Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anti-tumor activities of ACNU and X-irradiation on methylcholanthrene induced glioma in C57BL mice were studied in vitro and in vivo. In vitro experiments using cultured glioma cells (MGB cells), the synchronization of cell cycle was done by excess addition of thymidine, and the anti-tumor cell effect were investigated by mean of determinations of DNA synthesis, mitotic index and the number of the living cells following the treatments. As the results, it appeared obvious that ACNU was most effective on MGB cells in S phase and X-irradiation in M phase. As to the combined therapy of ACNU and X-irradiation, the anti-tumor effect was most remarkable when the cells were treated by X-irradiation in the G2, M phase, which were hervested by addition of ACNU 44 hours before irradiation. However simultaneous treatment of ACNU and X-irradiation on the cells in G1 phase was not so remarkable. In vivo experiments the anti-tumor effect of ACNU and X-irradiation on subcutaneously or intracranially transplanted glioma in mice was investigated. Either ACNU 10 mg/kg or local X-irradiation 1240 rads showed inhibitory effect on the tumor growth and prolonged the survival time of the tumor bearing mice. The combination therapy was more effective than ACNU or X-irradiation alone, particularly combination therapy of ACNU and repeated small doses irradiation of X-ray was remarkably effective. Evidence obtained indicates that the combination therapy of ACNU and X-irradiation have synnergistic anti-tumor effect on experimental mouse glioma.
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PMID:[The anti-tumor effect of ACNU and X-irradiation on mouse glioma (author's transl)]. 50 42

To evaluate new cytotoxic drugs for intrathecal treatment we developed an experimental model of leptomeningeal metastasis by intracisternal injection of 10(4) B16-F10 melanoma cells in nude rats. One hour in vitro incubation with 20 micrograms/ml ACNU (area under the drug concentration-time curve = 1200 microgramsxmin/ml) induced a 4-log kill of B16 melanoma cells. A single or repeated non-toxic dose of 1 mg/kg was injected into the cisterna magna of rats inoculated with tumor (area under the drug concentration-time curve assuming an even cerebrospinal fluid distribution greater than 7000 microgramsxmin/ml). Median survival free of symptoms was 16 days (range 14-27) for controls (n = 9) and 18 days (range 17-23) for rats treated with ACNU on day 4 (n = 9). Animals treated both on day 2 and 8 (n = 8) developed symptoms on day 21 (range 13-35). Neurological symptoms and neuropathological examination in animals with increased survival indicated local suppression of tumor growth in the cisterna magna but increased spinal seeding and mass growth. From these results and the available pharmacokinetic data on ACNU it is concluded that bolus injection of ACNU--although locally effective--is not a sufficient treatment of widespread leptomeningeal metastasis. An increased therapeutic efficacy might be achieved by ventriculolumbar perfusion.
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PMID:Intrathecal ACNU treatment of B16 melanoma leptomeningeal metastasis in a new athymic rat model. 143 39

Pancreatic cancer is one of the neoplasms resistant to chemotherapy. In the present study human pancreatic cancer xenografts (3 adenocarcinomas and 1 cystoadenocarcinoma) were subcutaneously transplanted in nude mice and after the tumors grew to 100-300 mm3, the mice were intraperitoneally administered with mitomycin C (MMC), adriamycin (ADR), 5-fluorouracil (5-FU), carboquone (CQ), cisplatinum (CDDP), nimustine chloride (ACNU) or DWA2114R at 1/3 LD50 on days 0.4, and 8. The tumor sizes on day 12 were compared with those on day 0. MMC and CQ significantly inhibited the tumor growth of 3 lines, and ACNU, CDDP and ADR inhibited the growth of 1 line. Further, 5-FU, futrafur, carmofur, UFT and L-phenylalanine mustard (L-PAM) were orally administered to mice into which 1 adenocarcinoma line had been transplanted. While none of fluoropyrimidines inhibited tumor growth, L-PAM at 4 mg/kg significantly inhibited growth, although it was accompanied by severe body weight loss. In the present study several agents significantly inhibited tumor growth, but none of them could induce the regression of the tumor when used singly. These results suggest that CQ, ACNU, CDDP and L-PAM may be applied to the chemotherapy of pancreatic cancer. However, the effect of a single agent is restricted and the development of new combination treatments is urgently required.
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PMID:In vivo inhibitory effect of anticancer agents on human pancreatic cancer xenografts transplanted in nude mice. 206 19

