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1. Prevalence of underlying malignancies in complex cysts of the breast

Author: F Aarts, F J Vogelaar, P C G Simons, M Kool, and J C W L Gerets
Subjects: Adult, Cancer Research, Pediatrics, medicine.medical_specialty, medicine.medical_treatment, Malignancy, Breast Cyst, Neoplasms, Prevalence, medicine, Humans, Cyst, Breast, Disease burden, Aged, Netherlands, Retrospective Studies, Aged, 80 and over, business.industry, Cyst Fluid, Biopsy, Needle, Absolute risk reduction, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, Oncology, Radiological weapon, Number needed to treat, Female, business, Watchful waiting
Abstract: INTRODUCTION: The management of complex cysts of the breast is an ongoing topic of discussion. The aim of this study was to determine the prevalence of underlying malignancy in radiologically diagnosed complex cysts, and to assess whether watchful waiting could be the preferred method to safely manage complex cysts of the breast. SUBJECTS AND METHODS: A single-center retrospective study was performed between May 2003 and November 2019 in the VieCuri Medical Centre. Women with a radiologically diagnosed complex cyst of the breast were included. Prevalence of underlying malignancy was calculated, as were absolute risk reduction and number needed to treat in order to diagnose malignancy. In addition, patient characteristics were compared to determine characteristics associated with malignancy. RESULTS: Of 78 radiologically diagnosed complex cysts of the breast, five (6,4%) were found to be malignant. The number needed to treat was calculated at 12,8 (absolute riks reduction 0,078). Age (P = 0,003) was associated with malignancy. CONCLUSION: Complex cysts of the breast could be managed more conservatively. Patient characteristics can be used to assess the eligibility for radiological follow-up. This, in turn, would lead to a lower NNT and possibly a decrease in disease burden and healthcare costs.
Published: 2021
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2. Inhibition of retinoic acid signaling induces aberrant pericyte coverage and differentiation resulting in vascular defects in congenital diaphragmatic hernia

Author: Ihsan Chrifi, Robbert J. Rottier, Inge de Laat, Heleen M. Kool, Anne Boerema-de Munck, Ismé de Kleer, Caroline Cheng, Dick Tibboel, Gert-Jan Kremers, Petra E. Bürgisser, Gabriela G Edel, Wiggert A. van Cappellen, Pediatric Surgery, Pulmonary Medicine, Cardiology, Pathology, and Cell biology
Subjects: Pulmonary and Respiratory Medicine, Pathology, medicine.medical_specialty, Physiology, Angiogenesis, Hypertension, Pulmonary, Retinoic acid, Tretinoin, Mice, chemistry.chemical_compound, Pericyte-Coverage, Physiology (medical), Animals, Humans, Medicine, Lung, business.industry, Persistent pulmonary hypertension, Endothelial Cells, Congenital diaphragmatic hernia, Cell Differentiation, Cell Biology, medicine.disease, Pulmonary hypertension, Disease Models, Animal, chemistry, Hernias, Diaphragmatic, Congenital, Pericytes, business, Signal Transduction
Abstract: The mortality and morbidity of patients with congenital diaphragmatic hernia (CDH) is primarily caused by treatment-resistant, persistent pulmonary hypertension. Structural vascular changes, exemplified by extensive muscularization, are already present early in gestation, but the origin of these abnormalities is unknown. Understanding the origin of the vascular defects is important to improve treatment modalities. Here, we show that the distribution of pericytes is different and may thereby potentially initiate the vascular pathology in CDH. Transient inhibition of retinoic acid (RA) signaling early during pregnancy, the basis of the CDH mouse model, led to an increase in the number of pericytes, thereby affecting the angiogenic potential of pericytes in the fetuses. Pericytes of CDH lungs showed reduced proliferation and an increased ACTA2 expression, which indicates that these pericytes are more contractile than in control lung pericytes. This resulted in increased pericyte coverage of pulmonary vessels and reduced expansion of the capillary bed, the earliest pathological sign of the structural changes in CDH. Furthermore, the pericytes had reduced and altered collagen IV deposition in CDH, pointing to a loss of basal membrane integrity between pericytes and endothelial cells. Inhibition of RA signaling in vitro resulted in reduced migration of pericytes, reduced angiogenesis, and loss of collagen IV expression. Importantly, we confirmed our findings in lungs of human CDH patient samples. In summary, inhibition of RA signaling affects the lung pericyte population, leading to increased contractility, reduced pulmonary angiogenesis, and aberrant lung development, as observed in CDH.
Published: 2019
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3. Informatiebeveiliging en de rol van de overheid

Author: K. J. M. Kool
Subjects: Business, HF5001-6182, Business mathematics. Commercial arithmetic. Including tables, etc., HF5691-5716
Published: 1996
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4. Treatment of rat congenital diaphragmatic hernia with sildenafil and NS-304, selexipag’s active compound, at the pseudoglandular stage improves lung vasculature

Author: Oleh Dzyubachyk, Robbert J. Rottier, Petra E. Bürgisser, Rene M. H. Wijnen, Marjon Buscop-van Kempen, Joost van Rosmalen, Heleen M. Kool, Koji Nagata, Daphne S. Mous, Anne Boerema-de Munck, Dick Tibboel, Pediatric Surgery, Epidemiology, and Cell biology
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Physiology, Sildenafil, Vasodilation, Selexipag, Sildenafil Citrate, lung, Rats, Sprague-Dawley, angiogenesis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Right ventricular hypertrophy, 030225 pediatrics, Physiology (medical), Internal medicine, Acetamides, pulmonary hypertension, medicine, Animals, Humans, development, Lung, business.industry, Congenital diaphragmatic hernia, Cell Biology, medicine.disease, Nitrofen, Pulmonary hypertension, Rats, 030104 developmental biology, medicine.anatomical_structure, chemistry, Pyrazines, Cardiology, Drug Therapy, Combination, Hernias, Diaphragmatic, Congenital, business
Abstract: Patients with congenital diaphragmatic hernia (CDH) often suffer from severe pulmonary hypertension, and the choice of current vasodilator therapy is mostly based on trial and error. Because pulmonary vascular abnormalities are already present early during development, we performed a study to modulate these pulmonary vascular changes at an early stage during gestation. Pregnant Sprague-Dawley rats were treated with nitrofen at day 9.5 of gestation (E9.5) to induce CDH in the offspring, and subsequently, the phosphodiesterase-5 inhibitor sildenafil and/or the novel prostaglandin-I receptor agonist selexipag (active compound NS-304) were administered from E17.5 until E20.5. The clinical relevant start of the treatment corresponds to week 20 of gestation in humans, when CDH is usually detected by ultrasound. CDH pups showed increased density of air saccules that was reverted after the use of only sildenafil. The pulmonary vascular wall was thickened, and right ventricular hypertrophy was present in the CDH group and improved both after single treatment with sildenafil or selexipag, whereas the combination therapy with both compounds did not have additive value. In conclusion, antenatal treatment with sildenafil improved airway morphogenesis and pulmonary vascular development, whereas selexipag only acted positively on pulmonary vascular development. The combination of both compounds did not act synergistically, probably because of a decreased efficiency of both compounds caused by cytochrome- P450 3A4 interaction and induction. These new insights create important possibilities for future treatment of pulmonary vascular abnormalities in CDH patients already in the antenatal period of life.
Published: 2018
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5. De Ziekte van Bechterew (Spondyloartritis)

Author: M. Kool and D. van Zeben
Subjects: Gynecology, medicine.medical_specialty, business.industry, Applied Mathematics, General Mathematics, Medicine, business
Abstract: Spondyloartritis (SpA) is een verzamelnaam voor reumatische aandoeningen waarbij ontstekingen aanwezig zijn in het bekken en de wervelkolom. Tegenwoordig wordt er een onderscheid gemaakt tussen axiale SpA en perifere SpA. Bij axiale SpA overheersen symptomen van het axiale skelet, de wervelkolom en het bekken (sacroiliitis, spondylitis). Ankyloserende spondylitis (de ziekte van Bechterew) is de bekendste vorm van axiale spondyloartritis.
Published: 2017
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6. ETMR-14. TREATMENT OF EMBRYONAL TUMOURS WITH MULTILAYERED ROSETTES (ETMR) WITH CARBOPLATIN-ETOPOSIDE INDUCTION AND TANDEM HIGH-DOSE CHEMOTHERAPY WITHIN THE PROSPECTIVE HIT-TRIALS AND REGISTRIES

Author: Nicolas U. Gerber, Monika Warmuth-Metz, Björn-Ole Juhnke, M Kool, Stefan Rutkowski, Ulrich Schüller, Christine Haberler, Brigitte Bison, Stefan M. Pfister, Torsten Pietsch, Katja von Hoff, Carsten Friedrich, Rolf-Dieter Kortmann, Martin Mynarek, and Marco Gessi
Subjects: Oncology, Cancer Research, medicine.medical_specialty, business.industry, medicine.medical_treatment, Chemotherapy regimen, Carboplatin, Radiation therapy, chemistry.chemical_compound, High dose chemotherapy, Innovative Therapies, chemistry, Internal medicine, medicine, AcademicSubjects/MED00300, AcademicSubjects/MED00310, ETMR and other Embryonal Tumors, Neurology (clinical), Progression-free survival, business, Carboplatin/etoposide, Etoposide, medicine.drug
Abstract: BACKGROUND Embryonal tumours with multilayered rosettes (ETMR) are highly aggressive tumors, mostly occurring in infants. Published clinical data refer to retrospective cohorts of inhomogeneously treated patients. Here, we describe the outcome of patients, who were prospectively treated within the P-HIT2000-trial, the subsequent HIT2000-interim-registry and earlier HIT-trials. PATIENTS AND METHODS Nineteen patients from the P-HIT2000-trial (2001–2011), 12 patients from the subsequent HIT2000-interim-registry (2012–2014) and 4 patients from earlier HIT-trials with centrally reviewed neuropathological and molecularly-confirmed diagnosis of ETMR were included. Outcome of 18 patients treated with carboplatin-etoposide-induction followed by tandem-high-dose chemotherapy (“CARBO-ETO+HDCT”) with stage-stratified radiotherapy administered in case of persistant disease, relapse or progression were compared to patients treated with HIT-SKK chemotherapy ± radiotherapy (n=9) or other regimens (n=8). RESULTS Median age at diagnosis was 2.9(1.0–5.3) years. Metastases at diagnosis were detected in 9 patients (26%). For the entire cohort of n=35, 5-year overall survival (OS) was 26.7%, and progression-free survival (PFS) was 18.5%. Five-year OS for patients with CARBO-ETO+HDCT, SKK chemotherapy or other regimens was 44.4%, 13.0% and 0%, respectively (p=0.006). Five-year PFS was 33.3%, 0% and 0%, respectively (p=0.119). Of 10 survivors, n=8 were treated with CARBO-ETO+HDCT; n=4 had craniospinal, n=2 local and n=4 no radiotherapy. Impact of initial gross-total-resection (p=0.231) and non-metastatic disease (p=0.097) was limited. CONCLUSIONS We show improved survival with carboplatin-etoposide-induction followed by tandem-high-dose chemotherapy, indicating that a cure is possible for some patients. However, despite intensive treatment, outcome is unsatisfactory and innovative therapies urgently need to be included in an upfront setting.
Published: 2020
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7. Fair allocation of cryopreserved donor oocytes: towards an accountable process

Author: Annelies M E Bos, Bart C.J.M. Fauser, E M Kool, Annelien L. Bredenoord, and R van der Graaf
Subjects: Prioritization, Process (engineering), media_common.quotation_subject, Resource Allocation, Part iii, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Humans, 030212 general & internal medicine, Function (engineering), Child, media_common, Social Responsibility, 030219 obstetrics & reproductive medicine, Actuarial science, Oocyte Donation, Rehabilitation, Obstetrics and Gynecology, Tissue Donors, Variety (cybernetics), Reproductive Medicine, Oocyte donation, Accountability, Oocytes, Female, Business, Ethical analysis
Abstract: A growing number of people desire ART with cryopreserved donor oocytes. The allocation of these oocytes to couples and mothers to be is a 2-fold process. The first step is to select a pool of recipients. The second step is to decide who should be treated first. Prioritizing recipients is critical in settings where demand outstrips supply. So far, the issue of how to fairly allocate cryopreserved donor oocytes has been poorly addressed. Our ethical analysis aims to support clinics involved in allocation decisions by formulating criteria for recipient selection irrespective of supply (Part I) and recipient prioritization in case supply is limited (Part II). Relevant criteria for recipient selection are: a need for treatment to experience parenthood; a reasonable chance for successful treatment; the ability to safely undergo an oocyte donation pregnancy; and the ability to establish a stable and loving relationship with the child. Recipients eligible for priority include those who: have limited time left for treatment; have not yet experienced parenthood; did not undergo previous treatment with cryopreserved donor oocytes; and contributed to the supply of donor oocytes by bringing a donor to the bank. While selection criteria function as a threshold principle, we argue that the different prioritization criteria should be carefully balanced. Since specifying and balancing the allocation criteria undoubtedly raises a moral dispute, a fair and legitimate allocation process is warranted (Part III). We argue that allocation decisions should be made by a multidisciplinary committee, staffed by relevant experts with a variety of perspectives. Furthermore, the committees’ reasoning behind decisions should be transparent and accessible to those affected: clinicians, donors, recipients and children born from treatment. Insight into the reasons that underpin allocation decisions allows these stakeholders to understand, review and challenge decisions, which is also known as accountability for reasonableness.
Published: 2019

