Involvement of Adrenomedullin Expression in Tumor Cells and Stroma in the Development of Diabetes in Pancreatic Cancer Patients

Some studies have reported that adrenomedullin （AM） is involved in diabetes mellitus （DM） associated with pancreatic cancer. Therefore, in this study we investigated the relationship between diabetes and AM expression in patients with pancreatic cancer. We examined 48 biopsies and 26 surgical resections from 74 patients with histologically diagnosed pancreatic cancer. Patients were classified into either DM or non-DM groups. The immunohistochemical expression of AM and various clinicopathological factors were compared between the two groups. Among the biopsy cases, 21 were classified as DM and 27 as non-DM. AM expression in pancreatic cancer cells was significantly lower in the DM group （p＝0.03）. No significant differences were noted in age, body mass index, tumor diameter or location, serum CA19-9, amylase, or C-reactive protein levels, pancreatic ductal dilatation, portal vein invasion, clinical stage, or histological differentiation between the DM and non-DM groups. The proportion of men was significantly lower in the DM group （p＝0.04）, as was the frequency of liver metastasis at diagnosis （p＝0.03）. Among the resection cases, 13 were classified as DM and 13 as non-DM. There were no significant differences in AM expression in pancreatic cancer cells between the two groups. However, marked AM expression was observed in the inflammatory cells and fibroblasts of the tumor stroma in all cases. In addition, the inflammatory response in the tumor stroma tended to be stronger in the DM group. Although the present study failed to find a positive correlation between diabetes and AM expression in pancreatic cancer cells, the results indicate that AM expression in stromal cells may be more closely related to the development of DM in pancreatic cancer patients

C-arm Cone-beam CT-guided Needle Biopsies through the Erector Spinal Muscle for Posterior Thoracic Pulmonary Lesions

This study investigated retrospectively the diagnostic yield and complication rate of transthoracic needle biopsies for posterior thoracic pulmonary lesions using C-arm cone-beam computed tomography （CBCT）. The risk factors for pulmonary hemorrhage were evaluated. Our study included 113 patients with 113 posterior pulmonary lesions （mean longest diameter: 30.6mm, and mean depth: 4.7mm） through the erector spinal muscles using a 19/20-gauge coaxial system. The diagnostic performances of procedures for malignant lesions and the incidence of complications after biopsies were also assessed. The patient-related and procedure-related variables were investigated. Risk factors for pulmonary hemorrhage were analyzed with a multivariate logistic regression analysis. Findings revealed 99 malignant, 13 benign, and one intermediate lesion. Sensitivity, specificity, and diagnostic accuracy rates were 100％ （99/99）, 92.3％ （12/13）, and 99.1％ （111/112）, respectively. Air embolization, hemothorax, hemoptysis, pneumothorax, and pulmonary hemorrhage, occurred in 0, 2, 12, 48, and 70 procedures. The averaged spinous process-pleura depth and the traversed lung parenchyma depth achieved by the introducer needles were 54.2mm and 27.4mm, respectively. The needle position at the pleural puncture site within the intercostal space was in middle （31％） and inferior （69％） areas. The incidence of pulmonary hemorrhage was significantly higher in smaller lesions （p＝0.001）. Manual evacuation was performed in five procedures for patients with pneumothorax. The chest tube placement （trocar＞8 Fr） was performed in two procedures in patients with hemothorax and pneumothorax. In conclusion, the biopsy method with a posterior intercostal approach for posterior thoracic pulmonary lesions yielded high diagnostic accuracy and few major complications

Functional tooth restoration by next-generation bio-hybrid implant as a bio-hybrid artificial organ replacement therapy

Bio-hybrid artificial organs are an attractive concept to restore organ function through precise biological cooperation with surrounding tissues in vivo. However, in bio-hybrid artificial organs, an artificial organ with fibrous connective tissues, including muscles, tendons and ligaments, has not been developed. Here, we have enveloped with embryonic dental follicle tissue around a HA-coated dental implant, and transplanted into the lower first molar region of a murine tooth-loss model. We successfully developed a novel fibrous connected tooth implant using a HA-coated dental implant and dental follicle stem cells as a bio-hybrid organ. This bio-hybrid implant restored physiological functions, including bone remodelling, regeneration of severe bone-defect and responsiveness to noxious stimuli, through regeneration with periodontal tissues, such as periodontal ligament and cementum. Thus, this study represents the potential for a next-generation bio-hybrid implant for tooth loss as a future bio-hybrid artificial organ replacement therapy

