Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies, using plasmapheresis to remove blocking factors of cell-mediated cytotoxicity to melanoma cells from the circulation of melanoma patients, suggested that leucocyte-dependent antibody to melanoma cells may also be blocked by factors in their sera. The present study confirms these findings, by showing that most patients with disseminated melanoma had melanoma LDA activity in the IgG fraction when this was separated from their sera. This also applied to a high percentage of patients with primary melanoma. Evidence that the blocking factors may be immune complexes was shown by experiments in which LDA activity to melanoma cells was revealed after acidification of melanoma sera to dissociate immune complexes, followed by ultrafiltration through membranes retaining molecules of size greater than 100,000 daltons. Blocking of LDA activity in the retentate recurred when the retentate was recombined with the filtrate. Further studies indicated that the blocking activity showed affinity for the target cell and not the effector cell. Preliminary analysis of the specificity of the blocking suggests that this was similar to that of melanoma antisera. These results appear to show that blocking of LDA activity to melanoma cells is common in melanoma patients and that the assay system may provide a quantitative method for their analysis that may yield information of biological importance in the management of melanoma patients.
Br J Cancer 1977 Jul
PMID:Blocking factors against leucocyte-dependent melanoma antibody in the sera of melanoma patients. 1 29

Compounds with known psychotropic properties were tested for activity in murine ip L1210 leukemia and B 16 melanoma in a protocol designed to obtain leads for new antitumor agents which might also possess central nervous system (CNS) antitumor properties. Barbiturates and hallucinogenic compounds were the only compound types deliberately excluded. Representatives from most of the other known CNS agent classes were included among the 297 psychotropic drugs evaluated. Sixteen of these agents were reproducibly active against the L1210 tumor system with T/C values of 125%. Phenothiazines such as fluphenazine and butyrophenones such as triperidol were prominent among the confirmed active structural types. Dopamine, a beta-phenethylamine neurotrasmitter, was active. While reproducible B16 melanoma activity was not observed among the psychotropic drugs, most of the L1210 confirmed active agents were effective against the ip P388 tumor model and also were active in vitro against KB cells. Ic L1210 activity was not observed among the few compounds chosen for testing in that tumor system. The yield of ip L1210 confirmed actives from this group of psychotropic agents was 18 times that which would have been expected from the random screening of compounds.
Cancer Treat Rep 1978 Jan
PMID:Psychotropic drugs as potential antitumor agents: a selective screening study. 2 98

In an evaluation of indium-111-bleomycin as a tumor-imaging agent, 357 whole-body tumor scans were performed in 293 patients. Of 246 studies performed in patients with a variety of active solid tumors, 218 (89%) were true-positive studies and 28 (11%) were false-negative. Of 69 scans in patients thought to be free of tumor after therapy, 32 (46%) were false-positive studies and 37 (54%) were true-negative. The true-positive rates by major tumor type were: adenocarcinoma of gastrointestinal tract origin (95%), lymphoma (88%), melanoma (87%), sarcomas (82%), lung (77%), breast (77%), childhood tumors (71%), gynecologic tumors (70%), and genitourinary tumors (68%). Soft tissue and lymphatic sites of tumor, both above and below the diaphragm, were easily visualized, whereas hepatic and bone marrow sites of involvement were less easily discerned. False-positive uptake with 111In-bleomycin was noted in lungs (6%), gut (3%), mediastinum (2%), normal breast tissue (0.8%), and in occasional inflammatory lesions. In 19 patients with multiple myeloma or leukemia, a pattern of diminished bone marrow uptake associated with abnormal accumulation of 111In-bleomycin in extramedullary sites of involvement was the rule. In another 23 patients in whom scans were performed because an occult tumor was suspected, scanning did not lead to specific diagnosis of tumor in a single instance. We conclude that 111In-bleomycin is a safe, effective, and useful new tumor-imaging agent in the initial staging and followup of patients with a variety of solid tumors. Significant advantages of this agent over other currently available radiopharmaceuticals include: A) a broader spectrum of tumors taking up the radio-pharmaceutical, and B) generally better delineation of abdominal and pelvic disease due to lack of interference from gut uptake.
Cancer 1975 Apr
PMID:A clinical evaluation of indium-111 bleomycin as a tumor-imaging agent. 4 76

Xeno-antisera, prepared by immunization with soluble membrane material obtained from melanoma tumours and partially purified by column chromatography, were found to detect an antigenic specificity common to some tumour extracts and sera of melanoma patients. The presence of this antigen in patients' sera allows speculation for its possible use for early diagnosis of metastases and its role in the blocking of the immunological defences of the melanoma patients. Preparation of monospecific antisera by immunization with insoluble serum-antigen/antibody complexes has been successfully undertaken.
Int J Cancer 1975 Aug 15
PMID:Identification of an antigen associated with malignant melanoma. 5 Feb 97

