Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Equinatoxin, a highly basic protein extracted from Actinia equina, causes an increase in the survival time of mice bearing the ascitic form of Ehrlich carcinoma, whereas it has no effect on L1210 leukaemia. When tested for in vitro cytotoxicity by the dye exclusion test, it shows a potent activity on both tumour cell lines, with ED50 of a few ng/ml. Higher concentrations produce an extensive lysis of the cells. The cytotoxic effects of Equinatoxin are inhibited by phospholipids, thus suggesting that its mechanism of action may be related to interactions with lipids or other charged components of cell membrane. The observed lack of in vivo activity against L1210 leukaemia presumably is due to poor systemic absorption of the protein and/or neutralization by serum factors.
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PMID:Antitumor activity of equinatoxin. 0 94

Morphologic, tissue culture, immunologic, and biochemical methods have been used in an attempt to detect and characterize oncogenic viruses or their subviral components in cells derived from human prostatic carcinoma (PrCa) or benign prostatic hyperplasia (BPH). Electron microscopy was used to characterize the ultrastructural features of normal and neoplastic prostatic tissue. Examination of specimens of prostatic tissue from 34 patients with PrCa, ten patients with BPH, and three patients with bladder tumor (BT) revealed the presence of particles resembling type-C virus in three cases of PrCa and structures resembling budding type-C virus particles in one case of BPH. Fifty human prostatic tissue specimens have been set in tissue culture, of which 30 have been successfully grown for varying periods of time. Of 20 currently active cultures, nine consist primarily of epithelial cells. Immunofluorescence and mixed hemadsorption tests of cells derived from benign and malignant prostatic tissue and sera derived from patients with PrCa, BPH, BT, and other types of tumors, and from normal donors revealed that sera from patients with PrCa, BPH, or BT contain antibodies to antigens in cells derived from PrCa, BPH, or BT. The nature of these antigen-antibody reactions is under study. Initial biochemical studies have not detected reverse transcriptase in the tissue culture fluid from a small number of sparsely growing PrCa cultures nor specific gene sequences homologous to murine leukemia virus-Rauscher genomic RNA in preparations of either normal or malignant prostatic cell DNA. The results of these preliminary studies have demonstrated the applicability of the techniques employed to the study of the relationship of viruses to human PrCa and have provided a number of promising leads for further investigation.
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PMID:Virologic and immunologic studies of human prostatic carcinoma. 4 14

The existence of oncornavirus genetic information in human prostatic tissue was studied by assaying tissue extracts for products of viral gene expression (ie, the p30 antigen). Tissue samples from patients with benign prostatic hyperplasia (BPH) or prostatic carcinoma (CaP) were assayed by the competetive radioimmunoassay. The competing antigens used were p30 proteins derived from the simian sarcoma virus type-1 (SSV-1) and the Rauscher murine leukemia virus (RLV). Of the 40 extracts tested, three of 20 extracts from BPH patients and one of 20 from CaP patients competed with the SSV-1 p30 antigen and only one of ten extracts from BPH patients competed with the RLV p30 antigen. The significance of these findings has yet to be established.
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PMID:Role of oncornaviruses in carcinoma of the prostate. 6 18

Electron microscopic, immunologic, and biochemical methods have been used in an attempt to detect and characterize oncornaviruses in human prostatic carcinoma (PCa) and benign prostatic hyperplasia (BPH), and in prostates of mice of high and low mammary cancer or leukemia strains. Ultrastructural examination of 37 PCa and nine BPH specimens has revealed the presence of particles resembling type C virus in five cases of PCa and one of BPH, and also two different types of intracisternal virus-like particles in seven other cases of PCa. Type B virus particles have been observed in prostate of old mice of high mammary cancer strains, while type C virus particles have been found in the prostates of most mice of all the ten strains examined. Immunofluorescence tests with sera from patients with PCa and BPH and with cells derived in vitro from PCa have shown that sera of patients with PCa contained antibodies directed mainly against Forssman-like and tumor-related antigens. In immunofluorescence tests of antisera to major proteins of oncornaviruses with cells of PCa and BPH tissues grown in vitro, positive reactions have been obtained with antisera to p30 protein of murine, feline, and simian type C viruses. Fixed immunofluorescence (FIF) tests of sera of PCa (38%) and BPH (25%) and of some normal donors (27%) gave positive cytoplasmic reaction with mouse prostate cells infected with Soehner-Dmochowski murine sarcoma virus (SD-MSV). Immunoferritin tests of 11 sera positive by FIF gave ferritin labeling of type C virus particles in the SD-MSV-infected mouse prostate cells...
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PMID:Search for oncogenic viruses in human prostate cancer. 6 17

