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[Anticancer drug sensitivity test using the short-term microplate culture and MTT dye reduction assay].

We have applied the MTT dye reduction assay to the anticancer drugs sensitivity test using short-term microplate cultures. The tumor cells were cultured with the anticancer drugs for 2 and 4 days. After culture, MTT dye was placed in each microwell and culture was carried out again for 4 more hours. The formazans generated by living cells were dissolved in acidified isopropyl alcohol and the absorbances of each well were measured at a wavelength of 540 nm. When tables of cytotoxicity indices classified into anticancer drugs, concentrations and durations of culture for each type of leukemic cell were made, it became possible to compare each drug and to select the effective ones. This assay is simple, precise, rapid, has no washing steps and is convenient for handling a large volume of material. We apply this assay in clinical practice.

Antineoplastic Agents↗

[Combined cell killing effects of anticancer drugs and hyperthermia in vitro].

Using an in vitro colony forming assay system, cytotoxic effects of anticancer drugs, adriamycin (ADM) and peplomycin (PEP), and the combined effect of hyperthermia and anticancer drugs on cultivated KK-47 cells were investigated. From the response curves obtained at 42 and 43 degrees C hyperthermia, 20% growth inhibition time (IT20) at 42 and 43 degrees C hyperthermia and 50% growth inhibition time (IT50) at 43 degrees C were calculated. The IT20 and IT50 hyperthermia were combined with a 2-hour treatment of each of the anticancer drugs. When the hyperthermia was combined with various concentrations of ADM ranging from 0.005 to 0.1 microgram/ml, enhanced cell killing effects were obtained at the concentrations of less than 0.02 microgram/ml of ADM, whereas, there was no increase in cell killing effect at the concentrations of more than 0.05 microgram/ml of ADM. The combination of hyperthermia with PEP considerably enhanced the cell killing effects with an increase of PEP concentration.

Bleomycin↗

[Effects of buzhong yiqi decoction on the anticancer activity and toxicity induced by cyclophosphamide].

Effects of Buzhong Yiqi decoction on anticancer activity and toxicity induced by cyclophosphamide were investigated. The results showed that the decoction significantly increased the anticancer activity and simultaneously decreased the toxicity of cyclophosphamide. These data suggest that anticancer chemotherapeutic drugs combined with traditional Chinese medicine Buzhong Yiqi decoction can raise curative effect and reduce toxicity.

Animals↗

[Effect of anticancer agents on rat prostate. Evaluation of organ weight, histological finding and 5 alpha-reductase activities].

To evaluate the effect of anticancer chemotherapeutic antigens on rat prostate, ten kinds of anticancer agents corresponding to the dose generally used for humans were intraperitoneally injected to 63-day-old Wistar rats. The anticancer agents were administered as follows: Cyclophosphamide (CPM) was used at the dose of 8 mg/kg for 7 days. Methotrexate (MTX), actinomycin-D (ACD) and cis-platinum (CDDP), 163 micrograms/kg, 8 micrograms/kg and 833 micrograms/kg for 5 days, respectively. Nitrogen mustard (NM), bleomycin (BLM), peplomycin (PLM), adriamycin (ADM), vincristine (VCR), and vinblastine (VBL), 500 micrograms/kg, 250 micrograms/kg, 170 micrograms/kg, 2.5 mg/kg, 33 micrograms/kg and 83 micrograms/kg, twice in a week, respectively. The rats were killed on the fifth day after completion of the schedule. Then, the weight of the body, the prostate, the epididymis and the adrenal gland were measured. In addition, 5 alpha-reductase activities and histological findings in the prostate were examined. For determination of 5 alpha-reductase activities, cell-free homogenate obtained from the rat ventral prostate was incubated with C14-testosterone at 37 degrees C for 30 minutes in an atmosphere of 95% of O2 and 5% of CO2. Subsequently, the metabolites from testosterone were separated and purified with thin layer chromatography using the solvent system with benzene acetone, 4:1 (v/v). 5 alpha-Reductase activity was determined with the sum of dihydrotestosterone (DHT) and androstanediol converted from testosterone and indicated as pmol product/mg protein. The 5 alpha-reductase activity was employed as a biological marker for the degree of androgenic dependency in the prostate. The results were summarized as follows. CDDP significantly reduced the weight of the body (p less than 0.001, n = 7), but not the activity of 5 alpha-reductase. NM and VBL had a specific action to reduce the weight of the prostate (p less than 0.01, n = 8) without causing loss of body weight. NM and VBL showed no influence on 5 alpha-reductase activities. The activity of 5 alpha-reductase was markedly damaged by BLM (p less than 0.05, n = 6) and PLM (p less than 0.05, n = 5). However no significant reduction was recognized in the weight of the body and the prostate. CPM, MTX, ACD, ADM and VCR were ineffectual on the body and the prostate weight and 5 alpha-reductase activities. In the histological examination, atrophy and degeneration of the glandular epithelium were revealed in the prostate treated with NM, VBL and CDDP.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

