Blog of Signaling Pathways

The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase

0 views | Jul 16 2023

The chromatin kinase VRK1 plays a crucial role in regulating the epigenetic patterns of histone H3 acetylation and methylation, thereby influencing chromatin organization and associated nuclear functions. [Read the Full Post]

Regulation, genomics, and clinical characteristics of cuproptosis regulators in pan-cancer

60 views | Jul 16 2023

This study comprehensively elucidated the expression, prognostic significance, biological functions, genomic characteristics, immune microenvironment interactions, and drug sensitivity of cuproptosis regulators in pan-cancer, providing valuable insights into their potential role in cancer biology. [Read the Full Post]

A Point Mutation at C151 of Keap1 of Mice Abrogates NRF2 Signaling, Cytoprotection In Vitro and Hepatoprotection In Vivo by Bardoxolone Methyl (CDDO-Me)

115 views | Jul 16 2023

The mutation of the KEAP1 cysteine 151 sensor in mouse models abrogates the induction of NRF2 signaling and the subsequent cytoprotective actions of bardoxolone methyl (CDDO-Me), emphasizing its crucial role in mediating the drug's therapeutic effects. [Read the Full Post]

Dynamin-independent CaV1.2 and KCa1.1 channels regulation and vascular tone modulation by the mitochondrial fission inhibitors dynasore and dyngo-4a

45 views | Jul 15 2023

The study raises caution regarding the use of dynasore, mdivi-1, and dyngo-4a as tools to investigate the role of mitochondrial fission in vascular contraction, emphasizing the need for a selective dynamin inhibitor and/or alternative experimental approaches. [Read the Full Post]

Venetoclax Penetrates the Blood Brain Barrier: A Pharmacokinetic Analysis in Pediatric Leukemia Patients

87 views | Jul 15 2023

The results of a Phase 1 study in pediatric patients with relapsed or refractory malignancies indicate that venetoclax can penetrate the central nervous system, with measurable concentrations in the cerebrospinal fluid, and its presence correlates with improved resolution of central nervous system involvement. [Read the Full Post]

A comparative analysis to determine the optimum histone deacetylase inhibitors and administration route for improving survival and organ injury in rats after hemorrhagic shock

0 views | Jul 15 2023

The study found that intravenous administration of histone deacetylase inhibitors (HDACIs) was more effective than intraperitoneal administration, and both nonselective and isoform-specific HDACIs showed similar effects in improving survival and reducing histopathological damage, apoptosis, and inflammation in rats with hemorrhagic shock. [Read the Full Post]

Pharmacotherapeutic advances for splenomegaly in myelofibrosis

0 views | Jul 15 2023

Myelofibrosis, a hematologic malignancy characterized by splenomegaly, is primarily treated with JAK inhibitors, although spleen size reduction is not consistent, and new pharmacotherapies and combination treatments are being explored to improve outcomes. [Read the Full Post]

Comprehensive profiling of clinical JAK inhibitors in myeloproliferative neoplasms

92 views | Jul 15 2023

The comprehensive profiling of four JAK2 inhibitors revealed their distinct clinical profiles, including differential effects on JAK-STAT signaling, inflammatory response, erythroid colony formation, leukemic engraftment, and iron regulation, providing valuable insights for personalized therapy in myeloproliferative neoplasm patients. [Read the Full Post]

Specific gene module pair-based target identification and drug discovery

0 views | Jul 14 2023

The GMPTI method extracts target-induced gene modules to identify target signatures and predict novel compound-target interactions, leading to the discovery of novel inhibitors for three proteins in the PI3K pathway. [Read the Full Post]

Activity and safety of first-line treatments for advanced melanoma: A network meta-analysis

120 views | Jul 14 2023

The systematic review and network meta-analysis revealed that relatlimab/nivolumab demonstrated similar progression-free survival and overall response rate to ipilimumab/nivolumab in the first-line treatment of advanced melanoma, with a potential advantage of a better safety profile. [Read the Full Post]

Simultaneous Inhibition of Histone Deacetylases and RNA Synthesis Enables Totipotency Reprogramming in Pig SCNT Embryos

