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)

Monocyte chemotactic proteins (MCP) belong to a group of structurally and functionally related factors, called chemokines. To facilitate additional characterization of the recently identified MCP-2, the 76-residue protein was chemically synthesized. The synthetic 7-kDa monomeric protein was chemotactic for monocytes at 1 nM and was biochemically similar to natural MCP-2. Sensitive radioimmunoassays for both MCP-1 and MCP-2 were developed. These RIAs were specific in that no cross-reactivity could be observed, and other chemokines or cytokines were not detected. Induction of MCP-1 and MCP-2 in human diploid fibroblasts and peripheral blood leukocytes as well as osteosarcoma, epidermal carcinoma, and melanoma cells by the cytokines IL-1 beta, IFN-beta, and IFN-gamma and cytokine inducers such as dsRNA, virus, endotoxin, mitogen, and phorbol ester was studied. In connective tissue cells, IL-1 beta was the best inducer of MCP-1, but IFN-gamma was a superior inducer of MCP-2. Mononuclear cells also proved to be a source of MCP-1 and MCP-2 when stimulated by most of the inducers tested. Granulocytes, however, were inefficient producers. Measles virus induced MCP-1 and MCP-2 in most cell types. In general, the yields of MCP-2 were at least 10-fold lower than those of MCP-1. It is concluded that, although MCP-2 is often coproduced with MCP-1, regulation of expression of the two chemokines is not identical. It remains to be studied under which pathological conditions MCP-2 is released in vivo and whether MCP-1 and MCP-2 can activate different target cells.
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PMID:Induction of monocyte chemotactic proteins MCP-1 and MCP-2 in human fibroblasts and leukocytes by cytokines and cytokine inducers. Chemical synthesis of MCP-2 and development of a specific RIA. 818 67

Microcolonies were obtained by culturing cells of two human osteosarcoma lines (OHS and KPDX) and one human melanoma line (WIX-c) for either 24 or 72 h. The microcolonies were treated with either alpha-particle radiation emitted by the 211At-labelled monoclonal antibody (MAb) TP-3 or external beam X-rays. Survival of microcolonies was assayed by colony formation. Therapeutic gain factor (TGF) values were calculated for two survival levels, 50% and 20% microcolony regeneration (i.e. at least one cell in 50% or 20% of the colonies survived the treatments). The TGF values were affected by the specific activity of the 211At-MAb conjugate, the antigen expression of the cells and the size and growth pattern of the microcolonies. Treatment with 211At-TP-3 gave TGF values that varied from 1.3 +/- 0.4 to 4.5 +/- 0.7 (mean +/- s.e.). The antigen-rich OHS cell line had on average 1.6 times higher TGF than the antigen-poor KPDX cell line. The TGF increased significantly with colony size for the densely packed colonies of the KPDX cell line but not for the OHS cell line, which had colonies with cells growing in a more scattered pattern. Control experiments with the two non-specific 211At forms, free 211At and 211At-labelled bovine serum albumin, gave TGF values from 0.6 +/- 0.1 to 1.0 +/- 0.3. This study suggests that in vivo evaluation of 211At-MAbs using relevant tumour models is desirable.
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PMID:Analysis of the therapeutic gain in the treatment of human osteosarcoma microcolonies in vitro with 211At-labelled monoclonal antibody. 819 60

Liposomal muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) is a biological agent in phase I and II trials for osteosarcoma and melanoma. Its mechanism of action has been linked to its ability to activate monocyte tumoricidal function and to stimulate monocyte production of tumor necrosis factor (TNF) and interleukins(IL)-1, -6, and -8. Our ultimate goal is to combine L-MTP-PE with chemotherapy. The purpose of this study was to determine whether doxorubicin (Adriamycin) interfered with the ability of L-MTP-PE to activate monocyte cytokine production. Human monocytes were cultured with or without 5-500 ng/ml of Adriamycin for 3 h and washed before being exposed to 2 micrograms/ml L-MTP-PE for 16 h. Cultured supernatants were collected and assayed for TNF, IL-1, IL-6, and IL-8. The messenger RNA expression of IL-1 alpha, IL-1 beta, TNF alpha, IL-6, and IL-8 was quantified with northern blot analysis. Adriamycin did not suppress the up-regulation of any of these cytokines. We concluded that combination therapy with L-MTP-PE and Adriamycin is feasible and that this combination warrants further investigation in a clinical setting.
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PMID:Effect of Adriamycin on liposomal muramyl tripeptide's ability to up-regulate monocyte cytokine expression. 824 65

