TGF-beta/Smad

ROCK Inhibitors as an Alternative Therapy for Corneal Grafting: A Systematic Review

329 | Feb 15 2024

The review on ROCK inhibitors for corneal wound healing showcases their diverse therapeutic potential across various ocular conditions, offering promise as an effective alternative to human donor tissue for addressing the significant unmet medical need in corneal blindness. [Read the Full Post]

Proteomic and Phosphoproteomic Profiling Reveals the Oncogenic Role of Protein Kinase D Family Kinases in Cholangiocarcinoma

281 | Feb 15 2024

The comprehensive analysis of protein and phosphorylation signatures in cholangiocarcinoma revealed the PRKD family's pivotal role, highlighting their potential as novel treatment targets validated by the inhibitory effects of 1-naphthyl PP1 on CCA cell proliferation, migration, and invasion. [Read the Full Post]

Cell-Penetrating Peptide-Bismuth Bicycles

104 | Feb 09 2024

The development of peptide-bismuth bicycles as cell-penetrating peptides showcases a groundbreaking leap in cellular uptake efficiency, offering a promising avenue for diverse biomedical applications. [Read the Full Post]

PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, relieves airway hyperresponsiveness, mucus hypersecretion and inflammation in a murine asthma model

218 | Jan 14 2024

PP121, a dual tyrosine and phosphoinositide kinase inhibitor, demonstrates promising anti-contractile and anti-inflammatory effects in asthma treatment, suggesting its potential as a novel therapeutic compound for managing the condition. [Read the Full Post]

Correlating Basal Gene Expression across Chemical Sensitivity Data to Screen for Novel Synergistic Interactors of HDAC Inhibitors in Pancreatic Carcinoma

120 | Dec 22 2023

This study employs a bioinformatics screening protocol integrating drug-sensitivity data and basal gene expression to predict synergistic combinations of histone deacetylase inhibitors (HDACi), identifying the sphingolipid signaling pathway as a promising target; further experimental validation reveals novel synergisms between HDACi and a Rho-associated protein kinase (ROCK) inhibitor RKI-1447, as well as between HDACi and a sphingosine 1-phosphate (S1P) receptor agonist fingolimod in the treatment of pancreatic ductal adenocarcinoma (PDAC). [Read the Full Post]

Identification of potential biomarkers and immune infiltration characteristics in recurrent implantation failure using bioinformatics analysis

98 | Dec 20 2023

This study reveals altered immune cell infiltration, identifies key signaling pathways, and proposes potential diagnostic markers and therapeutic compounds for recurrent implantation failure, offering valuable insights for improving endometrial receptivity in reproductive medicine. [Read the Full Post]

Synthesis and biological evaluation of 4-(pyridin-4-oxy)-3-(3,3-difluorocyclobutyl)-pyrazole derivatives as novel potent transforming growth factor-β type 1 receptor inhibitors

85 | Dec 19 2023

Compound 15r, a novel 4-(pyridin-4-oxy)-3-(3,3-difluorocyclobutyl)-pyrazole derivative, demonstrated potent inhibition of the TGF-β type 1 receptor (ALK5), with favorable pharmacokinetic properties, superior bioavailability to LY-3200882, and significant efficacy in inhibiting tumor growth in a CT26 xenograft mouse model. [Read the Full Post]

Claudin-3 facilitates the progression and mediates the tumorigenic effects of TGF-β in glioblastoma multiforme

83 | Dec 17 2023

The study demonstrates that upregulated Claudin-3 in glioblastoma multiforme stimulates tumor cell growth, promotes epithelial-mesenchymal transition, and enhances the tumorigenic effects of transforming growth factor-β, suggesting that specific inhibitors targeting Claudin-3 could represent a promising approach for treating this aggressive brain tumor. [Read the Full Post]

5-HT6 receptor antagonists. Design, synthesis, and structure-activity relationship of substituted 2-(1-methyl-4-piperazinyl)pyridines

124 | Dec 16 2023

The study presents a novel series of 6-piperazinyl-7-azaindoles demonstrating potent 5-HT6 receptor antagonism, with a focus on optimizing the lead structure and exploring structure-activity relationships, highlighting Compound 29 as a promising candidate for further drug development. [Read the Full Post]

Cardiac RGS7 and RGS11 drive TGFβ1-dependent liver damage following chemotherapy exposure

59 | Dec 14 2023

The research findings reveal that RGS7 controls the release of TGFβ1 from the heart, influencing the multiorgan damage caused by chemotherapy and emphasizing the importance of cardiokine signaling in this process. [Read the Full Post]

Optimization of the Lead Compound NVP-BHG712 as a Colorectal Cancer Inhibitor

162 | Dec 12 2023

In this study, a series of EPHA2 kinase inhibitors, including derivatives of NVP-BHG712 and triazine-based compounds, were synthesized and evaluated, revealing eight inhibitors with low-nanomolar affinities (KD <10 nM) that demonstrated promising effects in controlling human colon carcinoma, highlighting their potential as therapeutic tools in cancer research. [Read the Full Post]

Regulatory mechanism of NOV/CCN3 in the inflammation and apoptosis of lung epithelial alveolar cells upon lipopolysaccharide stimulation

58 | Dec 12 2023

In the LPS-induced acute lung injury model, CCN3 knockdown significantly attenuated inflammatory cytokine expression, reduced apoptosis in alveolar epithelial cells, and inhibited NF-κB activation, indicating its pivotal role in regulating lung inflammation and apoptosis via the TGF-β/p-Smad or NF-κB pathway. [Read the Full Post]

Regional regulatory harmonisation initiatives: Their potential contribution to the newly established African medicines agency

276 | Nov 30 2023

The study highlights the foundational role of regional medicines regulatory harmonization programs, such as the African Medicines Regulatory Harmonisation (AMRH) and East African Community Medicines Regulatory Harmonisation (EAC-MRH) initiatives, in supporting the operationalization of the African Medicine Agency (AMA), emphasizing the importance of strong national regulatory authorities and increased ratification of the AMA Treaty for ensuring access to essential medical products and technologies for the African people. [Read the Full Post]

Overfit deep neural network for predicting drug-target interactions

267 | Nov 27 2023

The OverfitDTI framework utilizes intentionally overfitted deep neural networks to accurately capture the intricate relationships between drugs and targets, enabling precise drug-target interaction predictions, as demonstrated by the successful identification and experimental validation of TEK inhibitors. [Read the Full Post]

Identifying promising GSK3β inhibitors for cancer management: a computational pipeline combining virtual screening and molecular dynamics simulations

126 | Nov 21 2023

The computational screening study identified BMS-754807 and GSK429286A as promising GSK3β inhibitors with high binding affinities, suggesting their potential as novel anticancer drugs pending experimental validation. [Read the Full Post]

Combined inhibition of aurora kinases and Bcl-xL induces apoptosis through select BH3-only proteins

222 | Nov 08 2023

The study demonstrates that combining small-molecule inhibitors of AURK with BH3-mimetic inhibitors targeting Bcl-xL potently induces apoptosis and may overcome resistance to AURK inhibitors in colon cancer cells. [Read the Full Post]

RBM15 silencing promotes ferroptosis by regulating the TGF-β/Smad2 pathway in lung cancer

123 | Oct 22 2023

Silencing of RNA binding motif protein 15 (RBM15) promotes ferroptosis and inhibits lung cancer cell growth through the TGF-β/Smad2 pathway, offering potential therapeutic implications for lung cancer treatment. [Read the Full Post]

BMP9-ID1 Signaling Activates HIF-1α and VEGFA Expression to Promote Tumor Angiogenesis in Hepatocellular Carcinoma

101 | Oct 15 2023

The study indicates that targeting BMP9-ID1 signaling may serve as a promising therapeutic strategy for advanced hepatocellular carcinoma (HCC) by inhibiting angiogenesis. [Read the Full Post]

Olverembatinib Treatment in Pediatric Patients With Relapsed Philadelphia-Chromosome-Positive Acute Lymphoblastic Leukemia

155 | Oct 13 2023

In this study, olverembatinib demonstrated both safety and efficacy in children with relapsed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), including some achieving complete remission as a single agent. [Read the Full Post]

Screening and Analysis of Possible Drugs Binding to PDGFRα: A Molecular Modeling Study

157 | Oct 09 2023

This study aimed to identify new ligands for the platelet-derived growth factor receptor (PDGFR) through screening of thousands of compounds, resulting in the selection of potential drugs and natural compounds with high affinity, providing valuable insights for the development of more effective treatments for PDGFR-related diseases. [Read the Full Post]

Tamoxifen resistance induction results in the upregulation of ABCG2 expression and mitoxantrone resistance in MCF-7 breast cancer cells

184 | Oct 07 2023

The study found that prolonged exposure of ER+ MCF-7 breast cancer cells to tamoxifen led to increased expression of the ABCG2 pump, associated with TAM resistance and potential cross-resistance to mitoxantrone. [Read the Full Post]

Ultrasound-triggered in situ gelation with ROS-controlled drug release for cartilage repair

66 | Oct 05 2023

A novel ROS-responsive in situ nanocomposite hydrogel loaded with kartogenin (KGN) and bone marrow-derived stem cells (BMSCs) effectively promotes chondrogenic differentiation and improves cartilage regeneration, offering potential for efficient cartilage repair. [Read the Full Post]

Effectiveness of netarsudil 0.02% in lowering intraocular pressure in patients with secondary glaucoma

133 | Oct 01 2023

Netarsudil, 0.02%, was found to be effective in lowering intraocular pressure (IOP) in patients with secondary forms of glaucoma, especially uveitic glaucoma. [Read the Full Post]

Bone impact after two years of low-dose oral contraceptive use during adolescence

184 | Sep 29 2023

The present study indicates that the use of combined hormonal contraceptives in healthy adolescents is associated with compromised bone mass acquisition, with a more pronounced negative impact observed in those using contraceptives containing 30 μg of Ethinylestradiol. [Read the Full Post]

TXNIP Suppresses the Osteochondrogenic Switch of Vascular Smooth Muscle Cells in Atherosclerosis

90 | Sep 28 2023

TXNIP is identified as a novel regulator of atherosclerotic calcification by suppressing bone morphogenetic protein signaling and inhibiting the phenotypic transition of vascular smooth muscle cells towards an osteochondrogenic phenotype. [Read the Full Post]

Effectiveness of netarsudil 0.02% in lowering intraocular pressure in patients with secondary glaucoma

181 | Sep 27 2023

Netarsudil, 0.02%, was found to effectively lower intraocular pressure in patients with secondary forms of glaucoma, particularly uveitic glaucoma, based on a retrospective study. [Read the Full Post]

Artificial Intelligence Assisted Pharmacophore Design for Philadelphia Chromosome-Positive Leukemia with Gamma-Tocotrienol: A Toxicity Comparison Approach with Asciminib

124 | Aug 11 2023

This study proposes the use of AI-designed gamma-tocotrienol (AIGT) as a potential therapeutic option for chronic myeloid leukemia (CML) by targeting the BCR-ABL1 fusion protein, exhibiting promising efficacy and potential hepatoprotective properties compared to existing medications. [Read the Full Post]

The EMA Assessment of Asciminib for the Treatment of Adult Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase Who Were Previously Treated With At Least 2 Tyrosine Kinase Inhibitors

150 | Aug 11 2023

Asciminib, an allosteric high-affinity tyrosine kinase inhibitor, received marketing authorization from the European Commission for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase after evaluating its clinical efficacy and safety in the phase III ASCEMBL study. [Read the Full Post]

Mitochondrial impairment and downregulation of Drp1 phosphorylation underlie the antiproliferative and proapoptotic effects of alantolactone on oral squamous cell carcinoma cells

82 | Jul 28 2023

The study found that alantolactone (ALT) inhibited the proliferation and promoted apoptosis of oral squamous cell carcinoma (OSCC) cells by disrupting mitochondrial homeostasis and regulating dynamin-related protein 1 (Drp1), suggesting its potential as a therapeutic candidate for OSCC. [Read the Full Post]

The tumor stroma influences immune cell distribution and recruitment in a PDAC-on-a-chip model

199 | Jul 20 2023

This study utilized a 3D PDAC model to investigate the interaction between tumor stroma and immune cells, revealing that stromal cells create a physical and biochemical barrier that hinders immune cell infiltration, and targeting the stroma can increase immune cell infiltration, offering potential therapeutic strategies for PDAC. [Read the Full Post]

