Building a national biobank and registry of large and giant congenital melanocytic nevi )

  1. Missing user
    about 1 year ago

    Quoi de neuf?


    La doctorante qui travaille avec nous à Aix-Marseille Université, Pauline Heux, a récemment écrit ce rapport sur l'avancement de ses travaux avant de présenter quelque chose plus technique à la réunion annuelle de la Société Française de Biologie du Développement à la fin mai 2016.

    Le nævus congénital est dû à une multiplication incontrôlée des cellules pigmentaires au cours du développement de l’embryon. Dans la plupart des cas, le nӕvus est visible dès la naissance. Une mutation dans l’ADN, au niveau des gènes NRAS ou BRAF, est le plus souvent retrouvée, mutation présente seulement dans les cellules de ce nӕvus. Cette mutation conduit à une sur-activation des protéines correspondantes NRAS ou BRAF. Quand ils sont trop actives, ces protéines perturbent le développement des cellules pigmentaires.

    Les formes les plus larges de nӕvus sont plus fréquemment associées à des tumeurs, des malformations du cerveau et/ou une pigmentation des méninges, appelée alors mélanocytose neurocutanée. Nos travaux consistent à étudier des modèles animaux de nӕvus congénital, en sur-activant les protéines Nras ou Braf chez la souris embryonnaire dans ses futurs cellules pigmentaires.

    L'introduction de la même mutation Braf que retrouvé dans les nævi humains, même si elle n’est que dans les précurseurs des cellules pigmentaires, entraîne la mort des embryons de souris à la mi-gestation. La cause reste à identifier précisément, mais nous constatons des malformations du cœur et du cerveau. L’effet de cette mutation chez la souris semble nettement plus important que chez l’homme. Des nӕvi de taille parfois importante peuvent porter cette même mutation sans pour autant présenter de pathologies associées. Nous recherchons des moyens de compenser la sévérité de ces conséquences chez les souris, moyens qui pourront ensuite être envisagés pour soigner certains aspects spécifiques au nӕvi géants mutés BRAF chez l’enfant.

    Quant aux souris chez lesquelles la protéine Nras est sur-activée, celles-ci sont viables mais présentent des cellules pigmentaires dans des sites inhabituels et notamment au niveau des valves cardiaques et des méninges, ce qui rappelle le cas des mélanocytose neurocutanée chez l’homme. Bien que les souris soient viables, leur taux de survie à un âge donné est inférieur à celui des souris contrôles. C'est une seconde différence avec ce que l’on peut observer chez l’homme, peut-être due à la proportion de cellules atteintes, plus importante chez la souris que chez l’homme.

    En raison de la localisation des mélanocytes chez ces souris, des défauts fonctionnels cérébraux ou cardiaques pourraient être responsables de la mortalité. Des explorations de ces deux fonctions vitales sont donc en cours, par des techniques spécialisées d’IRM ou échocardiographie spécifiques au petit animal.

    Nos souris présentent également des zones où la peau est plus pigmentée (voir l’image), mais que l’on ne peut définir comme des nӕvi, car la pigmentation est restreinte aux follicules pileux et non diffuse dans le derme. Ces zones, plus nombreuses et plus grandes chez les souris mutantes, reflètent une certaine phase du cycle du follicule pileux, qui semble donc être affectée par la mutation. De plus, la densité folliculaire, déterminée par le nombre de follicules pileux sur une surface de peau donnée, est augmentée chez les souris mutantes de manière congénitale. Ces données sont intéressantes dans le contexte des nӕvi présentant une pilosité importante, et peuvent nous permettre de mieux comprendre le lien entre nӕvus/cellules pigmentaires et poils.

    En ce qui concerne les deux mutations, des expériences in vitro sont aussi en cours afin de caractériser plus finement les cellules atteintes sur le plan moléculaire, et de développer des modèles afin de tester des agents pharmacologiques.

    Depuis que nous avons monté ce projet avec RE(ACT) Community, nous disposons également de nombreux échantillons de nӕvi humains, desquels nous avons pu dériver des lignées cellulaires primaires. Ces échantillons ont été analysés par l'assistante ingénieur que nous avons pu recruter grâce à vos dons. Nous avons mis en place une biobanque de tissus nӕviques humains ainsi qu’une base de données cliniques, pour mieux comprendre la diversité des nӕvi congénitaux et identifier d’autres acteurs moléculaires impliqués dans leur développement. Ces ressources nous permettront de confirmer la pertinence de notre modèle murin et des hypothèses émises.

    Missing user
    over 1 year ago

    Final push in 2015 and looking ahead


    En français, plus loin.


    What an end to 2015, for so many. We are lucky to only be generally affected by the rise of actions based on hate and fear, and to have your support in spreading light over the dark waters around the world. While none of the children in our French registry died from complications due to their giant nevi, others have, and we mourn their loss and our current impotence.


    Relative to our project, we have met and exceeded all of our goals for the milestones achieved, and will be deriving our first pluripotent cell line in January, 2016, with the remaining funds and some last donations. Unless a sudden windfall occurs, this will wrap up our RE(ACT) project. We will have constituted some vital resources for future work, and some preliminary data to develop and with which to interest larger grant organizations. Fatoumata has moved to Paris to look for a job there, and I will get back to the drawing board. Meanwhile, nearly 200 local high school students now know about our research project and what it is like to live with a giant congenital melanocytic nevus, among other rare diseases.


    Our hopes lie in the present and also in the future. May your new year dawn merry and bright.


