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

Malignant melanoma of the female genital tract comprises 3% of all melanomas afflicting females. Melanoma of the vulva is most common, comprising 45 patients treated by the author. Thirty-two percent had metastases to the regional lymph nodes on presentation. Five-year survival is 31.6%. Radical vulvectomy and radical groin dissection is the treatment of choice. Only 80 melanomas of the vagina have been reported, with cures being an extreme rarity. Forty cases of the female urethra reported in the literature and only five survivors have been reported. Melanoma of the uterus is extremely rare, with no cures recorded. Melanoma of the ovary may occur within a teratoma but most frequently is metastatic.
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PMID:Malignant melanoma of the female genital system: a report of 48 patients and review of the literature. 725 56

The autopsy material of the USSR AMS Cancer Research Center for 1960--1977 was studied. Among 3327 patients dying of malignant tumours, secondary tumour involvement of the heart was revealed in 170 (5.1%) cases, in 119 patients the tumour metastasized into the heart, in 51 grew into the pericardium. Most frequently, tumour involvement of the heart occurred in lung cancer, systemic diseases of the hemopoietic tissue, melanoma, and mammary gland carcinoma. Growth of the tumour into the heart, as a rule, was found in systemic diseases and lung cancer. Melanoma, renal carcinoma, and carcinoma of the oral cavity were characterized by small- and large-nodular forms of metastasis. The tumour involvement was most frequently found in the pericardium followed by the myocardium. In outgrowths of the tumour, the outer layer of the pericardium and in small-nodular metastases the visceral layer (epicardium) were affected most frequently. Hemorrhagic pericarditis was frequently observed in tumour alterations of the heart. Metastases and outgrowths into the heart were always associated with progression of the tumour.
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PMID:[Secondary tumors of the heart (based on autopsy materials in the Oncology Research Center of the Academy of Medical Sciences of the USSR over the period of 1960-1977)]. 740 18

The prognostic significance of 2 histological parameters, the level of invasion and maximum thickness is evaluated in 248 cases of malignant melanoma of the limbs staged T 1-3 N0M0 which were collected for Trial No. 1 of the W.H.O. Collaborating Centres for the Evaluation of Methods of Diagnosis and Treatment of Melanoma between September 1967 and December 1974. There is a linear relation of tumor thickness to mortality with a high statistical significance (P = 0.0002). Mortality also increases with progression of the level of invasion. The incidence of occult metastases to the regional lymph nodes increases with increasing thickness or level of invasion. Moreover, the age and sex adjusted survival curves are also dependent on both parameters. The comparison of the two methods revealed that the maximal tumor thickness is a more reliable prognostic factor than is the determination of the level of invasion.
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PMID:[1st Stage I melanoma of the limbs. Prognosis on the basis of the depth of invasion and maximum thickness]. 745 19

Melanoma cells often display a multidrug-resistant phenotype, but the mechanisms involved are largely unknown. We have studied here the recently identified transport-associated proteins, MRP and LRP, and the well-known drug resistance marker P-glycoprotein using a panel of 16 human melanoma cell lines and 71 benign and malignant melanocytic tissue samples. By flow cytometry and immunohistochemistry, expression of P-glycoprotein was not detectable on the protein level in the 10 cell lines analyzed, although by reverse transcriptase polymerase chain reaction, MDR-1 gene expression was demonstrated in 2 of 10 cell lines. In addition, immunohistology revealed P-glycoprotein expression in only 1 of 71 melanocytic lesions. In contrast, MRP was detected in a subset of melanoma cell lines by reverse transcriptase polymerase chain reaction and immunohistology (4 of 10). LRP expression was observed in 8 of 10 melanoma cell lines by immunochemistry and in 10 of 10 by reverse transcriptase polymerase chain reaction. Furthermore, MRP was detected immunohistologically in almost 50% of primary and metastatic melanoma specimens, although no significant differences were found between metastases taken before or after chemotherapy. Expression of LRP was detected in a subset of nevi with nevus cells exhibiting up to 25% positive LRP reactivity. In 13 of 21 primary melanomas and 23 of 37 metastases, more than 25% of tumor cells were stained by the LRP-56 monoclonal antibody. Particularly in the group of metastases with more than 50% of LRP-positive cells, 7 of 11 of the metastases had been previously exposed to chemotherapeutic drugs. Although the expression of membrane transport proteins may explain only the chemoresistance toward lipophilic, natural compounds and not resistance against alkylating agents, the lack of P-glycoprotein expression after chemotherapeutic treatment and the significant expression of MRP and LRP in melanoma cells provide first insights into the drug-resistant phenotype in melanoma. Additional studies analyzing the role of MRP and LRP in chemoresistance of melanoma are warranted.
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PMID:Membrane transport proteins associated with drug resistance expressed in human melanoma. 749 78

