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Autor(en)	Titel	Quelle

Jackson HA, Carter K, Darke C, Guttridge MG, Ravine D, Hutton RD, Napier JA, Worwood M	HFE mutations, iron deficiency and overload in 10,500 blood donors.	British journal of haematology 2001, 114: 474
People with genetic haemochromatosis (GH) accumulate iron from excessive dietary absorption. In populations of northern European origin, over 90% of patients are homozygous for the C282Y mutation of the HFE gene. While about 1 in 200 people in the general population have this genotype the proportion who develop clinical haemochromatosis is not known. The influence of HFE genotype on iron status was investigated in 10 556 blood donors. The allele frequencies of the C282Y and H63D mutations were 8.23% and 15.3% respectively. Heterozygosity for C282Y occurred in 1 in 7.9 donors, for H63D in 1 in 4.2 donors, and 1 in 42 were compound heterozygotes. Homozygosity for H63D occurred in 1 in 42 donors and 1 in 147 (72) were homozygous for C282Y. Mean values increased for transferrin saturation (TS) and serum ferritin (sFn), and decreased for unsaturated iron binding capacity (UIBC) in the order: donors lacking the mutations, H63D heterozygotes, C282Y heterozygotes, H63D homozygotes, compound heterozygotes and C282Y homozygotes, but serum ferritin (sFn) concentrations were no higher in H63D heterozygotes and C282Y heterozygous women than in donors lacking mutations. The percentage of donors failing the screening test for anaemia or of those with sFn < 15 microg/l did not differ among the genotype groups. C282Y and H63D heterozygotes and donors homozygous for H63D were at no greater risk of iron accumulation than donors lacking mutations, of whom 1 in 1200 had both a raised TS and sFn. The risk was higher for compound heterozygotes (1 in 80, P = 0.003) and for C282Y homozygotes (1 in 5, P < 0.0001). There was no correlation between sFn and either age or donation frequency in C282Y homozygotes. None of the 63 C282Y homozygous donors interviewed showed physical signs of overload or were aware of relatives with haemochromatosis. The Welsh Blood Service collects blood from about 140 000 people each year including an estimated 950 who are homozygous for HFE C282Y. They are probably healthy and unaware of any family history of iron overload.
Jacobi G, Korinthenberg R, Rutkowski S	Diagnostik der Hirntumoren.	Interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft (in Zusammenarbeit der Gesellschaft für Neuropädiatrie und der Gesellschaft für Pädiatrische Onkologie und Hämatologie 2006
Jackson TJ, Brisse HJ, Pritchard-Jones K, Nakata K, Morosi C, Oue T, Irtan S, Vujanic G, van den Heuvel-Eibrink MM, Graf N, Chowdhury T, SIOP RTSG Biopsy Working Group	How we approach paediatric renal tumour core needle biopsy in the setting of preoperative chemotherapy: A Review from the SIOP Renal Tumour Study Group.	Pediatric blood & cancer 2022, 69:e29702
The International Society of Paediatric Oncology Renal Tumour Study Group (SIOP-RTSG) advocate treating children with Wilms tumour (WT) with preoperative chemotherapy, whereas the Renal Tumor Committee of the Children's Oncology Group (COG) advocates primary nephrectomy (without biopsy) when feasible. Successive SIOP-RTSG trial protocols recommended pretreatment biopsy of children with unilateral tumours only where there were features to suggest an increased probability of a non-WT requiring a change in management. The UK experience in the SIOP WT 2001 trial showed that an alternate approach of performing biopsies on all children with renal tumour masses to determine histology at diagnosis rarely changes management, and can result in misdiagnosis (particularly patients in the age range typical for WT). Although a more selective approach to biopsy has been routine practice in all other countries participating in SIOP-RTSG trials, there was variation between national groups. To address this variation and provide evidence-based recommendations for the indications and recommended approach to renal tumour biopsy within the SIOP paradigm, an international, multidisciplinary working group of SIOP-RTSG members was convened. We describe the resulting recommendations of this group, which are to be incorporated in the ongoing SIOP-RTSG UMBRELLA study.
Jaffe ES et al.	World Health Organization classification of tumours. Pathology and genetics of tumours of hematopoietic and lymphoid tissues.	IARC Press, Lyon 2001
Jaffe ES, Harris NL, Stein H, Isaacson PG	Classification of lymphoid neoplasms: the microscope as a tool for disease discovery.	Blood 2008 Dec 1; 112: 4384
In the past 50 years, we have witnessed explosive growth in the understanding of normal and neoplastic lymphoid cells. B-cell, T-cell, and natural killer (NK)-cell neoplasms in many respects recapitulate normal stages of lymphoid cell differentiation and function, so that they can be to some extent classified according to the corresponding normal stage. Likewise, the molecular mechanisms involved the pathogenesis of lymphomas and lymphoid leukemias are often based on the physiology of the lymphoid cells, capitalizing on deregulated normal physiology by harnessing the promoters of genes essential for lymphocyte function. The clinical manifestations of lymphomas likewise reflect the normal function of lymphoid cells in vivo. The multiparameter approach to classification adopted by the World Health Organization (WHO) classification has been validated in international studies as being highly reproducible, and enhancing the interpretation of clinical and translational studies. In addition, accurate and precise classification of disease entities facilitates the discovery of the molecular basis of lymphoid neoplasms in the basic science laboratory.
Jaffe N, Bruland O S, Bielack S	Pediatric and Adolescent Osteosarcoma.	Cancer Treatment and Research Vol. 152 2010
James RM, Kinsey SE	The investigation and management of chronic neutropenia in children.	Archives of disease in childhood 2006, 91: 852
Unravelling the cause of a neutropenia poses a complex diagnostic challenge. The differential diagnosis ranges from life threatening disease to transient benign causes of little clinical significance. This review offers a practical guide to investigating the neutropenic child, and highlights features that merit specialist referral. Therapeutic options, the role of long term follow up, and the complications of severe chronic neutropenia are considered.
