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K Komuro

Publications and source records attributed to K Komuro.

At least 55 records · Page 3Linked to original sources
PubMed1990

Improved antitumor effects of 3'-deamino-3'-morpholino derivatives of pirarubicin.

The preparation and antitumor effects of 3'-deamino-3'-morpholino derivatives of pirarubicin are described. Di-N-alkylation of pirarubicin with bis(2-iodoethyl)ether gave 3'-morpholino-pirarubicin, which was converted into its 13-tosylhydrazone, 13-deoxy derivative and 13-(S)- and 13-(R)-dihydro derivatives. Intraperitoneal administration to murine tumors indicated that the effective dose ranges of the compounds having sp3 carbon at C-13 position were broader than those of the compounds having sp2 carbon. By oral administration, 13-(S)-dihydro isomer was more effective than 13-(R)-dihydro isomer.

Administration, Oral↗
PubMed1990

Biological activities of new anthracyclines containing fluorine, FAD104 and its metabolites.

From various new anthracyclines containing fluorine in their sugar moieties, 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl)adriamycinone-14-hemi pimerate (FAD104) has been selected for clinical investigation, because of its excellent antitumor activity and solubility. In this paper, the mechanism whereby FAD104 exhibits good antitumor activity in vivo was studied through experiments in vitro in comparison with doxorubicin (DOX). FAD104 had weaker activity than DOX in DNA single and double strand scission in P388 cells and in binding to calf thymus DNA. FAD104 was taken up by P388 cells faster than DOX. The ester linkage in FAD104 was gradually hydrolyzed at neutral pH. FAD104 was metabolized to 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl)adriamycinone (FT-ADM) when incubated with mouse or human serum. In mouse serum the esterase activity was about 100 times higher than in human serum. The product of nonenzymatic and enzymatic esterolysis, FT-ADM, was rapidly taken up by P388 cells and accumulated, reaching at a 9.7-fold higher level than DOX. Thus FAD104 was less active than DOX in itself, but it showed much higher activity through conversion into FT-ADM, due to the action of esterase or to spontaneous and gradual hydrolysis at physiological pH. 7-O-(2,6-Dideoxy-2-fluoro-alpha-L-talopyranosyl)adriamycinol (FT-ADM-OH), another metabolite found in mouse serum had the least biological activity among the fluorine-containing anthracycline glycosides, but its activity was still higher than DOX.

Animals↗
PubMed1989

N-salicylidene derivatives of pirarubicin.

The preparation and biological evaluation of N-salicylidene derivatives of pirarubicin are described. Pirarubicin was treated with various kinds of aryl aldehydes. Most of compounds synthesized here were more active than pirarubicin in vitro. Some of them showed significant prolongation of the survival period in experimental mice by oral administration. Interestingly, a derivative containing forphenicine exhibited the broadest dose-response range by intraperitoneal administration.

Animals↗
PubMed1988

Antitumour activity of new semi-synthetic anthracyclines containing fluorotalopyranose.

The authors have synthesized 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl) adriamycinone (FT-ADM) which exhibited strong antitumour activity and weak toxicity. These characteristics of FT-ADM are partly due to the presence of a 2'-fluoro atom which strengthens the glycoside bond. FT-ADM, however, is sparingly soluble in water because of lack of the 3'-amino group of adriamycin. To increase the solubility of FT-ADM, a hydrophilic group was added at the 14-OH group. Then, the 14-hemisuccinate, 14-hemiglutarate, 14-hemiadipiate, 14-hemipimelate and 14-hemisuberate derivatives of FT-ADM were synthesized. Among them, the 14-hemipimelate derivative (FAD-104) was selected for further development because of its potent antitumour activity and weak toxicity. When drugs were injected intraperitoneally every day from day 1 to 9, FAD-104 showed an apparently stronger antitumour effect against mouse L-1210 leukaemia than adriamycin with lower toxicities. FAD-104 was also more effective than adriamycin on L-1210 using other administration schedules. A characteristic feature is that FAD-104 is effective over a very broad range, which will be advantageous for safe clinical use. FAD-104 also showed marked antitumour effect against L-1210 when it was injected intravenously either once on day 1 or three times on days 1, 5 and 9. Thus, FAD-104 may be a more potent antitumour anthracycline than adriamycin.

