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)

A phase I-II study of cyclocytidine was conducted in 102 patients, 96 of whom had metastatic solid tumors and six of whom had acute leukemia. The drug was administered in 5- or 10-day courses of single daily iv or sc injections of 100-675 mg/m2 day. Two complete and six partial responses were observed in 64 solid tumor patients evaluable for response, 52 of whom had malignant melanoma or adenocarcinoma of gastrointestinal origin. The median duration of the responses was 6 months. An additional seven patients achieved stabilization of their disease for greater than or equal to 2 months. No responses occurred in six patients with acute leukemia. Side effects included nausea and vomiting, postural hypotension, and parotid pain, occurring in approximatley one third of patients receiving greater than 200 mg/m2/day. No myelosuppression was observed in six patients receiving 5-day courses of 100-200 mg/m2/day. Myelosuppressive toxicity became increasingly severe with doses greater than 200 mg/m2/day x 10, related at least in part to prior chemotherapy exposure including the nitrosoureas.
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PMID:Phase I-II evaluation of cyclocytidine. 6 28

N-(Phosphonacetyl)-L-aspartate (PALA) is an analog of the transition state for the aspartate transcarbamylase reaction and has been reported previously to be a potent and specific inhibitor of de novo pyrimidine nucleotide biosynthesis. It is now shown that PALA has considerable antitumor activity against certain transplantable tumors in mice. PALA, unlike other antimetabolites, was less effective against ascitic leukemias than against two solid tumors, B16 melanoma and Lewis lung carcinoma. Another solid tumor, Ridgway osteogenic sarcoma, which is sensitivie to many established chemotherapeutic agents, did not respond to PALA. Daily or intermittent treatment with PALA did not significantly increase the life-span of mice bearing i.p. leukemia L1210. The survival time of mice bearing i.p. P388 leukemia was prolonged by PALA treatment by up to 64%. In a number of experiments mice bearing i.p. B16 melanoma survived 77 to 86% longer than did controls when treated with PALA (490 mg/kg) on Days 1, 5, and 9. Lewis lung carcinoma, a tumor refractory to most established antineoplastic agents, was highly sensitive to PALA. Treatment on Days 1, 5, and 9 following s.c. implantation of Lewis lung carcinoma was curative to 50% of the mice. If treatment was delayed until s.c. Lewis lung tumors had reached about 500 mg, PALA neither cured the mice nor produced significant tumor regression. However, extensive delay of tumor growth and prolongation of survival were still observed.
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PMID:Antitumor activity of N-(phosphonacetyl)-L-aspartic acid, a transition-state inhibitor of aspartate transcarbamylase. 106 66

Seven human malignant melanoma lines were maintained in vitro for various periods of time. One line, established in this laboratory from a metastatic solid tumor by repeated treatment of the primary outgrowth with 0.02 percent EDTA, allowed a continuous culture of melanoma cells free of fibroblasts. By light microscopy, cells in each line could be classified into one of three morphologic types: elongated dendritic, cuboidal, or triangular dendritic. Four of the seven lines exhibited various degrees of pigmentation. The growth pattern was determined by plating efficiency and saturation density for each line. Cytogenetic analysis with the fluorescent banding technique revealed only human chromosomes with gross aneuploidy. Major marker chromosomes specific for each line were identified. None of the parameters studied showed any correlation or interdependence with one another, except for an association of elongated dendritic morphology with poor plating efficiency and low saturation density.
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PMID:Characterization of human maligant melanoma cell lines. I. Morphology and growth characteristics in culture. 112 34

In vitro assays of cell-mediated tumor immunity utilizing 51Chromium (51Cr) labelling of cultured adherent solid tumor cells were designed which allowed an effector cell/target cell incubation time of 48 h without overriding spontaneous 51Cr release. In a series of 16 consecutive experiments, blood lymphocytes from healthy human donors, from patients with tumors unrelated to the cultural tumor target cells, and from colon carcinoma and melanoma patients were tested for their cytotoxic effects on various target cell pairs, human colon carcinoma, melanoma, or skin fibroblasts. The same reagents were used in simultaneously performed microplate and 51Cr assays. Results obtained by visual counting of microplate tests and by 24-h assays of 51Cr release or 51Cr retention correlated in 20/25 effector-cell/target-cell combinations. In a series of six consecutive experiments, lymph-node cells from untreated Wistar/Furth rats, and rats bearing either chemically-induced colon carcinoma NG-W1 or polyoma virus-induced sarcoma P-W13 were tested for their cytotoxicity on syngeneic rat colon carcinoma and sarcoma target cells. Criss-cross type experiments were performed by microplate and 15Cr techniques done in parallel. Results obtained by visual counting of microplate tests and by 48 h assays of 51Cr release or 51Cr retention correlated in 15/18 effector-cell/target-cell combinations.
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PMID:A long-term 51chromium assay for in vitro cell-mediated tumor immunity. Correlation with simultaneously performed microplate assays. 117 12