8. EMBR-01. MOLECULAR AND CLINICAL HETEROGENEITY IN HISTOLOGICALLY-DIAGNOSED CNS-PNET PATIENTS PROSPECTIVELY TREATED AS A SINGLE ENTITY: A REPORT FROM THE CHILDREN’S ONCOLOGY GROUP ACNS0332 TRIAL

Author: David TWJones, Peter C. Burger, Andreas vonDiemling, Stefan M. Pfister, Catherine A. Billups, Linda Heier, Jeff M. Michalski, Chris Williams-Hughes, Lukas Chavez, Ian Pollack, Sebastian Brabetz, Yimei Li, Roger J. Packer, Maryam Fouladi, Tianni Zhou, Amar Gajjar, James M. Olson, Eugene Hwang, David Capper, Sarah Leary, M Kool, and Alok Jaju
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Cns pnet, business.industry, Craniospinal Irradiation, Abstracts, Text mining, Pharmaceutical Adjuvants, Single entity, Internal medicine, Clinical heterogeneity, Medicine, Neurology (clinical), business, Isotretinoin, medicine.drug
Abstract: INTRODUCTION: Children with high-risk medulloblastoma, supratentorial primitive neuroectodermal tumor (CNS-PNET) and pineoblastoma (PBLs) have poor survival and were enrolled in this prospective trial. However, subsequent molecular profiling uncovered diagnostic discrepancies not detectable at protocol inception. Outcomes for patients with CNS-PNET/PBL are reported here. METHODS: In this phase 3 trial, children aged 3–22 years with newly-diagnosed CNS-PNET/PBL were randomly assigned to receive carboplatin during radiation and/or adjuvant isotretinoin after standard intensive therapy. DNA methylation profiling was retrospectively completed in patients with sufficient tissue. RESULTS: Out of eighty-five participants with institutionally-diagnosed CNS-PNETs/PBLs, 60 patients underwent molecular analysis. 31/60 were non-pineal in location, of which 22 (71%) represented tumors not intended for trial inclusion, including 18 high-grade gliomas (HGG), two atypical teratoid rhabdoid tumors, and two ependymomas. Retrospective central review was more consistent with molecular diagnosis, but maintained the discrepancy in some cases. Outcomes across tumor types were strikingly different. Patients with supratentorial embryonal tumors/PBLs exhibited 5-year event-free (EFS) and overall survival (OS) of 62.8% (95%CI,43.4%-82.2%) and 78.5% (95%CI,62.2–94.8%), respectively, while patients with molecularly-classified HGG had EFS/OS of 5.6% (95%CI,0%-13.0%) and 12.0% (95%CI,0%-24.7%), respectively. Neither carboplatin nor isotretinoin significantly altered outcomes. Survival for patients with HGG was similar to historic studies without craniospinal irradiation or intensive chemotherapy. CONCLUSIONS: For patients with CNS-PNETs/PBLs, prognosis is considerably better than previously assumed when molecularly-confirmed HGG are removed. Identification of HGG may spare children from unhelpful intensive treatment. This trial highlights the challenges of histology-based diagnosis and indicates that molecular profiling should become a standard component of initial diagnosis.
Published: 2018

9. Pulmonary vascular development in congenital diaphragmatic hernia

Author: Rene M. H. Wijnen, Dick Tibboel, Heleen M. Kool, Daphne S. Mous, Robbert J. Rottier, and Pediatric Surgery
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Pulmonary Circulation, medicine.medical_specialty, Hypertension, Pulmonary, Neovascularization, Physiologic, Diaphragmatic breathing, Hemodynamics, Diaphragmatic defect, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, 030225 pediatrics, Internal medicine, Animals, Humans, Medicine, Lung hypoplasia, Lung, lcsh:RC705-779, business.industry, Congenital diaphragmatic hernia, lcsh:Diseases of the respiratory system, Prognosis, medicine.disease, Capillaries, Arterioles, 030104 developmental biology, Cardiology, Respiratory epithelium, Gestation, Abnormality, Hernias, Diaphragmatic, Congenital, business, Signal Transduction
Abstract: Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly characterised by a diaphragmatic defect, persistent pulmonary hypertension (PH) and lung hypoplasia. The relative contribution of these three elements can vary considerably in individual patients. Most affected children suffer primarily from the associated PH, for which the therapeutic modalities are limited and frequently not evidence based. The vascular defects associated with PH, which is characterised by increased muscularisation of arterioles and capillaries, start to develop early in gestation. Pulmonary vascular development is integrated with the development of the airway epithelium. Although our knowledge is still incomplete, the processes involved in the growth and expansion of the vasculature are beginning to be unravelled. It is clear that early disturbances of this process lead to major pulmonary growth abnormalities, resulting in serious clinical challenges and in many cases death in the newborn. Here we provide an overview of the current molecular pathways involved in pulmonary vascular development. Moreover, we describe the abnormalities associated with CDH and the potential therapeutic approaches for this severe abnormality.
Published: 2018

10. Ethics of oocyte banking for third-party assisted reproduction: a systematic review

Author: A L Bredenoord, E M Kool, Bart C.J.M. Fauser, Annelies M. E. Bos, and R. Van Der Graaf
Subjects: medicine.medical_specialty, media_common.quotation_subject, education, Medical tourism, Reproductive medicine, recipient selection, Disclosure, 0603 philosophy, ethics and religion, Research Support, Scarcity, 03 medical and health sciences, 0302 clinical medicine, systematic review, Biological Specimen Banks/ethics, Medical Tourism, Informed consent, Obstetrics and Gynaecology, medicine, Journal Article, Humans, Confidentiality, Non-U.S. Gov't, media_common, Biological Specimen Banks, Cryopreservation, 030219 obstetrics & reproductive medicine, Informed Consent, Oocyte Donation, business.industry, Corporate governance, Research Support, Non-U.S. Gov't, Obstetrics and Gynecology, 06 humanities and the arts, Public relations, donor recruitment, ethics, Variety (cybernetics), Reproductive Medicine, Donation, Oocytes, third-party ART, Oocyte Donation/ethics, Female, 060301 applied ethics, oocyte banking, business
Abstract: Background The demand for donor oocytes has increased dramatically over the years. Today people in need of ART with the use of donor oocytes can appeal to commercial or public donor oocyte banks. The introduction of oocyte banks has shed a new light on the practice of ART using donor oocytes. The establishment and maintenance of oocyte banks should be sensitive to the ethical considerations. However, it is currently unclear which ethical aspects have to be taken into account. Objective and rationale The aim of this article is to identify the ethical aspects of establishing and maintaining oocyte banks for third-party ART. Search methods A systematic search was performed in July 2016 and February 2017 in both PubMed and Embase using a search string that combined synonyms for oocytes, donation or banking, reproductive care and ethics. We included a wide variety of English-language articles with a reasoned description of ethical aspects or moral considerations on oocyte donation or banking for third-party ART. Outcomes The practice of oocyte banking consists of three components, namely, the intake, storage and distribution of donor oocytes, and each is associated with multiple ethical challenges. The majority of the literature discusses ethical aspects with regard to the intake of donor oocytes, taking into account both the interests of the donor and those of the potential child. Ethical aspects related to the donor are the risks and psychosocial impact of donation, motivations and compensation in donor recruitment, and requirements for informed consent. Ethical aspects related to the potential child are 2-fold: first, the welfare standard and the selection of donors, and second, anonymity and disclosure. Ethical aspects of storing donor oocytes for ART are quality standards, confidentiality, issues of ownership and control, and international transport of donor oocytes. Ethical aspects of the distribution of donor oocytes concern the selection of recipients and the acceptability of treatment of 'non-traditional' families in particular, prioritization of recipients in case of scarcity, cross-border reproductive care, matching of recipients and donor oocytes, informed consent and counselling for recipients. Wider implications Our review demonstrates that multiple ethical aspects have to be taken into account when establishing and maintaining an oocyte bank. Yet, for many of these aspects there is no consensus regarding what approach should be employed. Remarkably, the existing literature focuses mainly on ethical aspects related to the intake of donor oocytes, while aspects related to storage and distribution of donor oocytes are less often addressed. An important gap in the existing literature should therefore be acknowledged. To conclude, our findings can serve as a starting point for clinicians in the field of ART, to conceptualize what challenges arise when establishing and maintaining oocyte banks for third-party ART. The review may also stimulate policy makers to set up a trustworthy and adaptive governance structure for the intake, storage and distribution of donor oocytes.
Published: 2017

11. Pulmonary vascular development goes awry in congenital lung abnormalities

Author: Annelies de Klein, Dick Tibboel, Robbert J. Rottier, Daphne S. Mous, and Heleen M. Kool
Subjects: Alveolar capillary dysplasia, Embryology, Pathology, medicine.medical_specialty, Lung, business.industry, Vascular disease, Congenital diaphragmatic hernia, General Medicine, medicine.disease, medicine.anatomical_structure, Bronchopulmonary dysplasia, Normal lung, Intensive care, Medicine, business, Pathological, Developmental Biology
Abstract: Pulmonary vascular diseases of the newborn comprise a wide range of pathological conditions with developmental abnormalities in the pulmonary vasculature. Clinically, pulmonary arterial hypertension (PH) is characterized by persistent increased resistance of the vasculature and abnormal vascular response. The classification of PH is primarily based on clinical parameters instead of morphology and distinguishes five groups of PH. Congenital lung anomalies, such as alveolar capillary dysplasia (ACD) and PH associated with congenital diaphragmatic hernia (CDH), but also bronchopulmonary dysplasia (BPD), are classified in group three. Clearly, tight and correct regulation of pulmonary vascular development is crucial for normal lung development. Human and animal model systems have increased our knowledge and make it possible to identify and characterize affected pathways and study pivotal genes. Understanding of the normal development of the pulmonary vasculature will give new insights in the origin of the spectrum of rare diseases, such as CDH, ACD, and BPD, which render a significant clinical problem in neonatal intensive care units around the world. In this review, we describe normal pulmonary vascular development, and focus on four diseases of the newborn in which abnormal pulmonary vascular development play a critical role in morbidity and mortality. In the future perspective, we indicate the lines of research that seem to be very promising for elucidating the molecular pathways involved in the origin of congenital pulmonary vascular disease.
Published: 2014
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12. MEDULLOBLASTOMA

