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SynVec participated to the Oncology Business Convention MEET2WIN Bordeaux 2017

SynVec team was present at the 3thd edition of the Oncology Business convention MEET2WIN organized by MATWIN which is nationwide service platform that supports the maturation of research projects in Oncology up to the pre-clinical proof of concept.

It was an opportunity for SynVec to present its competencies in vectors development for the drug delivery and its services in custom chemical synthesis.

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Metformin has promising results in cancer treatment and prevention

Metformin used for treatment of type 2 diabetes, shows good results in survivalfor breast cancer patients and was promising for treatment of endometrial hyperplasia. These results were presented by researchers from the Prelman Scool of Medecine at the University of Pennsylvania at the American Society of Clinical Oncology annual meeting.

For more details please fllow this link

https://www.eurekalert.org/pub_releases/2016-06/uops-ddm060316.php

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SynVec labellisée plateforme du SIRIC BRIO (Bordeaux Recherche Intégrée Oncologie)

Depuis le mois de Mars 2016, SynVec fait désormais partie du réseau SIRIC BRIO qui regroupe les hôpitaux Universitaires (l’Institut Bergonié et CHU Bordeaux), les institutions de recherche (CNRS, INSRM), l’Université de Bordeaux ainsi que les institutions régionales régionales (Cancéropole Grad-Sud-Ouest, Réseau de Cancérologie d’Aquitaine, Groupement des Industries Pharmaceutiques et de Santé d’Aquitaine, Conseil Régional d’Aquitaine).

SynVec devient ainsi une plateforme labellisée du SIRIC BRIO ce qui permettrait aux laboratoires et Institutions faisant partie de ce réseau de pouvoir profiter du savoir faire de l’équipe de SynVec dans le domaine de la synthèse chimique à façon et de la R&D en chimie organique. Ces laboratoires pourront donc bénéficier des prestations en synthèse et R&D en chimie de SynVec afin de développer leurs programmes de recherche en Oncologie suivant les différents axes et thématiques proposés par le SIRIC. Un soutien financier est donc proposé par le SRIRIC BRIO aux laboratoires et institutions qui feront appel aux prestations SynVec dans le cadre de leurs programmes de recherche en Oncologie.

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SynVec : Relevance to cancer research

In order to show the relevance to cancer research for SynVec activies, we give you some exemples of our last projects :

SynVec worked on a project of monitoring MMPs (Matrix Metallo-Proteinases)  activities allowing the design and synthesis of peptidic biochips which are able to inform about the tumor aggressiveness. The ANR (Agence Nationale de Recherche) project in which SynVec participated is a program to develop new drug delivery system (chemical vector) to target cancerous tumor angiogenesis.
In another project, modified Nucleosides, nucleolipids and  phosphoramidites synthesized by SynVec are used in order to formulate new lipidic systems to target cancerous tumors by delivering therapeutic agents in the close environment of these tumors.
These projects are examples of validated applications in cancer research treated by SynVec team. Several chemical molecules which could be synthesized by our team could be potential candidates for cancer treatment. Our experiences in the chemical synthesis and chemical vectors design allow us to take part in different projects for cancer treatment. We have an expertise in the chemical biology field and interface, specially in the medical side of the chemical synthesis which could be considered as a real asset to be a privileged partner for cancer research projects.

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Les statines pour retarder l’apparition et la progression de la dégénérescence maculaire liée à l’âge

La dégénérescence maculaire liée à l’âge (DMLA) est une maladie évolutive de la macula à déclenchement tardif qui affecte la vision centrale. Des études ont montré que certains des facteurs pouvant conduire à l’athérosclérose et aux accidents vasculaires cérébraux sont les mêmes que ceux pouvant conduire à la DMLA. Les statines se sont avérées très efficaces dans la prévention des accidents vasculaires cérébraux, de sorte qu’il est possible qu’elles puissent aussi protéger de la DMLA. Un certain nombre d’études observationnelles avaient examiné la relation entre la DMLA et l’utilisation de statines, mais les résultats étaient contradictoires.

