Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A murine model of immune responsiveness had been adapted to study anergic conditions associated with neoplasia. Marked anergy observed in mice bearing L1210 leukemia and P-388 lymphoma is contrasted to the minimal immune depression associated with B-16 melanotic melanoma and Sarcoma 180J. The ability of N,N-bis(2-chloroethyl)-N-nitrosourea chemotherapy to reduce tumor burden without prolonged suppression of delayed cutaneous hypersensitivity is compared to the profound suppression of the cutaneous response observed with Adriamycin cytoreductive therapy. The applications of our model are discussed in relation to tumor-associated anergy, new approaches to the evaluation of pharmaceuticals, and studies of combined chemoimmunotherapy regimens.
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PMID:Delayed cutaneous hypersensitivity to oxazolone in mice with tumors. 63 44

The effects of adriamycin were compared to a combination program of methyl-CCNU and imidozole carboxamide (DTIC) in 44 patients with disseminated malignant melanoma. There were objective clinical responses in 6 of 21 patients with the combination of DTIC and methyl-CCNU who received this program as primary treatment and none in 23 patients receiving adriamycin as primary treatment. Secondary responses were not observed with either treatment regimen. Toxicity with the combination program included leukocyte depression (less than 3,000/cu mm) in 25% and platelet depression (less than 100,000/cu mm) in 40% compared to 52% leukocyte depression and 16% platelet depression after adriamycin. There were no responses after the combination treatment program in the absence of myelosuppression. There was nausea and vomiting in virtually all patients, which was moderately severe in one third of the patients receiving the combination and in only 10% of those receiving adriamycin. Alopecia developed in all who received adriamycin but in only 15% of the combination treatment group. The combination treatment response of 28% was of the same order as most response rates previously reported in this disease. This randomized controlled clinical trail found adriamycin without clinical benefit and not worthy of further trial in patients with disseminated malignant melanoma.
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PMID:Clinical comparison of adriamycin and a combination of methyl-CCNU and imidazole carboxamide in disseminated malignant melanoma. 77 89

Large variations in intraocular pressure occur during enucleation, scleral depression, 32P testing, and vigorous rubbing of an eye. Data from animal studies show that during a critical phase of an intraocular malignant melanoma, ocular massage significantly decreased longevity due to increased metastastic disease. We report "no-touch" technique to prevent tumor spread from occurring secondary to ocular manipulation during enucleation. This technique avoids IOP elevations above 50 mm Hg before freezing completely around the tumor, thereby preventing flow of fluid and blood to or from the tumor prior to the manipulation necessary for enucleation. Theoretically, the patient with an ocular tumor should be warned against vigorous rubbing of his eyes and hard lid squeezes or diagnostic techniques that elevate IOP. The ophthalmologist should perform enucleation with gentieness and avoid pressure on the globe. Patients who are being followed up with a suspected ocular tumor should be warned not to rub or vigorously squeeze their eyelids.
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PMID:No-touch technique for intraocular malignant melanomas. 90 Dec 71

The relationship between tumour volume response and cell kill in B16 melanoma following treatment in vivo with cyclophosphamide (CY) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was investigated. Tumour volume response, expressed as growth delay, was estimated from measurements of tumour dimensions. Depression of in vitro colony-forming ability of cells from treated tumours was used as the measure of tumour cell kill. The relationship between these parameters was clearly different for the two agents studied. CY produced more growth delay (7.5 days) per decade of tumour cell kill than CCNU (2 to 3.5 days). The possibility that this was due to a technical artefact was rejected in favour of an alternative explanation that different rates of cellular repopulation in tumours treated with CY and CCNU might be responsible. Cellular repopulation was measured directly, by performing cell-survival assays at various times after treatment with doses of CY and CCNU which produced about 3 decades of cell kill. The rate of repopulation by clonogenic cells was much slower after treatment with CY than with CCNU, and this appears to account for the longer duration of the growth delay obtained with CY.
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PMID:Tumour volume response, initial cell kill and cellular repopulation in B16 melanoma treated with cyclophosphamide and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. 92 88

