Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neoplasms of APUD cell origin are quite variable in their metastatic behavior. Whereas pituitary and parathyroid tumors almost never metastasize, all oat cell lung cancers, malignant melanomas, trabecular carcinomas of the skin and medullary thyroid cancers are capable of dissemination. The metastatic proclivity of individual carcinoids, pancreatic and extrapancreatic islet cell tumors, and paragangliomas is much less predictable. In particular, there are no reliable histological markers of risk for lymphatic or hematogenous dissemination. The behavior of many carcinoids, islet cell carcinomas and paragangliomas is relatively indolent, even when metastatic disease is already present. However, unresectable distant metastases, especially liver involvement, connote a poor prognosis. Mortality is more often related to uncontrolled tumor growth and metastasis than to associated endocrinopathies. Curative or debulking surgical resection should be aggressively pursued as recent data show that worthwhile clinical disease-free survival can be realized in at least some patients.
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PMID:Metastatic proclivities and patterns among APUD cell neoplasms. 790 11

Neoplasms progress through genetic and epigenetic mutations that deregulate pathways in the malignant cell that stimulate more aggressive growth of the malignant cell itself and/or remodel the tumor microenvironment to support the developing tumor mass. The appearance of new blood vessels in malignant tumors is known as the "angiogenic switch." The angiogenic switch triggers a stage of rapid tumor growth supported by extensive tumor angiogenesis and a more aggressive tumor phenotype and its onset is a poor prognostic indicator for host survival. Identification of the factors that stimulate the angiogenic switch thus is of high importance. Pleiotrophin (PTN the protein, Ptn the gene) is an angiogenic factor and the Ptn gene has been found to be constitutively expressed in many human tumors of different cell types. These studies use a nude mouse model to test if Ptn constitutively expressed in premalignant cells is sufficient to trigger an angiogenic switch in vivo. We introduced an ectopic Ptn gene into "premalignant" SW-13 cells and analyzed the phenotype of SW-13 Ptn cell tumor implants in the flanks of nude mice. SW-13 Ptn cell subcutaneous tumor implants grew very rapidly and had a striking increase in the density of new blood vessels compared to the SW-13 cell tumor implants, suggesting that constitutive PTN signaling in the premalignant SW-13 cell implants in the nude mouse recapitulates fully the angiogenic switch. It was found also that ectopic expression of the C-terminal domain of PTN in SW-13 cell implants was equally effective in initiating an angiogenic switch as the full-length PTN whereas implants of SW-13 cells in nude mice that express the N-terminal domain of PTN grew rapidly but failed to develop tumor angiogenesis. The data suggest the possibility that mutations that activate Ptn in premalignant cells are sufficient to stimulate an angiogenic switch in vivo and, since these mutations are frequently found in human malignancies, that constitutive PTN signaling may be an important contributor to progression of human tumors. The data also suggest that the C-terminal and the N-terminal domains of PTN equally initiate switches in premalignant cells to cells of a more aggressive tumor phenotype but the separate domains of PTN signal different mechanisms and perhaps signal through activation of a separate receptor-like protein.
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PMID:Identification of the angiogenesis signaling domain in pleiotrophin defines a mechanism of the angiogenic switch. 1655 21

In the rat spleen, reactive and proliferative changes of the reticulum cells are rare events and seem to occur almost exclusively in the red pulp. The normal structure of the splenic reticulum cell and fiber lattice and examples of spontaneous and induced pathological alterations were investigated by immunohistochemistry (smooth muscle-actin, vimentin, S100 and proliferating cell nuclear antigen) and special stains for extracellular fibers (silver impregnation, azan). In response to congestion, systemic tumor growth or treatment with a hematotoxic compound, the scaffold cells increased either their contractile properties or their production of extracellular fibers. Primary focal hyperplasias of stromal cells which had developed without obvious cause were characterized by vanishing of sinuses, increased fiber content, increased expression of sm-actin or foci of lipomatosis. The borders of focal hyperplasias were indistinct and they did not infiltrate the white pulp compartments. Neoplasms of the stromal reticulum cells resembled soft tissue tumors in other organs. Specific tumor entities as described in other species have so far not been observed in the rat.
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PMID:Reactive and proliferative changes of splenic reticulum cells of rats investigated with special staining methods and immunohistochemistry. 1805 13

Neoplasms contain distinct subpopulations of cells known as tumor-initiating stem-like cells (TICs) that have been identified as key drivers of tumor growth and malignant progression with drug resistance. Stem cells normally proliferate through self-renewing divisions in which the two daughter cells differ markedly in their proliferative potential, with one displaying the differentiation phenotypes and another retaining self-renewing activity. Therefore, understanding the molecular mechanisms of hepatocarcinogenesis will be required for the eventual development of improved therapeutic modalities for treating hepatocellular carcinoma (HCC). Hepatitis C virus (HCV) and hepatitis B virus is a major cause of HCC. Compelling epidemiologic evidence identifies obesity and alcohol as co-morbidity factors that can increase the risk of HCV patients for HCC, especially in alcoholics or obese patients. The mechanisms underlying liver oncogenesis, and how environmental factors contribute to this process, are not yet understood. The HCV-Toll-like receptor 4 (TLR4)-Nanog signaling network is established since alcohol/obesity-associated endotoxemia then activates TLR4 signaling, resulting in the induction of the stem cell marker Nanog expression and liver tumors. Liver TICs are highly sensitized to leptin and exposure of TICs to leptin increases the expression and activity of an intrinsic pluripotency-associated transcriptional network comprised of signal transducer and activator of transcription 3, SOX2, OCT4, and Nanog. Stimulation of the pluripotency network may have significant implications for hepatocellular oncogenesis via genesis and maintenance of TICs. It is important to understand how HCV induces liver cancer through genesis of TICs so that better prevention and treatment can be found. This article reviews the oncogenic pathways to generate TICs.
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PMID:Tumor-initiating stem-like cells and drug resistance: carcinogenesis through Toll-like receptors, environmental factors, and virus. 2578 83

Significance: Neoplasms contain tumor-initiating stem-like cells (TICs) that drive malignant progression and tumor growth with drug resistance. TICs proliferate through a self-renewal process in which the two daughter cells differ in their proliferative potential, with one retaining the self-renewing phenotype and another displaying the differentiated phenotype. Recent Advances: Cancer traits (hepatocellular carcinoma) are triggered by alcoholism, obesity, and hepatitis B or C virus (HBV and HCV), including genetic changes, angiogenesis, defective tumor immunity, immortalization, metabolic reprogramming, excessive and prolonged inflammation, migration/invasion/metastasis, evasion of cell cycle arrest, anticell death, and compensatory regeneration/proliferation. Critical Issues: This review describes how metabolic reprogramming in mitochondria promotes self-renewal and oncogenicity of TICs. Pluripotency transcription factors (TFs), NANOG, OCT4, MYC, and SOX2, contribute to cancer progression by mitochondrial reprogramming, leading to the genesis of TICs and cancer. For example, oxidative phosphorylation (OXPHOS) and fatty acid metabolism are identified as major pathways contributing to pluripotency TF-mediated oncogenesis. Future Directions: Identification of novel metabolic pathways provides potential drug targets for neutralizing the activity of highly malignant TICs found in cancer patients. Antioxid. Redox Signal. 28, 1080-1089.
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PMID:Pluripotency Transcription Factors and Metabolic Reprogramming of Mitochondria in Tumor-Initiating Stem-like Cells. 2925 36