Direct and Indirect Effects of Androgens on Survival of Hematopoietic Progenitor Cells In Vitro

Androgens remain a common treatment for certain type of anemia, based upon its myelostimulating effects; however, it has not been established whether androgens affect apoptosis of hematopoietic progenitor cells (HPCs). We investigated the effects of the androgens, such as testosterone, 5β-dihydrotestosterone (5-DHT), and oxymetholone, on apoptosis of normal hematopoietic progenitor cells in vitro. Androgens did not rescue normal bone marrow (BM) CD34+ cells and colony-forming cells (CFCs), other than mature erythroid CFCs, from apoptosis induced by serum- and growth factor deprivation. Oxymetholone did not affect growth factor-mediated survival of normal CD34+ cells or its inhibition by interferon-gamma (IFN-γ). In a standard methylcellulose clonogenic assay, low concentrations of oxymetholone and 5-DHT stimulated the clonal growth of colony-forming unit (CFU)-erythroid, but did not affect growth of CFU-granulocyte/macrophage or burst-forming unit-erythroid. Oxymetholone and 5-DHT stimulated the production of stem cell factor in normal bone marrow stromal cells (BMSCs) via transcriptional regulation. In agreement with this, oxymetholone-treated BMSCs better supported the survival of HPCs. These data indicate that survival-enhancing or growth-stimulatory effects of androgens on hematopoietic progenitor cells are minimal and mostly restricted to mature erythroid progenitors, and its myelostimulating effects could be attributed, at least in part, to the stimulation of production of hematopoietic growth factors in BMSCs

The role of the CXCR4/CXCL12 axis and its clinical implications in gastric cancer

Gastric cancer is the second leading cause of cancer deaths worldwide. Despite the extensive body of research on gastric cancer, the prognosis of patients with advanced gastric cancer remains poor, and therapy for advanced gastric cancer relies largely on cytotoxic chemotherapy. Therefore, identifying the distinct molecular pathways underlying disease progression and treatment resistance may lead to novel therapeutic approaches, as well as improve the quality of life and survival of patients. The chemokine CXCL12 and its receptor CXCR4 are now known to play an important role in cancer development and progression. Here, we review the expression and function of CXCR4 and CXCL12, as well as their clinical relevance in gastric cancer. We also cover the current molecular mechanism, specifically the cell-signaling pathway, by which gastric cancer progresses through the CXCR4/CXCL12 axis, and discuss the potential of that axis as a therapeutic target in the treatment of gastric cance