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OER in vitro

Hassan Rh Elsaidi, Xiao-Hong Yang, Fatemeh Ahmadi, Michael Weinfeld, Leonard I Wiebe, Piyush Kumar
INTRODUCTION: The redox characteristics of 1,2,4-benzotriazine-1,4-dioxides (BTDOs) make them potential radiosensitizing agents for hypoxic cells in solid human cancers. Tirapazamine (TPZ) is the most clinically tested BTDO radiosensitizer, despite its toxicity at effective doses. To date, no BTDOs have been developed as diagnostic markers of tissue hypoxia. HYPOTHESIS: TPZ analogues with appropriate reporting groups can act as potential radiosensitizers and hypoxia selective diagnostics...
January 14, 2019: European Journal of Medicinal Chemistry
Christopher A Baker, Ben Schudel, Mangesh I Chaudhari, Kerrie Wu, Derek Dunford, Anup K Singh, Susan B Rempe, Anson V Hatch
The ability to observe lethal anthrax exotoxins translocating through size-constricting nanopores in vitro, combined with detailed sequence and structural data, has aided in elucidated mechanisms of exotoxin cell entry and toxicity. However, due to limited observations of anthrax exotoxins translocating through protective antigen nanopores in vitro and the instability of protective antigen-functionalized suspended lipid bilayers, questions remain regarding the native mechanisms of cell entry. Nanoporous hydrogel membranes offer a robust tool for studying protein translocation with ensemble measurements that complement conventional single-molecule translocation measurements...
April 25, 2018: ACS Applied Materials & Interfaces
L Strigari, F Torriani, L Manganaro, T Inaniwa, F Dalmasso, R Cirio, A Attili
Few attempts have been made to include the oxygen enhancement ratio (OER) in treatment planning for ion beam therapy, and systematic studies to evaluate the impact of hypoxia in treatment with the beam of different ion species are sorely needed. The radiobiological models used to quantify the OER in such studies are mainly based on the dose-averaged LET estimates, and do not explicitly distinguish between the ion species and fractionation schemes. In this study, a new type of OER modelling, based on the microdosimetric kinetic model, taking into account the specificity of the different ions, LET spectra, tissues and fractionation schemes, has been developed...
March 16, 2018: Physics in Medicine and Biology
M G Gerritsen, P Brinkman, N Escobar, L D Bos, K de Heer, M Meijer, H-G Janssen, H de Cock, H A B Wösten, C E Visser, M H J van Oers, P J Sterk
Volatile organic compounds (VOCs) in exhaled breath may identify the presence of invasive pulmonary aspergillosis. We aimed to detect VOC profiles emitted by in vitro cultured, clinical Aspergillus isolates using gas chromatography-mass spectrometry (GC-MS). Three clinical Aspergillus isolates and a reference strain were cultured while conidiation was prevented. Headspace samples were analyzed using a standardized method. Breath samples of patients from which the cultures were obtained were checked for the presence of the VOCs found in vitro...
February 1, 2018: Medical Mycology
Fie J Vojdeman, Sarah E M Herman, Nikolai Kirkby, Adrian Wiestner, Mars B van T' Veer, Geir E Tjønnfjord, Maija A Itälä-Remes, Eva Kimby, Mohammed Z Farooqui, Aaron Polliack, Ka Lung Wu, Jeanette K Doorduijn, Wendimagegn G Alemayehu, Shulamiet Wittebol, Tomas Kozak, Jan Walewski, Martine C J Abrahamse-Testroote, Marinus H J van Oers, Christian H Geisler, Carsten U Niemann
CD52 is a glycoprotein expressed on normal as well as leukemic immune cells and shed as soluble CD52 (sCD52). We studied sCD52 levels in three CLL cohorts: the 'early', the 'high-risk', and the 'ibrutinib-treated'. The 'high-risk' patients had significantly higher sCD52 levels than the 'early' patients. For the 'early' patients, high sCD52 levels were associated with a significantly shorter time to first treatment. Regarding prognostic factors, no clear correlations with stage, IGHV, or beta-2-microglobulin were found; in a cox multivariate analysis of the 'early' patients, sCD52 and IGHV both had independent prognostic value...
