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Biomedical subjects

T Sasabe

Publications and source records attributed to T Sasabe.

At least 37 records · Page 2Linked to original sources

Etoposide microcrystals suspended in oil: a new dosage form to peritoneal carcinomatosis in mice.

Etoposide microcrystals suspended in oil (ETOP-OIL) were examined for their therapeutic effects on peritoneal carcinomatosis in mice. Two days after intraperitoneal inoculation with 10(5) P388 leukemia cells/mouse to CDF1 male mice, etoposide at 10-80 mg/kg was administered intraperitoneally in bolus in the form of ETOP-OIL or in the aqueous solution form. In every dose, the survival curve of the mice given ETOP-OIL was statistically significantly improved in spite of its small lethal toxicity, as compared with those given the identical dose of etoposide aqueous solution.

Animals↗

Lymph nodal vital staining with newer carbon particle suspensions compared with India ink: experimental and clinical observations.

CH40 and CH1500AA are newly prepared carbon suspensions which were examined as vital staining dyes for their usefulness in visualizing lymphatics at operation and to blacken lymph nodes. In mice, these carbon suspensions at 0.001 ml/g of body weight and India ink were injected subcutaneously into the footpad of the right hindpaw. Regional lymph nodes were visualized and were examined stereomicroscopically to determine how intensely these nodes blackened with carbon suspensions. Compared with India ink, CH40 and CH1500AA blackened the regional lymph nodes much faster and more vividly (1-8 min. after subcutaneous injection). As analyzed by centrifugal particle size distribution, CH40 and CH1500AA are narrowly distributed with a small particle size (150 and 167 nm, respectively, in mean diameter). By contrast, India ink is comprised of widely distributed and relatively large particles in suspension (mean diameter--254 nm). In 10 patients undergoing radical gastrectomy for treatment of stomach cancer, CH40 blackened 69% of regional lymph nodes with metastases (38 of 55) and 76% of those nodes without metastases (387 of 512).

Animals↗

Enhancement of cytotoxicity in mouse regional lymph nodes by local tissue injection of aclacinomycin A.

The effect of local tissue injection of activated carbon particle adsorbing aclacinomycin A (ACR-CH) on the cytotoxicity in popliteal, inguinal, paraaortic, and axillary lymph nodes was investigated in mice. Aclacinomycin (0.2 mg/kg), a potent antineoplastic drug was injected subcutaneously into the footpad of mice in the form of ACR-CH or as an ACR solution. After a single injection of ACR-CH, the regional nodal cytotoxic response against mouse YAC-1 lymphoma cells was markedly increased and sustained for 7-10 days. The immune response was also increased after ACR solution but to a much lesser extent. These effects were found in popliteal, inguinal, and paraaortic lymph nodal effector cells but not in the more remote axillary nodes. Absorption of adherence cells largely abrogated the cytotoxic response. These results suggest that ACR-CH did not impair but rather stimulated nodal immunoregulatory cells. Potentially ACR-CH may enhance immune responsiveness of regional lymph nodes after subcutaneous administration while concomitantly curtailing neoplastic growth in these same lymph nodes.

Aclarubicin↗

A new dosage form comprising a suspension of activated carbon particles adsorbing aclarubicin: toxicity in mice.

A new dosage form (ACR-CH), a suspension of small activated carbon particles adsorbing aclarubicin, was studied for its toxicity and histopathological effects on organs in mice. The 50% lethal subcutaneous dose of ACR-CH was 83.5 mg/kg, a value 2.42 times that (34.5 mg/kg) of the aclarubicin aqueous solution. The duration of the toxic effects of ACR-CH was prolonged compared with that of the aclarubicin aqueous solution. On autopsy there was no remarkable difference in macroscopic and microscopic examinations between the two dosage forms.

Aclarubicin↗

[Toxic reduction and superior therapeutic effects on peritoneal carcinomatosis of etoposide particles suspended in oil in mice].

