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)

Forty-three patients with disseminated refractory malignancies each received an individually-specified combination of either Adriamycin (24 patients) or mitomycin-C (19 patients) conjugated murine monoclonal antibodies. Tumors were typed using a panel of antibodies with both immunohistochemistry and flow cytometry. Cocktails of up to six antibodies were selected based on binding greater than 80% of the malignant cells in the biopsy specimen. These monoclonal antibody cocktails were drug conjugated and administered intravenously. Seventeen out of twenty-four patients had reactions to the administration of Adriamycin immunoconjugates, but these were tolerable in all but two patients. Fever, chills, pruritus and skin rash were by far the most common transitory reactions. All were well controlled with premedication. In several patients it was demonstrated that there was limited antigenic drift among various biopsies within the same patient over time. Up to 1 gram of Adriamycin and up to 5 grams of monoclonal antibody were administered. The limiting factor appeared to be a variable dissociation of active Adriamycin from the antibody which unpredictably caused hemopoietic depression. Similar findings were noted in 19 patients with mitomycin-C conjugates. Thrombocytopenia at a 60mg dose of mitomycin-C in this schedule was dose limiting. Preliminary serological evidence suggests that the development of an IgM antibody which is specific against the mouse monoclonal antibody has the specificity and sensitivity to predict clinical reactions. These antibodies were quantitatively less in mitomycin-C patients. Selected patients were re-treated. One patient with chronic lymphocytic leukemia had re-treatment on three occasions and demonstrated regression of peripheral lymph nodes. Two patients with breast carcinoma had definite improvement in ulcerating skin lesions and two patients with tongue carcinoma had shrinkage of their lesions. No responses were seen with mitomycin-C conjugates but binding was noted to tumors and colon with likely drug induced colitis seen after colon binding. This study demonstrates the feasibility and illustrates technical considerations in preparing drug immunoconjugate cocktails for patients with refractory malignancies. Cocktail formulation and antibody delivery was accomplished. The major technical hurdle appears to be the selection of effective conjugation methods that can be used to optimally bind drugs to monoclonal antibodies for targeted cancer therapy.
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PMID:Individually specified drug immunoconjugates in cancer treatment. 250 30

The present study investigated the in vitro effect of four different chemotherapeutic agents, namely, cyclophosphamide (CTX), vincristine (VCR), Adriamycin (Adria Laboratories, Columbus, Ohio) (ADR), and actinomycin D (ACT-D) on human polymorphonuclear leukocyte (PMN) function. Human PMNs suspended in phosphate-buffered saline (PBS) at 1 X 10(7) cells/mL were incubated with increasing concentrations of CTX (0, 10(-5), 10(-4), 10(-3) mol/L) or VCR (0, 10(-7), 10(-6), 10(-5), 10(-4) mol/L), ADR (0, 10(-6), 10(-5), 10(-4), 10(-3) mol/L), or ACT-D (0, 5 X 10(-8), 1 X 10(-7), 5 X 10(-7), and 10(-6) mol/L). The cells were then tested for bacterial killing against Staphylococcus aureus, chemotaxis activity stimulated by Escherichia coli endotoxin, N-formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated aggregation, and cytochalasin B (Cyto B)/FMLP-stimulated superoxide production and enzyme degranulation. High concentration of CTX, an alkylating agent, showed a significant depression of PMN superoxide production, (124 +/- 13 v 161 +/- 15 nmol/10(7) cells, 5 minutes, P less than or equal to .025). ADR, an intercalating agent and membrane inhibitor, showed a significant depression of PMN degranulation and lysozyme release at 10(-4) and 10(-3) mol/L (15.3% +/- 1.7% v 24% +/- 7%, P less than .01; and 15.0% +/- 2.5% v 24% +/- 7%, P less than or equal to .025). VCR, a microtubule inhibitor, showed a significant depression of PMN aggregation at 10(-6), 10(-5), and 10(-4) mol/L (P less than .05), lysozyme release at 10(-4) mol/L (P less than .004), and beta-glucuronidase release at 10(-4) mol/L (P less than .004). In addition, chemotaxis was inhibited by VCR in a dose-dependent manner at all concentrations (10(-7) mol/L, P less than .02; 10(-6) mol/L, P less than .007; 10(-5) mol/L, P less than .006, and 10(-4) mol/L, P less than .003). ACT-D showed no significant effect on the PMN functions tested. These studies conclude that chemotherapeutic agents have modulating in vitro effects on PMN function. Further in vivo studies are therefore needed to assess PMN abnormalities in patients receiving cancer chemotherapy to determine their role in infectious complications.
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PMID:Impaired in vitro polymorphonuclear function secondary to the chemotherapeutic effects of vincristine, adriamycin, cyclophosphamide, and actinomycin D. 300 27

