Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antitumor activity of mafosfamide (MFA), and its parent compound cyclophosphamide (CTX), was investigated against an ovarian reticular cell sarcoma growing i.m. in C57BI/6 mice (M5), which is very sensitive to CTX, and against a subline of this tumor (R16) resistant to CTX. MFA is the prototype of a class of oxazaphosphorines which do not require metabolic activation since under physiologic conditions they undergo rapid spontaneous hydrolyzation to the activated 4-hydroxyoxazaphosphorine and retain a spectrum of activity very similar to the parent compound. After a single dose (300 mg/kg X 1) or repeated low doses (100 mg/kg X 6) the antitumoral activity of MFA on the M5 tumor appeared comparable to or only slightly lower than CTX; the highest T/C value for median survival times was 167% in MFA-treated mice vs. 176% in the CTX group. MFA showed no activity against the R16 subline, thus indicating cross-resistance between the two drugs. Marked thickening of the glissonian capsule with compression of the lobular area of the liver, observed on i.p. administration of MFA, did not result in histopathologic abnormalities of the hepatic parenchyma. The therapeutic efficacy of MFA was similar with i.p. and the i.v. route. MFA may represent a good candidate to replace CTX in cases in which a compound acting per se, and not through metabolites, is preferred.
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PMID:Antitumoral activity of the oxazaphosphorine derivative, mafosfamide-cyclohexylamine salt (ASTA 7557) on a murine ovarian reticular cell sarcoma and its subline resistant to cyclophosphamide. 354 4

A prospective randomized trial has compared cyclophosphamide (CTX) with CTX plus cis-diamminodichloroplatinum (DDP) as the initial chemotherapy for advanced ovarian carcinoma. A secondary randomization compared the addition of BCG treatment to either chemotherapy. The addition of DDP had no measurable impact on survival, but a small survival trend favoring BCG-treated patients was noted (P less than 0.08). Toxicity from BCG treatment was insignificant, but the addition of DDP increased both early nausea and vomiting and later hematologic toxicity. There were three long-term complete remission patients, and these all came from the group of six patients with pretreatment residual disease less than 2 cm. A univariate analysis of pretreatment prognostic factors indicated significantly better prognosis (P less than 0.02) for patients with no palpable tumor, platelet count less than 400,000/mm3, residual tumor less than 2 cm, resting pulse less than 91/min. and LDH less than 250 U/L. The authors conclude that for patients with large (greater than 2 cm) residual disease, there is no compelling evidence that initial combination therapy is superior to aggressive single alkylating agent treatment.
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PMID:Randomized trial of the addition of cis-platin (DDP) and/or BCG to cyclophosphamide (CTX) chemotherapy for ovarian carcinoma. 354 49

Circulating immune complexes (CIC) levels were evaluated in two groups of cancerous patients to try to correlate CIC levels, tumor stage and chemotherapy received. There were 40 patients with Lung Cancer (LC) clinical stages III and IV; 60 patients with Breast Cancer (BC) stages II, III and IV and 38 normal controls. LC patients showed significant increase in CIC values before, during and after treatment as compared to controls, without any difference among groups under different treatment combinations and tumor stage. Stage II BC patients showed decreased CIC levels during treatment (p less than 0.01 vs initial value). This decrease was maintained after treatment (p less than 0.02). Stage III BC patients showed different behaviour according to treatment: those who only received chemotherapy (ADM + CTX) showed no significant differences during treatment, and those treated with ADM + CTX and megestol acetate (MA) displayed decreased CIC levels after treatment (p less than 0.05) reaching similar control values. Stage IV patients treated with ADM + CTX + MA returned to normal CIC values during treatment. These results proved that combined treatment of chemotherapy and hormone therapy diminished CIC levels in BC patients, while therapy given to LC patients did not present any modifications.
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PMID:Circulating immune complexes in breast and lung cancer, before and after chemotherapy. 360 38

Fifty-two patients received one of two doxorubicin (DOX)-based admixtures; DOX plus cyclophosphamide (CTX) or DOX plus vinblastine (VBL) administered as a continuous 24-hour infusion for protracted periods. Compatibility and stability of the two-drug admixture was established for a minimum of 7 days. Twenty patients on the DOX/CTX admixture were infused for a median of 20 days (range, 7-56 days). DOX/VLB was infused in 32 patients for a median of 18 days (range, 5-48 days). Dose limiting toxicity was leukopenia observed in 14/52 patients; 4/20 on DOX/CTX and 10/32 on DOX/VLB. Additional toxicities observed included stomatitis (15%) and subclavian vein thrombosis (23%). Tumor responses were observed in 11 patients, including 6/13 breast cancer; 2/2 hepatoma; 2/4 sarcoma and 1/1 ovarian cancer. Responses were relatively short-lived and no responses were noted in known anthracycline resistant tumors. Admixtures of chemotherapeutic agents represents a novel, but feasible, mechanism for delivery of multiple drugs with an infusion schedule and can be considered for Phase III comparative clinical trials.
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PMID:Doxorubicin/vinblastine and doxorubicin/cyclophosphamide combination chemotherapy by continuous infusion. 373 Oct 35

