Blog of Signaling Pathways

Mutiple myeloma resistant to melphalan (NSC-8806) treated with cyclophosphamide (NSC-26271), prednisone (NSC-10023), and chloroquine (NSC-187208)

41 views | May 17 2023

This prospective randomized study compared the effectiveness of two therapeutic regimens in 41 patients with multiple myeloma resistant to melphalan, with no significant differences in response or toxicity observed between the groups, despite the addition of chloroquine to one regimen. [Read the Full Post]

The Effect of Direct and Indirect EZH2 Inhibition in Rhabdomyosarcoma Cell Lines

49 views | May 17 2023

The study found that direct and indirect inhibition of EZH2 affect cellular functions differently, and the alveolar cell line RH30 is more sensitive to epigenetic intervention than the embryonal cell line RD, suggesting EZH2 as a potential therapeutic target in RMS. [Read the Full Post]

Low gamma-butyrobetaine dioxygenase (BBOX1) expression as a prognostic biomarker in patients with clear cell renal cell carcinoma: a machine learning approach

38 views | May 17 2023

This study found that low BBOX1 expression in clear cell renal cell carcinoma (RCC) patients is associated with poor prognosis, decreased CD8+ T cells, and increased neutrophils, and identified potential drugs, including midostaurin, that can inhibit RCC cells with low BBOX1 expression. [Read the Full Post]

Ocular adverse events associated with BRAF and MEK inhibitor combination therapy: a pharmacovigilance disproportionality analysis of the FDA adverse event reporting system

67 views | May 17 2023

The authors conducted a retrospective study using FAERS data to investigate oAEs associated with three BRAF and MEK inhibitor combination therapies, identifying both previously reported and new oAEs and noting that oAE profiles varied across treatment regimens. [Read the Full Post]

ANCHOR CRC: Results From a Single-Arm, Phase II Study of Encorafenib Plus Binimetinib and Cetuximab in Previously Untreated BRAFV600E-Mutant Metastatic Colorectal Cancer

70 views | May 17 2023

The ANCHOR CRC study showed that the first-line combination of encorafenib + binimetinib + cetuximab was effective and safe in treating BRAFV600E-mutated metastatic colorectal cancer patients with a locally assessed confirmed objective response rate of 47.4%. [Read the Full Post]

An overview of PROTACs: a promising drug discovery paradigm

49 views | May 16 2023

PROTAC technology has emerged as a promising therapeutic approach due to its ability to target "undruggable" proteins and induce complete protein degradation, but further research and development are needed to optimize its efficacy and overcome its limitations. [Read the Full Post]

Targeting androgen receptor degradation with PROTACs from bench to bedside

30 views | May 16 2023

Recent advances in the development of small-molecule PROTAC AR degraders have shown promising clinical efficacy in the treatment of prostate cancer, overcoming resistance mechanisms and improving current therapies. [Read the Full Post]

Orally bioavailable BTK PROTAC active against wild-type and C481 mutant BTKs in human lymphoma CDX mouse models

104 views | May 16 2023

UBX-382 is a potent and orally available PROTAC that effectively targets both wild-type and mutant BTK proteins to inactivate B-cell receptor signaling, leading to complete tumor regression in murine xenograft models within 2 weeks of oral dosing. [Read the Full Post]

A myeloid leukemia factor homolog is involved in tolerance to stresses and stress-induced protein metabolism in Giardia lamblia

37 views | May 16 2023

This study investigated the role of MLF vesicles in G. lamblia and found that they share similar stress-induced characteristics with autophagy compartments and are important for survival in stress conditions. [Read the Full Post]

Efficient production of recombinant proteins in suspension CHO cells culture using the Tol2 transposon system coupled with cycloheximide resistance selection

31 views | May 16 2023

The study demonstrates an efficient method for producing therapeutic proteins using DNA recombination techniques in mammalian cells, combining the Tol2 transposon system and cell selection by cycloheximide resistance to produce stable cell lines with constant productivity and cell growth suitable for commercial production. [Read the Full Post]

