Blog of Signaling Pathways

SLC26A3 (DRA) is stimulated in a synergistic, intracellular Ca2+ dependent manner by cAMP and ATP in intestinal epithelial cells

12 views | Jun 14 2023

The study demonstrated that the combined presence of subthreshold concentrations of forskolin and ATP synergistically stimulated DRA activity and intracellular calcium levels, potentially contributing to increased anion secretion in diarrheal diseases with elevated cAMP and Ca2+ levels. [Read the Full Post]

From preclinical efficacy to 2022 updated CROWN trial, lorlatinib is the preferred 1st-line treatment of advanced ALK+ NSCLC

118 views | Jun 14 2023

The data from the CROWN trial, including the sustained and durable responses, favorable 3-year progression-free survival rates, and manageable CNS adverse events, strongly support lorlatinib as the preferred treatment for advanced ALK+ NSCLC. [Read the Full Post]

High-Content Drug Discovery Targeting Molecular Bladder Cancer Subtypes

51 views | Jun 14 2023

This study utilized high-content screening drug discovery to identify subtype-specific therapies for muscle-invasive bladder cancer (MIBC), uncovering sensitivities to HDAC and CHK inhibitors in basal subtype, MDM2 inhibitors in luminal subtype, and an ITGAV inhibitor in mesenchymal-like subtype, with potential implications for personalized treatment strategies in clinical trials. [Read the Full Post]

Identifying CDC7 as a synergistic target of chemotherapy in resistant small-cell lung cancer via CRISPR/Cas9 screening

0 views | Jun 14 2023

Silencing CDC7 and combining the CDC7 inhibitor XL413 with chemotherapy demonstrated synergistic effects, increasing apoptosis, inducing cell cycle arrest, and improving the efficacy of chemotherapy in chemo-resistant small-cell lung cancer (SCLC) cells both in vitro and in vivo. [Read the Full Post]

Identification of Piperlongumine as Potent Inhibitor of Necroptosis

74 views | Jun 14 2023

Piperlongumine, an alkaloid derived from the long pepper plant, has demonstrated potent anti-necroptosis effects by inhibiting the phosphorylation of RIPK1 and showed potential therapeutic value for inflammatory and neurodegenerative diseases associated with necroptosis. [Read the Full Post]

Targeting Akt/PKB in pediatric tumors: A review from preclinical to clinical trials

0 views | Jun 13 2023

Akt inhibitors show promise as a feasible and potentially effective approach for treating pediatric tumors by targeting the PI3K/Akt/mTOR signaling pathway. [Read the Full Post]

GEF-H1 Transduces FcεRI Signaling in Mast Cells to Activate RhoA and Focal Adhesion Formation during Exocytosis

84 views | Jun 13 2023

The study found that GEF-H1 acts as a signal transducer, activating RhoA and promoting mast cell spreading and exocytosis, thus playing a crucial role in antigen-stimulated mast cell activation. [Read the Full Post]

Entospletinib with decitabine in acute myeloid leukemia with mutant TP53 or complex karyotype: A phase 2 substudy of the Beat AML Master Trial

28 views | Jun 13 2023

The combination of entospletinib and decitabine showed limited efficacy with low complete remission rates and short overall survival in older patients with acute myeloid leukemia (AML) and specific genetic mutations or karyotype abnormalities. [Read the Full Post]

Effect of Extracellular Signal-Regulated Protein Kinase 5 Inhibition in Clear Cell Renal Cell Carcinoma

32 views | Jun 13 2023

The study demonstrates that the inhibition of ERK5, regulated by miR-143, holds promise as a potential therapeutic target for the treatment of clear cell renal cell carcinoma (ccRCC). [Read the Full Post]

USP1 promotes the aerobic glycolysis and progression of T-cell acute lymphoblastic leukemia via PLK1/LDHA axis

32 views | Jun 13 2023

The study demonstrated that the upregulation of deubiquitinase USP1 in pediatric T-ALL correlated with poor prognosis, and its inhibition attenuated glycolytic metabolism and cellular proliferation, suggesting USP1 as a promising therapeutic target. [Read the Full Post]

Targeting mitochondrial energetics reverses panobinostat- and marizomib-induced resistance in pediatric and adult high-grade gliomas

