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Stem Cells & Wnt

Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis

4 | Oct 09 2019

Sandborn WJ et al. showed that in patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo. [Read the Full Post]

Nuclear localization of β-catenin and expression of target genes are associated with increased Wnt secretion in oral dysplasia

3 | Oct 02 2019

Reyes M et al. indicated that secretion of Wnt ligands is critical for β-catenin nuclear localization and expression of target genes in oral dysplasia. [Read the Full Post]

Influence of Wilms' tumor suppressor gene WT1 on bovine Sertoli cells polarity and tight junctions via non-canonical WNT signaling pathway

12 | Oct 01 2019

Wang X et al. indicated that WT1 mediates the regulation of several proteins involved in bovine SCs polarity maintenance and intercellular tight junctions (TJ) by non-canonical WNT signaling pathway. [Read the Full Post]

Pharmacokinetics and Biodistribution of GDC-0449 Loaded Micelles in Normal and Liver Fibrotic Mice

18 | Sep 26 2019

Dutta R et al. showed that M6P-conjugated GDC-0449 loaded mixed micelles may be used as a potential drug delivery vehicle for treating liver fibrosis. [Read the Full Post]

Cellular Cholesterol Directly Activates Smoothened in Hedgehog Signaling

18 | Sep 23 2019

Huang P et al. proposed that the endogenous Smoothened activator is cholesterol, not oxysterols, and that vertebrate Hedgehog signaling controls Smoothened by regulating its access to cholesterol. [Read the Full Post]

NK2 receptor mediated detrusor muscle contraction involves Gq/11-dependent activation of voltage-dependent calcium channels and the RhoA-Rho kinase pathway

43 | Aug 30 2019

Dér B et al. identified potential therapeutic targets of bladder dysfunctions related to upregulation of TKs. [Read the Full Post]

Notch signaling pathway is a potential therapeutic target for extracranial vascular malformations

46 | Aug 18 2019

Davis RB et al. showed that two gamma secretase inhibitors (GSIs), DAPT (GSI-IX) and RO4929097, cause dose-dependent inhibition of Notch target gene expression (Hey1) and rate of migration of monolayer cultures of lymphatic endothelial cells (hLECs) and blood endothelial cells (HUVEC). GSIs also inhibit HUVEC network formation. hLECs are more sensitive to GSIs compared to HUVEC. GSIs have been found to be safe in clinical trials in patients with Alzheimer's disease or cancer. Our results provide further rationale to support testing of Notch inhibitors in patients with extracranial vascular malformations. [Read the Full Post]

Clinical relevance of ticagrelor monotherapy following 1-month dual antiplatelet therapy after bifurcation percutaneous coronary intervention: Insight from GLOBAL LEADERS trial

41 | Aug 16 2019

Kogame N et al. found that after PCI for bifurcation lesions using 1-month of DAPT followed by ticagrelor monotherapy for 23 months did not demonstrate explicit benefit regarding all-cause death or new Q-wave MI as in the overall trial. [Read the Full Post]

Use of Antiplatelet Therapy/DAPT for Post-PCI Patients Undergoing Noncardiac Surgery

41 | Aug 14 2019

Banerjee S et al. present3 commonly encountered clinical scenarios that lead into an evidence-based discussion of practical strategies for managing perioperative antiplatelet therapy in patients following percutaneous coronary intervention. [Read the Full Post]

First-in-human dose study of the novel transforming growth factor-β receptor I kinase inhibitor LY2157299 monohydrate in patients with advanced cancer and glioma

68 | Aug 12 2019

Rodon J et al. showed that on the basis of the safety, pharmacokinetics, and antitumor activity in patients with glioma, the intermittent administration of LY2157299 at 300 mg/day is safe for future clinical investigation. [Read the Full Post]

The Wnt inhibitor LGK-974 enhances radiosensitivity of HepG2 cells by modulating Nrf2 signaling

31 | Aug 11 2019

Tian D et al. found that HepG2 cells became more sensitive to radiation with increasing LGK-974 concentrations. Upon 2 Gy or 4 Gy irradiation, the cells treated with LGK-974 more frequently underwent apoptosis and grew less rapidly. PCR and western blot results showed that inhibiting the secretion of Wnt3A blocked the Wnt signaling pathway and prevented Nrf2 signaling. Notably, the Wnt inhibitor may serve as a radiosensitizing drug. [Read the Full Post]

Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway

31 | Aug 11 2019

Herbertz S et al. summarized the past and current experiences with different pharmacological treatments that enabled galunisertib to be investigated in patients. [Read the Full Post]

Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis

66 | Aug 07 2019

Verstovsek S et al. indicated that INCB018424 was associated with marked and durable clinical benefits in patients with myelofibrosis for whom no approved therapies existed. [Read the Full Post]

Conversion of Terminally Committed Hepatocytes to Culturable Bipotent Progenitor Cells with Regenerative Capacity

47 | Aug 03 2019

Katsuda T et al. reported that a cocktail of small molecules, Y-27632, A-83-01, and CHIR99021, can convert rat and mouse MHs in vitro into proliferative bipotent cells, which we term chemically induced liver progenitors (CLiPs). CLiPs can differentiate into both MHs and biliary epithelial cells that can form functional ductal structures. CLiPs in long-term culture did not lose their proliferative capacity or their hepatic differentiation ability, and rat CLiPs were shown to extensively repopulate chronically injured liver tissue. Thus, our study advances the goals of liver regenerative medicine. [Read the Full Post]

Radiosensitization of Non-Small Cell Lung Cancer Cells by Inhibition of TGF-β1 Signaling With SB431542 Is Dependent on p53 Status

106 | Jul 22 2019

Zhao Y et al. concluded that the radiosensitizing effect of inhibition of TGF-β1 signaling in NSCLC cells by SB431542 was p53 dependent, suggesting that using TGF-β1 inhibitor in radiotherapy may be more complicated than previously thought and may need further investigation. [Read the Full Post]

Cytotoxicity and activation of the Wnt/beta-catenin pathway in mouse embryonic stem cells treated with four GSK3 inhibitors

0 | Jul 18 2019

Naujok O et al. indicated that out of the four tested GSK3 inhibitors, only CHIR-99021 and CHIR-98014 proved to be potent pharmacological activators of the Wnt/beta-catenin signaling pathway. But only in the case of CHIR-99021 high potency was combined with very low toxicity. [Read the Full Post]

Antiproliferative and Antimigratory Effects of a Novel YAP-TEAD Interaction Inhibitor Identified Using in Silico Molecular Docking

62 | Jul 13 2019

Smith SA et al. reported the identification of a novel compound (CPD3.1) with the ability to disrupt YAP-TEAD protein-protein interaction and inhibit TEAD activity, cell proliferation, and cell migration. The YAP-TEAD complex is a viable drug target, and CPD3.1 is a lead compound for the development of more potent TEAD inhibitors for treating cancer and other hyperproliferative pathologies. [Read the Full Post]

Airway Progenitor Clone Formation Is Enhanced by Y-27632-Dependent Changes in the Transcriptome

68 | Jul 10 2019

Reynolds SD et al. concluded that Y-27632 fundamentally alters cell-cell and cell-ECM interactions, which preserves basal progenitor cells and allows greater cell amplification. [Read the Full Post]

JAK1/2 Inhibitors AZD1480 and CYT387 Inhibit Canine B-Cell Lymphoma Growth by Increasing Apoptosis and Disrupting Cell Proliferation

59 | Jul 08 2019

Lu Z et al. justified further phase I/II clinical investigations of the safety and efficacy of JAK1/2 inhibitors in canine DLBCL and suggest new opportunities for novel anticancer therapies. [Read the Full Post]

Exogenous mesenchymal stem cells affect the function of endogenous lung stem cells (club cells) in phosgene-induced lung injury

48 | Jul 05 2019

Ye K et al. showed that MSCs reduced the secretion of club cells. And MSCs enhanced the proliferation of club cells partly via activating the Notch signaling pathway, which promoted lung injury repair. [Read the Full Post]

Safety, Tolerability, and Preliminary Efficacy of the Anti-Fibrotic Small Molecule PRI-724, a CBP/β-Catenin Inhibitor, in Patients with Hepatitis C Virus-related Cirrhosis: A Single-Center, Open-Label, Dose Escalation Phase 1 Trial

37 | Jun 19 2019

Kimura K et al. showed that administration of 10 or 40mg/m2/day intravenous PRI-724 over 12weeks was well-tolerated by patients with HCV cirrhosis; however, liver injury as a possible related serious adverse event was observed in the 160mg/m2/day cohort. [Read the Full Post]

CX-4945, a Selective Inhibitor of Casein Kinase 2, Synergizes with B Cell Receptor Signaling Inhibitors in Inducing Diffuse Large B Cell Lymphoma Cell Death

108 | Jun 08 2019

Mandato E et al. suggested a role for CK2 downstream of the BCR in controlling survival pathways crucial for cell growth of different DLBCL subtypes. Also, the use of CX-4945 in combination with BCR signaling blockers could represent a novel rational therapeutic approach in the DLBCL. [Read the Full Post]

Small molecules dorsomorphin and LDN-193189 inhibit myostatin/GDF8 signaling and promote functional myoblast differentiation

62 | Jun 05 2019

Horbelt D et al. suggested these inhibitors as suitable tools to promote functional myogenesis. [Read the Full Post]

Regulation of Skeletal Muscle DRP-1 and FIS-1 Protein Expression by IL-6 Signaling

86 | Jun 03 2019

Fix DK et al. elevated IL-6 can directly induce DRP-1 and FIS-1 expression through gp130 signaling in cultured myotubes and skeletal muscle. Furthermore, ERK 1/2 signaling is necessary for the IL-6 induction of DRP-1 and FIS-1 expression in myotubes. [Read the Full Post]

KD025 (SLx-2119) suppresses adipogenesis at intermediate stage in human adipose-derived stem cells

121 | May 31 2019

Diep DTV et al. indicated that KD025suppresses adipocyte differentiation by modulation of key factors activated at the intermediate stage of differentiation, and not by inhibition of ROCK2. [Read the Full Post]

Strategies to Enhance Metabolic Stabilities

47 | May 29 2019

Khatri B et al. noted that any chemical modification that helps in providing either local or global conformational rigidity to these macrocyclic peptides aids in improving their metabolic stability typically by slowing the cleavage kinetics by the proteases. [Read the Full Post]

Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial

103 | May 21 2019

Rummel M et al. indicated that in combination with rituximab, bendamustine was more effective than fludarabine, suggesting that bendamustine plus rituximab may be the preferred treatment option for patients with relapsed indolent and mantle-cell lymphomas. [Read the Full Post]

Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway.

92 | May 17 2019

Herbertz S et al. summarized the past and current experiences with different pharmacological treatments that enabled galunisertib to be investigated in patients. [Read the Full Post]

First-in-human dose study of the novel transforming growth factor-β receptor I kinase inhibitor LY2157299 monohydrate in patients with advanced cancer and glioma

94 | May 16 2019

On the basis of the safety, pharmacokinetics, and antitumor activity in patients with glioma, the intermittent administration of LY2157299 at 300 mg/day is safe for future clinical investigation. [Read the Full Post]

Embryonic stem cells differentiated into neuron-like cells using SB431542 small molecule on nanofibrous PLA/CS/Wax scaffold

93 | May 03 2019

Hoveizi E et al. revealed that electrospun PLA/CS/Wax scaffolds associated with the induction medium can assemble proper conditions for stem cell differentiation into NLCs. [Read the Full Post]

Thromboembolic events in polycythemia vera

196 | Apr 27 2019

Griesshammer M et al. discussed factors associated with thrombosis and recent data on current treatments, including anticoagulation, highlighting the need for more controlled studies to determine the most effective cytoreductive therapies for reducing the risk of thrombosis in patients with PV. [Read the Full Post]

Mechanisms of Action of Ruxolitinib in Murine Models of Hemophagocytic Lymphohistiocytosis

208 | Apr 26 2019

Ruxolitinib operates through IFNγ-dependent and independent mechanisms to dampen HLH by targeting the deleterious effects of T cells and neutrophils, the latter representing an unappreciated and understudied cell type that contributes to HLH pathogenesis. [Read the Full Post]

CK2 inhibition with silmitasertib promotes methuosis-like cell death associated to catastrophic massive vacuolization of colorectal cancer cells

136 | Apr 13 2019

Silva-Pavez E et al. suggested that an aberrantly elevated expression/activity of CK2 may play a key role in CRC, promoting cell viability and proliferation in untreated cells, however, its inhibition with silmitasertib promotes methuosis-like cell death associated to massive catastrophic vacuolization, accounting for decreased tumorigenicity at later times. These characteristics of silmitasertib support a potential therapeutic use in CRC patients and probably other CK2-dependent cancers. [Read the Full Post]

Combining Smoothened Agonist and NEL-Like Protein-1 Enhances Bone Healing

148 | Apr 12 2019

Lee S et al. suggested that combining the hedgehog signaling agonist SAG and NELL-1 has potential as a novel therapeutic strategy for the healing of critical-size bone defects. Future directions will include optimization of dosage and delivery strategy for an SAG and NELL-1 combination product. [Read the Full Post]

