Biomedical subjects

S Kase

Publications and source records attributed to S Kase.

63 records · Page 4Linked to original sources

PubMedDate not supplied

Combined effect of 5-fluorouracil and carboplatin against human gastric cancer cell lines in vitro and in vivo.

The antitumor activity of a sequential combination of 5-fluorouracil (5-FU) and carboplatin (JM-8) was evaluated using gastric cancer cell lines in vitro and in vivo. In the in vitro study, the sequence of 5-FU followed by JM-8 showed higher antitumor activity than that of the reverse sequence. The sequence of 5-FU at 5 micrograms/ml for 24 h followed by 5 micrograms/ml JM-8 for 24 h showed antitumor activity almost equivalent to that of 10 micrograms/ml 5-FU for 24 h and higher activity than that of 10 micrograms/ml JM-8 for 24 h on two cell lines. To evaluate the antitumor activity and toxicity of 5-FU and JM-8 in vivo, BALB/cA nu/nu mice bearing human gastric cancer xenografts St-15, St-40 and SC-1-NU were administered 5-FU and JM-8 intraperitoneally. The sequence of 5-FU prior to JM-8 showed higher antitumor activity than that of the reverse sequence on all the xenografts, and simultaneous administration of 5-FU and JM-8 showed the most potent antitumor activity on St-40 and SC-1-NU. On the other hand, the sequence of 5-FU before JM-8 showed the lowest toxicity in all the treated groups, in terms of death rate, body weight loss and spleen weight loss. This combination is thought to be a promising chemotherapy regimen, showing high antitumor activity without an increment of toxicity.

Adenocarcinoma↗

PubMedDate not supplied

Antitumor activity of (2''R)-4'-O-tetrahydropyranyl adriamycin on human gastric cancer cell lines in vitro and in vivo.

The antitumor activity of (2''R)-4'-O-tetrahydropyranyl adriamycin (pirarubicin; THP) was assessed using human gastric cancer cell lines in vitro and in vivo. The cytotoxicity of THP on MKN-28 and MKN-45 was superior to that of adriamycin (ADM) as detected by a growth assay with an MTT colorimetric endpoint. When the same doses of THP and ADM were administered intraperitoneally to nude mice bearing St-15, St-40 and SC-1-NU, the antitumor activity of THP was almost equivalent to ADM in terms of relative mean tumor weight. However, the adverse effects of THP were also significantly lower than those of ADM in terms of death rate, body weight loss and spleen weight loss. This was also confirmed in THP or ADM combination chemotherapy with mitomycin C and 5-fluorouracil on St-15 and MKN-45. These results indicated that THP is a candidate anthracycline to replace ADM for combination cancer chemotherapy in gastric carcinoma.

Animals↗

PubMedDate not supplied

Recombinant human interferon alpha-2a increases 5-fluorouracil efficacy by elevating fluorouridine concentration in tumor tissue.

The modulating effect of recombinant human interferon alpha (IFN-alpha) on the antitumor efficacy of 5-fluorouracil (5-FU) against human carcinoma cell lines was investigated in vitro and in vivo. 5-FU, fluorouridine (FUR) or fluoro-5'-deoxyuridine (FUdR) were tested against cultured human colon tumor C-1 cells with or without IFN-alpha. The in vitro antitumor activity of 5-FU was enhanced by the addition of IFN-alpha, but IFN-alpha did not increase the effect of FUR or FUdR. The in vivo antitumor activity of 5-FU with or without IFN-alpha was assessed using Co-4, a human colon carcinoma xenograft, in nude mice. Thymidylate synthetase inhibition and concentration of FUR in the treated tumor tissues were concomitantly measured. A synergistic effect of 5-FU and IFN-alpha was observed on Co-4 in nude mice, and this in vivo synergism was obtained without any increment of thymidylate synthetase inhibition or side effects in terms of death rate and body weight loss. The intratumoral concentration of FUR was significantly increased by the addition of IFN-alpha in Co-4 tumor tissue treated with 5-FU. These results suggest that the mechanism of the combined effect of 5-FU and IFN-alpha is not related to enhancement of thymidylate synthetase inhibition, but to an increase of FUR concentration in the target tumor tissue. It is expected that this combination method will be clinically useful for the treatment of advanced colorectal carcinoma.

