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Background: Tri-phosphorylated trifluridine (FTD) incorporation into DNA is TAS-102's main anti-tumor action. We tested whether genetic polymorphisms in homologous recombination (HR) and cell cycle checkpoint pathway for DNA repair is associated with outcomes in refractory metastatic colorectal cancer (mCRC) patients treated with TAS-102. Patients and methods: We analyzed genomic DNA extracted from 233 samples of three cohorts: an evaluation cohort of 52 patients receiving TAS-102, a validation cohort of 129 patients receiving TAS-102 and a control cohort of 52 patients receiving regorafenib. Single nucleotide polymorphisms of genes involved in HR (ATM, BRCA1, BRCA2, XRCC3, FANCD2, H2AX, RAD51) and cell cycle checkpoint (ATR, CHEK1, CHEK2, CDKN1A, TP53, CHE1, PIN1, PCNA) were analyzed by PCR-based direct sequencing. Results: In univariate analysis for the evaluation cohort, patients with any G allele in ATM rs609429 had longer overall survival (OS) than those with the C/C variant (8.7 vs. 4.4 months, HR 0.37, 95% CI: 0.14-0.99, P = 0.022). Patients carrying any A allele in XRCC3 rs861539 had significantly longer progression-free survival (PFS) (3.8 vs. 2.3 months, HR 0.44, 95% CI: 0.21-0.92, P = 0.024) and OS (15.6 vs. 6.3 months, HR 0.25, 95% CI: 0.08-0.79, P = 0.012) than those with the G/G variant. In multivariable analysis, ATM rs609429 remained significant for OS (P = 0.020). In the validation cohort, patients having ATM rs609429 with any G allele showed longer OS and PFS; the G/A variant in XRCC3 rs861539 showed longer OS, though without statistical significance. Conclusion: Genetic variants in the HR pathway may predict clinical outcome in mCRC patients receiving TAS-102. [ABSTRACT FROM AUTHOR]

Abstract: The effects of a ferromagnetic substrate on ac losses of a YBa2Cu3O7, YBCO, coated conductor in perpendicular ac magnetic fields were investigated by measuring the losses of a set of the specimens which were made by placing one Ni-5at.% W tape on one or both sides of a YBCO layer on a Hastelloy tape. For applied field amplitude, μ0H0, <∼5mT, the losses with the Ni-W tape(s) were higher than those of the YBCO tape, but for ∼5mT<μ0 H 0 <∼0.1T, the losses were reduced by putting the Ni-W tape(s) on the YBCO tape. For μ0 H 0 >∼0.1T, the losses became the same for all of the specimens. Also, the geometric portion χ 0 of the susceptibility χ was determined from the hysteresis loops for these specimens, and was found to decease with the addition of the magnetic substrate. These observations agreed very well with the theoretical calculations for the losses and χ 0 for a YBCO layer on a ferromagnetic substrate, by [Mawatari, arVir:0710:2151v1, (cond-mat.supr-con)]. [Copyright &y& Elsevier]

A series of multifilament composite conductors (tapes), (Bi,Pb)2Sr2Ca2Cu3Oy (Bi-2223)/Ag, was studied by transmission synchrotron X-ray diffraction, including c-axis texture studies, and by critical current measurements. The diffraction measurements indicate that the tapes typically consist of ∼90% Bi-2223 phase. Rocking curve studies of the Bi-2223 (2 0 0) peak reveal full widths at half maximum (FWHMs) in the range 13–19°. A weak correlation between rocking curve FWHMs and critical current densities suggests that the critical current values in these tapes may not be limited by the Bi-2223 c-axis orientation. [Copyright &y& Elsevier]

AC losses in perpendicular applied magnetic fields were measured for stacks of Bi2Sr2Ca2Cu3O10/Ag tapes having two different tape-stacking arrangements, straight and staggered tapes. Although the losses were the same at high fields, (above full penetration fields), they were significantly different at low fields. Also, a comparison of the losses was made in single stacks with and without paper insulation between the tapes in the stacks while the heights of the stacks were kept the same. These results were qualitatively explained by considering the relative ease of the magnetic flux penetration into the tapes in the stacks. [Copyright &y& Elsevier]

