12 results on '"Sven Krengel"'
Search Results
2. Development of an international core domain set for medium, large and giant congenital melanocytic naevi as a first step towards a core outcome set for clinical practice and research
- Author
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M S van Kessel, Sven Krengel, C. M. A. M. van der Horst, Heather C. Etchevers, W Oei, Albert Wolkerstorfer, A C Fledderus, Ph.I. Spuls, Suzanne G.M.A. Pasmans, I.J. Korfage, C.A.M. Eggen, Jan Kottner, Dermatology, APH - Methodology, APH - Quality of Care, Plastic, Reconstructive and Hand Surgery, ACS - Atherosclerosis & ischemic syndromes, AMS - Musculoskeletal Health, AMS - Rehabilitation & Development, Amsterdam Movement Sciences, ACS - Diabetes & metabolism, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Naevus International Patient Representative Working Group Leader, Dermatological group practice, Lübeck, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Association du Naevus Géant Congénital, Naevus 2000 France-Europe and the Asociación Española de Nevus Gigante Congénito, Gall, Valérie, and Public Health
- Subjects
medicine.medical_specialty ,Consensus ,Delphi Technique ,Best practice ,MEDLINE ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Dermatology ,Outcome (game theory) ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,melanoma ,Humans ,Medicine ,Patient Reported Outcome Measures ,Set (psychology) ,Nevus, Pigmented ,congenital nevi ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,business.industry ,outcome domains ,Core outcome set ,Focus group ,3. Good health ,Clinical trial ,Treatment Outcome ,clinical research ,Research Design ,Family medicine ,Quality of Life ,business ,Psychosocial ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Background: Medium, large and giant congenital melanocytic naevi (CMN) can impose a psychosocial burden on patients and families, and are associated with increased risk of developing melanoma or neurological symptoms. Lack of consensus on what outcomes to measure makes it difficult to advise patients and families about treatment and to set up best practice for CMN. Objectives: Fostering consensus among patient representatives and professionals, we aim to develop a core outcome set, defined as the minimum set of outcomes to measure and report in care and all clinical trials of a specific health condition. We focused on the ‘what to measure’ aspect, the so-called core domain set (CDS), following the COMET and CS-COUSIN guidelines. Methods: We conducted a systematic review to identify outcomes reported in the literature. Focus groups with patient representatives identified patient-reported outcomes. All these outcomes were classified into domains. Through e-Delphi surveys, 144 stakeholders from 27 countries iteratively rated the importance of domains and outcomes. An online consensus meeting attended by seven patient representatives and seven professionals finalized the CDS. Results: We reached consensus on six domains, four of which were applied to both care and research: ‘quality of life’, ‘neoplasms’, ‘nervous system’ and ‘anatomy of skin’. ‘Adverse events’ was specific to care and ‘pathology’ to research. Conclusions: We have developed a CDS for medium-to-giant CMN. Its application in reporting care and research of CMN will facilitate treatment comparisons. The next step will be to reach consensus on the specific outcomes for each of the domains and what instruments should be used to measure these domains and outcomes.
- Published
- 2021
3. Combinatorial effects of azacitidine and trametinib on NRAS ‐mutated melanoma
- Author
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Klara‐Maria Hanft, Ebrahem Hamed, Max Kaiser, Julia Würtemberger, Michaela Schneider, Torsten Pietsch, Ursula Feige, Frank Meiss, Sven Krengel, Charlotte Niemeyer, and Simone Hettmer
- Subjects
Male ,Mitogen-Activated Protein Kinase Kinases ,Nevus, Pigmented ,Skin Neoplasms ,Pyridones ,Membrane Proteins ,Pyrimidinones ,Hematology ,GTP Phosphohydrolases ,Oncology ,Child, Preschool ,Mutation ,Pediatrics, Perinatology and Child Health ,Azacitidine ,Meningeal Neoplasms ,Humans ,Melanoma ,Protein Kinase Inhibitors - Abstract
Congenital melanocytic nevus (CMN) syndrome represents a mosaic RASopathy, typically caused by postzygotic NRAS codon 61 mutations, which originate in ectodermal precursor cells and result in melanocyte deposits in the skin and central nervous system (CNS). Affected patients are prone to develop uniformly fatal melanomas in the skin and CNS. Here, we report the case of a 2.7-year-old male with CMN syndrome, diffuse leptomeningeal melanosis and CNS melanoma, who underwent experimental therapy with the DNA methyltransferase inhibitor azacitidine in combination with the mitogen-activated protein kinase (MEK) inhibitor trametinib with exceptional clinical and radiological response. Response to combination therapy appeared to be more durable than the treatment response observed in several other severely affected patients treated with trametinib for late-stage disease. Correspondingly, concomitant exposure to trametinib and azacitidine prevented development of trametinib resistance in NRAS-mutated human melanoma cells in vitro. Also, azacitidine was shown to inhibit growth and mitogen-activated protein kinase 1/2 (ERK1/2) phosphorylation of melanoma cells and act synergistically with trametinib to inhibit the growth of trametinib-resistant melanoma cells. These observations suggest that azacitidine enhances trametinib monotherapy and may represent a promising candidate drug for combination therapies to enhance the efficacy of MEK inhibitors in RAS-driven diseases.
