CUDC-101 as a dual-target inhibitor of EGFR and HDAC enhances the anti-myeloma effects of bortezomib by regulating G2/M cell cycle arrest / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

CUDC-101, an effective and multi-target inhibitor of epidermal growth factor receptor (EGFR), histone deacetylase (HDAC), and human epidermal growth factor receptor 2 (HER2), has been reported to inhibit many kinds of cancers, such as acute promyelocytic leukemia and non-Hodgkin's lymphoma. However, no studies have yet investigated whether CUDC-101 is effective against myeloma. Herein, we proved that CUDC-101 effectively inhibits the proliferation of multiple myeloma (MM) cell lines and induces cell apoptosis in a time- and dose-dependent manner. Moreover, CUDC-101 markedly blocked the signaling pathway of EGFR/phosphoinositide-3-kinase (PI3K) and HDAC, and regulated the cell cycle G2/M arrest. Moreover, we revealed through in vivo experiment that CUDC-101 is a potent anti-myeloma drug. Bortezomib is one of the important drugs in MM treatment, and we investigated whether CUDC-101 has a synergistic or additive effect with bortezomib. The results showed that this drug combination had a synergistic anti-myeloma effect by inducing G2/M phase blockade. Collectively, our findings revealed that CUDC-101 could act on its own or in conjunction with bortezomib, which provides insights into exploring new strategies for MM treatment.

Graft failure in allogeneic hematopoietic stem cell trans-plantation / 浙江大学学报·医学版

With the progress of medical technology, the development of new drugs and the improvement of the therapeutic effect of graft-versus host disease in the last two decades, the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) have been greatly improved. However, graft failure is still a rare but serious complication of allo-HSCT. HLA incompatibility, virus infection, elderly donor, uncontrolled primary disease, damage of bone marrow hematopoietic microenvironment, ABO blood group incompatibility, T cell depletion, reduced intensity conditioning, and low nucleated cell number are all risk factors for graft failure. In recent years, with the implementation of HLA haplo-identical hematopoietic stem cell transplantation, the role of donor-specific antibodies in graft failure has attracted attention increasingly. This article reviews the recent studies involving the mechanism, risk factors and prevention measures of graft failure in allo-HSCT.