Napabucasin: An Update on the First-in-Class Cancer Stemness Inhibitor

135 | Apr 11 2019

Hubbard JM et al. showed that napabucasin may prove useful in targeting cancer stem cells, with the potential to suppress metastasis and prevent relapse in patients with varying cancer types. [Read the Full Post]

ICG-001 suppresses growth of gastric cancer cells and reduces chemoresistance of cancer stem cell-like population

107 | Apr 10 2019

Liu Y et al. suggested that ICG-001 suppresses GC cell line growth, metastasis and reduces its stem cell-like properties and chemoresistance, indicating that ICG-001 is a potentially useful small molecule therapeutic for GC. [Read the Full Post]

Exploration of MST1-Mediated Secondary Brain Injury Induced by Intracerebral Hemorrhage in Rats via Hippo Signaling Pathway

76 | Apr 09 2019

Zhang P et al. revealed that MST1 played an important role in the SBI following ICH, and inhibition of MST1 could alleviate ICH-induced SBI. Therefore, MST1 may be considered as a potential therapeutic target for SBI following ICH. [Read the Full Post]

White light emitting diode induces autophagy in hippocampal neuron cells through GSK-3-mediated GR and RORα pathways

126 | Apr 03 2019

Yang Y et al. demonstrated that GSK-3-mediated GR/RORα signaling pathway is involved in white LED light-induced autophagy in hippocampal neuron cells. [Read the Full Post]

Grem2 mediates podocyte apoptosis in high glucose milieu

145 | Apr 02 2019

Wen H et al. indicated high glucose increases Grem2 expression in kidney cells. Grem2 mediates podocyte apoptosis through Smads. [Read the Full Post]

Mechanisms of U46619-induced contraction in mice intrarenal arteries

203 | Mar 27 2019

Yan H et al. suggested that the U46619-induced contraction of mouse intrarenal arteries is mediated by Cav1.2 and SOC channel, through the activation of thromboxane-prostanoid receptors and its downstream signaling pathway. [Read the Full Post]

Generation of Urine Cell-Derived Non-integrative Human iPSCs and iNSCs: A Step-by-Step Optimized Protocol

189 | Mar 24 2019

Cheng L et al. showed the optimized protocol is an easy and fast procedure to yield both iPSC and iNSC lines from a convenient source of human urine in a single experiment. [Read the Full Post]

IWR-1 Inhibits Collagen-Induced Platelet Activation and Protects against Thrombogenesis

134 | Mar 12 2019

Wang W et al. demonstrated that IWR-1 could effectively block collagen-induced platelet activity in vitro and in vivo, and suggest its candidacy as a new antiplatelet agent. [Read the Full Post]

UBE2S mediates tumor progression via SOX6/β-Catenin signaling in endometrial cancer

367 | Mar 03 2019

Lin M et al. suggested UBE2S may serve as a promising prognostic factor and function as an oncogene in EMC. The newly identified UBE2S/SOX6/β-Catenin axis represents a new potential therapeutic target for EMC intervention. [Read the Full Post]

Cyclopamine: from cyclops lambs to cancer treatment

113 | Mar 01 2019

Lee ST et al. showed inhibitors of the Hh signaling pathway, including cyclopamine derivatives, have been targeted as potential treatments for certain cancers and other diseases associated with the Hh signaling pathway. [Read the Full Post]

LY2109761 inhibits metastasis and enhances chemosensitivity in osteosarcoma MG-63 cells

159 | Feb 27 2019

Ren XF et al. indicated that LY2109761 suppresses OS metastasis and enhanced chemosensitivity by targeting S100A4. LY2109761 may have important implications for the development of strategies for inhibiting metastasis and overcoming OS cell resistance to chemotherapy. [Read the Full Post]

Potent in vivo lung cancer Wnt signaling inhibition via cyclodextrin-LGK974 inclusion complexes

170 | Feb 21 2019

Guimaraes PPG et al. indicated the development of these complexes enables safer and repeated oral or parenteral administration of Wnt signaling inhibitors, which hold promise for the treatment of multiple types of malignancies. [Read the Full Post]

Ionizing Radiation Blocks Hair Cell Regeneration in Zebrafish Lateral Line Neuromasts by Preventing Wnt Signaling

199 | Feb 15 2019

Li R et al. suggested that radiation suppressed hair cell regeneration in zebrafish lateral line neuromasts through inhibition of Wnt signaling in supporting cells possibly by secreting anti-proliferation factors like dkk2. Maintaining a healthy supporting cell pool is vital for regeneration of hair cells. [Read the Full Post]

Inhibition of the NOTCH pathway using γ-secretase inhibitor RO4929097 has limited antitumor activity in established glial tumors

737 | Feb 05 2019

Dantas-Barbosa C et al. indicated that RO4929097-mediated effects were independent of NOTCH1 mutation status or expression levels, but associated with low IL-6 levels. In established glial tumor models, NOTCH inhibition had limited effects as a single agent, but enhanced efficacy when combined with DNA-interfering agents. These preclinical data need to be considered for further clinical development of NOTCH inhibitors in glial tumors. [Read the Full Post]

Molecular regulation of apoptotic machinery and lipid metabolism by mTORC1/mTORC2 dual inhibitors in preclinical models of HER2+/PIK3CAmut breast cancer

201 | Jan 30 2019

Qian J et al. found that the basal levels of carnitine palmitoyltransferase 1A and lipid catabolism were elevated in HER2+/PIK3CAmut breast cells and were inhibited upon mTOR-KI treatment. [Read the Full Post]

Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment

0 | Jan 27 2019

Du J et al. suggested SBE as a novel drug candidate for NSCLC which specifically and sensitively targets SHH signaling pathway. [Read the Full Post]

The thrombopoietin/MPL axis is activated in the Gata1low mouse model of myelofibrosis and is associated with a defective RPS14 signature

428 | Dec 30 2018

Zingariello M et al. showed that Gata1low mice are a bona fide model of MF, which recapitulates the hyperactivation of the TPO/MPL/JAK2 axis observed in megakaryocytes from myelofibrotic patients. [Read the Full Post]

Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice

0 | Dec 30 2018

Satoh M et al. indicated that interactions between NKT cells and CD1d-expressing adipocytes producing endogenous NKT cell ligands play a critical role in the induction of inflammation and functional modulation of adipose tissue that leads to obesity. [Read the Full Post]

WNT5A: a motility-promoting factor in Hodgkin lymphoma

237 | Dec 22 2018

Linke F et al. proposed a model where WNT signaling has an important role in regulating tumor-promoting processes. [Read the Full Post]

PI3K Catalytic Isoform Alteration Promotes the LIMK1-related Metastasis Through the PAK1 or ROCK1/2 Activation in Cigarette Smoke-exposed Ovarian Cancer Cells

0 | Dec 18 2018

Park GB et al. showed that characterization of the p110 isotypes of PI3K is critical for regulating cancer metastasis; LIMK1 could be a common therapeutic target of ovarian cancer metastasis. [Read the Full Post]

FAM83A is amplified and promotes cancer stem cell-like traits and chemoresistance in pancreatic cancer

327 | Dec 15 2018

Chen S et al. indicated that FAM83A has a vital oncogenic role to promote pancreatic cancer progression and may represent a potential clinical target. [Read the Full Post]

Testosterone improves the differentiation efficiency of insulin-producing cells from human induced pluripotent stem cells

202 | Dec 12 2018

Liu H et al. found that T improves the differentiation efficiency of insulin-producing cells from hiPSCs. The addition of T into routine differentiation formula for pancreatic β cells increases the differentiation efficiency from 12% to 35%. The administration of T promotes the expression of key genes associated with β cells differentiation including NGN3, NEUROD1 and INS. This finding benefits the ongoing process to optimize the differentiation protocol of pancreatic β cells from hiPSCs, and provides some degree of understanding the clinical management of T for type 2 diabetes. [Read the Full Post]

TGF-β sensu stricto signaling regulates skeletal morphogenesis in the sea urchin embryo

590 | Dec 11 2018

Sun Z et al. revealed that this model morphogenetic process involves an even more diverse suite of cell signaling pathways than previously appreciated and show that PMCs integrate a complex set of both generalized and spatially localized cues in assembling the endoskeleton. [Read the Full Post]

Integrated High Throughput Analysis Identifies GSK3 as a Crucial Determinant of p53-Mediated Apoptosis in Lung Cancer Cells

226 | Dec 03 2018

Zhang Y et al. provided us with new insights regarding the mechanism by which p53 mediates A549 apoptosis and may cast light on the development of more efficient p53-based strategies for treating lung cancer. [Read the Full Post]

Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment

269 | Nov 30 2018

Du J et al. suggested SBE as a novel drug candidate for NSCLC which specifically and sensitively targets SHH signaling pathway. [Read the Full Post]

SOCS3 overexpression enhances ADM resistance in bladder cancer T24 cells

427 | Nov 28 2018

Li MZ et al. indicated that SOCS3 reduction was associated with bladder cancer sensitivity to ADM. SOCS3 overexpression decreased JAK-STAT3 signaling pathway activity, declined Bcl-2 expression, inhibited cell proliferation, elevated cell apoptosis, and enhanced ADM sensitivity in T24 cells. [Read the Full Post]

Cancer stem cell marker phenotypes are reversible and functionally homogeneous in a preclinical model of pancreatic cancer

0 | Nov 27 2018

Dosch JS et al. showed that the hierarchical organization of CSCs in human disease is not recapitulated in a commonly used mouse model of pancreatic cancer and therefore provide a new view of the phenotypic and functional heterogeneity of tumor cells. [Read the Full Post]

Host Serine/Threonine Kinases mTOR and Protein Kinase C-α Promote InlB-Mediated Entry of Listeria monocytogenes

1921 | Nov 21 2018

Bhalla M et al. identified mTOR and PKC-α to be host factors exploited by Listeria to promote infection. PKC-α controls Listeria entry, at least in part, by regulating the actin cytoskeleton downstream of the Met receptor. [Read the Full Post]

JAK2 inhibitor CEP-33779 prevents mouse oocyte maturation in vitro

467 | Nov 15 2018

Wu C et al. suggested that JAK2 regulated the microfilaments aggregation during the mouse oocyte maturation. [Read the Full Post]

Treatment to sustain a Th17-type phenotype to prevent skewing toward Treg and to limit premalignant lesion progression to cancer

285 | Nov 05 2018

Young MR et al. showed that the treatment approach not only sustained the Th17 phenotype, but also increased distal spleen cell and regional lymph node cell production of other stimulatory/inflammatory mediators and slowed premalignant lesion progression to cancer. [Read the Full Post]

Stress-induced dynamic regulation of mitochondrial STAT3 and its association with cyclophilin D reduce mitochondrial ROS production

305 | Nov 03 2018

Meier JA et al. outlined a role for mitochondrially localized STAT3 in sensing and responding to external stimuli. [Read the Full Post]

Vitamin D prevents articular cartilage erosion by regulating collagen II turnover through TGF-β1 in ovariectomized rats

269 | Nov 02 2018

Li S et al. showed protective effects in OVX-induced OA partly through the TGF-β1 pathway. [Read the Full Post]

Construction of a novel cell-based assay for the evaluation of anti-EGFR drug efficacy against EGFR mutation

0 | Oct 25 2018

Hoshi H et al. successfully developed a novel cell-based assay for evaluating the efficacy of anti-EGFR drugs against EGFR mutation. [Read the Full Post]

Construction of a novel cell-based assay for the evaluation of anti-EGFR drug efficacy against EGFR mutation

681 | Oct 20 2018

Hoshi H et al. successfully developed a novel cell-based assay for evaluating the efficacy of anti-EGFR drugs against EGFR mutation. [Read the Full Post]

Retinoic acid and TGF-β signalling cooperate to overcome MYCN-induced retinoid resistance

636 | Oct 15 2018

Duffy DJ et al. provided a powerful precision oncology tool for identifying the driving signalling networks for malignancies not primarily driven by somatic mutations, such as paediatric cancers. By applying global omics approaches to the signalling networks regulating neuroblastoma differentiation and stemness, we have determined the pathways involved in the MYCN-mediated retinoid resistance, with TGF-β signalling being a key regulator. These findings revealed a number of combination treatments likely to improve clinical response to retinoid therapy, including co-treatment with retinoids and KGN, which may prove valuable in the treatment of high-risk MYCN-amplified neuroblastoma. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

0 | Oct 14 2018

Grygielewicz P et al. provided experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

Activation of Wnt/β-catenin signalling is required for TGF-β/Smad2/3 signalling during myofibroblast proliferation

304 | Oct 12 2018

Xu L et al. found that a major outcome of this study is improved insight into the mechanisms by which epithelial and mesenchymal cells activated by TGFβ1-smad2/3 signalling through Wnt/β-catenin contribute to lung fibrosis. [Read the Full Post]

