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Makoto Hamada

Publications and source records attributed to Makoto Hamada.

5 recordsLinked to original sources

Total synthesis of (-)-kaitocephalin.

[reaction: see text] Total synthesis of the potent AMPA/KA receptor antagonist (-)-kaitocephalin (1) and its three diastereomers has been accomplished. The synthesis features strictly substrate-controlled operations to alpha-formylglutamate 3 starting with alpha-hydroxymethylglutamate 4. The requisite 2R,3S,7R-stereocenters were efficiently constructed by manipulation of stereoselective reactions: dihydroxylation of 7 followed by azide substitution of the corresponding thionocarbonate 10 and Cu-mediated allylation of an acyliminium ion 21. All of the protecting groups in 26 were removed simultaneously by AlCl3/Me2S to give 1.

Lactams↗

The expression of the aurora-A gene and its significance with tumorgenesis in non-Hodgkin's lymphoma.

Non-Hodgkin's lymphoma (NHL) has a wide biological heterogeneity with various cell origin and biological features. Recent WHO classification of lymphoid neoplasms gives importance to immunological and cytogenetic features in addition to morphologic aspects of tumors. Several investigators have performed NHL subclassification based on other biological features of tumor cells. It is extremely important to clarify the proliferation mechanism of tumor cells, and understanding this mechanism may provide insight not only into the biology of tumors but also into the treatment strategy for NHL. Therefore, research focused on the cell cycle is one of the major approaches to the biology and the oncogenesis of NHL. The Aurora kinase family recently identified from Drosophila melamogaster is believed to be an essential kinase involved in mitotic cell cycles. Several groups have reported that Aurora kinases are overexpressed in some solid tumors, suggesting that Aurora kinases may be involved in tumor survival and proliferation. Here, we focus on the role of Aurora-A kinase in the tumorgenesis of NHL using our recent research data, and discuss the possibility of Aurora-A as a new molecular target of NHL treatment.

Animals↗

Role of CD21 antigen in diffuse large B-cell lymphoma and its clinical significance.

Recent advances in immunological and molecular technology have prompted proposals to change tumour classification and treatment strategies. Cell surface antigens are now easy to access, and tumour origins and clinical characteristics are now readily identifiable. However, in diffuse large B-cell lymphoma (DLBCL), one of the heterogeneous forms of haematological malignancy, the clinical significance of tumour surface antigens has not been well documented. We analysed the tumour surface antigens of 50 tumours from newly diagnosed DLBCL patients by flow cytometry in accordance with their clinical characteristics and followed the patients for a median 3.7 years. Statistical analysis showed that CD21 expression was significantly negatively associated with mortality in DLBCL (CD21 negative versus positive; relative risk = 2.36, P < 0.05). As a result of these clinical observations, we generated CD21-overexpressed (CD21(+)) lymphoma cell lines after gene transfection and analysed tumour cell growth in vivo in immunocompromised mice. Mice challenged with vector-only transfectants and parental cells as controls died within 50 d. In contrast, mice injected with CD21(+) transfectants exhibited significantly reduced tumour growth and 83% survived long term (versus control groups; P < 0.05). Interestingly, all established CD21(+) transfectants (six clones from different bulks) showed homotypic aggregation during in vitro cell culture, and anti-CD21 antibodies did not block this aggregation. Expression of CD21 is strongly associated with increased survival in DLBCL in vivo. CD21 expression may be indirectly concerned with the expression of additional cell adhesion molecules.

Animals↗

Aurora2/BTAK/STK15 is involved in cell cycle checkpoint and cell survival of aggressive non-Hodgkin's lymphoma.

Non-Hodgkin's lymphoma (NHL) has a wide biological heterogeneity and shows extremely variable responses to therapeutic measures. However, markers that indicate disease activity and determine treatment strategies for this malignancy are little recognized. Using the differential display method, we have identified Aurora2/BTAK/STK15, a centrosome-associated serine/threonine kinase, whose overexpression leads to centrosome amplification, chromosomal instability and transformation of mammalian solid tumours. Northern analysis with mRNA from a single tumour cell suspension of NHL confirmed that Aurora2/BTAK/STK15 was highly expressed in histologically aggressive types. To elucidate the function of Aurora2/BTAK/STK15 in NHL, Aurora2/BTAK/STK15 sense or antisense genes were transfected to B-cell lymphoma cell lines to generate overexpressed or under-regulated tumour cells. Aurora2/BTAK/STK15 antisense transfectant was barely established compared with a sense or vector-only transfectant. Two clones were finally established that exhibited a low proliferation rate and significantly increased G1 arrest compared with vector-only transfectants. Moreover, antisense oligo treatment in vitro showed that restriction of cell growth appeared in proportion to antisense oligo concentration. These results suggest that Aurora2/BTAK/STK15 is an effective candidate to indicate not only disease activity but also tumorigenesis of non-Hodgkin's lymphoma. Retardation of tumour cell growth resulting from the restriction of this gene's functions may be a novel therapeutic approach for non-Hodgkin's lymphoma.

Aurora Kinase A↗