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[Activity and induction of CYP2B, CYP2C, and CYP3A in tissues of cyclophosphane-sensitive and resistant neoplasms and the liver of neoplasm-carrying mice]

https://arctichealth.org/en/permalink/ahliterature18154
Source
Biomed Khim. 2003 Jan-Feb;49(1):27-34
Publication Type
Article
Author
A Iu Grishanov
V I Kaledin
T V Zueva
E K Nekhoroshkova
V P Nikolin
V V Liakhovich
Author Affiliation
Institute of Molecular Biology and Biophysics, Siberian Branch of Russian Academy of Medical Sciences, Timakova str., 2, Novosibirsk, 630117, Russia. agrish@cyber.ma.nsc.ru
Source
Biomed Khim. 2003 Jan-Feb;49(1):27-34
Language
Russian
Publication Type
Article
Keywords
Animals
Antineoplastic Agents - pharmacology - therapeutic use
Aryl Hydrocarbon Hydroxylases - biosynthesis - metabolism
Cyclophosphamide - pharmacology - therapeutic use
Cytochrome P-450 CYP2B1 - biosynthesis - metabolism
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System - biosynthesis - metabolism
Drug Resistance, Neoplasm
English Abstract
Enzyme Induction
Liver Neoplasms - drug therapy - enzymology
Lymphoma, Diffuse - drug therapy - enzymology
Male
Mice
Mice, Inbred CBA
Microsomes - enzymology
Neoplasm Transplantation
Oxidoreductases, N-Demethylating - biosynthesis - metabolism
Abstract
The activities of three cytochrome P450 families involved in metabolic transformation of cyclophosphamide (CP) (CYP2B and CYP2C responsible for metabolic activation of CP and CYP3A responsible for inactivation of CP) have been investigated in lymphosarcoma and liver microsomes of tumor-bearing CBA mice. Two strains of mouse lymphosarcoma distinguished by their sensitivity to cytostatic action of CP were used in this study for implantation in mice femur muscle. There was certain relationship between CP resistance of lymphosarcoma and tumor P450s activity. CYP2B, CYP2C and CYP3A activities in the CP sensitive tumor were comparable to those in liver, and CYP2B, CYP2C were induced by phenobarbital and dexamethasone. CYP2B and CYP2C in the CP resistant tumor were inactive and only slightly induced by dexamethasone. CYP3A activity was lower than in LS tumor and unchanged during drug treatment. Implantation of LS and RLS tumor in mice caused different effects on P450 activities. LS insignificantly influenced liver CYP2B, CYP2C and CYP3A activities and their inducibility by phenobarbital and dexamethasone was similar to that obtained in liver of mice without tumor. At the same time, CYP2B and CYP2C activity in liver of RLS-bearing mice were essentially reduced, the activity CYP3A remained unchanged, and inducibility of CYP2B, CYP2C and CYP3A by phenobarbital and dexamethasone was similar to that in liver of mice without tumor. These results prove the role of cytochromes P450 activating CP in formation drug resistant phenotype of mice lymphosarcoma and suggest possibility of overcoming of this resistance using cytochrome P450 inducers.
PubMed ID
14569871 View in PubMed
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Adrenergic regulation of erythropoiesis during cytostatic-induced myelosuppressions.

https://arctichealth.org/en/permalink/ahliterature88844
Source
Bull Exp Biol Med. 2008 Oct;146(4):405-10
Publication Type
Article
Date
Oct-2008
Author
Skurikhin E G
Pershina O V
Minakova M Yu
Ermakova N N
Firsova T V
Dygai A M
Gol'dberg E D
Author Affiliation
Institute of Pharmacology, Tomsk Research Center, Siberian Division of the Russian Academy of Medical Sciences, Tomsk, Russia.
Source
Bull Exp Biol Med. 2008 Oct;146(4):405-10
Date
Oct-2008
Language
English
Publication Type
Article
Keywords
Animals
Bone Marrow - drug effects - metabolism
Cell Differentiation - drug effects
Cell Proliferation - drug effects
Central Nervous System - drug effects - physiology
Cyclophosphamide - pharmacology
Cytostatic Agents - pharmacology
Erythroid Precursor Cells - cytology - drug effects
Erythropoiesis - drug effects
Erythropoietin - metabolism
Female
Fluorouracil - pharmacology
Hematopoiesis - drug effects - physiology
Mice
Mice, Inbred CBA
Norepinephrine - pharmacology
S Phase
Abstract
The role of central adrenergic structures in the regulation of the erythroid hematopoietic stem was studied during administration of cyclophosphamide and 5-fluorouracil. The central nervous system contributed to suppression of erythropoiesis during cytostatic treatment. The suppressive effect of brain adrenergic structures on the erythron after treatment with cyclophosphamide and 5-fluorouracil was related to dysfunction of adherent cells in the hemopoiesis-inducing microenvironment (formation of hemopoietic islets and secretion of erythropoietic activity) and production of growth factors by myelokaryocytes, respectively. Brain norepinephrine had an inhibitory effect on proliferative activity and differentiation of erythroid precursors that were associated with the erythropoietin and peripheral alpha-adrenergic structures. However, stimulation of beta-adrenergic structures was followed by an increase in the rate of erythroid cell maturation.
PubMed ID
19489307 View in PubMed
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Adverse effects of tumour necrosis factor in cyclophosphamide-treated mice subjected to gut-derived Pseudomonas aeruginosa sepsis.