Novel role of STRAP in progression and metastasis of colorectal cancer through Wnt/β-catenin signaling

0 | Oct 06 2018

Yuan G et al. suggest that STRAP increases invasion and metastasis of CRC partly through inhibiting ubiquitin-dependent degradation of β-catenin and promoting Wnt/β-catenin signaling. [Read the Full Post]

TGF-β and NF-κB signaling pathway crosstalk potentiates corneal epithelial senescence through an RNA stress response

369 | Sep 29 2018

Li ZY et al. indicated that TGF-β-driven NF-κB activation contributes to corneal epithelial senescence via RNA metabolism and the inflammation blockade can attenuate TGF-β-induced senescence. [Read the Full Post]

Dual inhibition of Bcl-2 and Bcl-xL strikingly enhances PI3K inhibition-induced apoptosis in human myeloid leukemia cells through a GSK3- and Bim-dependent mechanism

415 | Sep 23 2018

Rahmani M et al. argued that combining PI3K/AKT/mTOR inhibitors with BH3 mimetics warrants attention in AML, particularly in the setting of basal AKT activation and/or addiction. [Read the Full Post]

Identification of ACTG2 functions as a promoter gene in hepatocellular carcinoma cells migration and tumor metastasis

553 | Sep 11 2018

Wu Y et al. revealed a critical role of ACTG2 in HCC tumor metastasis, and renders it a novel target for the treatment of HCC. [Read the Full Post]

Fascin Is Critical for the Maintenance of Breast Cancer Stem Cell Pool Predominantly via the Activation of the Notch Self-Renewal Pathway

608 | Sep 11 2018

Barnawi R et al. demonstrated fascin as a critical regulator of breast CSC pool at least partially via activation of the Notch self-renewal signaling pathway and modification of the expression embryonic transcriptional factors. Targeting fascin may halt CSCs and thus presents a novel therapeutic approach for effective treatment of breast cancer. [Read the Full Post]

JAK/STAT signaling pathway-mediated immune response in silkworm (Bombyx mori) challenged by Beauveria bassiana

422 | Sep 09 2018

Geng T et al. suggested that BmCTL5 might be one pattern recognition receptors for JAK/STAT signaling pathway in silkworm. These findings yield insights for better understand the molecular mechanisms of JAK/STAT signaling pathway in antifungal immune response in silkworm. [Read the Full Post]

microRNA-200a silencing protects neural stem cells against cerebral ischemia/reperfusion injury

410 | Sep 09 2018

Ma J et al. indicated miR-200a silencing protects NSCs from OGD/R-induced injury, possibly via regulating the STATs/c-Myc and MAPK/c-Myc signalings. [Read the Full Post]

Differences in gene expression and alterations in cell cycle of acute myeloid leukemia cell lines after treatment with JAK inhibitors

650 | Sep 07 2018

Gunerka P et al. suggested that observed effect of JAK2 inhibitors on transcription and cell cycle level in different cell lines are associated not with activity within JAK family, but presumably with other off-target activities. [Read the Full Post]

Niclosamide inhibition of STAT3 synergizes with erlotinib in human colon cancer

0 | Sep 05 2018

Shi L et al. suggested that erlotinib and niclosamide combination provides an effective therapeutic approach to improving the prognosis of colon cancer. [Read the Full Post]

MicroRNA-17 regulates autophagy to promote hepatic ischemia/reperfusion injury via suppression of signal transductions and activation of transcription-3 expression

411 | Sep 02 2018

Li S et al. showed that high levels of miR-17 expression can function to up-regulate autophagy to aggravate hepatic IRI by suppressing Stat3 expression. Liver Transplantation 22 1697-1709 2016 AASLD. [Read the Full Post]

Upregulation of programmed cell death ligand 1 promotes resistance response in non-small-cell lung cancer patients treated with neo-adjuvant chemotherapy

1245 | Aug 26 2018

Zhang P et al. suggested that the upregulation of PD-L1 promotes a resistance response in lung cancer cells that might be through activation of the phosphatidylinositol 3-kinase/protein kinase B pathway and suppression of tumor-infiltrating lymphocytes. The high expression of PD-L1 after NAC could be an indication of therapeutic resistance and poor prognosis in patients with non-small-cell lung cancer. [Read the Full Post]

Downregulation of the Syk Signaling Pathway in Intestinal Dendritic Cells Is Sufficient To Induce Dendritic Cells That Inhibit Colitis

861 | Aug 22 2018

Hang L et al. indicated that downmodulation of Syk expression and phosphorylation in intestinal DCs could be important mechanisms through which helminths induce regulatory DCs that limit colitis. [Read the Full Post]

BMS-708163 and Nilotinib restore synaptic dysfunction in human embryonic stem cell-derived Alzheimer's disease models

829 | Aug 07 2018

Nishioka H et al. suggested that the AD models we developed are promising materials for the discovery of AD drugs that target the expression of pre-synaptic proteins and synaptic function. [Read the Full Post]

Cellular Prion Protein Mediates Pancreatic Cancer Cell Survival and Invasion through Association with and Enhanced Signaling of Notch1

679 | Jul 29 2018

Wang Y et al. unraveled a novel molecular pathway driven by interactions between PrP and Notch1 in the progression of PDAC, supporting a critical tumor-promoting role of Notch1 in PrP-expressing PDAC tumors. [Read the Full Post]

Notch and Hedgehog in the thymus/parathyroid common primordium: Crosstalk in organ formation

686 | Jul 27 2018

Figueiredo M et al. offered novel evidence on the role of Notch signalling in T/PT common primordium development, in an Hh-dependent manner. [Read the Full Post]

Thyroid Hormone-Induced Activation of Notch Signaling is Required for Adult Intestinal Stem Cell Development During Xenopus Laevis Metamorphosis

709 | Jul 27 2018

Hasebe T et al. provided evidence for evolutionarily conserved role of Notch signaling in intestinal cell fate determination but more importantly reveal, for the first time, an important role of Notch pathway in the formation of adult intestinal stem cells during vertebrate development. Stem Cells 2017;35:1028-1039. [Read the Full Post]

Aberrant Notch Signaling in the Bone Marrow Microenvironment of Acute Lymphoid Leukemia Suppresses Osteoblast-Mediated Support of Hematopoietic Niche Function

820 | Jul 25 2018

Wang W et al. suggested that therapeutically targeting the leukemia-infiltrated hematopoietic niche may restore HSPC homeostasis and improve the outcome of ALL patients. [Read the Full Post]

Cross-talk between Notch and Hedgehog regulates hepatic stellate cell fate in mice

537 | Jul 14 2018

Xie G, et al. found that the Notch and Hedgehog pathways interact to control the fate of key cell types involved in adult liver repair by modulating epithelial-to-mesenchymal-like/mesenchymal-to-epithelial-like transitions. [Read the Full Post]

B7-H4 facilitates proliferation of esophageal squamous cell carcinoma cells through promoting interleukin-6/signal transducer and activator of transcription 3 pathway activation

844 | Jul 13 2018

Chen X et al. provided the first evidence that B7-H4 facilitated ESCC cell proliferation through promoting IL-6/STAT3 positive loopback pathway activation. [Read the Full Post]

Inhibiting PLK1 induces autophagy of acute myeloid leukemia cells via mammalian target of rapamycin pathway dephosphorylation

895 | Jul 10 2018

Tao YF et al. provided new insights into the molecular mechanism of PLK1 in regulating autophagy. [Read the Full Post]

Fibroblastic foci, covered with alveolar epithelia exhibiting epithelial-mesenchymal transition, destroy alveolar septa by disrupting blood flow in idiopathic pulmonary fibrosis

543 | Jul 10 2018

Yamaguchi M et al. showed that inhibition of transforming growth factor-β signaling, which can suppress EMT of the alveolar epithelial cells in vitro, is a potential strategy for treating IPF. [Read the Full Post]

Adenovirus-mediated TIPE2 overexpression inhibits gastric cancer metastasis via reversal of epithelial-mesenchymal transition

627 | Jun 25 2018

Yin H et al. provided the first evidence that TIPE2 inhibits gastric cancer cell migration, invasion and metastasis very probably via reversal of EMT, revealing that TIPE2 may be a novel therapeutic target for human gastric cancer EMT and metastasis. [Read the Full Post]

AT13148, a first-in-class multi-AGC kinase inhibitor, potently inhibits gastric cancer cells both in vitro and in vivo

1954 | Jun 20 2018

Xi Y et al. supported the progression of this molecule into future evaluation as a valuable anti-gastric cancer candidate. [Read the Full Post]

Niclosamide inhibition of STAT3 synergizes with erlotinib in human colon cancer

751 | May 28 2018

Shi L et al. suggested that erlotinib and niclosamide combination provides an effective therapeutic approach to improving the prognosis of colon cancer. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

0 | May 21 2018

Grygielewicz P et al. provided experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

Gli1-Mediated Regulation of Sox2 Facilitates Self-Renewal of Stem-Like Cells and Confers Resistance to EGFR Inhibitors in Non-Small Cell Lung Cancer

563 | May 18 2018

Bora-Singhal N et al. demonstrated a cooperative functioning of the EGFR signaling and Hedgehog pathways in governing the stem-like functions of NSCLC cancer stem cells and presents a novel therapeutic strategy to combat NSCLC harboring EGFR mutations. [Read the Full Post]

Long non-coding RNA NKILA inhibits migration and invasion of non-small cell lung cancer via NF-κB/Snail pathway

1502 | May 17 2018

Lu Z et al. found that the expression of NKILA was downregulated in tumor tissues of NSCLC, which improved the metastasis of NSCLC patients. In vitro studies further clarified that the expression of NKILA was regulated through classical TGF-β signal pathway, which subsequently inhibited migration and invasion of NSCLC cells through interfering NF-κB/Snail signal pathway in NSCLC cells. [Read the Full Post]

FAM83D associates with high tumor recurrence after liver transplantation involving expansion of CD44+ carcinoma stem cells

0 | May 17 2018

Lin B et al. indicated that FAM83D promotes HCC recurrence by promoting CD44 expression and CD44+ CSCs malignancy. FAM83D provides a novel therapeutic approach against HCC recurrence after LT. [Read the Full Post]

Jumonji AT-rich interactive domain 1B overexpression is associated with the development and progression of glioma

556 | May 05 2018

Fang L et al. suggested that JARID1B is involved in the pathogenesis of glioma, and that the downregulation of JARID1B in glioma cells may be a therapeutic target for the treatment of patients with glioma. [Read the Full Post]

FGF19 promotes epithelial-mesenchymal transition in hepatocellular carcinoma cells by modulating the GSK3β/β- catenin signaling cascade via FGFR4 activation

1518 | May 03 2018

Zhao H et al. indicated that FGFR4/GSK3β/β-catenin axis may play a pivotal role in FGF19-induced EMT in HCC cells. As FGF19 and its specific receptor FGFR4 are frequently amplified in HCC cells, selective targeting this signaling node may lend insights into a potential effective therapeutic approach for blocking metastasis of HCC. [Read the Full Post]

GSK3ß-dependent dysregulation of neurodevelopment in SPG11-patient iPSC model

1590 | May 02 2018

Mishra HK et al. provided the first evidence for an early neurodevelopmental phenotype in SPG11, with GSK3ß as a potential novel target to reverse the disease phenotype. This article is protected by copyright. All rights reserved. [Read the Full Post]

Pharmacologic Inhibition of JAK1/JAK2 Signaling Reduces Experimental Murine Acute GVHD While Preserving GVT Effects

982 | Apr 24 2018

Carniti C et al. provided further evidence that JAK inhibition represents a new and potentially clinically relevant approach to GVHD prevention. [Read the Full Post]

Novel Akt activator SC-79 is a potential treatment for alcohol-induced osteonecrosis of the femoral head

1043 | Apr 09 2018

Chen YX et al. showed that alcohol-induced ONFH is associated with suppression of p-Akt-Ser473 in the Akt/GSK3β/β-catenin signaling pathway in bone mesenchymal stem cells. We propose that SC-79 treatment to rescue Akt activation could be tested in the clinic as a potential therapeutic approach to preventing the development of alcohol-induced ONFH. [Read the Full Post]

Cancer-associated fibroblasts attenuate Cisplatin-induced apoptosis in ovarian cancer cells by promoting STAT3 signaling

604 | Apr 06 2018

Yan H et al. suggested that CAFs could activate the anti-apoptotic STAT3 signaling, thereby decrease the Cisplatin-induced apoptosis and promote chemoresistance in ovarian cancer. [Read the Full Post]

Anti-leukaemic activity of the TYK2 selective inhibitor NDI-031301 in T-cell acute lymphoblastic leukaemia

1170 | Mar 23 2018

Akahane K et al. supported selective inhibition of TYK2 as a promising potential therapeutic strategy for T-ALL. [Read the Full Post]

MST2 phosphorylation at serine 385 in mitosis inhibits its tumor suppressing activity

676 | Mar 20 2018

Chen X et al. revealed a novel layer of regulation for MST2 in mitosis and its role in tumorigenesis. [Read the Full Post]

