Biomedical subjects

K Horibe

Publications and source records attributed to K Horibe.

At least 55 records · Page 3Linked to original sources

PubMed1998

Etoposide-related acute promyelocytic leukemia.

The development of therapy-related acute myeloid leukemia (t-AML) has become a growing concern over the past decade, because of the increase in the percentage of long-term survivors of primary malignancy. We reviewed 17 cases with etoposide-related acute promyelocytic leukemia (APL) reported in the literature. The close association between treatment with etoposide for Langerhans cell histiocytosis (LCH) and the development of etoposide-related APL was demonstrated among Japanese and Italians. Our data on the breakpoints (b/ps) of the PML and RARalpha genes are presented. It is suggested that chromatin structure might be more important than specific consensus sequence in the distribution of b/ps in etoposide-related APL.

Adult↗

PubMed1998

Enhancement of in vitro and in vivo anti-tumor activity of anti-GD2 monoclonal antibody 220-51 against human neuroblastoma by granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor.

We have evaluated the anti-tumor effect of anti-GD2 mouse monoclonal antibody (mAb) 220-51 against human neuroblastoma cell line TGW in vitro and in vivo. The mAb 220-51 was able to mediate complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) using human effector cells. In the presence of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte ADCC was significantly augmented in vitro. When mAb 220-51 was administered to tumor-bearing nude mice, tumor growth was significantly inhibited as compared with untreated controls. Administration of recombinant murine GM-CSF in combination with mAb 220-51 significantly enhanced the anti-tumor effect of mAb in vivo. Recombinant human granulocyte colony-stimulating factor (G-CSF) combined with mAb 220-51 was also able to enhance it, although granulocyte ADCC was not affected by the presence of recombinant human G-CSF in vitro. Moreover, GM-CSF and G-CSF work additively to enhance the anti-tumor effect of mAb 220-51 in vivo. The GM-CSF and G-CSF may have a clinical potency in immunotherapy with anti-GD2 mAb for the treatment of neuroblastoma.

Animals↗

PubMed1998

[Efficacy of granisetron, a 5-HT3 antagonist, in the prevention of nausea and vomiting induced by conditioning for hematopoietic stem cell transplantation].

One hundred and eleven patients receiving conditioning regimens for hematopoietic stem cell transplantation (HSCT) were administered a single intravenous dose (40 micrograms/kg) of granisetron before chemo-radio therapy. The efficacy of the drug was assessed every 24 hours, rating the control of nausea and vomiting as complete, major, minor or failure. On day 1, 23 of 48 patients (47.9%) who received cyclophosphamide (60 mg/kg/day), achieved control of emesis with complete or major response. On day 2, 17 of 47 patients (36.2%) achieved control emesis. During total body irradiation (TBI) (10 approximately 12 Gy/2 approximately 3 days), 21 of 33 patients (63.6%) achieved control of emesis on day 1 and 22 of 32 patients (68.6%) achieved control of emesis on day 2. During melphalan administration (60 approximately 100 mg/m2/day), 20 of 28 patients (71.4%) achieved control of emesis on day 1. Adverse effects were observed in seven patients but were not serious. We concluded that granisetron has a major role in preparation for HSCT.

Adolescent↗

PubMed1998

Treatment of hepatoblastoma: less extensive hepatectomy after effective preoperative chemotherapy with cisplatin and adriamycin.

BACKGROUND: Although the prognosis of hepatoblastoma was improved by the introduction of cisplatin and doxorubicin (Adriamycin) for adjuvant chemotherapy, extensive hepatectomy continues to be the usual practice. We retrospectively reviewed our recent experience with hepatoblastoma to determine whether the new modality of intensive chemotherapy could change the resectability, extent of hepatectomy, operative complications, and prognosis. METHODS: The clinical features of 15 children with hepatoblastoma treated between 1985 and 1995 were reviewed. Intensive chemotherapy was added before surgical resection not only when a tumor was unresectable but also when it was large enough to increase the risk of operative morbidity. RESULTS: There was 100% resectability, and the overall mortality rate was only 6.7%. Fourteen patients have been free of disease for 2 to 12 years. Preoperative chemotherapy enabled resection of six previously unresectable hepatoblastomas. Moreover, hepatic resection tended to be less invasive in several patients whose tumors had been much reduced after preoperative chemotherapy. Intraoperative and postoperative complications were minimal, with a short operative time and small amount of blood loss, especially in the group with delayed primary operation. CONCLUSIONS: The preoperative administration of cisplatin and Adriamycin reduced the tumor size so that a safe hepatectomy could be performed with less blood loss and minimal technical complications. Unnecessary sacrifice of the normal hepatic tissue was avoided by performing the less extensive hepatectomy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript.