[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↗

[The role of antineoplastic solution in transcatheter hepatic arterial embolization--in terms of survival rates affecting anticancer agents together with gelatin sponge].

In a multicentered randomized prospective study, hepatic arterial embolization using gelatin sponge (GS) alone or together with anticancer agents was performed in a total of 112 patients with hepatocellular carcinoma to ascertain the clinical availability of the anticancer agents combined with gelatin sponge. Envelopes, each of which contained a note mentioning one of the following three kinds of regimens, were allocated at random to the participating institutes: 1) GS + mitomycin C (MMC) 10 mg + adriamycin (ADR) 20 mg (group A, n = 45), 2) GS + MMC 10 mg + ADR 20 mg + 200 mg/day of oral 5-fluorouracil (5-FU) (group B, n = 36), and 3) GS + 200 mg/day of 5-FU (group C, n = 31). The envelopes so allocated were opened just prior to embolization, and the treatment was carried out as instructed. Survival rates were estimated according to the method of Kaplan-Meier for comparative analysis. The survival rate was significantly higher in group A than in group C on days 465 (p less than 0.05). It was also significantly higher in group B than in group C on days 279, 558 and 651 (p less than 0.05) as well as on days 372 and 465 (p less than 0.01). These observations suggest that this embolization using anticancer agents such as MMC and ADR, compared with the embolization using gelatin sponge alone, may exert a life-prolonging effect in patients with hepatocellular carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

[Effects of antipyretics and anticancer drug on human cells at high temperature condition].

The effects of antifebriles and anticancer drug on human vascular endothelial cells (HVE) and several cultured human cells were investigated. The HVE were isolated from umbilical cord veins by enzyme treatment and cultured successively in aerated synthetic medium, RPMI-1640, with 20% preclostrum new born calf serum. The presence of factor VIII antigen in the HVE was determined by enzyme-labeled antibody method. Cell count and protein amount were examined at regular intervals. At 3 hour-expose, sulpyrine was more toxic to the cultured cells than aspirin at 37 degrees C. The cytotoxicity of sulpyrine was markedly enhanced at 40 degrees C than at 37 degrees C. However, there was no enhancement in the cytotoxicity of aspirin at 40 degrees C. Cultured HVE and normal human fetal lung (HAIN-55) cells at 37 degrees C were sensitive to sulpyrine, and their sensitivity of the cells to the drug were markedly enhanced when they were incubated at 41 degrees C. In contrast, sensitivity of malignant human cells (HeLa cells) to sulpyrine was not found at 37 degrees C, however sensitivity of the cells to the drug was manifested at 41 degrees C of incubation. There was no effect of 5-fluorouracil (FU) on the growth of HVE and HAIN-55 cells at 41 degrees C, while HeLa cells showed high susceptibility to FU at the same temperature. The results showed the possibility that normal human cells may be sensitive to antifebrile drugs but not to anticancer drug at ordinary and high temperature, whereas malignant human cell may be susceptible to both antifebrile drugs and anticancer drug at high temperature.

Aspirin↗

Reduction of hepatic metastases in rabbits by administration of an oily anticancer agent into the portal vein.