Author: G. Vaidyanathan, S. Gururangan, D. Bigner, M. Zalutsky, M. Morfouace, A. Shelat, J. Megan, B. B. Freeman, S. Robinson, S. Throm, J. M. Olson, X.-N. Li, K. R. Guy, G. Robinson, C. Stewart, A. Gajjar, M. Roussel, N. Sirachainan, S. Pakakasama, U. Anurathapan, A. Hansasuta, M. Dhanachai, C. Khongkhatithum, S. Hongeng, A. Feroze, K.-S. Lee, S. Gholamin, Z. Wu, B. Lu, S. Mitra, S. Cheshier, P. Northcott, C. Lee, T. Zichner, P. Lichter, J. Korbel, R. Wechsler-Reya, S. Pfister, I. P. T. Project, K. K.-W. Li, T. Xia, F. M. T. Ma, R. Zhang, L. Zhou, K.-M. Lau, H.-K. Ng, L. Lafay-Cousin, S. Chi, J. Madden, A. Smith, E. Wells, E. Owens, D. Strother, N. Foreman, R. Packer, E. Bouffet, T. Wataya, J. Peacock, M. D. Taylor, D. Ivanov, M. Garnett, T. Parker, C. Alexander, L. Meijer, R. Grundy, P. Gellert, M. Ashford, D. Walker, J. Brent, F. Z. Cader, D. Ford, A. Kay, R. Walsh, G. Solanki, A. Peet, M. English, T. Shalaby, G. Fiaschetti, S. Baulande, N. Gerber, M. Baumgartner, M. Grotzer, T. Hayase, Y. Kawahara, M. Yagi, T. Minami, N. Kanai, T. Yamaguchi, A. Gomi, A. Morimoto, R. Hill, S. Kuijper, J. Lindsey, E. Schwalbe, K. Barker, J. Boult, D. Williamson, Z. Ahmad, A. Hallsworth, S. Ryan, E. Poon, R. Ruddle, F. Raynaud, L. Howell, C. Kwok, A. Joshi, S. L. Nicholson, S. Crosier, S. Wharton, K. Robson, A. Michalski, D. Hargrave, T. Jacques, B. Pizer, S. Bailey, F. Swartling, K. Petrie, W. Weiss, L. Chesler, S. Clifford, L. Kitanovski, T. Prelog, B. F. Kotnik, M. Debeljak, M. A. Grotzer, A. Gevorgian, E. Morozova, I. Kazantsev, T. Iukhta, S. Safonova, E. Kumirova, Y. Punanov, B. Afanasyev, O. Zheludkova, W. Grajkowska, M. Pronicki, B. Cukrowska, B. Dembowska-Baginska, M. Lastowska, A. Murase, S. Nobusawa, Y. Gemma, F. Yamazaki, A. Masuzawa, T. Uno, T. Osumi, Y. Shioda, C. Kiyotani, T. Mori, K. Matsumoto, H. Ogiwara, N. Morota, J. Hirato, A. Nakazawa, K. Terashima, T. Fay-McClymont, K. Walsh, D. Mabbott, D. Sturm, P. A. Northcott, D. T. W. Jones, A. Korshunov, S. M. Pfister, M. Kool, C. Hooper, S. Hawes, U. Kees, N. Gottardo, P. Dallas, A. Siegfried, A. I. Bertozzi, A. Sevely, N. Loukh, C. Munzer, C. Miquel, F. Bourdeaut, T. Pietsch, C. Dufour, M. B. Delisle, D. Kawauchi, J. Rehg, D. Finkelstein, F. Zindy, T. Phoenix, R. Gilbertson, J. Trubicka, M. Borucka-Mankiewicz, E. Ciara, K. Chrzanowska, M. Perek-Polnik, D. Abramczuk-Piekutowska, D. Jurkiewicz, S. Luczak, P. Kowalski, M. Krajewska-Walasek, C. Sheila, S. Lee, C. Foster, B. Manoranjan, M. Pambit, R. Berns, A. Fotovati, C. Venugopal, K. O'Halloran, A. Narendran, C. Hawkins, V. Ramaswamy, M. Taylor, A. Singhal, J. Hukin, R. Rassekh, S. Yip, S. Singh, C. Duhman, S. Dunn, T. Chen, S. Rush, H. Fuji, Y. Ishida, T. Onoe, T. Kanda, Y. Kase, H. Yamashita, S. Murayama, Y. Nakasu, T. Kurimoto, A. Kondo, S. Sakaguchi, J. Fujimura, M. Saito, T. Arakawa, H. Arai, T. Shimizu, E. Jurkiewicz, P. Daszkiewicz, M. Drogosiewicz, V. Hovestadt, I. Buchhalter, N. N. Jager, A. Stuetz, P. Johann, C. Schmidt, M. Ryzhova, P. Landgraf, M. Hasselblatt, U. Schuller, M.-L. Yaspo, A. von Deimling, R. Eils, A. Modi, M. Patel, M. Berk, L.-x. Wang, G. Plautz, H. Camara-Costa, A. Resch, C. Lalande, V. Kieffer, G. Poggi, C. Kennedy, K. Bull, G. Calaminus, J. Grill, F. Doz, S. Rutkowski, M. Massimino, R.-D. Kortmann, B. Lannering, G. Dellatolas, M. Chevignard, D. Solecki, P. McKinnon, J. Olson, J. Hayden, D. Ellison, M. Buss, M. Remke, J. Lee, T. Caspary, R. Castellino, M. Sabel, G. Gustafsson, G. Fleischhack, M. Benesch, A. Navajas, R. Reddingius, M.-B. Delisle, D. Lafon, N. Sevenet, G. Pierron, O. Delattre, J. Ecker, I. Oehme, R. Mazitschek, M. Lodrini, H. E. Deubzer, A. E. Kulozik, O. Witt, T. Milde, D. Patmore, N. Boulos, K. Wright, S. Boop, T. Janicki, S. Burzynski, G. Burzynski, A. Marszalek, J. Triscott, M. Green, S. R. Rassekh, B. Toyota, C. Dunham, S. E. Dunn, K.-W. Liu, Y. Pei, L. Genovesi, P. Ji, M. Davis, C. G. Ng, Y.-J. Cho, N. Jenkins, N. Copeland, B. Wainwright, Y. Tang, S. Schubert, B. Nguyen, S. Masoud, A. Lee, M. Willardson, P. Bandopadhayay, G. Bergthold, S. Atwood, R. Whitson, J. Qi, R. Beroukhim, J. Tang, A. Oro, B. Link, J. Bradner, S. G. Vallero, D. Bertin, M. E. Basso, C. Milanaccio, P. Peretta, A. Cama, A. Mussano, S. Barra, G. Morana, I. Morra, P. Nozza, F. Fagioli, M. L. Garre, A. Darabi, E. Sanden, E. Visse, N. Stahl, P. Siesjo, D. Vaka, F. Vasquez, B. Weir, G. Cowley, C. Keller, W. Hahn, I. C. Gibbs, S. Partap, K. Yeom, M. Martinez, H. Vogel, S. S. Donaldson, P. Fisher, S. Perreault, L. Guerrini-Rousseau, S. Pujet, V. Kieffer-Renaux, M. A. Raquin, P. Varlet, A. Longaud, C. Sainte-Rose, D. Valteau-Couanet, J. Staal, L. S. Lau, H. Zhang, W. J. Ingram, Y. J. Cho, Y. Hathout, K. Brown, B. R. Rood, M. Handler, T. Hankinson, B. K. Kleinschmidt-Demasters, S. Hutter, D. T. Jones, N. Kagawa, R. Hirayama, N. Kijima, Y. Chiba, M. Kinoshita, K. Takano, D. Eino, S. Fukuya, F. Yamamoto, K. Nakanishi, N. Hashimoto, Y. Hashii, J. Hara, T. Yoshimine, J. Wang, C. Guo, Q. Yang, Z. Chen, I. Filipek, E. Swieszkowska, M. Tarasinska, D. Perek, R. Kebudi, B. Koc, O. Gorgun, F. Y. Agaoglu, J. Wolff, E. Darendeliler, K. Kerl, J. Gronych, J. McGlade, R. Endersby, H. Hii, T. Johns, J. Sastry, D. Murphy, M. Ronghe, C. Cunningham, F. Cowie, R. Jones, A. Calisto, M. Sangra, C. Mathieson, J. Brown, K. Phuakpet, V. Larouche, U. Bartels, T. Ishida, D. Hasegawa, K. Miyata, S. Ochi, A. Saito, A. Kozaki, T. Yanai, K. Kawasaki, K. Yamamoto, A. Kawamura, T. Nagashima, Y. Akasaka, T. Soejima, M. Yoshida, Y. Kosaka, A. von Bueren, T. Goschzik, R. Kortmann, K. von Hoff, C. Friedrich, A. z. Muehlen, M. Warmuth-Metz, N. Soerensen, F. Deinlein, I. Zwiener, A. Faldum, J. Kuehl, K. KRAMER, N. P. -Taskar, P. Zanzonico, J. L. Humm, S. L. Wolden, N.-K. V. Cheung, S. Venkataraman, I. Alimova, P. Harris, D. Birks, I. Balakrishnan, A. Griesinger, N. K. Foreman, R. Vibhakar, A. Margol, N. Robison, J. Gnanachandran, L. Hung, R. Kennedy, M. Vali, G. Dhall, J. Finlay, A. Erdrich-Epstein, M. Krieger, R. Drissi, M. Fouladi, F. Gilles, A. Judkins, R. Sposto, S. Asgharzadeh, A. Peyrl, M. Chocholous, S. Holm, P. Grillner, K. Blomgren, A. Azizi, T. Czech, B. Gustafsson, K. Dieckmann, U. Leiss, I. Slavc, S. Babelyan, I. Dolgopolov, R. Pimenov, G. Mentkevich, S. Gorelishev, M. Laskov, A. O. von Bueren, J. Nowak, R. D. Kortmann, M. Mynarek, K. Muller, N. U. Gerber, H. Ottensmeier, R. Kwiecien, M. Yankelevich, V. Boyarshinov, I. Glekov, S. Ozerov, S. Gorelyshev, A. Popa, N. Subbotina, A. M. Martin, C. Nirschl, M. Polanczyk, R. Bell, D. Martinez, L. M. Sullivan, M. Santi, P. C. Burger, J. M. Taube, C. G. Drake, D. M. Pardoll, M. Lim, L. Li, W.-G. Wang, J.-X. Pu, H.-D. Sun, R. Ruggieri, M. H. Symons, M. I. Vanan, S. Bolin, S. Schumacher, R. Zeid, F. Yu, N. Vue, W. Gibson, B. Paolella, F. J. Swartling, M. W. Kieran, J. E. Bradner, O. Maher, S. Khatua, N. Tarek, W. Zaky, T. Gupta, S. Mohanty, S. Kannan, R. Jalali, E. Kapitza, D. Denkhaus, A. z. Muhlen, D. G. van Vuurden, M. Garami, J. Fangusaro, T. B. Davidson, M. J. G. da Costa, J. Sterba, S. C. Clifford, J. L. Finlay, R. Schmidt, J. Felsberg, H. Skladny, F. Cremer, G. Reifenberger, R. Kunder, E. Sridhar, A. A. Moiyadi, A. Goel, N. Goel, N. Shirsat, R. Othman, L. Storer, I. Kerr, B. Coyle, N. Law, M. L. Smith, M. Greenberg, S. Laughlin, D. Malkin, F. Liu, I. Moxon-Emre, N. Scantlebury, A. Nasir, D. Onion, A. Lourdusamy, A. Grabowska, Y. Cai, T. Bradshaw, R. S. S. de Medeiros, A. Beaugrand, S. Soares, S. Epelman, W. Wang, M. Sultan, R. J. Wechsler-Reya, M. Zapatka, B. Radlwimmer, D. Alderete, L. Baroni, F. Lubinieki, F. Auad, M. L. Gonzalez, W. Puya, P. Pacheco, O. Aurtenetxe, A. Gaffar, L. Gros, O. Cruz, C. Calvo, N. Shinojima, H. Nakamura, J.-i. Kuratsu, A. Hanaford, C. Eberhart, T. Archer, P. Tamayo, S. Pomeroy, E. Raabe, K. De Braganca, S. Gilheeney, Y. Khakoo, K. Kramer, S. Wolden, I. Dunkel, R. R. Lulla, J. Laskowski, S. Goldman, V. Gopalakrishnan, D. Shih, X. Wang, C. Faria, C. Raybaud, U. Tabori, J. Rutka, S. Jacobs, F. De Vathaire, I. Diallo, D. Llanas, C. Verez, F. Diop, A. Kahlouche, S. Puget, E. Thompson, E. Prince, V. Amani, P. Sin-Chan, M. Lu, C. Kleinman, T. Spence, D. Picard, K. C. Ho, J. Chan, J. Majewski, N. Jabado, P. Dirks, A. Huang, J. R. Madden, A. M. Donson, D. M. Mirsky, A. Dubuc, S. Mack, D. Gendoo, B. Luu, T. MacDonald, T. Van Meter, S. Croul, A. Laureano, W. Brugmann, C. Denman, H. Singh, H. Huls, J. Moyes, D. Sandberg, L. Silla, L. Cooper, and D. Lee
Subjects: Oncology, Abstracts, Cancer Research, medicine.medical_specialty, Cns pnet, business.industry, Internal medicine, Meta-analysis, medicine, Neurology (clinical), business
Published: 2014
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13. EPENDYMOMA

