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)

Morphometric techniques in diagnostic pathology of pigmented skin lesions are not yet well established. The so-called maturation of melanocytes (nevus cells) with progressive descent into the dermis is one important criterion to differentiate benign from malignant melanocytic lesions in conventional histology. We therefore examined morphometrically the nuclear parameters of melanocytes (nevus cells) in the superficial and deep portion of 120 pigmented skin tumors (40 cases each of malignant melanoma. Spitz's nevus and benign dermal nevus) with special emphasis on the "maturation to the depth". A "maturation parameter" (MP) was assessed in each individual case, calculating the ratio of the nuclear area in the deep portion and in the superficial portion. The mean values of MP were 0.720 +/- 0.11 for dermal nevi, 0.725 +/- 0.10 for Spitz's nevi and 1.125 +/- 0.11 for malignant melanoma. The difference between malignant melanoma and both groups of benign nevi was statistically significant (p less than or equal to 0.01). The efficiency of the maturation parameter was 0.95 for the distinction of dermal nevi and malignant melanomas, and 0.97 for the distinction of Spitz's nevi and malignant melanoma. Measurements of the superficial portion only revealed comparatively low efficiency values (0.70 and 0.56, respectively). Our results indicate that morphometric evaluations of the nuclear area of melanocytes (nevus cells) in the deep portion of the infiltrate are more discriminative than those in the superficial portions. The establishment of the MP allows a better differentiation between benign and malignant melanocytic lesions and therefore morphometric methods may obviously be a helpful tool in the diagnosis of melanocytic skin tumors.
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PMID:Nuclear parameters in the superficial and deep portion of melanocytic lesions--a morphometrical investigation. 342 29

To identify melanoma associated antigens (MAAs) shared by human and guinea pig melanoma cells, a battery of murine monoclonal antibodies (MoAbs) to human MAA and an antiserum to S100 protein were tested with four newly established guinea pig melanoma cell lines. Only the monoclonal antibodies 149.53 and 225.28 which recognize distinct determinants of the human high molecular weight-MAA (HMW-MAA) reacted with all four guinea pig melanoma cell lines. To compare the binding site of MoAbs 149.53 and 225.28 with guinea pig and human melanoma cells, inhibition binding experiments were performed with antiidiotypic monoclonal antibodies which completely inhibit the binding of MoAbs 149.53 and 225.28 to human melanoma cells. The binding of MoAb 149.53 to guinea pig melanoma cells was partially inhibited by antiidiotypic MoAbs MF9-10 and MK1-180 which recognize distinct private idiotopes within the antigen combining site of MoAb 149.53. On the other hand the binding of MoAb 225.28 to guinea pig melanoma cells was completely inhibited by antiidiotypic MoAbs MF11-30 and TK1-F2 which recognize distinct private idiotopes within the antigen combining site of MoAb 225.28. These results suggest that the determinant recognized by MoAb 149.53 on guinea pig melanoma cells is similar but not identical to that recognized on human melanoma cells, while the determinants recognized by MoAb 225.28 on the two types of cells do not display any detectable differences under the experimental conditions tested. The target structure on the guinea pig melanoma cells identified by MoAbs 149.53 and 225.28 is a Mr 280,000 molecule which has the same apparent molecular weight as one of the two subunits of the HMW-MAA synthesized by human melanoma cells. Sequential immunoprecipitation experiments with guinea pig melanoma cells showed that the determinant recognized by MoAb 149.53 is expressed on a subpopulation of the molecules recognized by MoAb 225.28. Immunohistochemical staining with MoAb 225.28 of a variety of different tissues from normal adult guinea pigs showed that the corresponding antigenic determinant is detectable only in basal cells of epidermis and hair follicles of skin. S100 protein, which is a cytoplasmic constituent of normal human melanocytes, benign nevi, and malignant melanocytes, was also detected in the cytoplasm of the four cultured guinea pig melanoma cells lines. The results of the present investigation may lead to a better understanding of the phylogenetic evolution of the human HMW-MAA and suggest that guinea pig melanoma may serve as a useful animal model for immunobiological studies and carcinogen-induced tumorigenesis investigations.
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PMID:Cross-reactivity of murine anti-human high molecular weight-melanoma associated antigen monoclonal antibodies with guinea pig melanoma cells. 347 98

