TGFβ1, TGFβ2, and TGFβ3 Protein Expression in Gastric Carcinomas: Correlation with Prognostics Factors and Patient Survival

Vagenas, Konstantinos; Spyropoulos, Charalambos; Gavala, Vasiliki; Tsamandas, Athanassios C.

doi:10.1016/j.jss.2006.10.005

Cited by 46 publications

(33 citation statements)

References 21 publications

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“…Although studies have shown that TGFβ1 expression is closely linked to the prognosis of gastric cancer (26,27), neither the polymorphisms of TGFB1 -509C/T and TGFBR2 -875A/G nor the combination of the two SNPs revealed a correlation with patient survival in this study, consistent with the study in the uS population (11). A possible explanation is that overall survival is determined, not only by factors involved in gastric cancer disease activity, but also by underlying diseases and other complications.…”

Section: Discussionmentioning

confidence: 99%

Association between the TGFB1 -509C/T and TGFBR2 -875A/G polymorphisms and gastric cancer: a case-control study

Zeng

Chen

et al. 2011

Oncology Letters

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Abstract.The transforming growth factor-β (TGFβ) pathway plays an important role in various types of human cancer. However, the role of TGFB1 -509C/T and TGFBR2 -875A/G polymorphisms in gastric cancer is controversial. We aimed to investigate the associations between these polymorphisms and gastric cancer susceptibility, clinicopathological parameters and survival. A case-control study was conducted in 1,010 gastric cancer patients and 1,500 healthy controls. Genotypes were determined by PCR-restriction fragment length polymorphism and DNA sequencing. Compared with the TT genotype, the TGFB1 -509 C allele (CT/CC) was significantly associated with a reduced risk of gastric cancer (OR, 0.71; 95% CI, 0.58-0.87; P=0.001) and certain subtypes of gastric cancer including intestinal type (OR, 0.70; 95% CI, 0.57-0.87; P=0.001), poorly differentiated (OR, 0.67; 95% CI, 0.54-0.85; P=0.001) and stage TNM III+IV (OR, 0.73; 95% CI, 0.58-0.92; P=0.008). Compared with the TGFBR2 -875 GG genotype, carriers of the A allele (AA/AG) had a significantly decreased gastric cancer risk (OR, 0.58; 95% CI, P<0.001). A combination of the TGFB1 -509 C and TGFBR2 -875 A alleles was associated with a further decreased risk of gastric cancer (OR, 0.42; 95% CI, 0.32-0.57, P<0.001). No significant correlation was observed between polymorphisms and survival of gastric cancer patients. Our results suggest that both the TGFB1 -509 and TGFBR2 -875 polymorphisms contribute to a decreased gastric cancer risk. The TGFB1 -509 polymorphism affects certain subtypes of gastric cancer according to clinicopathological parameters. A combination of the TGFB1 -509 C and TGFBR2 -875 A alleles conferred a further decreased gastric cancer risk. These findings provide clues to the biological mechanisms that underline tumor heterogeneity.

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Section: Discussionmentioning

confidence: 99%

Association between the TGFB1 -509C/T and TGFBR2 -875A/G polymorphisms and gastric cancer: a case-control study

Zeng

Chen

et al. 2011

Oncology Letters

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“…Although TGF-b produced by cancer cells and/or by cancer-associated fibroblasts enhances the fibrosis, the role of TGF-b in the development of diffuse-type gastric carcinoma still remains controversial (Mizoi et al, 1993;Mishra et al, 2005). Either increased or decreased survival in diffuse-type carcinoma patients were reported to correlate with the expression of TGF-b (Kinugasa et al, 1998;Vagenas et al, 2007). However, our present findings suggest that TGF-b suppresses the progression of tumor by induction of the differentiation of CICs of this type of cancer.…”