    Please contact me directly to learn about how to continue to support our or other research projects concerning the giant congenital melanocytic nevus. Thank you again!


    ------------------------------------------------------------

    Quelle fin d’année, pour tant de personnes. Nous avons beaucoup de chance de n’être touchés qu’indirectement par la croissance d’actions basées sur la peur et la haine, et de jouir de votre soutien dans l’épandage de la lumière sur les eaux sombres autour du monde. Alors qu’aucun enfant dans notre registre en France n’est décédé des complications de son naevus géant, d’autres si. Nous faisons le deuil de leur perte et de notre impuissance qui reste toujours actuelle.


    En ce qui concerne notre projet en cours, nous avons bien réussi à atteindre tous les buts fixés par rapport aux paliers atteints. Nous allons dériver notre première lignée de cellules souches pluripotentes induites en janvier 2016, avec ce qui reste de nos fonds et l’aide de quelques derniers dons. Sauf surprise exceptionnelle, ceci terminera notre projet RE(ACT). Nous aurons constitué des ressources vitales pour travailler à l’avenir, ainsi que quelques données préliminaires à développer pour intéresser des organismes financeurs. Fatoumata a déménagé à Paris pour y cherche un autre emploi, et je me remets au travail à la paillasse comme à l’ordinateur. Entretemps, près de 200 lycéens ont pu en apprendre plus sur notre projet de recherche et ce que c’est un naevus géant congénital et la vie avec une maladie rare.


    Nos espoirs sont dans le présent mais aussi dans l’avenir. Que votre nouvelle année recèle du bonheur et de la lumière pour vous.


    Veuillez me contacter directement afin d’apprendre comment continuer à soutenir nos ou d’autres projets de recherche concernant le naevus géant congénital. Merci encore !


  2. Missing user
    over 1 year ago

    Remarquable! 36 000 € total !


    Pendant que j’étais en Ecosse la semaine dernière, au congrès Européen de la recherche sur les cellules pigmentaires (ESPCR), j’ai croisé de nombreuses collègues qui se sont engagés à mes côtés pour focaliser sur la maladie rare qu’est le naevus géant congénital ainsi que sur la prévention et le traitement de ses complications, le mélanome malin et la mélanocytose neurocutanée.


    J’ai aussi reçu les nouvelles d’un effort extraordinaire de la première association de personnes atteintes du naevus géant congénital à laquelle j’ai proposé une collaboration, il y a presque seize ans. L’association Naevus 2000 France-Europe, ainsi nommée fin 1999 en vue de son espoir de favoriser des connexions entre personnes atteintes et entre professionnels de santé en France et à l’international, a travaillé d’arrache-pied depuis le printemps pour apporter encore un don fantastique et très conséquent de la part de ses adhérentes et issue d’une action de communication très originale à mes recherches et à ce projet. Merci du fond du cœur à tous ceux qui ont rendu possible le fait d’atteindre encore un palier, de poursuivre notre travail en avant. Merci infiniment de votre confiance.


    Pauline a gagné un prix du voyage de la part de l’ESPCR, ce qui a rendu sa présence possible la semaine dernière avec moi. Ainsi, nous avons beaucoup appris sur les autres acteurs de la communauté de scientifiques et médecins qui travaillent pour améliorer la vie de personnes avec des désordres des cellules pigmentaires, et sur leurs recherches pas encore publiées. Cette communication favorise des collaborations insolites et est très motivante.


    --

    While I was in Scotland last week at the European Society for Pigment Cell Research (ESPCR) meeting, I met many colleagues who, like me, are committed to studying the giant congenital melanocytic nevus (CMN) and preventing and treating its complications, malignant melanoma and neurocutaneous melanocytosis.


    I also received the news of an extraordinary effort from the very first patient group for CMN to which I proposed my collaboration nearly sixteen years ago. The Naevus 2000 France-Europe association, named thus at the end of 1999 to convey its hope to favor connections between affected people and between health professionals in France and beyond, worked non-stop since the springtime to bring yet another extraordinary and large financial gift from its members and a particularly original fundraising and consciousness-raising activity to my research project. We've all raised a total of 36 000 € for this research project! Thank you from the bottom of my heart to all those who have made it possible once again to reach the next milestone, and for us to carry our work forward. Thank you so very much for your trust and confidence.


    Pauline also won a travel award from the ESPCR (in the center of the awardee lineup), which made it possible for both of us to attend last week. Thus, we both learned a lot about the other people in the scientific and medical community who are working to improve the lives of people affected with pigment cell disorders, and on their as-yet unpublished research. This communication favors unusual collaborations and is very motivating.


  3. Missing user
    over 1 year ago
    While Pauline and I ready our results and their presentation to the European Society for Pigment Cell Research in a couple of weeks, I have compiled a list of recommended reading on congenital melanocytic nevi, their complications and their care.



    The articles listed at the permanent link and below have been proposed by six professionals from the Scientific Advisory Council of Naevus Global, spanning most disciplines of relevant expertise. All are significant and classic papers that have advanced knowledge about simple or syndromic congenital melanocytic nevi and their potential complications. We asked volunteers to exclude recommending their own work. In many cases, full text is available online; in others, please contact Naevus Global. We can usually obtain a reprint from the authors or the publisher as needed.

    Permanent link to this list, complete with abstracts and links to publisher pages, for which one must also enroll for a free account with the U.S. National Center for Biotechnology Information (NCBI).


    • Summarized at this link.

