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)

The synthetic non-steroidal antioestrogen nafoxidine (U-11, 100A) was given by mouth to 52 women with locally advanced or metastatic breast cancer, in 85% of whom the disease had become resistant to, or relapsed after, previous endocrine treatment. The objective response rate (complete or partial regression of disease) among 48 cases treated for at least four weeks was 37%. Tumours in soft tissue seemed to respond better than skeletal metastases. The patients in all but one of the 52 cases were postmenopausal. Those who had had an objective response to previous hormone treatment had a greater chance of deriving benefit from nafoxidine than those who had been resistant to hormone treatment.Side effects of nafoxidine were dryness of skin, increased loss of scalp hair, and heightened sensitivity to sunlight. None were serious, and they could be lessened by protection from solar radiation or a decrease in dosage. No obvious depression of thyroid or adrenal function or obvious water retention or masculinization was seen. Cataract was a possible complication.This clinical trial was preceded by laboratory studies in which a transplantable oestrogen-dependent tumour in the Syrian hamster was notably inhibited by the administration of nafoxidine. This experimental model may prove useful in screening potentially useful antioestrogenic agents against breast cancer before a human trial.
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PMID:Antioestrogens in treatment of breast cancer: value of nafoxidine in 52 advanced cases. 436 55

This report gives the findings after two years of a study of long-term oral cytotoxic chemotherapy with busulphan or cyclophoshamide in carcinoma of the bronchus compared with two placebos, identical in appearance to the drug-containing tablets. A total of 753 patients who had had a total resection of the tumour, who had no detectable extrathoracic metastasis, and who were able to attend chest clinics monthly were admitted to the study from January 1965 to January 1968. Twenty-seven patients were excluded from all the analyses.The 217 patients admitted up to December 1965 form the "early" intake, the remaining 509 the "late" intake. There were no significant differences between the series in either intake period in a number of pretreatment factors studied. At 24 months 46% of the busulphan, 44% of the cyclophosphamide, and 49% of the placebo series were alive in the early intake, as were 49%, 50%, and 50% respectively in the late intake. There were no important differences between the series in survival related to pretreatment condition, cause of death, time of detection of metastases, and condition of the survivors at 24 months. Maintenance chemotherapy was interrupted to a greater extent in the busulphan than in the cyclophosphamide series and least in the placebo series.In both intakes clinical toxicity was more frequent in the cyclophosphamide series and similar in frequency in the busulphan and placebo series. Haematological toxicity was particularly frequent and severe in the busulphan series, especially in the early intake, platelet depression being the predominant manifestation.It is concluded that there is no evidence that either of the two cytotoxic drugs in the dosage prescribed improved survival for the two-year period of observation, though a final evaluation of the adjuvant chemotherapy as studied in this investigation will have to await the results at five years.
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PMID:Study of cytotoxic chemotherapy as an adjuvant to surgery in carcinoma of the bronchus. Report by a Medical Research Council Working Party. 493 Mar 89

Within 1 year 74 children with neuroblastoma were registered, 30 patients with stage I-III (= 41%) and 44 with stage IV-metastatic disease (= 59%). An aggressive chemotherapy regimen employing Adriamycine, Cyclophosphamide, Vincristine, and Dacarbazine yielded 10/24 partial and 9/24 complete remissions after 9 weeks. 5/24 children were treated less than 9 weeks so far. At the end of the chemotherapy protocol (week 33) 6 recurrences were observed; 3 of these children died. 5 patients remained in complete remission, 1 in partial remission. 12/24 of patients were not evaluable because of treatment less than 33 weeks so far. The one year run of the study is too short to evaluate the benefit of Interferon (randomized trial). The toxicity of the regimen is tolerable, including bone marrow depression, vomiting and hyperpyrexia. Breaking off therapy was only necessary in one patient.
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PMID:[Neuroblastoma study NBL79-society of pediatric oncology -- report after 1 year (author's transl)]. 616 57

