SEARCH · PubMed Health

Results for “CYCLOPHOSPHAMIDE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,099 records · Page 61Linked to original sources

PubMed1986

[Combination of etoposide with cisplatin or cyclophosphamide in the treatment of mouse Lewis lung carcinoma].

The effect of sequential combination of etoposide with cisplatin or cyclophosphamide on mouse Lewis lung carcinoma was investigated. Tumor cells were inoculated i.v. on day 0. Drugs were administered i.p. In combined treatment etoposide was consecutively administered once daily for 5 days on days 1 to 5 and 2 to 6 when cisplatin or cyclophosphamide were administered singly on days 6 and 1, respectively. In the combination of etoposide with cisplatin a highly synergistic effect was observed irrespective of the day of cisplatin administration. In the other combination with cyclophosphamide, a synergistic effect was similarly observed but the degree was much higher when cyclophosphamide was administered prior to etoposide administration.

Animals↗

PubMed1986

Pharmacokinetic interactions of cyclophosphamide and 5-fluorouracil with methotrexate in an animal model.

In tumor-bearing WAG/Rij rats the interaction of cyclophosphamide and/or 5-fluorouracil (5-FU) with methotrexate as manifested at the pharmacokinetic level was studied. Four groups were formed of at least ten animals. The control group, which received single-agent methotrexate, was compared with groups that received methotrexate plus cyclophosphamide, methotrexate plus 5-FU, and methotrexate plus cyclophosphamide plus 5-FU. There appeared to be an increase of 40% in the clearance of methotrexate by the triple combination. Cyclophosphamide especially diminished the terminal part of the concentration-time curve of methotrexate.

Animals↗

PubMed1986

Immunotoxic effects of T-2 toxin on cell-mediated immunity to listeriosis in mice: comparison with cyclophosphamide.

Immunotoxic effects of T-2 toxin and cyclophosphamide on cell-mediated resistance were evaluated in mice exposed to Listeria monocytogenes infection. Mice were inoculated intraperitoneally with 4.0 X 10(5) (LD50) or 4.0 X 10(4) (nonlethal) L monocytogenes and were treated with 4.0 mg of T-2 toxin/kg of body weight or 180 mg of cyclophosphamide/kg. The immunosuppressive effect of the toxin and cyclophosphamide was indicated by the rapid growth of Listeria and significant (P less than 0.005) increases in mortality because of listeriosis. Necrosis and depletion of lymphoid tissue, lymphopenia, and significant (P less than 0.005) decreases in the influx and number of lymphocytes and macrophages occurred in Listeria-elicited peritoneal exudates and at sites of infection in the liver and spleen of the toxin- and cyclophosphamide-treated mice. Immunotoxic effects of T-2 toxin and cyclophosphamide were comparable and attributed primarily to the depletion of T lymphocytes and the subsequent failure of surviving immunologically committed T cells and T-cell dependent immune-activated macrophages to clear the host of bacteria.

Animals↗

PubMed1985

Randomized trial of doxorubicin versus cyclophosphamide in diffuse malignant pleural mesothelioma.

The effect of doxorubicin and cyclophosphamide in the treatment of diffuse, malignant pleural mesothelioma was evaluated in a randomized study. All patients were treated on an outpatient basis and none had previously received antineoplastic treatment. All patients had a measurable lesion other than pleural effusion. The treatment consisted of doxorubicin at a dose of 60 mg/m2 every 3 weeks, to a total dose of 550 mg/m2, or cyclophosphamide at a dose of 1500 mg/m2 every 3 weeks for 1 year. At disease progression the treatment was changed to the alternate drug. The dose was increased or decreased according to hematologic effects. Thirty of 32 patients were evaluable for response. Remissions were not achieved in any patient. During treatment with doxorubicin, none of the patients developed cardiotoxicity, while one patient developed hemorrhagic cystitis during treatment with cyclophosphamide. Sepsis or bleeding was not observed in either of the treatment arms. Thus, the trial showed no antineoplastic activity of either doxorubicin or cyclophosphamide in the treatment of malignant pleural mesothelioma.

