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Cytoskeletal Signaling

Alkylation of Staurosporine to Derive a Kinase Probe for Fluorescence Applications

1 | 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]

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

5 | Aug 11 2019

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

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

43 | 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]

A Phase II Trial of Neoadjuvant MK-2206, an AKT Inhibitor, with Anastrozole in Clinical Stage II or III PIK3CA-Mutant ER-Positive and HER2-Negative Breast Cancer

6 | Jul 24 2019

Ma CX et al. indicated that MK-2206 is unlikely to add to the efficacy of anastrozole alone in PIK3CA-mutant ER+ breast cancer and should not be studied further in the target patient population. [Read the Full Post]

Maintenance Defactinib Versus Placebo After First-Line Chemotherapy in Patients With Merlin-Stratified Pleural Mesothelioma: COMMAND-A Double-Blind, Randomized, Phase II Study

12 | Jul 07 2019

Fennell DA et al. indicated that neither PFS nor OS was improved by defactinib after first-line chemotherapy in patients with merlin-low MPM. Defactinibcannot be recommended as maintenance therapy for advanced MPM. [Read the Full Post]

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

17 | 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

38 | 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]

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

16 | Jun 19 2019

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

Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation

64 | 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]

NVP-AUY922, a novel HSP90 inhibitor, inhibits the progression of malignant pheochromocytoma in vitro and in vivo

57 | May 31 2019

Lian J et al. showed that NVP-AUY922 exhibits potent anti-PCC activities in vitro and in vivo and represents a promising therapeutic small molecule for treating malignant PCC. [Read the Full Post]

Quantitative phosphoproteomic analysis of acquired cancer drug resistance to pazopanib and dasatinib

68 | May 26 2019

Vyse S et al. provided a useful resource detailing the candidate signalling determinants of acquired TKI resistance; and reveals a therapeutic approach of inhibiting HSP90 function as a means of salvage therapy to overcome pazopanib and dasatinib resistance. [Read the Full Post]

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

49 | 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]

Drug sensitivity profiling identifies potential therapies for lymphoproliferative disorders with overactive JAK/STAT3 signaling

87 | May 06 2019

Kuusanmäki H et al. showed alternative approaches to inhibit STAT3 activity and suggest Hsp90 as a therapeutic target in lymphoproliferative disorders with constitutively active STAT3. [Read the Full Post]

High-throughput Chemical Screening Identifies Focal Adhesion Kinase and Aurora Kinase B Inhibition as a Synergistic Treatment Combination in Ewing Sarcoma

66 | Apr 14 2019

Wang S et al. indicated that FAK and Aurora kinase B inhibitors synergistically impair Ewing sarcoma cell viability and significantly inhibit tumor progression. This study provides preclinical support for the consideration of a clinical trial testing the safety and efficacy of this combination for patients with Ewing sarcoma. [Read the Full Post]

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

73 | Apr 10 2019

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

Oncogenic role of ABHD5 in endometrial cancer

102 | Apr 04 2019

Zhou Q suggested that ABHD5 may play an oncogenic role in endometrial cancer via the AKT pathway. [Read the Full Post]

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

90 | Mar 12 2019

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

Combination AZD5363 with Enzalutamide Significantly Delays Enzalutamide-resistant Prostate Cancer in Preclinical Models

96 | Mar 11 2019

Toren P et al. provided preclinical data to support evaluation of combination targeting of the PI3K/Akt pathway and the androgen-receptor axis in the clinic using AZD5363 and ENZ, respectively. [Read the Full Post]

Combination treatment with docetaxel and histone deacetylase inhibitors downregulates androgen receptor signaling in castration-resistant prostate cancer

67 | Mar 06 2019

Park SE et al. suggested that docetaxel, in combination with HDACIs, suppressed the expression and nuclear translocation of AR-FL and AR-Vs and showed synergistic anti-proliferative effect in CRPC cells. This combination therapy may be useful for the treatment of patients with CRPC. [Read the Full Post]

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

95 | 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]

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

270 | Mar 03 2019

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

Tanespimycin as antitumor therapy

163 | Feb 24 2019

Dimopoulos MA et al. showed that tanespimycin represents a promising new agent for the treatment of relapsed/refractory MM. Results of ongoing and future trials will determine the role of tanespimycin both in MM and other malignancies, including breast cancer. [Read the Full Post]

Effects of cancer-associated point mutations on the structure, function, and stability of succinate dehydrogenase A

150 | Feb 22 2019

Cao ZF et al. provided information important for understanding the molecular mechanisms of SDHA mutations in tumors. [Read the Full Post]

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

120 | Feb 21 2019

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

ABCB1 Mediates Cabazitaxel-Docetaxel Cross-Resistance in Advanced Prostate Cancer

100 | Feb 16 2019

Lombard AP et al. suggested the potential in using combinations of antiandrogens with cabazitaxel for increased effect in treating advanced CRPC. [Read the Full Post]

27 T ultra-high static magnetic field changes orientation and morphology of mitotic spindles in human cells

85 | Jan 25 2019

Zhang L et al. not only found that ultra-high magnetic field can change the orientation and morphology of mitotic spindles, but also provided a tool to probe the role of spindle orientation and perturbation in developmental and cancer biology. [Read the Full Post]

Pharmacology and pharmacokinetics of imatinib in pediatric patients

300 | 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]

Ex vivo AKT-inhibition facilitates generation of polyfunctional stem cell memory-like CD8+ T cells for adoptive immunotherapy

0 | Jan 21 2019

Mousset CM et al. demonstrated that AKT-inhibitors with different modality of action promote the ex vivo generation of stem cell memory-like CD8+ T cells with a unique metabolic profile and retained polyfunctionality. Akt-inhibitor VIII and GDC-0068 outperformed other inhibitors, and are therefore promising candidates for ex vivo generation of superior tumor-reactive T cells for adoptive immunotherapy in cancer patients. [Read the Full Post]

A phase II, randomised study of mFOLFOX6 with or without the Akt inhibitor ipatasertib in patients with locally advanced or metastatic gastric or gastroesophageal junction cancer

260 | Jan 18 2019

Bang YJ et al. showed that Ipatasertib/mFOLFOX6 compared with placebo/mFOLFOX6 did not improve PFS in unselected or biomarker-selected patients. No unexpected safety concerns were observed. [Read the Full Post]

Inhibition of related JAK/STAT pathways with molecular targeted drugs shows strong synergy with ruxolitinib in chronic myeloproliferative neoplasm

246 | Jan 08 2019

Barrio S et al. showed the combination of ruxolitinib with inhibitors that target these pathways has a strong synergistic effect, which may be due to decreased activation of the common effector, STAT5. [Read the Full Post]

Selective HDAC inhibition by ACY-241 enhances the activity of paclitaxel in solid tumor models

91 | Jan 04 2019

Huang P et al. provided a strong rationale for clinical development of this combination in patients with advanced solid tumors. [Read the Full Post]

WNT5A: a motility-promoting factor in Hodgkin lymphoma

187 | Dec 22 2018

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

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

255 | Dec 15 2018

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

Identification of DNA-PKcs as a primary resistance factor of TIC10 in hepatocellular carcinoma cells

195 | Dec 14 2018

Cheng L et al. found that TIC10 showed promising anti-HCC activity, alone or together with DNA-PKcs inhibitors. [Read the Full Post]

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

0 | Nov 27 2018

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

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

349 | Nov 23 2018

Park GB et al. found that LIMK1 could be a common therapeutic target of ovarian cancer metastasis. [Read the Full Post]

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

1553 | 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]

Identification of approved and investigational drugs that inhibit hypoxia-inducible factor-1 signaling

0 | Nov 17 2018

Hsu CW et al. underlined the importance of developing a battery of robust assay platforms and confirmation studies that focus on endogenous protein targets so that only relevant and reliable data will be taken into pre-clinical and clinical studies. [Read the Full Post]

Stathmin decreases cholangiocarcinoma cell line sensitivity to staurosporine-triggered apoptosis via the induction of ERK and Akt signaling

252 | Nov 04 2018

Wang Y et al. indicated that understanding the regulation of anti-apoptosis effect by Stathmin might provide new insight into how to overcome therapeutic resistance in cholangiocarcinoma. [Read the Full Post]

Curdione attenuates thrombin-induced human platelet activation: β1-tubulin as a potential therapeutic target

366 | Oct 24 2018

Zhang D et al. indicated that β1-tubulin may be a potential target of curdione, which attenuates thrombin-induced human platelet activation. [Read the Full Post]

Reversible lysine-specific demethylase 1 antagonist HCI-2509 inhibits growth and decreases c-MYC in castration- and docetaxel-resistant prostate cancer cells

0 | Oct 18 2018

Gupta S et al. found that LSD1 inhibition with HCI-2509 decreases the c-MYC level in poorly differentiated prostate cancer cell lines and has a therapeutic potential in castration- and docetaxel-resistant prostate cancer. [Read the Full Post]

