The Reliabilities of Several Measurement Methods of Cervical Sagittal Alignment in Cases with Cervical Spine Rotation Using X-ray Findings in Cervical Spine Disorders.

INTRODUCTION: Several measurement methods designed to provide an understanding of cervical sagittal alignment have been reported, but few studies have compared the reliabilities of these measurement methods. The purpose of the present study was to investigate the intraexaminer and interexaminer reliabilities of several cervical sagittal alignment measurement methods and of the rotated cervical spine using plain lateral cervical spine X-rays of patients with cervical spine disorders. METHODS: Five different measurement methods (Borden's method; Ishihara index method (Ishihara method); C2-7 Cobb method (C2-7 Cobb); posterior tangent method: absolute rotation angle C2-7 (ARA); and classification of cervical spine alignment (CCSA)) were applied by seven examiners to plain lateral cervical spine X-rays of 20 patients (10 randomly extracted cases from a rotated cervical spine group and 10 from a nonrotated group) with cervical spine disorders. Case 1 and Case 2 intraclass correlation coefficients (ICCs) were used to analyze intraexaminer and interexaminer reliabilities. The necessary number of measurements and the necessary number of examiners were also determined. The target coefficient of correlation was set at ≥0.81 (almost perfect ICC). RESULTS: In both groups, an ICC(1, 1) ≥ 0.81 was obtained with Borden's method, the Ishihara method, C2-7 Cobb, and ARA by all examiners. The necessary number of measurements was 1. With CCSA, a kappa coefficient of at least 0.9 was obtained. In both groups, with Borden's method, the Ishihara method, C2-7 Cobb, and ARA, the ICC(2, 1) was ≥0.9, indicating that the necessary number of examiners was 1. The standard error of measurement (SEM) was lowest with Borden's method, and the Ishihara method and C2-7 Cobb had almost the same values. CONCLUSIONS: Among cervical sagittal alignment measurement methods for cervical spine disorders, regardless of cervical spine rotation, Borden's method, Ishihara method, and C2-7 Cobb offer stronger reliability in terms of the ICC and SEM.

Rhenium-catalysed dehydrogenative borylation of primary and secondary C(sp3)-H bonds adjacent to a nitrogen atom.

Rhenium-catalysed C(sp(3))-H bond borylation in the absence of any oxidant, hydrogen acceptor, or external ligand, with the generation of H2 as the sole byproduct is described. The transformation, which represents a rare example of rhenium-catalysed C(sp(3))-H bond functionalisation, features high atom efficiency and simple reaction conditions.

MicroRNA profiles to predict postoperative prognosis in patients with small cell carcinoma of the esophagus.

BACKGROUND/AIM: Small cell carcinoma of the esophagus (SCCE) is a rare but very aggressive disease with poor prognosis. The aim of the present study was to identify a molecular signature to predict postoperative outcomes in patients with SCCE. MATERIALS AND METHODS: Expression of microRNA was detected in surgically-removed SCCE tumors using microarrays. A SCCE cell line (TYUC-1) was established to investigate the biological role of differentially expressed microRNAs. RESULTS: Hierarchical clustering of microRNA expression revealed two discrete clusters that were identical to the cases with rapid tumor relapse (n=3; median survival, 5.1 months) and the cases with long-term survival (n=3; median observation, 144.7 months), respectively. Eight microRNAs (miR-4323, miR-625, miR-3619-3p, miR-4419b, miR-1249, miR-4648, miR-4664-3p and miR-1203) showed significant correlation with tumor relapse (p<0.01). Migration of TYUC-1 was significantly inhibited by down-regulation of miR-625. CONCLUSION: The expression profiles of microRNAs in tumors may represent a novel predictor for postoperative outcomes in patients with SCCE.

Relapse-associated microRNA in gastric cancer patients after S-1 adjuvant chemotherapy.

S-1 has been recommended as adjuvant chemotherapy in patients after curative surgery for gastric cancer. However, some patients suffer recurrence even after S-1 adjuvant chemotherapy. The present study was conducted to find a predictive marker of the efficacy of S-1 adjuvant chemotherapy. We examined the microRNA (miRNA) expression of 35 patients who underwent S-1 adjuvant chemotherapy after curative surgery (R0) for pathological stage II or III gastric cancer. miRNAs were extracted from formalin-fixed, paraffin-embedded specimens for analysis and miRNA expression was examined using miRNA oligo chips. Fifteen patients relapsed and 20 did not over 5 years. Five miRNAs (miR-92b, 422a, 4732-5p, 4758-3p and 221) were highly expressed according to the tumor/normal (T/N) ratio in the patients who relapsed but not in those who did not relapse (P-value <0.05) by microarray analysis. If tumors showed high expression of 4 miRNAs (miR-92b, 422a, 4732-5p and 4758-3p) their positive predictive value of relapse was 93.8% and negative predictive value was 92.3%. In this case, their disease-free survival rate and overall survival rate were very poor. Our findings indicate that miR-92b, miR­422a, miR-4732-5p and miR-4758-3p are closely associated with relapse following S-1 adjuvant chemotherapy in gastric cancer.