An initial clinical phase I trial of inosine dialdehyde has been carried out in 40 patients at dose levels of 30-4000 mg/m2 for 5 days given intravenously (iv) monthly. At 1.5 g/m2, noncumulative dose-related toxicity occurred in all patients which consisted of nausea and vomiting, local pain, alterations in coagulation mechanism, elevated partial thromboplastin time, and positive Coombs' test. No dose-limiting leukopenia, thrombocytopenia, anemia, or bleeding occurred; however, depression of the leukocyte and platelet counts, and decreased hemoglobin value were observed. The dose-limiting toxic effect was renal tubular damage with reversible acute renal failure in one of four patients who received 3000 mg/m2 iv for 5 days. Refractory hypercalcemia was controlled in three of three patients without tumor effect. Responses occurred in patients with seminoma, oat cell carcinoma, and melanoma. A starting dose of 2 g/m2 for 3 days monthly is recommended for phase II trials and a trial in lung carcinoma is now being conducted.
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PMID:Clinical phase I trial of inosine dialdehyde (NSC-118994). 110 41

Sequential assays for cell-mediated reactivity (CMR) and serum blocking factor (SBF) were performed in a group of 12 melanoma patients who were treated with one or both of the clinically available imidazole carboxamide derivatives, DTIC and TIC Mustard, in order to consider the effects of treatment and changing patterns of disease on the results of in vitro tests in individual patients. Microcytotoxicity assays and the dilute agar colony inhibition test were employed. Of the 12 patients, 8 had no change in CMR and 5 had no change in SBF. Three patients demonstrated a fall in both CMR and SBF to nondetectable levels, and 3 additional patients showed a fall in SBF only. From these results, we conclude that there is no significant depression of CMR in melanoma patients by either of the imidazole carboxamide derivatives used. The results of SBF are less conclusive and more open to question, since it is just a likely that any depression to undetectable levels may be due to a change in disease status rather than to coincident drug use. It appears that microcytotoxicity assay results on individual patients may be fortuitous and difficult to interpret, even though results seen in patients as a group indicate important trends. The microcytotoxicity assay is a useful tool for the experimental tumor immunologist, but its clinical usefulness in individual patients is limited.
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PMID:Evaluation of cell-mediated reactivity and serum blocking factors in melanoma patients on chemotherapy. 123 28

The newly diagnosed CA patient faces psychosocial as well as physical problems. To assess the impact of diagnosis, and to find significant clues for later emotional distress, 163 new patients with CA of the breast, colon, lung, Hodgkin's disease, and malignant melanoma were evaluated by interviews, psychological testing, and personality inventories, then followed regularly for six months. Vulnerability was but one parameter that measured emotional distress and faltering capacity to cope with concurrent problems. It was found that the more vulnerable patients had more symptoms when first diagnosed, and that systemic symptoms were more significant than the type of CA or the staging. High vulnerability patients were generally pessimistic, anticipating little recovery and practically no support from significant others. They had more marital problems, tended to suppress feelings, but often had a history of depression. Denial in itself did not mean vulnerability. Indecision about treatment and regrets about the past were more indicative of future emotional problems than was delay. Most patients showed little denial throughout the period of observation, but more vulnerable patients tended to vacillate between denial and acceptance. By learning to listen and ask tactful questions, this information can be elicited by the physician who can then intervene effectively.
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PMID:Early diagnosis of vulnerability in cancer patients. 126 89