Radial immunodiffusion assay was used to measure fetal hemoglobin (HbF) concentrations in 312 patients with various malignancies. In 305 of these, alpha-fetoprotein (AFP) was measured by radioimmunoassay. The concentration of HbF exceeded 3 SDs above the normal mean in 68 of 312 patients, most notably in patients with leukemia, multiple myeloma, lymphoma, bladder carcinoma and testicular tumors. HbF was correlated with total hemoglobin concentration and with serum AFP concentration in hepatoma and bladder carcinoma.
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PMID:Fetal proteins in various tumors. 8 98

The antimicrobial and antitumor activities, and the pulmonary toxicity of pepleomycin (NK631) were studied in comparison with bleomycin (BLM). NK631 showed a broad antimicrobial spectrum against gram positive and gram negative bacteria equally to BLM, and its activity was about twice higher than BLM. NK631 showed higher activity on cultured HeLa S3 cells and higher antitumor effect on the transplanted tumors of Ehrlich solid carcinoma in mice, AH66 and AH66F ascites hepatoma in rats, and lower antitumor effect on Ehrlich ascites carcinoma in mice than BLM. Similarly to BLM, NK631 did not show satisfactory activity on L1210 leukemia in mice. NK631 showed marked effect on chemically induced squamous cell carcinoma, spontaneous lymph sarcoma of a dog, human and dog gastric cancer heterotransplanted in nude mice equally to BLM. Furthermore NK631 exhibited remarkably higher antitumor activity on lymph node metastasis of AH66 ascites hepatoma of rats and chemically induced gastric carcinoma of rats than BLM. Pulmonary toxicity of NK631 was low as 1/3 in incidence and 1/4 in grade of the BLM in old mice system. This trend was confirmed by chemical analysis of hydroxyproline in lung.
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PMID:[Studies on antitumor activities and pulmonary toxicity of pepleomycin sulfate (NK631) (author's transl)]. 8 10

Syngeneic A.SW mice were immunized with sublethal viable cells of a spontaneous mammary adenocarcinoma S3W. The serum was tested by complement-dependent cytotoxicity against in vitro-cultured S3W cells and a spectrum of controls. S3W cells were found to react with at least four different kinds of antibodies in the serum. One antigen was present on several leukemia cell lines. A second cross-reactive antigen was detected on polyoma virus-induced tumors. A third was demonstrated on other mammary carcinoma lines and in a sarcoma of C3H origin. Following the removal of all three antibodies by absorption with the appropriate cross-reactive target cells, a fourth antibody remained that gave a strong cytotoxic reaction with S3W but with no other target line tested.
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PMID:Serologically defined, unique surface antigen on a mouse mammary adenocarcinoma. 8 92

