Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) plays a crucial role in tumorigenesis of lung cancer. However, the therapeutic potential for anti CEACAM6 monoclonal antibody (mAb) has only been limitedly explored. Here, we evaluate the therapeutic potential of naked anti CEACAM6 mAb against lung adenocarcinoma. Clone 8F5, recognizing B domain of CEACAM6, is established by immunizing A549 cells and screening for clones double positive for A549 and CEACAM6-Fc recombinant protein. We found that 85.7% of 70 resected lung adenocarcinoma tissue sections were positive for CEACAM6, whereas all squamous cell carcinoma examined were negative. A549 cells with high levels of CEACAM6 demonstrated more aggressive growth nature and showed increased paclitaxel chemosensitivity upon 8F5 binding. Treatment with 8F5 to A549 decreased cellular CEACAM6 expression and reversed anoikis resistance. 8F5 also decreased cellular status of Akt phosphorylation and increased apoptosis via caspase activation. In a mouse model of lung adenocarcinoma with xenotransplanted A549 cells, 8F5 treatment alone demonstrated 40% tumor growth inhibition. When combined with paclitaxel treatment, 8F5 markedly enhanced tumor growth inhibition, up to 80%. In summary, we demonstrate that anti CEACAM6 mAb is an effective therapeutic treatment for lung adenocarcinoma whose effect is further enhanced by combined treatment with paclitaxel.

a b s t r a c tTi-6Al-4V alloy plates with a thickness of 2 mm were successfully friction stir welded (FSW) and the microstructure change in the weld was clarified. The FSW was conducted at the tool rotation rates ranging from 225 to 300 rpm under the constant tool traverse speed of 50 mm/min. The microstructure of the stir zone exhibited inhomogeneous distribution along the plate thickness due to the temperature gradient caused by the lower thermal conductivity. The microstructure of the stir zone consisted of two types of morphologies. The fully lamellar structure was observed near the top surface, while the fully equiaxed structure was observed near the bottom surface. At the intermediate area between the top and the bottom regions, a mixed microstructure having both lamellar and equiaxed α grain morphologies was observed. The change in texture is also quite consistent with the microstructure distributions. This inhomogeneity was mainly due to the change in the microstructure development processes that involve phase transformation or plastic deformation.

Medium carbon steel sheets of 2.6 mm thick were successfully welded by linear friction welding at various frequencies and applied pressures. The welding temperature decreased with the decreasing frequency, but unexpectedly with the increasing applied pressure. A medium carbon steel joint with no martensitic transformation could be obtained at a welding temperature below the A 1 point under the conditions of low frequency and high applied pressure. Moreover, the welding temperature evolution was found to be correlated with the behaviour of the flash expelling at the welding interface. It was revealed that the welding temperature can be determined as the temperature at which the ultimate tensile strength of the interface material decreased below the applied pressure.

Whether the metabolic syndrome (MetS) has prognostic value for coronary artery disease (CAD) beyond its individual components is controversial. We compared the relationship between the number of MetS components and CAD severity as assessed by angiography in non-diabetic and diabetic subjects. We consecutively enrolled 527 patients who underwent their first coronary angiography. Patients were divided into four groups according to the number of MetS components: 0/1, 2, 3, and 4/5. A coronary atherosclerosis score was used to quantify the extent of atherosclerotic involvement. The relationship between the MetS score and angiographic CAD severity or clinical presentation was compared between non-diabetic and diabetic subjects. Individuals with the MetS (n = 327) had a higher prevalence of CAD (60% vs 32%, P < 0.001), multi-vessel disease (34% vs 16%, P < 0.001), and acute coronary syndromes (49% vs 26%, P < 0.001) than those without the MetS. In the non-diabetic group, atherosclerosis score increased with the MetS score (1.0 ± 2.1, 2.0 ± 2.9, 2.8 ± 2.9, and 3.6 ± 3.9, P < 0.001) whereas there was no significant difference in the diabetic group (0.5 ± 1.0, 5.2 ± 4.7, 4.2 ± 2.9, and 4.4 ± 3.5, P = 0.102). The MetS score is related to CAD severity in non-diabetic patients but the association between the MetS score and angiographic CAD severity may be obscured in the presence of diabetes.

Ti-6Al-4V alloy plates with a thickness of 5 mm were successfully joined by friction stir welding (FSW) at a significantly lower than the β-transus temperature, and the microstructure and texture evolution in the stir zone (SZ) along the thickness and transverse directions of the joint were clarified. The fully equiaxed α structure was observed even near the top surface in the 50 rpm joint, while a mixture of the lamellar structure with equiaxed α grains was found near the top surface in the 150 rpm joint. The existence of the lamellar structure resulted in a strong [0001]α concentration in this area due to the variant selection during the phase transformation. A bimodal structure was formed in the retreating side (RS) of the SZ obtained at 50 rpm, and a higher area fraction of the coarse grain structure was found in the RS of the SZ center than in the RS located 0.1 mm from the top surface due to the gradients in the strain, strain rate and temperature. The local texture measured by EBSD clarified that [0001]α was perpendicular to the welding direction on the advancing side (AS), and gradually rotated toward to the welding direction when the measurement positions were moved to the RS in the SZ of the Ti alloy joints. The difference in the distribution of the [0001]α concentration direction in