Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 21 patients with a variety of skin tumors (squamous cell carcinomas, malignant melanomas, basal cell epitheliomas and mycosis fungoides) or pre-cancerous lesions (Bowen's disease, actinic keratosis, junctional nevus cell nevus) the radioactive phosphorus uptake test demonstrates a significantly increased concentration of P32 in those tumors. There were no false negative tests. The possibility of differentiation of malignant melanoma from benign nevus cell nevus and the early recognition of cutaneous metastases is described. Furthermore recurrence of previously irradiated or excised basal cell epitheliomas can be detected without a biopsy. No hematological side-effects were observed.
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PMID:[The radiophosphorus (32P)-test in precanceroses and malignant tumors of the skin]. 127 Feb 58

Data obtained in experimental murine tumors and in clinical specimens of human breast cancer have suggested that the nm23 gene may function as a metastasis suppressor gene. In this report we examined the nm23 mRNA level in tumor tissue obtained from distant metastases in 33 patients with malignant melanoma. The gene was differentially expressed in the tumors with a 20-fold range in hybridization intensities. The levels of nm23 mRNA in benign nevi obtained from 12 of the 33 patients were relatively low, with a mean value of 17% of that in the melanomas. In attempts to relate the level of nm23 expression in the tumor metastases to progression of the disease, the time from biopsy of the primary tumor to the appearance of metastases was used as a clinical end point. It was found that patients developing metastases during the first 2 years after diagnosis had significantly lower levels of tumor nm23 expression (56% of the mean value) compared to patients with less aggressive disease (164%) (P < 0.0004). In concordance with previous data the association found here between low levels of nm23 mRNA and the malignant potential of melanomas suggests that the nm23 gene may be implicated in the mechanism of disease progression in some types of human cancer.
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PMID:Levels of nm23 messenger RNA in metastatic malignant melanomas: inverse correlation to disease progression. 135 24

We have used polymerase chain reaction (PCR), an amplification procedure, and oligonucleotide hybridization to detect ras gene point mutations in DNA from melanoma tumor samples. Genomic DNA was examined from 40 specimens of melanotic lesions, including benign nevi, primary melanomas, lymph node metastases, and systemic metastases. Adjacent normal skin or peripheral blood was analyzed as control material in 28 cases. ras mutations were detected overall in 25% of malignant tumors. In addition, mutations of all three ras genes were detected. We observed ras mutations in 2 of 4 benign atypical nevi (2 X K12), 4 of 22 primary melanomas (3 X K12, 1 X H12, 1 X N61), and 4 of 14 secondary (5 X K12, 1 X N61) tumors. One with a primary melanoma had concurrent K12 and H12, and two patients with secondary tumors had concurrent K12/N61 and K12 Asp/K12 Val mutations, respectively, making a total of 10 of 40 (25%) patients with ras mutations. This is the first demonstration of K-ras mutations in human melanoma. The presence of K-ras mutations in nevi, putative melanoma precursors, suggests that ras activation may be an early event in melanoma development. No correlation between tumor thickness and the presence of a ras mutation was observed.
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PMID:ras mutations in human melanotic lesions: K-ras activation is a frequent and early event in melanoma development. 269 57

Using the murine monoclonal antibody (MoAb) B1.1 we have analyzed the immunochemical profile and the tissue distribution of a human melanoma associated antigen (MAA) carrying an epitope shared by the 180 kd CEA. Results of this study have demonstrated that the epitope expressed by the MAA is carried by a distinct set of molecules of 110-140 kd. Similarly to the 180 kd CEA molecules synthesized by carcinomas, the expression of the melanoma associated CEA like components (MA-CEA) is upregulated by IFN-alpha. The tissue distribution of MA-CEA is not restricted to malignant primary and metastatic melanocytic lesions but is found also at low levels in 64% of benign nevi. No circulating CEA was found in patients bearing widespread metastatic disease of MA-CEA positive lesions. Preliminary clinical evaluation of stage I melanoma patients bearing MoAb B1.1 positive lesions has not shown a significative prognostic association of this phenotypic marker with clinical course of the disease.
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PMID:Molecular profile, tissue distribution and prognostic evaluation of a human melanoma-carcinoma antigen recognized by the murine monoclonal antibody B1.1. 323 49

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

Two axillary lymph nodes from a patient who underwent modified radical mastectomy for carcinoma of the breast showed benign nevus cells in the fibrous capsule and within afferent lymphatics. Subsequently, an intradermal nevus from the area of drainage of the axillary lymph nodes was excised, which showed groups of nevus cells lying within small lymphatic channels. It is postulated that the nevus cells in the lymph node capsule could represent benign metastases from the intradermal nevus.
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PMID:Nevus cells within lymph nodes. Possible metastases from a benign intradermal nevus. 402 28