Aged↗

PubMedDate not supplied

[Dependence of the embryotoxic action of dioxidine and cyclophosphamide on the immunoreactivity of the maternal-fetal system in mice].

It has been shown that the embryotoxic action of cyclophosphamide and dioxydin (an antibacterial drug) was more pronounced upon syngeneic than upon reciprocal crossing of CBA and C57BL/6 mice. Preliminary (21 days before crossing intrauterine sensitization of C57BL/6 mice with syngeneic or allogeneic lymphocytes obtained from males' spleen led to the attenuation of the embryotoxic action of cyclophosphamide and dioxydin. During sensitization with allogeneic lymphocytes, the embryotoxic action was attenuated more appreciably. Extirpation of the paraaortal lymph nodes in female C57BL/6 mice performed 14-15 days before crossing potentiated the embryotoxic action of cyclophosphamide in the case of allogeneic crossing of females. Upon syngeneic crossing of females with the extirpated paraaortal lymph nodes the intensity of the embryotoxic action of cyclophosphamide remained unchanged. It is concluded that the immune status of the mother-embryo system can, under the definite conditions, determine the intensity of the embryotoxic action of xenobiotics on the mammals.

Animals↗

PubMed1972

Effects of viral infection on nervous system development. II. Attempts to modify bluetongue-virus-induced malformations with cyclophosphamide and antithymocyte serum.

Treatment with cyclophosphamide and antithymocyte serum (ATS) did not significantly increase the susceptibility of mice to bluetongue virus infections of the nervous system. Cyclophosphamide actually inhibited virus growth in newborn and 2-week-old mice and, in newborn mice, diminished the severity of virus-induced pathologic sequelae. Autoradiographic studies suggested this inhibition resulted from the effect of cyclophosphamide on the immature cells of the subventricular zone which were the cell population selectively infected by bluetongue virus. In newborn mice ATS inhibited the inflammatory reaction and development of antibody, but did not result in alterations in mortality, initial virus growth and localization or early necrosis of cells in the subventricular zone. Antithymocyte serum only caused longer persistence of virus and slight extension of late pathologic lesions. The failure of cyclophosphamide and ATS treatment to induce more extensive lesions in older mice show that the age-dependency of bluetongue lesions is not determined by the immaturity of immune responses.

Age Factors↗

PubMed1979

Regulation of secondary antibody responses in rodents. I. Potentiation of IgG production by cyclophosphamide.

This paper describes the effects of a single dose of cyclophosphamide on specific IgG production in rats during an established secondary immune response. (PVG X Agus)F1 rats were immunized twice (days 0 and 28) with chicken erythrocytes (CRBC), received cyclophosphamide (100 mg/m2 of body surface area) on day 33 and were killed 8 days later. The production of anti-CRBC IgG antibodies was assessed by testing the supernatants of spleen cell cultures in a cytotoxicity assay with 51Cr-labelled CRBC as target cells and normal rat spleen cells as effector cells. In observations of fifty-nine pairs of treated and untreated rats from eight separate experiments, the administration of cyclophosphamide resulted in: (1) a decrease in the number of spleen cell to a median of 10(8.63) from a median of 10(8.7) (P less than 0.0025); (2) an increase in the anti-CRBC IgG antibody titre of the supernatants of cultured spleen cells to a median of 10(0.67) from a median of 10(0.27 (P less than 0.0025); and (3) the calculated anti-CRBC. IgG antibody production per spleen to be increased in the drug-treated rats to a median of 10(2.26) from a median of 10(2.0) (P less than 0.005). In a cyclophosphamide dose-response study, it was shown that some enhancement of antibody production was induced by doses between 12.5 and 50 mg/m2 and consistently elevated levels of antibody production were associated with doses between 100 and 400 mg/m2.

Animals↗

PubMed1979

Histopathological changes induced in the urinary bladder and liver of female BALB/c mice treated simultaneously with 2-naph-thylamine and cyclophosphamide.

