Pathologic evaluation of tumor-associated macrophage density and vessel inflammation in invasive breast carcinomas

Tumor-associated macrophages (TAMs) are major constituents of the tumor microenvironment in solid tumors and have been implicated as mediators of tumor progression, invasion and metastasis. Correspondingly, accumulation of TAMs is associated with unfavorable clinical outcomes in numerous types of solid tumors. E-selectin is a hallmark of inflammation and a key adhesion molecule that accommodates the initial contact of circulating immune cells with the inflamed vessel surface. Currently, the association between E-selectin and TAMs is not fully elucidated; therefore, the present study investigated the association between vessel inflammation, TAM infiltration, and clinical outcome in breast cancer. A total of 53 procedure-naïve invasive breast cancer cases were immunohistochemically analyzed for the presence of cluster of differentiation (CD)68+ TAMs, E-selectin+ vessels and tumor inflammation. The association between CD68 and E-selectin expression, and tumor inflammation as well as overall survival was evaluated using Kaplan-Meier survival curves and multivariable Cox\u27s proportional hazards regression analysis. The abundance of TAMs was identified to be positively associated with tumor inflammation, estrogen receptor and E-selectin expression levels. A greater prevalence of TAMs and tumor inflammation was significantly associated with shorter overall survival times. E-selectin expression levels were significantly higher in tumor vessels among elderly patients, but were not associated with overall survival. The abundance of TAMs was associated with the presence of E-selectin-expressing inflamed tumor vessels and tumor inflammation, as well as overall survival in patients with invasive breast carcinoma. © 2017, Spandidos Publications. All rights reserved

Trajectory analysis for fusion path in superheavy-mass region

We propose an effective method for the precise investigation of the fusion-fission mechanism in the superheavy-mass region, using the fluctuation-dissipation model. The trajectory calculation with friction is performed in the nuclear deformation space using the Langevin equation. In the reaction $^{48}$Ca+$^{244}$Pu, the trajectories are classified into the fusion-fission process, the quasi-fission process and the deep quasi-fission process. By analyzing the time evolution of each trajectory, the mechanism of each process is clearly revealed, i.e., it is explained why a trajectory takes a characteristic path in this model. We discuss, in particular, the condition under which the fusion path is followed, which is crucial in the discussion of the possibility of synthesizing superheavy elements.Comment: 25 pages, 12 figures, accepted for publication in Nuclear Physics

Flap Reconstruction for Esophageal Perforation Following Anterior Cervical Plate Fixation

Anterior cervical plate fixation is a common surgical treatment for cervical spine trauma, disc herniation, or cervical spondylosis. Esophageal perforation following anterior cervical plate fixation is a rare but serious complication. Management of esophageal perforation is controversial; however, we suggest treating most cases surgically because this condition is slow to heal and often fatal. We managed 2 cases of esophageal perforation following anterior cervical plate fixation by flap reconstruction with the pectoralis major muscle in one case and a jejunal free flap in the other. Here, we report our experience and review the surgical indications

Network of two-Chinese-character compound words in Japanese language

Some statistical properties of a network of two-Chinese-character compound words in Japanese language are reported. In this network, a node represents a Chinese character and an edge represents a two-Chinese-character compound word. It is found that this network has properties of "small-world" and "scale-free." A network formed by only Chinese characters for common use ({\it joyo-kanji} in Japanese), which is regarded as a subclass of the original network, also has small-world property. However, a degree distribution of the network exhibits no clear power law. In order to reproduce disappearance of the power-law property, a model for a selecting process of the Chinese characters for common use is proposed

Functional Blockade of E-Selectin in Tumor-Associated Vessels Enhances Anti-Tumor Effect of Doxorubicin in Breast Cancer

Chemotherapy is a mainstay of treatment for solid tumors. However, little is known about how therapy-induced immune cell infiltration may affect therapy response. We found substantial CD45+ immune cell density adjacent to E-selectin expressing inflamed vessels in doxorubicin (DOX)-treated residual human breast tumors. While CD45 level was significantly elevated in DOX-treated wildtype mice, it remained unchanged in DOX-treated tumors from E-selectin null mice. Similarly, intravenous administration of anti-E-selectin aptamer (ESTA) resulted in a significant reduction in CD45+ immune cell density in DOX-treated residual tumors, which coincided with a delay in tumor growth and lung metastasis in MMTV-pyMT mice. Additionally, both tumor infiltrating T-lymphocytes and tumor associated-macrophages were skewed towards TH2 in DOX-treated residual breast tumors; however, ESTA suppressed these changes. This study suggests that DOX treatment instigates de novo intratumoral infiltration of immune cells through E-selectin, and functional blockade of E-selectin may reduce residual tumor burden as well as metastasis through suppression of TH2 shift

Evidence of mature adipocyte proliferation regulated by proliferin

Despite much research, whether mature adipocytes proliferate remains controversial. Here, we examined 5-bromo-2′-deoxyuridine (BrdU)-labelling of mature adipocytes. Although BrdU incorporation into subcutaneous adipocytes was less than that in visceral adipocytes, pioglitazone (Pio) treatment increased BrdU incorporation in subcutaneous, but not visceral, adipocytes in rats. Fully differentiated 3T3-L1 adipocytes exhibited an increase in cell number and BrdU incorporation with time, with this increase enhanced by Pio treatment. We therefore screened for genes that encode growth factors regulated by Pio, and selected proliferin (PLF). Both gene silencing of PLF by small interfering RNA and treatment with anti-PLF antibody suppressed proliferation in 3T3-L1 adipocytes. In adipocytes isolated from Pio-treated rats, the tissue-specific pattern of PLF expression was similar to that of BrdU incorporation. Administration of an anti-PLF antibody to mice reduced BrdU incorporation into adipocytes. Mature adipocytes thus have the ability to replicate, and this proliferation is positively regulated by PLF