Increased Sensitivity to Cisplatin in Gastric Cancer by Antisense Inhibition of the HER-2/neu (c-erbB-2) Gene

Funato, Tadao; Kozawa, Kanoko; Fujimaki, Shin; Miura, Takeshi; Kaku, Mitsuo

doi:10.1159/000048537

Cited by 23 publications

(11 citation statements)

References 24 publications

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“…The prognosis of patients with peritoneal metastasis of gastric cancer is poor, and a standard regimen against peritoneal metastasis of gastric cancer has not yet been established [3,25] . Combinations of conventional agents, such as FAMTX (fl uorouracil/doxorubicin/methotrexate), MTX/5-FU (methotrexate/fl uorouracil), FAM (fl uorouracil/doxorubicin/mitomycin) and FP (fl uorouracil/ cisplatin), have been employed for treatment of such patients [26] .…”

Section: Discussionmentioning

confidence: 99%

Efficacy of S-1 for Patients with Peritoneal Metastasis of Gastric Cancer

Ishizone

Maruta²,

Saito³

et al. 2006

Chemotherapy

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Background: This study was designed to examine the efficacy and compliance of S-1 for the patients with peritoneal metastasis of gastric cancer. Methods: Sixteen consecutive patients with peritoneal metastasis of gastric cancer were treated with S-1. Their survival was compared with that of the historical control group (25 patients). Thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase and orotate phosphoribosyl transferase mRNA expression in the tumor were evaluated. Results: The median survival time of S-1-treated patients was 550 days, which was significantly longer than that of the historical control group (215 days). We elucidated some factors to prolong the survival of the patients treated with S-1 for peritoneal metastasis: peritoneal metastasis without other distant metastases, the combination of S-1 treatment and gastrectomy, and low expression of thymidine phosphorylase mRNA in primary tumors. Conclusions: S-1 showed a surprisingly long-term survival with minimum toxicity in patients with peritoneal metastasis of gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Efficacy of S-1 for Patients with Peritoneal Metastasis of Gastric Cancer

Ishizone

Maruta²,

Saito³

et al. 2006

Chemotherapy

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“…The 5-year survival rate was 16% for the patients treated with radiotherapy alone [10]. The differences in the response rates are caused by various factors including the primary site, differentiation of tumor, tumor size, progression, general nutritional status, mutant p53, the amount of DNA in cancer cells, the action mechanism of anticancer drugs, and the nature of arrest/apoptotic stimulus [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Effects of Cisplatin, 5-Fluorouracil, and Radiation on Cell Cycle Regulation and Apoptosis in the Hypopharyngeal Carcinoma Cell Line

et al. 2005

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In head and neck cancer including hypopharyngeal cancer, cisplatin and 5-fluorouracil (5-FU) usually have been used as neoadjuvant chemotherapeutic agents. We investigated the effects of cisplatin, 5-FU and radiation on p53 protein expression and cell responses (cell cycle arrest and/or apoptosis) in the hypopharyngeal carcinoma cell line (PNUH-12; mutant type p53). PNUH-12 cells were treated with cisplatin, 5-FU and radiation. The changes in the cells were assessed by a cell cytotoxicity assay, Western blotting (p53 and p21^WAF1/CIP1 proteins), a DNA fragmentation assay, propidium iodide (PI) staining and DNA flow cytometry. The expression of p53 protein was increased after treatment with cisplatin and 5-FU, but not radiation. The expression of p21^WAF1/CIP1 protein was increased only after treatment with 5-FU, not cisplatin or radiation. With cisplatin and radiation, we observed apoptosis both by DNA fragmentation and PI staining and increased S phase in cisplatin and G2 phase in radiation by DNA flow cytometry. But, with 5-FU, we could not observe apoptosis by DNA fragmentation and PI stain but only an increased G1 phase by DNA flow cytometry. In PNUH-12, radiation induced p53-independent apoptosis and p21^WAF1/CIP1-independent G2-phase cell cycle arrest. Cisplatin induced p53-dependent apoptosis and p21^WAF1/CIP1-independent S-phase cell cycle arrest and 5-FU induced p53 and p21^WAF1/CIP1-dependent G1-phase cell cycle arrest, not apoptosis. Cisplatin and 5-FU induced p53-dependent pathways, but radiation p53-independent pathway. The cell responses by cisplatin, 5-FU and radiation were all different pathways.

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“…Amplification of the EGF-R and/or the HER2/NEU oncogenes, and over-expression of their proteins, have been reported at various levels in gastric adenocarcinoma (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). In fact, correlations between Her-2/neu protein overexpression and HER2/NEU gene amplification have been reported (49)(50)(51)(52), and overexpression of Her-2/neu appears to be an independent prognostic factor in gastric cancer (18,(45)(46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

“…Studies using cell lines (51,53) have revealed a potential therapeutic use in targeting the Her-2/neu signaling pathway. Ex vivo analysis of our tumors, however, reveal a high degree of intra-tumor heterogeneity in Her-2/neu expression.…”

Section: Discussionmentioning

confidence: 99%

Signal Transduction Proteins in Tumors From Puerto Rican and Caucasian Gastric Adenocarcinoma Patients: Expression Differences With Potential for Specific Targeted Therapies

Cangiano¹,

Centeno

Garrett

et al. 2008

Dig Dis Sci

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Gastric cancer is the second cause of cancer death with approximately 800,000 annual new cases reported worldwide. The incidence of gastric adenocarcinoma has progressively increased, while 5-year survival rates of 20% have remained unchanged for several decades. New strategies for early detection and treatment remain a significant unmet medical need. Advances in our understanding of signal transduction mechanisms have led to novel treatment approaches in a variety of tumors. Over-expression of the HER2/NEU gene is associated with aggressive behavior and poor prognosis in breast cancer, and this has made the Her2/neu protein a target for directed therapy. Several reports indicate that there are ethnic differences in the clinical behavior of gastric cancer, but the reasons for this observation are not clearly understood. We have investigated potential differences in the expression of selected signal transduction proteins (Her2/neu, EGF-R, Cyclin D1 and p-Stat3) in gastric cancers from 100 Puerto Rican and 95 Caucasian patients. Puerto Rican patients had higher disease stages at presentation (Stage IV disease was observed in 44% of Puerto Ricans and in 18% of Caucasians). The majority of tumors in both populations showed over-expression of p-Stat3 but there were no statistical significant differences between the two groups. Her2/neu was over-expressed in the tumors of both patient populations but at higher HHS Public Access

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Increased Sensitivity to Cisplatin in Gastric Cancer by Antisense Inhibition of the HER-2/neu (c-erbB-2) Gene

Cited by 23 publications

References 24 publications

Efficacy of S-1 for Patients with Peritoneal Metastasis of Gastric Cancer

Efficacy of S-1 for Patients with Peritoneal Metastasis of Gastric Cancer

Effects of Cisplatin, 5-Fluorouracil, and Radiation on Cell Cycle Regulation and Apoptosis in the Hypopharyngeal Carcinoma Cell Line

Signal Transduction Proteins in Tumors From Puerto Rican and Caucasian Gastric Adenocarcinoma Patients: Expression Differences With Potential for Specific Targeted Therapies

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