  4. Missing user
    almost 2 years ago

    Pigment cells differentiating in vitro.
  5. Missing user
    almost 2 years ago

    Mid-term update


    Yes, not exactly half-way through, but somewhere in the middle...

    Cells, tissues, people


    Few complex projects proceed entirely as anticipated from the outset. This one has been no exception, but we are making a lot of headway and I am pleasantly surprised to look at my proposal from a year ago and see how far we have come.


    Fatoumata Djitte joined our group as assistant engineer back in February, 2015, in charge of DNA extractions, sequencing and analysis, and data entry into our French registry. This data comes from two sources. First, our direct recruitments through the participating surgeons, with particular thanks to the exceptional doctors Nathalie Degardin, Isabelle James and Guillaume Captier. Fatou processes samples, doses DNA, and finds the mutations responsible for that person's CMN when possible. She is currently adapting a protocol to render our mutation detection capacity much more sensitive.


    A second source of data has been through the eager participation of two French patient associations in providing their archives and standardizing information provided by families over the last fifteen years or so. This is in order to attempt to contact individuals to renew their consent to participate in today’s data collection about congenital melanocytic nevi (CMN), since it is not of much use to research in its current state. It may well be that such information is similar to that amassed in other parts of the world by our colleagues, but a replication cohort would still be useful to have, even for internal comparison with our current prospective group.


    For instance, early last year, colleagues in Paris published an article entitled “NRAS mutation is the sole recurrent somatic mutation in large congenital melanocytic nevi”. It was true for the 19 patients with large and giant CMN from whom they had collected DNA at the time – 18 of them had NRAS mutations and only one had a BRAF mutation. Similar to earlier findings by other groups, more people with small to medium congenital nevi had BRAF mutations. However, in a paper from this year, a different cohort of patients examined by our colleagues in Pittsburgh helped establish not only that BRAF mutations can also be recurrent, if still in the minority, in patients with large and giant CMN, but those patients have slightly different clinical characteristics: all (5) patients with BRAF mutations had benign dermal or subcutaneous nodules, and two of them also had neurocutaneous melanocytosis (NCM). This new information allows the scientific community to adapt its hypotheses. Do CMN with different types of mutations have different outcomes? Does inherited genetic information impinge on those outcomes? If melanoma or symptomatic NCM develop, might they respond differently to chemotherapies developed specifically for BRAF- or NRAS-mutated melanomas?


    Hypotheses are cheap, but research is expensive. Thanks to your direct participation, Fatou will be with us through mid-October. She doesn’t like to have her picture taken and posted online, though, otherwise I’d put a snapshot of our little team, which also includes a young scientist preparing her Ph.D. thesis for another two years under my supervision, Pauline Heux.


    In accordance with the three milestones that you have currently funded, we have made assessments of the database software and recruited a qualified research engineer, who is now competent for data entry and has many other useful skills for the project. I have met in person with both the Association du Naevus Géant Congénital and the Naevus 2000 France-Europe groups to present our project, and samples are now being sent to us from most of the foreseen surgical centers.


    Since the beginning of this project, we have received fifteen new large and giant nevus samples and successfully established the conditions to derive primary cell lines from ten of them. Fatou has found mutations in either NRAS or BRAF in nearly all so far. This resource enables us to make fruitful comparisons to precursor cell lines that Pauline derives from our mouse models bearing similar mutations. Ultimately, but not at the moment, as the project has not been sufficiently funded, we would like to use our in-house induced pluripotent stem cell (iPS) derivation platform to ensure the long-term “immortalization” of these cells and their greatest use to the scientific community at large. iPS cells are finicky and demand a great deal of time to maintain, so in the meantime, ten cell lines from different individuals are stored safely at -150°C (-238°F) at varying stages of development, while another one is currently growing to the appropriate stage of purity and cell numbers in the incubator at the moment. It takes us about 3-4 weeks to get from skin to freezer.


    We have therefore doubled recruitment relative to our hopes in the original milestone goals! This is the kind of unanticipated development we can really enjoy. Now we can finally move on to functional studies with these precious resources.


    Meanwhile, if you are in Edinburgh in September, come by to meet Drs. Bernhard Wehrle-Haller, Veronica Kinsler, Lionel Larue, Caroline Le Poole and myself (and possibly others from the Naevus Global Scientific Advisory Council), as well as Greg Barsh, Lukas Sommer, Dot Bennett, Eugene Healy and many other pigment cell researchers, at the upcoming European Society for Pigment Cell Research conference. Pauline has won a travel award to present a poster of our work with a Nras mouse model for CMN and NCM, to be written up and submitted for publication before the end of this project. Keep your eyes on this space...

  6. Missing user
    over 2 years ago

    GREAT NEWS ! In English below; click here.


    La Journée Internationale des Maladies Rares est le 28 février : ce samedi. Le paradoxe des maladies rares est qu'elles peinent à trouver les financements pour que les chercheurs puissent mieux les cerner et les vaincre. Mais grâce à l’exceptionnelle mobilisation de quatre associations nationales pour le naevus géant congénital, il y a eu un élan populaire extraordinaire pour soutenir notre projet de recherche. Mon groupe de recherche à l’INSERM constitue les ressources biologiques nécessaires à étudier, comprendre et développer des systèmes caractérisés qui permettront de tester des nouvelles thérapies pour aider à bien vivre avec un naevus géant congénital. Nous recueillons des informations cliniques et des échantillons, tout comme des homologues dans quelques rares autres pays, pour qu’on travaille ensemble au niveau international.


