transforming-growth-factor-beta and Digestive-System-Neoplasms

Genetic alterations affecting transforming growth factor-β (TGF-β) signaling are exceptionally common in diseases and cancers of the gastrointestinal system. As a regulator of tissue renewal, TGF-β signaling and the downstream SMAD-dependent transcriptional events play complex roles in the transition from a noncancerous disease state to cancer in the gastrointestinal tract, liver, and pancreas. Furthermore, this pathway also regulates the stromal cells and the immune system, which may contribute to evasion of the tumors from immune-mediated elimination. Here, we review the involvement of the TGF-β pathway mediated by the transcriptional regulators SMADs in disease progression to cancer in the digestive system. The review integrates human genomic studies with animal models that provide clues toward understanding and managing the complexity of the pathway in disease and cancer.

Topics: Animals; Digestive System Neoplasms; Disease Progression; Gastrointestinal Diseases; Gene Expression Regulation, Neoplastic; Humans; Liver Diseases; Pancreatic Diseases; Receptors, Transforming Growth Factor beta; Signal Transduction; Smad Proteins; Transforming Growth Factor beta; Tumor Microenvironment

To systematically evaluate whether the expression level of long non-coding RNA activated by transforming growth factor-β (lncRNA-ATB) is correlated with the prognosis of digestive system cancer (DSC) patients.. PubMed, Embase, Cochrane Library, Web of Science, Springerlink, Nature, and Karger databases were searched up to April 20, 2019 by 2 experienced researchers independently. The quality of studies was assessed with the Newcastle-Ottawa scale. The Review Manager 5.2 and STATA 12.0 software were used for this meta-analysis.. Eleven studies with 1227 DSC patients were included in the meta-analysis. Except for pancreatic cancer, high expression of lncRNA-ATB was associated with lymph node metastasis (risk ratio (RR) = 1.26, 95% confidence interval (CI): 1.12-1.42, P < .001), advanced clinical staging (RR = 1.44, 95%CI: 1.23-1.69, P < .001), reduced overall survival rate (OS) (hazard ratio (HR) = 2.33, 95%CI: 1.22-4.50, P = .01), and recurrence-free survival (RFS) (HR = 2.61, 95%CI: 1.46-4.65, P = .001) compared with low lncRNA-ATB expression in DSCs.. High expression of lncRNA-ATB was significantly correlated with poor prognosis for most DSCs. The expression level of lncRNA-ATB could be a promising prognostic biomarker for DSC patients.

Topics: Aged; Biomarkers, Tumor; Case-Control Studies; Digestive System Neoplasms; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Prognosis; RNA, Long Noncoding; Survival Rate; Transforming Growth Factor beta

Clubbing was first described by Hippocrates more than 2.500 years ago. It may be seen alone or as part of an entity called hypertrophic osteoarthropathy which include periostitis, arthritis and sometimes thickening and edema of the skin around the affected joints. Pulmonary diseases such as cancer, abscess, empyema, bronchiectasis and cystic fibrosis are the major diseases known to be associate with hypertrophic osteoarthropathy. Digestive tract cancer, cyanogenic congenital heart disease are well known association. Many theories have attempted to explain the appearance of this sign but few have persisted. In this article, we review characteristics, relation with etiology and the basis of the pathophysiology of hypertrophic osteoarthropathy and particularly of clubbing.

Topics: Bronchiectasis; Causality; Cystic Fibrosis; Digestive System Neoplasms; Empyema; Ferritins; Heart Defects, Congenital; Humans; Lung Abscess; Lung Neoplasms; Osteoarthropathy, Secondary Hypertrophic; Platelet-Derived Growth Factor; Prostaglandins; Transforming Growth Factor beta

Topics: Carcinogens; Digestive System Diseases; Digestive System Neoplasms; Female; Humans; Male; Risk Assessment; Sensitivity and Specificity; Signal Transduction; Transforming Growth Factor beta

Transforming growth factor-beta (TGF-beta) and TGF-beta-related proteins, such as the bone morphogenetic proteins, have emerged as key regulators of stem cell renewal and differentiation. These proteins have disparate roles in regulating the biology of embryonic stem cells and tumor suppression, and they help define the selection of cell fate and the progression of differentiation along a lineage. Here we illustrate their roles in embryonic stem cells and in the differentiation of neural, hematopoietic, mesenchymal, and gastrointestinal epithelial stem cells.

Topics: Animals; Cell Differentiation; Cell Lineage; Digestive System; Digestive System Neoplasms; Embryo, Mammalian; Epithelial Cells; Hematopoietic Stem Cells; Humans; Mesenchymal Stem Cells; Neurons; Signal Transduction; Stem Cells; Transforming Growth Factor beta

Neuroendocrine tumors of the digestive system are slow growing neoplasms which often present with pronounced fibrosis around tumor cells and in the peritoneal cavity. In this report 30 midgut carcinoids and endocrine pancreatic tumors were examined for the expression of peptide growth factors and their receptors, both by immunohistochemistry and in situ hybridization. Our data indicate that multiple peptide growth factors, PDGF, TGF-beta, and bFGF are expressed by these tumors. PDGF was expressed on tumor cells and stroma in 70% of tissues examined. PDGF alpha-receptor was seen on clusters of tumor cells and occasionally on adjacent stroma, whereas PDGF beta-receptor was seen only in the stroma. Our data suggest that PDGF may be involved in the autocrine stimulation of tumor cells and stimulation of stromal cell growth through paracrine and possibly autocrine mechanism. In addition, tumor tissues express all three isoforms of TGF-beta in more than half of the tissues examined. Tumor cells produce small latent complexes causing an escape from potent inhibitory effect of TGF-beta and stimulation of stromal cell growth and matrix deposition through paracrine mechanism. bFGF, a potent stimulant of endothelial cell growth, was expressed by all tumor tissues examined. Our data suggest that multiple peptide growth factors may have an important role in tumor progression and desmoplastic reaction accompanying these tumors.

Topics: Adenoma, Islet Cell; Adolescent; Adult; Aged; Aged, 80 and over; Animals; Carcinoid Tumor; Digestive System Neoplasms; Fibroblast Growth Factor 2; Growth Substances; Humans; Immunohistochemistry; Mice; Middle Aged; Neoplasm Proteins; Pancreatic Neoplasms; Peptide Biosynthesis; Peptides; Platelet-Derived Growth Factor; Rabbits; Receptors, Platelet-Derived Growth Factor; Receptors, Somatotropin; Transforming Growth Factor beta