Janka-Schaub G, Stuehrk H, Kortuem B, Graubner U, Haas R, Göbel U, Jürgens H, Spaar H, Winkler K	Bone marrow blast count at day 28 as the single most important prognostic factor in childhood acute lymphoblastic leukemia.	Haematol Blood Transfus 1992, 34A92211, 233
Janka-Schaub G	Immunological factors and childhood leukaemias-pathophysiological and clinical perspectives.	Anonymous Medizinische Forschung 1993, 183
Janka-Schaub G, Gobrecht O, Gross S	Dose intensity and prognosis in acute lymphocytic leukemia in childhood.	Hämatol Blood Transf 1994, 36
Janka-Schaub G, Harms D, Goebel U, Graubner U, Gutjahr P, Haas R, Jürgens H, Spaar H, Winkler K	Randomized comparison of rotational chemotherapy in high-risk acute lymphoblastic leukaemia of childhood--follow up after 9 years. Coall Study Group.	Eur J Pediatr 1996, 155: 640
Janka-Schaub G, Harms D, Den Boer M, Veerman A, Pieters R	In vitro drug resistance as independent prognostic factor in the study COALL-O5-92 Treatment of childhood acute lymphoblastic leukemia; two-tiered classification of treatments based on accepted risk criteria and drug sensitivity profiles in study COALL-06-97.	Klin Pädiatr 1999, 211: 233
Janoueix-Lerosey I, Penther D, Thioux M, de Cremoux P, Derre J, Ambros P, Vielh P, Benard J, Aurias A, Delattre O	Molecular analysis of chromosome arm 17q gain in neuroblastoma.	Genes Chromosomes Cancer 2000, 28: 276
Jankovic M, Reciputo A, Haupt R, Micalizzi C, Manganini C, Frey E, Lackner H, Maurus R, Beck J, Langer T, Marx M, Krappmann P, Magyarosy E, Feldges A, Weel-Sipman M	ELTEC.	Med Pediatr Oncol 2002, 38
Janßen K	Chemische Umwelttoxikologie, in: Gutjahr P (Hrsg.): Krebs bei Kindern und Jugendlichen.	Deutscher Ärzte-Verlag Köln 5. Aufl. 2004, 64
Janka GE	Familial and acquired hemophagocytic lymphohistiocytosis.	European journal of pediatrics 2007, 166: 95
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of severe hyperinflammation caused by the uncontrolled proliferation of activated lymphocytes and histiocytes secreting high amounts of inflammatory cytokines. Cardinal signs and symptoms are prolonged fever, hepatosplenomegaly and pancytopenia. Characteristic biochemical markers include elevated triglycerides, ferritin and low fibrinogen. HLH occurs on the basis of various inherited or acquired immune deficiencies. Impaired function of natural killer (NK) cells and cytotoxic T-cells (CTL) is shared by all forms of HLH. Genetic HLH occurs in familial forms (FHLH) in which HLH is the primary and only manifestation, and in association with the immune deficiencies Chédiak-Higashi syndrome 1 (CHS 1), Griscelli syndrome 2 (GS 2) and x-linked lymphoproliferative syndrome (XLP), in which HLH is a sporadic event. Most patients with acquired HLH have no known underlying immune deficiency. Both acquired and genetic forms are triggered by infections, mostly viral, or other stimuli. HLH also occurs as a complication of rheumatic diseases (macrophage activation syndrome) and of malignancies. Several genetic defects causing FHLH have recently been discovered and have elucidated the pathophysiology of HLH. The immediate aim of therapy in genetic and acquired HLH is suppression of the severe hyperinflammation, which can be achieved with immunosuppressive/immunomodulatary agents and cytostatic drugs. Patients with genetic forms have to undergo stem cell transplantation to exchange the defective immune system with normally functioning immune effector cells.In conclusion, awareness of the clinical symptoms and of the diagnostic criteria of HLH is crucial in order not to overlook HLH and to start life-saving therapy in time.
Janka GE	Hemophagocytic syndromes.	Blood reviews 2007, 21: 245
Hemophagocytic syndromes (hemophagocytic lymphohistiocytosis, HLH) represent a severe hyperinflammatory condition with the cardinal symptoms prolonged fever, cytopenias, hepatosplenomegaly, and hemophagocytosis by activated, morphologically benign macrophages. Biochemical markers include elevated ferritin and triglycerides, and low fibrinogen. Whereas in children several inherited immune deficiencies may lead to this syndrome, most adults with HLH have no known underlying immune defect. Nevertheless, impaired function of natural killer (NK) cells and cytotoxic T-cells (CTL) is characteristic for both genetic and acquired forms of HLH. Frequent triggers are infectious agents, mostly viruses of the herpes group. Malignant lymphomas, especially in adults, may be associated with HLH. A special form of HLH in rheumatic diseases is called macrophage-activation syndrome. Initially HLH may masquerade as a normal infection since all symptoms, even though less pronounced, may also be found in immune competent patients. Patients with HLH, however, cannot control the hyperinflammatory response which, if untreated, is fatal in genetic cases and in a high percentage of acquired cases. Awareness of the clinical symptoms and of the diagnostic criteria of HLH is important to start life-saving therapy with immunosuppressive/immunomodulatory agents in time.
Janka GE	Familial and acquired hemophagocytic lymphohistiocytosis.	Annual review of medicine 2012, 63: 233
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome in which an uncontrolled and ineffective immune response, triggered in most cases by infectious agents, leads to severe hyperinflammation. Familial forms of HLH (FHL), which are increasingly found also in adolescents and adults, are due to genetic defects leading to impaired function of natural killer cells and cytotoxic T cells. These mutations occur either in the perforin gene or in genes important for the exocytosis of cytotoxic granules. Cytotoxic granules contain perforin and granzymes, which induce apoptosis upon entering (infected) target cells. Additionally, perforin is important for the downregulation of the immune response. Acquired forms of HLH are encountered in association with (usually) viral infections, autoinflammatory/autoimmune diseases, malignant diseases, and acquired immune deficiency states (e.g., after organ transplantation). Treatment of HLH includes immune-suppressive and immune-modulatory agents, cytostatic drugs, and biological response modifiers. For patients with FHL, stem cell transplantation is indicated and can be curative.