    Quatre associations de patients, tous membres de Naevus Global, ont fait au nom de leurs adhérents des dons énormes à notre projet pour compléter la participation directe de beaucoup d’entre vous. Une cinquième a renouvelé son soutien au fil du temps. MERCI A TOUS. Rien ne se passerait sans le soutien direct des citoyens concernés eux-mêmes ou au niveau du cœur par cette malformation et maladie rare.


    15 530 euros EN PLUS pour notre projet de recherche !


    Caring Matters Now a ouvert le bal avec une contribution de 1 000 euros, suite à une soirée caritative organisée en octobre à Londres. Un de leurs petits adhérents de 4 ans est mort cette semaine, et nous sommes de tout cœur avec eux. Voilà L’Association du Naevus Géant Congénital, discret mais ultra-efficace, a voté le don d’un époustouflant 5 000 euros lors de leur dernière assemblée générale à l’automne 2014. A ceci s’ajoute le recueil continu au fil de ces derniers mois de dons d’individus français, fléchés pour ce projet, de 2 530 euros supplémentaires !


    Asonevus, la Asociación Española de Nevus Gigante Congénito, a aussi explosé les compteurs, avec des évènements comme une course d’enfants du village d’une des adhérentes et la vente de calendriers 2015 (il se peut, toujours disponibles ). Ils ont rassemblé la somme extraordinaire de 7 000 euros (!) pour la recherche, et notre projet a été bénéficiaire de leur confiance.


    Nos fidèles partenaires en matière de subvention, Nevus Outreach Inc. et Tout un Cirque, le premier BD du monde dont l’héroïne est un enfant avec un naevus géant qui apprend à apprivoiser sa différence visible en même temps qu’elle apprend à apprécier l’histoire unique de la cirque et des individus qui y participent pour que les spectacles émerveillent tout le monde. En attendant la traduction dans d’autres langues, vous pouvez voir et procurer pour vous-même la qualité de cette production directement chez l’éditeur (pour qu’un maximum de bénéfices revienne à la recherche).


    Je suis extrêmement émue par tant de solidarité et confiance. Nous avancerons main dans la main, scientifiques, médecins, familles et citoyens, dans l’esprit exact de la Journée Internationale des Maladies Rares. MERCI.



    Here’s our GREAT NEWS!


    15 530 euros IN ADDITION for our research project!


    International Rare Disease Day is February 28th – this coming Saturday. Although approximately one in twenty of us is affected by a rare disease – many more, if you count being affected meaning that someone you love has one of these conditions – it is still very difficult to attract funding so that scientists like myself can study and conquer them. But thanks to the exceptional actions of many national associations for the giant congenital melanocytic nevus (CMN), there has been an extraordinary wave of support for our research project. My team at the INSERM, France’s National Institutes of Health, is building the biological resources so desperately needed to study, understand and develop characterized assays which will ultimately allow the development of new therapies to treat CMN. We are collecting both clinical information and samples, as are colleagues in a few other countries, all of us working and cooperating across political and institutional borders.


    Four patient groups, members of the Naevus Global federation, have made particularly sizeable gifts on behalf of their members to our research project, adding thereby to the direct support of so many of you. A fifth group has also shown its support by channeling donations. THANK YOU TO ALL OF YOU. Nothing would happen without this direct engagement by citizens who are directly, or through generous solidarity, indirectly concerned with this rare malformation and its attendant complications.


    Caring Matters Now in the U.K. opened the dance (as we say in French), with a fabulous gift of 1,000 euros following a charity ball last October in London. Our hearts and thoughts are particularly with this group as they yet again mourn the death of a four-year-old member last week. This is our greatest motivation to act.


    The French Association du Naevus Géant Congénital, discreet but very effective, voted at their last general assembly to make a phenomenal gift of 5,000 euros to my project. In addition, they have been the conduit for an additional 2,530 euros in directed donations from members and friends of the group. This gift has been credited to our RE(ACT) counter today; there goes another milestone!


    Asonevus, or the Asociación Española de Nevus Gigante Congénito, has exploded the next milestone with events such as a children’s race in the Spanish village of one of its members, and the sale of 2015 calendars. They have gathered and donated 7,000 euros (!) to research, and our project is the proud recipient of their trust and generosity.


    Our faithful partners in research funding, Nevus Outreach Inc. and Naevus 2000 France-Europe, have massively supported past ventures in my laboratory from which the results have not yet been published (but are being prepared for submission even as I write). These have given us the necessary leads and credibility for the current project underway. Nevus Outreach centralized and passed along a few U.S.-based donations, which enabled us to reach our first and most nerve-wracking crowdfunding milestone in the autumn. Naevus 2000 France-Europe has assembled for our project since only last December, the marvelous sum of 1,000 euros. Their original approach was to team up with a family of volunteers comprising among others, a professional journalist author and a professional illustrator of comic books. In this manner was born Tout un Cirque, the first comic book in the world where the heroine (with natural powers, but she encounters magic!) has a facial CMN and learns to come to terms with her visible difference by appreciating the history of the circus and meeting some of the unique people who populate this four-dimensional world of wonder and awe. While we await its translation into other languages, you can peruse and procure a copy for yourself at the editor.


    I am extremely moved by such a show of solidarity and trust in me and my laboratory. We are advancing hand in hand together – scientists, doctors, families and concerned citizens, in the precise spirit of this International Rare Disease Day 2015. Join your hands to ours. THANK YOU.

