Gastric Cancer—An Enigmatic and Heterogeneous Disease

Shah, Manish A.; Ajani, Jaffer A.

doi:10.1001/jama.2010.553

Cited by 101 publications

(82 citation statements)

References 18 publications

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“…The availability of multiple active drugs, including fluoropyrimidines, platinum, anthracyclines, taxanes, and irinotecan, encourages clinical trials of combination chemotherapy for both advanced diseases and for adjuvant/ neoadjuvant therapy [3]. However, heterogeneity issues in clinical trial design and patient population, which are important confounding factors of gastric cancer trials, are not adequately addressed in previous analyses [4].…”

Section: Introductionmentioning

confidence: 99%

Geographic difference in safety and efficacy of systemic chemotherapy for advanced gastric or gastroesophageal carcinoma: a meta-analysis and meta-regression

et al. 2012

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Background The standard of chemotherapy regimens for advanced or metastatic gastric cancer and the clinical outcome were heterogeneous in Asian versus non-Asian countries. This study aimed to explore predictors of safety and efficacy of chemotherapy for patients with advanced or metastatic gastric cancer. Methods Treatment group-based meta-analysis and metaregression were performed to analyze results of randomized trials published since 2005 for advanced or metastatic gastric cancer patients who received systemic chemotherapy as first-line treatment. Data were extracted and synthesized according to the Cochrane guidelines. Results Twenty-five trials (8 Asian, 17 Western or international) with 56 treatment groups were analyzed.Asian trials reported a lower percentage of gastroesophageal junctional carcinoma, higher percentage of diffusetype histology, and more frequent use of second-line chemotherapy. Meta-analysis revealed significant heterogeneity both in treatment safety (grade 3-4 neutropenia and diarrhea) and efficacy [6-month progression-free survival (PFS) and 1-year overall survival (OS)]. Meta-regression analyses indicate that Asian trials are associated with an 8.2% lower incidence of grade 3-4 neutropenia and 2.1% lower incidence of grade 3-4 diarrhea. A lower percentage of patients with gastroesophageal junction carcinoma and the use of combination regimens predicted better PFS. The use of second-line chemotherapy predicts better 1-year OS, which will increase by 10% for every 10% increase in patients who received second-line chemotherapy. Conclusion Geographic region (Asian vs. non-Asian) is an independent predictor of safety in systemic therapy for gastric cancer.C. Hsu and Y.-C. Shen contributed equally to this work.Electronic supplementary material The online version of this article

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Section: Introductionmentioning

confidence: 99%

Geographic difference in safety and efficacy of systemic chemotherapy for advanced gastric or gastroesophageal carcinoma: a meta-analysis and meta-regression

et al. 2012

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“…Gastric cancer is the second leading cause of cancer-related mortalities worldwide (17,18). As symptoms are often absent in the early stages of disease, gastric cancer is usually diagnosed at an advanced stage and there is <20% 5-year survival for patients.…”

Section: Discussionmentioning

confidence: 99%

Krüppel-like factor 8 involved in hypoxia promotes the invasion and metastasis of gastric cancer via epithelial to mesenchymal transition

Liu¹,

Wang²,

Zhou³

et al. 2014

Oncology Reports

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Abstract. Previously, we reported that hypoxia was able to induce invasion and metastasis in gastric cancer and that hypoxia-inducible factor-1 (HIF-1) is a key factor involved in this tumor type. Krüppel-like factor 8 (KLF8) as a transcriptional repressor has been suggested as a promoter of tumor metastasis in breast cancer and an inducer of the epithelial-mesenchymal transition (EMT). KLF8 is also highly expressed in gastric cancer tissues, contributing to poor prognosis. However, the association between KLF8 and HIF-1 in regulating the progression of human gastric cancer in hypoxia is unclear. In the present study, we found that KLF8 was overexpressed in gastric cancer metastatic tissues and cells. Additionally, KLF8 siRNA significantly inhibited SGC7901 cell invasion and migration compared with SGC7901, SGC7901/Scr-si cells. Hypoxia is thus able to induce KLF8 expression and EMT in SGC7901 cells. However, following the examination of changes in cell morphology and epithelial and mesenchymal markers, it was found that KLF8 siRNA and HIF-1 siRNA strongly reversed EMT in cells undergoing hypoxia. Furthermore, hypoxia-induced KLF8 overexpression was attenuated by HIF-1 siRNA. Experiments using luciferase promoter constructs resulted in a marked increase in the activity of cells exposed to hypoxia and decreased activity in cells co-transfected with HIF-1 siRNA. The chromatin immunoprecipitation assay revealed proximal HRE at -133 is the main HIF-1 binding site in the KLF8 promoter.In conclusion, the results demonstrated that KLF8 is actively enhanced by hypoxia and is a novel HIF-1 target. KLF8 is a novel EMT regulating transcription factor that involved in the progression of gastric cancer. The specific anti-EMT drugs in combination with anti-hypoxia are new promising cancer therapies.

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“…Gastric cancer is the fourth most common cancer, and its prognosis remains poor despite adequate surgery with radical lymphadenectomy (1). Most patients with gastric cancer demonstrate locally advanced disease at the time of diagnosis and may also require chemotherapy and/or radiotherapy (1)(2).…”

Section: Introductionmentioning

confidence: 99%

Chemotherapy-Induced miRNA-29c/Catenin-δ Signaling Suppresses Metastasis in Gastric Cancer

et al. 2015

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Chemotherapy has improved the survival of patients with gastric cancer by unknown mechanisms. In this study, we showed that cisplatin and docetaxel used in gastric cancer treatment increase the expression of miRNA-29 (miR-29) family members and decrease the expression of their oncogenic targets, mediating a significant part of the efficacious benefits of these chemotherapeutic agents. In particular, patients with gastric cancer who experienced recurrences after chemotherapy tended to exhibit low levels of miR-29c expression in their tumors, suggesting that miR29c activation may contribute to the chemotherapeutic efficacy.

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Gastric Cancer—An Enigmatic and Heterogeneous Disease

Cited by 101 publications

References 18 publications

Geographic difference in safety and efficacy of systemic chemotherapy for advanced gastric or gastroesophageal carcinoma: a meta-analysis and meta-regression

Geographic difference in safety and efficacy of systemic chemotherapy for advanced gastric or gastroesophageal carcinoma: a meta-analysis and meta-regression

Krüppel-like factor 8 involved in hypoxia promotes the invasion and metastasis of gastric cancer via epithelial to mesenchymal transition

Chemotherapy-Induced miRNA-29c/Catenin-δ Signaling Suppresses Metastasis in Gastric Cancer

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