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)

Anticoagulants of the coumarin type have long been reported to inhibit metastasis growth in experimental animals; however, the mechanisms of such effects has not been clarified. Systemic anticoagulation per se does not appear to account completely for such metastasis growth depression. More recent information gathered on a cell procoagulant activity, which is vitamin K-dependent, could probably supply a fresh insight into this problem. Indeed, vitamin K deficiency induced either dietarily or pharmacologically by warfarin, does inhibit the activity of a cysteine protease with direct factor-X-activating properties. This protease is only present in warfarin-sensitive tumors. The correlation of this activity with cancer cell invasiveness is supported by experimental data in metastatic variants and, lately, also by the observation of markedly higher cancer procoagulant activity in extracts from metastases than from primary human melanomas.
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PMID:Vitamin K-dependent procoagulant in cancer cells: a potential target for the antimetastatic effect of warfarin? 353 Sep 3

The optimum treatment of malignant choroidal melanoma remains controversial. Some authors have hypothesized that enucleation promotes metastatic disease. This hypothesis has been demonstrated in the B16F10 melanoma mouse model. The present study used this model to examine the effect of external beam irradiation as a means of reducing metastases induced by enucleation. The results show a dose-dependent reduction in the DNA synthesis of irradiated melanoma cells. Administration of 800 cGy (800 rad) of radiation produced a 90% reduction in DNA synthesis; however, higher levels of radiation failed to produce further depression of cell proliferation. Irradiation of melanoma cells before intravenous injection resulted in a significant dose-dependent reduction in the number of lung metastases. While there was no effect with 100 cGy (100 rad) of radiation, 1000 cGy (1000 rad) produced a 95% reduction in metastases. In the animal model of enucleation-induced metastasis, 2000 cGy (2000 rad) delivered to the orbit either before or after enucleation produced a significant reduction in the number of lung tumors, compared with animals that did not undergo irradiation; 1000 cGy (1000 rad) delivered before enucleation did not have such an effect. These studies provide evidence that periorbital external beam irradiation is useful in reducing metastases following enucleation of a malignant melanoma in this animal model.
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PMID:Reduction of enucleation-induced metastasis in intraocular melanoma by periorbital irradiation. 363 44

Thirty-three patients with malignant melanoma and regional lymph node metastases who underwent lymph node dissection were additionally given polychemotherapy with carmustine, hydroxycarbamide and dacarbazine immediately before surgery and up to five times postoperatively. Twenty-nine patients were only treated surgically. These two groups were comparable as regards prognostic criteria, in particular tumour size, ulceration and the number of lymph nodes affected, although the individual follow-up periods varied considerably. The group given chemotherapy showed better results than the control group undergoing surgery alone. The log rank test yielded a significant difference (P less than 0.05) with respect to the probability of relapse-free survival but not as regards probability of survival time. Patients with ulcerated primary melanomas and with a large number of affected lymph nodes had a less favourable prognosis. The major side effects of chemotherapy were transient nausea and bone marrow depression.
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PMID:[Adjuvant chemotherapy in addition to radical surgical treatment of regional lymph node metastases in malignant melanoma]. 369 50

The effects of 14AC1 monoclonal antibody (McAb) on 79FR-G-41 rat glioma cells in vitro, on the formation of metastases in lung by antibody coated glioma cells, and on the growth of glioma grafts in BALB/c-nu/nu mice were investigated. The 14AC1 antibodies - isotyped as IgG2a - were obtained from a hybridoma clone established after fusion of X63-Ag8.653 myeloma cells and spleen cells of BALB/c mice hyperimmunized with 79FR-G-41 glioma cells. Antibody treatment of glioma cells in vitro caused evident cell surface alterations and pronounced growth depression of most cells. However, a few tumor cells remained unchanged in morphology and continued to proliferate. Moreover, 14AC1 antibodies drastically reduced lung metastasis by pretreated and i.v. delivered glioma cells. Additionally, 14AC1 antibodies suppressed the growth of transplanted rat gliomas in nude mice as evidenced by a longer latency period and a smaller volume of glioma grafts in treated than in control tumor bearers. Nevertheless, glioma grafts showed accelerated growth after termination of antibody treatment. Further experimental investigation is required in order to identify the precise mechanisms of the effects of McAbs on tumor cells in vitro and in vivo.
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PMID:Growth inhibition of experimental glioma grafts by monoclonal antibody treatment. 377 19

After a simultaneous administration of adriamycin and antipyrine to 19 tumor patients, the plasma kinetics of both drugs, the therapeutic effect and the reaction to white blood cells were determined. Antipyrine was given orally at a dose of 875 mg, whereas adriamycin was administered by means of intravenous infusion for 20 min at 60 mg/m2. This application was repeated in eight patients after three weeks. Nine patients had a normal liver function. In ten patients, slight increases were found in individual liver function parameters. All patients were free from metastases of the liver and had bilirubin levels within the normal range. Antipyrine followed an open one-compartment model, whereas adriamycin followed an open two-compartment model. In the mean, t1/2 el and Cl tot of antipyrine were found to be 16.1 h and 32.9 ml/min, t1/2 beta and Cl tot of adriamycin were 23.1 h and 877 ml/min. For antipyrine and adriamycin, these parameters varied interindividually by the factors 2.8 and 3.1, respectively. No correlations were found between the liver function parameters, and the kinetic elimination parameters and the areas under the curves of both drugs. However, significant positive correlations were found to exist between t1/2 el antipyrine and t1/2 beta adriamycin and between the areas under the curves of the two drugs. A relationship between the AUC adriamycinol/AUC adriamycin ratio (which was 0.52 in the mean) and the antipyrine elimination rate did not exist. As compared to 12 persons with no response or progression, the seven patients with partial or complete response had a significantly higher AUC and a significantly lower Cl tot of adriamycin. As compared to the patients with elimination half-life values of less than 20 h, five patients with antipyrine elimination half-life values of more than 20 h had a significantly longer adriamycin elimination beta-phase and a stronger depressive effect on the white blood cells. The results obtained suggest that the antipyrine kinetics in patients with normal or slightly impaired liver function is a useful parameter for an assessment of the depression of white blood cells and the dose adjustment for adriamycin.
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PMID:Plasma pharmacokinetics of adriamycin and antipyrine and its relation to the therapeutic and toxic effects. 384 95

