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Spread through air spaces (STAS) is a unique form of lung cancer progression associated with a worse prognosis. However, the mechanisms underlying STAS and the associated proteins remain unclear. Annexin A2 (ANX A2), which is a membrane-binding protein involved in cell adhesion, is known to promote cancer invasion. In this report, we describe the immunohistochemical analysis of ANX A2 expression in an invasive mucinous adenocarcinoma (IMAC) resected from a 63-year-old man in whom the tumor cells had detached from the alveolar wall and exhibited STAS. At the detachment site, we observed cytoplasmic ANX A2 positivity on the basal side and in the exfoliative gap, as well as reduced collagen IV positivity expression. This biomarker pattern suggested an IMAC with gastric lineage. We hypothesize that ANX A2 is secreted from the basal sides of tumor cells and induces tumor cell detachment by degrading the basement membrane. A further comparison of this case with an IMAC with nongastric lineage suggested the following probabilities: (1) ANX A2 likely contributes to STAS in a manner that is dependent on its subcellular localization. (2) Both the subcellular localization of ANX A2 and the detachment site depend on tumor cell characteristics, including the biomarker immunophenotype.

Invasive micropapillary carcinoma (IMPC) is characterized by pseudopapillary tumor-cell clusters with a reverse polarity (RP) floating in lacunar spaces, with aggressive biological characteristics. The RP prevention is considered to inhibit IMPC, but its pathogenic mechanisms remain unclear. Annexin A2 (ANX A2), a cell-polarity protein, is known to be involved in lumenogenesis. ANX A2 expression is immunohistochemically examined, as well as both epithelial membrane antigen (EMA) and mucin-1 glycoprotein (MUC-1), the gold-standard markers for luminal differentiation, in the background tumor components of a case of IMPC. The following findings were noticed: (1) Apoptosis was scattered with peripheral apoptotic vacuolar change; (2) EMA and MUC-1 expressions were found, rimming the peripheral apoptotic vacuoles (including the contact surface with neighboring tumor cells), and these positions corresponded to the ones with a distinct ANX A2 positivity; and (3) partially detached tumor cells showed distinct positivity of three proteins at the stroma-facing surface, which is consistent with a RP. Taken together, frequent apoptosis in tumor cells with membranous accumulation of ANX A2 is considered to be indispensable for the reverse polarization of IMPC, and that secondary necrosis following apoptosis induces the cell-polarity disorder and creates detached tumor cells with a RP.

Classification of the adverse drug events reported in this study Adverse drug events. (DOC 71 kb)

Correlation between liver function test value at post-operative day (POD) 7 and hemoglobin at POD1. Significant correlation was not observed between hemoglobin level POD1 and liver function tests POD7, such as aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase. Statistical analysis were performed using Pearson correlation coefficient. The red ellipse represents 95% confidence interval. (PPT 185 kb)

Hemoglobin levels at POD1 and POD7 in anemia patients. In all 13 patients in the anemia (+) group, the hemoglobin value at POD 7 was lower than POD 1 with a significant difference (median: 8.9 g/dL vs 7.5 g/dL). The bottom and top of the box show the 25 and 75% rankings and therefore the interquartile range. The minimum and maximum rankings are denoted by the lower and upper whiskers. Outliers are denoted by circles. The two groups were compared using Wilcoxon signed-rank test. (PPTX 65 kb)

Comparison of the incidence rate of anemia in the bleeding (+) group and bleeding (-) group (DOC 70 kb)

Correlation between volume of bleeding during surgery and hemoglobin at post-operative day 7 (POD7). Significant correlation was not observed between volume of bleeding during surgery and hemoglobin at POD7. Statistical analysis were performed using Pearson correlation coefficient. The red ellipse represents 95% confidence interval. (PPTX 65 kb)

Comparison of the incidence rate of adverse drug events (ADE) in the effective and ineffective groups. (DOC 70 kb)

Clinical laboratory data at post-operative day (POD) 1 and POD7Alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) values at POD7 are significantly higher than POD1 (ALP (median): 185 IU/L vs 208 IU/L, LDH (median): 200 IU/L vs 214 IU/L, respectively). The bottom and top of the box show the 25 and 75% rankings and therefore the interquartile range. The minimum and maximum rankings are denoted by the lower and upper whiskers. Outliers are denoted by circles. Two groups were compared by Wilcoxon signed-rank. (PPTX 86 kb)

Correlation between liver function test value post-operative day (POD) 7 and hemoglobin at POD7. Significant correlation was not observed between hemoglobin level at POD7 and liver function tests POD7, such as aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase. Statistical analysis were performed using Pearson correlation coefficient. The red ellipse represents 95% confidence interval. (PPT 182 kb)

A unique linear synchronous motor (LSM) vehicle ME02 is designed to travel underwater based on the theory of new combined levitation and propulsion for the Marine-Express. This paper presents its stable levitation control in repulsive-mode underwater during standstill. The repulsive-mode levitation can be realized under a condition that the buoyancy of the water is smaller than the weight of the vehicle, which means that the ME02 can simulate the ME running on land. Because ME02 is a combined levitation and propulsion system, positioning control at a demand standstill-point is simultaneously carried out by the help of thrust force to levitate steadily at the standstill point. The experiment in our Laboratory has shown that ME02 vehicle had been controlled successfully to levitate underwater in repulsive-mode during standstill by applying the decoupledcontrol method of lift and thrust forces.