A thirty-four-year-old man was admitted to our hospital because of the disturbed visual acuity and pain on the eye movement of the right eye. He had prominent right eye and CT-scan and MRI of the brain disclosed a tumor which could be obviously distinguished from the extraocular muscles, optic nerve and the bulb of eye in the retrobulbar region. On operation we identified dark-red solid tumor which was 3.0cm in diameter, and diagnosed it malignant melanoma pathologically. Because postoperative study detected amelanotic melanoma in the white patch on the right upper extremity, this right orbital tumor was considered to be the metastasis of it from the right upper extremity. Metastatic malignant melanoma of the skin to the orbit is very rare, while most of the eye-associated malignant melanoma originates from uveal tract, special choroid, and conjunctiva. This case was the 26th case of these in the world and the first case in Japan, furthermore the 4th case in the world whose first symptoms were caused by the orbital metastasis.
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PMID:[A case of malignant melanoma with orbital metastasis which caused the first symptoms]. 128 95

Once thought to be rare, leptomeningeal carcinomatosis from systemic cancer is becoming more common as cancer patients are living longer. Lung, breast and malignant melanoma comprise the majority of solid tumor cases with this condition. The hallmark of the disease and the differential diagnosis are discussed. Only the identification of malignant cells in the cerebrospinal fluid provides as clear-cut diagnosis. Biochemical markers, thus far, cannot substitute for a positive cytology, but may aid in the diagnosis. We report and discuss 3 cases of complete biochemical and radiological assessment and variable degree of aggressiveness of treatment. Better control of the systemic cancer may result in prolongation of life.
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PMID:Leptomeningeal carcinomatosis: a report of 3 cases and review of the literature. 131 85

We have previously shown that 3F8, a murine IgG3, monoclonal antibody (MoAb) specific for the ganglioside GD2, mediates tumor cell kill in vitro and in vivo. We now describe receptor requirements of polymorphonuclear leukocytes (PMN) in 3F8-mediated cytotoxicity (ADCC) of human GD2 (+) melanoma and neuroblastoma cell lines. PMN from a child with leukocyte adhesion deficiency (LAD) were devoid of CD11/CD18 adhesion molecules and mounted no detectable ADCC. MoAb to CD11b, CD11c, and CD18 each efficiently blocked ADCC by normal PMN. In contrast, a panel of different MoAbs to CD11a had no significant inhibitory effect on ADCC, a finding consistent with the low-to-absent expression of the CD11a ligand, intercellular adhesion molecule-1, on the target cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly increased the expression of CD11b, CD11c, and CD18 on normal PMN, decreased the expression of Fc receptors (FcR), and enhanced ADCC by normal but not by LAD PMN. MoAbs to FcRII and FcRIII each efficiently blocked ADCC; anti-FcRI MoAb had no effect. Flow cytometry using anti-FcRII MoAb versus anti-FcRIII MoAb did not show cross competition, suggesting that inhibition of ADCC was not a steric effect resulting from FcRII proximity to FcRIII. PMN deficient in FcRIII (obtained from patients with paroxysmal nocturnal hemoglobinuria) and PMN depleted of FcRIII by treatment with elastase or phosphatidylinositol (PI)-specific phospholipase C produced low ADCC, supporting a role for the PI-liked FcRIII. Thus, optimal ADCC using human PMN, human solid tumor cells, and a clinically active MoAb (conditions that contrast with the heterologous antibodies and nonhuman or nonneoplastic targets used in most models of PMN ADCC) required CD11b, CD11c, FcRII, and the PI-linked FcRIII. Furthermore, in this clinically relevant system, GM-CSF enhancement of antitumor PMN ADCC correlated with increased expression of CD11/CD18 molecules.
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PMID:Absolute requirement of CD11/CD18 adhesion molecules, FcRII and the phosphatidylinositol-linked FcRIII for monoclonal antibody-mediated neutrophil antihuman tumor cytotoxicity. 134 7

