Background: Pulmonary veno-occlusive disease (PVOD) is a rare and devastating cause of pulmonary arterial hypertension with a non-specific clinical presentation and a relatively specific presentation in high-resolution thoracic CT scan images. Definitive diagnosis is made by histological examination in previous. According to the 2015 ESC/ERS Guidelines, detection of a mutation in the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) without histological confirmation is recommended to validate the diagnosis of PVOD. Methods: We report the case of a 27-year-old man who was admitted for persistent cough and dyspnea that had lasted for 5 months and had developed and experienced progressive dyspnea for the last 2 months. The echocardiogram and right heart catheterization without vasodilator challenge confirmed the diagnosis of pulmonary arterial hypertension. Other tests, such as high-resolution thoracic CT scan, V/Q scan, pulmonary function test with diffusion capacity, and blood tests, excluded other associated diseases which could have caused pulmonary hypertension. Results: The initial diagnosis at admission was idiopathic pulmonary arterial hypertension and an oral vasodilator (sildenafil) was given. However, the dyspnea subsequently worsened, and the patient was transferred to a regional lung transplant center, where he died of heart failure 1 week later. Using exome sequencing, we found an EIF2AK4 mutation, which was sufficient to confirm the diagnosis of PVOD. Conclusion: This is the first reported case of EIF2AK4 mutation in PVOD in a Chinese patient population. We found the frameshift EIF2AK4 mutation c.1392delT (p.Arg465fs) in this case. Up to now, there has been a paucity of data on this rare disease, and the exact role of EIF2AK4 loss-of-function mutations in the pathogenesis of PVOD is still unknown. More investigations should be conducted in the future.
Purpose: This study is a retrospective analysis of exploring the efficiency of surgical management on patients with synchronous colorectal liver metastasis (SCLM). Patients and Methods: Nine hundred fifty-three consecutive patients with SCLM from Weifang People's Hospital of Shandong Province between January 2006 and December 2015 were reviewed. The values of different factors were analyzed, such as different surgical indications of liver metastases, simultaneous or staged resection of primary colorectal cancer and liver metastases, and primary tumor resection (PTR) of asymptomatic patients with unresectable liver metastases. Results: Median survival time (47.3 months) and 5-year survival rate (31%) for patients with resected liver metastases were significantly superior to that of with nonoperative treatment (17.2 months, 4%, P< 0.001); enlarging the standard of liver metastases resection can improve the resection rates (31.0% vs 13.6%, P< 0.001); for patients with resectable liver metastases, the in-hospital cost for simultaneous resection group was lower than that in the staged resection group (36,698 vs 45,134 RMB, P< 0.001); for patients of the asymptomatic primary tumor with unresectable liver metastases, PTR was associated with improved median survival (18.0 vs 15.0 months, P=0.006). Conclusion: For patients with SCLM, liver resection is considered the best treatment; expanding indications of liver resection can improve the resection rates. Simultaneous resection of the primary tumor and liver metastases were indicated in patients with resectable SCLM; PTR was recommended for asymptomatic patients with unresectable hepatic metastases. Keywords: surgical treatment, synchronous colorectal liver metastases, survival analysis, primary tumor resection
Objective To investigate the occurrence of gastric cancer peritoneal relevant factors.Methods The first surgery in our hospital peritoneal not occurred when the 53 patients with gastric cancer between January 2005 to January 2006 peritoneal lavage fluid collected for cytology examination.Results After two years,40 cases occurred within the peritoneal.Conclusion The gastric cancer peritoneal relevant factors include:abdominal off cancer cells,intra-abdominal lymph nodes with metastasis,Bromann's type.
Key words:
Gastric cancer; Peritoneal metastasis; Cytology
The objective of this study is to preoperatively investigate the value of multiphasic contrast-enhanced computed tomography (CT)-based radiomics signatures for distinguishing high-risk thymic epithelial tumors (HTET) from low-risk thymic epithelial tumors (LTET) compared with conventional CT signatures.Pathologically confirmed 305 thymic epithelial tumors (TETs), including 147 LTET (Type A/AB/B1) and 158 HTET (Type B2/B3/C), were retrospectively analyzed, and were randomly divided into training (n = 214) and validation cohorts (n = 91). All patients underwent nonenhanced, arterial contrast-enhanced, and venous contrast-enhanced CT analysis. The least absolute shrinkage and selection operator regression with 10-fold cross-validation was performed for radiomic models building, and multivariate logistic regression analysis was performed for radiological and combined models building. The performance of the model was evaluated by the area under the receiver operating characteristic curve (AUC of ROC), and the AUCs were compared using the Delong test. Decision curve analysis was used to evaluate the clinical value of each model. Nomogram and calibration curves were plotted for the combined model.The AUCs for radiological model in the training and validation cohorts were 0.756 and 0.733, respectively. For nonenhanced, arterial contrast-enhanced, venous contrast-enhanced CT and 3-phase images combined radiomics models, the AUCs were 0.940, 0.946, 0.960, and 0.986, respectively, in the training cohort, whereas 0.859, 0.876, 0.930, and 0.923, respectively, in the validation cohort. The combined model, including CT morphology and radiomics signature, showed AUCs of 0.990 and 0.943 in the training and validation cohorts, respectively. Delong test and decision curve analysis showed that the predictive performance and clinical value of the 4 radiomics models and combined model were greater than the radiological model ( P < 0.05).The combined model, including CT morphology and radiomics signature, greatly improved the predictive performance for distinguishing HTET from LTET. Radiomics texture analysis can be used as a noninvasive method for preoperative prediction of the pathological subtypes of TET.