Guanidinobenzoatase is a trypsin-like protease capable of degrading fibronectin. An inactive form of guanidinobenzoatase is present on the surface of benign naevus cells and these cells stain very weakly with 9-aminoacridine, a known competitive inhibitor of guanidinobenzoatase. Malignant melanoma and metastatic malignant melanoma cells exhibit strong surface staining with 9-aminoacridine and also exhibit strong staining of cytoplasmic RNA with acridine orange. These simple fluorescent techniques have been used to distinguish benign naevus cells from malignant melanoma cells in human skin sections. This difference in cell surface staining with 9-aminoacridine has been demonstrated to be caused by the presence or absence of an inhibitor. The inhibitor can be displaced from the cell surface enzyme and then replaced by an affinity purified inhibitor obtained from fresh liver homogenates. It is proposed that the inhibition or control of cell surface guanidinobenzoatase may be one of the regulatory mechanisms by which benign naevus cells are prevented from developing into malignant melanoma cells.
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PMID:The role of inhibitors in the fluorescent staining of benign naevus and malignant melanoma cells with 9-amino acridine and acridine orange. 350 14

Human monoclonal antibodies were generated by fusing a nonsecretory variant of murine myeloma cells with lymphocytes obtained from the lymph nodes of patients with metastatic cutaneous malignant melanoma. Two human IgG monoclonal antibodies, designated 2-139-1 and 6-26-3, were extensively studied for their patterns of binding to cells in 64 specimens of formalin-fixed, paraffin-embedded tissue sections. These comprised: 23 cutaneous and 2 ocular melanomas; 4 specimens of lentigo maligna; 27 benign nevi; 2 basal and 2 squamous cell neoplasms of the skin; and 4 specimens of normal skin. A direct avidin-biotin-immunoperoxidase staining method was used. Under these conditions, the antibodies reacted with variable intensity to all 18 primary cutaneous malignant melanomas, 5 metastatic cutaneous melanomas, and both ocular melanomas. Antibody 2-139-1 reacted with 1 of 4 specimens and 6-26-3 with 3 of 4 specimens of lentigo maligna. Two of 5 dysplastic nevi reacted with both antibodies, each with a smaller proportion of cells than with melanomas. There was no reactivity with the 22 other nevi representing a spectrum of histologic types or with normal melanocytes. Basal cell and squamous cell carcinomas of the skin also were not stained. These human monoclonal antibodies appear to be useful in distinguishing malignant melanomas from benign nevi, with the exception of dysplastic nevi, and from basal and squamous cancers of the skin in routinely prepared tissue sections. They may also help to identify the cytoplasmic antigens that are immunogenic in humans.
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PMID:Human monoclonal antibodies that distinguish cutaneous malignant melanomas from benign nevi in fixed tissue sections. 352 8

The retinoids have been investigated extensively as chemopreventive and therapeutic agents in a variety of neoplasms. They have been shown to inhibit the proliferation of transformed cell lines in vitro and transplanted tumors in vivo. In cultured murine melanoma cells, retinoids inhibit proliferation and induce differentiation. Human melanoma cell lines have shown a mixed response. The clinical experience with retinoids in melanoma has been limited. Previously we investigated the activity of topical B-all-trans-retinoic acid (Retin-A, vitamin A acid, retinoic acid, and tretinoin) against intracutaneous metastases from malignant melanoma. We saw complete remission of multiple lesions in one individual and regression of several lesions in a second patient. This experience led us to conduct the present pilot trial of topical tretinoin in dysplastic nevus syndrome. The latter is a precursor of malignant melanoma. We saw regression of some of the treated lesions to benign nevi showing minimal or no dysplasia. Thus topical tretinoin appears to possess some activity against melanoma and at least one of its precursor conditions. In view of these preliminary results, more extensive trials are warranted to better define the role of tretinoin in the chemoprevention of malignant melanoma in high-risk lesions.
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PMID:Role of topical tretinoin in melanoma and dysplastic nevi. 353 20

A mouse monoclonal antibody (TNKH1) which recognizes a marker of benign nevus cell nevus has been obtained for the first time. A375 human melanoma cells were induced to differentiate with n-butyric acid and used as immunogen. When frozen sections of nevomelanocytic lesions were tested with TNKH1 obtained by this method, 15 of 15 acquired nevus cell nevi, and two of two congenital melanocytic nevi showed strong reactivity; whereas five of five primary melanomas (three nodular, one lentigo maligna, and one subungual), as well as 10 of 10 metastatic melanomas were nonreactive. One superficial spreading melanoma showed residual TNKH1-positive nevus cells, and TNKH1-negative melanoma cells. Four of six dysplastic nevi, which would be precursors of some malignant melanomas, showed heterogeneity in staining intensity with TNKH1; indicating the initial change of malignant transformation. No reaction was found with normal melanocytes. Thus, the antigen that TNKH1 defines is present on benign nevus cells, and absent on malignant cells as well as normal melanocytes. TNKH1 could be a powerful tool not only for the diagnosis of malignant melanoma, but also for the assessment of the ontogeny of various melanomas.
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PMID:The differential reactivity of benign and malignant nevomelanocytic lesions with mouse monoclonal antibody TNKH1. 354 36

