The effect of proteoglycans inhibited by RNA interference on metastatic characters of human salivary adenoid cystic carcinoma

<p>Abstract</p> <p>Background</p> <p>Salivary adenoid cystic carcinoma (SACC) is one of the most common malignancies of salivary gland. Recurrence or/and early metastasis is its biological properties. In SACC, neoplastic myoepithelial cells secrete proteoglycans unconventionally full of the cribriform or tubular and glandular structures of SACC. Literatures have demonstrated that extracellular matrix provided an essential microenvironment for the biological behavior of SACC. However, there is rare study of the effect of proteoglycans on the potential metastasis of SACC.</p> <p>In this study, human xylosyltransferase-I (XTLY-I) gene, which catalyzes the rate-limited step of proteoglycans biosynthesis, was knocked down by RNA interference (RNAi) to inhibit the proteoglycans biosynthesis in SACC cell line with high tendency of lung metastasis (SACC-M). The impact of down-regulated proteoglycans on the metastasis characters of SACC-M cells was analyzed and discussed. This research could provide a new idea for the clinical treatment of SACC.</p> <p>Methods</p> <p>The eukaryotic expression vector of short hairpin RNA (shRNA) targeting XTLY-I gene was constructed and transfected into SACC-M cells. A stably transfectant cell line named SACC-M-WJ4 was isolated. The XTLY-I expression was measured by real-time PCR and Western blot; the reduction of proteoglycans was measured. The invasion and metastasis of SACC-M-WJ4 cells were detected; the effect of down-regulated proteoglycans on the potential lung metastasis of nude mice was observed, respectively.</p> <p>Results</p> <p>The shRNA plasmid targeting XTLY-I gene showed powerful efficiency of RNAi. The mRNA level of target gene decreased by 86.81%, the protein level was decreased by 80.10%, respectively. The silence of XTLY-I gene resulted in the reduction of proteoglycans significantly in SACC-M-WJ4 cells. The inhibitory rate of proteoglycans was 58.17% (24 h), 66.06% (48 h), 57.91% (72 h), 59.36% (96 h), and 55.65% (120 h), respectively. The reduction of proteoglycans suppressed the adhesion, invasion and metastasis properties of SACC-M cells, and decreased the lung metastasis of SACC-M cells markedly either.</p> <p>Conclusion</p> <p>The data suggested that the silence of XTLY-I gene in SACC-M cells could suppress proteoglycans biosynthesis and secretion significantly. The reduction of proteoglycans inhibited cell adhesion, invasion and metastasis of SACC-M cells. There is a close relationship between proteoglycans and the biological behavior of SACC.</p

MRI Findings of Early Myositis Ossificans without Calcification or Ossification

Purpose. To characterize and evaluate the MR imaging features of early myositis ossificans (MO) without calcification or ossification. Methods. The MRI manifestations of seven patients with pathologically proven early MO were retrospectively analyzed with regard to tumor location, size, margins, signal intensity, and enhancement appearance in MR images. Additionally, the surrounding soft-tissue edema and adjacent bone change were assessed. Results. All cases (n=7) had intramuscular tumor-like masses without calcifications. The lesions appeared as isointense in T1-weighted images (T1-WI) and inhomogeneous hyperintense in T2-weighted MR images (T2-WI). On T2-WI and postcontrast T1-WI, the heterogeneously high signal intensity in the expanded muscle interspersed with a few hypointense linear structures consistent with intact muscle fibers showed “striate pattern” in the plane parallel with muscle fibers. The relatively hypointense areas with geometrical pattern consistent with the bundles of intact muscle fibers are found within the lesion with diffuse high signal intensity, displaying the “checkerboard-like pattern” in the plane vertical to muscle fibers. A “striate pattern” (n = 7) and “checkerboard-like pattern” (n = 3) in the lesion appeared in T2-WI. In contrast-enhanced MRI images, all cases showed diffuse “striate pattern” enhancement. Among them, one case demonstrated “checkerboard-like pattern” enhancement. All cases had diffuse and prominent muscle edema that preserved the muscle fascicles. For two lesions located in the deep muscle group, the adjacent bone showed bone marrow edema. Conclusion. MR imaging has unique advantages for diagnosis of early MO without calcification or ossification: the “striate pattern” and “checkerboard-like pattern” appearance shown in T2-WI and contrast-enhanced MRI images can be helpful for differential diagnosis. MRI can delineate the extent of the tumor and provides accurate anatomical information, which is important in diagnosis, treatment, and follow-up

Additional Diagnostic Value of Unenhanced Computed Tomography plus Diffusion-Weighted Imaging Combined with Routine Magnetic Resonance Imaging Findings of Early-Stage Gliblastoma