This article reported the high tumor targeting efficacy of RGD peptide labeled near-infrared (NIR) non-cadmium quantum dots (QDs). After using poly(ethylene glycol) to encapsulate InAs/InP/ZnSe QDs (emission maximum at about 800 nm), QD800-PEG dispersed well in PBS buffer with the hydrodynamic diameter (HD) of 15.9 nm and the circulation half-life of ∼29 min. After coupling QD800-PEG with arginine−glycine−aspartic acid (RGD) or arginine−alanine−aspartic acid (RAD) peptides, we used nude mice bearing subcutaneous U87MG tumor as models to test tumor-targeted fluorescence imaging. The results indicated that the tumor uptake of QD800-RGD is much higher than those of QD800-PEG and QD800-RAD. The semiquantitative analysis of the region of interest (ROI) showed a high tumor uptake of 10.7 ± 1.5%ID/g in mice injected with QD800-RGD, while the tumor uptakes of QD800-PEG and QD800-RAD were 2.9 ± 0.3%ID/g and 4.0 ± 0.5%ID/g, respectively, indicating the specific tumor targeting of QD800-RGD. The high reproducibility of bioconjunction between QDs and the RGD peptide and the feasibility of QD-RGD bioconjugates as tumor-targeted fluorescence probes warrant the successful application of QDs for in vivo molecular imaging.
507 Objectives The aim of this study was to develop a methodological platform for the screening of novel thymidine analogues that can be used as PET probes targeted to the measurement of thymidine kinase level in tumor proliferation. Methods Human recombinant TK-1 and TK-2 were expressed in E. coli as fusion protein containing an N-terminal His-tag and a thrombin cleavage site, and purified by using metal affinity chromatography. Kinetic binding parameters of thymidine analogues (FMAU as a control) were determined by using a phosphotransferase assay with 32P-ATP as a labeled substrate. The data were fitted into the Michaelis-Menten equation. The Km, Vmax, and kcat values were calculated using subunit molecular weight of the enzymes. Inhibition assays were performed using the DE-81 filter paper with 3H-dT as a substrate. The mode of inhibition and Ki values were derived from the Dixon plots. Results The specific activity of TK-1 and TK-2 was measured to be 2637±132 and 1872±95 nmol/min/mg, respectively. The phosphotransferase assay showed that FMAU is a substrate for both TK-1 (Km=32.5±1.2µM) and TK-2 (Km=72.3±3.7µM), whereas a new thymidine analogue (T07) is a good substrate of TK-2 (Km=44.6±5.0µM) but not TK-1. As determined by the inhibition assay, FMAU inhibited the phosphorylation of 3H-dT for both TK-1 (Ki=70±4µM) and TK-2 (Ki=4.9±0.3µM). However, T07 showed excellent potency and selectivity for TK-2. T07 was determined to be an uncompetitive inhibitor of 3H-dT for TK-1 (Ki=192.2±8µM), and a competitive inhibitor of 3H-dT for TK-2 (Ki=0.017±0.001µM). Conclusions A reliable method for the screening of thymidine analogues has been successfully developed. The hits identified from biological assays can be used as PET probes for specifically measuring thymidine kinase level in tumor proliferation. Research Support This work was supported by the SNMMI Mitzi & William Blahd Research Grant, the Whittier Grant for Translational Research, and the USC Department of Radiology.
// Hui Ye 1 , Jiansong Tong 2 , Jiangyi Liu 3 , Wenman Lin 3 , Chengshou Zhang 3 , Kai Chen 4 , Jie Zhao 5 , Wenjing Zhu 4 1 School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China 2 Department of Cellular and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA 3 School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China 4 School of Renji, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China 5 School of the First Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China Correspondence to: Hui Ye, email: wmcyh@wmu.edu.cn Keywords: gemcitabine, oxaliplatin, magnetoliposome, breast cancer, MCF-7 Received: February 27, 2016 Accepted: May 09, 2016 Published: May 27, 2016 ABSTRACT Breast cancer is a major global health problem with high incidence and case fatality rates. The use of magnetoliposomes has been suggested as an effective therapeutic approach because of their good specificity for cancers. In this study, we developed two novel magnetoliposomes, namely, Gemcitabine-containing magnetoliposome (GML) and Oxaliplatin-containing magnetoliposome (OML). These magnetoliposomes were combined (CGOML) was used to treat breast cancer under an external magnetic field. Biosafety test results showed that GML and OML were biologically safe to blood cells and did not adversely affect the behavior of mice. Pharmacokinetic and tissue distribution studies indicated that both magnetoliposomes exhibited stable structures and persisted at the target area under an external magnetic field. Cell and animal experiments revealed that CGOML can markedly suppress the growth of MCF-7 cells, and only the CGOML group can minimize the tumor size among all the groups. Finally, CGOML can significantly inhibit MCF-7cell growth both in vitro and vivo by activating the apoptotic signaling pathway of MCF-7 cells.
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