TY  - JOUR
AU  - Eissing, M.L.L.G.
AU  - Ripken, L.S.
AU  - Schreibelt, G.
AU  - Westdorp, H.
AU  - Ligtenberg, M.J.
AU  - Netea-Maier, R.T.
AU  - Netea, M.G.
AU  - Vries, I.J.M. de
AU  - Hoogerbrugge, N.
PY  - 2018
UR  - https://hdl.handle.net/2066/200303
AB  - Carriers of a pathogenic germline mutations in the PTEN gene, a well-known tumor suppressor gene, are at increased risk of multiple benign and malignant tumors, e.g. breast, thyroid, endometrial and colon cancer. This is called PTEN Hamartomous Tumor Syndrome (PHTS). PHTS patients may also have an increased risk of immunological dysregulation, such as autoimmunity and immune deficiencies. The effects of PTEN on the immune system have been studied in murine knockout models demonstrating that loss of PTEN function leads to dysregulation of the immune response. This results in susceptibility to autoimmunity, impaired B cell class switching with subsequent hypogammaglobulinemia. Additionally, a decreased ability of dendritic cells to prime CD8(+) T cells was observed, leading to impaired tumor eradication. Immune dysfunction in PHTS patients has not yet been extensively studied but might be a manageable contributing factor to the increased cancer risk in PHTS.
TI  - PTEN Hamartoma Tumor Syndrome and Immune Dysregulation
EP  - 367
SN  - 1936-5233
IS  - iss. 2
SP  - 361
JF  - Translational Oncology
VL  - vol. 12
DO  - https://doi.org/10.1016/j.tranon.2018.11.003
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/200303/200303.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Visser, S.M. de
AU  - Kirchner, Christian A.
AU  - Velden, B.G.J. van der
AU  - Wit, Alexander C. de
AU  - Dijkman, Anneke
AU  - Huisjes, Anjoke J.M.
AU  - Dillen, J.J. van
AU  - Vandenbussche, F.P.H.A.
AU  - Hulscher, M.E.J.L.
AU  - Woiski, M.D.
AU  - Hermens, R.P.M.G.
PY  - 2018
UR  - https://hdl.handle.net/2066/191920
TI  - Major obstetric hemorrhage: Patients' perspective on the quality of care
EP  - 152
SN  - 0301-2115
SP  - 146
JF  - European Journal of Obstetrics & Gynecology and Reproductive Biology
VL  - vol. 224
DO  - https://doi.org/10.1016/j.ejogrb.2018.03.032
ER  - 
TY  - JOUR
AU  - Tesselaar, M.H.
AU  - Crezee, T.
AU  - Schuurmans, Imke
AU  - Gerrits, D.
AU  - Nagarajah, J.
AU  - Boerman, O.C.
AU  - Grunsven, I. van
AU  - Netea-Maier, R.T.
AU  - Plantinga, T.S.
PY  - 2018
UR  - https://hdl.handle.net/2066/191396
TI  - Digitalislike Compounds Restore hNIS Expression and Iodide Uptake Capacity in Anaplastic Thyroid Cancer
EP  - 786
SN  - 0161-5505
IS  - iss. 5
SP  - 780
JF  - The Journal of Nuclear Medicine (1978)
VL  - vol. 59
DO  - https://doi.org/10.2967/jnumed.117.200675
ER  - 
TY  - JOUR
AU  - Koster, E.J. de
AU  - Geus-Oei, L.F. de
AU  - Dekkers, O.M.
AU  - Engen-van Grunsven, I.A. van
AU  - Hamming, J.
AU  - Corssmit, E.P.M.
AU  - Morreau, H.
AU  - Schepers, A.
AU  - Smit, J.W.A.
AU  - Oyen, W.J.G.
AU  - Vriens, D.
PY  - 2018
UR  - https://hdl.handle.net/2066/191293
AB  - Indeterminate thyroid cytology (Bethesda III and IV) corresponds to follicular-patterned benign and malignant lesions, which are particularly difficult to differentiate on cytology alone. As approximately 25% of these nodules harbor malignancy, diagnostic hemithyroidectomy is still custom. However, advanced preoperative diagnostics are rapidly evolving.This review provides an overview of additional molecular and imaging diagnostics for indeterminate thyroid nodules in a pre-operative clinical setting, including considerations regarding cost-effectiveness, availability, and feasibility of combining techniques. Addressed diagnostics include gene mutation analysis, microRNA, immunocytochemistry, ultrasonography, elastosonography, CT, sestamibi scintigraphy, FDG-PET and diffusion-weighted MRI.The best rule-out tests for malignancy were the Afirma(R) GEC and FDG-PET. The most accurate rule-in test was sole BRAF mutation analysis. No diagnostic had both near-perfect sensitivity and specificity, and estimated cost-effectiveness. Molecular techniques are rapidly advancing. However, given the currently available techniques a multimodality stepwise approach likely offers the most accurate diagnosis, sequentially applying one sensitive rule-out test and one specific rule-in test. Geographical variations in cytology (e.g. Hurthle cell neoplasms) and tumor genetics strongly influence local test performance and clinical utility. Multidisciplinary collaboration and implementation studies can aid the local decision for one or more eligible diagnostics.
TI  - Diagnostic Utility of Molecular and Imaging Biomarkers in Cytological Indeterminate Thyroid Nodules
EP  - 191
SN  - 0163-769X
IS  - iss. 2
SP  - 154
JF  - Endocrine Reviews
VL  - vol. 39
DO  - https://doi.org/10.1210/er.2017-00133
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/191293/191293.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Lachmandas, E.L.
AU  - Thiem, K.
AU  - Heuvel, C.N.A.M. van den
AU  - Hijmans, A.G.M.
AU  - Galan, B.E. de
AU  - Tack, C.J.
AU  - Netea, M.G.
AU  - Crevel, R. van
AU  - Diepen, J.A. van
PY  - 2018
UR  - https://hdl.handle.net/2066/183988
TI  - Patients with type 1 diabetes mellitus have impaired IL-1 beta production in response to Mycobacterium tuberculosis
EP  - 380
SN  - 0934-9723
IS  - iss. 2
SP  - 371
JF  - European Journal of Clinical Microbiology and Infectious Diseases
VL  - vol. 37
DO  - https://doi.org/10.1007/s10096-017-3145-y
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/183988/183988.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Visser, S.M. de
AU  - Woiski, M.D.
AU  - Grol, R.P.
AU  - Vandenbussche, F.P.H.A.
AU  - Hulscher, M.E.J.L.
AU  - Scheepers, Hubertina C. J.
AU  - Hermens, R.P.
PY  - 2018
UR  - https://hdl.handle.net/2066/183828
TI  - Development of a tailored strategy to improve postpartum hemorrhage guideline adherence
SN  - 1471-2393
JF  - BMC Pregnancy and Childbirth
VL  - vol. 18
DO  - https://doi.org/10.1186/s12884-018-1676-6
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/183828/183828.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Semango, G.
AU  - Heinhuis, B.
AU  - Plantinga, T.S.
AU  - Blokx, W.A.M.
AU  - Kibiki, G.S.
AU  - Sonda, Tolbert
AU  - Ven, A.J.A.M. van der
AU  - Joosten, L.A.B.
PY  - 2018
UR  - https://hdl.handle.net/2066/183852
TI  - Exploring the Role of IL-32 in HIV-Related Kaposi Sarcoma
EP  - 203
SN  - 0002-9440
IS  - iss. 1
SP  - 196
JF  - American Journal of Pathology
VL  - vol. 188
DO  - https://doi.org/10.1016/j.ajpath.2017.08.033
ER  - 
TY  - JOUR
AU  - Plantinga, T.S.
AU  - Petrulea, M.S.
AU  - Oosting, M.
AU  - Joosten, L.A.B.
AU  - Piciu, D.
AU  - Smit, J.W.A.
AU  - Netea-Maier, R.T.
AU  - Georgescu, C.E.
PY  - 2017
UR  - https://hdl.handle.net/2066/189791
TI  - Association of NF-kappa B polymorphisms with clinical outcome of non-medullary thyroid carcinoma
EP  - 318
SN  - 1351-0088
IS  - iss. 7
SP  - 307
JF  - Endocrine-Related Cancer
VL  - vol. 24
DO  - https://doi.org/10.1530/ERC-17-0033
ER  - 
TY  - JOUR
AU  - Engels, M.
AU  - Span, P.N.
AU  - Mitchell, R.T.
AU  - Heuvel, J.J.T.M.
AU  - Marijnissen-van Zanten, M.A.
AU  - Herwaarden, A.E. van
AU  - Hulsbergen-van de Kaa, C.A.
AU  - Oosterwijk, E.
AU  - Stikkelbroeck, N.
AU  - Smith, L.B.
AU  - Sweep, C.G.J.
AU  - Claahsen-van der Grinten, H.L.
PY  - 2017
UR  - https://hdl.handle.net/2066/181619
AB  - Testicular adrenal rest tumours (TARTs) are benign adrenal-like testicular tumours that frequently occur in male patients with congenital adrenal hyperplasia. Recently, GATA transcription factors have been linked to the development of TARTs in mice. The aim of our study was to determine GATA expression in human TARTs and other steroidogenic tissues. We determined GATA expression in TARTs (n = 16), Leydig cell tumours (LCTs; n = 7), adrenal (foetal (n = 6) + adult (n = 10)) and testis (foetal (n = 13) + adult (n = 8)). We found testis-like GATA4, and adrenal-like GATA3 and GATA6 gene expressions by qPCR in human TARTs, indicating mixed testicular and adrenal characteristics of TARTs. Currently, no marker is available to discriminate TARTs from LCTs, leading to misdiagnosis and incorrect treatment. GATA3 and GATA6 mRNAs exhibited excellent discriminative power (area under the curve of 0.908 and 0.816, respectively), while immunohistochemistry did not. GATA genes contain several CREB-binding sites and incubation with 0.1 mM dibutyryl cAMP for 4 h stimulated GATA3, GATA4 and GATA6 expressions in a human foetal testis cell line (hs181.tes). Incubation of adrenocortical cells (H295RA) with ACTH, however, did not induce GATA expression in vitro Although ACTH did not dysregulate GATA expression in the only human ACTH-sensitive in vitro model available, our results do suggest that aberrant expression of GATA transcription factors in human TARTs might be involved in TART formation.
TI  - GATA transcription factors in testicular adrenal rest tumours
EP  - 875
SN  - 2049-3614
IS  - iss. 8
SP  - 866
JF  - Endocrine Connections
VL  - vol. 6
DO  - https://doi.org/10.1530/EC-17-0215
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/181619/181619.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Plantinga, T.S.
AU  - Arts, P.
AU  - Knarren, G.H.
AU  - Mulder, A.H.
AU  - Wakelkamp, I.M.
