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Immunology & Inflammation

First-in-Human Phase I Study of the Oral Inhibitor of Indoleamine 2,3-Dioxygenase-1 Epacadostat (INCB024360) in Patients with Advanced Solid Malignancies

12 | Nov 25 2019

Beatty GL et al. showed that epacadostat was generally well tolerated, effectively normalized kynurenine levels, and produced maximal inhibition of IDO1 activity at doses of ≥100 mg BID. Studies investigating epacadostat in combination with other immunomodulatory drugs are ongoing. [Read the Full Post]

Updates in the Clinical Development of Epacadostat and Other Indoleamine 2,3-Dioxygenase 1 Inhibitors (IDO1) for Human Cancers

12 | Nov 24 2019

Komiya T et al. indicated that IDO1 is a promising target that can improve the treatment outcome in the field of Immuno-oncology. Several orally available IDO1 inhibitors including Epacadostat have entered human clinical trials over the last few years without a major safety concern. Although there is no objective response in single-agent trials, combination regimens with PD-1 inhibitors appear to exceed the activity of PD-1 inhibitors alone. Recent phase III ECHO 301 trial testing the combination of Epacadostat with Pembrolizumab in melanoma did not show superior outcome compared to Pembrolizumab alone. This lead to halting of other phase III trials using IDO1 inhibitors. In this minireview, we will discuss the recent clinical development of Epacadostat and other IDO1 inhibitors. [Read the Full Post]

Protection of Mcc950 against high-glucose-induced human retinal endothelial cell dysfunction

45 | Aug 08 2019

Zhang Y et al. showed that Mcc950 inhibited HREC dysfunction under high-glucose conditions and this research may offer insight for future pharmaceutical approaches for treating DR. [Read the Full Post]

PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations

115 | Aug 05 2019

Zou HY et al. indicated that PF-06463922 has potential for treating ROS1 fusion-positive cancers, including those requiring agents with CNS-penetrating properties, as well as for overcoming crizotinib resistance driven by ROS1 mutation. [Read the Full Post]

Effects of EF-24, RAD001, and paclitaxel on the expression profiles of apoptotic and anti-apoptotic genes

146 | May 15 2019

Alp E et al. showed that response of these cells to paclitaxel, EF-24, and RAD001 was found different at the transcriptional level of apoptotic and antiapoptotic genes. [Read the Full Post]

Effects of Epacadostat on Brain Extracellular Fluid Concentrations of Serotonin -- An Intracerebral Microdialysis Study in Sprague-Dawley Rats

127 | May 14 2019

Zhang Y et al. suggested that serotonin syndrome is unlikely following treatment with either epacadostat alone or with combination with MAOIs such as linezolid. [Read the Full Post]

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

157 | 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]

Protection of Mcc950 against high-glucose-induced human retinal endothelial cell dysfunction

115 | Apr 08 2019

Zhang Y et al indicated Mcc950 inhibited HREC dysfunction under high-glucose conditions and this research may offer insight for future pharmaceutical approaches for treating DR. [Read the Full Post]

Loss of ARID1A expression leads to sensitivity to ROS-inducing agent elesclomol in gynecologic cancer cells

0 | Feb 16 2019

Kwan SY et al. demonstrated for the first time that loss of ARID1A leads to accumulation of ROS and suggest that elesclomol may be used to target ARID1A-mutant gynecologic cancer cells. [Read the Full Post]

Comparison of cell-based assays for the identification and evaluation of competitive CXCR4 inhibitors

292 | Feb 07 2019

CXCL12 competition binding studies were proven to be highly valuable as an initial screening assay and indicative for the pharmacological and functional profile of competitive CXCR4 antagonists, which will help the design of new potent CXCR4 inhibitors. [Read the Full Post]

The pharmacokinetics and metabolism of lumiracoxib in chimeric humanized and murinized FRG mice

256 | Jan 06 2019

Dickie AP et al. showed taht comparison of the metabolic profiles obtained from the present study with previously published data from C57bl/6J mice and humans, revealed a greater though not complete match between chimeric humanized mice and humans, such that the liver-humanized FRG model may represent a useful approach to assessing the biotransformation of such compounds in humans. [Read the Full Post]

FBW7 mutations mediate resistance of colorectal cancer to targeted therapies by blocking Mcl-1 degradation

0 | Dec 19 2018

Tong J et al. demonstrated FBW7 mutational status as a key genetic determinant of CRC response to targeted therapies, and Mcl-1 as an attractive therapeutic target. [Read the Full Post]

