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Biomedical subjects

S Kase

Publications and source records attributed to S Kase.

At least 55 records · Page 3Linked to original sources

Increased drug resistance of cultured human cancer cell lines in three-dimensional cellular growth assay using collagen gel matrix.

We have conducted a three-dimensional cellular growth assay using collagen gel matrix with an endpoint of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay, on four human gastric and colonic cancer cell lines. Three-dimensionally growing cells in collagen gel matrix were 2- to 180-fold more resistant to mitomycin C, doxorubicin, 5-fluorouracil, and cisplatin than those in monolayer culture, and these resistances were increased further when the cells increased their three-dimensionality. Furthermore, the influence of fibroblasts in the collagen gel matrix on the chemosensitivity of cancer cells was less than that in monolayer culture. Since this new assay using collagen gel matrix with an endpoint of the MTT assay was able to detect the increase of drug resistance of human cancer cell lines by three-dimensional cellular growth using a simple and convenient procedure, it was considered to be more useful than conventional monolayer cultures for evaluating the chemosensitivity of cancer cells.

Adenocarcinoma↗

High human IgG levels in severe combined immunodeficient mouse reconstituted with human splenic tissues from patients with gastric cancer.

We implanted normal peripheral blood lymphocytes (PBL) from healthy donors and splenic tissues from patients with gastric cancers into the severe combined immunodeficient (SCID) mouse, demonstrating that SCID mouse with splenic tissue can produce a high level of human immunoglobulin G (IgG). The normal PBLs at 10(7) and 10(8)/mouse were implanted intraperitoneally, and three splenic tissues with a size of 3 x 3 x 3 mm from gastric cancer patients were inoculated subcutaneously into the bilateral backs of the mice. At 2, 4, 6 and 8 weeks after inoculation, mice were killed, and the human IgG was assessed by an ELISA method. SCID mice with splenic tissue revealed high human IgG levels from 2 weeks after inoculation and approximately 2 mg of IgG per ml was observed at 8 weeks post-implantation, while the IgG levels in mice treated with PBLs were limited. Since the half life of the extrinsic human IgG was 10.2 days, the high level of human IgG in the SCID mice was supposed to be produced by human plasma cells in the splenic tissue from gastric cancer patients. This model was thought to be adequate for evaluating human immunological functions in vivo.

Animals↗

Clinical usefulness of chemosensitivity testing using the MTT assay.

The results of in vitro chemosensitivity testing using the MTT assay of tumor cells from 140 patients were analyzed with reference to the clinical antitumor effects of the chemotherapy. One hundred and twenty-four (88.6%) of 140 specimens were successfully tested by the method of Mosmann (J Immunol Methods 65:55-63, 1983) with some modifications. When the results of the assay were compared with the clinical effects of chemotherapy in 22 patients with remaining measurable tumor lesions, the overall prediction rate was 86.4% (19/22). Among 31 patients with stage III-V gastric and colorectal carcinomas without remaining measurable tumor lesions, the survival rate of nine patients treated with drugs shown to be effective in the assay was significantly (P less than 0.05) better than that of 22 patients treated with drugs shown to be ineffective.

Adult↗

[Establishment of transplantable human colon cancer cell lines, chemosensitivity of colon carcinomas and the serially transplantable strains with MTT assay].

Three human colon carcinoma xenografts serially transplantable into nude mice were established and named Co-6, Co-7, and Co-8. The chemosensitivity of these stains were assessed by MTT assay of the fresh surgical specimens (primary MTT assay) and the serially passaged xenografts (xenografts MTT assay), in vivo chemosensitivity test in nude mice (nude mouse system) and clinical responses. Drugs used for the experiments are mitomycin C (MMC), adriamycin (ADM), 5-fluorouracil (5-FU) and cisplatin (DDP). The primary MTT assay revealed true negative with MMC and 5-FU on Co-7 and Co-8 cases. The chemosensitivity of the tumor cells seemed to be increased in the xenografts MTT assay and nude mouse system, in which MMC and DDP were evaluated to be positive on Co-6 and Co-7. However, the chemosensitivity pattern of the tumor cells seemed to be stable in these chemosensitivity tests, indicating better to choose the agent with the highest inhibition rate among various tested agents, even when none have an inhibition rate equal to or more than 50%.