AU  - Hermus, A.R.M.M.
AU  - Joosten, L.A.
AU  - Netea, M.G.
AU  - Gilissen, C.F.
AU  - Veltman, J.A.
AU  - Hoischen, A.
AU  - Smit, J.W.A.
AU  - Netea-Maier, R.T.
PY  - 2017
UR  - https://hdl.handle.net/2066/179606
TI  - Rare NOX3 Variants Confer Susceptibility to Agranulocytosis During Thyrostatic Treatment of Graves' Disease
EP  - 1024
SN  - 0009-9236
IS  - iss. 6
SP  - 1017
JF  - Clinical Pharmacology and Therapeutics
VL  - vol. 102
DO  - https://doi.org/10.1002/cpt.733
ER  - 
TY  - JOUR
AU  - Ham, J.C.
AU  - Tops, B.B.J.
AU  - Driessen, C.M.L.
AU  - Raaij, A.W. van
AU  - Slootweg, P.J.
AU  - Melchers, W.J.G.
AU  - Ligtenberg, M.J.L.
AU  - Herpen, C.M.L. van
PY  - 2017
UR  - https://hdl.handle.net/2066/174696
AB  - OBJECTIVES: The aim of this study was to assess the feasibility of testing actionable mutations in small amounts of formalin-fixed paraffin-embedded material in multiple genes of the receptor tyrosine kinase pathway and to determine the frequency of these mutations in human papillomavirus (HPV)-positive and HPV-negative oropharyngeal cancer (OPC). DESIGN: A retrospective pilot study was performed. SETTING: In OPC, no predictive markers for response to epidermal growth factor receptor inhibition are known. Therefore, identifying predictive biomarkers is of utmost importance, but is often hampered by the small amount of tumour material available. PARTICIPANTS: We included the archival material of 45 OPC, all treated with concomitant chemoradiotherapy between 2003 and 2010. MAIN OUTCOME MEASURES: Besides the HPV status, we assessed mutations using a gene panel that targets 16 genes in the receptor tyrosine kinase pathway and six other genes. The polymerase chain reaction required only 10 ng DNA. RESULTS: In total, 42 of the 45 biopsies have been successfully analysed. In total 20 of 42 samples were HPV-positive and 22 of 42 were HPV-negative. In the receptor tyrosine kinase pathway, mutations in PIK3CA were most frequently identified. A TP53 mutation was identified in one HPV-positive sample and in 13 HPV-negative samples. Additionally, three mutations in three different genes were found. CONCLUSIONS: We evaluated an assay to identify mutations in the receptor tyrosine kinase pathway. As only small amounts of formalin-fixed paraffin-embedded material are sufficient for reliable analysis, this test opens up new possibilities for personalised medicine.
TI  - Using a semi-conductor sequencing-based panel for genotyping of HPV-positive and HPV-negative oropharyngeal cancer: a retrospective pilot study
EP  - 686
SN  - 0307-7772
IS  - iss. 3
SP  - 681
JF  - Clinical Otolaryngology
VL  - vol. 42
DO  - https://doi.org/10.1111/coa.12800
ER  - 
TY  - JOUR
AU  - Tesselaar, M.H.
AU  - Crezee, T.
AU  - Swarts, H.G.
AU  - Gerrits, D.
AU  - Boerman, O.C.
AU  - Koenderink, J.B.
AU  - Stunnenberg, H.
AU  - Netea, M.G.
AU  - Smit, J.W.A.
AU  - Netea-Maier, R.T.
AU  - Plantinga, T.S.
PY  - 2017
UR  - https://hdl.handle.net/2066/165740
AB  - Up to 20%-30% of patients with metastatic non-medullary thyroid cancer have persistent or recurrent disease resulting from tumor dedifferentiation. Tumor redifferentiation to restore sensitivity to radioactive iodide (RAI) therapy is considered a promising strategy to overcome RAI resistance. Autophagy has emerged as an important mechanism in cancer dedifferentiation. Here, we demonstrate the therapeutic potential of autophagy activators for redifferentiation of thyroid cancer cell lines. Five autophagy-activating compounds, all known as digitalis-like compounds, restored hNIS expression and iodide uptake in thyroid cancer cell lines. Upregulation of hNIS was mediated by intracellular Ca2+ and FOS activation. Cell proliferation was inhibited by downregulating AKT1 and by induction of autophagy and p21-dependent cell-cycle arrest. Digitalis-like compounds, also designated as cardiac glycosides for their well-characterized beneficial effects in the treatment of heart disease, could therefore represent a promising repositioned treatment modality for patients with RAI-refractory thyroid carcinoma. Mol Cancer Ther; 16(1); 169-81. (c)2016 AACR.
TI  - Digitalis-like Compounds Facilitate Non-Medullary Thyroid Cancer Redifferentiation through Intracellular Ca2+, FOS, and Autophagy-Dependent Pathways
EP  - 181
SN  - 1535-7163
IS  - iss. 1
SP  - 169
JF  - Molecular Cancer Therapeutics
VL  - vol. 16
PS  - 13 p.
DO  - https://doi.org/10.1158/1535-7163.MCT-16-0460
ER  - 
TY  - JOUR
AU  - Tesselaar, M.H.
AU  - Smit, J.W.A.
AU  - Nagarajah, J.
AU  - Netea-Maier, R.T.
AU  - Plantinga, T.S.
PY  - 2017
UR  - https://hdl.handle.net/2066/181780
AB  - While in most patients with non-medullary thyroid cancer (TC), disease remission is achieved by thyroidectomy and ablation of tumor remnants by radioactive iodide (RAI), a substantial subgroup of patients with metastatic disease present tumor lesions that have acquired RAI resistance as a result of dedifferentiation. Although oncogenic mutations in BRAF, TERT promoter and TP53 are associated with an increased propensity for induction of dedifferentiation, the role of genetic and epigenetic aberrations and their effects on important intracellular signaling pathways is not yet fully elucidated. Also immune, metabolic, stemness and microRNA pathways have emerged as important determinants of TC dedifferentiation and RAI resistance. These signaling pathways have major clinical implications since their targeting could inhibit TC progression and could enable redifferentiation to restore RAI sensitivity. In this review, we discuss the current insights into the pathological processes conferring dedifferentiation and RAI resistance in TC and elaborate on novel advances in diagnostics and therapy to improve the clinical outcome of RAI-refractory TC patients.
TI  - Pathological processes and therapeutic advances in radioiodide refractory thyroid cancer
EP  - r154
SN  - 0952-5041
IS  - iss. 4
SP  - R141
JF  - Journal of Molecular Endocrinology
VL  - vol. 59
DO  - https://doi.org/10.1530/JME-17-0134
ER  - 
TY  - JOUR
AU  - Roerink, S.H.P.P.
AU  - Wagenmakers, M.A.E.M.
AU  - Langenhuijsen, J.F.
AU  - Ballak, D.B.
AU  - Rooijackers, H.M.M.
AU  - D'Ancona, F.C.H.
AU  - Dielen, F.M. van
AU  - Smit, J.W.A.
AU  - Plantinga, T.S.
AU  - Netea-Maier, R.T.
AU  - Hermus, A.R.M.M.
PY  - 2017
UR  - https://hdl.handle.net/2066/177370
AB  - OBJECTIVE: To analyze changes in fat cell size, macrophage infiltration, and local adipose tissue adipokine profiles in different fat depots in patients with active Cushing's syndrome. METHODS: Subcutaneous (SC) and perirenal (PR) adipose tissue of 10 patients with Cushing's syndrome was compared to adipose tissue of 10 gender-, age-, and BMI-matched controls with regard to adipocyte size determined by digital image analysis on hematoxylin and eosin stainings, macrophage infiltration determined by digital image analysis on CD68 stainings, and adipose tissue leptin and adiponectin levels using fluorescent bead immunoassays and ELISA techniques. RESULTS: Compared to the controls, mean adipocyte size was larger in PR adipose tissue in patients. The percentage of macrophage infiltration of the PR adipose tissue and PR adipose tissue lysate leptin levels were higher and adiponectin levels were lower in SC and PR adipose tissue lysates in patients. The adiponectin levels were also lower in the SC adipose tissue supernatants of patients. Associations were found between the severity of hypercortisolism and PR adipocyte size. CONCLUSIONS: Cushing's syndrome is associated with hypertrophy of PR adipocytes and a higher percentage of macrophage infiltration in PR adipose tissue. These changes are associated with an adverse local adipokine profile.
TI  - Increased Adipocyte Size, Macrophage Infiltration, and Adverse Local Adipokine Profile in Perirenal Fat in Cushing's Syndrome
EP  - 1374
SN  - 1930-7381
IS  - iss. 8
SP  - 1369
JF  - Obesity
VL  - vol. 25
DO  - https://doi.org/10.1002/oby.21887
ER  - 
TY  - JOUR
AU  - Becker, K.L.
AU  - Arts, P.
AU  - Jaeger, M.
AU  - Plantinga, T.S.
AU  - Gilissen, C.F.
AU  - Laarhoven, A. van
AU  - Ingen, J. van
AU  - Veltman, J.A.
AU  - Joosten, L.A.B.
AU  - Hoischen, A.
AU  - Netea, M.G.
AU  - Iseman, M.D.
AU  - Chan, E.D.
AU  - Veerdonk, F.L. van de
PY  - 2017
UR  - https://hdl.handle.net/2066/169740
TI  - MST1R mutation as a genetic cause of Lady Windermere syndrome
SN  - 0903-1936
IS  - iss. 1
JF  - European Respiratory Journal
VL  - vol. 49
DO  - https://doi.org/10.1183/13993003.01478-2016
ER  - 
TY  - JOUR
AU  - Volker-Touw, C.M.
AU  - Koning, H.D. de
AU  - Giltay, J.C.
AU  - Kovel, C.G. de
AU  - Kempen, T.S. van
AU  - Oberndorff, K.M.
AU  - Boes, M.L.
AU  - Steensel, M.A. van
AU  - Well, G.T. van
AU  - Blokx, W.A.M.
AU  - Schalkwijk, J.
AU  - Simon, A.
AU  - Frenkel, J.
AU  - Gijn, M.E. van
PY  - 2017
UR  - https://hdl.handle.net/2066/169658
TI  - Erythematous nodes, urticarial rash and arthralgias in a large pedigree with NLRC4-related autoinflammatory disease, expansion of the phenotype
EP  - 248
SN  - 0007-0963
IS  - iss. 1
SP  - 244
JF  - British Journal of Dermatology
VL  - vol. 176
DO  - https://doi.org/10.1111/bjd.14757
ER  - 
TY  - JOUR
AU  - Maicas Blasco, N.
AU  - Vlag, J. van der
AU  - Bublitz, J.
AU  - Florquin, S.
AU  - Bakker-van Bebber, M.A.H.
AU  - Dinarello, C.A.
