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)

8 patients suffering from malignant melanoma have been found to have various degrees of hypomelanoses of the skin. Depigmentation of the skin and/or hair associated with malignant melanoma may take several forms. Schematically six clinical types are described: - vitiligo-like hypomelanoses distant from cutaneous tumors; - vitiligo-like depigmentation associated with uveitis (incomplete Vogt-Koyanagi); - hypomelanoses in the primary tumor and/or its metastases; - "halo melanoma" in which the hypomelanoses encircles the primary tumor and/or its metastases; - halo nevi around preexisting benign nevocellular nevi; - "non-specific depigmentary phenomen" distant from the primary tumor or its metastases. Histological and ultrastructural studies of the depigmented skin show an absence of melanocytes. The association of hypomelanoses of the skin with malignant melanoma is probably not coincidental. Various hypothesis are discussed as well as the prognostic significance of such an association.
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PMID:[Hypomelanosis of the skin and malignant melanoma (author's transl)]. 75 17

In 1975, 117 patients with malignant melanoma attented the Department of Dermatology at the University of Cologne, and three of these had had a superficial spreading melanoma (SSM) over a long period-one patient most probably for more than 25 years. With these patients another primary malignant melanoma developed, though not a metastasis. It appears that SSM gives no protection against other melanomas of the superficial or nodular type. In comparison, a 70-year-old patient had had a pigmented tumour for about 40 years and this suddenly spread five years ago; however, at least some of the metastases regressed to form vitiligo-like lesions surrounding deposits of melanin in macrophages. In this case the spontaneous regression did not protect the patient against new metastases in the lymph nodes and probably in the liver as well.
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PMID:[Primary multiple malignant melanomas of unusually long duration]. 100 59

We have tested the diagnostic value in malignant melanoma of HMB45, a monoclonal antibody available for use on paraffin-embedded tissue. MATERIAL AND METHOD. Tissues tested. The following pathological tissues were tested: 10 intradermal and 11 compound naevi; 6 spitz naevi; 20 dysplastic naevi; 10 blue naevi; 2 Bednar's tumours; 6 Sutton naevi; 15 melanonychias; 21 cutaneous and 11 ocular malignant melanomas (MM), and 3 achromic metastases. Control tissues were: vitiligo (20), carcinoma (5), malignant schwannoma of the orbit (1), soft tissue sarcoma (5) and malignant lymphoma (5). Antibodies. The antibodies used were antiprotein S100, antivimentin, anticytokeratin (KL1), monoclonal antileucocyte (CD45) antibodies and HMB45, a monoclonal antibody of the IgG 1 type obtained from lymph node metastases from pigmented malignant melanomas. RESULTS. None of the control tissues were stained by the HMB Ab. Intradermal naevi did not react positively. Compound naevi: the juntional cells were stained by HMB45 in 2/10 cases. Dysplastic naevi: HMB45 showed heterogeneous reactivity of junctional cells in 15/20 cases, and this correlated with the degree of atypia. Blue naevi: HMB45 stained the superficial and deep cells in 3/10 cases. Bednar's tumour: no cell was stained by HMB45. Spitz naevi: HMB45 gave an intensely positive reaction of junctional cells in 4/5 cases and a weaker reaction of dermal cells. Sutton naevi: the naevus cells were not stained by HMB45 in 5/6 cases. In simple melanocytic hyperplasia of the nail bed, only a few atypical cells were stained. In superficially spreading melanoma (SSM) all neoplastic cells were stained by HMB45 in proportion to their degree of atypia. Residual naevus cells were negative. The anti S100 and the antivimentin antibodies stained all neoplastic and naevus cells. In nodular melanoma (NM), HMB45 stained all neoplastic cells in proportion to their degree of atypia. The antivimentin Ab stained the neoplastic cells, and so did the anti-S100 Ab which also stained inflammatory cells. In acral-lentiginous melanoma (ALM), HMB stained the dermal tumoral cells moderately and the junctional cells more strongly. In ocular melanoma, HMB45 strongly stained the fusiform cells and less strongly the epithelioid cells. In achromic metastases from cutaneous malignant melanomas, HMB45 strongly stained the neoplastic cells but did not stain the peritumoral cells. DISCUSSION. The purpose of this study was to compare the value of HMB45 with that of other immunohistochemical staining methods A. Main data from the literature. (ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Contribution of monoclonal antibody HMB45 in the histopathologic diagnosis of melanoma]. 170 64

