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T Yano

Publications and source records attributed to T Yano.

819 records · Page 46Linked to original sources
PubMedDate not supplied

Chemosensitivity testing of human lung cancer tissues using the succinate dehydrogenase inhibition test.

We examined the chemosensitivity of 57 primary lung cancer specimens to 9 antitumor drugs, using the succinate dehydrogenase inhibition (SDI) test. Average succinate dehydrogenase (SD) activity was reduced to less than 50% by cis-diaminedichloroplatinum (II) (DDP), cyclophosphamide (CPA), carboquone (CQ), mitomycin C (MMC) and adriamycin (ADM). The lung cancer cells were relatively resistant to pepleomycin (PEP), 5-fluorouracil (5 FU), vincristine (VCR) and vindesine (VDS). Small cell lung cancers, or early stage lung cancers, tended to be more sensitive to these antitumor drugs. However, differences in sensitivity with respect to either histology, staging or degree of differentiation were not statistically significant. Correlation of SD activity between 2 drugs was high among those which inhibit DNA synthesis (DDP, CPA, CQ or MMC), or between VCR and VDS (inhibitor of mitosis), however, the correlation between VDS and CPA, CQ or DDP was weak. The SDI test is a simple in vitro method readily available to aid in selecting drugs to treat patients with lung cancer.

Adult↗
PubMedDate not supplied

Intra-arterial injection of adriamycin/mitomycin C lipiodol suspension in liver metastases.

Intra-arterial injection of a suspension of adriamycin and/or mitomycin C in Lipiodol was performed in 17 patients with hepatic metastases, which at angiography were poorly vascularized. Accumulation of Lipiodol in the tumors was demonstrated at computed tomography (CT) in 15 of 17 patients examined within one week. Follow-up with CT showed that Lipiodol remained in the tumor during the first month in 94 per cent, after 2 months in 31 per cent, and after 3 months in 17 per cent. In the non-tumor part of the liver Lipiodol disappeared earlier, and one month after injection it could no longer be traced on CT. In 8/17 cases (47%) CT, after intra-arterial injection of Lipiodol, gave superior information compared with CT after intravenous contrast enhancement. Tumor response was achieved in 9 of 16 cases. Particularly in metastases originating from cancer of the colon and stomach response was observed with a decrease in tumor size in 8 of 10 patients.

Adult↗
PubMedDate not supplied

Enhancement effect of an anti-angiogenic agent, TNP-470, on hyperthermia-induced growth suppression of human esophageal and gastric cancers transplantable to nude mice.

The effect of a combination of TNP-470 (AGM-1470, an anti-angiogenic agent) and hyperthermia on tumor growth was examined using human esophageal (ESO-2) and gastric (NSC-8) cancers transplantable to nude mice. TNP-470 alone at a dose of 30 mg/kg three times a week for 2 weeks was sufficient to obtain an antitumor effect. A combination of this dose of TNP-470 and 43 degrees C hyperthermia for 30 min inhibited tumor growth markedly in comparison with either treatment alone. It was considered that angiogenesis after hyperthermia was inhibited by TNP-470, and then regrowth of the tumor cells was potently suppressed by reduction of O2 pressure, pH and nutrient supply in the tumor tissue.

Animals↗
PubMedDate not supplied

Ubiquitous interleukin-1 alpha in fetal bovine serum may mislead the experimental results in vitro.

Fetal bovine sera (FBS) from several commercial suppliers were fractionated by gel filtration. Interleukin-1 (IL-1) activity was bioassayed using the IL-1-specific murine T cell line D10(N4)M. All the sera examined contained IL-1-like activity, with molecular weights (M(r)) of 30 kDa and 15-10 kDa. Under isoelectric focusing (IEF), the majority of IL-1 activity in either 30 kDa or 15-10 kDa fractions was focused into a position of pl 5. The activity recovered from either IEF or gel filtration was inhibited by either recombinant human IL-1 receptor antagonist (rhlL-1ra) or by the antibody against human IL-1 alpha. These biological and physicochemical properties strongly suggest that the active molecules were bovine IL-1 alpha and its precursor. There was no correlation between the amount of endotoxin and IL-1 activity. Quantification of the fractionated IL-1 indicated its presence in concentrations of 200-5000 pg/ml equivalent to human IL-1. However, high levels of IL-1 were not apparent in unfractionated FBS. Proliferation of T cells in the presence of FBS absorbed with protein A-Sepharose was greater than that of cells in original FBS. Therefore, the activity in FBS as a whole appeared to result from the balance between IL-1 and the inhibitory molecule(s). These results suggest that data obtained from experiments conducted in the presence of FBS may be influenced by the effect of bovine IL-1.

Animals↗
PubMedDate not supplied

Hyperthermic enhancement of cis-diamminedichloroplatinum (II)-induced DNA damage in human esophageal cancer transplantable to nude mice.

The effects of a combination of cis-diamminedichloroplatinum (II) (CDDP) and hyperthermia on tumor growth were examined using nude mice bearing a transplantable human esophageal cancer (ESO-2). A combination of 4 mg/kg CDDP and 43 degrees C hyperthermia for 30 min effectively inhibited tumor growth in comparison with either treatment alone. Whereas the S-phase fraction was decreased for only 3 days with hyperthermia alone, it was decreased for at least 7 days with the combination of CDDP and hyperthermia. Though the intratumoral concentration of CDDP in the heated tumor was 1.4 times higher than that in the unheated tumor, the amount of DNA-bound CDDP in the heated tumor was 2.2 times higher. The repair efficiencies of CDDP-induced DNA damage showed no significant difference between the heated tumor and the unheated tumor. Therefore, it is suggested that the enhancement of the antitumor effects of CDDP by hyperthermia is dependent on the increase in the initial amount of CDDP-induced DNA damage.

