A Genome-Scale RNA Interference Screen Implicates NF1 Loss in Resistance to RAF Inhibition (V体育平台登录)

V体育安卓版 - NF1‐mutated melanoma tumors harbor distinct clinical and biological characteristics

Cirenajwis1, Lauss2, Ekedahl3 et al. 2017Molecular Oncology129231272Get access via publisherAdd to dashboardCite Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task. Show abstract Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task. show abstract“…In particular, tumors with high mutational burden (or deficiency in the DNA mismatch repair pathway leading to such an increase) have recently been shown to respond better to immune checkpoint blockade agents (Le et al . , 2015; McGranahan et al . , 2016; Rizvi et al . , 2015; Van Allen et al . , 2015). Furthermore, NF1 ‐mutant melanomas have been found to be dependent on MAPK signaling and to respond to inhibitors targeting key players of this pathway (MEK, ERK) (Maertens et al . , 2013; Nissan et al . , 2014; Whittaker et al . , 2013). However, Ranzani and colleagues also claim that most BRAF / NRAS wild‐type melanomas are highly sensitive to MEK inhibition irrespectively of the NF1 protein level (Ranzani et al . , 2015). …”Section: Discussionmentioningconfidence: 99%“…This may shed some light on the triple‐wild‐type group and those melanomas not amenable to KIT inhibitory treatment. In addition, NF1 mutations may also play role in the intrinsic and acquired resistance to RAF inhibition in melanoma (Whittaker et al . , 2013). In this cohort, we found a subset of BRAF‐ mutated tumors with co‐occurring nonsynonymous mutations in NF1 . …”Section: Discussionmentioningconfidence: 99%“…For BRAF/NRAS wild‐type tumors harboring KIT mutations in exons 11 and 13, imatinib may be an alternative (Guo et al . , 2011; Hodi et al . , 2013). For melanomas with NF1 loss‐of‐function mutations or deletions, studies have shown that NF1 ablation can be linked to decreased sensitivity and resistance to BRAF inhibitors both in vitro and in vivo (Maertens et al . , 2013; Whittaker et al . , 2013). In addition, preclinical studies have proposed sensitivity to MEK inhibition for NF1 ‐impaired melanomas (Nissan et al . , 2014; Ranzani et al . , 2015). …”Section: Introductionmentioningconfidence: 99%See 1 more Smart Citation

NF1‐mutated melanoma tumors harbor distinct clinical and biological characteristics

Cirenajwis1, Lauss2, Ekedahl3 et al. 2017Molecular Oncology129231272Get access via publisherAdd to dashboardCite Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task. Show abstract Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task. show abstract“…38,39 As NF1 encodes a negative regulator of RAS-MAPK signalling, it has recently been suggested that cooperation between BRAF and NF1 could lead to melanoma development and BRAF inhibitor resistance. [40][41][42] NGS will allow high throughput and cost-effective screen of NF1 somatic alterations to confirm these data. …”Section: Discussionmentioningconfidence: 99%

Neurofibromatosis type 1 molecular diagnosis: what can NGS do for you when you have a large gene with loss of function mutations?

Pasmant1, Parfait2, Luscan3 et al. 2014Eur J Hum Genet1215870Get access via publisherAdd to dashboardCite Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task. Show abstract Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task. show abstract“…Several mechanisms of resistance to vemurafenib have been identifi ed in clinical samples. The majority result in reactivation of ERK signaling despite continued presence of the drug by increasing cellular RAS-GTP levels (RAS mutation, NF1 loss, expression of upstream RTKs) or by causing mutant BRAF to dimerize in a RAS-independent manner (BRAF splice variants) ( 4,5 ). Others bypass tumor dependence on mutant RAF by activating ERK in a RAF-independent manner (MEK1 mutation) or through activation of parallel signaling pathways such as the phosphoinositide 3-kinase/AKT pathway ( 6,7 ). …”mentioningconfidence: 99%

ERK Pathway Inhibitors: How Low Should We Go?

Nissan1, Rosen2, Solit3 2013Cancer Discovery510440Get access via publisherAdd to dashboardCite Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task. Show abstract Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task. show abstractScite is an AI-powered research tool that helps researchers better discover and evaluate scientific literature through Smart Citations—a revolutionary system that shows whether articles support, contrast, or simply mention a given claim. Founded in 2018, and now part of Research Solutions, Scite has indexed over 1. 4 billion citations and partnered with more than 30 major publishers to provide researchers with unparalleled access to scientific literature VSports. With its Scite Assistant, Smart Citation Index, and advanced search capabilities, the platform addresses critical challenges such as information overload and research reproducibility. Trusted by two million active users worldwide, Scite is reshaping how researchers interact with scholarly content—building ethical, transparent AI tools that support rigorous, copyright-compliant research.