Background: The MAPK-interacting kinase 1 (MKNK1) is localized downstream of the RAS/RAF/ERK and the MAP3K1/MKK/p38 signaling pathway. Through phosphorylation MKNK1 regulates the function of eukaryotic translation initiation factor 4E, a key player in translational control, whose expression is often upregulated in metastatic colorectal cancer patients (mCRC). Preclinical data suggest that MKNK1 increases angiogenesis by upregulating angiogenic factors. We therefore hypothesize that variations in the MKNK1 gene predict outcome in mCRC patients treated with first-line FOLFIRI and bevacizumab (bev). Patients and methods: A total of 567 patients with KRAS wild-type mCRC in the randomized phase III FIRE-3 and TRIBE trials treated with first-line FOLFIRI/bev (discovery and validation cohorts) or FOLFIRI and cetuximab (cet) (control cohort) were included in this study. Five single-nucleotide polymorphisms in the MAPK signaling pathway were analyzed. Results: AA genotype carriers of the MKNK1 rs8602 single-nucleotide polymorphism treated with FOLFIRI/bev in the discovery cohort (FIRE-3) had a shorter progression-free survival (PFS) than those harboring any C (7.9 versus 10.3 months, Hazard ratio (HR) 1.73, P=0.038). This association could be confirmed in the validation cohort (TRIBE) in multivariable analysis (PFS 9.0 versus 11.0 months, HR 3.04, P=0.029). Furthermore, AA carriers in the validation cohort had a decreased overall response rate (25% versus 66%, P=0.049). Conversely, AA genotype carriers in the control group receiving FOLFIRI/cet did not show a shorter PFS. By combining both FOLFIRI/bev cohorts the worse outcome among AA carriers became more significant (PFS 9.0 versus 10.5 months) in univariable (HR 1.74, P=0.015) and multivariable analysis (HR 1.76, P=0.022). Accordingly, AA carriers did also exhibit an inferior overall response rate compared with those harboring any C (36% versus 65%, P=0.005). Conclusion: MKNK1 polymorphism rs8602 might serve as a predictive marker in KRAS wild-type mCRC patients treated with FOLFIRI/bev in the first-line setting. Additionally, MKNK1 might be a promising target for drug development. [ABSTRACT FROM AUTHOR]

Background Carcinoembryonic antigen (CEA) is the most widespread tumour marker of colorectal cancer, however, it is not helpful to judge for recurrence of the disease because of low sensitivity and specificity. It is recommended for patients who were diagnosed with pStage III colorectal cancer to receive adjuvant chemotherapy after curative resection and to measure CEA every 3 months. Moreover, It is reported that postoperative CEA level is more informative than preoperative CEA level about the impact for prognosis but the association between postoperative, post adjuvant CEA level and the prognosis is still unclear. This study aimed to evaluate whether perioperative and post adjuvant CEA level was useful for estimation of the prognosis in stage III CRC. Methods This retrospective study was conducted at the Cancer Institute Hospital of JFCR. A total of 567 consecutive patients who underwent curative resection for stage III colon adenocarcinoma and adjuvant chemotherapy in our hospital from March 2005 to December 2013 were identified. The patients who received bevacizumab as adjuvant chemotherapy and didn't measure CEA were excluded. Results The 3-year DFS rate in patients with normal preoperative CEA is superior to patients with high preoperative CEA (HR:1.59;95%CI:1.10-2.31, p = 0.014). There was no significant difference in the 5-year OD between the two groups (HR1.17;95%CI:0.62–2.20, p = 0.63). The 3-year DFS rate and 5-year OS rate in patients with normal postoperative CEA were superior to patients with high postoperative CEA (HR:2.18;95%CI:1.23–3.88, p = 0.0079, and HR:2.40;95%CI:1.02–5.69, p = 0.046). The 3-year DFS in patients with normal postadjuvant CEA was superior to patients with high postadjuvant CEA(HR1.79;95%CI:1.23–3.88, p = 0.022), whereas regarding the 5-year OS there was no significant difference between the two groups (HR2.10;95%CI:0.98–4.53, p = 0.057).In the multivariate analysis, the histological type and N-stage were predictive factors of OS. Conclusions High postoperative and post adjuvant CEA level may be negative prognosis factors for OS in patients who underwent curative resection for stage III CRC. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]