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Xiao-Jie L.,Tongji University | Hui-Ying X.,The Reproductive Center | Zun-Ping K.,Fudan University | Jin-Lian C.,Tongji University | And 2 more authors.
Journal of Medical Genetics | Year: 2015

First introduced into mammalian organisms in 2013, the RNA-guided genome editing tool CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats/CRISPRassociated nuclease 9) offers several advantages over conventional ones, such as simple-to-design, easy-to-use and multiplexing (capable of editing multiple genes simultaneously). Consequently, it has become a costeffective and convenient tool for various genome editing purposes including gene therapy studies. In cell lines or animal models, CRISPR-Cas9 can be applied for therapeutic purposes in several ways. It can correct the causal mutations in monogenic disorders and thus rescue the disease phenotypes, which currently represents the most translatable field in CRISPR-Cas9- mediated gene therapy. CRISPR-Cas9 can also engineer pathogen genome such as HIV for therapeutic purposes, or induce protective or therapeutic mutations in host tissues. Moreover, CRISPR-Cas9 has shown potentials in cancer gene therapy such as deactivating oncogenic virus and inducing oncosuppressor expressions. Herein, we review the research on CRISPR-mediated gene therapy, discuss its advantages, limitations and possible solutions, and propose directions for future research, with an emphasis on the opportunities and challenges of CRISPR-Cas9 in cancer gene therapy. Source

Lv S.-X.,Suzhou University | Gan J.-H.,Suzhou University | Wang C.-C.,The Second Peoples Hospital of Huaian | Luo E.-P.,Suzhou University | And 3 more authors.
Medical Hypotheses | Year: 2011

Gastric cancer is one of the most common malignancies in the world; however, its exact mechanism of development which may be relevant to many factors is still unclear, such as age, diet, Helicobacter pylori infection, smoking, polyps, chronic gastric ulcer and so on. Chronic gastric ulcer is considered as precancerous lesion of gastric cancer. The above-mentioned diseases are usually diagnosed by endoscopy and biopsy. In general, biopsy specimens are usually taken from the edges of lesions, seldom from the base. In patients with chronic gastric ulcer, especially healing or healed benign ulcer, we took the biopsy specimens from both the edges and the base of ulcers in the follow-up. Malignant lesions were found in several cases of chronic gastric ulcer, in which specimens were taken from the base of lesions. Therefore, we hypothesize that biopsy from the base of healing or healed chronic gastric ulcer in the second or third endoscopy may find gastric cancer earlier than traditional biopsy. © 2010 Elsevier Ltd. Source

Cheng D.-L.,Hubei University of Medicine | Xiang Y.-Y.,Cervical disease clinic | Ji L.-J.,The Second Peoples Hospital of Huaian | Lu X.-J.,Tongji University
Tumor Biology | Year: 2015

Competing endogenous RNAs (ceRNAs) refer to RNA transcripts, such as mRNAs, non-coding RNAs, pseudogene transcripts, and circular RNAs, that can regulate each other by competing for the same pool of miRNAs. ceRNAs involve in the pathogenesis of several common cancers such as prostate cancer, liver cancer, breast cancer, lung cancer, gastric cancer, endometrial cancer, and so on. ceRNA activity is determined by factors such as miRNA/ceRNA abundance, ceRNAs binding affinity to miRNAs, RNA editing, and RNA-binding proteins. The alteration of any of these factors may lead to ceRNA network imbalance and thus contribute to cancer initiation and progression. There are generally three steps in ceRNA research conductions: ceRNA prediction, ceRNA validation, and ceRNA functional investigation. Deciphering ceRNA interplay in cancer provides new insight into cancer pathogenesis and opportunities for therapy exploration. In this review, we try to give readers a concise and reliable illustration on the mechanism, functions, research approaches, and perspective of ceRNA in cancer. © 2015, International Society of Oncology and BioMarkers (ISOBM). Source

Ma L.,Tongji University | Ji L.,The Second Peoples Hospital of Huaian | Yu Y.,Shanghai University | Wang J.,Tongji University
Discovery Medicine | Year: 2015

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide and the third leading cause of cancer death. There have been many changes and challenges in the diagnosis and treatment of HCC in the past few decades. Liver cancer progresses with no clinical symptoms in the early stage, whereas clinical symptoms become obvious in the advanced stage when the diagnosis is usually made, leading to a poor prognosis. Chemotherapy, radiotherapy, surgical resection, and liver transplantation therapies have improved the treatment of advanced HCC; however, it is of critical importance to explore new diagnostic and therapeutic molecular targets of HCC. Numerous signaling pathways, such as Hippo-YAP, VEGFR/EGFR, Wnt/β-catenin, PI3K/AKT/mTOR, and MAPK/ERK, have been suggested being involved in the hepatic carcinogenesis. Although advances in molecular biology methodologies have contributed to the recognition of new tumor markers, which can be used in the diagnosis and treatment of HCC, additional liver cancer biomarkers are required for effective early diagnosis and monitoring of efficacy of therapies. This review summarizes the latest developments of molecular diagnostics and therapeutics of HCC in recent years. © Discovery Medicine. Source

Ke Z.,Fudan University | Gao A.,Fudan University | Xu P.,Fudan University | Wang J.,Hubei University of Medicine | And 2 more authors.
Experimental and Therapeutic Medicine | Year: 2015

PEP 1-Cu/Zn superoxide dismutase (PEP-1-SOD1) fusion protein preconditioning has been reported to protect the myocardium from ischemia/reperfusion (I/R)-induced injury by decreasing the infarct size, reducing levels of cardiomyocyte apoptosis and reducing the release of myocardial-specific biomarkers. The aim of the present study was to examine the effects of PEP-1-SOD1 pretreatment on I/R-induced ventricular arrhythmias in Langendorff-perfused rat hearts. The isolated rat hearts were pretreated with PEP-1-SOD1 prior to I/R, and the I/R-induced hemodynamic parameters, infarct size and ventricular arrhythmias were then assessed. Compared with the unprotected hearts, PEP-1-SOD1 preconditioning significantly improved the hemodynamic parameters, decreased the cardiac lactate dehydrogenase and creatine kinase-MB (CK-MB) levels, reduced the infarct size and attenuated the ventricular arrhythmia. Further investigation showed that PEP-1-SOD1 preconditioning reduced both the incidence and duration of ventricular tachycardia/ventricular fibrillation. In addition, the intracellular reactive oxygen species (ROS) levels were decreased. The results of the present study suggest that PEP-1-SOD1 preconditioning can protect the heart against I/R injury and attenuate I/R-induced arrhythmia by downregulating the generation of ROS. © 2015, Spandidos Publications. All rights reserved. Source

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