Safety and outcome of definitive chemoradiotherapy in elderly patients with oesophageal cancer

Little is known about chemoradiotherapy (CRT) in elderly patients with a locally advanced oesophageal cancer (OC). The aim of our study was to evaluate the tolerance and the outcome of elderly patients older than 70 years treated with CRT for a non-metastatic OC. Chemoradiotherapy was based on radiotherapy combined with a cisplatin-based chemotherapy. Clinical complete response (CCR) to CRT was evaluated on upper digestive endoscopy and computed tomography scan 6–8 weeks after CRT completion. One hundred and nine consecutive patients were included. A CCR was observed in 63 patients (57.8%) and 2-year survival was 35.5%. Adverse events ⩾grade 3 were observed in 26 (23.8%) patients. Chemotherapy dose reduction, chemotherapy delays more than 1 week, and treatment discontinuation were observed in 33 (30.3%), 45 (41.3%), and 17 patients (15.6%), respectively. Comorbidity index according to Charlson score was significantly associated with treatment tolerance. In multivariate analysis, a CCR to CRT (P<0.01), a dose of radiotherapy ⩾80% (P=0.02), and a Charlson score ⩽2 (P=0.046) were identified as independent prognostic factors of overall survival. These results suggest that CRT could be considered as an effective treatment without major toxicity in elderly patients with OC

Differential Selection on Carotenoid Biosynthesis Genes as a Function of Gene Position in the Metabolic Pathway: A Study on the Carrot and Dicots

Background: Selection of genes involved in metabolic pathways could target them differently depending on the position of genes in the pathway and on their role in controlling metabolic fluxes. This hypothesis was tested in the carotenoid biosynthesis pathway using population genetics and phylogenetics. Methodology/Principal Findings: Evolutionary rates of seven genes distributed along the carotenoid biosynthesis pathway

The wonders of flap endonucleases: structure, function, mechanism and regulation.

Processing of Okazaki fragments to complete lagging strand DNA synthesis requires coordination among several proteins. RNA primers and DNA synthesised by DNA polymerase α are displaced by DNA polymerase δ to create bifurcated nucleic acid structures known as 5'-flaps. These 5'-flaps are removed by Flap Endonuclease 1 (FEN), a structure-specific nuclease whose divalent metal ion-dependent phosphodiesterase activity cleaves 5'-flaps with exquisite specificity. FENs are paradigms for the 5' nuclease superfamily, whose members perform a wide variety of roles in nucleic acid metabolism using a similar nuclease core domain that displays common biochemical properties and structural features. A detailed review of FEN structure is undertaken to show how DNA substrate recognition occurs and how FEN achieves cleavage at a single phosphate diester. A proposed double nucleotide unpairing trap (DoNUT) is discussed with regards to FEN and has relevance to the wider 5' nuclease superfamily. The homotrimeric proliferating cell nuclear antigen protein (PCNA) coordinates the actions of DNA polymerase, FEN and DNA ligase by facilitating the hand-off intermediates between each protein during Okazaki fragment maturation to maximise through-put and minimise consequences of intermediates being released into the wider cellular environment. FEN has numerous partner proteins that modulate and control its action during DNA replication and is also controlled by several post-translational modification events, all acting in concert to maintain precise and appropriate cleavage of Okazaki fragment intermediates during DNA replication