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121.
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Otilija Keta Tanja Bulat Igor Golić Sebastien Incerti Aleksandra Korać Ivan Petrović Aleksandra Ristić-Fira 《Cell biology and toxicology》2016,32(2):83-101
In most patients with lung cancer radiation treatment is used either as single agent or in combination with radiosensitizing drugs. However, the mechanisms underlying combined therapy and its impact on different modes of cell death have not yet been fully elucidated. We aimed to examine effects of single and combined treatments with γ-rays and erlotinib on radioresistant CRL-5876 human lung adenocarcinoma cells with particular emphasis on cell death. CRL-5876 cells were treated with γ-rays and/or erlotinib and changes in cell cycle, DNA repair dynamics, ultrastructure, nuclear morphology and protein expression were monitored at different time points. To reveal the relationship between types of cell death that arise after these treatments, autophagy was blocked with chloroquine. We found that higher dose of γ-rays causes G2/M arrest while adding of erlotinib to this treatment decreases the number of cells in S phase. Impact of erlotinib on kinetics of disappearance of irradiation-induced DNA double strand breaks is reflected in the increase of residual γ-H2AX foci after 24 h. γ-rays provoke cytoprotective autophagy which precedes development of senescence. Erlotinib predominantly induces apoptosis and enlarges the number of apoptotic cells in the irradiated CRL-5876 cells. Chloroquine improved cytotoxicity induced by radiation and erlotinib, increased apoptosis and decreased senescence in the CRL-5876 cells. The results obtained on CRL-5876 cells indicate significant radiosensitizing effect of erlotinib and suggest that chloroquine in the combination with the above treatments may have an additional antitumor effect in lung adenocarcinoma. 相似文献
123.
The red fluorescent protein KillerRed, engineered from the hydrozoan chromoprotein anm2CP, has been reported to induce strong cytotoxicity through the chromophore assisted light inactivation (CALI) effect. Here, we present the X-ray structures of KillerRed in its native and bleached states. A long water-filled channel is revealed, connecting the methylene bridge of the chromophore to the solvent. This channel facilitates the transit of oxygen and of reactive oxygen species (ROS) formed by reaction with the excited chromophore. The functional roles of key mutations used to produce KillerRed are discussed, strong chromophore distortions in the bleached state are revealed, and mechanisms for ROS production and self protection are proposed. The presence of a partially mature, photo-resistant, green-emitting state is characterized, which accounts for enhanced CALI by “pre-bleached” KillerRed. 相似文献
124.
Michael Hothorn Iva Guberovic Imke K Mandemaker Charlotte Blessing Judith Sporn Arturo Gutierrez‐Triana Rebecca Smith Thomas Portmann Mathias Treier Klaus Scheffzek Sebastien Huet Gyula Timinszky Marcus Buschbeck Andreas G Ladurner 《EMBO reports》2018,19(10)
MacroH2A histone variants suppress tumor progression and act as epigenetic barriers to induced pluripotency. How they impart their influence on chromatin plasticity is not well understood. Here, we analyze how the different domains of macroH2A proteins contribute to chromatin structure and dynamics. By solving the crystal structure of the macrodomain of human macroH2A2 at 1.7 Å, we find that its putative binding pocket exhibits marked structural differences compared with the macroH2A1.1 isoform, rendering macroH2A2 unable to bind ADP‐ribose. Quantitative binding assays show that this specificity is conserved among vertebrate macroH2A isoforms. We further find that macroH2A histones reduce the transient, PARP1‐dependent chromatin relaxation that occurs in living cells upon DNA damage through two distinct mechanisms. First, macroH2A1.1 mediates an isoform‐specific effect through its ability to suppress PARP1 activity. Second, the unstructured linker region exerts an additional repressive effect that is common to all macroH2A proteins. In the absence of DNA damage, the macroH2A linker is also sufficient for rescuing heterochromatin architecture in cells deficient for macroH2A. 相似文献
125.