CCND1 mutations increase protein stability and promote ibrutinib resistance in mantle cell lymphoma

638 | Mar 20 2018

Mohanty A et al. uncover a new mechanism that is critical for the regulation of CCND1 protein levels, and is directly relevant to primary ibrutinib resistance in MCL. [Read the Full Post]

NF-YA promotes invasion and angiogenesis by upregulating EZH2-STAT3 signaling in human melanoma cells

985 | Mar 15 2018

Xu Z et al. indicated that overexpression of NF-YA contributes to tumor angiogenesis through EZH2-STAT3 signaling in human melanoma cells, highlighting NF-YA as a potential therapeutic target in human melanoma. [Read the Full Post]

Endothelial STAT3 Activation Increases Vascular Leakage Through Downregulating Tight Junction Proteins: Implications for Diabetic Retinopathy

902 | Mar 15 2018

Yun JH et al. suggested the potential importance of IL-6/STAT3 signaling in regulating endothelial permeability and provide a therapeutic target to prevent the pathology of diabetic retinopathy. [Read the Full Post]

Aberrant activation of hedgehog signaling promotes cell proliferation via the transcriptional activation of forkhead Box M1 in colorectal cancer cells

735 | Mar 13 2018

Wang D et al. indicated the dysregulation of the Hh-Gli1-FoxM1 axis is essential for the proliferation and growth of human CRC cells and offers a potent target for therapeutic intervention in CRC. [Read the Full Post]

A Novel Antifibrotic Mechanism of Nintedanib and Pirfenidone. Inhibition of Collagen Fibril Assembly

835 | Mar 12 2018

Knüppel L et al. indicated both drugs act on important regulatory levels in collagen synthesis and processing. Nintedanib was more effective in down-regulating profibrotic gene expression and collagen secretion. Importantly, both drugs inhibited collagen I fibril formation and caused a reduction in and an altered appearance of collagen fibril bundles, representing a completely novel mechanism of action for both drugs. [Read the Full Post]

Nek2A/SuFu feedback loop regulates Gli-mediated Hedgehog signaling pathway

675 | Mar 12 2018

Zhou F et al. uncovered one of the mechanisms by which Nek2A acts as a modulator of the Hh signaling pathway in the context of a novel negative-feedback loop, which may offer new insights into Gli-mediated Hh signaling regulation in development and human diseases. [Read the Full Post]

PI-3K Inhibitors Preferentially Target CD15+ Cancer Stem Cell Population in SHH Driven Medulloblastoma

652 | Feb 28 2018

Singh AR, et al. suggested a sequential combination of PI-3K inhibitors and chemotherapy will have augmented efficacy in the treatment of this disease. [Read the Full Post]

Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency

696 | Feb 24 2018

Yang Y et al. found a first step toward capturing pluripotent stem cells with extraembryonic developmental potentials in culture and open new avenues for basic and translational research. VIDEO ABSTRACT. [Read the Full Post]

Principles of early human development and germ cell program from conserved model systems

678 | Feb 22 2018

Kobayashi T et al. used human, porcine and monkey in vivo and in vitro models provides synthetic insights into early human development. [Read the Full Post]

Inhibition of TGF-β signaling promotes expansion of human epidermal keratinocytes in feeder cell co-culture

667 | Feb 10 2018

Suzuki D et al. found important implications for the use of TGF-β signaling inhibition as a viable therapeutic strategy for improving Green's methodology and for more efficient production of customized skin autografts with human feeder cells. [Read the Full Post]

Cocktail of chemical compounds robustly promoting cell reprogramming protects liver against acute injury

633 | Feb 05 2018

Tang Y et al. offered proof-of-concept evidence that cocktail of clinical compounds improving cell reprogramming favors tissue recovery after acute damages, which is an attractive strategy for regenerative purpose. [Read the Full Post]

Differentiation of induced pluripotent stem cell-derived neutrophil granulocytes from common marmoset monkey (Callithrix jacchus).

1225 | Jan 27 2018

Schrimpf C et al. indicated cj-iPSC-derived neutrophils bare high hopes in hematologic cell replacement therapy. They exhibit high morphologic similarity to native neutrophils and present neutrophil-specific surface antigens, antimicrobial proteins, and gene products yielding an auspicious approach for continuative experiments including tests in living animals. [Read the Full Post]

Extracellular heat shock protein 90α mediates HDM-induced bronchial epithelial barrier dysfunction by activating RhoA/MLC signaling

996 | Jan 04 2018

Dong HM et al. suggested that eHsp90α is a potential therapeutic target for treatment of asthma. [Read the Full Post]

Tyrosine receptor kinase B is a drug target in astrocytomas

2412 | Dec 31 2017

Ni J et al. proposed NTRK2 as a potential therapeutic target in the subset of astrocytoma patients defined by QKI-NTRK2 fusion. [Read the Full Post]

PD-L1 Is Upregulated by Simultaneous Amplification of the PD-L1 and JAK2 Genes in Non-Small Cell Lung Cancer

1209 | Dec 25 2017

Ikeda S et al. suggested that expression of PD-L1 protein is upregulated by the simultaneous amplification of the PD-L1 and JAK2 genes through JAK-STAT signaling in NCSLC. [Read the Full Post]

THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors

844 | Dec 14 2017

Cayrol F et al. showed that the combination of THZ1 and the BH3 mimetic obatoclax improves lymphoma growth control in a primary PTCL ex vivo culture and in two STAT3-mutant PTCL xenografts, delineating a potential targeted agent-based therapeutic option for these patients. [Read the Full Post]

Interleukin-6 suppression reduces tumour self-seeding by circulating tumour cells in a human osteosarcoma nude mouse model

819 | Dec 12 2017

Zhang Y et al. provided a novel strategy for future therapeutic interventions to prevent osteosarcoma progression and recurrence. [Read the Full Post]

CK2α' Drives Lung Cancer Metastasis by Targeting BRMS1 Nuclear Export and Degradation

0 | Dec 02 2017

Liu Y et al. identified a therapeutically exploitable posttranslational mechanism by which CK2α-mediated degradation of BRMS1 promotes metastases in lung cancer. [Read the Full Post]

Integrative Network Analysis Combined with Quantitative Phosphoproteomics Reveals Transforming Growth Factor-beta Receptor type-2 (TGFBR2) as a Novel Regulator of Glioblastoma Stem Cell Properties

743 | Nov 28 2017

Narushima Y et al. indicated that transforming growth factor-β receptor type-2 could play an important role as a novel cell fate determinant in glioblastoma stem cell regulation. [Read the Full Post]

Activation of anaphase-promoting complex by p53 induces a state of dormancy in cancer cells against chemotherapeutic stress

951 | Nov 28 2017

Dai Y et al. provided a mechanism to unravel cancer cell dormancy and reactivation of the cancer cell population. [Read the Full Post]

MicroRNA-520e suppresses non-small-cell lung cancer cell growth by targeting Zbtb7a-mediated Wnt signaling pathway

938 | Nov 26 2017

Zhijun Z et al. indicated that overexpressing miR-520e is involved in regulating the NSCLC cell growth, invasion and migration by targeting Zbtb7a partly depending on Wnt signaling. [Read the Full Post]

Hedgehog pathway is involved in nitidine chloride induced inhibition of epithelial-mesenchymal transition and cancer stem cells-like properties in breast cancer cells

1026 | Nov 25 2017

Sun M et al. suggested that NC may be a potential anticancer agent for breast cancer. [Read the Full Post]

Photodynamic therapy activated STAT3 associated pathways: Targeting intrinsic apoptotic pathways to increase PDT efficacy in human squamous carcinoma cells

1254 | Nov 23 2017

Qiao L et al. confirmed that 5-ALA-PDT might be an effective treatment for human squamous carcinoma by inhibiting the tumor cell A431growth and for the first time demonstrated that the expression of STAT3 was significantly reduced at 24h after 5-ALA-PDT treatment. [Read the Full Post]

AZGP1 suppresses epithelial-to-mesenchymal transition and hepatic carcinogenesis by blocking TGFβ1-ERK2 pathways

2092 | Nov 19 2017

Xu MY et al. showed that loss of AZGP1 could trigger EMT induced by TGFβ1-ERK2 signaling, confuse in energy metabolism, reduce cell proliferation and apoptosis, activate survival signals and promote invasion. Up-regulation of AZGP1 should be proposed to reverse EMT and might be a new promising therapy for HCC. [Read the Full Post]

JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma

1561 | Nov 05 2017

Nairismägi ML et al. showed that inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available. [Read the Full Post]

Inhibition of β-Catenin to Overcome Endocrine Resistance in Tamoxifen-Resistant Breast Cancer Cell Line

0 | Oct 31 2017

Won HS et al. suggested that beta-catenin plays a role in tamoxifen-resistant breast cancer, and the inhibition of beta-catenin may be a potential target in tamoxifen-resistant breast cancer. [Read the Full Post]

Coordinate involvement of Nodal-dependent inhibition and Wnt-dependent activation in the maintenance of organizer-specific bmp2b in zebrafish

997 | Oct 30 2017

Xue Y et al. suggested that maintenance of organizer-specific bmp2b expression involves opposite and concerted regulation by Nodal and Wnt signaling. [Read the Full Post]

Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment

1577 | Oct 24 2017

Katsushima K et al. showed that highlight the importance of the Notch-lncRNA axis in regulating self-renewal of glioma cells and provide a strong rationale for targeting TUG1 as a specific and potent therapeutic approach to eliminate the GSC population. [Read the Full Post]

Transforming growth factor-β1 suppresses bone morphogenetic protein-2-induced mesenchymal-epithelial transition in HSC-4 human oral squamous cell carcinoma cells via Smad1/5/9 pathway suppression

973 | Oct 21 2017

Chiba T et al. suggested that TGF-β positively regulates hOSCC invasion in the primary tumor, whereas BMP-2 facilitates cancer cell colonization at secondary metastatic sites. Thus, the invasive and metastatic characteristics of hOSCC appear to be reciprocally regulated by BMP and TGF-β. [Read the Full Post]

Epithelial-mesenchymal transition confers resistance to selective FGFR inhibitors in SNU-16 gastric cancer cells

2838 | Oct 09 2017

Grygielewicz P et al. provide experimental evidence that EMT-mediated resistance might emerge in gastric cancer patients following treatment with FGFR inhibitors, and mubritinib or AUY922 treatment may be an alternative therapeutic strategy for these patients. [Read the Full Post]

STAT1 as a downstream mediator of ERK signaling contributes to bone cancer pain by regulating MHC II expression in spinal microglia

1272 | Oct 04 2017

Song Z et al. suggested that STAT1 contributes to bone cancer pain as a downstream mediator of ERK signaling by regulating MHC II expression in spinal microglia. [Read the Full Post]

Malignant gliomas induce and exploit astrocytic mesenchymal-like transition by activating canonical Wnt/β-catenin signaling

1165 | Sep 29 2017

Lu P et al. established that glioma cells remarkably activated astrocytes via upregulating Wnt/β-catenin signaling, with obviously mesenchymal-like transition and increased migration and invasion ability, indicating that glioma cells may stimulate adjacent astrocytes to degrade extracellular matrix and thereby promoting tumor invasiveness. [Read the Full Post]

Serpine2, a potential novel target for combating melanoma metastasis

0 | Sep 15 2017

Wu QW et al. suggested a novel mechanism underlying the metastasis of melanoma cells which might serve as a new intervention target for the treatment of melanoma. [Read the Full Post]

Anterior-Posterior Patterning of Definitive Endoderm Generated from Human Embryonic Stem Cells Depends on the Differential Signaling of Retinoic Acid, Wnt-, and BMP-Signaling

1191 | Sep 10 2017

Davenport C et al. provided new insights into the mechanisms behind cell specification of human DE derived from pluripotent stem cells. VHL deficiency is dependent on HIF activation. Moreover, HIF1α or HIF2α overexpression in CC-RCCVHL cells is sufficient to sensitize them to ROCK inhibition. Finally, Y-27632 treatment inhibited growth of subcutaneous 786-OT1 CC-RCC tumors in mice. Thus, ROCK inhibitors represent potential therapeutics for VHL-deficient CC-RCC. [Read the Full Post]

Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma

1594 | Sep 09 2017

Thompson JM et al. suggested that synthetic lethality between ROCK inhibition and VHL deficiency is dependent on HIF activation. Moreover, HIF1α or HIF2α overexpression in CC-RCCVHL cells is sufficient to sensitize them to ROCK inhibition. Finally, Y-27632 treatment inhibited growth of subcutaneous 786-OT1 CC-RCC tumors in mice. Thus, ROCK inhibitors represent potential therapeutics for VHL-deficient CC-RCC. [Read the Full Post]

Regulation of TRPM7 Function by IL-6 through the JAK2-STAT3 Signaling Pathway

910 | Sep 05 2017

Liu A et al. indicated IL-6 inhibits the inward TRPM7 current via the JAK2-STAT3 signaling pathway. [Read the Full Post]

