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)

The ability of L-dopa to arrest pain can be used to predict objective response of skeletal disease to endocrine ablation or additive therapy. In the present study, 43 patients with painful skeletal metastases were evaluated for the relief of pain by L-dopa, given 250 mg to 500 mg orally every 4 hours for 4 days. Sixteen of the 25 responders to L-dopa had objective response to either previous or later hormonal therapy while all the 18 non-responders did not benefit from endocrine ablation. The results of L-dopa responses also correlated well to the presence of absence of cytoplasmic ER in tumor. These results demonstrate that both tests (L-dopa and ER) are reliable indicators, one complimenting the other, in prognosticating response to endocrine therapy and should be used prior to hormone treatment. Alternative therapy should be considered for patients who are non-responders to the L-dopa test and/or whose tumors contain negligible ER. The long term therapeutic value of L-Dopa, however, is limited.
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PMID:LevoDopa test and estrogen receptor assay in prognosticating responses of patients with advanced cancer of the breast to endocrine therapy. 17 77

Sinclair swine melanoma usually regresses in vivo. In the present study, swine melanoma cells were adapted to long-term growth in culture. The morphology of cultured melanoma cells ranged from dendritic to cuboidal, similar to that described for human melanoma cells. Doubling times of the swine melanoma cells were also similar to those of human melanoma cells in vitro. 3,4-Dihydroxy-L-phenylalanine oxidase-positive cells were detected by light microscopy, and melanin and premelanosomes were detected by electron microscopy. Cell cultures could be propagated from progressing, partially regressed, and primary cutaneous lesions, as well as from visceral metastases. Thus, it appears that, under these cell culture conditions, Sinclair swine melanoma cells can be adapted to prolonged growth in vitro.
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PMID:Adaptation of Sinclair swine melanoma cells to long-term growth in vitro. 49 21

By using ion-exchange column chromatography with effluent monitoring using the stable, free radical alpha,alpha-diphenyl-beta-picryhydrazyl as a colorimetric reagent, we have demonstrated the occurrence of elevated levels of five peaks in the urine of patients with metastatic disease. The tentative assignment of two of the peaks as 3,4-dihydroxyphenylalanine and as 3-methoxy-4-hydroxyphenylalanine has been made. Three remain unknown. The correlation of these peaks with the clinical status of melanoma patients shows that, while the individual excretion pattern of these compounds may be variable, the sustained occurrence of one or more of them in a patient's urine is evidence of recurrent or continuing disease. The excretion levels appear to be proportional to the tumor burden. The results with a group of 39 melanoma patientshaving Stage II or Stage III disease indicate that this chromatography technique provides earlier evidenc eof liver metastases than doses the liver scan, may detect occult metastases generally, and has detected tumor in clinically enlarged lymph nodes. This method, in its present form, does not detect small pulmonary lesions earlier than chest X-ray or tomography do or brain metastases earlier than do brain scan or computerized axial tomography. The technique is clinically useful for the diagnosis of melanoma patients and in their follow-up while under treatment.
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PMID:Detection of occult metastatic melanoma by urine chromatography. 97 93

The purpose of this study was to examine the differentiation of variant tumors of the B16 metastatic melanoma when tumors were grown serially under different culture conditions and transplanted into C57BL/6J black mice, lethal yellow Ay/a, albino c/c, and C+/c mutant mice. Morphological and biochemical markers of melanogenesis were examined in cells in culture and in the corresponding tumors. Cellular pigmentation was assessed in terms of the levels of DOPA and 5-S-CD and in terms of tyrosinase activity in the various cell lines and tumors. The observed change from high to low metastatic capacity, which was dependent on culture conditions, appeared to be unrelated to melanogenesis even though changes were observed in the biochemical melanotic phenotype. Overall, tumor cells from spontaneous pulmonary metastases appear to differentiate in ways that are unrelated to the instability of experimental metastatic capacity. The melanotic phenotype in albino c/c and C+/c mice was dependent on the phenotype of the parental tumors. A marked difference was observed between two pigmentation compartments, one of which was stable in the B16 control, while the other was unstable in YB16 and MB16 variant cells and in the tumors derived from them. It appears, therefore, that the metastatic capacity of B16 metastatic variants is changeable and is independent of the unstable melanogenic behavior. The production of metastases and the differentiation of tumors in the present experiments appeared to be related to the genetic background of the mice and the epigenetic metabolic environment of tumors and cells.
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PMID:Differentiation of new metastatic variants of B16 melanoma under different culture conditions. 163 Oct 17

Different combinations and doses of neurotropic drugs of the central action (spasmolytine, midantane, L-DOPA) coupled with the surgical removal of the lung Lewis carcinoma were studied for their effect on the metastatic spreading in C57BL/6 mice. It has been established that the long-term use of spasmolytine and midantane before and after the operation inhibits the metastatic process, that is expressed in the total volume reduction of lung metastases, lack of metastases in a number of mice and augmentation of the average life. Such method of drug application is more effective in the metastatic growth inhibition as against their application only in the pre- or postoperation periods as well as with the use of the other neurotropic drug combinations.
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PMID:[Inhibition of the metastasis of Lewis lung carcinoma in mice by the administration of spasmolytin, midantan and L-DOPA]. 196 41

