Tumor-associated macrophages and angiogenesis in early stage esophageal squamous cell carcinoma

Background

The association between angiogenesis and tumor-associated macrophages (TAMs) is unclear. Mononuclear cell infiltration was reported to induce angiogenesis in early stage esophageal squamous cell carcinoma (ESCC).

Methods

The study materials included 14 samples of normal squamous epithelium, 11 samples of low-grade intraepithelial neoplasia, and 64 samples of superficial esophageal cancer (M1 and M2 cancer 27; M3 or deeper cancer 37). We assessed microvessel density (MVD) using CD34 and CD105 immunostaining and monocyte count (MC) using CD68 and CD163 immunostaining in relation to the histological type or grade of mononuclear cell infiltration, as well as the correlation between MVD and MC.

Results

MVD and MC increased in accordance with histological type, and the differences were significant (P < 0.001). MVD and MC were significantly higher in M1 and M2 lesions than in normal squamous epithelium (P < 0.05). MVD (CD34 and CD105) and MC (CD68 and CD163) were significantly correlated with the degree of mononuclear cell infiltration (P < 0.001), and there was a strong correlation between MC assessed using CD68 and MC assessed using CD163 (rS = 0.93, P < 0.001). The CD163/CD68 ratio did not differ significantly according to histological type. There was a significant correlation between MVD assessed using CD105 and MC assessed using CD68 (rS = 0.69, P < 0.001) and CD163 (rS = 0.67, P < 0.001). MVD assessed using CD34 was also significantly correlated with MC assessed using both CD68 (rS = 0.59, P < 0.001) and CD163 (rS = 0.57, P < 0.001).

Conclusion

The number of TAMs is significantly associated with the development of neovasculature in the early stage of ESCC progression.

     

Mechanical properties of new self-adhesive resin-based cement

PurposeThe aim of this study was to compare the bonding strength, flexural strength, elastic modulus, water absorption and the expansion after water storage of new self-adhesive resin cements to commercially available dental cements.MethodsTwo types (hand-mix and auto-mix) of new self-adhesive resin cements (SAC-H and SAC-A, Kuraray Medical), one conventional resin cement (Panavia F2.0), three self-adhesive resin cements (Relyx Unicem, Maxcem and G-Cem), and two resin-modified glass-ionomer cements (Fuji Luting S and Vitremer) were used. Shear bond strengths, flexural strengths and elastic moduli (ISO 4049), water absorption (ISO 4049), and the expansion rate after water storage were investigated.ResultsBoth SAC-H and SAC-A provided adhesion to enamel and dentin, and had the same bond strength to gold alloy and zirconia as conventional resin cements. SAC-H and SAC-A had greater flexural strengths (86.4–93.5 MPa) than commercial self-adhesive resin cements or glass-ionomer cements. The elastic moduli of self-adhesive and glass-ionomer cements were 5.2–7.4 GPa and 2.3–3.4 GPa, respectively. The water absorption of SAC-H and SAC-A (26.3–27.7 μg/mm³) were significantly lower than commercial self-adhesive resin cements. SAC-H and SAC-A showed significantly lower expansion rates (0.17–0.26%) than commercial self-adhesive cements and glass-ionomer cements after 4 weeks water storage.ConclusionsIt is suggested that the new self-adhesive resin cements exhibited a favorable bonding capability and mechanical properties.     

Chemokine CCL2/MCP-1 negatively regulates metastasis in a highly bone marrow-metastatic mouse breast cancer model

Bone is the most frequent site of breast cancer metastasis, and once such metastasis occurs, complete remission is extremely difficult to achieve. In an effort to define the mechanisms underlying metastatic spread of breast cancer to bone, we previously developed and characterized the highly bone metastatic 4T1E/M3 mouse breast cancer cells. We found that following injection into mice, 4T1E/M3 cells exhibited greater bone metastasis and greater in vitro anchorage-independent growth and cell migration than their parental cells (4T1E). We also found that expression of intracellular adhesion molecule-1 (ICAM-1) is crucially involved in these metastatic activities of 4T1E/M3 cells. In the present study, our analysis of gene and protein expression revealed that production of chemokine CCL2 (MCP-1) is dramatically reduced in 4T1E/M3 cells, and that restoration of CCL2 expression in 4T1E/M3 cells diminishes their metastasis to bone and lung. Overexpression of CCL2 in 4T1E/M3 cells significantly reduced not only in vitro anchorage-independent cell growth and cell migration, but also mRNA and cell surface expression of ICAM-1. Conversely, knocking down CCL2 in 4T1E parental cells augmented their metastatic spread to spine and lung. The expression of ICAM-1 was also upregulated in 4T1E-derived CCL2 knockdown cells. Taken together, these results suggest that CCL2 expression may negatively regulate breast cancer metastasis to bone marrow and lung in our model and that expression of ICAM-1 plays a crucial role in that process.     