AU  - Verweij, V.G.M.
AU  - Masereeuw, R.
AU  - Joosten, L.A.B.
AU  - Hilbrands, L.B.
PY  - 2017
UR  - https://hdl.handle.net/2066/169694
AB  - Several lines of evidence have demonstrated the anti-inflammatory and cytoprotective effects of alpha-1-antitrypsin (AAT), the major serum serine protease inhibitor. The aim of the present study was to investigate the effects of human AAT (hAAT) monotherapy during the early and recovery phase of ischemia-induced acute kidney injury. Mild renal ischemia-reperfusion (I/R) injury was induced in male C57Bl/6 mice by bilateral clamping of the renal artery and vein for 20 min. hAAT (80 mg/kg, Prolastin(R)) was administered daily intraperitoneally (i.p.) from day -1 until day 7 after surgery. Control animals received the same amount of human serum albumin (hAlb). Plasma, urine and kidneys were collected at 2h, 1, 2, 3, 8 and 15 days after reperfusion for histological and biochemical analysis. hAAT partially preserved renal function and tubular integrity after induction of bilateral kidney I/R injury, which was accompanied with reduced renal influx of macrophages and a significant decrease of neutrophil gelatinase-associated lipocalin (NGAL) protein levels in urine and plasma. During the recovery phase, hAAT significantly decreased kidney injury molecule-1 (KIM-1) protein levels in urine but showed no significant effect on renal fibrosis. Although the observed effect size of hAAT administration was limited and therefore the clinical relevance of our findings should be evaluated carefully, these data support the potential of this natural protein to ameliorate ischemic and inflammatory conditions.
TI  - Human Alpha-1-Antitrypsin (hAAT) therapy reduces renal dysfunction and acute tubular necrosis in a murine model of bilateral kidney ischemia-reperfusion injury
SN  - 1932-6203
IS  - iss. 2
JF  - PLoS One
VL  - vol. 12
DO  - https://doi.org/10.1371/journal.pone.0168981
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/169694/169694.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Puar, T.
AU  - Engels, M.
AU  - Herwaarden, A.E. van
AU  - Sweep, C.G.J.
AU  - Hulsbergen-van de Kaa, C.A.
AU  - Kamphuis-van Ulzen, K.
AU  - Chortis, V.
AU  - Arlt, W.
AU  - Stikkelbroeck, N.
AU  - Claahsen-van der Grinten, H.L.
AU  - Hermus, A.R.M.M.
PY  - 2017
UR  - https://hdl.handle.net/2066/170123
AB  - Context: Recurrence of hypercortisolism in patients after bilateral adrenalectomy for Cushing disease is extremely rare. Patient: We present a 27-year-old man who previously underwent bilateral adrenalectomy for Cushing disease with complete clinical resolution. Cushingoid features recurred 12 years later, with bilateral testicular enlargement. Hormonal tests confirmed adrenocorticotropic hormone (ACTH)-dependent Cushing disease. Surgical resection of the testicular tumors led to clinical and biochemical remission. Design and Results: Gene expression analysis of the tumor tissue by quantitative polymerase chain reaction showed high expression of all key steroidogenic enzymes. Adrenocortical-specific genes were 5.1 x 105 (CYP11B1), 1.8 x 102 (CYP11B2), and 6.3 x 104 (MC2R) times higher than nonsteroidogenic fibroblast control. This correlated with urine steroid metabolome profiling showing 2 fivefold increases in the excretion of the metabolites of 11-deoxycortisol, 21-deoxycortisol, and total glucocorticoids. Leydig-specific genes were 4.3 x 101 (LHCGR) and 9.3 x 100 (HSD17B3) times higher than control, and urinary steroid profiling showed twofold increased excretion of the major androgen metabolites androsterone and etiocholanolone. These distinctly increased steroid metabolites were suppressed by dexamethasone but unresponsive to human chorionic gonadotropin stimulation, supporting the role of ACTH, but not luteinizing hormone, in regulating tumor-specific steroid excess. Conclusion: We report bilateral testicular tumors occurring in a patient with recurrent Cushing disease 12 years after bilateral adrenalectomy. Using mRNA expression analysis and steroid metabolome profiling, the tumors demonstrated both adrenocortical and gonadal steroidogenic properties, similar to testicular adrenal rest tumors found in patients with congenital adrenal hyperplasia, suggesting the presence of pluripotent cells even in patients without congenital adrenal hyperplasia.
TI  - Bilateral Testicular Tumors Resulting in Recurrent Cushing Disease After Bilateral Adrenalectomy
EP  - 344
SN  - 0021-972X
IS  - iss. 2
SP  - 339
JF  - Journal of Clinical Endocrinology and Metabolism
VL  - vol. 102
DO  - https://doi.org/10.1210/jc.2016-2702
ER  - 
TY  - JOUR
AU  - Neveling, K.
AU  - Mensenkamp, A.R.
AU  - Derks, R
AU  - Kwint, M.P.
AU  - Ouchene, H.
AU  - Steehouwer, M.
AU  - Lier, L.A. van
AU  - Bosgoed, E.A.J.
AU  - Rikken, A.
AU  - Tychon, M.W.J.
AU  - Zafeiropoulou, D.
AU  - Castelein, S.
AU  - Hehir-Kwa, J.Y.
AU  - Thung, G.W.
AU  - Hofste, T.
AU  - Lelieveld, S.H.
AU  - Bertens, S.M.
AU  - Adan, I.B.
AU  - Eijkelenboom, A.
AU  - Tops, B.B.J.
AU  - Yntema, H.G.
AU  - Stokowy, T.
AU  - Knappskog, P.M.
AU  - Hoberg-Vetti, H.
AU  - Steen, V.M.
AU  - Boyle, E.
AU  - Martin, B.
AU  - Ligtenberg, M.J.L.
AU  - Shendure, J.
AU  - Nelen, M.R.
AU  - Hoischen, A.
PY  - 2017
UR  - https://hdl.handle.net/2066/169902
AB  - BACKGROUND: Despite advances in next generation DNA sequencing (NGS), NGS-based single gene tests for diagnostic purposes require improvements in terms of completeness, quality, speed, and cost. Single-molecule molecular inversion probes (smMIPs) are a technology with unrealized potential in the area of clinical genetic testing. In this proof-of-concept study, we selected 2 frequently requested gene tests, those for the breast cancer genes BRCA1 and BRCA2, and developed an automated work flow based on smMIPs. METHODS: The BRCA1 and BRCA2 smMIPs were validated using 166 human genomic DNA samples with known variant status. A generic automated work flow was built to perform smMIP-based enrichment and sequencing for BRCA1, BRCA2, and the checkpoint kinase 2 (CHEK2) c.1100del variant. RESULTS: Pathogenic and benign variants were analyzed in a subset of 152 previously BRCA-genotyped samples, yielding an analytical sensitivity and specificity of 100%. Following automation, blind analysis of 65 in-house samples and 267 Norwegian samples correctly identified all true-positive variants (>3000), with no false positives. Consequent to process optimization, turnaround times were reduced by 60% to currently 10-15 days. Copy number variants were detected with an analytical sensitivity of 100% and an analytical specificity of 88%. CONCLUSIONS: smMIP-based genetic testing enables automated and reliable analysis of the coding sequences of BRCA1 and BRCA2. The use of single-molecule tags, double-tiled targeted enrichment, and capturing and sequencing in duplo, in combination with automated library preparation and data analysis, results in a robust process and reduces routine turnaround times. Furthermore, smMIP-based copy number variation analysis could make independent copy number variation tools like multiplex ligation-dependent probes amplification dispensable.
TI  - BRCA Testing by Single-Molecule Molecular Inversion Probes
EP  - 512
SN  - 0009-9147
IS  - iss. 2
SP  - 503
JF  - Clinical Chemistry
VL  - vol. 63
DO  - https://doi.org/10.1373/clinchem.2016.263897
ER  - 
TY  - JOUR
AU  - Voermans, N.C.
AU  - Preisler, N.
AU  - Madsen, K.L.
AU  - Janssen, M.C.H.
AU  - Kusters, B.
AU  - AbuBakar, N. Bin
AU  - Conte, F.
AU  - Lamberti, V.M.
AU  - Nusman, F.
AU  - Engelen, B.G.M. van
AU  - Scherpenzeel, M. van
AU  - Vissing, J.
AU  - Lefeber, D.J.
PY  - 2017
UR  - https://hdl.handle.net/2066/169774
AB  - Mutations in PGM1 (phosphoglucomutase 1) cause Glycogen Storage Disease type XIV, which is also a congenital disorder of protein N-glycosylation. It presents throughout life as myopathy with additional systemic symptoms. We report the effect of oral galactose treatment during five months in a patient with biochemically and genetically confirmed PGM1 deficiency. The 12-minute-walking distance increased by 225 m (65%) and transferrin glycosylation was restored to near-normal levels. The exercise assessments showed a severe exercise intolerance due to a block in skeletal muscle glycogenolytic capacity and that galactose treatment tended to normalize skeletal muscle substrate use from fat to carbohydrates during exercise.
TI  - PGM1 deficiency: Substrate use during exercise and effect of treatment with galactose
EP  - 376
SN  - 0960-8966
IS  - iss. 4
SP  - 370
JF  - Neuromuscular Disorders
VL  - vol. 27
DO  - https://doi.org/10.1016/j.nmd.2017.01.014
ER  - 
TY  - JOUR
AU  - Weren, R.D.A.
AU  - Mensenkamp, A.R.
AU  - Simons, M.
AU  - Eijkelenboom, A.
AU  - Sie, A.S.
AU  - Ouchene, H.
AU  - Asseldonk, M. van
AU  - Gomez-Garcia, E.B.
AU  - Blok, M.J.
AU  - Hullu, J.A. de
AU  - Nelen, M.R.
AU  - Hoischen, A.
AU  - Bulten, J.
AU  - Tops, B.B.J.
AU  - Hoogerbrugge, N.
AU  - Ligtenberg, M.J.L.
PY  - 2017
UR  - https://hdl.handle.net/2066/170272
TI  - Novel BRCA1 and BRCA2 Tumor Test as Basis for Treatment Decisions and Referral for Genetic Counselling of Patients with Ovarian Carcinomas.
EP  - 235
SN  - 1059-7794
IS  - iss. 2
SP  - 226
JF  - Human Mutation
VL  - vol. 38
DO  - https://doi.org/10.1002/humu.23137
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/170272/170272.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Gudmundsson, J.
AU  - Thorleifsson, G.
AU  - Sigurdsson, J.K.
AU  - Stefansdottir, L.
AU  - Jonasson, J.G.
AU  - Gudjonsson, S.A.
AU  - Gudbjartsson, D.F.
AU  - Masson, G.
AU  - Johannsdottir, H.
AU  - Halldorsson, G.H.
