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Évry, France

Khalili-Harbi N.,Otto Von Guericke University of Magdeburg | Herath N.,DNA Therapeutics | Solass W.,Ruhr University Bochum | Giger-Pabst U.,Ruhr University Bochum | And 3 more authors.
Endoscopy | Year: 2016

Background and study aims: A novel therapeutic concept, pressurized intraluminal aerosol chemotherapy (PILAC), and a corresponding device for distributing drugs to the mucosa and submucosa of the distal esophagus are presented. Materials and methods: The endoscopic device that was designed consisted of (i) a double-balloon catheter, similar to a Sengstaken-Blakemore tube; (ii) a carbon dioxide (CO2) line, used to create a gaseous, pressurized environment; and (iii) a micropump, used to generate a therapeutic aerosol. The device was inserted into the distal esophagus in three narcotized Landrace pigs. Dbait (short interfering DNA, or siDNA) was aerosolized under pressure (12mmHg) in CO2 at 37°C for 30 minutes. Results: The procedure was well tolerated by all animals. At autopsy, no mucosal or muscular tear was observed. Fluorescence microscopy revealed a homogeneous intramural distribution of Dbait-cyanine 5 in the esophageal wall down to the circular muscular layer (400-600μm). Conclusions: PILAC is feasible in a large animal model and appears to be safe. Therapy of the entire "tissue at risk" for the development of cancer in the distal esophagus is possible without the prior endoscopic identification of diseased tissue. © Georg Thieme Verlag KG. Source

Dna Therapeutics and Institute Curie | Date: 2012-05-25

The present invention relates to a method for treating a cancer including a combination of a treatment by a nucleic acid molecule mimicking double strand breaks with hyperthermia.

Dna Therapeutics, French National Center for Scientific Research and Institute Curie | Date: 2011-06-21

The present invention relates to an optimized in vivo delivery system with endosomolytic agents for nucleic acid of therapeutic interest conjugated to molecules facilitating endocytosis, in particular for use in the treatment of cancer.

Solass W.,Otto Von Guericke University of Magdeburg | Herbette A.,Institute Curie | Schwarz T.,Reger Medizintechnik | Hetzel A.,Reger Medizintechnik | And 4 more authors.
Surgical Endoscopy and Other Interventional Techniques | Year: 2012

Background: Peritoneal carcinomatosis is an unmet medical need. Laparoscopy offers a unique opportunity to control and to steer the operating environment during surgery by loading carbon dioxide with a therapeutic substance and creating the so-called therapeutic capnoperitoneum. We have treated a human sample of peritoneal carcinomatosis from an endometrial adenocarcinoma ex vivo just after surgery. Methods: A nontoxic therapeutic agent (Dbait) was aerosolized into a box containing diseased human peritoneum under a pressure of 12 mmHg CO2. Dbait (noncoding DNA fragments) acts through jamming DNA damage sensing and signaling, ultimately inhibiting DNA repair system of cancer cells. Dbait were coupled to cholesterol molecules to facilitate intracellular uptake, and to Cyanine (Cy5) to allow detection by fluorescence. In a control experiment, the same solution was applied to the other half of the sample using conventional lavage. Results: Physical results revealed fluorescence within the tumor up to 1 mm depth in the therapeutic capnoperitoneum sample and no uptake in the lavage sample. Biological results showed intranuclear phosphorylation of H2AX in the nebulized sample and no activity in the lavage sample. Importantly, tumor nodules showed more activity than the neighbor, normal peritoneum. Detection of histone gamma-H2AX (phosphorylated H2AX) reveals activation of DNA-dependent protein kinase (DNA-PK) by Dbait, which has been shown to be the key step for sensitization to genotoxic therapy. Conclusions: Dbait are taken up by cancer cells and have a biological activity up to 1 mm depth. Nebulization of the molecule is significantly more effective than conventional lavage. This proof of principle supports the need for clinical studies applying therapeutic capnoperitoneum together with Dbait for treating peritoneal carcinomatosis. © 2011 The Author(s). Source

Dutreix M.,Institute Curie Hospital | Cosset J.M.,University Pierre and Marie Curie | Sun J.-S.,DNA Therapeutics | Sun J.-S.,French Natural History Museum
Mutation Research - Reviews in Mutation Research | Year: 2010

Approximately half of all cancer patients are treated with radiation therapy. However, some tumor cells can escape the lethal effects of irradiation by hypoxia, deregulation of the cell cycle or apoptosis or by increasing their ability to repair the DNA damage induced, resulting in recurrence of disease. In order to overcome these resistance mechanisms, various strategies have been developed. Over the last decade, extensive progress in human genomics and genetic tools has been made. Several methods using DNA or RNA molecules have been developed to target angiogenesis or other cellular functions in order to restore sensitivity to irradiation. In this review, we focus on five classes of nucleic acid-based approaches, (i) gene transfer by recombinant plasmid or virus, (ii) immune-stimulating oligonucleotides, (iii) antisense oligonucleotides, (iv) siRNA and shRNA, and (v) siDNA (signal interfering DNA), which target specific proteins or pathways involved in radioresistance. We review the results of the preclinical studies and clinical trials conducted to date by combining nucleic acid-based molecular therapy and radiotherapy. © 2010 Elsevier B.V. All rights reserved. Source

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