We studied a prophylactic chemotherapy against hepatic metastases arising from the shedding of tumor cells into the portal circulation. The therapy was done with a lymphographic oily contrast medium, Lipiodol, and a high molecular weight anticancer agent named poly(styrene-maleic acid) copolymer conjugated neocarzinostatin (SMANCS), developed in our laboratory. SMANCS was dissolved in Lipiodol by sonication (SMANCS/Lipiodol, 1 mg of SMANCS in 1 ml of Lipiodol). Twelve rabbits were simply inoculated with the highly malignant carcinoma VX-2. Fifteen rabbits were given injections of SMANCS in glucose and Lipiodol into the portal vein and were subsequently inoculated with the tumor cells. Eighteen were given injections of SMANCS/Lipiodol and then the tumor cells. These rabbits were killed 12 days later. Thirteen were given injections of the tumor cells alone and were allowed to survive. Sixteen were given injections of SMANCS/Lipiodol and then with the tumor cells; they were allowed to survive. Rabbits given injections of SMANCS/Lipiodol before tumor inoculation had significantly fewer (P less than 0.001) metastases than those not treated or those given SMANCS in glucose and Lipiodol. Survival was significantly longer [P less than 0.005; 36.0 +/- 7.7 (SD) days] with SMANCS/Lipiodol before tumor inoculation than without treatment [23.5 +/- 3.0 days]. SMANCS/Lipiodol has a prolonged anticancer effect because it remains in the portal vein and allows sustained drug release from the oil (Lipiodol) to aqueous spaces. Hepatic metastases might be prevented by portal administration of the appropriate oily anticancer agent.

Animals↗

Selective anticancer effects of 3',5'-dioctanoyl-5-fluoro-2'-deoxyuridine, a lipophilic prodrug of 5-fluoro-2'-deoxyuridine, dissolved in an oily lymphographic agent on hepatic cancer of rabbits bearing VX-2 tumor.

3',5'-Dioctanoyl-5-fluoro-2'-deoxyuridine (FdUrd-C8), one of the lipophilic prodrugs of 5-fluoro-2'-deoxyuridine (FdUrd) was dissolved in an oily lymphographic agent (Lipiodol Ultra-Fluid), which had been studied as a carrier of the anticancer drug for hepatic cancer. The prodrug was administered into the left proper hepatic artery of rabbits bearing VX-2 tumor in the liver in order to examine the anticancer effects and possible adverse effects on nontumorous hepatic cells. Lipiodol or FdUrd-C8*Lipiodol selectively remained in the hepatic cancer area but disappeared from nontumorous parts of the liver 7 days after injection. Tumor growth rates in 1 week of the untreated group, a group given injections of 0.2 ml of Lipiodol alone, and groups given injections of 0.2 ml of Lipiodol containing 30, 50, 70, and 100 mg of FdUrd-C8 were 636, 436, 34.8, 14.9, -2.4, and -10.4% of the size at the time of treatment, respectively. Pathological observation also showed that FdUrd-C8 had a strong anticancer effect on VX-2 tumor growing in the liver of the rabbits. In contrast to the effect on the cancerous cells, that on nontumorous hepatic cells was very slight. In pathological observation, necrosis or degeneration of nontumorous hepatic cells was hardly observed. Plasma glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase levels temporarily rose 1 day after injection but returned to the initial levels within 7 days in all groups.

Animals↗

[A model for the sensitivity determination of anticancer agents against human cancer using nude mice].

Human tumors transplanted into nude BALB/c-nu mice have been used to test the sensitivity of the tumors to various anticancer agents. Three cancer cell lines from the stomach and one from the colon were transplanted into nude mice to establish a standard assay method for selection of effective drugs on individual tumors using the criteria of the Japanese Association of Sensitivity Determination for Carcinostatic Agents. From the LD values of anticancer drugs in nude mice, the appropriate doses of drugs were 6 mg/kg of MMC X 1(i.p.), 50 mg/kg of 5-FU q4d X 3 (i.p.), 120 mg/kg of CPA (i.p.), 30 mg/kg of ACNU (i.p.) 8 mg/kg of CDDP (i.p.) and 8 mg/kg of ADM (i.v.). At 3 weeks after initial treatment, the inhibition rate (IR) of the tumor was calculated from the formula IR = (1-T/C) X 100%, where T is the mean tumor weight of the treated group and C is the mean weight of the untreated group at that time. The tumors respond well to the anticancer agents when IR is more than 58%.