Animals↗

PubMedDate not supplied

A newly developed hexamethylmelamine derivative, SAE9 with both antitumor and aromatase-inhibitory activity.

Hexamethylmelamine (HMM) has previously been shown to be active against ovarian, breast and small cell lung cancer. However HMM dose not have aromatase-inhibitory activity. A newly developed HMM derivative, 2-N,N-dimethylamino-4, 6-bis (1-H-imidazol-1-yl)-1,3,5-triazine (SAE9), was found to have direct antitumor activity as well as aromatase-inhibitory activity. The direct antitumor activity on breast carcinoma cell lines (MCF-7, R-27 and MDA-MB-231) was assessed using the 3-(4,5-dimethylthiazol-2yl)-2, 5-diphenyl tetrazolium bromide (MTT) on cells growing in monolayer culture. The 50% inhibitory concentrations (IC50) of SAE9 were found to be approximately 10(-4) M for each cell line, roughly equivalent to those of HMM. When the aromatase-inhibitory effect was assessed using a human placental aromatase-inhibitory assay, the IC50 of SAE9 was 5.5 x 10(-7) M, which was superior to that of aminoglutethimide (AG) (3.8 x 10(-5) M). In a rat uterine growth model treated with androstenedione as the in vivo aromatase inhibition assay, SAE9 had an effect equivalent to that of AG. Since SAE9 has both antitumor and aromatase-inhibitory activity on breast carcinoma cell lines with estrogen dependency, this and similar non-steroidal aromatase inhibitors are thought to be promising for further study.

Altretamine↗

PubMedDate not supplied

Different chemo- and endocrino-sensitivity of MCF-7 cells with or without estradiol supplement in vitro.

The sensitivity of MCF-7 cells to tamoxifen (TAM) and mitomycin C (MMC) was assessed in rapidly and slowly growing cells with or without estradiol supplementation, respectively. The growth of MCF-7 was inhibited by MMC in a concentration-dependent manner with or without estradiol (E2) supplementation. Preincubation with MMC suppressed subsequent E2 stimulated growth of MCF-7. TAM inhibited the growth of MCF-7 supplemented with E2 and preincubation with TAM prevented subsequent E2 stimulated growth of MCF-7. However, TAM did not inhibit the growth of MCF-7 cells in E2 free medium. These results suggested that MMC may be more effective than TAM on breast cancer cells in the dormant or slow-growth phase.

Breast Neoplasms↗

PubMedDate not supplied

Site-specific chemosensitivity of human small-cell lung carcinoma growing orthotopically compared to subcutaneously in SCID mice: the importance of orthotopic models to obtain relevant drug evaluation data.

We have developed a novel in vivo model of human small-cell lung carcinoma (SCLC) using orthotopic reconstitution by injecting human SCLC in the tail vein of severe combined immunodeficient (SCID) mice whereby the SCLC grows in the lung and other organs. Cisplatin (DDP) had significant antitumor effects on the SCLC growing orthotopically in the lung whereas mitomycin C (MMC) did not, thereby reflecting the clinical situation. However, the opposite effects were found when the SCLC was growing subcutaneously, where the tumors responded to MMC and not to DDP. This suggests that the tumors growing orthotopically reflect the clinical effects of drugs on human SCLC more closely than the tumors growing subcutaneously. Therefore, this orthotopic reconstitution model of human SCLC in SCID mice is thought to be useful for studies on the treatment of human SCLC and emphasizes the need for orthotopic models for relevant cancer drug evaluation.

Animals↗

PubMedDate not supplied

Immunochemotherapy prevents human colon cancer metastasis after orthotopic onplantation of histologically-intact tumor tissue in nude mice.