HDAC10 promotes lung cancer proliferation via AKT phosphorylation

241 | Dec 12 2018

Yang Y et al. demonstrated that HDAC10 localizes and functions in the cytoplasm of lung cancer cells, thereby underscoring its potential role in the diagnosis and treatment of lung cancer. [Read the Full Post]

Anti-invasive effects of CXCR4 and FAK inhibitors in non-small cell lung carcinomas with mutually inactivated p53 and PTEN tumor suppressors

431 | Dec 07 2018

Dragoj M et al. demonstrated that p53/PTEN deficient NSCLCs have extremely invasive phenotype and provided a rationale for the use of CXCR4 or FAK inhibitors for the suppression of NSCLC dissemination. [Read the Full Post]

Curcumin and its cyclohexanone analogue inhibited human Equilibrative nucleoside transporter 1 (ENT1) in pancreatic cancer cells

658 | Nov 08 2018

Revalde JL et al. concluded that curcumin and A13 are inhibitors of the ENT1 transporter, but only at high concentrations (2-20µM). [Read the Full Post]

EpCAM Intracellular Domain Promotes Porcine Cell Reprogramming by Upregulation of Pluripotent Gene Expression via Beta-catenin Signaling

240 | Oct 21 2018

Yu T et al. showed that EpCAM intracellular domain required beta-catenin signaling to enhance porcine cell reprogramming. [Read the Full Post]

Dopamine D2 receptor and β-arrestin 2 mediate Amyloid-β elevation induced by anti-parkinson's disease drugs, levodopa and piribedil, in neuronal cells

374 | Oct 21 2018

Lu J et al. suggested that targeting D2R-mediated β-arrestin function may have potential risk in the modulation of Aβ pathology. [Read the Full Post]

Severity-of-pancreatitis‑associated-intestinal-mucosal-barrier-injury-is-reduced-following-treatment-with-the-NADPH-oxidase-inhibitor-apocynin

725 | Oct 01 2018

Deng W et al. provided novel insight suggesting that pharmacological inhibition of NOX by apocynin may be considered a novel therapeutic method for the treatment of intestinal injury in SAP. [Read the Full Post]

Angiotensin II induces apoptosis of human pulmonary microvascular endothelial cells in acute aortic dissection complicated with lung injury patients through modulating the expression of monocyte chemoattractant protein-1

244 | Sep 29 2018

Wu Z et al. found that the production of MCP-1 and cellular apoptosis induced by AngII in hPMVECs are closely related to the pathogenesis of AAD complicated with ALI. The association between MCP-1 and AngII is crucial in the apoptosis of hPMVECs. [Read the Full Post]

Downregulation of mitochondrial cyclooxygenase-2 inhibits the stemness of nasopharyngeal carcinoma by decreasing the activity of dynamin-related protein 1

404 | Sep 19 2018

Zhou TJ et al. suggested that mitochondrial COX-2 is a potential theranostic target for the CSCs in NPC. Inhibition of mitochondrial COX-2 could be an attractive therapeutic option for the effective clinical treatment of therapy-resistant NPC. [Read the Full Post]

A regulatory circuit of miR-125b/miR-20b and Wnt signalling controls glioblastoma phenotypes through FZD6-modulated pathways

543 | Sep 19 2018

Huang T et al. confirmed by targeting differentially enriched pathways in PN versus MES GBM that results in inhibition of distinct GBM subtypes. Correlative expressions of the components of this circuit are prognostic relevant for clinical GBM. Our findings provide insights for understanding GBM pathogenesis and for improving treatment of GBM. [Read the Full Post]

Dihydromyricetin promotes autophagy and apoptosis through ROS-STAT3 signaling in head and neck squamous cell carcinoma

614 | Sep 13 2018

Fan TF et al. found that inhibiting autophagy could enhance DHM-induced apoptosis in head and neck squamous cell carcinoma. [Read the Full Post]

Impacts of ABCB1 (G1199A) polymorphism on resistance, uptake, and efflux to steroid drugs.

