We propose that L. rhamnosus modulates DC function to induce a novel form of T cell hyporesponsiveness; this mechanism might be an explanation for the observed beneficial effects of probiotic treatment in clinical disease.
Background & AimsBarrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations.MethodsWe performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls.ResultsWe identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09–1.18; P = 1.8 × 10−11) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86–0.93; P = 7.5 × 10−9). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87–0.93; P = 3.72 × 10−9).ConclusionsWe identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.
Background:The study aimed to demonstrate the noninferiority of capecitabine to 5-fluorouracil (5-FU)/folinic acid (FA), in relation to progression-free survival (PFS) after first-line treatment of metastatic colorectal cancer and the benefit of adding celecoxib (C) to irinotecan/fluoropyrimidine regimens compared with placebo (P).
Results:The trial was closed following eight deaths unrelated to disease progression in the 85 enrolled (629 planned) patients. Response rates were 22% for CAPIRI + C, 48% for CAPIRI + P, 32% for FOLFIRI + C and 46% for FOLFIRI + P. Median PFS and overall survival (OS) times were shorter for CAPIRI versus FOLFIRI (PFS 5.9 versus 9.6 months and OS 14.8 versus 19.9 months) and celecoxib versus placebo (PFS 6.9 versus 7.8 months and OS 18.3 versus 19.9 months).
Conclusion:Due to the small sample size following early termination, no definitive conclusions can be drawn in relation to the noninferiority of CAPIRI compared with FOLFIRI. metastases but also in the context of disease management with regard to improving the quality of life and lengthening the survival of nonresectable patients. For many years, 5-fluorouracil (5-FU), generally combined with the biological response modifier folinic acid (FA) [4], has been the mainstay of treatment regimens for mCRC, with meta-analyses suggesting that infusional delivery is more effective [5] and associated with less grade 3/4 hematological toxicity than bolus administration [6]. The introduction of two further cytotoxic chemotherapy agents, irinotecan and oxaliplatin, have more recently allowed the development of multiline combination therapy for mCRC patients. The European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Group and others were able to demonstrate that median survival times of >20 months are now achievable [7,8], with the use of three active drugs during the course of a patient's treatment conferring maximum survival benefit [9]. It is anticipated that the use of targeted biological agents in this setting will further improve the performance of existing cytotoxic therapies [10].Currently, infusional 5-FU/FA combined with irinotecan (FOLFIRI) or oxaliplatin (FOLFOX) are regarded as standard first-line chemotherapy regimens of equivalent efficacy. The devices used during the infusion process may be associated with infection or thrombosis [11]. One possible solution to this problem might be the oral delivery of fluorouracil. Capecitabine is an inactive oral prodrug which is preferentially enzymatically converted in tumors to fluorouracil [12]. Although there are no reported studies comparing the safety and efficacy of capecitabine with infusional 5-FU, the oral prodrug has been shown to be less toxic and at least as effective as the Mayo Clinic bolus 5-FU regimen [13,14]. As combination therapy is now the first-line treatment of choice for most mCRC patients, opportunities to formally compare the efficacy and safety of infusional 5-FU/FA monotherapy versus capecitabine monotherapy are limited. Such informat...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.