Author: L. M. Hoffman, A. M. Donson, I. Nakachi, A. M. Griesinger, D. K. Birks, V. Amani, M. S. Hemenway, A. K. Liu, M. Wang, T. C. Hankinson, M. H. Handler, N. K. Foreman, M. Zakrzewska, K. Zakrzewski, W. Fendler, L. Stefanczyk, P. P. Liberski, M. Massimino, L. Gandola, P. Ferroli, L. Valentini, V. Biassoni, M. L. Garre, I. Sardi, L. Genitori, C. Giussani, L. Massimi, D. Bertin, A. Mussano, E. Viscardi, P. Modena, A. Mastronuzzi, S. Barra, G. Scarzello, G. Cinalli, P. Peretta, F. Giangaspero, L. Boschetti, E. Schiavello, G. Calareso, M. Antonelli, E. Pecori, F. Di Meco, R. Migliorati, A. Taborelli, H. Witt, M. Sill, K. Wani, S. C. Mack, D. Capper, K. Pajtler, S. Lambert, T. Tzaridis, T. Milde, P. A. Northcott, A. E. Kulozik, O. Witt, V. P. Collins, D. W. Ellison, M. D. Taylor, M. Kool, D. T. W. Jones, A. Korshunov, A. Ken, S. M. Pfister, K. Makino, H. Nakamura, J.-i. Kuroda, J.-i. Kuratsu, H. Toledano, Y. Margolin, A. Ohali, S. Michowiz, P. Johann, U. Tabori, E. Walker, C. Hawkins, M. Taylor, I. Yaniv, S. Avigad, L. Hoffman, S. R. Plimpton, N. V. Stence, R. Vibhakar, A. Lourdusamy, R. Rahman, J. Ward, H. Rogers, R. Grundy, C. Punchihewa, R. Lee, T. Lin, W. Orisme, J. Dalton, E. Aronica, A. Smith, A. Gajjar, A. Onar, S. Pounds, R. Tatevossian, T. Merchant, D. Ellison, M. Parker, K. Mohankumar, R. Weinlich, T. Phoenix, R. Thiruvenkatam, E. White, K. Gupta, F. Boop, L. Ding, E. Mardis, R. Wilson, J. Downing, R. Gilbertson, D. Speed, T. Gould, t. I. E. Consortium, A. Griesinger, A. Donson, D. Birks, N. Ohe, H. Yano, N. Nakayama, T. Iwama, K. Wright, T. Hassall, D. C. Bowers, J. Crawford, A. Bendel, P. G. Fisher, P. Klimo, G. Armstrong, I. Qaddoumi, G. Robinson, C. Wetmore, A. Broniscer, R. Chapman, C. Mayne, H. Duane, J.-P. Kilday, B. Coyle, A. Graul-Conroy, W. Hartsell, T. Bragg, S. Goldman, S. Rebsamen, D. Puccetti, S. Salamat, N. J. Patel, A. Gomi, H. Oguma, T. Hayase, Y. Kawahara, M. Yagi, A. Morimoto, C. Wilbur, C. Dunham, D. Mabbott, A.-S. Carret, L. Lafay-Cousin, P. D. McNeely, D. Eisenstat, B. Wilson, D. Johnston, J. Hukin, M. Mynarek, R. D. Kortmann, P. Kaatsch, T. Pietsch, B. Timmermann, G. Fleischhack, M. Benesch, C. Friedrich, A. O. von Bueren, N. U. Gerber, K. Muller, S. Tippelt, M. Warmuth-Metz, S. Rutkowski, K. von Hoff, M. K. Murugesan, H. Poppleton, S. Currle, T. Kranenburg, C. Eden, N. Boulos, J. Dapper, Y. Patel, B. Freeman, A. Shelat, C. Stewart, R. Guy, J. Adamski, A. Huang, U. Bartels, V. Ramaswamy, R. Krishnatry, N. Laperriere, E. Bouffet, A. Araki, M. Chocholous, J. Gojo, C. Dorfer, T. Czech, K. Dieckmann, I. Slavc, C. Haberler, E. Doerner, A. z. Muehlen, R. Kortmann, A. von Buehren, H. Ottensmeier, A. Resch, R. Kwiecien, A. Faldum, J. Kuehl, D. Sabnis, L. Storer, L. Simmonds, S. Blackburn, J. Lowe, I. Kerr, I. Wohlers, T. Goschzik, V. Dreschmann, D. Denkhaus, S. Rahmann, L. Klein-Hitpass, M. J. L. Iglesias, F. G. Riet, F. D. Dhermain, S. Canale, C. Dufour, C. S. Rose, S. Puget, J. Grill, S. Bolle, J. Parkes, A. Davidson, A. Figaji, K. Pillay, T. Kilborn, L. Padayachy, M. Hendricks, A. Van Eyssen, E. Piccinin, E. Lorenzetto, M. Brenca, K. Aldape, Y.-J. Cho, W. Weiss, J. Phillips, N. Jabado, J. Mora, X. Fan, S. Jung, J. Y. Lee, K. Zitterbart, P. French, J. M. Kros, P. Hauser, C. Faria, and S. Pfister
Subjects: Abstracts, Cancer Research, Tumor grade, Oncology, Expression pattern, business.industry, microRNA, Cancer research, Medicine, Neurology (clinical), business
Published: 2014
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14. OMICS AND PROGNSTIC MARKERS

Author: K. Adachi, H. Sasaki, S. Nagahisa, K. Yoshida, N. Hattori, Y. Nishiyama, T. Kawase, M. Hasegawa, M. Abe, Y. Hirose, A. Alentorn, Y. Marie, S. Poggioli, H. Alshehhi, B. Boisselier, C. Carpentier, K. Mokhtari, L. Capelle, D. Figarella-Branger, K. Hoang-Xuan, M. Sanson, J.-Y. Delattre, A. Idbaih, S. Yust-Katz, M. Anderson, A. Olar, A. Eterovic, N. Ezzeddine, K. Chen, H. Zhao, G. Fuller, K. Aldape, J. de Groot, N. Andor, J. Harness, S. G. Lopez, T. L. Fung, H. W. Mewes, C. Petritsch, A. Arivazhagan, K. Somasundaram, K. Thennarasu, P. Pandey, B. Anandh, V. Santosh, B. Chandramouli, A. Hegde, P. Kondaiah, M. Rao, R. Bell, R. Kang, C. Hong, J. Song, J. Costello, R. Nagarajan, B. Zhang, A. Diaz, T. Wang, L. Bie, Y. Li, H. Liu, W. F. C. Luyo, M. H. Carnero, M. E. P. Iruegas, A. R. Morell, M. C. Figueiras, R. L. Lopez, C. F. Valverde, A. K.-Y. Chan, J. C.-S. Pang, N. Y.-F. Chung, K. K.-W. Li, W. S. Poon, D. T.-M. Chan, Y. Wang, H.-a. K. Ng, M. Chaumeil, P. Larson, H. Yoshihara, D. Vigneron, S. Nelson, R. Pieper, J. Phillips, S. Ronen, V. Clark, Z. E. Omay, A. Serin, J. Gunel, B. Omay, C. Grady, M. Youngblood, K. Bilguvar, J. Baehring, J. Piepmeier, P. Gutin, A. Vortmeyer, C. Brennan, M. N. Pamir, T. Kilic, B. Krischek, M. Simon, K. Yasuno, M. Gunel, A. L. Cohen, M. Sato, K. D. Aldape, C. Mason, K. Diefes, L. Heathcock, L. Abegglen, D. Shrieve, W. Couldwell, J. D. Schiffman, H. Colman, Q. G. D'Alessandris, T. Cenci, M. Martini, L. Ricci-Vitiani, R. De Maria, L. M. Larocca, R. Pallini, B. Theeler, F. Lang, G. Rao, M. Gilbert, E. Sulman, R. Luthra, K. Eterovic, M. Routbort, R. Verhaak, G. Mills, J. Mendelsohn, F. Meric-Bernstam, A. Yung, K. MacArthur, S. Hahn, G. Kao, R. Lustig, M. Alonso-Basanta, S. Chandrasekaran, E. P. Wileyto, E. Reyes, J. Dorsey, K. Fujii, K. Kurozumi, T. Ichikawa, M. Onishi, J. Ishida, Y. Shimazu, B. Kaur, E. A. Chiocca, I. Date, C. Geisenberger, A. Mock, R. Warta, C. Schwager, C. Hartmann, A. von Deimling, A. Abdollahi, C. Herold-Mende, O. Gevaert, A. Achrol, S. Gholamin, S. Mitra, E. Westbroek, J. Loya, L. Mitchell, S. Chang, G. Steinberg, S. Plevritis, S. Cheshier, J. Xu, S. Napel, G. Zaharchuk, G. Harsh, D. Gutman, C. Holder, R. Colen, W. Dunn, R. Jain, L. Cooper, S. Hwang, A. Flanders, D. Brat, J. Hayes, A. Droop, H. Thygesen, M. Boissinot, D. Westhead, S. Short, S. Lawler, P. Bady, S. Kurscheid, M. Delorenzi, M. E. Hegi, C. Crosby, C. Faulkner, T. Smye-Rumsby, K. Kurian, M. Williams, K. Hopkins, A. Palmer, H. Williams, C. Wragg, H. R. Haynes, K. M. Kurian, P. White, T. Oka, L. Jalbert, A. Elkhaled, R. Jensen, K. Salzman, M. Schabel, D. Gillespie, M. Mumert, B. Johnson, T. Mazor, M. Barnes, S. Yamamoto, H. Ueda, K. Tatsuno, K. Aihara, A. Bollen, M. Hirst, M. Marra, A. Mukasa, N. Saito, H. Aburatani, M. Berger, B. Taylor, S. Popov, A. Mackay, W. Ingram, A. Burford, A. Jury, M. Vinci, C. Jones, D. T. W. Jones, V. Hovestadt, S. Picelli, W. Wang, P. A. Northcott, M. Kool, G. Reifenberger, T. Pietsch, M. Sultan, H. Lehrach, M.-L. Yaspo, A. Borkhardt, P. Landgraf, R. Eils, A. Korshunov, M. Zapatka, B. Radlwimmer, S. M. Pfister, P. Lichter, A. Joy, I. Smirnov, M. Reiser, W. Shapiro, S. Kim, B. Feuerstein, C. Jungk, S. Friauf, A. Unterberg, T. A. Juratli, J. McElroy, W. Meng, A. Huebner, K. D. Geiger, D. Krex, G. Schackert, A. Chakravarti, T. Lautenschlaeger, B. Y. Kim, W. Jiang, J. Beiko, S. Prabhu, F. DeMonte, R. Sawaya, D. Cahill, I. McCutcheon, C. Lau, L. Wang, K. Terashima, S. Yamaguchi, M. Burstein, J. Sun, T. Suzuki, R. Nishikawa, H. Nakamura, A. Natsume, S. Terasaka, H.-K. Ng, D. Muzny, R. Gibbs, D. Wheeler, X.-q. Zhang, S. Sun, K.-f. Lam, K. M. Y. Kiang, J. K. S. Pu, A. S. W. Ho, G. K. K. Leung, F. Loebel, W. T. Curry, F. G. Barker, N. Lelic, A. S. Chi, D. P. Cahill, D. Lu, J. Yin, C. Teo, K. McDonald, A. Madhankumar, C. Weston, B. Slagle-Webb, J. Sheehan, A. Patel, M. Glantz, J. Connor, C. Maire, J. Francis, C.-Z. Zhang, J. Jung, V. Manzo, V. Adalsteinsson, H. Homer, B. Blumenstiel, C. S. Pedamallu, E. Nickerson, A. Ligon, C. Love, M. Meyerson, K. Ligon, L. E. Jalbert, S. J. Nelson, A. W. Bollen, I. V. Smirnov, J. S. Song, A. B. Olshen, M. S. Berger, S. M. Chang, B. S. Taylor, J. F. Costello, S. Mehta, B. Armstrong, S. Peng, A. Bapat, M. Berens, B. Melendez, M. Mollejo, P. Mur, T. Hernandez-Iglesias, C. Fiano, J. Ruiz, J. A. Rey, V. Stadler, A. Schulte, K. Lamszus, C. Schichor, M. Westphal, J.-C. Tonn, O. Morozova, S. Katzman, M. Grifford, S. Salama, D. Haussler, A. Olshen, S. Fouse, S. Nakamizo, T. Sasayama, H. Tanaka, K. Tanaka, K. Mizukawa, M. Yoshida, E. Kohmura, P. Northcott, D. Jones, S. Pfister, R. Otani, S. Takayanagi, K. Saito, S. Tanaka, M. Shin, T. Ozawa, M. Riester, Y.-K. Cheng, J. Huse, K. Helmy, N. Charles, M. Squatrito, F. Michor, E. Holland, M. Perrech, L. Dreher, G. Rohn, R. Goldbrunner, M. Timmer, B. Pollo, V. Palumbo, C. Calatozzolo, M. Patane, R. Nunziata, M. Farinotti, A. Silvani, S. Lodrini, G. Finocchiaro, E. Lopez, A. Rioscovian, R. Ruiz, G. Siordia, A. P. de Leon, C. Rostomily, R. Rostomily, D. Silbergeld, D. Kolstoe, M. Chamberlain, J. Silber, P. Roth, A. Keller, J. Hoheisel, P. Codo, A. Bauer, C. Backes, P. Leidinger, E. Meese, E. Thiel, A. Korfel, M. Weller, G. Nagae, M. Nagane, J. Z. Sanborn, T. Mikkelsen, S. Jhanwar, L. Chin, M. Nishihara, M. Schliesser, C. Grimm, E. Weiss, R. Claus, D. Weichenhan, M. Weiler, T. Hielscher, F. Sahm, B. Wiestler, A.-C. Klein, J. Blaes, C. Plass, W. Wick, G. Stragliotto, A. Rahbar, C. Soderberg-Naucler, M. Won, R. Ezhilarasan, P. Sun, D. Blumenthal, M. Vogelbaum, R. Jenkins, R. Jeraj, P. Brown, K. Jaeckle, D. Schiff, J. Dignam, J. Atkins, D. Brachman, M. Werner-Wasik, M. Mehta, J. Shen, J. Luan, A. Yu, M. Matsutani, Y. Liang, T.-K. Man, A. Trister, M. Tokita, S. Mikheeva, A. Mikheev, S. Friend, M. van den Bent, L. Erdem, T. Gorlia, M. Taphoorn, J. Kros, P. Wesseling, H. Dubbink, A. Ibdaih, P. French, H. van Thuijl, J. Heimans, B. Ylstra, J. Reijneveld, A. Prabowo, I. Scheinin, H. van Essen, W. Spliet, C. Ferrier, P. van Rijen, T. Veersema, M. Thom, A. S.-v. Meeteren, E. Aronica, H. Kim, S. Zheng, D. J. Brat, S. Virk, S. Amini, C. Sougnez, J. Barnholtz-Sloan, R. G. W. Verhaak, C. Watts, A. Sottoriva, I. Spiteri, S. Piccirillo, A. Touloumis, P. Collins, J. Marioni, C. Curtis, S. Tavare, B. Tews, T. P. C. Yeung, B. Al-Khazraji, L. Morrison, L. Hoffman, D. Jackson, T.-Y. Lee, S. Yartsev, G. Bauman, J. Fu, R. Vegesna, Y. Mao, L. E. Heathcock, W. Torres-Garcia, S. Wang, A. McKenna, C. W. Brennan, W. K. A. Yung, J. N. Weinstein, E. P. Sulman, and D. Koul
Subjects: Abstracts, Cancer Research, Text mining, Oncology, business.industry, Neurology (clinical), Computational biology, Biology, Omics, business
Published: 2013
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15. Perioperative Bone-Conducted Ocular Vestibular-Evoked Myogenic Potentials in Otosclerosis Patients

