Biomedical subjects

N Horikoshi

Publications and source records attributed to N Horikoshi.

At least 55 records · Page 3Linked to original sources

PubMed1994

Reliability of data obtained by radionuclide angiocardiography in follow-up studies with special reference to intra- and interobserver variations.

The reproducibility of the data obtained by radionuclide angiocardiography was studied in terms of the intra- and intervariations of three technicians. Three parameters were chosen: the left ventricular ejection fraction (LVEF), the 1/3 filling fraction (1/3FF), and the ratio of the time from end systole to the point of peak filling rate against the entire diastolic period (TRPFR). First, each technician studied an independent consecutive series of 40 patients for the initial analysis. The original data of each patient, composed of 26 frames for one beat, were stored on an optical disc for the intra- and intervariation studies. In this study, analysis of the volume curve was performed by using both 3rd order and 4th order Fourier series. The region of interest (ROI) for the left ventricle, which was set for the initial analysis, was recorded by Polaroid photography to be used as a reference for the later analyses for the variation studies. The least variation was noted in the LVEF not only for the intravariation study but also for the intervariation study, no matter which order of the Fourier series was used. However, the 3rd order Fourier series seemed to give better curve fitting to avoid fluctuation of the diastolic parameters. The results indicate that we can expect more steady and reliable information from LVEF than from the diastolic parameters, even when various technicians perform the follow-up study of a particular patient.

Angiocardiography↗

PubMed1994

[Phase I study of paclitaxel].

Paclitaxel, a novel antimicrotubule agent that enhances tubulin polymerization and microtubule stability, was administered as a 24-hour infusion in a phase I study. Twelve patients received 32 courses at 50, 100, 150, and 200 mg/m2. A premedication regimen of dexamethasone, diphenhydramine, and ranitidine was used to prevent the acute hypersensitivity reactions (HSRs). The dose-limiting factor was leukopenia (granulocytopenia) associated with Grade 4 infection. The maximum tolerated dose was 200 mg/m2. Other non-hematological effects included peripheral neuropathy, myalgia, alopecia, and elevations of transaminase and alkaline phosphatase. Severe HSRs were not observed. The paclitaxel plasma concentration declined with a half-life of 10.0 to 24.9 hours. Excretion into urine within 72 hours was in the range of 7.28 to 11.34% of paclitaxel dosage. Two patients with breast cancer at the 200 mg/m2 dose level had partial responses. The recommended dose of paclitaxel for phase II study, when administered as a 24-hour infusion, is considered to be 150 mg/m2 every 3 weeks.

Adolescent↗

PubMed1994

[Detection of thymidylate synthase mRNA in 5-fluorouracil resistant human colon adenocarcinoma cells].

To investigate the resistance against 5-fluorouracil (FU), thymidylate synthase (TS) mRNA level was measured by reverse transcription PCR (RT-PCR) technique and quantitated by a competitive-PCR method in human colon adenocarcinoma cell line, SNU-C1 and its FU resistant cell line, C1/FU. Using a set of primers covering 3'-untranslated region of mRNA, PCR products were amplified from cDNAs prepared from both SNU-C1 and C1/FU. However, only a cDNA extracted from C1/FU was amplified in a stationary growth phase. Then, the amount of mRNA was quantitated by competitive-PCR technique in both cell lines using another set of primer enable to amplify product in both stationary and logarithmic cell growth phase. The amount of mRNA in C1/FU was four times more than that of C1. The gene level in TS gene in genome DNA in these cell lines were not different incidentally. These data suggest that TS mRNA was more increased and can be more stable in C1/FU, accounting for FU resistance.

Adenocarcinoma↗

PubMed1992

Wild-type p53 binds to the TATA-binding protein and represses transcription.

p53 activates transcription of genes with a p53 response element, and it can repress genes lacking the element. Here we demonstrate that wild-type but not mutant p53 inhibits transcription in a HeLa nuclear extract from minimal promoters. Wild-type but not mutant p53 binds to human TATA-binding protein (TBP). p53 does not bind to yeast TBP, and it cannot inhibit transcription in a HeLa extract where yeast TBP substitutes for human TBP. These results suggest a model in which p53 binds to TBP and interferes with transcriptional initiation.

Animals↗

PubMed1992

[Therapeutic difference by TAE between HCC with HCV-Ab and HBV-Ag].

Transarterial infusion therapy using adriamycin-Lipiodol emulsion (TAE) was used for 30 patients of HCC with HCV-Ab and 20 patients with HBV-Ag. We compared the tumor effect and prognosis in terms of several clinico-pathological factors. The response rate (PR+MR) after TAE was 43% in HCC patients with HCV-Ab and 30% in those with HBV-Ag. One-year survival rate was 89% in HCC patients with HCV-Ab and 58% in HCC patients with HBV-Ag. Thus, there was a significant difference between the two groups. No definite reasons between two groups influencing tumor effect and prognosis is obviously revealed except for portal vein invasion.

