Effects Of Antitumor Agents Research Articles

Tests for tumor induction by antitumor agents.

We have a long-standing interest in studies of the cytotoxic effects of antitumor agents in vivo and we have been struck by their high capacity to induce selective lesions in cell-renewal systems. In this respect antitumor agents have appeared to be unique among various classes of pharmacologically active substances. For this reason we were greatly interested in the reports by HUGGINS (6) and other workers (8) that the potent carcinogen 7,12-dimethyl- benz(a)anthracene, (DMBA), has toxic effects on hematopoietic cells in bone marrow, thymus, and spleen, on spermatogenesis, and on intestinal crypt epithelium. It seemed appropriate to ask whether antitumor agents which have similar cytotoxic effects might also have carcinogenic activity like DMBA. We chose to study this possibility by testing for tumor induction in mammary epithelium of virgin, female rats. As shown by HUGGINS and others this system is highly susceptible to polycyclic aromatic hydrocarbon carcinogens. It is also susceptible to the carcinogenic effects of X-irradiation (3).

Enhancing effect of clamping of the portal vein on the effectiveness of antitumor agents against abdominal tumor growth.

Enhancing effect of clamping of the portal vein on the effectiveness of antitumor agents against abdominal tumor growth.

Effectiveness of antitumor agents administered subcutaneously to L1210 leukemic mice in silicone rubber devices.

The therapeutic effects of a number of antineoplastic agents administered subcutaneously to L1210 leukemic mice in silicone polymer (Silastic®, Dow Corning Medical Grade) implants is reported. 1-β-d-a

Platelet transfusions and supportive care. A requirement for currently effective chemotherapy.

Two major obstacles to optimal chemotherapy were observed by Sidney Farber not long after he discovered in 1947 that folic acid antagonists can produce remissions in children with acute leukemia. Those obstacles were the massive hemorrhages and infection secondary to thrombocytopenia and leukopenia, caused by the disease or by complications of the treatment. Control of bleeding and infection was needed to bring about the full effectiveness of antitumor agents. Accordingly, Farber proposed the concept of supportive therapy and initiated programs of research to remove those obstacles. 1 In 1954,I joined in this research effort with Dr. Farber and his colleagues, Dr. Gustave Freeman, who had separated platelets from whole blood successfully, and Dr. Edmund Klein, who developed the closed plastic bag method for separation of platelets and other blood components. The safety and the efficacy of platelet transfusions were reevaluated and established. 2 Further studies provided guidelines for dose-scheduling of

口腔癌化学療法に対する実験的研究

To approximate as nearly as possible to clinical condition for fractionated intra-arterial chemotherapy in oral cancer chemotherapy KB cells of 100x10^4/10ml LY-BSS cultivated at 37℃ for 3 days were exposed for a 30 or 60 minutes period at 37℃ to each of the following antitumor agents such as Nitromin (1mcg/ml, 10mcg/ml), Endoxan (2mcg/ml, 20mcg/ml), Toyomycin (0.01mcg/ml, 0.1mcg/ml), Mitomycin C (0.04mcg/ml, 0.4mcg/ml) and Bleomycin (3mcg/ml, 30mcg/ml) prepared with LY-culture medium containing 10% inactivated bovine serum. The antitumor agents were then washed out with Hanks's BSS. Then new LY-culture medium was added to the cells and kept at 37℃ for 3 days. Then the effects of antitumor agents from standpoint of viable cell number, morphologic changes, succinic dehydrogenase activity were studied. Subculture to another culture flasks was carried out simultaneously. Forgowing operation was repeated 5 times. The results obtained were as follows : 1. The results in inhibition of propagation of cells : Effect of Toyomycin varied with concentration and period of treatment. Nitromin and Mitomycin C had nearly the same tendency in inhibition of propagation in cells but they were affected more by time than concentration of treatment. Endoxan and Bleomycin showed different results from above three agents and it was rather affected by concentration than time of treatment. 2. No significant difference was apparent between any two agents in morphologic changes. However, slight tendency for degeneration of cytoplasm was observed in Nitromin ; regressive changes of nucleolus in Mitomycin C ; multinucleated cells in treatment of 20mcg/ml for 60 minutes in Endoxan, compared with other agents. In addition, segregation, cohesion in chromatin, pycnosis, atrophy, fragmentation as regressive changes in nuclei, atrophy in nucleolus, cytolysis were somewhat more noticeable when propagation of cells was inhibited. 3. Giant cells, microcells were observed in each of experimental series but types of agents, time, concentration and number of treatment did not cause any significant difference. The number of giant cells appeared was higher in lower concentration of agents. Also regressive changes of nuclei in giant cells was stronger in higher concentration of agents. Somewhat more microcells were observed in Bleomycin compared with other agents. 4. Increase and decrease in mitosis nearly agreed with increase and decrease in cells in Nitromin and Toyomycin but did not obtain so close an agreement in Mitomycin C. A lot of mitosis and aberrant division were observed through each of experimental series in Endoxan and Bleomycin compared with other agents. 5. No significant difference in changes of succinic dehydrogenase activity was evident depending on type of agents, time, concentration and number of treatment. The changes, however, had a correlation with increase and decrease in cells.

