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Blog of Signaling Pathways

[Evolving 5-Fluorouracil Therapy to Achieve Enhanced Efficacy-Past and Current Efforts of Researchers]

188 views | Mar 20 2019

Maehara Y et al. indicated that in the current standard treatment for gastrointestinal cancers, anticancer 5-FU derivatives serve as a platform for combination regimens with other cytotoxic agents or molecular- targeted drugs. To provide further improvements in anticancer therapy outcomes, novel molecular-targeted agents, immune checkpoint inhibitors, and other drugs are being developed, but 5-FU remains an attractive target that shows further potential for increased efficacy. In the future, the evolution of anticancer therapy with 5-FU derivatives is expected to continue via a variety of approaches. [Read the Full Post]

Down-regulation of JMJD5 suppresses metastasis and induces apoptosis in oral squamous cell carcinoma by regulating p53/NF-κB pathway

877 views | Mar 19 2019

Yao Y et al. supplied mechanistic insights into the effects of JMJD5 on the modulation of OSCC development, illustrating that JMJD5 might be an essential prognostic indicator and therapeutic target against OSCC progression. [Read the Full Post]

Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial

578 views | Mar 19 2019

Martin M et al. showed that at the 5-year follow-up, 1 year of extended adjuvant therapy with neratinib, administered after chemotherapy and trastuzumab, significantly reduced the proportion of clinically relevant breast cancer relapses-ie, those that might lead to death, such as distant and locoregional relapses outside the preserved breast-without increasing the risk of long-term toxicity. An analysis of overall survival is planned after 248 events. [Read the Full Post]

The CDK4/6 inhibitor LY2835219 has potent activity in combination with mTOR inhibitor in head and neck squamous cell carcinoma

148 views | Mar 18 2019

Ku BM et al. suggested that a combinational treatment with LY2835219 and mTOR inhibitor is a promising therapeutic approach for HNSCC. [Read the Full Post]

Neuroprotection with the P53-Inhibitor Pifithrin-μ after Cardiac Arrest in a Rodent Model

915 views | Mar 18 2019

Glas M et al. indicated that temporarily inhibition of apoptosis with pifithrin-μ after cardiac arrest decreases the number of injured neurons in the CA1 segment of hippocampus in a cardiac arrest rat model, without clinical correlate. Further studies should elucidate the role of this neuroprotective agent in different settings and with longer cardiac arrest. [Read the Full Post]

Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma

412 views | Mar 17 2019

Moreau P et al. showed the addition of ixazomib to a regimen of lenalidomide and dexamethasone was associated with significantly longer progression-free survival; the additional toxic effects with this all-oral regimen were limited. (Funded by Millennium Pharmaceuticals; TOURMALINE-MM1 ClinicalTrials.gov number, NCT01564537.). [Read the Full Post]

MLN2238 synergizes BH3 mimetic ABT-263 in castration-resistant prostate cancer cells by induction of NOXA

396 views | Mar 17 2019

Wei X et al. indicated that NOXA knockdown by short hairpin RNA significantly attenuated the cytotoxicity of ABT-263 and MLN2238 co-administration. In conclusion, MLN2238 and ABT-263 synergistically triggered apoptosis in CRPC cells by upregulating NOXA and activating Bax, indicating a promising therapeutic strategy for the treatment of CRPC. [Read the Full Post]

Ultraviolet A eye irradiation ameliorates colon carcinoma induced by azoxymethane and dextran sodium sulfate through β-endorphin and methionine-enkephalin

0 views | Mar 16 2019

Hiramoto K et al. suggested that UVA eye irradiation exerts major effects on AOM + DSS-induced colon carcinoma. [Read the Full Post]

The microRNA-7-mediated reduction in EPAC-1 contributes to vascular endothelial permeability and eNOS uncoupling in murine experimental retinopathy

211 views | Mar 16 2019

Garcia-Morales V et al. indicated that EPAC-1 resembles an efficacious and druggable target molecule for the amelioration of (diabetic) retinopathy. [Read the Full Post]

Clinical evaluation of laboratory methods to monitor exposure of rivaroxaban at trough and peak in patients with atrial fibrillation

217 views | Mar 15 2019

Al-Aieshy F et al. found that the POC assay for PT-INR could be useful to indicate high exposure to rivaroxaban in emergency situations although further validation is required. [Read the Full Post]