Janka GE, Lehmberg K	Hemophagocytic syndromes-an update.	Blood reviews 2014, 28: 135
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome and not an independent disease. HLH represents the extreme end of a severe uncontrolled hyperinflammatory reaction that can occur in many underlying conditions. Genetic forms of HLHs are due to defects in transport, processing and function of cytotoxic granules in natural killer cells and cytotoxic T lymphocytes, and are not restricted to manifestation in childhood. Acquired forms of HLH are encountered in infections, autoinflammatory and autoimmune diseases, malignancies, acquired immune deficiency. Functional tests allow for differentiation between genetic and acquired HLH. Treatment aims at suppressing hypercytokinemia and eliminating activated and infected cells. It includes immunomodulatory and immunosuppressive agents, cytostatics, T-cell and cytokine antibodies. In genetic HLH cure can only be achieved with hematopoietic stem cell transplantation. Reduced-intensity conditioning regimens have considerably improved survival.
Janssens GO, Melchior P, Mul J, Saunders D, Bolle S, Cameron AL, Claude L, Gurtner K, van de Ven KP, van Grotel M, Harrabi S, Lassen-Ramshad Y, Lavan N, Magelssen H, Muracciole X, Boterberg T, Mandeville H, Godzinski J, Graf N, van den Heuvel-Eibrink MM, Rübe C	The SIOP-Renal Tumour Study Group consensus statement on flank target volume delineation for highly conformal radiotherapy.	The Lancet 2020, 4: 846
For decades, radiotherapy with two opposing photon beams has been the standard technique used to cover the flank target volume in paediatric patients with renal tumours. Nowadays, many institutes are implementing advanced radiotherapy techniques that spare healthy tissue. To decrease the radiotherapy dose to healthy structures while preserving oncological efficacy, the conventional approach of flank irradiation has been adapted into a guideline for highly conformal flank target-volume delineation by paediatric radiation oncologists and representatives of the International Society of Paediatric Oncology's Renal Tumour Study Group (SIOP-RTSG) board during four live international consensus meetings. The consensus was refined by delineation exercises and videoconferences by ten collaborating paediatric radiation oncologists. The final guideline includes eight chronological steps to generate the tumour bed and clinical, internal, and planning target volumes, and it describes the optional use of surgical clips to optimise treatment planning. This guideline will be added into the radiotherapy guideline of the UMBRELLA SIOP-RTSG protocol for paediatric renal tumours to improve international consistency of highly conformal flank target-volume delineation.
Japp AS, Gessi M, Messing-Jünger M, Denkhaus D, Zur Mühlen A, Wolff JE, Hartung S, Kordes U, Klein-Hitpass L, Pietsch T	High-resolution genomic analysis does not qualify atypical plexus papilloma as a separate entity among choroid plexus tumors.	Journal of neuropathology and experimental neurology 2015, 74: 110
Jarrett RF	Risk factors for Hodgkin's lymphoma by EBV status and significance of detection of EBV genomes in serum of patients with EBV-associated Hodgkin's lymphoma.	Leukemia & lymphoma 2003, 44 Suppl 3:S27
Epstein Barr virus (EBV) is associated with around one-third of Hodgkin's lymphoma (HL) cases and this association is believed to be causal. In these EBV-associated cases, there is a clonal EBV infection within tumors, and EBV genomes and gene products are detectable in Hodgkin and Reed-Sternberg (HRS) cells. The proportion of EBV-associated HL in any population varies with age, sex, ethnicity and histologic subtype. Two population-based epidemiologic studies have examined risk factor profiles in HL with cases stratified according to EBV status. For EBV-associated HL cases, there is a small peak in incidence in young adults (15-24 years) and a second larger peak in older adults. By contrast, HL that is not associated with EBV (EBV-negative HL) accounts for the major part of the young adult incidence peak after which the incidence of this disease entity then declines. Prior infectious mononucleosis (IM) is associated with an increased risk of developing HL, and there is a specific, probably causal, association between previous IM and young adult EBV-associated HL. We therefore believe that the small peak in the incidence of EBV-associated HL in young adults is real and related to late infection by EBV. EBV-associated HL in childhood and young adults, therefore, appears to follow primary infection by the virus. At the time of diagnosis, EBV-associated HL patients have an increased frequency of circulating EBV-infected cells compared to patients with EBV-negative HL and normal controls. The EBV is present in memory B cells and most probably reflects increased viral replication at another site, such as the oropharynx. EBV genomes are detectable in the serum and plasma of EBV-associated HL cases. The origin of EBV genomes in serum/plasma differs in different disease states; in HL viral genomes are present as naked DNA and are probably shed from tumors. EBV genome copy number in serum/plasma may provide an indication of tumor burden and may prove to be a useful marker for monitoring HL patients. The etiology of EBV-negative HL remains unknown and, while the involvement of an infectious agent may be suspected, none has yet been identified. Overall, epidemiologic studies support the idea that HL can be divided into two etiologic subgroups on the basis of EBV status and suggest that EBV-associated cases can be further divided into three groups related to age at diagnosis.
Jazmati D, Butzer S, Hero B, Ahmad Khalil D, Merta J, Bäumer C, Plum G, Fuchs J, Koerber F, Steinmeier T, Peters S, Doyen J, Thole T, Schmidt M, Blase C, Tippelt S, Eggert A, Schwarz R, Simon T, Timmermann B	Proton Beam Therapy for Children With Neuroblastoma: Experiences From the Prospective KiProReg Registry.	Frontiers in oncology 2020, 10: 617506
Radiotherapy (RT) is an integral part of the interdisciplinary treatment of patients with high-risk neuroblastoma (NB). With the continuous improvements of outcome, the interest in local treatment strategies that reduce treatment-related side effects while achieving optimal oncological results is growing. Proton beam therapy (PBT) represents a promising alternative to conventional photon irradiation with regard to the reduction of treatment burden.
Jazmati D, Steinmeier T, Ahamd Khalil D, Frisch S, Peters S, Schulze Schleithoff S, Bäumer C, Rutkowski S, Frühwald MC, Blase C, Tippelt S, Timmermann B	Feasibility of Proton Beam Therapy for Infants with Brain Tumours: Experiences from the Prospective KiProReg Registry Study.	Clinical oncology 2021, 33:e295-e304
Proton beam therapy (PBT) has increasingly been applied for the treatment of young children when radiotherapy is needed. The treatment requires intensive multimodality care and is logistically demanding. In this analysis, we evaluated our experiences in treating infants with tumours of the central nervous system with PBT.