AU  - Stacey, S.N.
AU  - Helgason, H.
AU  - Sulem, P.
AU  - Senter, L.
AU  - He, H.
AU  - Liyanarachchi, S.
AU  - Ringel, M.D.
AU  - Aguillo, E.
AU  - Panadero, A.
AU  - Prats, E.
AU  - Garcia-Castano, A.
AU  - Juan, A. de
AU  - Rivera, F.
AU  - Xu, L.
AU  - Kiemeney, L.A.L.M.
AU  - Eyjolfsson, G.I.
AU  - Sigurdardottir, O.
AU  - Olafsson, I.
AU  - Kristvinsson, H.
AU  - Netea-Maier, R.T.
AU  - Jonsson, T.
AU  - Mayordomo, J.I.
AU  - Plantinga, T.S.
AU  - Hjartarson, H.
AU  - Hrafnkelsson, J.
AU  - Sturgis, E.M.
AU  - Thorsteinsdottir, U.
AU  - Rafnar, T.
AU  - Chapelle, A. de la
AU  - Stefansson, K.
PY  - 2017
UR  - https://hdl.handle.net/2066/169947
AB  - The great majority of thyroid cancers are of the non-medullary type. Here we report findings from a genome-wide association study of non-medullary thyroid cancer, including in total 3,001 patients and 287,550 controls from five study groups of European descent. Our results yield five novel loci (all with Pcombined<3 x 10-8): 1q42.2 (rs12129938 in PCNXL2), 3q26.2 (rs6793295 a missense mutation in LRCC34 near TERC), 5q22.1 (rs73227498 between NREP and EPB41L4A), 10q24.33 (rs7902587 near OBFC1), and two independently associated variants at 15q22.33 (rs2289261 and rs56062135; both in SMAD3). We also confirm recently published association results from a Chinese study of a variant on 5p15.33 (rs2736100 near the TERT gene) and present a stronger association result for a moderately correlated variant (rs10069690; OR=1.20, P=3.2 x 10-7) based on our study of individuals of European ancestry. In combination, these results raise several opportunities for future studies of the pathogenesis of thyroid cancer.
TI  - A genome-wide association study yields five novel thyroid cancer risk loci
SN  - 2041-1723
SP  - 14517
JF  - Nature Communications
VL  - vol. 8
DO  - https://doi.org/10.1038/ncomms14517
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/169947/169947.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Zhang, J.
AU  - Wang, W.
AU  - Voer, R.M. de
AU  - Hehir-Kwa, J.Y.
AU  - Kamping, E.J.
AU  - Weren, R.D.A.
AU  - Nelen, M.
AU  - Hoischen, A.
AU  - Ligtenberg, M.J.L.
AU  - Hoogerbrugge, N.
AU  - Yang, X
AU  - Yang, Z
AU  - Fan, X.
AU  - Wang, L.
AU  - Liu, H.
AU  - Wang, J
AU  - Kuiper, R.P.
AU  - Geurts van Kessel, A.H.M.
PY  - 2017
UR  - https://hdl.handle.net/2066/169654
TI  - A molecular inversion probe-based next-generation sequencing panel to detect germline mutations in Chinese early-onset colorectal cancer patients.
EP  - 24547
SN  - 1949-2553
SP  - 24533
JF  - Oncotarget
VL  - vol. 8
DO  - https://doi.org/10.18632/oncotarget.15593
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/169654/169654.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Vogelaar, I.P.
AU  - Post, R.S. van der
AU  - Krieken, J.H. van
AU  - Spruijt, L.
AU  - Zelst-Stams, W.A.G. van
AU  - Kets, C.M.
AU  - Lubinski, J.
AU  - Jakubowska, A.
AU  - Teodorczyk, U.
AU  - Aalfs, C.M.
AU  - Hest, L.P. van
AU  - Pinheiro, H.
AU  - Oliveira, C. de
AU  - Jhangiani, S.N.
AU  - Muzny, D.M.
AU  - Gibbs, R.A.
AU  - Lupski, J.R.
AU  - Ligt, J. de
AU  - Vissers, L.E.L.M.
AU  - Hoischen, A.
AU  - Gilissen, C.
AU  - Vorst, J.M. van de
AU  - Goeman, J.J.
AU  - Schackert, H.K.
AU  - Ranzani, G.N.
AU  - Molinaro, V.
AU  - Garcia, E.B.
AU  - Hes, F.J.
AU  - Holinski-Feder, E.
AU  - Genuardi, M.
AU  - Ausems, M.
AU  - Sijmons, R.H.
AU  - Wagner, A.
AU  - Kolk, L.E. van der
AU  - Bjornevoll, I.
AU  - Hoberg-Vetti, H.
AU  - Geurts van Kessel, A.H.M.
AU  - Kuiper, R.P.
AU  - Ligtenberg, M.J.L.
AU  - Hoogerbrugge, N.
PY  - 2017
UR  - https://hdl.handle.net/2066/182216
AB  - Recognition of individuals with a genetic predisposition to gastric cancer (GC) enables preventive measures. However, the underlying cause of genetic susceptibility to gastric cancer remains largely unexplained. We performed germline whole-exome sequencing on leukocyte DNA of 54 patients from 53 families with genetically unexplained diffuse-type and intestinal-type GC to identify novel GC-predisposing candidate genes. As young age at diagnosis and familial clustering are hallmarks of genetic tumor susceptibility, we selected patients that were diagnosed below the age of 35, patients from families with two cases of GC at or below age 60 and patients from families with three GC cases at or below age 70. All included individuals were tested negative for germline CDH1 mutations before or during the study. Variants that were possibly deleterious according to in silico predictions were filtered using several independent approaches that were based on gene function and gene mutation burden in controls. Despite a rigorous search, no obvious candidate GC predisposition genes were identified. This negative result stresses the importance of future research studies in large, homogeneous cohorts.
TI  - Unraveling genetic predisposition to familial or early onset gastric cancer using germline whole-exome sequencing
EP  - 1252
SN  - 1018-4813
IS  - iss. 11
SP  - 1246
JF  - European Journal of Human Genetics
VL  - vol. 25
DO  - https://doi.org/10.1038/ejhg.2017.138
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/182216/182216.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Ifrim, D.C.
AU  - Quintin, J.
AU  - Courjol, F.
AU  - Verschueren, I.
AU  - Krieken, J.H.J.M. van
AU  - Koentgen, F.
AU  - Fradin, C.
AU  - Gow, N.A.
AU  - Joosten, L.A.B.
AU  - Meer, J.W.M. van der
AU  - Veerdonk, F.L. van de
AU  - Netea, M.G.
PY  - 2016
UR  - https://hdl.handle.net/2066/171684
AB  - Despite the fact that Candida albicans is an important human fungal pathogen and Dectin-2 is a major pattern recognition receptor for fungi, our knowledge regarding the role of Dectin-2 for the host defense against disseminated candidiasis is limited. Dectin-2 deficient (Dectin-2(-/-)) mice were more susceptible to systemic candidiasis, and the susceptibility was mirrored by an elevated fungal load in the kidneys that correlated with the presence of large inflammatory foci. Phagocytosis of Candida by the macrophages lacking the Dectin-2 receptor was moderately decreased, while production of most of the macrophage-derived cytokines from Dectin-2(-/-) mice with systemic candidiasis was decreased. No striking differences among several Candida mutants defective in mannans could be detected between naive wild-type and Dectin-2(-/-) mice, apart from the beta-mannan-deficient bmt1Delta/bmt2Delta/bmt5Delta triple mutant, suggesting that beta-mannan may partially mask alpha-mannan detection, which is the major fungal structure recognized by Dectin-2. Deciphering the mechanisms responsible for host defense against the majority of C. albicans strains represents an important step in understanding the pathophysiology of systemic candidiasis, which might lead to the development of novel immunotherapeutic strategies.
TI  - The Role of Dectin-2 for Host Defense Against Disseminated Candidiasis
EP  - 276
SN  - 1079-9907
IS  - iss. 4
SP  - 267
JF  - Journal of Interferon and Cytokine Research
VL  - vol. 36
DO  - http://dx.doi.org/10.1089/jir.2015.0040
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/171684/171684.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Arts, R.W.
AU  - Plantinga, T.S.
AU  - Tuit, S.
AU  - Ulas, T.
AU  - Heinhuis, B.
AU  - Tesselaar, M.
AU  - Sloot, Y.
AU  - Adema, G.J.
AU  - Joosten, L.A.B.
AU  - Smit, J.W.A.
AU  - Netea, M.G.
AU  - Netea, R.T.
PY  - 2016
UR  - https://hdl.handle.net/2066/171836
TI  - Transcriptional and metabolic reprogramming induce an inflammatory phenotype in non-medullary thyroid carcinoma-induced macrophages.
SN  - 2162-4011
IS  - iss. 12
SP  - e1229725
JF  - Oncoimmunology
VL  - vol. 5
DO  - https://doi.org/10.1080/2162402X.2016.1229725
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/171836/171836.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Plantinga, T.S.
AU  - Tesselaar, M.H.
AU  - Morreau, H.
AU  - Corssmit, E.P.
AU  - Willemsen, B.K.T.
AU  - Kusters, B.
AU  - Grunsven, A.C.H. van
AU  - Smit, J.W.A.
AU  - Netea-Maier, R.T.
PY  - 2016
UR  - https://hdl.handle.net/2066/165918
AB  - Although non-medullary thyroid cancer (NMTC) generally has a good prognosis, 30-40% of patients with distant metastases develop resistance to radioactive iodine (RAI) therapy due to tumor dedifferentiation. For these patients, treatment options are limited and prognosis is poor. In the present study, expression and activity of autophagy was assessed in large sets of normal, benign and malignant tissues and was correlated with pathology, SLC5A5/hNIS (solute carrier family 5 member 5) protein expression, and with clinical response to RAI ablation therapy in NMTC patients. Fluorescent immunostaining for the autophagy marker LC3 was performed on 100 benign and 80 malignant thyroid tissues. Semiquantitative scoring was generated for both diffuse LC3-I intensity and number of LC3-II-positive puncta and was correlated with SLC5A5 protein expression and clinical parameters. Degree of diffuse LC3-I intensity and number of LC3-II-positive puncta scoring were not discriminative for benign vs. malignant thyroid lesions. Interestingly, however, in NMTC patients significant associations were observed between diffuse LC3-I intensity and LC3-II-positive puncta scoring on the one hand and clinical response to RAI therapy on the other hand (odds ratio [OR] = 3.13, 95% confidence interval [CI] =1.91-5.12, P = 0.01; OR = 5.68, 95%CI = 3.02-10.05, P = 0.002, respectively). Mechanistically, the number of LC3-II-positive puncta correlated with membranous SLC5A5 expression (OR = 7.71, 95%CI = 4.15-11.75, P<0.001), number of RAI treatments required to reach remission (P = 0.014), cumulative RAI dose (P = 0.026) and with overall remission and recurrence rates (P = 0.031). In conclusion, autophagy activity strongly correlates with clinical response of NMTC patients to RAI therapy, potentially by its capacity to maintain tumor cell differentiation and to preserve functional iodide uptake.