We have identified and studied twenty-seven patients with melanoma who also had vitiligo. Four patients had vitiligo before the diagnosis of melanoma, and twenty-three developed depigmentation after the diagnosis of malignancy. We also have reviewed published reports about twenty-four other patients with melanoma who developed vitiligo. The clinical course of the melanoma in the fifty-one patients was remarkably similar. Thirty-seven had a melanoma arising at a site which tends to carry a poor prognosis, for example, on the trunk, under the nail, or on the mucous membranes. Forty-nine patients had metastases in regional lymph nodes or at distal sites. Thirty-three patients survived 5 years, and twenty-five survived 10 years. These data suggest that the appearance of vitiligo in patients with metastatic melanoma portends a longer survival than expected. The patients with vitiligo are not necessarily cured and eventually may succumb to metastatic disease. We were unable to determine whether the vitiligo caused retardation of tumor growth or whether the melanoma caused vitiligo.
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PMID:Vitiligo in patients with metastatic melanoma: a good prognostic sign. 664 67

Vitiligo frequently develops in patients with cutaneous melanomas, especially those who have survived with metastases for prolonged periods. To our knowledge, only one patient with an ocular melanoma in whom vitiligo developed has been described. We have observed a second patient in whom vitiligo developed six to eight years after he had undergone an enucleation for ocular melanoma. Multiple hao nevi developed in a third patient who had an ocular melanoma. The association of vitiligo and ocular melanomas in these patients may not be the result of chance alone.
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PMID:Vitiligo or halo nevi occurring in two patients with choroidal melanoma. 705 98

Antigens, antibodies and immune complexes seem to play a major role in the course of malignant melanoma, in detection of the disease progression, in treatment planning and monitoring. Of particular interest are cell and matrix adhesion molecules, growth factors and cytokines, proteases, gangliosides and major histocompatibility complex class I and II molecules. Antigens expressed on melanoma cells, but not on mature melanocytes, may be used as markers for the degree of the differentiation of the melanoma cells. The more the melanoma cells are dedifferentiated, the smaller is the antigenic similarity to normal melanocytes. Also, different antigens may be identified in various stages of the disease and may be used as tumor markers for disease recurrence or progression. Certain melanoma-associated antigens (MAA) such as epidermal growth factor receptor and adhesium molecules can be modulated by cytokines. Early melanoma evokes an antigen-derived T cell response, which becomes attenuated with the progression of the disease. A variety of cell adhesion molecules present on melanoma cell surfaces may play a role in regulation of cellular cytotoxicity. Free antimelanoma antibodies are usually not detectable in the sera of patients with melanoma, possibly due to their binding to shed antigens and formation of immune complexes or to tissue antigens. When bound to normal melanocytes, they cause the appearance of associated hypopigmentation. The identification of melanoma surface antigens led to generation of monoclonal antimelanoma antibodies (MAb) by laboratories. Strategies utilizing MAb based on immunologic approaches have been developed. MAb to tumor-associated antigens of melanoma cells may be used for therapeutic purposes in man. Sera of patients with vitiligo were capable of causing regression of melanoma metastases in mice due to the presence of a high titer of naturally occurring antimelanoma antibodies. Immunization of melanoma patients with vaccines containing treated melanoma cells or specific melanoma antigens or anti-idiotypic antibodies resulted in an increasing titer of antimelanoma antibodies and regression of the tumor to some extent. The appearance of hypopigmentation in patients with melanoma serves as proof for the activity of antimelanoma antibodies, although its association with the prognosis is still not clear. The thorough investigation in the field of MAA and related antibodies is aimed at improving specific antimelanoma immunotherapy, such as antigenic targeting or enhancement of production of autoantibodies, as well as better understanding of the process of metastasis and the melanoma-immune system interaction.
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PMID:Antigens and antibodies in malignant melanoma. 793 69