February 7, 2017: Leukemia & Lymphoma
K de Heer, S I Vonk, M Kok, M Kolader, A H Zwinderman, M H J van Oers, P J Sterk, C E Visser
Invasive pulmonary mold disease (IPMD) is often fatal in neutropenic patients. This is because IPMD is difficult to diagnose timely, especially when non-Aspergillus molds are the causative agent, as they are usually not associated with a positive galactomannan assay. In 2013 we showed that exhaled breath analysis might be used to diagnose invasive aspergillosis through profiling of patterns in exhaled volatile organic compounds (VOCs) by electronic nose (eNose) technology. The current study aimed to determine (1) whether molds can be discriminated from other microorganisms (using two mold species: Aspergillus fumigatus and a pathogenic mold not associated with a positive galactomannan assay, i...
July 22, 2016: Journal of Breath Research
Ryoichi Hirayama, Akiko Uzawa, Maki Obara, Nobuhiro Takase, Kana Koda, Masakuni Ozaki, Miho Noguchi, Yoshitaka Matsumoto, Huizi Li, Kei Yamashita, Sachiko Koike, Koichi Ando, Toshiyuki Shirai, Naruhiro Matsufuji, Yoshiya Furusawa
We determined the relative biological effectiveness (RBE) and oxygen enhancement ratio (OER) of micronuclei (MN) formation in clamped (hypoxic) and non-clamped (normoxic) solid tumors in mice legs following exposure to X-rays and heavy ions. Single-cell suspensions (aerobic) of non-irradiated tumors were prepared in parallel and used directly to determine the radiation response for aerobic cells. Squamous cell carcinoma (SCCVII) cells were transplanted into the right hind legs of syngeneic C3H/He male mice...
November 2015: Mutation Research. Genetic Toxicology and Environmental Mutagenesis
R Thijssen, J Ter Burg, G G W van Bochove, M F M de Rooij, A Kuil, M H Jansen, T W Kuijpers, J W Baars, A Virone-Oddos, M Spaargaren, C Egile, M H J van Oers, E Eldering, M J Kersten, A P Kater
The phosphoinositide 3-kinases (PI3Ks) are critical components of the B-cell receptor (BCR) pathway and have an important role in the pathobiology of chronic lymphocytic leukemia (CLL). Inhibitors of PI3Kδ block BCR-mediated cross-talk between CLL cells and the lymph node microenvironment and provide significant clinical benefit to CLL patients. However, the PI3Kδ inhibitors applied thus far have limited direct impact on leukemia cell survival and thus are unlikely to eradicate the disease. The use of inhibitors of multiple isoforms of PI3K might lead to deeper remissions...
February 2016: Leukemia
Johanna W M Aarts, Marjan J Faber, Ben J Cohlen, Anne Van Oers, WillianNe L D M Nelen, Jan A M Kremer
The Internet is expected to innovate healthcare, in particular patient-centredness of care. Within fertility care, information provision, communication with healthcare providers and support from peers are important components of patient-centred care. An online infertility community added to an in vitro fertilisation or IVF clinic's practice provides tools to healthcare providers to meet these. This study's online infertility community facilitates peer-to-peer support, information provision to patients and patient provider communication within one clinic...
2015: Human Fertility: Journal of the British Fertility Society
René F M van Oers, Hong Wang, Rommel G Bacabac
There is considerable variation in the shape of osteocyte lacunae, which is likely to influence the function of osteocytes as the professional mechanosensors of bone. In this review, we first discussed how mechanical loading could affect the shape of osteocyte lacunae. Recent studies show that osteocyte lacunae are aligned to collagen. Since collagen fiber orientation is affected by loading mode, this alignment may help to understand how mechanical loading shapes the osteocyte lacuna. Secondly, we discussed how the shape of osteocytes could influence their mechanosensation...
April 2015: Current Osteoporosis Reports
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
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
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
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
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
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
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
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
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
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
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