We report here our study of the role of natural host defense mechanisms mediated by macrophages and natural killer (NK) cells in an experimental model of spontaneous pulmonary metastases of a mammary adenocarcinoma SST-2 in spontaneously hypertensive rats (SHR) with congenital T-cell depression. To activate macrophages and NK cells, Listeria monocytogenes (LM) was injected IV into SHR which had received a transplantation of SST-2. To assess the antimetastatic responses induced by LM, the number of lung nodules and the lung weight in SHR were evaluated 30 days after tumor inoculation. The growth of lung metastases, though not of primary tumors, was significantly reduced if 10(7) LM were injected IV into SHR 2, 10 and 20 days after the SC transplantation of 5 X 10(4) or 5 X 10(5) SST-2. An inhibitory effect of LM on pulmonary metastases was also observed in tumor-excised rats, in which the number of lung metastases and the lung weight were enhanced as compared with those in tumor-bearing rats which had not undergone surgery. Peritoneal resident cells which were harvested from rats injected with LM showed a significant augmentation of tumoricidal activity against SST-2 cells as measured by in vitro cytotoxicity. Similarly, the NK activity of spleen cells of SHR injected with LM increased significantly when compared with untreated SHR. These data suggest that the inhibition of metastatic growth, though not of primary tumor growth, was accomplished by the, possibly T-cell independent, activation of macrophages and NK cells.
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PMID:Activation of natural resistance against lung metastasis of an adenocarcinoma in T-cell depressed spontaneously hypertensive rats by infection with Listeria monocytogenes. 387 51

The levels of a trypsin-like neutral proteinase present on tumor cell surface (SNP) have been determined in P388, L1210, TLX5 leukemias, and in two lines of Lewis lung carcinoma having different metastatic potential. No correlation between metastatic potential and SNP levels of the tumor lines examined has been observed, and metastasis depression by antimetastatic and antineoplastic drugs was not accompanied by SNP inhibition. These data seem to support the view that metastatic potential is not necessarily related to tumor proteinase levels.
Invasion Metastasis 1985
PMID:Tumor cell metastasis and surface neutral proteinase: effects of antimetastatic and antitumor drugs. 390 87

A scheduled regimen of oral narcotic analgesics was compared with a regimen of oral narcotic analgesics plus ibuprofen for analgesic efficacy in patients with cancer. Ten patients with metastatic cancer were randomly assigned to receive either ibuprofen 400 mg or a look-alike placebo four times daily in addition to each patient's existing regimen of scheduled oral narcotics. A two-period changeover study design was used. The 24-hour narcotic intake equated to injectable morphine was computed for each patient at baseline and during the nine study days. A visual analogue scale was used to evaluate pain relief, nausea, mood depression, daytime drowsiness and nighttime sleeplessness. The analgesic efficacy of the narcotic-ibuprofen combination was significantly greater than the analgesic efficacy of the narcotic-placebo combination. Eight patients demonstrated a positive treatment effect with added ibuprofen; the overall improvement in analgesia averaged 39.1% in these patients. There was no significant increase from baseline in the incidence of nausea, mood depression, daytime drowsiness or nighttime sleeplessness. At the doses used in this study, a treatment regimen of oral narcotic analgesics plus ibuprofen was more effective than oral narcotics alone in relieving pain associated with cancer.
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PMID:Analgesia with oral narcotics and added ibuprofen in cancer patients. 397 83

Twenty-two (16%) of 134 lung cancer patients had symptoms of a major depressive illness at the time they first presented to hospital. This was a higher prevalence than that found in patients with non-malignant chest conditions, or in controls without serious disease. A past history of psychiatric illness, and the presence of metastatic disease, were the most significant correlates of depression. The depressive symptoms had often preceded the physical ones and apparently arisen in reaction to social stress.
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PMID:Depressive illness and lung cancer. I. Depression before diagnosis. 398 8

We have studied the role of natural killer activity during the growth and dissemination of a transplantable renal adenocarcinoma (Renca) of spontaneous origin in BALB/c mice. The pattern of growth of this tumor accurately mimics that of adult human renal cell carcinoma in terms of clinical stages I-IV, particularly with regard to spontaneous metastasis to lung and liver. Renca is moderately sensitive to lysis by natural killer cells from normal mice and is more efficiently lysed by natural killer cells from mice treated with the biological response modifier maleic anhydride divinyl ether, a pyran copolymer. Our studies demonstrate that selective depression of natural killer activity by administration of antiserum specific for the neutral glycosphingolipid asialo GM1 correlated with increased formation of spontaneous metastases in the lungs, liver, and lymph nodes. Conversely, augmentation of natural killer activity by the biological response modifier decreased the formation of spontaneous metastases in lungs, liver and lymph nodes. Further, the suppression of natural killer activity and subsequent increased formation of metastases were accompanied by a significantly reduced survival time, whereas the augmented natural killer activity and decreased incidence of metastases in biological response modifier-treated mice were accompanied by an increase in time of survival. These results demonstrate a significant role for natural killer cells in the control of spontaneous metastasis during growth of this murine renal cancer.
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PMID:Role of natural killer activity in development of spontaneous metastases in murine renal cancer. 405 25


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