Targeting FLT3 Mutation in Acute Myeloid Leukemia: Current Strategies and Future Directions

89 | Jul 16 2023

FLT3 inhibitors have improved clinical outcomes for acute myeloid leukemia patients with FLT3 mutations, but the emergence of resistance and the need for novel therapeutic strategies remain ongoing challenges. [Read the Full Post]

Topical Ripasudil for the Treatment of Segmental Corneal Edema: A Case Series

198 | Jul 10 2023

Topical ripasudil has shown promising results in improving vision and resolving corneal edema in patients with focal corneal edema following anterior segment surgeries, serving as an effective treatment option that may reduce the need for endothelial transplantation. [Read the Full Post]

Ripasudil-Brimonidine Fixed-Dose Combination vs Ripasudil or Brimonidine: Two Phase 3 Randomized Clinical Trials

140 | Jul 10 2023

The results of the study demonstrated that the ripasudil-brimonidine fixed-dose combination (RBFC) had a greater ability to lower intraocular pressure (IOP) compared to ripasudil or brimonidine alone. [Read the Full Post]

Comparative transcriptome profile of mouse macrophages treated with the RhoA/Rock pathway inhibitors Y27632, Fingolimod (Gilenya), and Rezurock (Belumosudil, SLx-2119)

113 | Jul 07 2023

The transcriptome profiling study comparing macrophages treated with Y27632, Fingolimod, and Rezurock revealed distinct downregulation of GTPase and actin pathways in cell migration for Y27632 and Fingolimod, while Rezurock specifically downregulated fibrosis-related genes, providing insights into the differences in their anti-chronic rejection properties and aiding in the development of targeted therapies. [Read the Full Post]

Discovery of indoline-based derivatives as effective ROCK2 inhibitors for the potential new treatment of idiopathic pulmonary fibrosis

163 | Jul 07 2023

A new series of selective ROCK2 inhibitors based on indoline, particularly compound 9b, showed promising results in inhibiting collagen gel contraction, suppressing fibrotic markers, and exhibiting anti-pulmonary fibrosis effects in a bleomycin-induced IPF rat model, suggesting its potential as a lead compound for IPF treatment. [Read the Full Post]

Isoxazole 9 (ISX9), a small molecule targeting Axin, activates Wnt/β-catenin signalling and promotes hair regrowth

121 | Jul 05 2023

The study identified ISX9 as a novel activator of the Wnt/β-catenin pathway, promoting hair regrowth and suggesting its potential as a therapeutic agent for alopecia treatment. [Read the Full Post]

ISX-9 potentiates CaMKIIδ-mediated BMAL1 activation to enhance circadian amplitude

82 | Jul 05 2023

ISX-9, a neurogenic small molecule, has shown promising effects in improving circadian amplitude, metabolic rhythms, sleep homeostasis, and locomotive activity, making it a potential candidate for treating circadian-related disorders. [Read the Full Post]

The effect of sex on retinopathy of prematurity severity among premature mixed-sex multiple gestation infants

110 | Jun 29 2023

This retrospective study of 68 premature infants found no significant difference between male and female mixed-sex multiple gestation infants in terms of the most severe stage of retinopathy of prematurity (ROP) developed or the need for ROP treatment, but males received treatment at an earlier postmenstrual age (PMA) despite females having lower birthweight and slower growth velocity. [Read the Full Post]

Identifying a selective inhibitor of autophagy that targets ATG12-ATG3 protein-protein interaction

132 | Jun 29 2023

Compound 189, identified through a high throughput compound screen, selectively inhibits the ATG12-ATG3 protein-protein interaction involved in autophagy, demonstrating potential as a therapeutic drug for autophagy-dependent tumors and inflammation. [Read the Full Post]

Prognostic implication and immunotherapy response prediction of a ubiquitination-related gene signature in breast cancer

94 | Jun 23 2023

[Read the Full Post]

Small molecule drugs promote repopulation of transplanted hepatocytes by stimulating cell dedifferentiation

0 | Jun 23 2023

In summary, our findings suggest that the utilization of small molecule compounds that promote hepatocyte dedifferentiation may enhance the proliferation and efficacy of transplanted hepatocytes, offering potential advancements in hepatocyte therapy for end-stage liver disease. [Read the Full Post]

Rapid direct conversion of bovine non-adipogenic fibroblasts into adipocyte-like cells by a small-molecule cocktail

57 | May 30 2023

The study established a rapid chemically induced platform for transdifferentiation of bovine ear fibroblasts into adipocyte-like cells using a small-molecule cocktail and provided valuable evidence to deepen our understanding of the molecular mechanism of small molecule cocktails in regulating adipogenesis. [Read the Full Post]

Aerobic exercise alleviates ventilator-induced lung injury by inhibiting NLRP3 inflammasome activation

93 | May 29 2023

The study found that exercise can reduce ventilator-induced lung injury by inhibiting PKCɑ and NLRP3 activation. [Read the Full Post]

Temperature sensing by the calcium-sensing receptor

105 | May 29 2023

The study suggests that CaSRs, a type of GPCR, may contribute to temperature sensing through a mechanism dependent on repetitive phosphorylation and dephosphorylation. [Read the Full Post]

ID3 mediates BMP2-induced downregulation of ICAM1 expression in human endometiral stromal cells and decidual cells

76 | May 24 2023

This study highlights a potential molecular mechanism by which BMP2 regulates ICAM1 in the human endometrium, which could have therapeutic implications for unexplained recurrent pregnancy loss (uRPL). [Read the Full Post]

Commiphora myrrha stimulates insulin secretion from β-cells through activation of atypical protein kinase C and mitogen-activated protein kinase

152 | May 22 2023

The study investigated the molecular mechanism of action of Commiphora myrrha (CM)-induced insulin secretion and found that CM directly stimulates insulin secretion through activating known downstream effectors of insulin-stimulus secretion coupling, which is completely dependent on protein kinase activation, particularly the phosphorylation and activation of PKCζ and ERK1/2. [Read the Full Post]

PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain

71 | May 13 2023

The study found that LRRK1 is activated by PKC-dependent phosphorylation of a cluster of conserved residues within a region of the CORB domain, which promotes interaction and stabilization of the αC-helix on the kinase domain, revealing a novel activation mechanism. [Read the Full Post]

A Phase Ib Study of Sotrastaurin, a PKC Inhibitor, and Alpelisib, a PI3Kα Inhibitor, in Patients with Metastatic Uveal Melanoma

101 | May 13 2023

The phase Ib study found that the combination of sotrastaurin and alpelisib was tolerable but showed limited clinical activity in patients with metastatic uveal melanoma or GNAQ/11 mutant cutaneous melanoma. [Read the Full Post]

Pirfenidone suppresses tumor necrosis factor-alpha, enhances interleukin-10 and protects mice from endotoxic shock

156 | Apr 12 2023

The study found that pirfenidone provided prophylactic and therapeutic benefits for murine endotoxic shock by inhibiting pro-inflammatory cytokines, enhancing interleukin-10, and suppressing apoptotic cells and TGF-beta1 in the liver. [Read the Full Post]

O-linked N-acetylglucosamine modification induced by lipopolysaccharide is involved in inflammatory signaling pathway in endothelial cells

71 | Apr 12 2023

The study investigated the involvement of O-GlcNAc modification in the inflammatory signaling pathway of endothelial cells under LPS stimulation and found that increasing OGT expression could inhibit the activation of the inflammatory signal pathway and reduce inflammatory cytokine expression, and that the PI3K/Akt pathway is involved in regulating O-GlcNAc modification in response to LPS stimulation. [Read the Full Post]

Inhaled pirfenidone solution (AP01) for IPF: a randomised, open-label, dose-response trial

124 | Apr 11 2023

The phase 1b trial evaluated the safety, tolerability, and efficacy of inhaled pirfenidone in patients with IPF and showed that the treatment was well-tolerated and may be a safe and effective alternative to oral pirfenidone or nintedanib. [Read the Full Post]

Distinct Protein Kinase C isoforms drive the cell cycle re-entry of two separate populations of neonatal rat ventricular cardiomyocytes

66 | Apr 06 2023

The study found that distinct PKC isoforms are responsible for the preferential appearance of nestin(+)- or nestin(-)-NNVMs that re-enter the cell cycle in the presence of SB203580. [Read the Full Post]

The role of transforming growth factor-β2 in cigarette smoke-induced lung inflammation and injury

250 | Apr 06 2023

The study found that TGF-β2 attenuated CSE-induced IL-8 production in PBECs and alleviated lung inflammation/injury in CS-exposed mice through the Smad3 signaling pathway. [Read the Full Post]

Methyltransferase K-D-K-E motif influences the intercellular transmission of Newcastle disease virus

297 | Apr 05 2023

This research demonstrates that mutations in the K-D-K-E methyltransferase motif restrict the cell-to-cell spread of Newcastle disease virus via tunnelling nanotubes. [Read the Full Post]

Monitoring paxillin in astrocytes reveals the significance of the adhesion GPCR VLGR1/ADGRV1 for focal adhesion assembly

193 | Apr 04 2023

VLGR1 is a vital component of focal adhesions and regulates cell migration by controlling focal adhesion turnover during their assembly, and its dysfunctions may contribute to the pathogenesis of Usher syndrome, epilepsy, and other related diseases. [Read the Full Post]

Neurotherapeutic Effects of Quercetin and Its Metabolite Compounds on Cognitive Impairment and Parkinson's Disease: An In Silico Study

259 | Mar 22 2023

This study identified the metabolomic profile and potential therapeutic effects of quercetin and its metabolites in cognitive impairment and Parkinson's disease, but further research is needed to confirm these findings in vivo and address potential adverse effects. [Read the Full Post]

Managing Vibration Training Safety by Using Knee Flexion Angle and Rating Perceived Exertion

245 | Mar 22 2023

This study found that a knee flexion angle of approximately 110 degrees is most effective in reducing vibration transmissibility during whole-body vibration exercise, while also observing a positive correlation between the rating of perceived exertion and the platform-to-head transmissibility. [Read the Full Post]

WP1130 relieves septic shock in mice by inhibiting NLRP3 inflammasome activation

130 | Mar 20 2023

WP1130 specifically inhibits NLRP3 inflammasome activation and alleviates septic shock in mice. [Read the Full Post]

USP9x promotes CD8 + T-cell dysfunction in association with autophagy inhibition in septic liver injury

133 | Mar 20 2023

This study suggests that USP9x inhibition could be a potential therapeutic target for septic liver injury by promoting CD8+ T-cell function via autophagy regulation. [Read the Full Post]

Derivation of Limbal Stem Cells from Human Adult Mesenchymal Stem Cells for the Treatment of Limbal Stem Cell Deficiency

112 | Mar 16 2023

This study presents a protocol for deriving human limbal stem cells from adipose-derived mesenchymal stem cells, which can aid in restoring vision for patients with LSC deficiency. [Read the Full Post]

Endothelial-specific targeting of RhoA signaling via CD31 antibody-conjugated nanoparticles

314 | Feb 26 2023

The study aimed to develop a CD31-targeting liposome with Fasudil, a clinically-relevant Rho kinase inhibitor, to target the RhoA signaling in endothelial cells for potential anti-angiogenic therapy by minimizing toxicity. [Read the Full Post]

Predictive factors for improvement of symptomatic cerebral vasospasm following subarachnoid hemorrhage by selective intra-arterial administration of fasudil hydrochloride

336 | Feb 26 2023

Selective intra-arterial administration of fasudil improves neurological findings in 72.2% of patients with cerebral vasospasm following subarachnoid hemorrhage and is most effective when the spasm is limited to peripheral vessels and the patient is younger and does not have a large cerebral infarction in the spasm artery perfusion area. [Read the Full Post]

Case report: Ponatinib as a bridge to CAR-T cells and subsequent maintenance in a patient with relapsed/refractory Philadelphia-like acute lymphoblastic leukemia

138 | Feb 22 2023

A young patient with relapsed/refractory Ph-like ALL was successfully treated with chimeric antigen receptor T (CAR-T) cells after bridging with compassionate-use ponatinib and low-dose prednisone, and maintained with low-dose ponatinib, resulting in measurable residual disease negativity and B-cell aplasia 20 months later, marking this as the first reported use of ponatinib in Ph-like ALL as a bridge to and maintenance after CAR-T cell therapy. [Read the Full Post]