MicroRNA-203 inhibits the progression of esophageal squamous cell carcinoma with restored epithelial tissue architecture in vivo.

MicroRNA (miR)-203 has been shown to induce squamous differentiation of epidermal stem cells through the suppression of p63. The aim of this study was to assess the tumor suppressor effect of miR-203 in esophageal squamous cell carcinoma (ESCC) with focus on the regulation of the cell fate decisions and organization of tumor tissue architecture in vivo. Our investigation establishing stable clones from ESCC cell lines with induced miR-203 expression resulted in significant growth inhibition in a mouse xenograft model. Small foci were observed in xenograft tumors with stratified squamous differentiation in conjunction with restored baso-apical polarity. The expression of the basement membrane protein laminine was localized at the center of the foci and the basal cell marker p75NTR was expressed in the innermost layer. The expression of ki67 and p63 was co-localized at the center layers, while involucrin was expressed in the outer layers. Flow cytometry revealed that the p75NTR-positive cells expressing p63 and Bmi1 were well maintained, while the expression of p63 was suppressed in the p75NTR-negative cells. Our cDNA microarray analysis demonstrated the upregulation of genes involved in regulating tissue architecture, such as BMP-4 and ZO-1 in the mir-203 transfectant. Investigation using surgically removed ESCC specimens revealed that the expression of miR-203 significantly correlated with a favorable prognosis. These results demonstrated that miR-203 regulated both basal and supra-basal cell components to induce differentiation with restored epithelial tissue architecture, leading to significant tumor growth inhibition in vivo. Those results suggest the use of miR-203 as a novel therapeutic and diagnostic target in patients with ESCC.

Establishment and characterization of a novel xenograft model of human gastrointestinal stromal tumor in mice.

BACKGROUND: The clinical outcome of gastrointestinal stromal tumor (GIST) has been improved by the introduction of molecular-targeting drugs. However, resistance to these drugs appears during the course of treatment. The aim of this study was to establish and characterize a human xenograft model of GIST. MATERIALS AND METHODS: GIST tissue from a patient with esophageal GIST was implanted under the skin of a NOD-SCID mouse. The tumor became successfully engrafted and we investigated the effects of imatinib and sunitinib on this model. KIT mutation was investigated by complementary DNA analysis, and c-KIT (CD117) expression was evaluated by immunohistological staining. RESULTS: cDNA analysis of the tumor revealed a KIT mutation in exon 11. c-KIT expression was observed in each passaged tumor. Both imatinib and sunitinib significantly reduced the size of the xenograft tumor. CONCLUSION: We established a novel xenograft model of human GIST in mice. This xenograft model may be useful for studying GIST.

Prognostic significance of aquaporins in human biliary tract carcinoma.

Aquaporins (AQPs) are important in controlling bile formation, however, the exact role of AQPs in human biliary tract carcinogenesis has not been clearly defined. In this study, we analyzed AQP-1, -4, -5 and -8 expression immunohistochemically using tissue microarrays (TMAs) in 81 samples. (45 gallbladder carcinomas and 36 bile duct carcinomas). The survival of patients with high AQP-5 expression was longer compared to that of patients with low AQP-5 expression (P=0.017). Cox's proportional hazard model revealed that AQP-5 expression was an independent prognostic factor (RR, 0.38; P=0.025). Chi-square analysis revealed that high AQP-5 expression correlated to small tumor size in biliary tract carcinoma patients (P=0.006). With regard to the expression of other AQPs, depth of tumor invasion, histological type and serum carbohydrate antigen 19-9 (CA19-9) were associated with high AQP-1 expression (P=0.039, 0.011 and 0.032). However, AQP-4 and AQP-8 expression had no association with clinicopathological factors. Among the 10 patients who underwent gemcitabine (GEM) plus S-1 postoperative chemotherapy, the group of patients (n=5) with high AQP-5 expression were associated with higher rates of both overall and disease-free survival (log-rank P=0.033, 0.002). In conclusion, the results of this study suggest that AQP-5 expression may be associated with prognosis and drug sensitivity in biliary tract carcinoma.