Interleukin 6 induces cell proliferation of clear cell renal cell carcinoma by suppressing hepaCAM via the STAT3-dependent up-regulation of DNMT1 or DNMT3b

1245 | Aug 17 2017

Quan Z et al. provided a novel signal pathway regulating cell proliferation, potentially representing a therapeutic target for RCC. [Read the Full Post]

Cholesterol Synthetase DHCR24 Induced by Insulin Aggravates Cancer Invasion and Progesterone Resistance in Endometrial Carcinoma

1190 | Aug 17 2017

Dai M et al. demonstrated for the first time the crucial role of the insulin/STAT3/DHCR24/PGR axis in the progression of EC by modulating the metastasis and progesterone response, which could serve as potential therapeutic targets for the treatment of EC with progesterone receptor loss. [Read the Full Post]

Lipopolysaccharide increases IL-6 secretion via activation of the ERK1/2 signaling pathway to up-regulate RANKL gene expression in MLO-Y4 cells

1208 | Aug 16 2017

Yu K et al. indicated that LPS up-regulates osteocyte expression of RANKL and IL-6, and the increased RANKL is associated with the up-regulation of IL-6, which involves the ERK1/2 pathway. [Read the Full Post]

BRG1 targeting STAT3/VEGFC signaling regulates lymphangiogenesis in colorectal cancer

1042 | Aug 09 2017

Zhu X et al. demonstration of the important roles of the BRG1/STAT3/VEGFC in tumor-associated lymphangiogenesis might lead to the discovery of novel therapeutic targets in the treatment of cancers with BRG1 loss of function. [Read the Full Post]

Essential role of Notch4/STAT3 signaling in epithelial-mesenchymal transition of tamoxifen-resistant human breast cancer

1710 | Jul 25 2017

Bui QT et al. concluded Notch4 could be a potential target to prevent metastasis in TAM-resistant breast cancer. [Read the Full Post]

Endosulfan inhibits proliferation through the Notch signaling pathway in human umbilical vein endothelial cells

1642 | Jul 25 2017

Wei J et al. demonstrated that endosulfan inhibited proliferation through the Notch signaling pathway as a result of oxidative stress. In addition, endosulfan can damage the cytoskeleton and block mitosis, which may add another layer of toxic effects on endothelial cells. [Read the Full Post]

Synergistic effects of CD44 and TGF-β1 through AKT/GSK-3β/β-catenin signaling during epithelial-mesenchymal transition in liver cancer cells

1003 | Jul 21 2017

Park NR et al. demonstrated the synergistic interactions between CD44 and TGF-β1 in EMT induction and CSC properties through the AKT/GSK-3β/β-catenin pathway in HCC cells. [Read the Full Post]

Effect of alpha lipoic acid on retinal ganglion cell survival in an optic nerve crush model

1877 | Jul 17 2017

Liu R et al. conclude that the endogenous EPO/EPOR signaling pathway may contribute to the protective effects of ALA in the retina after ONC injury. [Read the Full Post]

The positional identity of iPSC-derived neural progenitor cells along the anterior-posterior axis is controlled in a dosage-dependent manner by bFGF and EGF

0 | Jul 14 2017

Zhou S et al. indicated that different concentrations of bFGF and EGF supplemented during propagation of neural rosettes are involved in altering the identity of the resultant neural cells. [Read the Full Post]

WNT/β-catenin signaling promotes VSMCs to osteogenic transdifferentiation and calcification through directly modulating Runx2 gene expression.

0 | Jul 08 2017

Cai T et al. suggested that high-phosphate may activate WNT/β-catenin signaling through different pathways, and the activated WNT/β-catenin signaling, through direct downstream target Runx2, could play an important role in promoting VOT and AMC. [Read the Full Post]

Suppression of Virulent Porcine Epidemic Diarrhea Virus Proliferation by the PI3K/Akt/GSK-3α/β Pathway

2502 | Jul 04 2017

Kong N et al. suggested that PI3K/Akt/GSK-3α/β signaling pathway is activated by PEDV and functions in inhibiting PEDV replication. [Read the Full Post]

Generation of Cardiomyocytes from Pluripotent Stem Cells

1244 | Jul 03 2017

Nakahama H et al. described two different methods for acquiring CMs from human pluripotent lines. One method involves the generation of embryoid bodies, which emulates the natural developmental process, while the other method chemically activates the canonical Wnt signaling pathway to induce a monolayer of cardiac differentiation. [Read the Full Post]

Role of Wnt/β-catenin, Wnt/c-Jun N-terminal kinase and Wnt/Ca2+ pathways in cisplatin-induced chemoresistance in ovarian cancer

2276 | Jul 03 2017

Huang L et al. indicated that β-catenin, JNK and CaMKII are potential therapeutic targets in chemoresistant ovarian cancers. [Read the Full Post]

Structural basis of Smoothened regulation by its extracellular domains

1300 | Jun 22 2017

Byrne EF et al. clarified the structural mechanism by which the activity of a GPCR is controlled by ligand-regulated interactions between its extracellular and transmembrane domains. [Read the Full Post]

Platelet-derived growth factor (PDGF)-induced activation of Erk5 MAP-kinase is dependent on Mekk2, Mek1/2, PKC and PI3-kinase, and affects BMP signaling

4710 | Jun 14 2017

Tsioumpekou M et al. found that PDGF-BB-induced Erk5 activation involves parallel stimulatory and inhibitory pathways and promotes Smad1/5/8 signaling. [Read the Full Post]

Analysis of Endogenous Protein Interactions of Polycomb Group of Proteins in Mouse Embryonic Stem Cells.

1930 | Jun 14 2017

Morey L et al. described several methods to study Polycomb architecture, and identification of novel interactors in both pluripotent and differentiating mouse embryonic stem cells. [Read the Full Post]

Transmembrane protein 88 attenuates liver fibrosis by promoting apoptosis and reversion of activated hepatic stellate cells

1465 | Jun 13 2017

Cai SP et al. found that Tmem88 played an important role in HSCs activation, proliferation and apoptosis, and Tmem88 expression might be modulated by Dnmt3a. [Read the Full Post]

DDX17 nucleocytoplasmic shuttling promotes acquired gefitinib resistance in non-small cell lung cancer cells via activation of β-catenin

2681 | Jun 12 2017

Li K et al. revealed a novel and important mechanism by which DDX17 contributes to acquired gefitinib resistance through exportin/importin-dependent cytoplasmic shuttling and followed by activation of β-catenin, and DDX17 inhibition may be a promising strategy to overcome acquired resistance of gefitinib in NSCLC patients. [Read the Full Post]

Adipocyte-specific CD1d-deficiency mitigates diet-induced obesity and insulin resistance in mice

2564 | Jun 11 2017

Satoh M et al. indicated that interactions between NKT cells and CD1d-expressing adipocytes producing endogenous NKT cell ligands play a critical role in the induction of inflammation and functional modulation of adipose tissue that leads to obesity. [Read the Full Post]

Combretastatin A-1 phosphate, a microtubule inhibitor, acts on both hepatocellular carcinoma cells and tumor-associated macrophages by inhibiting the Wnt/β-catenin pathway

1118 | Jun 09 2017

Mao J et al. indicated that CA1P has great potential to impact both cancer cells and the microenvironment. [Read the Full Post]

Inhibition of green tea polyphenol EGCG((-)-epigallocatechin-3-gallate) on the proliferation of gastric cancer cells by suppressing canonical wnt/β-catenin signalling pathway

1478 | Jun 08 2017

Yang C et al. established that EGCG suppressed gastric cancer cell proliferation and demonstrate that this inhibitory effect is related to canonical Wnt/β-catenin signalling. [Read the Full Post]

Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model

2446 | Jun 06 2017

Guo SC et al. provided evidence of the probable molecular mechanisms underlying the PRP effect on healing of chronic ulcers and describe a promising resource of growth factors from exosomes without species restriction. [Read the Full Post]

The Expression and Regulation of Interleukin-33 in Human Epidermal Keratinocytes: A New Mediator of Atopic Dermatitis and Its Possible Signaling Pathway

2254 | May 26 2017

Du HY et al. found that IL-33 plays an important role in the pathogenesis of immune inflammatory responses in AD, which might be a possible therapeutic target in the treatment of AD. [Read the Full Post]

Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells

0 | May 22 2017

Massa MG et al. provided an avenue for studies with a greater cell- and human-specific focus, specifically in the context of genetic contributions to neurodegeneration and drug discovery. [Read the Full Post]

Identification of Novel Inhibitors of the Type I Interferon Induction Pathway Using Cell-Based High-Throughput Screening

2055 | May 17 2017

Gage ZO et al. demonstrate that one of these compounds acts at or upstream of IRF3 phosphorylation. [Read the Full Post]

Myocardial commitment from human pluripotent stem cells: Rapid production of human heart grafts

0 | May 16 2017

Garreta E et al. provided a suitable platform for cardiac engineering and disease modeling in the human setting. [Read the Full Post]

Fast and Efficient Transfection of Mouse Embryonic Stem Cells Using Non-Viral Reagents.

0 | May 11 2017

Tamm C et al. demonstrated that simplified and highly efficient transfection method will be valuable for both basic research and high-throughput applications. [Read the Full Post]

Transforming growth factor-β-dependent Wnt secretion controls myofibroblast formation and myocardial fibrosis progression in experimental autoimmune myocarditis

0 | May 08 2017

Blyszczuk P et al. identified TAK1-mediated rapid Wnt protein secretion as a novel downstream key mechanism of TGF-β-mediated myofibroblast differentiation and myocardial fibrosis progression in human and mouse myocarditis. [Read the Full Post]

GLI inhibitor GANT61 kills melanoma cells and acts in synergy with obatoclax

0 | May 05 2017

Vlčková K et al. found that GANT61 treatment might become a hopeful and effective anti-melanoma targeted therapy, especially when combined with the BCL2 family inhibitor obatoclax. [Read the Full Post]

Induction and differentiation of human induced pluripotent stem cells into functional cardiomyocytes on a compartmented monolayer of gelatin nanofibers

1231 | May 05 2017

Tang Y et al. showed that representative field potential waveforms of matured cardiac tissues with appropriate drug responses. [Read the Full Post]

Fast and Efficient Transfection of Mouse Embryonic Stem Cells Using Non-Viral Reagents

1399 | Apr 30 2017

Tamm C et al. found that simplified and highly efficient transfection method will be valuable for both basic research and high-throughput applications. [Read the Full Post]

Cell alignment induced by anisotropic electrospun fibrous scaffolds alone has limited effect on cardiomyocyte maturation

0 | Apr 28 2017

Han J et al suggested that electrospun anisotropic fibrous scaffolds, as a single method, have limited effect on improving the maturation of hPSC-CMs. [Read the Full Post]

Induction and differentiation of human induced pluripotent stem cells into functional cardiomyocytes on a compartmented monolayer of gelatin nanofibers

978 | Apr 28 2017

Tang Y et al. found that representative field potential waveforms of matured cardiac tissues with appropriate drug responses. [Read the Full Post]

GLI inhibitor GANT61 kills melanoma cells and acts in synergy with obatoclax

1316 | Apr 27 2017

Vlčková K et al. found that GANT61 treatment might become a hopeful and effective anti-melanoma targeted therapy, especially when combined with the BCL2 family inhibitor obatoclax. [Read the Full Post]

High glucose-induced Matrilin-2 expression in mouse mesangial cells was mediated by transforming growth factor beta 1 (TGF-β1).