- Published
- 2021
4. Giant Congenital Melanocytic Nevus Accompanied by an Intracranial Arachnoid Cyst
- Author
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Sven Krengel, Sara Dusel, Alexander Enk, Christine Fink, Ferdinand Toberer, Nina Trenkler, and Holger A. Haenssle
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Intracranial arachnoid ,Pathology ,medicine.medical_specialty ,business.industry ,giant congenital melanocytic nevus ,Articles ,Dermatology ,medicine.disease ,Oncology ,Arachnoid cyst ,Congenital melanocytic nevus ,RL1-803 ,arachnoid cyst ,Genetics ,medicine ,melanoma risk ,Cyst ,neurocutaneous melanocytosis ,business ,Molecular Biology ,Neurocutaneous melanocytosis - Published
- 2019
5. Giant congenital melanocytic nevus with vascular malformation and epidermal cysts associated with a somatic activating mutation in BRAF
- Author
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Frédéric Fina, Helmuth Vorbringer, Christian Rose, Pauline Heux, Benjamin Schwarz, Nicolas Macagno, Birgit Kahle, Stéphane Zaffran, Sven Krengel, Irina Berger, Heather C. Etchevers, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Catholique de Lille - Faculté de Médecine, Maïeutique, Sciences de la santé (FMMS), Institut Catholique de Lille (ICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Universitätsklinikum Schleswig-Holstein, Service d'Anatomo-Cyto-Pathologie et de NeuroPathologie [Hôpital de la Timone - APHM] (ACPNP), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), This study was supported by grants from Nevus Outreach, Inc., Asociación Española de afectados por Nevus Gigante Congénito, Association du Naevus Géant Congénital, Naevus 2000 France-Europe, Caring Matters Now, the RE(ACT) Community and aid-in-kind from the BeHeard Rare Disease Science Challenge., Université catholique de Lille - Faculté de médecine et de maïeutique (UCL FMM), Université catholique de Lille (UCL), and Etchevers, Heather
- Subjects
Male ,Proto-Oncogene Proteins B-raf ,0301 basic medicine ,Neuroblastoma RAS viral oncogene homolog ,Pathology ,medicine.medical_specialty ,melanocyte ,Vascular Malformations ,[SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Epidermal Cyst ,Dermatology ,[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics ,Biology ,General Biochemistry, Genetics and Molecular Biology ,BRAF ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Congenital melanocytic nevus ,medicine ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Humans ,Nevus ,HRAS ,skin and connective tissue diseases ,neoplasms ,Aged ,Nevus, Pigmented ,venous ,GNA11 ,integumentary system ,Vascular malformation ,congenital ,[SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology ,medicine.disease ,malformation ,030104 developmental biology ,Oncology ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Mutation ,Venous malformation ,GNAQ ,[SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology ,nevus - Abstract
International audience; Giant congenital melanocytic nevi may be symptomatically isolated, or syndromic. Associations with capillary malformations are exceptional, and development of epidermal cysts has not been described. A 71-year old patient with a giant congenital melanocytic nevus of the lower back, buttocks and thighs was asymptomatic except for unexpected hemorrhage during partial surgical excision years before. Blunt trauma at age 64 initiated recurrent, severe pain under the nevus; multiple large epidermal cysts developed within it. Imaging and biopsy showed a large, non-pulsatile venous malformation intermingled with the deep nevus. A low-abundance, heterozygous BRAF c.1799T>A (p.V600E) mutation was present in both the gluteal and occipital “satellite” nevi; additional mutations in NRAS, GNAQ, GNA11, HRAS and PIK3CA were undetectable. This is the first demonstration of an identical BRAF mutation in multiple congenital nevi from the same individual, confirming genetic heterogeneity in giant nevi. This exceptional case indicates that constitutive activation of BRAF can be an underlying cause of unusual associations of giant nevi with vascular malformations, and that the latter may be included among the somatic RASopathies.
