Enhanced prostate cancer gene transfer and therapy using a novel serotype chimera cancer terminator virus (Ad.5/3?CTV)

Abstract
Few options are available for treating patients with advanced prostate cancer (PC). As PC is a slow growing disease and accessible by ultrasound, gene therapy could provide a viable option for this neoplasm. Conditionally replication?competent adenoviruses (CRCAs) represent potentially useful reagents for treating prostate cancer (PC). We previously constructed a CRCA, Cancer Terminator Virus (CTV), which showed efficacy both in vitro and in vivo for PC. The CTV was generated on a serotype 5?background (Ad.5?CTV) with infectivity depending on Coxsackie?Adenovirus Receptors (CARs). CARs are frequently reduced in many tumor types, including PCs thereby limiting effective Ad?mediated therapy. Using serotype chimerism, a novel CTV (Ad.5/3?CTV) was created by replacing the ...

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Google CEO s Condition Spotlights Vocal Cord Paralysis and Its Treatment

When Google CEO Larry Page blogged about his struggles speaking and, at times, breathing last week on his Google+ page he spotlighted a rare condition, bilateral vocal cord paralysis , which leaves sufferers short of breath and with few viable treatment options. This is likely to change in coming years. Page has deep pockets and has promised to fund research into the disorder via the Voice Health Institute . In the meantime scientists are experimenting with electrical stimulation technologies to enhance existing voice therapy as well as surgical treatments. [More]

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Music to your ears? Try a headphones implant like Rich Lee

'Grinder' can listen to music player by wearing a loose wire coil around his neckDon't offer Rich Lee a pair of headphones to listen to music: he's already got a pair, even though you can't see them. They're implanted in his ears – a procedure carried out by a "body modification" expert.Now, by connecting his music player to a loose wire coil around his neck (which he can tuck under his shirt), Lee can listen to music without blocking out the outside world. The tiny magnets implanted invisibly in his outer ears pick up the signal and generate sound.But that's only the beginning. Lee, 34, who works as a salesman, intends to hook it up to an ultrasonic rangefinder – effectively giving himself bat-like echolocation. And he would like to have X-ray vision, super-strength, and anything else...

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Yes, a Child Has Been Pronounced Cured of HIV but Can It Be Duplicated?

A child born to an HIV-infected mother in Mississippi may be cured after a swiftly administered course of drugs. A number of factors make the child’s case unique, however, and clinicians caution that we have not discovered a general cure for HIV yet. Still, the medical first may hint at ways to fight the AIDS-causing virus .

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[Development of an adenovirus vector containing a hepatitis C virus expression cassette and its application].

Authors: Yoshida T, Kondoh M, Mizuguchi H, Yagi K
Abstract
Hepatitis C virus (HCV) is a hepatotropic member of the Flaviviridae family and contains a 9.6 kb positive-sense RNA genome. Approximately 170-million people are infected with HCV worldwide. These people face increased risks of chronic hepatitis, cirrhosis and hepatocellular carcinoma compared with the general population. Transduction of the HCV genome into hepatocytes is essential for understanding the mode of action of HCV infection, and for preparing HCV, evaluating HCV replication, and screening anti-HCV drugs. Although electroporation of in vitro-synthesized HCV genome and transduction of plasmid vectors containing the HCV genome are widely used in HCV research, a more convenient system with higher transduction efficie...

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Be Mine Forever: Oxytocin May Help Build Long-Lasting Love

If cupid had studied neuroscience, he’d know to aim his arrows at the brain rather than the heart. Recent research suggests that for love to last, it’s best he dip those arrows in oxytocin. Although scientists have long known that this hormone is essential for monogamous rodents to stay true to their mates, and that it makes humans more trusting toward one another, they are now finding that it is also crucial to how we form and maintain romantic relationships.

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Truncated dystrophins reduce muscle stiffness in the extensor digitorum longus muscle of mdx mice

Muscle stiffness is a major clinical feature in Duchenne muscular dystrophy (DMD). DMD is the most common lethal inherited muscle-wasting disease in boys, and it is caused by the lack of the dystrophin protein. We recently showed that the extensor digitorum longus (EDL) muscle of mdx mice (a DMD mouse model) exhibits disease-associated muscle stiffness. Truncated micro- and mini-dystrophins are the leading candidates for DMD gene therapy. Unfortunately, it has never been clear whether these truncated genes can mitigate muscle stiffness. To address this question, we examined the passive properties of the EDL muscle in transgenic mdx mice that expressed a representative mini- or micro-gene (H2-R15, R2-15/R18-23/C, or R4-23/C). The passive properties were measured at the ages of 6 and 20 mo a...

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http://www.medworm.com/index.php?rid=7067339&cid=c_449_68_f&fid=33708&url=http%3A%2F%2Fjap.physiology.org%2Fcgi%2Fcontent%2Fabstract%2F114%2F4%2F482%3Frss%3D1

Protection of genetic heritage in the era of cloning

Research on human beings has expanded greatly due to progress and the evolution of society as well as customs. Not only the unceasing development of research on human beings, but also interference in the beginning and end of life with homologous and heterogonous human reproduction, surrogate motherhood, cloning, gene therapies, eugenics,euthanasia, dysthanasia, orthothanasia, assisted suicide, genetic engineering, reassignment surgery in cases of transsexuality, the use of recombinant DNA technology and embryonic stem cells, transplantation of human organs and tissues, biotechnology and many other scientific advances. Scientific progress goes faster than the real needs of human beings, who are the final recipient of the entire evolutionary progress. Hence, there is the need to scrutinize w...