Jazmati D, Butzer S, Hero B, Doyen J, Ahmad Khalil D, Steinmeier T, Schulze Schleithoff S, Eggert A, Simon T, Timmermann B	Long-term follow-up of children with neuroblastoma receiving radiotherapy to metastatic lesions within the German Neuroblastoma Trials NB97 and NB 2004.	Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 2021, 197: 683
Neuroblastoma (NB) is the most common extracranial solid malignancy during childhood. Despite a multimodal treatment approach, the prognosis of patients with metastatic NB is not satisfactory. Although radiotherapy (RT) has become an integral part of treatment of the primary tumor, the role of RT in osteomedullary lesions is not well defined. A retrospective analysis was conducted to evaluate the impact of RT for metastatic sites in children with high-risk NB.
Jazmati D, Hero B, Thole-Kliesch TM, Merta J, Deubzer HE, Bäumer C, Heinzelmann F, Schleithoff SS, Koerber F, Eggert A, Schwarz R, Simon T, Timmermann B	Efficacy and Feasibility of Proton Beam Therapy in Relapsed High-Risk Neuroblastoma-Experiences from the Prospective KiProReg Registry.	Current oncology 2022, 29: 8222
Despite an intensive multimodal treatment approach, approximately 50% of high-risk (HR) neuroblastoma (NB) patients experience progression. Despite the advances in targeted therapy, high-dose chemotherapy, and other systemic treatment options, radiation therapy (RT) to sites of relapsed disease can be an option to reduce tumor burden and improve chance for disease control.
Jazmati D, Brualla L, Littooij AS, Webber B, Dieckmann K, Janssens GO, Simon T, Gaze MN, Merta J, Serrano A, Dietzsch S, Kramer PH, Wulff J, Boterberg T, Timmermann B	Overcoming inter-observer planning variability in target volume contouring and dose planning for high-risk neuroblastoma - a European multicenter effort of the SIOPEN radiotherapy committee.	Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 2023, 181: 109464
To establish an international quality standard for contouring and planning for high-risk neuroblastoma within the prospective High-Risk Neuroblastoma Study 2 of SIOP-Europe-Neuroblastoma (SIOPEN HR-NBL2), which includes a randomized question on dose escalation for residual disease.
Jenkin D, Goddard K, Armstrong D, Becker L, Berry M, Chan H, Doherty M, Greenberg M, Hendrick B, Hoffman H, et al.	Posterior fossa medulloblastoma in childhood: treatment results and a proposal for a new staging system.	Int J Radiat Oncol Biol Phys 1990, 19: 265
Seventy-two children with posterior fossa medulloblastoma were diagnosed at the Hospital for Sick Children, Toronto, from 1977 to 1987 and treated by standard methods. The 5- and 10-year survival and disease-free survival rates were 71% and 63%, and 64% and 63%, respectively. Total tumor resection, as determined by the surgeon was the most significant favorable prognostic factor. Post-operative meningitis, a residual enhancing mass lesion on the post-operative, pre irradiation CT scan and dissemination to the brain or cord at diagnosis were unfavorable factors. These four easily definable factors were used to define a staging system with prognostic significance. Five-year disease-free survival rates were for Stage I (total resection, no adverse factor) 100%, Stage II (total resection with one or more adverse factor or less than total resection with no other adverse factor) 78%, and Stage III (less than total resection with one or more adverse factor) 18%. Evaluation of treatment results in medulloblastoma requires that these prognostic factors be known.
Jensen M, Ernestus K, Kemshead J, Klehr M, Von Bergwelt-Baildon MS, Schinkothe T, Schultze JL, Berthold F	The bi-specific CD3 x NCAM antibody: a model to preactivate T cells prior to tumour cell lysis.	Clinical and experimental immunology 2003, 134: 253
To target the neural cell adhesion molecule (NCAM, CD56) on neuroblastoma by T cell-based immunotherapy we have generated a bi-specific CD3 x NCAM antibody (OE-1). This antibody can be used to redirect T cells to NCAM+ cells. Expectedly, the antibody binds specifically to NCAM+ neuroblastoma cells and CD3+ T cells. OE-1 induces T cell activation, expansion and effector function in peripheral blood mononuclear cell (PBMC)-derived CD4+ and CD8+ T cells. T cell activation was shown to depend on the presence of normal natural killer (NK) cells in the culture. Interestingly, while PBMC- derived T cells were activated by OE-1, NK cells were almost completely depleted, suggesting that T cells activated by OE-1 deleted the NK cells. Activated CD4+ and CD8+ T cells differentiate into a larger CCR7+ central memory and a smaller CCR7- effector memory cell population. Most importantly, preactivated T cells were highly cytotoxic for neuroblastoma cells. In eight of 11 experiments tumour-directed cytotoxicity was enhanced when NK cells were present during preactivation with OE-1. These data strongly support a bi-phasic therapeutic concept of primarily stimulating T cells with the bi-specific antibody in the presence of normal NCAM+ cells to induce T cell activation, migratory capacity and finally tumour cell lysis.
Jensen M, Tawadros S, Sedlacek HH, Schultze JL, Berthold F	NK cell depletion diminish tumour-specific B cell responses.	Immunology letters 2004, 93(2-3): 205
Natural killer (NK) cells can exercise immediate cytotoxicity against malignant cells and thus far modulate the development of tumour directed T cell immunity. To investigate the impact of NK cells on the development of tumour directed B cell immunity mice were immunised with IMR5-75 human neuroblastoma cells with or without prior in vivo NK cell depletion. Flow cytometry analyses gave evidence for an impaired IgG response against the cells immunised with. Dissection of Th1 (IgG2a) and Th2 (IgG1) oriented B cell responses revealed Th1 responses as primarily affected, while Th2 oriented B cell responses as measured by flow cytometry and GD2 ganglioside-specific ELISA were enforced. The data reveal an unexpected impact of NK cells on the development of tumour directed B cell responses. Consequently, NK cell function has also to be taken into account when developing B cell-based cancer immunotherapy.
