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Blog of Signaling Pathways

Epigenetic Profiling Identifies LIF as a Super-enhancer-Controlled Regulator of Stem Cell-like Properties in Osteosarcoma

44 views | Nov 12 2019

Lu B et al. revealed osteosarcoma SE profiles and uncovers a distinct tumor-stemness epigenetic regulatory mechanism in which an osteosarcoma-specific SE-mediated factor, LIF, promotes osteosarcoma stemness gene activation via NOTCH1 signaling pathway. [Read the Full Post]

Corrector VX-809 promotes interactions between cytoplasmic loop one and the first nucleotide-binding domain of CFTR

33 views | Nov 12 2019

Loo TW et al. suggested that the mechanism by which VX-809 promotes maturation and stability of CFTR is by promoting CL1/NBD1 interactions. [Read the Full Post]

The Sirt1 activator, SRT1720, attenuates renal fibrosis by inhibiting CTGF and oxidative stress

0 views | Nov 11 2019

Ren Y et al. showed the Sirt1 activator may therefore be prove to be a potent therapeutic agent for the treatment of fibrotic kidney disease. [Read the Full Post]

Effects of pentoxifylline and H-89 on epileptogenic activity of bucladesine in pentylenetetrazol-treated mice

26 views | Nov 11 2019

Hosseini-Zare MS et al. showed that seizure activities were affected by pentoxifylline, H-89 and bucladesine via interactions with intracellular cAMP and cGMP signaling pathways, cyclic nucleotide-dependent protein kinases, and related neurotransmitters. [Read the Full Post]

Treatment with XAV-939 prevents in vitro calcification of human valvular interstitial cells

41 views | Nov 10 2019

Dittfeld C et al. indicated that XAV-939 was therefore able to prevent calcification of human VIC cultures, and XAV-939 treatment was accompanied by upregulation of active non-phospho-β-catenin. Although XAV-939 does not downregulate active β-catenin, treatment with XAV-939 results in Sox9 upregulation that may prevent the calcification process. [Read the Full Post]

The novel inhibitor PRI-724 for Wnt/β-catenin/CBP signaling ameliorates bleomycin-induced pulmonary fibrosis in mice

142 views | Nov 10 2019

Okazaki H et al. suggested that the β-catenin/CBP inhibitor PRI-724 is a potent antifibrotic agent that acts by modulating the activity of macrophages in the lungs. [Read the Full Post]

Dual mTORC1/2 inhibition by INK-128 results in antitumor activity in preclinical models of osteosarcoma

0 views | Nov 08 2019

Jiang H et al. showed that INK-128 exerts potent anti-OS activity in vitro and in vivo. INK-128 might be further investigated as a novel anti-OS agent. [Read the Full Post]

Pan-mTOR inhibitor MLN0128 is effective against intrahepatic cholangiocarcinoma in mice

27 views | Nov 08 2019

Zhang S et al. suggested that mTOR kinase inhibitors may be beneficial for the treatment of ICC, even in tumors that are resistant to standard of care chemotherapeutics, such as gemcitabine/oxaliplatin-based regimens, especially in the subset of tumors exhibiting activated AKT/mTOR cascade. Lay summary: We established a novel mouse model of intrahepatic cholangiocarcinoma (ICC). Using this new preclinical model, we evaluated the therapeutic potential of mTOR inhibitor MLN0128 vs. gemcitabine/oxaliplatin (the standard chemotherapy for ICC treatment). Our study shows the anti-neoplastic potential of MLN0128, suggesting that it may be superior to gemcitabine/oxaliplatin-based chemotherapy for the treatment of ICC, especially in the tumors exhibiting activated AKT/mTOR cascade. [Read the Full Post]

An integrative pharmacogenomics analysis identifies therapeutic targets in KRAS-mutant lung cancer

57 views | Nov 07 2019

Wang H et al. developed a genotype-based strategy that identifies CK2 as a promising co-target in KRAS(G12C) mutant NSCLC by using available pharmacogenomics gene expression datasets. This approach is applicable to other oncogene driven cancers. [Read the Full Post]

CX-4945: the protein kinase CK2 inhibitor and anti-cancer drug shows anti-fungal activity