Four patients with advanced hepatocellular carcinoma, but with stage I functional disease, were treated with intrahepatic arterial lipoidal mixed with small doses of Adriamycin (20 mg) and Mitomycin C (10 mg). Regression was seen in 3 out of the 4 patients. In 2 patients, there was substantial regression of tumour clinically, radiologically and biochemically. The treatment was tolerable without marrow depression or deterioration of liver function. Mild fever (37 degrees C) was seen in 2 and epigastric pain in 1. This form of treatment opens up scope for further improvement in the management of irresectable hepatocellular carcinoma.
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PMID:Treatment of irresectible hepatocellular carcinoma with intrahepatic arterial lipoidal mixed with adriamycin and mitomycin C. 301 14

Twenty-three patients with disseminated refractory malignancies each received a tailored combination of adriamycin-conjugated murine monoclonal antibodies. Tumors were typed using a panel of antibodies. Cocktails of up to six antibodies were selected based on binding greater than 80% of the malignant cells as tested by immunoperoxidase and flow cytometry. These monoclonal antibodies were then conjugated to Adriamycin and administered intravenously. Seventeen of 23 patients had reactions to the administration of immunoconjugates, but these were tolerable in all but two patients. Fever, chills, pruritus, and skin rash were by far the most common transitory reactions. All were well controlled with premedication. In several patients there was limited antigenic drift among various biopsies within the same patient over time. This observation confirms the necessity for the use of a cocktail of antibodies if one wishes to cover all tumor cells. Preliminary serologic evidence suggests that the development of an IgM antibody, which is specific against the mouse monoclonal antibody, has the specificity and sensitivity to predict clinical reactions. Selected patients were re-treated. One patient with chronic lymphocytic leukemia had re-treatment on three occasions and demonstrated regression of peripheral lymph nodes. Two patients with breast carcinoma had definite improvement in ulcerating skin lesions and two patients with tongue carcinoma had shrinkage of their lesions. In the course of the study free Adriamycin released from the monoclonal antibodies was discovered to be a limiting factor in the amount of antibody that could be administered. Up to 1 g of Adriamycin and up to 5 g of monoclonal antibody were administered. The limiting factor appeared to be a variable dissociation of active Adriamycin from the antibody that unpredictably caused hemopoietic depression. This study demonstrates the feasibility and reviews technical considerations in preparing immunoconjugate cocktails for patients with refractory malignancies. The major technical hurdle appears to be the selection of an effective conjugation method that can be used to optimally bind Adriamycin to monoclonal antibodies for targeted cancer therapy.
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PMID:Adriamycin custom-tailored immunoconjugates in the treatment of human malignancies. 326 48