Staurosporine analogues from microbial and synthetic sources and their biological activities

249 | Feb 20 2023

Staurosporine and its analogues have strong inhibitory effects against a variety of kinases and have various biological properties such as antifungal, antibacterial, and immunosuppressive activities, but have limited clinical effectiveness due to cross-reactivity and poor selectivity. [Read the Full Post]

Interactive webtool for analyzing drug sensitivity and resistance associated with genetic signatures of cancer cell lines

293 | Jan 19 2023

Myriam Boeschen et al. found support for the described sensitivity of H1047 mutants to GSK690693 targeting the AKT pathway. [Read the Full Post]

Guhong Injection Alleviates Cerebral Ischemia-Reperfusion Injury via the PKC/HIF-1α Pathway in Rats

115 | Jan 08 2023

Li Yu et al. confirmed GHI could ameliorate cerebral I/R injury in MCAO rats possibly via the PKC/HIF-1α pathway. [Read the Full Post]

PKCβ Facilitates Leukemogenesis in Chronic Lymphocytic Leukaemia by Promoting Constitutive BCR-Mediated Signalling

76 | Jan 08 2023

Jodie Hay et al. demonstrated that PKCβ expression facilitates leukemogenesis and identified that BCR-mediated signalling was a key driver of CLL development in the PKCα-KR model. [Read the Full Post]

Single-cell profiling reveals molecular basis of malignant phenotypes and tumor microenvironments in small bowel adenocarcinomas

142 | Jan 06 2023

Jingwei Yang et al. showed that the duodenal subtype of SBA exhibited molecular features more similar to gastric cancer whereas jejunal subtype of SBA more similar to colorectal cancer. [Read the Full Post]

Alteration of Autophagy and Glial Activity in Nilotinib-Treated Huntington's Disease Patients

151 | Dec 31 2022

Karen E Anderson et al. explored the effects of a low dose of nilotinib (150 mg) on behavioral changes and motor symptoms in manifest HD patients. [Read the Full Post]

The Economic Burden of Chronic Myeloid Leukemia in Patients with Later Lines: Findings from a Real-World Analysis in Italy

168 | Dec 30 2022

Massimo Breccia et al. suggested that further efforts were needed to improve the therapeutic management of later lines of CML. [Read the Full Post]

Attenuated Dose Dasatinib in Newly Diagnosed Chronic Myeloid Leukemia Chronic Phase Patients in India

75 | Dec 29 2022

Rayaz Ahmed et al. thought that low dose dasatinib was safe and effective as an upfront therapy in CML-CP. [Read the Full Post]

Combined use of dasatinib and quercetin alleviates overtraining-induced deficits in learning and memory through eliminating senescent cells and reducing apoptotic cells in rat hippocampus

121 | Dec 28 2022

Chenkang Wang found that D+Q alleviated overtraining-induced deficits in learning and memory through elimination of senescent cells and reduction of apoptotic cell number. [Read the Full Post]

Clinical impact of minimal residual disease and genetic subtypes on the prognosis of childhood acute lymphoblastic leukemia

153 | Dec 27 2022

Chih-Hsiang Yu et al. found that MRD-directed therapy improved the outcomes for pediatric ALL, especially standard-risk patients. [Read the Full Post]

A mitophagy-related gene signature associated with prognosis and immune microenvironment in colorectal cancer

238 | Dec 24 2022

Cong Zhang et al. developed a novel mitophagy-related gene signature that could be utilized not only as an independent predictive biomarker but also as a tool for tailoring personalizing treatment for CRC patients. [Read the Full Post]

Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): A multicentre, open-label, dose-escalation phase 1 trial

196 | Dec 23 2022

Keiko Imamura et al. found that the treatment-responsive patients could be distinguished by lower levels of plasma NFL. [Read the Full Post]

Protein kinase C-β distinctly regulates blood-brain barrier-forming capacity of Brain Microvascular endothelial cells and outgrowth endothelial cells

74 | Dec 06 2022

Rais Reskiawan A Kadir et al. thought that targeting PKC-β signalling pathway in ischaemic settings required close attention while using OECs as cellular therapeutic. [Read the Full Post]

PKCβ Inhibition Promotes TXNIP Degradation to Ameliorate Pancreatic β-Cell Dysfunction

85 | Dec 05 2022

Shijun He et al. suggested that KCβ inhibitor was a promising agent for ameliorating β-cell dysfunction through TXNIP. [Read the Full Post]

LAMC2 marks a tumor-initiating cell population with an aggressive signature in pancreatic cancer

104 | Nov 23 2022

Donatella Delle Cave et al. identified a highly metastatic subpopulation of TICs marked by LAMC2. [Read the Full Post]

Therapeutic function of a novel rat induced pluripotent stem cell line in a 6‑OHDA‑induced rat model of Parkinson's disease

79 | Nov 02 2022

Jiajia Xu et al. found that RiPSCs‑6F/CR induced by small molecules could be used as potential donor material for neural grafting to remodel basal ganglia circuitry in neurodegenerative diseases. [Read the Full Post]

TGF-β1 Promotes Zika Virus Infection in Immortalized Human First-Trimester Trophoblasts via the Smad Pathway

61 | Oct 22 2022

Quang Duy Trinh et al. found that TGF-β1 promotes the virus infection via the Smad pathway. [Read the Full Post]

URMC-099 prophylaxis prevents hippocampal vascular vulnerability and synaptic damage in an orthopedic model of delirium superimposed on dementia

154 | Oct 19 2022

Patrick Miller-Rhodes et al. linked post-surgical endothelial activation, microglial MafB immunoreactivity, and synapse loss as key substrates for DSD, all of which could be prevented by URMC-099. [Read the Full Post]

Reducing tumor invasiveness by ramucirumab and TGF-β receptor kinase inhibitor in a diffuse-type gastric cancer patient-derived cell model

62 | Sep 25 2022

Song-Yi Lee et al. confirmed that combination of TEW-7197 and ramucirumab reduced tumor spheroid and GC PDC-induced blood vessel formation concomitantly in the spheroid-on-a-chip model. [Read the Full Post]

FLT3 Inhibitors as Maintenance Therapy after Allogeneic Stem-Cell Transplantation

159 | Sep 23 2022

Amanda Blackmon et al. reviewed the toxicities and efficacy of FLT3 inhibitors as posttransplant maintenance, recommendations on the use of FLT3 inhibitors by international consensus guidelines, and highlighted key remaining questions. [Read the Full Post]

Differential prognostic impact of stratified additional chromosome abnormalities on disease progression among Malaysian chronic myeloid leukemia patients undergoing treatment with imatinib mesylate

104 | Aug 29 2022

Ismail Siti Mariam et al. concluded that the stratification based on individual ACAs had a differential prognostic impact and might be a potential novel risk predictive system to prognosticate and guided the treatment of CML patients at diagnosis and during treatment. [Read the Full Post]

Epiprofin Transcriptional Activation Promotes Ameloblast Induction From Mouse Induced Pluripotent Stem Cells via the BMP-Smad Signaling Axis

51 | Aug 14 2022

Xinchao Miaosuggested that Epfn was a promising target for inducing the differentiation of ameloblasts, which could be used in enamel and tooth regeneration. [Read the Full Post]

Protein kinase C targeting of luminal (T-47D), luminal/HER2-positive (BT474), and triple negative (HCC1806) breast cancer cells in-vitro with AEB071 (Sotrastaurin) is efficient but mediated by subtype specific molecular effects

73 | Aug 12 2022

Veruschka Albert et al. thought that a combined targeting of PKC and a subtype specific driver molecule might complement specified breast cancer treatment. [Read the Full Post]

Inhibiting SRC activity attenuates kainic-acid induced mouse epilepsy via reducing NR2B phosphorylation and full-length NR2B expression

73 | Aug 12 2022

Lu Liu et al. found that the early application of SRC inhibitors exerted protective effects on seizure severity, loss of neurons, and sprouting of mossy fibres in KA-induced mouse epilepsy. [Read the Full Post]

Effect of ALA-PDT on inhibition of oral precancerous cell growth and its related mechanisms

89 | Aug 09 2022

Jian-Qiu Jin et al. indicated that ALA-PDT could be a promising alternative treatment against oral precancerous lesions. [Read the Full Post]

Inhibition of AHNAK nucleoprotein 2 alleviates pulmonary fibrosis by downregulating the TGF-β1/Smad3 signaling pathway

64 | Jul 28 2022

Dongyi Zhu et al. thought that AHNAK2 was a potential therapeutic target for IPF. [Read the Full Post]

AMPK-ChREBP axis mediates de novo milk fatty acid synthesis promoted by glucose in the mammary gland of lactating goats

150 | Jul 21 2022

Hengbo Shi et al. thought that glucose supplementation promoted de novo fatty acid synthesis via the AMPK-ChREBP axis, hence increasing milk fat yield in the goat mammary gland. [Read the Full Post]

Antifungal activity of dehydrocurvularin for Candida spp. through the inhibition of adhesion to human adenocarcinoma cells

143 | Jul 21 2022

Hitoshi Kamauchi et al. reported that dehydrocurvularin (1), isolated from the marine-derived fungus Curvularia aeria, exhibited anti-fungal activities for Candida albicans and Candida auris. [Read the Full Post]

Reengineering Ponatinib to Minimize Cardiovascular Toxicity

288 | Jul 03 2022

Anna Pavlovna Hnatiuk et al. suggested that ponatinib cardiotoxicity was mediated by a few kinases, some of which were previously unassociated with cardiovascular disease. [Read the Full Post]

Synthesis, structural characterization, DFT calculations, molecular docking, and molecular dynamics simulations of a novel ferrocene derivative to unravel its potential antitumor activity

505 | Jun 12 2022

Mohamed M Hammoud et al. revealed the antitumor potential of ferrocene derivative (10) through targeting and inhibiting mitogen-activated protein (MAP) kinases interacting kinase (Mnk) 1.Communicated by Ramaswamy H. Sarma. [Read the Full Post]

In vitro modeling of liver fibrosis in 3D microtissues using scalable micropatterning system

142 | Jun 08 2022

Ensieh Zahmatkesh et al. found that aHSCs could lead to EMT in hepatocytes during liver fibrogenesis. [Read the Full Post]

Insights into Immune Escape During Tumor Evolution and Response to Immunotherapy Using a Rat Model of Breast Cancer

137 | Jun 08 2022

Carlos R Gil Del Alcazar et al. demonstrated the usefulness of this preclinical model for immunotherapy and suggested examination to expand immunotherapy to a subset of patients with ER+ disease. [Read the Full Post]

Origin of M2 Mϕ and its macrophage polarization by TGF-β in a mice intervertebral injury model

212 | May 23 2022

Ayumu Kawakubo et al. suggested that M2 Mϕ following IVD injury might originate from resident Mϕ. [Read the Full Post]

ARHGAP29 Regulates Keratinocyte Migration through the RhoA/ROCK Pathway

278 | May 15 2022

Lindsey Rhea et al. demonstrated that ARHGAP29 regulated keratinocyte morphology and promoted migration speed and directionality through the RhoA/ROCK pathway, providing potential insight into its importance in craniofacial development. [Read the Full Post]

Individualization in the first-line treatment of advanced ovarian cancer based on the mechanism of action of molecularly targeted drugs

445 | Apr 23 2022

Hidekatsu Nakai et al, found that the importance of achieving complete surgery and aiming for cure in the treatment of ovarian cancer and how the use of bevacizumab, olaparib, and niraparib should be individualized. [Read the Full Post]

B7-H4 expression is upregulated by PKCδ activation and contributes to PKCδ-induced cell motility in colorectal cancer

348 | Apr 13 2022

Bin Zhou et al. found that B7-H4 expression was upregulated by STAT3 activation via PKCδ and played roles in PKCδ-induced cancer cell motility and metastasis, suggesting that the PKCδ/STAT3/B7-H4 axis might be a potential therapeutic target for CRC. [Read the Full Post]

Effect of Maternal Docosahexaenoic Acid Supplementation on Very Preterm Infant Growth: Secondary Outcome of a Randomized Clinical Trial