  7. Missing user
    over 2 years ago
    Happy New Year - despite a rocky start in France. Updates have been few and far between because (a) I've been working at the bench, rather than actively promoting our project to the public, and (b) our project period only starts on February 1st. RE(ACT) transferred the money from all your donations toward our first milestone to the Université Aix-Marseille at the end of last year, and we have recruited the technician who will work on this project for the next five months. I'll introduce the whole team once that has been finalized, hopefully by next week.

    We have also restructured the milestones to be closer together, in the likelihood that other donations will be coming in, and to offer you visibility as to how the increments are being applied. You will see how that looks, shortly, especially as I will actively be seeking contributions once more. I have also decided to use the publicly available GESBIOL application of the 4D relational database management system, and am currently working with the developers for a customized version specific to this biobank and registry project.

    Bonne année 2015, malgré un début difficile pour tous les français. Je n'ai pas ajouté de mise à jour depuis un moment, pour deux raisons. D'abord, j'ai été beaucoup à la paillasse plutôt que de promouvoir nos activités pour le grand public ; ensuite, le projet proprement dit commence le 1er février. RE(ACT) a bien transféré l'ensemble des fonds que vous avez donnés vers le premier palier vers l'Université Aix-Marseille à la fin de l'année, et nous avons recruté la technicienne qui travaillera sur notre projet pour les cinq mois à venir. Je vous présenterai l'ensemble de l'équipe une fois que tout cela est finalisé, j'espère la semaine prochaine.

    Nous avons aussi restructuré les paliers pour les rapprocher, dans l'attente de d'autres dons cette année, et afin de vous montrer avec un peu plus de granularité ce qu'on en fera. Vous verrez bientôt comment cela se présente, d'autant plus que je me remettrai à solliciter des contributions. J'ai également décidé d'utiliser pour ce projet, l'application GESBIOL du système de gestion de bases de données 4D, donc je travaille actuellement avec ses auteurs afin de faire un interface à façon pour gérer notre biobanque et registre du nævus géant congénital.

  8. Missing user
    over 2 years ago
    Time flies when you're having fun, and placing and unpacking orders for reagents is part of the fun. Reagents that I will continue to be able to purchase in 2015, thanks to you. I am reorganizing how I present the project for further participation in its funding. I appreciate your patience and above all, your support and participation!

    On s'amuse comme on peut, et le temps passe pendant que je place et reçois des commandes pour les réactifs. Ces réactifs que je continuerai à pouvoir acheter grâce à vos dons. Je réorganise la présentation de la financement ultérieure du projet afin que la participation continue soit visible. J'apprécie beaucoup votre patience, votre soutien et surtout, votre participation.



  9. Missing user
    over 2 years ago
    If you're here, you realize we've attained our first milestone. This represents a few month's salary to take on a qualified research technician who has been working on a different rare disease project to date, and who would otherwise have had to leave our group in 2015. Now, we can look forward, we can buy reagents, and we can dream. All because of YOU.

    Si vous êtes en train de lire ceci, vous comprenez que nous avons atteint le premier palier de ce projet de recherche. Vous nous avez offert quelques mois de salaire d'une technicienne de recherche qui aurait du nous quitter en 2015 sans travailler sur le nævus géant congénital, alors qu'elle est très qualifiée. Maintenant, nous pouvons tous aller vers l'avant, acheter quelques réactifs, et surtout : rêver. Tout cela grâce à VOUS.

  10. Missing user
    over 2 years ago
    WOW. 1 130 € in under 24 hours / dans moins de 24h !
  11. Missing user
    over 2 years ago
    (en français plus loin)

    I would like to post a photo of our cultured nevus cells - they are very pretty. Most cell biologists are used to what fibroblasts look like - we also derive those from the skin samples donated - but these are something special. The nevus cells look something like the middle picture, though more like little fat, light brown sunbursts, and we're hoping we still have favored the persistence of cells that look like the top one (courtesy Dr. Lanfrancone). I'd take pictures myself but we are currently using a culture room without its own camera-equipped microscope, so I'll wait until we have more cultures and that we don't take risks by bringing the cells to another culture room.


    Last week to attain our first milestone! I am confident we can make it, together, and thank you already for your support.

    __________________________


    J'essaie maintenant en français - le formattage n'est pas simple! En tout cas, voilà à quoi ressemble nos cellules issues de peau de nævus géant déjà donnée à notre projet incipient. Ce n'est pas ma photo mais celle du Dr. Lanfrancone). J'en prendrai quand les choses sont plus avancées et nous avons plus encore de cellules, parce qu'il faut changer de salle et ceci risque d'introduire des contaminations.


    Dernière semaine pour atteindre notre premier but et je suis confiante que nous y arriverons tous ensemble. Merci de votre soutien !
  12. Missing user
    over 2 years ago
    En français plus loin.


    We received another sample today, from a little girl. What a relief on the research end, when all the information is filled in correctly, from the consent forms to the clinical information! Data entry will have to wait until someone is available; there's a bit of a backlog on the papers, but living samples must get priority.

    In the next few updates, I'll describe some of the things we do and aspire to do with the biological resources.

    When patients and their parents agree to participate in the biobank part of the study (as opposed to the registry only), they agree that some of the tissue after a nevus excision will be set aside for research. This means it ends up in one of the vials with the pink medium in one of those pictures below. It's pink to let us know that the salt/nutrient solution is normal pH; if it gets contaminated it tends to go acidic and turn yellow. Samples are either shipped to my lab or I walk over to the hospital and pick them up in the surgery departmental fridge.

