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At least 523 records · Page 29Linked to original sources
PubMed1985

[A new in vitro chemosensitivity test. Individualized chemotherapy against ovarian cancer and its clinical effect].

A new in vitro chemosensitivity test was developed from comparative studies on the cytotoxicity of anticancer drugs against human tumor tissues xenografted into nude mice and their cultivated cells in vitro. Half a gram of the material was sufficient to examine the sensitivity of the tissues to 10 kinds of potential anticancer drugs and the results were obtained within 24 hours. The test was applied to all of 20 patients with advanced ovarian cancer. The predictive accuracy was 58% in 12 evaluable patients. This response rate was higher than those of conventional combination chemotherapy with or without cisplatin and adriamycin. Individual ovarian cancers showed different sensitivities to the drugs. These results indicate that heterogeneity of sensitivity to anticancer drugs exists among individual ovarian cancers and that our new type of in vitro chemosensitivity test is useful for selecting the most effective drugs for each individual type of ovarian cancer.

Adult↗
PubMed1986

[Flow cytometric studies of brain tumors--5: New sensitivity test of antineoplastic agents for brain tumors and its clinical application].

Flow cytometry (FCM) has been used not only for the judgement of malignant tumor cells but also for the evaluation of chemotherapy. Recently, we established a new application of FCM for the choice of the best antineoplastic agent in the chemotherapy of brain tumor. At first, the system of sensitivity test was developed through the preliminary study using established brain tumor cell line. Antineoplastic agents were contacted with the cells in the monolayered culture and the cell viability and the changes of DNA-histogram were analyzed by FCM. The cell viability was measured with the staining of fluorescein diacetate, and DNA-histogram was analyzed by the staining of propidium iodide. The best agent was judged based on the changes of the cell viability and cell cycle. The cytocidal and cytostatic effects were evaluated quantitatively, showing coincidence with the sensitivity of the cells to the appropriate antineoplastic agent. Secondary, this system was applied for the 15 malignant tumor cases. In these cases, the best antineoplastic agent could be selected through this method. Present system will be applied for the clinical cases continuously. Sensitivity test by FCM could be established in vitro system, and will be of much value clinically.

Animals↗
PubMed1987

[Application of flow cytometry to the chemosensitivity test by the BrdU labeling method; a preliminary report].

In the present paper we discussed whether a new method of chemosensitivity test could be developed using FCM (flow cytometry) and applied to malignant brain tumor cells labelled with BrdU monoclonal antibody. For this purpose, a basic study was performed with an ACNU-resistant C6 cell line and a sensitive one to see if this method was able to detect the difference of sensitivity between these cell lines. After 8 hours treatment with ACNU (concentration: 10 micrograms/ml), ACNU-sensitive cells revealed on LI (labeling index) of 46%, which was very high in comparison with controls, whereas the figure for ACNU-resistant cells was 34%, which was almost the same LI value as non-treated control cells. This means that change in the BrdU labeling index after chemotherapy in vitro can be used to determine the chemosensitivity of malignant brain tumors when FCM is employed. Furthermore, this method can detect the chemosensitivity of each clone in polyclonal human tumors which is impossible for the HCSA method, since the latter can reveal only the chemosensitivity as a whole in such tumors.

Antibodies, Monoclonal↗
PubMed1988

Immunogenic potential of tumor cells after treatment with antitumor chemotherapeutic agents.

Mouse EL-4 lymphoma cells exposed in vitro for short periods to 4-hydroperoxycyclophosphamide, an in vitro active derivative of cyclophosphamide, and to another alkylating agent, cis-diamminedichloroplatinum(II), as well as to mitomycin C, induced development of antitumor immunity in syngeneic mice co-administered with OK-432, an immunostimulator prepared from streptococci. The anthracyclines (adriamycin and daunomycin) were very slightly effective. The efficacy of the alkylating agents in inducing tumor immunity was also demonstrated by their ability to stimulate secondary in vitro generation of splenic cytotoxicity. These data supported the proposed explanation for effectiveness of chemoimmunotherapy against poorly immunogenic tumors.

Adjuvants, Immunologic↗
PubMed1989

[Adverse reactions to carcinostatics and countermeasures].

