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

55 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

65 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

82 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

51 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

85 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

67 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

116 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

92 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]

Combining Smoothened Agonist and NEL-Like Protein-1 Enhances Bone Healing

105 views | Apr 12 2019

Lee S et al. suggested that combining the hedgehog signaling agonist SAG and NELL-1 has potential as a novel therapeutic strategy for the healing of critical-size bone defects. Future directions will include optimization of dosage and delivery strategy for an SAG and NELL-1 combination product. [Read the Full Post]

Chemoproteomic Selectivity Profiling of PIKK and PI3K Kinase Inhibitors

77 views | Apr 12 2019

Reinecke M et al. showed that NVP-BEZ235 is not a PI3K inhibitor. Surprisingly, the designated ATM inhibitor CP466722 was found to bind strongly to ALK2, identifying a new chemotype for drug discovery to treat fibrodysplasia ossificans progressiva. [Read the Full Post]

Copanlisib: First Global ApprovalMarkham A

72 views | Apr 11 2019

Markham A had summarize the milestones in the development of copanlisib leading to this first approval for relapsed follicular lymphoma. [Read the Full Post]

Napabucasin: An Update on the First-in-Class Cancer Stemness Inhibitor

94 views | Apr 11 2019

Hubbard JM et al. showed that napabucasin may prove useful in targeting cancer stem cells, with the potential to suppress metastasis and prevent relapse in patients with varying cancer types. [Read the Full Post]

lncRNA MIR100HG-derived miR-100 and miR-125b mediate cetuximab resistance via Wnt/β-catenin signaling

0 views | Apr 10 2019

Lu Y et al. described a double-negative feedback loop between MIR100HG and the transcription factor GATA6, whereby GATA6 represses MIR100HG, but this repression is relieved by miR-125b targeting of GATA6. These findings identify a clinically actionable, epigenetic cause of cetuximab resistance. [Read the Full Post]

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

73 views | 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]

Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial

74 views | Apr 09 2019

Moore KN et al. identified no new safety signals. Our data support expansion of the treatment indication for poly(ADP-ribose) polymerase inhibitors to include patients with HRD-positive ovarian cancer beyond those with BRCA mutations. [Read the Full Post]

Exploration of MST1-Mediated Secondary Brain Injury Induced by Intracerebral Hemorrhage in Rats via Hippo Signaling Pathway

56 views | Apr 09 2019

Zhang P et al. revealed that MST1 played an important role in the SBI following ICH, and inhibition of MST1 could alleviate ICH-induced SBI. Therefore, MST1 may be considered as a potential therapeutic target for SBI following ICH. [Read the Full Post]

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

62 views | 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]

Lipoxygenase-mediated generation of lipid peroxides enhances ferroptosis induced by erastin and RSL3

64 views | Apr 08 2019

Shintoku R et al suggested that tumor ferroptosis is promoted by LOX-catalyzed lipid hydroperoxide generation in cellular membranes. [Read the Full Post]

MicroRNA-496 and Mechanistic Target of Rapamycin Expression are Associated with Type 2 Diabetes Mellitus and Obesity in Elderly People

51 views | Apr 06 2019

Rubie C et al. concluded that mTOR signaling through TORC1 may be affected in the regulation of T2DM. [Read the Full Post]