Identification of novel genes associated with the response to 5-FU treatment in gastric cancer cell lines using a cDNA microarray

Park, Ji‐Seon; Yoon, Sun Young; Kim, Jeongmin; Yeom, Young Il; Kim, Yong‐Sung; Kim, Nam-Soon

doi:10.1016/j.canlet.2004.04.012

Cited by 42 publications

(24 citation statements)

References 29 publications

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“…Recently, a number of studies have examined the potential of DNA microarrays to provide insight into the factors that determine 5-FU response by analyzing genes acutely altered following exposure to this agent (22)(23)(24). Despite this, the downstream molecular events underlying the cytotoxic effects of 5-FU remain poorly characterized.…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenomic Identification of Novel Determinants of Response to Chemotherapy in Colon Cancer

et al. 2006

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DNA microarray analysis was used to analyze the transcriptional profile of HCT116 colorectal cancer cells that were treated with 5-fluorouracil (5-FU) or oxaliplatin and selected for resistance to these agents. Bioinformatic analyses identified sets of genes that were constitutively dysregulated in drug-resistant cells and transiently altered following acute exposure of parental cells to drug. We propose that these genes may represent molecular signatures of sensitivity to 5-FU and oxaliplatin. Using real-time reverse transcription-PCR (RT-PCR), the robustness of our microarray data was shown with a strong overall concordance of expression trends for z82% (oxaliplatin) and z85% (5-FU) of a representative subset of genes. Furthermore, strong correlations between the microarray and real-time RT-PCR measurements of average fold changes in gene expression were observed for both the 5-FU (R 2 z 0.73) and oxaliplatin gene sets (R 2 z 0.63). Functional analysis of three genes identified in the microarray study [prostate-derived factor (PDF), calretinin, and spermidine/spermine N 1 -acetyl transferase (SSAT)] revealed their importance as novel regulators of cytotoxic drug response. These data show the power of this novel microarray-based approach to identify genes which may be important markers of response to treatment and/or targets for therapeutic intervention. (Cancer Res 2006; 66(5): 2765-77)

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Section: Discussionmentioning

confidence: 99%

Pharmacogenomic Identification of Novel Determinants of Response to Chemotherapy in Colon Cancer

et al. 2006

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“…Recently, a wide variety of factors involved in the prediction of chemotherapy with 5-FU against gastrointestinal carcinoma including OSCC was identified (13). The degree of thymidylate synthase (TS), DPD and OPRT protein expression is thought to be one of the most reliable factors.…”

Section: Introductionmentioning

confidence: 99%

Effects of Lentinan alone and in combination with fluoropyrimidine anticancer agent on growth of human oral squamous cell carcinoma in vitro and in vivo

Harada

Itashiki²,

Takenawa³

et al. 2010

Int J Oncol

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Abstract. Chemotherapy has shown little antitumor activity against advanced oral squamous cell carcinoma (OSCC) patients. Therefore, there is an urgent need to develop more effective therapeutic methods for patients with advanced OSCC. Lentinan, ß-(1➝3)-D-glucan, an extract from the edible mushroom, Lentinus edodes, has been reported to show direct antitumor effects and various immunomodulatory effects. S-1 is an oral antineoplastic agent that can induce apoptosis in various types of cancer cells, including OSCC. Hence, combined treatment of cancer cells with Lentinan and S-1 might exert dramatic antitumor effects on OSCC cells. In this study, the response of human OSCC cells to Lentinan alone and in combination with S-1 was examined using nude mouse xenograft models. S-1 (6.9 mg/kg/day, 7 times/week) was administered orally and Lentinan (0.1 mg/kg/day, 2 times/ week) was injected into peritumoral tissue for three weeks. Apoptotic cells were detected by a TUNEL method. The gene expression level of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT) was determined using microdissection and RT-PCR, and their protein levels were determined using ELISA. Combined therapy of Lentinan and S-1 markedly exerted antitumor effects on human OSCC xenografts and significantly induced apoptotic cells in tumors treated with Lentinan plus S-1. Microdissection and RT-PCR revealed that the expression of TS and DPD mRNA was downregulated and that expression of OPRT mRNA was upregulated in tumors administered the combined treatment. Moreover, ELISA indicated that the protein levels of TS and DPD were down-regulated, and that OPRT was up-regulated in tumors treated with the combined therapy. During the experimental period, no loss of body weight was observed in mice treated with the combined therapy. These findings demonstrate that the combination of Lentinan and S-1 is effective against OSCC and has the potential of being a new therapeutic tool for future treatment of these tumors.

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“…Thus, we used untreated colorectal cancer cell lines instead of cell lines with acquired drug-resistance (20), or cell lines immediately following drug treatment (21). Although we used a small number of cell lines, we were able to identify representative cell lines resistant and sensitive to particular anticancer drugs used for colorectal cancer and identify the genes which could predict chemosensitivity.…”

Section: Discussionmentioning

confidence: 99%

Putative chemosensitivity predictive genes in colorectal cancer cell lines for anticancer agents

et al. 2007

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Abstract. In order to identify genes which could predict chemosensitivity in colorectal cancer, gene expression and chemosensitivity were examined in colorectal cancer cell lines. Gene expression profiling of 5 colorectal cancer and 3 normal cell lines was performed using a 22K spotted oligonucleotide microarray. The IC 50 s of 17 anticancer drugs were determined using the MTT assay for chemosensitivity. The SOURCE database, KEGG Pathway database, and Molecular Diagnosis Score (MDS) were used for data analysis. Two representative colorectal cancer cell lines were identified which were resistant or sensitive to drugs commonly used for colon cancer treatment (5-FU, irinotecan and topotecan). Six hundred and eighty-three genes that were up-or down-regulated by >4-fold between the two cell lines were selected. Pathway analysis was performed with 147 of the 683 genes using the KEGG Pathway database. This analysis revealed 27 genes in the apoptosis, MAPK signaling, and focal adhesion pathways, which could explain the mechanism of chemosensitivity in colorectal cancer cell lines. In addition, the chemosensitivity of other colorectal cancer and normal cell lines was predictable with the selected 27 genes. These genes may act as putative predictive markers for chemosensitivity in chemo-naive colorectal cancer patients following functional analysis and clinical validation.

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Identification of novel genes associated with the response to 5-FU treatment in gastric cancer cell lines using a cDNA microarray

Cited by 42 publications

References 29 publications

Pharmacogenomic Identification of Novel Determinants of Response to Chemotherapy in Colon Cancer

Pharmacogenomic Identification of Novel Determinants of Response to Chemotherapy in Colon Cancer

Effects of Lentinan alone and in combination with fluoropyrimidine anticancer agent on growth of human oral squamous cell carcinoma in vitro and in vivo

Putative chemosensitivity predictive genes in colorectal cancer cell lines for anticancer agents

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