Effect of taxane‐based neoadjuvant chemotherapy on fibroglandular tissue volume and percent breast density in the contralateral normal breast evaluated by 3T MR

The aim of this study was to evaluate the change of breast density in the normal breast of patients receiving neoadjuvant chemotherapy (NAC). Forty‐four breast cancer patients were studied. MRI acquisition was performed before treatment (baseline), and 4 and 12 weeks after treatment. A computer‐algorithm‐based program was used to segment breast tissue and calculate breast volume (BV), fibroglandular tissue volume (FV), and percent density (PD) (the ratio of FV over BV × 100%). The reduction of FV and PD after treatment was compared with baseline using paired t‐tests with a Bonferroni–Holm correction. The association of density reduction with age was analyzed. FV and PD after NAC showed significant decreases compared with the baseline. FV was 110.0 ml (67.2, 189.8) (geometric mean (interquartile range)) at baseline, 104.3 ml (66.6, 164.4) after 4 weeks (p < 0.0001), and 94.7 ml (60.2, 144.4) after 12 weeks (comparison with baseline, p < 0.0001; comparison with 4 weeks, p = 0.016). PD was 11.2% (6.4, 22.4) at baseline, 10.6% (6.6, 20.3) after 4 weeks (p < 0.0001), and 9.7% (6.2, 17.9) after 12 weeks (comparison with baseline, p = 0.0001; comparison with 4 weeks, p = 0.018). Younger patients tended to show a higher density reduction, but overall correlation with age was only moderate (r = 0.28 for FV, p = 0.07, and r = 0.52 for PD, p = 0.0003). Our study showed that breast density measured from MR images acquired at 3T MR can be accurately quantified using a robust computer‐aided algorithm based on non‐parametric non‐uniformity normalization (N3) and an adaptive fuzzy C‐means algorithm. Similar to doxorubicin and cyclophosphamide regimens, the taxane‐based NAC regimen also caused density atrophy in the normal breast and showed reduction in FV and PD. The effect of breast density reduction was age related and duration related. Copyright © 2013 John Wiley & Sons, Ltd.     

Atonal homolog 1 expression in lung cancer correlates with inhibitors of the Wnt pathway as well as the differentiation and primary tumor stage

Atonal homolog 1 (Atoh1) is crucial to the differentiation of many cell types and participates in tumorigenesis and progression. This study investigated the role of Atoh1 in lung cancer development and its correlation with key members of the Wnt pathway. We used immunohistochemistry to examine the expressions of Atoh1, β‐catenin, Axin, chibby, and Disabled‐2 (Dab2) in 118 samples of lung cancer. We also detected the cytoplasmic and nuclear expression of Atoh1 in lung cancer tissues using western blot. Atoh1 nuclear expression was negatively correlated with differentiation level (p = 0.004) and primary tumor stage (p = 0.044) of lung cancer. Nuclear Atoh1 expression was positively correlated with nuclear expression of chibby (p < 0.001) and Dab2 (p < 0.001). Cytoplasmic Atoh1 expression was positively correlated with the cytoplasmic expression of Axin (p = 0.028), chibby (p < 0.001), and Dab2 (p < 0.001). We conclude that the nuclear expression of Atoh1 was inversely correlated with the differentiation and primary tumor stage of lung cancers. The expression and localization of Atoh1 correlated with Axin, chibby, or Dab2. Atoh1 may be a potential therapeutic target for the inhibition of growth and progression of lung cancers.     

Pyroptosis: An inflammatory cell death implicates in atherosclerosis

Cell death and inflammation are the fundamental biological processes in both normal physiology and pathology. Apoptosis is the most well-studied process of cell death, but there are also many other forms of cell death such as necrosis, autophagy and pyroptosis. Cell death could be observed throughout atherosclerosis and plays an important role in determining the fate of atherosclerotic lesion. Inflammation, the primary response of innate immunity, is considered essential in initiating and driving atherosclerosis. Apoptosis and autophagy had been reported in atherosclerosis, however, the mechanism of cell death involved in atherosclerosis still remain largely unknown. Cell death and inflammation are inextricably linked with their effectors modulating the process of atherosclerosis. Therefore, we proposed hypothesis that pyroptosis, an inflammatory form of cell death, may be implicated in atherosclerosis and play an important role in lesion instability.     