44 views | Jul 14 2023

In this study, the combined inhibition of histone deacetylases and RNA synthesis in swine SCNT embryos improved their developmental outcomes and increased the efficiency of the genome-editing + SCNT platform. [Read the Full Post]

Exploring the common pathogenesis of Alzheimer's disease and type 2 diabetes mellitus via microarray data analysis

67 views | Jul 14 2023

This study identified common differentially expressed genes, highlighted the importance of immune, hormonal, and neurotransmitter pathways, and identified potential drug candidates and key hub genes associated with Alzheimer's Disease and Type 2 Diabetes Mellitus. [Read the Full Post]

THZ531 Induces a State of BRCAness in Multiple Myeloma Cells: Synthetic Lethality with Combination Treatment of THZ 531 with DNA Repair Inhibitors

31 views | Jul 14 2023

Combining the CDK12 inhibitor THZ531 with DNA repair inhibitors such as Olaparib holds potential as an effective therapeutic approach for multiple myeloma by inducing synergistic cell death and reducing tumor burden. [Read the Full Post]

Novel hybrids of sclareol and 1,2,4-triazolo[1,5-a]pyrimidine show collateral sensitivity in multidrug-resistant glioblastoma cells

40 views | Jul 13 2023

This study describes the synthesis and evaluation of hybrid molecules combining sclareol and synthetic 1,2,4-triazolo[1,5-a]pyrimidines, resulting in compounds with improved cytotoxic properties, selectivity towards glioblastoma cells, and evasion of multidrug resistance. [Read the Full Post]

MDR1 Inhibition Reverses Doxorubicin-Resistance in Six Doxorubicin-Resistant Canine Prostate and Bladder Cancer Cell Lines

23 views | Jul 13 2023

This study generated doxorubicin-resistant sublines of canine prostate adenocarcinoma and urothelial cell carcinoma cell lines, identifying drug efflux via MDR1 overexpression as a common mechanism, and suggesting the use of MDR1 inhibitors and combination therapies to address acquired chemoresistance. [Read the Full Post]

Higher efficacy of Etoposide + Cytarabine Plus Pegfilgrastim in poorly mobilizing Multiple Myeloma and lymphoma Patients

70 views | Jul 13 2023

The retrospective analysis suggests that chemo-mobilization with etoposide, cytarabine, and pegfilgrastim is a highly effective and tolerable strategy for mobilizing hematopoietic stem cells in poorly mobilizing patients with multiple myeloma (MM) or lymphoma. [Read the Full Post]

AMD3100-mediated CXCR4 inhibition impairs development of primary lymphoma of the central nervous system

140 views | Jul 13 2023

The inhibition of CXCR4-CXCL12 interactions by AMD3100 in primary lymphoma of the central nervous system (PCNSL) downregulates CD200 expression in lymphoma cells, leading to increased microglial activation, impaired lymphoma cell invasion, and reduced tumor size, suggesting the potential therapeutic utility of AMD3100 in PCNSL. [Read the Full Post]

Kinesin Family Member C1 Overexpression Exerts Tumor-Promoting Properties in Head and Neck Squamous Cell Carcinoma via the Rac1/Wnt/β-catenin Pathway

61 views | Jul 13 2023

Abnormal upregulation of Kinesin family member C1 (KIFC1) in head and neck squamous cell carcinoma (HNSCC) is regulated by N6-methyladenosine (m6A) RNA methylation via interaction with demethylase alkB homolog 5, promoting HNSCC progression through activation of the Rac1/Wnt/β-catenin pathway. [Read the Full Post]

Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors

53 views | Jul 12 2023

The phase 3 clinical trial showed that nirogacestat, an oral γ-secretase inhibitor, significantly improved progression-free survival, objective response rates, and patient-reported outcomes while presenting common but mostly low-grade adverse events in adults with progressing desmoid tumors. [Read the Full Post]

Timed Notch Inhibition Drives Photoreceptor Fate Specification in Human Retinal Organoids

129 views | Jul 12 2023

In this study, the researchers demonstrated that timing the inhibition of the Notch signaling pathway in human retinal organoids can enhance and synchronize the differentiation of photoreceptor cells, potentially leading to an enriched population of early cone or rod photoreceptors for transplantation therapies in vision loss disorders. [Read the Full Post]