16;21 translocation is a recurrent primary abnormality in acute myeloid leukemia (AML). The genes involved in this translocation are ERG on chromosome 21 and TLS/FUS on chromosome 16. The rearrangement of the two chromosomes forms the TLS/FUS-ERG fusion gene and produces a consistent chimeric transcript on the der (21) chromosome. In this study, we analyzed the clinical characteristics of 19 patients with t(16;21)-AML, including 2 patients who evolved from myelodysplastic syndrome, and detected the chimeric transcripts of the TLS/FUS-ERG fusion gene in the patients during various clinical stages by the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. We found that the patients with t(16;21) are characterized by a relatively younger age (median age, 22 years old), involvement of various subtypes of French-American-British classification and a poor prognosis: 18 of the 19 patients died of the disease (median survival was 16 months). Four types of TLS/FUS-ERG chimeric transcripts including a novel type were noted in the RT-PCR analysis. The novel transcript contained an additional 138 nucleotides consisting of TLS/FUS exon 8 and ERG exons 7 and 8 and had an in-frame fusion. These chimeric transcripts were consistently detectable in the samples obtained not only at diagnosis and relapse but also in short and long complete remission, suggesting that t(16;21)-AML is resistant to conventional chemotherapy. Thus, we recommend that t(16;21) should be monitored by RT-PCR even in clinical remission and the patients should be treated by other more powerful modality like stem-cell transplantation in the first remission.

Acute Disease↗

PubMed1997

Obstructive jaundice, an unusual initial manifestation of intraabdominal non-Hodgkin's lymphoma in children: complications of percutaneous transhepatic cholangial drainage.

Obstructive jaundice is an unusual initial manifestation of non-Hodgkin's lymphoma in children. Two pediatric patients with primary intraabdominal non-Hodgkin's lymphoma causing obstructive jaundice are presented. Although percutaneous transhepatic cholangial drainage (PTCD) is frequently used to treat obstructive jaundice, there was no definite rule for management of PTCD during chemotherapy, which may rapidly resolve the obstruction. Biliary peritonitis occurred in both patients soon after removal of the PTCD tube after chemotherapy. It was speculated that secure formation of the fistula for PTCD was impaired because of chemotherapy for a considerably long period. The PTCD tube that was already placed for obstructive jaundice in a non-Hodgkin's lymphoma patient should be maintained during chemotherapy with great care for displacement of the tube. PTCD can result in complications, and is probably unnecessary when lymphoma has been diagnosed before PTCD.

Abdominal Neoplasms↗

PubMed1997

Unusual feature of the T-cell receptor genes in T-lineage acute lymphoblastic leukemia.

We characterized the T-cell receptor (TCR) gene rearrangements and sequences in 15 T-lineage acute lymphoblastic leukemia (T-ALL) and seven adult T-cell leukemia (ATL) samples. Southern blot analysis showed that neither of the two TCR delta alleles was deleted in two T-ALL samples, suggesting that the TCR alpha loci have a germ line configuration. The TCR alpha and beta sequences were cloned and sequenced by reverse transcriptase-inverse polymerase chain reaction. Two T-ALL samples had a long complementarity determining region (CDR), three of the alpha chain and the other two T-ALL samples had long CDR3 of the beta chain, compared with normal peripheral blood lymphocytes (PBL). Thus, a total of six T-ALL samples had unusual TCR gene structure, which was unrelated to the immunophenotype. On the other hand, CDR3 length in ATL samples was similar to normal PBL. These data suggest that T-ALL is derived from an immature T-cell repertoire which undergoes TCR gene rearrangement or has not been negatively selected.

