Antitumor activity of trastuzumab in combination with chemotherapy in human gastric cancer xenograft models

Fujimoto-Ouchi, Kaori; Sekiguchi, Fumiko; Yasuno, Hideyuki; Moriya, Yoichiro; Mori, Kazushige; Tanaka, Yutaka

doi:10.1007/s00280-006-0337-z

Cited by 173 publications

(116 citation statements)

References 17 publications

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“…12,48,49,52 For HER2 amplification, NCI-N87 cells were used as positive control and MKN-45 and AGS cells were used as negative control. 53,54 In a pilot study of MET, MST1R and HER2 FISH in human GEC, tissue sections from three patients mounted on conventional slides were processed according to Vysis/Abbott Molecular pretreatment protocol for formalin-fixed paraffin-embedded specimens adjusted for gastric epithelia. In all FISH experiments, the hybridization procedure and post-hybridization washes were done as described by Vysis/Abbott Molecular.…”

Section: Methodsmentioning

confidence: 99%

“…To verify the efficiency of homebrewed MET and MST1R probes in formalin fixed and paraffin embedded (FFPE) human gastric cancer sections and to compare GCN FISH results with those of quantitative polymerase chain reaction (qPCR) and array comparative genomic hybridization (aCGH) assays, we performed a pilot FISH study of three randomly selected gastric cancer cases from the cohort of tumors with defined status of GCN detected by these two methods. Results are presented in 53,54 (Fig. 6E).…”

Section: Alterations In Mst1r (Ron) Gene By Fishmentioning

confidence: 99%

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RON(MST1R)is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma

Catenacci

Cervantes

Yala

et al. 2011

Cancer Biology & Therapy

107

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Section: Methodsmentioning

confidence: 99%

Section: Alterations In Mst1r (Ron) Gene By Fishmentioning

confidence: 99%

RON(MST1R)is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma

Catenacci

Cervantes

Yala

et al. 2011

Cancer Biology & Therapy

107

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“…NCI-N87 and SNU216 are cell lines in which HER2 is amplified. The copy number ratio of the HER2 gene determined by FISH analysis was found to be 4.34 for SNU216 cells and 8.4 for N87 cells (14,15). Upon receipt, all cell lines were stored in liquid nitrogen, and passaged for less than 6 months before use for this study.…”

Section: Cell Lines and Culturingmentioning

confidence: 99%

Antitumor Activity of Saracatinib (AZD0530), a c-Src/Abl Kinase Inhibitor, Alone or in Combination with Chemotherapeutic Agents in Gastric Cancer

Nam

et al. 2013

Molecular Cancer Therapeutics

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Src is a nonreceptor tyrosine kinase involved in the cross-talk and mediation of many signaling pathways that promote cell proliferation, adhesion, invasion, migration, and tumorigenesis. Increased Src activity has been reported in many types of human cancer, including gastric cancer. Therefore, this factor has been identified as a promising therapeutic target for cancer treatments, and targeting Src in gastric cancer is predicted to have potent effects. We evaluated the antitumor effect of a c-Src/Abl kinase inhibitor, saracatinib (AZD0530), alone or combined with chemotherapeutic agents in gastric cancer cell lines and a NCI-N87 xenograft model. Among 10 gastric cancer cell lines, saracatinib specifically inhibited the growth and migration/invasion of SNU216 and NCI-N87 cells. Saracatinib blocked the Src/FAK, HER family, and oncogenic signaling pathways, and it induced G 1 arrest and apoptosis in SNU216 and NCI-N87 cells. Apoptosis required induction of the proapoptotic BCL2 family member Bim. Knockdown of Bim using siRNA decreased apoptosis induced by treatment with saracatinib, suggesting that Bim has an important role in saracatinibinduced apoptosis. Saracatinib enhanced the effects of lapatinib, an EGFR/HER2 dual inhibitor, in SNU216 and NCI-N87 cells. Furthermore, combined treatment with saracatinib and 5-fluorouracil (5-FU) or cisplatin exerted synergistic effects in both saracatinib-sensitive and saracatinib-resistant cells. Consistent with our in vitro findings, cotreatment with saracatinib and 5-FU resulted in enhanced antitumor activity in the NCI-N87 xenografts. These data indicate that the inhibition of Src kinase activity by saracatinib alone or in combination with other agents can be a strategy to target gastric cancer.