One hundred eighty-nine patients received a four-drug combination consisting of cyclophosphamide, Oncovin (vincristine), methyl CCNU, and bleomycin (COMB), according to three different drug regimens, performed sequentially. Of the 189, 62 had a partial response (33%) including 11/33 with squamous lung cancer, 11/32 with squamous carcinoma of the head and neck, 13/15 with oat cell carcinoma of the lung, and 7/41 with malignant melanoma. The response rate for patients with squamous lung or head and neck cancer appeared to be higher at weekly bleomycin doses of 30 and 60 mg (15/33 = 45%), compared to a weekly bleomycin dose of 15 mg (7/32 = 25%). A median survival from treatment of 30 weeks was observed in oat cell carcinoma, which represents considerable prolongation over that expected from supportive care alone or single-agent chemotherapy. Toxicity included: 1) myelosuppression, resulting in hospitalization for antibiotics in 20% of patients; 2) probable bleomycin lung damage in 4% of patients; and 3) dose-limiting vincristine neuropathy in 11%. The combination of twice-weekly vincristine and bleomycin for more than 6 weeks produced a disturbing "debilitation syndrome," characterized by weakness, anorexia, weight loss, and apathy. The encouraging response rate suggests a future role for these drugs in combination, especially for vincristine and bleomycin, with other agents showing activity in squamous and oat cell carcinoma. Toxicity precludes recommendation of this combination, in the regimens tested, for broader Phase III studies.
Cancer 1975 Aug
PMID:COMB (cyclophosphamide, oncovin, methyl-CCNU, and bleomycin): a four-drug combination in solid tumors. 5 Aug 70

In malignant melanoma, using Sephadex G-200 chromatography and polyacrylamide gel electrophoresis (PAGE), it has been possible to separate two types of skin reactive antigens. The first, found in Sephadex fraction II and PAGE region a appears specific for melanoma. Allogeneic extracts have produced positive reactions in many patients with skin or ocular melanoma, and have given negative reactions in patients with other types of cancer or in patients with ocular lesions simulating melanoma. The second group of antigens, in Sephadex fraction III and PAGE region b were less specific. These antigens produced positive skin reactions in some patients with breast cancer, as well as in patients with melanoma. Reactivity to PAGE region a appeared to be confined to one protein band, but three different bands in region b gave positive reactions. A study was made of the presence or absence of similar antigens in metastatic deposits of malignant melanoma. Metastatic lesions in the following tissues were analyzed: liver, lung, adrenal, skin, and colon. These were compared with pooled primary skin melanomas by skin testing in the same patients. The tumor-associated melanoma antigen, found in Sephadex fraction II and PAGE region a appeared to be strongest in adrenal, lung, and liver metastases. It was found that the protein yield in this region was not indicative of the strength of the antigen. Therefore, a careful, detailed analysis of the protein bands present in PAGE regions a and b from primary skin melanoma was conducted. Only one band in PAGE region a was found to be responsible for positive skin reactivity. This band was found to be a glycolipoprotein. Further studies were also conducted in order to determine whether or not some of the antigens present might be fetal antigens. Some of the protein bands present in Sephadex fraction III and PAGE region b of melanoma appeared to be similar to some of the PAGE region b proteins present in fetal skin cells. Two bands from fetal skin also had the same location on PAGE as two bands from ductal breast cancer, although the relationship to melanoma region b antigens was not exact. These fetal proteins, which seemed to be present both in ductal breast cancer cell membranes and in melanoma cell membranes, might account for the positive skin reactivity seen in this region, and also for the cross reactivity of skin tests with this antigen.
Cancer 1975 Oct
PMID:Analysis of soluble melanoma cell membrane antigens in metastatic cells of various organs and further studies of antigens present in primary melanoma. 5 80

The specificity of cell-mediated cytotoxicity against melanoma cells in vitro has been analyzed in a large number of studies with cells both from normal and melanoma subjects. As in a number of other, recent, similar human studies, no evidence for tumour specificity was found. Effector cells in peripheral blood responsible for the cytotoxic raction were examined by cell separation methods based on red cell rosette formation and separation through Hypaque-Ficoll mixtures. The evidence suggests that non-specificity results from killing by cells separating largely in the non-sheep red blood cell rosetting fraction and which have cytotoxic specificity directed broadly to cells with abnormal membranes. Further analysis revealed that the cells were non-phagocytic and did not bear receptors for complement. They appear to be activated into cell division and to bear surface receptors for the Fc portion of IgG. Additional evidence is presented suggesting that the cells mainly responsible are activated thymus-dependent cells present in the circulation of both tumour-bearing and normal subjects.
Int J Cancer 1975 Jul 15
PMID:Specificity of cell-mediated cytotoxicity against human melanoma lines: evidence for "non-specific" killing by activated T-cells. 5 32