Adolescent↗

PubMed1997

Treatment outcome of AT-B88 regimen for B-cell non-Hodgkin's lymphoma and surface immunoglobulin-positive acute lymphoblastic leukemia in children.

We conducted a multicenter study to improve the treatment of B-cell non-Hodgkin's lymphoma and acute lymphoblastic leukemia (NHL/ALL) in Japanese children. The subjects were a total of 57 untreated patients with the B-cell type of either NHL (27 Burkitt's and 9 diffuse large) or ALL between 2 and 15 years old (median: 8 years) seen between 1988 and 1994. All patients received the same cytoreductive therapy (half doses of vincristine and prednisolone) and the same first and second induction courses (vincristine, prednisolone, high-dose methotrexate, repetitive high-dose cyclophosphamide, and adriamycin). Three cycles of consolidation blocks A and B (consisting of reduced doses of similar agents used in the second induction course) followed for patients with stage III or IV NHL or B-ALL, while only one cycle was given for stage I or II disease. Fifty-three patients (93.0%) achieved complete remission. Eight patients had relapse all occurring within 1 year. Another patient had secondary myelodysplastic syndrome. The median follow-up period was 48 months (range: 24-94 months). The overall survival and event-free survival (EFS) rates for all patients were, respectively, 75.9% (S.E.: 5.9) and 70.1 (S.E.: 6.1). The relapse-free interval rate of the 53 patients who achieved CR was 83.5% (S.E.: 5.3). EFS was 75.0% (S.E.: 21.7) in stage I, 84.6% (S.E.: 10.0) in stage II, 78.63% (S.E.: 11.0) in stage III, 80.0% (S.E.: 17.9) in stage IV, and 52.4% (S.E.: 10.9) in ALL. Among the stage IV NHL and ALL patients, EFS was significantly worse in patients with initial CNS involvement than in those without it (14.3% (S.E.: 13.2) vs. 73.7% (S.E.: 10.1); P = 0.0025). In conclusion, our regimen (AT-B88) produced a more than 70% cure-rate for children with any stage of B-cell NHL/ALL without initial CNS involvement. However, a new regimen is needed for patients with initial CNS involvement.

Adolescent↗

PubMed1997

Comparison of the immunoglobulin gene transcripts between immature B lineage acute lymphoblastic leukemia and the normal phenotypic counterparts in the bone marrow.

Immature B lineage acute lymphoblastic leukemia (ALL) is divided into two subtypes, 'pre-B' and 'early pre-B' ALL, by the presence or absence of cytoplasmic immunoglobulin (cIg). To study their clonal origin, we compared mu-chain transcripts in six cIg+ and eight cIg- ALL samples (CD10+/- CD19+ surface Ig-) with those in the normal phenotypic counterparts (CD10+ CD19+ surface Ig-) sorted from the bone marrow (BM). Northern blot analysis showed that the cIg+ ALL samples expressed greater amounts of mu-chain transcripts than the cIg- ALL samples. In the ALL samples and their counterparts, sequence analysis of mu-chain transcripts revealed infrequent somatic mutations of the V(H) genes and the similar usage of D and J(H) gene segments, but the length of complementarity determining region (CDR)-3 in the ALL samples was longer than that in the counterparts (50.0 +/- 15.5 vs 40.8 +/- 12.7 bp, P = 0.01). The mu-chain transcripts in the six cIg+ ALL samples and the counterparts (119/120 clones) had productive sequences, whereas those in the eight cIg- ALL samples had nonsense codons and/or frame shifts in their CDR-3. Our data suggest that a phenotype of ALL, 'pre-B' or 'early pre-B', is associated with V(H)-D-J(H) gene recombinatorial events, and that the CD10+ CD19+ surface Ig- population in the BM is not simply the cellular origin of ALL.

Antigens, CD19↗

PubMed1997

[Effect of discodermin A, an antimicrobial peptide, on the cytoplasm membrane].