Section: Reduction Of Sp Cells In Gastric Cancer By Tgf-b S Ehata Et Almentioning

confidence: 99%

Transforming growth factor-β decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells

et al. 2010

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Stem cells in normal tissues and cancer-initiating cells (CICs) are known to be enriched in side population (SP) cells. However, the factors responsible for the regulation of expression of ABCG2, involved in efflux of dyes, in SP cells have not been fully investigated. Here, we characterized the SP cells within diffuse-type gastric carcinoma, and examined the effects of transforming growth factor-b (TGF-b) on SP cells. Diffuse-type gastric carcinoma cells established from four independent patients universally contained SP cells between 1 and 4% of total cells, which displayed greater tumorigenicity than non-SP cells did. TGF-b repressed the transcription of ABCG2 through direct binding of Smad2/3 to its promoter/enhancer, and the number of SP cells and the tumor-forming ability of cancer cells were decreased by TGF-b, although ABCG2 is not directly involved in the tumor-forming ability of SP cells. Cancer cells from metastatic site expressed much higher levels of ABCG2 and included a greater percentage of SP cells than parental cancer cells did. SP cells are thus responsible for the progression of diffuse-type gastric carcinoma, and TGF-b negatively contributes to maintain the CICs within the cancer.

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“…Many clinical studies have shown positive correlations of TGFβ1 expression with lymph node metastasis and poor prognosis in gastric cancer [68,69]. Saito et al [70] emphasized that there was a strong correlation between TGFβ1 expression and vascular endothelial growth factor (VEGF) expression in gastric cancer tissue, suggesting that tumor progression was promoted indirectly by the stimulation of angiogenesis through the upregulation of VEGF expression in gastric carcinoma.…”

Section: Transforming Growth Factor β (Tgfβ)mentioning

confidence: 99%

Roles of inflammatory cytokines in the progression of gastric cancer: friends or foes?

et al. 2010

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Although the etiology of gastric cancer has been completely obscure for many decades, several considerable advances in the knowledge of the carcinogenesis and development of gastric cancer have been made in the present era. First, it is well known that Helicobacter pylori infection is associated with the carcinogenesis and development of gastric cancer, suggesting that chronic infl ammation may be implicated in the development of intestinal metaplasia and mutations in oncogenes that precede the development of gastric cancer; indeed, the International Agency for Research on Cancer classifi ed H. pylori as a class I human carcinogen in 1994 [2]. Second, the long-suspected infl uence of genetic susceptibility has been elucidated and several polymorphisms of infl ammatory cytokine genes have been implicated as risk factors for gastric cancer [3][4][5][6][7].Although immune cells constitute an additional and prominent component of the host response to cancer, their participation in tumor pathogenesis remains unclear. Increasing evidence is being reported regarding the hypothesis that several proinfl ammatory and antiinfl ammatory cytokines may promote tumor progression and affect the host antitumor response. Efforts to understand cytokine function during tumor development are complicated by the pleiotropy and redundancy of cytokine action and the manner in which the overall cytokine environment shapes the effects of individual cytokines [8]. At present, most current data support the notion that acute infl ammation triggered by tumorinfi ltrating lymphocytes (TILs) does not induce the normal immunoprotective mechanisms that lead to the eradication of an evolving cancer. Instead, excessively and chronically produced proinfl ammatory mediators are thought to promote tumor progression [9][10][11][12]. In the tumor microenvironment, there is a delicate balance between antitumor immunity and tumor-originated proinfl ammatory activity, which weakens antitumor immunity [12][13][14]. Many researchers have reported that perioperative blood transfusion [15,16], postoperative Abstract Increasing evidence is being reported regarding the hypothesis that several proinfl ammatory and anti-infl ammatory cytokines may promote tumor progression and affect the host antitumor response. However, the manner in which a local cytokine network operates in tumor development remains unclear. We reviewed the literature to examine the consequences of novel insights into infl ammatory cytokines associated with gastric cancer progression. The Medline and EMBASE databases were searched for publications regarding the role of infl ammatory cytokines in the development of gastric cancer. A number of studies have suggested that several proinfl ammatory and anti-infl ammatory cytokines promote tumor progression through the direct activation of nuclear factor-κB (NF-κB) and the upregulation of angiogenesis and adhesion molecules. Furthermore, these processes suppress host antitumor immunity, leading to tumor progression and metastasis. In patients with ad...

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TGFβ1, TGFβ2, and TGFβ3 Protein Expression in Gastric Carcinomas: Correlation with Prognostics Factors and Patient Survival

Cited by 46 publications

References 21 publications

Association between the TGFB1 -509C/T and TGFBR2 -875A/G polymorphisms and gastric cancer: a case-control study

Association between the TGFB1 -509C/T and TGFBR2 -875A/G polymorphisms and gastric cancer: a case-control study

Transforming growth factor-β decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells

Roles of inflammatory cytokines in the progression of gastric cancer: friends or foes?

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