TI  - Autophagy activity is associated with membranous sodium iodide symporter expression and clinical response to radioiodine therapy in non-medullary thyroid cancer
EP  - 1205
SN  - 1554-8627
IS  - iss. 7
SP  - 1195
JF  - Autophagy
VL  - vol. 12
DO  - https://doi.org/10.1080/15548627.2016.1174802
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/165918/165918.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Roerink, S.H.P.P.
AU  - Wagenmakers, M.A.E.M.
AU  - Smit, J.W.A.
AU  - Rossum, E.F. van
AU  - Netea-Maier, R.T.
AU  - Plantinga, T.S.
AU  - Hermus, A.R.M.M.
PY  - 2016
UR  - https://hdl.handle.net/2066/167252
AB  - CONTEXT: Glucocorticoid receptor (GR) polymorphisms modulate glucocorticoid (GC) sensitivity and are associated with altered metabolic profiles. OBJECTIVE: To evaluate the presence of GR polymorphisms (BclI (rs41423247), N363S (rs56149945), ER22/23EK (rs6189/rs6190), and 9beta (rs6198) and investigate their associations with metabolic alterations in patients in long-term remission of Cushing's syndrome (CS). DESIGN AND SETTING: Cross-sectional case-control study. PATIENTS AND METHODS: Sixty patients in long-term remission of CS were genotyped. Associations between GR polymorphisms and multiple vascular, body composition and metabolic parameters were investigated. MAIN OUTCOME MEASURES: Allelic frequencies of the polymorphisms and their associations with several cardiometabolic risk factors. RESULTS: This study shows that carriers of the 9beta polymorphism have a higher systolic blood pressure and lower resistin levels. The GC sensitizing BclI polymorphism is associated with an adverse cardiometabolic risk factor profile: higher fat percentages of extremities and legs, higher serum leptin and E-selectin levels, and higher intima media thickness in carriers versus non-carriers. CONCLUSIONS: The 9beta and BclI polymorphisms of the GR adversely affect the cardiometabolic profile in patients who are in remission after the treatment of CS. This suggests that genetically altered GC sensitivity modulates the long-term adverse cardiometabolic effects resulting from (endogenous) hypercortisolism.
TI  - Glucocorticoid receptor polymorphisms modulate cardiometabolic risk factors in patients in long-term remission of Cushing's syndrome
EP  - 70
SN  - 1355-008X
IS  - iss. 1
SP  - 63
JF  - Endocrine
VL  - vol. 53
DO  - https://doi.org/10.1007/s12020-016-0883-z
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/167252/167252.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Wagenmakers, M.A.E.M.
AU  - Roerink, S.H.
AU  - Schreuder, T.H.
AU  - Plantinga, T.S.
AU  - Holewijn, S.
AU  - Thijssen, D.H.J.
AU  - Smit, J.W.A.
AU  - Rongen, G.A.P.J.M.
AU  - Pereira, A.M.
AU  - Wagenmakers, A.
AU  - Netea-Maier, R.T.
AU  - Hermus, A.R.
PY  - 2016
UR  - https://hdl.handle.net/2066/165838
AB  - CONTEXT: In active Cushing's syndrome (CS), patients suffer from endothelial dysfunction and premature atherosclerosis. However, it is uncertain to what extent vascular health recovers after long-term remission. This is highly relevant as this topic relates to future development of cardiovascular disease. OBJECTIVE: To investigate whether micro- and macrovascular health is impaired after long-term remission of CS, in patients with no or adequately treated co-morbidities. DESIGN AND SETTING: Cross-sectional case-control study in two tertiary referral centers. PATIENTS AND MAIN OUTCOME MEASURES: 63 patients (remission of CS for >/= 4 years) and 63 healthy, well-matched controls were compared. In group A (58 patients and 58 controls) serum biomarkers associated with endothelial dysfunction, intima media thickness, pulse wave velocity and pulse wave analysis were studied. In group B (14 patients and 14 controls) endothelium-dependent and-independent vasodilatation was studied in conduit arteries (flow mediated dilation of the brachial artery) and forearm skeletal muscle resistance arteries (vasodilator response to intra-arterial acetylcholine, sodium-nitroprusside and NG-monomethyl-L-arginine using venous occlusion plethysmography). RESULTS: There were no significant differences between the outcome measures of vascular health of patients and controls in group A and B. CONCLUSION: Vascular health of patients in long-term remission of Cushing's syndrome seems to be comparable to that of healthy gender-, age and BMI matched controls, provided that the patients have no, or adequately controlled co-morbidities. Therefore, the effects of hypercortisolism per se on the vasculature may be reversible. This accentuates the need for stringent treatment of metabolic co-morbidities in these patients.
TI  - Vascular health in patients in remission of Cushing's syndrome is comparable to that in BMI-matched controls.
EP  - 4150
SN  - 0021-972X
IS  - iss. 11
SP  - 4142
JF  - Journal of Clinical Endocrinology and Metabolism
VL  - vol. 101
DO  - https://doi.org/10.1210/jc.2016-1674
ER  - 
TY  - JOUR
AU  - Vogelaar, I.P.
AU  - Ligtenberg, M.J.
AU  - Post, R.S. van der
AU  - Voer, R.M. de
AU  - Kets, C.M.
AU  - Jansen, T.J.
AU  - Jacobs, L.
AU  - Schreibelt, G.
AU  - Vries, I.J. de
AU  - Netea, M.G.
AU  - Hoogerbrugge, N.
PY  - 2016
UR  - https://hdl.handle.net/2066/171354
AB  - Gastric cancer is caused by both genetic and environmental factors. A woman who suffered from recurrent candidiasis throughout her life developed diffuse-type gastric cancer at the age of 23 years. Using whole-exome sequencing we identified a germline homozygous missense variant in MYD88. Immunological assays on peripheral blood mononuclear cells revealed an impaired immune response upon stimulation with Candida albicans, characterized by a defective production of the cytokine interleukin-17. Our data suggest that a genetic defect in MYD88 results in an impaired immune response and may increase gastric cancer risk.
TI  - Recurrent candidiasis and early-onset gastric cancer in a patient with a genetically defined partial MYD88 defect
EP  - 296
SN  - 1389-9600
IS  - iss. 2
SP  - 289
JF  - Familial Cancer
VL  - vol. 15
DO  - https://doi.org/10.1007/s10689-015-9859-z
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/171354/171354.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Keijmel, S.P.
AU  - Raijmakers, R.P.H.
AU  - Schoffelen, T.
AU  - Salet, M.C.W.
AU  - Bleeker-Rovers, C.P.
PY  - 2016
UR  - https://hdl.handle.net/2066/172211
AB  - BACKGROUND: Chronic Q fever is a rare infection, which mainly manifests as endocarditis, infection of vascular prostheses or aortic aneurysms. We present the case of a 74-year-old immunocompromised man with a haematologically disseminated Coxiella burnetii infection, which has never been reported before. CASE REPORT: He was diagnosed with a chronic Q fever infection of an aneurysm with an endovascular prosthesis in 2015, but he died despite optimal treatment. Autopsy revealed a disseminated C. burnetii infection, confirmed by a positive PCR on samples from several organs. Retrospectively, he already had complaints and signs of inflammation since 2012, for which he had already been admitted in February 2014. At that time, Q fever diagnostics using PCR, complement fixation assay, and enzyme-linked immunosorbent assay on serum were all negative. In retrospect however, retesting available samples from February 2014 using immunofluorescence assay (IFA) already revealed serology compatible with chronic Q fever. CONCLUSION: Clinicians should be aware of this silent killer, especially in case of risk factors, and perform an appropriate diagnostic work-up for Q fever including IFA serology and PCR.
TI  - A fatal case of disseminated chronic Q fever: a case report and brief review of the literature
EP  - 682
SN  - 0300-8126
IS  - iss. 5
SP  - 677
JF  - Infection
VL  - vol. 44
DO  - https://doi.org/10.1007/s15010-016-0884-0
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/172211/172211.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Jaeger, M.
AU  - Carvalho, A.
AU  - Cunha, C.
AU  - Plantinga, T.S.
AU  - Veerdonk, F.L. van de
AU  - Puccetti, M.
AU  - Galosi, C.
AU  - Joosten, L.A.B.
AU  - DuPont, B.
AU  - Kullberg, B.J.
AU  - Sobel, J.D.
AU  - Romani, L.
AU  - Netea, M.G.
PY  - 2016
UR  - https://hdl.handle.net/2066/171893
AB  - Vaginal infections with Candida spp. frequently occur in women of childbearing age. A small proportion of these women experience recurrent vulvovaginal candidosis (RVVC), which is characterized by at least three episodes of infection in one year. In addition to known risk factors such as antibiotics, diabetes, or pregnancy, host genetic variation and inflammatory pathways such as the IL-1/Th17 axis have been reported to play a substantial role in the pathogenesis of RVVC. In this study, we assessed a variable number tandem repeat (VNTR) polymorphism in the NLRP3 gene that encodes a component of the inflammasome, processing the proinflammatory cytokines IL-1beta and IL-18. A total of 270 RVVC patients and 583 healthy controls were analyzed, and increased diseases susceptibility was associated with the presence of the 12/9 genotype. Furthermore, functional studies demonstrate that IL-1beta production at the vaginal surface is higher in RVVC patients bearing the 12/9 genotype compared to controls, whereas IL-1Ra levels were decreased and IL-18 levels remained unchanged. These findings suggest that IL-1beta-mediated hyperinflammation conveyed by the NLRP3 gene plays a causal role in the pathogenesis of RVVC and may identify this pathway as a potential therapeutic target in the disease.
TI  - Association of a variable number tandem repeat in the NLRP3 gene in women with susceptibility to RVVC
EP  - 801
SN  - 0934-9723
IS  - iss. 5
SP  - 797
JF  - European Journal of Clinical Microbiology and Infectious Diseases
VL  - vol. 35
DO  - https://doi.org/10.1007/s10096-016-2600-5
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/171893/171893.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Heinhuis, B.
AU  - Plantinga, T.S.
AU  - Semango, G.
AU  - Kusters, B.
AU  - Netea, M.G.
AU  - Dinarello, C.A.
AU  - Smit, J.W.A.
AU  - Netea-Maier, R.T.
AU  - Joosten, L.A.B.