The 6-day subrenal capsule assay for determining chemotherapeutic sensitivities of brain tumors was studied. Rat glioma 9L and ACNU resistant 9L-2 were transplanted under the renal capsule of normal immunocompetent WKA rats for laboratory investigation. Evaluation of implanted tumor growth till 12 days was performed. The effects of chemotherapeutic agents administered intravenously were evaluated by measuring the growth rate of implanted tumor specimens. The results obtained from SRC were compared with the results from colony forming assay. Both were correlated to each other. On the other hand, histological investigation revealed that implanted human tumor cells had been diminished and implanted tumor was replaced by immunoreactive cells from the host in many cases. These results threw doubt on a reliability of SRC. To avoid this immunoreaction, cyclophosphamide was injected as immunosuppressive agent subcutaneously 24 hours before implantation. In such cases, the growth rates of implanted tumors were increased and histologically the implanted tumor cells existed for 6 days after implantation. Twenty-three malignant brain tumors (malignant astrocytomas 16, metastatic tumors 5, malignant lymphoma 2) were obtained as surgical specimens. Evaluable assay rate of our study were 89%. 15 patients with malignant astrocytomas were studied about correlation between the sensitivities of ACNU and post-operative clinical courses. Overall clinical correlation of 15 cases of malignant astrocytomas was 47%. These results from subrenal capsule assay are not seemed to be beneficial for clinical use. Immunoreactive response when using immunocompetent rats must be solved in future.
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PMID:[Chemotherapy responsiveness of brain tumors in subrenal capsule assay]. 232 45

Single-dose BCNU or chlorozotocin (CLZ) treatment of EMT6 mammary carcinoma tumors of the BALB/c mouse has only a transient effect on tumor growth, after which tumors follow control growth patterns. To test the hypothesis that drug access to tumor cells might be a factor in cell killing, we adapted the EMT6/KY tumor to ascites form. Injection of 10(5) EMT6/KY cells i.p. kills BALB/c mice with a mean survival time of 13.0 +/- 1.0 days. We have surveyed several nitrosoureas for their effects on the EMT6/KY ascites tumor after intraperitoneal injection of the drugs. Cure rates and percent increase in life span were used as endpoints. Also, we tested for induced host tumor resistance (TR) in cured mice, by challenging survivors with live EMT6 cells. Highest cure rates were obtained for treatment on days 2, 3, or 4 after inocula of 10(5) cells: CLZ (10 mg/kg), 83.3%; cis-acid (20 mg/kg), 75%, and CCNU (30 mg/kg), 70%. Other nitrosoureas, i.e. BCNU, PCNU, GANU, STZN, FCNU, ACNU, MeCCNU, NSC-88104 produced lower cure rates. Cured mice surviving challenges of 10(6) EMT6 cells were considered TR. TR mice did not correlate with cure rates for the 3 nitrosoureas giving high cure rates. As percent of survivors, TR mice were (for day 3 treatment): FCNU, 100%, BCNU, 100.0% and CLZ, 50.0%. Thus, cure rates and TR seem to depend on the structure of the nitrosourea, but through different mechanisms.
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PMID:Cure rates and tumor resistance in cured mice after nitrosourea treatment of EMT6 ascites tumors. 294 85

Female C3H/HeN mice bearing solid FM3A tumors were treated with a combination of ACNU (or Nimustine hydrochloride) and radiation in order to investigate the antitumor effects and also to determine the optimal treatment schedule of ACNU in such combined therapy. ACNU was intravenously injected either twice with an interval of 2 weeks and a dose of 30 mg/kg (intermittent large-dose treatment), or as 4 weekly doses of 15 mg/kg (fractionated small-dose treatment). Local irradiation (5 Gy) at the tumor site was performed twice with an interval of 2 weeks between the doses. Synergistic effects were obtained by the combination of ACNU and radiotherapy in terms of tumor growth inhibition and prolongation of survival. Histology also revealed much greater reduction of viable tumor cells in the case of combination treatment. With either treatment with ACNU alone or in combination with irradiation, the intermittent large-dose injections resulted in better inhibition of tumor growth than did the fractionated small-dose injections, but the survival times with the intermittent treatments were not as prolonged as would be expected from the direct effects. Loss of body weight and depression of WBC number were also much more severe in the intermittent treatment group. Thus, it may be concluded that when ACNU is combined with radiotherapy, the intermittent large-dose regimen is not necessarily superior to the fractionated small-dose one.
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PMID:Effects of combined treatment with nimustine hydrochloride and radiation on solid FM3A tumor in mice. 311 2