https://arctichealth.org/en/permalink/ahliterature207458
Source
Cytokine. 1997 Oct;9(10):763-9
Publication Type
Article
Date
Oct-1997
Author
T. Matsumoto
K. Tateda
S. Miyazaki
N. Furuya
A. Ohno
Y. Ishii
Y. Hirakata
K. Yamaguchi
Author Affiliation
Department of Microbiology, Toho University School of Medicine, Omori-Nishi, Ota-ku, Tokyo, Japan.
Source
Cytokine. 1997 Oct;9(10):763-9
Date
Oct-1997
Language
English
Publication Type
Article
Keywords
Animals
Antibodies, Monoclonal - administration & dosage
Bacteremia - blood - etiology - microbiology - mortality
Colony Count, Microbial
Cyclophosphamide - pharmacology
Humans
Immunosuppressive Agents - pharmacology
Intestines - microbiology
Mice
Pseudomonas Infections - blood - etiology - microbiology - mortality
Recombinant Proteins - adverse effects
Tumor Necrosis Factor-alpha - adverse effects - physiology
Abstract
To evaluate the role of tumour necrosis factor (TNF) in gut-derived sepsis, mice were given Pseudomomas aeruginosa strain D4 by bacterial suspension in their drinking water during which time ampicillin (200 mg/kg) was given to disrupt the normal indigenous bacterial flora. Cyclophosphamide was additionally administered to induce bacterial translocation of the P. aeruginosa that had colonized the gastrointestinal tract, and thereby to cause gut-derived sepsis. In this model, TNF-alpha was detected in serum from the next day after the second cyclophosphamide administration, increasing to level of 3 ng/ml in lethal conditions. Average serum TNF-alpha level was significantly higher in mice with bacteraemia than in those without bacteraemia. Treatment with 0.8 microg/kg of recombinant human TNF-alpha (rhTNF-alpha) did not affect the mortality, whereas administration of either 4 and 20 microg/kg of rhTNF-alpha significantly increased the mortality rate in comparison with saline-treated mice. Bacterial counts in liver and blood were significantly higher in 20 microg/kg of rhTNF-alpha treated mice than in saline-treated mice. Treatment with murine anti-TNF-alpha monoclonal antibody significantly reduced the mortality from septic infection. We conclude that TNF-alpha may facilitate bacterial translocation and causes deterioration of gut-derived sepsis due to P. aeruginosa in mice.
PubMed ID
9344509 View in PubMed
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Behaviorally conditioned suppression of a graft-versus-host response.

https://arctichealth.org/en/permalink/ahliterature57901
Source
Proc Natl Acad Sci U S A. 1982 Jan;79(2):583-5
Publication Type
Article
Date
Jan-1982
Author
D. Bovbjerg
R. Ader
N. Cohen
Source
Proc Natl Acad Sci U S A. 1982 Jan;79(2):583-5
Date
Jan-1982
Language
English
Publication Type
Article
Keywords
Animals
Behavior, Animal - physiology
Brain - physiology
Conditioning (Psychology) - physiology
Cyclophosphamide - pharmacology
Female
Graft vs Host Reaction - drug effects
Rats
Research Support, U.S. Gov't, P.H.S.
Abstract
Cyclophosphamide (CY), previously used to condition suppression of humoral immune responses, was used to condition suppression of a graft-versus-host response (GvHR). Female (Lewis x Brown Norway) F1 rats were conditioned by pairing consumption of a saccharin solution with an intraperitoneal injection of CY at 50 mg/kg of body weight 48 days before immunization. On day 0, all animals were injected with a suspension of splenic leukocytes (2 x 10(7) cells per footpad) obtained from female Lewis donors. The regional GvHR was assessed on day 5 by weighing popliteal nodes. Conditioned animals given a single low-dose injection of CY and reexposed to conditioned stimuli had lymph node weights significantly lower than control groups and did not differ from animals given three injections of CY during the ongoing GvHR. The results suggest that conditioned immunosuppression, previously demonstrated in thymus-dependent and thymus-independent humoral immune responses, also affects the popliteal GvHR, a cellular immune response.
PubMed ID
6952209 View in PubMed
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Chitotriosidase as a new marker of macrophage stimulation in a tumor model treated with cyclophosphamide and Ukrain.