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

732 | 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]

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

250 | Oct 12 2018

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

Synergistic cytotoxicity of BIIB021 with triptolide through suppression of PI3K/Akt/mTOR and NF-κB signal pathways in thyroid carcinoma cells

1107 | Oct 07 2018

Kim SH et al. suggested that BIIB021 has a cytotoxic activity accompanied by regulation of hsp90 client proteins in thyroid carcinoma cells. Moreover, the synergism between BIIB021 and triptolide in induction of cytotoxicity is associated with the inhibition of PI3K/Akt/mTOR and NF-κB signal pathways, the underexpression of survivin and the activation of DNA damage response in thyroid carcinoma cells. [Read the Full Post]

Efficacy of focal adhesion kinase inhibition in non-small cell lung cancer with oncogenically activated MAPK pathways

335 | Sep 27 2018

Zhang H, et al. demonstrated efficacy both in vitro and in vivo in lung cancers with either oncogenic RAS or EGFR mutations. In addition, FAK inhibition in combination with inhibitors of Bcl-2 family of anti-apoptotic proteins has synergistic activity in these MAPK-activated non-small cell lung cancer cell line models. [Read the Full Post]

Inhibition of adhesion, migration and of α5β1 integrin in the HCT-116 colorectal cancer cells treated with the ruthenium drug NAMI-A

884 | Sep 26 2018

Pelillo C et al. supported the new concept that metal-based drugs can inhibit tumour metastases through targeting of integrins and of other proteins which mediate tumour progression-related cell functions such as adhesion and migration. [Read the Full Post]

Novel Allosteric Pathway of Eg5 Regulation Identified through Multivariate Statistical Analysis of Hydrogen-Exchange Mass Spectrometry (HX-MS) Ligand Screening Data

0 | Sep 02 2018

Sheff JG et al. suggested that a different approach to inhibitor development may be fruitful. [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

1094 | 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]

Novel Allosteric Pathway of Eg5 Regulation Identified through Multivariate Statistical Analysis of Hydrogen-Exchange Mass Spectrometry (HX-MS) Ligand Screening Data

0 | Aug 24 2018

Sheff JG et al. suggested that a different approach to inhibitor development may be fruitful. [Read the Full Post]

Honokiol Induces Apoptosis, G1 Arrest, and Autophagy in KRAS Mutant Lung Cancer Cells

633 | Aug 22 2018

Luo LX et al. indicated these results broaden our understanding of the mechanisms on honokiol effects in lung cancer, and reinforce the possibility of its potential anticancer benefit as a popular Chinese herbal medicine (CHM). [Read the Full Post]

Novel Allosteric Pathway of Eg5 Regulation Identified through Multivariate Statistical Analysis of Hydrogen-Exchange Mass Spectrometry (HX-MS) Ligand Screening Data

0 | Aug 15 2018

Sheff JG et al. suggested that a different approach to inhibitor development may be fruitful. [Read the Full Post]

Loss-of-function screens of druggable targetome against cancer stem-like cells

0 | Aug 14 2018

Song M et al. indicated that small interfering RNA (siRNA)-based screening of ∼4800 druggable genes in 3-dimensional CSLC cultures in comparison to 2-dimensional bulk cultures of U87 glioma cells revealed 3 groups of genes essential for the following: survival of the CSLC population only, bulk-cultured population only, or both populations. [Read the Full Post]

Loss-of-function screens of druggable targetome against cancer stem-like cells

0 | Aug 13 2018

Song M et al. provided a useful resource that can be exploited for the selective elimination of CSLCs.-Song, M., Lee, H., Nam, M.-H., Jeong, E., Kim, S., Hong, Y., Kim, N., Yim, H. Y., Yoo, Y.-J., Kim, J. S., Kim, J.-S., Cho, Y.-Y., Mills, G. B., Kim, W.-Y., Yoon, S. Loss-of-function screens of druggable targetome against cancer stem-like cells. [Read the Full Post]

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

408 | 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]

Small Molecular TRAIL Inducer ONC201 Induces Death in Lung Cancer Cells: A Preclinical Study

554 | Jul 17 2018

Feng Y et al. demonstrated the potent anti-lung cancer activity by ONC201. [Read the Full Post]

PI3Kα isoform-dependent activation of RhoA regulates Wnt5a-induced osteosarcoma cell migration

0 | Jul 15 2018

Zhang A et al. demonstrated that RhoA acts as the downstream of PI3K/Akt signaling (specific PI3Kα, Akt1 and Akt2 isoforms) and mediated Wnt5a-induced the migration of osteosarcoma cells. [Read the Full Post]

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

1727 | 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

789 | 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

867 | 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]

The non-Geldanamycin Hsp90 inhibitors enhanced the antifungal activity of fluconazole

572 | Jun 09 2018

Li L et al. showed that the activity of FLC against C. albicans biofilm formation in vitro is significantly enhanced when used in combination with HSP990. [Read the Full Post]

Aurora kinase A revives dormant laryngeal squamous cell carcinoma cells via FAK/PI3K/Akt pathway activation

572 | May 29 2018

Yang LY et al. concluded that AURKA may revive dormant tumor cells via FAK/PI3K/Akt pathway activation, thereby promoting migration and invasion in laryngeal cancer. AURKA/FAK/PI3K/Akt inhibitors may thus represent potential targets for clinical LSCC treatment. [Read the Full Post]

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

0 | May 27 2018

Chen YX et al. proposed that SC-79 treatment to rescue Akt activation could be tested in the clinic as a potential therapeutic approach to preventing the development of alcohol-induced ONFH. [Read the Full Post]

SC79 protects retinal pigment epithelium cells from UV radiation via activating Akt-Nrf2 signaling

508 | May 27 2018

Gong YQ et al. suggest that SC79 protects RPE cells from UV damages possibly via activating Akt-Nrf2 signaling axis. [Read the Full Post]

Unique roles of Akt1 and Akt2 in IGF-IR mediated lung tumorigenesis

875 | May 21 2018

Franks SE et al. suggested that compounds selectively targeting AKT1 may prove more effective than compounds that inhibit all three AKT isoforms at least in the treatment of lung adenocarcinoma. [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]

PI3Kα isoform-dependent activation of RhoA regulates Wnt5a-induced osteosarcoma cell migration

2608 | May 20 2018

Zhang A et al. demonstrated that RhoA acts as the downstream of PI3K/Akt signaling (specific PI3Kα, Akt1 and Akt2 isoforms) and mediated Wnt5a-induced the migration of osteosarcoma cells. [Read the Full Post]

Oncogenic epithelial cell-derived exosomes containing Rac1 and PAK2 induce angiogenesis in recipient endothelial cells

0 | May 07 2018

Gopal SK et al. demonstrated for the first time that oncogenic cells undergoing EMT can communicate with endothelial cells via exosomes, and establish exosomal Rac1/PAK2 as angiogenic promoters that may function from early stages of the metastatic cascade. [Read the Full Post]

Phosphoproteome Profiling of SH-SY5y Neuroblastoma Cells Treated with Anesthetics: Sevoflurane and Isoflurane Affect the Phosphorylation of Proteins Involved in Cytoskeletal Regulation

281 | May 07 2018

Lee J et al. showed that anesthetics affect the phosphorylation of proteins involved in cytoskeletal remodeling pathways. [Read the Full Post]

Co-occurring Mutations of Tumor Suppressor Genes, LATS2 and NF2, in Malignant Pleural Mesothelioma

663 | May 05 2018

Tranchant R et al. identified a new MPM molecular subgroup that shares common genetic and transcriptomic characteristics. Our results made it possible to highlight a greater sensitivity to an anticancer compound for this MPM subgroup and to identify a specific potential biomarker. [Read the Full Post]

Uterine RAC1 via Pak1-ERM signaling directs normal luminal epithelial integrity conducive to on-time embryo implantation in mice

298 | May 03 2018

Tu Z et al. demonstrated that Rac1 via P38 MAPK signaling ensures timely epithelial apoptotic death at postimplantation. Besides uncovering a potentially important molecule machinery governing uterine luminal integrity for embryo implantation, our finding has high clinical relevance, because Rac1 is essential for normal endometrial functions in women. [Read the Full Post]

Lipopolysaccharide and heat stress impair the estradiol biosynthesis in granulosa cells via increase of HSP70 and inhibition of smad3 phosphorylation and nuclear translocation

669 | May 01 2018

Li H et al. suggested that LPS and heat stress could impair estradiol biosynthesis in GCs via increased HSP70 and indirect inhibition of Smad3 phosphorylation and nuclear translocation. [Read the Full Post]

Focal adhesion kinase depletion reduces human hepatocellular carcinoma growth by repressing enhancer of zeste homolog 2