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

The immune regulation of phytohemagglutinin (PHA) and concanavalin A (Con A) mitogen responses by prostaglandin (PG)-producing suppressor monocytes was examined in 57 patients with colorectal cancer and 55 normal individuals. The blood lymphocyte responses to either PHA or Con A were significantly depressed in 74% of patients compared to normal controls. The mean PHA response for the patients was significantly lower than that for controls (17,649 versus 25,549 cpm, P = 0.02), while the mean Con A response for the patients was also depressed but not as significantly (13,551 versus 18,623 cpm, P = 0.09). The depression of immune competence was greatest in older patients and those with metastatic disease. The addition of indomethacin (1 microgram/ml) to cell cultures of both patients and normal individuals enhanced the mitogen response, suggesting that PGE-producing suppressor cells were operative in both groups. Among the patient group, however, a differential modulation of the immune response by indomethacin was observed. Thus, the addition of indomethacin restored the PHA response in patients almost to normal levels, while the Con A increase was less pronounced. Even after indomethacin treatment, the Con A proliferative response by lymphocytes was significantly depressed in patients as compared to controls (P = 0.002). To prove that indomethacin was blocking excessive PG production by suppressor monocytes in colon cancer patients, we directly measured PGE2 production by peripheral blood mononuclear cells (PBMCs) using a radioimmunoassay. PBMCs from the patients produced significantly greater amounts of PGE2 compared to controls (10.1 versus 5.1 ng/ml, P = 0.0001). This comparison was still significant after adjustment for age and sex. The increased PGE2 production appeared to be selective, since the levels of two other arachidonic acid metabolites, PGF1 alpha and thromboxane B2, were the same or less than control levels. PG-mediated immune suppression of mitogenesis thus appears to be abnormally increased in colon cancer patients, particularly for the PHA response. This abnormality was partially corrected in vitro by incubation of the PBMCs with indomethacin, a prostaglandin synthetase inhibitor.
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PMID:Prostaglandin E2-mediated suppression of cellular immunity in colon cancer patients. 622 53

Naturally-occurring hyperadrenocorticism was diagnosed in an 11-year-old female Dachshund with signs of polydipsia, polyuria, pendulous abdomen, weakness, depression and lethargy, and laboratory test abnormalities comprising lymphocytopaenia, eosinopaenia, hypercholesterolaemia and increased plasma alkaline phosphatase concentration. While awaiting hormonal test results, an adrenocorticolytic drug (o,p'-DDD) was administered for 14 days, during which the patient deteriorated. Hormonal assays suggested a functioning adrenocortical tumour, but the poor condition of the patient precluded adrenalectomy. An adrenocortical carcinoma with hepatic metastases was found at necropsy.
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PMID:Functioning adrenocortical tumour in a dog. 628 91

Peripheral blood lymphocytes from female patients with early breast cancer were examined before surgery for their ability to develop a primary antibody response in vitro against sheep red blood cells in soft agar cultures containing autologous plasma. After 6 days incubation, foci of proliferating hemolysin-forming cells surrounded by a lytic area were detected on the surface of the plates and counted with a dissection microscope; this response was antigen-dependent and antigen-specific. We applied this assay to a group of women suffering from early breast cancer and devoid of distant metastases. From our data, it appears that if all the patients are grouped together, cancer-bearing women produce somewhat fewer (P less than 0.05) haemolytic foci than healthy controls. However, division of the cancer patients into two subgroups, according to the TNM pretreatment clinical classification of regional lymph nodes, generated an interesting finding: N1 patients (N1b or N1a) produced definitely fewer foci than N0 patients, and the difference was highly statistically significant (P less than 0.001). The depression of anti sheep red blood cell antibody production observed in N1 patients was unrelated to the presence or absence of metastatic growth in their regional lymph nodes.
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PMID:Antibody production in cultured blood lymphocytes from breast cancer patients. 635 85