Fifty-three evaluable patients with metastatic malignant melanoma were enrolled in a phase II prospective study designed to assess the response rate, time to progression and survival after dacarbazine (DTIC) and interferon-alpha 2a (IFN-alpha 2a) treatment in patients with local metastatic disease compared with patients with distant metastases. Patients received intravenous DTIC from day 1 at a dosage of 400-500 mg/m2, repeated every 21 days (in the case of good tolerance--25 patients--the dose was increased to 600-800 mg/m2) combined with subcutaneous IFN-alpha 2a (9 x 10(6) U three times/week, increased in the case of good tolerance to 15 x 10(6) U three times/week). Forty-two patients with distant metastases were compared with 11 patients who had local metastatic disease. Three complete (6%) and six partial (11%) responses were seen, with an overall response rate of 17% (95% confidence interval 8-29). Patients with local metastases had a higher response rate (50%) compared with patients with distant metastases (visceral involvement, mediastinal and para-aortic lymph node metastases) (10%; p = 0.01). The median overall survival was 4.5 months. The progression-free interval for responders with distant metastases was significantly longer (11 months), than for responders with local metastases (4.5 months) (p = 0.004). These results may suggest that the combination treatment DTIC/IFN-alpha has a greater benefit in terms of longer progression-free interval in responders with distant metastases.
Melanoma Res 1995 Aug
PMID:Dacarbazine and interferon-alpha 2a in advanced malignant melanoma: high response rate and prolongation of response duration occur in different patient subpopulations. 749 65

Immunohistochemical analysis of the N-ras p21 and the p53 proteins was carried out on formalin-fixed sections of naevi, primary melanomas and metastases from patients with sporadic melanoma (SCMM) and with hereditary melanoma (HCMM)/dysplastic naevus syndrome (DNS). Seven out of 11 (64%) common naevi and three out of nine (33%) dysplastic naevi showed increased cytoplasmic N-ras expression. No p53 immunopositivity could be recognized in any of the naevus samples. However, strong N-ras expression as well as immunopositivity for p53 was recognized among primary melanomas and metastases with significantly higher frequency among samples from patients with HCMM compared with samples from SCMM cases (for N-ras, 40% vs 10%, P < 0.01; and for p53 43% vs 17%, P < 0.05). We have earlier registered N-ras codon 61 mutations among metastases from 59% of patients with HCMM and from 24% of subjects with SCMM. A comparison of the genetic data with the immunohistochemical results showed occurrence of increased N-ras p21 expression in the presence and absence of detectable N-ras mutant alleles. Increased expression of wildtype N-ras p21 may contribute to tumorigenicity in the absence of mutational activation, at least in a subset of melanomas. Altogether, N-ras p21 alterations are registered at earlier stages than p53 alterations in melanoma development and may be of aetiological importance, whereas p53 alterations may be associated with tumour progression in the late stages.(ABSTRACT TRUNCATED AT 250 WORDS)
Melanoma Res 1995 Apr
PMID:Immunohistochemical analysis of the N-ras p21 and the p53 proteins in naevi, primary tumours and metastases of human cutaneous malignant melanoma: increased immunopositivity in hereditary melanoma. 762 Mar 36