https://arctichealth.org/en/permalink/ahliterature19811
Source
Drugs Exp Clin Res. 2000;26(5-6):279-83
Publication Type
Article
Date
2000
Author
T A Korolenko
S J Djanayeva
O V Falameyeva
R A Wevers
E E Filjushina
I I Buzueva
V I Kaledin
J. Sandula
J. Nowicky
Author Affiliation
Institute of Physiology, Siberian Branch, Russian Academy of Medical Sciences, Novosibirsk, Russia.
Source
Drugs Exp Clin Res. 2000;26(5-6):279-83
Date
2000
Language
English
Publication Type
Article
Keywords
Alkaloids - pharmacology
Animals
Antineoplastic Agents, Alkylating - pharmacology
Antineoplastic Agents, Phytogenic - pharmacology
Cyclophosphamide - pharmacology
Hexosaminidases - blood - metabolism
Liver - pathology
Lymphoma, Diffuse - drug therapy - enzymology
Macrophages - drug effects - enzymology
Male
Mice
Mice, Inbred CBA
Neoplasms, Experimental - drug therapy - enzymology
Tumor Markers, Biological
Abstract
Ukrain has previously been demonstrated to exert a malignotoxic effect in vivo. This antitumor drug has been effective in the treatment of some malignancies in experimental animals as a result of immunostimulation (macrophage stimulation). In the present study, serum chitotriosidase activity was measured as a biochemical marker of macrophage stimulation in several murine and rat models of macrophage stimulation. It was shown that zymosan, carboxymethylated glucan and Triton WR 1339 administration to CBA mice or Wistar rats was followed by a considerable increase in serum chitotriosidase activity. Murine LS lymphosarcoma development decreased serum chitotriosidase activity. Antitumor treatment by Ukrain or cyclophosphamide did not restore this index to the normal value.
PubMed ID
11345039 View in PubMed
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Comparative cytogenetic analysis between cyclophosphamide-sensitive and -resistant lines of acute myeloid leukemia in the Lewis Brown Norway hybrid rat.

https://arctichealth.org/en/permalink/ahliterature25086
Source
Genes Chromosomes Cancer. 1990 Nov;2(4):290-5
Publication Type
Article
Date
Nov-1990
Author
W. Kearns
T. Koelling
A. Yeager
Author Affiliation
Kennedy Institute, Baltimore, MD 21205.
Source
Genes Chromosomes Cancer. 1990 Nov;2(4):290-5
Date
Nov-1990
Language
English
Publication Type
Article
Keywords
Acute Disease
Animals
Chromosome Banding
Cyclophosphamide - pharmacology
Drug Resistance - genetics
Female
Karyotyping
Leukemia, Myeloid - drug therapy - genetics
Rats
Rats, Inbred Lew
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Tumor Cells, Cultured
Abstract
An animal model of acute myeloid leukemia (AML) has been developed in the Brown Norway (BN) rat and has successfully been introduced into the Lewis x BN F1 hybrid (LBN) and designated LBN AML. The original LBN AML is sensitive to the chemotherapeutic agent cyclophosphamide (CY). Recently, a CY-resistant cell line of LBN AML has been established. To characterize this animal model of human leukemia better, we analyzed and compared the chromosomal makeup of both the CY-sensitive and CY-resistant LBN AML lines. The CY-sensitive LBN AML cultures contained two cell lines--line I (88%): 41,XX,-1,-2,-9,del(12)(q16), + der(1)t(1;?8)(p13;q31), + der(2)t(2;9)(p11;q11); and line II (12%): 41,XX,-1,-2,-9,del(12),del(20)(q13) + der(1)t(1;?8)(p13;q31), + der(2)t(2;9)(p11;q11). The recently developed CY-resistant AML cells contained two cell lines--line I (88%): 41,XX,-1,-2,-9,del(3)(q36q42.1),del(4) (q42.2),?t(5;?)(q35;?),?t(8;?)(q24;?),del(12)(q16), + der(1)t(1;?8)(p13;q31), + der(2)t(2;9)(p11;q11); and line II (12%): 42,XX (probably represents host contamination). The new chromosomal aberrations in the CY-resistant line I [del(3)(q36q42.1),del(4)(q42.2),?t(5;?)(q35;?), and ?t(8;?)(q24;?)] suggest a possible interrelationship between these secondary karyotypic abnormalities and acquisition of resistance to the chemotherapeutic agent.
PubMed ID
2268578 View in PubMed
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Compensatory reactions during impairment of granulocytic stem in patients with lung cancer receiving antitumor chemotherapy.

