Biomedical subjects

Y Ariyoshi

Publications and source records attributed to Y Ariyoshi.

At least 91 records · Page 5Linked to original sources

PubMed1993

Inhibition of passive sensitization of human peripheral basophils by synthetic human immunoglobulin E peptide fragments.

To delineate the binding site in the human immunoglobulin E (IgE) molecule to the Fc epsilon receptor on basophils and mast cells, we chemically synthesized a total of 71 peptide fragments within the sequence Ser300-Lys547 in the human IgE molecule. The synthetic peptides were tested for their capacity to inhibit passive sensitization of human peripheral basophils with atopic patient's serum containing the specific IgE against dust mites in vitro. It was found that a peptide fragment, Pro345-Ile356, potently inhibited the passive sensitization. To clarify the minimal active core, various analogues, such as shortened, substituted (by Gly or Ala residue), omission and retro-sequence peptides, were synthesized and assayed. The results suggested that the sequence Pro345-Lys352 in the human IgE molecule would be an IgE binding site, and that a synthetic octapeptide, Pro345-Phe-Asp-Leu-Phe-Ile-Arg-Lys352, inhibited the passive sensitization, probably by occupying the Fc epsilon receptor sites on the cells.

Allergens↗

PubMed1993

[CT appearance of thorotrast-related and non-thorotrast-related peripheral cholangiocarcinoma].

To assess the differences in CT findings among patients with peripheral cholangiocarcinoma with and without a history of Thorotrast administration, CT studies from 13 Thorotrast patients and eight non-Thorotrast patients were reviewed. Diagnostic and prognostic differences were evaluated between the two groups. Despite periodic imaging surveillance, eight of the 13 (62%) lesions discovered by CT were larger than 6 cm. The prognosis for Thorotrast patients was unfavourable due to difficulties in early detection and complications from associated hepatic fibrosis. The main problem with early detection was that a background of uneven Thorotrast deposits visualized in the liver disguised the tumor as Thorotrast granulations. Although non-Thorotrast patients were not monitored regularly, they had a better chance of undergoing curative resection for the following three reasons: 1) it was easy to detect the tumor (detection rate, 100%); 2) this group rarely had associated liver cirrhosis in noncancerous areas, and 3) non-Thorotrast patients were younger than Thorotrast patients. Early detection of cancer by CA19-9 assay and imaging in asymptomatic subjects without any history of liver disease could be important steps toward the early and radical resection of cancer to achieve a better prognosis.

Adenoma, Bile Duct↗

PubMed1993

Phase II study of NK313 in malignant lymphomas: an NK313 Malignant Lymphoma Study Group trial.

Liblomycin (NK313) is a bleomycin analog that has proved to be associated with less pulmonary toxicity and with more potent antitumor activity than bleomycin in animal tumors. In a phase I study, pulmonary toxicity was not observed, whereas myelosuppression was the dose-limiting factor. The maximum tolerated dose was 140 mg/m2 given once a week for 4 weeks. In the present phase II study, patients with malignant lymphomas received liblomycin at 80 or 100 mg/m2 by intravenous infusion over 15 min once a week for 4 weeks. A total of 39 patients were entered, and 31 [4 with Hodgkin's disease (HD) and 27 with non-Hodgkin's lymphoma (NHL)] were evaluable. The median age of the patients was 52 years (range, 22-74 years), and their performance status ranged from 0 to 3. In all, 28 of the patients had a history of intensive anticancer chemotherapy. Responses were evaluated according to WHO criteria. We obtained 1 complete remission and 9 partial remissions (PRs), for an overall response rate of 37%, in the 27 patients with NHL, whereas 1 PR was achieved in the 4 patients with HD. In all, 9 PRs (32.1%) were obtained in patients who had been exposed to prior chemotherapy, including 4 PRs (33.3%) in 12 patients who had previously been treated with bleomycin. Myelosuppression and nausea and vomiting were the major toxicities, which occurred in about 50% of the patients, and myelosuppression was severe in two patients treated at a dose of 100 mg/m2. We concluded that liblomycin demonstrated significant antitumor activity against malignant lymphomas.