Using radioiodinated Staphylococcus aureus protein A [125I]SPA to measure syngeneic, allogeneic and heterogeneic IgG bound to murine tumor cells, we performed a serological analysis of surface antigens of 8 solid tumors and 2 leukemias of BALB/c mice (3 chemically-induced colon carcinomas, 3 chemically-induced sarcomas, 1 murine leukemia virus (MuLV) induced leukemia, 1 irradiation induced leukemia, 1 spontaneous melanoma and 1 spontaneous sarcoma). We were able to detect and distinguish between at least five separate antigenic specificities on these tumors. Unique tumor-associated antigens were found on 3 of the tumors, MuLV related antigens on 8 tumors, fetal antigens on 7 tumors and two distinct common antigens on 7 tumors (common antigen 1 (CA-1) on 5 tumors and common antigen 2 (CA-2) on 2 tumors). Neither of the common antigens was found to be sarcoma, carcinoma or tissue-tupe specific. A number of tumors which did not originally express either MuLV or fetal antigens in primary cultures expressed these antigens after several serial passages in vitro.
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PMID:Tumor-associated antigens of chemically-induced murine tumors; the emergence of MuLV and fetal antigens after serial passage in culture. 8 20

The results of a phase I--II study of a combination chemotherapy with AAFC and ICRF-159 in advanced adenocarcinoma of digestive origin are presented. Myelosuppression was the dose-limiting toxicity with anemia, leukopenia, and thrombocytopenia. The maximum tolerated dose of AAFC in the combination program was 650 mg/m2 I.V. weekly. ICRF-159 was given in a 3-day course every 3 weeks and the dose was escalated from 125 mg/m2 to 500 mg/m2 daily. Bone marrow toxicity was noticied at the first escalation level and all dose levels were similarly toxic. The results of this combination chemotherapy were: two partial responses in 14 patients with gastric cancer; no responses in nine patients with colorectal cancer; no responses in three patients with pancreatic cancer; and no responses in two patients with biliary tree cancer. In conclusion, AAFC and ICRF-159 combination chemotherapy demonstrated a low level of activity in advanced carcinoma of digestive origin. The peculiar hematologic toxicity found at the low-level dose requires further documentation and could make this drug association suitable for a phase II study in leukemia and/or lymphoma.
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PMID:Phase I and II clinical study of anhydro-ara-5-fluorocytosine (AAFC) and ICRF-159 combination in adenocarcinoma of digestive origin. 9 30

1. Nine patients in whom acute non-lymphoblastic leukemia (ANLL) developed following prolonged alkylating agent therapy are described. Five of the patients received no radiotherapy. The conditions treated were: Hodgkin's disease (four patients), primary amyloidosis, primary macroglobulinemia, malignant lymphoma, multiple myeloma, and carcinoma of the tonsil. 2. Prior to the advent of chemotherapy, this complication was not observed in large series of patients with lymphoproliferative disorders and multiple myeloma. However, the medical literature now contains at least 125 other detailed reports of ANLL developing after prolonged cytotoxic agent therapy. 3. Multiple myeloma and Hodgkin's disease, both of which commonly have good responses to chemotherapy, predominate as the underlying diseases. However, 35% of the case reports involve patients with other illnesses, including 12 patients who did not have neoplasms. 4. More than half of the patients developing ANLL have received chemotherapy alone without radiotherapy. 5. At least half of the patients developing ANLL experienced long periods of significant cytopenia during therapy, often with documentation of bone marrow dysplasia. 6. The wide variety of drugs associated with this complication suggests that any cytotoxic agent may be leukemogenic. However, alkylating agents overwhelmingly predominate as the class of compounds which are most often associated with terminal ANLL. 7. The vast majority of patients reported in the literature with ANLL complicating underlying malignancies have received cytotoxic drugs for prolonged periods (median 3 1/2 years) and leukemia developed most commonly 3 to 5 years after the diagnosis of the underlying disease. Most of these patients benefited from therapy and survived longer (median 5 years) than historical control of untreated patients. 8. The leukemogenic potential in man of prolonged cytotoxic agents therapy, especially with alkylating agents, seems to be well established. This evidence admonishes against the prolonged use of these drugs in non-fatal disorders. 9. More accurate assessment of risk: benefit ratios awaits the results of prospective controlled studies. The results of these studies could also lead to significant modifications in recommendations for long-term maintenance therapy with cytotoxic agents.
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PMID:Acute leukemia following prolonged cytotoxic agent therapy. 10 27


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