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Biomedical subjects

R Kanamaru

Publications and source records attributed to R Kanamaru.

At least 109 records · Page 6Linked to original sources

[Randomized study of lentinan on patients with advanced gastric and colorectal cancer. Tohoku Lentinan Study Group].

A randomized study of mitomycin C (MMC)+5-FU [control group] vs MMC+5-FU+lentinan (LNT) [LNT group] was conducted in order to evaluate the effect of LNT against advanced gastric and colorectal cancers by the envelope method in 166 patients, comprising of 115 cases of gastric cancer and 51 cases of colorectal cancer. Significant increases were observed in the survival rates for the LNT group (p less than 0.05) for both patients with gastric and colorectal cancer. No significant difference was observed in response rates between the aforesaid two groups, though the response rate in the LNT group was slightly higher than the control group. These results suggest that LNT in combination with anticancer drugs prolong the survival time of patients with advanced gastric and colorectal cancer.

Adult↗

[Phase I study of 5'-deoxy-5-fluorouridine (5'-DFUR)].

A phase I study of a new fluorinated pyrimidine compound, 5'-deoxy-5-fluorouridine (5'-DFUR), was performed in 37 patients with various malignant cancers. Starting dose was 600 mg/m2/day (900 mg/body/day) and escalated up to 3900 mg/body/day. The dose given was divided into 3 administrations a day for 5 consecutive days. Subjective symptoms were observed in cases given a dose of over 2,100 mg/body/day. Gastro-intestinal disturbances such as nausea, vomiting and anorexia were the major side effects. In the hematological and urinary examinations, no severe abnormal signs were observed. The maximum tolerated dose was considered to be 2.100 mg/body/day, and the dose-limiting factor was gastro-intestinal disturbance. 5-FU levels were determined in the serum and tumor tissues. 5'-DFUR was well absorbed. The 5-FU level in tumor tissue was very high at 2 to 3 hours post-dose and then rapidly decreased, being 0.05 microgram/g 12 hours after administration. The optimal dosage for a phase II study was suggested to be less than 2,100 mg/body/day.

Administration, Oral↗

[Phase II study with methyl-6[[[2-chloroethyl) nitrosoamino] carbonyl] amino]-6-deoxy-alpha-D-glucopyranoside (MCNU) in hematological malignancies].

A total of 117 cases with hematological malignancies were treated with MCNU at doses of 70-100 mg/m2. Following are the results obtained. 1. MCNU showed a marked depression of cells in the cases with CML, polycythemia vera and thrombocythemia. The low level of cells was maintained for 2 to 7 months. 2. A good response was observed in several cases with blastic crises of CML. 3. No response was observed in two cases with acute leukemia. 4. Although a fair response was observed in several cases with malignant lymphoma or multiple myeloma, moderate bone marrow suppression was observed in a majority of the cases.

Adult↗

In vitro mode of action, pharmacokinetics, and organ specificity of poly (maleic acid-styrene)-conjugated neocarzinostatin, SMANCS.

The organ specificity and pharmacokinetics of SMANCS, poly (maleic acid-styrene)-conjugated neocarzinostatin (NCS), were investigated in rats. The drug activity accumulated primarily in the regional lymph nodes after subcutaneous injection. After intravenous injection, the drug was found in the kidney, lymph nodes, and bladder in very high concentrations, and in lesser concentrations in the bone marrow, lung, small intestine, liver and spleen. The urinary excretion rate and total recovery of the drug after intravenous injection were higher than those after subcutaneous injection. SMANCS, having a molecular weight of 2.5 x 10(4) daltons, was degraded in vivo to NCS (mol. wt. about 1.1 x 10(4)). This was also confirmed in vitro by incubating the drug with cell homogenates. SMANCS caused strand scission of DNA similarly to NCS in lymphoblastoid cells. However, in a cell-free system using colicin E1 plasmid DNA, a high concentration of SMANCS was required to produce DNA degradation detectable by the alkaline sucrose gradient method.

Animals↗

[Clinical trial of K-247].

The clinical trial of K-247, an anticancer drug showing antitumor effect by new mechanism of action, was performed in a total of 22 patients with a variety of advanced cancers, consisting of 10 cases administered singly and 12 cases combined with other anticancer agents. All patients were treated three or four times every day with oral administration of K-247 (600-800 mg/day). Including one patient receiving a high dosage (over 200 g totally) of K-247, in all cases, no appreciable side effect causing suspension of the administration was recognized. In combination therapies with other anticancer drugs there was rather found a tendency to rescue WBC from decrease. As a clinical result, although all cases tested were insusceptible to prior chemotherapy with various anticancer drugs, one case, which has received palliative operation for rectal cancer accompanied with pelvic infiltration, was experienced after administration of K-247 only, in which the destructive lesion of left sacral on X-ray photograph was restored to almost normal condition and the patient's complaints such as severe pain in the lower legs and difficulty in walking were completely disappeared.

4-Aminobenzoic Acid↗

[A giant chondromyxoid fibroma originated from the right orbital roof.--A case report--].

