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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melanoma rarely occurs in children not over 14 years of age. We report on the clinical and pathological features of three patients (two girls and one boy aged 6, 12 and 11 years respectively) from the St Laurentius hospital (Roermond, Netherlands) with melanoma of the skin, in whom the lesions histologically resembled the more frequently occurring spindle and epithelioid cell naevus (SE naevus). In all three cases, metastases were found in the regional lymph nodes. Further metastases were found in the last patient only, after follow-up periods of 29, 8 and 3 years respectively. The problems in distinguishing between melanoma and SE naevus are discussed, on the basis of a literature study and a retrospective analysis of 40 cases retrieved from PALGA (the nationwide computerized pathological archive in the Netherlands) up to and including 1990. As the diagnosis in such cases has important therapeutic consequences, we advise to submit the slides to experienced pathologists in the field, such as the Pathology Panel of the Dutch Melanoma Committee (Nederlandse Melanoom Werkgroep).
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PMID:[3 children with a melanoma of the skin]. 174 Oct 70

The importance of thioproteins, essential to the ribonucleotide reduction pathway, has been demonstrated in human primary and metastatic melanoma tissues. The thioredoxin reductase/thioredoxin and the glutathione reductase/glutathione/glutaredoxin electron transfer pathways represent alternative electron donors for ribonucleotide reductase and regulate the synthesis of deoxyribonucleotides, the substrates for DNA synthesis, in the S phase of the cell cycle. In addition to their important role in DNA synthesis and cell division, these thioproteins provide effective antioxidant defence against oxygen radicals and hydrogen peroxide. In human metastatic melanoma cells and tissues the thioredoxin reductase/thioredoxin system is located both in the cell cytosol and on plasma membranes and is under allosteric regulation by calcium. As a consequence, calcium plays an important role in determining the intracellular redox status, cell division and differentiation. Recently, the intracellular redox conditions have been shown to be important in the reaction of alkylating anti-tumour drugs such as the chloroethylnitrosoureas. In addition to previously established mechanisms, these highly reactive drugs inhibit thioredoxin reductase, glutathione reductase and ribonucleotide reductase by chloroethylation of their respective thiolate active sites. Incorporation of the 14C chloroethyl group in drug sensitive and resistant human metastatic melanoma cell lines depends on the redox status, with resistant cells being more oxic than sensitive cells. Thioredoxin reductase is 500-fold more sensitive than glutathione reductase to the newly developed nitrosourea, Fotemustine (diethyl-1-[3,2 chloroethyl]-3-nitrosoureido ethyl phosphonate). It has been shown that melanomas which respond to Fotemustine therapy contain more thioredoxin reductase whereas resistant metastases yielded the opposite result.(ABSTRACT TRUNCATED AT 250 WORDS)
Melanoma Res
PMID:New aspects in the pathophysiology of cutaneous melanoma: a review of the role of thioproteins and the effect of nitrosoureas. 184 12

Melanoma is a valuable model to study phenotypic traits that are regulated during cell differentiation and malignant transformation. Melanoma cells display extensive phenotypic and antigenic heterogeneity. Studies of this attribute have provided insight into events that take place during normal melanocyte differentiation and give clues to traits that contribute to malignancy. It is possible that the phenotypic and genotypic heterogeneity present among melanoma cells within a single lesion includes a subset of cells with traits that favor tumor progression and metastasis. This review discusses the identification and characterization of antigens expressed by melanoma cells and their potential contribution to melanocyte differentiation and malignant transformation.
Cancer Metastasis Rev 1991 Jun
PMID:Antigens of melanocytes and melanoma. 187 54

Human melanoma cells in culture are the source of a wide variety of polypeptide growth factors. Melanoma-derived basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF)-A and PDGF-B chains, transforming growth factor (TGF)-alpha and TGF-beta, interleukin (IL)-1 alpha and IL-1 beta, and melanoma growth stimulatory activity (MGSA) have similar biochemical and functional properties when compared to their counterparts produced by untransformed cells. In contrast to melanoma cells, normal melanocytes, even under optimal growth conditions, express only TGF-beta 1 and MGSA at detectable levels suggesting that production of the other growth factors is a tumor-associated phenomenon. Recent evidence suggests that at least two of the growth factors, bFGF and MGSA, contribute to autocrine growth stimulation of melanoma cells. Whether PDGF, TGF-alpha, IL-1, and TGF-beta act in an autocrine mode is unclear at present. However, these four growth factors are among those secreted by melanoma cells and, therefore, can be expected to interact with normal cells of the tumor stroma in vivo. Such paracrine effects include not only growth modulation in the context of angiogenesis and stroma formation, but also tissue degradation by proteolytic enzymes, the modification of extracellular matrix composition, and expression of adhesion receptors.
Cancer Metastasis Rev 1991 Jun
PMID:Growth factors in melanoma. 187 58

