The cag pathogenicity island (PAI) has about 30 genes, part of which code for a complex type IV secretion system. The low GC-content of the cag PAI relative to the rest of the Helicobacter genome suggests the island was acquired by horizontal transfer from another bacterial species. The serine protease HtrA also plays a major role in the pathogenesis of H. pylori. The HtrA protein enables the bacterium to transmigrate across the host cells epithelium, and is also needed for the translocation of CagA.The vacA (Q48245) gene codes for another major H. pylori virulence protein. There are four main subtypes of vacA: s1/m1, s1/m2, s2/m1, and s2/m2. s1/m1 and s1/m2 subtypes are known to cause increased risk of gastric cancer. This has been linked to the ability for toxigenic vacA to promote the generation of intracellular reservoirs of H. pylori via disruption of calcium channel TRPML1. Proteome
The proteins of H. pylori have been systematically analyzed by multiple studies. As a consequence, more than 70% of its proteome have been detected by mass spectrometry and other biochemical methods. In fact, about 50% of the proteome have been quantified, that is, we know how many copies of each protein are present in a typical cell. Furthermore, the interactome of H. pylori has been systematically studied and more than 3000 protein-protein interactions have been identified. The latter provide information of how proteins interact with each other, e.g. in stable protein complexes or in more dynamic, transient interactions.
Clinical trials
In March 2011, Regeneron reported that aflibercept failed its primary endpoint of overall survival in the Vital phase III trial for second-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), although it improved the secondary endpoint of progression-free survival.In April 2011, Regeneron reported that aflibercept improved its primary endpoint of overall survival in the Velour phase III clinical trial for second-line treatment for metastatic colorectal cancer (mCRC).Aflibercept was also in a phase III trial for hormone-refractory metastatic prostate cancer as of April 2011.A 2016 Cochrane Review examined outcomes comparing aflibercept versus ranibizumab injections in over 2400 patients with neovascular AMD, from two randomized controlled trials. Both treatment options yielded similar improvements in visual acuity and morphological outcomes in patients, though the authors note that the aflibercept treatment regimen has the potential to reduce treatment burden other risks from injections.A 2017 review update studying the effects of anti-VEGF drugs on diabetic macular edema found that while all three studied treatments have advantages over laser therapy, there was moderate evidence that aflibercept is significantly favored in all measured efficacy outcomes over ranibizumab and bevacizumab, after one year. Society and culture
Legal status
In November 2011, the United States Food and Drug Administration (FDA) approved aflibercept for the treatment of wet macular degeneration.On 3 August 2012, the FDA approved aflibercept for use in combination with 5-fluorouracil, folinic acid and irinotecan to treat adults with metastatic colorectal cancer that is resistant to or has progressed following an oxaliplatin‑containing regimen.