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In various epithelial tissues, the epithelial monolayer acts as a barrier. To fulfill its function, the structural integrity of the epithelium is tightly controlled. When normal epithelial cells detach from the basal substratum and delaminate into the apical lumen, the apically extruded cells undergo apoptosis, which is termed anoikis. In contrast, transformed cells often become resistant to anoikis and able to survive and grow in the apical luminal space, leading to the formation of multilayered structures, which can be observed at the early stage of carcinogenesis. However, the underlying molecular mechanisms still remain elusive. In this study, we first demonstrate that S100A10 and ANXA2 (Annexin A2) accumulate in apically extruded, transformed cells in both various cell culture systems and murine epithelial tissues in vivo. ANXA2 acts upstream of S100A10 accumulation. Knockdown of ANXA2 promotes apoptosis of apically extruded RasV12-transformed cells and suppresses the formation of multilayered epithelia. In addition, the intracellular reactive oxygen species (ROS) are elevated in apically extruded RasV12 cells. Treatment with ROS scavenger Trolox reduces the occurrence of apoptosis of apically extruded ANXA2-knockdown RasV12 cells and restores the formation of multilayered epithelia. Furthermore, ROS-mediated p38MAPK activation is observed in apically delaminated RasV12 cells, and ANXA2 knockdown further enhances the p38MAPK activity. Moreover, the p38MAPK inhibitor promotes the formation of multilayered epithelia of ANXA2-knockdown RasV12 cells. These results indicate that accumulated ANXA2 diminishes the ROS-mediated p38MAPK activation in apically extruded transformed cells, thereby blocking the induction of apoptosis. Hence, ANXA2 can be a potential therapeutic target to prevent multilayered, precancerous lesions. [ABSTRACT FROM AUTHOR]

Newly emerging transformed cells are often eliminated from epithelial tissues. Recent studies have revealed that this cancer-preventive process involves the interaction with the surrounding normal epithelial cells; however, the molecular mechanisms underlying this phenomenon remain largely unknown. In this study, using mammalian cell culture and zebrafish embryo systems, we have elucidated the functional involvement of endocytosis in the elimination of RasV12-transformed cells. First, we show that Rab5, a crucial regulator of endocytosis, is accumulated in RasV12-transformed cells that are surrounded by normal epithelial cells, which is accompanied by upregulation of clathrin-dependent endocytosis. Addition of chlorpromazine or coexpression of a dominant-negative mutant of Rab5 suppresses apical extrusion of RasV12 cells from the epithelium. We also show in zebrafish embryos that Rab5 plays an important role in the elimination of transformed cells from the enveloping layer epithelium. In addition, Rab5-mediated endocytosis of E-cadherin is enhanced at the boundary between normal and RasV12 cells. Rab5 functions upstream of epithelial protein lost in neoplasm (EPLIN), which plays a positive role in apical extrusion of RasV12 cells by regulating protein kinase A. Furthermore, we have revealed that epithelial defense against cancer (EDAC) from normal epithelial cells substantially impacts on Rab5 accumulation in the neighboring transformed cells. This report demonstrates that Rab5-mediated endocytosis is a crucial regulator for the competitive interaction between normal and transformed epithelial cells in mammals. [ABSTRACT FROM AUTHOR]

At the initial stage of carcinogenesis, a mutation occurs in a single cell within a normal epithelial layer. We have previously shown that RasV12-transformed cells are apically extruded from the epithelium when surrounded by normal cells. However, the molecular mechanisms underlying this phenomenon remain elusive. Here, we demonstrate that Cav-1-containing microdomains and EPLIN (also known as LIMA1) are accumulated in RasV12-transformed cells that are surrounded by normal cells. We also show that knockdown of Cav-1 or EPLIN suppresses apical extrusion of RasV12-transformed cells, suggesting their positive role in the elimination of transformed cells from epithelia. EPLIN functions upstream of Cav-1 and affects its enrichment in RasV12-transformed cells that are surrounded by normal cells. Furthermore, EPLIN regulates non-cell-autonomous activation of myosin-II and protein kinase A (PKA) in RasV12- transformed cells. In addition, EPLIN substantially affects the accumulation of filamin A, a vital player in epithelial defense against cancer (EDAC), in the neighboring normal cells, and vice versa. These results indicate that EPLIN is a crucial regulator of the interaction between normal and transformed epithelial cells. [ABSTRACT FROM AUTHOR]

Purpose The aim of this study was to evaluate the screening procedures in Japan economically focusing on the screening costs and the hospital costs for abdominal aortic aneurysm (AAA) surgery. Methods A total of 10?057 residents, 60 years of age or older, including 4?247 men and 5?810 women, participated in the screening test for AAA using ultrasound. Results Aneurysms were detected in 34 participants, including 32 men and 2 women. The detection rate of AAA was 0.8% in men, 0.03% in women, and 0.3% in total. It cost US$8 to screen each participant, and the cost to detect each aneurysm was thus estimated at $1?250 in men, $23?240 in women, and $2?366 in total. The difference in the mean hospital cost between ruptured and nonruptured AAA was $21?833 in our recent cases. Obesity, male sex, and smoking habits were all significant risk factors for AAA. Conclusion Screening for AAA using ultrasound is useful not only for the early detection of AAA but also for a reduction in the overall medical cost. [ABSTRACT FROM AUTHOR]

In this paper, we prove that an $n$-dimensional closed minimal hypersurface $M$ with Ricci curvature $Ric(M) \geq \dfrac{n}{2}$ of a unit sphere $S^{n+1}(1)$ is isometric to a Clifford torus if $n\leq S\leq n+\frac{14(n+4)}{9n+30}$, where $S$ is the squared norm of the second fundamental form of $M$. [ABSTRACT FROM AUTHOR]

An 18-year-old man was admitted to our hospital with abdominal distension and edema of both legs. His total serum bilirubin level was 5.2?mg/dl. Echocardiography showed impaired left ventricular contraction, and computed tomography showed a thickened pericardium with massive pleural effusion and ascites. Cardiac catheterization showed both a dip and a plateau in the right ventricle pressure curve, based on which we diagnosed constrictive pericarditis. The selected treatment option was a pericardiectomy. We dissected the thickened pericardium, which was about 7?10?mm thick, and removed as much as possible through a median sternotomy without cardiopulmonary bypass. Postoperatively, his hemodynamics and renal dysfunction improved, and the serum bilirubin level gradually decreased. We report this case to show how pericardiectomy was effective not only for improving this patient?s hemodynamics, but also for resolving his hyperbilirubinemia. The relevant literature is reviewed following this case report. [ABSTRACT FROM AUTHOR]