Balloon cell melanoma of the skin was found in the left axillary region of a 60-year-old man. The tumour was very large, grew local, not forming metastases. The histological picture corresponded to a solid alveolar pattern, in some places with pseudoglandular structures. The cytoplasm of the balloon cells proved to contain lipid vacuoles and glycogen. The Masson-Fontana reaction was negative: the Warthin-Starry method gave positive results in sporadic tumour cells. The DOPA oxidase reaction was negative. Histochemistry demonstrated remarkable presence of histiocytic elements among the neoplastic cells. Reaction for the proof of alpha mannosidase was positive both in the tumour cells and in the histiocytic elements. Reaction with the NKI-C3 antibody was found to be positive in many tumour cells, the anti S-100 protein antibody less positive. Most of the cells reacted strongly positively with anticytokeratin antibody CAM 5.2. Findings of anticytokeratin antibody positive melanomas have not been published yet. Electron microscopy showed rare melanosomes in some of the neoplastic cells, making it possible to include the tumour in melanomas.
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PMID:Balloon cell melanoma of the skin. part I: Histology, immunohistology and histochemistry. 215 Nov 3

There are 36 reported cases of metastatic pituitary carcinoma and almost half (44%) of these were associated with syndromes of hormonal hypersecretion. The case of a 56-year-old acromegalic man with cervical lymphatic and spinal metastases from a primary pituitary carcinoma is described. Elevated basal levels of plasma growth hormone (GH) and insulin growth factor-1/Somatomedin C (IGF-1/SmC) were found. GH levels did not increase after TRH or LHRH administration but decreased after L-Dopa and glucose. Immunostaining of the metastatic tumor for GH and electron microscopy findings confirmed the diagnosis of pituitary GH-secreting carcinoma. Striking clinical improvement and a 46% decrease in plasma GH levels were observed with bromocriptine treatment, although IGF-1/SmC levels increased during therapy. The clinical course of most reported cases of pituitary adenocarcinoma has been one of progressive intracranial expansion of a pituitary neoplasm. In only 25% were metastatic lesions discovered antemortem, and disabling symptomatology caused by metastases was rare. Only four previously reported patients of 36 with pituitary carcinoma had acromegaly.
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PMID:Pituitary adenocarcinoma in an acromegalic patient: response to bromocriptine and pituitary testing: a review of the literature on 36 cases of pituitary carcinoma. 266 75

A correlation between reactions of the sympathoadrenal system and the activity of adenosine transformation enzymes in lymphocytes is demonstrated in the dynamics of metastatic Lewis carcinoma development in C57Bl mice. In the period when metastases arise a decrease in the adenosine deaminase activity in lymphoid cells of the thymus and spleen is accompanied by drop in the content of DOPA, noradrenalin and adrenalin in adrenals. At the late stages of the tumour process a decrease in the amount of these compounds in adrenals is accompanied by the diminution of the adenosine deaminase activity and by an increase in the 5'-nucleotidase activity in the thymus. Contrary changes are observed in spleen lymphocytes. The revealed disturbances may stimulate to a considerable extent the appearance and growth of metastases.
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PMID:[Enzymes of adenosine metabolism in lymphocytes and the functional state of the sympatho-adrenal system in tumor processes]. 301 May 22

A spontaneous, hypomelanotic variant (MI) of the highly melanotic transplantable hamster melanoma of Bomirski (Ma) is the subject of this report. Tyrosinase activity is 2-3 times higher, but melanin content significantly lower than in the parental Ma melanotic melanoma. Acid phosphatase activity is similar in both, but beta-glucuronidase and aryl-sulfatase A are 2-3 times higher in the hypomelanotic variant. Transplanted MI melanomas grow more slowly than the parental tumor, but metastasize with similar incidence and localization. Hypomelanotic variant melanoma cells, even those in grossly nonnecrotic parts of the transplants, show signs of low viability like swelling of the cytoplasm or cellular condensation, and disintegration. Autophagic vacuoles are numerous. They appear to be formed by enclosure of a portion of cytoplasm by cisternae of smooth endoplasmic reticulum or trans-Golgi network. These limiting cisternae contain tyrosinase as evidenced by deposition of electron dense reaction product on incubation with tyrosine or DOPA. Other sites of ultrastructural tyrosinase reaction are melanosomes and the smooth-surfaced cisternae and vesicles of the trans-Golgi network. We postulate the low cell viability, associated with autophagosome formation, is the cause for the growth retardation of the MI variant, and that the lower melanin content of these tyrosinase-rich cells is due to sequestration of a substantial portion of newly synthesized enzyme into autophagic vacuoles before it has the chance of being incorporated into melanosomes.
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PMID:Pathology and ultrastructural characteristics of a hypomelanotic variant of transplantable hamster melanoma with elevated tyrosinase activity. 311 4

Levodopa-carbidopa has been widely used in the treatment of Parkinson's disease. We are currently investigating the effectiveness of this combination for the treatment of patients with advanced malignant melanoma. As part of this study, we have examined the effects of this combination on the phytohemagglutinin-induced transformation of human lymphocytes, isolated from patients with malignant melanoma prior to undergoing treatment. Levodopa, as well as carbidopa and 3 additional levodopa synthetic analogs, inhibited the transformation of phytohemagglutinin-stimulated DNA synthesis at pharmacologically attainable levels. These results confirm our earlier preclinical observations suggesting that catechols have profound intracellular metabolic effects in a variety of cells other than melanoma cells. It is possible that some of the effects of catechols in other diseases might also be mediated by similar intracellular metabolic effects, and effects on human melanoma might be mediated in part through effects on the immune system. We are currently awaiting introduction of synthetic catechols, including 3,4-dihydroxybenzylamine (NSC 263475), to extend these observations to our clinical studies in patients with advanced metastatic disease.
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PMID:Inhibition of transformation by levodopa-carbidopa in lymphocytes derived from patients with melanoma. 357 25


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