1096 | Apr 24 2017

Zhang S et al showed that high-glucose-induced Matrilin-2 expression that was mediated by the TGF-β1/Smad3 signaling pathway might play a role in Diabetic nephropathy (DN) pathogenesis and our finding provided a potential diagnostic and/or therapeutic target for DN. [Read the Full Post]

MAP3K19-Is-a-Novel-Regulator-of-TGF-B-Signaling-That-Impacts-Bleomycin-Induced-Lung-Injury-and-Pulmonary-Fibrosis

5086 | Apr 23 2017

Boehme SA et al suggested that inhibition of MAP3K19 may have a beneficial therapeutic effect in the treatment of IPF and represents a novel strategy to target this disease. [Read the Full Post]

Electrochemical biosensor for protein kinase A activity assay based on gold nanoparticles-carbon nanospheres, phos-tag-biotin and β-galactosidase

2276 | Apr 21 2017

Zhou Y et al. found the fabricated biosensor can be applied to detect PKA in human normal gastricepithelial cell line and human gastric carcinoma cell line with satisfactory results. [Read the Full Post]

Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1

2050 | Apr 19 2017

Baris S et al. found thatJAK kinase inhibitors may potentially be useful in some patients as adjunct therapy pending definitive treatment with bone marrow transplantation. [Read the Full Post]

Developmental expression of STATs, nuclear factor-κB and inflammatory genes in the jejunum of piglets during weaning

1991 | Apr 18 2017

Yi H et al found weaning caused severe inflammation associated with activation of the NF-κB and STAT-3 pathways and suppression of STAT-1 and STAT-6 in the jejunum of piglets. [Read the Full Post]

A chemical with proven clinical safety rescues Down-syndrome-related phenotypes in through DYRK1A inhibition

1635 | Apr 06 2017

Kim H et al. demonstrated that CX-4945 is a potent DYRK1A inhibitor and also suggested that it has therapeutic potential for DYRK1A-associated diseases. [Read the Full Post]

Distinct MicroRNA Expression Signatures of Porcine Induced Pluripotent Stem Cells under Mouse and Human ESC Culture Conditions

1121 | Apr 04 2017

Zhang W et al. found that significant differences in the miRNA signatures of hpiPSCs and mpiPSCs under different pluripotent states that were derived from different culture conditions. [Read the Full Post]

SMO Gene Amplification and Activation of the Hedgehog Pathway as Novel Mechanisms of Resistance to Anti-Epidermal Growth Factor Receptor Drugs in Human Lung Cancer

1416 | Feb 21 2017

Della Corte CM, et al.'s result supports the role of the Hh pathway in mediating resistance to anti-EGFR-TKIs through the induction of EMT and suggests new opportunities to design new treatment strategies in lung cancer. [Read the Full Post]

Targeting hedgehog signaling reduces self-renewal in embryonal rhabdomyosarcoma

0 | Feb 20 2017

Satheesha S, et al.‘s ’ work identifies novel functional aspects of hedgehog signaling in ERMS, redefines the rationale for its targeting as means to control ERMS self-renewal and underscores the importance of studying functional tumor heterogeneity in pediatric cancers. [Read the Full Post]

Targeting Wnt pathway in mantle cell lymphoma-initiating cells

0 | Feb 20 2017

Mathur R, et al.‘s’ results suggest that Wnt signaling is critical for the maintenance and survival of MCL-ICs, and effective MCL therapy should aim to eliminate MCL-ICs through Wnt signaling inhibitors. [Read the Full Post]

Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma

0 | Feb 19 2017

Brun SN, et al.'s studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease. [Read the Full Post]

Opposing roles of TGF-β and EGF in the regulation of TRAIL-induced apoptosis in human breast epithelial cells

1390 | Feb 15 2017

Li W et al. revealed a fine regulation by EGF and TGF-β of sensitivity of human breast epithelial cells to TRAIL which may be relevant during morphogenesis. [Read the Full Post]

AKT and 14-3-3 Regulate Notch4 Nuclear Localization

2569 | Feb 06 2017

Ramakrishnan G, et al.'s findings provide a novel mechanism for Notch4-ICD regulation, suggesting a negative regulatory role for the PI3K-AKT pathway in Notch4 nuclear signaling. [Read the Full Post]

Wnt/b-Catenin-Signaling and the Formation of M€uller Glia-Derived Progenitors in the Chick Retina

1432 | Feb 04 2017

Gallina D, et al 's findings indicate that Wnt-signaling is part of a network initiated by FGF2/MAPK or retinal damage, and activation of canonical Wnt-signaling is required for the formation of proliferating MGPCs. [Read the Full Post]

Delayed Administration of WP1066, an STAT3 Inhibitor, Ameliorates Radiation-Induced Lung Injury in Mice

2514 | Jan 28 2017

The activation of STAT3 pathway might play an important part in the pathogenesis of radiation-induced lung injury. The protective effects of delayed treatment of WP1066 suggested STAT3 signaling could be a therapeutic target for radiation pneumonitis. [Read the Full Post]

GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats

1316 | Jan 27 2017

Wang W et al. suggested that TWS119 reduces rtPA-induced HT and attenuates blood-brain barrier disruption, possibly through activation of the Wnt/β-catenin signaling pathway. This study provides a potential therapeutic strategy to prevent tPA-induced HT after acute ischemic stroke. [Read the Full Post]

Wnt/β-catenin-signaling and the formation of Müller glia-derived progenitors in the chick retina

0 | Jan 26 2017

Gallina D et al. indicated that Wnt-signaling is part of a network initiated by FGF2/MAPK or retinal damage, and activation of canonical Wnt-signaling is required for the formation of proliferating MGPCs. [Read the Full Post]

SMO Gene Amplification and Activation of the Hedgehog Pathway as Novel Mechanisms of Resistance to Anti-Epidermal Growth Factor Receptor Drugs in Human Lung Cancer

1007 | Jan 11 2017

Della Corte CM et al. found that the role of the Hh pathway in mediating resistance to anti-EGFR-TKIs through the induction of EMT and suggests new opportunities to design new treatment strategies in lung cancer. [Read the Full Post]

Targeting Wnt pathway in mantle cell lymphoma-initiating cells

3587 | Jan 10 2017

Mathur R, et al.'s results suggest that Wnt signaling is critical for the maintenance and survival of MCL-ICs, and effective MCL therapy should aim to eliminate MCL-ICs through Wnt signaling inhibitors. [Read the Full Post]

Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma

1288 | Jan 09 2017

Brun SN, et al.'s studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease. [Read the Full Post]

Targeting hedgehog signaling reduces self-renewal in embryonal rhabdomyosarcoma

1371 | Jan 09 2017

Satheesha S, et al.'s work identifies novel functional aspects of hedgehog signaling in ERMS, redefines the rationale for its targeting as means to control ERMS self-renewal and underscores the importance of studying functional tumor heterogeneity in pediatric cancers. [Read the Full Post]

Wnt/β-catenin-signaling and the formation of Müller glia-derived progenitors in the chick retina

1530 | Jan 01 2017

Gallina D et al. indicated that Wnt-signaling is part of a network initiated by FGF2/MAPK or retinal damage, and activation of canonical Wnt-signaling is required for the formation of proliferating MGPCs. [Read the Full Post]

AKT and 14-3-3 Regulate Notch4 Nuclear Localization

2889 | Dec 29 2016

Ramakrishnan G, et al.'s findings provide a novel mechanism for Notch4-ICD regulation, suggesting a negative regulatory role for the PI3K-AKT pathway in Notch4 nuclear signaling. [Read the Full Post]

WNT/β-catenin signaling promotes VSMCs to osteogenic transdifferentiation and calcification through directly modulating Runx2 gene expression.

1723 | Dec 21 2016

Cai T et al.'s study suggested that high-phosphate may activate WNT/β-catenin signaling through different pathways, and the activated WNT/β-catenin signaling, through direct downstream target Runx2, could play an important role in promoting VOT and AMC. [Read the Full Post]

The positional identity of iPSC-derived neural progenitor cells along the anterior-posterior axis is controlled in a dosage-dependent manner by bFGF and EGF

2093 | Dec 17 2016

The results of Zhou S et al. indicated that different concentrations of bFGF and EGF supplemented during propagation of neural rosettes are involved in altering the identity of the resultant neural cells. [Read the Full Post]

Synergistic effects of CD44 and TGF-β1 through AKT/GSK-3β/β-catenin signaling during epithelial-mesenchymal transition in liver cancer cells

1675 | Dec 16 2016

Park NR, et al. demonstrated the synergistic interactions between CD44 and TGF-β1 in EMT induction and CSC properties through the AKT/GSK-3β/β-catenin pathway in HCC cells. [Read the Full Post]

Synergistic effects of CD44 and TGF-β1 through AKT/GSK-3β/β-catenin signaling during epithelial-mesenchymal transition in liver cancer cells

1733 | Dec 15 2016

Park NR et al.'s study demonstrated the synergistic interactions between CD44 and TGF-β1 in EMT induction and CSC properties through the AKT/GSK-3β/β-catenin pathway in HCC cells [Read the Full Post]

Hedgehog pathway is involved in nitidine chloride induced inhibition of epithelial-mesenchymal transition and cancer stem cells-like properties in breast cancer cells

1289 | Dec 09 2016

The study of Sun M et al. suggested that NC may be a potential anticancer agent for breast cancer. [Read the Full Post]

Serpine2, a potential novel target for combating melanoma metastasis

1785 | Nov 30 2016

Wu QW et al. suggested a novel mechanism underlying the metastasis of melanoma cells which might serve as a new intervention target for the treatment of melanoma. [Read the Full Post]

Inhibition of β-Catenin to Overcome Endocrine Resistance in Tamoxifen-Resistant Breast Cancer Cell Line

1974 | Nov 11 2016

Won HS et al. suggested that β-catenin plays a role in tamoxifen-resistant breast cancer, and the inhibition of β-catenin may be a potential target in tamoxifen-resistant breast cancer. [Read the Full Post]

Opposing roles of TGF-β and EGF in the regulation of TRAIL-induced apoptosis in human breast epithelial cells

1736 | Nov 07 2016

Li W et al. revealed a fine regulation by EGF and TGF-β of sensitivity of human breast epithelial cells to TRAIL which may be relevant during morphogenesis. [Read the Full Post]

Multiple Sclerosis Patient-Specific Primary Neurons Differentiated from Urinary Renal Epithelial Cells via Induced Pluripotent Stem Cells

3558 | Oct 19 2016

[Read the Full Post]

Myocardial commitment from human pluripotent stem cells: Rapid production of human heart grafts

1904 | Oct 12 2016

Garreta E et al. provided a suitable platform for cardiac engineering and disease modeling in the human setting. [Read the Full Post]

Transforming growth factor-β-dependent Wnt secretion controls myofibroblast formation and myocardial fibrosis progression in experimental autoimmune myocarditis

2104 | Oct 08 2016

Blyszczuk P et al. identified TAK1-mediated rapid Wnt protein secretion as a novel downstream key mechanism of TGF-β-mediated myofibroblast differentiation and myocardial fibrosis progression in human and mouse myocarditis. [Read the Full Post]

Cell alignment induced by anisotropic electrospun fibrous scaffolds alone has limited effect on cardiomyocyte maturation

2470 | Sep 27 2016

Han J et al. suggested that electrospun anisotropic fibrous scaffolds, as a single method, have limited effect on improving the maturation of hPSC-CMs. [Read the Full Post]

High glucose-induced Matrilin-2 expression in mouse mesangial cells was mediated by transforming growth factor beta 1 (TGF-β1)

1688 | Sep 26 2016

Zhang S et al. found that high-glucose-induced Matrilin-2 expression that was mediated by the TGF-β1/Smad3 signaling pathway might play a role in Diabetic nephropathy (DN) pathogenesis. [Read the Full Post]

MAP3K19 Is a Novel Regulator of TGF-β Signaling That Impacts Bleomycin-Induced Lung Injury and Pulmonary Fibrosis

1825 | Sep 22 2016

Boehme SA et al. suggested that inhibition of MAP3K19 may have a beneficial therapeutic effect in the treatment of IPF and represents a novel strategy to target this disease. [Read the Full Post]

Developmental expression of STATs, nuclear factor-κB and inflammatory genes in the jejunum of piglets during weaning

4814 | Sep 20 2016

Yi H et al. found that weaning caused severe inflammation associated with activation of the NF-κB and STAT-3 pathways and suppression of STAT-1 and STAT-6 in the jejunum of piglets. [Read the Full Post]

CY190602, a novel DNA/HDAC dual-targeting drug with enhanced anti-cancer potency

8152 | Mar 19 2015

Liu et al. demonstrated a novel bendamustine-derived drug, CY190602, enhanced anticancer potency. [Read the Full Post]

Inhibition of proteasome restores bortesomib-induced thrombocytopenia

8663 | Feb 10 2015

Shi et al. reported clinical proteasome inhibitor enable to block proplatelet formation by megakaryocytes in human and mouse model. [Read the Full Post]

A protocol for human pluripotent stem cell differentiation into endoderm related cells

6160 | Feb 02 2015

Diekmann et al. showed a detailed protocol started from a defined cell number of dispersed single cells of three different human ESC lines, and one human iPSC line. [Read the Full Post]

Unexpected role of Notch signaling on directing the trophectoderm lineage in the mouse blastocyst

5380 | Jan 30 2015

Rayon et al. showed that Notch signaling plays a key role in mediating TE-specific expression of Cdx2, though interaction with the transcription factor TEAD4. [Read the Full Post]

BUB1 plays a key role in promoting TGF-β signaling

6001 | Jan 20 2015

By using human kinome siRNA screen and a live-cell reporter for TGF-β receptor (TGFBR) activity, Nyati et al. identified the kinase budding uninhibited by benzimidazoles-1 (BUB1) plays a critical role in regulating TGF-β signaling. [Read the Full Post]

Tofacitinib promotes myeloid-derived suppressor cells expansion and reduces disease severity of arthritis SKG mice

5723 | Jan 14 2015

Nishimura et al. revealed that tofacitinib has effect on promoting MDSCs expansion and ameliorating arthritis in SKG mice. [Read the Full Post]

Generate hypothalamic neurons from hESCs and human iPSCs

3281 | Jan 08 2015

Wang et al. reported a protocol of differeiciating human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) into hypothalamic cells. [Read the Full Post]

The important role of HSF1 expressed by cancer-associated fibroblasts

3419 | Dec 29 2014

Scherz-Shouval et al. found cancer-associated fibroblasts (CAFs) frequently express heat shock factor 1 (HSF1), which acts as a strong enabler of tumorigenesis. [Read the Full Post]