An Umpolung Approach to Acyclic 1,4-Dicarbonyl Amides via Photoredox-Generated Carbamoyl Radicals

103 views | May 15 2023

This passage describes a method for the generation and reaction of carbamoyl radicals from oxamate salts followed by reaction with electron-poor olefins, which enables the mild and mass-efficient formation of 1,4-dicarbonyl products, supported by ab initio calculations, and designed to be environmentally friendly. [Read the Full Post]

A phase I/II study of epertinib plus trastuzumab with or without chemotherapy in patients with HER2-positive metastatic breast cancer

103 views | May 15 2023

This study evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of daily oral epertinib combined with trastuzumab, vinorelbine, or capecitabine in patients with pre-treated HER2-positive metastatic breast cancer, with promising results. [Read the Full Post]

Investigation of the relationship between betatrophin and certain key enzymes involved in carbohydrate and lipid metabolism in insulin-resistant mice

88 views | May 15 2023

The study found that insulin resistance increased betatrophin expression and serum levels, but did not correlate with the expression of LDH5, ACC1, and CS enzymes in mice. [Read the Full Post]

Impact of SNPs, off-targets, and passive permeability on efficacy of BCL6 degrading drugs assigned by virtual screening and 3D-QSAR approach

33 views | May 15 2023

The study utilized computational methods to identify potential BCL6 inhibitors from a library of approved drugs and highlighted the importance of considering off-target effects and membrane permeability in drug design and evaluation. [Read the Full Post]

Inhibition of MALT1 reduces ferroptosis in rat hearts following ischemia/reperfusion via enhancing the Nrf2/SLC7A11 pathway

31 views | May 15 2023

Inhibition of MALT1 can reduce I/R-induced myocardial ferroptosis through enhancing the Nrf2/SLC7A11 pathway, making MALT1 a potential therapeutic target for treating myocardial infarction. [Read the Full Post]

Health-related quality of life of patients with resistant/intolerant chronic phase chronic myeloid leukemia treated with asciminib or bosutinib in the phase 3 ASCEMBL trial

74 views | May 14 2023

The ASCEMBL study evaluated the health-related quality of life of patients with chronic myeloid leukemia in chronic phase treated with asciminib and showed stable CML symptoms and HRQOL with asciminib and a clinically meaningful increase in diarrhea severity with bosutinib. [Read the Full Post]

MET overexpression contributes to STAT4-PD-L1 signaling activation associated with tumor-associated, macrophages-mediated immunosuppression in primary glioblastomas

12 views | May 14 2023

The study found that the dysregulated receptor tyrosine kinase MET and its interaction with the tumor microenvironment, specifically the MET-STAT4-PD-L1 axis and tumor-associated macrophages, may contribute to immune evasion in primary glioblastoma and are associated with poor prognosis. [Read the Full Post]

Bifidobacterium pseudocatenulatum-Mediated Bile Acid Metabolism to Prevent Rheumatoid Arthritis via the Gut-Joint Axis

21 views | May 14 2023

The study found that Bifidobacterium pseudocatenulatum protected against joint damage in a mouse model of rheumatoid arthritis by reshaping gut microbial composition and increasing bile acid metabolism, suggesting that probiotics could be an effective preventative therapy. [Read the Full Post]

Comparative effectiveness of mobocertinib and standard of care in patients with NSCLC with EGFR exon 20 insertion mutations: An indirect comparison

53 views | May 14 2023

This study compared the effectiveness of mobocertinib, a novel EGFR tyrosine kinase inhibitor, with real-world treatments in platinum-pretreated patients with advanced EGFR ex20ins-mutant NSCLC, and found that mobocertinib provided substantially improved outcomes. [Read the Full Post]

Regulation of neuropathic pain by microglial Orai1 channels

60 views | May 14 2023

The study found that Orai1 channels are key regulators of microglial reactivity in neuropathic pain, with sex-specific effects observed in female mice. [Read the Full Post]