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

Current therapy for children with cancer includes a variety of invasive procedures many of which require repeated venous access over a considerable period of time. Such procedures are poorly tolerated by children and by their veins. Recently it has become possible to undertake the majority of such procedures by means of permanent indwelling silastic catheters improving the quality of life of the children and their parents and increasing the scope of therapeutic intervention. In the period July '83 - August '84 we have used 46 of these catheters in 45 children with malignant disease, 12 with acute myeloid leukaemia, 12 with neuroblastoma, 7 with B cell leukaemia-lymphoma, 6 with rhabdomyosarcomas, 2 with Ewing's Sarcoma, 2 with Wilms' tumor and 1 case each of Hodgkin's disease, teratocarcinoma, osteosarcoma and juvenile chronic myeloid leukaemia. The children's ages ranged from 2 months to 14 years; 22 were male and 23 female. The catheters were inserted under general anaesthesia (duration 20-40 minutes) usually without difficulty, except for a single patient in whom no suitable vein could be found. No complications connected with the placement of the catheter were observed. Subsequent management of the catheter was initially complicated and time-consuming, but was subsequently simplified so that acceptance by parents, children and nursing staff was eventually excellent. The duration of use of 46 catheters ranges from 7 to 350+ days; 24 catheters are presently in use at 30-350+ days from insertion. Eight children died as a result of disease progression and two of sepsis with the catheter in place.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Advantages of a permanent venous access in children treated for cancer. Preliminary results]. 383 38

The present paper describes 4-amino-N-(2'-aminophenyl)benzamide (GOE1734) with regard to synthesis; toxicity in mice, rats, and dogs; and differential therapeutic efficacy in slowly and rapidly proliferating rat tumors. GOE1734, an analog of a group of compounds known for other than antitumor effects with relatively simple N-acyl-O-phenylenediamine structure, is characterized by a low bacterial mutagenic potential after in vitro metabolic activation and DNA-DNA crosslinking activity after in vivo treatment. Maximum tolerated doses in rats and dogs amount to 4 and 1 mg/kg, respectively. High growth-inhibiting efficacy was obtained in intratibially implanted osteosarcoma, in methylnitrosourea-induced primary mammary carcinoma, and in acetoxymethyl-methylnitrosamine-induced colorectal adenocarcinoma. GOE1734 proved to be ineffective in transplanted Yoshida sarcoma and Walker 256 carcinosarcoma when single or multiple doses were administered at dose levels that were moderately toxic or not toxic. Some antitumor effects were observed in L5222 leukemia after ip transplantation, but no effect could be observed after ic implantation or in vitro incubation and subsequent retransplantation of these cells. Since the latter three rat tumors are characterized by relatively short tumor volume doubling times (0.5-2 days), whereas the first three grow slower (tumor volume doubling time, 11-19 days), the remarkable differential antitumor activity of GOE1734 in fast and slowly growing malignancies is striking.
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PMID:Synthesis, toxicity, and therapeutic efficacy of 4-amino-N-(2'-aminophenyl)-benzamide: a new compound preferentially active in slowly growing tumors. 384 Oct 25

Diaziquone (AZQ), a new lipid-soluble antitumor agent, was given by 15-30-minute infusion on a daily X 5 schedule to 47 children with refractory solid tumors and leukemia. The starting daily dose of 6 mg/m2 was escalated to 10 and 35 mg/m2 in patients with solid tumors and leukemia, respectively. In patients with solid tumors, myelosuppression was dose-limiting at a daily dose of 10 mg/m2. In patients with leukemia, prolonged pancytopenia and bone marrow hypoplasia were observed at daily doses greater than or equal to 25 mg/m2. At these higher doses, significant hyperbilirubinemia associated with sepsis was also seen. Corresponding increases of transaminases or alkaline phosphatase and significant hemolysis were not noted. The maximum tolerated dose for this daily dose schedule was 9 mg/m2 in children with solid tumors and 25 mg/m2 in children with relapsed leukemia. Responses to AZQ included stabilization of disease in osteosarcoma, neurofibrosarcoma, pinealoma, and ependymoma. A patient with juvenile chronic myelocytic leukemia in blast crisis converted back to the chronic phase. A patient with acute lymphoblastic leukemia had a substantial decrease in cerebrospinal fluid blast count. Bone marrow aplasia was achieved in children with acute lymphoblastic leukemia and acute nonlymphoblastic leukemia; however, remissions were not achieved. A phase II study of AZQ in children with refractory malignancies is now being performed by the Childrens Cancer Study Group.
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PMID:Phase I clinical evaluation of diaziquone in childhood cancer. 385 80

