Oral capecitabine is at least equivalent to i.v. 5-FU in terms of overall survival in patients with gastrointestinal cancers. Capecitabine and 5-FU can be used interchangeably in these patient populations.

The exceptional ability of B cells to diversify through somatic mutation and improve affinity of the repertoire towards the antigens is the cornerstone of adaptive immunity. Somatic mutation is not evenly distributed and exhibits certain micro-sequence specificities. We show here that the combination of somatic mutation targeting and the codon usage in human B cell receptor (BCR) Variable (V) genes create expected patterns of mutation and post mutation changes that are focused on their complementarity determining regions (CDR). T cell V genes are also skewed in targeting mutations but to a lesser extent and are lacking the codon usage bias observed in BCRs. This suggests that the observed skew in T cell receptors is due to their amino acid usage, which is similar to that of BCRs. The mutation targeting and the codon bias allow B cell CDRs to diversify by specifically accumulating nonconservative changes. We counted the distribution of mutations to CDR in 4 different human datasets. In all four cases we found that the number of actual mutations in the CDR correlated significantly with the V gene mutation biases to the CDR predicted by our models. Finally, it appears that the mutation bias in V genes indeed relates to their long-term survival in actual human repertoires. We observed that resting repertoires of B cells overexpressed V genes that were especially biased towards focused mutation and change in the CDR. This bias in V gene usage was somewhat relaxed at the height of the immune response to a vaccine, presumably because of the need for a wider diversity in a primary response. However, older patients did not retain this flexibility and were biased towards using only highly skewed V genes at all stages of their response.

A guanine insertion polymorphism in matrix metalloproteinase-1 promoter (MMP-1 2G) is linked to early onset and aggressiveness in cancer. We determined the role of MMP-1 2G on the level of MMP-1 expression and breast cancer severity in benign breast disease, atypical hyperplasia, invasive and non invasive (in situ) breast cancer. We observed no significant difference in genotype distribution among the different breast disease groups. However, the level of MMP-1 expression was significantly higher in atypical ductal hyperplasia compared to benign breast disease; and in invasive breast cancer compared to in situ breast cancer. MMP-1 2G insertion polymorphism in the invasive group also correlated significantly with the expression of MMP-1 and breast cancer prognostic markers HER2 and P53.

Background Inflammatory bowel disease (IBD) is characterized by chronic inflammation leading to extracellular matrix remodeling, reactive stroma and activated inflammatory cells. In the pursuit of non-invasive biomarkers of disease severity and treatment response for IBD, we evaluated Protein FingerPrint Assay (PFA) of collagen formation and degradation (PRO-C3, C3M, PRO-C4, C4M), neutrophil elastase cleaved calprotectin (CPa9-HNE) and citrullinated vimentin degradation (VICM) in serum collected from 2 clinical trials in Ulcerative Colitis (UC) and Crohns Disease (CD) (NCT01466374 and NCT01294410) and matched healthy volunteers (NHV). Methods PFA were generated from serum of 88 UC, 120 CD at baseline and at Day 78 of treatment and 78 NHV. Clinical remission in UC was defined as Mayo score 2 with no individual subscore >1. Clinical response as reduction from baseline in Mayo score 3 and 30%, and decrease from baseline in rectal bleeding subscore 1 or absolute rectal bleeding subscore 1. Clinical remission in CD was defined by an absolute CD Activity Index [CDAI] score < 150 and clinical response as a reduction in CDAI100 points from baseline or an absolute CDAI score < 150. Endoscopic remission was defined as SES-CD of 0. Statistical analysis was performed on all markers between diseased and NHV, pooled responders/remitters vs non-response independent of treatment arm and longitudinally. Results At baseline, C3M, C4M and PRO-C4 had significantly higher median levels in UC and CD patients than NHVs. CPa9-HNE and VICM were significantly higher in CD compared to NHV, an increase in these markers was observed but did not meet significance in UC patients (Figure 1). Decrease of VICM from baseline at Day 78 were associated with remission (median -55%, p<0.05) in UC, while VICM decrease from baseline (median -56%, p<0.05) at Day 78 was associated with CD patients achieving endoscopic remission. In CD C3M and C4M was present at lower levels at baseline and during study in patients with clinical remission compared with those without remission. SES-CD scores were positively correlated with C4M, C3M, CPa9-HNE and PRO-C4 at both baseline and Day 78. CD patients achieving endoscopic remission had lower levels of C3M, C4M, PRO-C4 and CPa9-HNE at both baseline and Day 78. Conclusion C4M, C3M, PRO-C4, CPa9-HNE and VICM were found at higher levels in serum of IBD patients. VICM demonstrated potential as a biomarker for monitoring disease activity changes. Association of C4M, C3M and PRO-C4 with endoscopic remission in CD patients suggest that these markers may predict disease progress or regression in CD patients. However, further studies are warranted to evaluate these biomarkers in IBD patients.