https://arctichealth.org/en/permalink/ahliterature19531
Source
Bull Exp Biol Med. 2001 Jun;131(6):564-7
Publication Type
Article
Date
Jun-2001
Author
V E Gol'dberg
V V Zhdanov
M G Matyash
E I Simolina
T Y Khrichkova
V V Vysotskaya
N O Popova
D A Boldyshev
Author Affiliation
Institute of Pharmacology, Tomsk Research Center, Siberian Division of the Russian Academy of Medical Sciences.
Source
Bull Exp Biol Med. 2001 Jun;131(6):564-7
Date
Jun-2001
Language
English
Publication Type
Article
Keywords
Antineoplastic Combined Chemotherapy Protocols - pharmacology - therapeutic use
Carboplatin - pharmacology - therapeutic use
Comparative Study
Cyclophosphamide - pharmacology - therapeutic use
Doxorubicin - pharmacology - therapeutic use
Granulocytes - drug effects - pathology
Humans
Leukopoiesis - drug effects
Lung Neoplasms - drug therapy - physiopathology
Methotrexate - pharmacology - therapeutic use
Vincristine - pharmacology - therapeutic use
Abstract
We compared changes in the granulocytic hemopoietic stem in patients with stage III-IV lung cancer receiving cytostatic therapy by the original CVC and standard CAM schemes. In patients treated with the CVC regimen, the granulocytic hemopoietic stem possessed more potent compensatory capacities.
PubMed ID
11586408 View in PubMed
Less detail

[Cyclophosphamide-induced apoptosis of murine lymphosarcoma cells in vivo]

https://arctichealth.org/en/permalink/ahliterature20005
Source
Vopr Onkol. 2000;46(5):588-93
Publication Type
Article
Date
2000
Author
V I Kaledin
V P Nikolin
T A Ageeva
O A Timofeeva
M L Filipenko
G M Ronichevskaia
T S Morozkova
N A Popova
T Iu Baimak
Author Affiliation
Institute of Cytology and Genetics, Russian Academy of Sciences, Siberian Branch.
Source
Vopr Onkol. 2000;46(5):588-93
Date
2000
Language
Russian
Publication Type
Article
Keywords
Animals
Antineoplastic Agents, Alkylating - pharmacology
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Apoptosis - drug effects - genetics
Cyclophosphamide - pharmacology
DNA, Neoplasm - drug effects
Dose-Response Relationship, Drug
English Abstract
Lymphoma, Diffuse - chemically induced - drug therapy - pathology
Male
Methylnitrosourea
Mice
Mice, Inbred CBA
Time Factors
Abstract
The antitumor action of combination chemotherapy (cyclophosphamide + adriamycin + vincristin + prednisolone) for transplantable nitrosomethylurea-induced lymphosarcoma was studied in male CBA mice. Single injections of the mixture were followed by complete regression of tumors of up to 2 cm in diameter. The effect was shown to be caused by cyclophosphamide (CP) alone, by inducing apoptosis. The other components failed to potentiate the CD effect. Being useless, they are likely to cause harm by contributing to the overall toxic effect of therapy. The nature and duration of CP-induced remission appeared dose-dependent: on day 50 of the administration of 50, 100 and 150 mg/kg body, tumors were detected in 100, 55 and 0% of the animals, respectively. Such means of apoptosis induction as glycocorticoid treatment and ionizing radiation did not cause complete regression.
PubMed ID
11202193 View in PubMed
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Cystatin C in LS lymphosarcoma and HA-1 hepatoma treated with Ukrain and cyclophosphamide and involvement of apoptosis.