The effects of discodermin A, an antimicrobial peptide extracted from sea sponge Discodermia kiiensis, on cell membranes were investigated using vascular smooth muscle cells and erythrocytes. At lower concentrations (0.1-3 microM), discodermin A increased muscle tension with an increase in intracellular free Ca2+ concentration ([Ca2+]i) indicated by the fluorescence of Ca2+ indicator, fura-PE3, in rat aortic smooth muscle. On the other hand, the higher concentration of discodermin A (10-30 microM) accelerated the leakage of loaded fura-PE3 from cells. In rabbit mesenteric artery treaded with discodermin A, addition of micromolar concentration of Ca2+ evoked contraction in the presence of ATP, suggesting that permeability of the membrane to Ca2+ and ATP is increased by discodermin A. Confocal fluorescence microscopy showed that discodermin A permeabilized the plasma membrane of A10 cells to fluorescent agents EthD-1 and the intracellular esterase coupled with another fluorescent agent calcein. Discodermin A also showed a hemolytic effect on rabbit erythrocytes, suggesting that discodermin A permitted transmembrane passage of hemoglobin. These results suggest that discodermin A form pores of different sizes on the cytoplasm membrane in concentration- and time-dependent manners. Discodermin A may be a saponin-like bioactive peptide.

Amphibian Proteins↗

PubMed1997

Molecular analysis of the t(15;17) translocation in de novo and secondary acute promyelocytic leukemia.

To study mechanism of chromosomal translocation, we analyzed the breakpoints (b/p) of the PML and RARA genes in 120 and 5 patients with de novo and secondary (therapy-related) acute promyelocytic leukemia (APL), respectively. In de novo APL, the b/p in the PML gene were clustered in introns 3 (bcr 3; 30%) and around intron 6 (bcr 1 and 2: 70%). The b/p of the RARA gene were widely distributed in intron 2. In studied 8 de novo APL patients, no consensus sequence-motif was found around the b/p, but there were identical stretches of one to seven nucleotides between the PML and RARA genes in the joining regions, suggesting non-selective DNA double strand cleavage followed by single strand base-pairing within identical short stretches as a molecular mechanism of the translocation. In 4 secondary APL patients after chemotherapy including etoposide against Langerhans cell histiocytosis, the b/p of the PML gene were located in intron 6, and those of the RARA gene were in a restricted region within intron 2, 1 kb EcoRI-BamHI fragment, while in an APL patient after chemotherapy without etoposide against breast cancer, the b/p of the PML and RARA genes were located in intron 6 and another region within intron 2, respectively. These data suggest that a different mechanism was associated with the t(15;17) translocation in etoposide-related APL.

Antineoplastic Agents, Phytogenic↗

PubMed1997

[Alterations of the p53 gene and clinical features in childhood acute lymphoblastic leukemia].

Correlations between alterations of the p53 gene and clinical features were examined in childhood acute lymphoblastic leukemia (ALL). We analyzed 147 patients and 38 cell lines for p53 mutations within exons 5 to 9 (2 to 11 in some of them) by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing. p53 gene mutations were found in 3 of 62 (5%) patients at diagnosis, 1 of 14 (7%) patients at relapse, and 13 of 20 (65%) cell lines in T-ALL, 2 of 20 (10%) patients at diagnosis, 4 of 4 (100%) patients at relapse, and 4 of 5 (80%) cell lines in t(1;19)-ALL, 1 of 23 (4%) patients at diagnosis, 2 of 22 (9%) patients at relapse, and 5 of 12 (42%) cell lines in common ALL other than t(1;19) or t(9;22)-ALL and 3 of 3 (100%) patients at diagnosis in B-ALL. In t(1;19)-ALL, p53 gene alterations were associated with a poor prognosis. The patients with p53 mutations had a trend towards poor prognosis in childhood ALL without B-ALL. p53 gene mutation is not always associated with the current prognostic factors. This alteration may become one of the important prognostic factors, if the detection of a small number of the leukemic cells with the p53 gene mutation would be possible.