Anti-tyrosinase antibodies were measured by enzyme-linked immunosorbent assay in sera of patients with malignant melanoma with either metastatic disease or no evidence of disease, in patients with melanoma and associated hypopigmentation (MAH), in patients with vitiligo and in healthy volunteers. The mean relative absorbance (Arel) was calculated by dividing the absorbance of each sample by the mean value for the control group. Using this method, the Arel of the control group was 1.000(SE 0.083). Arel of patients with metastatic disease (1.516; SE 0.225) was significantly higher (P = 0.03) than the value for the controls, but insignificantly higher than that for patients with no evidence of disease (1.216; SE 0.148). Patients with no evidence of disease, in whom the primary lesion originated in the lower limb, had a significantly higher (P = 0.01) Arel than the healthy volunteers. Patients with metastatic disease showed higher Arel if their primary lesions were confined to the area of the head and neck or to the lower limb. Patients with vitiligo had higher Arel values for their anti-tyrosinase antibody than any of the other groups. However, those with melanoma and MAH (vitiligo-like) had the same Arel of anti-tyrosinase antibodies as the controls or the patients with metastatic melanoma. This observation reflected the possible absorption of anti-tyrosinase antibodies to melanoma antigens, and pointed to the participation of anti-tyrosinase antibodies in the destruction of normal melanocytes in patients with melanoma, as part of the immune reaction towards this disease.
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PMID:Anti-tyrosinase antibodies in malignant melanoma. 870 52

Our purpose was to determine the maximum tolerated dose and toxicity associated with soluble Chinese hamster ovary [s(CHO)] recombinant human interleukin (IL) 1 receptor (IL-1R; Immunex, Seattle, WA) administration in humans and to determine the effective biological dose and/or maximum tolerated dose of the s(CHO) IL-1R in combination with high-dose IL-2 as determined by reduction in IL-2 toxicity and modulation of its biological effects. Twenty-seven patients with metastatic cancer were treated with escalating doses of s(CHO) IL-1R at 1, 1, 5, 10, 20, 40, and 55 mg/m2 i.v. on days -6 (except cohort 2), 1, and 15 and IL-2 at doses of 300,000 IU/kg (cohort 1) and 600,000 IU/kg (cohorts 2-7) i.v. every 8 h on days 1-5 and 15-19. No toxicity directly attributable to s(CHO) IL-1R was observed. The median number of IL-2 doses was 23. Hypotension and neurotoxicity were the major dose-limiting toxicities for the IL-2/s(CHO) IL-1R combination. Of the 24 patients treated with full-dose IL-2, there were six responses, three complete and three partial (response rate, 25%). Three patients developed thyroid dysfunction, and all 3 responding melanoma patients exhibited vitiligo. The t1/2 of s(CHO) IL-1R alone was 24-30 h and was not significantly altered by coadministration with IL-2. Whole-blood functional assays indicated that sufficient s(CHO) IL-1R was present in the circulation at top dose levels to inhibit the in vitro effects of IL-1beta on IL-8 induction; however, no effect on IL-2-induced IL-8 induction, or on the IL-1beta- or IL-2-induced tumor necrosis factor production, was observed. Suppression of IL-2-mediated tumor necrosis factor alpha and IL-6 induction in vivo during the first 24 h after IL-2 administration was observed, and the neutrophil chemotactic defect normally seen with IL-2 was not observed. IL-1R antagonist induction far exceeded that seen previously with IL-2 alone. No inhibition of either serum C-reactive protein induction or enhanced urinary nitrate excretion and no consistent effect on IL-2-related changes in peripheral blood mononuclear cell phenotype or endothelial adhesion molecule expression were seen. The coadministration of s(CHO) IL-1R produced no apparent reduction in IL-2 clinical toxicity manifested by either the ability to administer more IL-2 than anticipated or a reduction in the toxicity associated with a given amount of IL-2. Therefore, no effective biological dose could be identified for the s(CHO) IL-1R.
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PMID:A two-part phase I trial of high-dose interleukin 2 in combination with soluble (Chinese hamster ovary) interleukin 1 receptor. 960 78