Gene Expression of Cancer Stem Cell in Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC), like many solid tumors, contains a heterogeneous population of cancer cells. Recent data suggest that a rare subpopulation of cancer cells, known as cancer stem cells (CSCs), is capable of initiating, maintaining, and expanding the growth of tumors. Identification and characterization of CSCs from OSCC would facilitate the monitoring, therapy, or prevention of this cancer. CD133 is considered a marker molecule for CSCs; however, its role in OSCC is yet to be determined. In this study, we isolated CD133-positive cells from OSCC cell lines using a magnetic-activated cell sorter (MACS). The differential expression of genes between OSCC/CD133-positive cells and parental cells was determined by polymerase chain reaction (PCR). Up-regulated genes (CD133-positive vs. parental cells) included ALDH 1, Keratin15 (Krt15), SOX2, and WNT 1, while the down-regulated genes included Fgfr1 and Pparg. Additionally, immunohistochemical analysis revealed that expression of Krt15 and SOX2 was localized to cancer cells of OSCC specimens. Their elevated expression levels were detected in poorly differentiated and chemoresistant OSCC. Our results possibly demonstrate that CD133-positive cells, when compared with parental cells, are a more concentrated population of CSCs in OSCC

Expression of Keratin 75 (K6hf) in Oral Squamous Cell Carcinoma

Cytokeratin is commonly used diagnostic markers of oral squamous cell carcinoma (OSCC). Especially, Keratin17 (K17) is reported to be up-regulated in OSCC. Recently, identification and quantification of proteins from tissue section become possible by using laser microdissection and LC/MS/MS method. In this study, we performed nano-flow liquid chromatography, mass spectrometry and protein identification by tandem mass spectrometry (LC/MS/MS) analysis on pooled protein extracts from OSCC tissue section and compared the results with those from normal epithelium. As a result, Keratin 6hf is considered as a candidate marker of OSCC. From more validation, the expression of K6hf may be associated with malignancy of oral epithelial lesion. In previous study, K6hf is known to be specifically expressed in a hair follicle and specifically cross a partner with K17. But, there are no report about correlation between K6hf and carcinoma. In conclusion, K6hf expression may play an important role in the carcinogenesis progression of OSCC. However, further studies on the molecular function of K6hf are encouraged to clear the precise mechanism of K6hf in OSCC

Clinicopathological Study of Mass-forming Gallbladder Cancer Focusing on the Grade of Cellular Dysplasia

The relationship between the clinicopathological features and the grade of cellular dysplasia of the neoplastic glands in mass-forming gallbladder cancer was investigated. In this retrospective study, 41 mass-forming （≧1cm） gallbladder cancer specimens from 83 resected cases were examined. Tumors were classified into three groups: Group A had intraluminal masses consisting of neoplastic glands with only low-grade dysplasia; Group B had mixed low- and high-grade dysplasia, and Group C had only high-grade dysplasia. Of the 41 tumors, 13 were classified as Group A, 11 as Group B, and 17 as Group C. For Group A, B, and C, respectively, the mean tumor diameter was 1.6, 3.7 and 3.4cm; macroscopic type （pedunculated/semi-pedunculated/sessile） was 7/5/1, 4/6/1 and 0/10/7; frequency of an invasive component inside the mass was 0％, 9％ and 82％; and cell lineage （biliary/metaplastic/mixed） was 2/1/10, 8/1/2 and 14/1/2. In addition, invasion depth （Tis＋T1/T2/T3） was 13/0/0, 7/4/0 and 3/10/4; lymph node metastases were present in 0％, 9％ and 24％ of patients; 3-year survival rate was 100％, 100％ and 82％; and 5-year survival rate was 100％, 100％ and 69％, for A, B and C, respectively. Significant intergroup differences were seen for positive lymph node metastasis rate and 5-year survival rate. The present study indicates that the clinicopathological features of mass-forming gallbladder cancer are different depending on the grade of cellular dysplasia of the mass lesion. The tumors in Groups A and B were of lower malignancy than those in Group C and the prognosis of patients in the former groups was excellent. Group A and B tumors may be intracholecystic papillary-tubular neoplasms, a recently proposed new disease concept