Two dosage forms of etoposide diluted by saline solution (Etp-sol) and etoposide particles suspended in oil (Etp-oil) were examined for the toxicity and therapeutic effects when injected intraperitoneally (ip) in mice. The 50% lethal dose (LD50) values for two weeks observation were 135 mg/kg in Etp-oil and 108 mg/kg in Etp-sol. Two days after intraperitoneal transplantation of 10(6) cells/mouse of P388 leukemia to CDF1 male mice, etoposide was injected intraperitoneally in the form of Etp-oil or Etp-sol. In the mice receiving 20mg/kg of etoposide, 11 of 19 mice given Etp-oil and 3 of 20 given Etp-sol survived to day 60. In the mice receiving 80 mg/kg of etoposide, 1 in 20 treated with Etp-oil and 8 of 20 treated with Etp-sol died from by the toxicity.

Animals↗

Enhanced anti-cancer efficacy on lymph node metastasis using peplomycin adsorbed on small activated carbon particles.

A new dosage form (PEP-CH) of peplomycin was tested for therapeutic efficacy against lymph node metastasis in mice. PEP-CH is a suspension comprising 4 mg/ml of activated carbon, 2 mg/ml of peplomycin and 1.6 mg/ml of polyvinylpyrrolidone in saline. Mice were subcutaneously inoculated with 3 x 10(5) MH134 tumor cells into the left hind paw. Drugs were given on day 10 when cancer had been metastasized in the left popliteal lymph node. Mice were killed on day 17 and the left popliteal lymph node and the left deep inguinal lymph node were extirpated. Since the degree of the metastatic lesion and the lymph node weight correlated with a statistically high probability with each other, the degree of metastatic lesion was evaluated through comparison of lymph node weight. The left popliteal lymph node and the deep inguinal lymph node were 10.5 mg and 4.5 mg in average weight, respectively, in the mice given PEP-CH containing 0.1 mg of peplomycin subcutaneously into the left hind foot-pad. The weights were significantly smaller than those in the mice given an identical dose of peplomycin aqueous solution subcutaneously into the left hind foot-pad or intraperitoneally.

Adsorption↗

Mechanism of suppression of malignancy in hybrids between Y79 retinoblastoma and NIH3T3 cells.

Hybrids were prepared between Y79 retinoblastoma (RB) and nonmalignant NIH3T3 cells and studied to confirm the presumed recessiveness of RB. Twenty hybrids containing both of the dominant gene markers, pSV2neo and pSV2GPT, initially transfected into the parent cells were isolated. All of the hybrids showed a fibroblastic morphology and anchorage-dependent growth. None of the tested hybrids or the parent NIH3T3 cells showed growth in soft agar; the parent RB cells showed a 15% growth in soft agar. The results indicate suppression of the malignant phenotype in the hybrids, confirming the recessiveness of the malignant phenotype of RB at the cellular functional level. Karyotyping of selected hybrids and the parent cells indicated a cumulative representation of all of the Y79 chromosomes in the hybrids, excluding loss of a specific Y79 chromosome causing the suppression of malignancy. Northern analysis of RNA from the hybrids demonstrated the mRNA of the reported putative mouse RB gene, consistent with the complementation of the Y79 RB gene defect by the normal mouse RB gene in the hybrids. Such a complementation may be a factor in the suppression of the malignant phenotype. Interestingly, the abnormal Y79 RB mRNA was absent in the hybrids, suggesting a possible negative feedback control by the normal mouse RB gene product.

Animals↗

Glutathione conjugation of methazolamide and subsequent reactions in the ciliary body in vitro.