As the cure rate for childhood malignancies increases, the number of patients at risk for development of second malignancies also increases. Due to the potentially long remaining life span, long-term follow-up is difficult and patients are often at risk after presumptive cures. Some authors believe that cure rates for second malignancies are similar to cure rates for primary malignancies. We reviewed the records of 162 patients seen at our institution who had developed a second malignancy after treatment for childhood cancer. Presentation, age at diagnosis, tumor histology, extent of tumor, treatment (including radiotherapy with dosage when available, and chemotherapy) plus outcome were recorded. Mean age at diagnosis of the primary malignancy was 10.3 years. The most common primary malignancy was Hodgkin's disease (33) followed by soft tissue sarcoma (28), retinoblastoma (20), bone tumor (17), central nervous system (CNS) tumor (13), leukemia (8), Wilms' tumor (7), non-Hodgkin's lymphoma (6), neuroblastoma (5), thyroid neoplasm (5), and others (20). The average interval between diagnosis of the first and second malignancy was 10.8 years. These second tumors carried a high mortality. Only 56 patients have no evidence of disease. Five patients are known to be alive with disease and 92 patients have expired due to their second malignancy. Disease status in 8 patients is unknown. The most common second malignancy was osteosarcoma (35) followed by soft tissue sarcoma (24), breast cancer (15), leukemia (14), thyroid carcinoma (14), CNS tumors (12), melanoma (8), nonmelanomatous skin cancer (8), lymphoma (5), and others (27).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Forty-year experience with second malignancies after treatment of childhood cancer: analysis of outcome following the development of the second malignancy. 826 99

Thrombospondin-1 is a component of the extracellular matrix which is thought to play important roles in cell migration and proliferation, during embryogenesis and wound repair. To understand the basis for these activities, we are mapping the regions of the molecule with cell adhesive activity. Here, we use antagonists of specific cell binding sites, adhesion-perturbing thrombospondin monoclonal antibodies and proteolytic fragments of platelet thrombospondin, to investigate the adhesive mechanisms used by G361 melanoma cells, human intestinal smooth muscle cells (HISM), epidermal keratinocytes and MG-63 osteosarcoma cells. When attached to the same preparations of platelet thrombospondin, HISM and MG-63 cells underwent spreading, whereas G361 cells and keratinocytes did not. Attachment of all four cell types involved the carboxyterminal domain. The type 1 repeats and the amino-terminal heparin binding domain were important for stable attachment of G361, HISM and MG-63 cells, but were not involved in keratinocyte attachment. GRGDSP peptide caused near complete inhibition of HISM and MG-63 cell attachment, partially inhibited G361 attachment, but did not inhibit keratinocyte attachment. Attachment of HISM and MG-63 cells involved the alpha v beta 3 integrin. The integrity of the thrombospondin molecule was important for its adhesivity towards G361, HISM, and MG-63 cells, whereas keratinocytes attached to the 140 kDa tryptic fragment as effectively as they did to the intact molecule. These results show that cell attachment to platelet thrombospondin typically involves multiple binding interactions, but the exact profile of interactions is cell type specific. Usage of particular cell-binding sites does not predict whether cells will undergo spreading or not. These data may, in part, explain some of the current controversies surrounding the mechanisms of cell attachment to thrombospondin.
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PMID:Diverse mechanisms for cell attachment to platelet thrombospondin. 831 91

We reviewed the clinical course and the results of various treatment modalities of 80 patients with rare pulmonary neoplasms, who constituted 0.8% of all patients with primary lung cancer treated at the Mayo Clinic from 1980 through 1990. The 50 male and 30 female patients had a median age of 60 years (range, 20 to 87). The histopathologic types of these rare pulmonary neoplasms were non-Hodgkin's lymphoma (41%), carcinosarcoma (20%), mucoepidermoid carcinoma (15%), malignant fibrous histiocytoma (5%), malignant melanoma (4%), fibrosarcoma (4%), leiomyosarcoma (4%), angiosarcoma (2%), hemangiopericytoma (2%), osteosarcoma (1%), and blastoma (1%). Follow-up was complete in all 80 patients, and the median duration of follow-up was 59 months (range, 15 to 130). Of the 80 patients, 63 (79%) underwent pulmonary resection. Of the other 17 patients, 8 underwent only bronchoscopy for diagnosis, 4 had unresectable disease at thoracotomy, 3 had metastatic disease on initial assessment, and 2 had mediastinal involvement detected on mediastinoscopy. Fifty-four patients (68%) received chemotherapy or radiation treatment (or both). The overall 5-year survival was 39%. The strongest factors that influenced survival were cell type and extent of disease at time of initial examination.
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PMID:Rare pulmonary neoplasms. 838 92

The human fibroblast activation protein (FAP), defined by monoclonal antibody F19, is expressed in vivo in reactive stromal fibroblasts of epithelial cancers, subsets of bone and soft tissue sarcomas, and granulation tissue of healing wounds. FAP is generally absent from the stroma of benign epithelial tumors and normal adult tissues. In vitro FAP induction is observed in proliferating cultured fibroblasts and in melanocytes grown with fibroblast growth factor and phorbol ester. In the present study, we show that fibroblast and melanocyte FAP is a cell surface protein comprising noncovalently linked M(r) 95,000 (p95) and M(r) 105,000 (p105) subunits. In contrast, cultured sarcoma and melanoma cell lines express only p95 or are FAP negative. Immunoblot experiments show that p95, but not p105, carries the epitope defined by monoclonal antibody F19. Furthermore, peptide maps of purified p95 and p105 differ, suggesting that they may be distinct gene products. Loss of FAP or a change from p95/p105 to p95 expression accompanies the acquisition of growth factor independence and tumorigenicity in several in vitro test systems, including simian virus 40 transformation of normal fibroblasts, Ha-ras transformation of normal melanocytes, supertransformation of osteosarcoma cells, and enhanced N-MYC expression in variant neuroblastoma cells, whereas serum-starved normal fibroblasts continue to express p95/p105. Thus, fAP expression appears to be linked to the growth factor-dependent proliferative capacity of normal cells and is not merely a secondary event in proliferating cells; furthermore, FAP expression is inversely correlated with growth factor independence and tumorigenicity in transformed cell lines. This distribution pattern is consistent with a role for p95/p105 in mediating extrinsic, growth regulatory signals in normal cells, possibly as a heteromeric cell surface receptor. Such a physiological function may be obviated when oncogenes with cytoplasmic or nuclear sites of action are activated, reducing extrinsic growth factor dependence and permitting down-regulation of FAP in certain transformed cells.
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PMID:Regulation and heteromeric structure of the fibroblast activation protein in normal and transformed cells of mesenchymal and neuroectodermal origin. 839 23