The combined effect of adjuvant Cyclophosphamide (CTX) and the hypoxic radiosensitizer, Nimorazole (NIM), on the radiation response was studied in a C3H mammary carcinoma in CDF1 mice. The effect of NIM and CTX alone or in combination without radiation was assessed by tumor growth delay measured by tumor growth time (TGT). Administration of CTX (100 mg/kg) increased the TGT from 5.2 days in untreated controls to 18.8 days. NIM (1000 mg/kg) had no effect on the TGT. The combined treatment with NIM given 4 hrs before CTX did not increase the TGT compared with CTX alone, which suggests that NIM does not potentiate CTX. The possible effect of an interaction between the therapeutic parameters was determined by administration of NIM, CTX, and radiation in different sequences to C3H mammary tumor bearing mice. The drugs were administered as single doses before or after graded single doses of irradiation. The end point was the radiation dose required to achieve local tumor control in 50% of the mice (TCD50). The enhancement ratio (ER)--defined as TCD50 for radiation alone relative to TCD50 for radiation combined with drug--was 1.2 for CTX given either 15 min before or 4 hrs after radiation. NIM given 30 min before radiation showed an ER of 1.6, but no enhancement was obtained when NIM was given after radiation. When NIM was given immediately after radiation, followed 4 hrs later by CTX, the ER was 1.2. However, applying NIM 30 min before radiation and CTX 3.5 hrs after radiation, the ER increased to 1.6. NIM given 30 min before, together with CTX given 15 min before radiation, showed an ER of 1.8. Our data suggest that: an improved tumor response may be expected when CTX is added to a radiation and hypoxic radiosensitizer treatment; this improvement is attributable to an additive effect based on the chemotherapy response alone rather than to chemopotentiation by the hypoxic radiosensitizer.
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PMID:Interactions of radiation, cyclophosphamide and nimorazole in a C3H mammary carcinoma in vivo. 375 71

The effect of pretreating the C3H/He mouse MBT-2 tumor with diethyl maleate (DEM), buthionine-S R-sulfoximine (BSO), or misonidazole (MISO) before administration of cyclophosphamide (CTX) was studied with the use of tumor volume-doubling time delay as an endpoint. The kinetics of glutathione (GSH) depletion and regeneration in the tumor and in the host liver were determined after treatment with the thiol-depleting agents. CTX was administered at appropriate time points. MISO was the most effective chemosensitizer at a time point at which tumor GSH content was 80-85% of the control value. Both BSO and DEM were chemosensitizers in relation to the degree they had reduced tumor GSH levels. This chemosensitization was significant at 50% GSH reduction. By combining MISO and BSO at doses lower than previously used for each agent alone, highly effective sensitization of subsequent CTX was obtained.
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PMID:Relationship between thiol depletion and chemosensitization in a transplantable murine bladder tumor. 385 95

We performed chemoimmune prophylaxis in 130 patients with superficial urothelial transitional cell carcinoma of the bladder. Two weeks after complete TUR 700 mg Cyclophosphamide (CTX)/m2 were injected intravenously followed by 6 weekly intravesical instillations of 120 mg BCG/50 ml saline together with BCG skin scarifications two weeks later. After 5 years the calculated frequency of recurrence was 18% in the treated group compared with 54% in the untreated historical control group. In a sub-group of 48 patients with recurrent tumors the CTX/BCG treatment success was well documented by comparison of the tumor recurrences during the appropriate time intervals before and after chemoimmune prophylaxis. The progression rate of the disease was generally more favourable in patients treated by CTX/BCG. No significant side effects of this treatment were noticed.
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PMID:[Chemo-immunoprevention in superficial bladder cancer]. 396 45

Six patients with inoperable, nonoperative, or recurrent meningiomas were treated with the antiestrogenic agent tamoxifen (Nolvadex) during an 8-12-month period. Computer tomographic, scintigraphic, and clinical evidence of an unspecific tumor response was only encountered in one patient after 4 months of therapy with tamoxifen. The 2-year results did not indicate a favorable response to antiestrogenic treatment. The significance of sex-steroid receptors and their possible prognostic value in endocrine therapy of meningiomas is discussed.
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PMID:Antiestrogenic therapy of meningiomas--a pilot study. 402 3

We carried out only high orchiectomy for a 1-year and 7-month-old boy with stage 1 yolk sac tumor of the testis, after 13-months a bulky retroperitoneal metastatic tumor was found. Following chemotherapy with CDDP, ACD, VBL, PLM and CTX two times after tumor resection, elevated serum AFP was normalized. He has been in continuous complete remission with no evidence of disease for 3 years and 2 months. Combination chemotherapy with CDDP has a dramatic effect on the yolk sac tumor of infantile testis. We believe that "watchful waiting" after high orchiectomy alone is the best modality for all cases of stage 1 yolk sac tumor of the infantile testis.
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PMID:[A case of recurrent yolk sac tumor of the testis in childhood: bulky retroperitoneal metastatic tumors cured by tumor resection and chemotherapy]. 402 86

Variations in cytochrome P-450 levels may influence the responsiveness of uterine and breast tissue as well as carcinomas to endocrine therapy and may be of particular importance with agents such as tamoxifen (Nolvadex) where hydroxylation is known to alter therapeutic activities. Therefore, a sensitive spectrophotometric assay of cytochrome P-450 levels in reproductive tissue microsomes was developed to measure cyclohexane hydroxylase activity. Cyclohexane served as a substrate for several forms of cytochrome P-450. Human uterine leiomyomas (uterine fibroid tumor) contained significantly higher (p less than 0.01) cytochrome P-450 activity than adjacent normal myometrium. Specific activities for both leiomyomas (2.87 +/- 0.26 nmol/min/mg) and normal myometrium (1.60 +/- 0.11 nmol/min/mg) were in the range of those observed for untreated rabbit liver microsomes (1 to 3 nmol/min/mg). The contribution of smooth muscle in the specimen, the phase of the menstrual cycle, and the clinical diagnosis did not influence the level of cytochrome P-450 activity.
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PMID:Cytochrome P-450 activity in human leiomyoma and normal myometrium. 406 17


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