513 | May 01 2018

Gnani D et al. demonstrated that FAK depletion reduces HCC cell growth by affecting cancer-promoting genes including the pro-oncogene EZH2. Furthermore, we unveil a novel unprecedented FAK/EZH2 crosstalk in HCC cells, thus identifying a targetable network paving the way for new anticancer therapies. [Read the Full Post]

Mdivi-1 Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats, Possibly via Inhibition of Drp1-Activated Mitochondrial Fission and Oxidative Stress

303 | Apr 16 2018

Wu P et al. suggested that Mdivi-1 exerts neuroprotective effects against cell death induced by SAH and the underlying mechanism may be inhibition of Drp1-activated mitochondrial fission and oxidative stress. [Read the Full Post]

Polyphyllin I induces mitophagic and apoptotic cell death in human breast cancer cells by increasing mitochondrial PINK1 levels

329 | Apr 15 2018

Li GB, et al. describe the mechanism by which PINK1 contributes to polyphyllin I-induced mitophagy and apoptosis and suggest that polyphyllin I may be an effective drug for breast cancer treatment. [Read the Full Post]

Inhibition of autophagy enhances effects of PF-04691502 on apoptosis and DNA damage of lung cancer cells

1620 | Apr 14 2018

Fei HR et al. suggested that a strategy of blocking autophagy to enhance the activity of PI3K/mTOR inhibitors warrants further attention in treatment of NSCLC cells. [Read the Full Post]

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

1778 | 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]

Oncogenic epithelial cell-derived exosomes containing Rac1 and PAK2 induce angiogenesis in recipient endothelial cells

407 | Mar 19 2018

Gopal SK et al. demonstrated for the first time that oncogenic cells undergoing EMT can communicate with endothelial cells via exosomes, and establish exosomal Rac1/PAK2 as angiogenic promoters that may function from early stages of the metastatic cascade. [Read the Full Post]

Prolactin signaling through focal adhesion complexes is amplified by stiff extracellular matrices in breast cancer cells

588 | Mar 18 2018

Barcus CE et al. suggested that PRL signaling to FAK and SFKs may be useful targets in clinical aggressive ERα+ breast carcinomas. [Read the Full Post]

METTL13 is downregulated in bladder carcinoma and suppresses cell proliferation, migration and invasion

0 | Mar 18 2018

Zhang Z et al. identified METTL13 as a tumor suppressor and might provide promising approaches for bladder cancer treatment and prevention. [Read the Full Post]

Hypoxia-inducible factor 1α (HIF-1α) and reactive oxygen species (ROS) mediates radiation-induced invasiveness through the SDF-1α/CXCR4 pathway in non-small cell lung carcinoma cells

355 | Mar 17 2018

Gu Q et al. found the underlying mechanisms of the irradiation-enhanced invasiveness of NSCLC cells. [Read the Full Post]

Epothilone B induces apoptosis and enhances apoptotic effects of ABT-737 on human cancer cells via PI3K/AKT/mTOR pathway

0 | Mar 16 2018

Li YL et al. indicated that ABT-737 may be a pertinent sensitizer to epothilone B, and the strategy of combining epothilone B with ABT-737 appears to be an attractive option for overcoming the resistance and neurotoxicity of epothilone B. [Read the Full Post]

AURKA promotes cell migration and invasion of head and neck squamous cell carcinoma through regulation of the AURKA/Akt/FAK signaling pathway

0 | Mar 04 2018

Wu J, et al. indicated AURKA activates FAK through the AURKA/Akt/FAK signaling pathway, promoting the migration and invasion of HNSCC cells, which may subsequently provide a novel approach for the treatment of HNSCC. [Read the Full Post]

AURKA promotes cell migration and invasion of head and neck squamous cell carcinoma through regulation of the AURKA/Akt/FAK signaling pathway

630 | Mar 02 2018

Wu J et al. found that AURKA activates FAK through the AURKA/Akt/FAK signaling pathway, promoting the migration and invasion of HNSCC cells, which may subsequently provide a novel approach for the treatment of HNSCC. [Read the Full Post]

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

655 | Feb 24 2018

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

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

644 | Feb 22 2018

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

The effect of increased lipoproteins levels on the disposition of vincristine in rat

725 | Feb 20 2018

Khalil HA et al. found that HL can potentiate another drug-drug or drug-disease interaction involving VCR warrants further studying and monitoring to ensure therapeutic safety and efficiency. [Read the Full Post]

E-cadherin expression is correlated with focal adhesion kinase inhibitor resistance in Merlin-negative malignant mesothelioma cells

640 | Feb 19 2018

Kato T et al. suggested that E-cadherin serves as a predictive biomarker for molecular target therapy with FAK inhibitors for patients with mesothelioma and that its expression endows MM cells with resistance to FAK inhibitors. [Read the Full Post]

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

783 | 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

1542 | 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]

Three-dimensional matrix stiffness and adhesive ligands affect cancer cell response to toxins

477 | Feb 11 2018

Zustiak SP et al. indicated that both 3D matrix stiffness and cell-matrix adhesions are important parameters in the design of more predictive in vitro platforms for drug development and toxicity screening. [Read the Full Post]

ART3 regulates triple-negative breast cancer cell function via activation of Akt and ERK pathways

858 | Jan 30 2018

Tan L et al. showed that ART 3 overexpression activated AKT and ERK in vitro and in xenograft tumors. Together, our findings demonstrate that ART3 is a critical TNBC marker with functional significance. [Read the Full Post]

Targeting MUC1-C inhibits the AKT-S6K1-elF4A pathway regulating TIGAR translation in colorectal cancer

748 | Jan 29 2018

Ahmad R et al. indicated that MUC1-C is a potential target for the treatment of colorectal cancer. Colorectal cancer patients who overexpress MUC1-C may be candidates for treatment with the MUC1-C inhibitor alone or in combination therapy with other agents. [Read the Full Post]

Targeted inhibition of Focal Adhesion Kinase Attenuates Cardiac Fibrosis and Preserves Heart Function in Adverse Cardiac Remodeling

527 | Jan 21 2018

Zhang J et al. suggested that pharmacological inhibition of FAK may become an effective therapeutic strategy against adverse fibrosis. [Read the Full Post]

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

1749 | 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]

Noninvasive Bioluminescence Imaging of AKT Kinase Activity in Subcutaneous and Orthotopic NSCLC Xenografts: Correlation of AKT Activity with Tumor Growth Kinetics

652 | Jan 01 2018

Suchowski K et al. demonstrated that BAR can be applied to study drug dosing, drug combinations, and treatment efficacy in orthotopic mouse lung tumor models. [Read the Full Post]

Lenvatinib enhances the antitumor effects of paclitaxel in anaplastic thyroid cancer

799 | Dec 22 2017

Jing C et al. suggested that lenvatinib/paclitaxel combination may be a promising candidate therapeutic strategy for ATC. [Read the Full Post]

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

1634 | 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]

Perifosine and ABT-737 synergistically inhibit lung cancer cells in vitro and in vivo

753 | Dec 18 2017

Shen J et al. supported the feasibility of further investigation of the perifosine plus ABT-737 regimen in future lung cancer clinical tests. [Read the Full Post]

Proteome and Acetylome Analysis Identifies Novel Pathways and Targets Regulated by Perifosine in Neuroblastoma

753 | Dec 17 2017

Gu X et al. details the impact of perifosine on proteome and lysine acetylome in SK-N-AS cells and expands our understanding of the mechanisms of perifosine action in neuroblastoma. [Read the Full Post]

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

671 | Dec 14 2017

Chen X et al. showed that mitotic phosphorylation-deficient mutant MST2-S385A possesses higher activity in suppressing cell proliferation and anchorage-independent growth in vitro and tumorigenesis in vivo. Together, our findings reveal a novel layer of regulation for MST2 in mitosis and its role in tumorigenesis. [Read the Full Post]

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

3173 | Dec 10 2017

Abraham SA et al. found that LSCs can be eradicated. [Read the Full Post]

Differential regulation of mTOR signaling determines sensitivity to AKT inhibition in diffuse large B cell lymphoma

949 | Dec 08 2017

Combined inhibition of AKT and BTK, PIM2, or S6K1 proved to be an effective strategy to overcome resistance to AKT inhibition in DLBCL. [Read the Full Post]

Optogenetic clustering of CNK1 reveals mechanistic insights in RAF and AKT signalling controlling cell fate decisions

832 | Dec 08 2017

Fischer A et al. found that CNK1 expression, CNK1 clustering and the thereto related differential signalling processes decide on proliferation and differentiation in a cell type- and cell stage-dependent manner by orchestrating AKT and RAF signalling. [Read the Full Post]

Autophagy prevention sensitizes AKTi-1/2-induced anti-hepatocellular carcinoma cell activity in vitro and in vivo

0 | Nov 30 2017

Zhang Q et al. demonstrated that autophagy activation serves as a main resistance factor of AKTi-1/2 in HCC cells. Autophagy prevention therefore sensitizes AKTi-1/2-induced anti-HCC activity in vitro and in vivo. [Read the Full Post]