The effect of 2-naphthylamine and cyclophosphamide on the urinary bladder and liver of female BALB/c mice was investigated. The bladder mucosa of mice treated with 2-naphthylamine alone for 40 weeks showed diffuse hyperplasia. Oral administration of 2-naphthylamine for 40 weeks plus injections of cyclophosphamide produced bladder carcinomas in 30.8 approximately 35.7% of all animals, associated with downward growth of the bladder epithelium. All the bladder carcinomas were of the transitional cell type and most of them contained pseudoglandular areas. Hepatomas seemed to develop in higher incidence in mice treated with 2-naphthylamine plus cyclophosphamide than in mice treated with 2-naphthylamine alone. Most of the hepatomas were solitary and showed a trabecular pattern. Cyclophosphamide seemed to have a summative or promoting effect on carcinogenesis of the bladder mucosa and liver induced by 2-naphthylamine in female BALB/c mice.

2-Naphthylamine↗

PubMed1979

Teratogenic effect of cyclophosphamide and the preventive effects of pyrithinoldehydrochloride monohydrate.

Teratogenic effects were induced in outbred Swiss mice by treatment of 8-week-old pregnant females with one of five different doses (5, 10, 20, 30, 40 mg/kg b.w.) of cyclophosphamide. Because the 11.5th day of pregnancy was the most effective day to induce malformations in mice, animals treated on this day were used for prophylactic studies. A preliminary study had shown that 30 mg/kg b.w. cyclophosphamide was the ideal dose to produce 100% malformations on the 11.5th day of pregnancy. From day 7.5 to 9.5 all fetuses were resorbed with this dosage. Most malformations were induced with 20, 30 or 40 mg/kg b.w., whereas 5 and 10 mg/kg b.w. caused no alterations of the fetuses. The frequency distributions of the various induced malformations and combined malformations of a positive control group (30 mg/kg b.w. of cyclophosphamide on the 11.5th day of pregnancy) were compared to those found in groups receiving different doses of the prophylactic. This substance reduced significantly the rate of malformations; 1/160 LD50 pyrithinoldehydrochloride monohydrate administered 4 times prior to cyclophosphamide treatment was the most effective. However, a complete prevention of teratogenic effects could not be accomplished.

Abnormalities, Drug-Induced↗

PubMed1977

Effects of cyclophosphamide treatment before implantation on the development of rat embryos after implantation.

After treatment of pregnant rats 24 h before implantation with a single injection of cyclophosphamide (20--80 mg/kg), a dose-dependent increase in resorption was observed at term but no malformed fetuses could be found. The lowest cyclophosphamide dose that caused 100% resoprtion was 60 mg/kg. Somite number and wet weight indicated retardation of about 24 h during organogenesis. Determination of the time of implantation revealed that the developmental retardation in treated embryos was not due to delayed implantation. At implantation, 24 h after cyclophosphamide treatment, a significant and dose-dependent decrease of the cell number of blastocysts was found. Embryo transplantation experiments showed that early cyclophosphamide treatment interfered with the subsequent development of both the embryo and the mother. The decidual reaction seemed to be more affected by the treatment than the embryos. Most teratologists hold that mouse embryos after treatment in the preimplantation period either die before implantation or survive to term without being malformed. The present study, however, proves that the reaction of drugs at this early stage of pregnancy is more complex than is generally assumed.

Animals↗

PubMed1984

[Effect of various schedules of cyclophosphamide administration on the mortality of the adult mouse infected with Junín virus].

The object of this paper was to determine the influence of cyclophosphamide immunosuppression on the mortality of 40-45 day old Balb/c mice infected intracerebrally with a pathogenic strain of Junin virus, using different administration schedules. Up to 200 mg/kg of cyclophosphamide were not toxic. Results show that, unlike in other experimental models, three or four 50 mg/kg cyclophosphamide doses given both before and after viral infection were required to break-down resistance to Junin virus (90-96.5% mortality vs. 8% in controls). Taking into account the effect of cyclophosphamide on the cell populations involved in the immune response, causes likely to lead to the greater susceptibility of the suppressed adult mouse to Junin virus are discussed.

Animals↗

PubMed1980

Leucokinetic study. Morphology of the bone marrow and blood after experimental induction of marrow hypoplasia by cyclophosphamide in laboratory rats.