Carcinoma, Hepatocellular↗

PubMed1992

[High-dose thio-TEPA with escalating doses of epirubicin and autologous hematopoietic stem cell transplant for refractory cancers].

We studied high-dose chemotherapy with autologous hematopoietic stem cell transplant for patients (pts) with non-Hodgkin's lymphoma (NHL) and breast cancer (BC) refractory to conventional therapies. The conditioning regimen consisted of thio-TEPA 6 mg/kg/day for 3 consecutive days with escalating doses of epirubicin (EPI) in dose steps of 120, 150, 180 and 210 mg/m2 on day 1. Mucositis was dose limiting toxicity at 210 mg/m2 on this regimen, and the recommended dose of EPI was judged to be 180 mg/m2. No cardiotoxicities were observed. There were 3 with complete responses (CR), one partial response (PR) in pts with NHL, 3CR and 5PR in pts with BC. The median duration of response was 8 months (mos) and 4 mos, respectively. Hematological recovery was significantly earlier in the pts receiving both autologous bone marrow transplant (ABMT) and peripheral blood stem cell transplant (PBSCT) than ABMT alone. This approach made it possible to overcome the prolonged PLT recovery, which was one of the major problems on ABMT.

Adolescent↗

PubMed1992

[Phase I and pharmacokinetic study of SM-5887 by 5-day schedule].

Pharmacokinetics of SM-5887, a new totally synthetic anthracycline derivative, was studied in a phase I setting by 5-day schedule. The maximum tolerated dose was 25 mg/m2/d (total dose: 125 mg/m2/body) and the dose-limiting toxicity was myelosuppression which was consistent with the results of the phase I study by a single dose. In terms of subjective side effects, decreased nausea/vomiting and increased stomatitis were observed. In pharmacokinetic study, AUC of active form of SM-5887 increased on day 5 compared to that day 1. This result suggested that 5-day schedule of SM-5887 produced an accumulation of the active form. Five-day treatment schedule of SM-5887 seems to be more tolerable and further clinical study was recommended.

Adult↗

PubMed1991

Direct interaction between adenovirus E1A protein and the TATA box binding transcription factor IID.

Adenovirus E1A has long been known to activate/repress cellular and viral transcription. The transcriptional activity of nuclear extracts was depleted after chromatography on immobilized E1A protein columns that specifically retained the transcription factor (TF) IID. Stronger direct interactions between E1A and human TFIID than between E1A and yeast TFIID suggest that the unique sequences of the human protein may be involved. We have demonstrated that this interaction occurs directly between bacterially produced E1A and bacterially produced human TFIID in a protein blot assay. We propose that E1A protein may transduce regulatory signals from upstream activators to basal elements of the transcriptional machinery by contacting TFIID.

Adenovirus Early Proteins↗

PubMed1991

Evaluation of prognostic factors for 233 patients with recurrent advanced breast cancer.

We analyzed possible prognostic factors in 233 patients with recurrent advanced breast cancer treated primarily by adriamycin, cyclophosphamide and ftorafur (ACF) therapy and ACF modifications. The patients were in the Cancer Institute Hospital from 1977 to 1986, and were followed-up until 1989. In terms of chemotherapeutic response, complete and partial responses were observed in 31 (13%) and 100 (43%) patients, respectively. The overall median survival from the beginning of chemotherapy was 20.3 months. The factors evaluated were response to chemotherapy, performance status (PS), age, disease-free interval (DFI), menopausal status, number of metastatic sites (step classification), presence or absence of liver metastasis, presence or absence of malignant effusion, and presence or absence of prior radiotherapy. Out of the nine factors, response to chemotherapy, PS, age, DFI and liver metastasis were significant factors affecting survival in univariate analysis, and multivariate analysis of these five factors revealed the survival to be markedly affected by response to chemotherapy (P less than 0.00001), PS (P = 0.00001) and DFI (P less than 0.00001).

Adult↗

PubMed1991

[Combination chemotherapy of advanced Hodgkin's disease with vincristine, cyclophosphamide, procarbazine, and prednisolone].

Thirty-three patients with advanced Hodgkin's disease were treated with a combination chemotherapy consisting of vincristine 1 mg/m2 iv on day 1, 8, cyclophosphamide 500 mg/m2 iv on day 1, procarbazine 100 mg/m2 p.o. day 1-7, and prednisolone 40 mg/m2 p.o. day 1-7. Twenty patients received this regimen every 4 weeks (VCPP II regimen). Furthermore, we conducted higher dose intensive VCPP II-2 regimen which was repeated every two weeks for thirteen patients. Complete response rate of both regimens was 63% (VCPP II 45%, VCPP II-2 85%). The median duration of CR was 37 + months. Leukopenia, neurotoxicity and gastrointestinal toxicity were commonly observed but were clinically manageable. These results indicate that high dose intensive chemotherapy is effective for achieving high CR rate for advanced Hodgkin's disease.