Jennings I, Perry D, Watson H, Alikhan R, Laffan M, Gomez K, Kitchen S, Walker I, Haemostasis and Thrombosis Task Force of the British Society for Haematology & UK NEQAS for Blood Coagulation	Quality assurance and tests of platelet function.	British journal of haematology 2018, 181: 560
Jentzsch C, Fuchs J, Agaimy A, Vokuhl C, Escherich G, Blattmann C, Warmann SW, Schmidt A, Schäfer J, Brecht IB, Schneider DT, Abele M	Solid pseudopapillary neoplasms of the pancreas in childhood and adolescence-an analysis of the German Registry for Rare Pediatric Tumors (STEP).	European journal of pediatrics 2023,
Solid pseudopapillary neoplasms (SPNs) are the most common entity among pediatric pancreatic tumors. Still, these are rare tumors with an annual incidence of 0.1-0.2/1,000,000, and little is known about their optimal treatment. This analysis aimed to increase knowledge about the occurrence and treatment strategies of SPN in childhood. Data regarding diagnostics, treatment, and outcome of children aged 0-18 years with SPN recorded in the German Registry for Rare Pediatric Tumors (STEP) were analyzed. Thirty-eight patients were identified with a median age of 14.5 years at diagnosis (range: 8-18) and a female preponderance (81.6%). The most frequent location of the tumor was the pancreatic tail. In histopathological and immunohistochemical examination, pseudopapillary, solid, and cystic lesions as well as expression of beta-catenin, progesterone receptors, and cyclin D1 were the most common findings. All patients underwent surgical resection. Most patients underwent open resection, predominantly tail resection for tumors in the tail region and pylorus-preserving pancreaticoduodenectomy for tumors in the head region. The main postoperative sequela was exogenous pancreatic insufficiency (23.7%), especially with SPN in the pancreatic head. No recurrence occurred during follow-up, although two patients underwent resection with microscopic residue.
Jin Y, Mazza C, Christie JR, Giliani S, Fiorini M, Mella P, Gandellini F, Stewart DM, Zhu Q, Nelson DL, Notarangelo LD, Ochs HD	Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation.	Blood 2004 Dec 15; 104: 4010
The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive immune deficiency disorder characterized by thrombocytopenia, small platelet size, eczema, recurrent infections, and increased risk of autoimmune disorders and malignancies. X-linked thrombocytopenia (XLT) is an allelic variant of WAS which presents with a milder phenotype, generally limited to thrombocytopenia. WAS and XLT are caused by mutations of the Wiskott-Aldrich syndrome protein (WASP) gene which encodes a 502-amino acid protein, named WASP. WASP is thought to play a role in actin cytoskeleton organization and cell signaling. Here, we report the identification of 141 unique mutations, 71 not previously reported, from 227 WAS/XLT families with a total of 262 affected members. When possible we studied the effects of these mutations on transcription, RNA splicing, and protein expression. By analyzing a large number of patients with WAS/XLT at the molecular level we identified 5 mutational hotspots in the WASP gene and have been able to establish a strong association between genotype and phenotype.
Johnson P, Glennie M	The mechanisms of action of rituximab in the elimination of tumor cells.	Semin Oncol 2003, 30 (Suppl 2): 3
Johann PD, Erkek S, Zapatka M, Kerl K, Buchhalter I, Hovestadt V, Jones DT, Sturm D, Hermann C, Segura Wang M, Korshunov A, Rhyzova M, Gröbner S, Brabetz S, Chavez L, Bens S, Gröschel S, Kratochwil F, Wittmann A, Sieber L, Geörg C, Wolf S, Beck K, Oyen F, Capper D, van Sluis P, Volckmann R, Koster J, Versteeg R, von Deimling A, Milde T, Witt O, Kulozik AE, Ebinger M, Shalaby T, Grotzer M, Sumerauer D, Zamecnik J, Mora J, Jabado N, Taylor MD, Huang A, Aronica E, Bertoni A, Radlwimmer B, Pietsch T, Schüller U, Schneppenheim R, Northcott PA, Korbel JO, Siebert R, Frühwald MC, Lichter P, Eils R, Gajjar A, Hasselblatt M, Pfister SM, Kool M	Atypical Teratoid/Rhabdoid Tumors Are Comprised of Three Epigenetic Subgroups with Distinct Enhancer Landscapes.	Cancer cell 2016, 29: 379
Atypical teratoid/rhabdoid tumor (ATRT) is one of the most common brain tumors in infants. Although the prognosis of ATRT patients is poor, some patients respond favorably to current treatments, suggesting molecular inter-tumor heterogeneity. To investigate this further, we genetically and epigenetically analyzed 192 ATRTs. Three distinct molecular subgroups of ATRTs, associated with differences in demographics, tumor location, and type of SMARCB1 alterations, were identified. Whole-genome DNA and RNA sequencing found no recurrent mutations in addition to SMARCB1 that would explain the differences between subgroups. Whole-genome bisulfite sequencing and H3K27Ac chromatin-immunoprecipitation sequencing of primary tumors, however, revealed clear differences, leading to the identification of subgroup-specific regulatory networks and potential therapeutic targets.