48 views | Nov 07 2019

Masłyk M et al. indicated their data unveil the dual-activity of CX-4945; when used in anti-cancer therapy, it may simultaneously prevent cancer-associated candidiasis. [Read the Full Post]

Safety and efficacy of elvitegravir, dolutegravir, and raltegravir in a real-world cohort of treatment-naïve and -experienced patients

86 views | Nov 06 2019

Brehm TT et al. showed that side effects were only rarely observed and generally mild in all subgroups. In light of a slightly higher incidence of vertigo and sleep disturbances in patients switched to DTG, awareness of the potential onset of psychiatric symptoms is warranted during follow-up in those patients. [Read the Full Post]

The Caspase 1 Inhibitor VX-765 Protects the Isolated Rat Heart via the RISK Pathway

0 views | Nov 06 2019

Do Carmo H et al. indicated the caspase 1 inhibitor, VX-765, was able to reduce myocardial infarction in a model of IR injury. However, the addition of IPC did not demonstrate any further protection. [Read the Full Post]

Dual BRAF/MEK therapy in BRAF V600E-mutated primary brain tumors: a case series showing dramatic clinical and radiographic responses and a reduction in cutaneous toxicity

27 views | Nov 05 2019

Bernstein A et al. found that Dual BRAF/MEK inhibitor therapy represents an exciting treatment option for patients with BRAF V600E primary brain tumors. In addition to greater efficacy than single-agent dabrafenib, this combination has the potential to mitigate cutaneous toxicity, one of the most common and concerning BRAF inhibitor-related adverse events. [Read the Full Post]

CHIR-99021 regulates mitochondrial remodelling via β-catenin signalling and miRNA expression during endodermal differentiation

46 views | Nov 05 2019

Ma Y et al. demonstrated that CHIR-99021 plays a role in mitochondrial structure and function remodelling via activation of the β-catenin signalling pathway and inhibits the expression of miRNAs during definitive endodermal differentiation. [Read the Full Post]

Adverse drug events associated with ibrutinib for the treatment of elderly patients with chronic lymphocytic leukemia: A systematic review and meta-analysis of randomized trials

42 views | Nov 04 2019

Zhou Y et al. aimed to compare the adverse drug events which were associated with the use of ibrutinib for the treatment of patients with CLL. [Read the Full Post]

Real-world survival of patients with advanced BRAF V600 mutated melanoma treated with front-line BRAF/MEK inhibitors, anti-PD-1 antibodies, or nivolumab/ipilimumab

27 views | Nov 04 2019

Moser JC et al. found that patients with advanced BRAF mutant melanoma treated with front-line niv/ipi or aPD-1 had longer survival compared to those treated with front-line BRAF/MEKi. [Read the Full Post]

Transcriptomics-Guided Personalized Prescription of Targeted Therapeutics for Metastatic ALK-Positive Lung Cancer Case Following Recurrence on ALK Inhibitors

32 views | Nov 03 2019

Poddubskaya E et al. showed that transcriptomic-guided sequential personalized prescription of targeted therapies can be effective in terms of survival and quality of life in ALK-mutated NSCLC. [Read the Full Post]

Itraconazole increases ibrutinib exposure ten-fold and reduces inter-individual variation - A potentially beneficial drug-drug interaction

45 views | Nov 03 2019

Tapaninen T et al. found that itraconazole markedly increases ibrutinib bioavailability and decreases its inter-individual variability, offering a possibility to improved dosing accuracy and cost savings. [Read the Full Post]

The Potent ALK Inhibitor Brigatinib (AP26113) Overcomes Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in Preclinical Models

87 views | Nov 02 2019

Zhang S et al. provided the molecular basis for the promising activity being observed in ALK+, crizotinib-resistant patients with NSCLC being treated with brigatinib in clinical trials. [Read the Full Post]

FoxO1 regulates myocardial glucose oxidation rates via transcriptional control of pyruvate dehydrogenase kinase 4 expression

34 views | Nov 02 2019

Gopal K et al. demonstrated that pyruvate dehydrogenase kinase 4 is a direct transcriptional target of FoxO1 (but not FoxO3/FoxO4) in the heart. Furthermore, we report here, for the first time, that FoxO1 inhibition increases glucose oxidation in the isolated working mouse heart. [Read the Full Post]