https://arctichealth.org/en/permalink/ahliterature19810
Source
Drugs Exp Clin Res. 2000;26(5-6):285-92
Publication Type
Article
Date
2000
Author
T A Korolenko
O N Poteryaeva
S J Djanayeva
I G Svechnikova
V I Kaledin
O A Timofeyeva
M L Filipenko
J. Nowicky
Author Affiliation
Institute of Physiology, Siberian Branch, Russian Academy of Medical Sciences, Novosibirsk, Russia.
Source
Drugs Exp Clin Res. 2000;26(5-6):285-92
Date
2000
Language
English
Publication Type
Article
Keywords
Alkaloids - pharmacology
Animals
Antineoplastic Agents, Alkylating - pharmacology
Antineoplastic Agents, Phytogenic - pharmacology
Apoptosis - drug effects
Cyclophosphamide - pharmacology
Cystatins - metabolism
Enzyme-Linked Immunosorbent Assay
Liver - pathology
Liver Neoplasms, Experimental - metabolism - pathology
Lymphoma, Diffuse - metabolism - pathology
Male
Mice
Mice, Inbred CBA
Tumor Markers, Biological
Abstract
The concentration of cystatin C, a cysteine proteinase inhibitor, was measured during the treatment of murine LS lymphosarcoma with cyclophosphamide and HA-1 murine hepatoma with the antitumor drug Ukrain. It was shown that concentrations of cystatin C were very low in both the tumor tissues studied (HA-1 hepatoma cells and LS lymphosarcoma); increased cystatin C concentrations were found only in Ukrain-treated murine hepatoma, suggesting the mechanism of antitumor effect of this drug. Cyclophosphamide treatment in LS lymphosarcoma did not influence the concentration of cystatin C in tumor cells. At the same time, a marked increase in cathepsin B and cathepsin L activity in LS lymphosarcoma was found, indicating the involvement of apoptosis in the mechanism of antitumor action of cyclophosphamide. While the DNA from untreated LS lymphosarcoma was very homogenous and its molecular weight was high, the DNA from tumors of treated mice broke down, giving rise to the ladder figure characteristically produced by cells dying from apoptosis. Evidence was obtained that cyclophosphamide-induced tumor regression was effected by apoptosis.
PubMed ID
11345040 View in PubMed
Less detail

Development and characterization of a cyclophosphamide-resistant subline of acute myeloid leukemia in the Lewis x Brown Norway hybrid rat.

https://arctichealth.org/en/permalink/ahliterature25115
Source
Blood. 1990 Sep 15;76(6):1209-13
Publication Type
Article
Date
Sep-15-1990
Author
T M Koelling
A M Yeager
J. Hilton
D T Haynie
J M Wiley
Author Affiliation
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD.
Source
Blood. 1990 Sep 15;76(6):1209-13
Date
Sep-15-1990
Language
English
Publication Type
Article
Keywords
Aldehyde Dehydrogenase - metabolism
Animals
Bone Marrow Transplantation
Crosses, Genetic
Cyclophosphamide - pharmacology
Drug Resistance - genetics
Female
Hybrid Cells - drug effects - enzymology - physiology
Leukemia, Myelocytic, Acute - enzymology - genetics - pathology
Phosphoramide Mustards - pharmacology
Rats - genetics
Rats, Inbred Lew - genetics
Rats, Inbred Strains - genetics
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Tumor Cells, Cultured - drug effects - enzymology - pathology
Abstract
Preclinical studies of resistance to alkylating agents in the Lewis x Brown Norway hybrid (LBN) rat model of acute myeloid leukemia (AML) have hitherto been limited by the sensitivity of LBN AML cells to cyclophosphamide (CY). We developed a CY-resistant subline of LBN AML by serial intravenous (IV) passage of AML cells followed by in vivo exposure to CY (100 mg/kg) 14 days later. After 18 and subsequent passages, CY-treated AML cells remained viable despite ex vivo incubation with 70 to 100 mumol/L 4-hydroperoxycyclophosphamide (4HC) or in vivo exposure to 100 to 300 mg/kg of CY. Once established, resistance to incubation with 4HC was stable in LBN AML cells after at least six serial in vivo passages without exposure to CY. Nevertheless, both control and CY-treated AML cells demonstrated similar dose-dependent sensitivity to 100 to 500 mumol/L phosphoramide mustard (PhM), the active alkylating end-product of CY activation in vivo. Levels of aldehyde dehydrogenase (ALDH), which inactivates CY by prevention of formation of PhM, were significantly elevated in these CY-resistant AML cells: cytosolic and particulate ALDH fractions from these cells were 11 to 13 times control with NAD cofactor and propanal substrate and three to four times control with NADP cofactor and benzaldehyde substrate. Further studies with this animal model of AML, in which resistance to CY is mediated by elevated ALDH activity, may elucidate mechanisms for effective elimination of drug-resistant leukemic cells ex vivo and in vivo.
PubMed ID
2400809 View in PubMed
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15 records – page 1 of 2.