    On receipt, the skin gets cut into a number of fragments. Some are moved successively from one liquid to another to yet another in order to embed them into either paraffin, or a sugar solution that on freezing, makes them both the right consistency of hard and also cuttable at temperatures below zero. Each technique is good for certain kinds of experiments. In our lab, all that's done by hand. In the hospital, there are cool robots that are out of our price range, to take care of the process.

    Biological samples often need to be solidified to allow fine sectioning. Thin slices improve the access of dyes, probes, and antibodies and reduce the overlay of different cells layers in the z direction. For light microscopy, paraffin wax is the most frequently used hard matrix for cutting.

    The above schematic (click to enlarge) represents how to get from tissue to a treatable microscope slide that is representative of the structure of the nevus, and from there to gaining new information. We need slide to learn, for example, that cells within the nevus have a molecular property that will then teach us something about to how the nevus is structured and maintained over time.


    Nous avons reçu un autre prélèvement aujourd'hui, d'une petite fille ayant été opérée ici à Marseille. Quel soulagement, quand l'ensemble des consentements et questionnaires est bien rempli ! L’entrée des données papier dans notre base de données attendra la disponibilité de quelqu'un - priorité aux spécimens biologiques vivants.

    Au cours des mise a jours suivants, je parlerai de ce qu'on fait et espère faire avec les ressources biologiques que nous constituons.

    Quand les patients et leurs parents consentent à participer dans la biobanque (au-delà du registre des caractéristiques cliniques du naevus), un peu du tissu excisé après une intervention chirurgicale est mis de coté pour la recherche. Il finit dans une des petites fioles avec le milieu rose dans une des photos plus bas. Il est rose pour nous dire que le pH est toujours neutre; s'il y a contamination avec des micro-organismes il tend à virer au jaune. Les échantillons viennent par coursier ou si c'est à l’hôpital de la Timone, j'y vais à pied pour les chercher dans le frigo du service de chirurgie pédiatrique.

    En arrivant, le tissu est découpé en plusieurs morceaux à plusieurs destinations. Certains passent d'une solution à une autre pour arriver à l'inclusion dans un milieu qui durcit, tel la paraffine liquide ou un sirop de sucres qui devient dur sur congélation, mais les deux peuvent toutefois être coupées en très fines tranches pour la microscopie optique. Chaque technique pour une information différente.

    Le schéma (cliquer pour élargir) représente comment aller du tissu vers une lame de microscope qui peut être traitée et qui représente bien la structure du naevus, afin d'augmenter nos connaissances. Nous avons besoin, par exemple, d'apprendre que certaines cellules dans le naevus ont certaines propriétés moléculaires, ce qui nous indique comment le naevus se structure et s'entretient au fil du temps.
  13. Missing user
    over 2 years ago
    Below, I describe our research project in French. I am thrilled by the continuing participation now of nearly 50 people in an approach which is as much yours by so doing, as that of our laboratory!

    Voilà le descriptif de notre projet en français. Je suis ravie de la participation importante et continue de près d’une cinquantaine de personnes à ce jour, à cette approche qui sera la vôtre autant que la nôtre au laboratoire !

    Le nævus congénitale mélanocytaire de très grande taille, souvent appelé nævus géant congénital (NGC) est une malformation généralement sporadique de la peau. Elle est due à des mutations qui ont lieu pendant la grossesse et qui restent tolérées dans l’ADN des cellules mutées, sans cause spécifique connue. Ces cellules se propagent et se multiplient plus que leurs homologues avant la naissance. Elles deviennent alors sénescentes (elles ne se divisent plus autant) et donnent lieu à des régions mosaïques fortement pigmentées qui peuvent se trouver n'importe où sur la surface du corps. Les zones non pigmentées peuvent également être mosaïques mais l’étendu du mosaïsme n’est pas connu pour l’instant. Nous ne savons pas comment la dispersion et les modes de distribution finale, un peu stéréotypés de la CMN se produisent.

    Les NGC dépassant un diamètre prévu à l'âge adulte d'au moins 20 cm sont présents dans au moins une sur environ 50.000 naissances. Plus le NGC est grand en taille, plus il est rare et le plus souvent associé à d’autres symptômes potentiellement débilitants tels une neuropathologie, des tumeurs bénignes, ou un mélanome malin généralement juvénile, qui est sinon un cancer pédiatrique extrêmement rare. Pour ces raisons et d’autres, une terminologie récente qui gagne de terrain parle de «syndrome de CMN» qui peut présenter cliniquement une ou plusieurs signes.


    Les options de traitement pour les NGC sont exclusivement chirurgical en ce moment. Compte tenu des surfaces concernées qui sont grandes et parfois complexes, les interventions sont répétées et donc perturbent la vie des enfants en pleine croissance et de leurs familles. Des approches chirurgicales innovantes existent mais peuvent aussi causer d'autres complications. La chirurgie en plus demande une justification individuelle à l'assurance nationale ou privée, basée autant sur la psychologie que sur la prévention.

    La collecte systématique de divers échantillons biologiques après la chirurgie sera une première étape énorme pour comprendre la physiopathologie des NGC et leurs formes syndromiques. Notre groupe de recherche a obtenu toutes les autorisations nécessaires pour créer une biobanque nationale en France des échantillons de peau de patients atteints d'un NGC simple ou syndromique. Cette banque permettra de relier les données biologiques avec des données cliniques d'histoire naturelle des patients et de leurs familles.

