RESUMO
Dedicator of cytokinesis 2 (DOCK2) can activate the downstream small G protein Rac and regulate cytoskeletal reorganization. DOCK2 is essential for critical physiological processes such as migration, activation, proliferation, and effects of immune cells, including lymphocytes, neutrophils, macrophages, and dendritic cells. For example, DOCK2 is involved in the development and activation of T and B lymphocytes by affecting synapse formation and inhibiting the development of the Th2 lineage by downregulating IL-4Rα surface expression. Not only that, DOCK2 may be a molecular target for controlling cardiac transplant rejection and Alzheimer's disease (AD). Patients with defects in the DOCK2 gene also exhibit a variety of impaired cellular functions, such as chemotactic responses of lymphocytes and reactive oxygen species (ROS) production by neutrophils. To date, DOCK2 has been shown to be involved in the development of various diseases, including AD, pneumonia, myocarditis, colitis, tumors, etc. DOCK2 plays different roles in these diseases and the degree of inflammatory response has a different impact on the progression of disease. In this paper, we present a review of recent advances in the function of DOCK2 in various immune cells and its role in various diseases.
RESUMO
Human gastrointestinal cancer (e.g., gastric cancer and colorectal cancer) has been a leading cause of cancer-related deaths worldwide and has imposed a great threat to the public health. Although early-stage gastrointestinal cancer can be effectively treated by surgery, followed by postoperative chemotherapy, patients with advanced gastrointestinal cancer often exhibit poor prognosis and cancer relapse due to the absence of effective personalized treatment strategies. Patient-derived cancer organoid technology has been rapidly developed in recent years, and its emergence has opened up an unprecedented approach to model human cancers in vitro. Patient-derived cancer organoids involve the ex vivo culture of fragments of freshly resected human tumors that retain the histological features of original tumors. This review thoroughly discussed the evolutionary process of human gastrointestinal organoids cultured since 2009, and highlighted the potentials of patient-derived cancer organoids in clinical management of gastrointestinal cancer in terms of advances achieved in cancer modelling compared with conventional modelling methods, high-throughput drug screening, and development of personalized treatment selection. Additionally, the current limitations of patient-derived cancer organoids and the potential solutions to overcome these problems were summarized.