Purpose. This study was performed to determine whether diffusion-weighted imaging (DWI) plus unenhanced computed tomography (CT) of the brain increases the diagnostic value of routine magnetic resonance (MR) imaging findings of early-stage glioblastoma. Methods. Postcontrast MR images of eight unenhanced lesions that had been pathologically diagnosed as glioblastoma were retrospectively examined. The location, margin, signal intensity, and attenuation on MR imaging and CT were assessed. Results. On MR imaging, all lesions were ill-defined, small, and isointense to hypointense on T1-weighted images and hyperintense on T2-weighted images. Four patients had perilesional edema. In seven patients, DWI showed an inhomogeneous hyperintense lesion (n = 1) or isointense lesion with a hyperintense region (n = 6). On unenhanced CT, all masses presented as a hypoattenuated lesion with a hyperattenuated region (n = 7) or isoattenuated region (n = 1). The hyperattenuated region (n = 6) or isoattenuated region (n = 1) on CT appeared on DWI as an inhomogeneous hyperintense lesion (n = 1), isointense lesion with a hyperintense region (n = 3), or ring-like peritumoral hyperintensity (n = 3). Conclusions. MR imaging was the most sensitive imaging method for depicting early-stage glioblastoma. The CT finding of a hyperattenuated or isoattenuated region combined with the DWI finding of the same region containing an inhomogeneous hyperintense lesion or isointense lesion with a hyperintense region may be a specific diagnostic sign for early-stage glioblastoma. DWI plus unenhanced CT added diagnostic value to the routine MR imaging findings of early-stage glioblastoma

Quantitative Analysis of Enhanced Computed Tomography in Differentiating Cystitis Glandularis and Bladder Cancer

Objective. This study was performed to assess the value of quantitative analysis of enhanced computed tomography (CT) values in the differential diagnosis of bladder cancer and cystitis glandularis (CG). Methods. Eighty patients with bladder masses (39 with CG and 41 with bladder cancer) who underwent enhanced CT were retrospectively reviewed. The CT enhancement values of the lesion and normal bladder wall in the arterial phase, venous phase, and delayed phase were measured. The relative enhancement CT values (relative enhancement CT value=enhancement CT value of lesion−enhancement CT value of normal bladder) in the arterial phase, venous phase, and delayed phase were also calculated. The pathological results were used as the gold standard, and the area under the curve (AUC), sensitivity, and specificity were calculated for the six groups of quantitative indicators (enhanced CT values and relative enhanced CT values of CG and bladder cancer in the arterial, venous, and delayed phases). We performed the leave-group-out cross-validation method to validate the accuracy, AUC, sensitivity, and specificity. The differences in accuracy, AUC, sensitivity, and specificity among the six groups of quantitative indicators were compared by the t-test. Results. In a combined analysis of the AUC, sensitivity, and specificity performance, the best indicator was the arterial-phase relative enhancement CT value with a cut-off of 25.85 HU (AUC, 0.966; sensitivity, 95.1%; specificity, 92.3%). We used the 100-times leave-group-out cross-validation method to validate the accuracy, AUC, sensitivity, and specificity. Arterial-phase relative enhancement CT values showed the highest AUC and accuracy among the six groups, with statistical significance (P<0.05). Conclusion. Quantitative analysis of enhanced CT is of great clinical value in the differential diagnosis of CG and bladder cancer

CT-based deep learning radiomics nomogram for the prediction of pathological grade in bladder cancer: a multicenter study

Abstract Background To construct and assess a computed tomography (CT)-based deep learning radiomics nomogram (DLRN) for predicting the pathological grade of bladder cancer (BCa) preoperatively. Methods We retrospectively enrolled 688 patients with BCa (469 in the training cohort, 219 in the external test cohort) who underwent surgical resection. We extracted handcrafted radiomics (HCR) features and deep learning (DL) features from three-phase CT images (including corticomedullary-phase [C-phase], nephrographic-phase [N-phase] and excretory-phase [E-phase]). We constructed predictive models using 11 machine learning classifiers, and we developed a DLRN by combining the radiomic signature with clinical factors. We assessed performance and clinical utility of the models with reference to the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Results The support vector machine (SVM) classifier model based on HCR and DL combined features was the best radiomic signature, with AUC values of 0.953 and 0.943 in the training cohort and the external test cohort, respectively. The AUC values of the clinical model in the training cohort and the external test cohort were 0.752 and 0.745, respectively. DLRN performed well on both data cohorts (training cohort: AUC = 0.961; external test cohort: AUC = 0.947), and outperformed the clinical model and the optimal radiomic signature. Conclusion The proposed CT-based DLRN showed good diagnostic capability in distinguishing between high and low grade BCa