The new N-phenylbenzamide derivative Goe 1734 was tested for its antitumour effects against mouse, rat, and human tumours. The preparation showed marginal activity against leukaemia L1210, moderate activity against Lewis lung carcinoma, and high activity against osteosarcoma C22LR and Brown Norway myeloid leukaemia. In the subrenal capsule assay the drug was active against four (cisplatin: 2) of nine human tumours. An in vitro clonogenic assay did not reveal any activity of Goe 1734 when mouse osteosarcoma or human tumour cells were exposed for only 1 h. However, continuous exposure led to 70% or greater inhibition of colony formation at concentrations of 0.1-1 microgram/ml (osteosarcoma) or 0.2-2 micrograms/ml (human tumours).
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PMID:Effectiveness of P-aminobenzoyl-O-phenylenediamine (Goe 1734) against mouse, rat, and human tumour cells. 385 82

64 second neoplasms, occurring after therapy of malignant tumors or leukaemia in childhood, came to light in the course of a collaborative group investigation. Most frequent initial diseases were acute lymphoblastic leukaemia (n = 19), Morbus Hodgkin (n = 9), and retinoblastoma (n = 8), whereas osteosarcoma (n = 13), cancer of the thyroid (n = 10) and acute non-lymphoblastic leukaemia (n = 8) were predominant among the second malignant neoplasms. In 36 of 50 irradiated children there was a clear relationship between the localisation of the second neoplasm and the earlier irradiated zone. In other cases, in particular in children with retinoblastoma as initial disease or neurofibromatosis, genetic influences on the origin of the second neoplasms come into question. The preponderance of Morbus Hodgkin after acute lymphoblastic leukaemia (n = 7) must be regarded as extraordinary; in 6 of the 7 children the second neoplasm appeared after a very short interval. A distinct effect of previous treatment with cytostatics on the occurrence of second neoplasms was not seen. The differing time intervals between the occurrence of the first and the second neoplasms in the separate subgroups point toward heterogenous causes being involved in the development of second neoplasms.
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PMID:[Secondary neoplasms following tumor and leukemia therapy in childhood. Report of 64 cases]. 386 17

Radium-224 was injected into 12-week-old male CBA mice in the range 2-64 kBq per mouse either as a single injection or as eight injections spaced at 3.5 day intervals over 4 weeks. Small but significant yields of myeloid leukaemia or osteosarcoma were obtained in all but the control groups. An effect of mode of administration (single or multiple injections) could not be demonstrated but the combined results showed: a maximum yield of myeloid leukaemia in the region 8-16 kBq 224Ra; a greater yield of osteosarcoma than myeloid leukaemia at 64 kBq 224 Ra injected.
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PMID:The induction by 224Ra of myeloid leukaemia and osteosarcoma in male CBA mice. 387 76

Antigens associated with cells transformed in vivo by FBJ virus, a wild type murine sarcoma virus (MSV) complex originating from a spontaneously arising osteosarcoma in a CF1 mouse, have been partially characterized by complement fixation (CF). Using rat antisera against antigens specified by Gross leukaemia virus (GLV) the group specific (gs) antigen of C-type RNA murine tumour viruses was demonstrated in FBJ tumours as well as in GLV rat leukaemias, AKR lymphomata and sarcomata induced by MSV-H (Harvey), an MSV isolate of Friend-Moloney-Rauscher (FMR) subgroup specificity. Using mouse antisera against antigens present in FBJ cells the Gross (G) or wild type specificity of FBJ tumours was demonstrated by cross reactivity with antigens expressed on normal AKR lymphoid tissues and leukaemias. These antigens were absent from MSV-H induced sarcomata and in reciprocal tests mouse antisera to MSV-H failed to react with antigens present in FBJ tumour cells. No distinction between cellular and virion antigens expressed by FBJ cells was possible by CF although evidence for a cellular antigen with G specificity was obtained in tests using aged C57B1 antiserum containing a naturally occurring G antibody lacking significant virus neutralizing capacity. However, the likelihood that mouse FBJ antisera contain antibodies to type specific viral envelope antigens (VEA) as well as cellular antigen is discussed.
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PMID:Antigens of tumours induced by naturally occurring murine sarcoma virus (MSV-FBJ). I. Detection of group and type specific antigens by complement fixation. 482 Sep 43

