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Biomedical subjects

F Kanzawa

Publications and source records attributed to F Kanzawa.

At least 55 records · Page 3Linked to original sources
PubMed1985

Recurrence of thymoma with appearance of myasthenia gravis 18 years after surgery: a case report.

A 59-year-old woman was admitted to the hospital because of recurrence of thymoma with appearance of myasthenia gravis 18 years after excision of an invasive thymoma. Recurrence was observed in the anterior mediastinum, right pleura, pericardium and left supraclavicular lymph node. Hashimoto's thyroiditis, vitiligo vulgaris and leukopenia were also seen. After creation of a pericardial window for pericardial effusion, she received vincristine, then carbazilquinone intravenously as single chemotherapeutic agents based on the chemosensitivity by clonogenic assay of the supraclavicular tumor, but response was not achieved. At one and a half years after radiotherapy to the mediastinum, she is now doing well without symptoms and is receiving a fairly low dose of anticholinesterase medication.

Female↗
PubMed1984

Clonogenic cell assay for carcinoma of the lung.

Studies were performed with a clonogenic cell assay system to determine the in vitro sensitivity of carcinoma of the lung to standard chemotherapeutic drugs. Formation of colonies in vitro occurred in 22 of 29 specimens (76%), including 4 of 7 squamous cell carcinomas, 11 of 16 adenocarcinomas, all of 3 large cell carcinomas, and none of 3 small cell carcinomas. Eighteen of these 22 assays (82%) showed growth which was adequate for chemosensitivity testing. Antitumor drugs tested in this study were cis-diamminedichloroplatinum, 5-fluorouracil, adriamycin, mitomycin C, vindesine, vincristine, vinblastine, bleomycin, peplomycin and l-phenylalanine mustard, which are used clinically for chemotherapy of lung cancer. Of ten drugs tested against at least two different tumors, vindesine and mitomycin C were identified as being active against more than three tumors (17%). Twelve of 18 specimens (67%) were not sensitive in vitro to any of the drugs tested. Of the remaining 6 specimens (33%) showing sensitivity to any drug, four tumors were sensitive to only one drug, one tumor was sensitive to three drugs and another was sensitive to four drugs. The in vitro chemosensitivity results seemed well correlated with clinical experience. The human tumor clonogenic cell assay system appears to be a reasonable model for the study of chemosensitivity in carcinoma of the lung.

Adenocarcinoma↗
PubMed1984

Correlation between drug sensitivity determined by clonogenic cell assay and clinical effect of chemotherapy in patients with primary lung cancer.

Correlation studies between the sensitivity of tumor cells determined by clonogenic cell assay and the clinical effect of chemotherapy were performed in patients with primary lung cancer. Thirty-four of 48 patients showed adequate colony formation (greater than or equal to 30 colonies) to test in vitro chemosensitivity. Colony formation of tumor specimens did not differ with regards to prognostic factors such as sex, age, stage, performance status, and prior chemotherapy. The two criteria of in vitro chemosensitivity employed were greater than 70% and 50% reduction in colony numbers. When in vitro chemosensitivity was defined as a colony reduction of greater than 50%, the true positive rate in the assay was 57%, while the true negative rate was 85%. In this case, the predictive accuracy was 79%. When in vitro chemosensitivity was defined as a colony reduction of greater than 70%, the true positive rate for the assay was 100%, while the true negative rate was 81%. In this case, the predictive accuracy was 82%. By Fisher's exact probability test, the overall in vitro/in vivo correlation was statistically significant (P = 0.042 less than 0.05) with the 50% cut-off point, but was not significant (P = 0.053 greater than 0.05) with the 70% cut-off point.

Aged↗
PubMed1982

Antitumor activity of 1-acyloxymethyl derivatives of 5-fluorouracil against L1210 leukemia.

Antitumor activity of 15 1-acyloxymethyl derivatives of 5-fluorouracil was examined by both intraperitoneal injection and oral administration in L1210 leukemia system. Therapeutic ratio for dodecanoyloxymethyl derivative by intraperitoneal injection was 23 which was greater than that for 5-fluorouracil (11). On the other hand, undecanoyloxymethyl derivative of 5-fluorouracil showed the highest therapeutic ratio (5.8) when administered orally which was greater than that for 5-fluorouracil (1.9) and 1-(2-tetrahydrofuryl)-5-fluorouracil (1.0).

Administration, Oral↗
PubMed1982

Murine lymphoma L5178Y cells resistant to purine antagonists: differences in cross-resistance to thioguanine-platinum(II) and selenoguanine-platinum(II).