The authors reported a case of giant chondromyxoid fibroma of the right anterior cranial fossa, arising from the right orbital lamina of frontal bone. A fifteen-year-old boy was admitted because of a recent history of the right exophthalmus and headache. Neurological examination was essentially negative except papilledema in the both optic fundi and the right olfactory disturbance. Skull plain x-ray films showed the bony destruction of the right supraorbital bone and the some of abnormal calcification in the right anterior cranial fossa. CT scan showed cystic low density spots surrounded by irregular ring-like high density areas in the right anterior cranial fossa. Operation was performed on two stages and the tumor was removed totally. The tumor was arising from the orbital lamina of the frontal bone. The size of resected tumor was 7x5x4 cm. The pathological examination confirmed the diagnosis of chondromyxoid fibroma. Postoperatively, the patient is fully schooling without any disturbance 2 years and 7 months after the discharge. In Japan, two cases of intracranial chondromyxoid fibroma have been reported in literature. The authors discussed the histology of chondromyxoid fibroma and the genesis of the membraneous bone origin of the intracranial chondromatous tumor.

Adolescent↗

Studies on the mechanism of action of ACNU, 1-(4-amino-2-methylpyrimidine-5-yl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride: effects on cultured HeLa S3 cells.

Treatment of cultured HeLa S3 cells with ACNU, 100 microgram/ml, for 30 min inhibited the cell growth intensely. The cell number was minimum on the 4th day after the treatment and recovered gradually, but it was still 24% of control of the 14th day. The colony formation, as an index of proliferation ability of cells, was remarkably inhibited and the number of colony formed on the 14th day after the treatment was 8% of control. DNA synthesis was inhibited by 59%, whereas little or no effect was observed on RNA or protein synthesis after 24 hr. Ethylene-14C-ACNU was bound to DNA and RNA to a similar degree, and that bound to the acid-insoluble fraction within 30 min was decreased by half after 24 hr and sustained thereafter. A significant decrease in sedimentation velocity of DNA on alkaline sucrose density gradient centrifugation was observed after 24 hr, and the decrease on neutral sucrose density gradient centrifugation was noticeable already by 2 hr. From the results of this study and other reports, the mechanism of action of ACNU seems to be alkalization of DNA followed by damage to DNA, which progresses quite slowly compared with other alkylating agents, causing cell damage and cell death.

Cell Division↗

A lipophilic derivative of neocarzinostatin. A polymer conjugation of an antitumor protein antibiotic.

A lipophilic derivative of neocarzinostatin (NCS), an antitumor antibiotic, was prepared by reaction with a synthetic water-soluble polymer, [(styrene)1 approximately 3-(maleic acid 4 approximately 7/anhydride 1)]. The reaction was carried out at pH 8.6 for 3 h and aimed at modifying the two nonessential amino groups (alpha-amino of Ala-1, epsilon-amino of Lys-20). The NCS-polystyrene (SMANCS) was purified on a column of Sephadex G-100 in 0.05 M ammonium bicarbonate and the main product was obtained as a single peak. The elemental analysis showed an increased C and a decreased N content. U.v. and i.r. absorption spectra for SMANCS showed the presence of styrene. SDS-acrylamide gel electrophoresis at pH 8.5 and the decreased N content suggested a molecular weight of about 25 000, indicating the numbers of polymers conjugated to be about six units, two of which were found attached to the two amino groups. SMANCS was soluble in organic solvents, in contrast to NCS, and in water. SMANCS exhibited increased chemical and biological stability and appeared to possess similar in vitro biological activity.

Amino Acids↗

Antimetastatic and antitumor activity of a derivative of neocarzinostatin: an organic solvent- and water-soluble polymer-conjugated protein.

A highly lymphotropic derivative of a proteinaceous antitumor agent, Neocarzinostatin, was prepared by chemical conjugation of a water-soluble synthetic poly(maleic acid)-styrene oligomer. The derivative of 2.5 X 10(4) dalton exhibited a strong antitumor activity against AH109A and DBLA-6 as well as antimetastatic activity against metastatic AH109A with which experimental lymphatic metastasis was produced in rats. An increased lipophilicity and molecular weight of the derivative appear to be responsible for its improvement as lymphotropic antimetastatic agent.

Animals↗

Damage of DNA and its recovery in AH-109A cells treated with carboquone in vivo.

A single injection of carboquone at a dose of 0.1 mg/kg body weight induced damage of DNA of AH-109A cells as revealed by alkaline and neutral sucrose density gradient centrifugation. A significant decrease in the sedimentation velocity of DNA on alkaline sucrose density gradient centrifugation was observed 15 min after the injection, and it returned to that of control after 60 min. Thereafter, the size of DNA decreased progressively. When the cells were lysed with 2% sodium dodesyl sulfate solution and analyzed on neutral sucrose density gradient centrifugation, a similar change in the sedimentation velocity was observed. The results obtained from the studies of intraperitoneal growth of AH-109A cells pretreated with carboquone in vivo and the survival of host animals well corresponded to the extent of the damage of DNA as revealed by alkaline and neutral sucrose density gradient centrifugation.

Animals↗

Separation of gastric mucosal cells of rat with proteolytic enzymes, pronase and trypsin, with special reference to the collection, morphology and viability of the generative cells.

Methods to separate and collect gastric mucosal cells of the rat using proteolytic enzymes were devised. Pronase (1.0%) achieved better results than did trypsin (2.0%) in collecting single isolated cells with higher cell yields and viability. The cells dissociated with trypsin retained glandular structures as in situ. The measurement of radioactivity revealed that the incorporation of 3H-thymidine into generative cells was highest in the cell suspension collected by the second 15 min dissociation. It was concluded that the most effective method to obtain dissociated cells from the generative zone of the mucosa is to collect the cells dissociated with 1.0% pronase continuously for a period from 15 to 45 min after the start of dissociation. On autogradiographic analysis with 3H-thymidine, the ratio of generative cells was 10%, approximately 3 X 10(5) cells, in the specimens.

Animals↗