. To identify potential factors mediating drug resistance to melanoma cells, the mRNA expression profiles of the parental drug-sensitive human melanoma cell line MeWo and four derived drug-resistant sublines with acquired resistance against four commonly used drugs for melanoma treatment (cisplatin, etoposide, fotemustine and vindesine) were analysed. We investigated cDNA arrays with 43,000 cDNA clones ( approximately 30,000 unique genes) to study the expression patterns of these cell lines. We were able to simultaneously extract new candidate genes associated with drug resistance in malignant melanoma and to correlate the present findings with previously described resistance-associated genes. Using hierarchical clustering and analysing the overlap of genes with altered expression, we detected similarities between the expression signatures related to cisplatin and fotemustine resistance. The resistance against vindesine required a minimal set of changes in gene expression relative to the parental MeWo cell line. Our study provides new data that may be used to obtain further insight into the resistance characteristics of malignant melanoma.

Cell Line, Tumor↗

PubMed2006

Stromal myofibroblasts in breast cancer: relations between their occurrence, tumor grade and expression of some tumour markers.

It is suggested that tumour stromal myofibroblasts exert an unfavourable effect on the biology of breast cancer. We are aware of only a single study which examined relationships between manifestation of myofibroblasts in the stroma of breast cancer and clinicopathological data of the patients. The present study was aimed at estimation of the effect exerted by myofibroblasts present in the tumour stroma on principal pathological parameters and on expression of Ki67, P53 and HER-2 proteins in the group of the most frequent breast cancers, the ductal cancers. In paraffin sections of 60 ductal breast cancers (20 cases in G1, 20 in G2 and 20 in G3), immunohistochemical reactions were performed to detect expression of smooth muscle actin (SMA) in order to visualize myofibroblasts, Ki67, P53 and HER-2. The studies demonstrated that the most numerous myofibroblasts were present in G3 cases and they were the least frequent in G1 cases (P = 0.02). Positive correlations were observed between the presence of myofibroblasts in tumour stroma and expression of Ki67 and HER-2 in breast cancer cells in the entire group (P < 0.001 and P = 0.001, respectively), in G2 cases (P = 0.003 and P = 0.03) and in G3 cases (P = 0.01 and P = 0.03). Considering that the higher grade, Ki67 and HER-2 are thought to represent unfavourable prognostic factors, the elevated content of myofibroblasts in tumour stroma is probably typical for cases with worse prognosis.

Actins↗