To determine whether the antitumor activities of thioguanine-platinum(II) [TG-Pt(II)] and selenoguanine-platinum(II) [SeG-Pt(II)] are due to direct actions of these compounds or to the actions of their hydrolysis products, studies were made on a purine antagonist-resistant, murine lymphoma L5178Y/MP subline that lacked the anabolic enzyme hypoxanthine-guanine phosphoribosyltransferase necessary for tumor inhibition. The L5178Y/MP subline proved to be highly resistant to both TG-Pt(II) and thioguanine; the resistance ratios to the two compounds were almost identical. The subline showed high resistance to selenoguanine, but the cross-resistance to SeG-Pt(II) was negligible. Whether the compounds exhibit the delayed cytotoxicity characteristic of purine antagonists was also investigated. Delayed cytotoxicity was demonstrated for TG-Pt(II) as well as for thioguanine and other purine antagonists but not for SeG-Pt(II) or cis-dichlorodiammineplatinum(II). Experiments on cross-resistance and delayed cytotoxicity showed differences in the cytotoxicities of TG-Pt(II) and SeG-Pt(II): TG-Pt(II) exerted its activity through its hydrolysis product thioguanine, whereas SeG-Pt(II) compound was cytotoxic itself.

Animals↗
PubMed1981

Antitumor activity of 3',5'-diesters of 5-fluoro-2'-deoxyuridine against murine leukemia L1210 cells.

Antitumor activity of several 3',5'-diesters of 5-fluoro-2'-deoxyuridine (FUdR) against L1210 leukemia cells following intraperitoneal administration was examined. Esters of FUdR with aromatic acid or aliphatic acid of longer chain length were markedly active. Their activities, with respect to ILS30, were as much as 100 times that of unesterified FUdR. 3',5'-ditoluoyl FUdR also had an improved therapeutic effect: its therapeutic ratio was increased to 8.1, as against 2.0 for FUdR. On the other hand, 3',5'-diesters of FUdR with aliphatic acid of shorter chain length do not appear to be as active as FUdR. The relationship between the antitumor activity and plasma levels has also been examined. After 3',5'-diacetyl FUdR, which is one of the drug group showing low cytotoxicity, the plasma concentration rapidly decreased to an unmeasurable level 3 h after dosing. This tendency is similar to that shown in FUdR. On the other hand, with 3',5'-dipalmitoyl FUdR and 3',5'-dibenzoyl FUdR, each of which has a marked antitumor effect, plasma concentrations decreased slowly and were maintained for as long as 48 h after dosing. The results show that the cytotoxicity of diesters of FUdR is correlated with the duration of a high plasma level of FUdR.

Animals↗
PubMed1980

Mechanism of cytotoxicity of 5-fluorouracil: distinction between the irreversible cytotoxic effect of 5-fluorouridine and the reversible cytotoxic effect of 5-fluoro-2'-deoxyuridine on murine lymphoma L5178Y cells in culture.

To determine the relative importance of the DNA and RNA effects in the cytotoxicity of 5-fluorouracil, we determined the effects of brief exposure to 5-fluorouridine and 5-fluoro-2'-deoxyuridine, compared with 5-fluorouracil, on the subsequent growth of murine lymphoma L 5178 Y cells during prolonged incubations following the removal of the drug from the culture medium. 5-Fluoro-2'-deoxyuridine markedly inhibited cell proliferation by continuous exposure. However, its inhibitory effect by exposure even at 1,000 muM for 1 h easily disappeared within 1 week after removal of the drug from the culture medium. This result indicates that the cytotoxic effect of 5-fluoro-2'-deoxyuridine is reversible on cell proliferation. On the other hand, the exposure to 5-fluorouridine, even at the low concentration of 1.5 muM for 1 h, caused a substantial and irreversible inhibition on cell proliferation. The cytotoxic effect of 5-fluorouracil was also an irreversible action similar to that of 5-fluorouridine.

Animals↗
PubMed1980

Isolation and characterization of the murine lymphoma L5178Y cell line highly resistant to 5-fluorouracil.

5-Fluorouracil-resistant cell line designated as L5178Y/FU was established in this experiment. This is one of the colonies derived from the subculture which acquired resistance to 5-fluorouracil by passing the L5178Y cells through ten successive episodes of culture in Fischer's medium containing 5-fluorouracil, in which each 5-fluorouracil treatment was followed by recovery intervals. The resistance of this line is about 80-fold that of the IC99 of 5-fluorouracil, and also shows a cross resistance to both 5-fluorouridine and 5-fluoro-2'-deoxyuridine. 5-Fluoro-2'-deoxyuridine resistant subline designated as L5178Y/FUdR was also isolated from the subculture which acquired resistance to 5-fluoro-2'-deoxyuridine by using the same selection procedure. The resistance of this line is about 650-fold that of the IC99 of 5-fluoro-2'-deoxyuridine, and shows a partial cross-resistance to 5-fluorouridine, but not to 5-fluorouracil.

Animals↗
PubMed1979

Antitumor activity of alkylesters of 1-beta-D-ribofuranosyl-5-fluorouracil-5'-phosphate against murine lymphoma L5178Y resistant to 1-beta-D-ribofuranosyl-5-fluorouracil.

