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)

One hundred twenty-six dogs with histologically confirmed, measurable malignant tumors were evaluated in a prospective study to determine the response to the antineoplastic drug mitoxantrone. Ninety-five dogs had been refractory to one or more treatment modalities (surgery, n = 57; chemotherapy other than mitoxantrone, n = 37; radiation, n = 4; whole body hyperthermia, n = 1). The extent of neoplastic disease was determined immediately before each dose of mitoxantrone was administered (1 to 10 doses, 2.5 to 5 mg/m2 of body surface area, IV) 21 days apart. Each dog was treated with mitoxantrone until the dog developed progressive disease or until the dog's quality of life diminished to an unacceptable level as determined by the owner or attending veterinarian. A partial or complete remission (greater than 50% volume reduction) was obtained in 23% (29/126) of all dogs treated. Tumors in which there was a partial or complete remission included lymphoma (11/32), squamous cell carcinoma (4/9), fibrosarcoma (2/9), thyroid carcinoma (1/10), transitional cell carcinoma (1/6), mammary adenocarcinoma (1/6), hepatocellular carcinoma (1/4), renal adenocarcinoma (1/1), rectal carcinoma (1/1), chondrosarcoma (1/2), oral malignant melanoma (1/12), cutaneous malignant melanoma (1/1), myxosarcoma (1/1), mesothelioma (1/1), and hemangiopericytoma (1/1). Our results indicated that mitoxantrone induces measurable regression in various malignant tumors in dogs.
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PMID:Efficacy of mitoxantrone against various neoplasms in dogs. 206 Nov 77

Two murine monoclonal antibodies, 29-13 (IgG1) and 29-2 (IgG2a), generated against malignant fibrous histiocytoma plasma membranes immunoprecipitated a Mr 200,000 protein (p200), with an isoelectric point between 6.3 and 7.5. Two additional antibodies, 35-16 (IgG1) and 30-40 (IgG2a), generated against Ewing's sarcoma membranes, immunoprecipitated an acidic protein of Mr 160,000 (p160), with an isoelectric point between 5.8 and 6.7. Monoclonal antibodies 29-13 and 29-2 recognize a similar determinant(s) on p200 while 35-16 and 30-40 recognize different determinants on p160. Monoclonal antibody 29-13 exhibited significant binding to membranes isolated from fibrosarcoma and aggressive fibromatosis; moderate binding to osteosarcoma, hemangiopericytoma, and malignant fibrous histiocytoma; and minimal to no binding to other soft tissue sarcoma plasma membranes. The p200 protein was not expressed in 16 other malignant tumors and in only 3 of 35 normal human tissue specimens. High levels of p200 were selectively expressed by leiomyosarcoma, Ewing's sarcoma, and fibrosarcoma cells as well as neonatal fibroblasts in vitro, but not by other carcinoma cell lines or B-lymphoblasts. The p160 protein appeared to be selectively expressed by Ewing's sarcoma with little or no expression on other sarcomas, carcinomas, or normal tissues. However, the p160 antigen was expressed in Ewing's sarcoma, leiomyosarcoma, melanoma, 4 of 9 carcinomas, and neonatal fibroblasts in vitro. The affinity of MoAbs 29-13, 29-2, 35-16, and 30-40 ranged from 5.3 x 10(8) to 4.7 x 10(9) M-1 for sarcoma membranes with approximately 5 x 10(4) binding sites/sarcoma cell.
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PMID:Monoclonal antibody identification and characterization of two human sarcoma-associated antigens. 206 31

We determined whether the exposure of mouse epidermal cells to ultraviolet radiation (UVR) induces the production of factors that can stimulate the in vitro and in vivo growth of syngeneic melanoma cells. Epidermal sheets isolated from the back skin of C3H/HeN mice were placed into sterile medium and exposed to different doses of UVB radiation; 18 h later, culture supernatants were harvested. Supernatants of epidermal sheets not exposed to UVR served as controls. Supernatants from UVR-treated epidermal sheets, but not control supernatants, stimulated the in vitro and in vivo growth of some murine melanomas, but not cells of a fibrosarcoma, a hepatocellular carcinoma, or a squamous carcinoma. Supernatants of UVR-treated epidermal cells injected into the ears of syngeneic mice stimulated epidermal cell proliferation in a short-term assay. We conclude that UVR may contribute to the incidence of cutaneous melanoma by its ability to cause the release from epidermal cells of diffusible factors that promote the outgrowth of small numbers of melanoma cells.
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PMID:Ultraviolet-B-irradiated mouse epidermis releases mediators that stimulate melanoma cells. 208 Nov 19