As adverse reactions to the combination treatment by the digestive system, we observed the occurrence of nausea and vomiting in 15% of the cases who received FTP treatment consisting of 5-FU, toyomicin and prednisone, 25% of the cases who received MFU treatment consisting of MMC, 5-FU and ACNU, and in 64% of the cases who received PPQ treatment consisting of CDDP, Carboquone (CQ) and prednisone. The antiemetics usually used are metoclopramide and droperidol, and we preadminister valproate preparation when persistent and delayed emesis is predicted. Several randomized trials have been made, and good efficacies with drugs such as metoclopramide, domperidone and steroid have been reported. Efficacy was good with acute emesis, but nonexistent with delayed emesis. As to the liver injury, in our combination treatment, only one case showed elevation of GPT by more than 500 units in the cases treated with MFU, while, increase in liver enzymes in the blood was observed in 10-20% of the cases. Similarly, there were not so many cases of liver injury during PPQ treatment. Thus, liver injury due to carcinostatic would be less frequent. Moreover, autopsy revealed hepatocellular-type of liver injury, cholestatic type liver injury and fatty metamorphosis at reasonable incidence. There were no typical cases of veno-occlusive disease which are noticed recently. The most important point for prevention and countermeasures against liver injury is to be careful not to use the previously mentioned drugs exhibiting toxicity in the liver if hepatic disease exists.

Antiemetics↗
PubMed1989

[Therapeutic efficacy of intracarotid infusion of 20% mannitol with ACNU in Fischer rats with intracerebrally implanted 9L gliosarcoma].

The purpose of this study was to investigate the therapeutic effect of intracarotid infusion of 20% mannitol with ACNU chemotherapy in Fischer 344 rats with intracerebrally implanted 9L gliosarcoma, compared with giving them only ACNU intraperitoneally. Thirty 9L gliosarcoma bearing Fischer 344 rats were evaluated in the following 3 groups. Group I: control (no treatment); group II: treated by ACNU 20 mg/kg intraperitoneally on the 7th day after implantation of 9L gliosarcoma cells; group III: treated by intracarotid infusion of 20% mannitol 3.1 ml/min. and with the same dose of ACNU as in group II. Mean survival time after the inoculation of tumor cells into the brain was 15.1 days (group I), 21.8 days (group II) and 27.9 days (group III). In group II all tumor-bearing Fischer rats died within 24 days after inoculation of tumor cells, whereas in group III 5 out of 6 rats survived more than 25 days after them. Group III evidenced necrosis and degenerative findings with vacuole and microcyst without vascular proliferation in tumor tissues more than group II on the 7th day after ACNU treatment for the experimental brain tumor. On the 7th day after ACNU treatment of each group, BrdU labeling index was calculated in order to evaluate tumor proliferation. The Mean BrdU labeling index in tumor cells of group III demonstrated 7.5%, against 14.5% (about one half) in group II. From our experimental study of survival time and BrdU labeling index, it is suggested that osmotic blood brain barrier disruption chemotherapy by intracarotid infusion of 20% mannitol and ACNU was more effective than simple treatment by intraperitoneal injection of ACNU in the Fischer rats with intracerebrally implanted 9L gliosarcoma.

Animals↗
PubMed1989

[Intra-arterial chemotherapy of malignant glioma after osmotic blood-brain barrier disruption].

Reversible transient osmotic blood-brain barrier disruption was used to increase drug delivery to the brain. The authors treated 10 cases of malignant gliomas with intra-arterial chemotherapy after osmotic blood-brain barrier disruption. Ten patients received intra-arterial anticancer drugs (5-FU, ACNU, IFN-beta) after intra-arterial infusion of 20% mannitol to open the blood-brain barrier at the tumor site. Clinical responses in 9 evaluable cases were 1 Complete Response, 3 Partial Responses, 5 No Change and no Progressive Disease in CT examination. Response rate was 44.4% (4/9). The most untoward effect of this method was myelosuppression. Platelet and leukocyte count diminished below 20,000 and 2,000, respectively in 3 cases, and 2 out of these 3 cases died of severe infection. The other complications were eye pain during mannitol infusion in all cases, when the selective catheterization of the internal carotid artery failed to pass the origin of the ophthalmic artery. Decreased activity was seen in 70%, nausea and vomiting in 50%, swelling of external decompression area in 33%, increased neurological deficit in 20%, but all these side effects were transient. This method was considered an effective treatment for malignant gliomas.

Aged↗
PubMed1989

[A randomized phase II study of (2''R)-4'-0-tetrahydropyranyladriamycin and adriamycin in combination with vincristine and ACNU in small cell lung cancer--THP-ADM, VCR, ACNU vs ADM, VCR, ACNU].