HSP90 activity is required for MLKL oligomerisation and membrane translocation and the induction of necroptotic cell death

993 | Nov 29 2017

Jacobsen AV et al. implicated HSP90 as a modulator of necroptosis at the level of MLKL, a function that complements HSP90's previously demonstrated modulation of the upstream necroptosis effector kinases, RIPK1 and RIPK3. [Read the Full Post]

Autophagy prevention sensitizes AKTi-1/2-induced anti-hepatocellular carcinoma cell activity in vitro and in vivo

677 | Nov 29 2017

Zhang Q et al. demonstrate that autophagy activation serves as a main resistance factor of AKTi-1/2 in HCC cells. [Read the Full Post]

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

888 | Nov 26 2017

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

The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms

1272 | Nov 25 2017

Paraiso KH et al.showed that HSP90 inhibition may be a highly effective strategy at managing the diverse array of resistance mechanisms being reported to BRAF inhibitors and appears to be more effective at restoring BIM expression and downregulating Mcl-1 expression than combined MEK/PI3K inhibitor therapy. [Read the Full Post]

Hsp90β promoted endothelial cell-dependent tumor angiogenesis in hepatocellular carcinoma

1047 | Nov 24 2017

Meng J et al. investigated the correlation between Hsp90β expression and CD31+ endothelial cell-dependent vessel density. [Read the Full Post]

Hyperinsulinemia enhances interleukin-17-induced inflammation to promote prostate cancer development in obese mice through inhibiting glycogen synthase kinase 3-mediated phosphorylation and degradation of interleukin-17 receptor

615 | Nov 23 2017

Liu S et al.revealed a mechanism underlying the intensified inflammation in obesity and obesity-associated development of aggressive prostate cancer, suggesting that targeting GSK3 may be a potential therapeutic approach to suppress IL-17-mediated inflammation in the prevention and treatment of prostate cancer, particularly in obese men. [Read the Full Post]

Targeting protein kinase C in mantle cell lymphoma

944 | 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]

HSP90 Shapes the Consequences of Human Genetic Variation

0 | Nov 14 2017

Karras GI et al. provided one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. [Read the Full Post]

Novel Allosteric Pathway of Eg5 Regulation Identified through Multivariate Statistical Analysis of Hydrogen-Exchange Mass Spectrometry (HX-MS) Ligand Screening Data

498 | Nov 11 2017

Sheff JG et al. suggested that a different approach to inhibitor development may be fruitful. [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]

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

0 | Oct 31 2017

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

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

941 | Oct 30 2017

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

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]

Canonical hedgehog signalling regulates hepatic stellate cell-mediated angiogenesis in liver fibrosis

1173 | Oct 16 2017

Zhang F et al. provided evidence that the canonical hedgehog pathway controlled HSC-mediated liver angiogenesis. Selective inhibition of HSC hedgehog signalling could be a promising therapeutic approach for hepatic fibrosis. [Read the Full Post]

Antagonizing Integrin β3 Increases Immunosuppression in Cancer

566 | Oct 13 2017

Su X et al. suggest that effects of integrin β3 therapies on immune cells should be considered to improve outcomes. [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]

Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15

1796 | Sep 30 2017

Here Han T et al. showed that indisulam promotes the recruitment of RBM39 (RNA binding motif protein 39) to the CUL4-DCAF15 E3 ubiquitin ligase, leading to RBM39 polyubiquitination and proteasomal degradation. [Read the Full Post]

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

1104 | Sep 29 2017

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

HSP90 Shapes the Consequences of Human Genetic Variation

0 | Sep 26 2017

Karras GI et al. provided one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. [Read the Full Post]

HSP90 Shapes the Consequences of Human Genetic Variation

1167 | Sep 25 2017

Karras GI et al. provided one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. [Read the Full Post]

Hyperthermia reduces migration of osteosarcoma by suppression of autocrine motility factor

1212 | Sep 09 2017

Nakajima K et al. indicated hyperthermia reduced AMF expression and tumor cell motility via HSP27 and may therefore be applied as osteosarcoma treatment. [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

2178 | 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]

miR-18a promotes cell proliferation of esophageal squamous cell carcinoma cells by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis

0 | Aug 25 2017

Zhang W et al. demonstrated the upregulation of miR-18a promoted cell proliferation by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis, suggesting that small molecule inhibitors of AKT-mTOR signaling are potential agents for the treatment of ESCC patients with upregulation of miR-17-92 cluster. [Read the Full Post]

Downregulation of GLUT4 contributes to effective intervention of estrogen receptor-negative/HER2-overexpressing early stage breast disease progression by lapatinib

0 | Aug 19 2017

Acharya S et al. indicated that lapatinib, through its inhibition of key signaling pathways and tumor-promoting metabolic events, is a promising agent for the prevention/early intervention of ER-/HER2+ breast cancer progression. [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

1885 | 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

1934 | 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

2094 | 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

2062 | 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]

Xanthatin anti-tumor cytotoxicity is mediated via glycogen synthase kinase-3β and β-catenin.

0 | Jul 22 2017

Tao L et al. provided insight into how xanthatin and related molecules could be effectively targeted toward certain tumors. [Read the Full Post]

A PGC1α-mediated transcriptional axis suppresses melanoma metastasis

2157 | Jun 23 2017

Luo C et al. revealed that PGC1α maintains mitochondrial energetic metabolism and suppresses metastasis through direct regulation of parallel acting transcriptional programs. [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

4568 | 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]

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

1410 | Jun 13 2017

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

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

2568 | Jun 12 2017

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

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

1419 | Jun 08 2017

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

A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

0 | Jun 05 2017

Gillan V et al. provided proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties. [Read the Full Post]

The antitumor toxin CD437 is a direct inhibitor of DNA polymerase α

2631 | Jun 04 2017

Han T et al. found that CD437 is a retinoid-like small molecule that selectively induces apoptosis in cancer cells, but not in normal cells, through an unknown mechanism. [Read the Full Post]

Reversible lysine-specific demethylase 1 antagonist HCI-2509 inhibits growth and decreases c-MYC in castration- and docetaxel-resistant prostate cancer cells

846 | May 30 2017

Gupta S et al. found that LSD1 inhibition with HCI-2509 decreases the c-MYC level in poorly differentiated prostate cancer cell lines and has a therapeutic potential in castration- and docetaxel-resistant prostate cancer. [Read the Full Post]

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

1605 | 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]

Rictor/mTORC2 Drives Progression and Therapeutic Resistance of HER2-Amplified Breast Cancers

1389 | May 18 2017

Morrison-Joly M et al. found that Rictor/mTORC2 signaling drives Akt-dependent tumor progression in HER2-amplified breast cancers, rationalizing clinical investigation of dual mTORC1/2 kinase inhibitors and developing mTORC2-specific inhibitors for use in this setting. [Read the Full Post]

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

2830 | 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

2608 | 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]

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

0 | May 08 2017

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

Epidermal Growth Factor Receptor Mutation Enhances Expression of Cadherin-5 in Lung Cancer Cells

0 | May 06 2017

Hung MS et al. provided an insight into the association of mutant EGFR and CDH5 expression in lung cancer and aid further development of target therapy for NSCLC in the future. [Read the Full Post]

Uroguanylin modulates (Na(+)+K(+))ATPase in a proximal tubule cell line: Interactions among the cGMP/protein kinase G, cAMP/protein kinase A, and mTOR pathways.

1091 | May 01 2017

Arnaud-Batista FJ et al suggested that the molecular mechanism of action of UGN on sodium reabsorption in PT cells is more complex than previously thought. We propose that PKG-dependent activation of PKA leads to the inhibition of the mTORC2/PKB/mTORC1/S6K pathway, an important signaling pathway involved in the maintenance of the PT sodium pump expression and activity. [Read the Full Post]

Epidermal Growth Factor Receptor Mutation Enhances Expression of Cadherin-5 in Lung Cancer Cells

1213 | Apr 29 2017

Hung MS et al. provided an insight into the association of mutant EGFR and CDH5 expression in lung cancer and aid further development of target therapy for NSCLC in the future. [Read the Full Post]

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

0 | Apr 28 2017

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

Activation of G protein-coupled receptor 30 by thiodiphenol promotes proliferation of estrogen receptor α-positive breast cancer cells

2465 | Apr 20 2017

Lei B et al. indicated a novel mechanism through which TDP may exert relevant estrogenic action in ERα positive cancer cells. [Read the Full Post]

Dual Targeting of Akt and mTORC1 Impairs Repair of DNA Double-Strand Breaks and Increases Radiation Sensitivity of Human Tumor Cells

0 | Apr 19 2017

Holler M et al suggested that dual targeting of mTORC1 and Akt1 inhibits repair of DNA-DSB leading to radiosensitization of solid tumor cells. [Read the Full Post]

Inhibition of Phospho-S6 Kinase, a Protein Involved in the Compensatory Adaptive Response, Increases the Efficacy of Paclitaxel in Reducing the Viability of Matrix-Attached Ovarian Cancer Cells.