Adolescent↗

PubMed1991

Interactions between adenovirus E1A and members of the AP-1 family of cellular transcription factors.

We have studied interactions between bacterially produced E1A linked to Sepharose and the various DNA-binding proteins present in HeLa cell nuclear extracts (NE). DNA-binding activities and cross-reactive polypeptides recognizing the cAMP-responsive element (CRE) and the activator protein 1 (AP1) sites were bound to the E1A column, whereas nuclear factor 1 (NF1) and the activator protein 2 (AP2) DNA-binding activities were not retained by E1A. The binding activities that were retained belonged to the CRE and JUN protein family, as judged by Western blot analysis. Authentic CRE-BP1, c-Jun and c-Fos proteins produced by in-vitro translation also bound to the E1A column. However, efficient binding of in-vitro-translated CRE-BP1 and c-Fos proteins to E1A required preincubation with NE. We show here that immobilized E1A sequesters several cellular upstream transcription activators, and suggest a role for members of the AP1 family of transcription factors in E1A-mediated gene regulation.

Adenovirus Early Proteins↗

PubMed1991

[Phase I-II study of hepatic intraarterial one-shot administration of adriamycin in patients with metastatic liver cancer].

For the purpose of obtaining the optimal dose of adriamycin (ADM) in hepatic intraarterial one-shot administration, phase I-II study was conducted in 14 patients with various liver cancers. The starting dose of ADM was 20 mg/m2 (4 patients) and the doses were escalated to 40 mg/m2 (5 patients), 60 mg/m2 (4 patients) and 80 mg/m2 (3 patients). One patient with salivary gland cancer showed PR for the liver metastasis. Major toxicity was leukopenia. With a dose of 40 mg/m2, 3 out of 4 patients showed nadir of WBC counts below 4,000/mm3 (2,400, 2,900, 3,100), 60 mg/m2 (1,100, 1,500, 2,200 and 2,700), and 80 mg/m2 (900, 1,200, and 1,400). Nadirs of WBC counts were observed from 9 to 15 days after the one-shot administration, and recovered above 4,000/mm3 in 1 to 3 weeks. Plasma concentrations of ADM from the peripheral vein were determined by HPLC in 12 patients, 14 courses. The curves of ADM plasma levels after 20 and 40 mg/m2 bolus injections were almost the same, and in patients treated with 60 and 80 mg/m2 the curves were also quite similar, but higher in the plasma levels, comparing with in patients with 20 and 40 mg/m2. There might be a limit of ADM tissue absorption, and above the doses 60 mg/m2, ADM might be overflowed, followed by side effects, especially leukopenia. Upon these data of venous plasma concentrations of ADM and leukopenia, the optimal dose of ADM in the hepatic intraarterial one-shot administration seemed to be 40 mg/m2.

Adult↗

PubMed1990

Site-directed mutagenesis of arginine 246, glutamic acid 247, and histidine 248 in the eukaryotic transcription factor S-II.

When His248 of the transcription factor S-II was replaced by alanine or tyrosine, the activity of the resulting mutants was less than 30% of that of the wild-type S-II. When Arg246, Glu247, and His248 were all replaced by leucine, the resulting mutant showed complete loss of activity. These results indicate that the amino acid sequence Arg-Glu-His at positions 246-248 of S-II is important for its stimulatory activity. The mutant S-II with no activity could not form a complex with RNA polymerase II, unlike wild-type S-II, but retained ability to interact with DNA.

Amino Acid Sequence↗

PubMed1990

[High-dose cyclophosphamide, thio-TEPA, etoposide with autologous bone marrow transplantation for refractory cancers].

We studied high-dose chemotherapy with autologous bone marrow transplantation (ABMT) for 10 patients with malignant lymphoma or breast cancer refractory to conventional chemotherapy. Conditioning regimen was consisted of cyclophosphamide 60 mg/kg/day, thio-TEPA 6 mg/kg/day, Etoposide 500 or 600 mg/m2/day for 3 consecutive days. Of 9 patients with measurable lesions, there were 5 with complete responses (CR) and 4 with partial responses (PR). Severe bone marrow suppression, mucositis, and diarrhea were observed in all patients. Furthermore, biliary stasis, which was unpredictable side effect, was observed in most patients. So, mucositis and/or hepatotoxicity were thought to be the dose-limiting factors. But these were not life-threatening and clinically manageable. All patients were received recombinant human granulocyte colony stimulating factor (rhG-CSF) at a dose of 300 micrograms/m2/day and which was effective for shortening the duration of leukopenia. In vitro Colony Forming Unit-granulocyte macrophage assay (CFU-GM assay) showed a significant correlation between the ability of colony formation and the days to recovery of granulocytes.