Between April 1984 and March 1988, a comparative randomized phase II study was performed to compare the effects of (2''R)-4'-0-Tetrahydropyranyl-adriamycin (THP) and adriamycin in combination with vincristine (VCR) and ACNU in 60 previously untreated and evaluable patients with small cell lung cancer (SCLC). Arm AVA was constituted by adriamycin, VCR and ACNU, and arm TAVA by THP, VCR, ACNU. Of the 30 patients treated with AVA, there were 20 partial responses, 7 with no change and 3 with progressive disease, for an overall response rate of 66.7%. On the other hand, of the 30 patients on TAVA, one complete response and 22 partial responses were observed, for an overall response rate of 76.7% Median survival time of AVA was 10.0 M, that, of TAVA was 9.3 M. But significant differences between the two arms was not found. During induction therapy, leukopenia was the main side effect. Over WHO Grade 3 leukopenia was seen in 53.3% of patients on AVA and 70.0% of those on TAVA. Moderate hair loss (Grade 2) was significantly less frequent with TAVA than AVA. In conclusion, the results indicated that THP is active in SCLC with the same level of adriamycin, and has less toxicity. THP is a suitable drug as a first line combination chemotherapy for SCLC.

Adult↗
PubMed1985

[Experimental studies on combination chemotherapy based on cell cycle analysis].

Based on Peplomycin-induced cell cycle distribution analyzed by a flow-cytemetry using HeLa S-3 and SNG-M cells in vitro, we investigated reasonable periods and kinds of drug combined with pepleomycin (PEP). Changes in both the PEP treatment time and dosage produced a redistribution which decreases the number of cells in the G1 phase and increased the number of cells in the S and G2-M phases. The period with the maximum number of cells in the S phase was 12 hours in the HeLa S-3 and 16 hours in the SNG-M and, that in the G2-M phases, 16 hours in the HeLa S-3 and 22 hours in the SNG-M after the treatment. In the combination of the pep with CIS-DDP 4-hydroperoxy cyclophosphamide Adriamycin (ADR) and ACNU, the cytotoxic potency of the four drugs were CIS-DDP greater than 4-Hydroperoxy cyclophosphamide greater than ADR greater than ACNU in the HeLa S-3 and 4-Hydroperoxy cyclophosphamide greater than CIS-DDP greater than ADR greater than ACNU in the SNG-M. This suggests that the Cis and 4-Hydroperoxy cyclophosphamide were adequate for the combination with the PEP. The period of the combination should be at the time of the greatest accumulation of cells in the G2-M phase, because the pep effectively produced the G2-M partial synchronization. These results suggest that the combination chemotherapy should be based on the analysis of the cell cycle.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

[Intrathecal perfusion of ACNU neurotoxicity and intrathecal pharmacokinetics in dogs].

We studied the feasibility of intrathecal ACNU perfusion therapy against subarachnoid dissemination of malignant glioma. Intrathecal perfusion was performed in adult dogs by constant drip administration of 1 to 2 mg ACNU dissolved in 10 to 20 ml of lactate Ringer solution into the lateral ventricle and cerebrospinal fluid drainage through the lumbar puncture. The perfusion time was changed from 15 to 71 min. A bolus injection of 2 mg ACNU was also tested in one dog. No neurological symptom was noted during and after perfusion, and histological examination reveal only a minimum denudation of ependyma in a small area. Concentration of ACNU in CSF and serum were measured by HPLC (high-performance liquid chromatography). ACNU was detected in lumbar CSF only by perfusion, not by bolus injection, and the maximum concentrations were 6.26 to 25.76 micrograms/ml. The elimination phase of ACNU in lumbar CSF followed linear kinetics and the half-time was 18 min on average. AUCs (area under the drug concentration-time curve) were 346 to 896 micrograms.min/ml and they were the equivalent of in vitro cell kills in excess of 3 logs for rat 9L gliosarcoma and human glioma 126 cells. Serum concentration was 0.10 micrograms/ml in maximum. These findings suggest the feasibility of intrathecal ACNU perfusion therapy against subarachnoid dissemination of malignant glioma and warrant further studies.

Animals↗
PubMed1989

[Chemotherapeutic strategy in rat brain tumor cells resistant to ACNU using an in vitro colony formation assay].

Nitrosourea compounds have been widely used in the chemotherapy of malignant brain tumors, because of their blood-brain barrier permeability. However, drug resistance to nitrosoureas has been recently a major concern. Using an in vitro colony formation assay, intrinsic and acquired resistances to an anticancer nitrosourea, 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), were analyzed in rat 9L and C6 glioma cells. 9L and C6 cells were treated with varying doses of ACNU for 2 hours. Ten days after, the cells were fixed and stained with crystal violet. Colonies consisting more than 50 cells were counted. The survival fraction following treatment is the ratios of colony efficiency of treated cells to the colony efficiency of untreated control cells. The dose-response curve for ACNU indicated the existence of a shoulder (Dq, quasithreshold dose) at doses and an exponential cell-killing at higher doses with D0(37% survival dose). Based on dose-response curves corresponding to multitarget single-hit model, 9L cells showed 7.4 microM, 2.9 microM, and 14 microM at Dq, D0, and SD10 (10% survival dose) values, respectively, whereas C6 cells showed respective values of 6.4 microM, 30 microM, and 75 microM. 9L cells had significantly less intrinsic resistance to ACNU than C6 cells at the p less than 0.005 level by a covariance analysis of the curves. As with changes of drug susceptibility after ACNU treatment, both parent cells were treated every other day (1, 5, and 10 repeated times) with various doses up to approximately 1% survival dose of the parent cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[A trial of ACNU and radiation therapy with sensitizing agents for malignant gliomas].

