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Biomedical subjects

Ryuzo Ohno

Publications and source records attributed to Ryuzo Ohno.

42 records · Page 3Linked to original sources

Erythropoietin receptor in myelodysplastic syndrome and leukemia.

Erythropoietin (Epo) is one of the main regulators of growth and differentiation of hematopoietic cells. In normal bone marrow cells, the amount of erythropoietin receptor (EpoR) was highest in the CD34+ CD38- subset, and decreased on lineage committed progenitor cells expressing CD38 antigens. Among the erythroid cells expressing GpA antigens, CD34-positive fractions expressed more EpoR than CD34-negative fractions. Although the amounts of EpoR of bone marrow cells from patients with refractory anemia (RA) were less than those of normal bone marrow cells in all phenotypes examined, there was no statistical significant difference. EpoR was detected on leukemia cells from 60% of acute myeloblastic leukemia (AML) cases and 29% of acute lymphoblastic leukemia (ALL) cases, and distributed widely among all FAB-subtypes. In spite of the presence of EpoR, in vitro proliferative response to Epo was not observed in a large proportion of AML. And there was no correlation between the amount of EpoR and the in vitro response to EPO. Patients with both EpoR expression and in vitro response to Epo had shorter remission duration than those without EpoR.

Bone Marrow Cells↗

Report of the fifteenth international symposium of the foundation for promotion of cancer research: new horizons in the diagnosis and treatment of hematological malignancies based on molecular genetic features.

The Fifteenth International Symposium of the Foundation for Promotion of Cancer Research entitled 'New Horizons in the Diagnosis and Treatment of Hematological Malignancies Based on Molecular Genetic Features' was held in Tokyo on January 15-17, 2002. Twenty-nine invited speakers, including 12 from abroad and 17 from Japan, presented the updated results of their research. After an overview of the classification of hematological malignancies, new findings on some disease entities based on novel immunophenotypic and molecular genetic features were presented. The results of gene expression profiling and BCL6 and C-MYC gene rearrangement in diffuse large B-cell lymphoma were presented and oncogenic mechanism of acute myeloid leukemia was discussed. In the treatment of non-Hodgkin's lymphoma and acute leukemia, the present consensus and future directions were discussed based on the results of multicenter trials in the USA and Japan. As a molecular targeting therapy, the remarkable effect of a BCR-ABL tyrosine kinase inhibitor, STI571, in chronic myeloid leukemia and gastrointestinal stromal tumor was presented. Thereafter, promising results of active immunotherapy, chimeric anti-CD20 monoclonal antibody, anti-CD20 radioimmunoconjugate and anti-CD22 immunotoxin for B-cell lymphoma were presented. Finally, recent advances in allogeneic hematopoietic stem cell transplantation were discussed, focusing on reduced-intensity preparative regimens. The recent advances in basic and clinical research on hematological malignancies would lead to further improvement in the prognosis and quality of life of patients suffering from leukemia or lymphoma.

Biomedical Research↗

Prediction of sensitivity to STI571 among chronic myeloid leukemia patients by genome-wide cDNA microarray analysis.

One of the most critical issues to be solved in regard to cancer chemotherapy is the establishment of ways to predict the efficacy of anti-cancer drugs for individual patients. To develop a prediction system based on expression of specific genes, we analyzed expression profiles of mononuclear cells from 18 chronic myeloid leukemia (CML) patients who were treated with the tyrosine kinase inhibitor STI571. cDNA microarrays representing 23 040 genes identified 79 genes that were expressed differentially between responders and non-responders to STI571. On the basis of the expression patterns of 15 or 30 of these genes among the patients, we developed a "Prediction Score" system that could clearly separate the responder group from the non-responder group. Verification of this system using four additional ("test") cases succeeded in predicting the response of each of those four patients to the drug. These results provide the first evidence that gene-expression profiles can predict sensitivity of CML cells to STI571, and may eventually lead to the achievement of "personalized therapy" for this disease.

Adult↗

[Antibody directed therapy for leukemia].

Recently, monoclonal antibody(MoAb) therapies which direct at antigens such as CD33, CD45 and GM-CSF receptors on myeloid leukemia cells have been in progress. There are three major MoAb therapies against acute myeloid leukemia(AML), which include unconjugated MoAb, MoAb conjugated with chemotherapy or toxins, and MoAb conjugated with radioisotopes. Gemtuzumab ozogamicin is consisting of an engineered human anti-CD33 antibody linked with the potent anti-tumor antibiotic calicheamicin, which is the most effective for AML. However, recent studies suggested that calicheamicin was also pumped out by multi-drug resistance(MDR) related P-glycoprotein. The combination therapy with MDR modifiers may improve the effect of gemtuzumab ozogamicin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Prediction of chemosensitivity for patients with acute myeloid leukemia, according to expression levels of 28 genes selected by genome-wide complementary DNA microarray analysis.

To identify genes involved in the sensitivity of acute myeloid leukemia (AML) cells to chemotherapy, we monitored gene-expression profiles of cancer cells from 76 AML patients using a cDNA microarray consisting of 23,040 genes. We identified 63 genes that were commonly overexpressed and 372 genes suppressed in AML. Because these genes represent key molecules for disclosing the molecular mechanisms of AML, they may be potential targets for drug development. We also found 28 that revealed different expression levels between good and poor responders to chemotherapy and appeared to be associated with chemosensitivity. On that basis, we developed a "Drug Response Scoring" system that was correlated well with individual sensitivity to an anticancer drug regimen. Among the 44 cases with positive drug-response scores by our definition, 40 achieved complete remission after treatment, whereas the only 3 of the 20 cases with negative scores responded well to the treatment. An ability to predict chemosensitivity should eventually lead to achievement of our goal of "personalized therapy."

Adult↗

The effect of the configuration and the interior design of a virtual weightless space station on human spatial orientation.

In a virtual weightless environment, subjects' orientation skills were studied to examine what kind of cognitive errors people make when they moved through the interior space of virtual space stations and what kind of visual information effectively decreases those errors. Subjects wearing a head-mounted display moved from one end to the other end in space station-like routes constructed of rectangular and cubical modules, and did Pointing and Modeling tasks. In Experiment 1, configurations of the routes were changed with such variables as the number of bends, the number of embedding planes, and the number of planes with respect to the body posture. The results indicated that spatial orientation ability was relevant to the variables and that orientational errors were explained by two causes. One of these was that the place, the direction, and the sequence of turns were incorrect. The other was that subjects did not recognize the rotation of the frame of reference, especially when they turned in pitch direction rather than in yaw. In Experiment 2, the effect of the interior design was examined by testing three design settings. Wall colors that showed the allocentric frame of reference and the different interior design of vertical and horizontal modules were effective; however, there was a limit to the effectiveness in complicated configurations.

Adult↗