Blog of Signaling Pathways

The Impact of N-nitrosamine Impurities on Clinical Drug Development

85 views | Feb 26 2023

The presence of N-nitrosamine impurities in commercially available drugs has led to shortages of marketed drugs and complications in the clinical development of new investigational products, with alternative approaches being sought for commonly employed perpetrators in DDI studies. [Read the Full Post]

Clinical efficacy of retreatment of daratumumab-based therapy (D2) in daratumumab-refractory multiple myeloma

49 views | Feb 26 2023

In a study of 43 patients with daratumumab-refractory multiple myeloma, a combination of daratumumab-based retreatment with different classes of anti-myeloma drugs showed a 49% response rate, with a median progression-free survival of 7.97 months and a median overall survival of 32.6 months. [Read the Full Post]

Endothelial-specific targeting of RhoA signaling via CD31 antibody-conjugated nanoparticles

139 views | Feb 26 2023

The study aimed to develop a CD31-targeting liposome with Fasudil, a clinically-relevant Rho kinase inhibitor, to target the RhoA signaling in endothelial cells for potential anti-angiogenic therapy by minimizing toxicity. [Read the Full Post]

Predictive factors for improvement of symptomatic cerebral vasospasm following subarachnoid hemorrhage by selective intra-arterial administration of fasudil hydrochloride

162 views | Feb 26 2023

Selective intra-arterial administration of fasudil improves neurological findings in 72.2% of patients with cerebral vasospasm following subarachnoid hemorrhage and is most effective when the spasm is limited to peripheral vessels and the patient is younger and does not have a large cerebral infarction in the spasm artery perfusion area. [Read the Full Post]

Pregabalin Mediates Retinal Ganglion Cell Survival From Retinal Ischemia/Reperfusion Injury Via the Akt/GSK3β/β-Catenin Signaling Pathway

47 views | Feb 26 2023

Pregabalin protects retinal ganglion cells from ischemia/reperfusion injury-induced apoptosis by upregulating the Akt/GSK3β/β-catenin pathway. [Read the Full Post]

Role of pericytes in the development of cerebral cavernous malformations

71 views | Feb 25 2023

Pericytes in cerebral cavernous malformation (CCM) are essential for lesion development and fibronectin intervention may provide a novel target for therapeutic intervention, as pericyte function inhibition and increased fibronectin expression were found to be linked to CCM lesion development. [Read the Full Post]

Nanodroplet-enhanced sonodynamic therapy potentiates immune checkpoint blockade for systemic suppression of triple-negative breast cancer

130 views | Feb 25 2023

The combination of STING activation, hypoxia relief, and sonodynamic therapy with anti-PD-L1 therapy using an O2-filled nanodroplet shows strong efficacy in suppressing triple-negative breast cancer growth and improving therapeutic outcome by promoting mature DCs, inducing immunogenic cell death, and enhancing tumor infiltration of CTLs. [Read the Full Post]

CB2R activation ameliorates late adolescent chronic alcohol exposure-induced anxiety-like behaviors during withdrawal by preventing morphological changes and suppressing NLRP3 inflammasome activation in the microglia of the prefrontal cortex in mice

42 views | Feb 25 2023

Chronic alcohol exposure in late adolescence increases anxiety-like behaviors by activating microglia in the prefrontal cortex, which can be prevented by activating the cannabinoid type 2 receptor through CB2R agonist treatment. [Read the Full Post]

Dapagliflozin protects against dilated cardiomyopathy progression by targeting NLRP3 inflammasome activation

48 views | Feb 25 2023

Dapagliflozin, a SGLT2 inhibitor, improves cardiac function in doxorubicin-induced dilated cardiomyopathy by suppressing the activation of the NLRP3 inflammasome through decreased p38-dependent TLR4 expression. [Read the Full Post]

Metabolomic profiling in kidney cells treated with a sodium glucose-cotransporter 2 inhibitor

17 views | Feb 25 2023

Our study found that high glucose conditions in kidney cells altered the metabolomic profile, and treatment with SGLT2 inhibitor dapagliflozin led to significant changes in the levels of metabolites such as asparagine, PC ae C34:1 and PC ae C36:2 in tubular epithelial cells, and PC aa C32:0 in podocytes, which affected multiple metabolic pathways. [Read the Full Post]

