Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Integrins are heterodimeric transmembrane proteins with large ectodomains and a short cytoplasmic tail inside the cell. They mediate cell adhesion to extracellular matrix proteins and to the surfaces of other cells. In many cases the sequence recognised by the integrins in the extracellular matrix proteins is the tripeptide Arg-Gly-Asp (RGD). Short synthetic peptides containing this sequence can inhibit invasion in vitro and tumour dissemination in vivo. Thus, the alpha 5 beta 1 fibronectin binding integrin appears to be the key integrin in the invasion of at least melanoma, osteosarcoma and glioblastoma cells. Modulation of the level and activities of this integrin can suppress invasion, whereas the alpha v beta 3 vitronectin binding integrin appears to be associated with increased invasiveness. There is increasing evidence that some of these effects are mediated through signals elicited by the binding of integrins to their target proteins. This possibility has generated a great deal of interest in the cytoplasmic molecules that might mediate the integrin-associated signalling.
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PMID:The Walter Herbert Lecture. Control of cell motility and tumour invasion by extracellular matrix interactions. 150 96

To identify the sites important for the different biological activities of human interleukin-1 alpha (hIL-1 alpha), 56 single-amino acid-substituted mutants of hIL-1 alpha were produced in Escherichia coli using site-directed mutagenesis, and were examined for their biological activities such as mouse lymphocyte activating factor activity (LAF activity), cytostatic activity against human melanoma cells A-375 (A375 activity) and prostaglandin E2 (PGE2) inducing activity in human osteosarcoma cells MG-63 (PEI activity). Two amino acid residues, Asp26 and Asp151, were found to be important for these activities. The replacement of Asp26 by Val caused a decrease in LAF and PEI activities by one or two orders of magnitude and a slight decrease in A375 activity. The Tyr or Phe substitution for Asp151 caused decreases in LAF and A375 activities by one or two orders of magnitude and complete loss of PEI activity. The change from Asp151 to Lys or Arg resulted in marked decrease in LAF activity and complete loss of A375 and PEI activities. Since Asp26 and Asp151 are close to each other in the three-dimensional structure, the region involving these amino acids seems to be important for the biological activities of hIL-1 alpha.
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PMID:Structure-activity relationships in human interleukin-1 alpha: identification of key residues for expression of biological activities. 159 72

Reviewing the treatment perspectives with chemo- and immunotherapy in carcinomas and sarcomas to be treated by general or orthopedic surgeons, the following indications are regarded as recommendable: Adjuvant chemotherapy in breast cancer, neoadjuvant chemotherapy with radiation in anal carcinoma and neoadjuvant/adjuvant chemotherapy of high-grade malignant osteosarcoma. Isolation perfusion currently is the treatment of choice in melanoma metastasis limited to an extremity. With several indications, recent developments have produced promising results that should be urgently confirmed in appropriate studies. Therefore the following studies have a high priority: Neoadjuvant chemotherapy in esophageal carcinoma and in locally advanced breast and stomach cancer, adjuvant chemoimmunotherapy in colon carcinoma UICC III and chemoradiation in rectal carcinoma UICC II and III, systemic chemotherapy of metastasized stomach-, colorectal-, breast cancer and sarcomas. Isolated non-resectable liver metastases of colorectal origin and hepatocellular carcinoma should be included in studies evaluating the treatment advantage of regional chemotherapy. Those malignant "surgical" tumors not listed above should receive chemotherapy within experimental studies, after consideration of individual risk factors, or no chemotherapy. Immunotherapy with its various modalities is still in the experimental stage.
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PMID:[What is confirmed in chemo- and immunotherapy of solid tumors. Standard protocols, studies and new developments]. 160 55

Recent studies of Class II histocompatibility antigen expression in bone and soft tissue sarcomas have suggested that malignant fibrous histiocytoma (MFH) may express HLA-DR, whereas histologically similar pleomorphic, epithelioid, and spindle cell malignant neoplasms generally do not. To test whether these observations are reproducible in the differential diagnosis of soft tissue sarcomas, anti-HLA-DR antibodies LK8D3 and LN3 were applied to formalin-fixed, paraffin-embedded sections of MFH, neurofibrosarcoma (NFS), leiomyosarcoma (LMS), synovial sarcoma (SS), fibrosarcoma (FS), angiosarcoma (AS), Kaposi's sarcoma (KS), chondrosarcoma (ChS), "dedifferentiated" chondrosarcoma (DChS), osteosarcoma (OS), epithelioid sarcoma (ES), and clear cell sarcoma (CCS; malignant melanoma of soft parts). The only consistent difference in Class II antigen expression was seen in the group of neoplasms composed of large polygonal cells. Among the latter lesions, four of six clear cell sarcomas were labeled by LK8D3 or LN3, but none of 12 epithelioid sarcomas were reactive. Otherwise, a diversity of tumors in other morphologic categories expressed Class II antigens, with no clear diagnostic patterns. These results may be of use in the diagnostic separation of large cell epithelioid tumors of soft tissue, but neither LN3 nor LK8D3 appears to be helpful in the identification of other sarcomas.
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PMID:HLA-DR (Ia-like) reactivity in tumors of bone and soft tissue: an immunohistochemical comparison of monoclonal antibodies LN3 and LK8D3 in routinely processed specimens. 169 91