554 | Aug 29 2018

Peng R, et al. found that the ABCB1 (G1199A) polymorphism may affect effective steroids concentration in target cells by regulating the drug transport and distribution. [Read the Full Post]

Hypoxia potentiates the cytotoxic effect of piperlongumine in pheochromocytoma models

624 | Jul 12 2018

Bullova P et al. reported for the first time that PL mediates PHEO cell death by activating both apoptosis and necroptosis in vitro and in vivo. This effect is magnified in hypoxic conditions, making PL a promising potential candidate for use as a therapeutic option for patients with PHEO/PGL, including those with SDHB mutations. [Read the Full Post]

Pharmacological inhibition of NOX4 ameliorates alcohol-induced liver injury in mice through improving oxidative stress and mitochondrial function

391 | Jun 29 2018

Sun Q et al. found that pharmacological inhibition of NOX4 activity protects against alcohol-induced fat accumulation and activation of intrinsic apoptosis via improving mitochondrial function. [Read the Full Post]

Loss of ARID1A expression leads to sensitivity to ROS-inducing agent elesclomol in gynecologic cancer cells

590 | Jun 20 2018

Kwan SY et al. demonstrated for the first time that loss of ARID1A leads to accumulation of ROS and suggest that elesclomol may be used to target ARID1A-mutant gynecologic cancer cells. [Read the Full Post]

Encapsulation of curcumin in polyelectrolyte nanocapsules and their neuroprotective activity

1132 | Jun 10 2018

Szczepanowicz K et al. indicated the utility of PLL/PGA shell nanocapsules as a promising, alternative way of curcumin delivery for neuroprotective purposes with improved efficiency and reduced toxicity. [Read the Full Post]

Lumiracoxib metabolism in male C57bl/6J mice: characterisation of novel in vivo metabolites

692 | Apr 25 2018

P Dickie A et al. found that while there was significant overlap with reported human metabolites, a number of unique mouse metabolites were detected, particularly taurine conjugates of lumiracoxib and its oxidative metabolites. [Read the Full Post]

Suppression of chronic lymphocytic leukemia progression by CXCR4 inhibitor WZ811

864 | Apr 25 2018

Li SH et al. demonstrated that WZ811 may be a novel approach in the treatment of chronic lymphocytic leukemia. [Read the Full Post]

Critical role of CXCL4 in the lung pathogenesis of influenza (H1N1) respiratory infection

960 | Apr 02 2018

Guo L et al. identified CXCL4 as a vital immunoregulatory chemokine essential for protecting mice against influenza A virus infection, especially as it affects the development of lung injury and neutrophil mobilization to the inflamed lung. [Read the Full Post]

Adiponectin promotes human jaw bone marrow mesenchymal stem cell chemotaxis via CXCL1 and CXCL8

0 | Apr 01 2018

Pu Y et al. supported the above results. Our data suggest that APN can promote h-JBMMSC chemotaxis by up-regulating CXCL1 and CXCL8. [Read the Full Post]

Plumbagin Protects Mice from Lethal Sepsis by Modulating Immunometabolism Upstream of PKM2

410 | Mar 22 2018

Zhang Z et al. identified a new approach for inhibiting the NOX4/PKM2-dependent immunometabolism pathway in the treatment of sepsis and inflammatory diseases. [Read the Full Post]

Advanced Glycation End-Products Induce Apoptosis of Vascular Smooth Muscle Cells: A Mechanism for Vascular Calcification

499 | Mar 22 2018

Koike S et al. demonstrated that NAD(P)H oxidase-derived oxidative stress are involved in AGEs-induced apoptosis of VSMCs. These findings might be important to understand the pathogenesis of vascular calcification in diabetes and CKD. [Read the Full Post]

IgG subclasses determine pathways of anaphylaxis in mice

0 | Mar 09 2018

Beutier H et al. proposed that the differential expression of inhibitory FcγRIIB on myeloid cells and its differential binding of IgG subclasses controls the contributions of mast cells, basophils, neutrophils, and macrophages to IgG subclass-dependent anaphylaxis. [Read the Full Post]

Resveratrol sequentially induces replication and oxidative stresses to drive p53-CXCR2 mediated cellular senescence in cancer cells

440 | Feb 04 2018

Li B et al. provided more insights into the biology of RSV-induced stress and its cellular consequences. [Read the Full Post]

Nrf2 mediates redox adaptation in NOX4-overexpressed non-small cell lung cancer cells

491 | Jan 26 2018

Wu Q, et al. revealed that Nrf2 is critically involved in redox adaptation regulation in NOX4-overexpressed NSCLC cells. [Read the Full Post]

CXCL2/MIF-CXCR2 signaling promotes the recruitment of myeloid-derived suppressor cells and is correlated with prognosis in bladder cancer

1143 | Jan 25 2018

Zhang H et al. identified the CXCL2/MIF-CXCR2 axis as an important mediator in MDSC recruitment and as predictors and potential therapeutic targets in BC patients. [Read the Full Post]

mTORC2 mediates CXCL12-induced angiogenesis

1217 | Jan 07 2018

Ziegler ME et al. identified mTORC2 as a critical signaling nexus downstream of CXCL12/CXCR4 that represents a potential link between mTORC2, metabolic regulation, and angiogenesis. [Read the Full Post]

