Cyclin-dependent kinase like 3 promotes triple-negative breast cancer progression via inhibiting the p53 signaling pathway.

It has been reported that cyclin-dependent kinase like 3 (CDKL3) plays a crucial role in cell proliferation and migration in several cancers. However, the function of CDKL3 in triple-negative breast cancer (TNBC) is still unclear. In the present study, immunohistochemistry (IHC) was conducted to detect the CDKL3 expression. CCK-8, flow cytometry, Transwell assays, and mice xenograft models, were performed to explore the roles of CDKL3 on the proliferation and migration of TNBC in vitro and in vivo. Besides, protein chip analysis was used to screen the potential pathways, which was further confirmed by promoter activity assay, western blotting, and CCK-8 assay. Our findings reveal a high expression of CDKL3 in TNBC tissues, which is closely related to a poor prognosis of patients with TNBC. In TNBC cells, CDKL3 knockdown inhibits cell proliferation and migration, whereas CDKL3 overexpression has exactly the opposite effect. Consistently, CDKL3 knockdown induces cell apoptosis in vitro but suppresses tumor growth in vivo. Furthermore, CDKL3 knockdown increases p53 expression and reduces cell viability, and these effects are significantly weakened by the p53 inhibitor, PFT-α. In conclusion, the current study highlights that CDKL3 promotes TNBC progressions via regulating the p53 signaling pathway, suggesting that CDKL3 is a novel therapeutic target for TNBC treatment.

[Influence of intra-bone marrow infusion of donor lymphocytes on development of graft-versus-host disease and level of IL-4 and IFN-gamma in peripheral blood].

To investigate the effect of donor lymphocyte infusion (DLI) by intra-bone marrow (IBM) routes on the incidence of graft-versus-host disease(GVHD), level of IL-4 and IFN-gamma after allogeneic peripheral hematopoietic stem cell transplantation (allo-PBSCT). Female C57BL/6 mice as recipients received total body irradiation (TBI) on day 0, followed by injection of peripheral hematopoietic stem cells from mobilized donor of male BALB/c with the granulocyte-colony stimulating factor (rhG-CSF), and DLI was performed via ether IV or IBM routes. The severity of GVHD was compared in recipients received allogeneic IBM-DLI with those mice received IV-DLI; at 14 days after DLI, the levels of IL-4 and interferon (IFN)-gamma were tested by ELISA. The results showed that as compared with IV-DLI group the frequency and severity of GVHD were reduced in IBM-DLI (p < 0.01); the level of IL-4 significantly increased, while the level of IFN-gamma decreased in group IV-DLI (p < 0.01). It is concluded that IBM-DLI declines the incidence and severity of GVHD after allo-PBSCT.

[Influence of intra-bone marrow infusion of peripheral hematopoietic stem cells on graft-versus-host disease].

This study was aimed to explore whether the graft-versus-host disease (GVHD) could be alleviated by intra-bone marrow (IBM) infusion of allogeneic hematopoietic stem cells. Female C57BL/6 mice as recipients received total body irradiation (TBI) 4 Gy on day 0, followed by injection of peripheral hematopoietic stem cells (1 x 10(7)) from mobilized male BALB/c with granulocyte-colony stimulating factor (rhG-CSF), and cyclophosphamide (200 mg/kg) was injected intraperitoneally two days later. The results showed that the incidence and severity of GVHD were more low and alleviative in group IBM-PBSCT than that in group TV-PBSCT (p < 0.05). Y chromosome of donor mice could be detected in the bone marrow of recipient mice. It is concluded that the method of intra-bone marrow infusion is superior to injection via the tail vein in the engraftment of hematopoietic stem cells in terms of stem cell homing while the frequency and severity of GVHD in allogeneic mice decrease.