Animals↗

[Antitumor activity and toxicity of KB-5424 R, a newly developed antitumor platinum compound].

KB-5424 (ab-(3-aminopyrrolidine)-cd-[glycolato (2-)-0, 0'] platinum (II) is a newly developed antitumor platinum compound which was synthesized at Kanebo Institute for Cancer Research. When the antitumor activity of KB-5424 was evaluated using several rodent tumors, no significant differences were observed between the antitumor activities of KB-5424, cisplatin (CDDP) and DWA-2114 R (DWA). KB-5424 was divided into two kinds of optical isomers, KB-5424 R and KB-5424 S, of which antitumor activity was compared each other. The maximum increased life span (ILSmax) on L 1210 of KB-5424 R was almost equal to that of CDDP and better than those of KB-5424 S and carboplatin (CBDCA). The antitumor activity of KB-5424 R on a human tumor xenograft MX-1 was almost identical to those of CDDP and CBDCA and better than that of DWA. Since the nephrotoxicity of KB-5424 R was significantly reduced comparing with CDDP, this newly developed antitumor platinum compound was thought to be a promising agent for the clinical application.

Animals↗

Muscle strength testing in Parkinson's disease.

Isotonic muscle strength measured by a quantitative technique was decreased in early Parkinson's disease compared to age-matched controls. Weakness was present both on the affected and unaffected side in hemiparkinsonism. Similar degrees of weakness occurred in limbs with tremor or rigidity. Muscle weakness appears to be a primary symptom of Parkinson's disease which may relate to disturbed motor programming due to basal ganglia dysfunction.

Arm↗

Effect of furosemide on postprostatectomy blood loss.

The value of induced diuresis, employing furosemide, on blood loss during and after prostatectomy is evaluated. Two series of 100 patients (consecutive) undergoing prostatectomy, one series with furosemide and one without, are compared. The conclusion drawn from critical analysis is that induced diuresis with furosemide is beneficial in reducing blood loss.

Diuresis↗

Renal microaneurysms and hematuria.

An unusually rare case of chronic hematuria, secondary to an intraparenchymal renal aneurysm is presented. The triad of normal blood pressure, intrarenal aneurysm, and hematuria can be treated conservatively by partial nephrectomy with good results. This treatment is recommended since in a significant percentage of patients with these lesions spontaneous rupture can occur, which is a life-threatening disaster.

Adult↗

Clinical significance of the Rb expression in adenocarcinoma of the lung.

BACKGROUND: Altered retinoblastoma gene expression has been found in various types of cancers including non-small cell lung cancer (NSCLC) and some reports have shown it also to be associated with a poor clinical prognosis in NSCLC. MATERIALS AND METHODS: We evaluated the expression of Rb protein by immunohistochemistry in 90 patients with lung adenocarcinoma who underwent surgical resection and determined its prognostic significance. Also, the expression of p27 by immunohistochemistry and the mutations of the p53 gene by PCR-SSCP were evaluated. RESULTS: Fifty-one out of 90 tumors (56.7%) had reduced expression of the Rb gene. There were no statistical differences between the Rb expression level and clinicopathological status. There was no correlation between the Rb expression level and the p53 mutations or the p27 expression level. The 5-year survival rate in the normal group was 55.1%, which was poorer than that of 73.0% in the reduced group, but showed no statistical difference (p=0.0981). In patients with a reduced Rb-expression, the survival rate of the p53 mutation group tended to show a poorer prognosis than that of the p53 normal group (p=0.0880). In addition, the survival rate of the negative p27 expression group tended to show a poorer prognosis than that of the positive p27 expression group (p=0.0537). CONCLUSIONS: The Rb expression status was not significant as an individual factor for evaluating the prognosis in adenocarcinoma of the lung. Analyses of the accumulation of genetic alteration are necessary to identify the subset of patients with a poor prognosis.

Adenocarcinoma↗

Orthotopic reconstitution of human small-cell lung carcinoma after intravenous transplantation in SCID mice.