Natural killer (NK) cell activity and psychological status were measured at baseline and at 3 months into treatment, as part of the National Cancer Institute (NCI) Protocol 79-C-111, randomizing breast cancer patients to lumpectomy/radiation v mastectomy. Patients who were found to have positive axillary lymph nodes also received combination chemotherapy (Adriamycin [Adria Laboratories, Columbus, OH], plus Cytoxan [Mead Johnson Pharmaceuticals, Evansville, IN] or methotrexate, plus 5-fluorouracil [5-FU]). Seventy-five patients were entered onto this behavioral immunology protocol at the time of data analysis. We reported in an earlier publication that NK activity was an important predictor of patient baseline prognosis relevant to nodal status. In that study, by using multiple regression analyses, 51% of the baseline NK activity variance could be accounted for by entering three distress indicators into the equation (patient "adjustment," lack of social support, and fatigue/depression symptoms). On reassessment of NK activity after 3 months, it was found that NK activity was not affected by the interim administration of chemotherapy and/or radiotherapy. However, consistent with our earlier findings, NK activity levels remained markedly lower in patients with positive nodes than in patients with negative nodes (at 60 to 1 effector to target cell [E:T] ratio, mean of 18% lytic activity v mean of 31% lytic activity [t = 1.87, P less than .05]). Even though average levels of NK activity were lower for patients with more tumor burden, there was still a substantial range of NK activity levels within the node positive patient group, as well as within the patient group as a whole. We hypothesized that differences in levels of NK activity could be predicted on the basis of baseline distress factors found to be significant in our earlier report. In fact, we found that we could account for 30% of NK activity level variance at 3 months follow-up on the basis of baseline NK activity, fatigue/depression, and lack of social support. Therefore, although neither radiation nor chemotherapy appeared to affect NK activity, tumor burden was again clearly associated with NK activity levels, and a significant amount of baseline and 3-month NK activity could be predicted on the basis of CNS-mediated effects. At the least, such factors provide a psychological marker of host biological status.
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PMID:Correlation of stress factors with sustained depression of natural killer cell activity and predicted prognosis in patients with breast cancer. 354 12

Advanced malignant testicular tumors can be treated very successfully by chemotherapy. The most effective 3 or 4-drug combinations contain CisPlatin, Vinblastine, Bleomycin, Adriamycin, Cyclophosphamide, Ifosfamide and Vepesid. Complete remissions of 60% can be obtained; depending on histology, frequency of metastases, and former radiation therapy. Resection of residual pulmonary or retroperitoneal metastases render an additional 10-20% of the patients free of tumor. Side effects following chemotherapy should not be neglected: Depression of bone marrow, severe vomiting, alopecia, and azoospermia.
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PMID:[Modern chemotherapy of a malignant testicular tumors (author's transl)]. 617 87

Adriamycin, a widely employed anti-neoplastic agent, was found to have either inhibitory or stimulatory effects on NK activity, depending on the site examined. A single i.p. administration of ADM resulted in a rapid increase of cytolytic activity by PEC of various mouse strains. The effector cells appeared to be NK cells, being nonadherent and nonphagocytic; they expressed low amounts of Thy 1.2 antigen and had the same pattern of specificity as splenic NK cells. In contrast to the stimulatory effects of NK activity of PEC, ADM caused a transient dose-dependent depression of NK activity in the spleen, with a peak reduction at day 3 and recovery within a few days thereafter. The depressed NK activity could be reversed by removal of adherent cells by passage through a nylon column. Moreover, ADM induced cytostatic activity against tumor cells by macrophages, suggesting that activated macrophages may be responsible for suppression of splenic NK activity. The possible modulation of the levels of NK activity by ADM-induced macrophages was supported by mixture experiments, in which plastic adherent spleen cells from ADM-treated mice, but not from normal mice, inhibited the NK activity of normal spleen cells.
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PMID:Effects of adriamycin on the activity of mouse natural killer cells. 644 69

Adriamycin treatment in vivo or addition to incubation mixtures in vitro inhibits hepatic drug metabolism. It has been suggested that adriamycin-induced membrane lipid peroxidation may be a mechanism responsible for this activity in vitro. To determine if similar mechanisms operate in vivo, adriamycin inhibition of drug metabolism was compared in rats whose tissue lipid peroxidizability was altered by manipulating dietary levels of vitamin E. Weanling rats maintained on vitamin E deficient (0 ppm) or supplemented (10 or 100 ppm) diets for 12 weeks were given either adriamycin, 5 mg/kg/week, or equal volumes of the saline vehicle for 3 weeks intraperitoneally. Vitamin E deficiency alone (0 ppm, saline pretreatment) produced a 37% increase in hepatic lipid peroxidation without any appreciable alteration in hepatic aniline hydroxylase, ethylmorphine N-demethylase or aryl hydrocarbon hydroxylase activities. Adriamycin pretreatment altered hepatic lipid peroxidizability over corresponding saline pretreated controls dependent on dietary vitamin E. No increase was seen in the 100 ppm group, while 44% and 500% increases occurred at 10 and 0 ppm vitamin E, respectively. Adriamycin pretreatment decreased drug-metabolizing enzyme activity by an average of 32% for aniline hydroxylase, 26% for ethylmorphine N-demethylase and 63% for aryl hydrocarbon hydroxylase. Statistically, decreases in drug metabolism were independent of dietary vitamin E and did not correlate with lipid peroxidizability. These data would suggest that in vivo adriamycin-induced depression of hepatic drug-metabolizing enzymes is not mediated by elevated lipid peroxidation.
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PMID:Increasing lipid peroxidation by vitamin E deficiency does not augment adriamycin-induced inhibition of hepatic drug metabolism. 665 95

