ABSTRACT
Abstract Spleen tyrosine kinase (SYK) is not only a key kinase in the B-cell receptor (BCR) signaling pathway, but also a critical component of other signal transduction pathways such as Fc receptor, complement receptor and integrin. Abnormal activation of SYK closely related to the occurrence and development of hematological malignancies, thus targeting SYK has become a research hotspot. Several SYK inhibitors including Fostamatinib, Entospletinib and Cerdulatinib were being evaluated in clincal trials. As a second generation SYK inhibitor, Entospletinib has achieved good efficacy in lymphoid and myeloid hematologic tumors. Furthermore, Entospletinib can significantly relieve hematopoietic stem cell transplantation(HCT) related graft versus host disease (GVHD). In this review the role of SYK inhibitors in treatment of hematological malignancies is summarized brifely.
Subject(s)
Humans , Graft vs Host Disease , Hematologic Neoplasms , Protein Kinase Inhibitors , Spleen , Syk KinaseABSTRACT
Abstract In recent years, development of the targeted drugs according to the biological characteristics of tumors have provided more treatment options for tumor patients. It was found that the overactivation or abnormality of B cell receptor (BCR) signal pathway closely related to the occurrence and development of various B cell tumors, such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). As a key kinase in the BCR pathway, BTK inhibitors have obvious anti-tumor effect when its activity is being inhibitered. Currently, BTK inhibitors developed include the first-generation Ibrutinib and the second-generation Acalabrutinib, which can be targeted at the inhibition of BTK and its downstream signaling pathway, and have important therapeutic value for a variety of B-cell tumors, such as CLL and partial non-Hodgkin's lymphoma (NHL). However, its side effects and drug-resistance also gradually emerged, effective drug combination therapy has shown a certain clinical activity. This reviews summarizes briefly the mechanism and status of BTK inhibitors in the treatment of various B-cell tumors.
ABSTRACT
Epigenetic abnormalities play an important role in the pathogenesis of hematological malignancies, especially acute leukemia (AL). Similar to DNA methylation and histone modifications, RNA methylation is another important epigenetic modification. m6A methylation is one of the most prevalent and extensively studied RNA methylation. m6A methylation is involved in many biological and pathological process. Recent studies have found that m6A methylation is involved in the occurrence, development and drug-resistance of AL. This review focuses on the research progress of m6A methylation in AL.
Subject(s)
Humans , DNA Methylation , Epigenesis, Genetic , LeukemiaABSTRACT
<p><b>OBJECTIVE</b>To explore factors affecting occupational adaptability in nurses for offering basis to increase their occupational adaptability.</p><p><b>METHODS</b>Five hundred and forty-five nurses were investigated with work ability index questionnaire and occupational stress instruments.</p><p><b>RESULTS</b>There were many risk factors affecting occupational adaptability in nurses. The main variables that influenced occupational adaptability included work-overtime, mental load, social support, physical environment, and job hazards. The social support was the factor increasing the occupational adaptability of the nurses (P < 0.01, OR = 0.912). Five factors including work overtime, mental load, social support, physical environment and job hazards were introduced in the Logistic equation. The established functions were: Logit (P) = -11.357 + 1.011x(1) + 0.335x(2) - 0.076x(3) + 0.260x(4) + 0.129x(5).</p><p><b>CONCLUSION</b>There are many risk factors affecting occupational adaptability in nurses. Relevant measures should be taken to promote the occupational adaptability in nurses to reduce the risk factors.</p>