287 | Apr 13 2022

Georgina Angoa et al. showed that DHA positively affected female infants' neonatal weight profile and velocity and negatively affected male infants' weight at 36 weeks' PMA. [Read the Full Post]

Response to netarsudil in goniotomy-treated eyes and goniotomy-naïve eyes: a pilot study

658 | Mar 29 2022

Haochen Xu et al.showed that netarsudil had a greater IOP-lowering effect in eyes treated with prior goniotomy and might serve as a promising adjunctive ocular hypotensive agent to further reduce IOP in eyes with prior goniotomy. [Read the Full Post]

Bone morphogenetic protein receptor inhibitors suppress the growth of glioblastoma cells

306 | Mar 28 2022

Joel Kaye et al. suggested the need for development of BMP inhibitors and evaluation as potential therapeutic for GBMs. [Read the Full Post]

Modulation of KIF17/NR2B crosstalk by tozasertib attenuates inflammatory pain in rats

537 | Mar 27 2022

Ankit Uniyal et al. suggested that tozasertib mediates anti-nociceptive activity by inhibiting aurora kinase-mediated KIF17/mLin10/NR2B signaling. [Read the Full Post]

Aurora kinase A induces migration and invasion by inducing epithelial-to-mesenchymal transition in colon cancer cells

499 | Mar 27 2022

On-Yu Hong 1 et al. showed aurora kinase A is a key molecule in PKC-induced metastasis in colon cancer cells. [Read the Full Post]

Defining Endocytic Pathways of Fucoidan-Coated PIBCA Nanoparticles from the Design of their Surface Architecture

700 | Mar 19 2022

M C B Lira-Nogueira et al. found that internalization pathways of PIBCA nanoparticles by J774A.1 macrophages could be determined by nanoparticle fucoidan surface composition and architecture. [Read the Full Post]

The effect of danusertib, an Aurora kinase inhibitor, onto the cytotoxicity, cell cycle and apoptosis in pancreatic ductal adenocarcinoma cells

779 | Mar 11 2022

Ismail Ayberk Kirbiyik et al. thought that Aurora kinase inhibitor danusertib might be a potential alternative to the treatment of pancreatic cancers. [Read the Full Post]

Combined Inhibition of Polo-Like Kinase-1 and Wee1 as a New Therapeutic Strategy to Induce Apoptotic Cell Death in Neoplastic Mast Cells

758 | Mar 10 2022

Manuela Mancini et al. showed that repurposing Plk1 or AKA ± Wee1 inhibitors in advanced clinical development for other indications was a therapeutic strategy worthy of being explored, in order to improve the outcome of patients with advanced SM. [Read the Full Post]

Pro-Inflammatory and Pro-Oxidative Changes During Nilotinib Treatment in CML Patients: Results of a Prospective Multicenter Front-Line TKIs Study (KIARO Study)

483 | Feb 20 2022

Anna Sicuranza et al. showed a pro-inflammatory/pro-oxidative milieu increasing along treatment with nilotinib compared with imatinib or dasatinib. [Read the Full Post]

Phorbol-12-myristate 13-acetate inhibits Nephronectin gene expression via Protein kinase C alpha and c-Jun/c-Fos transcription factors

280 | Feb 07 2022

Mitsuhiro Kinoshita et al. suggested regulation of Npnt gene expression via the PKCα and c-Jun/c-Fos pathway. [Read the Full Post]

Inhibitor GSK690693 extends Drosophila lifespan via reduce AKT signaling pathway

1045 | Jan 27 2022

Xingyi Cheng et al. indicated that GSK690693 might become an effective compound for anti-aging intervention. [Read the Full Post]

The α1-adrenergic receptors in the amygdala regulate the induction of learned despair through protein kinase C-beta signaling

0 | Jan 12 2022

Shisui Fujita et al. suggested that the α1-adrenoreceptor in amygdala regulated the induction of learned despair via PKCβ. [Read the Full Post]

Signaling Pathway of Histamine H 1 Receptor-Mediated Histamine H 1 Receptor Gene Upregulation Induced by Histamine in U-373 MG Cells

294 | Jan 12 2022

Hiroyuki Mizuguchi et al. thought that the H1R-activated H1R gene expression signaling pathway in U-373 MG cells was different from that in HeLa cells, possibly by using different promoters. [Read the Full Post]

Penetration Cascade of Size Switchable Nanosystem in Desmoplastic Stroma for Improved Pancreatic Cancer Therapy

267 | Dec 31 2021

Xiaozheng Zhao et al. found that the inhibition of ECM hyperplasia by VAC allowed TAX more ready access to the cancer cells in addition to its small size. [Read the Full Post]

Peptide-coating 2D and small chemical molecules prolong the passage of porcine spermatogonia stem cells

335 | Dec 09 2021

Ying Zhang et al. found that feeder-free culture system optimized cell culture and might facilitate advanced research on SSC biology and genetic manipulation of germ cells. [Read the Full Post]

TGFβ1 Secreted by Cancer-Associated Fibroblasts as an Inductor of Resistance to Photodynamic Therapy in Squamous Cell Carcinoma Cells

278 | Nov 28 2021

María Gallego-Rentero et al. found that the comparatively higher intrinsic resistance to PDT of SCC13 cells was mediated by the elevated levels of TGFβ1 secreted by this cell line. [Read the Full Post]

MLK3 mediates impact of PKG1α on cardiac function and controls blood pressure through separate mechanisms

841 | Nov 25 2021

Timothy D Calamaras et al. suggested augmenting MLK3 kinase activity could preserve LV function in HF but avoid hypotension from PKG1α activation. [Read the Full Post]

Reducing tumor invasiveness by ramucirumab and TGF-β receptor kinase inhibitor in a diffuse-type gastric cancer patient-derived cell model

291 | Nov 03 2021

Song-Yi Lee et al. confirmed that combination of TEW-7197 and ramucirumab reduced tumor spheroid and GC PDC-induced blood vessel formation concomitantly in the spheroid-on-a-chip model. [Read the Full Post]

Chemical Genetics Screen Identifies COPB2 Tool Compounds That Alters ER Stress Response and Induces RTK Dysregulation in Lung Cancer Cells

471 | Nov 01 2021

Punit Saraon et al. found that targeting of COPB2 with EMI66 presented a viable approach to attenuate mutant EGFR signalling and growth in NSCLC. [Read the Full Post]

Chemical Reprogramming of Somatic Cells in Neural Direction: Myth or Reality?

0 | Oct 22 2021

E M Samoilova et al. thought that reprogramming with small molecules without additional factors modifying gene expression did not allow reproducible production of human neural stem cell-like progenitors that could be used as the source of neural tissue for the regenerative therapy. [Read the Full Post]

Aspiration Is Associated with Poor Treatment Response in Pediatric Pulmonary Vein Stenosis

1037 | Oct 06 2021

Maria Niccum et al. found that potentially modifiable risk factor for poor treatment response in pediatric multi-vessel intraluminal pulmonary vein stenosis in patients with 2-ventricle physiology. [Read the Full Post]

Graphene oxide-functionalized nanocomposites promote osteogenesis of human mesenchymal stem cells via enhancement of BMP-SMAD1/5 signaling pathway

463 | Sep 19 2021

Zhong Li et al. demonstrated the biological activity and mechanism of action of GO-based nanosheets in augmenting the osteogenic capability of hMSCs. [Read the Full Post]

Proteomics of resistance to Notch1 inhibition in acute lymphoblastic leukemia reveals targetable kinase signatures

598 | Sep 17 2021

Giulia Franciosa et al. highlighted the potential of proteomics to dissect alterations in cellular signaling and identified druggable pathways in cancer. [Read the Full Post]

High WHSC1L1 Expression Reduces Survival Rates in Operated Breast Cancer Patients with Decreased CD8+ T Cells: Machine Learning Approach

601 | Sep 15 2021

Hyung-Suk Kim et al. found that VX-11e, CZC24832, LY2109761, oxaliplatin and erlotinib were effective in inhibiting breast cancer cell lines with high WHSC1L1 expression. [Read the Full Post]

PM 2.5 and water-soluble components induce airway fibrosis through TGF-β1/Smad3 signaling pathway in asthmatic rats

444 | Sep 03 2021

Hongyan Wu et al. thought that TGF-β1/Smad3 signaling pathway might be responsible for the pathological process of airway fibrosis in asthmatic rats following PM2.5 and water-soluble components exposure. [Read the Full Post]

Limb Remote Ischemic Conditioning Ameliorates Cognitive Impairment in Rats with Chronic Cerebral Hypoperfusion by Regulating Glucose Transport

809 | Aug 27 2021

Changhong Ren et al. suggested that supplemental activation of glucose transport after CCH might provide a clinically applicable intervention for improving cognitive impairment. [Read the Full Post]

Inhibition of AKR1B10-mediated metabolism of daunorubicin as a novel off-target effect for the Bcr-Abl tyrosine kinase inhibitor dasatinib

1242 | Aug 09 2021

Neslihan Büküm et al. demonstrated that dasatinib could synergize with Daun in human cancer cells and enhance its therapeutic effectiveness. [Read the Full Post]

Angiokinase inhibition of VEGFR-2, PDGFR and FGFR and cell growth inhibition in lung cancer: Design, synthesis, biological evaluation and molecular docking of novel azaheterocyclic coumarin derivatives

1329 | Jul 21 2021

Eman Y Ahmed et al. found that 4a was capable of arresting the cell cycle at pre-G1 phase and S phase and inducing apoptosis. [Read the Full Post]

TGF-β Alters the Proportion of Infiltrating Immune Cells in a Pancreatic Ductal Adenocarcinoma

450 | Jul 18 2021

Kasia Trebska-McGowan et al. found that TGF-β had an overall immunosuppressive effect mediated by TAM PD-L1 expression and decreased presence of DCs. [Read the Full Post]

Synthesis and Evaluation of Chiral Rhodanine Derivatives Bearing Quinoxalinyl Imidazole Moiety as ALK5 Inhibitors

412 | Jul 18 2021

Li-Min Zhao et al. suggested that the synthesized rhodanine compounds had good ALK5 inhibitory activity and could be used for further research and development as potential antifungal drugs. [Read the Full Post]

Dual Targeting of Sorafenib-Resistant HCC-Derived Cancer Stem Cells

397 | Jul 04 2021

Ritu Shrestha et al. found that the combined targeting of EMT and immune checkpoint molecules with Sorafenib could effectively target the CSC tumour subpopulation. [Read the Full Post]

A Rho Kinase (ROCK) Inhibitor, Y-27632, Inhibits the Dissociation-Induced Cell Death of Salivary Gland Stem Cells

919 | Jun 23 2021

Kichul Kim et al. demonstrated the protective effects of Y-27632 against dissociation-induced apoptosis of SGSCs during their culture in vitro. [Read the Full Post]

The efficacy and safety of niraparib for ovarian cancer: a single-center observational study from China

1011 | May 28 2021

Jing Ni et al. found that it was feasible that patients receiving a bolus of 200 mg/d in patients from Chinese population could acquire promising efficacy and tolerance. [Read the Full Post]

Development and validation of an MRI-based radiomics nomogram for distinguishing Warthin's tumour from pleomorphic adenomas of the parotid gland

726 | May 07 2021

Ying-Mei Zheng et al. found that the MRI-based radiomics nomogram had good performance in distinguishing parotid WT from PMA, which could optimize clinical decision-making. [Read the Full Post]

A fluorometric erythrophagocytosis assay using differentiated monocytic THP-1 cells to assess the clinical significance of antibodies to red blood cells

640 | May 06 2021

Abdelwahab Hassan Ahmed Balola et al. thought that the flow cytometry-based erythrophagocytosis test described here was quantitative, highly reliable, and might be helpful for the assessment of the clinical significance of antibodies to RBCs. [Read the Full Post]

Netarsudil: A new ophthalmic drug in the treatment of chronic primary open angle glaucoma and ocular hypertension

785 | Apr 18 2021

Mansi Batra et al. showed that the discovery of netarsudil was a breakthrough in the therapy of glaucoma with proven efficacy in a wide range of eye pressures and was well tolerated in cases with ocular hypertension and chronic glaucoma. [Read the Full Post]

The anti-apoptotic proteins Bcl-2 and Bcl-xL suppress Beclin 1/Atg6-mediated lethal autophagy in polyploid cells

