Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278883 (metastatic melanoma)
 6,224 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of gamma/delta T cell antigen receptors (TcR) in T cell lines or clones derived from tumor-infiltrating lymphocytes (TIL) from patients with solid tumors was investigated. gamma/delta TcR T cell lines were derived from TIL from patients with Wilms tumor, sarcoma or metastatic melanoma by stimulation with autologous tumor cells alone and recombinant interleukin 2 and they exhibited nonspecific cytotoxicity against autologous and allogeneic tumor cells, or cells of the K562 or the MEL21 tumor cell lines. Two T cell lines were derived from a patient with Wilms tumor. One of them expressed a non-disulfide-linked gamma/delta TcR using the 60-kDa gamma chain, whereas, the other expressed a disulfide-linked gamma/delta TcR. A T cell line was derived from a patient with sarcoma and expressed a disulfide-linked gamma/delta TcR, whereas, a T cell line derived from a patient with melanoma expressed a non-disulfide-linked gamma chain of 62 kDa. Several T cell clones were developed from patients with metastatic melanoma or Wilms tumor and expressed either disulfide- or non-disulfide-linked gamma/delta TcR. Northern analysis of RNA from certain of these clones revealed a full-length gamma chain transcript, whereas, the alpha or beta chain transcripts were either absent or truncated. These T cell clones exhibited nonspecific cytotoxicity. Both disulfide- and non-disulfide-linked TIL T cell lines and clones expressed the delta TCS1 determinant. gamma/delta TcR+ cells in freshly prepared TIL from these patients were present in low proportions (less than 5%) and their delta TCS1/delta 1 ratios were within the range observed in the peripheral blood of normal donors. These results demonstrate that both disulfide- and non-disulfide-linked gamma/delta TcR are expressed on T cell lines and clones derived from TIL from solid tumors. Non-disulfide-linked gamma/delta TcR using the 56-66-kDa gamma chain are frequently found on TIL-derived T cell lines and clones. These 56-66-kDa gamma chains are rarely expressed on T cell lines or clones derived from peripheral blood lymphocytes of normal donors.
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PMID:Gamma/delta T cell antigen receptors expressed on tumor-infiltrating lymphocytes from patients with solid tumors. 131 72

Immunohistochemical deposition and distribution of fetal antigen 2 (FA2) was examined in normal brain tissue and in primary and metastatic tumors of the brain. In normal brain tissue FA2 was exclusively found linearly around the vessels, along pia and in arachnoidea. A similar localization was seen in primary brain tumors except in gliosarcoma where FA2 was distributed diffusely in the sarcoma region and was absent in the glioma region. In metastatic carcinoma with tumor stroma a diffuse staining reaction was seen in the stroma and with a basement membrane (BM) like staining at the tumor cell/stroma interface. Intracytoplasmic FA2 staining of the tumor cells was seen in areas without tumor stroma. In metastatic melanoma a BM like FA2 staining was seen around and between individual tumor cells. The staining patterns seen in the metastatic tumors were in accordance with that of the corresponding primary tumors.
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PMID:Fetal antigen 2 in primary and secondary brain tumors. 179 8

