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)

A cyclophosphamide resistant subline (BNML/CPR) was developed in vivo in the BN rat acute myelocytic leukaemia (BNML) model. Full resistance was achieved after in vivo exposure of leukaemic animals to cyclophosphamide with, in total, 15 intraperitoneal injections of 100 mg/kg. The CPR line was cross-resistant to ifosfamide, but less so to mafosfamide. Continuous transplantation of the BNML/CPR line without a cyclophosphamide selection pressure resulted in the emergence of a subline (BNML/CPR greater than S) whose sensitivity to cyclophosphamide was similar to that of the parent BNML/S line. Both in the BNML parent line and in the BNML/CPR greater than S line, a 2p+ marker chromosome was present, whereas a 2p+q+ marker chromosome was characteristic for the BNML/CPR line. The mechanism of cyclophosphamide resistance can now be investigated in the BNML model at the DNA, at the mRNA and at the protein level.
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PMID:Development and characterisation of a cyclophosphamide resistant variant of the BNML rat model for acute myelocytic leukaemia. 182 81

The development of drug resistance is an important factor contributing to failure of chemotherapy in cancer patients. Cyclophosphamide (CP) is a cytostatic drug widely used in the treatment of haematological malignancies and solid tumours. Because CP requires bioactivation to become cytotoxic, an in vivo approach was chosen to generate a subline of the Brown Norway rat acute myelocytic leukaemia (BNML/CPR) highly resistant to CP to serve as a model to investigate the molecular mechanism(s) of cyclophosphamide resistance. The role of the CP-detoxifying enzyme aldehyde dehydrogenase (ALDH) in the molecular mechanism of CP resistance in this subline of the BNML has been investigated. Compared to the parent BNML cell line, the BNML/CPR cell line displayed an approximately 6-fold higher level of ALDH enzyme activity. Pretreatment of leukaemic rats with the ALDH inhibitor disulfiram resulted in a restoration of CP sensitivity of animals carrying the BNML/CPR cells. Furthermore, in vitro incubation of BNML/CPR cells with disulfiram prior to incubation with the activated CP derivative mafosfamide resulted in an extra 2-3 log cell kill as indicated by the survival time of rats which were injected with disulfiram pretreated BNML/CPR cells compared to non-pretreated BNML/CPR cells. Data on the glutathione S-transferases (GSTs) isozyme profiles of cytoplasmic liver and spleen extracts of BNML- and BNML/CPR-carrying leukaemic rats indicated that the total GST enzyme amount was lower in BNML/CPR cells than in parent BNML cells. Furthermore, the BNML/CPR subline proved to be sensitive to phosphoramide mustard, both in vivo and in vitro.
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PMID:Aldehyde dehydrogenase involvement in a variant of the brown Norway rat acute myelocytic leukaemia (BNML) that acquired cyclophosphamide resistance in vivo. 785 14

Regarding problems in emergency and urgent immunoserologic tests, I mainly focused on infectious diseases and CPR and discussed the correspondence of dangerous needle stick injuries, and the significance of emergency CRP measurement in various body fluids using highly sensitive determination methods. The actual conditions and correspondence of infections due to dangerous needle stick injuries (accidental pricking with used needles) such as hepatitis, syphilis, acquired immunodeficiency syndrome (AIDS), adult T-cell leukemia (ATL), herpes simplex, falciparum malaria, tuberculosis, Rocky mountain spotted fever, and human colonic adenocarcinoma are discussed. With regard to emergency CRP measurement, application of highly sensitive determination methods and the significance of CRP measurement of various body fluids (healthy adult blood, cord blood, cerebrospinal fluid, urine and puncture fluid) are described. The reference values for CRP concentrations in various body fluids were established at 15 to 3,063 ng/ml for serum (male; 26 to 3.992 ng/ml, female; 11 to 1,672 ng/ml), 9 to 73 ng/ml for cord blood, 2 to 10 ng/ml for cerebrospinal fluid and less than 2 ng/ml for urine.
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PMID:[Future prospects of emergency laboratory tests--problems of immunoserologic tests]. 893 87