cDNA Microarray Analysis of Differential Gene Expression in Gastric Cancer Cells Sensitive and Resistant to 5-Fluorouracil and Cisplatin / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Gastric cancer is one of the most prevalent cancers worldwide. 5-fluorouracil (5-FU) and cisplatin are the most commonly used drugs for the treatment of gastric cancer. However, a significant number of tumors often fail to respond to chemotherapy. MATERIALS AND METHODS: To better understand the molecular mechanisms underlying drug resistance in gastric cancer the gene expression in gastric cancer cells, which were either sensitive or resistant to 5-FU and cisplatin, were examined using cDNA microarray analysis. To confirm the differential gene expression, as determined using the microarray, semiquantitative RT-PCR was performed on a subset of differentially expressed cDNAs. RESULTS: 69 and 45 genes, which were either up-regulated (9 and 22 genes) or down-regulated (60 and 25 genes), were identified in 5-FU- and cisplatin-resistant cells, respectively. Several genes, such as adaptor-related protein complex 1 and baculoviral IAP repeat-containing 3, were up-regulated in both drug-resistant cell types. Several genes, such as the ras homolog gene family, tropomyosin, tumor rejection antigen, protein disulfide isomerase-related protein, melanocortin 1 receptor, defensin, cyclophilin B, dual specificity phosphatase 8 and hepatocyte nuclear factor 3, were down-regulated in both drug-resistant cell types. CONCLUSION: These findings show that cDNA microarray analysis can be used to obtain gene expression profiles that reflect the effect of anticancer drugs on gastric cancer cells. Such data may lead to the assigning of signature expression profiles of drug-resistant tumors, which may help predict responses to drugs and assist in the design of tailored therapeutic regimens to overcome drug resistance.

Combination Chemotherapy of Heptaplatin, Paclitaxel and 5-Fluorouracil in Patients with Advanced Gastric Cancer: a Pilot Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the efficacy and toxicity of heptaplatin, paclitaxel, and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer. MATERIALS AND METHODS: Between July 2002 and September 2003, nineteen patients were enrolled in this study. Paclitaxel 135 mg/m(2) iv on day 1, heptaplatin 400 mg/m(2) iv on day 2 and 5-fluorouracil 800 mg/m(2) on day 2~4 were administered and the regimen was repeated every 3 weeks. RESULTS: The median age of the patients was 60 years (range: 32~74) and the most common sites of metastasis were liver and lymph nodes. In the 16 evaluated patients, the overall response rate was 43.8%, but this was without any complete response. The median time to disease progression was 3.93 months (range: 0.26~8.1) and the median response duration for the 7 responding patients was 3.83 months (range: 1.48~6.07). The median overall survival for 19 patients was 7.01 months (range: 0.26~17.44). A median of 3 cycles (range: 1~7) and a total of 65 cycles were administered and evaluated for toxicity. The most common hematologic toxicities were NCI grade I/II anemia (47.7%), neutropenia (9.2%) and thrombocytopenia (6.2%). The most common non-hematologic toxicities more than grade II were nausea/vomiting (30.8%/9.2%). One elderly patient with ECOG 2 had a life- threatening complication of pneumonia. CONCLUSION: The combination of heptaplatin, paclitaxel, and 5-fluorouracil showed significant activity and favorable toxicity profiles in patients with advanced gastric cancer. However, one elderly patient who had poor performance experienced a life-threatening toxicity/complication. Our results suggest that the efficacy of this combination chemotherapy can be maximized when administered to the patients with good performance status. Further studies with large numbers of patients and long-term follow-up study will be needed.

Combination Chemotherapy of Oxaliplatin and Capecitabine in Patients with Metastatic Colorectal Cancer: a Pilot Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the efficacy and toxicity of oxaliplatin and capecitabine in patients with metastatic colorectal cancer. MATERIALS AND METHODS: Between December 2001 and April 2003, fourteen patients were enrolled in this study. Oxaliplatin, 80 mg/m(2), was administered intravenously on day 1, and capecitabine, 1, 250 mg/m(2) bid po (total daily dose 2, 500 mg/m(2)), was given on days 1~14 of 3 week cycles. RESULTS: The median age of the patients was 57 years (range: 41~74), and the most common sites of metastasis were liver, lung or lymph node. Of the 12 evaluable patients, the overall response rate was 41.7%, but with no complete response. The median response duration and median progression free survival of 12 patients were 42 and 24.4 weeks, respectively. The median overall survival was not reached. A median 6 (range: 1~9), and a total 80, cycles were administered to 14 patients. 80 cycles were evaluable for toxicity. The most common hematological toxicities were NCI grades I/II anemia (45%), leucopenia (33.75%) and thrombocytopenia (17.5%). The most common non-hematological toxicities were nausea/ vomiting (28.75/5%) and neurotoxicity (8.75%). Hand and foot syndrome was noted in only 3.75%. There was no life-threatening toxicity. CONCLUSION: Oxaliplatin and oral capecitabine combination chemotherapy showed significant activity and favorable toxicity in patients with metastatic colorectal cancer. Further studies, with larger numbers of patients and long-tern follow-up will be needed.