Adenocarcinoma↗

Effects of L-histidinol on the susceptibility of P815 mastocytoma cells to selected anticancer drugs in vitro and in DBA/2J mice.

The effects of L-histidinol on the susceptibility of the transplantable murine mast-cell neoplasm P815 mastocytoma to selected anticancer drugs have been evaluated on cells growing in culture and in syngeneic DBA/2J mice. Combinations of L-histidinol and anticancer drugs of either phase specificity [cytarabine (ara-C) and vinblastine sulfate] or cycle specificity [5-fluorouracil (FUra) and methotrexate] had diverse effects on cultured mastocytoma cells as scored by clonogenic cell survival assays. Flow cytometric analysis of randomly proliferating P815 mastocytoma cells revealed that although exposure to L-histidinol did not preclude cells from traversing the cell cycle, the analogue nonetheless conferred a dose-dependent and apparently nonspecific delay of cell cycle transit. DBA/2J mice bearing intraperitoneal P815 mastocytoma cells were used to evaluate the in vivo efficacy of L-histidinol-ara-C and of L-histidinol-FUra combinations. Quantitative cell survival assays of murine bone marrow cells and of clonogenic tumor cells obtained from treated animals demonstrated that L-histidinol eliminated the bone marrow toxicity otherwise attending the use of the drugs ara-C and FUra. Simultaneously, the inclusion of L-histidinol provided a statistically significant increase in the capacity of these two anticancer drugs to eradicate intraperitoneal mastocytoma cells.

Animals↗

Interaction of nicotine with anticancer treatment.

Investigations on the in vivo interaction of nicotine and antineoplastic agents were prompted by the observation that nicotine lowered the carcinogenicity of the alkylating agent methylnitrosourea (MNU) in rats. Since alkylating agents play an important role as antitumor drugs, nicotine may influence the anticancer activity of anticancer drugs, especially alkylating agents. Two tumor models were selected: (a) autochthonous, MNU-induced mammary carcinoma and (b) transplanted rat leukemia L5222. The antitumor drugs investigated were cyclophosphamide (CPA) and 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl) urea (HECNU). Nicotine was administered continuously by Alzet-osmotic minipumps, at a dose of 2.5 and 5 mg/kg daily. Under these conditions the observed nicotine and cotinine plasma levels approximated levels measured in heavy smokers (nicotine peak level, 47 ng/ml; cotinine peak level, 635 ng/ml). In MNU-induced autochthonous mammary carcinoma, a solid hormone-dependent tumor, the combination of HECNU and nicotine yielded greater tumor inhibition than HECNU alone. The anticancer activity of CPA on transplanted L5222-leukemia, on the other hand, was decreased by continuous infusion of nicotine. The interpretation of both results has to take into account the following possibilities of nicotine action: influence on (a) microcirculation, (b) cell proliferation, (c) membrane transport, (d) metabolism of cytotoxic drugs, and (e) hormonal milieu. The results demonstrate that nicotine is able to influence the outcome of antitumor treatment. The mechanism of interaction needs clarification. Additionally, further combination studies with other classes of cytotoxic drugs are warranted.

Animals↗

[Quantitative analysis of cell-kill effects of anticancer drugs: consideration of both in vitro and in vivo experimental systems].