The production and detailed immunostaining properties of a new rat monoclonal antibody (ICR.2) to epithelial membrane antigen are reported. The antibody was selected for its ability to compete with the polyclonal antiserum (M7), used in the original immunohistological studies, in order that it might serve as a direct replacement in diagnosing epithelial tumours. Most of the staining reactions on normal tissues were identical to those previously reported with M7 but there were some important differences. They included: positivity of renal and adrenal capsular fibroblasts, perineurium, some myoepithelial and smooth muscle cells, occasional osteoblasts and squamous and thyroid follicular epithelium in the normal state. The intercellular canaliculi of sweat glands and secretory canaliculi of gastric oxyntic cells were clearly demonstrated. These staining reactions could be obtained with M7 when a sensitive detection system was used although the results were usually weak and inconsistent. Nearly all adenosquamous and transitional carcinomas were positive. The remaining tumours fell into three major groups: (1) those which were consistently or nearly consistently negative--melanoma, seminoma, rhabdomyosarcoma, alveolar soft part sarcoma, adrenal cortical carcinoma, granulocytic sarcoma, paraganglioma, non-Hodgkin's lymphoma. Hodgkin's disease and embryonal carcinoma: (2) those which were either negative or positive with distinctive patterns of staining--basal cell carcinoma, embryonal tumours: and (3) non-epithelial tumours that were consistently positive--epithelioid sarcoma, synovial sarcoma, osteosarcoma, chordoma and myeloma--or positive in a significant minority of cases--leiomyosarcoma, malignant fibrous histiocytoma, clear cell sarcoma of tendon sheath, various neuroectodermal tumours.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detailed investigation of the diagnostic value in tumour histopathology of ICR.2, a new monoclonal antibody to epithelial membrane antigen. 169 88

Some integrin receptors have been reported to be functionally distinct in different cell types. In endothelial and melanoma cells, the vitronectin receptor, alpha v beta 3 binds fibrinogen (fg) and von Willebrand factor (vWf) in addition to vitronectin itself, whereas it fails to do so in MG-63 osteosarcoma cells. In this report, it is shown that, in the presence of Mn2+, MG-63 cells attach more efficiently to vitronectin and acquire the de novo capacity to adhere to fg- and vWf-coated surfaces. The latter phenomenon occurs with full cell spreading, F-actin microfilament organization, and alpha v and beta 3 clustering at focal contacts. In contrast, beta 1 and beta 5 do not localize to adhesion plaques under the same experimental conditions. An antiserum to the beta 3 chain and a synthetic peptide containing the sequence Gly-Arg-Gly-Asp-Ser-Pro block MG-63 attachment to fg and vWf in the presence of Mn2+. The minimal active concentration of Mn2+ is in the range of 0.1 to 1 microns. These data suggest that the acquired capacity of MG-63 to attach to fg and vWf in the presence of Mn2+ is mediated by alpha v beta 3 and that differences in alpha v beta 3 receptor specificity may be modulated by exogenous factors.
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PMID:Role of manganese in MG-63 osteosarcoma cell attachment to fibrinogen and von Willebrand factor. 171 76

Activation of endothelial cells by the two inflammatory mediators interleukin-1 (IL-1) and tumor necrosis factor strongly increases tumor cell adhesion. We describe antibody inhibition studies showing that the endothelial leukocyte adhesion molecule-1 (ELAM-1), a cell-surface glycoprotein selectively expressed by cytokine-activated endothelial cells and responsible for neutrophil adhesion, is the major, if not the only, mediator of colon carcinoma cell adhesion to activated endothelial cells. Among the different tumor cell lines tested, seven colon carcinoma cell lines were sensitive to ELAM-1 antibodies. Adhesion of melanoma, osteosarcoma, and lung, cervix, or kidney carcinoma cell lines to IL-1-treated endothelial cells was not affected by the ELAM-1 antibody. This result suggests that ELAM-1 is selectively recognized by colon carcinoma cells and that adhesion of tumor cells to activated endothelial cells could be mediated by different and specific mechanisms.
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PMID:Tumor cell adhesion to endothelial cells: endothelial leukocyte adhesion molecule-1 as an inducible adhesive receptor specific for colon carcinoma cells. 171 24

