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Biomedical subjects

F Endoh

Publications and source records attributed to F Endoh.

At least 37 records · Page 2Linked to original sources
PubMed1985

Biodegradable mitomycin C microspheres given intra-arterially for inoperable hepatic cancer. With particular reference to a comparison with continuous infusion of mitomycin C and 5-fluorouracil.

Thirty-two patients with inoperable hepatic cancer underwent intra-arterial hepatic infusion using mitomycin C (MMC) and 5-fluorouracil (5-FU) or intra-arterial hepatic chemoembolization using heated albumin microspheres containing MMC with an average diameter 45 +/- 8 micron. Nineteen of the 32 patients received the MMC microsphere treatment and another 13 received the conventional infusion treatment, lasting for 3.4 months. The administered doses of MMC microspheres were 11.7 +/- 11.1 mg as MMC in the 12 with metastatic cancer and 6.9 +/- 2.1 mg as MMC in the 7 with hepatocellular cancer (HCC). On the contrary, the 13 patients who underwent conventional infusion had average doses of MMC 34.5 +/- 17.3 mg and of 5-FU 13.4 +/- 7.7 g, over 3.4 months. An objective tumor response was obtained in 13/19 (68.4%) under MMC microsphere chemoembolization, compared to 6/13 (46.2%) under the conventional infusion. The average level of CEA in the 12 with metastatic cancer, who underwent MMC microsphere therapy, dropped from 57.7 ng/ml to 16.5 ng/ml, while that in the 10 patients on conventional infusion dropped from 24.0 ng/ml to 17.4 ng/ml; that of alpha-fetoprotein dropped in all 7 with HCC on MMC microsphere chemoembolization, compared to a fall in 1/3 on conventional infusion. With the MMC microsphere treatment, 5 patients from colorectal cancer lived for 15.6 +/- 7.6 months, 2 are alive with a long life expectancy; and 7 patients from gastric or pancreatic cancer lived for only 9.3 +/- 3.3 months. In case of conventional infusion, 6 patients from colorectal cancer survived for 8.6 +/- 3.2 months; and 4 patients from gastric or gallbladder cancer survived for 6.0 +/- 1.0 months. The MMC microsphere treatment is superior at P = 0.059 in survival duration to the conventional infusion treatment. However, much the same survival occurred in 7 on MMC microsphere chemoembolization and 3 on continuous infusion.

Adult↗
PubMed1985

Effects of intra-arterially infused biodegradable microspheres containing mitomycin C.

We prepared biodegradable microspheres containing about 5% mitomycin C (MMC) and of 45 +/- 8 microns in diameter. These preparations were infused into the rat hepatic artery as a preclinical model of intra-arterial infusion treatment for patients with inoperable hepatic tumor. The leaked MMC levels in the hepatic vein decreased below the assay limitation 2 hours after conventional MMC injection, whereas in the case of MMC microsphere the leaked drug levels were maintained at almost the same concentration for over 2 hours after infusion. The entrapped period of MMC microspheres within the hepatic artery was at least 2 weeks, and the necrobiotic foci due to antitumor effects of the condensed MMC released from the microspheres were observed in the area fed by these entrapped arterioles. This phenomenon was never observed in the case of conventional MMC and placebo microspheres. Intra-arterial infusion of MMC microspheres may be a promising clinical treatment for patients with malignant hepatic tumor.

Animals↗
PubMed1985

Mitomycin C carrying microspheres as a novel method of drug delivery.

Biodegradable albumin microspheres containing about 5% mitomycin C (MMC) were prepared in an average diameter of 45 +/- 8 microns by heat denaturation in oil at 120 degrees C and/or cross-linking with glutaraldehyde. These MMC microspheres released, in vitro, about 20% of the contained MMC for over 3 days, and they were intra-arterially infused into albino rabbits and Wistar rats, as a preclinical model of intra-arterial infusion treatment for patients with inoperable hepatic tumor. We infused these microspheres into the femoral artery of rabbits with a VX-2 tumor implanted into the flank of the hindleg. High levels of MMC were maintained for several hours in the tumor and the entrapped MMC microspheres were detected within arterioles in the VX-2 tumors. The growth of VX-2 tumor was inhibited considerably, compared to findings in the control rabbits given conventional MMC. In the next studies, MMC microspheres were infused into the rat hepatic artery, and the levels of MMC in the hepatic vein blood were maintained at much the same concentration for over 2 hours after the infusion, in marked contrast to rapid decreases in the conventional MMC. Histologic findings revealed that MMC micro-spheres were entrapped within the hepatic arterioles for over 2 weeks and released biologically active MMC into the neighboring tissues for prolonged periods of time.