Conjugation reaction of methazolamide with glutathione and its subsequent reactions were studied in vitro. Glutathione, cysteinylglycine, and cysteine conjugates of methazolamide were chemically synthesized. All of the three compounds showed absorbance below 330 nm, with maximal absorbance at approximately 300 nm. At the wavelengths below 220 nm, absorbance was proportional to the number of the amino acids each compound had. Amino acid analysis of the glutathione conjugate showed that the conjugation reaction involved the cysteine residue of glutathione. In order to identify the chemical structure of the reaction product, cysteine conjugate was subjected to infrared, proton nuclear magnetic resonance, and mass spectral analyses. These studies indicated that the cysteine conjugate was S-(5-acetylimino-4-methyl-delta 2-1,3,4-thiadiazolinyl)cysteine. The reaction with glutathione was not catalyzed by glutathione S-transferases, but proceeded in the absence of the enzyme. The glutathione conjugate was degraded by bovine ciliary body homogenate to the cysteinylglycine conjugate and then to the cysteine conjugate.

Animals↗

Affinity of intraperitoneally injected activated carbon particles adsorbing mitomycin C to tumor surface of Yoshida sarcoma.

A new dosage form of mitomycin C (MMC-CH) comprising 0.75 mg/ml of activated carbon particles adsorbing mitomycin C at 124 micrograms/mg and 7 micrograms/ml of mitomycin C in a free state was injected intraperitoneally to male rats of Donryu strain transplanted intraperitoneally with 10(7) cells/rat of Yoshida sarcoma 4 days before injection. The rats were subjected to autopsy within 60 min after injection. MMC-CH adhered selectively to the tumor surface of Yoshida sarcoma growing intraperitoneally rather than to the surface of organs such as small intestines which the surface cancer did not affect. Within 120 min after injection, mitomycin C concentration in the tissue samples was bioassayed. Intraperitoneally injected MMC-CH distributed high levels of mitomycin C to the tumor rather than to the unaffected organ located intraperitoneally. Animals killed by cancer after the treatment of MMC-CH were autopsied. Histological effects of MMC-CH were studied microscopically. Mitomycin C adsorbed on activated carbon particles induced degenerative changes in the tissues of tumors to which the activated carbon particles had adhered.

Adsorption↗

[Toxicity of cis-platinum loaded with lactic acid oligomer microspheres in mice].

We have evaluated the acute toxicity of an experimental new dosage form administered intraperitoneally in mice, consisting of cis-platinum loaded with lactic acid oligomer microspheres (CDDP-ms). The LD50 value of the CDDP-ms was 23.8 mg/kg, which amounted to 176% of the LD50 of the cis-platinum solution (13.5 mg/kg). Autopsy findings revealed no additional toxicity due to this dosage form.

Animals↗

[Intracavitary microspheres incorporating cisplatinum in the treatment of malignant effusions--clinical trials].

A new dosage form of cisplatinum (CDDP), lactic acid oligomer microspheres incorporating cisplatinum (CDDP-ms), is designed to slowly release 70% of contained CDDP. CDDP-ms's acute toxicity is as low as 57% of the toxicity of CDDP aqueous solution, and its therapeutic efficacy is statistically significantly strong as compared with that of CDDP aqueous solution, when examined with experimental peritoneal carcinomatosis induced by mouse M5076 ovarian sarcoma. Clinical trials were carried out in 10 patients with malignant ascites (gastric cancer 6, pseudomyxoma peritonei 2, colon cancer 1, pancreas cancer 1) and in one patient with pleural effusion (lung cancer). CDDP-ms at 100 mg/person in terms of CDDP was injected at bolus into the affected cavity. In the 10 patients with ascites, 7 responded completely, two partially and one did not respond. The patient with pleural effusion responded partially. The response rate was 91%. Five of the 11 patients complained of temporary nausea or vomiting. In 5 patients fever higher than 38 degrees C was seen. No other side effect such as kidney, nor liver-damage or blood cell count abnormality was noted.

Animals↗

Adrenal myelolipoma discovered incidentally on abdominal CT and MR imaging.

This report describes an adrenal myelolipoma occurring in a 39-year-old man first noted incidentally by computed tomography (CT). The radiographic findings of this neoplasm are briefly discussed and magnetic resonance (MR) imaging of myelolipoma is also described. Myelolipomas can be distinguished from nonfunctioning adenomas by differences in signal intensity on T2-weighted images.