Human experience of the toxicity of radium acts as a guide for the setting of occupationally permissible levels for radioactive nucleides, especially bone-seekers. Reviewing the published statements and photomicrographs in early reports especially those of Martland (1931) one can make a case that malignancy was induced in bone-marrow (leukaemia, malignant myelosclerosis) as well as in bone (osteosarcoma) by radium, especially with large doses. Three case reports of radium intoxication in Britons are noted as compatible with this suggestion, after revised interpretation in two of them.
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PMID:Malignancy from radium. 527 Dec 69

The FBR murine osteosarcoma virus complex induces bone tumors with a similar latency and pathology to those induced by the FBJ virus complex. FBR murine sarcoma virus ( FBR -MSV) has been isolated from its helper virus(es) by the establishment of transformed nonproducer cells. These cells were found to express a 75,000-Da protein (P75) which was antigenically related to the p55 oncogene product of the FBJ murine osteosarcoma virus ( FBJ -MSV). P75 also contained antigenic determinants of murine leukemia virus (MLV) gag gene p15, p12, and p30 proteins, and is therefore a gag- fos fusion protein ( P75gag - fos ). P75gag - fos is a phosphoprotein and is found primarily in the nucleus. Only a single species of RNA, of 3.3 kb, was identified in FBR -MSV-transformed nonproducer cells using both fos and MLV probes, which suggested that P75gag - fos was expressed from genome-sized RNA. Chromosomal DNA from one nonproducer cell line was found to contain a single EcoRI restriction fragment of 12 kb pairs (kbp) which encompassed the FBR -MSV provirus. This DNA fragment was molecularly cloned into bacteriophage Charon 30 (lambda FBR -1), and a 7.5-kbp HindIII restriction fragment containing the entire provirus was subsequently subcloned into pBR322 ( pFBR -1). DNA from pFBR -1 was capable of inducing morphological transformation of mouse and rat fibroblasts in tissue culture. In addition, transfected cells expressed the FBR -MSV P75gag - fos protein.
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PMID:FBR murine osteosarcoma virus. I. Molecular analysis and characterization of a 75,000-Da gag-fos fusion product. 620 14

Studies were completed to establish the comparative cytotoxicity of 5'-deoxy-5-fluorouridine (5'-dFUrd) and other fluoropyrimidines in human bone marrow stem cells and several cultured human tumor cell lines (i.e., 47-DN and MCF-7 breast carcinomas, MG-63 osteosarcoma, HCT-8 colon tumor, Colo-357 pancreatic tumor, and HL-60 promyelocytic leukemia). In vitro clonogenic assays were used to measure cytotoxicity following a 3-hr drug exposure. 5'-dFUrd was less potent than was 5-fluorouracil or 5-fluoro-2'-deoxyuridine in all cells examined, exhibiting its best activity against the 47-DN [concentration that prevented 50% clonal growth compared to untreated control (LD50) = 32 microM] and MCF-7 (LD50 = 35 microM) breast carcinomas and MG-63 osteosarcoma (LD50 = 41 microM). Intermediate activity was observed against HCT-8 (LD50 = 200 microM) and Colo-357 (LD50 = 150 microM) gastrointestinal tumors. 5'-dFUrd had very poor activity against the HL-60 leukemia (LD50 = 470 microM). The suppression of the clonal growth of human bone marrow stem cells required the greatest amount of 5'-dFUrd (LD50 = 580 microM). With use of these studies, a therapeutic ratio (concentration that prevented 25% clonal growth compared to untreated control of bone marrow divided by LD50 of tumor) was calculated for each drug in each tumor. 5'-dFUrd had values ranging from 1.2 to 7.5 for the solid tumors and 0.5 in HL-60 cells. This was in marked contrast to 5-fluorouracil, or 5-fluoro-2'-deoxyuridine, which failed in all cases to have ratios greater than or equal to one. The results indicate that 5'-dFUrd can exhibit a cytotoxic selectivity for human tumor cells compared to human bone marrow stem cells that does not exist for 5-fluorouracil or 5-fluoro-2'-deoxyuridine. This suggests that 5'-dFUrd may be of greater therapeutic benefit in the treatment of certain human cancers than the fluoropyrimidines used currently.
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PMID:5'-Deoxy-5-fluorouridine selective toxicity for human tumor cells compared to human bone marrow. 622 92


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