2574 | Apr 17 2017

Choi JI et al found that addition of BX795 or CCT128930 to inhibit pS6 (S240/S244) or pS6 (S235/S236) restricted the compensatory adaptive response to paclitaxel in HeyA8 and SKOV3 cells. These inhibitors increased the efficacy of paclitaxel in reducing cancer cell viability. [Read the Full Post]

A causal link from ALK to hexokinase II overexpression and hyperactive glycolysis in EML4-ALK-positive lung cancer.

0 | Apr 16 2017

Ma Y et al revealed a novel EML4-ALK-HIF1α-HK2 cascade to enhance glucose metabolism in EML4-ALK-positive NSCLC. [Read the Full Post]

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

5857 | 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]

Centrosomal Protein of 55 Regulates Glucose Metabolism, Proliferation and Apoptosis of Glioma Cells via the Akt/mTOR Signaling Pathway

952 | Apr 08 2017

Wang G et al. found that CEP55 regulates glucose metabolism, proliferation and apoptosis of glioma cells via the Akt/mTOR signaling pathway, and its promotive effect on glioma tumorigenesis can be a potential target for glioma therapy in the future. [Read the Full Post]

A Repurposing Strategy for Hsp90 Inhibitors Demonstrates Their Potency against Filarial Nematodes

1 | Mar 27 2017

Gillan V et al provided proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties. [Read the Full Post]

Heat shock protein 90 inhibitors induce functional inhibition of human natural killer cells in a dose-dependent manner

1397 | Mar 14 2017

Huyan T et al. suggested that more attention should be given to the effect of Hsp90 inhibitors on NK cell function during clinical trials and also represent a potential immunosuppressant strategy. [Read the Full Post]

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

1993 | 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]

AURKA promotes cell migration and invasion of head and neck squamous cell carcinoma through regulation of the AURKA/Akt/FAK signaling pathway

1365 | Mar 07 2017

Wu J et al. found that AURKA activates FAK through the AURKA/Akt/FAK signaling pathway, promoting the migration and invasion of HNSCC cells, which may subsequently provide a novel approach for the treatment of HNSCC. [Read the Full Post]

Structural Insights into the Pharmacophore of Vinca Domain Inhibitors of Microtubules

1003 | Mar 03 2017

Wang Y et al. found that the rational design of novel vinca domain ligands and may facilitate the development of microtubule inhibitors with high specificity, affinity, and efficiency as payloads for ADCs in cancer therapy. [Read the Full Post]

Novel pyrimidine-2,4-diamine derivative suppresses the cell viability and spindle assembly checkpoint activity by targeting Aurora kinases

746 | Mar 02 2017

Salmela AL et al. suggested that this new pharmacophore possesses interesting anticancer properties that could be exploited in development of mitosis-targeting therapies. [Read the Full Post]

Suppressing Cyclooxygenase-2 prevents nonalcoholic steatohepatitis and inhibits apoptosis of hepatocytes that are involved in the Akt/p53 signal pathway

1067 | Feb 27 2017

Wu J, et al.'s findings suggested that suppressing COX-2 can improve steatohepatitis by inhibiting hepatocyte apoptosis in mice via regulating the Akt/p53 pathway. Celecoxib treatment may be a favorable treatment option for NASH. [Read the Full Post]

Epothilone B induces apoptosis and enhances apoptotic effects of ABT-737 on human cancer cells via PI3K/AKT/mTOR pathway

911 | Feb 25 2017

These data indicate that ABT-737 may be a pertinent sensitizer to epothilone B, and the strategy of combining epothilone B with ABT-737 appears to be an attractive option for overcoming the resistance and neurotoxicity of epothilone B. [Read the Full Post]

Hypoxia-inducible factor 1α (HIF-1α) and reactive oxygen species (ROS) mediates radiation-induced invasiveness through the SDF-1α/CXCR4 pathway in non-small cell lung carcinoma cells

1726 | Feb 24 2017

Gu Q et al.'s findings have elucidated the underlying mechanisms of the irradiation-enhanced invasiveness of NSCLC cells. [Read the Full Post]

Haploinsufficiency of the ESCRT Component HD-PTP Predisposes to Cancer

0 | Feb 17 2017

Manteghi S et al. establish HD-PTP/PTPN23 as a prominent haploinsufficient tumor suppressor gene preventing tumor progression through control of integrin trafficking. [Read the Full Post]

The PI3K/Akt Pathway Regulates Oxygen Metabolism via Pyruvate Dehydrogenase (PDH)-E1α Phosphorylation

3055 | Feb 12 2017

Cerniglia GJ, et al.‘s’ findings highlight an association between the PI3K/mTOR pathway and tumor cell oxygen consumption that is regulated in part by PDH phosphorylation. These results have important implications for understanding the effects of PI3K pathway activation in tumor metabolism and also in designing cancer therapy trials that use inhibitors of this pathway. [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]

Integrin αvβ1 Modulation Affects Subtype B Avian Metapneumovirus Fusion Protein-mediated Cell-Cell Fusion and Virus Infection

867 | Feb 09 2017

Yun B, et al. suggested that integrin αvβ1 is a functional receptor for aMPV/B F protein-mediated membrane fusion and virus infection, which will provide new insights on the fusogenic mechanism and pathogenesis of aMPV. [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]

Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia

0 | Feb 04 2017

Wang JY et al. suggested that NO exhibits a concentration-dependent dual action of weakening or enhancing oxidative injury in mixed glia, particularly microglia. [Read the Full Post]

A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

3210 | Jan 29 2017

Gillan V et al. provided proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties. [Read the Full Post]

Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia

0 | Jan 26 2017

Wang JY et al. suggested that NO exhibits a concentration-dependent dual action of weakening or enhancing oxidative injury in mixed glia, particularly microglia. [Read the Full Post]

Heat shock protein 90 inhibitors induce functional inhibition of human natural killer cells in a dose-dependent manner

1504 | Jan 22 2017

Huyan T, et al.'s findings suggest that more attention should be given to the effect of Hsp90 inhibitors on NK cell function during clinical trials and also represent a potential immunosuppressant strategy. [Read the Full Post]

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

2259 | 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]

Suppressing Cyclooxygenase-2 prevents nonalcoholic steatohepatitis and inhibits apoptosis of hepatocytes that are involved in the Akt/p53 signal pathway

0 | Jan 14 2017

Wu J, et al.'s findings suggested that suppressing COX-2 can improve steatohepatitis by inhibiting hepatocyte apoptosis in mice via regulating the Akt/p53 pathway. Celecoxib treatment may be a favorable treatment option for NASH. [Read the Full Post]

Delocalized Claudin-1 promotes metastasis of human osteosarcoma cells

2307 | 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]

The PI3K/Akt Pathway Regulates Oxygen Metabolism via Pyruvate Dehydrogenase (PDH)-E1α Phosphorylation

0 | Jan 04 2017

Cerniglia GJ, et al. 's results have important implications for understanding the effects of PI3K pathway activation in tumor metabolism and also in designing cancer therapy trials that use inhibitors of this pathway. [Read the Full Post]

Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia

1837 | Jan 01 2017

Wang JY et al. suggested that NO exhibits a concentration-dependent dual action of weakening or enhancing oxidative injury in mixed glia, particularly microglia. [Read the Full Post]

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

2021 | 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]

WISP1 overexpression promotes proliferation and migration of human vascular smooth muscle cells via AKT signaling pathway

2177 | Dec 18 2016

Lu S et al. demonstrated that Akt signaling pathway mediates WISP1-induced migration and proliferation of human VSMCs, suggesting that WISP1 may act as a novel potential therapeutic target for vascular restenosis. [Read the Full Post]

Xanthatin anti-tumor cytotoxicity is mediated via glycogen synthase kinase-3β and β-catenin

2119 | Dec 15 2016

Tao L, et al. provided insight into how xanthatin and related molecules could be effectively targeted toward certain tumors. [Read the Full Post]

Upregulation of AKT3 Confers Resistance to the AKT Inhibitor MK2206 in Breast Cancer.