- Published
- 2018
6. Symmetric Plantar Melanocytic Nevi - Site-Specific Phenomenon or Pure Chance
- Author
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O Haase and Sven Krengel
- Subjects
Medial part ,medicine.medical_specialty ,Skin cancer screening ,integumentary system ,business.industry ,Mean age ,Trunk ,Dermatology ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Plantar arch ,030220 oncology & carcinogenesis ,medicine.artery ,medicine ,Foot arch ,Random event ,skin and connective tissue diseases ,business ,neoplasms ,Prospective survey - Abstract
Background: Predilection sites of melanocytic nevi are highly variable; however, individual patterns (e.g. preponderant involvement of extremities, trunk, etc.) are often noticed. A symmetric appearance of nevi on both sides of the body has not been reported. Objective: Guided by an initial, incidental observation of symmetrically arranged plantar nevi, a prospective survey of palmoplantar nevi was carried out. Methods: Between January 2016, and January 2017, 886 patients underwent a full-body examination for skin cancer screening. Special attention was paid to the pigmentary characteristics of the palms and soles. Results: 12/886 patients exhibited symmetrically or nearly symmetrically distributed plantar nevi (1.35%; mean age 45 years; male-female ratio 1:1). The nevi were mostly situated on the medial part of the plantar arch (9/12 cases; 75%). Remarkably, not a single case of symmetric nevi was identified on the palms. Conclusion: Arguments in favour of the specifity of the finding are: 1) the lack of comparable findings in palmar skin, i.e., in a similar histological compartment and 2) the predominant localization in the foot arch. Symmetric plantar nevi appear to be a rare, but not a random event. Possible underlying causes of this phenomenon are discussed.
- Published
- 2017
7. Profiling the Response of Human Hair Follicles to Ultraviolet Radiation
- Author
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Wolfgang Funk, Tobias W. Fischer, Zhong-Fa Lu, Koji Sugawara, Mark Berneburg, Ralf Paus, York Kamenisch, Sven Krengel, and Sybille Hasse
- Subjects
Keratinocytes ,Programmed cell death ,Ultraviolet Rays ,Connective tissue ,Apoptosis ,Human skin ,DNA Fragmentation ,Dermatology ,Biology ,Biochemistry ,Inner root sheath ,Cell Degranulation ,Transforming Growth Factor beta2 ,chemistry.chemical_compound ,Organ Culture Techniques ,Adrenocorticotropic Hormone ,Lactate dehydrogenase ,medicine ,Humans ,Mast Cells ,Molecular Biology ,Melanins ,integumentary system ,Degranulation ,Cell Differentiation ,Dose-Response Relationship, Radiation ,Cell Biology ,Hair follicle ,Mitochondria ,Cell biology ,Oxidative Stress ,medicine.anatomical_structure ,chemistry ,alpha-MSH ,Immunology ,Female ,Keratinocyte ,Hair Follicle ,Cell Division ,Hair - Abstract
Excessive UVR ranks among the most harmful environmental influences on human skin. However, the direct impact of UVR on human skin appendages remains to be systematically investigated. Organ-cultured human anagen hair follicles in vitro were irradiated, and reduction of hair shaft elongation, premature catagen entry, and reduced hair matrix keratinocyte proliferation were observed upon irradiation with UVB (20/50 mJ cm(-2)). At 20 mJ cm(-2), apoptotic cell death prevailed (casp-3/p53 activation), whereas at 50 mJ cm(-2), necrotic cell death was predominant (lactate dehydrogenase increase). Mitochondrial common deletion and oxidatively damaged genomic DNA (8-OH-dG) was mainly observed at 20 mJ cm(-2). Follicular melanogenesis and ACTH immunoreactivity drastically declined, but alpha-melanocyte-stimulating hormone remained unchanged, whereas transforming growth factor-beta(2) expression shifted from the outer toward the inner root sheath. Both the number of Giemsa+ mast cells and the degree of mast-cell degranulation increased in the connective tissue sheath (CTS), and CD117 immunoreactivity of CTS cells and matrix keratinocytes was upregulated. Thus, UVR differentially modifies hair growth and cycle, promotes cell death, and induces complex regulatory events in human hair follicles in vitro. The leads from this human organ model, which is a living and human tissue interaction system under physiologically relevant in situ conditions, may encourage its use for general investigation of UV-induced effects as well as for testing possible agents for their UV-protective potency.
