Significance of MUC1 and ß-Catenin Localization in Mucinous Carcinoma of the Breast.

BACKGROUND/AIM: There are two main subtypes of mucinous carcinoma (MC) based on the quantification of the mucinous component: the pure variant (pMC) and the mixed variant (mMC). pMC has been subdivided into pure A with a hypocellular variant, and pure B with a hypercellular variant. PATIENTS AND METHODS: We retrospectively analyzed the clinicopathological features of 99 patients with MC who were treated at our institution from January 2002 to December 2014. We evaluated the expression profiles of markers, including mucin (MUC) family members, in the patients groups representing different MC subtypes by performing immunohistochemistry to identify factors involved in the differentiation and progression of MCs. RESULTS: Among the 99 patients, 76 (76.8%) had pure mucinous carcinomas (pMC) and the other 23 (23.2%) had mixed mucinous carcinomas (mMC). Of the pMCs, 54 were pure A and 22 were pure B. The prognosis was worse for pure B than pure A and worse for mMC than pMC. Although there was no significant difference in clinicopathological factors between the pure A and pure B groups, immunohistochemical staining revealed differences in the localization of mucin MUC1 and ß-catenin. A comparison of the pMC and mMC cases revealed more lymphovascular invasion in mMC and differences in the localization of ß-catenin between the two groups. CONCLUSION: The patients' prognoses were significantly poorer depending on the histologic subtype (in the order pure A, pure B, and mixed). MUC1 localization and ß-catenin were revealed as independent predictors contributing to the poorer prognosis.

Effect of the disulfide isomerase PDIa4 on the antibody production of Chinese hamster ovary cells.

Therapeutic monoclonal antibodies recognize and bind specific molecules on the surface of target cells, stimulating the immune system, which can attack these targeted cells. These antibodies are produced by mammalian cells, including Chinese hamster ovary (CHO) cells, because the formation of antibodies requires complicated posttranslational modifications, including peptidyl-prolyl cis/trans isomerization, disulfide bond formation, and glycosylation. Currently, it is thought that the efficient production of secretory proteins is limited by posttranslational processes. The ER is the biosynthesis site of all secreted and membrane proteins. The accumulation of unfolded proteins in the ER causes the ER stress response. During the ER stress state, various molecular chaperones are expressed to prevent proteins from the aggregate formation. The molecular chaperone involved in ER stress likely plays an essential role in the production of secretory proteins. The purpose of this study was to improve the production of monoclonal antibodies by cells. We elucidated the function of ER chaperones in the production of a monoclonal antibody. First, we quantitatively measured the mRNA expression levels of protein disulfide-isomerase family members. In CHO HcD6 cells treated with tunicamycin, the expression level of pdia4 was significantly increased. Second, we investigated the relationship between PDIa4 and antibody productivity in pdia4-knockdown cells. Both a decrease in the amount of secreted antibody and the accumulation of immature antibodies inside the cells were observed. Recombinant PDIa4 was able to refold the antibodies and Fabs. These results indicate that PDIa4 affects the production of monoclonal antibodies by catalyzing disulfide bond formation in these antibodies in CHO cells.

Evaluation of Root Canal Anatomy of Maxillary Premolars Using Swept-Source Optical Coherence Tomography in Comparison with Dental Operating Microscope and Cone Beam Computed Tomography.

OBJECTIVE: This study aimed to evaluate the ability of swept-source optical coherence tomography (OCT) to detect internal anatomy of maxillary premolars in comparison with dental operating microscope (DOM) and cone beam computed tomography (CBCT). BACKGROUND DATA: The ability of OCT to observe the pulp horn during cavity preparation and assess the remaining dentin thickness (RDT) has been demonstrated, whereas validation of OCT in comparison with other imaging techniques seems required. METHODS: Ten extracted human maxillary premolars were sectioned perpendicular to the tooth axis from the occlusal surface at approximately 2 mm increments. OCT and DOM were performed after each cut, and microfocus X-ray computed tomography (micro-CT; reference standard) and CBCT were conducted before sectioning and after the first and second cuts. Three examiners evaluated all images for presence of the pulp horn/pulp chamber, isthmus, lateral canals, and the number of root canals. RDT was determined from OCT, micro-CT, and CBCT images. Correlations were analyzed with Pearson's correlation coefficient. RESULTS: OCT had a sensitivity and specificity of 0.90 and 0.80 in detecting the pulp horn/pulp chamber and 0.84 and 0.71 in detecting the isthmus, respectively. The three techniques showed strong correlations in detecting the number of root canals compared with micro-CT. OCT and DOM did not detect lateral canals. For RDT values, strong correlations were observed between micro-CT and CBCT, micro-CT and OCT, and CBCT and OCT (p < 0.01 for all). CONCLUSIONS: Under the present experimental condition, OCT accurately measured RDT and detected internal tooth anatomy such as the pulp horn, isthmus, and root canals.

Expression patterns of claudins in patients with triple-negative breast cancer are associated with nodal metastasis and worse outcome.

