Hematology, Endocrinology and Metabolism

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1.Research Summary

The Department of Hematology, Endocrinology, and Metabolism is divided into the Endocrinology and Metabolism Group and the Hematology Group. Highly technical research is conducted in both areas. With the two groups working cooperatively we cover a wide range of disorders, from lifestyle-related diseases to tumors, in internal medicine.

2.Research Groups

3-1.Endocrinology and Metabolism GroupEndocrinology and Metabolism Group

Research subjects

Clinical epidemiology of lifestyle-related diseases, including diabetes mellitus, dyslipidemia, and obesity
Predictors for lifestyle-related diseases, including diabetes mellitus, in health check-up recipients
Mechanism of anti-diabetic action of new anti-diabetic candidate BDNF
Development of new anti-diabetic agents focusing on nuclear receptor regulation
Measurement of AGEs and investigation of their association with complications in diabetic patients
Treatment of periodontitis and kinetics of adipocytokines in diabetic patients
Analysis of autoregulation of renal blood flow in diabetes mellitus

3-2.Hematology Group

Research subjects

Pathological analysis of hematopoietic tumors
Treatment of chronic myelogenous leukemia
Analysis of prognostic factors in malignant lymphoma
Development of new therapies for refractory malignant lymphoma
Development of appropriate therapies using new drugs for myeloma
Allogeneic immunity and antitumor immunity in hematopoietic stem cell transplantation
Basic research on hematopoietic environment and hematopoietic stem cells, and the pathogenesis of hematopoietic tumors
Development of new hematopoietic stem cell transplantation techniques for refractory hematopoietic tumors

4.Research Results

[Area] Endocrinology and metabolism

[Research subject]

Clinical epidemiology of lifestyle-related diseases, including diabetes mellitus, dyslipidemia, and obesity

[DescriptionDescription]
Metabolic and endocrine diseases, such as diabetes mellitus, hyperlipidemia, hypertension, gout, obesity and excessive thinness, metabolic syndrome, and osteoporosis, have become epidemic and have become a threat to people’s health and lives in developed countries, including Japan, in recent years. To overcome such metabolic and endocrine diseases, or so-called lifestyle-related diseases, prophylaxis, diagnosis, and treatment must be performed based on the results (clinical evidence and large-scale epidemiologic data) of studies analyzing science-based data, in particular clinical data (including medical examination data) in a large group. The aim of this subject is to establish evidence facilitating the prophylaxis and treatment of metabolic and endocrine, or lifestyle-related, diseases through clinical research, epidemiologic studies, and clinical data analysis to contribute to the health and longevity of people worldwide. Particularly, we place the greatest importance on lifestyle habits, such as diet and exercise, and provide instructions in both of these areas. We believe interdisciplinary fusion of medicine or internal medicine, and general medical sciences (e.g., nutritional science, biomechanics, sports medicine, health science, and statistics), instead of investigations in the former field alone, to also be important for achieving our goal. We have already established a large body of evidence published in highly-regarded and peer-reviewed foreign medical journals. Our findings have proven to be useful in the clinical setting and for the preparation of guidelines.

[Area] Hematology

[Research subject]

Prognostic factors for diffuse large B-cell lymphoma

[Description]
For diffuse large B-cell lymphoma (DLBCL), R-CHOP therapy is regarded as the standard treatment, but there is known to be a group of treatment-refractory patients with poor outcomes. Using FISH analysis, we discovered that approximately 10% of DLBCL patients have translocations in the MYC gene region which portends a very poor prognosis (figure in right). We reported similar results in as many as 100 patients by conducting collaborative research with Tokai University and the University of Tsukuba (Leuk Lymphoma. 2013;54:2149). We are currently investigating an effective therapy for this group.

[Photographs]

Photographs

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[Area] Hematology

[Research subject]

Treatment of chronic myelogenous leukemia with tyrosine kinase inhibitors

[Description]
Tyrosine kinase inhibitors significantly changed the treatment of chronic myelogenous leukemia and set a precedent for molecular targeted therapy for malignant tumors. Molecular targeted drugs require specific management of adverse reactions and efficacy evaluation in the clinical setting as they have mechanisms of action different from those of conventional anticancer agents. We have been analyzing the clinical effect of imatinib against chronic myelogenous leukemia by conducting collaborative research with relevant hospitals.
Based on our analysis, we reported a significantly better prognosis in patients with an early mass reduction of at least 3 logs as confirmed by quantitative PCR or the FISH method 18 months after the initiation of treatment (Int J Hematol. 2011;93:336). In addition, in collaboration with Akita University, we discovered that blood imatinib concentrations are involved in the 3-log reduction (Clin Pharmacol Ther. 2010 88:809). Based on long-term clinical follow-up, we further reported that blood imatinib concentrations also affect the tolerability of long-term treatment (ASH meeting. 2012. Dec). We are also investigating cell biological factors that influence therapeutic effects.

[Area] Endocrinology and metabolism

[Research subject]

Mechanism of anti-diabetic action of new anti-diabetic candidate BDNF

[Description]
Amid a significant worldwide increase in diabetic patients, there are considerable numbers of patients whose blood glucose cannot be well controlled with instructions on lifestyle modifications or conventional medications, and novel anti-diabetics with new mechanisms of action are needed. We have reported that brain-derived neurotrophic factors (BDNFs) exert inhibitory effects on the secretion of glucagon from pancreatic alpha cells, in addition to suppressing appetite. BDNFs have also been reported to exert increasing effects on basal metabolism and are highly anticipated future anti-diabetic agents.

[Photographs]

[Expression of BDNF receptor TrkB in mouse pancreatic alpha cells]

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