A 1-beta-D-ribofuranosyl-5-fluorouracil-resistant clone, designated L5178Y/FUR, was established in this experiment. This is one of the colonies derived from a subculture which acquired resistance to 1-beta-D-ribofuranosyl-5-fluorouracil by passaging the L5178Y cells through four sucessive episodes of culture in Fischers' medium containing 1-beta-D-ribofuranosyl-5-fluorouracil; each analog treatment was followed by recovery intervals. In this subline, IC99 values for 1-beta-D-ribofuranosyl-5-fluorouracil was 0.57 muM, which was 24 times as great as in the parent line (0.0024 muM), and this subline showed a cross resistance to 5-fluorouracil. New alkylesters of 1-beta-D-ribofuranosyl-5-fluorouracil 5'-phosphate (FUMP-alkylesters) were synthesized and their antitumor activity was examined against 1-beta-D-5-fluorouracil-sensitive and -resistant L5178Y sublines. Only hexadecylester of 1-beta-D-ribofuranosyl-5-fluorouracil 5'-phosphate was effective, not only to 1-beta-D-ribofuranosyl-5-fluorouracil line but also to 1-beta-D-ribofuranolsyl-5-fluorouracil-resistant subline. Other compounds showed cross resistant in the 1-beta-D-ribofuranosyl-5-fluorouracil-resistant cells.

Animals↗
PubMed1977

Interaction of antitumor agents including doxorubicin or daunorubicin in sarcoma-180 system.

Combination effect of antitumor agents, including doxorubicin and daunorubicin, was evaluated on the concept of pharmacological synergism in ascites sarcoma-180 system. In alternate adminsitration, combinations of doxorubicin plus cyclophosphamide, thio-TEPA, carboquone, actinomycin-D, vinblastine, vincristine, methotrexate, cytarabine, 6-mercaptopurine, or L-asparaginase showed synergism, but in simultaneous one, only three agents, cyclophosphamide, carboquone, and cytarabine, were synergistic. On the other hand, combination of daunorubicin plus one of 8 agents (thio-TEPA, mitomycin-C, bleomycin, actinomycin-D, vinblastine, ancytabine, 6-mercaptopurine, and L-asparaginase) and 6 agents (cyclophosphamide, thio-TEPA, mitomycin-C, bleomycin, actinomycin-D, and vinblastine) provided synergism in alternate and simultaneous administration. Combination effect of agents was affected by the schedule of drug administration for doxorubicin, but weak for daunorubicin. Toxicity of doxorubicin or daunorubicin in combination with other drugs was also affected by the schedule of administration. Combination of a larger number of agents in simultaneous administration provided antagonism compared with an alternate administration.

Animals↗
PubMed1976

Effect of centrophenoxine on cyclophosphamide concentration in blood.

In order to clarify the mechanism of potentiation of cyclophosphamide activity by centrophenoxine, blood concentration of total and activated cyclophosphamide was examined. Blood concentration of cyclophosphamide increased by the compound and biological half-life of activated cyclophosphamide was markedly increased to 30 min from 18 min in intraperitoneal administration. At the same time, concentration of active form in ascites fluid was also increased and biological half-life of the active form was increased to 50 min from 18 min. Similar increase in blood level of active form was also shown by p-chlorophenoxyacetic acid and probenecid, but concentrations at early stages after injection was not increased. As a result, potentiation of cyclophosphamide activity by centrophenoxine was found to be due to maintenance of active form in both blood and ascites fluid at higher levels than those in the control.

Acetates↗
PubMed1975

Effect and toxicity of combination treatment including cyclocytidine or cytosine arabinoside in L-1210 and sarcoma-180 systems.

Combination effect of antitumor agents, including cyclocytidine and cytosine arabinoside, was evaluated on the conception of pharmacological synergism and not of therapeutic synergism. Ascites sarcoma-180 and L-1210 leukemia were used as tumor systems. In sarcoma-180 system, combinations of cyclophosphamide plus cyclocytidine or cytosine arabinoside by simultaneous administration and cyclocytidine plus Daunorubicin or Vinblastine by alternate administration provided synergism. In L-1210 system, many compounds in combination with cyclocytidine or cytosine arabinoside in both simultaneous and alternate administrations provided synergism. Combination effect of agents was affected by the schedule of drug administration. It was found that the combination effect of drugs in one tumor system cannot be generalized to that in other tumor systems, even though equally effective doses of agents were administered in both tumor systems. Toxicity of cytosine arabinoside in combination with other drugs was affected by the schedule of administration. Compounds which provided synergism in simultaneous administration provided antagonism in alternate one. As a result, it was found that alternate administration of drugs is advantageous for the activity and diminution of toxicity of the host animal.

Animals↗