On the basis of compelling preclinical data in cats and dogs we initiated a clinical gene therapy study in nine patients with advanced solid tumors using xenogeneic fibroblasts secreting human IL-2 (Vero-IL-2 cells). Cohorts of three successive patients with tumors accessible to CT- or ultrasound-guided injection were treated repeatedly with 5 x 10(5), 5 x 10(6), or 5 x 10(7) Vero-IL-2 cells. Endpoints of the study were feasibility, toxicity, and clinical and biological effects of this novel approach to immunotherapy of cancer. Histopathological, immunological and molecular analyses were performed on biopsy specimens of tumors and blood samples from before, during and after treatment. Low levels of serum antibodies to Vero cells developed in 2/9 patients. Analysis of tumor biopsies showed increased expression of CD3 mRNA and enhanced tumor infiltration with varying lymphocyte subpopulations after treatment. In addition, monoclonal alterations of the TCR repertoire of blood and tumor lymphocytes were observed. Treatment was well tolerated and toxicity consisted of transient fever in one patient and short-lived, mild itching and erythema in two others. One patient with soft tissue sarcoma showed a more than 90% and more than 50% reduction of the volume of two distant, non-injected metastases, respectively, lasting for 22+ months. Four other patients showed stabilization of their disease for three to nine months, among whom was a patient with melanoma who developed marked vitiligo. We conclude that repeated injection of up to 5 x 10(7) Vero-IL-2 cells was safe and showed biological and clinical activity in heavily pretreated patients with advanced solid tumors. Further evaluation of intratumoral application of Vero-IL-2 seems warranted.
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PMID:Gene therapy with cytokine-transfected xenogeneic cells in metastatic tumors. 1002 23

We performed a phase I trial to evaluate the safety and tolerability of repeated skin injections of IL-2-transfected autologous melanoma cells into patients with advanced disease. Cell suspensions, propagated from excised metastases, were IL-2 gene transfected by adenovirus-enhanced transferrinfection and X-irradiated prior to injection. Vaccine production was successful in 54% of the patients. Fifteen patients (37%) received two to eight skin vaccinations of either 3 x 10(6) (intradermal) or 1 x 10(7) (half intradermal, half subcutaneous) transfected melanoma cells per vaccination (secreting 140-17,060 biological response modifier program units of IL-2/10(6) cells/24 hr). Analyses of safety and efficacy were carried out in 15 and 14 patients, respectively. Overall, the vaccine was well tolerated. All patients displayed modest local reactions (erythema, induration, and pruritus) and some experienced flu-like symptoms. Apart from newly appearing (4 of 14) and increasing (5 of 14) anti-adenovirus and newly detectable anti-nuclear antibody titers (1 of 15), recipients developed de novo or exhibited increased melanoma cell-specific delayed-type hypersensitivity (DTH) reactions (8 of 15) and vitiligo (3 of 15) and showed signs of tumor regression (3 of 15). This supports the idea of a vaccine-induced or -amplified anti-cancer immune response. None of the patients exhibited complete or partial regressions, but five of them experienced periods of disease stabilization. Three of these individuals received more than the four planned vaccinations and their mean survival time was 15.7 +/- 3.5 months as compared to 7.8 +/- 4.6 months for the entire patient cohort. These data indicate that IL-2-producing, autologous cancer cells can be safely administered to stage IV melanoma patients and could conceivably be of benefit to patients with less advanced disease.
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PMID:Immunotherapy of metastatic malignant melanoma by a vaccine consisting of autologous interleukin 2-transfected cancer cells: outcome of a phase I study. 1022 32


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