Home About us Contact
|
Home About us Contact | ||
|
|
||
Signaling Factors (signaling + factor)
Selected AbstractsExpression analysis of chick Wnt and frizzled genes and selected inhibitors in early chick patterningDEVELOPMENTAL DYNAMICS, Issue 3 2004Susan C. Chapman Abstract Wnt signaling is an important component in patterning the early embryo and specifically the neural plate. Studies in Xenopus, mouse, and zebrafish have shown that signaling by members of the Wnt family of secreted signaling factors, their Frizzled receptors and several inhibitors (sFRP1, sFRP2, sFRP3/Frzb1, Crescent/Frzb2, Dkk1, and Cerberus) are involved. However, very little is known about the expression of genes in the Wnt signaling pathway during early anterior neural patterning in chick. We have performed an expression analysis at neural plate stages of several Wnts, Frizzled genes, and Wnt signaling pathway inhibitors using in situ hybridization. The gene expression patterns of these markers are extremely dynamic. We have identified two candidate molecules for anterior patterning of the neural plate, Wnt1 and Wnt8b, which are expressed in the rostral ectoderm at these stages. Further functional studies on the roles of these markers are underway. Developmental Dynamics 229:668,676, 2004. © 2004 Wiley-Liss, Inc. [source] Zebrafish smad7 is regulated by Smad3 and BMP signalsDEVELOPMENTAL DYNAMICS, Issue 3 2002Hans-Martin Pogoda Abstract Growth factors of the TGF-, superfamily such as BMPs and Nodals are important signaling factors during all stages of animal development. Smad proteins, the cytoplasmic mediators of most TGF-, signals in vertebrates, play central roles not only for transmission but also in controlling inductive TGF-, signals by feedback regulation. Here, we describe cloning, expression pattern, transcriptional regulation, and functional properties of two novel zebrafish Smad proteins: the TGF-, agonist Smad3b, and the anti-Smad Smad7. We show that zebrafish Smad3b, in contrast to the related zebrafish Smad2, can induce mesoderm independently of TGF-, signaling. Although mammalian Smad3 was shown to inhibit expression of the organizer-specific genes goosecoid, zebrafish smad3b activates organizer genes such as goosecoid. Furthermore, we show that Smad3 and BMP signals activate smad7. Because Smad7 blocks distinct TGF-, signals in early zebrafish development, our data provide hints for new roles of smad3 genes in the regulation and modulation of TGF-, signals. In summary, our analyses point out differences of Smad3b and Smad2 functions in zebrafish and provide the first link of smad3 and smad7 function in context of vertebrate development. © 2002 Wiley-Liss, Inc. [source] Dentinogenic potential of the dental pulp: facts and hypothesesENDODONTIC TOPICS, Issue 1 2007DIMITRIOS TZIAFAS The aim of the present article is to discuss observations and hypotheses from different experimental approaches on the biological mechanisms underlying initiation of tertiary dentin formation and therapeutic control of pulp,dentinal regeneration. The specific dentinogenic potential of dental pulp cells in up-regulating the biosynthetic activity of primary odontoblasts (reactionary dentinogenesis) and differentiation into odontoblast-like cells (reparative dentinogenesis) is described. The role of biologically active matrices and molecules as signaling factors in the expression of the dentinogenic potential of dental pulp cells, in numerous ex vivo and in vivo models, is reviewed. Data are focused on the mechanisms by which the signaling molecules, in the presence of the appropriate pulp microenvironment and specific mechanical support, can induce competent pulpal cells in the acquisition of odontoblast-like cell phenotype and reparative dentin formation. The ability of tissue engineering to stimulate reconstruction of the amputated pulp,dentin complex offers exciting opportunities for the future. Advances in molecular biology and bioengineering research might thus be integrated into the clinical problems of endodontology. Received 13 February 2009; accepted 2 September 2009. [source] Bystander signaling between glioma cells and fibroblasts targeted with counted particlesINTERNATIONAL JOURNAL OF CANCER, Issue 1 2005Chunlin Shao Abstract Radiation-induced bystander effects may play an important role in cancer risks associated with environmental, occupational and medical exposures and they may also present a therapeutic opportunity to modulate the efficacy of radiotherapy. However, the mechanisms underpinning these responses between tumor and normal cells are poorly understood. Using a microbeam, we investigated interactions between T98G malignant glioma cells and AG01522 normal fibroblasts by targeting cells through their nuclei in one population, then detecting cellular responses in the other co-cultured non-irradiated population. It was found that when a fraction of cells was individually