    Pour maintenir la biobanque, nous allons entrer des données dans un registre national, conçu pour être interopérable avec un projet de registre international du NGC défendu par une fédération d’associations de patients, Naevus Global. Nous allons également dériver et maintenir des cellules primaires, pour la production de cellules souches pluripotentes induites (iPS) et la conservation à longue terme pour la recherche.

    Cette ressource de biobanque va permettre le développement de modèles cellulaires ou xénogreffes qui permettront une exploration plus approfondie des aspects spécifiques du NGC, mais aussi des principes plus généraux qui sous-tendent les liens mécanistes entre les anomalies de développement, de la sénescence cellulaire et du cancer.

    Je suis à la recherche de fonds pour employer un technicien de recherche clinique dédié pendant deux ans, pour coordonner la saisie des données et le traitement des échantillons. Cette personne reverra également tous les dossiers proposés par les associations francophones des patients, voir coordonnera avec des internes en dermatologie qui souhaitent participer à notre projet de recherche, afin de stimuler le recrutement pour les registres nationaux et internationaux de cette malformation rare. Des financements partiels entre les étapes cibles seront appliquées à l’achat de réactifs nécessaires pour élaborer et commencer à étudier les lignées de cellules dérivées de NGC en culture.

    Merci encore de votre soutien!
  14. Missing user
    over 2 years ago
    40 donors today! and very nearly half-way there! - thank you all for your participation which is so important and valuable for our project.

    40 donateurs aujourd'hui et presque la moitié du but déjà atteint! Merci à tous de votre participation qui est si important et valable pour notre projet.
  15. Missing user
    over 2 years ago
    Version française!

  16. Missing user
    over 2 years ago
    Preparation of sample vials for nevus skin .... Préparation de fioles pour la peau naevique.



    Ready to go to the surgeon... Prêt à partir chez le chirurgien!

  17. Missing user
    almost 3 years ago
    Je n'ai pas oublié mes amis francophones... des nouvelles bientôt.

    Preparing the consentment packets for the collaborating surgeons!

    (Je prépare des paquets pour nos chirurgiens collaborateurs)

    Lots of nevus project papers

    Look at how much progress we've made: over six thousand euros with 21 donors so far. Together, we can bring those numbers up even higher. Thank you in particular to the massive underwriter who stepped in this weekend. We're doing a happy dance here in lab.

    (Nous sommes ravis d'en être à autant avec vingt-et-un donateurs à ce jour. Et si vous participiez, vous et vos amis aussi?)

    xo
  18. Missing user
    almost 3 years ago


    This morning, a guest blog post I wrote at The Guardian appeared in the U.K. It's getting passed around on Twitter and Facebook quite nicely and garnering some interesting discussion from many places in the English-speaking world. Now I need to really get after Francophonie, but that's harder for me.

    I'm so grateful to all who are participating.

    I think I will want to read Amanda Palmer's upcoming book, The Art of Asking, though it will only be out in November. She's a Boston-area native, like myself, and has certainly perfected that art. Its title reminds me of another book I found beneficial, Ask For It, by Linda Babcock and Sara Laschever.

    I'll be ramping up the personal requests by e-mail until such time as the cell lines, the mice and the PCRs get to be so much that I have no more time for that. As of September, getting this up and running will depend instead, on you faithful supporters.
  19. Missing user
    almost 3 years ago
    Putting this together was even harder than putting together a presentation for my peers in the ivory tower. This one is for everyone. Here is THE video introduction to our congenital melanocytic nevus research project (in English). French coming soon.

    Thank you to our TWENTY donors so far. If we can continue attracting new supporters/backers/donors, we'll get this show really started! So please share far and wide.



    For those who would rather read, this is about what I said:

    Hello – my name is Heather ETCHEVERS. I am a tenured scientist with the Institut National de la Santé et de la Recherche Médicale, which is France’s National Institute of Health. I work at the Aix-Marseille University medical school on the Timone campus in Marseille, France.

    This fundraiser is more than a way to raise money for research. It is a different approach to raising awareness about a situation which is fundamentally unfair, and it offers solutions.

    A little boy from Columbia, Didier Montalvo, became world-famous after he was featured in a documentary about his form of giant congenital melanocytic nevus. But giant nevi are as unique as the people who are born with them. I know this, because I have spent the last fourteen years getting to know nevus owners from all over the world.

    What is even more unfair than being born with a visible difference, is learning that one in ten to twenty people like you will develop either malignant cancer or debilitating neurological symptoms. What is unfair is that this condition is so rare, that it is nearly impossible to obtain standard governmental funding for research into it. This is true for the entire handful of professionals around the world committed to studying this birth defect.

    Yet, like for many other rare diseases, results from our research may well have direct clinical impact for more common conditions, like adult-onset melanoma.

    Our laboratory works with dermatologists and plastic surgeons from six major cities in France. Other projects are underway with support from many of the worldwide patient groups who are working together in the new Naevus Global federation.

    This video is giving you an idea of some of the infrastructure and techniques that will be used to study the skin, blood and clinical data we collect.

    If it were not for patient advocacy groups, there would be a series of case reports but no hypothesis-driven research into giant congenital melanocytic nevi. I need you to become an advocate, too.

    This project depends on our funding a clinical research technician’s salary. To succeed, we need you to participate now.
    You can join the RE(ACT) Community whether or not you or someone you love is affected with a giant congenital melanocytic nevus. By sharing this video, you support public attention and funding being directed to research into this rare condition.