Claudins (CLDNs) are key cell adhesion molecules, which compose tight junctions (TJs), and the disruption of TJs is associated with cancer development. Here we immunohistochemically studied expression patterns of CLDNs in 222 primary invasive breast cancers including 68 triple-negative breast cancers (TNBCs), and examined their correlation with epithelial-to-mesenchymal transition (EMT)-related markers, breast cancer stem cell (BCSC) markers, and clinicopathological features including patients' clinical outcome. Tumor margins were classified as three infiltrating growth patterns (expanding, intermediate and infiltrating). For CLDN1, 3, 4, and 7, their expression rates were more frequent in TNBCs than in other subtypes (11.8% vs 0.7%, 26.5% vs 2.0%, 48.5% vs 11.1%, and 32.4% vs 8.7%, respectively; P ≤ 0.001). In 68 TNBCs, we identified high Ki67 labeling index (LI) and the combination of CLDN4 high/CLDN7 low expression as independent predictors of axillary nodal metastasis (P = 0.019; OR, 4.36; 95%CI, 1.28-14.90 and P = 0.007; OR, 5.33; 95%CI, 1.58-17.90). Moreover, the combination of CLDN1 low/CLDN7 low/E-cadherin negative as well as tumor infiltrating patterns were predictors for worse recurrence-free survival by univariate analyses in TNBCs (P = 0.005 and P = 0.011). Our analyses provide further evidence that CLDNs would be valuable prognostic markers in TNBCs.

Ability of Cone-beam Computed Tomography to Detect Periapical Lesions That Were Not Detected by Periapical Radiography: A Retrospective Assessment According to Tooth Group.

INTRODUCTION: The detection of periapical lesions by periapical radiography (PR) can be hampered by structural noise, the impact of which differs among tooth groups. The aim of this study was to investigate the ability of cone-beam computed tomographic (CBCT) imaging to detect periapical lesions that could not be detected with PR according to tooth group. METHODS: This study retrospectively evaluated teeth that (1) had previously undergone root canal treatment (178 teeth from 86 patients), (2) had coincidentally been located within the field of view of CBCT scans performed for endodontic reasons, and (3) had also been examined with PR. The teeth of interest for the CBCT examinations were excluded to avoid sampling bias. Two dentists evaluated both the CBCT and PR images for periapical lesions. The McNemar test was used to compare the ability of CBCT imaging and PR to identify periapical lesions (α = 0.05). RESULTS: The overall periapical lesion detection rates of PR and CBCT imaging were 31.5% and 52.2%, respectively (P < .0001). The ability of CBCT imaging to identify periapical lesions that were not detected by PR was statistically significant for the maxillary incisors/canines (P < .0001) and maxillary molars (P < .005). CONCLUSIONS: Within the limitations of this investigation, it can be concluded that CBCT imaging is effective at detecting periapical lesions that cannot be detected on PR, particularly in the maxillary incisors/canines and molars. Our findings suggest that the influence of structural noise in the maxillary anterior region and maxillary posterior region should not be overlooked during the interpretation of PR images.

Evaluation of coronal leakage and pathway of dye leakage after obturation with various materials for open apical foramina.

The aim of this study was to investigate coronal leakage after obturation with mineral trioxide aggregate (MTA), resin-based sealer, and silicon-based sealer for open apical foramina and to evaluate pathway of leakage. Twenty-eight maxillary premolars were used, and instrumented to ISO size #80. Teeth were randomly divided into four groups as follows: Group A filled with MTA, Group B with gutta-percha and resin-based sealer, Group C with polymer-based material and resin-based sealer, and Group D with gutta-percha and silicon-based sealer. All samples were evaluated for coronal leakage with methylene blue solution and spectrophotometry. After leakage testing, samples were cut, and sections were observed. Dye leakage of Group A was significantly lowest among all groups at 15 days and 30 days. Defects which induced coronal leakage in resin-based sealer were observed at 7 mm from the apex. Coronal leakage after obturation with MTA for open apical foramina was significantly lower than resin-based sealer and silicon-based sealer.

Synthetic studies of the zoanthamine alkaloids: the total syntheses of norzoanthamine and zoanthamine.

The zoanthamine alkaloids, a type of heptacyclic marine alkaloid isolated from colonial zoanthids of the genus Zoanthus sp., have distinctive biological and pharmacological properties in addition to their unique chemical structures with stereochemical complexity. Namely, norzoanthamine (1) can suppress the loss of bone weight and strength in ovariectomized mice and has been expected as a promising candidate for a new type of antiosteoporotic drug, while zoanthamine (2) has exhibited potent inhibitory activity toward phorbol myristate-induced inflammation in addition to powerful analgesic effects. Recently, norzoanthamine derivatives were demonstrated to inhibit strongly the growth of P-388 murine leukemia cell lines, in addition to their potent antiplatelet activities on human platelet aggregation. Their distinctive biological properties, combined with novel chemical structures, make this family of alkaloids extremely attractive targets for chemical synthesis. However, the chemical synthesis of the zoanthamine alkaloids has been impeded owing to their densely functionalized complex stereostructures. In this paper, we report the first and highly efficient total syntheses of norzoanthamine (1) and zoanthamine (2) in full detail, which involve stereoselective synthesis of the requisite triene (18) for an intramolecular Diels-Alder reaction via the sequential three-component coupling reactions, the key intramolecular Diels-Alder reaction, and subsequent crucial bis-aminoacetalization as the key steps. Ultimately, we achieved the total synthesis of norzoanthamine (1) in 41 steps with an overall yield of 3.5 % (an average of 92 % yield each step) and that of zoanthamine (2) in 43 steps with an overall yield of 2.2 % (an average of 91 % yield each step) starting from (R)-5-methylcyclohexenone (3), respectively.

A regio- and stereoselective alpha-methylation of gamma,delta-epoxy-alpha,beta-unsaturated esters with a Me2Zn-CuCN reagent.

A highly regio- and stereoselective alpha-methylation reaction of gamma,delta-epoxy-alpha,beta-unsaturated esters was achieved by using a Me2Zn-CuCN reagent.