For the analysis of the mechanism of cancer metastasis, effects of anticancer agents on the NK activity of spleen cells and on the artificial metastasis of B-16 melanoma cells were comparatively studied. The inhibitory effect of these anticancer agents on the growth of B-16 melanoma inoculated to foot pad of C57/BL6 mice was also examined. The growth of B-16 melanoma was inhibited by intravenous administration of 6 mg/kg of MMC, 18 mg/kg of KW-2083 and 5 mg/kg of CDDP, but not of 6 mg/kg of KW-2083. The NK activities in spleen cells of C57/BL6 mice administered with 6 mg/kg of MMC and 18 mg/kg of KW-2083 were decreased, but they were not decreased in mice administered with 6 mg/kg of KW 2083 and 5 mg/kg of CDDP. Significant increases in the number of artificial pulmonary and liver metastasis were observed in mice administered with 6 mg/kg of MMC and 18 mg/kg of KW-2083. It is suggested that the depression of NK activity induced by anticancer agents results in the promotion of metastatic disease.
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PMID:[Analysis of the mechanism of cancer metastasis by using anticancer agents]. 642 Dec 47

About 80 per cent of patients with breast cancer ultimately die of metastatic disease in the following twenty years. Distant metastases are more important as cause of death than loco-regional relapses, it is why adjuvant chemotherapy is necessary, especially in young patients and in those with extensive disease. Initial chemotherapy preceding any locoregional treatment is justified on the basis that both surgery and anesthesia lead to immuno-depression. Further, the value of initial chemotherapy has been demonstrated in many experimental and clinical trials of Nissen-Meyer, Bonadonna and Cooper. We have treated 145 patients, including 67 with inflammatory breast cancer (IBC), with 4 to 6 weeks of Velbe, Thiotepa, Methotrexate Fluorouracil and Prednisone with Adriblastine added for those patients with IBC or T greater than 7 cm, or N2 N3. Because of tumor regression of more than 50 per cent observed in 80 per cent of the patients, the majority (123 patients) then received radiotherapy alone (cobalt + iridium) and are in a complete remission in all these cases after curietherapy. Maintenance treatment with the same drugs was prescribed for 6 to 18 months depending on the initial staging. Tumor regression appears to be an important prognostic factor. Median follow-up is only 17 months, the longest one being 42 months. The overall survival at 2 years for IBC, is 90 per cent with a disease-free survival of 80 per cent. Cosmetic results are excellent. While these results are encouraging, longer follow-up is needed to confirm this improvement.
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PMID:[Breast cancer: chemotherapy preceding locoregional treatment with extension of the indications for conservative treatment]. 643 62

Major intra-abdominal operations result in profound immunodepression. In addition, manipulation of malignant tumors may release tumor cells into the systemic and portal circulations. The additive effects of immunodepression and tumor cell release may enhance the metastatic potential of tumors. Perioperative correction of immune depression by levamisole can restore lymphocyte proliferation levels in rats. We have developed a model in which rat colon carcinoma cells transplanted into the portal venous system consistently induce hepatic metastases by 4 weeks and death within 9 weeks. Rats pretreated with levamisole (4 mg/kg administered intraperitoneally) the day before and the day of tumor implantation developed fewer metastases (41% of animals treated with levamisole compared with 6% of animals not treated with levamisole had less than or equal to two metastases per liver). Twenty percent of the rats treated with levamisole developed no hepatic metastases. Comparison of median liver weights between the group treated with levamisole and the nontreated, tumor-bearing group was highly significant (p less than 0.005). We conclude that the perioperative period is critical for the implantation and growth of metastases and that perioperative immunostimulation may be a factor in decreasing the incidence of metastases. This model may have relevance to the adjuvant treatment of human colon cancer.
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PMID:Prevention of rat colon cancer metastases by perioperative immunostimulation. 646 70


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