Relevance of O-acetyl and phosphoglycerol groups for the antigenicity of Streptococcus pneumoniae serotype 18C capsular polysaccharide

Capsular polysaccharides are important virulence factors of Streptococcus pneumoniae. The polysaccharide has been used as a component of vaccines against pneumococcal diseases either as plain polysaccharide or better conjugated to a protein. The last one is the vaccine of choice to target child protection. The immune responses depend on several polysaccharide physicochemical properties that can be affected during either purification or modification in the case of conjugate vaccines. In serotype 18C, the repeating unit has a complex structure having a branched pentasaccharide with two apparently labile subtituents: glycerol-phosphate and O-acetyl group. The loss of these groups may potentially reduce the ability of the 18C polysaccharide to induce the desired immune response. Therefore, the relationship of both groups with the antigenicity and immunogenicity of 18C capsular polysaccharide is explored. It is shown that glycerol-phosphate must be preserved for conserving adequate antigenicity of the 18C capsular polysaccharide. At the same time, it was proved that O-acetyl groups do not play any role for the antigenicity and immunogenicity.     

Down-regulation of ARNT promotes cancer metastasis by activating the fibronectin/integrin β1/FAK axis

The aryl hydrocarbon receptor nuclear translocator (ARNT) is broadly involved in regulating tumorigenesis by inducing genes that are involved in tumor growth and angiogenesis. Tumorigenesis usually involves normoxic conditions. However, the role of ARNT in tumor metastasis during normoxia remains unclear. Here, we demonstrate that ARNT protein levels were decreased in late-stage human colorectal cancer using immunohistochemical analysis. Down-regulation of ARNT protein promoted cancer cell migration and invasion, which was mediated by activation of the fibronectin/integrin β1/FAK signaling axis. In addition, the enhancement of migration and invasion in ANRT knockdown cells was blocked when ARNT was restored in the cells. In xenografts in severe combined immunodeficiency mice, tumor growth was significantly inhibited in the ARNT-knockdown condition. However, the tail-vein injection animal model revealed that the depletion of ARNT-induced metastatic lung colonies was further enhanced when ARNT expression was recovered post-injection. Interestingly, chemotherapeutic drugs inhibited ARNT expression and promoted the invasion of residual tumor cells. These results suggest that ARNT may play a positive role during tumor growth (either in early-stage tumor growth or in organ metastases), but plays a negative role in tumor migration and invasion. Therefore, the efficiency of ARNT-targeted therapy during different cancer stages should be carefully evaluated.     

Tissue‐Engineered Tracheal Reconstruction Using Three‐Dimensionally Printed Artificial Tracheal Graft: Preliminary Report

Three‐dimensional printing has come into the spotlight in the realm of tissue engineering. We intended to evaluate the plausibility of 3D‐printed (3DP) scaffold coated with mesenchymal stem cells (MSCs) seeded in fibrin for the repair of partial tracheal defects. MSCs from rabbit bone marrow were expanded and cultured. A half‐pipe‐shaped 3DP polycaprolactone scaffold was coated with the MSCs seeded in fibrin. The half‐pipe tracheal graft was implanted on a 10 × 10‐mm artificial tracheal defect in four rabbits. Four and eight weeks after the operation, the reconstructed sites were evaluated bronchoscopically, radiologically, histologically, and functionally. None of the four rabbits showed any sign of respiratory distress. Endoscopic examination and computed tomography showed successful reconstruction of trachea without any collapse or blockage. The replaced tracheas were completely covered with regenerated respiratory mucosa. Histologic analysis showed that the implanted 3DP tracheal grafts were successfully integrated with the adjacent trachea without disruption or granulation tissue formation. Neo‐cartilage formation inside the implanted graft was sufficient to maintain the patency of the reconstructed trachea. Scanning electron microscope examination confirmed the regeneration of the cilia, and beating frequency of regenerated cilia was not different from those of the normal adjacent mucosa. The shape and function of reconstructed trachea using 3DP scaffold coated with MSCs seeded in fibrin were restored successfully without any graft rejection.