Gursimran Chandhoke Bobby Shayegan Sebastien J. Hotte 《Journal of medical case reports》2018,12(1):373
Background
Over the last 40 years, there has been a significant increase in the incidence of testicular cancer. The epidemiologic evidence to understand this phenomenon is unclear, however exogenous estrogen exposure is thought to be a driver in the development of testicular cancer. This is of particular importance in the transgender population because utilization of exogenous estrogen therapy is an essential aspect of the transition process.Case
We present the case of a 38-year-old Caucasian male to female transgender patient who presented with metastatic testicular cancer 15 months after initiating estrogen therapy. She presented to our emergency department with worsening back pain and fatigue. A clinical examination revealed a right-sided testicular mass. A computed tomography scan of her abdomen/pelvis identified a right groin lesion measuring 6.4 cm, a retroperitoneal mass causing right-sided hydronephrosis, an extensive deep vein thrombosis, and pathologic abdominal lymphadenopathy. Germ cell tumor markers revealed an alpha-fetoprotein of <?2.5 μg/L and a beta-human chorionic gonadotrophin of 2526 IU/L. Her lactate dehydrogenase was 5294 U/L. Medical oncology advised the discontinuation of hormonal therapy at this time. On the basis of elevation in germ cell tumor markers and the burden of disease, she was treated with four cycles of bleomycin, etoposide, and cisplatin chemotherapy. A decision to defer upfront radical inguinal orchiectomy was made due to not wanting to have an early interruption in anticoagulation.Following the completion of the chemotherapy, a 6 cm retroperitoneal mass persisted. Due to the location of the mass and surgical morbidity associated with excision, she was followed with positron emission tomography-computed tomography by Uro-oncology, with no evidence of recurrent disease 2 years since the time of diagnosis.Conclusions
While there are recognized risks associated with estrogen therapy less is known about the extent to which exogenous estrogen can serve as a driver of malignancy. With recent experimental evidence revealing a pro-growth impact of estrogen on human testicular cells, continued reporting of similar cases in the literature is imperative to see if a link between exogenous estrogen exposure and testicular cancer exists.126.
127.
Gregory Lacraz Volatiana Rakotoarivelo Sebastien M. Labbé Mathieu Vernier Christophe Noll Marian Mayhue Jana Stankova Adel Schwertani Guillaume Grenier André Carpentier Denis Richard Gerardo Ferbeyre Julie Fradette Marek Rola-Pleszczynski Alfredo Menendez Marie-France Langlois Subburaj Ilangumaran Sheela Ramanathan 《PloS one》2016,11(11)
128.
Deoxyribonucleic acid (DNA) extracted from purified virions of Shope fibroma virus (SFV) (by using DNA from Microccocus lysodeikticus as marker) had a buoyant density of 1.6996 +/- 0.0003 g/ml), hence a guanine plus cytosine (G + C) content of 40.4 +/- 0.3%, which is close to the G + C content of the DNA of susceptible rabbit cells (40.9 +/- 0.4%) and different from that of vaccinia virus DNA (35.5 +/- 0.4%). For the determination of the molecular weight of DNA, SFV and vaccinia purified virions, treated with Pronase and detergent, were cosedimented in sucrose density gradients. Results showed that SFV-DNA has a molecular weight of about 153 x 10(6) daltons. By electron microscopy, only one molecule corresponding to this value was observed (its length was 80.3 mum). The others had a median size of 49.8 mum +/- 0.9. 相似文献
129.
Amaury Farce Cedric Loge Sebastien Gallet Nicolas Lebegue Pascal Carato 《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):541-547
Cancer is a major cause of mortality in developed countries, following only cardiovascular diseases. Death of cancerous cells can be achieved by stopping mitosis and the antimitotic class of drugs formed by the spindle poisons can be used for this purpose. Their role is to disorganize the mitotic spindle by targeting its main constituent, the microtubules, themselves made of heterodimers of α and β-tubulin. They disrupt the dynamics of the microtubules either by stabilizing them, as do paclitaxel or epothilones, or destabilizing them, as do colchicine. The binding site of colchicine seems to lie between the two units of the tubulin dimer. Here, we report on the characterization of this site by the docking of a series of reference compounds, and the subsequent docking of ligands prepared in our laboratory. 相似文献
130.