Animals↗
PubMed1987

Antitumor activity of erbstatin, a tyrosine protein kinase inhibitor.

A tyrosine protein kinase inhibitor, erbstatin, showed no antineoplastic effect on L-1210 mouse leukemia when it was injected alone. Erbstatin was found to be inactivated by incubation in serum, but not in dialyzed serum. It was also inactivated in reconstituted serum containing dialyzed serum components and ferric or ferrous ion. Because erbstatin was considered to be inactivated by the ferric or ferrous ion in serum, foroxymithine, which is a potent chelator for the ferric ion, was given to the mice together with erbstatin. Administration of both erbstatin and foroxymithine showed antineoplastic activity against L-1210 leukemia.

Animals↗
PubMed1986

[Foreign bodies of unknown origin found in a serosal hematoma between the stomach and the pancreas of a patient].

An autopsy of a 55-year-old man who had died suddenly revealed extensive intra-abdominal bleeding and a serosal hematoma between the stomach and the pancreas, in which numerous foreign bodies were found. They were located just adjacent to pancreatic tissue which had undergone changes of acute necrotizing pancreatitis. It was assumed that they had been shaped by a pathological mechanism contributing much to the sudden death of the patient. The nature of the foreign bodies was investigated by comparing their microscopic sections with those of various living organisms and by testing their chemical character with some histochemical methods. However, they had no similarities to known foreign bodies of animal or plant origin found in pathological sections of human tissues and no conclusive evidence on their chemical nature could be obtained either. Our unified opinion is that the foreign bodies might have been formed in human tissues in situ as a result of the pathological tissue changes. The morphological features of the bodies are described in detail and their significance is discussed.

Acute Disease↗
PubMed1986

[Clinical evaluation of a new tumor marker, CA 15-3, in breast cancer; a comparative study with CEA].

Recently, a new RIA method has been developed by Centocor Co., utilizing the monoclonal antibody CA 15-3. We performed a clinical trial to evaluate its utility as a tumor marker for breast cancer in comparison with CEA. We set 15 U/ml as the cut-off value of serum CA 15-3 level from results acquired from controls; 10 volunteers and 17 patients with non-malignant diseases. The CA 15-3 positive rate among the cases of primary breast cancer was 13.3%, which was of poor diagnostic value. In the recurrent cases the positive rate of CA 15-3 was 72.0%, which was valuable compared with that of serum CEA, 52.0%. In the cases of primary cancers other than breast cancer, the positive rate of CA 15-3 was 6.9%.

Adult↗
PubMed1985

[A case of remission of metastatic gastric cancer lesions in the chest and abdominal wall by 5'-DFUR administration].

52-year-old female was weakened and bed-ridden by metastasis of gastric cancer to the chest and abdominal wall, and peritonitis carcinomatosa 2 years after gastrectomy. One week after administration of 5'-DFUR, 1200 mg/d, p.o., a clinical effect was seen. In 3 weeks metastatic lesions had diminished in size, ascites had decreased and the patient had regained her appetite and put on weight. She recovered sufficiently to be able to do some daily work. Pathological degeneration and necrosis of cancer cells were observed. Although she died 8 months after remission, 5'-DFUR was effective in improving her condition and prolonging her life.

Abdominal Muscles↗
PubMed1985

Antitumor spectrum of a new anthracycline, (2"R)-4'-O-tetrahydropyranyladriamycin, and effect on the cellular immune response in mice.

(2''R)-4'-O-Tetrahydropyranyladriamycin (THP), a new anthracycline antibiotic, showed stronger inhibition of the growth of L1210, CCMT (mouse mammary adenocarcinoma) and Yoshida sarcoma in rats than did adriamycin (ADM). The antitumor activity of THP against P388 and Meth-A (mouse fibrosarcoma) was equal or slightly superior to that of ADM. Moreover, THP was active against an ADM-resistant subline of P388. THP at the optimal effective dose against experimental tumors had no toxic effect on the cellular immune system in normal and tumor-bearing mice.

Adenocarcinoma↗