7 research outputs found
Regulation 1/2003 (and Beyond): Balancing Effective Enforcement and Due Process in Cross-Border Antitrust Investigations
Enhanced Participation of Non-State Actors in EU Law-Making and Law-Enforcement Processes: A Quest for Legitimacy
The Theory of Abuse in Google Search: A Positive and Normative Assessment Under EU Competition Law
YWHAG Deficiency Disrupts the EMTâAssociated Network to Induce Oxidative Cell Death and Prevent Metastasis
Abstract Metastasis involves epithelialâtoâmesenchymal transition (EMT), a process that is regulated by complex gene networks, where their deliberate disruption may yield a promising outcome. However, little is known about mechanisms that coordinate these metastasisâassociated networks. To address this gap, hub genes with broad engagement across various human cancers by analyzing the transcriptomes of different cancer cell types undergoing EMT are identified. The oncogenic signaling adaptor protein tyrosine 3âmonooxygenase/tryptophan 5âmonooxygenase activation protein gamma (YWHAG) is ranked top for its clinical relevance and impact. The cellular kinome and transcriptome data are surveyed to construct the regulome of YWHAG, revealing stress responses and metabolic processes during cancer EMT. It is demonstrated that a YWHAGâdependent cytoprotective mechanism in the regulome is embedded in EMTâassociated networks to protect cancer cells from oxidative catastrophe through enhanced autophagy during EMT. YWHAG deficiency results in a rapid accumulation of reactive oxygen species (ROS), delayed EMT, and cell death. Tumor allografts show that metastasis potential and overall survival time are correlated with the YWHAG expression level of cancer cell lines. Metastasized tumors have higher expression of YWHAG and autophagyârelated genes than primary tumors. Silencing YWHAG diminishes primary tumor volumes, prevents metastasis, and prolongs the median survival period of the mice
High Risk of Anal and Rectal Cancer in Patients With Anal and/or Perianal Crohnâs Disease
International audienceBackground & AimsLittle is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohnâs disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohnâs perianal disease followed up in the Cancers Et Surrisque AssociĂ© aux Maladies Inflammatoires Intestinales En France (CESAME) cohort.MethodsWe collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohnâs disease. Subjects were followed up for a median time of 35 months (interquartile range, 29â40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex.ResultsAmong the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohnâs lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistulaârelated adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistulaârelated adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohnâs disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18-551.51; P = .03).ConclusionsIn an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohnâs disease have a high risk of anal cancer, including perianal fistulaârelated cancer, and a high risk of rectal cancer