A metastatic model of human colon cancer has been previously established using orthotopic onplantation of histologically intact in tissue nude mice. In this study, effects of immunochemotherapy using OK-432, 5-fluorouracil (5-FU) and mitomycin C (MMC) on Col-2-JCK, a human colon cancer xenograft, were evaluated using this model. When 5-FU and MMC were administered without OK-432, liver metastases were not reduced even at maximum tolerated doses of both drugs, although cecal tumor growth was significantly reduced. On the other hand, when combined with OK-432, both 5-FU and MMC reduced liver metastases with synergistic reduction of cecal tumor growth, demonstrating the potential of combining immunotherapy with chemotherapy against metastases.

Animals↗

PubMedDate not supplied

Interferon beta increases antitumor activity of 5-fluorouracil against human colon carcinoma cells in vitro and in vivo.

The modulating effect of human fibroblast-derived interferon beta (IFN-beta) on the antitumor effect of 5-fluorouracil (5-FU) against human colon carcinoma cells in vitro and in vivo was investigated. The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay was carried out in vitro using the cultured human colon cancer cell line C-1. IFN-beta at concentrations of 50, 500, 5,000 and 50,000 IU/ml was added to the cultured tumor cells with or without 5-FU at concentrations of 10, 50 and 500 micrograms/ml. The antitumor activity of 5-FU with or without IFN-beta was assessed using Co-4, a human colon carcinoma xenograft in nude mice, with reference to thymidylate synthetase inhibition. IFN-beta was administered subcutaneously daily for 14 days at doses of 6,000, 60,000 and 600,000 IU/mouse. The combined antitumor effect with 5-FU was evaluated by simultaneous intraperitoneal administration of 5-FU at doses of 10 and 20 mg/kg daily for 10 days. The antitumor activity of IFN-beta alone increased in a dose-dependent manner against Co-4 in nude mice, whereas its antitumor activity in vitro against C-1 was limited. The synergistic effect of 5-FU and IFN-beta was observed both in vitro and in vivo, and the in vivo synergism was obtained without any enhancement of thymidylate synthetase inhibition or side effects in terms of death rate and body weight loss. These results suggest that the mechanism of the combined effect of 5-FU and IFN-beta is not related to enhancement of thymidylate synthetase inhibition or the host immune system, since human fibroblastoid IFN-beta is species-specific to humans. The clinical usefulness of this combination method for the treatment of advanced colorectal carcinoma is expected.

Animals↗

PubMedDate not supplied

Interferons alpha-2a and beta increase the antitumor activity, detected by MTT assay, of 5-fluorouracil against experimental and clinical human gastrointestinal carcinomas.

In order to investigate the combined antitumor activity of 5-fluorouracil (5-FU), and recombinant human interferon alpha 2a (IFN alpha) or human fibroblastoid interferon beta (IFN beta), the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay was carried out using a cultured human colon cancer cell line (C-1) and fresh surgical specimens of gastric and colon carcinomas. IFNs did not show positive antitumor activity against C-1 cells, whereas 5-FU showed time- and concentration-dependent antitumor activity against C-1 cells. Furthermore, the antitumor activity of 5-FU on C-1 cells was augmented by IFN alpha or beta. When 5-FU (50 micrograms/ml) with IFN alpha (50 IU/ml). or IFN beta (50 IU/ml) was applied for the MTT assay with 48 hours incubation of fresh surgical specimens of gastric and colon carcinomas, the inhibition rates increased by 10% in 9 of 21 gastric specimens and in 18 of 36 colon carcinomas for IFN alpha (47.4% or 27/57), and in 8 of 15 gastric specimens and in 15 of 28 colon carcinomas for IFN beta (53.5% or 23/43). These results suggest that the chemosensitivity to 5-FU of human gastric and colon carcinomas is increased in the presence of IFNs, without involvement of the host-mediated immune system, and that this combined effect can be predicted by the MTT assay in vitro.

Antineoplastic Combined Chemotherapy Protocols↗