The prognostic value of cellular DNA content in melanoma metastases was investigated by flow cytometric analysis of fresh or paraffin-embedded tumour blocks from 95 consecutive patients referred to the Helsinki University Central Hospital Melanoma Team. Thirty-three per cent of the tumours were DNA diploid and 67% DNA aneuploid. S-phase fractions were lower in DNA diploid than in DNA aneuploid tumours (10.7% and 17.6%). Tumour ploidy and S-phase fraction were shown by multivariate Cox model analysis to be independent prognostic variables and major determinants of survival after first recurrence. Surprisingly, patients with DNA aneuploid tumours and with tumours with low SPF survived significantly longer than those with DNA diploid or high SPF tumours. This exceptional finding of favourable prognosis for DNA aneuploid tumours was more prominent among patients receiving intensive systemic therapy and among patients with stage IV disease, probably indicating a tendency for DNA aneuploid tumours to have higher sensitivity to systemic therapy.
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PMID:DNA aneuploidy and low S-phase fraction as favourable prognostic signs in metastatic melanoma. 191 Dec 24

Between 1960 and 1990, a total of 998 patients were treated at the Sydney Melanoma Unit for cutaneous melanoma of the head and neck. There were 595 male and 403 female patients, with a median age of 53 years. The most common primary lesion site was the face (47%), followed by the neck (29%), scalp (14%), and ear (10%). Histologic types were as follows: superficial spreading 30%, nodular melanoma 28%, lentigo maligna melanoma 16%, and other 26%. All patients underwent surgical treatment. Primary closure of wounds was achieved in 52% of patients, and excision margins were 2 cm or less in 45%. A total of 152 patients had therapeutic neck dissections, and 234 had elective neck dissections. The overall local recurrence rate was 13%, and this was significantly influenced by increasing tumor thickness and Clark level. The recurrence rate in the neck after neck dissection was 24%, and the rate of parotid recurrences was 14%. Melanoma-specific survival was 77% at 5 years and 66% at 10 years for the entire group. By univariate analysis, survival varied significantly with age, tumor thickness, ulceration, anatomic sub-site, histologically positive nodes, and the presence of distant metastases. A diagnosis of lentigo maligna melanoma and elective lymph node dissection both appeared to improve survival. With multivariate analysis, all of these factors remained significant prognostic factors except elective node dissection, which lost its beneficial influence.
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PMID:Experience with 998 cutaneous melanomas of the head and neck over 30 years. 195 80

Lymphoscintigraphy was performed on 82 patients with melanoma registered at the University Melanoma Clinic. From these data, precise lymphatic drainage basins could be drawn for the head, neck, shoulder, and trunk. These drawings differed significantly from the classic anatomic studies, providing a functional look at the cutaneous lymphatic drainage. This new method correlates much better with clinical experiences and demonstrates much larger areas of ambiguous drainage than previously reported. Data from the lymphoscintigrams also emphasize the individuality of cutaneous lymphatic flow. The implications of these data in planning elective node dissections for intermediate thickness melanomas are obvious, since it is estimated that up to 59% of the dissections for trunk and head and neck primary melanomas may be misdirected if based on classic anatomic studies. The data indicate that all patients with head, neck, and shoulder lesions should undergo lymphoscintigraphy to define possible drainage basins at risk for metastatic disease. Similarly, truncal lesions require scintigrams except when they are within four well-defined areas with an extremely low probability of ambiguous drainage. Lesions in these areas show very reliable and predictable drainage to a single nodal group.
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PMID:Redefinition of cutaneous lymphatic drainage with the use of lymphoscintigraphy for malignant melanoma. 195 4

