Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tyrosinase (EC 1.14.18.1) is the enzyme essential to pigment formation in mammals; this enzyme is specifically localized in melanocytes, which occur primarily in the skin, hair bulbs, and eyes. Three hybridomas, TMH-1, TMH-2, and TMH-3, which produce monoclonal antibodies directed against tyrosinase, were obtained by fusion of SP2/0 myeloma cells and lymphocytes of rats hyperimmunized with purified melanosomal tyrosinase. These three monoclonal antibodies bound specifically to the mature, T4 form of tyrosinase, and did not bind to either of the precursor forms (T1 or T2) of the enzyme, which demonstrates that further posttranslational modifications of this enzyme occur which had not previously been detected. Epitope mapping studies have shown that at least two different immunologic determinants on tyrosinase are recognized by these antibodies. All three antibodies showed positive immunofluorescence staining of pigmented murine melanocytes from various sources, including B16 melanoma growing in vivo and in vitro, epidermal melanocytes, and retinal melanocytes. The antibodies did not cross-react with unpigmented cells, including K1735 amelanotic melanoma cells, albino murine skin or eye tissue, fibrosarcoma cells, rat fibroblasts, or epidermal keratinocytes. These monoclonal antibodies are sensitive, highly specific probes for pigmented mammalian melanocytes.
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PMID:Anti-T4-tyrosinase monoclonal antibodies--specific markers for pigmented melanocytes. 241 67

Human tyrosinase was partially purified from the lysate of a melanoma cell line and used to immunize BALB/c mice. Spleen cells from the immunized mice were fused with a murine myeloma cell line (NS-1), yielding a hybridoma (5C12) that produced monoclonal antibody directed against tyrosinase. 5C12 antibody reacted with normal human melanocytes, neval cells, primary cultures of melanoma biopsies, and most melanoma cell lines, including amelanotic lines with very low levels of enzyme activity. No reaction was found with keratinocytes, lymphoid cells, fibroblasts, and nonmelanoma cell lines. The 5C12 antibody was used to affinity-purify tyrosinase directly from a cell lysate, giving a single protein of 60,000 daltons, electrophoretically identical with enzyme activity and immunoreactivity with 5C12 antibody. Treatment of melanoma cells with periodate significantly reduced antigenicity. It can be inferred from these results that 5C12 antibody is directed against a carbohydrate moiety present in active and inactive tyrosinase, and that amelanotic melanoma cells may contain significant levels of the latter protein.
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PMID:Monoclonal antibody against human tyrosinase and reactive with melanotic and amelanotic melanoma cells. 312 79

Aspiration of lytic bone lesions is an excellent diagnostic test in the initial evaluation of primary bone neoplasia. However, cytologically, it can be difficult to differentiate osteosarcoma (OSA) from other bone neoplasms, including fibrosarcoma, chondrosarcoma, synovial cell sarcoma, and plasma cell myeloma. The purpose of this study is to determine the sensitivity and specificity of alkaline phosphatase (ALP) staining to differentiate OSA from other tumors that express vimentin by immunocytochemistry or immunohistochemistry. ALP is a hydrolytic enzyme present in multiple tissues including liver, kidney, intestine, placenta, and bone. Hypothetically, neoplasms actively producing bone should be specifically positive for ALP staining. Unstained, cytologic specimens were incubated for 8-10 minutes with nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indolyl phosphate toluidine salt-phosphatase substrate. A positive reaction stains the membrane of the cells gray to black. Samples were counterstained with a Romanowsky's stain to determine whether the sample was of representative cellularity. A total of 61 vimentin-positive neoplasms have been evaluated and confirmed histopathologically. Tumors that expressed vimentin and were positive for ALP included 33 OSAs, one multi-lobular tumor of bone, one amelanotic melanoma, and one chondrosarcoma. Tumors that expressed vimentin and were negative for ALP included chondrosarcomas (three of four), multiple fibrosarcomas, and multiple synovial cell sarcomas. The sensitivity is 100%, and the specificity is 89%. In conclusion, ALP appears to be a highly sensitive and fairly specific marker in the diagnosis of OSA.
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PMID:Use of alkaline phosphatase staining to differentiate canine osteosarcoma from other vimentin-positive tumors. 1575 69

Amelanotic melanoma, a renowned impersonator, has taken on a new persona. A 63-year-old woman was seen in the emergency room with a chief complaint of back pain after a fall and was discovered to have a 15-cm fungating mottled gray mass independent of bone on the right elbow. Initial workup discovered lytic calvarial lesions, anemia (Hb 7; Hct 20%), and circulating plasma cells consistent with plasma cell myeloma. Biopsy of the elbow mass displayed sheets of plasmacytoid cells, some reactive for CD138. Flow cytometry revealed a substantial portion of the plasma cells in the tumor that were kappa restricted consistent with cutaneous plasmacytoma. The elbow mass was initially signed out as extramedullary involvement by her myeloma. Reevaluation of the mass after the patient experienced an explosive growth of multinodular jet black malignant melanoma on ipsilateral breast revealed MART-1 and S-100 reactivity of the majority of the cells. In retrospect, the elbow mass was a neglected primary amelanotic malignant melanoma with neoplastic plasma cells participating in its chronic inflammatory infiltrate.
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PMID:Large neglected ulcerated melanoma mimicking extramedullary plasmacytoma. 2200 18