24 views | Jun 12 2023

This study investigates the molecular mechanisms and vulnerabilities associated with acquired resistance to the combination therapy of panobinostat and marizomib in high-grade gliomas, highlighting the importance of targeting glycolysis and mitochondrial function to overcome resistance. [Read the Full Post]

PKM2/PDK1 dual-targeted shikonin derivatives restore the sensitivity of EGFR-mutated NSCLC cells to gefitinib by remodeling glucose metabolism

0 views | Jun 12 2023

Compound E5, a dual inhibitor of PKM2/PDK1, demonstrates potent inhibitory activity against EGFR mutant NSCLC cells, exhibits good anti-tumor efficacy in xenografted mouse models, and shows potential as an adjunct to gefitinib in the treatment of EGFR-TKI-resistant NSCLC. [Read the Full Post]

Serum Neurofilament Light Chain in Patients With Atrial Fibrillation

23 views | Jun 12 2023

Patients with atrial fibrillation (AF) exhibit elevated levels of serum neurofilament light chain (sNFL), a marker of neuroaxonal damage, compared to controls without AF, and ongoing AF rhythm is associated with even higher sNFL levels. [Read the Full Post]

Screening the Tocriscreen™ bioactive compound library in search for inhibitors of Candida biofilm formation

23 views | Jun 12 2023

The study identified several compounds, including toyocamycin and darapladib, with potent biofilm inhibitory activity against Candida species, offering potential for the development of new clinically approved antifungal agents for the treatment of Candida biofilms. [Read the Full Post]

Azeliragon inhibits PAK1 and enhances the therapeutic efficacy of AKT inhibitors in pancreatic cancer

58 views | Jun 12 2023

The study identified azeliragon as a potent inhibitor of PAK1 and demonstrated its ability to promote apoptosis in pancreatic cancer cells, inhibit tumor growth in a xenograft model, and exhibit a synergistic effect when combined with afuresertib, suggesting its potential as a novel treatment strategy for pancreatic cancer. [Read the Full Post]

TLR4 is one of the receptors for Chikungunya virus envelope protein E2 and regulates virus induced pro-inflammatory responses in host macrophages

81 views | Jun 11 2023

TLR4 inhibition using TAK-242 reduces CHIKV infection by decreasing viral copy number, CHIKV-E2 protein levels, and pro-inflammatory responses, highlighting TLR4 as a novel receptor involved in viral entry and modulation of infection-induced inflammation. [Read the Full Post]

Liver X Receptor Activation Attenuates Oxysterol-Induced Inflammatory Responses in Fetoplacental Endothelial Cells

76 views | Jun 11 2023

The study suggests that 7-ketocholesterol and 7β-hydroxycholesterol induce placental inflammation in gestational diabetes mellitus by activating TLR-4 and that pharmacological activation of LXR can attenuate the pro-inflammatory effects of these oxysterols in fetoplacental endothelial cells. [Read the Full Post]

Identifying the molecular mechanisms of sepsis-associated acute kidney injury and predicting potential drugs

73 views | Jun 11 2023

This study utilized weighted co-expression network analysis, machine learning, immune cell correlation, and drug prediction to identify key ferroptosis genes, potential diagnostic markers, and therapeutic targets, such as miR-650 and miR-296-3p genes, OLFM4, CLU, RRM2, SLC2A3, CCL5, ADAMTS1, and EPHX2, and suggested EHT1864 and salubrinal as potential therapeutic agents for septic acute kidney injury (SA-AKI). [Read the Full Post]

Dimethyloxalylglycine Attenuates Steroid-Associated Endothelial Progenitor Cell Impairment and Osteonecrosis of the Femoral Head by Regulating the HIF-1α Signaling Pathway

34 views | Jun 11 2023

Targeting hypoxia-inducible factor-1α (HIF-1α) in endothelial progenitor cells (EPCs) may offer a novel therapeutic approach for the treatment of steroid-associated osteonecrosis of the femoral head (SONFH) by alleviating glucocorticoid-induced endothelial impairment, promoting angiogenesis and osteogenesis, and enhancing the homing of EPCs to the injured endothelium. [Read the Full Post]

Proteasome inhibitors in medullary thyroid carcinoma: time to restart with clinical trials?

47 views | Jun 11 2023

This review summarizes the available in vitro and in vivo data on the role of proteasome inhibitors (PrIn) in medullary thyroid cancer (MTC) and highlights the need for further clinical trials to explore their potential as a treatment option for MTC patients. [Read the Full Post]