Author: Wilko Grolman, Sjaak F.L. Klis, Rinze A. Tange, Sophie A. C. Kraaijenga, Stephanie M. Winters, and Angelica C. M. Kool
Subjects: Adult, Male, Reoperation, medicine.medical_specialty, Stapes Surgery, Audiology, Dizziness, Tertiary care, Young Adult, Utricle, otorhinolaryngologic diseases, medicine, Humans, Saccule and Utricle, Perioperative Period, Aged, Vestibular system, business.industry, Healthy subjects, Ocular Vestibular Evoked Myogenic Potentials, Perioperative, Middle Aged, medicine.disease, Vestibular Evoked Myogenic Potentials, Sensory Systems, Otosclerosis, Treatment Outcome, medicine.anatomical_structure, Acoustic Stimulation, Otorhinolaryngology, Vertigo, Female, sense organs, Neurology (clinical), Otologic Surgical Procedures, business, Bone Conduction, After treatment, Muscle Contraction
Abstract: Objective: Vestibular symptoms are seen variably in patients with otosclerosis, both in patients with the disease and in patients after treatment with stapes surgery. The goal of this study was to objectify any changes of the bone-conducted (BC) ocular vestibular evoked myogenic potentials (oVEMPs) in patients with otosclerosis before and after stapes surgery. Study Design: Twenty-six healthy subjects and 27 patients with otosclerosis were tested in a tertiary care center, and 11 of the patients were tested preoperatively and postoperatively. The ears of patients were divided in 4 groups: normal ears, otosclerotic ears, ears after primary stapes surgery, and ears after revision surgery. The stimulus used in oVEMP testing was a BC stimulus delivered by a mini-shaker at stimulus frequencies of 250 and 500 Hz. oVEMP characteristics were the n1 and p1 latencies, n1 Y p1 amplitude, and threshold. Results: No significant differences were seen in all oVEMP characteristics between the 4 groups of ears without surgery nor in the ears that were tested preoperatively and postoperatively. Conclusion: No or undetectably little damage to the utricle is caused by both otosclerotic disease and stapes surgery. There is no additive value of screening with BC oVEMPs perioperatively in otosclerotic patients. Key Words: Bone-conducted stimuliVOcular vestibular evoked myogenic potentialVOtolith organsVOtosclerosisVStapes surgeryVStapedotomyVVestibular disorders. Otol Neurotol 34:1109Y1114, 2013.
Published: 2013
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16. NSAIDs can have adverse effects on bone healing

Author: Maurice M. Kool, Robert W. van Esch, and Saskia van As
Subjects: Fracture Healing, business.industry, Osteoimmunology, Anti-Inflammatory Agents, Non-Steroidal, Allostasis, Inflammation, General Medicine, Bone healing, Models, Theoretical, Bioinformatics, Bone resorption, Resorption, Bone remodeling, Immune system, Immunology, medicine, Humans, medicine.symptom, business
Abstract: The science of osteoimmunology, a relatively new field of research, reveals the important interactions between the immune system and skeletal system. Interactions occur between prostaglandin metabolism, inflammatory proteins and bone metabolism. Systemic as well as local sources of inflammation appear to be actively involved in both bone formation and resorption. Non Steroidal Anti-Inflammatory Drugs (NSAIDs) can play a detrimental role in bone fractures, opposing the aim of the intervention, and can have such a negative impact on the synthesis of prostaglandins that they could even promote bone resorption. When used for a prolonged time, NSAIDs can also cause the development of an inflammatory cascade starting from the gastro-intestinal system, possibly resulting in bone resorption. Several studies show that the use of either selective or non-selective NSAIDs are intimately related to disturbances in immunological allostasis, bone metabolism and the inhibition or impediment of bone healing.
Published: 2013
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17. The role of monocyte derived growth factors in BPD development

Author: Robbert J. Rottier, Heleen M. Kool, Esther van Mastrigt, Ismé de Kleer, Chris van Dijk, Rudi W. Hendriks, Irwin K.M. Reiss, Caroline Cheng, Johan C. de Jongste, Janneke N. Samsom, and Marielle W. Pijnenburg
Subjects: business.industry, Angiogenesis, Monocyte, Inflammation, medicine.disease, medicine.anatomical_structure, Bronchopulmonary dysplasia, Immunology, medicine, Macrophage, Tumor necrosis factor alpha, GDF15, medicine.symptom, business, Tissue homeostasis
Abstract: Bronchopulmonary dysplasia (BPD) is characterized by abnormal alveolar septation and microvascular development. Certain types of monocytes and macrophages have been implicated in epithelial growth and angiogenesis, while others play a role in immune defense and inflammation. Aims: To investigate whether monocyte/macrophage profiles and their products correlate with BPD development. Methods: We investigated lungs of neonatal mice and tracheal aspirates (TAs) from preterm born infants. Results: We found that M2-MDSC like monocytes are abundantly present in the lungs of neonatal mice. These monocytes also showed high expression of proangiogenic genes (a.o. EMMPRIN, ENA78, GDF15, VEGFR2 and IGF-1) and strong immune suppressive capacity i n vitro , supporting a role in maintaining tissue homeostasis and lung growth. Upon repetitive exposure to LPS the monocytes lost their M2-profile and suppressive capacity and upregulated inflammatory markers (IL-8, IL-1b and IL-6 but not TNFa). We also found monocytes/macrophages in TAs from preterm born infants. Proteome profiling these TAs revealed high concentrations of both M2 and inflammatory monocyte/macrophage derived factors and angiogenic mediators. Addition of TAs to pericyte-endothelial cell co-cultures either enhanced or inhibited angiogenesis. Luminex analysis of TAs of preterm infants with (n=22) and without (n=23) BPD showed significant lower concentrations of the angiogenic factors EMMPRIN, ENA78, MCP1, GDF15, TNF-α, Angiopoietin-1, -2 and HGF in those infants who developed BPD. Conclusion: Our data indicate that monocyte/macrophage profiles in TAs of premature children correlate with BPD development and may be used to identify new preventive or therapeutic targets.
Published: 2016
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18. Clinically relevant timing of antenatal sildenafil treatment reduces pulmonary vascular remodeling in congenital diaphragmatic hernia

Author: Rene M. H. Wijnen, Oleh Dzyubachyk, Marjon Buscop-van Kempen, Robbert J. Rottier, Heleen M. Kool, Daphne S. Mous, Anton H. J. Koning, Dick Tibboel, Pediatric Surgery, and Pathology
Subjects: Pulmonary and Respiratory Medicine, Physiology, Sildenafil, Angiogenesis, Drug Evaluation, Preclinical, 030204 cardiovascular system & hematology, Vascular Remodeling, Sildenafil Citrate, Rats, Sprague-Dawley, 03 medical and health sciences, chemistry.chemical_compound, angiogenesis, 0302 clinical medicine, Pregnancy, 030225 pediatrics, Physiology (medical), pulmonary hypertension, Medicine, Animals, development, Lung, Maternal-Fetal Exchange, business.industry, Phenyl Ethers, Congenital diaphragmatic hernia, Cell Biology, Phosphodiesterase 5 Inhibitors, medicine.disease, Pulmonary hypertension, medicine.anatomical_structure, chemistry, Maternal Exposure, Anesthesia, Female, Pulmonary vasculature, business, Hernias, Diaphragmatic, Congenital
Abstract: Patients with congenital diaphragmatic hernia (CDH) suffer from severe pulmonary hypertension attributable to altered development of the pulmonary vasculature, which is often resistant to vasodilator therapy. Present treatment starts postnatally even though significant differences in the pulmonary vasculature are already present early during pregnancy. We examined the effects of prenatal treatment with the phosphodiesterase-5 inhibitor sildenafil on pulmonary vascular development in experimental CDH starting at a clinically relevant time. The well-established, nitrofen-induced CDH rodent model was treated daily with 100 mg/kg sildenafil from day 17.5 until day 20.5 of gestation (E17.5–20.5). Importantly, this timing perfectly corresponds to the developmental stage of the lung at 20 wk of human gestation, when CDH is detectable by 2D-ultrasonography and/or MRI. At E21.5 pups were delivered by caesarean section and euthanized by lethal injection of pentobarbital. The lungs were isolated and subsequently analyzed using immunostaining, real-time PCR, and volume measurements. Prenatal treatment with sildenafil improved lung morphology and attenuated vascular remodeling with reduced muscularization of the smaller vessels. Pulmonary vascular volume was not affected by sildenafil treatment. We show that prenatal treatment with sildenafil within a clinically relevant period improves pulmonary vascular development in an experimental CDH model. This may have important implications for the management of this disease and related pulmonary vascular diseases in human.
Published: 2016

19. HIGH GRADE GLIOMAS

Author: A. Leonard, J. Wolff, R. Sengupta, J. Marassa, D. Piwnica-Worms, J. Rubin, I. Pollack, R. Jakacki, L. Butterfield, H. Okada, J. Fangusaro, K. E. Warren, C. Mullins, P. Jurgen, S. Julia, C. C. Friedrich, S. Keir, J. Saling, M. Roskoski, H. Friedman, D. Bigner, C. Moertel, M. Olin, T. Dahlheimer, M. Gustafson, D. Sumstad, D. McKenna, W. Low, D. Nascene, A. Dietz, J. Ohlfest, D. Sturm, H. Witt, V. Hovestadt, D. A. K. Quan, D. T. W. Jones, C. Konermann, E. Pfaff, A. Korshunov, M. Rizhova, T. Milde, O. Witt, M. Zapatka, V. P. Collins, M. Kool, G. Reifenberger, P. Lichter, A. M. Lindroth, C. Plass, N. Jabado, S. M. Pfister, B. Pizer, A. Salehzadeh, A. Brodbelt, C. Mallucci, M. Brassesco, J. Pezuk, A. Morales, J. de Oliveira, G. Roberto, K. Umezawa, E. Valera, E. Rego, C. Scrideli, L. Tone, S. J. E. Veringa, D. G. Van Vuurden, P. Wesseling, W. P. Vandertop, D. P. Noske, T. Wurdinger, G. J. L. Kaspers, E. Hulleman, K. Wright, A. Broniscer, A. Bendel, D. Bowers, J. Crawford, P. Fisher, T. Hassall, G. Armstrong, J. Baker, I. Qaddoumi, G. Robinson, C. Wetmore, P. Klimo, F. Boop, A. Onar-Thomas, D. Ellison, A. Gajjar, O. Cruz, C. de Torres, M. Sunol, E. Rodriguez, L. Alonso, A. Parareda, T. Cardesa, H. Salvador, V. Celis, A. Guillen, G. Garcia, J. Muchart, C. Trampal, M. L. Martin, M. Rebollo, J. Mora, A. Piotrowski, A. Kowalska, P. Coyle, S. Smith, H. Rogers, D. Macarthur, R. Grundy, D. Puccetti, S. Salamat, T. Kennedy, N. Patel, K. Bradley, K. Casey, B. Iskandar, Y. Nakano, K. Okada, Y. Osugi, K. Yamasaki, H. Fujisaki, H. Fukushima, T. Inoue, Y. Matsusaka, H. Sakamoto, J. Hara, S. De Vleeschouwer, H. Ardon, F. Van Calenbergh, R. Sciot, G. Wilms, J. Van Loon, J. Goffin, S. Van Gool, D. Rusinak, P. Knight, K. Onel, D. Wargowski, A. Stettner, A. Al-Ghafari, W. Punjaruk, B. Coyle, I. Kerr, E. Xipell, M. Rodriguez, M. Gonzalez-Huarriz, M. T. Tunon, I. Zazpe, S. Tejada-Solis, R. Diez-Valle, J. Fueyo, C. Gomez-Manzano, M. M. Alonso, D. Pastakia, C. McCully, R. Murphy, J. Bacher, M. Thomas, E. Steffen-Smith, K. Saleem, S. Waldbridge, B. Widemann, K. Warren, E. Miele, F. Buttarelli, A. Arcella, F. Begalli, A. Po, C. Baldi, G. Carissimo, M. Antonelli, V. Donofrio, I. Morra, P. Nozza, A. Gulino, F. Giangaspero, E. Ferretti, I. Elens, F. Pauwels, S. Fritzell, S. Eberstal, E. Sanden, E. Visse, A. Darabi, P. Siesjo, P. McDonald, J. Wrogemann, S. Krawitz, M. Del Bigio, D. Eisenstat, R. Kwiecien, T. Pietsch, A. Faldum, R.-D. Kortmann, M. Warmuth-Metz, S. Rutkowski, I. Slavc, C. M. Kramm, U. Uparkar, R. Geyer, R. Ermoian, R. Ellenbogen, S. Leary, J. Triscott, K. Hu, A. Fotovati, S. Yip, R. Kast, B. Toyota, S. Dunn, M. Hegde, A. Corder, K. Chow, M. Mukherjee, A. Ashoori, V. Brawley, H. Heslop, S. Gottschalk, E. Yvon, N. Ahmed, T.-T. Wong, F.-Y. Yang, M. Lu, H.-F. Liang, H.-E. Wang, R.-S. Liu, M.-C. Teng, C.-C. Yen, S. Agnihotri, C. Ternamian, C. Jones, G. Zadeh, J. Rutka, C. Hawkins, I. Filipek, M. Drogosiewicz, M. Perek-Polnik, E. Swieszkowska, B. D. Baginska, E. Jurkiewicz, D. Perek, A. Kuehn, F. Falkenstein, A. Gnekow, C. Kramm, M. D. Brooks, E. Jackson, R. D. Mitra, J. B. Rubin, X.-Y. Liu, J. Schwartzentruber, A. M. Fontebasso, D.-A. K. Quang, S. Albrecht, Z. Dong, P. Siegel, A. Von Diemling, D. Faury, U. Tabori, J. Majewski, R. Lulla, M. Echevarria, T. Alden, A. DiPatri, T. Tomita, S. Goldman, T. Lin, T. E. Merchant, M. Kocak, A. P. Panandiker, G. T. Armstrong, G. H. Gielen, A. z. Muehlen, C. Hubert, Y. Ding, C. Toledo, P. Paddison, J. Olson, M. Nandhabalan, L. Bjerke, D. Bax, D. Carvalho, I. Bajrami, A. Ashworth, C. Lord, D. Hargrave, R. Reis, P. Workman, S. Little, S. Popov, A. Jury, A. Burford, L. Doey, S. Al-Sarraj, J. Jurgensmeier, L. Chen, I. Kozarewa, S. Baker, L. Perryman, G. Box, F. Raynaud, S. Eccles, M. Viana-Pereira, M. Pereira, T. Forshew, R. Tatevossian, D. Sheer, J. Pimental, M. Pires, C. Sarkar, P. Jha, I. R. P. Patrick, K. Somasundaram, P. Pathak, M. C. Sharma, V. Suri, A. Suri, N. Gerges, T. Haque, A. Nantel, C. Lee, J. Chen, C. Venugopal, A. Singhal, C. Dunham, J. Kerr, M. Verreault, H. Wakimoto, A. Jayanthan, A. Narendran, S. Singh, G. Giraud, S. Holm, B. Gustavsson, R. Kizyma, Z. Kizyma, L. Dvornyak, B. Kotsay, S. Epari, P. Sharma, M. Gurav, T. Gupta, P. Shetty, A. Moiyadi, S. Kane, and R. Jalali
Subjects: Abstracts, 03 medical and health sciences, Cancer Research, 0302 clinical medicine, Oncology, business.industry, 030220 oncology & carcinogenesis, Medicine, Neurology (clinical), business, 030217 neurology & neurosurgery
Published: 2012
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20. Discrepancies in how the impact of gout is assessed in outcomes research compared to how health professionals view the impact of gout, using the lens of the International Classification of Functioning, Health and Disability (ICF)