On the study of the implantation of ascites tumor in urinary bladder. IV. Effect of antitumor agents (1)

The effects on tumor of chromomycin A3 (Cm A3), mytomycin C (M. M. C) and nitromin (N. M) were studied. For this rats were employed the urinary bladders of which were transplanted with Yoshida sarcoma and AH 130 hepatoma. The following results were obtained:-1. The relationship between the effect of the drug and its administration time was checked by comparing the 3 groups, the first beginning to receive the drug intravenously or into the peritoneum 3 prior to the transplantation, the second after the transplantation and the third 3 days after the transplantation.The best results were obtained among the group which began to receive the drug immediately after the transplantation.2. In rats which were transplanted with AH 130, 15γ, 30γ and 50γ/kg/day of Cm A3 was administered for 5 days immediately after the transplantation.In the case of administration into the peritoneum the effect of life prolongation was rarely seen, while in the case of intravenous administration the effect was good with 15γ and 50γ/kg administration.3. In rats which were transplanted with AH 130, the effect of M. M. C was observed by giving 0.1mg, 0.2mg, 0.5mg, 1mg and 2mg/kg of M. M. C into the peritoneum, and intravenously 0.1mg and 0.5mg/kg/day for 5 days continuously immediately after the transplantation. A good response was seen in groups which received 0.1mg, 0.2mg and 0.5mg of M. M. C into the peritoneum and in groups which received the drug intravenously.4. The effect of N. M also was checked in the same way as M. M. C. In the case of N. M administration with the dose of 1mg, 3mg and 5mg, the effect of life prolongation was remarkable both in intravenous groups and intraperitoneal groups.5. The effect of life prolongation was checked in the case of combined use of two drugs; 15γ/kg/ day of Cm A3, 0.1mg/kg/day of M. M. C and 1mg/kg/day of N. M were combined so that two of these three drugs constituted one combination, thus 6 combinations being formed, each combination was administered intraperitoneally or intravenously. In the case of intraperitoneal administration no prolongation of life was observed compared to single administration of each drug. However, in the case of intravenous administration good results were obtained by combined use of drugs, especially in the combined use of N. M and Cm A3, and also in the combinations of N. M and M. M. C.In these two combinations 30 day survival was 92%.

Effects of antitumor agents and hyperbaric oxygen in normal and tumor-bearing rodents.

Effects of antitumor agents and hyperbaric oxygen in normal and tumor-bearing rodents.

Effects of antitumor agents on in vitro cells from peritoneal effusion of patients with advanced stomach cancer

Effects of antitumor agents on in vitro cells from peritoneal effusion of patients with advanced stomach cancer

A favourable response in tongue cancer to arterial infusion chemotherapy.

THE CURRENT INTEREST in regional cancer chemotherapy has been stimulated by several factors: (1) Although many cancer chemotherapeutic compounds have been developed and are currently undergoing clinical investigation in patients with far-advanced cancer, most reports have shown that thesystemicadministration of these agents has not resulted in significant practical value in the management of most common forms of cancer. (2) Many common forms of cancer, although beyond conventional therapy, remain localized throughout their evolution and produce symptoms and death from the locally confined, yet uncontrolled, growths. Regional cancer chemotherapy has been developed in an effort to increase the regional effect of antitumor agents in patients with advanced cancer whose tumors are within the distribution of accessible arteries. A method of regional administration of anticancer drugs has been reported which consists of the continuous arterial administration of an antimetabolite through catheters inserted into the major vessels supplying a tumor-bearing area.

The Effect of Anti-tumor Agents on the Dehydrogenase Activity of Tumors.

The fact was presented in this paper that there was no quantitative parallelism between the tumor-growth retarding effect of a compound on animal tumors and its inhibiting effect on dehydrogenase activity in vitro of the living cells of the same kind of tumor. An attention should therefore be paid to this fact when a drug is to be selected for clinical purpose from the anti-cancer agents by comparing their inhibiting activity on this enzyme of tumor piece taken from a patient.