Johann PD, Altendorf L, Efremova EM, Holsten T, Steinbügl M, Nemes K, Eckhardt A, Kresbach C, Bockmayr M, Koch A, Haberler C, Antonelli M, DeSisto J, Schuhmann MU, Hauser P, Siebert R, Bens S, Kool M, Green AL, Hasselblatt M, Frühwald MC, Schüller U	Recurrent atypical teratoid/rhabdoid tumors (AT/RT) reveal discrete features of progression on histology, epigenetics, copy number profiling, and transcriptomics.	Acta neuropathologica 2023, 146: 527
Atypical teratoid/rhabdoid tumors (AT/RT) are the most common malignant brain tumors manifesting in infancy. They split into four molecular types. The major three (AT/RT-SHH, AT/RT-TYR, and AT/RT-MYC) all carry mutations in SMARCB1, the fourth quantitatively smaller type is characterized by SMARCA4 mutations (AT/RT-SMARCA4). Molecular characteristics of disease recurrence or metastatic spread, which go along with a particularly dismal outcome, are currently unclear. Here, we investigated tumor tissue from 26 patients affected by AT/RT to identify signatures of recurrences in comparison with matched primary tumor samples. Microscopically, AT/RT recurrences demonstrated a loss of architecture and significantly enhanced mitotic activity as compared to their related primary tumors. Based on DNA methylation profiling, primary tumor and related recurrence were grossly similar, but three out of 26 tumors belonged to a different molecular type or subtype after second surgery compared to related primary lesions. Copy number variations (CNVs) differed in six cases, showing novel gains on chromosome 1q or losses of chromosome 10 in recurrences as the most frequent alterations. To consolidate these observations, our cohort was combined with a data set of unmatched primary and recurrent AT/RT, which demonstrated chromosome 1q gain and 10 loss in 18% (n = 7) and 11% (n = 4) of the recurrences (n = 38) as compared to 7% (n = 3) and 0% (n = 0) in the primary tumors (n = 44), respectively. Similar to the observations made by DNA methylation profiling, RNA sequencing of our cohort revealed AT/RT primary tumors and matched recurrences clustering closely together. However, a number of genes showed significantly altered expression in AT/RT-SHH recurrences. Many of them are known tumor driving growth factors, involved in embryonal development and tumorigenesis, or are cell-cycle-associated. Overall, our work identifies subtle molecular changes that occur in the course of the disease and that may help define novel therapeutic targets for AT/RT recurrences.
Jones DT, Hutter B, Jäger N, Korshunov A, Kool M, Warnatz HJ, Zichner T, Lambert SR, Ryzhova M, Quang DA, Fontebasso AM, Stütz AM, Hutter S, Zuckermann M, Sturm D, Gronych J, Lasitschka B, Schmidt S, Seker-Cin H, Witt H, Sultan M, Ralser M, Northcott PA, Hovestadt V, Bender S, Pfaff E, Stark S, Faury D, Schwartzentruber J, Majewski J, Weber UD, Zapatka M, Raeder B, Schlesner M, Worth CL, Bartholomae CC, von Kalle C, Imbusch CD, Radomski S, Lawerenz C, van Sluis P, Koster J, Volckmann R, Versteeg R, Lehrach H, Monoranu C, Winkler B, Unterberg A, Herold-Mende C, Milde T, Kulozik AE, Ebinger M, Schuhmann MU, Cho YJ, Pomeroy SL, von Deimling A, Witt O, Taylor MD, Wolf S, Karajannis MA, Eberhart CG, Scheurlen W, Hasselblatt M, Ligon KL, Kieran MW, Korbel JO, Yaspo ML, Brors B, Felsberg J, Reifenberger G, Collins VP, Jabado N, Eils R, Lichter P, Pfister SM, International Cancer Genome Consortium PedBrain Tumor Project	Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma.	Nat Genet 2013, 45: 927
Pilocytic astrocytoma, the most common childhood brain tumor, is typically associated with mitogen-activated protein kinase (MAPK) pathway alterations. Surgically inaccessible midline tumors are therapeutically challenging, showing sustained tendency for progression and often becoming a chronic disease with substantial morbidities. Here we describe whole-genome sequencing of 96 pilocytic astrocytomas, with matched RNA sequencing (n = 73), conducted by the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. We identified recurrent activating mutations in FGFR1 and PTPN11 and new NTRK2 fusion genes in non-cerebellar tumors. New BRAF-activating changes were also observed. MAPK pathway alterations affected all tumors analyzed, with no other significant mutations identified, indicating that pilocytic astrocytoma is predominantly a single-pathway disease. Notably, we identified the same FGFR1 mutations in a subset of H3F3A-mutated pediatric glioblastoma with additional alterations in the NF1 gene. Our findings thus identify new potential therapeutic targets in distinct subsets of pilocytic astrocytoma and childhood glioblastoma.
Jones DTW, Kieran MW, Bouffet E, Alexandrescu S, Bandopadhayay P, Bornhorst M, Ellison D, Fangusaro J, Fisher MJ, Foreman N, Fouladi M, Hargrave D, Hawkins C, Jabado N, Massimino M, Mueller S, Perilongo G, Schouten van Meeteren AYN, Tabori U, Warren K, Waanders AJ, Walker D, Weiss W, Witt O, Wright K, Zhu Y, Bowers DC, Pfister SM, Packer RJ	Pediatric low-grade gliomas: next biologically driven steps.	Neuro-oncology 2018, 20: 160
Despite the fact that they are not typically life-threatening, low-grade gliomas (LGGs) remain a significant clinical challenge in pediatric neuro-oncology due to comorbidities associated with these tumors and/or their treatments, and their propensity to multiply recurs. LGGs, in total the most common brain tumors arising in childhood, can often become a chronic problem requiring decades of management. The Second International Consensus Conference on Pediatric Low-Grade Gliomas held in Padua, Italy in 2016 was convened in an attempt to advance the pace of translating biological discoveries on LGGs into meaningful clinical benefit. Topics discussed included: the implications of our growing biological understanding of the genomics underlying these tumors; the assessment of the model systems available; the implications of the molecular and histopathologic differences between adult and pediatric diffuse gliomas; and steps needed to expedite targeted therapy into late-stage clinical trials for newly diagnosed cases. Methods for the diagnostic assessment of alterations in the Ras/mitogen-activated protein kinase pathway, typical for these tumors, were also considered. While the overall tone was positive, with a consensus that progress is being and will continue to be made, the scale of the challenge presented by this complex group of tumors was also acknowledged. The conclusions and recommendations of the meeting panel are provided here as an outline of current thinking and a basis for further discussion.