Experimental hypoplasia of femoral bone marrow in rats was induced by cyclophosphamide, injected i.p. at various clock hours (08.00, 12.00, 16.00, 20.00, 24.00, and 04.00). Cyclophosphamide-induced neutropenia persisted for six days and was followed by transitory granulocytosis with subsequent decrease in the cont of circulating mature granulocytes. The absolute counts of circulating segmented neutrophils changed in parallel with the absolute counts of segmented neutrophils in the bone marrow. The count of circulating neutrophils was not essentially influenced by the clock hour of cyclophosphamide injection. The toxic action of cyclophosphamide upon the bone marrow exhibited a circadian rhythmicity: the greatest decrease in the count of nucleated marrow cells was found in the morning, and the least, in the evening. The minimal compartment transit times of the development stages of bone-marrow neutrophils, and the daily granulocyte production in the rat were calculated.

Animals↗

PubMed1983

Effects of cyclophosphamide on autoantibody synthesis in the Brown Norway rat.

The effects of cyclophosphamide on autoantibody synthesis were studied in an experimental model of glomerulonephritis due to autoantibodies to the glomerular basement membrane (GBM). Brown Norway rats develop anti-GBM antibodies, as part of a polyclonal response, when repeatedly injected with mercuric chloride (HgCl2). Anti-GBM antibody levels peak between days 11 and 14 and thereafter rapidly fall; convalescent animals show a time-dependent resistance to rechallenge with HgCl2 which remains significant for up to 3 months. The administration of cyclophosphamide, as a single intramuscular injection at day 0, has three distinct dose-dependent effects on anti-GBM antibody production. Firstly, lower doses (2.5 mg/kg) increase antibody levels at the time of peak response; secondly, higher doses (greater than or equal to 20 mg/kg) prevent antibody synthesis following HgCl2; and thirdly, the higher doses also reduce the response to rechallenge with HgCl2 3-4 months later. These effects of cyclophosphamide also apply to the polyclonal response to HgCl2, as judged by measurement of total IgG concentrations. Further investigation of the mechanisms of action of cyclophosphamide in this model should provide information relevant to the treatment of human autoimmune disease.

Animals↗

PubMed1982

Effects of cyclophosphamide and polycyclic aromatic hydrocarbons on cell growth and mixed-function oxidase activity in a human colon tumor cell line.

Human colon tumor cells (cell line LS174T) retain a cytochrome P-450-containing drug metabolism system capable of hydroxylating polycyclic hydrocarbons and the anticancer drug cyclophosphamide. The hydroxylation of benzo(a)pyrene by human colon tumor cells is highly inducible. Phenobarbital plus hydrocortisone induce benzo(a)pyrene hydroxylation activities 10-fold, while benz(a)anthracene induces the rate of hydroxylation 30-fold. Cytochrome P-450 specific content is increased 2- to 3-fold by treatment with phenobarbital plus hydrocortisone and benz(a)anthracene, respectively. Addition of cyclophosphamide alone results in no increase in hydroxylation activities but causes a decrease in cell growth rate. The combination of cyclophosphamide with either of the inducers phenobarbital plus hydrocortisone or benz(a)anthracene results in markedly enhanced inhibition of cell growth as judged both by a decrease in the number of cells per plate and in the incorporation of [3H]thymidine into DNA. Thus, these data show that cyclophosphamide is cytotoxic to human colon tumor cells and that the cytotoxicity is enhanced by simultaneous administration of benz(a)anthracene or phenobarbital plus hydrocortisone to the tissue cultures.

Adenocarcinoma↗

PubMed1984

Experimental rabies in skunks: effects of immunosuppression induced by cyclophosphamide.

Striped skunks (Mephitis mephitis) were inoculated with street rabies virus and immunosuppressed with several doses of cyclophosphamide. Control skunks were inoculated with street virus only. The skunks were killed in terminal stages of the disease and several tissues were collected for examination by immunofluorescence, light microscopy and viral titration. Sera collected at euthanasia from most of the principals did not contain detectable rabies neutralizing antibodies, whereas high titers occurred terminally in controls. Immunofluorescence was much more entensive in submandibular salivary glands of cyclophosphamide-treated than control skunks. Similarly, virus was isolated from this tissue more consistently and at higher titer from principals than from controls. Immunofluorescence was extensive in brains of all skunks (both groups), but virus was isolated consistently only from brains of cyclophosphamide-treated skunks. Most of the cyclophosphamide-treated skunks had very few inflammatory cells in brain and cerebrospinal ganglia. Neuronal degeneration occurred in dorsal root ganglia of both principals and controls. The results suggest that the immune response has no effect on the development of rabies-induced aggressive behavior, that the immune response may inhibit salivary gland infection and that it is not essential for the development of neuronal degeneration in dorsal root ganglia.