1142 | Apr 16 2021

Jing Zhang et al. found that Bcl-2 and Bcl-xL negatively modulated MYC-VX-680 synthetic lethality. [Read the Full Post]

ALK3-SMAD1/5 Signaling Mediates the BMP2-Induced Decrease in PGE2 Production in Human Endometrial Stromal Cells and Decidual Stromal Cells

455 | Apr 16 2021

Yu Zhang et al. found that BMP2 decreased PGE2 production by downregulating COX-1 expression. [Read the Full Post]

Inhibition of Cdc20 suppresses the metastasis in triple negative breast cancer (TNBC)

1548 | Apr 15 2021

Christine Song et al. suggested an essential role of Cdc20 in tumor formation and metastasis of TNBC, which might be a potential target therapy for TNBC treatment. [Read the Full Post]

Melanin Distribution in Human Skin: Influence of Cytoskeletal, Polarity, and Centrosome-Related Machinery of Stratum basale Keratinocytes

1147 | Apr 06 2021

Irene Castellano-Pellicena et al. explored the role of actin, microtubules, and centrosome-associated machinery in distributing melanin within KCs. [Read the Full Post]

Pharmacological Protein Kinase C Modulators Reveal a Pro-hypertrophic Role for Novel Protein Kinase C Isoforms in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

481 | Feb 16 2021

Lotta Pohjolainen et al. showed similar hypertrophic responses to PKC modulators in NRVMs and hiPSC-CMs. [Read the Full Post]

Augmenter of Liver Regeneration (ALR) regulates bile acid synthesis and attenuates bile acid-induced apoptosis via glycogen synthase kinase-3β (GSK-3β) inhibition

1435 | Feb 02 2021

Sara Ibrahim et al. thought that rALR might contribute to protecting hepatocytes from toxic concentrations of bile acids by down-regulating their denovo synthesis, attenuating apoptosis by activation of PI3K/Akt - GSK3β pathway and inhibition of JNK signaling. [Read the Full Post]

The α1-adrenergic receptors in the amygdala regulate the induction of learned despair through protein kinase C-beta signaling

606 | Jan 22 2021

Shisui Fujita et al. suggested that the α1-adrenoreceptor in amygdala regulated the induction of learned despair via PKCβ. [Read the Full Post]

Effect of leech-centipede medicine on improving erectile function in DIED rats via PKC signalling pathway-related molecules

542 | Jan 22 2021

Ji-Sheng Wang et al. found that "leech-centipede" medicine could improve erectile dysfunction by inhibiting the expression of PKC pathway-related molecules in DIED rats and protected endothelial function and anti-platelet activation. [Read the Full Post]

Inhibition of TGF-β signalling in combination with nal-IRI plus 5-Fluorouracil/Leucovorin suppresses invasion and prolongs survival in pancreatic tumour mouse models

334 | Jan 09 2021

Eunji Hong et al. suggested that combination therapy of nal-IRI/5-FU/LV with vactosertib could provide clinical benefits to pancreatic cancer patients. [Read the Full Post]

Small molecular compounds efficiently convert human fibroblasts directly into neurons

483 | Dec 21 2020

Jijuan Yang et al. provided a novel combination of existing small molecular compounds that efficiently reprogramed human fibroblasts into neurons. [Read the Full Post]

GPR91 antagonist and TGF-β inhibitor suppressed collagen production of high glucose and succinate induced HSC activation

516 | Dec 10 2020

Mutsuko Sakai et al. determined that even though HSCs had already been activated by high glucose or succinate conditions which persisted after activation, the GPR91 antagonist and the TGF-β1 receptor inhibitor were able to reduce the production of type I collagen from activated HSCs. [Read the Full Post]

Mixed lineage kinase 3 inhibition induces T cell activation and cytotoxicity

1023 | Dec 07 2020

Sandeep Kumar et al. demonstrated that MLK3 played an important role in T cell biology, and targeting MLK3 could serve as a potential therapeutic intervention via increasing T cell cytotoxicity in cancer. [Read the Full Post]

Activating JAK-mutations confer resistance to FLT3 kinase inhibitors in FLT3-ITD positive AML in vitro and in vivo

499 | Nov 10 2020

Christoph Rummelt et al. characterized a novel mechanism of resistance to FLT3-ITD inhibition and might offer a potential therapy, using dual JAK and FLT3 inhibition. [Read the Full Post]

Chemical Reprogramming of Somatic Cells in Neural Direction: Myth or Reality?

838 | Oct 27 2020

E M Samoilova et al. found that reprogramming with small molecules without additional factors modifying gene expression did not allow reproducible production of human neural stem cell-like progenitors that could be used as the source of neural tissue for the regenerative therapy. [Read the Full Post]

A rare maternal gastrointestinal stromal tumor found in the second trimester of pregnancy: A case report

888 | Oct 03 2020

Naoko Tanaka et al. believed that pregnant patients should be managed by a multidisciplinary team with expertise in gastrointestinal tumors and fetal-maternal medicine. [Read the Full Post]

Structural Basis of Activin Receptor-Like Kinase 2 (R206H) Inhibition by Bis-heteroaryl Pyrazole-Based Inhibitors for the Treatment of Fibrodysplasia Ossificans Progressiva Identified by the Integration of Ligand-Based and Structure-Based Drug Design Approaches

470 | Sep 13 2020

Tomohiro Sato et al. indicated the existence of the additional hydrogen bond via water molecules restricting the attachment point in the pyrazole scaffold [Read the Full Post]

Sotrastaurin, a PKC inhibitor, attenuates RANKL-induced bone resorption and attenuates osteochondral pathologies associated with the development of OA

502 | Sep 08 2020

Cong Pang et al. provided evidence for the protective effects of SO against OA by preventing aberrant subchondral bone and articular cartilage changes. [Read the Full Post]

Mast cells (MCs) induce ductular reaction mimicking liver injury in mice via MC-derived TGF-β1 signaling

568 | Sep 02 2020

Konstantina Kyritsi et al. demonstrated that reintroduction of MCs mimics cholestatic liver injury and MC-derived TGF-β1 might be a target in chronic cholestatic liver disease. [Read the Full Post]

CircPlekha7 plays an anti-fibrotic role in intrauterine adhesions by modulating endometrial stromal cell proliferation and apoptosis

364 | Aug 18 2020

Wei Xie et al. indicated that circPlekha7 played an anti-fibrotic role in IUA and might serve as a promising prognostic biomarker for patients with IUA. [Read the Full Post]

Irisin ameliorates high glucose-induced cardiomyocytes injury via AMPK/mTOR signal pathway

731 | Aug 10 2020

Jingyu Deng et al. showed that Irisin played a significant role in anti-apoptosis, anti-inflammation, anti-oxidative stress in HG-induced CMs via AMPK/mTOR signaling pathway. [Read the Full Post]

Pentraxin-3 Mediates Prosurvival Actions of Interferon Tau in Bovine Luteinized Granulosa Cells

740 | Aug 06 2020

Raghavendra Basavaraja et al. suggested a novel role for PTX3 during early pregnancy, as mediator of IFNT prosurvival actions supporting CL maintenance during this reproductive stage. [Read the Full Post]

A Global PROTAC Toolbox for Degrading BCR-ABL Overcomes Drug-Resistant Mutants and Adverse Effects

1208 | Jul 15 2020

Yiqing Yang et al. found that PROTACs showed better selectivity and less adverse effects than inhibitors, indicating that PROTACs had a great potential for overcoming clinical drug resistance and safety issues. [Read the Full Post]

Overexpression of Fibroblast Growth factor-21 (FGF-21) Protects Mesenchymal Stem Cells Against Caspase-Dependent Apoptosis Induced by Oxidative Stress and Inflammation

1358 | Jun 22 2020

Gabriel R Linares et al. provided compelling evidence that FGF-21 played a crucial role in protecting MSCs from apoptosis induced by oxidative stress and inflammation, and merited further investigation as a strategy for enhancing the therapeutic efficacy of stem cell-based therapies. [Read the Full Post]

Staurosporine and NEM Mainly Impair WNK-SPAK/OSR1 Mediated Phosphorylation of KCC2 and NKCC1

1312 | Jun 18 2020

Jinwei Zhang et al. identified phospho-sites that are responsive to staurosporine or NEM application. [Read the Full Post]

Xiaochaihu Decorction Relieves Liver Fibrosis Caused by Schistosoma Japonicum Infection via the HSP47/TGF-β Pathway

435 | Jun 16 2020

Yuzheng Huang et al. demonstrated that the hepatic protective effects of Xiaochaihu decoction were mediated by HSP47/TGF-β axis. [Read the Full Post]

Promotion of Liver Regeneration and Anti‑fibrotic Effects of the TGF‑β Receptor Kinase Inhibitor Galunisertib in CCl4‑treated Mice

928 | Jun 14 2020

Atsutaka Masuda et al. suggested that galunisertib might be an effective treatment for liver cirrhosis. [Read the Full Post]

Hypoxia Upregulates Cxcl12 in Hepatocytes by a Complex Mechanism Involving Hypoxia-Inducible Factors and Transforming Growth Factor-β

908 | May 27 2020

Jenna Strickland et al. demonstrated that hypoxia upregulated Cxcl12 in primary mouse hepatocytes by a mechanism that involved HIFs and TGF-β. [Read the Full Post]

Glucagon-like peptide 1 reverses myocardial hypertrophy through cAMP/PKA/RhoA/ROCK2 signaling.

1002 | May 14 2020

Fan S et al. suggested that GLP-1 might reverse myocardial hypertrophy through the PKA/RhoA/ROCK2 signaling pathway. [Read the Full Post]

The Rho-associated kinase inhibitor fasudil can replace Y-27632 for use in human pluripotent stem cell research

1361 | May 12 2020

So S et al. suggested that fasudil can replace Y-27632 for use in stem research. [Read the Full Post]

Small molecule inhibitor RepSox prevented ovariectomy-induced osteoporosis by suppressing osteoclast differentiation and bone resorption

418 | Mar 22 2020

Mei L et al. suggested that RepSox regulates osteoclast differentiation, bone resorption, and OVX-induced OP via the suppression of the Smad3 and JNK/AP-1 pathways. [Read the Full Post]

Resistance to RET-Inhibition in RET-Rearranged NSCLC Is Mediated By Reactivation of RAS/MAPK Signaling

1073 | Mar 14 2020

Nelson-Taylor SK et al. demonstrated that resistance to ponatinib in RET-rearranged lung adenocarcinoma is mediated by bypass signaling mechanisms that result in restored RAS/MAPK activation. [Read the Full Post]

Precision-cut lung slices from bleomycin treated animals as a model for testing potential therapies for idiopathic pulmonary fibrosis

453 | Mar 04 2020

Cedilak M et al. suggested that PCLS may be a suitable in vitro model for compound testing during drug development process. [Read the Full Post]

Rho-kinase ROCK inhibitors reduce oligomeric tau protein

1099 | Feb 10 2020

Hamano T et al. suggested that ROCK inhibitors represent a viable therapeutic route to reduce the pathogenic forms of tau protein in tauopathies, including Alzheimer's disease. [Read the Full Post]

Early diagnosis, clinical management, and follow-up of cardiovascular events with ponatinib

907 | Feb 07 2020

Casavecchia G et al. reported and discussed most relevant evidence currently available on cardiovascular events associated with the use of ponatinib. [Read the Full Post]

Cost-effectiveness of midostaurin in the treatment of newly diagnosed FLT3-mutated acute myeloid leukemia in France

591 | Jan 25 2020

Tremblay G et al. indicated that MIDO represents a clinically significant advancement in the management of newly diagnosed FLT3-mutated AML. In this analysis, MIDO add-on therapy showed gains in LYs and QALYs versus SOC alone and was found to be a cost-effective option at a €100,000 per QALY threshold for end-of-life treatment. [Read the Full Post]

Cirrhotic Human Liver Extracellular Matrix 3D Scaffolds Promote Smad-Dependent TGF-β1 Epithelial Mesenchymal Transition

478 | Jan 18 2020

Mazza G found that the inherent features of cirrhotic human liver ECM micro-environment were dissected and characterized for the first time as key pro-carcinogenic components in HCC development. [Read the Full Post]

Profiling of lincRNAs in human pluripotent stem cell derived forebrain neural progenitor cells

0 | Jan 10 2020

Grassi DA et al. were able to identify many previously uncharacterized long intergenic non-coding RNAs that display dynamic expression during human forebrain neurogenesis. [Read the Full Post]