Adult↗

PubMed1993

Molecular cloning of 19p13 breakpoint region in infantile leukemia with t(11;19)(q23;p13) translocation.

We studied the breakpoint regions involved in t(11;19)(q23;p13) translocation associated with infantile leukemias. Southern blot analysis with the partial cDNA clone for the MLL gene at 11q23 which we had isolated previously detected gene rearrangements in all three cell lines and three leukemia samples from the patients with t(11;19) translocation, indicating that these breakpoints were clustered within the 8.5 kb BamHI germline fragment detected by the probe. To study the breakpoint region, a genomic library of one of the cell lines, KOCL-33, was made. We have isolated the der(19) allele containing the breakpoint as well as the germline alleles at 19p13 and 11q23. Using the genomic probes on chromosome 19 near the breakpoint, Southern blot analysis was performed. The breakpoints at 19p13 of the two other cell lines and the three leukemia samples were not located within 36 kilobases of the KOCL-33 breakpoint, although pulsed-field gel electrophoresis showed that the breakpoints of all three cell lines were on the same NruI fragment of 230 kilobases. These results showed that the breakpoints at 19p13 were not clustered like those at 11q23 in t(11;19) translocation.

Base Sequence↗

PubMed1993

Characterization of OM-B monoclonal antibody-defined antigen associated with mucinous type human ovarian tumor.

Partial characterization of the OM-B antigen associated with mucinous-type ovarian tumors was conducted. This antigen was defined by OM-B monoclonal antibody, which was raised against a mucinous-type ovarian tumor, and was present in all the mucinous-type tumors tested, but only a fraction of serous-type tumors. The OM-B crude antigen preparation fractionated from cystic fluids had a density of 1.40-1.43 g/ml, with a high neutral sugar content. Molecular mass (M(r)) estimated by gel filtration was more than 2,000,000. Trypsinization of the antigen preparation under appropriate conditions resulted in two major bands and one minor band with molecular sizes of less than M(r) 250,000, as detected by immunoblotting. Immunoaffinity chromatography was then conducted and the amino acid composition of the purified product was determined; the high contents of serine, threonine and proline are characteristic of a mucin. Binding inhibition enzyme-linked immunosorbent assay was developed to measure OM-B antigen activity in cystic fluids and sera from patients with mucinous-type tumors. The antigen was easily detected in most cystic fluids, but not in sera, suggesting that improvement in the sensitivity of this assay is necessary before its utilization for serum diagnosis will be feasible.

Antibodies, Monoclonal↗

PubMed1993

Alterations of integrin expression in human lung cancer.

Integrins are cell-surface receptors which are involved in cell-matrix and/or cell-cell adhesion. They have been suggested to play a role in tumor invasion and metastasis. We examined the expression of various integrin subunits in normal and cancer cells of the lung using 33 human lung cancer cell lines as well as 6 lung cancer samples from which tumor cell lines could be established. This study clearly demonstrated that changes in the expression of certain integrins occur frequently in lung cancer, especially in small cell lung cancer. Loss of the alpha 1 subunit of the beta 1 integrin family appears to be the most prominent change, although loss of other integrin subunits such as alpha 2 or emergence of some integrin subunits such as alpha v can also be observed. These results suggest that changes in integrin expression may contribute to the invasive and/or metastatic behavior of lung cancer.

Carcinoma, Small Cell↗

PubMed1993

Synchronous lung cancer presenting with small cell carcinoma and adenocarcinoma.

We describe a case of synchronous primary lung cancer presenting with small cell carcinoma and adenocarcinoma, in which expression of the cell surface antigens and also tumor markers were evaluated immunohistologically. A review of the literature concerning synchronous or metachronous primary lung cancers is also presented.

Adenocarcinoma↗

PubMed1993

Expression of the c-kit protein in human solid tumors and in corresponding fetal and adult normal tissues.