Cette revue systématique a identifié un essai contrôlé randomisé achevé et un en cours. Pour ce qui concerne l’essai achevé, dans lequel 30 patients avaient reçu quotidiennement pendant trois mois soit 20 mg de simvastatine soit un placebo, les analyses n’ont pas montré de différence statistiquement significative dans l’acuité visuelle à la fin du traitement ou 45 jours après l’achèvement du traitement. Pour l’essai en cours, les analyses préliminaires après 12 mois de traitement n’ont pas montré de différence statistiquement significative entre 40 mg quotidiens de simvastatine et un placebo, au niveau de l’acuité visuelle, de l’accumulation des drusens ou de la fonction visuelle. Vues la petite taille de l’essai terminé et la courte durée du traitement et de la période de suivi, aucune conclusion concernant les effets des statines sur l’apparition ou la progression de la DMLA ne peut être tirée à ce jour. Nous mettrons à jour cette revue lorsque les données de l’essai en cours seront disponibles.

Souce link : http://www.cochrane.org/fr/CD006927/les-statines-pour-retarder-lapparition-et-la-progression-de-la-degenerescence-maculaire-liee-a-lage

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CANCER: Découverte d’un suppresseur de tumeur puissant et prometteur – Current Medicinal Chemistry –

C’est une découverte prometteuse de chercheurs du Centre de recherche sur le cancer de Toulouse d’un métabolite suppresseur de tumeur, issu du métabolisme combiné du cholestérol et de l’histamine -une molécule naturellement produite par le corps (ou apportée par l’alimentation). Ce métabolite humain rare pourrait donner lieu au développement de nouveaux traitements contre le cancer, selon ces travaux, présentés dans la revue Current Medicinal Chemistry.

Les chercheurs de Toulouse, Sandrine Silvente-Poirot, Florence Dalenc et Marc Poirot expliquent le processus qui les a conduits à découvrir ce métabolite et décrivent ses propriétés pharmacologiques : l’équipe identifie ici une enzyme impliquée dans le métabolisme du cholestérol -5,6-époxyde, cible du Tamoxifène* (*hormonothérapie qui va bloquer l’action des hormones oestrogènes sur les cellules cancéreuses) : précisément, le Tamoxifène  induit une production de 5,6-CE dans les cellules cancéreuses mammaires. Les chercheurs font donc l’hypothèse d’une nouvelle voie métabolique prometteuse, à partir de la transformation métabolique du cholestérol -5,6-époxyde. Ils montrent que le métabolisme du cholestérol  » 5,6α-EC  » avec l’histamine va produire cette molécule, la dendrogénine A (DDA).

Les promesses de la dendrogénine A : DDA présente une forte activité pour induire une activité de différenciation cellulaire à faible dose ce qui suggère son caractère endogène. Les chercheurs constatent ensuite que les niveaux de DDA sont fortement diminués dans les tumeurs, suggérant l’implication de DDA dans les cancers.

» Plus fort « , combler cette carence en DDA dans des tumeurs chez des souris modèles, induit un effet anticancéreux puissant et à de faibles doses, ce qui semble confirmer la fonction physiologique de DDA dans le maintien de l’intégrité cellulaire et la différenciation.

DDA, premier alcaloïde stéroïdien trouvé à ce jour chez les mammifères : sa découverte révèle ainsi l’existence d’une nouvelle voie métabolique chez les mammifères au carrefour du cholestérol et le métabolisme de l’histamine qui conduit à la production d’un gène suppresseur de tumeur métabolique.

On l’aura compris, cette étude un peu complexe, aboutit sur un composé anticancéreux puissant et prometteur.