Jones DTW, Witt O, Pfister SM	BRAF V600E Status Alone Is Not Sufficient as a Prognostic Biomarker in Pediatric Low-Grade Glioma.	Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2018, 36: 96
Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL	How I treat hemophagocytic lymphohistiocytosis.	Blood 2011, 118: 4041
Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of pathologic immune activation, occurring as either a familial disorder or a sporadic condition, in association with a variety of triggers. This immune dysregulatory disorder is prominently associated with cytopenias and a unique combination of clinical signs and symptoms of extreme inflammation. Prompt initiation of immunochemotherapy is essential for survival, but timely diagnosis may be challenging because of the rarity of HLH, its variable presentation, and the time required to perform diagnostic testing. Therapy is complicated by dynamic clinical course, high risk of treatment-related morbidity, and disease recurrence. Here, we review the clinical manifestations and patterns of HLH and describe our approach to the diagnosis and therapy for this elusive and potentially lethal condition.
Jost W H	Diagnostik und Therapie von neurogenen Blasenstörungen - Leitlinien für Diagnostik und Therapie in der Neurologie.	AWMF online 2015
Jozwiak S, Schwartz RA, Janniger CK, Bielicka-Cymerman J	Usefulness of diagnostic criteria of tuberous sclerosis complex in pediatric patients.	J Child Neurol 2000, 15: 652
Juergens C, Weston C, Lewis I, Whelan J, Paulussen M, Oberlin O, Michon J, Zoubek A, Jürgens H, Craft A	Safety assessment of intensive induction with vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) in the treatment of Ewing tumors in the EURO-E. W.I. N.G. 99 clinical trial.	Pediatric blood & cancer 2006, 47: 22
Jünger ST, Mynarek M, Wohlers I, Dörner E, Mühlen AZ, Velez-Char N, von Hoff K, Rutkowski S, Warmuth-Metz M, Kortmann RD, Timmermann B, Rahmann S, Klein-Hitpass L, von Bueren AO, Pietsch T	Improved risk-stratification for posterior fossa ependymoma of childhood considering clinical, histological and genetic features - a retrospective analysis of the HIT ependymoma trial cohort.	Acta neuropathologica communications 2019, 7: 181
Risk stratification of children with ependymomas of the posterior fossa in current therapeutic protocols is mainly based on clinical criteria. We aimed to identify independent outcome predictors for this disease entity by a systematic integrated analysis of clinical, histological and genetic information in a defined cohort of patients treated according to the German HIT protocols.
Jünger ST, Andreiuolo F, Mynarek M, Wohlers I, Rahmann S, Klein-Hitpass L, Dörner E, Zur Mühlen A, Velez-Char N, von Hoff K, Warmuth-Metz M, Kortmann RD, Timmermann B, von Bueren A, Rutkowski S, Pietsch T	CDKN2A deletion in supratentorial ependymoma with RELA alteration indicates a dismal prognosis: a retrospective analysis of the HIT ependymoma trial cohort.	Acta neuropathologica 2020, 140: 405
Jünger ST, Andreiuolo F, Mynarek M, Dörner E, Zur Mühlen A, Rutkowski S, von Bueren AO, Pietsch T	Ependymomas in infancy: underlying genetic alterations, histological features, and clinical outcome.	ChNS 2020, 36: 2693
Young age is an adverse prognostic factor in children with ependymomas. Treatment of these infants is challenging since beneficial therapeutic options are limited. As ependymomas are considered a biologically heterogeneous group, we aimed to characterize infant ependymomas with regard to their histological and genetic features.
Juhnke BO, Mynarek M, Rutkowski S	Refining medulloblastoma subgroups.	The Lancet. Oncology 2017, 18: 847
Juhnke BO, Gessi M, Gerber NU, Friedrich C, Mynarek M, von Bueren AO, Haberler C, Schüller U, Kortmann RD, Timmermann B, Bison B, Warmuth-Metz M, Kwiecien R, Pfister SM, Spix C, Pietsch T, Kool M, Rutkowski S, von Hoff K	Treatment of embryonal tumors with multilayered rosettes with carboplatin/etoposide induction and high-dose chemotherapy within the prospective P-HIT trial.	Neuro-oncology 2022, 24: 127
Embryonal tumors with multilayered rosettes (ETMR) are highly aggressive tumors occurring in early childhood. Published clinical data refer to retrospective, heterogeneously treated cohorts. Here, we describe the outcome of patients treated according to the prospective P-HIT trial and subsequent HIT2000-interim-registry.
Jumaa H, Bossaller L, Portugal K, Storch B, Lotz M, Flemming A, Schrappe M, Postila V, Riikonen P, Pelkonen J, Niemeyer C, Reth M	Deficiency of the adaptor SLP-65 in pre-B-cell acute lymphoblastic leukaemia.	Nature 2003, 423: 452
Jung R, Jacobs U, Krumbholz M, Langer T, Keller T, De Lorenzo P, Valsecchi MG, van der Velden VH, Moericke A, Stanulla M, Teigler-Schlegel A, Panzer-Gruemayer ER, van Dongen JJ, Schrappe M, den Boer ML, Pieters R, Rascher W, Metzler M	Bimodal distribution of genomic MLL breakpoints in infant acute lymphoblastic leukemia treatment.	Leukemia 2010, 24: 903
Junk S, Cario G, Wittner N, Stanulla M, Scherer R, Schlegelberger B, Schrappe M, von Neuhoff N, Lauten M	Bortezomib Treatment can Overcome Glucocorticoid Resistance in Childhood B-cell Precursor Acute Lymphoblastic Leukemia Cell Lines.	Klin Pädiatr 2015, 227: 123
BACKGROUND: The response to initial glucocorticoid (gc) treatment is a reliable stratification factor in childhood acute lymphoblastic leukemia (ALL) and may predict the response to multi-agent chemotherapy. In a former study we detected that the valosin-containing protein (VCP, cdc48), a member of the ubiquitin proteasome degradation system (UPS), is altered in gc-resistant leukemic cells suggesting that the associated pathways might be involved in chemotherapy resistance in childhood ALL. METHODS: Human B-cell precursor leukemia cell lines, gc-resistant MHH-cALL-2 and gc-sensitive MHH-cALL-3, were treated with prednisolone and various concentrations of bortezomib. Viability and apoptosis rates were determined. RESULTS: Both cell lines showed a dose-dependent increase in caspase activity after bortezomib single treatment. The gc-sensitive cells showed an additive effect after combined treatment with prednisolone and bortezomib. In contrast, both cell lines showed a reduced viability and enhanced propidium iodide positivity after combined treatment as determined by flow cytometry. Western blot analyses of poly-(ADP-ribose) polymerase 1 (PARP-1) suggested that combined treatment promote necrotic cleavage of PARP-1 in gc-resistant cells. Furthermore, after prednisolone treatment the UPS associated proteins VCP and NFκB-inhibitor IκBα were differentially modulated in gc-resistant cells. CONCLUSIONS: The proteasome inhibitor bortezomib seems to sensitize gc-resistant childhood ALL cells for prednisolone-induced cell death.
