Blog of Signaling Pathways

MCL1 Inhibition Overcomes the Aggressiveness Features of Triple-Negative Breast Cancer MDA-MB-231 Cells

16 views | Dec 22 2023

Inhibiting MCL1 through A-1210477 in triple-negative breast cancer (TNBC) MDA-MB-231 cells induces anoikis, impedes focal adhesion-mediated survival signaling pathways, diminishes migratory and invasive capabilities, reverses epithelial-mesenchymal transition (EMT) features, and suppresses stemness markers, suggesting a critical role for MCL1 in regulating TNBC aggressiveness and metastatic potential. [Read the Full Post]

Epigenetic upregulation of Schlafen11 renders WNT- and SHH-activated medulloblastomas sensitive to cisplatin

65 views | Dec 22 2023

High SLFN11 expression, identified as a top prognostic marker, is associated with longer survival in WNT-activated and a subset of SHH-activated medulloblastomas, possibly through enhanced sensitivity to DNA damaging agents such as cisplatin, with pharmacological upregulation by RG2833 showing promise for therapeutic intervention. [Read the Full Post]

Correlating Basal Gene Expression across Chemical Sensitivity Data to Screen for Novel Synergistic Interactors of HDAC Inhibitors in Pancreatic Carcinoma

50 views | Dec 22 2023

This study employs a bioinformatics screening protocol integrating drug-sensitivity data and basal gene expression to predict synergistic combinations of histone deacetylase inhibitors (HDACi), identifying the sphingolipid signaling pathway as a promising target; further experimental validation reveals novel synergisms between HDACi and a Rho-associated protein kinase (ROCK) inhibitor RKI-1447, as well as between HDACi and a sphingosine 1-phosphate (S1P) receptor agonist fingolimod in the treatment of pancreatic ductal adenocarcinoma (PDAC). [Read the Full Post]

AZ32 Reverses ABCG2-Mediated Multidrug Resistance in Colorectal Cancer

43 views | Dec 22 2023

The study established that the ATM kinase inhibitor AZ32 effectively sensitizes ABCG2-overexpressing colorectal cancer cells to chemotherapeutic drugs, such as mitoxantrone and doxorubicin, by retaining them inside cells, thus demonstrating its potential to reverse ABCG2-mediated multidrug resistance. [Read the Full Post]

Degradation of MK2 with natural compound andrographolide: A new modality for anti-inflammatory therapy

46 views | Dec 22 2023

Andrographolide, a natural compound, demonstrates anti-inflammatory effects by selectively inhibiting and promoting proteasome-mediated degradation of MK2 within the p38MAPK-MK2 signaling axis, offering a novel therapeutic approach for inflammatory diseases. [Read the Full Post]

Improving Speed and Affordability without Compromising Accuracy: Standard Binding Free-Energy Calculations Using an Enhanced Sampling Algorithm, Multiple-Time Stepping, and Hydrogen Mass Repartitioning

48 views | Dec 21 2023

The study proposes an accelerated computational strategy, combining longer time steps with hydrogen-mass repartitioning and multiple time-stepping, to efficiently calculate protein-ligand binding free energies using well-tempered metadynamics, significantly reducing computational time without compromising accuracy. [Read the Full Post]

Impact of antibiotic pharmacokinetics in urine on recurrent bacteriuria following treatment of complicated urinary tract infections

28 views | Dec 21 2023

The prolonged urinary clearance and dwell time of ertapenem, compared to tebipenem, in a study evaluating complicated urinary tract infections, introduced a temporal difference in bacterial repopulation, potentially confounding the assessment of efficacy and contributing to the ongoing controversy regarding the clinical relevance of bacteriuria post-antibiotic treatment. [Read the Full Post]

Human CYP1B1 enzyme-mediated, AhR enhanced activation of aflatoxin B1 for its genotoxicity in human cells

17 views | Dec 21 2023

This study demonstrates that human CYP1B1 metabolically activates aflatoxin B1 through the aryl hydrocarbon receptor (AhR) signaling pathway, resulting in increased genotoxic effects in human hepatocytes and lymphoblastoid cells. [Read the Full Post]

Medicare's Hospital Readmission Reduction Program reduced fall-related health care use: An unexpected benefit?