Chemotherapy does not only affect the viability of the tumor cell. It may also cause alterations in normal organs. Thus, tumor-free areas within human lung parenchyma of 63 surgical specimens of intrapulmonary metastases were analyzed to assess the extent of morphologic changes in response to previous cytostatic therapy. The material included 34 cases of sarcoma, 20 cases of germ cell tumors, 6 cases of hypernephroid carcinoma, two cases of mammary carcinoma and one case of metastatic melanoma. All patients had received cytostatic therapy in generally applied regimens for more than two years. Morphologic analysis was carried out by routine procedures. In addition to conventional staining procedures including HE, PAS, and Sirius stain, further tools were employed to extend the array of determined characteristics. To evaluate any changes in the tissue in order to specifically recognized carbohydrate structures, labeled neoglycoproteins or proteoglycans with specificity for endogenous receptors that bind to mannose, maltose, L-fucose, lactose, N-acetyl-D-glucosamine, and heparin were used. A monoclonal antibody binding the HLA-DR receptor was also included in the study. As a control, sections of 20 cases with intrapulmonary metastases without exposure to previous cytostatic therapy were included. To address the further question whether cytostatic therapy may induces changes in tumor-free lung that show similarities to the organ in question, sections from 18 cases with tuberculosis and from 37 cases suffering from sarcoidosis were similarly examined. Focal interstitial fibrosis was seen in 28/63 (44%) of the patients receiving chemotherapy. In contrast, only 2/20 (10%) patients of the untreated group exhibited this alteration. An active fibrosis with proliferating smooth muscle cells was found in two cases, dysplastic pneumocytes in 10 cases (16%) in the group with cytostatic therapy, but in no cases in the untreated group. Expression of the HLA-DR receptor in the pneumocytes was observed in 27/63 cases (43%) of the cytostatic cohort, in 21/37 (57%) patients of the sarcoidosis cohort, in 15/18 (83%) patients of the tuberculosis cohort, and in 1/20 (5%) of the untreated patients. In contrast to sections from treated patients, binding of neoglycoproteins was low in the untreated cohort. Interestingly, similarities between the tuberculosis cohort and the cytostatic cohort were seen for receptors that are specific for fucose and lactose, respectively. The results suggest that long-lasting cytostatic therapy induces focal fibrosis in 40%-50% of the patients, mainly via unspecific interstitial inflammatory infiltrates. A hypersensitivity reaction or direct toxicity may less frequently lead to pathologic alterations.
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PMID:Alterations in human lung parenchyma after cytostatic therapy. 200 Dec 78

From 1982-1989, 113 hyperthermic limb perfusions were carried out in 102 patients. Ninety-three patients were treated for malignant melanoma and nine for soft tissue sarcoma. 47/93 patients had high-risk stage I melanoma with a 5-year survival rate of 89%. For the 46 patients treated for recurrent and metastatic melanoma the projected 5-year survival rate was 40%. The nine patients with soft tissue sarcoma were perfused for local recurrences or because of anatomically difficult tumor locations. 3/9 patients subsequently developed recurrent disease of the extremity; two of these patients had to be treated by amputation. The rate of major complications was low: no patient died in the postoperative course, an amputation due to toxic reaction was never required. Erythema and oedema (57%), severe skin reaction (6%) and transient nerve palsy (15%) were common side effects of therapy. Only two cases of leucopenia were observed (2%). The favourable results after hyperthermic limb perfusion show the efficacy of this method in the treatment of malignant melanoma and selected cases of soft tissue sarcoma.
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PMID:Hyperthermic limb perfusion for malignant melanoma and soft tissue sarcoma. 237 95

One hundred and fifty-six thoracic operations have been performed over an 8-year period, from 1980 to 1987, for 118 patients with pulmonary metastases. In 27 instances, the disease has been bilateral requiring a midline approach or sequential lateral thoracotomies. Resection was achieved by wedge excision in 74%, lobectomy in 16%, pneumonectomy in 4%, lobectomy plus wedge excision in 2%, bilobectomy in 1%, segmentectomy in 2% and segmentectomy plus wedge excision in 1%. The operative mortality for the group as a whole was 1.6% per patient (70% confidence limits CL. 0.6%-4.2%) and 1.2% per operation (70% CL. 0.5-3.2%). Actuarial survival for the histological subgroups at 2 and 5 years were: carcinoma 50% (+/- 11% standard error) and 35% (+/- 12%), sarcoma 59% (+/- 10%) and 51% (+/- 12%), teratoma 89% (+/- 5%) and 84% (+/- 7%) respectively. No patient following resection for metastatic melanoma was alive at 2 years. The survival in the teratoma group was significantly higher than in the other groups (P less than 0.001 carcinoma; P less than 0.01 sarcoma; P less than 0.001 melanoma). Survival in all groups was significantly greater than for the melanoma group. Metastasectomy is well tolerated by the patient. Worthwhile longterm survival is obtained in those patients in whom the primary disease has been controlled and all secondary disease is encompassed by the proposed surgery.
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PMID:Survival following pulmonary metastasectomy. 262 59

