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Amsterdam-Zuidoost, Netherlands

Jacqueline Timmermans A.,Plesmanlaan | Brandsma D.,Netherlands Cancer Institute | Smeele L.E.,Plesmanlaan | Smeele L.E.,University of Amsterdam | And 4 more authors.
Annals of Otology, Rhinology and Laryngology | Year: 2013

Two patients with recurrent carcinoma of the posterior pharyngeal wall, previously treated with carbon dioxide (CO2) laser excision and (chemo)radiotherapy, presented with neck pain due to cervical osteomyelitis. In one patient this led to cervical spine instability, for which a haloframe was applied. Our working hypothesis was that cervical osteomyelitis was caused by an infected wound bed induced by CO2 laser excision of the tumor in the already vascular-compromised area of the irradiated posterior pharyngeal wall. We discuss the risks of leaving a wound for secondary granulation after CO 2 laser excision of the posterior pharyngeal wall and prophylactic antibiotic treatment. © 2013 Annals Publishing Company.

Baas P.,Plesmanlaan | Belderbos J.S.A.,Netherlands Cancer Institute | Van Den Heuvel M.,Plesmanlaan
Current Opinion in Oncology | Year: 2011

Purpose of review: The majority of patients with nonsmall cell lung cancer (NSCLC) present with locally advanced mediastinal disease. Radiation therapy is the backbone, and nowadays a combination with chemotherapy is considered standard treatment. In this review we present a short history of the developments in this field with an update of all new developments. We address the questions how to optimally combine chemotherapy, targeted agents and radiation therapy. Recent findings: The results from recently published papers dealing with combined chemoradiotherapy (CRT) and the data of two meta-analyses are reviewed. Some drugs are very suitable candidates for CRT such as cisplatin, pemetrexed and etoposide, whereas others should be avoided or used with caution (adriamycin, gemcitabine). Summary: Our evaluation indicates that there are quite a number of positive developments in the treatment of locally advanced NSCLC but there is still much to improve. Variables such as patient condition, tumor biology, dose of radiation therapy, method of application (intensity modulated radiation therapy, four-dimensional planning) and dose of chemotherapy all influence treatment outcome and should be taken into account in designing the best treatment. Well-defined studies should be undertaken balancing the possible positive effect of therapy and toxicity. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Deenen M.J.,Plesmanlaan | Cats A.,Netherlands Cancer Institute | Beijnen J.H.,Slotervaart Hospital | Beijnen J.H.,University Utrecht | And 2 more authors.
Oncologist | Year: 2011

Equivalent drug doses may lead to wide interpatient variability with regard to drug response, reflected by differences in drug activity and normal tissue toxicity. A major factor responsible for this variability is variation among patients in their genetic constitution. Genetic polymorphism may affect the activity of proteins en- coded, which in turn may lead to changes in the phar-macokinetic and pharmacodynamic behavior of a drug, observed as differences in drug transport, drug metabolism, and pharmacodynamic drug effects. Recent insights into the functional effect of polymorphism in genes that are involved in the pharmacokinetics and pharmacodynamics of anticancer drugs have provided opportunities for patient-tailored therapy in oncology. Individualized pharmacotherapy based on genotype will help to increase treatment efficacy while reducing unnecessary toxicity, especially of drugs characterized by a narrow therapeutic window, such as anticancer drugs. We provide a series of four reviews aimed at implementing pharmacogenetic-based drug and dose prescription in the daily clinical setting for the practicing oncologist. This first part in the series describes the functional impact of genetic polymorphism and provides a general background to and insight into possible clinical consequences of pharmacogenetic variability. It also discusses different methodologies for clinical pharmacogenetic studies and provides a concise overview about the different laboratory technologies for genetic mutation analysis that are currently widely applied. Subsequently, pharmacogenetic association studies in anticancer drug transport, phase I and II drug metabolism, and pharmacodynamic drug effects are discussed in the rest of the series. Opportunities for patient-tailored pharmacotherapy are highlighted.© AlphaMed Press.

Wilting R.H.,Plesmanlaan | Yanover E.,Plesmanlaan | Heideman M.R.,Plesmanlaan | Jacobs H.,Plesmanlaan | And 4 more authors.
EMBO Journal | Year: 2010

Histone deacetylases (HDACs) counterbalance acetylation of lysine residues, a protein modification involved in numerous biological processes. Here, Hdac1 and Hdac2 conditional knock-out alleles were used to study the function of class I Hdac1 and Hdac2 in cell cycle progression and haematopoietic differentiation. Combined deletion of Hdac1 and Hdac2, or inactivation of their deacetylase activity in primary or oncogenic-transformed fibroblasts, results in a senescence-like G1 cell cycle arrest, accompanied by up-regulation of the cyclin-dependent kinase inhibitor p21Cip. Notably, concomitant genetic inactivation of p53 or p21Cip indicates that Hdac1 and Hdac2 regulate p53-p21Cip-independent pathways critical for maintaining cell cycle progression. In vivo, we show that Hdac1 and Hdac2 are not essential for liver homeostasis. In contrast, total levels of Hdac1 and Hdac2 in the haematopoietic system are critical for erythrocyte-megakaryocyte differentiation. Dual inactivation of Hdac1 and Hdac2 results in apoptosis of megakaryocytes and thrombocytopenia. Together, these data indicate that Hdac1 and Hdac2 have overlapping functions in cell cycle regulation and haematopoiesis. In addition, this work provides insights into mechanism-based toxicities observed in patients treated with HDAC inhibitors. © 2010 European Molecular Biology Organization | All Rights Reserved.

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