16 views | Dec 21 2023

The study found that Medicare's Hospital Readmissions Reduction Program (HRRP) was associated with significant reductions in severe fall-related injuries, particularly for congestive heart failure and pneumonia patients, indicating potential improvements in transitional care and post-acute referral patterns. [Read the Full Post]

Influence of the Essential Oil of Foeniculum vulgare Mill. on Sunflower Oil during the Deep-frying Process of Chinese Maye

50 views | Dec 21 2023

Foeniculum vulgare Mill. essential oil, when added to sunflower oil during deep frying of Chinese Maye at 1 g/kg, exhibited antioxidant properties comparable to tert-butylhydroquinone at 0.01 g/kg, making it a potential natural alternative, though further research is needed to identify its key antioxidant constituents. [Read the Full Post]

Predictive model for treatment outcomes of peripheral T-cell lymphoma, not otherwise specified, in Taiwanese patients

86 views | Dec 20 2023

In this retrospective study of 104 peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) patients in Taiwan, the investigation revealed a poor prognosis, highlighted the potential efficacy of pralatrexate as salvage chemotherapy for eligible patients, identified adverse prognostic factors, and proposed a novel predictive index with distinct risk groups, emphasizing the need for further validation and exploration of improved treatment strategies. [Read the Full Post]

YBX1-interacting small RNAs and RUNX2 can be blocked in primary bone cancer using CADD522

51 views | Dec 20 2023

The study reveals that transfer RNA-derived small RNAs, specifically tRF-GlyTCC, function as a constitutive tumor suppressor mechanism in primary bone cancer, attenuating pro-metastatic protein-RNA interactions by targeting RUNX2 via a shared sequence motif with YBX1, leading to the development of the therapeutic agent CADD522 with significant efficacy in reducing tumor progression and metastasis in PBC. [Read the Full Post]

Identification of potential biomarkers and immune infiltration characteristics in recurrent implantation failure using bioinformatics analysis

39 views | Dec 20 2023

This study reveals altered immune cell infiltration, identifies key signaling pathways, and proposes potential diagnostic markers and therapeutic compounds for recurrent implantation failure, offering valuable insights for improving endometrial receptivity in reproductive medicine. [Read the Full Post]

Caffeic Acid Phenethyl Ester: A Potential Therapeutic Cancer Agent?

41 views | Dec 20 2023

This narrative review underscores the diverse biological benefits and promising antitumor effects of caffeic acid phenethyl ester (CAPE), derived from propolis, urging further clinical trials to assess its efficacy and safety in treating various forms of human cancer following comprehensive preclinical toxicity assessments. [Read the Full Post]

Advances in the treatment of metastatic prostate cancer

32 views | Dec 20 2023

The unprecedented therapeutic advances in metastatic prostate cancer, including recent approvals of triplet therapy regimens and novel agents, pose challenges in treatment selection and sequencing, emphasizing the need for a multidisciplinary approach informed by ongoing clinical trials and personalized medicine principles. [Read the Full Post]

In vitro antineoplastic effects of MK0752 in HPV-positive head and neck squamous cell carcinoma

59 views | Dec 19 2023

The study demonstrates the potential therapeutic efficacy of the gamma-secretase inhibitor MK0752 in head and neck squamous cell carcinoma, particularly inducing apoptosis in human-papillomavirus-positive tumors, suggesting its viability as a targeted treatment option pending further validation and mechanistic exploration. [Read the Full Post]

The Ubiquitin-Proteasome System Facilitates Membrane Fusion and Uncoating during Coronavirus Entry

39 views | Dec 19 2023

Inhibiting the ubiquitin-proteasome system (UPS) at the early infection stage severely impairs the infectivity of Infectious Bronchitis Virus (IBV) and Porcine Epidemic Diarrhea Virus (PEDV) by preventing membrane fusion, uncoating, initial translation, and replication events, highlighting the UPS as a potential target for antiviral therapies against coronaviruses. [Read the Full Post]

Heat stress upregulates aromatases expression through nuclear DAX-1 deficiency in R2C Leydig tumor cells

24 views | Dec 19 2023

Heat stress at 40 °C was found to increase aromatase expression in Leydig cells, leading to a decreased testosterone to estradiol ratio, potentially impacting spermatogenesis, with the mechanism involving interference with the DAX-1-SF-1 interaction and induction of SF-1-dependent aromatase transcription. [Read the Full Post]

Inhibition of p38 signaling curtails the SARS-CoV-2 induced inflammatory response but retains the IFN-dependent antiviral defense of the lung epithelial barrier

0 views | Dec 19 2023

In this study, researchers identified the p38 MAPK pathway as a crucial target for mitigating SARS-CoV-2-induced inflammatory responses, demonstrating that selective inhibitors PH-797804 and VX-702, when used individually or in combination with antiviral drugs Remdesivir and Molnupiravir, markedly reduced pro-inflammatory cytokine expression and suppressed viral replication without compromising the interferon-mediated antiviral response in human lung tissues. [Read the Full Post]

Synthesis and biological evaluation of 4-(pyridin-4-oxy)-3-(3,3-difluorocyclobutyl)-pyrazole derivatives as novel potent transforming growth factor-β type 1 receptor inhibitors

42 views | Dec 19 2023

Compound 15r, a novel 4-(pyridin-4-oxy)-3-(3,3-difluorocyclobutyl)-pyrazole derivative, demonstrated potent inhibition of the TGF-β type 1 receptor (ALK5), with favorable pharmacokinetic properties, superior bioavailability to LY-3200882, and significant efficacy in inhibiting tumor growth in a CT26 xenograft mouse model. [Read the Full Post]