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Blog of Signaling Pathways

Favorable predictors for survival in advanced ALK-positive non-small cell lung cancer patients beyond crizotinib resistance

341 views | Apr 24 2019

Xu H et al. found that long PFS with crizotinib (≥10.4 months), intracranial progression, and use of next-generation ALK inhibitors might be favorable predictors for OS in advanced ALK-positive NSCLC patients. [Read the Full Post]

Nicotinamide phosphoribosyltransferase inhibitor APO866 induces C6 glioblastoma cell death via autophagy

238 views | Apr 23 2019

Yang P et al indicated that APO866 induced pro-death autophagy in C6 glioblastoma cells by decreasing intracellular NAD, and low concentration of APO866 can be used as an autophagy inducer in autophagic-death sensitive glioblastoma. [Read the Full Post]

Population pharmacokinetics of tacrolimus in pediatric refractory nephrotic syndrome and a summary of other pediatric disease models

230 views | Apr 23 2019

Wang D et al. developed and validated the first TAC PPK model for patients with PRNS. The study also provided a summary of previous literature concerning other TAC PPK models in different pediatric diseases. [Read the Full Post]

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

387 views | Apr 22 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]

FK866-induced NAMPT inhibition activates AMPK and downregulates mTOR signaling in hepatocarcinoma cells

219 views | Apr 22 2019

Schuster S et al. revealed an important role of the NAMPT-mediated NAD salvage pathway in the energy homeostasis of hepatocarcinoma cells and suggest NAMPT inhibition as a potential treatment option for HCC. [Read the Full Post]

ITF2357 transactivates Id3 and regulate TGFβ/BMP7 signaling pathways to attenuate corneal fibrosis

1125 views | Apr 21 2019

Lim RR et al. concludd that ITF2357 is a potential anti-fibrotic drug that exerts its action via activation of Id3, a downstream target of TGFβ/BMP7 signaling pathways. [Read the Full Post]

The dual PI3K/mTOR inhibitor GSK2126458 is effective for treating solid renal tumours in Tsc2+/- mice through suppression of cell proliferation and induction of apoptosis

0 views | Apr 19 2019

Narov K et al. found that both GSK2126458 and rapamycin caused significant reduction in number and size of solid renal tumours. GSK2126458 also significantly reduced the number and size of all lesions (cystic, papillary and solid) although to a lesser extent compared to rapamycin. GSK2126458 inhibited both PI3K and mTOR while rapamycin exerted stronger inhibitory effect on mTORC1 in renal tumours. Furthermore, GSK2126458 and rapamycin suppressed proliferation of tumour cells. Importantly, GSK2126458 increased apoptosis of solid tumours but rapamycin did not. Further investigations are therefore needed to test whether rapamycin in combination with GSK2126458 could promote apoptosis and thus improve therapy of TSC-associated renal tumours. [Read the Full Post]

The HSP90 inhibitor, NVP-AUY922, attenuates intrinsic PI3K inhibitor resistance in KRAS-mutant non-small cell lung cancer

267 views | Apr 19 2019

Park KS et al. indicated that dual inhibition of the HSP90 and PI3K signaling pathways with sub-therapeutic doses of these combined anticancer drugs may represent a potent treatment strategy for KRAS-mutant NSCLC with intrinsic resistance to PI3K inhibition. [Read the Full Post]

Roscovitine ameliorates endotoxin-induced uveitis through neutrophil apoptosis

209 views | Apr 18 2019

Jiang ZX et al. showed that roscovitine ameliorates EIU by effecting neutrophil apoptosis. Timely apoptosis of neutrophils may be an effective process to promote the amelioration of EIU. [Read the Full Post]

Copanlisib: An Intravenous Phosphatidylinositol 3-Kinase (PI3K) Inhibitor for the Treatment of Relapsed Follicular Lymphoma

270 views | Apr 18 2019

Eltantawy A et al. indicated Copanlisib provides an alternative option for patients with relapsed FL. It is safe and effective and has an acceptable toxicity profile. [Read the Full Post]

Alleviation of Senescence via ATM Inhibition in Accelerated Aging Models

401 views | Apr 17 2019

Kuk MU et al. indicated that the mitochondrial functional recovery by ATM inhibition might represent a promising strategy to ameliorate the accelerated aging phenotypes and to treat age-related disease. [Read the Full Post]

In vitro anti-osteoclastogenic activity of p38 inhibitor doramapimod via inhibiting migration of pre-osteoclasts and NFATc1 activity

231 views | Apr 17 2019

Moon SH et al. suggested anti-osteoclastogenic activity of doramapimod via inhibiting migration/fusion of pre-osteoclasts and NFATc1 activity. [Read the Full Post]

Sublingual tacrolimus as an alternative to oral administration for solid organ transplant recipients

211 views | Apr 16 2019

Pennington CA et al. indicated that in addition to enteral tube and i.v. tacrolimus dosing, sublingual administration may be considered for short-term use in patients who are unable to receive medications orally. Based on the available data, it is reasonable to initiate sublingual tacrolimus at 50% of the current or anticipated oral dose in the absence of interacting medications. Dosing must be individualized, taking into consideration concomitant interacting medications, and adjusted to target levels based on therapeutic drug monitoring. [Read the Full Post]

Prevention of Intraabdominal Adhesions: An Experimental Study Using Mitomycin-C and 4% Icodextrin

0 views | Apr 16 2019

Urkan M et al. indicated that despite its potential for bone marrow toxicity, Mitomycin-C seems to effectively prevent adhesions. Further studies that prove an acceptable safety profile relating to this promising anti-adhesive agent are required before moving into clinical trials. [Read the Full Post]

Is maraviroc useful in multiple sclerosis patients with natalizumab-related progressive multifocal leukoencephalopathy

355 views | Apr 15 2019

Scarpazza C et al. showed that maraviroc did not show any clear effect in modulating the clinical course of PML preventing IRIS. Moreover, once PML-IRIS emerged, the clinical stabilization was achieved only with the use of corticosteroids. Thus, the use of maraviroc should be regarded with extreme caution due the potential adverse events associated with its use. [Read the Full Post]

Pre-B cell colony enhancing factor induces Nampt-dependent translocation of the insulin receptor out of lipid microdomains in A549 lung epithelial cells

237 views | Apr 15 2019

Peng Q et al. concluded that PBEF can inhibit insulin signaling through the IR by Nampt-dependent promotion of IR translocation into the nonraft domains of A549 epithelial cells. PBEF-induced alterations in the spatial geometry of the IR provide a mechanistic explanation for insulin resistance in inflammatory states associated with upregulation of PBEF. [Read the Full Post]

PIM kinase inhibitor AZD1208 for treatment of MYC-driven prostate cancer

367 views | Apr 14 2019

Kirschner AN et al. showed that PIM inhibition is a potential treatment for MYC-driven prostate cancers including CRPC, and its effectiveness may be enhanced by activators of the p53 pathway, such as radiation. [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

293 views | 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]

The histone deacetylase inhibitor givinostat (ITF2357) exhibits potent anti-tumor activity against CRLF2-rearranged BCP-ALL

418 views | Apr 13 2019

Savino AM et al. indicated givinostat killed ruxolitinib-resistant cells and potentiated the effect of current chemotherapy. Thus, givinostat in combination with conventional chemotherapy may represent an effective therapeutic option for these difficult-to-treat subsets of ALL. Lastly, the selective killing of cancer cells by givinostat may allow the design of reduced intensity regimens in CRLF2-rearranged Down syndrome-associated BCP-ALL patients with an overall benefit in terms of both toxicity and related complications. [Read the Full Post]

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

349 views | Apr 13 2019

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