Immunohistochemical study of epidermal growth factor and transforming growth factor-β in the penetrating type of early gastric cancer

Hirayama, Daisuke; Fujimori, Takahiro; Satonaka, Kazuhiro; Nakamura, Tetsuya; Kitazawa, Souhei; Horio, Mitsuzo; Maeda, Sakan; Nagasako, Kou

doi:10.1016/0046-8177(92)90325-w

Cited by 44 publications

(31 citation statements)

References 10 publications

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“…Evidence would suggest that the control of tissue TGF-,B levels is of critical importance since transgenic mice overexpressing TGF-fI die in the perinatal period and 'knockout' mice lacking the gene for TGF-j1 die within a few weeks of birth (McCartney-Francis and Wahl, 1994). Several studies indicate that tumour cells have an increased synthesis of TGF-f compared with their normal counterparts (Hirayama et al, 1992;LaRocca et al, 1992;Walker and Dearing, 1992). This implies that high levels of TGF-,B favour tumour growth and progression.…”

Section: Resultsmentioning

confidence: 99%

Transforming growth factor β 1 expression in human colorectal tumours: an independent prognostic marker in a subgroup of poor prognosis patients

Robson

Anderson²,

James³

et al. 1996

Br J Cancer

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Summary Members of the transforming growth factor ,B (TGF-fl family, in particular TGF-,B1, are some of the most potent inhibitory growth factors in a variety of cell types. Resistance to TGF-f,l-induced growth inhibition is frequently observed in colorectal carcinomas and is associated with tumour progression. Perturbations of TGF-,B1 expression and function, therefore, may contribute to the loss of some constraints on tumour cell growth. In this study we have examined the expression of TGF-f,l and its precursor latencyassociated peptide (LAP)-TGF-f, in human colorectal tumours using immunohistochemical techniques. In 86% of the tumours the LAP-TGF-,B complex was present in both the stromal and epithelial cells, whereas the mature TGF-fll peptide was expressed in the glandular epithelium of 58.3% of these tumours. Intense staining for TGF-,B1 was positively associated with advanced Dukes' stage. Furthermore, there was a significant correlation between the presence of TGF-f,l in the tumours and a shorter post-operative survival. This was most significant in a subgroup of patients who had received only a palliative operation. These results suggest that TGF-,B1 expression may be useful as an independent prognostic indicator for a subgroup of patients who have a particularly poor prognosis.

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Section: Resultsmentioning

confidence: 99%

Transforming growth factor β 1 expression in human colorectal tumours: an independent prognostic marker in a subgroup of poor prognosis patients

Robson

Anderson²,

James³

et al. 1996

Br J Cancer

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“…Recent studies reveal that TGF-␤1 is also involved in the development and progression of cancer and contrary to its wellknown inhibitory effects on normal epithelial cells, elevated levels of TGF-␤1 mRNA have been re- ported in many cancers such as liver, lung, breast, kidney and prostate (14,15). Furthermore, TGF-␤1 expression has been associated with increased cell proliferation in gastric and thyroid cancers (27,30) and with disease progression in breast and prostate cancer (31,32). Studies in human gastric, breast and prostate cancers have claimed the cancer cells as the source of increased TGF-␤1 and the overexpression of TGF-␤1 protein in these cancer cells have been confirmed by immunohistochemical stains (27,31,32).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, TGF-␤1 expression has been associated with increased cell proliferation in gastric and thyroid cancers (27,30) and with disease progression in breast and prostate cancer (31,32). Studies in human gastric, breast and prostate cancers have claimed the cancer cells as the source of increased TGF-␤1 and the overexpression of TGF-␤1 protein in these cancer cells have been confirmed by immunohistochemical stains (27,31,32). However, the source and site of TGF-␤1 expression in liver is still controversial.…”

Section: Discussionmentioning

confidence: 99%

Expression of Transforming Growth Factor-β1 and Transforming Growth Factor-β Receptors in Hepatocellular Carcinoma and Dysplastic Nodules

et al. 2003

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In this study we analyzed by immunohistochemistry the expression of TGF-␤1 protein and TGF-␤ receptors I and II in 4 low-grade dysplastic nodules, 2 high-grade dysplastic nodules, 6 early, 22 small, and 62 advanced hepatocellular carcinomas. The expression of TGF-␤1 protein by hepatocytes was decreased in advanced hepatocellular carcinoma compared with small or early hepatocellular carcinoma(P < .05). Frequent and intense staining of TGF-␤1 protein was noted in the sinusoidal endothelium of advanced hepatocellular carcinomas despite of its decreased staining in hepatocellular carcinoma cells. Reduced expression of TGF-␤ receptors I and II compared with surrounding nontumorous tissue were noted from the early hepatocellular carcinoma stage suggesting that downregulation of TGF-␤ receptors is correlated with progression from premalignant to malignant phenotype. Reduced expression of both TGF-␤1 and TGF-␤ receptor II in neoplastic hepatocytes were also significantly correlated with increased tumor size and increased proliferative activity(P < .05). These findings suggest that during hepatocarcinogenesis, the inhibitory effects of TGF-␤1 protein on hepatocellular carcinoma cells is outweighed by its effects on stromal elements, which, overall, contributes indirectly to a tumor growth stimulatory environment. Also, the growth-inhibitory effects of TGF-␤1 may have been further negated by reduced TGF-␤ receptors on hepatocellular carcinoma cells.

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“…These findings are compatible with the report of Yoshida et al [7], who found increased expression of TGF-1 mRNA in scirrhous gastric cancer tissues. Hirayama et al [20] found intense staining of TGF-1 on penetrating cells of the linitis plastica type of gastric cancer: this finding is consistent with the notion that cancer cells likely produce TGF-1 to promote the proliferation of nearby stromal tissue. On the other hand, Mizoi et al [8] have claimed that, despite the finding that both tumor cells and stromal cells were stained positively, fibrosis in gastrointestinal cancer is promoted by TGF-1, mainly secreted by stromal cells.…”

Section: Analysis Of Prognostic Factors In Patients With Advanced Gasmentioning

confidence: 52%

Expression of transforming growth factor β (TGF-β) may contribute, in part, to the variations in histogenesis and the prevalence of peritoneal dissemination in human gastric carcinoma

et al. 2000

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Immunohistochemical study of epidermal growth factor and transforming growth factor-β in the penetrating type of early gastric cancer

Cited by 44 publications

References 10 publications

Transforming growth factor β 1 expression in human colorectal tumours: an independent prognostic marker in a subgroup of poor prognosis patients

Transforming growth factor β 1 expression in human colorectal tumours: an independent prognostic marker in a subgroup of poor prognosis patients

Expression of Transforming Growth Factor-β1 and Transforming Growth Factor-β Receptors in Hepatocellular Carcinoma and Dysplastic Nodules

Expression of transforming growth factor β (TGF-β) may contribute, in part, to the variations in histogenesis and the prevalence of peritoneal dissemination in human gastric carcinoma

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