Aged↗
PubMedDate not supplied

Recovery of pituitary-gonadal function in male rats after long-term suppression induced by a single injection of microcapsules of LH-RH antagonist cetrorelix (SB-75).

The clinical utility of luteinizing hormone-releasing hormone (LH-RH) analogs can be greatly enhanced by a sustained delivery system, which could maintain elevated peptide levels in the blood for prolonged periods of time, up to several weeks. Recently, we developed long-acting microcapsules and microgranules of the LH-RH antagonist SB-75. In this study, we examined the suppressive effects of a single injection of microcapsules of antagonist SB-75 on gonadotropin and testosterone secretion, as well as on fertility, in male rats and the reversibility of those effects. Serum SB-75 levels were measured by RIA. A dose of 20 mg of microcapsules/rat containing 3.58 mg of antagonist in poly(D,L-lactide-co-glycolide), administered intramuscularly produced SB-75 levels higher than 20 ng/ml for approximately 24 days, and a significant elevation was maintained until day 90. Serum testosterone was decreased to castration values for 164 days and LH levels were suppressed below the detection limit of the RIA for a period of 102 days. Serum FSH was suppressed by more than 90%, as compared to control animals, for a period of 58 days and remained significantly decreased until day 164 after the injection. This treatment also caused a significant decrease in the weights of the testes, seminal vesicles, and ventral prostate 30 days after peptide administration. The histology of the testes from the treated rats showed that spermatogenesis was totally depressed. No mature elongated or round spermatids were found in the seminiferous tubules, spermatocytes being the most advanced germ cell form in 99.5% of the testicular tubules.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Chemotherapy for advanced non-small cell lung cancer.

Less than 20% of all cases of non-small cell lung cancer are operable. The treatment option available for such patients is either radiotherapy or chemotherapy. Various combinations of chemotherapeutic agents have been tried. The combination of cisplatin and 5-fluorouracil (5-FU) has been proved to have a synergistic antitumour effect in many experimental and clinical studies. In this paper the authors report the results of a trial using tegafur (which is a prodrug of 5-FU; 1-[2-tetrahydrofuryl]-5-FU) and uracil along with cisplatin in inoperable non-small cell lung cancer. Thirty-one patients were entered into the study, all of whom were less than 75 years old (mean age 61 years). The patients (except for 2) had either stage IIIB (12) or stage IV (17) disease with adenocarcinoma and squamous cell carcinoma in equal proportions (15 each). A combination of uracil and tegafur (400 mg/m2) in 100 mg capsules (100 mg tegafur and 224 mg of uracil), was given orally for 21 days. Most of the patients received 300 mg of the combination tablets twice a day. Cisplatin (80 mg/m2) was given as an infusion over 90 minutes on day 8 after adequately hydrating the patients. This cycle was repeated every 4 weeks. At least 2 treatment cycles were given, unless there was disease progression or toxicity. The response and survival rates were assessed after a follow up period which ranged between 9 and 30 months. The patients received 1 to 4 cycles of therapy and the response rates were: complete response--nil,partial response--11, no change--11 and disease progression--9. The overall response rate was 35% (95% CI: range 19-52%). Five patients achieved at least 50% tumour reduction after 2 cycles. Of the 11 patients who showed partial response, 5 (35%) had stage IV disease and 6 (36%) had other stages; 6 (40%) had squamous cell carcinomas and 5 (31%) had tumours of other histological types. The median duration of response was 6 months (3-13 months). In stage III disease, the 1-year survival rate was 31%, with a median survival time of 11 months, while in stage IV disease it was 29% with a median survival time of 8 months. There was a low incidence of toxicity, with anaemia (10%), leukopenia (6%) and thrombocytopenia (6%) being the most common side-effects. There were also no treatment-related deaths. The authors concluded that oral uracil and tegafur were as effective as other combinations with cisplatin. They also caused very few side-effects. They suggest that a larger trial needs to be carried out.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Pirarubicin might partly circumvent the P-glycoprotein-mediated drug resistance of human breast cancer tissues.

BACKGROUND: Anthracyclines are the first line antitumor agents against breast cancer, and P-glycoprotein (Pgp) is thought to be the main resistance mechanism against these agents. We have evaluated the chemosensitivity of fresh surgical specimens of breast cancer and compared them with their Pgp-expression. MATERIALS AND METHODS: The in vitro chemosensitivity of 65 surgical specimens obtained from 63 patients with advanced breast cancer was assessed by the histoculture drug response assay (HDRA) using doxorubicin (DXR), pirarubicin [(2"R)-4'-tetrahydropyranyladriamycin: THP], and epirubicin (EPIR). Breast cancer tissues were plated onto collagen gel matrix and incubated with 15 micrograms of DXR or EPIR, or 17 micrograms of THP per ml for 7 days with MTT assessed at the endpoint. The efficacy of the agents was evaluated by the inhibition index (I.I.) of the optical density detected by ELISA reader. RESULTS: When 60% or more I.I. was regarded as in vitro sensitive at each cut-off concentration of the drugs, the overall efficacy rates were 60.7%, 48.6%, and 78.6% for DXR, EPIR, and THP, respectively. Fifty-one surgical specimens were evaluated for the immunohistochemical analysis of Pgp and the correlation between the sensitivity to anthracyclines and the expression of Pgp was compared. Pgp was expressed in 23.5% (12/51) specimens and the efficacy of anthracyclines was reduced in Pgp-positive breast cancer tissues, although this reduction was low in THP with a statistically significant difference when comparing with DXR and EPIR. CONCLUSION: The present results suggest that THP might partly circumvent the mdr1/PgP-mediated drug resistance mechanism in human breast cancer tissue and would have some different antitumor spectra on breast cancer comparing with DXR and EPIR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