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)

An experimental model of meningeal carcinomatosis has been produced by subarachnoid inoculation of B16 melanoma cells into C57BL mice. Injection of 10(3) viable cells was sufficient to cause 100% tumor incidence and death within a median survival time of 17 days. The tumor infiltrated diffusely the meninges of the brain and spinal cord and filled the ventricular system. Electron microscopic study of the leptomeningeal tumor revealed newly formed microvessels with fenestrated endothelium. The integrity of the blood-brain barrier was studied by the extravasation of the Evans blue and the Horseradish peroxidase tracers. Barrier disruption became evident from the seventh day on, using Evans blue. Electron microscopy study showed peroxidase activity in the luminal and abluminal sides of the meningeal microvessels, and within the tight junctions. Similar findings were noted in cortical capillaries adjacent to the meningeal tumor. Brain concentrations of Adriamycin (ADR) following administration of an intravenous dose of either 10 mg/kg or 50 mg/kg were measured on days 0 to 14 after tumor inoculation. A significant increase in mean +/- SEM content of whole brain ADR was observed only with the 50 mg/kg dose in days 7 to 14 (0.69 +/- 0.02 micrograms/g wet tissue weight) as compared to tumor-free controls (0.43 +/- 0.01, p less than 0.05). Our study suggests that barrier alteration in meningeal carcinomatosis allows extravasation of tracer solutes. Still, in order to achieve a significant increase in a water soluble drug penetration through the disrupted barrier, a high-dose drug regimen is required.
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PMID:Alteration of blood-brain-CSF barrier in experimental meningeal carcinomatosis. A morphologic and adriamycin-penetration study. 355 64

Ten cases of melanoma and 5 ocular nevus were studied with the peroxidase-antiperoxidase method with S100 protein. All the cases showed positivity for this protein, this is why we can advise its use in the diagnosis of these entities.
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PMID:Value of the S100 protein in the study of nevus and ocular melanomas. 362 5

To analyze the humoral immune response to melanoma, human-mouse hybridomas were generated by the fusions of regional lymph node lymphocytes of patients with the mouse myeloma cell line M5. Six stable hybridomas were cloned from six separate lymphocyte parents obtained from three patients. Ascites were obtained from nude mice after i.p. injection with cultured hybridoma cells. The monoclonal antibodies, four immunoglobulin Gs and two pentameric immunoglobulin Ms, were partially purified to remove mouse immunoglobulin and then conjugated to biotin for immunocytochemical and immunohistochemical studies. With the avidin:biotin:peroxidase complex method to detect and amplify binding by the biotin-conjugated human monoclonal antibodies, we found the six antibodies to be reactive against cytoplasmic determinants in five short-term melanoma cultures and formalin-fixed paraffin-embedded melanoma tumors from four patients. The antigenic target of the antibodies identified was not carcinoembryonic antigen. Two antibodies, 2-139-1 and 6-26-3, were studied in more detail. Each stained 25 of 25 specimens of melanomas. Little or no reactivity was detected against fixed sections of normal skin, which included tissues such as epidermis, dermis, monocytes, lymphocytes, and vascular endothelium. More striking was the absence of binding to melanocytes in the basal layer of the skin or to pigmented nevus cells. Both antibodies showed cross-reactivity against other tumors, in particular colonic and prostatic carcinomas. In the normal colon, reactivity was restricted to the surface of the columnar epithelium; no reactivity was detected against normal prostatic epithelium. Reactivity was also not observed against liver and lung. However, the epithelia of the renal tubules, pancreatic ducts, and salivary ducts were all reactive. These human monoclonal antibodies identify cytoplasmic melanoma-associated tumor antigens that appear different from the membrane antigens defined by serological approaches and by most mouse monoclonal antibodies.
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PMID:Human monoclonal antibodies directed against melanoma tumor-associated antigens. 369 90