irradiated with exactly 1 or 5 helium particles (3He2+), the yield of micronuclei (MN) in the non-irradiated population was significantly increased. This increase was not related to the fraction of cells targeted or the number of particles delivered to those cells. Even when one cell was targeted with a single 3He2+, the induction of MN in the bystander non-irradiated population could be increased by 79% for AG01522 and 28% for T98G. Furthermore, studies showed that nitric oxide (NO) and reactive oxygen species (ROS) were involved in these bystander responses. Following nuclear irradiation in only 1% of cells, the NO level in the T98G population was increased by 31% and the ROS level in the AG0 population was increased by 18%. Treatment of cultures with 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (c-PTIO), an NO scavenger, abolished the bystander MN induction in non-irradiated AG01522 cells but only partially in non-irradiated T98G cells, and this could be eliminated by treatment with either DMSO or antioxidants. Our findings indicate that differential mechanisms involving NO and ROS signaling factors play a role in bystander responses generated from targeted T98G glioma and AG0 fibroblasts, respectively. These bystander interactions suggest that a mechanistic control of the bystander effect could be of benefit to radiotherapy. © 2005 Wiley-Liss, Inc. [source] Timing of ibuprofen use and bone mineral density adaptations to exercise trainingJOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2010Wendy M Kohrt Abstract Prostaglandins (PGs) are essential signaling factors in bone mechanotransduction. In animals, inhibition of the enzyme responsible for PG synthesis (cyclooxygenase) by nonsteroidal anti-inflammatory drugs (NSAIDs) blocks the bone-formation response to loading when administered before, but not immediately after, loading. The aim of this proof-of-concept study was to determine whether the timing of NSAID use influences bone mineral density (BMD) adaptations to exercise in humans. Healthy premenopausal women (n,=,73) aged 21 to 40 years completed a supervised 9-month weight-bearing exercise training program. They were randomized to take (1) ibuprofen (400,mg) before exercise, placebo after (IBUP/PLAC), (2) placebo before, ibuprofen after (PLAC/IBUP), or (3) placebo before and after (PLAC/PLAC) exercise. Relative changes in hip and lumbar spine BMD from before to after exercise training were assessed using a Hologic Delphi-W dual-energy X-ray absorptiometry (DXA) instrument. Because this was the first study to evaluate whether ibuprofen use affects skeletal adaptations to exercise, only women who were compliant with exercise were included in the primary analyses (IBUP/PLAC, n,=,17; PLAC/PLAC, n,=,23; and PLAC/IBUP, n,=,14). There was a significant effect of drug treatment, adjusted for baseline BMD, on the BMD response to exercise for regions of the hip (total, p,<,.001; neck, p,=,.026; trochanter, p,=,.040; shaft, p,=,.019) but not the spine (p,=,.242). The largest increases in BMD occurred in the group that took ibuprofen after exercise. Total-hip BMD changes averaged ,0.2%,±,1.3%, 0.4%,±,1.8%, and 2.1%,±,1.7% in the IBUP/PLAC, PLAC/PLAC, and PLAC/IBUP groups, respectively. This preliminary study suggests that taking NSAIDs after exercise enhances the adaptive response of BMD to exercise, whereas taking NSAIDs before may impair the adaptive response. © 2010 American Society for Bone and Mineral Research [source] Molecular and Cellular Mechanisms of Ectodomain SheddingTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 6 2010Kazutaka Hayashida Abstract The extracellular domain of several membrane-anchored proteins is released from the cell surface as soluble proteins through a regulated proteolytic mechanism called ectodomain shedding. Cells use ectodomain shedding to actively regulate the expression and function of surface molecules, and modulate a wide variety of cellular and physiological processes. Ectodomain shedding rapidly converts membrane-associated proteins into soluble effectors and, at the same time, rapidly reduces the level of cell surface expression. For some proteins, ectodomain shedding is also a prerequisite for intramembrane proteolysis, which liberates the cytoplasmic domain of the affected molecule and associated signaling factors to regulate transcription. Ectodomain shedding is a process that is highly regulated by specific agonists, antagonists, and intracellular signaling pathways. Moreover, only about 2% of cell surface proteins are released from the surface by ectodomain shedding, indicating that cells selectively shed their protein ectodomains. This review will describe the molecular and cellular mechanisms of ectodomain shedding, and discuss its major functions in lung development and disease. Anat Rec, 293:925,937, 2010. © 2010 Wiley,Liss, Inc. [source] Genetic engineering to study testicular