Aminopeptidases in Cancer, Biology and Prospects for Pharmacological Intervention

50 views | Feb 24 2023

Aminopeptidases play a crucial role in cellular processes and functions, including metabolism, signaling, angiogenesis, and immunology, and their overexpression in tumor cells can facilitate rapid proliferation, leading to potential use as a targeted approach for new oncological treatments. [Read the Full Post]

A randomised evaluation of low-dose cytosine arabinoside (ara-C) plus tosedostat versus low-dose ara-C in older patients with acute myeloid leukaemia: results of the LI-1 trial

55 views | Feb 24 2023

The "Pick-a-Winner" LI-1 trial of 243 older acute myeloid leukemia (AML) patients who were not suitable for intensive treatment showed no statistically significant improvement in complete remission, overall response, or overall survival with the addition of tosedostat, a selective oral aminopeptidase inhibitor, to low-dose cytosine arabinoside. [Read the Full Post]

Integrative genomic analysis facilitates precision strategies for glioblastoma treatment

52 views | Feb 24 2023

An integrative genomic analysis was conducted to advance individual-based therapies for Glioblastoma (GBM) by establishing a multiomics-based GBM classification, identifying subclass-specific efficacy of drugs, and developing a robust GBM poor prognostic signature score model that could be considered as potential biomarkers for immunotherapy response. [Read the Full Post]

Voxtalisib and low intensity pulsed ultrasound combinatorial effect on glioblastoma multiforme cancer stem cells via PI3K/AKT/mTOR

19 views | Feb 24 2023

The study found that the combination of the dual inhibitor Voxtalisib (Vox) and low intensity pulsed ultrasound (LIPUS) effectively targeted Glioblastoma (GBM) and GBMCSCs by suppressing the PI3K/AKT/mTOR pathway, reducing cell viability and motility, and increasing autophagy, providing insight into a potential therapeutic approach for GBM. [Read the Full Post]

Aberrant MEK5 signalling promotes clear cell renal cell carcinoma development via mTOR activation

83 views | Feb 24 2023

This study found that MEK5 is aberrantly expressed in clear cell renal cell carcinoma, activating the mTOR signaling pathway, and inhibiting MEK5 using BIX02189 shows promise as a new therapeutic strategy for ccRCC. [Read the Full Post]

Association between Quality of Life and Visual Acuity in a Randomized Clinical Trial of Patients with Uveitis Taking Antimetabolites

47 views | Feb 23 2023

The study evaluated the association between changes in visual acuity and quality of life among patients with non-infectious uveitis taking antimetabolites, and found that changes in visual acuity were significantly correlated with changes in quality of life, and the treatment group was not significantly associated with any quality of life measure. [Read the Full Post]

Influence of SLCO1B1 Polymorphisms on the Pharmacokinetics of Mycophenolic Acid in Renal Transplant Recipients

62 views | Feb 23 2023

This study found a correlation between 4 single nucleotide polymorphisms (SNPs) and the pharmacokinetics of mycophenolic acid (MPA) in renal transplant recipients, with the most relevant SNP being rs4149036 located in SLCO1B1, which had a stronger influence on older, male, or high-albumin recipients. [Read the Full Post]

Role of STAT3 in the initiation, progression, proliferation and metastasis of breast cancer and strategies to deliver JAK and STAT3 inhibitors

66 views | Feb 23 2023

This review article focuses on the role of STAT3 in the development and progression of breast cancer, and the potential of phytochemicals, synthetic molecules, and biologicals to inhibit JAK-STAT and STAT3, as a promising approach in the development of better therapeutics against breast cancer. [Read the Full Post]

The novel histone deacetylase inhibitor pracinostat suppresses the malignant phenotype in human glioma

33 views | Feb 23 2023

Pracinostat is a promising novel therapy for human glioma, as it inhibited proliferation, induced apoptosis, and reduced migration and invasion, while also affecting the PI3K/Akt and STAT3 pathways. [Read the Full Post]

Emergence of monkeypox: a worldwide public health crisis

29 views | Feb 23 2023

Monkeypox, a zoonotic virus similar to smallpox that infects humans, has become a global health threat with growing incidence and geographic distribution, and currently lacks a specific therapy but can be treated with vaccines and FDA-approved antiviral medications such as brincidofovir, tecovirimat, and cidofovir. [Read the Full Post]