Adolescent↗

PubMed1996

High expression of ganglioside alpha-2,8-sialyltransferase (GD3 synthase) gene in adult T-cell leukemia cells unrelated to the gene expression of human T-lymphotropic virus type I.

Expression of ganglioside alpha-2,8-sialyltransferase (GD3 synthetase; EC 2.4.99.8) gene and gangliosides in human leukemia cells were analyzed. Flow cytometric analysis of various types of leukemia cells using monoclonal antibodies revealed that GD3 was expressed at a moderate level on adult T-cell leukemia (ATL) cells and weakly on T-cell acute lymphocytic leukemia cells. Accordingly, high levels of GD3 synthase mRNA in ATL and low levels in T-cell acute lymphocytic leukemia were demonstrated by semiquantitative reverse transcription-PCR analysis. High-level expression of the GD3 synthase gene in ATL cells was detected in the uncultured state, and was not changed during short-term culture in vitro. This was in contrast with the rapid up-regulation of GM2/GD2 synthase gene, which was observed within 24 h after start of culture after the emergence of human T-lymphotropic virus type I (HTLV-I) gene expression in cultured normal T lymphocytes with or without HTLV-I p40tax protein, GD3 synthase gene was almost equally expressed, whereas GM2/GD2 synthase gene was much more strongly expressed in the p40tax-positive T cells. These findings indicated that the GD3 synthase gene was highly expressed in ATL cells unrelated to HTLV-I genome expression.

Acute Disease↗

PubMed1996

Sequential detection of tumor cells in the peripheral blood and bone marrow of patients with stage IV neuroblastoma by the reverse transcription-polymerase chain reaction for tyrosine hydroxylase mRNA.

BACKGROUND: The aim of this study was to evaluate the changes of tumor cell contamination in bone marrow (BM) and peripheral blood (PB) during the clinical course of patients with advanced neuroblastoma by detecting tyrosine hydroxylase (TH) mRNA to clarify the appropriate source and time for harvesting hematopoietic stem cells for transplantation. METHODS: A total of 15 patients with Stage IV neuroblastoma were studied. All 15 patients had peripheral blood stem cell (PBSC) samples and BM samples examined for TH mRNA by using the reverse transcription-polymerase chain reaction (RT-PCR) at the time of harvest. Nine of the 15 patients, also had BM and PB samples examined sequentially. RESULTS: Comparing the 45 paired samples concurrently drawn, 16 of 28 BM samples (57.1%) and 4 of 28 PB samples (14.2%) obtained during complete remission (CR) were positive for TH mRNA (P < 0.01), whereas 17 of 17 BM samples (100%) and 14 of 17 PB samples (82.3%) obtained before CR was achieved were positive (not significant). The incidence of TH mRNA positivity was significantly lower in the samples obtained during CR than those obtained before CR was achieved (P < 0.0001 for PB samples, P < 0.01 for BM samples). At the time of PBSC harvesting, the incidence of TH mRNA positivity was lower in PBSC samples (3 of 15, 20%) than in BM samples obtained concurrently (10 of 15, 66.7%; P < 0.03). CONCLUSIONS: These findings show that there is a substantial risk of tumor cell contamination in harvested PBSCs, although its incidence was lower than that in BM samples. We recommend that PBSCs would be better harvested during remission and should be examined for tumor contamination before use as a stem cell source.

Base Sequence↗

PubMed1996

Comparison of the immunoglobulin heavy-chain complementarity determining region-3 structure among the DNA sequences and the mu- and gamma-transcripts in human B-lineage cells.

To study the recombinational significance of the (immunoglobulin heavy) IgH chain gene in human B-cell development, we compared the complementarity determining region (CDR)-3 sequences of the DNA and the mu-transcripts from human normal pre-B cells and mature B cells, and the gamma-transcripts from bone marrow cells. The CDR-3 sequences were longer in the DNA than in the mu- and gamma-transcripts, and this was independent of whether or not the rearrangement was productive. The DLR family genes were less frequently used in the mu- and gamma-transcripts. When translated into amino acids, all CDR-3 sequences from the mu- and gamma-transcripts were productive, although 26.2% of the DNA sequences had stop codons in the D element and/or frameshifts of the JH gene segments. The CDR-3 of the productive DNA sequences in pre-B cells frequently (26.6%) contained at least three continuous hydrophobic amino acids, which were mainly coded by the DLR and DXP family genes at the third reading frame. However, such motifs were rate in the mu-transcripts of pre-B (7.7%) and mature B cells (3.9%), and in the gamma-transcripts of bone marrow cells (1.1%) as well as in the DNA of mature B cells (10.4%). These findings suggested that the length and/or hydrophobicity of the IgH CDR-3 might play a role in the selection mechanisms of B-cell development.

