Mmolecular mechanisms leading to basal cell carcinoma initiation uncovered

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ScienceDaily (Nov. 26, 2012) One of the most outstanding and unresolved questions in cancer biology is the identification of cells at the origin of cancer and the understanding of the molecular changes that occur in tumor initiating cells from the first oncogenic mutation to the development of invasive cancer. Basal cell carcinoma (BCC) is the most frequent cancer in human with more than million of new patients diagnosed each year with BCCs.

Recently, the group of Pr. Cdric Blanpain uncovered the cells at the origin of BCC (Youssef et al, Nature Cell Biology, 2010).

In a new study published in advanced online publication of Nature Cell Biology, researchers lead by Cdric Blanpain, MD/PhD, Professor at Universit libre de Bruxelles (ULB) and WELBIO investigator dissected for the first time the molecular changes occurring in basal cell carcinoma initiating cells from the first oncogenic mutation until the development of invasive cancer.

Khalil Kass Youssef and colleagues established the molecular signature of tumor initiating cells at different time during cancer initiation. They found that that cells at the origin of the basal cell carcinoma were progressively reprogrammed into embryonic hair follicle progenitor like fate before progressing into invasive carcinoma. "We were extremely surprised to see that tumor initiating cells were progressively and profoundly reprogram into a molecular identity that resemble to progenitor cells presented during embryonic development" comments Khalil Kass Youssef, the first author of this study.

In collaboration with bioinformaticians from the ULB and the KUL, the researchers demonstrate that Wnt/-catenin signaling pathway is activated in BCC-initiating cells soon after oncogene expression. Using genetic or pharmacologic inhibition of the Wnt/-catenin signaling, the researchers demonstrate that Wnt/beta-catenin signaling is essential for the reprograming of tumor initiating cells into embryonic hair follicle progenitors and for tumor initiation.

In collaboration with physicians from the Department of Dermatology, Pathology and Plastic Surgery from the Hospital Erasme, the group of Cdric Blanpain demonstrate that human BCCs also present signs of reprograming into embryonic hair follicle progenitors and activation of the Wnt/beta-catenin signaling, demonstrating the relevance of these findings for human patients.

This new work is at the frontier of multiple fields of biology and medicine and will be extremely important for researchers studying cancer, development, and stem cell biology. "I am particularly excited about this work, because this basic research turn out to be very relevant for human diseases, with the identification of potentially new avenues to treat or to prevent the occurrence of the most common cancer in humans " comments Pr Cdric Blanpain.

This work was supported by the FNRS, the program d'excellence CIBLES of the Wallonia Region, a research grant from the Fondation Contre le Cancer, the Fondation ULB, the Fond Yvonne Bol, the Fond Gaston Ithier, a starting grant of the European Research Council (ERC) and the EMBO Young Investigator Program.

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Mmolecular mechanisms leading to basal cell carcinoma initiation uncovered

DGAP-News: Evotec enters biology collaboration with Probiodrug

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Hamburg, Germany - 28 November 2012: Evotec AG (Frankfurt Stock Exchange: EVT, TecDAX) announced today that it has entered into a collaboration with Probiodrug AG, a privately owned biopharmaceutical company focused on the development of innovative drugs for the treatment of major age related diseases.

Under the terms of the agreement, Evotec will setup and validate assays to support the pre-clinical and clinical development of glutaminyl cyclase (QC) inhibitors for the treatment of Alzheimers disease. Glutaminyl cyclase is a novel proprietary enzyme target discovered and validated by Probiodrug which plays a crucial role in the pathogenesis of Alzheimers disease (AD) as well as potentially other diseases.

Dr Mario Polywka, Chief Operating Officer of Evotec commented: We are pleased to enter this collaboration with Probiodrug to use our first class assay development capabilities to support the pre-clinical and clinical development of QC inhibitors in Alzheimers disease and other indications. This is a good example of how Evotec can support Biotech companies with their specific drug discovery needs.

Hendrik Liebers, Chief Financial Officer of Probiodrug, added: The collaboration will allow us to focus on the further pre-clinical and clinical development of our programmes in neurodegeneration/AD. Evotec, with its proven track record, is ideally suited to accompany this process by running existing and developing new biological assays.

