keyword
https://read.qxmd.com/read/25511680/induction-of-tap73-by-platinum-based-compounds-to-overcome-drug-resistance-in-p53-dysfunctional-chronic-lymphocytic-leukemia
#21
JOURNAL ARTICLE
Sanne H Tonino, Chantal E Mulkens, Jacoline van Laar, Ingrid A M Derks, Guangli Suo, Fransien Croon-de Boer, Marinus H J van Oers, Eric Eldering, Jean Y Wang, Arnon P Kater
In chronic lymphocytic leukemia (CLL), strategies to overcome drug resistance due to p53 dysfunction are highly needed. Platinum-based compounds such as cisplatinum (CDDP) are active in fludarabine-refractory CLL through a largely unknown mechanism. We analyzed the mechanism of action of CDDP in the context of p53 dysfunctionality. In vitro treatment with CDDP did not induce death in quiescent CLL cells, but did induce apoptosis in CD40-ligand (and CpG) stimulated and proliferating cells, irrespective of p53 function...
2015: Leukemia & Lymphoma
https://read.qxmd.com/read/25121971/mechanical-cell-matrix-feedback-explains-pairwise-and-collective-endothelial-cell-behavior-in-vitro
#22
JOURNAL ARTICLE
René F M van Oers, Elisabeth G Rens, Danielle J LaValley, Cynthia A Reinhart-King, Roeland M H Merks
In vitro cultures of endothelial cells are a widely used model system of the collective behavior of endothelial cells during vasculogenesis and angiogenesis. When seeded in an extracellular matrix, endothelial cells can form blood vessel-like structures, including vascular networks and sprouts. Endothelial morphogenesis depends on a large number of chemical and mechanical factors, including the compliancy of the extracellular matrix, the available growth factors, the adhesion of cells to the extracellular matrix, cell-cell signaling, etc...
August 2014: PLoS Computational Biology
https://read.qxmd.com/read/25006078/live-imaging-of-baculovirus-infection-of-midgut-epithelium-cells-a-functional-assay-of-per-os-infectivity-factors
#23
JOURNAL ARTICLE
Jingfang Mu, Jan W M van Lent, Guy Smagghe, Yun Wang, Xinwen Chen, Just M Vlak, Monique M van Oers
The occlusion-derived viruses (ODVs) of baculoviruses are responsible for oral infection of insect hosts, whereas budded viruses (BVs) are responsible for systemic infection within the host. The ODV membrane proteins play crucial roles in mediating virus entry into midgut epithelium cells to initiate infection and are important factors in host-range determination. For Autographa californica multiple nucleopolyhedrovirus (AcMNPV), seven conserved ODV membrane proteins have been shown to be essential for oral infectivity and are called per os infectivity factors (PIFs)...
November 2014: Journal of General Virology
https://read.qxmd.com/read/24876271/rbe-and-oer-within-the-spread-out-bragg-peak-for-proton-beam-therapy-in-vitro-study-at-the-proton-medical-research-center-at-the-university-of-tsukuba
#24
JOURNAL ARTICLE
Ayae Kanemoto, Ryoichi Hirayama, Takashi Moritake, Yoshiya Furusawa, Lue Sun, Takeji Sakae, Akihiro Kuno, Toshiyuki Terunuma, Kiyoshi Yasuoka, Yutaro Mori, Koji Tsuboi, Hideyuki Sakurai
There are few reports on the biological homogeneity within the spread-out Bragg peak (SOBP) of proton beams. Therefore, to evaluate the relative biological effectiveness (RBE) and the oxygen enhancement ratio (OER), human salivary gland tumor (HSG) cells were irradiated at the plateau position (position A) and three different positions within a 6-cm-wide SOBP (position B, 26 mm proximal to the middle; position C, middle; position D, 26 mm distal to the middle) using 155-MeV/n proton beams under both normoxic and hypoxic conditions at the Proton Medical Research Center, University of Tsukuba, Japan...