All the consultants agree that, given this patient's history, a common skin tumor like squamous cell or basal cell carcinoma is unlikely. Melanoma or Merkel cell carcinoma belong in the differential. Interestingly, the consultants all suggest a biopsy of the lesion prior to other testing, and because this tumor is so accessible, a biopsy should not interfere with further testing or treatment. Drs. Weymuller and Marks would then proceed with a CT scan; Dr. Ridge favors an MRI scan. While a chest-ray is in order to rule out metastases, Dr. Weymuller also suggests immunocytochemistry. All the experts agree that the primary tumor should be excised. Dr. Weymuller would perform a total parotidectomy with facial nerve preservation, while Drs. Marks and Ridge suggest a superficial parotidectomy with facial nerve preservation. Drs. Weymuller and Ridge would also perform a modified radical neck dissection. In the absence of cervical disease, Dr. Marks would treat the neck primarily with radiotherapy. Only Dr. Weymuller favors immediate reconstruction and would use a lower trapezius island flap or a large rotational flap. Drs. Marks and Ridge prefer primary closure or skin graft. Drs. Weymuller and Ridge would treat this patient with combined therapy, giving radiotherapy to the primary area and the neck postoperatively at a dose of 55-60 Gy. However, Dr. Marks would treat the primary site postoperatively and the neck primarily with radiotherapy. He would treat the primary site with 59.40 Gy and the neck with 50.40 Gy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Merkel cell carcinoma of the ear. 198 33

Melanoma metastases were harvested from 82 patients for the purpose of growing and expanding tumor-infiltrating lymphocytes (TIL). Tumor tissue cell suspensions were incubated with interleukin-2 (IL-2), followed by repeated exposure to tumor antigen with or without OKT3 monoclonal antibody (MoAb). Initial growth success was achieved in 56 of 82 cultures (72%). Efforts were made to expand 26 of these 56 cultures for therapeutic TIL; 23 of 26 early cultures (88%) were successfully expanded for in vivo therapy. It took a mean of 78.5 +/- 25.4 days to grow sufficient TIL for treatment. Therapy included cyclophosphamide (1 g/m2) on day 1, followed by a 96-hour continuous infusion of IL-2 (18 x 10(6) IU/m2/d) on days 2 to 5, and approximately 10(11) (mean 1.49 +/- 0.93 x 10(11)) TIL on day 2. Patients who responded received monthly IL-2 as a 96-hour infusion. Median patient age was 45 years of age. Sixty-seven percent of the patients were men. Performance status was 0 to 1 in 77% of patients. Thirty-four percent of the patients had liver metastases. The usual IL-2 toxicities were seen. Response rate for 21 patients was 24% (95% confidence interval, 10% to 49%). One complete response was achieved with cells 98% CD4+; four partial responses were achieved with cells 80%, 94%, 98%, and 98% CD8+, respectively. Four of eight patients who received TIL, which had never been stimulated with OKT3, had tumor response. The authors conclude that a treatment plan for IL-2/TIL is technically difficult, costly, and effective for only a minority of patients. Overall, clinical results are not clearly superior to those obtained with other IL-2 regimens.
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PMID:Continuous interleukin-2 and tumor-infiltrating lymphocytes as treatment of advanced melanoma. A national biotherapy study group trial. 204 29

Fotemustine is a novel chloroethylnitrosourea derivative currently used in Phase III clinical trials for disseminated metastatic melanoma. This drug has been shown to inhibit enzymes in the ribonucleotide reduction pathway (i.e., thioredoxin reductase, glutathione reductase and ribonucleotide reductase). 14C chloroethyl-labelled Fotemustine covalently labels the thiolate active sites of thioredoxin reductase and glutathione reductase yielding 14C chloroethyl-thioether enzyme-inhibitor complexes. Enzyme activities can be restored by a reduced thioredoxin or reduced glutathione mediated beta-elimination of the chloroethyl group. 14C Fotemustine has been used to determine its reactivity and metabolism in drug sensitive and resistant melanoma metastases and in cultures of sensitive and resistant clones of human melanoma cells. Melanoma metastases from four different patients who were treated with Fotemustine could be labelled with radioactive drug only under reducing conditions with NADPH as electron donor and DTNB as substrate. FPLC analysis of these extracts revealed two radioactive proteins (I) glutathione reductase and (II) an unidentified protein with 95 and 50 kDa subunits. A similar labelling pattern was also found in extracts of Fotemustine sensitive melanoma cells (Cal 1). Fotemustine resistant tumors were melanotic and contained more glutathione reductase than thioredoxin reductase, whereas sensitive tumors were clinically amelanotic with more thioredoxin reductase than glutathione reductase. Fotemustine resistant melanoma cells (Cal 7) showed a slower uptake of 14C-label with 34% less isotope intracellularly in 1 h compared to sensitive melanoma cells (Cal 1). These results strongly indicate (I) the induction of alternate electron donors thioredoxin reductase or glutathione reductase for ribonucleotide reduction determines tumor and melanoma cell responses to the drug and (II) Fotemustine transport and the intracellular redox status seems to regulate resistance in melanoma cells and tissues.
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PMID:Sensitivity and resistance in human metastatic melanoma to the new chloroethylnitrosourea anti-tumor drug Fotemustine. 206 1


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