Research Status, Synthesis and Clinical Application of Recently Marketed and Clinical BCR-ABL Inhibitors.

Tyrosine kinases expressed by BCR-ABL fusion genes can cause changes in cell proliferation, adhesion, and survival properties, which are the main causes of chronic myelogenous leukemia (CML). Inhibiting the activity of BCR-ABL tyrosine kinase has become one of the effective methods for the treatment of chronic myelogenous leukemia. Initially, imatinib was the first small molecule of BCR-ABL tyrosine kinases inhibitors (TKIs) for the effective treatment of chronic myelogenous leukemia.

Exogenous R-Spondin1 Induces Precocious Telogen-to-Anagen Transition in Mouse Hair Follicles.

R-spondin proteins are novel Wnt/β-catenin agonists, which signal through their receptors leucine-rich repeat-containing G-protein coupled receptor (LGR) 4/5/6 and substantially enhance Wnt/β-catenin activity. R-spondins are reported to function in embryonic development. They also play important roles in stem cell functions in adult tissues, such as the intestine and mammary glands, which largely rely on Wnt/β-catenin signaling.

Egr1 protein acts downstream of estrogen-leukemia inhibitory factor (LIF)-STAT3 pathway and plays a role during implantation through targeting Wnt4.

Embryo implantation is a highly synchronized process between an activated blastocyst and a receptive uterus. Successful implantation relies on the dynamic interplay of estrogen and progesterone, but the key mediators underlying embryo implantation are not fully understood. Here we show that transcription factor early growth response 1 (Egr1) is regulated by estrogen as a downstream target through leukemia inhibitory factor (LIF) signal transducer and activator of transcription 3 (STAT3) pathway in mouse uterus.

NASA-approved rotary bioreactor enhances proliferation of human epidermal stem cells and supports formation of 3D epidermis-like structure.

The skin is susceptible to different injuries and diseases. One major obstacle in skin tissue engineering is how to develop functional three-dimensional (3D) substitute for damaged skin. Previous studies have proved a 3D dynamic simulated microgravity (SMG) culture system as a "stimulatory" environment for the proliferation and differentiation of stem cells.

Dickkopf-1 enhances migration of HEK293 cell by beta-catenin/E-cadherin degradation.

Migration is an important process during cellular activity and embryo development. We recently showed that Dickkopf-1(Dkk-1), an antagonist of Wnt/ beta-catenin signaling pathway, could promote trophoblast cell invasion during murine placentation. However, mechanism of Dkk-1 action on cell migration was not clear.

Roles of Dickkopf-1 and its receptor Kremen1 during embryonic implantation in mice.

Objective: To determine the roles of Dickkopf-1 (Dkk1) in mouse embryo implantation.

Design: Experimental prospective study.

Setting: Animal research and institute laboratory facility.

Nitric oxide affects preimplantation embryonic development in a rotating wall vessel bioreactor simulating microgravity.

Microgravity was simulated with a rotating wall vessel bioreactor (RWVB) in order to study its effect on pre-implantation embryonic development in mice. Three experimental groups were used: stationary control, rotational control and clinostat rotation. Three experiments were performed as follows.

Role of sonic hedgehog in maintaining a pool of proliferating stem cells in the human fetal epidermis.

Background: The mammalian epidermis is maintained by the ongoing proliferation of a subpopulation of keratinocytes known as epidermal stem cells. Sonic hedgehog (Shh) can regulate morphogenesis of hair follicles and several types of skin cancer, but the effect of Shh on proliferation of human putative epidermal stem cells (HPESCs) is poorly understood.

Methods And Results: We first found that Shh, its receptors Patched1 (Ptc1) as well as Smoothened (Smo) and its downstream transcription factor Gli-1 were expressed in the basal layer of human fetal epidermis and freshly sorted HPESCs.

Expression and hormonal regulation of calcyclin-binding protein (CacyBP) in the mouse uterus during early pregnancy.

Calcyclin-binding protein (Siah-1-Interacting Protein, CacyBP/SIP), is a calcium signaling protein involved in the degradation of beta-catenin, however, little is known about its role in reproductive biology. The present study was to character its temporospatial expression pattern and regulation in mouse uterus and to investigate whether it plays a role in the regulation of normal endometrial events. While prominently expressed in both luminal and glandular epithelia, CacyBP underwent dynamic changes during early pregnancy.

Leptin-directed embryo implantation: leptin regulates adhesion and outgrowth of mouse blastocysts and receptivity of endometrial epithelial cells.

Leptin is a 16-kDa multifunctional protein. Recent reports indicate that leptin is an important molecule during implantation and placentation, implicated in embryonic-maternal cross-talk and cytotrophoblast invasiveness, however, the role of leptin playing in the process of normal blastocyst implantation has not been well characterized. In the present study, the possible mechanisms of leptin playing in mouse blastocyst implantation were investigated.

Inhibition of the beta-catenin signaling pathway in blastocyst and uterus during the window of implantation in mice.

Beta-catenin, the mammalian homolog of Drosophila armadillo protein, was first identified as a cadherin-associated protein at cell-cell junctions. Another function of beta-catenin is the transduction of cytosolic signals to the nucleus in a variety of cellular contexts, which usually are elicited by the active form of beta-catenin. The aim of the present study was to examine the potential role of active beta-catenin in the mouse embryo and uterus during embryo implantation.

Enrichment and characterization of mouse putative epidermal stem cells.

Epidermis, a continuously renewing tissue, is maintained by stem cells that proliferate and replenish worn out or damaged cells in the tissue during life. Cultured epidermal stem cells have great potential in scientific research and clinical application. However, isolating a pure and viable population of epidermal stem cells and culturing them has been challenging.

Enrichment and identification of human 'fetal' epidermal stem cells.

Background: Human epidermis, a continuously renewing tissue, is maintained throughout life by stem cells that proliferate and replenish worn-out or damaged cells in the tissue. Cultured human epidermal stem cells have great potential in clinical application. However, isolating and culturing a pure population of epidermal stem cells has proven to be challenging.

Effects of fibronectin, VEGF and angiostatin on the expression of MMPs through different signaling pathways in the JEG-3 cells.

Problem: The objective of this study was to evaluate the possible signal pathway of fibronectin (FN), vascular endothelial growth factor (VEGF) and angiostatin (AS) on the expression of matrix metalloproteinases (MMPs) in JEG-3 cells.

Methods Of Study: JEG-3 cells were cultured and were examined for the effect of FN, VEGF and AS on the expression of MMPs by immunocytochemistry, gelatin zymography, Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR).

Results: We found that up-regulation of the expression of MMPs was induced by FN and VEGF through the focal adhesion kinase (FAK)/mitogen-activated protein kinase (MAPK) and Flt-1/p38SAPK/MAPKAPK2 signaling pathways, respectively.

Expression and implications of tissue inhibitor of metalloproteinases-4 in mouse embryo.

Matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinases (TIMP), and MMP-TIMP interactions may contribute to the highly programmed process of embryo implantation. The loss of the delicate MMP-TIMP balance may lead to abnormal implantation. The role of TIMP-4 in mouse implantation has not been reported.

Expression of matrix metalloproteinase-26 and tissue inhibitor of metalloproteinase-4 in human normal cytotrophoblast cells and a choriocarcinoma cell line, JEG-3.

The balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) is critical for embryo implantation. Disturbance of this balance may lead to tumour metastasis. To understand the roles of MMP-26 and TIMP-4 in physiological and pathological invasion, the expression of these proteins in normal human cytotrophoblast cells and in a malignant choriocarcinoma cell line, JEG-3, was investigated.