Overcoming the challenge of venous occlusion for lead implantation

Vein stenosis or occlusion is a frequent finding in patients with previously-implanted transvenous leads. This editorial describes the different techniques that may be used to overcome this hurdle in case a new lead needs to be implanted, and discusses two case reports in this issue of the journal.     

microRNA-10b confers cisplatin resistance by activating AKT/mTOR/P70S6K signaling via targeting PPARγ in esophageal cancer

It is well known that the acquisition of chemoresistance is a major obstacle for the effective treatment of human cancers. It is reported that microRNAs (miRNAs) are implicated in chemotherapy resistance of various malignancies. miR-10b was previously proved as an oncogene in multiple malignancies, including esophageal cancer. However, its biological significance in regulating cisplatin (DDP) resistance in esophageal cancer is still elusive. Here, we observed that miR-10b expression was upregulated and peroxisome proliferator-activated receptor-γ (PPARγ) expression was downregulated in esophageal cancer tumor tissues and cells. PPARγ was proved as a functional target of miR-10b. Moreover, suppression of miR-10b enhanced the chemosensitivity of esophageal cancer cells to DDP in vitro and in vivo. In addition, PPARγ-mediated DDP sensitivity was weakened by miR-10b overexpression. Furthermore, miR-10b-activated AKT/mTOR/p70S6K signaling pathway through targeting PPARγ. Inactivation of AKT/mTOR/p70S6K by AKT inhibitor (GSK690693) attenuated miR-10b-induced DDP resistance in esophageal cancer cells. Taken together these observation, miRNA-10b-mediated PPARγ inhibition enhanced DDP resistance by activating the AKT/mTOR/P70S6K signaling in esophageal cancer, suggesting a potential target to improve therapeutic response of patients with esophageal cancer to DDP.     

A Protocol for Genetic Induction and Visualization of Benign and Invasive Tumors in Cephalic Complexes of Drosophila melanogaster

Drosophila has illuminated our understanding of the genetic basis of normal development and disease for the past several decades and today it continues to contribute immensely to our understanding of complex diseases ^1-7. Progression of tumors from a benign to a metastatic state is a complex event ⁸ and has been modeled in Drosophila to help us better understand the genetic basis of this disease ⁹. Here I present a simple protocol to genetically induce, observe and then analyze the progression of tumors in Drosophila larvae. The tumor induction technique is based on the MARCM system ¹⁰ and exploits the cooperation between an activated oncogene, Ras^V12 and loss of cell polarity genes (scribbled, discs large and lethal giant larvae) to generate invasive tumors ⁹. I demonstrate how these tumors can be visualized in the intact larvae and then how these can be dissected out for further analysis. The simplified protocol presented here should make it possible for this technique to be utilized by investigators interested in understanding the role of a gene in tumor invasion.     

PTEN在人食管上皮永生化细胞株和食管癌细胞株中的表达

目的:探讨人胚食管上皮永生化细胞株SHEE、SHEEMT、食管癌细胞株EC8712中PTEN表达的差,判断食管上皮细胞在恶性转化过程中是否有PTEN缺失现象的发生;方法:培养三种细胞株,采用免疫组织化学、激光共聚焦显微镜、流式细胞仪和Westernblot等检测方法对三种细胞株中PTEN的表达进行检测。结果:三种细胞株均有PTEN的表达,表达强度与分化程度有关,PTEN在三种细胞株中表达强弱顺序为SHEE>SHEEMT>EC8712,差异有统计学意义(P<0.01);结论:PTEN在SHEE、SHEEMT和EC8712三种来源于食管鳞状上皮但分化程度不同的细胞株均中表达,表达强度与分化程度相关,分化程度越高,表达越强。     

Percutaneous comprehensive cryoablation for metastatic esophageal cancer after failure of radical surgery

Esophageal cancer is common in China. There is a lack of treatment strategies for metastatic esophageal cancer (MEC) after radical surgery on the primary tumor. Cryoablation is an attractive option because tumor necrosis can be safely induced in a minimally invasive manner. This study assessed its therapeutic effect in MEC after failure of radical surgery. One hundred and forty patients met the inclusion criteria from May, 2003 to March, 2011. Comprehensive cryotherapy of multiple metastases was performed on 105 patients; 35 received chemotherapy. No severe complications occurred during or after cryoablation. Overall survival (OS) was assessed according to therapeutic protocol, pathologic type, treatment timing and number of procedures. The OS of patients who received comprehensive cryoablation (44 ± 20 months) was significantly longer than that of those who underwent chemotherapy (23 ± 24 months; P = 0.0006). In the cryotherapy group, the OS for squamous cell carcinoma (45 ± 19 months) was longer than that for adenocarcinoma (33 ± 18 months; P = 0.0435); the OS for timely cryoablation (46 ± 19 months) was longer than that for delayed cryoablation (33 ± 20 months; P = 0.0193); the OS for multiple cryoablation (50 ± 17 months) was longer than that for single cryoablation (37 ± 20 months; P = 0.0172); and the OS for cryo-immunotherapy (56 ± 17 months) was longer than that for cryoablation alone (39 ± 19 months; P = 0.0011). Thus, comprehensive cryotherapy may have advantages over chemotherapy in the treatment of MEC and, in patients with squamous cell carcinoma, supplementary immunotherapy and timely and multiple cryoablation may be associated with a better prognosis.     

CFD simulation of flow through heart: a perspective review

This work addresses the problem of prescribing proper boundary conditions at the artificial boundaries that separate the vascular district from the remaining part of the circulatory system. A multiscale (MS) approach is used where the Navier–Stokes equations for the district of interest are coupled to a non-linear system of ordinary differential equations which describe the circulatory system. This technique is applied to three 3D models of a carotid bifurcation with increasing stenosis resembling three phases of a plaque growth. The results of the MS simulations are compared to those obtained by two stand-alone models. The MS shows a great flexibility in numerically predicting the haemodynamic changes due to the presence of a stenosis. Nonetheless, the results are not significantly different from a stand-alone approach where flows derived by the MS without stenosis are imposed. This is a consequence of the dominant role played by the outside districts with respect to the stenosis resistance.     

HER2 testing in gastric and esophageal adenocarcinoma: new diagnostic challenges arising from new therapeutic options

Abstract

Adenocarcinomas of the esophagus and stomach constitute a substantial number of cancer cases worldwide. Most patients in the United States are diagnosed at an advanced or metastatic stage and, therefore, the prognoses have been poor. New treatments are needed to augment standard surgical and medical management. Recent studies have shown that a subset of esophageal and gastric adenocarcinomas overexpress the HER2 protein, similar to the overexpression seen in breast cancer. Because trastuzumab, a monoclonal antibody to the HER2 receptor, has been used with success in primary and HER2 positive metastatic breast cancers, the phase III ToGA trial was designed to assess the impact of trastuzumab in patients with HER2 positive gastric cancers. They have reported an increase in overall survival time for patients treated with chemotherapy and trastuzumab compared to those treated with chemotherapy alone. They have reported an increase in overall survival time for patients treated with chemotherapy and trastuzumab compared to those treated with chemotherapy alone. This means that accurate HER2 testing in gastric and esophageal carcinomas is necessary. While the breast cancer scoring system can be used to determine HER2 status in most cases, modifications are necessary to accommodate the heterogeneity and incomplete membrane staining that are observed more frequently in gastric cancers. An understanding of the scoring modifications is required for proper stratification of gastric cancer patients for treatment.