- Published
- 2009
8. Clinical and epidemiological aspects of subtypes of melanocytic nevi (Flat nevi, Miescher nevi, Unna nevi)
- Author
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Constanze Witt and Sven Krengel
- Subjects
Adult ,Male ,medicine.medical_specialty ,Skin Neoplasms ,Keratosis ,Adolescent ,Dermatology ,Neoplasms, Multiple Primary ,Young Adult ,Epidemiology ,medicine ,Nevus ,Humans ,Age of Onset ,skin and connective tissue diseases ,Caucasian population ,Head and neck ,Child ,Keratosis, Seborrheic ,neoplasms ,Aged ,Aged, 80 and over ,Lentigo ,Nevus, Pigmented ,integumentary system ,business.industry ,Melanoma ,General Medicine ,Melanocytic nevus ,Middle Aged ,medicine.disease ,Child, Preschool ,Sunlight ,Female ,Age of onset ,Facial Neoplasms ,business - Abstract
The term "melanocytic nevus" comprises a group of clinically and pathologically distinct subtypes. In this prospective clinical study we evaluated the frequency, localization, and age and gender distribution of flat nevi (FN), Miescher nevi (MN), and Unna nevi (UN) in a caucasian population. Nevi were counted in 400 patients, of which 47 had a history of melanoma. Additionally, the patients answered to a detailed UV questionnaire. Flat nevi represented the most common type of melanocytic nevi, with a peak in the 3rd decade of life. They were mostly found on the extremities and on the trunk. Miescher nevi were most common in the 6th decade and were predominantly found in the head and neck region. Unna nevi showed a maximum in the 8th decade and they were mainly situated on the trunk. The counts of all three nevus subtypes were elevated in the melanoma group. Our results confirm that FN, MN, and UN represent melanocytic nevi with distinctive morphological and clinical characteristics. The role of sunlight seems to be more prominent in the pathogenesis of FN. The precise description of FN, MN, and UN may serve as a base for a pathogenetic distinction of subtypes of melanocytic nevi in the future.
- Published
- 2010
9. [The role of eotaxins in bronchial asthma and nasal polyposis]
- Author
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Luis M, Terán, Yadira, Ledesma-Soto, Sven, Krengel, and Diana, Lezcano-Meza
- Subjects
Chemokine CCL11 ,Nasal Polyps ,Chemokine CCL26 ,Chemokines, CC ,Chemokine CCL24 ,Humans ,Asthma - Abstract
Over the last few years, three specific eosinophil activating peptides, eotaxin-1, -2 and -3, members of the chemokine family have been identified. These cytokines exert a number of functions on eosinophils including chemotaxis, transendothelial migration and induction of the release of reactive oxygen species. Eosinophils are considered to play an important role in allergic disease by causing tissue damage through the release of toxic proteases, lipid mediators, cytokines and oxygen free radicals. This article reviews the role of eotaxins in asthma and nasal polyps. Discussion focuses on therapeutic guidelines, particularly as it has been shown that CCR3, the major chemokine receptor in eosinophils, serves as a eotaxin receptor.