Tenascin is a large extracellular matrix glycoprotein which is widely distributed in normal, hyperplastic and neoplastic tissues. Its function is unknown but it has been associated with the epithelial-stromal interactions, such as cell adhesion and movement which take place, e.g. in morphogenesis, cellular proliferation and neoplasia. In this study, we investigated tenascin expression in 70 benign, dysplastic and malignant melanocytic tumors by using immunohistochemistry and monoclonal anti-tenascin 143DB7C8 antibody on paraffin sections. In all types of benign nevi, both intradermal, compound and junctional, there was a moderate expression of tenascin at the dermoepidermal junction and in the papillary dermis. In dysplastic nevi, the fibrotic areas in the papillary dermis also showed a moderate staining for tenascin. Invasive malignant melanomas showed the strongest expression of tenascin. In addition to the staining at the dermo-epidermal junction and in the papillary dermis, there was a variable expression of tenascin in the reticular dermis. Intracytoplasmic tenascin was detected both in primary melanomas and melanoma metastases. In conclusion, we have shown that tenascin expression is moderately increased in benign and dysplastic melanocytic tumors and greatly increased in malignant melanomas and melanoma metastases. The function of tenascin may be related to the cellular-stromal interactions and it is possibly associated with the proliferation and spread of the melanocytic tumors.
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PMID:Increased tenascin expression in melanocytic tumors. 753 53

We have shown previously that overexpression of p-170 glycoprotein-mediated multidrug resistance plays only a minor role in conferring chemoresistance to human melanoma cells. In addition to membrane transporters like p-170, metabolizing enzyme systems have been implicated in altered drug sensitivity. Recently, glutathione and associated enzymes have been associated with resistance to alkylating substances, particularly in gastrointestinal and gynecologic cancers. In this study, we investigated whether increased levels of glutathione and related enzymes may play a role in chemoresistance in melanoma. Levels of glutathione, glutathione S-transferase (GST), glutathione reductase, and gamma-glutamyl transpeptidase were analyzed in melanoma and non-melanoma cell lines. In addition, 18 melanoma metastases derived from skin and lymph nodes were examined. Levels of gamma-glutamyl transpeptidase were statistically different in cells derived from melanocytic tumors compared with non-melanoma cell lines and normal cells. In addition, GST levels in metastases derived from skin or lymph nodes were significantly lower than those in permanent cell lines. However, levels of glutathione and related enzymes in metastases and cell lines fluctuated over a wide range, up to 40-fold, regardless of treatment status or origin of metastases. In a second part of the study, the expression of GST isoenzymes alpha, mu, and pi was studied by immunohistology in 10 benign nevi, 29 primary melanomas, and 39 melanoma metastases before and during chemotherapy. Expression of GST isoenzymes was increased with tumor progression, and GST pi was the strongest isoform expressed. However, no correlation was found between GST levels by immunohistochemistry and the course of tumor progression, between GST levels in metastases obtained before or during chemotherapy, or between GST levels and clinical response. These data suggest that alterations in glutathione metabolism and the expression of GST do not play a major role in resistance to chemotherapeutic drugs in melanoma.
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PMID:Glutathione and related enzymes in tumor progression and metastases of human melanoma. 761 63

Melanoma often develops from clinically and histologically well-defined precursor lesions. During progression of normal melanocytes to benign nevi, dramatic changes in the expression of adhesion receptors are observed, most notably loss of E-cadherin which mediates adhesion of melanocytes to keratinocytes, and gain of Mel-CAM which predominantly mediates heterotypic adhesion between cells. Major changes in adhesion receptors also occur when cells progress from dysplastic nevi or biologically early radial-growth-phase primary melanomas to biologically late (tumorigenic) vertical-growth-phase primary melanomas. The integrin subunit beta 3 is up-regulated, whereas other integrins such as alpha 6 beta 1 and alpha V beta 1 are down-regulated. This review highlights the major changes in adhesion receptor expression on melanocytes at various stages of tumor progression.
Invasion Metastasis
PMID:Adhesion receptors in human melanoma progression. 765 8

The records of sixty patients who had a malignant melanoma of the foot or ankle were reviewed retrospectively to determine the clinical features, prognostic factors, and distinguishing characteristics. Fifty-seven patients were white and three were black. There were forty-two women and eighteen men (a female-to-male ratio of 2.3 to 1). The mean age at the time of presentation was fifty-seven years (range, twenty-two to eighty-three years). The most common site of involvement was the plantar aspect of the foot. The mean duration of follow-up was forty-five months (range, three to 144 months). Kaplan-Meier life-table analysis revealed an over-all five-year survival rate of 63 per cent and an over-all ten-year survival rate of 51 per cent. The mean duration of survival for the patients who had a plantar or subungual lesion was significantly shorter than that for the patients who had a lesion at another site on the dorsal aspect of the foot or on the ankle (forty-seven compared with seventy-two months) (p = 0.02). The mean depth of the lesion, according to the criteria of Breslow, was 3.03 millimeters, and the mean level, according to the classification of Clark et al., was IV. According to the classification of the American Joint Commission on Cancer, forty-three patients had stage-I or II (local) disease, thirteen had stage-III disease (nodal or in-transit disease, defined as cutaneous or subcutaneous metastases more than two centimeters from the primary tumor but not beyond the regional lymph nodes), and four had stage-IV disease (distant visceral metastases) at the time of presentation. Lesions at plantar and subungual sites were also associated with a higher prevalence of clinical misdiagnosis compared with lesions on the dorsal aspect of the foot or on the ankle (p = 0.02). The misdiagnoses included a benign nevus (one patient), a paronychia (one patient), a pyogenic granuloma (two patients), a plantar wart (three patients), a ganglion cyst (one patient), a blister (two patients), and a traumatic lesion (five patients).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Malignant melanoma of the foot and ankle. 767 91


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