After examining the in vitro cell-kill kinetics of various anticancer drugs by using cultured human cell lines, Shimoyama et al. classified the drugs into two groups according to the types of action: 1) type-I drugs (cytocidal and concentration-dependent action) such as alkylating agents and anticancer antibiotics; 2) type-II drugs (cytostatic and time-dependent action) such as antimetabolites, Vinca alkaloids and L-asparaginase. In the present paper, we will present a rational basis for such a classification by using cell-kill pharmacodynamic models, and consider the optimal dosage regimen depending on the type of drugs by combining the cell-kill kinetic and pharmacokinetic models. In these models, classification of the drugs depends on whether the cell population is kinetically homogenous or not. It is assumed that cell population is homogenous for type-I drugs and there exist both drug sensitive and insensitive cell populations for type-II drugs. The concentration (or dose)-time-cell survival curves in both in vitro and in vivo, which are simulated based on the kinetic models, are consistent with the experimental data found in the literature. Further analysis on the optimal dose regimen according to these kinetic models clarified that the type-I drugs showed a similar cell-kill effect irrespective of the mode of administration as long as the area under the plasma unbound concentration curves (AUCp, free) is kept constant, while the type-II drugs are more effective by multiple dosing or infusion regimen than single administration of a large dose of drugs. In other words, the extents of AUCp, free and the residence time in the plasma (above certain concentrations of drugs) are determinants of the in vivo cell-kill effects of type-I drugs and type-II drugs, respectively. If the pharmacokinetics of newly developed anticancer drugs in human are predicted from the animal data according to the so-called "animal scale-up" technique and combined with the in vitro cell-kill kinetic data by the use of proposed kinetic models, one may obtain not only the optimal dosage regimen but also good screening systems for truly active drugs for the treatment of human cancer.

Antineoplastic Agents↗

[Preoperative treatment of lymph node metastasis in cases of gastric cancer by local injection of anticancer drugs--preliminary report].

For the purpose of producing an anticancer effect on the micrometastasis of the lymph nodes and free cancer cells in the lymphatic ducts in a gastric cancer, activated charcoal was endoscopically injected into the gastric wall preoperatively in 49 cases to adsorb anticancer drugs. The correlation between the histological degree of black staining of the dissected lymph nodes and the clinicopathological factors was studied. Among 2,426 dissected lymph nodes, the degree of black staining was found to amount to 49.9%. Among 201 metastatic lymph nodes, the degree of black staining was 24.9%. Thus, the possibility of an anticancer effect was realized in 25% of the metastatic lymph nodes. From a study of the clinicopathological findings, the degree of black staining was low in cases of advanced cancer. In a histological study, the degree of black staining was found to be higher in the undifferentiated types than in the differentiated types, suggesting that there is a difference in the function of the lymph-reticulo-endothelial system according to the histological type.

Antineoplastic Agents↗

[Basic and clinical study of anticancer effect of etoposide on choriocarcinoma].

To establish a new method for treating choriocarcinoma, basic and clinical studies were made on Etoposide, a newly developed anticancer drug. I. Basic study 1) The crystal violet uptake sensitivity tests for anticancer drugs were examined with 5 human choriocarcinoma cell lines, BeWo, SCH, HCCM-5, JEG and SMT-CCl. 2) A drug concentration which could reduce the survival rate of SMT-CCl cells to 50% was regarded as the standard concentration. 3) Etoposide showed the same strong anticancer activity on all the choriocarcinoma cell lines as Act-D and CPA. II. Clinical study 1) In the treatment of trophoblastic diseases (choriocarcinoma 15 cases and invasive mole 14 cases), Etoposide therapy manifested a much higher effective rate (93.3%) than conventional Act-D therapy (50.0%) and MTX therapy (21.0%). But side effects of Etoposide therapy were milder than those of the other drugs. 2) Especially in the high risk choriocarcinoma group, the remission rate was 50% (PR 3, NC 2 and PD 1) for the conventional MAC protocol and 100% (CR 3 and PR 2) for the MECA protocol. In conclusion, it was demonstrated basically and clinically that Etoposide was very effective in the treatment of choriocarcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

New screening system for selection of anticancer drugs for treatment of human colorectal cancer.