Adult↗

PubMed1990

[Combination chemotherapy of ifosfamide, cisplatin and vindesine for non-small cell lung cancer].

Twenty patients with advanced non-small cell lung cancer were treated with a combination chemotherapy consisting of ifosfamide (IFX), cisplatin (CDDP) and vindesine (VDS). The treatment schedule was IFX 1.3 g/m2 i.v., on days 1-5, CDDP 20 mg/m2 i.v., on days 1-5, and VDS 3 mg/m2 i.v., on days 1 & 8, and, in principle, the regimen was repeated every 4 weeks. Of 19 evaluable patients, there were 1 CR, 7 PR, 10 NC and 1 PD, with an overall response rate of 42.1%. The median duration of responses was 7.45 months, and the median survival time of all patients was 13.2 months. The major toxicities occurring were hematologic toxicity, alopecia, gastrointestinal toxicity and peripheral neuropathy. Hematologic toxicity was severe and was judged to be dose limiting, but clinically manageable. These results indicate that this combination chemotherapy is active against non-small cell lung cancer and deserves further studies.

Adult↗

PubMed1990

[Treatment of cancer in the elderly--cancer chemotherapy].

A retrospective analysis was made of elderly cancer patients (pts) who were treated with cancer chemotherapy in our Department of the Cancer Inst. Hosp. There were 180 pts above age 70 years at the start of chemotherapy between July of 1974 and December of 1988. Characteristics of these 180 pts were as follows: (1) 73 years of age in median (70-89 years), (2) 67 pts with malignant lymphoma (37%); 40 with lung ca. (22%), 20 with breast ca. (11%), stomach ca., colorectal ca., multiple myeloma and other; (3) Combination chemotherapy given to 174 pts; (4) OUTCOME: 41 pts (23%) were alive as September of 1989, and autopsy performed in 66 out of 87 pts who died in the hospital (76%). There were no special chemotherapeutic regimens only for elderly pts. Intensity of adequate chemotherapy based on therapeutic protocols was evaluated, dividing pts into two groups: full-dose group and reduced-dose group. Most pts (96%) with small cell lung cancer (SCL) were treated on protocols. For example, 12 elderly pts with SCL were treated with VEC regimen (VCR.VP-16.CTX); eight pts with full-dose and four reduced-dose, and their response rate (CR/PR) of 50%/38% and 25%/75%, respectively, and in 23 younger pts; 20 full-dose and three reduced-dose, and response rate 35%/35% and 33%/33%, respectively. There were 40 pts with acute non-lymphocytic leukemia over 60 years old, treated at Jikei University and in our Department. CR rates of these pts according to age showed a lower percentage with advancing age. Elderly pts with malignancies responsive to chemotherapy should be treated with the same regimen used in younger pts. But doses of each drug have to be adjusted to organ functions of each pt. patients with unresponsive malignancies, must be enrolled in clinical trials, and their responses and toxicities evaluated by age-stratified analysis.

Aged↗

PubMed1989

Production of functional S-II in Bombyx mori cells.

A cDNA for murine transcription factor S-II (Hirashima et al., J. Biol. Chem (1988) 263, 3858-3863) was inserted into a silkworm baculovirus vector and expressed in Bm-N cells, a cell line of Bombyx mori maintained in the laboratory. Recombinant S-II was purified from virus-infected cell extracts to near homogeneity by ammonium sulfate fractionation, and chromatographies on DEAE-cellulose and phosphocellulose. About 60 micrograms of recombinant S-II was obtained from 1 g of virus-infected cells. The molecular mass and specific activity of recombinant S-II were exactly the same as those of authentic S-II purified from Ehrlich ascites tumor cells.

Animals↗

PubMed1989

Phase I and pharmacokinetic study of SM-5887, a new anthracycline derivative.

SM-5887, a new totally synthetic anthracycline derivative was studied in a phase I setting. Twenty-nine evaluable courses of treatment were conducted in groups at doses increasing from 10 to 130 mg/m2. Myelosuppression was the dose-limiting toxicity and a MTD was 130 mg/m2. At 130 mg/m2 the median lowest white blood cell count was 0.7 x 10(3)/cmm (range: 0.3-1.8) and the median lowest granulocyte count was 0.1 x 10(3)/cmm (range: 0-0.7) and the median lowest platelet count was 57 x 10(3)/cmm (range: 4-176). Non-hematologic side effects were mild gastrointestinal symptoms and hair loss. The recommended dose and schedule for phase II setting is 100 mg/m2 every 3 weeks.

Adult↗