PY  - 2016
UR  - https://hdl.handle.net/2066/168061
AB  - Alternative splicing is a biological mechanism that enables the synthesis of several isoforms with different or even opposite functions. This process must be tightly regulated to prevent unwanted isoform expression favoring pathological processes. Some isoforms of interleukin 32 (IL-32) are reported to be more potent in inducing inflammation, however the role in cell death remains to be investigated. This study demonstrates that IL-32gamma and IL-32beta can induce caspase-8-dependent cell death whereas this was not observed for IL-32alpha. Overexpression of IL-32beta or IL-32gamma but not IL-32alpha, resulted in enhanced expression of the survival cytokine IL-8. Furthermore, restoring the IL-8 signaling pathway by overexpressing CXCR1 in HEK293 cells, rescued IL-32beta but not IL-32gamma-induced cell death. Interestingly, IL-32gamma was able to downregulate CXCR1 and thereby induce cell death. Subsequent studies into the role of IL-32 in thyroid cancer (TC) revealed that several IL-32 isoforms, IL-8, and CXCR1 are expressed in TC cell lines and specimens. Remarkably, TC cell lines were found to produce high concentrations of IL-8, indicating an important role for IL-8 in the survival-signaling pathway in these cells. Intriguingly, a significant correlation between the IL-8 receptor CXCR1 and IL-32gamma was observed in TC specimens, while this was not observed for the other IL-32 splice variants. Blocking IL-32 alternative splicing by Isoginkgetin resulted in predominant expression of IL-32gamma splice variants and cell death in TC cell lines. All together, modulation of IL-32 alternative splicing could represent a novel strategy for the treatment of malignancies, in particular thyroid cancer.
TI  - Alternatively spliced isoforms of IL-32 differentially influence cell death pathways in cancer cell lines
EP  - 205
SN  - 0143-3334
IS  - iss. 2
SP  - 197
JF  - Carcinogenesis
VL  - vol. 37
DO  - https://doi.org/10.1093/carcin/bgv172
ER  - 
TY  - JOUR
AU  - Netea-Maier, R.T.
AU  - Plantinga, T.S.
AU  - Veerdonk, F.L. van de
AU  - Smit, J.W.A.
AU  - Netea, M.G.
PY  - 2016
UR  - https://hdl.handle.net/2066/170985
AB  - Autophagy and inflammation are 2 fundamental biological processes involved in both physiological and pathological conditions. Through its crucial role in maintaining cellular homeostasis, autophagy is involved in modulation of cell metabolism, cell survival, and host defense. Defective autophagy is associated with pathological conditions such as cancer, autoimmune disease, neurodegenerative disease, and senescence. Inflammation represents a crucial line of defense against microorganisms and other pathogens, and there is increasing evidence that autophagy has important effects on the induction and modulation of the inflammatory reaction; understanding the balance between these 2 processes may point to important possibilities for therapeutic targeting. This review focuses on the crosstalk between autophagy and inflammation as an emerging field with major implications for understanding the host defense on the one hand, and for the pathogenesis and treatment of immune-mediated diseases on the other hand.
TI  - Modulation of inflammation by autophagy: Consequences for human disease
EP  - 260
SN  - 1554-8627
IS  - iss. 2
SP  - 245
JF  - Autophagy
VL  - vol. 12
DO  - https://doi.org/10.1080/15548627.2015.1071759
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/170985/170985.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Lachmandas, E.L.
AU  - Heuvel, C.N.A.M. van den
AU  - Damen, M.S.M.A.
AU  - Cleophas, M.C.P.
AU  - Netea, M.G.
AU  - Crevel, R. van
PY  - 2016
UR  - https://hdl.handle.net/2066/172304
AB  - Type 2 diabetes mellitus confers a threefold increased risk for tuberculosis, but the underlying immunological mechanisms are still largely unknown. Possible mediators of this increased susceptibility are short-chain fatty acids, levels of which have been shown to be altered in individuals with diabetes. We examined the influence of physiological concentrations of butyrate on cytokine responses to Mycobacterium tuberculosis (Mtb) in human peripheral blood mononuclear cells (PBMCs). Butyrate decreased Mtb-induced proinflammatory cytokine responses, while it increased production of IL-10. This anti-inflammatory effect was independent of butyrate's well-characterised inhibition of HDAC activity and was not accompanied by changes in Toll-like receptor signalling pathways, the eicosanoid pathway, or cellular metabolism. In contrast blocking IL-10 activity reversed the effects of butyrate on Mtb-induced inflammation. Alteration of the gut microbiota, thereby increasing butyrate concentrations, can reduce insulin resistance and obesity, but further studies are needed to determine how this affects susceptibility to tuberculosis.
TI  - Diabetes Mellitus and Increased Tuberculosis Susceptibility: The Role of Short-Chain Fatty Acids
SN  - 2314-6745
SP  - 6014631
JF  - Journal of Diabetes Research
VL  - vol. 2016
DO  - https://doi.org/10.1155/2016/6014631
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/172304/172304.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Kolwijck, E.
AU  - Hoeven, H. van der
AU  - Sevaux, R.G.L. de
AU  - Oever, J. ten
AU  - Rijstenberg, L.L.
AU  - Lee, H.A.L. van der
AU  - Zoll, J.
AU  - Melchers, W.J.G.
AU  - Verweij, P.E.
PY  - 2016
UR  - https://hdl.handle.net/2066/166535
TI  - Voriconazole-Susceptible and Voriconazole-Resistant Aspergillus fumigatus Coinfection
EP  - 929
SN  - 1073-449X
IS  - iss. 8
SP  - 927
JF  - American Journal of Respiratory and Critical Care Medicine
VL  - vol. 193
DO  - https://doi.org/10.1164/rccm.201510-2104LE
ER  - 
TY  - JOUR
AU  - Wagenmakers, M.A.E.M.
AU  - Roerink, S.H.P.P.
AU  - Gil, L.
AU  - Plantinga, T.S.
AU  - Smit, J.W.A.
AU  - Netea-Maier, R.T.
AU  - Hermus, A.R.M.M.
PY  - 2015
UR  - https://hdl.handle.net/2066/153629
AB  - OBJECTIVE: Centripetal obesity is associated with systemic low-grade inflammation and an increased cardiovascular risk. Patients in long-term remission of Cushing's syndrome (CS) report persisting abdominal fat accumulation. However, this has previously not been adequately objectified. Therefore, we investigated the adipose tissue distribution and adipocytokine profiles of patients in long-term remission of CS. DESIGN: Cross-sectional case-control study in a tertiary referral centre. PATIENTS: Fifty-eight patients, in remission of CS for at least 5 years, were compared to 58 age-, gender- and BMI-matched healthy control subjects. MEASUREMENTS: Measures of body composition (assessed with clinical evaluation and dual-energy X-ray absorptiometry (DEXA) scanning) and serum adipocytokine profiles. RESULTS: Compared to the matched control subjects, patients in long-term remission of CS had a greater waist circumference (P < 0.01), a smaller thigh circumference (P < 0.01), a higher waist-to-hip ratio (P < 0.01) and a higher hip-to-thigh ratio (P < 0.01). As measured with DEXA scanning, patients had a higher percentage of truncal fat mass (P = 0.01), and the truncal fat mass to leg fat mass ratio was greater (P < 0.01). Patients had lower adiponectin levels (P < 0.01), higher leptin levels (P < 0.01) and higher resistin levels (P = 0.04) than control subjects. CONCLUSION: Even after long-term remission, patients who suffered from CS in the past continue to have a centripetal adipose tissue distribution and an adverse adipokine profile. This is independent of aetiology of the CS, treatment strategies, hormonal deficiencies and comorbidity, and probably contributes to the persistent increased cardiovascular risk.
TI  - Persistent centripetal fat distribution and metabolic abnormalities in patients in long-term remission of Cushing's syndrome
EP  - 187
SN  - 0300-0664
IS  - iss. 2
SP  - 180
JF  - Clinical Endocrinology
VL  - vol. 82
DO  - https://doi.org/10.1111/cen.12639
ER  - 
TY  - JOUR
AU  - Roufosse, F.
AU  - Leval, L. de
AU  - Krieken, J.H. van
AU  - Deuren, M. van
PY  - 2015
UR  - https://hdl.handle.net/2066/153323
TI  - Lymphocytic variant hypereosinophilic syndrome progressing to angioimmunoblastic T-cell lymphoma
EP  - 1894
SN  - 1042-8194
IS  - iss. 6
SP  - 1891
JF  - Leukemia & Lymphoma
VL  - vol. 56
DO  - https://doi.org/10.3109/10428194.2014.976823
ER  - 
TY  - JOUR
AU  - Wilson, G.J.
AU  - Marakalala, M.J.
AU  - Hoving, J.C.
AU  - van Laarhoven, A.
AU  - Drummond, R.A.
AU  - Kerscher, B.
AU  - Keeton, R.
AU  - van de Vosse, E.
AU  - Ottenhoff, T.H.
AU  - Plantinga, T.S.
AU  - Alisjahbana, B.
AU  - Govender, D.
AU  - Besra, G.S.
AU  - Netea, M.G.
AU  - Reid, D.M.
AU  - Willment, J.A.
AU  - Jacobs, M.
AU  - Yamasaki, S.
AU  - Crevel, R. van
AU  - Brown, G.D.
PY  - 2015
UR  - https://hdl.handle.net/2066/154103
AB  - The interaction of microbes with pattern recognition receptors (PRRs) is essential for protective immunity. While many PRRs that recognize mycobacteria have been identified, none is essentially required for host defense in vivo. Here, we have identified the C-type lectin receptor CLECSF8 (CLEC4D, MCL) as a key molecule in anti-mycobacterial host defense. Clecsf8-/- mice exhibit higher bacterial burdens and increased mortality upon M. tuberculosis infection. Additionally, Clecsf8 deficiency is associated with exacerbated pulmonary inflammation, characterized by enhanced neutrophil recruitment. Clecsf8-/- mice show reduced mycobacterial uptake by pulmonary leukocytes, but infection with opsonized bacteria can restore this phagocytic defect as well as decrease bacterial burdens. Notably, a CLECSF8 polymorphism identified in humans is associated with an increased susceptibility to pulmonary tuberculosis. We conclude that CLECSF8 plays a non-redundant role in anti-mycobacterial immunity in mouse and in man.
TI  - The C-type lectin receptor CLECSF8/CLEC4D is a key component of anti-mycobacterial immunity
EP  - 259
SN  - 1931-3128
IS  - iss. 2
SP  - 252
JF  - Cell Host & Microbe
VL  - vol. 17
DO  - https://doi.org/10.1016/j.chom.2015.01.004
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/154103/154103.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Netea-Maier, R.T.
AU  - Kluck, V.
AU  - Plantinga, T.S.
AU  - Smit, J.W.A.
