A Massively Parallel Fluorescence Assay to Characterize the Effects of Synonymous Mutations on TP53 Expression

In this reporter context, several mutations within the exon caused strong expression changes including mutations that may cause potential gain or loss of function. Further analysis indicates that these effects are largely attributed to errors in splicing, including exon skipping, intron inclusion, and exon truncation, resulting from mutations both at exon–intron junctions and within the body of the exon. These mutations are found at extremely low frequencies in healthy populations and are enriched a few-fold in cancer genomes, suggesting that some of them may be driver mutations in TP53. This assay provides a general framework to identify previously unknown detrimental synonymous mutations in cancer genes. Implications: Using a massively parallel assay, this study demonstrates that synonymous mutations in the TP53 gene affect protein expression, largely through their impact on splicing. Visual Overview: http://mcr.aacrjournals.org/content/molcanres/15/10/1301/F1.large.jpg. Mol Cancer Res; 15(10); 1301–7. ©2017 AACR.
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Rapid Impact Source Type: research

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ConclusionsThese observations suggest that SYD is effective in the enhancement of antioxidant ability via activation of Nrf2 pathway and the up-regulation of Nrf2-downstream phase II enzymes expression. The anti-inflammation and antioxidant action of SYD together contributes to the prevention and treatment of ulcerrelated colorectal cancer.Graphical abstract
Source: Journal of Ethnopharmacology - Category: Drugs & Pharmacology Source Type: research
In this study, a novel vitamin E succinate-based formulation of Ir (VES-Ir) combined with nanoscaled characteristics and synergistic combination was constructed through esterification. The conjugation makes amphiphilic VES-Ir prodrug self-assemble into nanoparticles with a fine diameter (VES-Ir NPs, 75.4 nm) of spherical morphology. Furthermore, VES-Ir NPs with a 1:1 drug-to-drug ratio was demonstrated to possess respectable physiological stability within 72 h test, while can react to pH/esterase-sensitive drug release in lysosomes internalized into tumor cells, potentially highlighting their alleviating side effects. Comp...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 22 January 2020Source: International Journal of PharmaceuticsAuthor(s): Tao Tan, Yuqi Wang, Hong Wang, Haiqiang Cao, Zhiwan Wang, Jing Wang, Jie Li, Yaping Li, Zhiwen Zhang, Siling Wang
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research
Publication date: April 2020Source: Biomedicine &Pharmacotherapy, Volume 124Author(s): Danielle Kamato, Peter J. LittleAbstractThis review will cover the signalling pathways leading to the phosphorylation of the Smad linker region independent of Smad carboxy terminal phosphorylation. Characterising Smad linker region as a signalling pathway in its own right will encourage comprehensive signalling studies to provide solutions for successful discovery and exploitation of drug targets. The review describes Smad transcription factor signalling distinct from Transforming Growth Factor (TGF)-β signalling. Novel signalli...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
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Source: Expert Opinion on Drug Delivery - Category: Drugs & Pharmacology Authors: Source Type: research
Authors: Hou T, Fan Y, Dan W, Liu B, Wang Z, Zeng J, Li L Abstract Chaperone-mediated autophagy (CMA), a selective form of autophagy, where cellular proteins with KFERQ-like motif are targeted to the lysosome for degradation, is necessary to maintain cellular homeostasis. The role of CMA in neurodegenerative diseases has been extensively studied in the past decades, with defects in the pathway being strongly associated with disease. Recently, accumulating evidence has demonstrated a consistent increase in basal CMA activity in a wide array of cancer cell lines and human tumor biopsies, suggesting a potential link b...
Source: Histology and Histopathology - Category: Cytology Tags: Histol Histopathol Source Type: research
ConclusionsDespite the inherent bias of a retrospective analysis, our long-term results showed a low toxicity profile with a relatively low rate of biochemical control for HT re-treatment in patients affected by local radiorecurrent prostate cancer. Prospective trials are needed to investigate the role of EBRT in this setting.
Source: Reports of Practical Oncology and Radiotherapy - Category: Cancer & Oncology Source Type: research
Publication date: Available online 26 November 2019Source: Practical Radiation OncologyAuthor(s): Gabriela M. Alban, Daniela L. Buscariollo, Teresa Cheng, Jennifer Pretz, Betty Krechmer, Ivan Buzurovic, Lisa Singer, Martin King, Larissa LeeAbstractPurposeOur purpose was to evaluate outcomes and sites of failure for women with early stage endometrial adenocarcinoma treated with adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) with a low dose scheme.Methods and MaterialsRetrospective review identified 318 patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II endometrioid endometrial ca...
Source: Practical Radiation Oncology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 23 January 2020Source: Clinica Chimica ActaAuthor(s): Yuling Bin, Yong Ding, Weisheng Xiao, Aijun LiaoAbstractThe Ras association domain family 1 isoform A (RASSF1A), a tumor suppressor, regulates several tumor-related signaling pathways and interferes with diverse cellular processes. RASSF1A is frequently demonstrated to be inactivated by hypermethylation in numerous types of solid cancers. It is also associated with lymph node metastasis, vascular invasion, and chemo-resistance. Therefore, reactivation of RASSF1A may be a viable strategy to block tumor progress and reverse drug resistan...
Source: Clinica Chimica Acta - Category: Laboratory Medicine Source Type: research
Publication date: Available online 22 January 2020Source: The Annals of Thoracic SurgeryAuthor(s): Katrina Steiling, Taylor Loui, Sainath Asokan, Sarah Nims, Paulo Moreira, Anuradha Rebello, Virginia R. Litle, Kei SuzukiABSTRACTBackgroundWhile lung cancer screening improves cancer-specific mortality and is recommended for high-risk patients, barriers to screening still exist. We sought to determine our institution’s screening rate, an urban safety net hospital, and to identify socioeconomic barriers to lung cancer screening.MethodsWe identified 8,935 smokers aged 55-80 evaluated by a primary care physician between Ma...
Source: The Annals of Thoracic Surgery - Category: Cardiovascular & Thoracic Surgery Source Type: research
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