Albumins↗
PubMed1985

[Anticancer treatment with a combination of antimetabolites of polyamine and pyrimidine].

A combined efficacy of the polyamine antimetabolites, alpha-difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG) with two fluorinated pyrimidines was studied. DFMO, MGBG, 5-FU and 5'-deoxy-5-fluorouridine (5'-DFUR) were administered intraperitoneally to BALB/c nu/nu mice bearing xenotransplanted human gastric cancer for 5 consecutive days. Similar antitumor efficacies were observed in 3 groups treated with DFMO plus MGBG, DFMO, MGBG plus 5-FU as well as DFMO, MGBG plus 5'-DFUR. The two groups on 5-FU or 5'-DFUR alone did not differ in antitumor effects from the control, although reasonable levels of 5-FU were involved in tumor tissues. Hepatic and splenic 5-FU levels after 5-FU administration were significantly higher than those after 5'-DFUR, and marked decrease in mouse body weight was caused by 5-FU alone as well as 5-FU plus polyamine antimetabolites for 5 consecutive days. DNA biosynthesis and spermine levels in the tumor tissues on day 2 after cessation of the treatments dropped in 3 groups with DFMO plus MGBG, DFMO, MGBG plus 5'-DFUR as well as DFMO, MGBG plus 5-FU, while on day 6 there was little difference between the control and treated groups. These data suggest that combination with 5-FU or 5'-DFUR does not enhance the antitumor activity of polyamine antimetabolites by this experimental regimen.

Animals↗
PubMed1985

[Preoperative cancer chemotherapy for gastric cancer].

Preoperative cancer chemotherapy for gastric cancer was reviewed with special emphasis on histologic findings and survival. Preoperative chemotherapy with intravenous, split administration of MMC 40 mg caused considerable damage to "micro-solitary metastatic foci" in metastatic lymph nodes. In view of the lipid-adsorbing ability of the lymphatic stream, emulsified 5-FU was used orally in 182 patients with gastric cancer; histologic findings revealed that the emulsified 5-FU enhanced the antitumor efficacy for metastatic lymph nodes as well as the primary lesion. However, the 5-year survival rate for gastric cancer patients undergoing preoperative emulsified 5-FU therapy did not differ from the control, with only the exception of patients with Stage III gastric cancer. On the other hand, combined therapy involving preoperative intra-arterial infusion and surgery was carried out in 62 patients with gastric cancer. These preoperative treatments using MMC, 5-FU, VLB, MTX and/or cytosine arabinoside entailed continuous infusion for 15 to 20 hours; the histologic changes observed revealed marked antitumor effects on the primary focus as well as metastatic lymph nodes. The five-year survival rate for the 62 patients was compared with that for 99 patients with gastric cancer in the corresponding period. The survival rate was analyzed based on the degree of serosal invasion. The overall survivals in the 62 patients were higher than those in the controls for the first 3 years. At 4 to 5 years, the survival rates for both the treated and control groups were approximately equal. In patients without serosal invasion, the survival rates were higher in treated cases than in the controls for the first 2 years. Thirty-nine patients with serosal invasion had significantly higher survival rates than the controls for the first 3 years. The survival rates for the treated patients with cancerous infiltration of ther organs were about the same as those for the corresponding control patients.

Administration, Oral↗
PubMed1985

[Intra-arterial infusion chemotherapy with mitomycin C containing albumin microspheres].

Enhancement of anti-tumor effect by intraarterial embolization chemotherapy with albumin microspheres containing mitomycin C(MMC-ms) was studied. MMC-ms (1.2 mg/kg) was injected into the femoral artery of rabbits and the lower thigh muscle was extirpated to measure the MMC concentration within it. Although the concentration became rapidly decreased in the case of conventional MMC injection, a high MMC level was sustained by MMC-ms injection. In a further study, male Wistar rats weighing 300 to 350 g were injected with MMC-ms into the hepatic artery and then their livers were resected to investigate the process of degradation of MMC-ms. Microspheres were found to be retained in the hepatic arterioles for at least 2 weeks, but in thicker arterioles, fully-packed microspheres were not degraded even over 4 weeks. Clinically, in 22 patients with hepatic malignancies, consisting of 8 primary and 14 metastatic, MMC-ms was injected into the hepatic artery and its antitumor effect was evaluated by CT scan or sonography. Since effective tumor regression was observed in 14 patients (64%) and no serious side effect was seen, the clinical utility and efficacy of intraarterially administered MMC-ms were proved.