In an attempt to enhance the antitumor effects of hyperthermochemotherapy, methylglyoxal-bis-guanylhydrazone (MGBG) and alpha-difluoromethylornithine (DFMO) were used in combination with hyperthermochemotherapy of 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosoure a (ACNU) against human gastric cancer (ST-2) xenotransplanted into nude mice. After priming with DFMO and MGBG, ACNU was given ip and subsequently, a 23 minute-hyperthermia was carried out by placing the leg with the tumor into a water bath of a temperature of 43.5 +/- 0.1 degrees C. The second hyperthermic treatment was given in the same manner after 48 hours. MGBG and DFMO were administered for 4 successive days from the previous day of the first hyperthermia. In mice treated with DFMO plus MGBG, either tumor growth or tumor tripling time was much the same as in the control, while in mice given MGBG, DFMO plus heat, there was a diminution in tumor growth. Hyperthermia together with MGBG, DFMO plus ACNU brought about remarkable antiproliferative effects on ST-2 tumor growth, compared to three regimens with MGBG, DFMO plus heat, MGBG, DFMO plus ACNU, as well as ACNU plus heat. These data suggest that a combination of MGBG with DFMO leads to a favorable thermosensitization to the antitumor efficacy of ACNU.
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PMID:Enhanced antitumor efficacy with a combination of hyperthermochemotherapy and thermosensitization with polyamine antimetabolites in nude mice. 311 28

Two series of experiments were conducted to ascertain whether hyperbaric oxygenation (HBO) treatment with or without antineoplastic chemotherapy can really suppress tumor development in N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced bladder tumor in rats. HBO treatment of 2 ATA of air saturating with 30-35% of oxygen for 90 min daily plus 0.5 mg/100 g body weight of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) administration for 5 times suppressed the neoplastic spread of the bladder for 9 weeks and reduced the bladder weight in BBN-treated rats. Similar effects were also obtained in ACNU-treated rats, but to a lesser extent. HBO treatment associated with or without doxorubicin failed to suppress tumor growth in BBN-treated animals. Based on these findings combined with the previous study (part I), HBO treatment associated with ACNU might be available for the treatment of some cases of bladder tumors.
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PMID:Hyperbaric oxygenation for experimental bladder tumor. II. Hyperbaric oxygenation in combination with chemotherapy in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced bladder tumors. 316 73

Hemocirculatory and metabolic changes in tumor regions and the remote brain structure were analyzed using oxygen-15 and fluorine-18 positron emission tomography (PET) in eight patients with gliomas after radiation and chemotherapy of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and N-(2-tetrahydrofuryl)-5-fluorouracil (FT-207). In the tumor regions after the radiochemotherapy, regional cerebral blood flow (rCBF) and cerebral blood volume (rCBV) varied widely and there was a tendency for oxygen consumption (rCMRO2) to fall. The change in glucose consumption (rCMRG1) was especially noteworthy with regard to clinical correlations. Six patients with decreased rCMRG1 values had 16% to 29% regressions in tumor size measured by X-ray computerized tomography (CT), and showed some period of clinical relief. In contrast, one patient with an increased rCMRG1 value had some progression of tumor growth, and there were no clinical amelioration. The hemocirculation and metabolism of the contralateral gray matter seem to fluctuate by various factors as intracranial pressure and the effectiveness of the therapy. In gliomas therapy, tumor rCMRG1 values can be a good indicator of therapeutic effectiveness.
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PMID:Positron emission tomographic evaluation of radiochemotherapeutic effect on regional cerebral hemocirculation and metabolism in patients with gliomas. 350 Feb 81

In vitro sensitivity test of cultured human malignant glioma cells to ACNU[1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride] was performed on Falcon 3064 microtestplate. Early culture cells established from 10 clinical cases were examined by means of this method and the correlation between in vitro response and clinical response of tumor to ACNU was studied. In microtestplate assay, it was defined as ACNU sensitive when the tumor growth showed more than 60% suppression when tumor was cultured in the medium which contained 40 meg/ml of ACNU. Clinical responses were evaluated by means of CT scan, being divided into 4 classes, PR (partial response), CR (complete response), NC (no change) and PD (progressive disease). The former two groups were regarded as responder and the latter two as nonresponder. The correlationship between in vitro response and clinical response was higher in resistant group (100%) than in the sensitive group (60%), so the resistant tumor can be checked with this method. For this reason, the use of this assay may prove helpful in the selection of the chemotherapeutic agents.
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PMID:[Anti-tumor activity of ACNU against malignant glioma--a clinical application of in vitro sensitivity test of chemotherapeutic agent]. 630 97


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