September 2014: Journal of Radiation Research
https://read.qxmd.com/read/24556366/a-functional-cancer-genomics-screen-identifies-a-druggable-synthetic-lethal-interaction-between-msh3-and-prkdc
#25
JOURNAL ARTICLE
Felix Dietlein, Lisa Thelen, Mladen Jokic, Ron D Jachimowicz, Laura Ivan, Gero Knittel, Uschi Leeser, Johanna van Oers, Winfried Edelmann, Lukas C Heukamp, H Christian Reinhardt
Here, we use a large-scale cell line-based approach to identify cancer cell-specific mutations that are associated with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) dependence. For this purpose, we profiled the mutational landscape across 1,319 cancer-associated genes of 67 distinct cell lines and identified numerous genes involved in homologous recombination-mediated DNA repair, including BRCA1, BRCA2, ATM, PAXIP, and RAD50, as being associated with non-oncogene addiction to DNA-PKcs. Mutations in the mismatch repair gene MSH3, which have been reported to occur recurrently in numerous human cancer entities, emerged as the most significant predictors of DNA-PKcs addiction...
May 2014: Cancer Discovery
https://read.qxmd.com/read/24238639/dasatinib-in-combination-with-fludarabine-in-patients-with-refractory-chronic-lymphocytic-leukemia-a-multicenter-phase-2-study
#26
MULTICENTER STUDY
Arnon P Kater, Marjolein Spiering, Roberto D Liu, G Doreen Te Raa, E Slinger, Sanne H Tonino, Marielle M Beckers, Simon Daenen, Jeanette K Doorduijn, Nienke A G Lankheet, Dieuwertje M Luijks, Eric Eldering, Marinus H J van Oers
Resistance to chemotherapy-induced apoptosis in CLL is associated with overexpression of antiapoptotic proteins induced by signals from the microenvironment. In vitro, dasatinib effectively inhibits expression of anti-apoptotic regulators and restores fludarabine sensitivity in activated CLL. The aim of this study was to evaluate efficacy of one cycle of dasatinib monotherapy (100mg/day, days 1-28) followed by combination of dasatinib with fludarabine (40mg/m²/day, days 1-3 every 28 day) for a total of 6 cycles in fludarabine-refractory CLL...
January 2014: Leukemia Research
https://read.qxmd.com/read/24100449/chronic-lymphocytic-leukemia-disease-progression-is-accelerated-by-april-taci-interaction-in-the-tcl1-transgenic-mouse-model
#27
JOURNAL ARTICLE
Valeria Lascano, Marco Guadagnoli, Jan G Schot, Dieuwertje M Luijks, Jeroen E J Guikema, Katherine Cameron, Michael Hahne, Steven Pals, Erik Slinger, Thomas J Kipps, Marinus H J van Oers, Eric Eldering, Jan Paul Medema, Arnon P Kater
Although in vitro studies pointed to the tumor necrosis factor family member APRIL (a proliferation-inducing ligand) in mediating survival of chronic lymphocytic leukemia (CLL) cells, clear evidence for a role in leukemogenesis and progression in CLL is lacking. APRIL significantly prolonged in vitro survival of CD5(+)B220(dull) leukemic cells derived from the murine Eμ-TCL1-Tg (TCL1-Tg [transgenic]) model for CLL. APRIL-TCL1 double-Tg mice showed a significantly earlier onset of leukemia and disruption of splenic architecture, and survival was significantly reduced...
December 5, 2013: Blood
https://read.qxmd.com/read/24020629/let-painting-increases-tumour-control-probability-in-hypoxic-tumours
#28
JOURNAL ARTICLE
Niels Bassler, Jakob Toftegaard, Armin Lühr, Brita Singers Sørensen, Emanuele Scifoni, Michael Krämer, Oliver Jäkel, Lise Saksø Mortensen, Jens Overgaard, Jørgen B Petersen
LET-painting was suggested as a method to overcome tumour hypoxia. In vitro experiments have demonstrated a well-established relationship between the oxygen enhancement ratio (OER) and linear energy transfer (LET), where OER approaches unity for high-LET values. However, high-LET radiation also increases the risk for side effects in normal tissue. LET-painting attempts to restrict high-LET radiation to compartments that are found to be hypoxic, while applying lower LET radiation to normoxic tissues. Methods...