Albumins↗
PubMed1984

Intra-arterial administration of heated albumin microspheres containing mitomycin C to rabbits with VX-2 tumor.

In an attempt to enhance antitumor effects, we prepared heated albumin microspheres containing mitomycin C (MMC). These MMC microspheres have an average diameter of 45 +/- 8 micrometers and contain about 5 per cent of MMC. The intra-arterial MMC microsphere treatment, for albino rabbits with implanted VX-2 tumor, increased remarkably the tissue MMC levels, compared to that with conventional MMC, and resulted in conspicuous antitumor efficacy. This approach to antitumor chemotherapy should be effective for selected patients with malignant tumor receiving a blood supply from an end-artery.

Animals↗
PubMed1984

[Preclinical studies of intra-arterial chemotherapy using mitomycin C microspheres].

Heated albumin microspheres 45 +/- 8 microns dia. containing 5% mitomycin C were infused into rabbit femoral artery to assess the depot effects. MMC levels were measured in the muscle and VX -2 tumor tissues fed by the femoral artery as well as in the drainage vein blood. Furthermore, the histologic changes in the VX -2 tumor and the MMC microspheres entrapped in the arterioles were surveyed microscopically. Drug concentration in the case of MMC microspheres was maintained at high levels in both tissue and venous blood over 4 hours, but in the rabbits infused conventional MMC, drug levels decreased below the assay limitation 2 hours after injection. The microscopic findings 2 weeks later revealed necrotic VX -2 tumor tissue as well as the MMC microspheres remaining in the arterioles .

Animals↗
PubMed1984

[Combined therapy with polyamine biosynthesis inhibitors and mitomycin C].

An attempt was made to analyse tumor growth after cessation of combined therapy with the polyamine biosynthesis inhibitors, alpha-difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG), as well as mitomycin C (MMC). DFMO 1000 mg/kg, MGBG 50 mg/kg and/or MMC 2 mg/kg were given intraperitoneally to BALB/c nu/nu mice xenotransplanted human gastric cancer, and its growth as well as DNA biosynthesis were measured daily, after cessation of these combined treatments. Histological observation of the tumor was also performed by hematoxylin-eosin staining. The combination with DFMO and MGBG stunted tumor growth during the treatment, but 3 days later its growth and DNA biosynthesis were accelerated distinctly. MMC injection halted tumor growth, and 5 days after termination of MMC injection its growth rate and DNA biosynthesis almost completely recovered. The microscopic findings on the 4th day after termination of MMC injection were similar to those of DFMO + MGBG treatment. The combination DFMO, MGBG and MMC suppressed not only tumor growth during the treatment, but also tumor growth and DNA biosynthesis over 7 days. The histologic observation 4 days later revealed extensive damage.

Animals↗
PubMed1984

[Experimental studies on hepatic cancer chemo-embolization].

Mitomycin microspheres (MMC MS), which contain about 5% of MMC and have an average diameter of 45 +/- 8 microns, were administered into the rat hepatic artery in a preclinical study on antitumor treatment for human hepatic cancer. Plasma GOT and GPT activities increased markedly 24 hours after MMC MS injection; they decreased to within the normal range within 3 days of the injection. Hepatic necrobiosis was observed in the area adjacent to the hepatic arterioles containing MMC MS, but was not observed in rats injected with placebo microspheres. The hepatic vein blood of MMC MS treated rats contained a markedly high level of MMC, compared to rats treated in the conventional fashion with MMC. Furthermore, MMC MS remained within hepatic arterioles for over 3 weeks.

Alanine Transaminase↗
PubMed1984

[Experimental hyperthermo-chemotherapy for human gastric carcinoma transplanted in the nude mice].

