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Eindhoven, Netherlands

Bovenberg M.S.S.,Massachusetts General Hospital | Bovenberg M.S.S.,Harvard University | Bovenberg M.S.S.,Leiden University | Degeling M.H.,Massachusetts General Hospital | And 21 more authors.
Analytical Chemistry | Year: 2013

Reporters secreted into the conditioned medium of cells in culture or into blood in vivo have shown to be useful tools for simple and noninvasive monitoring of biological processes in real-time. Here, we characterize the naturally secreted Vargula luciferase as a secreted blood reporter and show that this reporter can be multiplexed with the secreted Gaussia luciferase and alkaline phosphatase for simultaneous monitoring of three different cellular processes in the same biological system. We applied this system to monitor the response of three different subsets of glioma cells to a clinically relevant chemotherapeutic agent in the same well in culture or animal in vivo. This system could be extended to any field to detect multiple processes in the same biological system and is amenable for high-throughput screening to find drugs that affect multiple cellular populations/phenomena simultaneously. © 2013 American Chemical Society.

Hiddingh L.,VU University Amsterdam | Raktoe R.S.,VU University Amsterdam | Jeuken J.,PAMM | Hulleman E.,VU University Amsterdam | And 7 more authors.
Scientific Reports | Year: 2014

Drug resistance is a major issue in the treatment of glioblastoma. Almost all glioblastomas are intrinsically resistant to chemotherapeutic temozolomide (TMZ) or develop resistance during treatment. The interaction networks of microRNAs (miRNAs) and mRNAs likely regulate most biological processes and can be employed to better understand complex processes including drug resistance in cancer. In this study, we examined if integrative miRNA/mRNA network analysis using the web-service tool mirConnX could be used to identify drug resistance factors in glioblastoma. We used TMZ-resistant glioblastoma cells and their integrated miRNA/mRNA networks to identify TMZ-sensitizing factors. TMZ resistance was previously induced in glioblastoma cell lines U87, Hs683, and LNZ308. miRNA/mRNA expression profiling of these cells and integration of the profiles using mirConnX resulted in the identification of plant homeodomain (PHD)-like finger 6 (PHF6) as a potential TMZ-sensitizing factor in resistant glioblastoma cells. Analysis of PHF6 expression showed significant upregulation in glioblastoma as compared to normal tissue. Interference with PHF6 expression in three TMZ-resistant subclones significantly enhanced TMZ-induced cell kill in two of these cell lines. Altogether, these results demonstrate that mirConnX is a feasible and useful tool to investigate miRNA/mRNA interactions in TMZ-resistant cells and has potential to identify drug resistance factors in glioblastoma.

Homan J.,Radboud University Nijmegen | Bokkerink G.M.,Radboud University Nijmegen | Aarts M.J.,Netherlands Comprehensive Cancer Organization | Lemmens V.E.,Netherlands Comprehensive Cancer Organization | And 6 more authors.
European Journal of Surgical Oncology | Year: 2015

Background Since the introduction of total mesorectal surgery the outcome of rectal cancer patients has improved significantly. Involvement of the circumferential resection margin (CRM) is an important predictor of increased local recurrence, distant metastases and decreased overall survival. Abdomino perineal excision (APE) is associated with increased risk of CRM involvement. Aim of this study was to analyze reporting of CRM and to identify predictive factors for CRM involvement. Methods A population-based dataset was used selecting 2153 patients diagnosed between 2008 and 2013 with primary rectal cancer undergoing surgery. Variation in CRM reporting was assessed and predictive factors for CRM involvement were calculated and used in multivariate analyses. Results Large variation in CRM reporting was found between pathology departments, with missing cases varying from 6% to 30%. CRM reporting increased from 77% in 2008 to 90% in 2012 (p < 0.001). CRM involvement significantly decreased from 12% to 6% over the years (p < 0.001). In multivariate analysis type of operation, low anterior resection or APE, did not influence the risk of CRM involvement. Clinical T4-stage [odds ratio (OR) = 3.51; 95% confidence interval (CI) = 1.85-6.65) was associated with increased risk of CRM involvement, whereas neoadjuvant treatment (5 × 5 gray radiotherapy [OR 0.39; CI 0.25-0.62] or chemoradiation therapy [OR 0.30; CI 0.17-0.53]) were associated with significant decreased risk of CRM involvement. Conclusion Although significant improvements are made during the last years there still is variation in reporting of CRM involvement in the Southern Netherlands. In multivariate analysis APE was no longer associated with increased risk of CRM involvement. © 2015 Elsevier Ltd.

Jansen S.C.P.,Maxima Medical Center | Groeneveld-Haenen C.P.M.,Maxima Medical Center | Klinkhamer P.J.J.M.,PAMM | Roumen R.M.H.,Maxima Medisch Centrum
BMJ Case Reports | Year: 2015

Merkel cell carcinoma (MCC) is a malignant neuroendocrine carcinoma originating in the skin. It is typically aggressive with a tendency to recur locally and metastasise. There have been several case reports about spontaneous regression of MCC over the past years, but to the best of our knowledge this is the first case of a regional lymph node metastasised MCC with complete spontaneous regression and recurrence. In addition, the primary tumour has an unusual localisation on the foot. © Copyright 2015 BMJ Publishing Group. All rights reserved.

Herremans T.,National Institute for Public Health and the Environment RIVM | Hogema B.M.,Sanquin Blood Supply Foundation | Nabuurs M.,UMCN | Peeters M.,St Elisabeth Hospital | And 15 more authors.
Diagnostic Microbiology and Infectious Disease | Year: 2013

The indirect immunofluorescence assay (IFA) is considered the reference method for diagnosing Q fever, but serology is also performed by complement fixation assay (CFA) or enzyme-linked immunosorbent assay (ELISA). However, comparability between these assays is not clear, and therefore a quality assessment was performed. A total of 25 serum samples from negative controls, Q fever patients, and a serial diluted high-positive sample were analyzed in 10 Dutch laboratories. Six laboratories performed CFA, 5 performed IFA, and 5 performed ELISAs. Three international reference laboratories from Australia, France, and the USA also participated in this study. Qualitative values between laboratories using the same methods were within close range, and all 3 methods correctly identified acute Q fever patients. The IFA, ELISA, and CFA are all suitable serodiagnostic assays to diagnose acute Q fever, but the IFA remains an important tool in the follow-up of patients and in identifying patients at risk for developing chronic Q fever. © 2013 Elsevier Inc..

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