Innate immunity-induced IRF3 signaling suppress TGF-β via Smad

4772 | Dec 23 2014

By investigating the innate host defense, Xu et al. found RIG-I-Like receptor (RLR) signaling suppress TGF-β via activation of Interferon regulatory factor 3 (IRF3). [Read the Full Post]

The inhibition of JAK signaling promotes the conversion from white to brown adipocytes

7192 | Dec 17 2014

By using a screening platform of small molecules identification, Moisan et al. found two inhibitors of JAK signaling were able to convert white adipocytes to brown adipocytes. [Read the Full Post]

The Notch signaling controls maintenance of memory CD4+ T cells

8376 | Dec 16 2014

Recently, Maekawa et al. demonstrated Notch signaling is important for the survival of memory CD4+ T cells by regulating glucose uptake. [Read the Full Post]

IncRNA BCAR4 regulates cancer development cooperated with chemokine signals

5935 | Dec 09 2014

Xing et al. demonstrated the mechanism of BCAR4, a disease-related Inc RNA, in regulation signaling pathways in breast cancer metastasis. [Read the Full Post]

MeCP2 S421 phosphorylation mediates neurogenesis via Notch signaling pathway

7375 | Dec 04 2014

Li et al. identified the Notch signaling is involved in the regulation of MeCP2 S421 phosphorylation other than neuronal activity. [Read the Full Post]

Retinoic acid and Wnt signaling are key regulators in development of hematopoietic stem cells

5368 | Dec 02 2014

Chanda et al. identified retinoic acid (RA) and Wnt signaling pathways as key mediators of HSC development. [Read the Full Post]

Mechanism of Cdo-induced Wnt suppression during neuronal differentication

3790 | Nov 28 2014

Jeong et al. found that Wnt signaling is negatively regulated by Cdo, a Shh multifunctional co-receptor which is highly expressed in the central nervous system, in order to promote neuronal differentiation. [Read the Full Post]

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

9071 | Nov 24 2014

Dechow et al. determined GP130/JAK/STAT3 signaling pathway is sufficient to induce MM generation in mice retroviral murine BM transduction-transplantation model. [Read the Full Post]

The mechanism of drug resistance in BRAF (V600E) mutant melanoma

8243 | Nov 19 2014

Sun et al. demonstrated the resistance of BRAF (V600E) is reversible and adaptive. The process involves several transduction factors, such as EGFR, PDGFRB, TGF-β, and SOX10. [Read the Full Post]

The activation of BMP and WNT signals specifies epicardial lineage from hESCs

5965 | Nov 12 2014

Witty et al. describe a new strategy of using human pluripotent stem cells (hESCs) to generate epicardial lineage cells by activation the BMP and WNT signaling pathways in a stage-specific way. [Read the Full Post]

Interactions between Slit-Robo and JAK-STAT signaling in regulation of stem cell-niche adhesion

7417 | Nov 10 2014

Rachel R. Stine et al. found Slit-Robo and JAK-STAT signaling pathways play key roles in stem cells competition within their niches. [Read the Full Post]

FGF21 is not required for CR-mediated IGF-1 reduction or cell proliferation inhibition

6826 | Nov 06 2014

Thompson et al. found that, in response to moderate CR, phosphorylated STAT5 may act as a key molecule, and FGF21 was not required for the down-regulation of IGF-1 expression level or cell proliferation rates. [Read the Full Post]

New platform of high efficiency iPSC reprogramming

7421 | Nov 05 2014

Vidal et al. found the inhibition of transforming growth factor β (TGF-β) or activation of Wnt signaling, or both, can provide a high efficient iPSC reprogramming in a cell-type-specific manner. [Read the Full Post]

JAK2 and MPL are two main regulators of TPO-induced megakaryopoiesis

6081 | Nov 03 2014

Megakaryopoiesis is regulated by TPO, which activates multiple signaling molecules. Besancenot et al. demonstrated that the protein levels of JAK2 and MPL determine TPO-induced megakaryopoiesis. [Read the Full Post]

Neural stem cells "heal" target cells via extracellular vesicles

3525 | Oct 29 2014

Cossetti et al. found NPCs communicate to the host via extracellular vesicles (EVs) and also investigated the cytokine-regulated pathways involved in the communication. It comes to a novel view in the understanding the mechanisms of stem cell therapy. [Read the Full Post]

The role of TGFβ target——LTBP4 in muscular dystrophy

3571 | Oct 24 2014

Ceco et al. found latent transforming growth factor-β (TGFβ) binding proteins 4 (LTBP4) play determinant roles in muscular dystrophy symptoms.Their data suggested that blocking LTBP4 results in reduced TGFβ release, and then leads to a reduction of muscle inflammation and damage in DMD. [Read the Full Post]

Notch signaling acts as a key regulator in generation of neurons from neural precursor cells

4766 | Oct 23 2014

Notch signaling plays a central role before asymmetric division and in the fate of Drosophila melanogaster neural precursor cells. It also acts as a critical factor in Numb distribution in neural precursor cells before cleavage. [Read the Full Post]

Two side roads toward conquest of HBV

2467 | May 05 2014

Vismodegib (GDC-0449) is a potent, novel and specific hedgehog inhibitor with IC50 of 3 nM and also inhibits P-gp with IC50 of 3.0 μM. [Read the Full Post]

How to survive the zombie apocalypse

2328 | Apr 02 2014

LDE225 (NVP-LDE225) is a Smoothened (Smo) antagonist, inhibiting Hedgehog (Hh) signaling with IC50 of 1.3 nM (mouse) and 2.5 nM (human), respectively. [Read the Full Post]

AZD1080 is a novel GSK3 inhibitor rescues synaptic plasticity deficits in rodent brain

3390 | Mar 06 2014

AZD1080 is a selective, orally active, brain permeable GSK3 inhibitor, inhibits human GSK3α and GSK3β with a Ki of 6.9 nM and 31 nM [Read the Full Post]

Y27632 is a biochemical tool used in the study of the ROCK

5035 | Mar 05 2014

Y-27632 2HCl inhibits ROCK-II while displaying little activity against PKC. [Read the Full Post]

SB431542 is a small molecule that acts as a specific inhibitor

3554 | Feb 13 2014

SB431542 is a potent and selective inhibitor of ALK5 with IC50 of 94 nM, 100-fold more selective for ALK5 than p38 MAPK and other kinases. [Read the Full Post]

SB525334 is a potent and selective inhibitor of TGFB

3419 | Feb 12 2014

SB 525334 (10 mg/kg/day) decreases the renal mRNA levels of PAI-1, procollagen α1(I), and procollagen α1(III) in a nephritis-induced renal fibrosis rat model. [Read the Full Post]

Y 27632 is available in a 5 mg format and has been optimized

4830 | Jan 17 2014

Y-27632 2HCl is a selective ROCK1 (p160ROCK) inhibitor with Ki of 140 nM, exhibits >200-fold selectivity over other kinases, including PKC, cAMP-dependent protein kinase, MLCK and PAK. [Read the Full Post]

WP1066 is a cell permeable AG 490 tyrphostin analog

5756 | Jan 15 2014

WP1066 is a novel inhibitor of JAK2 and STAT3 with IC50 of 2.30 μM and 2.43 μM in HEL cells; shows activity to JAK2, STAT3, STAT5, and ERK1/2 not JAK1 and JAK3. [Read the Full Post]

Y 27632 is a biochemical tool used in the study of the rho associated protein kinase

4965 | Jan 10 2014

Y-27632 2HCl is a selective ROCK1 inhibitor with Ki of 140 nM, exhibits >200-fold selectivity over other kinases, including PKC, cAMP-dependent protein kinase, MLCK and PAK. [Read the Full Post]

AZD1080 is a selective orally active brain permeable GSK3 inhibitor

0 | Jan 06 2014

AZD1080 reverses cognitive deficits and rescues dysfunctional synapses in mice. [Read the Full Post]

Wnt C59 was first disclosed in patent WO2010101849 as a potent

3581 | Dec 19 2013

Wnt-C59 is claimed to inhibit PORCN enzyme activity at nanomolar concentrations. [Read the Full Post]

XAV 939 is a small molecule and selective Wnt pathway

3861 | Dec 11 2013

XAV-939 specifically inhibits tankyrase PARP activity. [Read the Full Post]

SB 525334 is a selective inhibitor of transforming growth factor B

3114 | Dec 10 2013

SB525334 is a potent and selective inhibitor of TGFβ receptor I (ALK5) with IC50 of 14.3 nM, is 4-fold less potent to ALK4 than ALK5 and inactive to ALK2, 3, and 6. [Read the Full Post]

LDN193189 is a cell permeable

2958 | Dec 03 2013

LDN193189 is a selective BMP signaling inhibitor, inhibits the transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC50 of 5 nM and 30 nM, respectively, exhibits 200-fold selectivity for BMP versus TGF-β. [Read the Full Post]

Thiazovivin helps in promoting human embryonic stem cell

4734 | Nov 22 2013

Thiazovivin (Tzv) is a novel ROCK inhibitor with IC50 of 0.5 μM, promotes hESC survival after single-cell dissociation. [Read the Full Post]

AZD1080 is a selective orally active brain permeable GSK3 inhibitor

3837 | Nov 11 2013

AZD1080 is a selective, orally active, brain permeable GSK3 inhibitor, inhibits human GSK3α and GSK3β with a Ki of 6.9 nM and 31 nM, respectively, shows >14-fold selectivity against cdk2, cdk5, cdk1 and Erk2. [Read the Full Post]

Thiazovivin is a drug which dramatically improves the survival of hES

5009 | Nov 05 2013

Thiazovivin (Tzv) is a novel ROCK inhibitor with IC50 of 0.5 μM, promotes hESC survival after single-cell dissociation. [Read the Full Post]

This study is designed to evaluate the efficacy and safety of tofacitinib

6402 | Oct 30 2013

Tofacitinib citrate inhibits IL-2-mediated human T cell blast proliferation and IL-15-induced CD69 expression with IC50 of 11 nM and 48 nM, respectively. [Read the Full Post]

SANT1 is a potent inhibitor of Sonic hedgehog signaling

0 | Oct 16 2013

SANT-1 inhibits wild type and oncogenic Smo with equal potency. [Read the Full Post]

Y27632 is a selective inhibitor of the Rhoassociated kinase p160ROCK

4781 | Sep 12 2013

Y27632 2HCl inhibits ROCK-II while displaying little activity against PKC, cAMP-dependent protein kinase and myosin light-chain kinase (MLCK) with Ki of 26 μM, 25 μM and > 250 μM, respectively, as well as PKA activated by another Rho-family GTPase member, Cdc42. [Read the Full Post]

SANT1 is a potent inhibitor of Sonic hedgehog signaling

2252 | Sep 02 2013

SANT-1 inhibits wild type and oncogenic Smo with equal potency. SANT-1 counteracts SAG-induced pathway activation in Shh-LIGHT2 cells. [Read the Full Post]

Tideglusib might be useful for slowing atrophy rates

3408 | Aug 15 2013

Tideglusib (NP031112, NP-12) is an irreversible, non ATP-competitive GSK-3β inhibitor with IC50 of 60 nM; fails to inhibit kinases with a Cys homologous to Cys-199 located in the active site. Phase 1/2. [Read the Full Post]

TWS119 is thought to bind GSK with high affinity

3862 | Jul 11 2013

Treatment of a monolayer of P19 cells with 1 μM TWS119 causes 30–40% cells to differentiate specifically into neuronal lineages based on counting of TuJ1 positive cells with correct neuronal morphology (up to 60% neuronal differentiation occurred through the standard EB formation protocol with concomitant TWS119 treatment). [Read the Full Post]

y27632 is a biochemical tool used in the study of the rho associated protein kinase signaling pathways

5259 | Jun 07 2013

Oral administration of Y-27632 2HCl at 30 mg/kg significantly decreases the blood pressure in a dose-dependent manner in spontaneous hypertensive rats, renal hypertensive rats, as well as deoxycorticosterone acetate (DOCA)-salt hypertensive rats. [Read the Full Post]

Tideglusib may be useful for slowing atrophy rates

3742 | Jun 05 2013

Tideglusib (50 mg/kg) injected into the adult male Wistar rats hippocampus dramatically reduces kainic acid-induced inflammation and has a neuroprotective effect in the damaged areas of the hippocampus. [Read the Full Post]

Erismodegib is an orally bioavailable small molecule

2862 | Jan 07 2013

C Kit is a transmembrane receptor tyrosine kinase that binds stem cell factor SCF . CKit is encoded by the kit proto oncogene, localized to human chromosome and to mouse chromosome The c Kit SCF erismodegib interaction is critical for the survival and development of stem cells involved in hematopoiesis [Read the Full Post]

LY2109761 is a novel transforming growth factor

2781 | Jan 04 2013

The JAK2V617F mutated allele is present in virtually all patients with polycythemia vera (PV) and in about 60% of those with essential thrombocythemia (ET) and primary myelofibrosis (PMF), which are the other two main clinical entities included within the group of myeloproliferative LY2109761 neoplasms. [Read the Full Post]