Two-dimensional echocardiography was used to study malignant metastatic neoplasms of the heart and great vessels in 20 patients, 13 males and seven females, whose ages ranged from 15 to 72 years. Five patients had lung cancer; two each had breast cancer, malignant melanoma, hepatoma and one each had gastric cancer, urinary bladder cancer, adrenocortical carcinoma, malignant lymphoma, angiosarcoma, fibrosarcoma, leiomyosarcoma; and two had cancers with unknown primaries. Tumor invasion was demonstrated echocardiographically in the left atrium in one each with breast cancer, fibrosarcoma and gastric cancer; in the right atrium in two with hepatomas; in the right atrium and right ventricle in one patient with adrenocortical carcinoma; in the left ventricle in one with lung cancer; and in the pulmonary artery in one with malignant melanoma. Massive pericardial effusion was observed in 11 of 20 patients; two with pericardial tumors including malignant lymphoma and lung cancer. We conjectured that metastatic tumors in the right cardiac cavities came through the inferior vena cava, and other tumors in the left atrium, left ventricle and pericardium developed from direct extension of the primary lesions. There was an 80% mortality of the patients during the observation period, and the average survival period after the diagnosis of cardiac metastases was 5.5 months. However, one patient was still living after two years of radiation therapy and chemotherapy. Echocardiography proved a useful, non-invasive means for the detection and follow-up observation of metastatic cardiac tumors.
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PMID:[Echocardiography in patients with malignant metastatic neoplasms of the heart and great vessels]. 210 13

We have shown that a murine CD4+ PPD-reactive T lymphocyte clone was weakly cytotoxic towards the syngeneic tumour B16 melanoma and MC6A fibrosarcoma which had been coated with PPD using a monoclonal antibody-PPD heteroconjugate. Cell-free supernatants produced by PPD-stimulated T lymphocyte clones were however highly cytostatic for the two tumour targets when assayed over 48-72 h. In this study we have demonstrated good titres of tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma) in the supernatants, which accounted for their observed cytostatic activity on the tumour targets. The high level of cytostasis seen with the B16 melanoma using the supernatants could be attributed to their sensitivity to the cytostatic activity of IFN-gamma; the lower levels of cytostasis seen with the IFN-gamma-resistant MC6A target was the result of IFN-gamma increasing the sensitivity of this target to TNF. Antibodies to IFN-gamma were able to neutralize the majority of the cytostatic activity of the supernatants on both targets, consistent with the role demonstrated for this lymphokine.
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PMID:Cytostasis of different tumours by a murine PPD-reactive CD4+ T lymphocyte clone is mediated by interferon-gamma and tumour necrosis factor alone or synergistically. 212 29

We examined the antitumor effect of glycosylated recombinant lymphotoxin (LT) in combination with human interferon-gamma (IFN-gamma) on human tumors transplanted into nude mice and compared it with that of tumor necrosis factor (TNF). The results were as follows: (i) The systemic administration of glycosylated LT combined with IFN-gamma produced a significant antitumor activity against HT-1080 fibrosarcoma, G-361 malignant melanoma, KB nasopharyngeal carcinoma, and ZR-75-1 breast carcinoma, all of which are relatively resistant to a single treatment with LT or IFN-gamma. The synergistic effect was also seen in LT-sensitive HeLa S3 tumors. The effect was observed after either i.v. or s.c. injection. (ii) In contrast, no synergistic or additive effect on HeLa S3 tumors was observed in the case of TNF combined with IFN-gamma. (iii) The serum half-life of glycosylated LT in tumor-bearing mice was about 22-fold longer than that of TNF. In conclusion, glycosylated LT, especially in combination with IFN-gamma, appears to be a potent cytokine against tumor growth in vivo compared with TNF. Its long serum half-life can result in a strong antitumor effect in combination with IFN-gamma in vivo.
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PMID:Synergistic antitumor effect of glycosylated recombinant human lymphotoxin with human interferon-gamma on lymphotoxin-sensitive human tumor. 212 32

Extracellular matrix metalloproteases are secreted by the resident cells of the tissue in a proenzyme form, and their extracellular activity is regulated at the level of gene expression, proenzyme activation, and interaction with inhibitors. To understand the molecular mechanisms that control the activity of ECM metalloproteases and their effect on the cellular phenotype, we have established cell lines in which the transcription of the protease genes is repressed. We also have undertaken a detailed study of the pathway of extracellular activation of interstitial procollagenase. Stable transfection of three human tumor cell lines--H-ras-transformed bronchial epithelial cells TBE-1, fibrosarcoma cells HT1080, and melanoma cells A2058--with the adenovirus E1A gene dramatically repressed the expression of the secreted proteases, type IV and interstitial collagenases, and urokinase-type plasminogen activator. Concomitantly, E1A-expressing cells showed reduced metastatic activity in vivo and reduced ability to traverse a reconstituted basement membrane in vitro. Monospecific anti-type IV collagenase antibody inhibited the invasive activity of parental tumor cell lines in the in vitro system, suggesting a possible causal relationship between the effect of E1A on the expression of secreted proteases and the reduced metastatic potential of the E1A-expressing transformants. We have also studied the mechanism of regulation of metalloprotease activity at the level of extracellular activation by investigating the cascade of proteolytic events that results in the activation of interstitial procollagenase. Cocultivation of the major cellular components of skin, dermal fibroblasts, and epidermal keratinocytes induces activation of interstitial procollagenase and prostromelysin in the presence of plasminogen. This activation occurs through a uPA-plasmin-dependent pathway in which plasmin catalyzes the first step in activation of both collagenase and stromelysin by amino-terminal processing. Activated stromelysin can in turn convert plasmin-activated collagenase into a fully active enzyme by removal of approximately 15 amino acid residues from the carboxyl end of the enzyme. This second step of activation results in a 5-8-fold further increase in specific activity of collagenase. This cascade of proteolytic events may constitute a major physiologic pathway of collagenase activation.
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PMID:Secreted proteases. Regulation of their activity and their possible role in metastasis. 215 52