Hematogenous metastasis involves adhesive interactions between blood-borne tumor cells and the vessel wall. By the use of in vitro assays, the adhesion of human melanoma, osteosarcoma, and kidney carcinoma (but not colon carcinoma) cell lines was shown to involve the cytokine-inducible endothelial cell surface protein inducible cell adhesion molecule 110 (INCAM-110) and the alpha 4 beta 1 integrin, molecules normally involved in endothelial-leukocyte interactions. Tumor adhesion to human endothelial cell monolayers was increased 1.9- to 8.2-fold by endothelial activation with the cytokine tumor necrosis factor (TNF) and inhibited by the anti-INCAM-110 monoclonal antibody (mAb) E1/6. Each of these tumor cells expressed members of the beta 1 integrin family of adhesion molecules, and antibodies to the alpha 4 and beta 1 integrin subunits inhibited tumor-endothelial adhesion (48-87% inhibition). A cDNA encompassing the three N-terminal Ig-like domains of vascular cell adhesion molecule 1 (VCAM-1) encoded a protein recognized by the anti-INCAM-110 mAb E1/6 and, when captured onto plastic, supported melanoma cell adhesion by an alpha 4 integrin-dependent mechanism. In contrast to mAb E1/6, a second anti-INCAM-110 mAb Hu8/4 neither inhibited adhesion to activated endothelium nor bound the first three Ig-like domains of INCAM-110/VCAM-1. These data indicate that the adherence of several human tumors to activated endothelium is mediated by an interaction of alpha 4 beta 1 integrin and the N-terminal Ig-like domains of endothelial INCAM-110/VCAM-1. Tumor acquisition of the alpha 4 integrin subunit and endothelial expression of INCAM-110 may affect the frequency and distribution of metastasis.
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PMID:Tumor cell surface alpha 4 beta 1 integrin mediates adhesion to vascular endothelium: demonstration of an interaction with the N-terminal domains of INCAM-110/VCAM-1. 171 64

We investigated the effects of beta 1 integrins on tumor cell (TC) adhesion to unstimulated and interleukin-1 (IL-1) activated endothelial cells (EC). IL-1 treatment (20 units/ml for 6 hours) of cultured human umbilical vein EC significantly increased adhesion of seven human TC lines of different origin. A goat antiserum raised to purified alpha 5 beta 1 integrin abolished the IL-1 induced increment in adhesion of two osteosarcomas, one melanoma, one lung, and one kidney carcinoma, whereas it did not affect adhesion of two colon carcinoma cell lines. Further studies were performed on MG63 osteosarcoma cells. Adhesion of MG63 osteosarcoma cells to EC was dependent on time of EC treatment with IL-1: it was maximal at 12 hours and declined at 24 hours. alpha 5 beta 1 antiserum blocked IL-1 induced increase in MG63 adhesion at any time of EC treatment. This effect appears to be mainly directed to MG63 integrins since selective incubation of the antiserum with EC, but not with MG63, did not modify TC adhesion. Using a series of antibodies to different alpha and beta chains, we found that only monoclonal antibodies (mAb) to alpha 4, alpha 5, and beta 1 could inhibit MG63 adhesion to IL-1 activated EC, whereas alpha 2, alpha 6, and beta 3 antibodies were ineffective. Antibodies to fibronectin had very little activity on MG63 adhesion to EC matrix and did not significantly affect MG63 adhesion to control or IL-1 treated EC. Antibodies to alpha 4, alpha 5, and beta 1 were only partially effective in inhibiting MG63 adhesion to EC matrix. These data indicate that the capacity of alpha 4 beta 1 and alpha 5 beta 1 integrins to bind fibronectin contributed very little to MG63 adhesion to EC. The importance of beta 1 integrins in promoting a direct interaction between EC and MG63 was further shown by inhibition of rosette formation among these cells in suspension by the alpha 5 beta 1 antiserum. Only a VCAM-1/INCAM110 mAb, but not ELAM-1 or ICAM-1 mAbs, could inhibit MG63 adhesion to IL-1 activated EC. Overall these data indicate that at least two members of the beta 1 integrin subfamily (alpha 4 beta 1 and alpha 5 beta 1) are involved in MG63 adhesion to cytokine treated EC. This integrin function might be important at early stages of TC interaction with the vessel wall.
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PMID:Role of beta 1 integrins in tumor cell adhesion to cultured human endothelial cells. 175 2

An overview is presented of some common and uncommon non-plaque-related lesions and conditions of the periodontal tissues. Erosive lesions of the gingiva, such as lichen planus, may clinically be misdiagnosed as being the result of inflammation. Likewise, local and generalized gingival swelling may be based on non-plaque-related lesions and conditions. True leukoplakia of the gingiva is rare, but should be looked upon with suspicion. The reasons for pigmentation of the gingiva are many-fold. Especially in the maxilla, the clinician should be alert for an early malignant melanoma. A large variety of lesions may affect the periodontal bone structures, ranging from the common periapical granuloma to the rare, sometimes sclerosing, osteosarcoma. Irregular widening of the periodontal ligament and loss of the lamina dura are ominous radiographic signs.
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PMID:Non-plaque related periodontal lesions. An overview of some common and uncommon lesions. 189 Feb 25


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