    Welcome to YOUR laboratory, please look for more updates over the upcoming months, and thank you very much for your interest and support.
    (I welcome direct correspondance at heather.etchevers@inserm.fr)
  20. Missing user
    almost 3 years ago

    Our project has received pledges as of August 4th from 12 supporters. Thank you, you apostles! I don’t know who many of you are – I might if the campaign is successful at the end of the next couple of months and you’ve signed up as a visible supporter here on RE(ACT). Doing so in itself is the action of a patient advocate.

    Be proud of your solidarity. This is direct citizen implication in a scientific project with tangible outcomes for real people – you get to determine that it deserves a chance to succeed.

    I have and will continue to welcome volunteer efforts in my laboratory. It is part of my mission to educate and reach out to the general public, and I started doing it long ago. If you want to begin right away, please send the link about this project to your friends and family, and tell them that you are a part of it and want them to be, too. That will make a huge difference in the outcome. If you want to do even more, or come visit the lab, please contact me.

    Frequently asked questions (of me), so far:

    When you make a donation, you are clearly reminded that RE(ACT) will attribute 90% of your payment directly to my project, and keep 10% for its own expenses. I find that fair. Why? Because rare disease advocacy doesn’t happen in a vacuum.

    If I have picked this platform, it is because I am aware that what one advocacy group learns is a good lesson for another. Research into one condition more often than not is relevant to the next. Rare diseases affect one in twenty of us around the world. Not like you’d know that rare diseases present a major public health issue. France consecrates an annual equivalent of 0.75% of its total research budget – I can’t easily find out what portion of it is biomedical – to its much-vaunted, long-term “Plan Maladies Rares”. Meaning most everyone else does much less (with the apparent exception of the United States, with an Office for Rare Disease Research component of the NIH).

    And none of that is going directly to research on the giant congenital melanocytic nevus. You can change that.

    Don’t worry; I have built RE(ACT) Community’s overhead into my estimates, so I will have enough to do what I’ve said I will (and it’s a lot less than the overhead built into the NIH’s budget). And they will take the rest and do this:

    1. host and provide humans to operate a great website for you to follow this project over the next couple of years. You can consult and contribute other uploaded information about this and nearly seven thousand other rare conditions – that includes patient testimony about what it is to live their lives, which is necessary for improving care.
    2. make it easy for you to pay with a credit card and/or through PayPal.
    3. liaison with a Scientific Advisory Board to vet and - in theory - provide constructive criticism for applications for new projects. This is your guarantee that my peers really think this could work, not just random people from my pre-existing social network who believe in me, personally.

    From the Terms and Conditions:

    • Backers agree to provide their payment information at the time they pledge to a campaign. The payment will be collected at or after the campaign deadline and only if the amount of money pledged as of the deadline is at least equal to the fundraising goal. The amount Backers pledge is the amount they will be charged.
    • Backers consent to the RE(ACT) Community and its payments partners authorizing or reserving a charge on their payment card or other payment method for any amount up to the full pledge at any time between the pledge and collection of the funds.
    • Backers agree to have sufficient funds or credit available at the campaign deadline to ensure that the pledge will be collectible.


    Pigmented hugs to you.


    THANK YOU for your contributions of all sorts! We need each other.
  21. Missing user
    almost 3 years ago
    I went and wrote, go ahead, launch the campaign - unprepared, at the end of July. That said, we ARE going to succeed in raising the money we so desperately need to make concrete things happen in our lab: registering the very many families who have been willing to participate in this research for years now, and processing their biological samples to discover the answers to those questions that just keep coming.

    Why do some children with congenital melanocytic nevi (CMN) die of cancer or brain malfunctions? That's the big one. Far too many of them - and we as yet have no idea what distinguishes their CMN from the other kids who continue to live with the difficult social stigma of looking sometimes very different. A survey and registry, but above all, the biological specimens and comparing their characteristics to our animal models, will help us understand. Our lab is collecting them, but I need personnel to really make it happen.

    Therapies might already be on their way because of recent findings as to what genes can be mutated and in what tissues. However, we still don't know how these genes work during development or how the hyperactive proteins they encode might be counteracted safely. Our research is designed to answer these questions.

    The first genes identified were the same ones often mutated in adult-onset melanoma, only before birth and without sun exposure. CMN kids mostly don't have melanoma - except for those who then do develop melanoma. A vastly greater proportion than among children without CMN. I am aware of two children in the world fighting their CMN-related melanoma as I write you, and those are just the ones I know. It is heartbreaking.

    You would think that governments would recognize the potential impact of rare disease research in a condition affecting kids from birth, for understanding and treating a common adult cancer. It's exceedingly difficult anywhere in the world, to get so-called public funding for a condition that affects a tiny percentage of the population and their caregivers

    Therefore, I turn directly to the public. You. Please back this project. Show the world that the number of people affected with a difficult rare condition should not be part of the cost-benefit analysis for worthwhile research.


    Look how beautiful people with CMN are! (If you follow this link, click the little boy on the stairs, for a beautiful photo campaign sponsored by Nevus Outreach, Inc. in the U.S.)

    My major motivation - one of those lovely teens with CMN is my daughter. Another motivation - another one of those lovely teens had a piece of her brain removed a few years ago, to control her CMN-related epilepsy by removing the pigmented area. Another motivation - any of those lovely teens sometimes feels uncomfortably different from everyone around her, and that's outside of spending time in the hospital, which they all have.

    Look soon for a video introduction to my research group, and interests, and perhaps some more motivations.

    Thank you so much for your interest and support. (Google+)