PY  - 2015
UR  - https://hdl.handle.net/2066/154611
AB  - Thyroid cancer is the most common endocrine malignancy. Despite having a good prognosis in the majority of cases, when the tumor is dedifferentiated it does no longer respond to conventional treatment with radioactive iodine, the prognosis worsens significantly. Treatment options for advanced, dedifferentiated disease are limited and do not cure the disease. Autophagy, a process of self-digestion in which damaged molecules or organelles are degraded and recycled, has emerged as an important player in the pathogenesis of different diseases, including cancer. The role of autophagy in thyroid cancer pathogenesis is not yet elucidated. However, the available data indicate that autophagy is involved in several steps of thyroid tumor initiation and progression as well as in therapy resistance and therefore could be exploited for therapeutic applications. The present review summarizes the most recent data on the role of autophagy in the pathogenesis of thyroid cancer and we will provide a perspective on how this process can be targeted for potential therapeutic approaches and could be further explored in the context of multimodality treatment in cancer and personalized medicine.
TI  - Autophagy in thyroid cancer: present knowledge and future perspectives
SN  - 1664-2392
JF  - Frontiers in Endocrinology
VL  - vol. 6
DO  - https://doi.org/10.3389/fendo.2015.00022
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/154611/154611.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Jaeger, M.
AU  - Lee, R.T.J.G. van der
AU  - Cheng, S.C.
AU  - Johnson, M.D.
AU  - Kumar, V.
AU  - Ng, A.
AU  - Plantinga, T.S.
AU  - Smeekens, S.P.
AU  - Oosting, M.
AU  - Wang, X.
AU  - Barchet, W.
AU  - Fitzgerald, K.
AU  - Joosten, L.A.B.
AU  - Perfect, J.R.
AU  - Wijmenga, C.
AU  - Veerdonk, F.L. van de
AU  - Huijnen, M.A.
AU  - Xavier, R.J.
AU  - Kullberg, B.J.
AU  - Netea, M.G.
PY  - 2015
UR  - https://hdl.handle.net/2066/154134
AB  - The induction of host defense against Candida species is initiated by recognition of the fungi by pattern recognition receptors and activation of downstream pathways that produce inflammatory mediators essential for infection clearance. In this study, we present complementary evidence based on transcriptome analysis, genetics, and immunological studies in knockout mice and humans that the cytosolic RIG-I-like receptor MDA5 (IFIH1) has an important role in the host defense against C. albicans. Firstly, IFIH1 expression in macrophages is specifically induced by invasive C. albicans hyphae, and patients suffering from chronic mucocutaneous candidiasis (CMC) express lower levels of MDA5 than healthy controls. Secondly, there is a strong association between missense variants in the IFIH1 gene (rs1990760 and rs3747517) and susceptibility to systemic Candida infections. Thirdly, cells from Mda5 knockout mice and human peripheral blood mononuclear cells (PBMCs) with different IFIH1 genotypes display an altered cytokine response to C. albicans. These data strongly suggest that MDA5 is involved in immune responses to Candida infection. As a receptor for viral RNA, MDA5 until now has been linked to antiviral host defense, but these novel studies show unexpected effects in antifungal immunity as well. Future studies are warranted to explore the potential of MDA5 as a novel target for immunotherapeutic strategies.
TI  - The RIG-I-like helicase receptor MDA5 (IFIH1) is involved in the host defense against Candida infections
EP  - 974
SN  - 0934-9723
IS  - iss. 5
SP  - 963
JF  - European Journal of Clinical Microbiology and Infectious Diseases
VL  - vol. 34
DO  - https://doi.org/10.1007/s10096-014-2309-2
ER  - 
TY  - JOUR
AU  - Ifrim, D.C.
AU  - Bain, J.M.
AU  - Reid, D.M.
AU  - Oosting, M.
AU  - Verschueren, I.
AU  - Gow, N.A.
AU  - Krieken, J.H.J.M. van
AU  - Brown, G.D.
AU  - Kullberg, B.J.
AU  - Joosten, L.A.B.
AU  - Meer, J.W.M. van der
AU  - Koentgen, F.
AU  - Erwig, L.P.
AU  - Quintin, J.
AU  - Netea, M.G.
PY  - 2014
UR  - https://hdl.handle.net/2066/136746
AB  - Although Candida glabrata is an important pathogenic Candida species, relatively little is known about its innate immune recognition. Here, we explore the potential role of Dectin-2 for host defense against C. glabrata. Dectin-2-deficient (Dectin-2(-/-)) mice were found to be more susceptible to C. glabrata infections, showing a defective fungal clearance in kidneys but not in the liver. The increased susceptibility to infection was accompanied by lower production of T helper 1 (Th1) and Th17-derived cytokines by splenocytes of Dectin-2(-/-) mice, while macrophage-derived cytokines were less affected. These defects were associated with a moderate yet significant decrease in phagocytosis of the fungus by the Dectin-2(-/-) macrophages and neutrophils. Neutrophils of Dectin-2(-/-) mice also displayed lower production of reactive oxygen species (ROS) upon challenge with opsonized C. glabrata or C. albicans. This study suggests that Dectin-2 is important in host defense against C. glabrata and provides new insights into the host defense mechanisms against this important fungal pathogen.
TI  - Role of Dectin-2 for Host Defense against Systemic Infection with Candida glabrata
EP  - 1073
SN  - 0019-9567
IS  - iss. 3
SP  - 1064
JF  - Infection and Immunity
VL  - vol. 82
DO  - https://doi.org/10.1128/IAI.01189-13
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/136746/136746.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Roufosse, F.
AU  - Leval, L. de
AU  - Krieken, H. van
AU  - Deuren, M. van
PY  - 2014
UR  - https://hdl.handle.net/2066/138914
TI  - Lymphocytic variant hypereosinophilic syndrome progressing to angioimmunoblastic T-cell lymphoma
EP  - 4
SN  - 1042-8194
SP  - 1
JF  - Leukemia & Lymphoma
DO  - https://doi.org/10.3109/10428194.2014.976823
ER  - 
TY  - JOUR
AU  - Vriens, B.E.
AU  - Aarts, M.J.
AU  - Vries, B. de
AU  - Gastel, S.M. van
AU  - Wals, J.
AU  - Smilde, T.J.
AU  - Warmerdam, L.J. van
AU  - Boer, M. de
AU  - Spronsen, D.J. van
AU  - Borm, G.F.
AU  - Tjan-Heijnen, V.C.
AU  - Stienen, J.J.C.
AU  - Hermens, R.P.M.G.
AU  - Wennekes, L.
AU  - Schans, S.A. van de
AU  - Dekker, H.M.
AU  - Blijlevens, N.M.A.
AU  - Maazen, R.W.M. van der
AU  - Adang, E.M.M.
AU  - Krieken, J.H.J.M. van
AU  - Ottevanger, P.B.
AU  - et al.
PY  - 2013
UR  - http://repository.ubn.ru.nl/handle/2066/127295
AB  - Abstract
BACKGROUND: This study was designed to determine whether delivering neo-adjuvant chemotherapy at a higher dose in a shorter period of time improves outcome of breast cancer patients.

PATIENTS AND METHODS: Women with newly diagnosed breast cancer were randomly assigned to neoadjuvant chemotherapy of four cycles of doxorubicin and cyclophosphamide followed by four cycles of docetaxel (AC 60/600 - T 100mg/m(2)) or six cycles of TAC (75/50/500mg/m(2)) every 3 weeks. The primary endpoint was the pathologic complete response (pCR) rate, defined as no invasive tumour present in the breast.

RESULTS: In total, 201 patients were included. Baseline characteristics were well balanced. AC-T resulted in pCR in 21% and TAC in 16% of patients (odds ratio 1.44 (95% confidence interval (CI) 0.67-3.10). AC-T without primary granulocyte-colony stimulating factor (G-CSF) prophylaxis was associated with more febrile neutropenia compared to TAC with primary G-CSF prophylaxis (23% versus 9%), and with more grade 3/4 sensory neuropathy (5% versus 0%).

CONCLUSIONS: With a higher cumulative dose for the concurrent arm, no differences were observed between the two treatment arms with respect to pCR rate. The differential toxicity profile could partly be explained by different use of primary G-CSF prophylaxis.

Copyright © 2013 Elsevier Ltd. All rights reserved.

KEYWORDS: Breast cancer, Cyclophosphamide, Docetaxel, Doxorubicin, Neoadjuvant chemotherapy
TI  - Doxorubicin/cyclophosphamide with concurrent versus sequential docetaxel as neoadjuvant treatment in patients with breast cancer.
EP  - 3110
SN  - 0959-8049
IS  - iss. 15
SP  - 3102
JF  - European Journal of Cancer
VL  - vol. 49
DO  - https://doi.org/10.1016/j.ejca.2013.06.012
ER  - 
TY  - JOUR
AU  - Hoogerwerf, J.J.
AU  - van der Windt, G.J.
AU  - Blok, D.C.
AU  - Hoogendijk, A.J.
AU  - de Vos, A.F.
AU  - van 't Veer, C.
AU  - Florquin, S.
AU  - Kobayashi, K.S.
AU  - Flavell, R.A.
AU  - van der Poll, T.
PY  - 2012
UR  - https://hdl.handle.net/2066/108394
AB  - Pneumonia is a common cause of morbidity and mortality and the most frequent source of sepsis. Bacteria that try to invade normally sterile body sites are recognized by innate immune cells through pattern recognition receptors, among which toll-like receptors (TLRs) feature prominently. Interleukin-1 receptor (IL-1R)-associated kinase (IRAK)-M is a proximal inhibitor of TLR signaling expressed by epithelial cells and macrophages in the lung. To determine the role of IRAK-M in host defense against bacterial pneumonia, IRAK-M-deficient (IRAK-M(-/-)) and normal wild-type (WT) mice were infected intranasally with Klebsiella pneumoniae. IRAK-M mRNA was upregulated in lungs of WT mice with Klebsiella pneumonia, and the absence of IRAK-M resulted in a strongly improved host defense as reflected by reduced bacterial growth in the lungs, diminished dissemination to distant body sites, less peripheral tissue injury and better survival rates. Although IRAK-M(-/-) alveolar macrophages displayed enhanced responsiveness toward intact K. pneumoniae and Klebsiella lipopolysaccharide (LPS) in vitro, IRAK-M(-/-) mice did not show increased cytokine or chemokine levels in their lungs after infection in vivo. The extent of lung inflammation was increased in IRAK-M(-/-) mice shortly after K. pneumoniae infection, as determined by semiquantitative scoring of specific components of the inflammatory response in lung tissue slides. These data indicate that IRAK-M impairs host defense during pneumonia caused by a common gram-negative respiratory pathogen.
TI  - Interleukin-1 Receptor-Associated Kinase M-Deficient Mice Demonstrate an Improved Host Defense during Gram-negative Pneumonia
EP  - 1075
SN  - 1076-1551
IS  - iss. 1
SP  - 1067
JF  - Molecular Medicine
VL  - vol. 18
DO  - https://doi.org/10.2119/molmed.2011.00450
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/108394/108394.pdf?sequence=1
ER  - 
TY  - JOUR
AU  - Schuurs-Hoeijmakers, J.H.M.