ABOUT PROBIODRUG AG Probiodrug is a biopharmaceutical company dedicated to the discovery and development of small molecule drugs against novel molecular targets for the treatment of neuronal and inflammatory diseases. The Company has a dominant position in the area of glutaminyl cyclase inhibition. Glutaminyl cyclase, a novel enzyme target discovered and patented by Probiodrug, has a crucial role in the pathogenesis of Alzheimers disease (AD) as well as various peripheral inflammatory diseases. Probiodrug is backed by institutions such as BB Biotech, Edmond de Rothschild Investment Partners, Goodvent/IBG, HBM, TVM, Life Sciences Partners, Biogen Idec Ventures, CFH Group, funds managed by Wellington Management, and private investors. Probiodrugs core capabilities are based on its long-standing expertise in the elucidation of the structure and function of enzymes which play a central role in the maturation of hormones. The Company has pioneered the field of dipeptidyl peptidase 4 (DP4)-inhibition for the treatment of type 2 diabetes. Compounds and technology patents of its DP4 program in diabetes were licensed to various pharmaceutical companies. In 2004, all metabolic assets were sold to OSI Pharmaceuticals, Inc. The first drug based on Probiodrugs technologies reached the market in late 2006. Proceeds of the various transactions have been reinvested by the Company to fund the novel approach for the treatment of AD and inflammatory diseases. The Company was founded in 1997 by Prof Dr Hans-Ulrich Demuth and Dr Konrad Glund. Probiodrug has raised EUR71 m for its QC program. For more information please visit http://www.probiodrug.de.

FORWARD LOOKING STATEMENTS - Information set forth in this press release contains forward-looking statements, which involve a number of risks and uncertainties. The forward-looking statements contained herein represent the judgement of Evotec as of the date of this report. Such forward-looking statements are neither promises nor guarantees, but are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any such statements to reflect any change in our expectations or any change in events, conditions or circumstances on which any such statement is based.

Contact Evotec AG: Dr Mario Polywka, Chief Operating Officer, Phone: +44.(0)1235.441676, [emailprotected]

End of Corporate News

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DGAP-News: Evotec enters biology collaboration with Probiodrug

Scientists at the Institute of Molecular Biology identify key event for sex determination

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Public release date: 27-Nov-2012 [ | E-mail | Share ]

Contact: Ralf Dahm press@imb-mainz.de 49-613-139-21455 Johannes Gutenberg Universitaet Mainz

Scientists at the Institute of Molecular Biology (IMB) in Mainz have identified a protein essential for initiating the development of male sex organs. Loss of the gene Gadd45g results in complete sex reversal of male mice, making them appear female. The researchers' finding uncovers a novel signaling cascade, which acts early in development to determine the gonads in males. This discovery sheds light on the genetic network that controls how embryos develop as males or females. The research has just been published in the high-impact journal Developmental Cell.

Research carried out in the laboratory of IMB Director Professor Christof Niehrs uncovered that the deletion of just one gene, Gadd45g, results in male mice with external genitalia that are indistinguishable from those of female mice. Furthermore, the internal reproductive organs of the mutant male mice look like those of females, indicating that a complete sex reversal has occurred. Says Christof Niehrs, "when breeding Gadd45g mutant mice we were puzzled why we got only females, until we discovered that some of these females actually carry a Y-chromosome."

The researchers further showed that Gadd45g exerts its effect by regulating signaling cascades that control the gene Sry, which had previously shown to be a master regulator of male sex development. This study both identifies a new role for Gadd45g and suggests a novel signaling pathway that could have important implications for research into disorders of sexual development.

For male sex organs to develop correctly, it is essential that the gene Sry is expressed at high levels within a very narrow timeframe in the embryo. The group of Christof Niehrs has now shown that Gadd45g is expressed in a pattern highly similar to that of Sry. The Gadd45g gene is, however, active just before Sry is turned on. Importantly, in mice lacking Gadd45g, the Sry gene is not expressed correctly. This indicates that Gadd45g controls the expression of this master regulator and, in turn, male development.

