G-CSF/GM-CSF-induced hematopoietic dysregulation in the progression of solid tumors.

There are two types of abnormal hematopoiesis in solid tumor occurrence and treatment: pathological hematopoiesis, and myelosuppression induced by radiotherapy and chemotherapy. In this review we primarily focus on the abnormal pathological hematopoietic differentiation in cancer induced by tumor-released granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). As key factors in hematopoietic development, G-CSF/GM-CSF are well-known facilitators of myelopoiesis and mobilization of hematopoietic stem cells (HSCs). In addition, these two cytokines can also promote or inhibit tumors, dependent on tumor type. In multiple cancer types, hematopoiesis is greatly enhanced and abnormal lineage differentiation is induced by these two cytokines. Here, dysregulated hematopoiesis induced by G-CSF/GM-CSF in solid tumors and its mechanism are summarized, and the prognostic value of G-CSF/GM-CSF-associated dysregulated hematopoiesis for tumor metastasis is also briefly highlighted.

20(S)-Protopanaxdiol Suppresses the Abnormal Granule-Monocyte Differentiation of Hematopoietic Stem Cells in 4T1 Breast Cancer-Bearing Mouse.

Panax notoginseng (PN) has been used as a qi- and blood-activating (Huoxue) drug for thousands of years in China. It has also been widely used as an anticancer drug at present. As a Huoxue drug, the effect of PN on hematopoietic differentiation in tumor-bearing body has been paid more and more attention. Our research found that panax notoginseng saponins (PNS), especially panaxadiol saponins (PDS) and its aglucon 20(S)-Protopanaxdiol (PPD), could improve the immunosuppressive state by regulating the abnormal hematopoietic differentiation in a tumor-bearing body by multiple ways. An interesting phenomenon is that PDS reduced the neutrophil-lymphocyte ratio (NLR) via its inhibition effect on the granule-monocyte differentiation of spleen cells, which is associated with a decrease in the secretion of tumor MPO, G-CSF, PU.1, and C/EBPα. Otherwise, PDS increased the proportion of both hematopoietic stem cells and erythroid progenitor cells in the bone marrow, but inhibited spleen erythroid differentiation via inhibiting secretion of tumor EPO, GATA-1, and GATA-2. This study suggests that PNS regulated the tumor-induced abnormal granule-monocyte differentiation of hematopoietic stem cells, affecting the distribution and function of haemocytes in tumor-bearing mice.

Epimedin C Protects H2O2-Induced Peroxidation Injury by Enhancing the Function of Endothelial Progenitor HUVEC Populations.

Endothelial cell injury and apoptosis induced by oxidative stress serve important roles in many vascular diseases. The repair of endothelial cell vascular injury relies on the function of local endothelial progenitor cells (EPCs). Our previous study indicated that epimedin C, a major flavonoid derived from Herba epimedii (yin yang huo), could promote vascularization by inducing endothelial-like differentiation of mesenchymal stem cells C3H/10T1/2 both in vivo and in vitro. In view of the significant cardiovascular protective effects of Herba epimedii, we detected a protective effect of epimedin C on hydrogen peroxide (H2O2)-induced peroxidation injury in human umbilical vein endothelial cells (HUVECs) and the role of EPC in this process. The results show that epimedin C increased the expression of the stem cell marker, CD34 and PROM1, and subsequently enhanced the expression and function of vascular endothelial growth factor and matrix metalloproteinase (MMP)-2 in local vascular endothelial cells. In conclusion, epimedin C protects H2O2-induced peroxidation injury by enhancing the function of endothelial progenitor HUVEC populations.

Review camptothecin: current perspectives.

The review provides a detailed discussion of recent advances in the medicinal chemistry of camptothecin, a potent antitumor agent that targets topoisomerase I. Thousands of CPT derivatives have been synthesized. Two of them, Topotecan and Irinotecan, are commercially approved for use in clinic as antitumor agents while more are still in clinic trials. This review summarizes the current status of the modern synthetic approaches to CPT, the mechanism of action of CPT, the structure-activity relationship(SAR), a number of novel CPT analogs and their biologic activity. There is a systematic evaluation of A-, B- and E-ring- modified camptothecins reported recently.