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

0 | Jan 03 2020

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]

Targeting mitochondrial oxidative phosphorylation eradicates therapy-resistant chronic myeloid leukemia stem cells

988 | Dec 10 2019

Kuntz EM et al. provided a strong rationale for investigation of the use of TKIs in combination with tigecycline to treat patients with CML with minimal residual disease. [Read the Full Post]

Differential cellular responses induced by dorsomorphin and LDN-193189 in chemotherapy-sensitive and chemotherapy-resistant human epithelial ovarian cancer cells

480 | Nov 18 2019

Ali JL et al. showed that DM and LDN possess drug characteristics suitable for adjuvant agents used to treat chemotherapy-sensitive and -resistant EOC. [Read the Full Post]

LY2109761 enhances cisplatin antitumor activity in ovarian cancer cells

616 | Nov 14 2019

Gao Y et al. showed that chemotherapeutic approaches using LY2109761 might enhance the treatment benefit of the cisplatin in the treatment of ovarian cancer patients. [Read the Full Post]

TAZ promotes the proliferation and osteogenic differentiation of human periodontal ligament stem cells via the p-SMAD3

522 | Oct 28 2019

Gu K et al. indicated that Hippo/TAZ plays a positive role inside the proliferation, stemness maintenance, and osteogenic specialization of h-PDLSCs, and the specific downstream factor of osteogenic differentiation is SMAD3. [Read the Full Post]

Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models

1131 | Sep 23 2019

Gozgit JM et al. showed that ponatinib is a potent pan-FGFR inhibitor and provide strong rationale for its evaluation in patients with FGFR-driven cancers. [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

1117 | Aug 30 2019

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

Alkylation of Staurosporine to Derive a Kinase Probe for Fluorescence Applications

719 | Aug 18 2019

Disney AJ et al. reported that this fluorescein-staurosporine conjugate binds to cAMP-dependent protein kinase in the nanomolar range. Furthermore, its binding can be antagonised with unmodified staurosporine as well as ATP, indicating it targets the ATP binding site in a similar fashion to native staurosporine. This reagent has potential application as a screening tool for protein kinases of interest. [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

1217 | 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]

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

538 | 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]

Treatment Patterns in Patients with Chronic-Phase Chronic Myeloid Leukaemia in Routine Clinical Practice: the SIMPLICITY Italian Population

1443 | Aug 10 2019

Abruzzese E et al. provided valuable insights into management and treatment patterns in Italian patients with CML within routine clinical practice. [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

1435 | 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]

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

1273 | 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]

Disposition of asciminib, a potent BCR-ABL1 tyrosine kinase inhibitor, in healthy male subjects

856 | Jun 30 2019

Tran P et al. presented the results of human oral absorption, distribution, metabolism, excretion (ADME) and in vitro studies that together provide an overall understanding of the metabolism, distribution and clearance of asciminib in humans. [Read the Full Post]

TKI-Related Platelet Dysfunction Does Not Correlate With Bleeding in Patients With Chronic Phase-Chronic Myeloid Leukemia With Complete Hematological Response

950 | Jun 21 2019

Sener Y et al. concluded that TKIs may impair in vitro platelet aggregation but this impairment is not associated with bleeding diathesis. [Read the Full Post]

Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation

750 | Jun 07 2019

Stone RM et al. indicated the addition of the multitargeted kinase inhibitor midostaurin to standard chemotherapy significantly prolonged overall and event-free survival among patients with AML and a FLT3 mutation. [Read the Full Post]

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

563 | Jun 05 2019

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

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

1025 | 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]

Midostaurin/PKC412 for the treatment of newly diagnosed FLT3 mutation-positive acute myeloid leukemia

839 | May 25 2019

Luskin MR et al. indicated that expert commentary: The approval of midostaurin represents the first new therapy for AML in several decades. It is also the first targeted therapy approved for AML. Future studies will focus on defining mechanisms of resistance to midostaurin as well as establishing the role of midostaurin in combination with hypomethylating agents and as maintenance therapy. Second generation, more potent and selective FLT3 inhibitors are also in development; these agents need to be compared to midostaurin. [Read the Full Post]

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

603 | 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

567 | 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

604 | 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]

Grem2 mediates podocyte apoptosis in high glucose milieu

698 | 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

1297 | 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

1298 | 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]

Sotrastaurin in calcineurin inhibitor-free regimen using everolimus in de novo kidney transplant recipients

797 | Mar 03 2019

Tedesco-Silva H et al. indicated that sotrastaurin combined with EVR showed higher efficacy failure rates and some improvement in renal allograft function compared to a CsA-based therapy. [Read the Full Post]

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

735 | 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]

Pharmacology and pharmacokinetics of imatinib in pediatric patients

1484 | Jan 22 2019

Suttorp M et al. indicated that adherence to imatinib intake may be the most prominent factor influencing treatment outcome in teenagers thus pointing towards the potential benefits of regular drug monitoring. [Read the Full Post]

Pharmacology and pharmacokinetics of imatinib in pediatric patients

0 | Jan 22 2019

Suttorp M et al. indicated taht pharmacokinetic variables (e.g. alpha 1-acid glycoprotein binding, drug-drug/food-drug interactions via cytochrome P450 3A4/5, cellular uptake mediated via OCT-1-influx variations and P-glycoprotein-mediated drug efflux) still await to be addressed in pediatric patients systematically. [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]

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

746 | 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

1983 | 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]

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

6040 | 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]

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

774 | 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]

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

796 | Nov 02 2018

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

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

2097 | 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]

Resistance to RET-Inhibition in RET-Rearranged NSCLC Is Mediated By Reactivation of RAS/MAPK Signaling

1829 | Oct 12 2018

Nelson-Taylor SK et al. demonstrated that resistance to ponatinib in RET-rearranged lung adenocarcinoma is mediated by bypass signaling mechanisms that result in restored RAS/MAPK activation. [Read the Full Post]

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

914 | 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]

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

2566 | 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]

MKP1 mediates chemosensitizer effects of E1a in response to cisplatin in non-small cell lung carcinoma cells

1151 | Aug 05 2018

Cimas FJ et al. indicated that the present work reinforce the critical role of MKP1 in the cellular response to cisplatin highlighting the importance of this phosphatase in future gene therapy approach based on E1a gene. [Read the Full Post]

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

2145 | 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

975 | 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]

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

3526 | 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]

Inhibition of deubiquitinases primes glioblastoma cells to apoptosis in vitro and in vivo

1912 | Jun 18 2018

Karpel-Massler G et al. suggested that targeting deubiquitinases for glioma therapy is feasible and effective. [Read the Full Post]

The Deubiquitinase USP9X Maintains DNA Replication Fork Stability and DNA Damage Checkpoint Responses by Regulating CLASPIN during S-Phase

2136 | Jun 18 2018

McGarry E et al. revealed a novel role for USP9X in the maintenance of genomic stability during DNA replication and provide potential mechanistic insights into its tumor suppressor role in certain malignancies. [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]

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

3262 | 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

1071 | 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]

In situ electrochemical evaluation of dsDNA interaction with the anticancer drug danusertib nitrenium radical product using the DNA-electrochemical biosensor

3382 | Apr 05 2018

Diculescu VC et al. indicated the danusertib nitrenium cation radical redox metabolite was covalently attached to the C8 of guanine residues preventing their oxidation. An interaction mechanism of dsDNA-danusertib is proposed and the formation of the danusertib redox nitrenium radical metabolite-guanine adduct explained. [Read the Full Post]

Regulation of glutamate transporter trafficking by Nedd4-2 in a Parkinson's disease model

0 | Mar 23 2018

Zhang Y et al. indicated that Nedd4-2 may serve as a potential therapeutic target for the treatment of PD. [Read the Full Post]

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

1429 | 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]

Survivin inhibitor YM155 induces mitochondrial dysfunction, autophagy, DNA damage and apoptosis in Bcl-xL silenced glioma cell lines

1520 | Feb 14 2018

Jane EP et al. provided a new insight into the link between Bcl-xL and survivin inhibition for the development of novel therapies for glioma. [Read the Full Post]

Ligation of CD180 inhibits IFN-α signaling in a Lyn-PI3K-BTK-dependent manner in B cells

3565 | Feb 14 2018

You M et al. provided molecular insight into the mechanism of IFN-α signaling activation in SLE B cells and a potential therapeutic approach for SLE treatment. [Read the Full Post]

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

1196 | 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

1184 | 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).

1968 | 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]

CK1δ kinase activity is modulated by protein kinase C α (PKCα)-mediated site-specific phosphorylation

3839 | Jan 14 2018

Meng Z et al. contributed to a deeper understanding of cellular signal transduction networks thereby helping to form a basis for the development of future therapeutic concepts. [Read the Full Post]

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

1726 | Jan 04 2018

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

Dasatinib inhibits actin fiber reorganization and promotes endothelial cell permeability through RhoA-ROCK pathway

2609 | Dec 21 2017

Dasgupta SK et al. suggested that ROCK inhibitors could serve as therapeutic modalities to ameliorate the dasatinib-induced pulmonary changes. [Read the Full Post]

Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells

4093 | Dec 10 2017

Abraham SA et al. found that LSCs can be eradicated. [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

1242 | 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

1506 | 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]

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

3898 | 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]

Targeting protein kinase C in mantle cell lymphoma

1604 | Nov 16 2017

Rauert-Wunderlich H et al. showed that MCL cells are heterogeneous in their response to BTK or PKC inhibition, indicating the need for even more individualized targeted treatment approaches in subsets of MCL patients. [Read the Full Post]

Synergistic effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway or NUP214-ABL1 fusion protein in human Acute Lymphoblastic Leukemia

0 | Nov 08 2017

Simioni C et al. indicated that co-targeting NUP214-ABL1 fusion gene and PI3K/Akt/mTOR signaling pathway could represent a new and effective pharmacological strategy to improve the outcome in NUP214-ABL1 positive T-ALL. [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

1590 | 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]

Cytokine correlation analysis based on drug perturbation

0 | Oct 19 2017

Wallner FK et al. showed that cytokines are highly co-regulated, which provide valuable information for how a therapeutic drug might affect clusters of cytokines. In addition, a cytokine that is used as a therapeutic biomarker could be combined with its related cytokines into a biomarker panel to improve diagnostic accuracy. [Read the Full Post]

Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma

0 | Oct 12 2017

Saha SK et al. provided a systematic and broadly applicable approach to define targets of kinase inhibitors underlying drug responsiveness. [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

1698 | 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

2339 | 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]

Synergistic effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway or NUP214-ABL1 fusion protein in human Acute Lymphoblastic Leukemia

3284 | Sep 01 2017

Simioni C et al. showed that dephosphorylation of pAkt and pS6 showed the cytotoxicity of these compounds. Either single or combined administration of drugs against the different targets displayed inhibition of cellular viability associated with a concentration-dependent induction of apoptosis, cell cycle arrest in G0/G1 phase and autophagy, having the combined treatments a significant synergistic cytotoxic effect. Co-targeting NUP214-ABL1 fusion gene and PI3K/Akt/mTOR signaling pathway could represent a new and effective pharmacological strategy to improve the outcome in NUP214-ABL1 positive T-ALL. [Read the Full Post]

Cell Death Induction by the Indirubin Derivative 7BIO and the BH3 Mimetic Drugs ABT-737 and GX15-070 in Medullary Thyroid Carcinoma Cells

2476 | Aug 15 2017

Broecker-Preuss M et al. showed that although the exact kind of cell death and target molecules of 7BIO and GX15-070 are not yet defined, direct induction of cell death may be a new therapeutic option in medullary thyroid carcinoma cells. [Read the Full Post]

A novel sgRNA selection system for CRISPR-Cas9 in mammalian cells

2715 | Aug 14 2017

Zhang H et al. provided a potential application to optimize the sgRNAs in different species and to generate a powerful CRISPR-Cas9 genome-wide screening system with minimum amounts of sgRNAs. [Read the Full Post]

Image-Guided Radiotherapy Targets Macromolecules through Altering the Tumor Microenvironment

2955 | Aug 01 2017

Appelbe OK et al. suggest repurposing image-guided radiotherapy as a tool to guide cancer nanomedicine delivery, enhancing local control for primary tumors and metastatic disease while limiting systemic toxicity. [Read the Full Post]