Modulation of Cell-Mediated Immunity to Suppress High Fat Diet-Induced Obesity and Insulin Resistance

624 | Nov 14 2017

Yan L et al. showed that immune modulation represents an important intervention for obesity and obesity-associated insulin resistance. [Read the Full Post]

Differential expression of cyclooxygenase-2 in metastatic melanoma affects progression free survival

1032 | Nov 13 2017

Panza E et al. suggested that COX-2 expression may become an useful diagnostic tool in defining melanoma malignancy as well as argue for a possible therapeutic use of NSAID as add on therapy in selected cases. [Read the Full Post]

COX-2 expression positively correlates with PD-L1 expression in human melanoma cells

979 | Nov 13 2017

Botti G et al. showed that COX-2 expression correlates with and modulates PD-L1 expression in melanoma cells. These findings have clinical relevance since they provide a rationale to implement novel clinical trials to test COX-2 inhibition as a potential treatment to prevent melanoma progression and immune evasion as well as to enhance the anti-tumor activity of PD-1/PD-L1 based immunotherapy for the treatment of melanoma patients with or without BRAF/NRAS mutations. [Read the Full Post]

Cancer-associated fibroblasts promote hepatocellular carcinoma metastasis through chemokine-activated hedgehog and TGF-β pathways

997 | Oct 28 2017

Liu J et al. found that CAF-secreted CCL2, CCL5, CCL7 and CXCL16 promote HCC metastasis through the coordinate activation of Hh and TGF-β pathways in HCC cells. [Read the Full Post]

Nitric oxide generation by the organic nitrate NDBP attenuates oxidative stress and angiotensin II-mediated hypertension

0 | May 29 2017

Porpino SK et al. suggested that NDBP treatment is associated with sustained NO release and attenuated activity of NADPH oxidase, which to some extent requires functional xanthine oxidase. [Read the Full Post]

Signaling factors and pathways of α-particle irradiation induced bilateral bystander responses between Beas-2B and U937 cells

0 | Apr 12 2017

Fu J et al disclosed novel signaling cascades of macrophage-mediated bilateral bystander responses that the release of TNF-α and IL-8 regulated by MAPK and NF-κB pathways synergistically increased cellular injury after α-particle irradiation. [Read the Full Post]

Chemokine CXCL13 mediates orofacial neuropathic pain via CXCR5/ERK pathway in the trigeminal ganglion of mice

895 | Mar 29 2017

Zhang Q et al. found that targeting CXCL13/CXCR5/ERK/TNF-α and IL-1β pathway in the trigeminal ganglion may offer effective treatment for orofacial neuropathic pain. [Read the Full Post]

FBW7 mutations mediate resistance of colorectal cancer to targeted therapies by blocking Mcl-1 degradation

2054 | Mar 21 2017

Tong J et al. demonstrate FBW7 mutational status as a key genetic determinant of CRC response to targeted therapies, and Mcl-1 as an attractive therapeutic target. [Read the Full Post]

IgG subclasses determine pathways of anaphylaxis in mice

2138 | Feb 27 2017

Beutier H et al. proposed that the differential expression of inhibitory FcγRIIB on myeloid cells and its differential binding of IgG subclasses controls the contributions of mast cells, basophils, neutrophils, and macrophages to IgG subclass-dependent anaphylaxis. Collectively, our results unravel novel complexities in the involvement and regulation of cell populations in IgG-dependent reactions in vivo. [Read the Full Post]

Cyclopiazonic acid, an inhibitor of calcium-dependent ATPases with antiviral activity against human respiratory syncytial virus

0 | Feb 10 2017

Cui R et al.‘s’ findings provide a new strategy for anti-RSV therapy via increasing intracellular calcium concentration. [Read the Full Post]

Cancer-associated fibroblasts promote hepatocellular carcinoma metastasis through chemokine-activated hedgehog and TGF-β pathways

3246 | Nov 10 2016

Liu J et al. found thatCAF-secreted CCL2, CCL5, CCL7 and CXCL16 promote HCC metastasis through the coordinate activation of Hh and TGF-β pathways in HCC cells. [Read the Full Post]

Cyclopiazonic acid, an inhibitor of calcium-dependent ATPases with antiviral activity against human respiratory syncytial virus

2977 | Nov 03 2016

Cui R et al. provided a new strategy for anti-RSV therapy via increasing intracellular calcium concentration. [Read the Full Post]

PET imaging for chemokine receptor-4 detection in multiple myeloma

3617 | Mar 10 2015

Philipp-Abbrederis et al. developed a novel CXCR4 probe [68Ga]Pentixafor for mapping of CXCR4 expression density in vivo. [Read the Full Post]

