Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1326912 (tumorigenesis)
 57,481 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelet-derived growth factor (PDGF) is known to stimulate the proliferation of connective tissue-derived cells in vitro. Less is known about its functions in vivo, and the role of PDGF in the development of human tumors has not been clarified. The authors have investigated the occurrence of PDGF and PDGF receptors in a series of proliferative disorders of fibroblastic origin using immunohistochemical and in situ hybridization techniques. High expression of PDGF beta-receptor mRNA and protein was found in the malignant tumors, and also in some benign lesions, such as dermatofibroma. In all these cases, benign as well as malignant, the PDGF B-chain mRNA, and less clearly, the PDGF A-chain mRNA, were coexpressed with the beta-receptor. In contrast, high expression of PDGF alpha-receptor mRNA was only found in fully malignant lesions, i.e., malignant fibrous histiocytoma. These data indicate that an autocrine growth stimulation via the PDGF beta-receptor could occur in an early phase of tumorigenesis, and may be a necessary but insufficient event for the progression into fully malignant human connective tissue lesions.
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PMID:Expression of platelet-derived growth factor and its receptors in proliferative disorders of fibroblastic origin. 137 58

Asbestosis is an inflammatory and fibrotic process of the alveolar structures mediated, at least in part, by cytokines released by "activated" alveolar macrophages. The process of phagocytosis and "activation" of alveolar macrophages is poorly understood. Are all macrophages activated or only subpopulations? Which cytokines are up-regulated? How does the local milieu modulate profibrotic and antifibrotic mediators? Is protein release accompanied by up-regulation of gene transcription? Is there an ordered sequence of cytokine activity? What roles do neutrophils and lymphocytes play? How can disease progression best be quantified absent further exposure? Answers to these questions are important to direct rational strategies at interdicting the fibrotic process. The question of cancer and asbestos is more vexing. The processes of inflammation, fibrosis, and carcinogenesis appear to be closely intertwined. For example, proto-oncogenes such as c-sis (PDGF B-chain) are up-regulated in activated alveolar macrophages from fibrotic lungs; these and possibly others may play an important role in asbestos carcinogenesis. Second, asbestos can transfect DNA into cells. Furthermore, DNA can adhere to asbestos fibers, and these fibers are capable of direct transmigration into cells. The questions of the mechanisms of cigarette smoke cocarcinogenicity and latency remain. Lastly, if the bronchial epithelium is highly metaplastic throughout from cigarette smoking, what triggers a single (or several) nidus of cells to transform into carcinoma? Malignant mesothelioma poses the most challenging questions because of association with brief asbestos exposure by history. Mesothelial cells are susceptible to minute environmental manipulations, and changes occur after exposure to all fiber types. Yet epidemiologic studies point toward long amphiboles as having greater mesothelioma risk. To test this hypothesis, experimental data must be generated differentiating tumorigenesis risk from short, chrysotile fibers that can migrate to the parietal pleura from the associations of long amphiboles persisting in lung tissue. Despite the future decreasing numbers of clinical cases of asbestos-related disease, solving the important mechanistic questions remaining will contribute significantly to our understanding of fibrosis and cancer.
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PMID:Cellular and molecular basis of the asbestos-related diseases. 156 5

PDGF is a mitogenic protein stored in platelets and released upon platelet degranulation. Recent evidence indicates that PDGF plays an important role in both physiologic and pathophysiologic processes, particularly in tumorigenesis, wound healing, pulmonary fibrosis, and atherogenesis. In addition to its mitogenic potential, it has been reported that PDGF stimulates monocyte chemotaxis. Since the recruitment of monocytes from the peripheral vasculature is an important event in vivo, the potential role of PDGF as a monocyte chemoattractant has significant biologic implications. However, we now report that homogeneous human PDGF from platelets and a recombinant PDGF-2 homodimer do not stimulate monocyte chemotaxis. In contrast to previous reports these results indicate that PDGF is not a monocyte chemoattractant.
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PMID:Platelet-derived growth factor is not chemotactic for human peripheral blood monocytes. 291 81

In existing mouse models for malignant brain tumors, genes with no proven pathogenical relevance for humans have been used. Coexpression of platelet-derived growth factor (PDGF) and PDGF receptors suggests an autocrine mechanism of growth factor stimulation in the development of brain tumors in man. A murine retrovirus coding for the PDGF B-chain was, therefore, used to induce brain tumors in mice. Of 35 mice who received injections, 15 developed brain tumors of oligo- or monoclonal origin. They coexpressed PDGF B-chain and alpha-receptor mRNA, as expected, from an autocrine mechanism of transformation. Most tumors displayed characteristics of glioblastoma multiforme or of a primitive neuroectodermal tumor, and the consistent expression of nestin suggested that they were all derived from an immature neuroglial progenitor. The results show that an autocrine mechanism of transformation may be an initial or early event in neuro-oncogenesis. The present model provides an ideal system for studies of genetic mechanisms involved in the development of brain tumors.
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PMID:Induction of brain tumors in mice using a recombinant platelet-derived growth factor B-chain retrovirus. 985 47