A mouse monoclonal antibody, FKH1, was produced to detect cytoplasmic melanoma-associated antigen. FKH1 was raised using cultured human melanoma cell line KHm-6 as an immunogen. Reactivity of this antibody was assessed by immunohistochemical techniques against cell lines and normal and neoplastic tissues. Positive reactions were seen against 5 human melanoma cell lines. It stained cytoplasm of melanoma cells in a diffuse and granular pattern in indirect immunofluorescence. Immunoelectron microscopy showed diffuse distribution of immunoreactant in the cytoplasm of KHm-1 cells excluding melanosomes and other organelles. Reactivity against frozen and alcohol-fixed, paraffin-embedded melanocytic tumors was also tested with IIF or indirect or avidin biotinylated horseradish peroxidase complex immunoperoxidase techniques. All cases of frozen sections from benign and malignant melanocytic tumors showed positive staining with FKH1. In fixed tissues, however, reactivity was 11 of 14 (79%) in malignant melanoma and 28 of 42 (67%) in other melanocytic tumors. FKH1 did not react against normal melanocytes and nonmelanocytic tumors except APUDoma and 2 glioblastoma cell lines. It failed to stain the B-16 mouse melanoma cell line, neuroblastoma cell line, breast carcinoma cell line, and T-cell lymphoma cell line. Normal human peripheral nerves were nonreactive with FKH1. In immunoelectroblot study, FKH1 bound with proteins having molecular weight of 71,000 and 55,000 extracted from KHm-6 cells. It was suggested that FKH1 is a useful monoclonal antibody in diagnostic study of human malignant melanoma specimens.
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PMID:Mouse monoclonal antibody (FKH1) detecting human melanoma-associated antigens. 375 74

Two variants of B16 mouse melanoma cells, selected for their resistance to toxic levels of wheat germ agglutinin isolectin 1 (WGA-1) in serum-free medium, showed by chromosome analysis that they are still mouse cell-lines, continue to produce melanin, and are less tumorigenic in mice than the parent B16 cells. The variants showed a marked decrease in cell agglutination with the wheat germ lectin and a slight increase in cell agglutination with concanavalin A. The binding of 125I-labeled wheat germ agglutinin to the two variant lines was likewise decreased over a 10(3)-fold range of lectin concentrations. Terminal sialyl residues were critical in WGA-1 binding to the wild-type cells. The binding data indicated a decrease in high-affinity binding as well as a decrease in the total number of binding sites in the variants. Polyacrylamide gel electrophoresis, followed by affinity staining with 125I-wheat germ agglutinin, showed alterations in the wheat germ agglutinin-binding glycoproteins in the variants compared to those of the parent cell line. However, lactoperoxidase-catalyzed iodination revealed a similar cell-surface protein pattern among the three cell lines. Radioactive glycoproteins secreted or shed by the three cell lines grown in the presence of [3H]glucosamine in serum-free medium were fractionated on the basis of their interaction with WGA-Sepharose (2 mg/mL). The WGA-bound glycoproteins from the two variants had molecular weights of 92,000, 56,000, and 42,000. None of these components was detected in the parent cell-line. A major WGA-binding glycoprotein, which accounted for 37% of the total [3H]glucosamine incorporated, was isolated from the spent medium of the parent mouse melanoma cell-line. This glycoprotein was apparently absent in the WGA-1-resistant variants.
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PMID:Characteristics of two wheat germ agglutinin-resistant variants of B16 mouse melanoma cells with reduced tumorigenicity. 376 99

Murine monoclonal antibodies (MAbs) were produced with reactivity to human malignant melanoma. Six MAbs, 3 of the IgGI (LS113, LS140, LS152) and 3 of the IgG2a (LS59, LS62, LS76) subclasses, were selected for their binding, with an identical pattern of reactivity, to a novel melanoma-associated antigen. As characterized by the enzyme-linked immunosorbent assay (ELISA), these MAbs were found to be positive on n-octyl-beta-D-glucopyranoside extracts of all 10 melanoma cell lines tested and on extracts of 22 metastatic melanoma tumors. The antibodies had minimal reaction with a panel of 14 normal adult tissue extracts. A degree of cross-reactivity was observed with 50% of 39 non-melanoma tumor extracts. The results obtained with the ELISA on cell line and tissue extracts were duplicated using the ABC method of peroxidase staining. The pattern of cross-reactivity, as demonstrated by the intense staining of paraffin-embedded and frozen tissue sections of normal, benign and malignant tissues, defines the recognized protein as a neuroglandular antigen (NGA). Immunoadsorbents made with the antibodies were used to purify the antigen shed from cultured melanomas. All 6 MAbs recognized this purified antigen while 5 other antimelanoma antibodies did not react with it. On gel electrophoresis this antigen is a highly glycosylated glycoprotein with a protein core of 21 kDa.
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PMID:Characterization of a novel neuroglandular antigen (NGA) expressed on abnormal human melanocytes. 380 88