The proto-oncogene c-kit encodes a transmembrane tyrosine kinase receptor that is thought to play an important role in hematopoiesis, spermatogenesis, and melanogenesis. We previously showed that the c-kit messenger RNA is preferentially expressed in small cell lung cancer and that its ligand, stem cell factor, is expressed in a broad spectrum of human cancers. Using anti-c-kit antisera raised against synthetic peptides, in situ localization of the c-kit protein in various human solid tumors as well as in corresponding fetal and adult normal tissues was studied by the ABC method. The results suggest that the c-kit gene products may be involved in the pathogenesis of a very restricted subset of human solid tumors such as small cell lung cancer. Interestingly, nuclear protein immunologically related to c-kit was found in both normal and neoplastic medullary cells of the adrenal gland.

Adrenal Gland Neoplasms↗

PubMed1993

[Recombinant human granulocyte colony-stimulating factor (G-CSF)].

Colony-stimulating factors (CSFs) are glycoprotein growth factors that influence the proliferation and differentiation of hematopoietic progenitor cells. Among CFSs granulocyte colony-stimulating factor (G-CSF) is thought to be major stimulator of production of human neutrophilic granulocyte. G-CSF have recently moved from the basic research to the clinical use and have been suggested to have important roles in cancer management. Today two kinds of recombinant G-CSF which have similar specific activity are commercially available, one is derived from ovarian cells of Chinese hamster and the other from E. coli. (Variant type of E. coli is now in trial.) Difference of these two is whether carbohydrate chain primarily seen in molecule of natural form is contained or not. In this report recombinant product of G-CSF for the clinical use is introduced. Preclinical study with recombinant G-CSF have suggested that it would stimulate granulocyte production in cancer patients with myelosuppression due to chemotherapy. Thus, after evaluation of toxicities and possible efficacy recombinant G-CSF has been introduced into phase II trial for the prevention of chemotherapy-induced neutropenia in various cancers. In this setting 2 micrograms/kg of subcutaneous administration for 14 days after aggressive chemotherapy was suggested to be optimal and to be acceptable for toxicities including bone pain or headache. In conclusion recombinant G-CSF is thought to be very useful drug for reduction of nadir of cancer chemotherapy-induced neutropenia and shortening of period of neutropenia.

Animals↗

PubMed1993

[Intermittent hepatic arterial infusion of high-dose 5-FU for liver metastases from colorectal cancer].

A phase II study of weekly intermittent hepatic arterial infusion of high dose 5-FU for liver metastases from colorectal cancer was carried out. Thirty-two patients with unresectable liver metastases from colorectal cancer were entered in this study. Nausea (< or = grade 2) was observed in 31% of the cases, mild elevation of rGTP in 13%, biloma in 9%, and hepatic arterial occlusion in 22%. However, no major toxicity occurred. The response rate evaluated by CT-scans was 75% (4 CR + 20 PR/32), and the overall median survival was 22 months. Significant differences of median survival were observed in the extra-hepatic lesions [extrahepatic lesions: (-) 16 months vs (+) 22 months]. This regimen showed high activity without major toxicity and the reduction of pts' QOLs caused by pumps. It confirmed by a study involving a large number of cases, this regimen will become a standard regimen for unresectable liver metastases from colorectal cancer.

Colorectal Neoplasms↗

PubMed1993

Two distinct portions of LTG19/ENL at 19p13 are involved in t(11;19) leukemia.

We previously isolated cDNA clones, MLL-a and MLL-b, derived from the 11q23 breakpoint region and detected gene rearrangements with MLL-b cDNA in infantile leukemia cell lines with 11q23 abnormalities. We also showed chimeric mRNAs between MLL and genes on partner chromosomes such as 4q21 and 19p13. In the present study, we isolated overlapping MLL cDNA clones of 11 kb and demonstrated that MLL-a and MLL-b were derived from the same gene, MLL/ALL-1/HRX. Northern analysis with an MLL cDNA probe detected different signals in t(11;19) cell lines, one being sized 10 kb in two cell lines, KOCL-33 and KOCL-44, and the other being 9.2 kb in the cell line, KOPN-1. To elucidate the molecular basis for the heterogeneity, we isolated cDNA clones of a translocation-associated gene on chromosome 19, LTG19, as well as chimeric cDNAs from KOPN-1. Northern analysis with LTG19 cDNA demonstrated the identical gene, encoding serine/proline rich 559 amino acid polypeptide, to be involved in all three cell lines. Sequence comparison revealed that the LTG19 portion of the predicted chimeric protein of KOPN-1 was fused in frame and contained the C-terminal 189 amino acids. This was shorter by 366 amino acids than those of KOCL-33 and KOCL-44, also fused in frame. Reverse transcriptase-PCR analysis demonstrated complex chimeric mRNAs in cell lines and leukemia samples. Although a chimeric mRNA of KOPN-1 type was rare, its presence suggested that the shared C-terminal portion of 189 amino acids of LTG19 contains important signal(s) for malignant transformation.