Interleukin 2 (IL-2) receptor expression was examined on recombinant IL-2 (rIL-2)-propagated tumor-infiltrating lymphocytes (TIL) from eight metastatic melanoma and three sarcoma samples. All 11 TIL expanded with similar growth rates. rIL-2 propagated TIL from five of eight metastatic melanoma specimens contained no Tac antigen-positive lymphocytes as determined by immunofluorescence and flow cytometry performed multiple times during the 4 to 8 week culture period. However, "Tac-negative" TIL did express the non-Tac IL-2-binding peptide, p70-75 as determined by [125I]IL-2 cross-linking and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. IL-2-binding assays revealed that these "Tac-negative" TIL expressed only an intermediate affinity IL-2 receptor. In contrast, TIL from the other three of eight melanoma and all three sarcoma contained one-third Tac-positive cells as assessed by flow cytometry analysis, and expressed surface non-Tac (p70-75) and Tac (p55) peptides by [125I]IL-2 cross-linking. These "Tac-positive" TIL displayed both the high and intermediate affinity IL-2 receptors. However, rIL-2-dependent growth of both "Tac-negative" and "Tac-positive" TIL was significantly inhibited by anti-Tac mAb, suggesting a transient Tac expression on the "Tac-negative" TIL. Additionally, due to the limits of our methodology, we cannot rule out the possibility of a constitutive expression of a low level of Tac, with an indicible expression of higher levels. Addition of culture supernatants from phytohemagglutinin- and phorbol myristate acetate-stimulated peripheral blood mononuclear cells to the "Tac-negative" TIL-induced detectable Tac expression within 48 h. These results indicate that both non-Tac and Tac IL-2 receptors play important roles during IL-2-dependent proliferation of TIL.
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PMID:Involvement of both Tac and non-Tac interleukin 2-binding peptides in the interleukin 2-dependent proliferation of human tumor-infiltrating lymphocytes. 278 85

TIL from metastatic melanoma proliferated by greater than 1,000-fold (840-3,675, mean 1,543) after 6 wk in culture of mixtures of TIL and tumor cells with rIL-2 alone. Cytolysis was restricted to autologous tumor cells. CD8+ T cells were the predominant population of TIL before and after expansion, and were primarily responsible for autologous tumor-specific CTL activity. No other rIL-2-activated lymphocytes from peripheral blood, lymph nodes with melanoma metastasis, or TIL from sarcoma or renal cell carcinoma had autologous tumor-specific CTL activity. There were few or no CD16+ NK cells in TIL from metastatic melanoma before or after incubation with rIL-2, respectively. However, TIL from sarcoma or renal cell carcinoma contained a substantial proportion of CD3-CD16+ NK cells, which increased in number in culture with rIL-2. Purified CD16+ NK cells as well as CD3+CD16- T cells from rIL-2-activated TIL of renal cell carcinoma displayed MHC-nonrestricted cytotoxicity. At the clonal level as determined by limiting dilution, 8 of 10 clones from melanoma TIL displayed cytotoxicity restricted to autologous tumor cells, while all 13 clones from renal cancer TIL equally lysed autologous and allogeneic tumor cells. Anti-T cell receptor (TCR)-alpha/beta(WT31) mAb as well as anti-CD3 mAb inhibited autologous melanoma cell-specific CTL activity mediated by rIL-2-activated TIL at the effector phase. These two mAbs also inhibited rIL-2-dependent proliferation of these TIL when added to the culture. Pretreatment of fresh melanoma cells with mAb to MHC antigens followed by washing inhibited specific CTL activity. These results suggest that both TCR-alpha/beta on effector TIL and MHC antigens on fresh tumor cells are involved in the specific immune-recognition. After reaching maximum propagation, TIL from metastatic melanoma responded poorly to rIL-2 alone. However, stimulation with fresh autologous melanoma cells restored both CTL activity and proliferation in response to rIL-2. The latter is associated with IL-2 receptor (Tac antigen) expression on the surface. These results indicate that TIL from metastatic melanomas may have unique characteristics different from lymphocytes obtained from the other sources, and may contain precursor CTL sensitized in vivo to autologous tumor cells, and thus can be propagated in larger numbers with rIL-2 alone while retaining autologous tumor-specific CTL activity.
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PMID:Autologous tumor-specific cytotoxic T lymphocytes in the infiltrate of human metastatic melanomas. Activation by interleukin 2 and autologous tumor cells, and involvement of the T cell receptor. 326 10