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Potent growth-inhibitory effect of a dual cancer-specific oncolytic adenovirus expressing apoptin on prostate carcinoma.

Potent growth-inhibitory effect of a dual cancer-specific oncolytic adenovirus expressing apoptin on prostate carcinoma.
Int J Oncol. 2013 Mar;42(3):1052-60
Authors: Zhang M, Wang J, Li C, Hu N, Wang K, Ji H, He D, Quan C, Li X, Jin N, Li Y
Abstract
Apoptin is a chicken anemia virus-derived, p53-independent, bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis in various human tumor cells, but not in normal cells. To explore the use of apoptin in tumor gene therapy, we assessed a recombinant adenovirus expressing the apoptin protein (Ad-hTERTp-E1a-Apoptin) in order to determine its lethal and growth-inhibitory effects on PC-3 and RM-1 cells in vitro and its antitumor effect on solid tumors in vivo....

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Ocular gene delivery systems using ternary complexes of plasmid DNA, polyethylenimine, and anionic polymers.

Authors: Kurosaki T, Uematsu M, Shimoda K, Suzuma K, Nakai M, Nakamura T, Kitahara T, Kitaoka T, Sasaki H
Abstract
In this experiment, we developed anionic ternary complexes for effective and safe ocular gene delivery. Ternary complexes were constructed by coating plasmid DNA (pDNA)/polyethylenimine (PEI) complex with anionic polymers such as ?-polyglutamic acid (?-PGA) and chondroitin sulfate (CS). The cationic pDNA/PEI complex showed high gene expression on the human retinal pigment epithelial cell line, ARPE-19 cells. The pDNA/PEI complexes, however, also showed high cytotoxicity on the cells and aggregated strongly in the vitreous body. On the other hand, the anionic ternary complexes showed high gene expression on ARPE-19 cells without such cytotoxicity and aggregation. Afte...

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Misprocessing and functional arrest of microRNAs by miR-Pirate, roles of miR-378 in vitro and in vivo

MicroRNAs are short non-coding RNAs that can regulate gene expression in cancer development, which makes them valuable targets for therapeutic intervention. Here we report on an approach that can not only arrest the functions of mature miRNAs by binding to them but it can also induce the “mis-processing” of the target miRNA producing a non-functional truncated miRNA. This approach involves generating an expression construct that produces a RNA fragment with sixteen repeat sequences. The construct is named miR-Pirate or microRNA-interacting RNA—producing imperfect RNA and tangling endogenous miRNA. The transcript of the construct contained mismatches to the seed region, and thus it would not target the potential targets of the miRNA under study. The homology of the cons...

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Mucopolysacccharidoses: from understanding to treatment, a century of discoveries

After the first description of a patient recognized as a MPS case was made in 1917, several similar cases were described and identified. Observations reported in the middle of the twentieth century concerning the presence of acid mucopolysaccharides (later called glycosaminoglycans, or GAGs) in tissues and especially in urine of patients were instrumental in providing an identity for these diseases, which became referred as "mucopolysaccharidoses" (MPS). In the late 1960's it was demonstrated that MPS were caused by defects in the breakdown of GAGs, and the specific enzyme deficiencies for the 11 types and subtypes of MPS were identified thereafter. Genes involved in the MPS were subsequently identified, and a large number of disease-causing mutations were identified in each one. Although ...

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World Changing Ideas 2012 (preview)

Scientists and engineers dream about big advances that could change the world, and then they try to create them. On the following pages, Scientific American reveals 10 innovations that could be game changers: an artificial alternative to DNA, oil that cleans water, pacemakers powered by our blood, and more. These are not pie-in-the-sky notions but practical breakthroughs that have been proved or prototyped and are poised to scale up greatly. Each has the potential to make what may now seem impossible possible. -- The Editors

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ARE-Regulated Lentiviral HSV-TK/GCV Gene Therapy

In this study, we sought to examine whether this attribute could be exploited in cancer suicide gene therapy by using a lentiviral (LV) vector expressing herpes simplex virus thymidine kinase (HSV-TK/GCV) under the regulation of antioxidant response element (ARE), a cis-acting enhancer sequence that binds Nrf2. In human lung adenocarcinoma cells in which Nrf2 is constitutively overexpressed, ARE activity was found to be high under basal conditions. In this setting, ARE-HSV-TK was more effective than a vector in which HSV-TK expression was driven by a constitutively active promoter. In a mouse xenograft model of lung cancer, suicide gene therapy with LV-ARE-TK/GCV was effective compared with LV-PGK-TK/GCV in reducing tumor size. We conclude that ARE-regulated HSV-TK/GCV therapy offers a pro...

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