Adrenal Gland Neoplasms↗

Low-amplified N-myc gene and pp60src in retinoblastoma TOTL-1 cells which undergo neuron-like differentiation.

A cell line of retinoblastoma cells, TOTL-1, was established which had a very weakly amplified N-myc gene. It grew only in clumps that were hardly ever dispersed and showed retarded proliferation. Its doubling time was 160 h. TOTL-1 cells extended short thick processes in monolayer cultures on poly-D-lysine coated substratum, which were markedly different from those of Y79 cells. Light and electron microscopy observation of immunostaining with anti-pp60src antibody revealed that the staining was accumulated in the polar regions of the cells.

Cell Line↗

[Intraoperative chemotherapy with intraperitoneal activated carbon particles adsorbing mitomycin C against peritoneal dissemination of gastric cancer].

A new form of dosage (MMC-CH) was composed of activated carbon particles adsorbing mitomycin C. Intraperitoneal administration of MMC-CH was tested clinically for prophylactic and therapeutic effects on peritoneal carcinomatosis of gastric cancer. The criteria of MMC-CH's administration were equal or less than 70 years old, more than 40 kg in body weight, no disfunction of liver and kidney, no particular findings in electrocardiography, S2 or S3 in the grade of serosal invasion, P0, P1, P2 or P3 in the grade of peritoneal dissemination, according to the General Rules for the Gastric Cancer Study in Surgery and Pathology by the Japanese Research Society for Gastric Cancer. MMC-CH was given to 44 patients undergoing gastrectomy for gastric cancer in our department from 1985 to 1988. The 44 patients were composed of 12 patients with P0 findings (P0 patients), 8 patients with P1 findings (P1 patients), 12 patients with P2 findings (P2 patients), and 12 patients with P3 findings (P3 patients). MMC-CH at 50 mg/person in terms of mitomycin C was administered intraperitoneally before the operation wound was closed. Fifty-seven patients in our department from 1983 to 1987 for whom the same criteria were applicable and did not receive MMC-CH therapy, served as the control group. The 57 patients were composed of 23 P0 patients, 21 P1 patients, 10 P2 patients, and 3 P3 patients. There was statistically with chi 2 test no significant difference of age, sex, depth of infiltration macroscopically and microscopically defined progression of lymph-nodal metastases between the MMC-CH group and the control group. Survival rate was calculated with Kaplan-Meier's method in the overall patients in each of the MMC-CH group or the control group. The overall survival rate in the MMC-CH group was statistically significantly (p less than 0.01-0.05) higher from day 460 to day 552 and from day 736 to day 800 than that in the control group. Next, the patients were classified into two subgroups, namely the subgroup composed of P0 patients and the subgroup composed of P1, P2, and P3 patients, in order to examine each of the MMC-CH's prophylactic effects on subsequent dissemination or its therapeutic effects on established dissemination. Survival rate was calculated with Kaplan-Meier's method in the two subgroups through the same procedures used for the overall survival rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗

Detection of gangliosides as N-glycolylneuraminic acid-specific tumor-associated Hanganutziu-Deicher antigen in human retinoblastoma cells.

Gangliosides were shown to bear the tumor-associated N-glycolylneuraminic acid (NeuGc)-specific Hanganutziu-Deicher (HD) antigen expressed in human retinoblastoma cells. HD antigenic gangliosides were detected by thin-layer chromatography/enzyme-immunostaining using affinity-purified chicken antibody against GM3 containing NeuGc and horseradish peroxidase-conjugated anti-chicken IgG. One to four species of the antigenic gangliosides were detected from all of 4 cell lines, Y79, WERI-Rb1, TOTL1, and YK, as well as freshly cultured retinoblastoma cells and isolated tumor tissue. All cases contained GM3(NeuGc) as an HD antigen. No HD antigenic ganglioside was detected in normal retinal tissues by the same procedure.

Antigens, Heterophile↗