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Biomedical subjects

S Fujimoto

Publications and source records attributed to S Fujimoto.

At least 919 records · Page 51Linked to original sources

[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↗

[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↗

[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↗

[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↗

Phagocytic activity of hyalocytes in postnatal hyaloid artery.

The postnatal hyaloid arteries of rabbits aged between 7 and 21 days were investigated by transmission and scanning electron microscopy. The artery did not yet show significant degenerating processes on the 7th day, but many cells identifiable as hyalocytes were observed in the adventitia on the 10th day. Between 13 and 15 days, the artery began to undergo a marked degeneration. The number of myofilaments decreased in most smooth muscle cells in the media and the cells were transformed, resembling fibroblasts in this cytoplasmic feature. Around 3 weeks, the vascular lumen was completely closed with almost complete loss of the endothelial cells, and the degenerating cellular components were actively phagocytized by the hyalocytes.

Animals↗

Antitumor activity and toxicity of methyl 6-[3-(2-chloroethyl)- 3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside in experimental animals.

A new water-soluble nitrosourea derivative, methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU), was tested for antitumor activity against murine tumors (L1210 and P388 leukemias, B16 melanoma, and Lewis lung carcinoma) and BC-47 rat bladder carcinoma, and the results were compared with those for four other nitrosourea derivatives; chlorozotocin, 1-(2-chloroethyl)-3-(beta-D-glucopyranosyl)-1-nitrosourea (GANU), 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1- nitrosourea hydrochloride (ACNU), and 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU). MCNU was shown not only to have a broad antitumor spectrum against all the tumors tested, but also to be effective over a wide range of dosages. The antitumor activity of MCNU was superior to those of GANU and chlorozotocin and similar to those of ACNU and methyl-CCNU. Furthermore, MCNU and other nitrosoureas were evaluated for toxicity in BDF1 female mice with respect to body weight changes. Weight loss in mice given MCNU at a dose lethal to 10% of the mice was relatively mild and the treated mice regained body weight most rapidly to the pretreatment level among all groups receiving the above drugs at equitoxic doses. These results may suggest that MCNU is a new nitrosourea derivative worthwhile to perform clinical trials.

Animals↗

[An experimental study on the protective effect of nizofenone in cerebral ischemia].

Using the "canine model of complete ischemic brain regulated with a perfusion method" in which it is possible to control the degree of blood flow to a cerebral hemisphere via a perfusion pump, the protective effects of nizofenone against cerebral ischemia was investigated. After pre-treatment with nizofenone, blood flow was reduced via the pump to 1/10 of the normal state and 1 hour later, return to the normal state was allowed. Subsequent changes in EEG activity were observed and the effect of nizofenone evaluated. In the control group, no recovery of EEG was seen following recirculation, but in the group treated with nizofenone, gradual emergence of slow waves was observed. And the degree of recovery of EEG was better in the group administered a large dosage than in those given a low dosage. Our study suggested that within the dose ranges tested, nizofenone ameliorated ischemic brain damage in a dose dependent fashion. But the application of this experimental results to the human clinical situation requires that particular note should be paid to the dangers of transient fall of blood pressure at higher dosages.

Animals↗

Use of endoscopic ultrasonography in small pancreatic cancer.

In spite of recent progress of body imaging diagnostics, such as ERCP, angiography, CT and conventional echosonography, the diagnosis of small pancreatic cancer is still restricted. Conventional US has progressed dramatically; however, intestinal gas or body wall often prevents the demonstration of deeper organs, such as the pancreas head and tail. The development of endoscopic ultrasonography has enabled us to demonstrate clearer imaging of the pancreas head and tail. From May 1980 to December 1983, we have used three types of ultrasonic endoscopy (Olympus and Aloka Co. Ltd.) with sector scan transducer (5.0 MHz or 7.5 MHz) and have examined 118 cases, containing 32 cases of pancreatic diseases. Among 15 cases of pancreatic cancer, 13 were demonstrated by type III (3 cases under 20 mm in size, 1 case between 20 to 30 mm, 9 cases over 30 mm). The scope was introduced into the upper G.I. tract in the same way as in conventional endoscopy. After the balloon tip of the scope was filled with water, scanning was started , having the balloon properly in contact with the duodenal or gastric wall. Cancerous lesions of the pancreas were clearly shown as a low echo mass in all cases. Each size of the lesions measured by EUS corresponded well to the resected specimens. Compared with other diagnostics, such as ERCP, CT, angiography and conventional US, EUS was the most useful method for detection of small pancreatic cancer under 20 mm in size.

Adenocarcinoma↗

[Electron microscopic study of an experimental contusion cataract of a Japanese monkey].

The traumatic cataract was experimentally induced in the lens of a Japanese monkey and observed with the electron microscope. The purpose of this study was to shed some light on the origin of the cataract caused by various factors. The clinical examinations of the experimental animal showed the opacity of the posterior subcapsular cortex. Electronmicroscopic investigations revealed that lens fibers within the opaque region increased in number of mitochondrion, rough surfaced endoplasmic reticulum and other organelles when compared with those in the clinically normal region of the lens. Furthermore, the intercellular space in the opaque region increased to such an extent that large extracellular vacuoles were formed. Many of these lens fibers became swollen and decreased the interdigitation. Some swollen cells showed sparse arrangement of their cytoplasmic filaments. These morphological changes showed an acceleration of water absorption of the lens fibers from a relatively early stage of the traumatic contusion cataract. The increase in number of mitochondrion in such swollen (hydropic) fibers may play an important role in this process. The present experiment suggests that the appearance of so-called hydropic cells is an initial change in the cataractous lens.

Animals↗

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↗

Idiotype-specific T lymphocytes. II. capability of generation of idiotype-specific T lymphocytes is determined by corresponding VH gene.

MOPC-104E (M104E) idiotype-specific and major histocompatibility complex-restricted T lymphocyte activities were investigated in BALB/c (Igh-1a) and its Igh-1-congenic strains of mice, such as C.AL-20 (Igh-1d), BAB-14 (Igh-1b), and CB-20 (Igh-1b). Idiotype-specific T lymphocytes could be induced in BALB/c and BAB-14 by immunization of viable M104E tumor cells followed by surgical removal and in vitro restimulation with the homologous tumor cells. On the other hand, C.AL-20 and CB-20 mice did not show the idiotype-recognizing capacity even though they could mount comparable cytotoxic T lymphocyte activities against M104E to BALB/c and BAB-14. The results strongly suggest that the inducibility of M104E cross-reactive idiotypy closely paralleled the producibility of corresponding idiotype-specific T lymphocytes. Genetically defined VH gene products might act as internal images that construct idiotype network systems.

Animals↗