1450 | Dec 08 2016

Stottrup C et al. provided a rationale for developing therapeutics targeting AKT3 to circumvent acquired resistance in breast cancer. [Read the Full Post]

Downregulation of GLUT4 contributes to effective intervention of estrogen receptor-negative/HER2-overexpressing early stage breast disease progression by lapatinib

1785 | Dec 05 2016

Acharya S et al.’s results indicated that lapatinib, through its inhibition of key signaling pathways and tumor-promoting metabolic events, is a promising agent for the prevention/early intervention of ER-/HER2+ breast cancer progression. [Read the Full Post]

miR-18a promotes cell proliferation of esophageal squamous cell carcinoma cells by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis

1713 | Dec 04 2016

Zhang W et al.’s results demonstrated the upregulation of miR-18a promoted cell proliferation by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis, suggesting that small molecule inhibitors of AKT-mTOR signaling are potential agents for the treatment of ESCC patients with upregulation of miR-17-92 cluster. [Read the Full Post]

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

4307 | 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]

In Silico Analysis Guides Selection of BET Inhibitors for Triple-Negative Breast Cancer Treatment

1386 | Nov 26 2016

Perez-Peña J et al. demonstrated the antitumor effect of this new family of compounds in TNBC, paving the way for its future clinical development. [Read the Full Post]

Ultrasound Enhances the Expression of Brain-Derived Neurotrophic Factor in Astrocyte Through Activation of TrkB-Akt and Calcium-CaMK Signaling Pathways

2258 | Nov 24 2016

Liu SH et al. found that LIPUS stimulation might play a crucial and beneficial role in neurodegenerative diseases. [Read the Full Post]

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

3631 | 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]

Antagonizing Integrin β3 Increases Immunosuppression in Cancer

1106 | Nov 15 2016

Su X et al. suggested that effects of integrin β3 therapies on immune cells should be considered to improve outcomes. [Read the Full Post]

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

1929 | Nov 11 2016

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

Haploinsufficiency of the ESCRT Component HD-PTP Predisposes to Cancer.

2530 | Nov 08 2016

Manteghi S, et al.found that we establish HD-PTP/PTPN23 as a prominent haploinsufficient tumor suppressor gene preventing tumor progression through control of integrin trafficking. [Read the Full Post]

Ajuba Phosphorylation by CDK1 Promotes Cell Proliferation and Tumorigenesis

1793 | Nov 04 2016

Chen X et al. revealed a previously unrecognized mechanism for Ajuba regulation in mitosis and its role in tumorigenesis. [Read the Full Post]

Integrin αvβ1 Modulation Affects Subtype B Avian Metapneumovirus Fusion Protein-mediated Cell-Cell Fusion and Virus Infection

1098 | Nov 02 2016

Yun B et al. suggested that integrin αvβ1 is a functional receptor for aMPV/B F protein-mediated membrane fusion and virus infection, which will provide new insights on the fusogenic mechanism and pathogenesis of aMPV. [Read the Full Post]

The antitumor toxin CD437 is a direct inhibitor of DNA polymerase α

1546 | Nov 01 2016

The discovery of POLA1 as the direct anticancer target for CD437 has the potential to catalyze the development of CD437 into an anticancer therapeutic. [Read the Full Post]

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

2382 | Oct 28 2016

[Read the Full Post]

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

2245 | 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

3438 | 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]

Rictor/mTORC2 Drives Progression and Therapeutic Resistance of HER2-Amplified Breast Cancers

1689 | Oct 12 2016

Morrison-Joly M et al. that Rictor/mTORC2 signaling drives Akt-dependent tumor progression in HER2-amplified breast cancers, rationalizing clinical investigation of dual mTORC1/2 kinase inhibitors and developing mTORC2-specific inhibitors for use in this setting. [Read the Full Post]

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

2064 | Oct 08 2016

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

Uroguanylin modulates (Na++K+)ATPase in a proximal tubule cell line: Interactions among the cGMP/protein kinase G, cAMP/protein kinase A, and mTOR pathways

1698 | Sep 27 2016

Arnaud-Batista FJ et al. suggested that the molecular mechanism of action of UGN on sodium reabsorption in PT cells is more complex than previously thought. [Read the Full Post]

Dual Targeting of Akt and mTORC1 Impairs Repair of DNA Double-Strand Breaks and Increases Radiation Sensitivity of Human Tumor Cells

1802 | Sep 21 2016

Holler M et al. dual targeting of mTORC1 and Akt1 inhibits repair of DNA-DSB leading to radiosensitization of solid tumor cells. [Read the Full Post]

A causal link from ALK to hexokinase II overexpression and hyperactive glycolysis in EML4-ALK-positive lung cancer

1621 | Sep 19 2016

Ma Y et al. revealed a novel EML4-ALK-HIF1α-HK2 cascade to enhance glucose metabolism in EML4-ALK-positive NSCLC. [Read the Full Post]

Inhibition of Phospho-S6 Kinase, a Protein Involved in the Compensatory Adaptive Response, Increases the Efficacy of Paclitaxel in Reducing the Viability of Matrix-Attached Ovarian Cancer Cells

1570 | Sep 19 2016

[Read the Full Post]

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

2575 | 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]

The role of DNA-dependent protein kinase in dendritic cells in house dust mite-induced asthma

3597 | Mar 03 2015

Mishra et al. demonstrated the immune role of DNA-PK in response to house dust mite (HDM) antigen in dendritic cells (DCs). [Read the Full Post]

The small GTPase Rap1b acts as a negative regulator of neutrophil recruitment to inflamed lung with acute lung injury

2804 | Feb 11 2015

Kumar et al. found small GTPase Rap1b acts as a critical suppressor of neutrophil accumulation to inflamed lungs. [Read the Full Post]

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

4016 | 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]

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

12049 | 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]

MAPK cascade promotes early axonal degeneration in response to injury

4889 | Jan 21 2015

By using traumatic injury as a model, Yang et al. demonstrated a critical role of mitogen-activated protein kinase (MAPK) cascade in early axonal degeneration in response to injury. [Read the Full Post]

The new finding of PI3K signaling regulation provides a novel therapeutic strategy for luminal breast cancer

6958 | Jan 15 2015

Costa et al. found the high efficiency of p110α inhibition by BYL719 is attenuated due to p110β accumulation. [Read the Full Post]

The mechanism of kinase independent AKT in promoting cancer development

4948 | Jan 12 2015

Vivanco et al. revealed the mechanism and emphasized a kinase-independent function of AKT in regulating cancer cell survival. [Read the Full Post]

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

9786 | Jan 07 2015

Winter et al. identified the underlying mechanism of the emerging JAK2 inhibitor therapy resistance in MPNs patients, and found the RAS and pathways mediated by AKT and ERK contribute to the resistance. [Read the Full Post]

The mechanism of GSI resistance in T cell acute lymphoblastic leukemia

4815 | Dec 30 2014

Knoechel et al. identified BRD4 is an important regulator of GSI resistance in T-ALL cells, and the combination of GSI and JQ1, the BRD4 inhibitor, is effective against T-ALL in vivo. [Read the Full Post]

CCR4 mutations act as key factors in adult T-cell leukemia/lymphoma pathogenesis

3692 | Dec 22 2014

Nakagawa et al. reported the dysregulation of CCR4 is critical in ATLL pathogenesis, and the inhibition of CCR4 signaling may have clinical value for curative treatment of ATLL. [Read the Full Post]

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

5282 | Dec 02 2014

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

Mechanism of Cdo-induced Wnt suppression during neuronal differentication

3728 | Nov 28 2014

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

SGK3 and INPP4B mediate PI3K signaling pathway in breast cancer

4567 | Nov 18 2014

Gasser et al. found a new PI3K signaling axis, with SGK3 and INPP4B as key factors and in the absence of Akt activity, for regulation of tumorigenesis, tumor cell proliferation and invasive migration. [Read the Full Post]

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

5869 | 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]

The inhibition of AKT pathway by truncated CNT-1 enhances cell apoptosis

3887 | Nov 11 2014

Nakagawa et al. demonstrated a new negative regulator of AKT signaling, tCNT-1, can promote cell apoptosis and suppress cell growth and proliferation. [Read the Full Post]

New platform of high efficiency iPSC reprogramming

7305 | 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]

Perifosine is a drug candidate being developed for a variety of cancer indication

2912 | Mar 05 2014

Perifosine combining with temozolomide reduces tumor proliferation in vivo. [Read the Full Post]

GDC 0068 is a highly selective small molecule inhibitor of Akt

2947 | Feb 07 2014

GDC-0068 is a highly selective pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 5 nM/18 nM/8 nM, 620-fold selectivity over PKA. [Read the Full Post]

Perifosine is structurally related to miltefosine

3020 | Dec 26 2013

Perifosine develops anti-proliferative properties with IC50 of 0.6-8.9 μM in immortalized keratinocytes (HaCaT), and head and neck squamous carcinoma cells. [Read the Full Post]

Wnt C59 was first disclosed in patent WO2010101849 as a potent

3540 | Dec 19 2013

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

XAV 939 is a small molecule and selective Wnt pathway

3811 | Dec 11 2013

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

Triciribine is a synthetic tricyclic nucleoside which acts as a specific inhibitor of the Akt

3120 | Dec 04 2013

Triciribine is a DNA synthesis inhibitor, also inhibits Akt and HIV-1 with IC50 of 130 nM and 20 nM, respectively; does not inhibit PI3K/PDK1; 5000-fold less active in cells lacking adenosine kinase. [Read the Full Post]