We have recently described a new method for measurement of tyrosinase activity in small amounts of human serum (100 microliters), where the purification of tyrosinase is obtained by adsorption of the enzyme to concanavalin A sepharose. The method, which measures stereospecific dopa oxidation, was used in the winter of 1992-93 for the measurement of activity in serum obtained from 30 healthy subjects and from 10 patients with melanoma metastases. The serum tyrosinase values in the 30 subjects ranged from 0.1 to 1.0 nkatal/l, and the mean value and standard deviation was 0.4 +/- 0.2 nkatal/l. In the 10 patients with melanoma, the tyrosinase serum values ranged from 1.1 to 10.6 nkal/l, and the mean value was 3.1 nkatal/l.
Melanoma Res 1995 Apr
PMID:Tyrosinase activity in the serum of patients with malignant melanoma. 762 Mar 38

Between January 1956 and December 1990, 17 patients younger than 17 years with available pathological screens of de novo cutaneous melanoma, and with no other risk factors (xeroderma pigmentosum, giant congenital naevi, congenital melanoma or a proven family history of dysplastic naevus syndrome) were seen at the Gustave-Roussy Institute. The median age was 9 years and 9 months (range 2 years and 3 months-16 years and 9 months). The primary disease was located in the lower extremities in 10 cases, the trunk in five cases, and the upper extremities or head and neck in one case. The disease was localized for 10 patients at presentation (stage I), six had proven nodal metastasis (stage II) and one patient had nodal and breast metastases. The median thickness of the primary lesion was 2.89 mm (range 0.64-10). Five tumours were at level III on Clark's index, eight at level IV and four at level V. Six cases were classified as superficial spreading, two as unclassified radial growth, three nodular, three with Spitzoid cells, and three were unclassified. Two patients presented local recurrence with an initial unclassified melanoma, with a thickness greater than 2.5 mm. At a median follow-up time of 7 years, two patients had died from recurrent disease, and one patient had died from a second malignancy.
Melanoma Res 1995 Apr
PMID:Melanoma arising de novo in childhood: experience of the Gustave-Roussy Institute. 762 Mar 39

Restriction of the T cell receptor repertoire suggesting ongoing specific immune mechanisms has recently been described in melanoma tissue by several groups of investigators. The functional relevance for immunotherapy of melanoma, however, has not been established. We studied the T cell receptor repertoire in two melanoma metastases of a patient with a mixed response to immunotherapy. Expression of T cell receptor V beta regions was determined by subgroup-specific semiquantitative RNA polymerase chain reaction (PCR). In the regressing skin lesion a restricted expression of the T cell receptor repertoire and overexpression of three V beta subgroup genes was found; no restriction was present in the simultaneously progressing skin lesion of the same patient, compared with peripheral blood lymphocytes. Comparison of T cell receptor V beta gene expression in two metastatic lesions of a patient with simultaneously growing skin metastases, who did not receive immunotherapy, revealed only minor differences. These observations show for the first time an association between restricted T cell receptor repertoire and responsiveness of melanoma to immunotherapy and suggest a role of T cells using the overexpressed V beta genes for the cytokine-induced tumour regression.
Melanoma Res 1995 Apr
PMID:Restriction of T cell receptor V beta repertoire in melanoma metastasis responding to immunotherapy. 762 Mar 41

The liver metastasis formation of two human melanoma cell lines were compared in male and female SCID mice. The intrasplenic injection of both tumour lines resulted in a significantly higher number of liver metastases in male than in female mice; the incidence and weight of spleen tumours, as well as the incidence of metastases were similar. Both melanoma cell lines bound fluorescent oestradiol, progesterone and testosterone conjugates, and proved to be positive for oestrogen receptor-related protein by immunocytochemistry. These observations support the view that endocrine factors influence the progression of human melanomas. This SCID mouse model could be useful in studying the effects of hormonal manipulations on human melanoma metastases.
Melanoma Res 1995 Apr
PMID:Sex-dependent liver metastasis of human melanoma lines in SCID mice. 762 Mar 43


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