The scientists also provide a possible mechanism by which Gadd45g regulates Sry. Their model suggests that Gadd45g binds to and activates key signaling proteins, such as p38, which activate the transcription factor Gata4. When active, this factor binds to and activates the Sry gene. Similar results are co-published in the same issue of Developmental Cell by the group of Andy Greenfield in the UK. "As outsiders to the field of sex determination we were surprised by how little was known about the regulation of Sry on the molecular level. Our work is a leap forward in the understanding of this fundamental process", says Niehrs.

###

Original reference: Mathias S Gierl, Wolfram H Gruhn, Annika von Seggern, Nicole Maltry and Christof Niehrs (2012). Gadd45g functions in male sex determination by promoting p38 signaling and Sry expression. Developmental Cell 23(5):1032-42

INSTITUTE OF MOLECULAR BIOLOGY gGmbH (IMB)

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Scientists at the Institute of Molecular Biology identify key event for sex determination

Evotec Enters Biology Collaboration With Probiodrug

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HAMBURG, Germany, Nov. 28, 2012 (GLOBE NEWSWIRE) -- Evotec AG (EVT.F) (TecDAX) announced today that it has entered into a collaboration with Probiodrug AG, a privately owned biopharmaceutical company focused on the development of innovative drugs for the treatment of major age related diseases.

Under the terms of the agreement, Evotec will setup and validate assays to support the pre-clinical and clinical development of glutaminyl cyclase (QC) inhibitors for the treatment of Alzheimer's disease. Glutaminyl cyclase is a novel proprietary enzyme target discovered and validated by Probiodrug which plays a crucial role in the pathogenesis of Alzheimer's disease (AD) as well as potentially other diseases.

Dr Mario Polywka, Chief Operating Officer of Evotec commented: "We are pleased to enter this collaboration with Probiodrug to use our first class assay development capabilities to support the pre-clinical and clinical development of QC inhibitors in Alzheimer's disease and other indications. This is a good example of how Evotec can support Biotech companies with their specific drug discovery needs."

Hendrik Liebers, Chief Financial Officer of Probiodrug, added: "The collaboration will allow us to focus on the further pre-clinical and clinical development of our programmes in neurodegeneration/AD. Evotec, with its proven track record, is ideally suited to accompany this process by running existing and developing new biological assays."

ABOUT PROBIODRUG AG

Probiodrug is a biopharmaceutical company dedicated to the discovery and development of small molecule drugs against novel molecular targets for the treatment of neuronal and inflammatory diseases. The Company has a dominant position in the area of glutaminyl cyclase inhibition. Glutaminyl cyclase, a novel enzyme target discovered and patented by Probiodrug, has a crucial role in the pathogenesis of Alzheimer's disease (AD) as well as various peripheral inflammatory diseases.

Probiodrug is backed by institutions such as BB Biotech, Edmond de Rothschild Investment Partners, Goodvent/IBG, HBM, TVM, Life Sciences Partners, Biogen Idec Ventures, CFH Group, funds managed by Wellington Management, and private investors.

Probiodrug's core capabilities are based on its long-standing expertise in the elucidation of the structure and function of enzymes which play a central role in the maturation of hormones. The Company has pioneered the field of dipeptidyl peptidase 4 (DP4)-inhibition for the treatment of type 2 diabetes. Compounds and technology patents of its DP4 program in diabetes were licensed to various pharmaceutical companies. In 2004, all metabolic assets were sold to OSI Pharmaceuticals, Inc. The first drug based on Probiodrug's technologies reached the market in late 2006. Proceeds of the various transactions have been reinvested by the Company to fund the novel approach for the treatment of AD and inflammatory diseases.

The Company was founded in 1997 by Prof Dr Hans-Ulrich Demuth and Dr Konrad Glund. Probiodrug has raised EUR71 m for its QC program. For more information please visit http://www.probiodrug.de.