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

12564 | 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]

The inhibitor of CCR5 block metastasis of v-Src oncogene-transformed prostate cancer

2703 | Dec 11 2014

Sicoli et al. identified CCR5 signaling activation is important for v-Src oncogene-transformed prostate cancer metastasis, and it antagonist can attenuate the burden. [Read the Full Post]

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

9258 | Nov 24 2014

Dechow et al. determined GP130/JAK/STAT3 signaling pathway is sufficient to induce MM generation in mice retroviral murine BM transduction-transplantation model. [Read the Full Post]

Maraviroc is an antiretroviral drug in the CCR5 receptor antagonist class

2980 | Mar 13 2014

Maraviroc is a CCR5 antagonist for MIP-1α, MIP-1β and RANTES with IC50 of 3.3 nM, 7.2 nM and 5.2 nM, respectively. [Read the Full Post]

Maraviroc is an antiretroviral drug in the CCR5

0 | Jan 21 2014

Maraviroc is a CCR5 antagonist for MIP-1α, MIP-1β and RANTES with IC50 of 3.3 nM, 7.2 nM and 5.2 nM, respectively. [Read the Full Post]

Maraviroc is an antiretroviral drug in the CCR5 receptor

2992 | Dec 29 2013

Maraviroc is a CCR5 antagonist for MIP-1α, MIP-1β and RANTES with IC50 of 3.3 nM, 7.2 nM and 5.2 nM, respectively. [Read the Full Post]

Maraviroc is an antiretroviral drug in the CCR5

3066 | Nov 20 2013

Maraviroc is a CCR5 antagonist for MIP-1α, MIP-1β and RANTES with IC50 of 3.3 nM, 7.2 nM and 5.2 nM, respectively. [Read the Full Post]

Vicriviroci s a pyrimidine CCR5 entry inhibitor of HIV1

3001 | Jul 20 2013

Vicriviroc binds with higher affinity to CCR5 versus SCH-C (SCH-351125) in competition binding assays with Ki value of 0.8 nM versus 2.6 nM. [Read the Full Post]

MK 801 has a great deal of potential to be used in research in creating animal models of schizophrenia

3250 | May 10 2013

MK-801 has a great deal of potential to be used in research in creating animal models of schizophrenia. Unlike dopaminergic agonists, which mimic only the positive symptoms of schizophrenia, a single injection of MK801 was successful in modelling both the positive and negative symptoms of schizophrenia. [Read the Full Post]

Bufexamac is a drug used as an anti inflammatory agent on the skin

3519 | Jan 21 2013

The Bufexamac importance of the HGF/c-MET pathway in the control of tissue homeostasis is supported by the well established protective activity of HGF in several degenerative diseases, including progressive nephropathies , liver cirrhosis and lung fibrosis. [Read the Full Post]

LY2140023 is a novel investigational agent for the treatment of schizophrenia

3201 | Jan 18 2013

LY2140023 is a novel investigational agent for the treatment of schizophrenia. A member of a new class of antipsychotic drugs, LY2140023 is still in early stage clinical development. Nevertheless, analysts have hailed it as an exciting new medicine that may herald the arrival of third-generation antipsychotic drugs. [Read the Full Post]

Gamma secretase is a mult subunit protease complex

3052 | Jan 09 2013

The network of tumor blood vessels that perfuse a solid tumor plays a fundamental role in its growth and survival. Not only do the blood vessels feed the Gamma Secretase tumor with oxygen and nutrients through the blood, they also allow for the subsequent removal of cellular waste products. [Read the Full Post]

New and Potent COX receptor inhibitors are available

3274 | Dec 10 2012

PCR amplified cDNA COX Inhibitors fragment containing human EGFR kinase domain from amino acids 696 to 1022 was attached to the C-terminal coding region (3? region) of the glutathione S-transferase gene and the fused DNA fragment is cloned into a baculovirus expression vector pBacPAK8 (Clontech, Palo Alto, CA, USA). [Read the Full Post]

Maraviroc provide a mechanism to adjust the properties

3066 | Nov 28 2012

Our data also indicate that activity of AurA IFT88 localization affected during disassembly and suggest the integrity of t the Maraviroc is important for the process of removing animals, as in Chlamydomonas. [Read the Full Post]

Celecoxib was observed in our in vitro

2905 | Oct 24 2012

EGFR somatic doublet mutations are potentially more frequent than previously understood, with majority of them representing driver driver mutations rather than driver passenger mutations [Read the Full Post]