Staurosporine is a potent PKC inhibitor with IC50

5031 | 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]

Triciribine was initially described as a DNA synthesis inhibitor

3045 | Aug 21 2013

Triciribine is a DNA synthesis inhibitor, also inhibits Akt and HIV-1 with IC50 of 130 nM and 20 nM [Read the Full Post]

Perifosine is a drug candidate being developed for a variety of cancer indications

2966 | Jul 09 2013

Perifosine develops anti-proliferative properties with IC50 of 0.6-8.9 μM in immortalized keratinocytes (HaCaT), and head and neck squamous carcinoma cells. [Read the Full Post]

Taxol is a mitotic inhibitor used in cancer chemotherapy

2314 | May 06 2013

Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a US National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol. Later it was discovered that endophytic fungi in the bark synthesize paclitaxel. [Read the Full Post]

AEB071 is a potent selective pan PKC inhibitor

3885 | 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]

PKC Inhibitors is associated with endothelial dysfunction

3979 | 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]

MK-2206, a potent Akt inhibitor

5835 | Oct 16 2012

Characterization of MK-2206 Akt is identified as a serine-threonine kinase on the basis of its homology to protein kinase A (PKA), protein kinase C (PKC) and the retroviral oncogene, viral Akt. The known three human AKT isozymes (Akt1, Akt2 and Akt3) are highly homologous multi-domain proteins with both overlapping and distinct cellular functions. So far, there are a lot of AKT isozyme-selective allosteric inhibitors that have been reported, and MK-2206 is one member of them. MK-2206 is a potent, oral allosteric inhibitor of all AKT isoforms, which binds to a site outside the PH domain and binds very weakly to the PH domain of Akt. MK-2206 has the solubility around 96 mg/mL in both dimethyl sulfoxide (DMSO) and water, however it is scarcely soluble in ethanol with solubility of 2 mg/mL. And the approximate price of MK-2206 is $214 per 10 mg and $718 per 50 mg in selleckchem.com, and MK-2206 price may vary according to the proportion purity of the preparation and/or from one MK-2206 supplier to different ones. [Read the Full Post]

Perifosine as a potent Akt inhibitor

4240 | Oct 15 2012

FEATURES OF PERIFOSINE Perifosine, also known as KRX-0401, is a synthetic novel alkylphospholipid (ALP) and a potent antitumor agents which inhibits PH domain mediated AKT membrane recruitment and activation. Perifosine structure has been elucidated through X-ray crystallography and it shows the similar structure with phospholipids that are the main constituents of cellular membranes. Perifosine is soluble in water and ethanol with solubility of 14 mg/mL and 92 mg/mL, respectively. But Perifosine solubility in DMSO is poor. Commercially researchers can obtain Perifosine with the price of about $210/mg from suppliers selleck chemicals. Perifosine stability keeps good for at least 2 years for the dry solid when stored at -20°C and for 6 months at -80°C in DMSO. [Read the Full Post]

MK-2206, as a pan Akt inhibitor

6928 | Oct 09 2012

MK-2206 AKT/Protein Kinase B is a serine/threonine-specific protein kinase that constitutes an important pathway that regulates the signaling of multiple essential biological processes such as glucose metabolism, apoptosis, cell proliferation, and cell migration. AKT can be recruited to the membrane and activated with increases in PIP3 induced by PI3K. Since activating mutations of PI3K occur in human tumors, the AKT pathway is a promising potential target for cancer chemotherapy. MK-2206, is identified as an orally bioavailable allosteric inhibitor of Akt with potential antineoplastic activity. MK-2206 has shown cytotoxic activity in vitro cell line, such as T-cell acute lymphoblastic leukemia (T-ALL), and the efficacy of MK-2206 also has been proven in preclinical models of human cancers. [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]

ONCOGENES AND HSP90 INHIBITORS

4378 | Aug 24 2012

PATHWAY OF HSP90 AND CANCER CELL LINES: Heat shock protein 90 or Hsp90 is actually a non-fibrous protein which gained its name from its molecular weight that is 90kDa. Hsp90 is most abundant cytoplasmic protein which plays a significant role in cells by acting like a molecular chaperone for many proteins related to some important signaling cascades of the cell. Different proteins chaperones that are existing in the cell, involve serine/theronine kinases and tyrosine kinases as well hence they are very much important for the proper regulation of cell growth and cell cycle. A detailed research is carried out to describe the relation between Hsp90 and cancers. To inhibit this chaperone i.e. Hsp90, the simple strategy of designing Hsp protein inhibitor was developed when Hsp90 was found to be existing in different cancerous cell lines activated through the activation of oncogenes. It has been proved a very fruitful therapy for cancer. [Read the Full Post]

HSP90 INHIBITORS AND ONCOGENES

4632 | Aug 16 2012

HSP90 CASCADE AND CANCER CELLS: Hsp90 or the Heat shock protein 90 is a non fibrous protein that gained its name on the basis of its molecular weight i.e., 90kDa. Heat shock protein 90 is the most abundant protein present in cytoplasm that plays a significant role in the cells by acting as molecular chaperones for different proteins associated with some important signaling pathways in the cells. Various molecular chaperones existing in the cells, involves in the tyrosine kinases and serine/theronine kinases as well, so they are very important for proper regulation of cell cycle and cell growth. A complete research has been done to describe the relation between cancer and Hsp90. For the inhibition of Hsp90 chaperone a simple strategy is designed i.e., development of Hsp-60 inhibitor in case of presence of Hsp90 in the cancerous cells and activated by the activation of various oncogenes. It was proved to be an efficient therapy for the treatment of cancer. [Read the Full Post]

INHIBITON OF AKT FOR THE TREATMENT OF CANCER

3510 | Aug 10 2012

CELL PROLIFERATION AND AKT PATHWAY Signal transduction pathways involve various types of kinase enzymes. AKT kinase is such an enzyme that is responsible of phosphorylating the proteins on their specifically serine/threonine sites specifically. It is also named as PKB which means Protein kinase B. It is involved in different kinds of cellular processes like apoptosis, transcription, translation, metabolism and the most important of above all is the cell proliferation and cell migration. Many cancerous cells have been found to exhibit AKT dysfunction therefore it is thought to have an important role in the regulation of cell cycle. AKT pathway gets active by stimulation from PI3K and it also activates by itself mTOR protein to initiate the further process. When PI3K gets hyperactivated, there is an increase in rate of cell division process etc. hence caused tumorigenesis. As compared to any other pathway of signal transduction, this AKT pathway exists more frequently in the cancer cells due to event of amplification, mutation and translocation in its kinase proteins. To fight against various types of cancers and tumors the strategy applied is to target any one of these kinase proteins of this pathway and the AKT inhibitors were found quite good to be used for the treatment of cancer. [Read the Full Post]

INHIBITON OF AKT TO FIGHT CANCER

3216 | Aug 06 2012

AKT PATHWAY AND CELL PROLIFERATION Different types of kinases are involved in the signal transduction pathways. AKT kinase is one such kinase that specifically phosphorylates proteins at their serine/threonine amino acids site. It is also called as PKB i.e., Protein kinase B and is involved multiple types of cellular processes e.g., glucose metabolism, transcription, translation, apoptosis and important of all cell proliferation and its migration. Many of the cancer cells have been found to have AKT dysfunction in them therefore it is considered to have a very important role in cell cycle regulation. AKT gets activated by PI3K and activates itself mTOR protein and further process in the cell gets initiated. Hyperactivation of PI3K increases the rate of cellular process of division etc. and hence takes part in tumorigenesis. This pathway is more frequently found in cancer than any other signal transduction pathway due to the occurrence of mutation, translocation and amplification in its protein kinases. Targeting one of the kinases of this pathway is the strategy to fight against many types of cancers and PKB inhibitors have been found to be quite feasible to be used against cancer. [Read the Full Post]

HSP90 INHIBITORS AND ONCOGENES

4384 | Aug 02 2012

HSP90 PATHWAY AND CANCER CELLS: Heat shock protein 90 or Hsp90 is a non-fibrous protein that has gained its name from its 90kDa molecular weight. This is the most abundant protein present in cytoplasm and plays an important role in the cell by acting as a chaperone for many of the proteins involved in important signaling pathways of the cell. There are various proteins chaperones which are present in the cell, includes TKs or tyrosine kinases and theronine/serine kinases as well and these are very important for the regulation of cell cycle and growth. Detailed research has been conducted to connect cancers and Hsp90. As Hsp90 has shown by different cancerous cells which are activated via activating oncogenes a simple strategy for the inhibition of this chaperone has developed by designing Hsp90 inhibitors. This approach has been fruitful for cancer therapy. [Read the Full Post]

NILOTINIB AND PHILADELPHIA

5320 | 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]

