The altered expression of homing factors in CD34+ hematopoietic stem cells following G-CSF injection and its effects on transplantation quality in ALL patients.

Hematopoietic stem cells (HSCs) transplantation is considered a suitable treatment for malignant or nonmalignant hematological diseases. This study aims to investigate the HSCs homing factors in bone marrow (BM) donors of acute lymphoblastic leukemia (ALL) patients following granulocyte colony-stimulating factor (G-CSF) injection, as well as the G-CSF effects on BM transplantation quality in these patients. To mobilize HSCs into peripheral blood, G-CSF was used for ALL patient's BM donors. For HSCs counting, CD34+ cells were evaluated in analogous and autologous donors using flow cytometry. The expression of stem cell homing factors in CD34+ cells and peripheral blood mononuclear cells (PBMCs) were investigated using a real-time polymerase chain reaction. Finally, hematological factors after BM transplantation in ALL patients were assessed. According to our results, after G-CSF injection, the level of CD34+ HSCs was statistically increased. Besides, autologous donors showed a higher level of CD34+ cells compared to analogous donors before and after G-CSF injection. Additionally, a higher number of CD34+ HSCs was achieved in the autologous samples following G-CSF injection. Furthermore, after G-CSF injection, the expression of matrix metalloproteinase (MMP)-2, MMP-9 was increased; while, stromal cell-derived factor 1, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 expression were decreased. Moreover, the expression of C-X-C chemokine receptor type 4, lymphocyte function-associated antigen 1, and very late antigen-4 in CD34+ cells and PBMCs were decreased. BM transplantation on Day 90 also caused an increased level of white blood cells, red blood cells, and platelets as compared to the first day; however, no statistical differences were observed in hemoglobin level. In conclusion, G-CSF by altering the expression of HSCs homing factors in ALL donors improves BM transplantation quality in ALL patients.

Inhibition of HIF-1α/EP4 axis by hyaluronate-trimethyl chitosan-SPION nanoparticles markedly suppresses the growth and development of cancer cells.

Increased expression of Hypoxia-inducible factor-1α (HIF-1α) in the tumor microenvironment, mainly due to tumor growth, plays a major role in the growth of cancer. Tumor cells induce the expression of cyclooxygenase 2 (COX2) and its product, prostaglandin E2 (PGE2), through overexpression of HIF-1α. It has been shown that ligation of PGE2 with its receptor, EP4, robustly promotes cancer progression. HIF-1α/COX2/PGE2/EP4 signaling pathways appear to play an important role in tumor growth. Therefore, we decided to block the expansion of cancer cells by blocking the initiator (HIF-1α) and end (EP4) of this pathway. In this study, we used hyaluronate (HA), and trimethyl chitosan (TMC) recoated superparamagnetic iron oxide nanoparticles (SPIONs) loaded with HIF-1α-silencing siRNA and the EP4 antagonist (E7046) to treat cancer cells and assessed the effect of combination therapy on cancer progression. The results showed that optimum physicochemical characteristics of NPs (size 126.9 nm, zeta potential 27 mV, PDI < 0.2) and linkage of HA with CD44 molecules overexpressed on cancer cells could deliver siRNAs to cancer cells and significantly suppress the HIF-1α in them. Combination therapy of cancer cells by using HIF-1α siRNA-loaded SPION-TMC-HA NPs and E7046 also prevent proliferation, migration, invasion, angiogenesis, and colony formation of the cancer cells, remarkably.