A microcytotoxicity technique was used to determine the sequential in vitro reactivity against melanoma cells of lymphocytes from melanoma patients receiving immunotherapy and from healthy donors. Lymphocytes were collected 2 weeks for 2-3 months and were stored in liquid nitrogen until use. Preliminary studies had indicated that freezing did not effect the reactivity of lymphocytes. Lymphocytes from 10 healthy donors tested against melanoma cells exhibited substantial reactivity which showed no consistent pattern over time. Lymphocytes from 9 melanoma patients exhibited increased reactivity after immunotherapy. Patterns of reactivity against melanoma cells and against bladder carcinoma cells were similar, indicating lack of specificity for melanoma antigens. Correlations with clinical course of the disease were not apparent.
Int J Cancer 1975 Oct 15
PMID:Sequential in vitro reactivity of lymphocytes from melanoma patients receiving immunotherapy compared with the reactivity of lymphocytes from healthy donors. 5 35

The leukocyte adherence inhibition (LAI) test has been used to assess specific anti-tumour immunoreactivity in 80 patients with malignant melanoma, 21 of whom had apparently been successfully treated by surgery, and 44 control subjects. Reaction with melanoma extracts in vitro enabled the activity of blood leukocytes to be detected by inhibition of their adherence to glass, while serum was tested for factors which modified this inhibition. Of the patients with tumours (ranging from primary melanoma in situ to advanced disseminated disease), 22/24 had active leukocytes and 50/58 has serum blocking factor; two of the sera, from patients with regressing tumours were unblocking. After surgery with no clinical recurrence, leukocytes continued to be active except when tested several years after operation. Blocking factor rapidly disappeared in 16/20 patients tested, and in several patients examined serially the serum became unblocking. In three cases, persistence of serum blocking was followed by clinical diagnosis of metastases. Leukocyte activity was nerver detected in control subjects (0/10), many of whom had other kinds of tumours or skin lesions. Blocking activity in serum was found in only 3/38 controls with no history of melanoma (1 had a fibrosing cellular blue naevus and 2 had liver disease). Thus the LAI test correlated well with clinical and pathological findings, and shows great promise for the reliable, rapid and specific immunodiagnosis of malignant melanoma.
Int J Cancer 1975 Oct 15
PMID:Leukocyte adherence inhibition and specific immunoreactivity in malignant melanoma. 5 36

In vitro cell mediated cytotoxicity (CMC) assays have been conducted in a human melanoma system with a 3H-proline retention technique. Melanoma target cells from long-term cultures ("cell lines") are found to exhibit increased susceptibility for lymphocyte cytotoxicity in comparison to the same target cells from short-term culture. The higher sensitivity of the "cell line" derived target cells is seen with lymphocytes, irrespective of diagnosis of the donor. In parallel experiments with the target cells grown in medium supplemented with fetal calf serum (FCS) and AB+ human serum (from a normal male doner), the melanoma target cells grown with FCS do not show any enhanced cytotoxicity, suggesting no causal relationship of such enhanced sensitivity of "cell line"-derived target cells to "heterologous melanoma antigens" that might have been acquired by the target cells following the use of FCS in tissue culture. In controlled assays of in vitro CMC, lymphocytes from melanoma patients (14/44) exhibited selective cytotoxicity (destruction of only one target-cell type) against the melanoma target cells, whereas only 3/97 control lymphocytes (other malignancies and normal donors) showed such melanoma-selective cytotoxicity. This difference is statistically significant at p less than 0.001. Non-selective cytotoxicity (destruction of two or more unrelated target cell types) was seen with lymphocytes from 9/44 melanoma patients, 13/51 patients with other malignancies and 8/46 normal donors. No correlation of selective cytotoxicity could be established with donors' age, sex, stage of disease, therapy or history of blood transfusion. Such a correlation may emerge as our series becomes larger. Despite the lack of any correlation between selective cytotoxicity and disease status, our study reaffirms the existence of selective cytotoxicity by melanoma patients' lymphocytes against melanoma target cells.
Int J Cancer 1975 Dec 15
PMID:Selective and non-selective lymphocytotoxicity in human melanoma: observation on the effect of long-term culture and fetal bovine serum on target-cell sensitivity to lymphocytes. 5 12


1 2 3 4 5 6 7 8 9 10 Next >>