Mouse monoclonal antibodies (mAb) detecting 13 distinct systems of surface antigens on cultured melanocytes and melanomas were tested for reactivity with panels of (a) normal and malignant cultured cells; (b) normal adult and fetal tissues; and (c) specimens of metastatic melanoma and other tumor types. The objectives of this study were to compare antigen expression in cultured versus noncultured cells, to develop a panel of mAbs that identify subsets of melanomas, and to provide requisite information about antibody specificity in preparation for the use of antibodies in the diagnosis, imaging, and therapy of melanoma. Five of the melanoma surface antigens have been well characterized biochemically [GD3, chondroitin sulfate proteoglycan, HLA Class II antigens, glycoprotein of molecular weight 130,000 (gp130), and glycoprotein Mr 95,000/protein Mr 97,000 (gp95/p97)]. Three antigens have been related to melanocyte differentiation (HLA Class II, M111/M231, and M144), and six provide additional markers for subsets of cultured melanomas. mAb R24 reacts with the disialoganglioside GD3, a predominant ganglioside on cultured melanoma cells and other cells of neuroectodermal origin. A high proportion of melanoma, astrocytoma, and sarcoma tissue specimens were GD3+. In normal tissues, reactivity of mAb R24 was restricted to melanocytes, neuronal and glial cells in the central nervous system, parotid gland, adrenal medullary cells, and rare cells in the connective tissue. mAb B5 detects a chondroitin sulfate proteoglycan that is expressed by most melanoma and astrocytoma cell lines and by cultured melanocytes. Most of the melanoma and astrocytoma specimens were B5+, whereas other tumor types tested were B5-. mAb 13-17, which detects a monomorphic determinant of HLA Class II antigens, reacted with melanomas, and with a variety of other cancers, but not with normal skin melanocytes. There is considerable variability in the expression of GD3 and HLA Class II antigens in individual melanoma specimens; cotyping for these two antigens showed no evidence for coordinate expression. mAb L101 detects gp130 and mAb L235 detects gp95, antigens that are strongly expressed on a broad range of cultured cell types. In contrast to their wide distribution on cultured cells, gp130 expression in tissues was generally restricted to a subset of melanomas and some normal cells, and gp95 was detected on only a small number of melanomas. mAb M111/mAb M231 and mAb M144 define intermediate and late stage differentiation markers of cultured melanocytes and melanomas.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Surface antigens of melanomas and melanocytes defined by mouse monoclonal antibodies: specificity analysis and comparison of antigen expression in cultured cells and tissues. 402 24

Three different human tumor lines in culture, a rhabdomyosarcoma, a bronchogenic carcinoma and a metastatic melanoma, release proteins (transforming growth factors, TGFs) into the medium that confer the transformed phenotype on untransformed fibroblasts. These proteins are acid and heat-stable; produce profound morphologic changes in rat and human fibroblasts; and enable normal anchorage-dependent cells to grow in agar. Removal of the transforming protein results in a reversion of cell phenotype. The major activity interacts with epidermal growth factor (EGF) cell membrane receptors. The peptides from these tumor cells are similar in their action to the sarcoma growth factor (SGF) released by murine sarcoma virus-transformed rodent cells. The most anchorage-independent tumor cells released the most TGFs. EGF-related TGFs were not detectable in fluids from cultures of cells with high numbers of free EGF membrane receptors (normal human fibroblasts and human carcinomas).
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PMID:Transforming growth factors produced by certain human tumor cells: polypeptides that interact with epidermal growth factor receptors. 625 71

Transforming growth factors (TGFs) stimulate cells to divide in monolayer cultures and to form colonies that grow progressively in soft agar. TGFs are a family of polypeptide hormones that, in vitro, confer on fibroblasts and epithelial cells properties associated with the transformed phenotype. They have been isolated from the supernatant fluids of several human and animal carcinoma and sarcoma cells. TGFs interact with epidermal growth factor (EGF) membrane receptors. They are not detectable in culture fluids from cells that contain high numbers of free EGF cell membrane receptors. One TGF is sarcoma growth factor (SGF), which is released by murine sarcoma virus-transformed cells. Studies have shown EGF and SGF to be two distinct growth factors despite the fact that SGF exerts its effects by specifically interacting with EGF receptors. Addition of SGF to normal indicator cells results in expression of the transformed phenotype. The effects of SGF are reversible; the cells resume their normal growth pattern when the growth factor is removed. Three different human tumor cell lines in culture, a rhabdomyosarcoma, a bronchogenic carcinoma, and a metastatic melanoma, release TGFs that also confer the transformed phenotype on normal fibroblasts. One would expect that, as research into this area continues, new TGFs and their interaction with different specific cell membrane receptors will be described.
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PMID:Sarcoma growth factor and other transforming peptides produced by human cells: interactions with membrane receptors. 629 3


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