Author: Marieke J. Nijsten, William J. Taylor, Annelies E. van Ede, T.L.Th.A. Jansen, and Eveline M. Kool
Subjects: musculoskeletal diseases, medicine.medical_specialty, Activities of daily living, Delphi Technique, Gout, Health Status, education, Alternative medicine, Delphi method, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Quality of life (healthcare), Rheumatology, International Classification of Functioning, Disability and Health, Surveys and Questionnaires, Activities of Daily Living, medicine, Content validity, Humans, Disabled Persons, 030212 general & internal medicine, computer.programming_language, 030203 arthritis & rheumatology, business.industry, General Medicine, social sciences, humanities, Family medicine, Physical therapy, Quality of Life, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], Outcomes research, business, computer, human activities, Delphi
Abstract: Item does not contain fulltext The International Classification of Functioning, Disability and Health (ICF) provides a common language to understand what health means. An ICF core set, a list of ICF categories affected by a certain disease, is useful to objectify the content validity of a health status measurement. This study aims to identify the potential items of a gout specific 'ICF core set'. A three-round Delphi exercise was conducted, using web-based questionnaires. Health professionals, specialized in gout, nominated and subsequently rated the relevance of life areas divided into ICF categories. Agreement was determined by using the UCLA/RAND criteria. Simultaneously, a systematic review of gout measure outcomes was conducted. The results of these studies were compared using the second level of the ICF categories. In the Delphi study, consensus was found for 136 relevant ICF categories. The literature study extracted 134 different ICF categories in 149 articles. Three hundred and ten were non-defined outcomes. A large number of ICF categories were deemed to be relevant for people with gout. Only 29.7 % (19/64) of the level 2 categories, deemed to be relevant by health professionals, had been assessed as relevant in at least 5 % of gout outcome studies. Conversely, 70 % (19/27) of level 2 ICF categories assessed in at least 5 % of outcome studies were deemed relevant by health professionals. These ICF codes, which are found relevant in both studies, should be considered as mandatory in further research to a validated and practical core set of ICF categories. Published gout outcomes research fails to evaluate many life areas that are thought relevant by health professionals.
Published: 2016

21. Targeting MYC/HDAC2 interaction in Group 3 medulloblastoma – rationales for an innovative therapeutic approach

Author: Ina Oehme, Till Milde, M Kool, SM Pfister, Jonas Ecker, Andrey Korshunov, Andreas E. Kulozik, and Olaf Witt
Subjects: Oncology, Medulloblastoma, medicine.medical_specialty, Therapeutic approach, business.industry, Internal medicine, Pediatrics, Perinatology and Child Health, Immunology, medicine, business, medicine.disease
Published: 2015
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22. Preclinical evaluation and translational consequences of EZH2-inhibition in malignant brain tumors

Author: SM Pfister, Olaf Witt, Till Milde, Andreas E. Kulozik, Jonas Ecker, A Leibner, Florian Selt, Ina Oehme, and M Kool
Subjects: Pathology, medicine.medical_specialty, business.industry, Pediatrics, Perinatology and Child Health, EZH2, medicine, business
Published: 2015
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23. Foretinib is effective therapy for metastatic sonic hedgehog medulloblastoma

Author: Samantha Olsen, Sameer Agnihotri, Michael D. Taylor, Paul A. Northcott, Michael Leadley, Marc Remke, Amanda Luck, Xin Wang, Livia Garzia, Sidney Croul, M Kool, Claudia C. Faria, Stefan M. Pfister, Andrey Korshunov, Denis Reynaud, Stephen C. Mack, Roberto J. Diaz, Adrian M. Dubuc, Christian A. Smith, Leonardo Ermini, Brian Golbourn, Xiaochong Wu, James T. Rutka, Nesrin Sabha, Martin Post, and Vijay Ramaswamy
Subjects: Oncology, Cancer Research, Pathology, medicine.medical_treatment, Nude, Transgenic, abstracts, Targeted therapy, chemistry.chemical_compound, Mice, Medicine, Anilides, Sonic hedgehog, Neoplasm Metastasis, Tumor, biology, Kinase, Proto-Oncogene Proteins c-met, Primary tumor, Platelet-Derived Growth Factor beta, Blood-Brain Barrier, Quinolines, Immunohistochemistry, Receptor, Signal Transduction, Genetically modified mouse, medicine.medical_specialty, Mice, Nude, Mice, Transgenic, Cell Line, Receptor, Platelet-Derived Growth Factor beta, In vivo, Cell Line, Tumor, Internal medicine, Animals, Humans, Hedgehog Proteins, Cerebellar Neoplasms, Cell Proliferation, Medulloblastoma, business.industry, Gene Expression Profiling, Cancer, Foretinib, medicine.disease, Xenograft Model Antitumor Assays, nervous system diseases, chemistry, Tumor progression, biology.protein, Cancer research, Neurology (clinical), business
Abstract: BACKGROUND: (blind field). METHODS: Expression profiling, molecular subgrouping and analysis of somatic copy number alterations were conducted on multiple independent cohorts of patient tumour samples to examine intermediates of the MET signaling pathway in medulloblastoma. To examine the in vitro and in vivo effects of foretinib treatment; MET signalling biochemical analysis; migration and invasion assays; and foretinib pharmacokinetic studies were performed. Medulloblastoma xenografts and transgenic mouse models were used to evaluate foretinib treatment in vivo. RESULTS: We analyzed three large non-overlapping cohorts of medulloblastoma patients (discovery cohort, n = 199; validation cohort 1, n = 439; validation cohort 2, n = 285) and demonstrated that cMET, known to be involved in tumor progression and dissemination, is a marker of sonic hedgehog (SHH) medulloblastoma. Importantly, immunohistochemical analysis of activated cMET (phosphorylated cMET) in another independent patient cohort (n = 385) revealed that cMET activation correlates with increased tumor relapse and a poor survival in pediatric patients with SHH medulloblastomas, thus defining a subset of patients that may benefit from cMET targeted therapy. We show that foretinib, an FDA approved inhibitor of cMET, suppresses cMET activation, decreases proliferation and induces apoptosis, both in medulloblastoma cell lines and in SHH medulloblastoma xenografts. Furthermore foretinib penetrates the blood-brain barrier and is effective both in the primary and in the metastatic compartments. Treatment of mouse xenografts and of an aggressive transgenic model of metastatic SHH medulloblastoma with foretinib reduced primary medulloblastoma growth, decreased the incidence of metastases by 36% and increased survival by 45%. CONCLUSIONS: Our results provide strong rationale for advancing foretinib into clinical trials for SHH-driven medulloblastomas. SECONDARY CATEGORY: Tumor Biology.
Published: 2015

24. TMOD-05. MOLECULAR CHARACTERIZATION OF ORTHOTOPIC PATIENT-DERIVED XENOGRAFT MODELS OF PEDIATRIC BRAIN TUMORS AND THEIR USE IN PRECLINICAL EXPERIMENTS

Author: Lukas Chavez, Till Milde, Jones Dtw, Susanne N. Groebner, Olaf Witt, Xiao-Nan Li, Robert J. Wechsler-Reya, M Kool, Huriye Seker-Cin, Sebastian Brabetz, Sarah Leary, James Olson, Norman Mack, S Pfister, and Christin Schmidt
Subjects: Abstracts, Cancer Research, Text mining, Oncology, business.industry, Pediatric brain, Cancer research, Medicine, Neurology (clinical), business, Tumor xenograft
Abstract: Genomic studies have shown that multiple molecular subtypes of pediatric brain tumors exist that are biologically and clinically highly distinct. These findings ask for novel subtype specific treatments. To develop these we need more and better preclinical models that correctly reflect the proper tumor (sub)type. Orthotopic patient-derived xenograft (PDX) models generated by intracranial injection of primary patient material into the brain of NSG mice offer the unique possibility to test novel substances in primary patient tissue in an in vivo environment. Prior to drug selection and testing, extensive molecular characterizations of PDX and matching primary tumor/blood (DNA methylation, DNA sequencing, and gene expression) are needed to see how the PDX represents the original disease and to learn about targetable oncogenic drivers in each model. In collaboration with several groups around the world we have generated and fully characterized thus far 75 PDX models reflecting 15 distinct subtypes of pediatric brain cancer. PDX models always retain their molecular subtype and in the vast majority of cases also mutations and copy number alterations compared to matching primary tumors. Most aggressive tumors, harboring MYC(N) amplifications, are overrepresented in the cohort, but also subtypes which have not been available for preclinical testing before due to lack of genetically engineered mouse models or suitable cell lines, such as Group 4 medulloblastoma, are included. All models and corresponding molecular data will become available for the community for preclinical research. Examples of such preclinical experiments will be presented. PDX models of pediatric brain tumors are still quite rare. Our repertoire of PDX models and corresponding molecular characterizations allow researchers all over the world to find the right models for their specific scientific questions. It will provide an unprecedented resource to study tumor biology and pave the way for improving treatment strategies for children with malignant brain tumors.
Published: 2017
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25. ATYPICAL TERATOID RHABDOID TUMOUR