AKT INHIBITORS AS ANTI TUMOR AGENTS

3614 | Jul 24 2012

AKT PATHWAY AND CANCERS: AKT is a kinase specific for threonine/serine amino acids which is also known as Protein kinase kinase B (PKB). This kinase is involved in various cellular pathways such as glucose metabolism, apoptosis, transcription and the most important functions are cell migration and proliferation. In cancer cells many of the crucial functions are controlled by AKT which depicts its importance. AKT is downstream to PI3K and mostly it is hyper activated during formations of cancers therefore taking a part in tumorigenesis through a hyperactive PI3K/AKT/mTOR pathway. As mutations, translocations and amplifications in PI3K/AKT/mTOR pathway result into hyperactivation of this pathway are more frequent than other signaling pathways. AKT inhibitors are one of the most feasible approaches to fight against cancer. [Read the Full Post]

NILOTINIB 

6037 | 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

4914 | 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

5771 | 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+

5549 | 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

5749 | 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

5687 | 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

4879 | 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

3620 | 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]

PACLITAXEL – A MICROTUBULE INHIBITOR WITH MULTIPLE ROLES

2660 | Apr 04 2012

PACLITAXEL: Paclitaxel is an inhibitor of mitosis and it was discovered in the bark of a tree called Taxus brevifolia and later on its presence was also reported in hazel cells. Many of the cancer drugs target microtubules in the cancer cells, Paclitaxel microtubules inhibitor is a new hope for cancer treatment. The structure of this compound is complex as it contains diterpene along with an oxatane ring and taxane. The generic name has been changed by the manufacturers of Paclitaxel that was Taxol the brand name of this inhibitor is Abraxane and any one can buy Paclitaxel for medicinal usage. Paclitaxel is soluble in methanol and DMSO and in order to gain long term stability for this compound one should keep it away from any strong acidic or alkaline solution. The Paclitxel price is variable as it depends on its purity and Paclitaxel supplier. Its cost is reasonable and one can purchase Paclitaxel for research purposes as well. [Read the Full Post]

STAUROSPORINE: A PKC INHIBITOR

5443 | 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]

PACLITAXEL – MULTIPLE ROLES AS MICROTUBULE STABILIZER

2942 | Mar 19 2012

Introduction: Mitosis and Cytokinesis An essential part of the cell cycle is the M phase where the cell physically divides into two unique cells. This process is consists of two different phases mitosis and cytokinesis. Cytokinesis is the phase where the contents of the cell are divided into two equal portions along with the duplicate chromosomes and nuclei. The cell membrane then pinches together and eventually splits into two segments. Mitosis, on the other hand is the division of the duplicate chromosomes and nuclei into opposite ends of the cell. To do this; microtubule form from one end of the elongated cell to the newly formed chromosomes, these tubules then decrease in length pulling the chromosomes pairs apart. The same happens for the nuclei. This process is complex and involved but it is sufficient to indicate that action of inhibitors against the dismantling of the microtubules would halt the cell separation causing apoptosis to initiate. A small molecule that can induce such a reaction is Paclitaxel microtubule stabilization has been used as the standard treatment for a variety of cancer types for many years. [Read the Full Post]

HSP INHIBITORS AGAINST PROTEIN FOLDING

3692 | Mar 19 2012

Introduction: Cellular Quality Assurance The network of chemical reactions linked to the mechanisms behind cellular growth, proliferation and differentiation are complex. Referred to as biochemical pathways these mechanisms operate on some simple principles starting with the receipt of a message from the host system to the cell itself. The pathway system can be likened to a production line facility with the product being a normal health cell. So mechanisms exists for stock piling of raw materials, for the synthesis of component parts, for the recycling of waste materials, for the removal of unwelcome molecules, quality assurance and final product viability. One the key aspects of cellular growth is the delicacy of the whole process, it does not take much to drive a mechanism off balance and produce a faulty product, to ensure quality under stress induced conditions a series of proteins exist referred to as Heat Shock Proteins that assess the quality of proteins being constructed for cell growth purposes. [Read the Full Post]

ENZASTAURIN AGAINST MALIGNANCIES

3585 | 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]

TAXOL: BEFORE AND NOW

2396 | Mar 18 2012

Inhibition of cell division A well know cellular function is that of mitosis; which is the biological function whereby a cells nucleus splits into two identical units. The process is accompanied by cytokinesis where the cell membrane, cytosole and separate nuclei divide into to cells. This complete process is referred to as the”M” phase in the cell cycle theory. The complete process is supported by a scaffolding type structure called microtubules which provide the framework for cytokinesis and mitosi. A mitotic inhibitor is one which interferes with the stability of the microtubules which is of relevance in chemotherapy since unregulated cell division is one the strongest difference between tumor and normal cells. This difference can be exploited by a specifically designed inhibitor. Taxol, more commonly called Paclitaxel, is an inhibitor which disrupts the dismantling of the microtubules during cell division, hence cell mitosis cannot occur. Taxol is standard therapy in many forms of cancer including sarcoma, breast cancer, NSCLC, SCLC, ovarian cancer as well as head and neck cancer. [Read the Full Post]

FINGOLIMOD – THE IMMUNOMODULATOR

3799 | 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

3279 | 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

3327 | 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]

AKT INHIBITORS AGAINST TUMOR GROWTH

3926 | Mar 13 2012

AKT PATHWAY AND ITS LINK WITH CANCERS: With the emergence of the tyrosine kinase inhibitors attention was directed toward Akt, a serine/ threonine kinase of the protein kinase family. Akt is more formally known as protein kinase B and exists in three isoforms. Its role in the cellular signaling cascades has been well documented with downstream effects on mTOR, BAD and GSK3 The PI3K/Akt/mTOR pathway has been established as having an important role in apoptosis, cell migration and proliferation, transcription and glucose metabolism. In various known forms of malignancies Akt has been established as playing a crucial role, an elevated expression of phosphorylated Akt is a contraindication of survival. Hence focus was placed on the development of AKT inhibitor drugs. AKT inhibition has been achieved with Perifosine, MK-2206, RX-0201, Erucylphosphocholine (ErPC), PBI-05204, GSK690693, A-443654 and XL-418. [Read the Full Post]

DASATINIB – THE DOUBLE-EDGED SWORD

4215 | 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]

MK-2206, as an Akt Inhibitor, enhances antitumor efficacy by chemotherapeutic agents

3185 | Nov 17 2011

Development and maintenance of many tumors have been reported to be associated with abnormal activation of PI3K. Akt is a critical downstream factor of PI3K signaling pathway and is important in promoting cell survival and inhibiting apoptosis. Clinically, Akt activation and overexpression is often associated with resistance to chemotherapy or radiotherapy. Thus, clinically available small-molecule inhibitors of Akt have remarkable potential in cancer treatment. [Read the Full Post]

Roles of Hsp90 in wound healing and cancer

4876 | Oct 24 2011

Wound healing is an intricate process in which the skin (or another organ-tissue) repairs itself after injury. At present, local growth factors are considered to be the driving force for wound healing and only recombinant human platelet-derived growth factor-BB (PDGF-BB) has been approved by US FDA for topical treatment of diabetic ulcers. However, the use of PDGF-BB in clinical trials has been limited for its modest efficacy, high cost and risk of causing cancer. Thus, novel treatment for wound healing is needed to be explored. [Read the Full Post]

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

4321 | 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.

4387 | 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]

Chin, Y. R. and A. Toker (2009). "Function of Akt/PKB signaling to cell motility, invasion and the tumor stroma in cancer." Cell Signal 21(4): 470-476.

3020 | Jun 23 2011

This article gives an introduction of akt signal pathway in cell motility, invasion and the tumor stroma in cancer. We can learn this overview of relationship between Akt and cancer. [Read the Full Post]

Sarli, V. and A. Giannis (2008). "Targeting the kinesin spindle protein: basic principles and clinical implications." Clin Cancer Res 14(23): 7583-7587.

3562 | Jun 2 2011

This review describles the function of the kinesin spindle protein. This article also summary the inhibitors of the kinesin spindle protein. [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.

4051 | 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]

Chiosis, G., M. Vilenchik, et al. (2004). "Hsp90: the vulnerable chaperone." Drug Discov Today 9(20): 881-888.

3607 | Apr 19 2011

Agents that interact with its C-terminus or modify its post-translational status represent additional ways of interfering with chaperone activity. This review will discuss several emerging classes of Hsp90 inhibitors and their modes of action. [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.

3640 | 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]

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

4317 | Apr 8 2011

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

Yap, T. A., M. D. Garrett, et al. (2008). "Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises." Curr Opin Pharmacol 8(4): 393-412.

2974 | Apr 4 2011

This review is about the drug discovery of cancer which is targeting the PI3K-AKT-mTOR pathway. Basic knowledge of the PI3K-AKT-mTOR pathway and anticancer therapeutics are both in this article. Anyone who is interested in drug discovery can benefit after reading this article. [Read the Full Post]