Prognostic value of lymph node ratio and extramural vascular invasion on survival for patients undergoing curative colon cancer resection

There was no study funding. We are grateful to Tony Rafferty (Tailored Information for the People of Scotland, TIPs) for providing survival data.Peer reviewedPublisher PD

Biomimetic Biomolecules in Next Generation Xeno-Hybrid Bone Graft Material Show Enhanced In Vitro Bone Cells Response

[eng] Bone defects resulting from trauma, disease, surgery or congenital malformations are a significant health problem worldwide. Consequently, bone is the second most transplanted tissue just after blood. Although bone grafts (BGs) have been used for decades to improve bone repairs, none of the currently available BGs possesses all the desirable characteristics. One way to overcome such limitations is to introduce the feature of controlled release of active bone-promoting biomolecules: however, the administration of, e.g., recombinant Bone morphogenetic proteins (BMPs) have been used in concentrations overshooting physiologically occurring concentrations and has thus raised concerns as documented side effects were recorded. Secondly, most such biomolecules are very sensitive to organic solvents and this hinders their use. Here, we present a novel xeno-hybrid bone graft, SmartBonePep®, with a new type of biomolecule (i.e., intrinsically disordered proteins, IDPs) that is both resistant to processing with organic solvent and both triggers bone cells proliferation and differentiation. SmartBonePep® is an advanced and improved modification of SmartBone®, which is a bone substitute produced by combining naturally-derived mineral bone structures with resorbable polymers and collagen fragments. Not only have we demonstrated that Intrinsically Disordered Proteins (IDPs) can be successfully and safely loaded onto a SmartBonePep®, withstanding the hefty manufacturing processes, but also made them bioavailable in a tuneable manner and proved that these biomolecules are a robust and resilient biomolecule family, being a better candidate with respect to other biomolecules for effectively producing the next generation bone grafts. Most other biomolecules which enhances bone formation, e.g., BMP, would not have tolerated the organic solvent used to produce SmartBonePep®

Supplementary Material for: Risk Factors for Local Recurrence of Large, Flat Colorectal Polyps after Endoscopic Mucosal Resection

<b><i>Aims:</i></b> Removal of large, flat colorectal polyps by endoscopic mucosal resection (EMR) is effective, but local recurrences occur regularly. This study investigated risk factors for local recurrence. <b><i>Method:</i></b> Cases of EMR of flat colorectal polyps ≥20 mm at an academic center from 2004 to 2011 were retrospectively analyzed for polyp features, resection technique, complications and local recurrences. Behavioral risk factors were retrospectively determined by self-administered questionnaires. <b><i>Results:</i></b> Data were collected for 129 patients (57.3% male, mean age at time of EMR: 65.0 years). Mean polyp size was 37.2 mm. Polyps were mostly adenoma with low-grade dysplasia (58.1%) and predominantly located in the right colon (62%). En bloc resection was performed in 31.8%. The median follow-up time was 40 months. Local recurrence occurred in 26.3% of patients, with 87% being recurrence-free after 1 year (95% CI 81-93%). A history of smoking was reported by 51.6% of patients and 88.4% reported regular alcohol consumption. Univariate analysis showed that polyp size and piecemeal resection were associated with risk of local recurrence. In multivariate analysis, only polyp size was predictive for local recurrence. No association was found for behavioral risk factors. <b><i>Conclusion:</i></b> Polyp size is the main predictor of local recurrence after EMR of large, flat colorectal polyps

Epigenetic silencing of tumor suppressor candidate 3 confers adverse prognosis in early colorectal cancer.

Colorectal cancer (CRC) is a biologically and clinically heterogeneous disease. Even though many recurrent genomic alterations have been identified that may characterize distinct subgroups, their biological impact and clinical significance as prognostic indicators remain to be defined. The tumor suppressor candidate-3 (TUSC3/N33) locates to a genomic region frequently deleted or silenced in cancers. TUSC3 is a subunit of the oligosaccharyltransferase (OST) complex at the endoplasmic reticulum (ER) which catalyzes bulk N-glycosylation of membrane and secretory proteins. However, the consequences of TUSC3 loss are largely unknown. Thus, the aim of the study was to characterize the functional and clinical relevance of TUSC3 expression in CRC patients' tissues (n=306 cases) and cell lines. TUSC3 mRNA expression was silenced by promoter methylation in 85 % of benign adenomas (n=46 cases) and 35 % of CRCs (n =74 cases). Epidermal growth factor receptor (EGFR) was selected as one exemplary ER-derived target protein of TUSC3-mediated posttranslational modification. We found that TUSC3 inhibited EGFR-signaling and promoted apoptosis in human CRC cells, whereas TUSC3 siRNA knock-down increased EGFR-signaling. Accordingly, in stage I/II node negative CRC patients (n=156 cases) loss of TUSC3 protein expression was associated with poor overall survival. In sum, our data suggested that epigenetic silencing of TUSC3 may be useful as a molecular marker for progression of early CRC.This work was supported by grants to ME from the State of Baden-Württemberg for “Center of Geriatric Biology and Oncology (ZOBEL) - Perspektivförderung” and “Biology of Frailty - Sonderlinie Medizin”. EB received funding from the Deutsche Krebshilfe (#108287, #111086), the Deutsche Forschungsgemeinschaft (DFG, BU2285) and the German Cancer Research Center (DKFZ-MOST, Ca158)