Animals↗

PubMed1984

Mitoxantrone and cyclophosphamide in advanced breast cancer: a pilot study.

A trial of combination chemotherapy using mitoxantrone-cyclophosphamide was started in 1983. Sixteen patients with widely metastatic cancer of the breast, including one man, received mitoxantrone, 10 mg/m2 intravenously (IV) over 30 minutes on day 1, followed by cyclophosphamide, 200 mg/m2 by mouth (PO) daily in divided doses on days 3 to 6. It is too early to evaluate four patients at present. The remaining 12 received three or more courses of treatment, and three of these patients achieved a complete response. Another four patients went into partial remission, amounting to an overall response rate of 58%. The other evaluable patients showed stable disease with improved symptoms. Hematologic toxicity was mainly granulocytopenia, but thrombocytopenia occurred in two patients. Alopecia, nausea, and vomiting were attributed to the cyclophosphamide component of the therapy. Mitoxantrone appeared to have no cardiac toxicity. It was concluded that mitoxantrone-cyclophosphamide is an effective chemotherapeutic combination with minimal toxicity and should be further studied in larger controlled trials.

Adult↗

PubMed1981

Kinetics and effects of activated cyclophosphamide in serum.

The effects of sera containing in vivo activated cyclophosphamide were tested on macrophage granulocyte colony growth (CFUc) and mixed leukocyte cultures (MLC). Bone marrow reconstitution and the growth of a canine tumor after incubation of transplanted cells with active sera were studied in vivo. The following experiments were performed: 1) peripheral blood CFUc values were determined in 6 dogs 5 min to 72 h after intravenous administration of 100 mg/kg cyclophosphamide. Inhibition was apparent at 5 min and lasted for 24 h. 2) Sera samples were obtained from 10 dogs after cyclophosphamide administration. The half life of serum inhibitory activity measured against normal dog cells was approximately 6 h. Inhibitory effects were noted 5 min following drug administration and complete at 30 min. 3) Timed incubation with 1 h postcyclophosphamide sera revealed preferential inhibition of MLC activity compared to CFUc activity, 4) In vitro incubation for 30 min in active sera did not affect the bone marrow repopulating potential of hematopoietic cells compared to nonincubated cells. 5) At least a tenfold reduction in the growth potential of a transplantable canine tumor could be produced by in vitro incubation of tumor cells with active sera. It is concluded that varying sensitivities of hematopoietic, immunocompetent and tumor cell populations to cyclophosphamide metabolites may provide a basis for in vitro chemoseparation of mixtures of these cell types.

Animals↗

PubMed1984

[Pathogenicity of various species of Candida in mice immunodepressed with cyclophosphamide].

The resistance of outbred CD1 mice immunodepressed with cyclophosphamide to the systemic infection induced by the three species of Candida: C. albicans, C. krusei and C. viswanathii was studied. The administration of cyclophosphamide, three days before the challange of the Candida species causes a degree of immunodepression in relation to the dose of drug: decrease of leucocytes of the peripheral blood and decrease of the weight and of the cellularity of the spleens. The CD1 mice were immunodepressed with cyclophosphamide (150mg/Kg) three days before the intravenous challange with graded doses of cells of the three species of Candida. They are much more susceptible, compared to normal mice, to the systemic infection induced by C. albicans and also by C. viswanathii but in this case only when inoculated at the highest concentration. They are resistant, like normal mice, towards the C. krusei even in the case in which the degree of immunodepression of the animal is furtherly increased (with stronger doses of the drug). The number of colony forming units (CFU) from the kidneys of the immunodepressed mice with cyclophosphamide correlates the median survival times.

Animals↗