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“…It has been reported that trastuzumab has significant antitumor activity related to Her 2/neu expression in gastric cancer cells and xenograft models (4)(5)(6). This finding has prompted investigation of the potential clinical benefits of trastuzumab in gastric cancer.…”

Section: Introductionmentioning

confidence: 99%

HER 2/neu protein expression in gastric cancer is associated with poor survival

Xie

Cheng²,

Shen³

et al. 2009

Mol Med Rep

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Abstract. The presence of Her 2/neu has been reported in gastric cancer, but its impact on patient survival remains unclear. The purpose of this study was to investigate the expression of Her 2/neu in gastric cancer. a total of 218 paired resected gastric cancer and corresponding normal specimens were collected. Her 2/neu protein expression was assessed by immunohistochemical staining. The correlation between Her 2/neu expression and patient clinicopathological parameters was evaluated and the prognostic significance of Her 2/neu expression was assessed by univariate and multivariate analyses. Forty-one out of 218 (18.8%) gastric cancer specimens showed Her 2/neu-positive expression. no relationship was found between membranous Her 2/neu expression and clinicopathological parameters. However, Her 2/neu expression was correlated with poorer overall survival (p<0.001). in multivariate analysis, Her 2/neu expression was a significant independent prognostic predictor of gastric cancer (p<0.001), and was associated with poor survival in gastric cancer patients. These data indicate that Her 2/neu may play a major role in the therapeutic management of gastric cancer. Introductiongastric cancer is the second leading cause of cancer-related death worldwide (1). Surgery remains the mainstay of any curative treatment. unfortunately, in advanced gastric cancer, currently available treatments including surgery, chemotherapy and radiotherapy have limited success. Since surgery is an insufficient treatment for most patients, developing active drugs against advanced gastric cancer is required (2,3).It has been reported that trastuzumab has significant antitumor activity related to Her 2/neu expression in gastric cancer cells and xenograft models (4-6). This finding has prompted investigation of the potential clinical benefits of trastuzumab in gastric cancer. However, conflicting results have been obtained in studies on Her 2/neu and its relationship with prognosis in gastric cancer. Some studies have reported that Her 2/neu overexpression is a poor prognostic factor for gastric cancer (7-10), while others have failed to find any association between Her 2/neu overexpression and prognosis (11,12). This discrepancy indicates that there may be factors othen than HER 2/neu expression levels influencing the effect of trastuzumab in gastric cancer. accurate assessment of Her 2/neu status is therefore essential to determine which patients may benefit from trastuzumab treatment.The purpose of the present study was to examine the expression status of Her 2/neu in gastric cancer and to evaluate whether Her 2/neu expression level is correlated with clinicopathological parameters and total prognosis or gender. Materials and methodsCase selection. Specimens were obtained from 218 patients who underwent curative resection (r0) of gastric cancer at the department of Surgical oncology of Sir run run Shaw Hospital, Zhejiang university college of Medicine, between July 1999 and august 2006. informed consent was obtained from all patients, and th...

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Antitumor activity of trastuzumab in combination with chemotherapy in human gastric cancer xenograft models

Abstract: The antitumor activity of trastuzumab observed in human gastric cancer models warrants consideration of its use in clinical treatment regimens for human gastric cancer as a single agent or a combination drug with various chemotherapeutic agents.

Cited by 173 publications

References 17 publications

RON(MST1R)is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma

RON(MST1R)is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma

Antitumor Activity of Saracatinib (AZD0530), a c-Src/Abl Kinase Inhibitor, Alone or in Combination with Chemotherapeutic Agents in Gastric Cancer

HER 2/neu protein expression in gastric cancer is associated with poor survival

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