Amino Acid Sequence↗

PubMed1993

[Pharmacokinetics in arterial infusion chemotherapy].

The pharmacokinetics of arterial infusion chemotherapy was introduced. The pharmacokinetic rationales were based on the theories of "first pass effect" and "increased local concentration without first pass effect" advocated by Dr. Collins. These theories can offer much information to select the drug and to determine the administration schedule. However, for most of the drugs, the clinical pharmacokinetic studies are poor, and the optimal dose in bolus intraarterial infusion and the administration schedule is uncertain in terms of the dosage and hours. There are also some differences between pharmacokinetic understanding and clinical effect. Thus, further pharmacokinetic investigations and clinical studies are required to establish effective regimens for arterial infusion chemotherapy.

Drug Administration Schedule↗

PubMed1993

Glutathione S-transferase pi levels in a panel of lung cancer cell lines and its relation to chemo-radiosensitivity.

The human placental form of glutathione S-transferase pi (GST-pi) was measured by a sandwich enzyme-linked immunosorbent assay in lung cancer cell lines established in our laboratories. In classic-type small cell lung cancer (SCLC), variant-type SCLC and non-small cell lung cancer (NSCLC), the respective mean GST-pi values were 0.83 +/- 0.88, 3.27 +/- 2.85 and 2.40 +/- 0.76 micrograms/mg protein. Cell lines with high GST-pi content had low levels of neuron specific enolase, which is known as a representative tumor marker for SCLC. This suggests that GST-pi may also be used as a potential marker for NSCLC. The lines with low GST-pi content were more sensitive to radiation than those with high GST-pi content. Cell lines not subjected to prior therapy also showed a good correlation between GST-pi levels and chemosensitivity to cisplatin. The findings suggest that GST-pi can be used as an adjunctive marker for lung cancer.

Carcinoma, Non-Small-Cell Lung↗

PubMed1993

MLLT3 gene on 9p22 involved in t(9;11) leukemia encodes a serine/proline rich protein homologous to MLLT1 on 19p13.

Recently, the MLL gene at 11q23 was found to be involved in a subset of leukemias with an 11q23 abnormality. In the present study, we isolated chimeric cDNAs between the MLL and a gene designated MLLT3 at 9p22 from a cDNA library of an IMS-M1 cell line with a t(9;11)(p22;q23) translocation, a representative karyotypic abnormality seen in acute monocytic leukemia. We also isolated a normal MLLT3 cDNA and found an open reading frame encoding at least 318 amino acids with high serine/proline content (24.8%). The chimeric mRNAs were demonstrated to be fused to MLL in frame, as found in t(11;19) and t(4;11) leukemias. The predicted MLLT3 protein demonstrated a significant homology to that of the MLLT1 gene at 19p13 involved in t(11;19) leukemia. The highest homology, up to 74.1%, was found in 86 amino acids of the C-terminus, suggesting that this region is of particular importance for leukemogenesis in t(9;11) leukemia. Northern blot analysis with the MLLT3 cDNA probe against normal tissues revealed multiple transcripts in lymphoid organs. A survey of hematopoietic cell lines demonstrated relatively stronger signals in cells belonging to megakaryocytic and erythroid lineages. As previously found in t(11;19) leukemia, heterogeneous MLL-MLLT3 chimeric mRNAs could be detected by the reverse transcriptase-polymerase chain reaction (RT-PCR) in t(9;11) leukemia samples.

Adult↗

PubMed1993

[New anthracyclines].