Oral flora in independent over 80-year-olds with more than 20 teeth

The purpose of this study was to investigate oral flora in independent persons aged over 80 years with more than 20 remaining teeth. The subjects were 22 participants of the 8020 campaign (6 males and 16 females) with a mean age of 81.3+/-1.6 years and an average of 24.7 teeth (Independent 8020 group). This group was compared with a group of 38 elderly people residing in nursing homes (10 males and 28 females) who had a mean age of 81.3+/-8.5 years and an average of 4.2 teeth (Nursing group with fewer teeth). Saliva samples were collected from the vestibular areas of the maxilla and mandible using cotton swabs. Cell numbers of microorganisms were expressed as colony forming units/ml (CFUs/ml) and compared between the two groups. The average number of Staphylococcus species was 65.2+/-74.4 CFUs/ml in the Independent 8020 group and 400.3+/-352.1 CFUs/ml in the group with fewer teeth (p<0.01); that of Candida albicans was 18.0+/-37.7 CFUs/ml in the Independent 8020 group and 152.9+/-211.9 CFUs/ml in the Nursing group with fewer teeth (p<0.05). Both species showed statistically significant differences between the two groups. This suggests that the Independent 8020 achiever group had better oral hygiene and that the presence of many teeth may be associated with an increased awareness of dental health.     

Possible activation of murine T lymphocyte through CD98 is independent of interleukin 2/interleukin 2 receptor system

CD98 is a widely expressed cell surface heterodimeric protein of 125 kDa. Its expression is upregulated during lymphocyte activation induced by mitogen, superantigen, conventional antigen, and a combination of phorbol myristate acetate (PMA) and ionomycin. However, the role of CD98 in the immune system is not so well understood. The role of CD98 in murine T lymphocyte proliferation was investigated, especially in correlation with the interleukin 2 (IL-2)/interleukin 2 receptor (IL-2R) system. Monoclonal antibody (mAb) directed against murine CD98 heavy chain (mCD98HC) suppressed the proliferation of lymphocytes stimulated with concanavalin A (Con A). Anti-mCD98HC mAb did not suppress the expression of IL-2Ralpha. Anti-IL-2Ralpha mAb, which suppressed DNA synthesis, did not inhibit the expression of CD98HC. Murine IL-2 (recombinant), which induced considerable DNA synthesis by lymphocytes stimulated with a sub-optimal dose of Con A, did not induce CD98HC expression in lymphocytes. In addition, anti-mCD98HC mAb did not inhibit the production of IL-2 by lymphocyte stimulated with Con A. Taken together with these findings, it was speculated that the CD98 system is independent of the IL-2/IL-2R system in murine T lymphocyte activation.     

Moxibustion at mingmen reduces inflammation and decreases IL-6 in a collagen-induced arthritis mouse model

The purpose of this study was to compare the effectiveness of moxibustion (MOX) treatment at the GV4 and CV12 acupoints, and to determine the correlations between MOX treatment and interleukin (IL)-6 and corticosterone levels in a collagen-induced arthritis (CIA) mouse model. CIA mice were immunized twice intradermally over a 3-week interval with bovine type II collagen. After the second immunization (day 21), MOX was applied to the mouse equivalent of the GV4 and CV12 acupoints with a 1mg moxa cone five times/day. Clinical symptoms of CIA were observed three times/week until day 35. The concentrations of IL-6 and corticosterone in the blood samples were measured by immunoassay kits. At day 35, the incidence of CIA was significantly decreased in mice treated with MOX at the GV4 acupoint (78%, n=23, p<0.05), compared to untreated CIA mice (100%) and mice treated with MOX at the CV12 acupoint (100%). IL-6 and corticosterone levels were significantly increased by immunization. IL-6 levels significantly decreased in mice treated with MOX at the GV4 acupoint. These results suggest that MOX treatment suppressed CIA at the GV4 acupoint, not at the CV12 acupoint, possibly through inhibition of IL-6 production.