tumorigenesisAPMIS, Issue 1 2003WEI YAN In humans, Sertoli cell tumors account for approximately 4% of all testicular tumors, and 20% of these are malignant. The mechanisms underlying Sertoli cell tumorigenesis remain largely unknown. Using gene knockout technology, we previously generated mutant mice lacking the , subunit of inhibin dimers. The inhibin ,-null male mice develop testicular Sertoli cell tumors with 100% penetrance. These tumors develop as early as 4 weeks of age and cause a cachexia-like wasting syndrome. Castrated inhibin , knockout mice develop sex steroidogenic adrenal cortical tumors. These studies have identified inhibins as secreted tumor suppressors with specificity for the gonads and adrenal glands. It had been suggested that endocrine factors play roles in Sertoli cell tumorigenesis by altering cell cycle machinery of the Sertoli cells. To test the potential of these factors to function as modifiers of Sertoli cell tumorigenesis, we have employed a genetic intercross strategy, breeding inhibin , mutant mice with mutant mice deficient in endocrine signaling factors including gonadotropin releasing hormone (hypogonadal, hpg mice), follicle stimulating hormone, anti-Müllerian hormone (MH), activin receptor type II, or androgen receptor (testicular feminization, tfm mice), or mice overexpressing follistatin. We are also investigating the effects of loss of critical cell cycle regulators, such as cyclin dependent kinase inhibitor p27, on Sertoli cell tumorigenesis in inhibin , knockout males. These studies clearly demonstrate the roles of these factors as modifiers of the Sertoli cell tumorigenesis. Activin signaling through activin receptor type II is responsible for the cachexia-like syndrome observed in the inhibin , knockout mice with tumors. The gonadotropin hormones are essential for testicular tumor development, but elevated FSH levels are not sufficient to cause Sertoli cell tumors. Absence of FSH, lack of androgen receptor, or overexpression of follistatin slows the tumor growth and minimizes the cachexia symptoms, thus prolonging the life span of these double mutant mice. In contrast, absence of AMH or p27 causes earlier onset and more aggressive development of testicular tumor, with an earlier death of double mutant mice. We are currently investigating roles of estrogen signaling pathways, and other cell cycle regulators, in tumor development in the inhibin , knockout mice by generating mice with double or triple mutations. Genetic engineering in mouse models provides a powerful tool to study the mechanisms of testicular tumorigenesis and define the important genetic modifiers in vivo. [source] It takes two to tango: Combinations of conventional cytotoxics with compounds targeting the vascular endothelial growth factor,vascular endothelial growth factor receptor pathway in patients with solid malignanciesCANCER SCIENCE, Issue 1 2010Ingrid A. Boere Through advances in molecular biology, insight into the mechanisms driving malignancies has improved immensely and as a result, various factors playing an essential role in the biology of numerous tumor types have been revealed. By using compounds that specifically block the function of a single factor being crucial for tumor pathogenesis, it was hoped to exert antitumor activity while avoiding toxicities characteristic for conventional chemotherapy. One of the processes of crucial importance in the development of cancer, and consequently an attractive target, is angiogenesis. In recent years, several key factors for angiogenesis have been identified, including ligands, receptors, and transduction signaling factors. Of these, the vascular endothelial growth factor (VEGF) pathway has been found to be activated in numerous tumor types and considered one of the main drivers of angiogenesis. Roughly, VEGF-mediated angiogenesis can be inhibited by two approaches: either by monoclonal antibodies directed towards VEGF or its corresponding receptors, or by kinase inhibitors targeting the signal transduction of the VEGF receptors. As monotherapy, several kinase inhibitors exert antitumor activity in tumor types such as renal cell carcinoma. However, in most tumor types, the antitumor activity of compounds targeting the VEGF pathway is limited. In recent years, evidence is mounting that the paradigm of one single factor that drives malignant behavior applies rarely and is an oversimplification for most tumors in which there are multiple driving pathways. Consequently, multitargeting rather than single-targeting approaches are required. One of the means is by combining targeted agents with conventional cytotoxics. As the VEGF pathway also affects the sensitivity of tumor cells to chemotherapeutics, combinations of compounds targeting this pathway and conventional cytotoxics have been explored. This review addresses such combinations. (Cancer Sci 2009; 00: 000,000) [source] | |||||||||||||