Y-632 inhibits heat shock protein 90 (Hsp90) function by disrupting the interaction between Hsp90 and Hsp70/Hsp90 organizing protein, and exerts antitumor activity in vitro and in vivo

2844 | Aug 01 2017

Wang W et al. believe that Y-632, acting as a novel small-molecule inhibitor of the Hsp90-Hsp70/Hsp90 organizing protein complex, has great potential to be a promising Hsp90 inhibitor for cancer therapy, such as for imatinib-resistant leukemia. [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

1472 | 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]

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]

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

5939 | 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]

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

3295 | 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]

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]

Bafetinib (INNO-406) reverses multidrug resistance by inhibiting the efflux function of ABCB1 and ABCG2 transporters

2431 | May 22 2017

Zhang YK et al. found that bafetinib reversed ABCB1- and ABCG2-mediated MDR by blocking the drug efflux function of these transporters [Read the Full Post]

Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib

3767 | May 17 2017

Miller RE et al. suggested that dasatinib merits investigation for the treatment of patients with ARID1A-mutant OCCC. [Read the Full Post]

Hiding inside? Intracellular expression of non-glycosylated c-kit protein in cardiac progenitor cells

3432 | May 15 2017

Shi H et al. demonstrated for the first time that c-kit is not only expressed in CDCs but may also directly participate in CDC differentiation into an endothelial lineage. [Read the Full Post]

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

1565 | 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

8803 | 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

3084 | 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]

Phosphatidylinositol 3-Kinase/Akt Mediates Integrin Signaling To Control RNA Polymerase I Transcriptional Activity

7347 | Apr 09 2017

Collectively, Wu C et al revealed, for the first time, a pivotal role of integrin signaling in regulation of RNA polymerase I transcriptional activity and shed light on the downstream signaling axis that participates in regulation of this key aspect of cell growth. [Read the Full Post]

Nicotine-Mediated Ca2+ -Influx Induces IL-8 Secretion in Oral Squamous Cell Carcinoma Cell

2680 | Mar 14 2017

Tsunoda K et al. suggested that the binding of nicotine to nAChR induces Ca(2+) influx, which results in the activation and phosphorylation of CaMK II and NF-κB p65, respectively. Nicotine-mediated IL-8 induction should be a trigger for the initiation of various diseases. [Read the Full Post]

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

1906 | 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]

Delocalized Claudin-1 promotes metastasis of human osteosarcoma cells

0 | Feb 12 2017

Jian Y, et al.'s study implied that delocalization of claudin-1 induced by PKC phosphorylation contributes to metastatic capacity of OS cells. [Read the Full Post]

Ph-like ALL-related novel fusion kinase ATF7IP-PDGFRB exhibits high sensitivity to tyrosine kinase inhibitors in murine cells.

0 | Feb 05 2017

Ishibashi T, et al.'s observations suggest the therapeutic importance of tyrosine kinase inhibitors and possibly MEK inhibitor for a subset of BCP-ALL harboring PDGFRB-related fusion kinases. [Read the Full Post]

Nicotine-Mediated Ca2+ -Influx Induces IL-8 Secretion in Oral Squamous Cell Carcinoma Cell

2885 | Jan 22 2017

The results fromTsunoda K, et al.'s study indicate that the binding of nicotine to nAChR induces Ca(2+) influx, which results in the activation and phosphorylation of CaMK II and NF-κB p65, respectively. Nicotine-mediated IL-8 induction should be a trigger for the initiation of various diseases. [Read the Full Post]

Delocalized Claudin-1 promotes metastasis of human osteosarcoma cells

2920 | Jan 05 2017

Jian Y, et al.'s our study implied that delocalization of claudin-1 induced by PKC phosphorylation contributes to metastatic capacity of OS cells. [Read the Full Post]

Ph-like ALL-related novel fusion kinase ATF7IP-PDGFRB exhibits high sensitivity to tyrosine kinase inhibitors in murine cells

2858 | Dec 29 2016

Ishibashi T, et al.‘’s observations suggest the therapeutic importance of tyrosine kinase inhibitors and possibly MEK inhibitor for a subset of BCP-ALL harboring PDGFRB-related fusion kinases. [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

2729 | 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

2123 | 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

2240 | 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]

Basic FGF and PDGF-BB synergistically stimulate hyaluronan and IL-6 production by orbital fibroblasts

5677 | Nov 26 2016

Multi-target therapy directed at the bFGF and PDGF pathways may potentially be of interest for the treatment of GO. [Read the Full Post]

Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and SRC Dependence in Intrahepatic Cholangiocarcinoma

4540 | Nov 16 2016

Saha SK et al. showed that IDHm ICC cells have a unique dependency on SRC and suggested that dasatinib may have therapeutic benefit against IDHm ICC. [Read the Full Post]

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

2200 | 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]

SB-224289 Antagonizes the Antifungal Mechanism of the Marine Depsipeptide Papuamide A

2963 | Oct 28 2016

[Read the Full Post]

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

4360 | Oct 19 2016

[Read the Full Post]

Bafetinib (INNO-406) reverses multidrug resistance by inhibiting the efflux function of ABCB1 and ABCG2 transporters

3189 | Oct 19 2016

Zhang YK et al. found that bafetinib reversed ABCB1- and ABCG2-mediated MDR by blocking the drug efflux function of these transporters. [Read the Full Post]

Hiding inside? Intracellular expression of non-glycosylated c-kit protein in cardiac progenitor cells

4318 | Oct 13 2016

Shi H et al. demonstrated for the first time that c-kit is not only expressed in CDCs but may also directly participate in CDC differentiation into an endothelial lineage. [Read the Full Post]

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

2182 | 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

2386 | 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]

Phosphatidylinositol 3-Kinase/Akt Mediates Integrin Signaling To Control RNA Polymerase I Transcriptional Activity

3461 | Sep 12 2016

Wu C et al. revealed that a pivotal role of integrin signaling in regulation of RNA polymerase I transcriptional activity and shed light on the downstream signaling axis that participates in regulation of this key aspect of cell growth. [Read the Full Post]

Inhibition of proteasome restores bortesomib-induced thrombocytopenia

10589 | 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]

Star27 overcomes synthetic lethal toxicity for FLT3-targeted therapy against acute myeloid leukemia

4941 | Feb 06 2015

For overcoming myelosuppression, Warkentin et al. reported a staurosporine analog, Star27, that enable to inhibit FLT3 while avoiding KIT inhibition. [Read the Full Post]

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

7559 | 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]

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

15430 | Jan 23 2015

Dubrovsky et al. developed an antibody, ESKM, which is therapeutically effective on acute and chronic leukemias in murine models. [Read the Full Post]

BUB1 plays a key role in promoting TGF-β signaling

7914 | 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]

Generate hypothalamic neurons from hESCs and human iPSCs

4030 | 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

4319 | 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

5913 | 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 mechanism of drug resistance in BRAF (V600E) mutant melanoma

9791 | 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

7060 | 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]

New platform of high efficiency iPSC reprogramming

8824 | 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]

The role of TGFβ target——LTBP4 in muscular dystrophy

4315 | 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]

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

5872 | 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

4045 | 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

3923 | 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

5560 | 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]

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

5643 | 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]

SB 525334 is a selective inhibitor of transforming growth factor B

3612 | 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

3446 | 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

5364 | 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]

Thiazovivin is a drug which dramatically improves the survival of hES

5733 | 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]

Staurosporine is a potent PKC inhibitor with IC50

5942 | Sep 24 2013

Staurosporine, a microbial alkaloid, significantly inhibits protein kinase C from rat brain with IC50 of 2.7 nM. [Read the Full Post]

Y27632 is a selective inhibitor of the Rhoassociated kinase p160ROCK

5564 | 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]

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

5908 | 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]

AEB071 is a potent selective pan PKC inhibitor

4610 | Jan 16 2013

Multiple sclerosis is a chronic and debilitating immune-mediated disease of the central nervous system . Recent epidemiological data supports the established view that the incidence of AEB071 MS peaks at about 30 years of age and that it is a disease with a positive female-to-male ratio. [Read the Full Post]

LY2109761 is a novel transforming growth factor

3250 | 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]

PKC Inhibitors is associated with endothelial dysfunction

4724 | Dec 06 2012

Atherosclerosis is initiated by the deposition, retention and oxidative modification of apolipoprotein (apo)B-containing lipoproteins, notably low-density lipoprotein cholesterol (LDL-C) in the vessel wall. This is associated with endothelial PKC Inhibitors dysfunction and recruitment of monocytes that take up oxidised LDL to become macrophage-derived foam cells, collectively apparent macroscopically as "fatty streaks". [Read the Full Post]

ROCK Kinase is involved in cytokinesis

5920 | 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]

DASATINIB; An Inhibitor of Receptor Tyrosine Kinase

0 | Sep 06 2012

CHARACTERISTICS OF DASATINIB Experts and also scientists are trying hard to find improve drug that will be able to possess efficiency as against cancer which has become responsible of heavy death all over the world and also resistance towards the available drugs in cancer cells is also motivating scientists. Cancer cells avoid both the action of particular medicine by mutating themselves in a number of steps. Metastasis is actually also other problem related to disease. For chemotherapy of disease cell toxicity increases the problem. To attack these afore mentioned errors the only key to combat it to be able to devise new medication. Imatinib was used for many years but toxicity and other consequences mentioned above it obligate scientists to develop one less harmful and more efficient prescription. So in this respect Jagabandhu Das developed one medicine known as Dasatinib. Dasatinib BMS 354825 got very popular compared to Imatinib because of its less toxicity and more performance. It's developed through a pharmaceutical business Squibb and offered under the trade name on Sprycel. [Read the Full Post]

NILOTINIB AND PHILADELPHIA

6344 | Jul 25 2012

CML AND PHILADELPHIA CHROMOSOME During meiosis the fusion of two genes including BCR a breakpoint cluster and ABL tyrosine kinase results in the formation of Philadelphia chromosome. The resultant fusion protein expressed due to Philadelphia chromosome is not controlled and function abnormally leading to an oncoprotein. Chronic myelogenous leukemia or CML is caused by this fusion oncoprotein in 90% of the patients of CML. Due to huge part of this protein in CML, in drug development for cancer treatment this protein is being targeted by researchers by the help of small molecule screening. Nilotinib AMN-107 is one of the inhibitor used for this purpose to cure CML. [Read the Full Post]

NILOTINIB 

7003 | Jul 12 2012

ASSOCIATION OF PHILADELPHIA CHROMOSOME WITH CHRONIC MYELOGENOUS LEUKEMIA Philadelphia chromosome is composed by fusion of a tyrosine kinase ABL (Abelson) and BCR (break point cluster) gene during the cross linking of chromosomes in meiosis. This Philadelphia chromosome promotes fusion protein that functions in an uncontrolled manner as a tyrosine kinase making it an oncoprotein. This fusion oncoprotein is involved in causing CML i.e., chronic myelogenous leukemia in 90 % of patients of this disease. Due to the involvement of this fusion protein in CML, it is being targeted in lots of research going on for cancer therapeutics. Nilotinib bcr-abl inhibitor is one these inhibitors being used against CML. [Read the Full Post]

NILOTINIB

5879 | Jul 05 2012

CHRONIC MYELOGENOUS LEUKEMIA AND PHILADELPHIA CHROMOSOME During meiosis if BCR and tyrosine kinase ABL are unable to separate and fuse together it leads to condition called Philadelphia chromosome. Due to the fusion of these genes it leads to translation of abnormal protein which acts as malfunctioned tyrosine kinase that makes it oncoprotein. Around 90% of patients suffering from Ph+ also suffer from chronic myelogenous leukemia or CML. This fusion protein is being targeted for therapy of cancer since it is involved in CML and various researches are being carried out in this regard. An inhibitor of this protein is Nilotinib bcr-abl inhibitor which is used to treat CML. [Read the Full Post]

NILOTINIB

6741 | Jun 28 2012

CHRONIC MYELOGENOUS LEUKEMIA AND PHILADELPHIA CHROMOSOME During meiosis if BCR and tyrosine kinase ABL are unable to separate and fuse together it leads to condition called Philadelphia chromosome. Due to the fusion of these genes it leads to translation of abnormal protein which acts as malfunctioned tyrosine kinase that makes it oncoprotein. Around 90% of patients suffering from Ph+ also suffer from chronic myelogenous leukemia or CML. This fusion protein is being targeted for therapy of cancer since it is involved in CML and various researches are being carried out in this regard. An inhibitor of this protein is Nilotinib bcr-abl inhibitor which is used to treat CML. [Read the Full Post]