Human stem cell factor (SCF) acts in the presence of other growth factors to stimulate the growth of primitive hematopoietic progenitor cells. These effects are performed by activation of the SCF receptor, c-kit. Because of the potential use of SCF in patients undergoing chemotherapy and bone marrow transplantation, the effect of SCF on nonhematopoietic tumors requires investigation. To determine whether human tumor cell lines display c-kit receptors, we performed binding experiments with 125I-SCF on a breast carcinoma cell line (Du4475), a gastric carcinoma cell line (KATO III), a melanoma cell line (HTT144), as well as two small cell lung carcinoma cell lines (H69 and H128). The biologic effect of SCF on tumor cell lines was assessed by its ability to stimulate tritiated thymidine uptake and to enhance colony growth in methylcellulose. The breast carcinoma cell line, Du4475, as well as two small cell lung carcinoma cell lines, H69 and H128, exhibit high-affinity c-kit receptors with approximate binding affinities of 40, 100, and 90 pmol/L, respectively. The number of high-affinity receptors per cell ranged from 700 to 9,500. The gastric carcinoma cell line, as well as the melanoma cell line, showed trace binding of 125I-SCF. In the presence of SCF alone, or in combination with granulocyte-macrophage colony-stimulating factor or interleukin-3, there was less than a 17% increase in the colony growth of Du4475, H69, or H128 cell lines. Postulating that the lack of growth response could be secondary to endogenous SCF production by the tumor cell lines, we used an RNAse protection assay to determine whether the tumor cell lines contain SCF messenger RNA (mRNA). In addition, we tested tumor cell line supernatants for the presence of secreted SCF protein by enzyme immunoassay, and analyzed the tumor cell lines for membrane-bound SCF by indirect immunofluorescence. Our results show that the Du4475, H69, and H128 cell lines, as well as a melanoma cell line (HTT144), have multiple copies of SCF mRNA. Soluble SCF protein was detected in the cell supernatants in the Du4475 and H69 cell lines and SCF was found on the surface of all four cell lines. These data show that some human solid tumor cell lines display high-affinity c-kit receptors and produce SCF, which can be detected on the cell surface. These results suggest the possibility that autocrine production of SCF by c-kit receptor-bearing tumor cells may enhance cell growth in tumor cell lines.
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PMID:Nonhematopoietic tumor cell lines express stem cell factor and display c-kit receptors. 137 16

The distributions of acidic fibroblast growth factor (aFGF) and basic FGF (bFGF) in extracts of various cultured mammalian cells were determined from their elution profiles on heparin-affinity chromatography, and assay of activity as ability to stimulate DNA synthesis in BALB/c3T3 cells. Only aFGF was found in extracts of mouse melanoma B 16 cell and rat Morris hepatoma cell (MH1C1) lines. Other tumor cell lines established from solid tumors and some normal cells contained bFGF as a main component, but blood tumor cell lines contained no aFGF or bFGF. The FGFs in extracts of solid tumor tissues derived by transplantations of these cultured tumor cells and various normal tissues of mice were also examined. Tumors formed by all cell lines, regardless of whether they produced aFGF, bFGF, or neither, contained bFGF that was probably derived from host cells including capillary endothelial cells, in addition to the tumor-derived aFGF or bFGF, if produced. The content of bFGF, possibly derived from the host, in these tumor tissues was comparable to those of various mouse organs other than thymus, lung, spleen, and testis, which have higher bFGF contents. Tumor tissues derived from cultured cells producing bFGF had relatively higher bFGF contents. Like bFGF, aFGF was distributed almost ubiquitously in normal mouse tissues.
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PMID:Distribution of fibroblast growth factors in cultured tumor cells and their transplants. 137 29

The efficacy of present day antineoplastic regimens depends upon the delivery and penetration of therapeutic agents through the tumor vascular and interstitial spaces to the tumor cell target. The distribution of relevant molecules or cells in a solid tumor is often poor and heterogeneous and is believed to be due to a number of pathophysiological factors, including elevated interstitial fluid pressure (IFP). Using the wick-in-needle technique, IFP was measured in primary breast and colorectal carcinomas as well as their respective metastases to the lymph nodes and liver in a total of 17 patients. IFP was also measured in one recurrent renal cell carcinoma, one melanoma metastasis to the lymph nodes, and another melanoma metastasis to the lung. IFP varied from 4 to 50 mm Hg with a mean +/- SD of 20 +/- 13 mm Hg in the neoplasms (n = 41 measurements; n = 21 tumors), while IFP in normal tissues had a mean of 2 +/- 4 mm Hg (n = 11). The mean IFPs for metastatic melanoma, primary breast carcinoma, and liver metastases from a colorectal primary were found to be 33 +/- 14, 15 +/- 9, and 21 +/- 12 mm Hg, respectively. In the renal cell carcinoma, the pressure was 38 mm Hg. These results agree with the findings of our 3 previous studies examining IFP in human superficial melanomas (14.3 +/- 12.5 mm Hg, n = 12), cervical carcinomas (15.7 +/- 5.7 mm Hg, n = 12), and head and neck tumors (13.2 +/- 8.8 mm Hg, n = 19), and indicate that in all types of human tumors studied to date, IFP was significantly elevated above that of normal tissue. This observation may be useful in localizing tumors during needle biopsy.
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PMID:Interstitial hypertension in human breast and colorectal tumors. 142 83


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