This study was designed to evaluate the usefulness of Coenzyme Q10 (CoQ10) in the prevention of side effects due to anthracycline agents-Adriamycin (ADM) and Daunorubicin (DNR)-by comparing the preventive effect between CoQ10-treated and non-treated groups. The subjects were 79 patients, 55 of whom had malignant lymphoma. The age range was from 16 to 77 years with a mean age of 45.4 years. CoQ10 was administered by intravenous drip at 1 mg/kg/day the day before ADM or DNR administration, on the day and for a further 2 days after administration. In mean total dose, complete remission rate and mortality, no significant differences were observed between the 2 groups. Although there were also no significant differences in the degree of alopecia, fever, nausea and vomiting, the incidences of diarrhea and stomatitis were significantly (p less than 0.10 and p less than 0.05, respectively) reduced in the CoQ10-treated group. Depression of ST waves (more than 0.05 mV) and changes in T waves (R/10 greater than T, flat, inversion) on ECG were regarded as a parameter of aggravation. Such ECG aggravation was found in 20 of 40 patients given CoQ10 (50.0%) and in 18 of 25 receiving none (72.0%); a cardiotoxicity-inhibiting tendency was thus evident (p less than 0.10). In heart rate, tachycardia was noted in the nontreated group when the period of use of anthracycline agents exceeded 8 weeks. Twenty nine patients received ADM or DNR for 8 weeks or more, and, of them, 17 were treated with CoQ10; 11 of the 17 (64.7%) showed ECG aggravation, while 11 of 12 patients (91.7%) not treated with CoQ10 showed ECG aggravation. A tendency to depress ECG aggravation was thus observed in the treated group (p less than 0.10).
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PMID:[Investigation of the preventive effect of CoQ10 against the side-effects of anthracycline antineoplastic agents]. 674 67

The Third Department of Medicine, Tokyo Medical and Dental University Medical School The cardiotoxic effect of aclacinomycin A or adriamycin given by a single intravenous injection was evaluated in golden hamsters by electrocardiography (ECG) and electron microscopy. Aclacinomycin A caused slight ECG alterations at a dose of 75 mg/kg or 100 mg/kg such as bradycardia, Ta wave formation, ST segment depression and T wave flattening. On the other hand, adriamycin caused moderate to remarkable alterations in ECG at a dose of 3.13 mg/kg or 6.25 mg/kg, such as arrhythmia, bradycardia, auriculoventricular block, bundle branch block, ST segment changes and T wave flattening. Alterations in ultrastructure of the myocardium caused by aclacinomycin A at a dose of 25 mg/kg contained some cardiac cells with mild changes, ie, dilations of sarcoplasmic reticulum and swelling of mitochondria. At a dose of 100 mg/kg, it caused moderate to remarkable alterations such as separation of myofilaments, appearance of myelin figures, and decreases in intramitochondrial granules and glycogen particles. Adriamycin, however, gave remarkable changes even at a dose of 6.25 mg/kg which involved separation of myofilaments, lower electron-density of mitochondrial matrix, vacuolization and swelling of capillary endothelial cells. From these findings, both antibiotics may cause cardiotoxicity by similar mechanism. But aclacinomycin A affected the heart milder than adriamycin.
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PMID:[Cardiotoxic study of aclacinomycin A: Acute cardiotoxic effect of aclacinomycin A in hamsters (author's transl)]. 693 Dec 36


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