Immunoreactive plasminogen activators were studied in tissue sections using a peroxidase method and monospecific antibodies to tissue plasminogen activator produced by a melanoma. Tissue plasminogen activator reactivity was found in skin melanomas and in endothelial and smooth muscle cells of arteries and veins. Vessels of the umbilical cord showed higher reactivity than peripheral vessels. Only faint antiurokinase reactivity was found. By means of the fibrin slide technique, fibrinolytic activity could be shown in peripheral vessel walls but not in the umbilical cord, which suggests that immunoreactivity of tissue plasminogen activator bound to an inhibitor can also be demonstrated. This method may be a useful tool in further studies of tissue plasminogen activator in physiological as well as pathological processes.
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PMID:Immunohistochemical localisation of tissue plasminogen activator and urokinase in the vessel wall. 388 80

The immunoperoxidase technique, using antibodies against human urinary urokinase (Mr 55,000), was used for the localization of this enzyme in histological preparations of human colon tumors and normal colon tissue. The localization of tissue (vascular) activator was also investigated using antibodies against enzyme purified from human malignant melanoma. Both the "indirect method" and the peroxidase-antiperoxidase technique were found to be useful. Urokinase-reactive material was found in all tissues examined (33 primary cancers, 11 metastases, and 8 adenomas). In the normal colon, urokinase was found only in some of the goblet cells of the mucosal epithelium. In colon cancer, diffuse specific staining was observed in the cytoplasm, but the most intense staining was localized at the edge of the cancer cells bordering the lumen of the glands. In some cases, intense supranuclear staining could be observed in a location corresponding to the Golgi apparatus. In a few instances, urokinase could be seen associated with fibroblasts near the advancing front of an invading tumor. Adenoma, a benign tumor but often a precursor of cancer, also showed the presence of urokinase. Most significant were the observations showing that, in regions of the mucosal glands where normal epithelial cells were abruptly replaced by cancer cells, the appearance of cytoplasmic urokinase showed strict and exclusive association with the malignant cells, and the same was the case in transitions from normal epithelium to adenoma. In contrast to urokinase, tissue plasminogen activator was not associated with cancer cells, but was consistently present in the stroma which separates the cancer glands and was localized in the endothelium of the blood vessels. This visual evidence was supported by results of extraction of plasminogen activators from tumors, and from the separated mucosal and submucosal layers of the normal colon of the same patients, which showed that urokinase is most abundant in the tumor tissue and least abundant in the submucosa, while tissue activator is most prevalent in the well-vascularized mucosa and submucosa and scarce in the usually poorly vascularized adenocarcinomas.
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PMID:Localization of plasminogen activators in human colon cancer by immunoperoxidase staining. 388 45

Fourteen biopsy specimens from ten patients with atypical fibroxanthoma were studied with the peroxidase-antiperoxidase method for binding of S-100 antibody. Six specimens from four patients were minimally positive. The S-100-positive cells were observed in greatest concentrations at the periphery of the lesions and were associated with perivascular inflammatory cells. By this method, it appears that there is not a Langerhans' cell type of atypical fibroxanthoma. The S-100 antibody can help differentiate desmoplastic juvenile melanoma and malignant melanoma from atypical fibroxanthoma.
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PMID:Atypical fibroxanthoma. A study with antibody to S-100 protein. 389 Jul 60

A series of seven monoclonal antibodies recognizing cell surface antigens of similar distribution on a panel of leukemia/lymphoma and lymphoblastoid human cell lines was prepared by hybridoma technique after immunization with non-T, non-B acute lymphoblastic leukemia cell line REH. Immune reactivity of these monoclonal antibodies with B-lymphoblastoid and lymphoma cell lines, as well as with non-T, non-B leukemia cell lines but not with T-leukemic and myeloid leukemic cell lines (with the exception of myeloid leukemia cell line KG 1) was demonstrated by indirect immunofluorescence. No reactivity was observed with the examined human non-hemopoietic tumor cell lines, except melanoma cell lines HMB-2 and SK 1477. These antibodies immunoprecipitated a similar cell surface bimolecular glycoprotein complex consisting of two glycosylated chains (gp30, 35), as demonstrated by immunoprecipitation of cell surface 125I-lactoperoxidase radioiodinated, periodate/tritiated borohydride radiolabeled and 35S-methionine metabolically radiolabeled proteins of REH cells. These properties, typical of MHC class II antigens correspond also to immunoperoxidase staining of lymph nodes with some selected antibodies.
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PMID:Monoclonal antibodies against MHC class II antigens elicited with a human non-T, non-B acute lymphoblastic leukemia cell line. 391 Oct 80


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