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Biomedical subjects

M Hashida

Publications and source records attributed to M Hashida.

105 records · Page 6Linked to original sources
PubMed1981

Antitumor activity of mitomycin C-dextran conjugate against various murine tumors.

The antitumor activity of a high molecular weight pro-drug of mitomycin C(MMC), MMC-dextran conjugate (MMC-D), was examined against various murine tumors under different experimental conditions. A single intraperitoneal injection of MMC-D exhibited higher antitumor activity against intraperitoneally inoculated B16 melanoma, Ehrlich ascites carcinoma, and P388 leukemia than MMC, but lower activity against BDF1 mouse-transplanted L1210 leukemia. Intratumoral injection of MMC-D showed a superior effect on subcutaneously implanted B16 melanoma, while intravenous injection of MMC-D exhibited reduced activity against P388 and L1210 leukemia compared with MMC. Prior administration of MMC-D at 24 hr before tumor inoculation resulted in a significant increase of the life span of mice bearing L1210 leukemia, suggesting that it shows sustained pharmacological activity. These differences between the activities of MMC-D and MMC in various tumor systems are considered to reflect the improved biopharmaceutical properties of MMC-D resulting from the modification of MMC into a polymeric drug.

Animals↗
PubMed1980

Mitomycin C-dextran conjugate: a novel high molecular weight pro-drug of mitomycin C.

A high molecular weight derivative of mitomycin C (MMC), mitomycin C-dextran conjugate (MMC-D) has been synthesized and its biological and pharmacological properties investigated. MMC is released from MMC-D in vitro with a half-life of 24 h. After intraperitoneal injection of MMC-D, free MMC could be detected in plasma and urine of mouse for 5--8 h, while MMC administered as a free form was eliminated rapidly. After MMC-D, given to mice bearing Ehrlich ascites carcinoma or B16 melanoma there was a reduction in toxicitst that the high molecular weight MMC-dextran derivative is a kind of pro-drug which persists in the body giving a sustained release of free MMC thus significantly increasing the antitumour activity of the parent drug.

Animals↗
PubMed1980

Surgical chemotherapy against lymph node metastases: an experimental study.

Accompanying surgical resection of the primary tumor is removal of its drainage lymph nodes. However, all of the minute regional lymph nodes cannot be identified and some may be left behind. If a certain anticancer agent in the form of an emulsion is injected topically into the lymph nodes, it may suppress the lymphatic metastases. Domestic rabbits were used as experimental animals, because transplantable VX2 tumors are available. The vermiform appendix was selected as the transplantation site because of its rich supply of lymph follicles, simulating lymph nodes histologically, and because the path of lymph drainage is very simple. The drainage lymph node, which is located at the root of the appendix, was selected for study. The rate of transfer of bleomycin into lymph nodes and of its sustained release from the nodes was extremely enhanced by the use of a sphere-in-oil-type emulsion--more than two times higher than in the use of a W/O emulsion. Although prolongation of survival time did not take place in animals receiving the bleomycin solution topically or intravenously, five of the seven rabbits receiving the local administration of bleomycin as a sphere-in-oil or a water-in-oil emulsion, between which differences were not found in tumor effects, survived with complete reduction of the lymph node metastases.

Animals↗
PubMed1978

Antitumor activity of prolonged-release derivative of cytosine arabinoside, cytosine arabinoside-agarose conjugate.

A prolonged-release derivative of cytosine arabinoside (Ara-C), cytosine arabinoside-agarose bead conjugate (Ara-C-AB), was synthesized and its pharmaceutical and pharmacological characteristics were examined. Ara-C was released successively for considerably long period from Ara-C-AB in vitro. Following intraperitoneal injection of 3H-Ara-C-AB, radioactivity could be detected in plasma and urine of BDF1 mouse for four days, while 3H-Ara-C administered as a free form was excreted completely in the first 24 hr. Increase in lifespan of L1210 leukemia-bearing mice was demonstrated after intraperitoneal injection of Ara-C-AB with both the dosage schedules of three days before and one day after inoculation of L1210 cells at the dose of 30 mg equivalent Ara-C/kg.

Animals↗
PubMed1976

Effect of prolonged administration of clonidine to spontaneously hypertensive rats on blood pressure, cerebral norpinephrine content and angiographic finding in the kidney.

