Blocking oncogenic signaling induced by the BRAFV600E mutation is a promising approach for melanoma treatment. We tested the anti-tumor effects of a specific inhibitor of Raf protein kinases, PLX4032/RG7204, in melanoma cell lines. PLX4032 decreased signaling through the MAPK pathway only in cell lines with the BRAFV600E mutation. Seven out of 10 BRAFV600E mutant cell lines displayed sensitivity based on cell viability assays and three were resistant at concentrations up to 10 muM. Among the sensitive cell lines, four were highly sensitive with IC50 values below 1 muM, and three were moderately sensitive with IC50 values between 1 and 10 muM. There was evidence of MAPK pathway inhibition and cell cycle arrest in both sensitive and resistant cell lines. Genomic analysis by sequencing, genotyping of close to 400 oncogeninc mutations by mass spectrometry, and SNP arrays demonstrated no major differences in BRAF locus amplification or in other oncogenic events between sensitive and resistant cell lines. However, metabolic tracer uptake studies demonstrated that sensitive cell lines had a more profound inhibition of FDG uptake upon exposure to PLX4032 than resistant cell lines. In conclusion, BRAFV600E mutant melanoma cell lines displayed a range of sensitivities to PLX4032 and metabolic imaging using PET probes can be used to assess sensitivity.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2876068 | PMC |
http://dx.doi.org/10.1186/1479-5876-8-39 | DOI Listing |
Sci Rep
December 2024
Department of Pharmaceutical Chemistry, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, India.
The emergence of self-propelling magnetic nanobots represents a significant advancement in the field of drug delivery. These magneto-nanobots offer precise control over drug targeting and possess the capability to navigate deep into tumor tissues, thereby addressing multiple challenges associated with conventional cancer therapies. Here, Fe-GSH-Protein-Dox, a novel self-propelling magnetic nanobot conjugated with a biocompatible protein surface and loaded with doxorubicin for the treatment of triple-negative breast cancer (TNBC), is reported.
View Article and Find Full Text PDFSci Rep
December 2024
Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, 422-8526, Shizuoka, Japan.
The cell painting assay is useful for understanding cellular phenotypic changes and drug effects. To identify other aspects of well-known chemicals, we screened 258 compounds with the cell painting assay and focused on a mitochondrial punctate phenotype seen with disulfiram. To elucidate the reason for this punctate phenotype, we looked for clues by examining staining steps and gene knockdown as well as examining protein solubility and comparing cell lines.
View Article and Find Full Text PDFSci Rep
December 2024
Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Lines of evidence have indicated that type 2 diabetes mellitus (T2DM) is an independent risk factor for osteoarthritis (OA) progression. However, the study focused on the relationship between T2DM and OA at the transcriptional level remains empty. We downloaded OA- and T2DM-related bulk RNA-sequencing and single-cell RNA sequencing data from the Gene Expression Omnibus (GEO) dataset.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Pathology, The Tumor Immuno-Pathology Laboratory, Erasmus University Medical Center, Wytemaweg 80, 3000 DR, Rotterdam, The Netherlands.
In previous work we discovered that T lymphocytes play a prominent role in the rise of brain metastases of ER-negative breast cancers. In the present study we explored how T lymphocytes promote breast cancer cell penetration through the blood brain barrier (BBB). An in vitro BBB model was employed to study the effects of T lymphocytes on BBB trespassing capacity of three different breast carcinoma cell lines.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Biochemistry, Faculty of Science, Mahidol University, 272 Rama VI Road, Thung Phayathai, Ratchathewi, Bangkok, 10400, Thailand.
Wnt signaling is a critical pathway implicated in cancer development, with Frizzled proteins, particularly FZD10, playing key roles in tumorigenesis and recurrence. This study focuses on the potential of repurposed FDA-approved drugs targeting FZD10 as a therapeutic strategy for nasopharyngeal carcinoma (NPC). The tertiary structure of human FZD10 was constructed using homology modeling, validated by Ramachandran plot and ProQ analysis.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!