Adult↗

PubMed1996

Acute leukemias expressing p210-and p 190-type bcr/abl mRNAs: report of two cases and review of the literature.

We report two patients with acute leukemias who expressed two types of bcr/abl mRNA. The first case was an 8-year-old boy with acute mixed leukemia in whom the Ph1 chromosome and p210/p190 types of bcr/abl mRNAs were detected at diagnosis. The second case was a 39-year-old male with acute nonlymphocytic leukemia transformed from myelodysplastic syndrome (refractory anemia with excess of blasts). In the latter case, the p210-type mRNA appeared after leukemic transformation, and the p190-type transcript was detected only during the late stage when the Ph1 chromosome was first observed. The leukemias in these two patients were aggressive in their clinical courses. We conclude that the dual expression of p210 and p190 types of bcr/abl is a factor indicating a poor prognosis, and that, in some patients, p190-type bcr/abl may contribute to disease progression.

Acute Disease↗

PubMed1996

Analysis of 55 transplantations from unrelated volunteer donors facilitated by Tokai Marrow Donor Bank.

In October, 1989, the Tokai Marrow Donor Bank (TMDB) was established through the cooperation of patients' families, the branches of blood centers of Japanese Red Cross and the hematologists' group in Tokai Area (Aichi, Shizuoka, Gifu and Mie Prefectùres) in Japan to facilitate the procurement of suitable marrow from unrelated volunteer donors for patients lacking related donors. The number of human leukocyte antigen (HLA)-A, B typed donors totaled 3,083 and the number of patients registered for donor search totaled 1,415 by June 1992, when the activities of TMDB were transferred to the newly created Japan Marrow Donor Program (JMDP), and 55 transplanations from unrelated donors facilitated by TMDD were performed.

Adolescent↗

PubMed1996

Homozygous deletions of p16/MTS1 and p15/MTS2 genes are frequent in t(1;19)-negative but not in t(1;19)-positive B precursor acute lymphoblastic leukemia in childhood.

We analyzed 60 B precursor acute lymphoblastic leukemia (ALL) primary samples and 15 cell lines for homozygous deletions of p16 and p15 genes and mutations of p16 gene. These included five cell lines and 13 primary samples with the t(1;19)(q23;pl3), and eight primary samples with the t(9;22)(q34;qll). Of 10 cell lines without t(1;19), homozygous deletion of both p16 and p15 genes was found in eight cell lines (80%), and a rearrangement of p16 in one cell line (10%). In contrast, only one (20%) of the five cell lines with t(1;19) showed homozygous deletion or rearrangement of p16/p15 gene. Thirteen of 60 (22%) primary samples demonstrated p16 gene homozygous deletion. No case with t(1;19) showed homozygous deletion of p16 gene (0/13, 0%), while cases without t(1;19) showed considerable incidence of p16 gene homozygous deletion (13/47, 28%). These results suggest that the incidence of deletions of p16 gene differs according to the subtypes of B precursor ALL. We also compared the frequency of p16 gene homozygous deletion between the patients at diagnosis and at relapse. Nine of 45 (20%) samples at diagnosis and four of 22 (18%) samples at relapse showed p16 homozygous deletions. The similarity of the rate in these two groups raises the question of the role of p16 gene in progression of B precursor ALL. Mutations were found in three of the primary cases (5%); the mutations included two nonsense mutations at codon 72 and one missense mutation at codon 98. All the mutations found in this study were heterozygous, and the clinical relevance of p16 gene mutation is yet to be determined in these case

Base Sequence↗