ROCK Kinase is involved in cytokinesis

5142 | Dec 03 2012

The first evidence that the JNK pathway, the low level of expression in SMC Lon RGS4 ch Lt, then led end F F promotion from SMC contraction. Inhibition of tonic RGS4 expression by JNK pathway represents a novel mechanism for the contribution of the JNK pathway in the regulation of smooth muscle contraction. crosstalk between MAPK and JNK by other means NFkB not well ROCK Kinase understood. [Read the Full Post]

Gamma Secretase were grown in 5 ml of medium

4762 | Nov 28 2012

The cells were pelleted by centrifugation, the medium was Gamma Secretase removed with the drug, and the cells were washed washed with sterile PBS and centrifuged again. [Read the Full Post]

CP-690550: THE CURE FOR ARTHRITIS

6102 | Mar 20 2012

Introduction: JAK and its role in signaling pathways The protein kinase family plays an essential role in the government of the growth or death properties of mammalian tissues. These proteins form an interrelated, redundant system that is capable of selectively initiating the growth of certain cell types in response to the needs of the host system. To do this the protein kinase super family is subdivided into a series of related protein kinases which make up a signaling pathway, traveling from the extracellular matrix into the cell nucleus. The Janus kinase pathway is one which is activated in response to the action of cytokines on the cytokine transmembrane receptors. Since these receptors have no kinase ability themselves they are total dependant on the Janus kinases (JAK) for activity. [Read the Full Post]

INCB18424 – JACKING THE JAK2

6765 | Mar 20 2012

Introduction: JAK2 in relation to metabolic blood disorders The transmission of signals from extracellular factors through the cell membrane to effect actions within the cell cytosole and nucleus is conducted along pathways of protein to protein interactions. Many metabolic disorders have been associated with aberrations in these pathways causing a variety of destructive cellular actions. Many of these diseases possess no known cure and in response research has focused on the mechanisms behind the progression of these diseases. One area that has received a lot of attention is the possibility that the natural immune function can be detrimental to healthy growth patterns if over stimulated by mutations in the genetic information of individuals. A key series of proteins in the immune response is the Janus kinases (JAK), a series of four distinct but domain related kinases located in the cellular cytosole. These kinases form a distinct link between extracellular immune function ligands and a direct regulation of transcription of genetic information. However, a mutation of the JAK2 isoform has been associated with degenerative effects such as myeloproliferative neoplasms, thrombocythemia, polycythemia vera and psoriasis. [Read the Full Post]

RO4929097 – CHECKS NOTCH SIGNALING IN CANCERS

5211 | Mar 20 2012

RO4929097: A GAMMA SECRETASE INHIBITOR: Among well known proteases Gamma secretase is one which is made up of various subunits. This is present in the membrane hence is a protein in membrane which is also capable of cleaving certain transmembrane proteins therefore also known as the intramembrane protease. In case of Alzheimer’s disease amyloid plaques are formed in brain, these plaques are resulted due to the amyloid beta peptide and these peptides are produced due to the action of gamma secretase, this is one of the well known examples of this protease. Presently, we are focusing on the important role of gamma secretase in the Notch protein processing. In case of many cancers and tumors this Notch protein signaling is found to be abnormal, therefore the arresting of this pathway can be an authentic way to get rid of abnormal cell growth. In the light of this idea a novel RO4929097 gamma secretase inhibitor is discovered. The inhibitory effect of this inhibitor has been confirmed by various methods like western blotting. [Read the Full Post]

THIAZOVIVIN: THE PLURIPOTENCY INDUCER

4106 | Mar 20 2012

POTENTIAL OF EMBRYONIC STEM CELLS OF HUMAN (hESCs): The stem cells are not only known for their property of pluripotency in nature which means they have the potency to replicate in an indefinite manner but also famous for their capability of getting differentiate into all other kinds of cells and organelles from the three basic germinal layers named as ectoderm, mesoderm and endoderm. Embryonic stem cells of human (hESCs) have the ability of producing various numbers of types of cells in contrast to adult stem cells having the capability of producing only a limited cell types. Due to their pluripotency hESCs or human embryonic stem cells are of great interest and importance for the scientists and researchers as they are being used for detection and analysis of different genetic disorders of human in their research. The successful models of Human Embryonic Stem Cells are made for Fragile-X syndrome and Cystic fibrosis (CF) etc like genetic maladies and their will be many more in upcoming years. In olden years the usual practice was to use embryo to generate pluripotent stem cells which is brought down very significantly due to the process of insertion of various genes like Sox2, Oct4 and Klf4 etc into differentiated cells. These genes can enhance the pluripotency in differentiated cells and make them exactly like embryonic stem cells. A recent more advanced approach is to use molecules like Thiazovivin. [Read the Full Post]

TASOCITINIB: THE REVOLUTION IN ARTHRITIS MANAGEMENT

6424 | Mar 18 2012

Introduction: Inhibition of the JAK pathway The protein kinases are a super family of protein that govern the control of cellular growth, creation of vascular structure and many other processes the control the way in which cells and tissue regenerate. In is estimated that 30% of all cellular regulation is governed by protein kinases. Protein kinases are subdivided into 7 different classifications of which one is the tyrosine kinases. These kinases operate by phosphorylation of a tyrosine amino acid residue transferring a signal down a cascade of protein to regulate cellular processes. A further subdivision of the tyrosine kinases can be made into receptor based kinases and non receptor based kinases. The Janus kinases (JAK) are a sub family of the receptor based tyrosine kinases. Signals from the JAK regulate the cytokines, the GM-CSF family and the GP130 receptor family. JAK kinases exist in the 4 distinct isoforms with twinned phosphorylation domains. Inhibitors of the JAK kinases have been demonstrated to have a positive effect on cancerous cells both in vivo and in vitro. [Read the Full Post]

RUXOLITINIB: THE JACK FOR JAK INHIBITION

6501 | Mar 13 2012

Ruxolitinib: Inhibition of the Janus Kinases The janus kinases are a sub family of the protein kinases and are refer to as non receptor tyrosine kinases. Signals from the Janus kinases regulate several different types of proteins such as the cytokine receptor family (interferon), the GM-CSF family and the GP130 receptor family. The JAK kinases occur in four isoforms, with two matching phosphorylation domains, one for activity one for regulation. JAK2 in been shown to be mutated in several conditions including thrombocthemia and myeloprliferation disorders. In relation to haematological maliganacies the JAK2 mutation have been shown to essential for tumor growth and proliferation. Inhibiting the JAK2 kinase offers a potential mechanism for chemotherapeutic action. Ruxolitinib is a small, molecule inhibitor that has been established to inhibit the Janus kinases; early clinic work established that Ruxolitinib has sufficient anti-tumor activity to warrant further investigation. [Read the Full Post]

RO4929097 – TARGETING NOTCH SIGNALING IN CANCER

5659 | Mar 13 2012

RO4929097: INHIBIT GAMMA SECRETASE: Gamma secretase is famous protease consists of several subunits complex. This enzyme is also recognized as inter-membrane protease as it cuts trans-membrane proteins. The most eminent gamma secretase example is breakage of amyloid precursor, a protein to produce amyloid beta peptide which is involved in the formation of amyloid plaques in patient’s brain who suffer with Alzheimer’s disease. In the present situation though, we concentrate on the key role of gamma secretase in the Notch protein processing. It has been found as there is link between anomalous notch signaling and many cancers. Hence the idea of targeting those enzymes which are responsible for the processing of Notch protein became the reason of RO4929097 gamma secretase inhibitor discovery. The inhibiting Notch signaling by using RO4929097 GS inhibitor has been confirmed by protein estimation methods like Biuret method etc. [Read the Full Post]

RO4929097 – CONTROLLING NOTCH SIGNALING IN TUMORS

5947 | Mar 13 2012

Introduction: Gamma secretase Inhibition Gamma secretase is an internal protease enzyme that is a complex of a number of subunits. Its mode of action is to cleave proteins that lie within the membrane-spanning domain, these include the amyloid precursor protein (APP) and the Notch. The Notch signaling pathway processes four different Notch receptors (1, 2, 3 and 4) which span the cell membrane. Upon extracellular interaction with a substrate protein the internal domain is released. This section of the protein then induced a signaling cascade within the cell nucleus to alter gene expression. The function of the various NOTCH proteins is varied but in terms of cancer notch receptors have been demonstrated to be down regulated in basal cells carcinomas and cervical cancers. Notch 1 over-expression is associated with acute T cell leukemia and breast cancer, Notch 3 receptor is over-expressed in 20% of ovarian cancers [5-7] while overexpression of Notch 4 is evident in murine models of breast cancer. The field of research into NOTCH signaling is vast and beyond the scope of this document, simple put there existed evidence that inhibition of aberrant NOTCH over-expression would be an ideal target for chemotherapeutic activity. The development of inhibitors which would affect the action of NOTCH led to the targeting of the Gamma secretase enzyme. Developed by Roche the RO4929097 gamma secretase inhibitor represents a potent novel small molecule that is orally bioavailable. [Read the Full Post]

GSK3 and Alzheimer’s disease

5669 | Nov 24 2011

Glycogen synthase kinase 3 (GSK-3), as a serine/threonine protein kinase, can contribute to phosphorylating and thus inactivating glycogen synthase, and also been involved in the control of cellular response to damaged DNA. [Read the Full Post]

The hedgehog signaling pathway, as the target in cancer treatment

8553 | Nov 18 2011

The hedgehog(Hh) signaling pathway is one of the key regulators of animal development and is present in all bilaterians. The Hh family of proteins have since been recognized to involve in many fundamental processes in vertebrate embryonic development and play an important role in regulating cell fate, patterning, proliferation, survival and differentiation of many different regions. In the embryonic period, dysfunction in the Hh signaling pathway will lead to brain, facial and other midline defects such as holoprosencephaly, cyclopia, absent nose or cleft palate. [Read the Full Post]

Li, C., S. Chi, et al. (2011). "Hedgehog signaling in skin cancers." Cell Signal 23(8): 1235-1243.

2961 | Aug 20 2011

This article introduces the relationship between hedgehog signal transduction and cancer including Skin cancers linked to aberrant hedgehog pathway activity, models of Hh pathway activity in cancer and implications for therapy, and inhibitors and modulators of Hh pathway and their application in skin cancers. [Read the Full Post]

Yin, L., O. C. Velazquez, et al. (2010). "Notch signaling: emerging molecular targets for cancer therapy." Biochem Pharmacol 80(5): 690-701.

5095 | Jul 13 2011

This article is a review which give a presentation of Notch signal pathway and how the researchers target Notch signal pathway for a cancer therapy. [Read the Full Post]

Eldar-Finkelman, H., A. Licht-Murava, et al. (2010). "Substrate competitive GSK-3 inhibitors - strategy and implications." Biochim Biophys Acta 1804(3): 598-603.

4072 | Jul 11 2011

A short article introduces the substrates and inhibitors of GSK-3 and the relationship between substrates of GSK-3 and GSK-3. [Read the Full Post]

Narumiya, S., M. Tanji, et al. (2009). "Rho signaling, ROCK and mDia1, in transformation, metastasis and invasion." Cancer Metastasis Rev 28(1-2): 65-76.

4930 | Jun 7 2011

This review summaries the Rho signaling in transformation, metastasis and invasion. It explains the relationship between Rho signaling and tumor cells, and it gives the perspectives in this review. [Read the Full Post]

Jacob, L. and L. Lum (2007). "Hedgehog signaling pathway." Sci STKE 2007(407): cm6.

2635 | May 12 2011

A brief introduction of hedgehog signal transduction with good hedgehog signal transduction map. [Read the Full Post]

Yardy, G. W. and S. F. Brewster (2005). "Wnt signalling and prostate cancer." Prostate Cancer Prostatic Dis 8(2): 119-126.

4366 | Apr 8 2011

This article introduce the wnt pathway and the relationship between wnt and cancer. It really give athe detail information of wnt signal pathway. [Read the Full Post]

Doble, B. W. and J. R. Woodgett (2003). "GSK-3: tricks of the trade for a multi-tasking kinase." J Cell Sci 116(Pt 7): 1175-1186.

3862 | Mar 20 2011

This article introduces the insights of GSK-3 phosphorylation from crystal structures. It also introduces the role of GSK-3 in human disease, the role of GSK-3 in the Hedgehog pathway, the role of GSK-3 in the Wnt/beta-catenin pathway, GSK-3-binding proteins, GSK-3 substrates, and small molecule inhibitors of GSK-3. [Read the Full Post]

Riento, K. and A. J. Ridley (2003). "Rocks: multifunctional kinases in cell behaviour." Nat Rev Mol Cell Biol 4(6): 446-456.

4272 | Mar 3 2011

This article introduces regulation of ROCK activity, ROCK function and ROCK inhibitors. This review concludes knowledge of ROCK in different ways. [Read the Full Post]