- Published
- 2006
10. Absence of autoantibodies against correctly folded recombinant fibrillin-1 protein in systemic sclerosis patients
- Author
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Jürgen, Brinckmann, Nico, Hunzelmann, Ehab, El-Hallous, Thomas, Krieg, Lynn Y, Sakai, Sven, Krengel, and Dieter P, Reinhardt
- Subjects
Male ,Extracellular Matrix Proteins ,Protein Folding ,Scleroderma, Systemic ,integumentary system ,Fibrillin-1 ,Microfilament Proteins ,Enzyme-Linked Immunosorbent Assay ,macromolecular substances ,Middle Aged ,Fibrillins ,Recombinant Proteins ,Microscopy, Electron, Transmission ,Humans ,Female ,skin and connective tissue diseases ,Protein Structure, Quaternary ,Cells, Cultured ,Autoantibodies ,Research Article - Abstract
Autoantibodies against short recombinant fragments of fibrillin-1 produced in bacterial expression systems have been found in tight-skin mouse, systemic sclerosis, mixed connective tissue disease, and primary pulmonary hypertension syndrome. In patients with scleroderma, the frequency of anti-fibrillin-1 antibodies was 42% in Caucasians. Until now it has been unclear whether this immune response has a primary function in disease pathogenesis or is a secondary phenomenon. In the present study we analyzed the frequency of autoantibodies against two overlapping recombinant polypeptides spanning the N-terminal and C-terminal halves of human fibrillin-1, which were produced in human embryonic kidney (HEK-293) cells. Correct three-dimensional structures of the recombinant fibrillin-1 polypeptides were shown by electron microscopy and immunoreactivity with antibodies. Screening of fibrillin-1 antibodies was performed in 41 sera from systemic sclerosis patients and in 44 healthy controls with a Caucasian background. Microtiter plates were coated with the recombinant polypeptides of fibrillin-1 and incubated with 1:100 diluted sera. Positive binding was defined as being more than 2 SD above the mean of the control group. ELISAs showed that none of the sera of patients with systemic sclerosis contained autoantibodies against the N-terminal or C-terminal recombinant fibrillin-1 polypeptide. The data show the absence of autoantibodies against recombinant fibrillin-1 protein in Caucasian systemic sclerosis patients. Because the correct three-dimensional folding of the recombinant proteins has been substantiated by several independent methods, we conclude that autoantibodies against correctly folded fibrillin are not a primary phenomenon in the pathogenesis of systemic sclerosis.
- Published
- 2005
11. Rheumatoid Nodules Developing under Methotrexate Treatment for Rheumatoid Arthritis
- Author
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Christos C. Zouboulis, Ulrike Blume-Peytavi, C. E. Orfanos, T. N. Y. Duong, and Sven Krengel
- Subjects
Methotrexate treatment ,medicine.medical_specialty ,business.industry ,Rheumatoid arthritis ,Medicine ,Rheumatoid nodule ,Dermatology ,General Medicine ,medicine.symptom ,business ,medicine.disease - Published
- 1999
12. [Untitled]
- Author
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Thomas Krieg, Nico Hunzelmann, Dieter P. Reinhardt, Lynn Y. Sakai, Jürgen Brinckmann, Ehab I. El-Hallous, and Sven Krengel
- Subjects
Pathology ,medicine.medical_specialty ,integumentary system ,Immunology ,Autoantibody ,macromolecular substances ,Biology ,medicine.disease ,Scleroderma ,law.invention ,Pathogenesis ,Mixed connective tissue disease ,Immune system ,Rheumatology ,law ,medicine ,biology.protein ,Recombinant DNA ,Immunology and Allergy ,Antibody ,skin and connective tissue diseases ,Fibrillin - Abstract
Autoantibodies against short recombinant fragments of fibrillin-1 produced in bacterial expression systems have been found in tight-skin mouse, systemic sclerosis, mixed connective tissue disease, and primary pulmonary hypertension syndrome. In patients with scleroderma, the frequency of anti-fibrillin-1 antibodies was 42% in Caucasians. Until now it has been unclear whether this immune response has a primary function in disease pathogenesis or is a secondary phenomenon. In the present study we analyzed the frequency of autoantibodies against two overlapping recombinant polypeptides spanning the N-terminal and C-terminal halves of human fibrillin-1, which were produced in human embryonic kidney (HEK-293) cells. Correct three-dimensional structures of the recombinant fibrillin-1 polypeptides were shown by electron microscopy and immunoreactivity with antibodies. Screening of fibrillin-1 antibodies was performed in 41 sera from systemic sclerosis patients and in 44 healthy controls with a Caucasian background. Microtiter plates were coated with the recombinant polypeptides of fibrillin-1 and incubated with 1:100 diluted sera. Positive binding was defined as being more than 2 SD above the mean of the control group. ELISAs showed that none of the sera of patients with systemic sclerosis contained autoantibodies against the N-terminal or C-terminal recombinant fibrillin-1 polypeptide. The data show the absence of autoantibodies against recombinant fibrillin-1 protein in Caucasian systemic sclerosis patients. Because the correct three-dimensional folding of the recombinant proteins has been substantiated by several independent methods, we conclude that autoantibodies against correctly folded fibrillin are not a primary phenomenon in the pathogenesis of systemic sclerosis.
- Published
- 2005
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