1. The effects of clonidine on blood pressure, cerebral norepinephrine content and vascular structures of the kidneys were investigated in 21 SHR. Although the body weight was not affected by long term clonidine treatment up to 36 weeks, the syatolic blood pressure was significantly reduced. The reduction of the blood pressure was already obvious after 1 week administration of clonidine but the effect was more prominent after long term treatment of 30 weeks or longer. 2. The cerebral norepinephrine content was significantly lower in SHR, regardless of with or without clonidine treatment, than in the control Wistar rats. Although the cerebral norepinephrine content was slightly increased following clonidine treatment SHR, the increase was not statistically significant. 3. Angiographic study of the kidneys revealed a poor opacification of the blood vessels and glomeruli in SHR compared with the control Wistar rats. There was no difference in the sizes of the arcuate and interlobular arteries in SHR and the control Wistar rats, although the medial muscular hypertrophy of the arteries was slightly more prominent in the SHR histologically. The more prominent in the SHR histologically. The angiographic and histologic findings of the renal arteries were not altered following long term clonidine treatment. A possibility was considered that the renal arterioles are mainly functionally affected in SHR.

Animals↗
PubMed1976

Serum gamma-glutamyl transpeptidase as a diagnostic aid in the periodic health examination.

Serum gamma-glutamyl transpeptidase is one of the enzymes in diagnosis of liver diseases, since a new colorimetric method was devised by Orlowski, M. et al. Forty mU/ml of serum gamma-glutamyl transpeptidase activity is said to be the upper limit at clinical level. When this value is set up as a screening level in the periodic health examination, about 35% of the subjects including daily drinkers can be evaluated as abnormal. In the present study, the upper limits of serum gamma-glutamyl transpeptidase activity were 102 mU/ml for 147 normal subjects including daily drinkers and 49 mU/ml in 70 non-drinkers selected from the subjects. Therefore, we propose that the standards for screening the abnormal from the normal in the periodic health examination should be 50 mU/ml for non-drinkers and 100 mU/ml for drinkers.

Adult↗
PubMedDate not supplied

Preparation and properties of the immunoconjugate composed of anti-human colon cancer monoclonal antibody and mitomycin C-dextran conjugate.

Monoclonal antibody (mAb) A7, produced against human colon cancer, was conjugated with a polymeric prodrug of mitomycin C (MMC), the MMC-dextran conjugate with an anionic charge (MMCDan) and a molecular weight of 70,000. The amino groups were introduced into the MMCDan by reacting ethylenediamine with the carboxyl group in the spacer arm of the dextran bridge by a carbodiimide-catalyzed reaction. The coupling to mAb A7 was performed using SPDP. A 15 M excess of ethylenediamine produced an optimal MMCDan with amino groups, which resulted in a homogenous conjugate (A7-MMCD) with minimal formation of high-molecular-weight aggregates in about a 30% yield of both IgG and MMC. The molar binding ratio of IgG:dextran:MMC in A7-MMCD was estimated to be 1:1.2:40. A7-MMCD, having MMC prodrug properties, released active MMC with a half-life of 29.1 h and had an almost neutral electric charge under physiological conditions. A competitive binding assay using 125I-labeled A7 revealed that the A7-MMCD almost fully retained its antibody-binding activity. The cytotoxicity of A7-MMCD was assayed by determining the degree of inhibition of [3H]-thymidine in corporation in two different ways using the human colon cancer cell line SW1116. A 48-h continuous exposure test revealed that the pharmacological activity of MMC in A7-MMCD was completely preserved. In addition, A7-MMCD exhibited about a 14-fold greater cytotoxicity than MMCDan when the IC50 values determined using a 2-h pretreatment exposure system were compared. These results suggest that A7-MMCD could be useful in immunotargeting chemotherapy for colorectal cancer.

Antibodies, Monoclonal↗
PubMedDate not supplied

Disposition and pharmacokinetics of a polymeric prodrug of mitomycin C, mitomycin C-dextran conjugate, in the rat.

The disposition and pharmacokinetics of a polymeric prodrug of mitomycin C (MMC), mitomycin C-dextran conjugate (MMCD), following iv bolus administration was studied in rats. Three types of MMCD, conjugates with dextran of molecular weights of 10,000, 70,000, and 500,000, were tested and disposition of carrier dextran and MMC was determined by 14C radioactivity counting and bioassay, respectively. Radioactivity was accumulated in the reticuloendothelial system such as the liver, spleen, and lymph nodes after injection of all three types of 14C-MMCD, but not in the lung, heart, and muscle. Renal distribution of 14C-MMCD varied with the molecular size of the carrier. After injection of cold MMCD, plasma concentrations of MMC in the free and conjugated forms were determined separately on the bases of bioassay. Similar sustained plasma levels of MMC were detected regardless of the carrier size although the concentration-time profiles of MMCD varied with the size of dextran. These plasma concentration data were fitted to a compartment model including a first order conversion process from MMCD to MMC in the central and peripheral compartments of MMCD. Kinetical analysis revealed that MMCD acts as a reservoir of MMC which behaves characteristically as a macromolecule while supplying active MMC in the body.

Animals↗