NILOTINIB AND PH+

6547 | Jun 10 2012

PHILADELPHIA CHROMOSOME AND CML Philadelphia chromosome is formed by fusion of a tyrosine kinase ABL (Abelson) and BCR (break point cluster) gene during the cross linking of chromosomes in meiosis. This Philadelphia chromosome gives rise to a fusion protein that is functions in an uncontrolled manner as a tyrosine kinase making it an oncoprotein. This fusion oncoprotein is involved in causing CML i.e., chronic myelogenous leukemia in 90 % of patients of this disease. Due to the involvement of this fusion protein in CML, it is being targeted in lots of research going on for cancer therapeutics. Nilotinib bcr-abl inhibitor is one these inhibitors being used against CML. [Read the Full Post]

DASATINIB- A DRUG OF CHOICE

7062 | Jun 04 2012

INTRODUCTION Diverse types of cellular systems are there in human bodies that differ structurally and functionally from one another. Each cellular system is controlled by a variety of controllers called cell cycle regulatory proteins. Defective controllers may lead to abnormal cellular systems and the condition known as cancer may develop. Cancer may be of different types depending upon the defect in the cell cycle regulatory proteins. Cancer may also vary on the basis of stage of the defective condition. Many therapies have been devised in order to treat cancerous cells. Further research is also being done for developing better, more specific and less toxic therapies and to cope with the development of resistance in the defective cells against existing therapies. Besides resistance, metastasis is also another issue to be resolved in case of cancerous cells. Imatinib has been used against leukemia for several years but due to high levels of toxicity scientists discovered a new drug, called Dasatinib, for the same therapy. Dasatinib BMS-354825 is more efficient and less toxic as compared to Imatinib. The drug is being marketed by the name of Sprycel. As Dasatinib was discovered by Jagabandhu Das, it was named Dasatinib. Development of the drug was done by Squibb Company. [Read the Full Post]

NILOTINIB

6909 | May 30 2012

ROLE OF BCR-ABL TYROSINE KINASES IN CML: A chimeric BCR-ABL oncogene is obtained by the fusion of Abelson (ABL) tyrosine kinase (TK) gene and break-point cluster (BCR) gene, and here TK has been related to pathogenesis of CML (Chronic Myelogenous Leukemia), 90% of this debilitating disease involves chromosomal abnormalities leading to formation of so-called Philadelphia chromosome. As there is a confirmed participation of BCR-ABL TK in PH+ CML, different inhibitors that target this TK have registered remarkable success in treatment of CML and among them Nilotinib bcr-abl inhibitor is the most valuable one. It is a form of tyrosine kinase inhibitor and is a hydrochloride monohydrate salt. [Read the Full Post]

IMATINIB – INHIBITS MULTIPLE KINASES

6035 | May 07 2012

INTRODUCTION: SRC inhibitors are the molecules specific for targeting the non rector tyrosine kinase enzymes of SRC family and have the potential of inhibiting the 2 or more members of two SRC subfamilies, Fyn, Src. Fgr, Yes, Lck, Blk, Frk and Hck SRC kinases. These kinase enzymes take part in various pathways, so targeting them has became an attractive and valuable approach in the field of chemotherapy. Imatinib is commonly known as STI-571. Imatinib SRC inhibitor is a molecule originally named as STI571 and marketed by the company Novartis in the form of its mesylate salt hence known as STI-571 Imatinib Mesylate. This salt form is especially developed for targeting the cancer cells sparing the normal cells from them hence developed as personalized drug. [Read the Full Post]

NILOTINIB

4454 | Apr 08 2012

ROLE OF BCR-ABL IN CML BCR (break-point cluster) and (ABL) Abelson genes code for the protein tyrosine kinases that are involved in signal transduction fusion of these two genes occur when a philadalphia chromosome is formed after some mistake in the process of crossing over. This chimeric oncogene is known as BCR-ABL and is known to be involved in the development of leukemia especially (CML) Chronic Myelogenous Leukemia. This type of fusion is known to be responsible for almost 90% CML cases and is known as PH+ CML. The participation of BCR-ABL in PH+ CML has urged the scientists to inhibit this fusion protein. Different types of inhibitors targeting this oncogenic fusion protein have been registered. Nilotinib Src-bcr-Abl inhibitor is one of such inhibitors against CML. [Read the Full Post]

STAUROSPORINE: A PKC INHIBITOR

6280 | Mar 25 2012

STAUROSPORINE PROPERTIES AND ORIGIN: The discovery of Staurosporine was done during the research on a bacterium Streptomyces staurosporeus in 1977, this compound was identified as an antibiotic and now this molecules has been studied thoroughly. Another alternate name of this molecule is STS or Staurosporine AM-2282, its configuration and structure was identified by certain physical techniques such as analysis of X-ray. Staurosporine PKC inhibitor is also found as active against a good number of protein kinases (PKs), Staurosporine IC50 for PKA, PKC and PKG is 7.0 nM, 0.7 nM and 8.5 nM respectively. When Staurosporine is stored at -20 oC it’s stability remains un-affected for two years. This compound is soluble in DMSO. Molecular weight of Staurosporine is 466.53 and it is expensive as Staurosporine price for 1 mg is more than $500, however the price is variable from one Staurosporine supplierto other. Staurosporine PKC inhibitor is available easily and if someone wants to purchase Staurosporine for laboratory and research use one can buy Staurosporine easily. [Read the Full Post]

ENZASTAURIN AGAINST MALIGNANCIES

4140 | Mar 20 2012

Introduction: The Protein Kinase C family A cytosolic protein kinase isolated in the late 1970’s by the Nishizuka group of Kobe University, Japan has been found to be a key factor in the regulation of the cell cycle. Established as the protein kinase C family several isoforms have subsequently be isolated. These serine / threonine kinases are activated by the diacylglycerol (DAG) which is generated by the agonist induced hydrolysis of Trans-membrane G-protein kinases or tyrosine kinases. Activation of protein kinase C leads to a movement of the protein to the either the cytosolic skeleton or to the cellular membrane triggering a cascade of downstream signals which induce cell growth, differentiation or proliferation activities, this process appears to be mediated by the release of Ca2+. One of the key elements to be discovered concerning this protein was the discovery that phorbol esters were also a ligand for activating this protein; this created a direct link between PKC and the formation of various tumors. [Read the Full Post]

THIAZOVIVIN: THE PLURIPOTENCY INDUCER

4828 | 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]

FINGOLIMOD – THE IMMUNOMODULATOR

4657 | Mar 19 2012

Introduction: Fingolimod and Multiple Sclerosis One of the most widely used fungi in Chinese herbal medication is the ascomycete “Isaria sinclairii”. Known for its medical properties for centauries it was examined more closely after the immunosuppressant cyclosporin was discovered from a fungal source. From a screening of the extracts from this fungus came the molecule myriocin which demonstrated immunosuppressant properties as hope, however, it also killed the host in animal models. This molecule proved to be far too toxic for clinical use hence the molecule skeleton was used as a template to derive a series of derivatives in the effort to reduce the toxicity but preserve the immunosuppression potency. From this process came FTY720 which was researched pre-clinically in the area of transplant rejection, before being released in clinical trials as Fingolimod . [Read the Full Post]

IMATINIB – THE MULTI KINASE INHIBITOR

4037 | Mar 19 2012

Introduction: The kinase super family In recent years the broadening of technology has enabled researchers to investigate the role of ligands in relation to cellular responses. To achieve understanding the binding properties, conformation changes, receptor response and protein binding domains similarity have been extensively researched, most notably in the field of oncology. The protein kinases are not really a new discovery but the relationship between proteins is now beginning to be understood. Over 500 different distinct proteins exist under the super family heading of protein kinases. These proteins govern the growth, proliferation, differentiation and apoptosis of nearly all aspects of the mammalian system. The protein kinase family is subdivided into small related protein series that seem to work together to receive a signal from an extracellular source and translated this into cellular activity. [Read the Full Post]

FTY720 – THE IMMUNE CELLS’ TRAFFIC CONTROLLER

4169 | Mar 19 2012

Introduction: Multiple Sclerosis Multiple sclerosis is probably a condition that everybody has heard off but not many really understand the cause or nature of this destructive disease. Basically this disease is what is known as an inflammatory disease which affects area of the lining in the spinal cord or brain stem. The effect of this is the slow degradation of the functions of the spinal cord and brain stem. This means a loss of motor control, loss of communicative functions, loss of sight and digestive difficulties. Accompanying these debilitating symptoms are almost constant pain and fatigue, life quality of most suffers becomes very poor. There is currently no known cure for this disease, while treatment focuses on alleviating the symptoms or retarding the progression of the disease but always the end point is the same. Patients with this disease are known to try any form of treatment scientifically proven or not in the hope a remission can be triggered. Remission is the peculiar aspect of this disease in that it appears in phases with periods of relative peace in-between. However, relapses are usually progressively worse accumulating damage to essential functions that cannot be repaired. [Read the Full Post]

DASATINIB – THE DOUBLE-EDGED SWORD

5351 | Mar 13 2012

Introduction: BCR-ABL and SCR targets Researchers are continuously searching for the magic compound which will cure all diseases but most know that this is a physical impossibility. Every disease is different and especially cancers where even tumors of the same site / type can be radically different. In CML, AML and ALL a mutation in two chromosomes has been linked to the onset of these diseases in a proportion of patients. The defect is referred to as the “Philadelphia chromosome”, here a section of chromosome 9 and chromosome 22 have swapped places (translocated). The end result is that chromosome 9 is longer than it should be while chromosome 22 is shorter than it should be. The significance of this change is that the coding for the BCR gene and the ABL gene become mixed up (fused). The protein from this genetic fusion is referred to as the BCR-ABL fusion protein. Studies have shown that this protein is related to the protein kinase super family and has serine / threonine kinase activity, it also has phosphorylation activity for the cytoskeletal enzyme p21 Rac (Cdc42). Imatinib is a small molecule inhibitor of the ABL in Chronic Myeloid Leukemia, Acute Myeloid Leukemia and Acute Lymphoblast Leukemia tumors that has been proven very successful in the clinic. However, patients with the translocated gene demonstrate resistance to Imatinib due in part to the nature of fused BCR-ABL gene. [Read the Full Post]

Enzastaurin, as the inhibitor of PKC, may be a novel PNC medical therapy

4930 | Sep 29 2011

Pancreatic cancer is the fourth most common cause of cancer death both in the United States. Regarding the pathology, pancreatic cancer mainly includes exocrine pancreas cancers, pancreatic cystic neoplasms and endocrine pancreatic cancers. Pancreatic neuroendocrine cancers (PNC) account for less than 3% of pancreatic tumors and the main treatments are surgery, hormone therapy, chemotherapy and so on at this stage. However, It is still needed to search for effective treatments for PNC, and understand the molecular pathways regulating neuroendocrine tumor cell proliferation. [Read the Full Post]

Rosse, C., M. Linch, et al. (2010). "PKC and the control of localized signal dynamics." Nat Rev Mol Cell Biol 11(2): 103-112.

5053 | Jul 19 2011

This review which was published in Nature review summary the role of PKC in different pathways and show the importance of PKCs in controlling spatial resolution in signaling processes using the MET and STAT3 example. [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.

5726 | 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]

Mackay, H. J. and C. J. Twelves (2007). "Targeting the protein kinase C family: are we there yet?" Nat Rev Cancer 7(7): 554-562.

4655 | May 18 2011

This review summary the development of PKC inhibitors for cancer. It also explains the difficulties we meet. The author also give a prospect of PKC inhibitors. [Read the Full Post]

Ren, R. (2005). "Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia." Nat Rev Cancer 5(3): 172-183.

4316 | Apr 15 2011

The review which was published in Nature Review Cancer introduces the relationships between CML and BCR-ABL. The researchers introduce not only the BCR–ABL and oncogenic activities of BCR–ABL, roles of BCR–ABL domains in leukaemogenesis, but pathways downstream of BCR–ABL as well. [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.

4944 | 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]