Source:  Current Medicinal Chemistry Jan, 2016 DOI: 10.2174/0929867322666150716114912 Dendrogenin A: A Mammalian Metabolite of Cholesterol with Tumor Suppressor and Neurostimulating Properties (Visuel@Bentham Science Publishers & Dr. Marc Poirot)

link : http://blog.santelog.com/2016/01/18/cancer-decouverte-dun-suppresseur-de-tumeur-puissant-et-prometteur-current-medicinal-chemistry/

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Gut Bacteria Make Pomegranate Metabolites That May Protect Against Alzheimer’s

In a quest to stay healthy, many people are seeking natural ways to prevent neurodegenerative diseases. Recent studies show that pomegranate extract, which is a rich source of disease-fighting polyphenols, can help protect against the development of Alzheimer’s disease. But researchers weren’t sure which molecules to thank. A team reports in ACS Chemical Neuroscience that the responsible compounds may be urolithins, which are made when gut bacteria break down the polyphenols in the extract.

Alzheimer’s disease is associated with ß-amyloid (Aß) fibrillation, a process in which amyloid proteins in the brain form clumps. To fight the formation of these fibrils, however, a molecule would have to cross the blood-brain barrier — a series of cell junctions that prevent certain substances from entering the brain. In previous work, the researchers showed that a pomegranate extract has anti-Alzheimer’s effects in animals, but they did not identify the compounds responsible. Navindra Seeram and colleagues wanted to investigate which compounds in pomegranate could both pass through the blood-brain barrier and prevent Aß fibrils from forming.

The team isolated and identified 21 compounds — mostly polyphenols — from the pomegranate extract. Computational studies found that polyphenols could not cross the blood-brain barrier, but that urolithins could. Urolithins are anti-inflammatory and neuroprotective compounds that are formed when ellagitannins, a type of polyphenol, are metabolized by gut bacteria. The researchers then showed that urolithins reduced Aß fibrillation levels in vitro. Additionally, these compounds increased the lifespan of an Alzheimer’s roundworm model. They say further tests are needed to determine whether the protective effects of these compounds could ultimately help prevent or treat Alzheimer’s in humans.

Souce link : http://neurosciencenews.com/pomegranate-gut-bacteria-alzheimers-3252/

Original Research: Abstract for “Pomegranate’s Neuroprotective Effects against Alzheimer’s Disease Are Mediated by Urolithins, Its Ellagitannin-Gut Microbial Derived Metabolites” by Tao Yuan, Hang Ma, Weixi Liu, Daniel B. Niesen, Nishan Shah, Rebecca Crews, Kenneth N. Rose, Dhiraj A. Vattem, and Navindra P. Seeram in ACS Chemical Neuroscience. Published online November 11 2015doi:10.1021/acschemneuro.5b00260

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Promising drug combination for advanced prostate cancer

A new drug combination may be effective in treating men with metastatic prostate cancer. Preliminary results of this new approach are encouraging and have led to an ongoing international study being conducted in 196 hospitals worldwide.

“We hope to find a well-tolerated and effective treatment to slow the progression of prostate cancer in men with advanced prostate cancer. The approach combines several drugs and attacks the cancer on several fronts,” said Dr. Fred Saad, researcher at the University of Montreal Hospital Research Centre (CRCHUM) and principal investigator of the study.

Antonio Paris, 59, is one of the patients participating in the CRCHUM. “Since I started the new treatment 14 months ago, my cancer first remitted and now is stable,” he said.

With early detection, prostate cancer is treatable. The vast majority of men recover. But it’s a different story for castration-resistant metastatic prostate cancer. In this most advanced form of the disease, the cancer progresses despite treatment options which include radiation therapy, hormone administration, and even removal of the prostate or testicles. Few options are available to halt the cancer that has spread outside the prostate and is resistant to hormone treatment. Since 2011, abiraterone acetate, sold under the name Zytiga®, has been administered orally in addition to standard hormone treatment. It blocks the production of testosterone, the male hormone, which acts as a fuel for cancerous tumours. “This treatment and other recent advances have extended the survival rates of men with the most advanced stages of prostate cancer while improving their quality of life. Life expectancy has increased from 18 months on average in 2004 to three years in 2015.

In a Phase 1 clinical trial, researchers tested the safety of a preliminary combination treatment of abiraterone acetate and another drug not yet approved for market, JNJ-56021927. Antonio Paris participated in this initial research phase. “I take 14 pills a day, and it’s going very well. I have the sweats and I’m tired a bit, but it doesn’t stop me from doing all kinds of activities and even renovations,” he said.

