Significance of ZO-1, an Intercellular Adhesion Molecule, as a Prognostic Marker in Lung Adenocarcinoma.

In epithelial tissues, intercellular adhesion structures are formed between adjacent cells via intercellular adhesion factors, such as zonula occludens (ZO-1), to maintain the structure and function of tissues and organs, thereby contributing to homeostasis. Epithelial cells are polarized into apical and basal regions by tight junctions (TJs), a type of intercellular adhesion structure, and thus, their intracellular organelles are asymmetrically distributed. Normal epithelial cells maintain their cellular function by controlling cytoskeletal reorganization, motility, and division by maintaining asymmetry in their intracellular organelles. Among the features common to many cancer tissues are abnormalities in cell polarity and intercellular adhesion. Lung adenocarcinoma consists of a mixture of five different histologic types that can be distinguished in the same section: lepidic, papillary, acinar, micropapillary, and solid patterns. Therefore, it is often difficult to accurately assess histological images because the staining differs according to the histological types. In the present study, we evaluated ZO-1 staining based on histological features observed in a single section and examined its relationship to clinicopathological features. In non-tumor areas, ZO-1 was expressed on the plasma membrane and in the cytoplasm of normal alveolar epithelial cells. However, in tumor areas, ZO-1 staining was mainly localized in the cytoplasm and on the plasma membrane only in a few cells. ZO-1-negative cases tended to have poorer prognoses in all histological types, with a poorer prognosis in the solid pattern. These results suggest that ZO-1 expression in solid-pattern lung adenocarcinoma may be a useful prognostic marker.

Protective effect of ebselen on bleomycin-induced lung fibrosis: analysis of the molecular mechanism of lung fibrosis mediated by oxidized diacylglycerol.

The molecular mechanisms underlying the development of pulmonary fibrosis remain unknown, and effective treatments have not yet been developed. It has been shown that oxidative stress is involved in lung fibrosis. Oxidized diacylglycerol (DAG) produced by oxidative stress is thought to play an important role in lung fibrosis. This study assessed the effect of oxidized DAG in an animal model of pulmonary fibrosis induced by aspiration of bleomycin (BLM) into the lungs. The inhibitory effect of ebselen on pulmonary fibrosis was also investigated. In lung fibrotic tissue induced by BLM, an increase in lipid peroxides and collagen accumulation was observed. Moreover, the levels of oxidized DAG, which has strong protein kinase C (PKC) activation activity, were significantly increased over time following the administration of BLM. Western blotting showed that phosphorylation of PKCα and δ isoforms was increased by BLM. Oral administration of ebselen significantly suppressed the increase in oxidized DAG induced by BLM and improved lung fibrosis. PKCα and δ phosphorylation were also significantly inhibited. The mRNA expression of α-smooth muscle actin and collagen I (marker molecules for fibrosis), as well as the production of transforming growth factor-ß and tumor necrosis factor-α(a potentially important factor in the fibrotic process), were increased by BLM and significantly decreased by ebselen. The administration of BLM may induce lipid peroxidation in lung tissue, while the oxidized DAG produced by BLM may induce overactivation of PKCα and δ, resulting in the induction of lung fibrosis.

Enteric-type thymic adenocarcinoma: a case report and literature review focusing on prognosis based on histological subtypes.

Thymic adenocarcinoma is a rare disease and enteric-type thymic adenocarcinoma is even more rarely found. We report a resected case of a non-mucinous, enteric-type thymic adenocarcinoma in a 53-year-old woman. The operation was performed by median sternotomy, and the tumor was stage II in the Masaoka classification. Six months after the operation, recurrence-free follow-up is currently underway. Knowledge of enteric-type thymic adenocarcinoma can prevent misdiagnosis of metastatic tumors. We also determined the prognosis of enteric-type thymic adenocarcinoma based on histological subtypes through our literature review.

Par3 and ZO-1 Membrane Clustering is an Indicator of Poor Prognosis in Lung Squamous Cell Carcinoma.

Epithelial cells form epithelial tissue structures by joining together via intercellular adhesion structures composed of intercellular adhesion factors such as zona occludins-1 (ZO-1). Epithelial cells are polarized at the apical and basal regions, and are bordered by intercellular adhesion structures called tight junctions; the organelles within epithelial cells are distributed asymmetrically. Maintenance of this asymmetry in normal epithelial cells is essential for normal cytoskeletal remodeling, movement, and cell division. The key factor regulating cell polarity is called partitioning-defective protein 3 (Par3). Abnormalities in cell polarity and intercellular adhesion are common features of many cancer tissues. Mutation and loss of cell polarity regulators contributes to the immortalization of normal cells and to the malignant transformation of cancer cells. In this study, we investigated the relationship between the subcellular localization of Par3 and ZO-1 and clinicopathological features of lung squamous cell carcinoma (lung SqCC). Both molecules were localized to the cell membrane in normal lung tissue, but the levels were lower at this location in pulmonary tumor tissue compared with normal lung tissue. Both Par3 and ZO-1 accumulated in clusters on the cell membrane (hereinafter, "foci"). Tumor size, recurrence rate, and mortality rate were significantly higher in patients with Par3 foci compared to those without Par3 foci. Rates of lymph node metastasis, recurrence, and mortality were significantly higher in patients with ZO-1 foci than in those without ZO-1 foci. The expression of Par3 and ZO-1 mRNA was not s ignificantly different in s amples from p atients with foci versus those without. These results strongly suggest that the presence of Par3 and ZO-1 foci on the membrane may be a useful prognostic marker for lung SqCC.

