Background:There have been controversies in prognostic impact of mucinous histology on colorectal cancer, and its implication in patients treated with adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is unclear.Methods:Stage II and III colorectal cancer patients who underwent curative resection followed by adjuvant FOLFOX were included. Patients were grouped according to the mucinous content: >50%, mucinous adenocarcinoma (MAC); <50%, adenocarcinoma with intermediated mucinous component (AIM); and without any mucinous component, non-MAC (NMA). Clinicopathological features and disease-free survival (DFS) were compared.Results:Among a total of 521 patients, 27 patients (5.2%) had MAC, 41 patients (7.9%) had AIM, and 453 patients (86.9%) had NMA. Mucinous adenocarcinoma and AIM had higher frequency of proximal location and microsatellite instability, but lower frequency of angiolymphatic invasion. Disease-free survival was significantly worse in the MAC compared with NMA (3-year DFS 57% and 86%, respectively; P<0.001) and AIM (3-year DFS 87%, P=0.01 vs MAC). Multivariate analysis revealed MAC as an independent negative prognostic factor of DFS (adjusted hazard ratio 7.96, 95% confidence interval 3.76–16.8).Conclusion:Adenocarcinoma with intermediated mucinous component and MAC have distinct clinicopathological features compared with NMA. Mucinous adenocarcinoma has an adverse prognostic impact on stage II or III colorectal cancer treated with adjuvant FOLFOX.
A beam combination laser with stimulated Brillouin scattering-phase conjugate mirrors~SBS-PCMs!, which is expected to produce a high output energy and power with a repetition rate over 10 Hz, is a candidate for a practically useful laser fusion driver in the future. In order to develop the beam combination laser with SBS-PCMs, it is necessary to control the phase of each SBS wave whose phases are known as inherently random. We have proposed a new phase control technique and demonstrated experimentally that the relative phase difference between two SBS waves can be controlled to a certain value and locked to it with an accuracy less than l04. Additionally we have proposed and demonstrated a new technique to preserve the pulse shape of the SBS wave. Based on these experimental results, we have proposed two schemes of the new schemes for the high repetition and high energy0power beam combination laser system~laser fusion driver! using the SBS-PCMs of amplitude division and wave-front division techniques, which can operate with repetition rate over 10 Hz, in this paper.
A growing body of evidence implicates the noncanonical NF-κB pathway as a key driver of glioma invasiveness and a major factor underlying poor patient prognoses. Here, we show that NF-κB-inducing kinase (NIK/MAP3K14), a critical upstream regulator of the noncanonical NF-κB pathway, is both necessary and sufficient for cell-intrinsic invasion, as well as invasion induced by the cytokine TWEAK, which is strongly associated with tumor pathogenicity. NIK promotes dramatic alterations in glioma cell morphology that are characterized by extensive membrane branching and elongated pseudopodial protrusions. Correspondingly, NIK increases the phosphorylation, enzymatic activity and pseudopodial localization of membrane type-1 matrix metalloproteinase (MT1-MMP/MMP14), which is associated with enhanced tumor cell invasion of three-dimensional collagen matrices. Moreover, NIK regulates MT1-MMP activity in cells lacking the canonical NF-κB p65 and cRel proteins. Finally, increased expression of NIK is associated with elevated MT1-MMP phosphorylation in orthotopic xenografts and co-expression of NIK and MT1-MMP in human tumors is associated with poor glioma patient survival. These data reveal a novel role of NIK to enhance pseudopodia formation, MT1-MMP enzymatic activity and tumor cell invasion independently of p65. Collectively, our findings underscore the therapeutic potential of approaches targeting NIK in highly invasive tumors.
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