Author: A. I. Bertozzi, C. Munzer, F. Fouyssac, N. Andre, S. Boetto, P. Leblond, F. Bourdeaut, C. Dufour, R. K. Deshpande, K. G. Bhat, S. Mahalingam, A. Muscat, J. Cain, M. Ferguson, D. Popovski, E. Algar, F. J. Rossello, S. Jayasekara, D. N. Watkins, J. Hodge, D. Ashley, M. Hishii, M. Saito, H. Arai, Z. Y. Han, W. Richer, C. Lucchesi, P. Freneaux, A. Nicolas, C. Grison, G. Pierron, O. Delattre, S. Epari, N. TS, T. Gupta, G. Chinnaswamy, J. G. Sastri, P. Shetty, A. Moiyadi, R. Jalali, T. Fay-McClymont, D. Johnston, L. Janzen, S. Guger, K. Scheinemann, A. Fleming, C. Fryer, J. Hukin, D. Mabbott, A. Huang, E. Bouffet, L. Lafay-Cousin, A. Kawamura, K. Yamamoto, T. Nagashima, K. Bartelheim, M. Benesch, J. Buchner, J. Gerss, M. Hasselblatt, R.-D. Kortmann, G. Fleischack, E. Quiroga, H. Reinhard, R. Schneppenheim, A. Seeringer, R. Siebert, B. Timmermann, M. Warmuth-Metz, I. Schmid, M. C. Fruhwald, K. Kerl, T. Klingebiel, A. Al-Kofide, Y. Khafaga, H. Al-Hindi, M. Dababo, A. Ul-Haq, M. Anas, M. G. Barria, K. Siddiqui, M. Hassounah, M. Ayas, E. Al-Shail, A. Jeibmann, K. Eikmeier, A. Linge, P. Johann, B. Koos, M. Kool, S. M. Pfister, W. Paulus, U. Schuller, R. Junckerstorff, M. K. Rosenblum, A. H. Alassiri, S. Rossi, N. Gottardo, H. Toledano, E. Viscardi, L. Witkowski, I. Nagel, F. Oyen, W. D. Foulkes, D. Schrey, G. Malietzis, S. Chi, L. Marshall, F. Carceller, L. Moreno, S. Zacharoulis, R. Bhardwaj, M. Chakravadhanula, V. Ozals, C. Hampton, R. Metpally, P. Grillner, J. Asmundsson, B. Gustavsson, S. Holm, P. D. Johann, A. Korshunov, M. Ryzhova, T. Milde, O. Witt, D. T. W. Jones, V. Hovestadt, A. Gajjar, M. Fruhwald, S. Pfister, M. Finetti, A. d. C. Pons, M. Selby, A. Smith, S. Crosier, J. Wood, B. Skalkoyannis, S. Bailey, S. Clifford, D. Williamson, S. Rutkowski, R. D. Kortmann, N. Graf, J. Boos, K. Nysom, N. Moreno, T. Holsten, J. Ahlfeld, J. Mertins, M. Hotfilder, S. Schleicher, R. Handgretinger, M. Meisterernst, C. Schmidt, S. Dittmar, G. C. F. Chan, M. M. K. Shing, H. L. Yuen, R. C. H. Li, S. L. Ling, I. Slavc, A. Peyrl, M. Chocholous, A. Azizi, T. Czech, K. Dieckmann, C. Haberler, U. Leiss, G. Gotti, V. Biassoni, E. Schiavello, F. Spreafico, E. Pecori, L. Gandola, M. Massimino, K. Kornelius, H. Yano, N. Nakayama, N. Ohe, M. Ozeki, K. Kanda, T. Kimura, T. Hori, T. Fukao, T. Iwama, A. G. Weil, A. Diaz, J. Gernsback, S. Bhatia, J. Ragheb, T. Niazi, Z. Khatib, A. Zoghbi, a. M. Meisterernst, D. Birks, A. Griesinger, V. Amani, A. Donson, R. Posner, C. Dunham, B. K. Kleinschmidt-DeMasters, M. Handler, R. Vibhakar, N. Foreman, L. Zhou, D. Catchpoole, A. Kakkar, A. Biswas, V. Suri, M. Sharma, S. Kale, A. Mahapatra, C. Sarkar, J. Torchia, D. Picard, K. C. Ho, D.-A. Khuong-Quang, L. Louterneau, M. Bourgey, T. Chan, B. Golbourn, L.-L. Cousin, M. D. Taylor, P. Dirks, J. T. Rutka, C. Hawkins, J. Majewski, S.-K. Kim, N. Jabado, J. H.-C. Chang, M. Confer, A. Chang, S. Goldman, M. Dunn, and W. Hartsell
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Poor prognosis, Chemotherapy, Demographics, business.industry, medicine.medical_treatment, Improved survival, medicine.disease, Abstracts, Atypical teratoid/rhabdoid tumour, Internal medicine, Atypical teratoid rhabdoid tumor, Epidemiology, medicine, Conventional chemotherapy, Neurology (clinical), business
Abstract: Atypical teratoid rhabdoid tumor of the brain is a rare embryonal tumor of infancy which has become more widely recognized due to specific immunostaining now more routinely available. These tumors still carry a poor prognosis and no standard therapy is currently available. However, the recent development of aggressive multimodality strategies seems to be associated with improved survival rates. In this chapter, we provide a review of our current knowledge on the demographics and epidemiology, pathology, and molecular characteristics. We review each individual therapeutic modality used (surgery, conventional chemotherapy, high-dose chemotherapy with stem cell rescue, intrathecal chemotherapy, and radiation) and the contribution of each to outcome when available. We provide an overview of the most recent therapeutic trials published and discuss the future options in development.
Published: 2014

26. The Pediatric Brain Tumor Preclinical Testing Program: update and perspectives

Author: S Pfister, Andrey Korshunov, Till Milde, M Kool, Manfred Jugold, A. von Deimling, Hendrik Witt, Andreas E. Kulozik, Olaf Witt, Axel Benner, and Manuela Zucknick
Subjects: medicine.medical_specialty, business.industry, Preclinical testing, Pediatrics, Perinatology and Child Health, Pediatric Brain Tumor, Medicine, Medical physics, business
Published: 2013
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27. PEDIATRICS LABORATORY RESEARCH

Author: V. Caretti, A. Noll, P. Woo, M. Monje, J. Cockle, A. Bruning-Richardson, S. Picton, J. Levesley, E. Ilett, S. Short, A. Melcher, S. Lawler, L. Garzia, A. Dubuc, G. Pitcher, P. Northcott, A. Mariampillai, S. Mack, K. Zayne, T. Chan, P. Skowron, X. Wu, A. Lionel, S. Morrisy, C. Hawkins, P. Kongkham, J. Rutka, A. Huang, A. Kenney, V. Yang, M. Salter, M. Taylor, S. Jelveh, P. Lindsay, D. Largaespada, L. Collier, A. Dupuy, R. Hill, T.-H. Hsieh, H.-W. Wang, W.-C. Cheng, T.-T. Wong, X. Huang, Y. He, R. Hashizume, W. Zhang, S. Stehbens, S. Younger, S. Barshow, S. Zhu, S. Mueller, W. Weiss, D. James, M. Shuman, Y. N. Jan, L. Jan, M. Marigil, P. Jauregi, M. A. Idoate, E. Xipell, G. Aldave, M. Gonzalez-Huarriz, S. Tejada-Solis, R. Diez-Valle, A. Montero-Carcaboso, J. Mora, M. M. Alonso, K. Taylor, A. Mackay, N. Truffaux, O. Morozova, Y. Butterfield, C. Phillipe, M. Vinci, C. de Torres, O. Cruz, D. Hargrave, S. Puget, S. Yip, C. Jones, J. Grill, A. Kaul, Y.-H. Chen, S. Dahiya, R. Emnett, S. Gianino, D. Gutmann, T. Miwa, S. Oi, Y. Nonaka, H. Sasaki, K. Yoshida, E. Lopez, A. P. de Leon, C. Sepulveda, L. Zarate, J. Diego-Perez, W. Pong, L. Ding, M. McLellan, I. Hussain, S. Higer, J. Leonard, A. Guha, E. Mardis, C. Sarkar, P. Pathak, P. Jha, S. Purkait, V. Sharma, M. C. Sharma, V. Suri, M. Faruq, M. Mukherjee, B. Sivasankaran, R. P. Velayutham, I. R. Fraschilla, K. J. Morris, T. J. MacDonald, T.-A. Read, D. Sturm, D. Jones, A. Korshunov, D. Picard, P. Lichter, S. Pfister, M. Kool, T.-W. Yao, J. Zhang, B. Anna, T. Brummer, N. Gupta, T. Nicolaides, K.-M. Chan, D. Fang, H. Gan, C. Yu, M. Schroeder, R. Jenkins, J. Sarkaria, and Z. Zhang
Subjects: Cancer Research, Engineering, Medical education, Abstracts, Oncology, business.industry, Neurology (clinical), business, Laboratory research
Published: 2013

28. Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma

Author: Janet C. Lindsey, Almos Klekner, Charles G. Eberhart, Scott L. Pomeroy, Andrey Korshunov, Rebecca M Hill, Berivan Baskin, Young Shin Ra, Eric Bouffet, Stefan Rutkowski, William A. Weiss, Ulrich Schüller, Nataliya Zhukova, Steven C. Clifford, Anne Jouvet, David T.W. Jones, Peter Hauser, Peter N. Ray, David W. Ellison, David Shih, Jeffrey R. Leonard, Byung Kyu Cho, Luca Massimi, Toshihiro Kumabe, Seung-Ki Kim, Wiesława Grajkowska, Paul A. Northcott, Dominik Sturm, Nalin Gupta, Cynthia Hawkins, Pedro Castelo-Branco, Trevor J. Pugh, Marco Gessi, David Malkin, Torsten Pietsch, Kyu-Chang Wang, Dianna Martin, M Kool, Karel Zitterbart, Joshua B. Rubin, Linda M. Liau, Erwin G. Van Meir, Simon Bailey, Elke Pfaff, László Bognár, Vijay Ramaswamy, Uri Tabori, Michelle Fèvre-Montange, Marc Remke, André O. von Bueren, Pim J. French, Michael D. Taylor, Nada Jabado, Edward C. Schwalbe, Ian F. Pollack, Maryam Fouladi, Stefan M. Pfister, Shin Jung, Yoon Jae Cho, Max Kros, Boleslaw Lach, Neurology, Pathology, and Pulmonary Medicine
Subjects: Oncology, Gerontology, p53, Male, Cancer Research, endocrine system diseases, Tp53 mutation, Craniospinal radiotherapy, 0302 clinical medicine, 10. No inequality, Child, Cancer, Pediatric, Chromothripsis, ORIGINAL REPORTS, Middle Aged, Prognosis, 030220 oncology & carcinogenesis, Child, Preschool, Female, Adult, medicine.medical_specialty, Adolescent, Pediatric Cancer, Clinical Sciences, Oncology and Carcinogenesis, 03 medical and health sciences, Young Adult, Rare Diseases, Internal medicine, medicine, Genetics, Humans, Oncology & Carcinogenesis, Cerebellar Neoplasms, Preschool, neoplasms, Medulloblastoma, business.industry, Gene Expression Profiling, Neurosciences, Infant, medicine.disease, Genes, p53, Brain Disorders, Brain Cancer, Genes, Li–Fraumeni syndrome, Mutation, business, 030217 neurology & neurosurgery
Abstract: Purpose Reports detailing the prognostic impact of TP53 mutations in medulloblastoma offer conflicting conclusions. We resolve this issue through the inclusion of molecular subgroup profiles. Patients and Methods We determined subgroup affiliation, TP53 mutation status, and clinical outcome in a discovery cohort of 397 medulloblastomas. We subsequently validated our results on an independent cohort of 156 medulloblastomas. Results TP53 mutations are enriched in wingless (WNT; 16%) and sonic hedgehog (SHH; 21%) medulloblastomas and are virtually absent in subgroups 3 and 4 tumors (P < .001). Patients with SHH/TP53 mutant tumors are almost exclusively between ages 5 and 18 years, dramatically different from the general SHH distribution (P < .001). Children with SHH/TP53 mutant tumors harbor 56% germline TP53 mutations, which are not observed in children with WNT/TP53 mutant tumors. Five-year overall survival (OS; ± SE) was 41% ± 9% and 81% ± 5% for patients with SHH medulloblastomas with and without TP53 mutations, respectively (P < .001). Furthermore, TP53 mutations accounted for 72% of deaths in children older than 5 years with SHH medulloblastomas. In contrast, 5-year OS rates were 90% ± 9% and 97% ± 3% for patients with WNT tumors with and without TP53 mutations (P = .21). Multivariate analysis revealed that TP53 status was the most important risk factor for SHH medulloblastoma. Survival rates in the validation cohort mimicked the discovery results, revealing that poor survival of TP53 mutations is restricted to patients with SHH medulloblastomas (P = .012) and not WNT tumors. Conclusion Subgroup-specific analysis reconciles prior conflicting publications and confirms that TP53 mutations are enriched among SHH medulloblastomas, in which they portend poor outcome and account for a large proportion of treatment failures in these patients.
Published: 2013
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29. The Pediatric Brain Tumor Preclinical Testing Program: an update on the current status

Author: Till Milde, Manfred Jugold, S Pfister, Axel Benner, Manuela Zucknick, Hendrik Witt, Andreas E. Kulozik, Andrey Korshunov, Olaf Witt, M Kool, and A. von Deimling
Subjects: medicine.medical_specialty, business.industry, Preclinical testing, Pediatrics, Perinatology and Child Health, Pediatric Brain Tumor, medicine, Medical physics, Current (fluid), business
Published: 2012
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30. LAB-PEDIATRICS LABORATORY RESEARCH