ABOUT EVOTEC AG

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Evotec Enters Biology Collaboration With Probiodrug

Why 80% of young christians deny Jesus, Part-1 – Video

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Why 80% of young christians deny Jesus, Part-1
http://www.missionarymandate.org Why 80% of young Christians deny Jesus and leave the faith when they go off to college. Transcript of the video by Ken Acha I knew that the secular university biochemistry, physics, evolutionary science professors who despise God and calls everyone who believes an idiot where part of the reason. My first response was to have our young people taught apologetics. Just show them how to defend the faith from a scientific point of view and show them how solid scientific evidence points to God #39;s existence. Evidence such as The fine-tuning of the universe (the laws and order of the universe) The existence of morality The first-cause argument --cosmological argument. The Ontological argument --prove God #39;s existence from logic alone. Have more smart people like Ravi Zacharias, William Lane Craig, and Lee Strobel who can debate these atheists and help teach our young people. Have more ministries like reasons to believe. My plan was to have a TV show on Christian television that makes apologetics a big part of the show. These things are important. But I think fully understanding why 80% of our young men are leaving the faith is important before we start rushing to solve the problem. Before you blow this away, consider that if this is true, it means that - all of my two biological sons will be lost - 80% percent of all our children in our orphanage will be lost - 80% of all your children will be lost That #39;s unless we do something about it. Something ...From:ourshapingdestinyViews:0 0ratingsTime:08:21More inFilm Animation

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Why 80% of young christians deny Jesus, Part-1 - Video

Joe Dispenza ” The Infinite Mind’ By Pablo Arellano – Video

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Joe Dispenza " The Infinite Mind #39; By Pablo Arellano
Joseph Dispenza DC Neuroscientist, Chiropractor, Lecturer and Author Helping You Break the Habit of Being Yourself Joe Dispenza, DC, studied biochemistry at Rutgers University in New Brunswick, NJ He also holds a BS degree with an emphasis in Neuroscience. Dr. Dispenza also received his Doctor of Chiropractic Degree at Life University in Atlanta, Georgia, graduating magna cum laude. Dr. Dispenza #39;s postgraduate training and continuing education has been in neurology; neuroscience; brain function and chemistry; cellular biology; memory formation; and aging and longevity. He is an invited member of Who #39;s Who in America, an honorary member of the National Board of Chiropractic Examiners, the recipient of a Clinical Proficiency Citation for clinical excellence in doctor-patient relationships from Life University, and a member of Pi Tau Delta -- the International Chiropractic Honor Society. Over the past decade, Dr. Dispenza has lectured in 24 different countries on six continents educating people about the role and function of the human brain. He has taught thousands of people how to re-program their thinking through scientifically proven neuro-physiologic principles. As a result, this information has taught many individuals to reach their specific goals and visions by eliminating self-destructive habits. His approach, taught in a very simple method, creates a bridge between true human potential and the latest scientific theories of neuroplasticity. He explains how thinking in ...From:Pablo ArellanoViews:17 1ratingsTime:02:27:15More inEntertainment

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Joe Dispenza " The Infinite Mind' By Pablo Arellano - Video

Kaplan USMLE[HD] – Biochemistry – Hormones and Signal Transduction (Chapter 9a) – Video

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Kaplan USMLE[HD] - Biochemistry - Hormones and Signal Transduction (Chapter 9a)
Latest Kaplan videos for preparation of USMLE Exam in HD. Click Subscribe to remain updated.From:KaplanVideos1Views:0 0ratingsTime:07:39More inPeople Blogs

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Kaplan USMLE[HD] - Biochemistry - Hormones and Signal Transduction (Chapter 9a) - Video

Park Slope Dentist : Dr. Sophia Milito – Video

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Park Slope Dentist : Dr. Sophia Milito
parkdentistry.net Park Slope Dentist Dr. Milito received her bachelor #39;s degree in biochemistry from Binghamton University in Binghamton, NY, and went on to earn her dental degree from NYU. She is a proud member of the American Dental Association and the Academy of General Dentistry. Outside of the office, Dr. Milito enjoys spending time with her husband and walking their french bulldog "Silly" around the neighborhood. Her hobbies include traveling, drawing, cycling, and cooking. Park Slope Dentist httpFrom:YourBrooklynDentistViews:0 0ratingsTime:01:39More inPeople Blogs

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Park Slope Dentist : Dr. Sophia Milito - Video