Human gastric carcinomas serially xenotransplanted into BALB/c nu/nu mice were treated by hyperthermo-chemotherapy with mitomycin C (MMC). The antitumor efficacy was assessed by both single and double treatments of 25-minute hyperthermia (43.5 degrees C) and/or 2.0 mg/kg of MMC (ip). Tumor weight was estimated using Battelle's Columbus Laboratories protocol. To assess DNA biosynthesis in the tumor cells, the xenotransplanted tumors were excised at prescribed times after these treatments 60 minutes after 3H-thymidine injection (ip), and were examined microscopically. In the group treated twice by hyperthermo-chemotherapy marked growth inhibition and microscopic damage of the tumors were observed, while such features were not recorded in groups treated twice by hyperthermia only and chemotherapy only, nor in groups given single hyperthermo-chemotherapy, or hyperhermia and chemotherapy. In the single-treated groups, DNA biosynthesis was remarkably inhibited by hyperthermo-chemotherapy over 24 hours. The present results suggest that repeated treatments of hyperthermo-chemotherapy with MMC may be effective in the treatment of human gastrointestinal cancer.

Animals↗
PubMed1984

[Evaluation of severe side effects of high-dose methotrexate in osteosarcoma].

Severe toxicity associated with high-dose methotrexate (HD-MTX) combined with citrovorum factor rescue (CR-Rescue) was evaluated in the 365 courses in 54 patients with osteosarcoma. Anaphylactoid reaction developed in 8 patients (14.8%), 8 courses (2.2%). The mean age was 14 years old. The total dose given was 85770mg in mean and 1840 mg per body weight (kg). The occurrence was proportional to the dose and the number of the course. Plasma MTX concentration remained under 10(-7) mol/l during the episode. Delayed clearance of MTX from plasma was treated with massive CF-Rescue in 10 patients (19%) (the mean age of 13.6), in 12 courses (3.3%), which was observed on an average at the 7th course when the total dose reached to 59530 mg, or 1390 mg per body weight (kg). Neurotoxicity was observed in only one patient (1.9%), one course (0.3%). Severe toxicity associated with HD-MTX therapy tended to occur according to dose escalation and the number of administration. To overcome severe toxicity careful observation of clinical symptoms and signs as well as adequate treatment of side effects without delay are of importance.

Adolescent↗
PubMed1983

Continued in vitro and in vivo release of an antitumor drug from albumin microspheres.

Heated albumin microspheres with an average diameter of 45 +/- 8 microns and containing mitomycin C, released, in vitro, about 20% of this antibiotic over a 3-day period. VX-2 tumors were implanted into the hind leg of rabbits and the drug-containing microspheres were injected into the femoral artery of these animals. High levels of the drug were maintained for several hours in the tumor and growth of the tumor was inhibited considerably, compared to findings in control rabbits given the conventional mitomycin C. Half the number of the rabbits treated with our new method are alive with no evidence of tumor.

Animals↗
PubMed1983

[Studies on biodegradable microspheres containing mitomycin C].

For the purpose of enhancing antitumor effects, we prepared heated albumin microspheres containing an antitumor drug, mitomycin C. The biodegradable MMC microspheres which have an average diameter of 45 +/- 8 mum contain approximately 10% of MMC and release in vitro approximately 20% of the MMC over 3-day period. The microspheres were injected into albino rabbit femoral artery of the hind leg into which a VX-2 tumor had been implanted. Peripheral blood levels of MMC were reduced as compared to the conventional MMC group, within 60 minutes after injection. Subsequently in the MMC-microsphere administered rabbits, the level was higher than in the conventional MMC administered group. The survival of VX-2 tumor-bearing rabbits prolonged markedly with MMC microspheres.

Animals↗
PubMed1983

[Combined antitumor therapy with polyamine biosynthesis inhibitors and mitomycin C].

A combined effect of the polyamine biosynthesis inhibitors, alpha-difluoromethylornithine (DFMO) and methyglyoxal-bis-guanylhydrazone (MGBG) with mitomycin C (MMC) was studied. DFMO, MGBG and MMC were given intraperitoneally to nude mice xenotransplanted human gastric cancer. This new combination of the three drugs resulted in the complete halt of the xenotransplanted tumor growth and marked decline of spermine levels in the tumor tissues. The other treatments with DFMO and MGBG as well as MMC alone were inferior to this new combined therapy in suppression in both tumor growth and tissue spermine level. These data suggest that this new combined treatment be effective against human gastric cancer.

Animals↗