Author: D. Carvalho, L. Bjerke, D. Bax, L. Chen, I. Kozarewa, S. Baker, R. Grundy, A. Ashworth, C. Lord, D. Hargrave, R. M. Reis, C. Jones, S. Bender, W. Feng, D. T. Jones, M. Kool, H. Cin, S. Pleier, S. Hutter, D. Sturm, H.-K. Liu, A. Korshunov, P. Lichter, S. M. Pfister, I. Alimova, D. K. Birks, P. Harris, S. Venkataraman, V. E. Marquez, N. K. Foreman, R. Vibhakar, S. Whiteway, A. Donson, E. Xipell, P. Jauregui, M. Gonzalez, s. tejada-solis, R. Diez-Valle, T. Tunon, I. Zazpe, J. Mora, A. M. Carcaboso, C. Gomez-MAnzano, J. Fueyo, M. Alonso, K. Dorris, M. Sobo, P. Holden, E. Panditharatna, S. Li, A. Margol, C. Stephenson, L. Miles, S. Goldman, S. Asgharzadeh, A. Onar, M. Fouladi, R. Drissi, A. Erdreich-Epstein, X. Ren, H. Zhou, K. Snyder, M. Stamper, J. Perez, J. Nazarian, T. Gershon, A. Crowther, I. Garcia, V. Gama, H. Yuan, S. Chang, M. Deshmukh, M. Hutt, W. Goldstein, A. Price, K. J. Lim, K. Warren, H. Chang, C. G. Eberhart, E. H. Raabe, K. Karakoula, K. P. Phipps, W. Harkness, R. Hayward, D. Thompson, T. S. Jacques, J. L. Darling, T. J. Warr, C. Guldal, C. Potts, R. Rotenberry, A. M. Kenney, V. Amani, A. M. Griesinger, A. M. Donson, L. T. Bemis, S. K. Schittone, M. Morgan, A. Thorburn, J. Mulcahy-Levy, I. Kolkowitz, N. Andor, T. Jensen, A. Banerjee, N. Gupta, C. Petritsch, M. Taylor, R. Hashizume, M. Tom, D. Haas-Kogan, S. Mueller, D. Stearns, N. Ma, R. Levy, D. Gate, J. Rodriguez, J. Breunig, M. Danielpour, and T. Town
Subjects: Cancer Research, medicine.medical_specialty, business.industry, 03 medical and health sciences, Abstracts, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, medicine, Medical physics, Neurology (clinical), Laboratory research, business, 030217 neurology & neurosurgery
Published: 2012

31. Molecular subtypes in medulloblastoma: an International meta-analysis for profiles, genetic aberrations, clinicopathological features AND SURVIVAL

Author: Scott L. Pomeroy, Michael D. Taylor, David W. Ellison, Yoon Jae Cho, S Pfister, A von Buehren, Hendrik Witt, Stefan Rutkowski, François Doz, Olivier Delattre, M Remke, M Kool, Rogier Versteeg, Richard J. Gilbertson, Thorsten Pietsch, Thomas Hielscher, A. Y. N. Schouten-van Meeteren, Steve Clifford, Jan Koster, Paul A. Northcott, Christine Haberler, and Andrey Korshunov
Subjects: Oncology, Medulloblastoma, medicine.medical_specialty, Pathology, business.industry, Meta-analysis, Internal medicine, Pediatrics, Perinatology and Child Health, Medicine, Clinicopathological features, Gene deletion, business, medicine.disease
Published: 2011
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32. Abstracts of papers and posters Clinical Pharmacological Meeting

Author: J. H. G. Jonkman, M. E. L. van der Burg, Th. Thien, A. J. M. Meulendijk, J. Bongaard van den Born, W. Bakker, N. G. M. Schipper, Frans W. H. M. Merkus, S. G. Romeijn, H. Van Belle, M. T. Esselink, D. J. Touw, J. A. Leusink, G. A. Rongen, R. Janknegt, K. Zech, G. Stoter, H. J. Guchelaar, H. Buikema, R. Huber, M. Kool, P. F. M. Kuks, E. Vellenga, M. de Boer-Dennert, J. W. M. Lenders, B. Steffens, L. E. Visser, E. G. E. de Vries, P. G. G. Gerlag, P. A. Van Zwieten, A.H. De Boer, Arijan J. Porsius, L. J. Bras, H. A. J. Struijker Boudier, B. M. de Jonah, H. A. Tissot van Patot, M. Doornbos, H. S. Lau, W. H. Van Gilst, T. A. Bruning, A. J. M. Loonen, John Verhoef, C. A. Verhagen, C. Meijer, J. J. Kraaijenga, A. K. S. van Musscher, A. Bakker, C. D. J. de Langen, P. H. M. van der Kuy, B. H. Ch. Stricker, J. Verweij, K. Ver Donck, P. A. M. Peeters, P.A. de Graeff, Jo Hermans, B. M. de Jongh, A. H. P. Paes, M. Hartmann, T. Dormans, J. H. M. Schellens, M. H. Steurs, D. de Boer, J. G. Grandiean, H. G. M. Heijerman, A. A. T. M. M. Vinks, M. Oosterga, J. J. H. Thijssen, J. Ma, G. Th. J. Fabius, H. Mattie, A. Hoeks, E. van Strijen, Harry Wesseling, P. Smits, J. van der Velden, J. Spek, D. R. A. Uges, A. S. T. Planting, J. J. M. van Mevel, C. H. Doorschot, B. Oosterhuis, P. C. Chang, M. H. A. Engberink, L. Van Bortel, and N. H. Mulder
Subjects: Pharmacology, Medical education, business.industry, Pharmaceutical Science, Medicine, Pharmacology (medical), Pharmacy, General Medicine, Toxicology, business
Published: 1993
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33. Rotary‐screen printing, alive and kicking

Author: R J M Kool
Subjects: Engineering, Polymers and Plastics, business.industry, Western europe, Screen printing, Textile printing, Nanotechnology, business, Telecommunications
Abstract: Over the last three decades rotary-screen printing has become the most important technique for textile printing. In discussing the challenges for the next decade, this paper identifies the trend towards shorter run lengths, particularly in Western Europe, as a major issue. It goes on to discuss the recent technical developments in the field of machine manufacturing, showing that rotary-screen printing is still very much alive.
Published: 1993
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34. The KidsCancerKinome - Validation of Drug Targets for High Risk Childhood Cancers

Author: Katia Scotlandi, M Holst, Gilles Vassal, Rob Pieters, H.N. Caron, Thorsten Pietsch, B Geoerger, Steve Clifford, C Lanvers, Ellen M. Westerhout, M Kool, Stefanie Segers, O Degrand, M L den Boer, Peter Stroeken, J Shipley, Olivier Delattre, Jan J. Molenaar, Rogier Versteeg, Jane Renshaw, R Warps, M Serra, M Benetkiewicz, and Arnauld Verschuur
Subjects: Drug, Oncology, medicine.medical_specialty, business.industry, media_common.quotation_subject, Internal medicine, Pediatrics, Perinatology and Child Health, medicine, business, media_common
Published: 2010
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35. Thoughts on the harmonization of some proposals for a new international actuarial notation

Author: P. Leepin, Carl Boehm, A. I. M. Kool, Manfred Helbig, J. Engelfriet, E. Neuburger, and A. D. Wilkie
Subjects: Actuarial science, business.industry, Applied Mathematics, Accounting, Political science, Mathematical finance, Harmonization, Statistics, Probability and Uncertainty, business, Actuarial notation
Published: 1975
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36. Translation of some sections of C.W. Jordan, society of actuaries textbook on life contingencies, 1967, into the publication language proposed in the paper 'Some thoughts on a harmonization of some proposals for a new international actuarial notation'

Author: A. I. M. Kool, P. Leepin, A. D. Wilkie, J. Engelfriet, Manfred Helbig, Carl Boehm, and E. Neuburger
Subjects: Actuarial science, Present value, Endowment, business.industry, Applied Mathematics, media_common.quotation_subject, Mathematical finance, Harmonization, Public administration, Accounts payable, Actuarial notation, Accounting, Political science, Cash, Statistics, Probability and Uncertainty, business, health care economics and organizations, Retirement age, media_common
Abstract: Many insurers offer policies which provide a combination of insurance coverage up to a fixed retirement age and an annuity income after retirement. Premiums are normally payable until the retirement age is reached. The retirement income is often at the rate of $10 per month for each $1000 of face amount and is customarily payable for a fixed number of years certain and the remainder of life. Under normal circumstances the present value at the retirement age of the annuity income of $10 per month exceeds the face amount of $1000. This means that the policy must nature at the retirement age for an amount greater than the face amount, and that the policy reserves and cash values, in building up to the required maturi ty value, will also exceed the face amount for a period prior to retirement. Since it is impractical to have the face amount of insurance loss than the cash value, these policies provide that the death benefit will be equal to the cash value during the period when the cash value exceeds the face amount. Let 1 ~ k denote the present value at the retirement age, x ~ n, of the annuity to be provided at that age for each unit of face amount issued at age x. Then the policy can be regarded as a combination of a pure endowment of 1 ~ k due at the retirement age and a term insurance up to that age providing a death benefit equal to 1 or the total cash value on the policy whichever is greater. The net premium, P, for tho policy can therefore be written
Published: 1976
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37. A contribution to the discussion on a new international actuarial notation

Author: J. Engelfriet and A. I. M. Kool
Subjects: business.industry, Computer science, Programming language, Applied Mathematics, Mathematical finance, media_common.quotation_subject, USable, Notation, computer.software_genre, Field (computer science), Actuarial notation, Accounting, Artificial intelligence, Statistics, Probability and Uncertainty, business, Function (engineering), computer, Direct transformation, media_common
Abstract: 1. Function names in a computer language have to be unique. 2. Direct transformation of the function names of the present notation into computer names seems highly impracticable. 3. Computer names are not usable for publication purposes by lag of mnemotechnical facilities. 4. An intermediary linearized system of unique function names with a maximum of mnemotechnical facilities and offering the possibility of extending the field of an international notation may be advisable. Other than technical aspects may play a role in the decision to be taken. 5. It seems possible to develop a language satisfying the demands formulated in 4.
Published: 1973
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38. MANIP A Modelling and Simulation Tool for Thermal Engineers

Author: A. Lebru and R. J. M. Kool
Subjects: Engineering, business.industry, Thermal, Systems engineering, business
Published: 1989
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39. WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma

Author: Marc Remke, André O. von Bueren, Alexandre Vasiljevic, Nataliya Zhukova, Wiesława Grajkowska, Pim J. French, Luca Massimi, Byung Kyu Cho, Cynthia Hawkins, M Kool, Uri Tabori, Pedro Castelo-Branco, Marco Gessi, Berivan Baskin, Dianna Martin, William A. Weiss, Karel Zitterbart, Peter Hauser, Charles G. Eberhart, Joshua B. Rubin, Raymond Poon, Eric Bouffet, Seung-Ki Kim, Cecile Faure Conter, Boleslaw Lach, Michael D. Taylor, László Bognár, Steven C. Clifford, Stefan M. Pfister, Scott L. Pomeroy, Shin Jung, David Malkin, Yoon Jae Cho, Torsten Pietsch, Toshihiro Kumabe, Peter N. Ray, Young Shin Ra, Nada Jabado, David T.W. Jones, Erwin G. Van Meir, Linda M. Liau, Andrey Korshunov, Cindy Zhang, Ken Tse, Elke Pfaff, Michael Fraser, Ian F. Pollack, Robert G. Bristow, Maryam Fouladi, Stefan Rutkowski, Peter B. Dirks, Paul A. Northcott, Nalin Gupta, Trevor J. Pugh, Kyu-Chang Wang, David Shih, Jeffrey R. Leonard, Benjamin A. Alman, Vijay Ramaswamy, Almos Klekner, and Neurology
Subjects: Male, Pathology, endocrine system diseases, medicine.medical_treatment, International Cooperation, Mutant, medicine.disease_cause, Cohort Studies, 0302 clinical medicine, Child, Wnt Signaling Pathway, beta Catenin, 0303 health sciences, Mutation, biology, Wnt signaling pathway, Neural stem cell, 3. Good health, 030220 oncology & carcinogenesis, Child, Preschool, Neoplastic Stem Cells, Female, medicine.medical_specialty, Beta-catenin, Adolescent, Cell Survival, Lithium, Pathology and Forensic Medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, Radioresistance, Cell Line, Tumor, medicine, Humans, Cerebellar Neoplasms, neoplasms, 030304 developmental biology, Medulloblastoma, Radiotherapy, business.industry, Research, medicine.disease, Radiation therapy, Wnt Proteins, biology.protein, Cancer research, Neurology (clinical), Tumor Suppressor Protein p53, business
Abstract: TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6% +/- 8.7%, respectively (p < 0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89% +/- 2% vs. 57.4% +/- 1.8% (p < 0.01)). In contrast, beta-catenin mutation sensitized TP53 mutant cells to radiation (p < 0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5% +/- 1.5% in lithium treated cells vs. 56.6 +/- 3% (p < 0.01)) accompanied by increased number of.H2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33% +/- 8% for lithium treated cells vs. 27% +/- 3% for untreated controls (p = 0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas. B.R.A.I.N Child Canada; Cancer Research UK; Brain Tumour Charity; Hungarian Brain Research Program [KTIA_13_NAP-A-V/3]; Janos Bolyai Scholarship of the Hungarian Academy of Sciences [TAMOP-4.2.2. A-11/1/KONV-2012-0025]; German Cancer Aid/Dr. Mildred Scheel Foundation for Cancer Research; Cure Childhood Cancer Foundation; St. Baldrick's Foundation; Southeastern Brain Tumor Foundation; Action Medical Research; [CZ.1.05/2.1.00/03.0101]; [CZ.1.07/2.3.00/20.0183]
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