January 2014: Acta Oncologica
https://read.qxmd.com/read/23990022/cll-cells-are-resistant-to-smac-mimetics-because-of-an-inability-to-form-a-ripoptosome-complex
#29
JOURNAL ARTICLE
C Maas, J M Tromp, J van Laar, R Thijssen, J A Elias, A Malara, A Krippner-Heidenreich, J Silke, M Hj van Oers, E Eldering
In the lymph node (LN) environment, chronic lymphocytic leukemia (CLL) cells display increased NF-κB activity compared with peripheral blood CLL cells, which contributes to chemoresistance. Antagonists of cellular inhibitor of apoptosis proteins (cIAPs) can induce apoptosis in various cancer cells in a tumor necrosis factor-α (TNFα)-dependent manner and are in preclinical development. Smac-mimetics promote degradation of cIAP1 and cIAP2, which results in TNFR-mediated apoptosis via formation of a ripoptosome complex, comprising RIPK1, Fas-associated protein with death domain, FLICE-like inhibitory protein and caspase-8...
August 29, 2013: Cell Death & Disease
https://read.qxmd.com/read/23735375/evaluation-of-sccvii-tumor-cell-survival-in-clamped-and-non-clamped-solid-tumors-exposed-to-carbon-ion-beams-in-comparison-to-x-rays
#30
COMPARATIVE STUDY
Ryoichi Hirayama, Akiko Uzawa, Nobuhiro Takase, Yoshitaka Matsumoto, Miho Noguchi, Kana Koda, Masakuni Ozaki, Kei Yamashita, Huizi Li, Yuki Kase, Naruhiro Matsufuji, Sachiko Koike, Shin-ichiro Masunaga, Koichi Ando, Ryuichi Okayasu, Yoshiya Furusawa
The aim of this study was to measure the RBE (relative biological effectiveness) and OER (oxygen enhancement ratio) for survival of cells within implanted solid tumors following exposure to 290MeV/nucleon carbon-ion beams or X-rays. Squamous cell carcinoma cells (SCCVII) were transplanted into the right hind legs of syngeneic C3H male mice. Irradiation with either carbon-ion beams with a 6-cm spread-out Bragg peak (SOBP, at 46 and 80keV/μm) or X-rays was delivered to 5-mm or less diameter tumors. We defined three different oxygen statuses of the irradiated cells...
August 30, 2013: Mutation Research
https://read.qxmd.com/read/23561552/cloning-and-expression-of-candidate-allergens-from-culicoides-obsoletus-for-diagnosis-of-insect-bite-hypersensitivity-in-horses
#31
JOURNAL ARTICLE
Nathalie M A van der Meide, Nathalie Roders, Marianne M Sloet van Oldruitenborgh-Oosterbaan, Peter J Schaap, Monique M van Oers, Wolfgang Leibold, Huub F J Savelkoul, Edwin Tijhaar
Insect bite hypersensitivity (IBH) is an IgE-mediated (Type I) hypersensitivity reaction induced by allergens from biting midges of the Culicoides spp. The aim of the present study was to identify, clone and express recombinant allergens from C. obsoletus, the main species found feeding on horses in the Netherlands, by sequence homology searches on the C. obsoletus specific RNA database, with previously described allergens from C. nubeculosus and C. sonorensis. BLAST searches with these described allergens resulted in similarity hits with 7 genes coding for C...
June 15, 2013: Veterinary Immunology and Immunopathology
https://read.qxmd.com/read/22397719/expansion-of-effector-t-cells-associated-with-decreased-pd-1-expression-in-patients-with-indolent-b-cell-lymphomas-and-chronic-lymphocytic-leukemia
#32
JOURNAL ARTICLE
Sanne H Tonino, Pablo J van de Berg, Si La Yong, Ineke J ten Berge, Marie José Kersten, René A W van Lier, Marinus H van Oers, Arnon P Kater
In patients with chronic lymphocytic leukemia (CLL), numbers of CD8 + CD45RA +/- CD27- effector T cells are expanded. We investigated whether this expansion is also present in other B cell malignancies and the possible mechanism underlying these changes. Whereas an increase in total CD4+and CD8+ T cell numbers was found only in CLL, numbers of CD4+ and CD8+ effector T cells were significantly increased in both CLL and indolent lymphoma, but not aggressive lymphoma and myeloma. Interestingly, PD-1 expression was decreased on effector T cells and inversely correlated with effector T cell numbers, suggesting a functional role for PD-1 in regulating T cell homeostasis...