Tricyclic antidepressants, such as amitriptyline (Elavil), and the nontricyclic agent, fluoxetine (Prozac), bind to growth-regulatory intracellular histamine receptors, associated with anti-estrogen binding sites in microsomes and nuclei. The prototype anti-estrogen binding site/intracellular histamine receptor ligand, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl, inhibits normal cell proliferation in vitro but stimulates tumor growth in vivo. Because of their structural similarity to N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl, we carried out studies to determine whether amitriptyline and fluoxetine stimulate tumor growth and/or development in rodents at concentrations relevant to the treatment of human depression (equivalent human dose range, approximately 100-150 mg/day for amitriptyline and approximately 20-80 mg/day for fluoxetine). All experiments were performed blinded. In studies of growth stimulation of transplantable syngeneic tumors, groups of mice were inoculated s.c. with C-3 fibrosarcoma cells or given i.v. or s.c. injections of B16f10 melanoma cells, followed 24 h later by daily i.p. injections of saline, amitriptyline, or fluoxetine. Tumor latency (fibrosarcoma), aggregate tumor weight (s.c. injected melanoma), or time to death from pulmonary metastasis (i.v. injected melanoma) was determined; drug-induced stimulation of DNA synthesis in C-3 fibrosarcoma cells in vitro was correlated with tumor growth acceleration in vivo. In a mammary carcinogenesis model, the effects of chronic saline, amitriptyline, or fluoxetine administration on the rate and frequency of development of mammary tumors in rats fed dimethylbenzanthracene (DMBA) were compared. Eight of 20 amitriptyline- or fluoxetine-treated mice developed fibrosarcoma tumors by day 5, as compared to none of 20 saline controls (P less than 0.002). Similarly, 20 of 21 DMBA-treated rats receiving the antidepressant drugs developed 33 mammary tumors by week 15 as compared to 5 tumors in 4 of 7 DMBA-treated rats receiving saline (P less than 0.001). For both models, tumor latency decreased 30-40% and, in the DMBA model, tumor frequency increased greater than 2-fold in the antidepressant-treated rats as compared to controls. Stimulation of fibrosarcoma growth in vivo correlated with a corresponding bell-shaped drug-induced increase in DNA synthesis in vitro. While the median time to death from pulmonary metastases did not differ among groups given i.v. injections of melanoma cells, a significant (P less than 0.01) stimulation of growth of s.c. injected melanoma was observed in mice receiving the antidepressants.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Stimulation of malignant growth in rodents by antidepressant drugs at clinically relevant doses. 161 49

BMY-25551, 7-(2-hydroxyethoxy)mitosane, was selected from a series of mitomycin A (MMA) analogues for more detailed study. As with other members of this class, it was shown to be 8 to 20 times more potent than mitomycin C (MMC) in cytotoxicity to murine and human tumor cell lines in vitro, in causing DNA cross links in vitro, and in dose levels for tumor inhibition in vivo. BMY-25551 appeared to be more effective in tumor inhibition than MMC against P388 leukemia and B16 melanoma in mice and comparable to MMC against L1210 leukemia and Madison 109 lung carcinoma. BMY-25551 was also comparable to MMC in hematologic depression in mice. Factors affecting its possible utility in humans are discussed.
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PMID:Experimental tumor inhibitory and toxic properties of the mitomycin A analogue 7-(2-hydroxyethoxy) mitosane (BMY-25551). 162 54

The mechanism of a novel melanin synthesis inhibitor, BMY-28565, was studied using mouse B16 melanoma cells. This compound was active in depressing the intracellular accumulation of melanin with an IC50 of 5 microM. At dose levels causing no cytotoxicity, the melanolytic effect of this compound was correlated strongly with depression of the enzymatic activity of tyrosinase (monophenol oxygenase, EC 1.14.18.1), the key enzyme in the melanin synthesis pathway. Transcription of the tyrosinase gene was not inhibited by BMY-28565, as determined by RNA blotting analysis. BMY-28565 and three other active derivatives of this compound caused increased glycosylation of proteins in B16 melanoma cells, as assessed by radioactive mannose incorporation. It is, thus, suggested that the mechanism of inhibition of tyrosinase might be related to modifications of the sugar moiety of this enzyme or of a protein(s) that is essential for the expression of its enzymatic activity.
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PMID:Inhibition of melanogenesis by BMY-28565, a novel compound depressing tyrosinase activity in B16 melanoma cells. 173 7


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