A positive association between agonist-stimulated cyclic AMP production in vitro and both experimentally induced (B16 melanoma) and spontaneous (fibrosarcoma) metastases were found. Five B16 melanoma cell lines producing varying degrees of lung colonization following intravenous injection and three hamster fibrosarcoma cell lines producing a varying number of metastases in lungs and regional lymph nodes after removal of the primary tumour were studied. Agonist-stimulated (forskolin and melanocyte-stimulating hormone), but not basal cyclic AMP accumulation, increased with increasing metastatic potential. This relationship did not extend to other intracellular signalling systems as determined by investigation of basal or foetal-calf stimulated phosphatidylinositol hydrolysis for either tumour type. Intracellular free calcium was also similar in B16 melanoma cell lines of varying metastatic potential.
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PMID:A positive association between agonist-induced cyclic AMP production in vitro and metastatic potential in murine B16 melanoma and hamster fibrosarcoma. 216 81

Although the hematoporphyrin derivative (Hpd) is one of the most studied photosensitisers for photodynamic therapy (PDT), it is far from ideal. Therefore, many laboratories have been investigating a new group of sensitisers, the phthalocyanines. Particularly, in our laboratory we decided to study the aluminum disulfonated phthalocyanines (AlS2PC). They are chemically stable, readily soluble in water and have a strong absorption in the red part of the spectrum at 675 nm. Mice bearing the MS-2 fibrosarcoma treated with 5 mg/kg of AlS2PC survived indefinitely also using a low laser power of 100 mW/cm2 X 10' of exposure time, in contrast to experiments carried out with Hpd where the optical therapeutic laser power was 400 mW/cm2 X 10' and the dose of Hpd was 25 mg/kg. Furthermore, treatment of mice bearing the highly metastatic tumor, B16 melanoma, with 5 mg/kg of AlS2PC and laser light (100 mW/cm2 X 10'), significantly prolonged the survival time in respect to mice treated with 25 mg/kg of Hpd and laser light (400 mW/cm2 X 10').
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PMID:Comparative study of the therapeutic effect of photoactivated hematoporphyrin derivative and aluminum disulfonated phthalocyanines on tumor bearing mice. 220 71

The DNA content and nuclear pleomorphism (NPM), which are two cellular features consistently employed in the assessment of tumour malignancy, have been measured in B16 murine melanoma metastatic variants and in hamster primary lymphoma and its liver metastasis as tumour models using image analysis techniques. The three melanoma variants studied were the low metastasis variant F1, the BL6 variant selected for high lung metastasis and invasive ability, and ML8, a line isolated from pulmonary metastasis of the BL6 tumour. The cellularity of the melanomas bore no relationship to metastatic ability. The cell cycle distribution of nuclei based on integrated nuclear density (IND) was studied. The ML8 tumour showed higher DNA ploidy. Also, in this tumour the S-phase fraction was approximately 2.0-fold larger than that of the BL6 tumour. Flow cytometry of nuclei isolated from paraffin-embedded tumour tissue showed all three melanomas were aneuploid. In both F1 and BL6, two distinct subpopulations (p2 and p3) of nuclei, based on the degree of their pleomorphism, could be discerned. A significantly higher proportion of the more pleomorphic subpopulation (p2) occurred in BL6 than in F1. In the ML8 alone, a third subpopulation (p1), which was more pleomorphic than p2, was found. The hamster lymphomas (HALY-malignant and N-HALY-non-malignant) were less cellular than the metastatic tumour (HALY-met) in liver. The lymphomas N-HALY and HALY-met had a higher DNA ploidy as compared with its primary tumour HALY. However, the non-malignant lymphoma N-HALY and the moderately malignant hamster fibrosarcoma were also found to be hyperdiploid. The metastatic lymphoma (HALY-met) showed a more pleomorphic nuclear subpopulation as compared with the primary. No differences were found in the size of the S-phase fractions of the hamster tumours. The present work shows that image analysis techniques enable one to make objective measurements of DNA content and nuclear pleomorphism of tumour cells, and suggests that in the tumour models investigated there is increased nuclear pleomorphism and DNA ploidy associated with tumour progression.
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PMID:Measurement of DNA content and nuclear pleomorphism in metastatic variants of the B16 murine melanoma and hamster lymphoma and its liver metastasis using image analysis techniques. 222 69


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