Twelve cases of malignant gliomas (anaplastic astrocytoma 4, glioblastoma 8, recurrent 3, primary 9) were treated with ACNU and radiation with sensitizing agents after the surgical removal of the tumor. BUdR, Vidarabine (Ara-A), Aciclovir (ACV) were applied for sensitizing agents. BUdR was administrated intraarterially prior to radiation (380 rad, two times a week), and Ara-A and ACV intravenously during and after the radiation. Total dosage of the radiation was 50-60 Grey for each case. All recurrent and eight primary patients died. The mean survival time of the recurrent patients was 17.7 months, while that of the primary patients was 13.4 months. One of the primary patient was glioblastoma and is still surviving more than 24 months by now. The complete response (CR) rate of the primary tumor patients observed by computerized tomography (CT) scan was 5/9. We can expect the availability of this trial for malignant gliomas because of high CR rate in primary tumor cases.

Acyclovir↗
PubMed1989

[Experimental studies of anticancer drugs more appropriate for high-dose chemotherapy in bone marrow transplantation and their administration methods].

We studied in rats the anticancer drugs which can utilize more the advantage of bone marrow transplantation (BMT) and on their administration ways in high-dose chemotherapy (HC) with BMT. Among six anticancer drugs tested (ACNU, ADR, CY, MMC, VDS, VP-16), a beneficial effect of BMT was observed only with CY and ACNU. In order to increase the beneficial effect of BMT observed with CY and ACNU, the methods of administering these two drugs were carefully designed, and better survival curves were obtained in the following administration groups: 1) (CY 200 mg/kg, days 0 & 1) + BMT greater than (CY 400 mg/kg, day 0) + BMT, (ACNU 20 mg/kg, day 0 & 1) + BMT greater than (ACNU 40 mg/kg, day 0) + BMT. 2) (CY 200 mg/kg + ACNU 20 mg/kg, day 0) + BMT greater than (CY 400 mg/kg or ACNU 40 mg/kg, day 0) + BMT. 3) (CY 200 mg/kg, day 0) + (ACNU 20 mg/kg, day 1) + BMT greater than (ACNU 20 mg/kg, day 0) + (CY 200 mg/kg, day 1) + BMT. Further studies on anticancer drugs more appropriate for HC-BMT and on their administration methods were considered to be very necessary.

Animals↗
PubMed1989

[Autologous bone marrow transplantation as a measure against myelosuppression in cancer chemotherapy].

One hundred seventy-three patients were treated 256 times with chemotherapy supported by autologous bone marrow transplantation during the past 9 years. The two most commonly used protocols were (cyclophosphamide 1,600-2,400 mg/m2 + adriamycin 80 mg/m2 + ACNU 3 mg/kg) and (cyclophosphamide 1,600-2,400 mg/m2 + adriamycin 100 mg/m2 + CDDP 100-150 mg/m2). Among 115 patients in the therapeutic setting in which two courses were usually given, 75 were evaluable and the overall response rate was 42.7% with 12.0% CR rate. Breast and pediatric groups responded well; the response rate in breast cancer was 67.9% with 21.4% CR rate. Two patients with breast cancer who had multiple distant metastases and 2 pediatric patients are now alive with NED after 5 years of the treatment and seem to have been cured. The results in adjuvant settings have also been quite promising, e.g., 79.4% 5-year survival probability among breast patients mainly in stage III. Although drops of blood cell counts to the nadirs (WBC counts: less than 100-300) could not be prevented, the periods of myelosuppression appeared to have been effectively shortened so that the patients could be safely managed with intensified general supportive measures. Platelet counts are usually less affected, but the recovery is slower than for WBC counts. There were 13 patients who died within 10 weeks of the initiation of the treatment. Two of them succumbed to sepsis, and progressive disease was the cause of death in 8 patients whose terminal phases were undoubtedly affected by some infectious problems. We have shown that there are inverse relationships between infused numbers of CFU-GM and marrow recovery judged by the duration of neutropenia and the time required for neutrophils to recover over 500. Our recent laboratory experiments testing CFU-E, BFU-E and CFU-Mk in addition to MNC counts and CFU-GM showed that vulnerabilities of marrow progenitors seem to differ from cell lineage to cell lineage. This must therefore be taken into careful consideration in pursuing marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