We report a constitutional mutation of codon 273 in exon 8 of the p53 gene. The affected individual has developed multiple independent benign and malignant tumours (tricholemmoma of the scalp, multiple trichoepitheliomata of the face, osteosarcoma of the ovary, bilateral breast cancer, malignant fibrous histiocytoma of the thigh and endometrial adenocarcinoma) and belongs to a family with some, but not all, features of the Li-Fraumeni syndrome. The mutation, found in both blood lymphocyte and tumour specimens, is a cytosine to thymine transition at codon 273, resulting in an amino acid change from arginine to cysteine. The mother and sister of the index case both died of tumours at an early age. We have demonstrated that formalin-preserved material from these tumours contains the same C-->T mutation at codon 273, indicating that this mutation has probably been transmitted through the germline. All tumours from the index case, both benign and malignant, showed immunohistochemical positivity with four antibodies to the p53 protein. Positive staining was also seen in scattered nuclei of morphologically normal epidermal keratinocytes and pilosebaceous cells, but not in lymphocytes or other morphologically normal cells from the index case. However, a similar staining pattern in apparently normal tissue was also observed in 13/48 sections from other individuals with various skin conditions (melanocytic naevi, psoriasis and normal skin adjacent to malignant melanoma and fibrous histiocytomas), suggesting that this pattern of p53 staining may not be unique to individuals with constitutional p53 mutations.
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PMID:Constitutional mutation in exon 8 of the p53 gene in a patient with multiple primary tumours: molecular and immunohistochemical findings. 847 49

Osteogenic melanoma is a rare variant of malignant melanoma; only eight cases have been reported. To characterize this unusual neoplasm further, we present four new cases. Two patients were men and two were women (average age, 56 years; range, 47-78 years). All tumors arose from acral lentiginous melanomas. Three were subungual finger lesions and one was on the sole of the foot. All four had been previously diagnosed as or were suspected to have been primary osseous lesions. The vertical growth components were high-grade, amelanotic sarcomatoid malignancies with abundant osteoid matrix. Two tumors also had chondroblastic differentiation. Cells with epithelioid features, including prominent eosinophilic nucleoli, were discernible in every tumor. Regional lymph node metastases in two cases retained osteocartilaginous differentiation, whereas metastatic cells in another case were purely epithelioid. Tumor cells in every case were immunoreactive for S-100 protein and vimentin, and non-reactive for cytokeratin. Two tumors also expressed HMB-45. Melanosomes were identified ultrastructurally in every tumor. Follow-up information was available on every patient. Three developed regional lymph node metastases and are currently alive and well after 14, 39, and 101 months. The fourth patient died of metastatic uterine carcinoma 20 months postoperatively. The differential diagnosis of osteogenic melanoma includes osteosarcoma as well as atypical fibro-osseous proliferations. Clinico-pathologic features that support a diagnosis of osteogenic melanoma include junctional activity, absence of primary bony involvement, regional nodal metastases, immunoreactivity for S-100 protein and/or HMB-45, lack of cytokeratin reactivity, and ultrastructural identification of melanosomes.
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PMID:Osteogenic melanoma. A rare variant of malignant melanoma. 803 2

The data of the Australian Paediatric Cancer Registry on childhood cancer incidence in Australia for the 10-year period 1982-1991 are presented. The crude average annual incidence of cancer in children under the age of 15 years was 13.8 per 100,000. The incidence of childhood cancer in Australia is rising. Significant increases were seen in acute non-lymphoblastic leukaemia, astrocytoma and melanoma. The age-standardised incidence of 14.4 per 100,000 is about 34% higher than in the UK. Most types of cancer had a higher incidence in Australia than in the UK, and the difference was significant for acute lymphoblastic leukaemia, astrocytoma and melanoma. Of particular interest is malignant melanoma, whose incidence in Australia is more than 5 times that in the UK, as a result of excessive UV exposure. Australia has a higher incidence of Ewing's tumour than osteosarcoma, nearly twice that of the UK. International comparative studies may help to elucidate the aetiology of these tumours.
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PMID:Childhood cancer incidence in Australia, 1982-1991. 854 93


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