We report an evaluation of a new radiometric technique (BACTEC assay) as a potential screening system for cytotoxic compounds with activity against cancer of the large bowel. Exponentially growing cells of nine different human colorectal cancer cell lines were exposed to a variety of standard anticancer agents with or without documented clinical activity. Each drug was tested in a series of 1-h and continuous exposure studies utilizing three different concentrations. Antineoplastic effects were analyzed as a function of in vivo achievable serum concentrations, namely by a ratio of the concentration required to decrease cell growth to 10% of control to one-tenth of the peak plasma concentration in humans. Our results suggest that COLO 320DM, OM-1, and Ht-29 cells manifest responsiveness to anticancer drugs consistent with that noted in clinical studies with most agents tested. The radiometric technique provides several advantages for a screening system, including reproducibility, a good agreement with the cloning assay, speed, and low costs. The combined use of the BACTEC technique and the three colon cancer cell lines could prove useful as a screen for new anticancer compounds with activity in colorectal cancer.

Antineoplastic Agents↗

A novel nontoxic alkyl-phospholipid with selective antitumor activity, plasmanyl-(N-acyl)-ethanolamine (PNAE), isolated from degenerating chick embryonal tissues and from an anticancer biopreparation cACPL.

A novel alkyl-phospholipid with selective antitumor activity was isolated from an anticancer biopreparation cACPL (crude anticancer phospholipids) and from tissues of degenerating chick embryos. The alkyl-phospholipid was isolated and purified by chromatographic methods using silicic acid column chromatography and thin layer chromatography. The chemical structure of the alkyl-phospholipid was characterized by thin-layer chromatographic analysis of the degradation products after enzymatic digestion with phospholipase C from Bacillus cereus and with phospholipase D, by two-dimensional thin-layer chromatography, infrared spectrum, and mass spectrometric analysis. The alkyl-phospholipid was identified as 1-O-alkyl-2-acyl-sn-glycero-3-phospho-(N-acyl)-ethanolamine, i.e. plasmanyl-(N-acyl)-ethanolamine (PNAE), the main molecular species being 1-O-octadecyl-2-oleoyl-sn-glycero-3-phospho-(N-palmitoyl)-ethanol-amine. PNAE exhibits a selective cytolytic effect on human tumor cells HEp-2, HeLa and T24 in tissue cultures at the concentration of 25 micrograms PNAE per ml and 66-98% inhibition of DNA synthesis in the human tumor cells at concentration as low as 2.5 micrograms/ml, but it does not inhibit at a 50-fold higher concentration the DNA synthesis and normal growth of human fibroblasts (cell line LEP). PNAE represents the main biologically active antitumor component of the cACPL biopreparation and exhibits a significant antitumor effect in vivo in B10/An mice bearing Mc11 fibrosarcoma. Possible molecular mechanism of the selective antitumor activity of PNAE is discussed, involving the selective disturbance of phospholipid metabolism in tumor cells, leading to progressive destruction of tumor cell membranes. The fact that PNAE is nontoxic and selectively active against tumor cells at nanomolar concentrations in vitro as well as in vivo, indicates the possibility of its clinical use. PNAE and cACPL biopreparation might provide a very useful new tool for human anticancer chemotherapy.

Animals↗

[Anticancer drug sensitivity test and its clinical evaluation in 15 cases of acute leukemia and lymphoma].

We carried out in vitro anticancer drug sensitivity tests a total of 24 times in 15 cases of childhood leukemias and lymphomas using the microplate culture and crystal violet staining method. We then compared them with the clinical effects. As a result, the in vitro efficacy rate at onset of cases was 40%, which was less than that for relapsed cases, which was 100%. Especially, cases of ALL at onset all failed. As for the relation between in vitro and in vivo effects, cases for which it was possible to make evaluation both in vitro and in vivo numbered 16. The results for these cases were; true positive rate, 71%; true negative rate, 50%; predictive accuracy, 69%. The true positive rate was higher than the usual rate. As for the efficiency of each anticancer drug, in vitro predictive accuracy for ADR, Ara-C and 4 HCP (CPM) was higher than for other drugs. From these results, it became clear that our method is very useful for the screening of effective anticancer drugs.

Acute Disease↗