Electrostatic interaction effects on tension-induced pore formation in lipid membranes.

We investigated the effects of electrostatic interactions on the rate constant (k(p)) for tension-induced pore formation in lipid membranes of giant unilamellar vesicles under constant applied tension. A decrease in salt concentration in solution as well as an increase in surface charge density of the membranes increased k(p). These data indicate that k(p) increases as the extent of electrostatic interaction increases. We developed a theory on the effect of the electrostatic interactions on the free energy profile of the membrane containing a prepore and also on the values of k(p); this theory explains the experimental results and fits the experimental data reasonably well in the presence of weak electrostatic interactions. Based on these results, we conclude that a decrease in the free energy barrier of the prepore state due to electrostatic interactions is the main factor causing an increase in k(p).

Sternal Segment Dislocation in a Child Treated by Conservative Observation.

Sternal segment dislocation is rare in children, with only eight cases appearing in the literature. Four of the six reports recommended surgical treatment such as excision or open reduction and fixation [1-4], while the remaining two reports recommended conservative observation. Therefore, it remains unclear whether surgical treatment is necessary. We report a case of sternal segment dislocation in a child. Although the segment had rotated 90°, it was remodeled. We now believe that surgical treatment is not necessary for this condition.

Initial step of pH-jump-induced lamellar to bicontinuous cubic phase transition in dioleoylphosphatidylserine/monoolein.

Electrostatic interactions (EI) are an important factor for phase transitions between lamellar liquid-crystalline (L(α)) and inverse bicontinuous cubic (Q(II)) phases. We investigated the low pH-induced L(α) to double-diamond cubic (Q(II)(D)) phase transition in dioleoylphosphatidylserine (DOPS)/monoolein (MO) using time-resolved small-angle X-ray scattering. Using a stopped-flow apparatus, a suspension of liposomes (multilamellar vesicles (MLVs) or large unilamellar vesicles (LUVs)) of 20%-DOPS/80%-MO membrane at neutral pH was rapidly mixed with a low pH buffer, and then the structural change of the membranes in the resultant suspension was observed as a function of time (i.e., pH-jump experiment). At the initial step, the L(α) phase was directly transformed into the hexagonal II (H(II)) phase, and subsequently, the H(II) phase slowly converted into the Q(II)(D) phase. We obtained the rate constants of the initial step (i.e., the L(α) to H(II) phase transition) and of the second step (i.e., the H(II) to Q(II)(D) phase transition) using the non-negative matrix factorization method. The rate constant of the initial step was independent of the MLV concentration, indicating that single MLVs can convert into the HII phase without any interaction with other MLVs. On the other hand, the rate constant of the initial step increased with a decrease in pH, 0.041 s(-1) at pH 2.6 and 0.013 s(-1) at pH 2.8, and also exhibited a size dependence; for smaller vesicles such as LUVs and smaller MLVs with diameters of ~1 µm, the rate constant was smaller. They were reasonably explained by the classical nucleation theory. These results provide the first experimental evidence of the total kinetics of EI-induced L(α)/Q(II) phase transitions.

Rate constant of tension-induced pore formation in lipid membranes.

We investigated the effects of tension induced by micropipet aspiration on giant unilamellar vesicles (GUVs) composed of dioleoylphosphatidylglycerol (DOPG) and dioleoylphosphatidylcholine (DOPC). We analyzed the time course of the fraction of intact GUVs among all of the GUVs under constant tension σ and obtained the rate constants of pore formation kp(σ). To determine kp, we developed an approach using the mean first passage time. The fitting of the theoretical curves of kp versus σ to the experimental data determined the line tension of a prepore, Γ. The value of Γ of a DOPG/DOPC bilayer was smaller than that of a DOPC bilayer.

Preparation and photosensitizing property of novel Cd10S16 molecular cluster dendrimer.

A new Cd10S16 molecular cluster dendrimer has been prepared and characterized; photooxygenation reaction using the molecular cluster dendrimer as a photosensitizer was successful.

Preparation and electrochemical and optical properties of unsymmetrically substituted phthalocyanines with one or two trithiole rings and related symmetric derivatives.

4,5-Bis(benzylthio)-3,6-diethylphthalonitrile (1) was mixed with 4 -t-butylphthalonitrile and then treated with lithium alkoxide in n-hexanol to produce the corresponding unsymmetrically substituted phthalocyanines (2) and (3) with two or four benzylthio groups, respectively. Treatment of phthalocyanine (2) with nickel(II) acetate yielded the corresponding metal complex 2-Ni. Two benzyl groups of 2 and 2-Ni were removed with lithium/THF/ammonia at -78 degrees C under argon, and the dithiolate anions generated were then reacted with elemental sulfur to give monotrithiolophthalocyanines (5) and (5-Ni). A similar treatment of 3 produced bistrithiolophthalocyanine (6). Tetrakistrithiolophthalocyanine (7-Ni) was prepared by complexation of phthalocyanine (4) with nickel(II) acetate, followed by a Birch reduction of the resulting nickel(II) complex (4-Ni), and then sulfurization and cyclization of the octathiolate anions that were generated. The structures of the phthalocyanines were determined by (1)H NMR and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The optical and electrochemical properties of the phthalocyanines were examined by UV-vis absorption spectroscopy and cyclic voltammetry. Treatment of 5, 5-Ni, 6, 7, and 7-Ni with trifluoroacetic acid in chloroform generated positively charged species, which were characterized by UV-vis and/or NMR spectroscopy.