September 2012: Leukemia & Lymphoma
https://read.qxmd.com/read/21948297/cd40-stimulation-sensitizes-cll-cells-to-lysosomal-cell-death-induction-by-type-ii-anti-cd20-mab-ga101
#33
JOURNAL ARTICLE
Margot Jak, Gregor G W van Bochove, Eric A Reits, Wouter W Kallemeijn, Jacqueline M Tromp, Pablo Umana, Christian Klein, Rene A W van Lier, Marinus H J van Oers, Eric Eldering
Sensitivity of chronic lymphocytic leukemia (CLL) cells to anti-CD20 mAbs is low and, therefore, the efficacy of monotherapy with current anti-CD20 mAbs is limited. At present, it is not known whether sensitivity of CLL cells to CD20 mAbs is modulated by microenvironmental stimuli. We have shown previously that in vitro CD40 stimulation of peripheral blood-derived CLL cells results in resistance to cytotoxic drugs. In the present study, we show that, in contrast, CD40 stimulation sensitizes CLL cells to the recently described novel type II anti-CD20 mAb GA101...
November 10, 2011: Blood
https://read.qxmd.com/read/21540489/modelling-of-the-oxygen-enhancement-ratio-for-ion-beam-radiation-therapy
#34
JOURNAL ARTICLE
Tatiana Wenzl, Jan J Wilkens
The poor treatment prognosis for tumours with oxygen-deficient areas is usually attributed to the increased radioresistance of hypoxic cells. It can be expressed by the oxygen enhancement ratio (OER), which decreases with increasing linear energy transfer (LET) suggesting a potential clinical advantage of high-LET radiotherapy with heavy ion beams compared to low-LET photon or proton irradiation. The aim of this work is to review the experimental cell survival data from the literature and, based on them, to develop a simple OER model to estimate the clinical impact of OER variations...
June 7, 2011: Physics in Medicine and Biology
https://read.qxmd.com/read/21437769/small-interfering-rna-targeting-hif-1%C3%AE-reduces-hypoxia-dependent-transcription-and-radiosensitizes-hypoxic-ht-1080-human-fibrosarcoma-cells-in-vitro
#35
JOURNAL ARTICLE
Adrian Staab, Markus Fleischer, Juergen Loeffler, Harun M Said, Astrid Katzer, Christian Plathow, Herrmann Einsele, Michael Flentje, Dirk Vordermark
BACKGROUND: Hypoxia inducible factor-1 has been identified as a potential target to overcome hypoxia-induced radioresistance The aim of the present study was to investigate whether selective HIF-1 inhibition via small interfering RNA (siRNA) targeting hypoxia-inducible factor 1α (HIF-1α) affects hypoxia-induced radioresistance in HT 1080 human fibrosarcoma cells. MATERIAL AND METHODS: HIF-1α expression in HT 1080 human fibrosarcoma cells in vitro was silenced using HIF-1α siRNA sequence primers...
April 2011: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://read.qxmd.com/read/21403646/cd40-stimulation-sensitizes-cll-cells-to-rituximab-induced-cell-death
#36
JOURNAL ARTICLE
M Jak, G G W van Bochove, R A W van Lier, E Eldering, M H J van Oers
In vitro CD40-stimulated chronic lymphocytic leukemia (CLL) cells are resistant to cytotoxic drugs. In sharp contrast, we here show that CD40 stimulation sensitizes CLL cells to rituximab-mediated cell death. This increased sensitivity is specific for anti-CD20 treatment. Rituximab-mediated death in CD40-stimulated CLL cells shows rapid kinetics (within hours), and is caspase and p53 independent, but depends on extracellular Ca(2+) and reactive oxygen species (ROS) production. By increasing basal ROS production, CD40 stimulation sensitizes CLL cells to rituximab-mediated death...