Jung EW, Murphy ES, Jung DL, Chao ST, Suh JH	Pediatric radiosurgery: A review.	Appl Rad Oncol 2015
Junk SV, Klein N, Schreek S, Zimmermann M, Moericke A, Bleckmann K, Alten J, Dagdan E, Cario G, Kratz CP, Schrappe M, Stanulla M	TP53, ETV6 and RUNX1 germline variants in a case series of patients developing secondary neoplasms after treatment for childhood acute lymphoblastic leukemia.	Haematologica 2019, 104:e402-e405
Junk SV, Schaeffeler E, Zimmermann M, Möricke A, Beier R, Schütte P, Fedders B, Alten J, Hinze L, Klein N, Kulozik A, Muckenthaler MU, Koehler R, Borkhardt A, Vijayakrishnan J, Ellinghaus D, Forster M, Franke A, Wintering A, Kratz CP, Schrappe M, Schwab M, Houlston RS, Cario G, Stanulla M	Chemotherapy-related hyperbilirubinemia in pediatric acute lymphoblastic leukemia: a genome-wide association study from the AIEOP-BFM ALL study group.	Journal of experimental & clinical cancer research 2023, 42: 21
Junk SV, Schaeffeler E, Zimmermann M, Möricke A, Beier R, Schütte P, Fedders B, Alten J, Hinze L, Klein N, Kulozik A, Muckenthaler MU, Koehler R, Borkhardt A, Vijayakrishnan J, Ellinghaus D, Forster M, Franke A, Wintering A, Kratz CP, Schrappe M, Schwab M, Houlston RS, Cario G, Stanulla M	Chemotherapy-related hyperbilirubinemia in pediatric acute lymphoblastic leukemia: a genome-wide association study from the AIEOP-BFM ALL study group.	Journal of experimental & clinical cancer research : CR 2023, 42: 21
Characterization of clinical phenotypes in context with tumor and host genomic information can aid in the development of more effective and less toxic risk-adapted and targeted treatment strategies. To analyze the impact of therapy-related hyperbilirubinemia on treatment outcome and to identify contributing genetic risk factors of this well-recognized adverse effect we evaluated serum bilirubin levels in 1547 pediatric patients with acute lymphoblastic leukemia (ALL) and conducted a genome-wide association study (GWAS).
Jurklies C	Das Retinoblastom - Diagnose und Therapie.	WIR Informationsschrift der Aktion für krebskranke Kinder e.V. (Bonn) 2007, 1: 26
Jürgens H, Janka-Schaub G, Ibrahim M, Tonert C, Winkler K, Göbel U	Prognostic significance of exposure to intermediate-dose Methotrexate in children with standard risk ALL:the COALL 82/85 experience.	Hämatol Blood Transf 1992, 34: 238
Jürgens H	Interdisciplinary therapy of Ewing sarcoma.	Schweiz Rundsch Med Prax 1995, 84: 1005
Jürgens H, Ritter J	Lungenmetastasen bei Malignomen im Kindesalter.	Z Herz-Thorax-Gefäáchir 1996, 10: 9
Jürgens H	Recent advances in childhood cancer.	Eur J Cancer 1997, 33: 15
Juergens C, Weston C, Lewis I, Whelan J, Paulussen M, Oberlin O, Michon J, Zoubek A, Jürgens H, Craft A	Safety assessment of intensive induction with vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) in the treatment of Ewing tumors in the EURO-E. W.I. N.G. 99 clinical trial.	Pediatric blood & cancer 2006, 47: 22
BACKGROUND: The EUROpean Ewing tumour Working Initiative of National Groups 1999 (EURO-E.W.I.N.G. 99) protocol prescribes six courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) as intensive induction chemotherapy for Ewing tumors (ET). Granulocyte-colony stimulating factor (G-CSF) is recommended. Adverse reactions (AR) were evaluated; quality assurance of data collection reviewed. PROCEDURE: Safety data from 4,746 courses of VIDE in 851 patients less than 50 years with ET were collected using a checklist and evaluated using descriptive statistics with sub-groups including gender, age, and tumor volume, analyzed by Wilcoxon and Kruskal-Wallis tests. RESULTS: Myelosuppression and infections were the major AR but with appropriate supportive therapy targeted dose intensity was maintained. Five VIDE-related deaths with three due to sepsis were reported. Renal and cardiac toxicity were reflected by glomerular filtration rate (GFR) <39 ml/min/1.73 m2 in 0.1%, tubular phosphate reabsorption < or = 0.80 in 1.9%, and left ventricular shortening fracture <28% in 2.5% VIDE courses. Statistically significant gender-associated AR concerning hemoglobin and platelets were observed with females > males as were age-associated AR concerning hemoglobin, WBC, platelets, stomatitis, and vomiting with AR decreasing with age, that is, children > adolescents > adults. No association of AR to tumor volume was found. In VIDE courses with and without G-CSF, neutropenia-related fever in 60.8% and 65.8%, and infection in 54.7% and 61.0% courses, respectively, were recorded. CONCLUSIONS: AR under VIDE remained within the expected range. Some AR, for example, hematotoxicity were significantly influenced by age and gender but not by tumor volume. G-CSF did not significantly influence neutropenia-related fever and infection. Solicited safety collection with checklists adequately reflects the burden per course.
Jürgens H, Paulussen M, Zoubek A	Ewing-Tumoren, in: Gadner H, Gaedicke G, Niemeyer CH, Ritter J (Hrsg.): Pädiatrische Hämatologie und Onkologie.	Springer Verlag 2006, 894
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