Cytological atypia, revealed in the course of routine light microscopy, is considered a valuable indicator of malignancy in melanocytic lesions. A clear definition of the term cytological atypia, however, is lacking. Therefore, by morphometric analysis of ultrathin sections of 11 malignant melanomas (7 invasive, 3 in situ, and 1 lentigo maligna melanoma) and 10 compound nevi, we evaluated the discriminating power of the various facets of cytological atypia, i.e., nuclear area, area of the nucleolus, area of the total cell, and nuclear irregularity. In each case, at least 50 intraepidermal melanocytic cells were examined. The two-sided U-test showed significant differences between intraepidermal nevus and melanoma cells, with regard to the mean values (mean) and standard deviations (s) of the nuclear area (mean and s, p = 0.00011), area of the nucleolus (mean, p = 0.00043; s, p = 0.00011), and area of the total cell (mean, p = 0.00011; s, p = 0.00093). However, only the mean values and standard deviations of the nuclear area allowed a clear distinction in each individual case. The area of the nucleus can be estimated in the course of routine histology. We therefore think that the size and variation of the nuclear area should be considered in the histological differential diagnosis between malignant melanomas and benign nevi.
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PMID:Morphometric and ultrastructural analyses of melanocytes, nevus cells, and melanoma cells. 359 44

A young Caucasian woman had a large area of blue-gray discoloration on the flank and palpable axillary lymph nodes. The discolored area had enlarged during a recent pregnancy, contained multiple subcutaneous nodules, demonstrated increased cellularity and mitotic activity, and was associated with an axillary lymph node containing black streaks within the capsule. Although the lesion was initially considered to be a metastatic malignant melanoma, re-evaluation showed it to be a benign cellular blue nevus with benign nevus-cell aggregates within a regional lymph node. We report this case to emphasize how cellular blue nevus can simulate malignant melanoma and to increase physician awareness of this benign variant of melanocytic nevus so that inappropriate surgery and chemotherapy can be avoided.
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PMID:Cellular blue nevus simulating metastatic melanoma: report of an unusually large lesion associated with nevus-cell aggregates in regional lymph nodes. 362 65

A murine monoclonal antibody, VM-1, which binds to basal cells of normal human epidermis, reduces the ability of human squamous cell carcinoma cells (SCL-1) derived from the skin to attach and spread on collagen by about 50% and causes cell rounding. Similar effects have been previously shown using normal human keratinocytes. The attachment of cell lines derived from human lung squamous cell carcinomas (SW1271 and SW900), melanoma A375, glioblastoma 126, and fibrosarcoma HT1080 is also inhibited by this antibody. VM-1 antibody does not bind to normal human fibroblasts, benign nevus cells, or the human B-cell-derived line 8866. VM-1 antibody inhibits the growth of SCL-1 cells in vitro as measured by cell numbers and [3H]thymidine ([3H]TdR) incorporation. It is not cytolytic in the presence of complement as measured by 51Cr release. Repeated treatment of SCL-1 cells with VM-1 antibody significantly reduces the proportion of SCL-1 cells that attach to collagen. In addition, after treatment of SCL-1 cells with VM-1 antibody, several proteins can no longer be demonstrated by gel electrophoresis of the cell-free supernatant. The VM-1 antibody effect on attachment and spreading is partially reversed by pretreatment of the collagen surface with laminin and fibronectin, but not with the carbohydrates chondroitin-6-sulfate or hyaluronic acid or with the protein lysozyme. By fluorescence staining, the antigen recognized by VM-1 antibody is membrane-bound and Triton X-100 extractable. The VM-1 antigen is excluded from Bio-Sil TSK-400 and sediments at about 10.5 S. It has a covalent molecular weight on the order of 10(6). Proteinase K digestion produces VM-1 antibody reactive fragments, assumed to be polysaccharides, with a polydisperse molecular weight distribution in the range 5000 to 30,000. The VM-1 antigen is partially lost from solution on boiling and is no longer detectable in the aqueous or organic phase after chloroform-methanol extraction. The properties of the VM-1 antigen are consistent with those of a proteoglycan involved in attachment and spreading of keratinocytes and certain tumor cells on collagen.
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PMID:Inhibition of attachment and growth of tumor cells on collagen by a monoclonal antibody. 369 49

By means of architectural and cytological features, atypic and severe atypic melanocytic hyperplasia (AMH and SMH) as well as severe melanocytic dysplasia may be differentiated from malignant melanoma on one hand and benign nevus on the other.
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PMID:[Atypical melanocyte hyperplasia]. 371 27


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