Monitoring the Activation of the DNA Damage Response Pathway in a 3D Spheroid Model

349 views | Mar 15 2019

Mondesert O et al. demonstrated that DDR activation and its pharmacological manipulation with inhibitory and activatory compounds can be efficiently monitored in live 3D spheroid model. [Read the Full Post]

Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom macroglobulinemia

288 views | Mar 14 2019

Chen C et al. concluded that selinexor in combination with dexamethasone is active in heavily pretreated MM and propose a RP2D of 45 mg/m2 (80 mg) plus 20 mg dexamethasone given twice weekly. This trial was registered at clinicaltrials.gov as #NCT01607892. [Read the Full Post]

Selinexor (KPT-330) demonstrates anti-tumor efficacy in preclinical models of triple-negative breast cancer

242 views | Mar 14 2019

Arango NP et al. showed that Selinexor demonstrated growth inhibition in all 14 TNBC cell lines tested; TNBC cell lines were more sensitive to selinexor (median IC50 44 nM, range 11 to 550 nM) than were estrogen receptor (ER)-positive breast cancer cell lines (median IC50 > 1000 nM, range 40 to >1000 nM; P = 0.017). In multiple TNBC cell lines, selinexor was synergistic with paclitaxel, carboplatin, eribulin, and doxorubicin in vitro. Selinexor as a single agent reduced tumor growth in vivo in four of five different TNBC PDX models, with a median tumor growth inhibition ratio (T/C: treatment/control) of 42% (range 31 to 73%) and demonstrated greater antitumor efficacy in combination with paclitaxel or eribulin (average T/C ratios of 27% and 12%, respectively). [Read the Full Post]

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

357 views | 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]

Targeting HDAC3 Activity with RGFP966 Protects Against Retinal Ganglion Cell Nuclear Atrophy and Apoptosis After Optic Nerve Injury

402 views | Mar 12 2019

Schmitt HM et al. showed the inhibition of HDAC3 activity with systemic dosing of RGFP966 prevents apoptosis-related histone deacetylation and attenuates RGC loss after acute optic nerve injury. [Read the Full Post]

Histone acetyltransferase p300/CBP inhibitor C646 blocks the survival and invasion pathways of gastric cancer cell lines

233 views | Mar 11 2019

Wang YM et al. suggested that C646 inhibits the acetylation of histone H3 via inactivation of p300 and CBP, resulting in antineoplastic effects toward GC cells. Thus, the selective HAT inhibitor C646 could be a promising antitumour reagent for GC treatment. [Read the Full Post]

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

394 views | 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]

Metformin use in pregnancy: promises and uncertainties

230 views | Mar 10 2019

Lindsay RS et al. indicated that in this short review, we will discuss the history of metformin in pregnancy and highlight some of the key clinical trials. We will then consider some of the remaining controversies associated with metformin use in pregnancy, most important of these being the potential for long-term 'programming' effects on the fetus as a result of metformin being able to cross the placenta. We will also consider clinical situations where metformin might be avoided. Finally, we will discuss some future directions for this drug as it reaches its sixtieth anniversary. [Read the Full Post]

Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN

458 views | Mar 10 2019

Jabbour E et al. indicated that treatment was well tolerated, with a 6-week mortality rate of 0%. The use of low-dose HMAs is safe and effective in patients with lower-risk MDS and MDS/MPN. Their effect on the natural history of lower-risk disease needs to be further studied. [Read the Full Post]

Compound C induces protective autophagy in human cholangiocarcinoma cells via Akt/mTOR-independent pathway

205 views | Mar 08 2019

Zhao X et al. demonstrated that compound C inhibited the phosphorylation of JNK and its target c-Jun. Blocking JNK by SP600125 or siRNA suppressed autophagy induction upon compound C treatment. Moreover, compound C induced p38 MAPK activation, and its inhibition promoted autophagy induction via JNK activation. In addition, compound C induced p53 expression, and its inhibition attenuated compound C-induced autophagic response. Thus, compound C triggers autophagy, at least in part, via the JNK and p53 pathways in human CCA cells. In conclusion, suppresses autophagy could increase compound C sensitivity in human CCA. [Read the Full Post]