“Our trial conducted on forty patients indicate that this treatment is safe. The combined drugs are well tolerated and the treatment appears effective,” said Dr. Saad. Given these encouraging results, the U.S. Food and Drug Administration and Health Canada authorized the start of a Phase 3 clinical study. The trial is designed to compare the efficacy of abiraterone acetate (1000 mg) and a placebo versus treatment combining abiraterone acetate (1000 mg) and JNJ-56021927 (240 mg). In both groups, patients also receive small doses of prednisone to help the treatment and reduce the side effects of abiraterone acetate. Dr. Saad co-directs this randomized, double-blind trial involving 960 patients worldwide.

The findings of this international study will not be known for about another three years. The future treatment will therefore not be marketed for several years. But the researchers are enthusiastic. They hope this first combination treatment will successfully delay progression of the disease and prolong life. And above all, that it will improve the quality of life of patients with this devastating disease.

http://www.eurekalert.org/pub_releases/2015-11/uomh-pdc112415.php

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Study reveals structure of tuberculosis enzyme, could offer drug target

A team of scientists, including several from the U.S. Department of Energy’s Argonne National Laboratory, have determined the structures of several important tuberculosis enzymes, which could lead to new drugs for the disease.

Tuberculosis, caused by Mycobacterium tuberculosis bacteria, has proved incredibly stubborn even in the age of powerful antibiotics, infecting about one third of all people worldwide. Treatment can take up to nine months. It has stealth properties that protect it from antibiotics; it can hide inside human cells, avoiding the body’s immune system while it waits for the opportune moment to multiply; and it’s very resourceful at acquiring resistance.

“What we have now may not work in a few years,” said Andrzej Joachimiak, an Argonne Distinguished Fellow, head of the Structural Biology Center, co-principal investigator at the Center for Structural Genomics of Infectious Diseases and a corresponding author on the new study.

In order to make new drugs, researchers need to search through the thousands of proteins in the bacterial world to find one that does something so important the bacterium can’t live without it—and then make a little block to match.

One such entry point might be IMPDH (inosine-5?-monophosphate dehydrogenase), which is part of a cellular process that controls the making of guanine nucleotides, one of the building blocks for DNA and RNA. It’s so essential that virtually all living organisms, including human and bacterial pathogens, have versions of it.

“What we discovered earlier this year is that the human and bacterial versions bind molecules differently,” Joachimiak said. “This is very important for finding a molecule to build a drug around—you don’t want to inhibit a human enzyme, just the pathogen one.”

Researchers have been interested in the mycobacterium IMPDH enzyme as a drug target for years, Joachimiak said, but haven’t been able to produce it well enough to study it.

The team observed that one part of the enzyme’s structure was particularly wobbly, so they engineered a version without it using resources at the Advanced Protein Characterization Facility and then then determined the structure employing synchrotron protein crystallography at the Advanced Photon Source, a DOE Office of Science User Facility (both at Argonne).

The modified version functions very similarly to the original, Joachimiak said, but is much easier to purify and crystallize for study.

Brandeis University professor Lizbeth Hedstrom and University of Minnesota professor Courtney Aldrich, two of the study’s other research collaborators, had identified several inhibitor molecules that bind to IMPDH, and thus might be a starting point for a drug—but they couldn’t be imaged while interacting with the enzyme. The new engineered enzyme allowed them to capture the structures of Hedstrom’s and Aldrich’s inhibitors in action, locked with IMPDH.

Helena Boshoff at the National Institute of Allergies and Infectious Diseases performed complementary studies showing that these inhibitors do in fact efficiently block mycobacterium growth.

The new structures were deposited into the Protein Data Bank for continued study

More information: Magdalena Makowska-Grzyska et al. Mycobacterium tuberculosis IMPDH in Complexes with Substrates, Products and Antitubercular Compounds, PLOS ONE (2015). DOI: 10.1371/journal.pone.0138976

Source link: http://phys.org/news/2015-11-reveals-tuberculosis-enzyme-drug.html#jCp

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