Gastric cancer treatment: a systematic review

Berardi, Rossana; Scartozzi, Mario; Romagnoli, Emanuela; Antognoli, Stefania; Cascinu, Stefano

doi:10.3892/or.11.4.911

Cited by 16 publications

(18 citation statements)

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“…Despite the advances in treatment and research efforts over the past few decades, the outcome of gastric cancer remains poor. The overall 5-year survival rate in the United States and most other western countries ranges from 5 to 15% [2], largely because many gastric cancers are diagnosed at an advanced stage. The aggressive nature of human gastric carcinoma is related to a variety of intracellular events, including activation of various oncogenes, inactivation of tumor suppressor genes, and abnormal expression of growth factors and their receptors [3,4].…”

Section: Introductionmentioning

confidence: 99%

Association of elevated GRP78 expression with increased lymph node metastasis and poor prognosis in patients with gastric cancer

Zhang

Jiang

Jia

et al. 2006

Clin Exp Metastasis

168

147

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Glucose-regulated protein 78 (GRP78) has been implicated in the protection of tumor cells from cytotoxic damage and apoptosis and thus assists cells in survival under oxygen-deprivation and nutrient-stress conditions. However, its expression and potential role in gastric cancer development and progression have not been reported. In the present study, we determined the level of GRP78 expression in the primary tumor in 86 cases of resected gastric cancer by using immunohistochemistry and analyzed the relationships between GRP78 and clinicopathological characteristics. We found that GRP78 was overexpressed in the tumor specimens when compared with the expression in adjacent tumor-free gastric mucosa. Furthermore, the level of GRP78 expression in both primary tumors and metastatic lymph nodes was inversely correlated with patient survival. Overexpression of GRP78 was directly correlated with Sp1 expression and increased lymph node metastasis. Knocking down GRP78 expression inhibited tumor cell invasion in vitro and growth and metastasis in a xenograft nude mouse model. Therefore, our data imply that dysregulated expression of GRP78 may contribute to the development and progression of gastric cancer.

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Section: Introductionmentioning

confidence: 99%

Association of elevated GRP78 expression with increased lymph node metastasis and poor prognosis in patients with gastric cancer

Zhang

Jiang

Jia

et al. 2006

Clin Exp Metastasis

168

147

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“…Current treatment includes surgical resection of localized disease, and cytotoxic chemotherapy with 5-fluorouracil (5-FU) and platinum-based agents are often employed as first-line therapy (Berardi et al, 2004;Rivera et al, 2007). However, chemoresistance is a problem with GC as it is with other tumours.…”

Section: Introductionmentioning

confidence: 99%

Increased drug resistance is associated with reduced glucose levels and an enhanced glycolysis phenotype

Bhattacharya

Low

Soh

et al. 2014

British J Pharmacology

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BACKGROUND AND PURPOSEThe testing of anticancer compounds in vitro is usually performed in hyperglycaemic cell cultures, although many tumours and their in vivo microenvironments are hypoglycaemic. Here, we have assessed, in cultures of tumour cells, the effects of reduced glucose levels on resistance to anticancer drugs and investigated the underlying cellular mechanisms. EXPERIMENTAL APPROACHPIK3CA mutant (AGS, HGC27), and wild-type (MKN45, NUGC4) gastric cancer cells were cultured in high-glucose (HG, 25 mM) or low-glucose (LG, 5 mM) media and tested for sensitivity to two cytotoxic compounds, 5-fluorouracil (5-FU) and carboplatin, the PI3K/mTOR inhibitor, PI103 and the mTOR inhibitor, Ku-0063794. KEY RESULTSAll cells had increased resistance to 5-FU and carboplatin when cultured in LG compared with HG conditions despite having similar growth and cell cycle characteristics. On treatment with PI103 or Ku-0063794, only the PIK3CA mutant cells displayed increased resistance in LG conditions. The PIK3CA mutant LG cells had selectively increased p-mTOR, p-S6, p-4EBP1, GLUT1 and lactate production, and reduced reactive oxygen species, consistent with increased glycolysis. Combination analysis indicated PI103 and Ku-0063794 were synergistic in PIK3CA mutant LG cells only. Synergism was accompanied by reduced mTOR signalling and increased autophagy. CONCLUSIONS AND IMPLICATIONSHypoglycaemia increased resistance to cytotoxic agents, especially in tumour cells with a high dependence on glycolysis. Dual inhibition of the PI3K/mTOR pathway may be able to attenuate such hypoglycaemia-associated resistance. Abbreviations

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“…About 60% of cases occur in developing countries, and about 38% of cases are in China (Parkin et al 1999). Most gastric cancer patients are diagnosed at an advanced stage, with poor prognosis and a 5-year survival rate between 5 and 15% (Berardi et al 2004). Treatment of early stage, or locally advanced, gastric cancer is mainly surgical.…”

Section: Introductionmentioning

confidence: 99%

Polymorphism in the 3′-untranslated region of the thymidylate synthase gene and sensitivity of stomach cancer to fluoropyrimidine-based chemotherapy

Gao

et al. 2006

J Hum Genet

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Polymorphism in the 3¢-untranslated region of the thymidylate synthase gene and sensitivity of stomach cancer to fluoropyrimidine-based chemotherapy Abstract To investigate the relationship between polymorphism in the 3¢-untranslated region (3¢-UTR) of the thymidylate synthase (TS) gene and sensitivity of gastric cancer to 5-fluorouracil (5-FU)-based chemotherapy, 106 cases of advanced gastric cancer were analyzed. All patients were treated with 5-FU-based chemotherapy; DNA from peripheral blood leukocytes was obtained before therapy. TS 3¢-UTR genotypes were detected by PCR-RFLP. Polymorphism in the TS 3¢-UTR can be classified into three groups according to the presence or absence of a 6 bp nucleotide fragment: the À6/À6 bp, À6/+6 bp and +6/+6 bp groups. The response rate of the À6/À6 bp and À6/+6 bp groups was found to be significantly higher than the +6/+6 bp group. These results show that the presence of the TS 3¢-UTR 6 bp nucleotide fragment can be correlated with the sensitivity of gastric cancer to 5-FU-based chemotherapy, and that the TS 3¢-UTR polymorphism profile can be used to guide the choice of 5-FU-based chemotherapy in advanced gastric cancer.

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Gastric cancer treatment: a systematic review

Cited by 16 publications

References 0 publications

Association of elevated GRP78 expression with increased lymph node metastasis and poor prognosis in patients with gastric cancer

Association of elevated GRP78 expression with increased lymph node metastasis and poor prognosis in patients with gastric cancer

Increased drug resistance is associated with reduced glucose levels and an enhanced glycolysis phenotype

Polymorphism in the 3′-untranslated region of the thymidylate synthase gene and sensitivity of stomach cancer to fluoropyrimidine-based chemotherapy

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