AU  - Geraghty, M.T.
AU  - Kamsteeg, E.J.
AU  - Ben-Salem, S.
AU  - Bot, S.T. de
AU  - Nijhof, B.
AU  - van de, V., II
AU  - Graaf, M. van der
AU  - Nobau, A.C.
AU  - Otte-Holler, I.
AU  - Vermeer, S.
AU  - Smith, A.C.
AU  - Humphreys, P.
AU  - Schwartzentruber, J.
AU  - Consortium, F.C.
AU  - Ali, B.R.
AU  - Al-Yahyaee, S.A.
AU  - Tariq, S.
AU  - Pramathan, T.
AU  - Bayoumi, R.
AU  - Kremer, H.P.H.
AU  - Warrenburg, B.P.C. van de
AU  - van den Akker, W.M.
AU  - Gilissen, C.F.H.A.
AU  - Veltman, J.A.
AU  - Janssen, I.M.
AU  - Vulto-van Silfhout, A.T.
AU  - van der Velde-Visser, S.
AU  - Lefeber, D.J.
AU  - Diekstra, A.
AU  - Erasmus, C.E.
AU  - Willemsen, M.A.A.P.
AU  - Peart-Vissers, L.E.L.M.
AU  - Lammens, M.M.Y.
AU  - Bokhoven, J.H.L.M. van
AU  - Brunner, H.G.
AU  - Wevers, R.A.
AU  - Schenck, A.
AU  - Al-Gazali, L.
AU  - Vries, L.B.A. de
AU  - Brouwer, A.P.M. de
PY  - 2012
UR  - https://hdl.handle.net/2066/108770
AB  - We report on four families affected by a clinical presentation of complex hereditary spastic paraplegia (HSP) due to recessive mutations in DDHD2, encoding one of the three mammalian intracellular phospholipases A(1) (iPLA(1)). The core phenotype of this HSP syndrome consists of very early-onset (<2 years) spastic paraplegia, intellectual disability, and a specific pattern of brain abnormalities on cerebral imaging. An essential role for DDHD2 in the human CNS, and perhaps more specifically in synaptic functioning, is supported by a reduced number of active zones at synaptic terminals in Ddhd-knockdown Drosophila models. All identified mutations affect the protein's DDHD domain, which is vital for its phospholipase activity. In line with the function of DDHD2 in lipid metabolism and its role in the CNS, an abnormal lipid peak indicating accumulation of lipids was detected with cerebral magnetic resonance spectroscopy, which provides an applicable diagnostic biomarker that can distinguish the DDHD2 phenotype from other complex HSP phenotypes. We show that mutations in DDHD2 cause a specific complex HSP subtype (SPG54), thereby linking a member of the PLA(1) family to human neurologic disease.
TI  - Mutations in DDHD2, Encoding an Intracellular Phospholipase A(1), Cause a Recessive Form of Complex Hereditary Spastic Paraplegia
EP  - 1081
SN  - 0002-9297
IS  - iss. 6
SP  - 1073
JF  - American Journal of Human Genetics
VL  - vol. 91
DO  - https://doi.org/10.1016/j.ajhg.2012.10.017
ER  - 
TY  - JOUR
AU  - Brand, M. van den
AU  - Flucke, U.E.
AU  - Bult, P.
AU  - Weemaes, C.M.R.
AU  - Deuren, M. van
PY  - 2011
UR  - https://hdl.handle.net/2066/95645
AB  - The Immunodeficiency, Centromeric region instability, and Facial anomalies (ICF) syndrome (OMIM #242860) is a rare autosomal recessive disorder caused by defective DNA methylation. Hematological disease and malignancy (macrophage activation syndrome, myelodysplastic syndrome, and Hodgkin lymphoma) have been reported in three patients. To date, there have been no reports of either epithelial or mesenchymal malignancies. We present a patient with all clinical and laboratory findings of the ICF syndrome who died of a metastatic angiosarcoma of the liver. This is the first report of a non-hematological malignancy in the ICF syndrome. The young age at which our patient developed an angiosarcoma suggests an effect of the defective DNA methylation observed in the ICF syndrome. Therefore, with improvement of recognition and treatment of the ICF syndrome, malignancy could become more common in this condition.
TI  - Angiosarcoma in a patient with immunodeficiency, centromeric region instability, facial anomalies (ICF) syndrome
EP  - 625
SN  - 1552-4825
IS  - iss. 3
SP  - 622
JF  - American Journal of Medical Genetics. Part A
VL  - vol. 155A
DO  - https://doi.org/10.1002/ajmg.a.33831
ER  - 
TY  - JOUR
AU  - Span, P.N.
AU  - Rao, J.U.
AU  - Oude Ophuis, S.B.
AU  - Lenders, J.W.M.
AU  - Sweep, C.G.J.
AU  - Wesseling, P.
AU  - Kusters, B.
AU  - Nederveen, F.H. van
AU  - Krijger, R.R. de
AU  - Hermus, A.R.M.M.
AU  - Timmers, H.J.L.M.
PY  - 2011
UR  - https://hdl.handle.net/2066/96170
AB  - Paragangliomas (PGLs) have widely different metastastic potentials. Two different types of PGLs can be defined by expression profiling. Cluster 1 PGLs exhibit VHL and/or succinate dehydrogenase (SDH) mutations and a pseudohypoxic phenotype. RET and neurofibromatosis type 1 (NF1) mutations occur in cluster 2 tumors characterized by deregulation of the RAS/RAF/MAP kinase signaling cascade. Sporadic PGLs can exhibit either profile. During sustained hypoxia, a natural antisense transcript of hypoxia-inducible factor 1 (aHIF) is expressed. The role of aHIF in the metastatic potential of PGL has not yet been investigated. The aim was to test the hypothesis that genotype-specific overexpression of aHIF is associated with an increased metastatic potential. Tumor samples were collected from 87 patients with PGL. Quantitative PCR was performed for aHIF, vascular endothelial growth factor (VEGF), aquaporin 3, cytochrome b561, p57Kip2, slit homolog 3, and SDHC. Expression was related to mutation status, benign versus malignant tumors, and metastasis-free survival. We found that both aHIF and VEGF were overexpressed in cluster 1 PGLs and in metastatic tumors. In contrast, slit homolog 3, p57Kip2, cytochrome b561, and SDHC showed overexpression in non-metastatic tumors, whereas no such difference was observed for aquaporin 3. Patients with higher expression levels of aHIF and VEGF had a significantly decreased metastasis-free survival. Higher expression levels of SDHC are correlated with an increased metastasis-free survival. In conclusion, we not only demonstrate a higher expression of VEGF in cluster 1 PGL, fitting a profile of pseudohypoxia and angiogenesis, but also of aHIF. Moreover, overexpression of aHIF and VEGF marks a higher metastatic potential in PGL.
TI  - Overexpression of the natural antisense hypoxia-inducible factor-1alpha transcript is associated with malignant pheochromocytoma/paraganglioma
EP  - 331
SN  - 1351-0088
IS  - iss. 3
SP  - 323
JF  - Endocrine-Related Cancer
VL  - vol. 18
DO  - https://doi.org/10.1530/ERC-10-0184
ER  - 
TY  - JOUR
AU  - Asseldonk, E.J.P. van
AU  - Sevaux, R.G.L. de
AU  - Flucke, U.E.
AU  - Rooy, J.W.J. de
AU  - Netea-Maier, R.T.
AU  - Timmers, H.J.L.M.
PY  - 2011
UR  - https://hdl.handle.net/2066/98122
TI  - Multiple osteolytic bone lesions
EP  - 403
SN  - 0300-2977
IS  - iss. 9
SP  - 399,
JF  - Netherlands Journal of Medicine
VL  - vol. 69
ER  - 
TY  - JOUR
AU  - Smits, B.
AU  - Heuvel, L.P.W.J. van den
AU  - Knoop, H.
AU  - Kusters, B.
AU  - Janssen, A.
AU  - Borm, G.F.
AU  - Bleijenberg, G.
AU  - Rodenburg, R.J.T.
AU  - Engelen, B.G.M. van
PY  - 2011
UR  - https://hdl.handle.net/2066/97119
AB  - We studied the extent of mitochondrial involvement in chronic fatigue syndrome (CFS) and investigated whether measurement of mitochondrial respiratory chain complex (RCC) activities discriminates between CFS and mitochondrial disorders. Mitochondrial content was decreased in CFS compared to healthy controls, whereas RCC activities corrected for mitochondrial content were not. Conversely, mitochondrial content did not discriminate between CFS and two groups of mitochondrial disorders, whereas ATP production rate and complex I, III and IV activity did, all with higher activities in CFS. We conclude that the ATP production rate and RCC activities can reliably discriminate between mitochondrial disorders and CFS.
TI  - Mitochondrial enzymes discriminate between mitochondrial disorders and chronic fatigue syndrome
EP  - 738
SN  - 1567-7249
IS  - iss. 5
SP  - 735
JF  - Mitochondrion
VL  - vol. 11
DO  - https://doi.org/10.1016/j.mito.2011.05.005
ER  - 
TY  - JOUR
AU  - Luijtgaarden, A.C.M. van de
AU  - Ven, A.J.A.M. van der
AU  - Leenders, W.P.J.
AU  - Kaal, S.
AU  - Flucke, U.E.
AU  - Oyen, W.J.G.
AU  - Graaf, W.T.A. van der
PY  - 2010
UR  - https://hdl.handle.net/2066/88205
TI  - Imaging of HIV-associated Kaposi sarcoma; F-18-FDG-PET/CT and In-111-bevacizumabscintigraphy.
EP  - 446
SN  - 1525-4135
IS  - iss. 4
SP  - 444
JF  - JAIDS : Journal of Acquired Immune Deficiency Syndromes
VL  - vol. 54
DO  - https://doi.org/10.1097/QAI.0b013e3181cdf61f
ER  - 
TY  - JOUR
AU  - Vriens, D.
AU  - Geus-Oei, L.F. de
AU  - Flucke, U.E.
AU  - Kogel, A.J. van der
AU  - Oyen, W.J.G.
AU  - Vierhout, M.E.
AU  - Meer, J.W.M. van der
PY  - 2010
UR  - https://hdl.handle.net/2066/88574
TI  - Benign uterine uptake of FDG: a case report and review of literature.
EP  - 380
SN  - 0300-2977
IS  - iss. 9
SP  - 379
JF  - Netherlands Journal of Medicine
VL  - vol. 68
N1  - 1 september 2010
L1  - https://repository.ubn.ru.nl/bitstream/handle/2066/88574/88574_pub.pdf?sequence=1
ER  -