We have constructed an orthotopically reconstituted model of human small-cell lung carcinoma (SCLC) by intravenous transplantation in severe combined immunodeficient (SCID) mice. Two human SCLC xenografts, H-69 and Lu-130, were disaggregated and injected through the tail vein of SCID mice. Human SCLCs were orthotopically reconstituted with multi-focal lung tumor growth in all SCID mice after intravenous injection of 5 x 10(6) tumor cells per mouse. The heart and liver were also seeded with actively growing SCLC. This orthotopic reconstitution model of human SCLC in SCID mice should be useful for further studies on the biological behavior and treatment of human SCLC.

Animals↗

Chemosensitivity testing of clinical gastrointestinal cancers using histoculture and the MTT end-point.

Three-dimensional histoculture with the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) end-point was utilized for chemosensitivity testing of 100 clinical gastrointestinal cancers and the results were compared with those obtained with cell-suspension culture with the MTT end-point. Of the 100 surgical specimens, 91 were evaluable using histoculture assay and 66 were evaluable using the cell-suspension assay. When the assay results were compared with historical frequency of clinical response to chemotherapy, the results of the histoculture assay showed a closer correlation than those of the cell-suspension assay. Therefore, the histoculture assay seems to have a higher evaluability rate and a closer correlation with clinical chemosensitivity of gastrointestinal cancers than the cell-suspension assay.

Antineoplastic Agents↗

Modulation by l-leucovorin of 1-hexylcarbamoyl-5-fluorouracil antitumor activity on human gastric and colon carcinomas serially transplanted into nude mice.

Experimental biochemical modulation of 1-hexylcarbamoyl-5-fluorouracil (HCFU) with l-leucovorin (LV) was carried out using human gastric (H-111) and colon (Co-4) carcinoma xenografts serially transplanted into nude mice. Thirty-five or 70 mg/kg HCFU dissolved in 0.2 ml of 1% hydroxymethyl cellulose was administered po daily for 3 weeks except Sundays, and 50, 100, 200 or 300 mg/kg LV dissolved in 0.2 ml physiological saline was administered po 30 min before administration of HCFU. The biochemically modulated antitumor activity was evaluated in terms of actual tumor weight, the relative mean tumor weight and the degree of inhibition of thymidylate synthetase (TS) in the tumors at the end of the experiments, assayed according to the method of Spears et al. Although 35 mg/kg HCFU was ineffective against gastric carcinoma H-111, combination with 200 or 300 mg/kg LV resulted in a positive antitumor effect of HCFU on this strain without any increase of side effects in terms of body weight loss and mouse mortality. The colon carcinoma strain Co-4 showed marginal sensitivity to HCFU (35 mg/kg) alone, but 50 or 100 mg/kg LV modulated the antitumor activity of HCFU on Co-4 to produce a significant positive effect without any increase in toxicity, and HCFU administered with 100 mg/kg LV was more effective than the maximum tolerated dose of HCFU (70 mg/kg) alone. The TS inhibition rate was closely related to the biochemical modulation of HCFU antitumor activity by LV, suggesting that the modulation involves an increase of the ternary complex of TS, 5,10-methylene tetrahydrofolate from LV and 5-fluorodeoxyuridine 5'-monophosphate (FdUMP). Combination of HCFU and LV is therefore thought to be useful in increasing the antitumor activity of HCFU on gastrointestinal carcinomas without enhancing its toxicity.

Animals↗

Recombinant human interferon alpha-2a increases the antitumor activity of 5-fluorouracil on human colon carcinoma xenograft Co-4 without any change in 5-FU pharmacokinetics.

We investigated the modulating effect of recombinant human interferon alpha-2a (IFN-alpha) on the antitumor activity of 5-fluorouracil (5-FU) against a human colon carcinoma xenograft (Co-4) in nude mice with reference to changes in the pharmacokinetic pattern of 5-FU. Mice bearing Co-4 received 5-FU ip at a dose of 90 mg/kg once with or without IFN-alpha, which was administered sc at a dose of 60.000 IU/mouse daily for 7 days before 5-FU treatment. When the area under the curve (AUC) and peak plasma concentration (Cmax) of 5-FU with or without IFN-alpha were measured as pharmacokinetic parameters, the pharmacokinetics of 5-FU was not changed by IFN-alpha administration. This result suggests that the modulating effect of IFN-alpha on 5-FU does not involve augmentation of 5-FU pharmacokinetic parameters.

Animals↗