Idarubicin showed the superior activity against Acute Non-Lymphocytic Leukemia (ANLL) in the prospective randomized trials comparing to daunorubicin and it is judged that the analog will become the first choice in the treatment on ANLL. Anthracyclines including SM-5887, KRN-8602, ME-2303 under studies in Japan have shown comparable or superior antitumor activities and lower cardiac toxicities compared to doxorubicin in preclinical studies and therefore the results obtained in clinical trials are expected. Phase II trials of anthrapyrazoles which is an analog of mitoxantrone are in progress. Among three compounds entered it is of note that CI-941 has demonstrated an excellent activity against advanced breast cancer.

Animals↗

PubMed1993

[Phase I study of 5-fluorouracil and l-leucovorin].

Leucovorin, given usually by i.v. injection or orally changes to 5, 10-methylene tetrahydrofolate in tumor as well as normal cells. And in normal FdUMP, an active metabolite of 5-FU, binds tightly to thymidylate synthase in the presence of cofactor, 5, 10-methylene tetrahydrofolate. This interaction leads to potentiate the cytotoxic effect of 5-FU by prolonged inhibition of thymidylate synthase. Phase I study using l-leucovorin (l-LV), an active form of leucovorin, combined with 5-FU, was conducted. In the weekly schedule, 5-FU was fixed to 600mg/m2, and l-LV dose was escalated from 125 mg/m2 to 250mg/m2, if toxicity was acceptable. On the other hand, in the five consecutive-day schedule, 5-FU was fixed to 370mg/m2 and l-LV was escalated from 25mg/m2 to 50mg/m2, 100mg/m2 and 200 mg/m2. l-LV 10mg/m2 was tested as reference. On weekly schedule of l-LV 250mg/m2, grade III diarrhea was seen in 2 cases and grade IV leucopenia was seen in one. In five consecutive-day schedule, at each dose of l-LV, stomatitis, nausea plus vomiting, anorexia, anemia and leucopenia were seen. However, the increase of toxicities were not seen by dose escalation of l-LV. Then, we have been conducted a randomized early phase II study using 250 mg/m2 of l-LV weekly (arm A) and 100mg/m2 (arm B) or 10mg/m2 (arm C) of l-LV for 5 consecutive days in gastric and colorectal cancer by multicenter cooperative study. Plasma concentrations of l-LV were maintained > 10(-5) mol/L for over 5 hrs. after 2 hrs. infusion of 250 mg/m2 of l-LV and for over one hr. after a rapid injection of 100mg/m2 of l-LV.

Adult↗

PubMed1992

Inhibition of passive cutaneous anaphylaxis by synthetic human immunoglobulin E peptide fragments.

In an attempt to determine the regions responsible for type I immediate hypersensitivity, a total of 42 peptide fragments, which cover the CH3-CH4 domains in human immunoglobulin E (IgE), were chemically synthesized. Several peptide fragments located in the amino acid sequences Ala329-Thr357 and Arg419-Ala463, inhibited passive cutaneous anaphylaxis (PCA) in vivo. In order to pinpoint the sites responsible for the inhibition of the PCA reaction, various fragment peptides in these two regions were synthesized. As a result, residues Pro343-Leu348, Pro426-Thr433, and Ser456-Thr461 were suggested to be involved in type I immediate hypersensitivity.

Amino Acid Sequence↗

PubMed1992

p53 mutations in non-small cell lung cancer in Japan: association between mutations and smoking.

The p53 gene has been implicated as a tumor suppressor gene involved in the pathogenesis of lung cancer. Our previous study revealed that the p53 gene is frequently mutated with a distinct nucleotide substitution pattern in small cell lung cancer specimens in Japanese patients. In this study, we examined 30 primary, resected non-small cell lung cancer samples in Japanese patients using complementary DNA-polymerase chain reaction and sequencing. Mutations changing the p53 coding sequence were found in 14 of 30 tumor samples (47%), while G:C to T:A transversions which are uncommon in other cancers such as colon cancer were the most frequently observed mutations, in agreement with an earlier report on non-small cell lung cancer in American patients. Furthermore, the present study shows for the first time that in univariate and multivariate analyses, the presence of p53 mutations is closely associated with lifetime cigarette consumption.

Amino Acid Sequence↗