June 2011: Leukemia
https://read.qxmd.com/read/20652730/a-novel-missense-mutation-in-the-nuclear-factor-%C3%AE%C2%BAb-essential-modulator-nemo-gene-resulting-in-impaired-activation-of-the-nf-%C3%AE%C2%BAb-pathway-and-a-unique-clinical-phenotype-presenting-as-mrsa-subdural-empyema
#37
JOURNAL ARTICLE
Gene A Devora, Lijun Sun, Zhijian Chen, Nicolai S C van Oers, Eric P Hanson, Jordan S Orange, M Teresa de la Morena
INTRODUCTION: We describe a previously unreported 437 T→G missense mutation producing a V146G substitution in the first coiled-coil (CC1) domain of nuclear factor-κB essential modulator (NEMO) in a 9-month-old boy with ectodermal dysplasia with immunodeficiency who presented with methicillin-resistant Staphylococcus aureus subdural empyema. We performed in vitro experiments to determine if this novel mutation resulted in impaired NF-κB signaling. METHODS: IκBα phosphorylation experiments were performed using a Jurkat T cell line lacking endogenous NEMO expression that was transfected with vectors containing either the wild type or the patient's V146G mutation...
November 2010: Journal of Clinical Immunology
https://read.qxmd.com/read/20581863/dichotomy-in-nf-kappab-signaling-and-chemoresistance-in-immunoglobulin-variable-heavy-chain-mutated-versus-unmutated-cll-cells-upon-cd40-tlr9-triggering
#38
JOURNAL ARTICLE
J M Tromp, S H Tonino, J A Elias, A Jaspers, D M Luijks, A P Kater, R A W van Lier, M H J van Oers, E Eldering
Chronic lymphocytic leukemia (CLL) cells circulating in peripheral blood (PB) differ from the leukemic fraction in lymph nodes (LNs) with respect to cell division and drug sensitivity. CD40 stimulation of PB CLL cells in vitro results in chemoresistance and provides a partial model for the LN microenvironment. The TLR9 ligand CpG induces proliferation in immunoglobulin variable heavy-chain-unmutated CLL, but apoptosis in immunoglobulin variable heavy-chain-mutated CLL. To juxtapose proliferative with antiapoptotic signals, we investigated the effects of CpG in the context of CD40 ligation in mutated versus unmutated CLL cells in this study...
September 9, 2010: Oncogene
https://read.qxmd.com/read/18796631/c-abl-kinase-inhibitors-overcome-cd40-mediated-drug-resistance-in-cll-implications-for-therapeutic-targeting-of-chemoresistant-niches
#39
JOURNAL ARTICLE
Delfine Y H Hallaert, Annelieke Jaspers, Carel J van Noesel, Marinus H J van Oers, Arnon P Kater, Eric Eldering
In lymph node (LN) proliferation centers in chronic lymphocytic leukemia (CLL), the environment protects from apoptotic and cytotoxic triggers. Here, we aimed to define the molecular basis for the increased drug resistance and searched for novel strategies to circumvent it. The situation in CLL LN could be mimicked by prolonged in vitro CD40 stimulation, which resulted in up-regulation of antiapoptotic Bcl-xL, A1/Bfl-1, and Mcl-1 proteins, and afforded resistance to various classes of drugs (fludarabine, bortezomib, roscovitine)...
December 15, 2008: Blood
https://read.qxmd.com/read/18678665/haemophilus-ducreyi-lspa-proteins-are-tyrosine-phosphorylated-by-macrophage-encoded-protein-tyrosine-kinases
#40
JOURNAL ARTICLE
Kaiping Deng, Jason R Mock, Steven Greenberg, Nicolai S C van Oers, Eric J Hansen
The LspA proteins (LspA1 and LspA2) of Haemophilus ducreyi are necessary for this pathogen to inhibit the phagocytic activity of macrophage cell lines, an event that can be correlated with a reduction in the level of active Src family protein tyrosine kinases (PTKs) in these eukaryotic cells. During studies investigating this inhibitory mechanism, it was discovered that the LspA proteins themselves were tyrosine phosphorylated after wild-type H. ducreyi cells were incubated with macrophages. LspA proteins in cell-free concentrated H...
October 2008: Infection and Immunity
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