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https://www.readbyqxmd.com/read/28339723/leveraging-molecular-datasets-for-biomarker-based-clinical-trial-design-in-glioblastoma
#1
Shyam K Tanguturi, Lorenzo Trippa, Shakti H Ramkissoon, Kristine Pelton, David Knoff, David Sandak, Neal I Lindeman, Azra H Ligon, Rameen Beroukhim, Giovanni Parmigiani, Patrick Y Wen, Keith L Ligon, Brian M Alexander
Background.: Biomarkers can improve clinical trial efficiency, but designing and interpreting biomarker-driven trials require knowledge of relationships among biomarkers, clinical covariates, and endpoints. We investigated these relationships across genomic subgroups of glioblastoma (GBM) within our institution (DF/BWCC), validated results in The Cancer Genome Atlas (TCGA), and demonstrated potential impacts on clinical trial design and interpretation. Methods.: We identified genotyped patients at DF/BWCC, and clinical associations across 4 common GBM genomic biomarker groups were compared along with overall survival (OS), progression-free survival (PFS), and survival post-progression (SPP)...
February 20, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28338623/a-study-of-intramolecular-hydrogen-bonding-in-levoglucosan-derivatives
#2
Lucas Quiquempoix, Elena Bogdan, Neil J Wells, Jean-Yves Le Questel, Jérôme Graton, Bruno Linclau
Organofluorine is a weak hydrogen-bond (HB) acceptor. Bernet et al. have demonstrated its capability to perturb OH···O intramolecular hydrogen bonds (IMHBs), using conformationally rigid carbohydrate scaffolds including levoglucosan derivatives. These investigations are supplemented here by experimental and theoretical studies involving six new levoglucosan derivatives, and complement the findings of Bernet et al. However, it is shown that conformational analysis is instrumental in interpreting the experimental data, due to the occurrence of non-intramolecular hydrogen-bonded populations which, although minor, cannot be neglected and appears surprisingly significant...
March 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28328619/evaluation-of-o6-methylguanine-dna-methyltransferase-as-a-predicting-factor-of-response-to-temozolomide-based-chemotherapy-in-well-differentiated-metastatic-pancreatic-neuroendocrine-tumors
#3
Paul Girot, Clotilde Dumars, Jean-François Mosnier, Léa Muzellec, Hélène Senellart, Fanny Foubert, François-Xavier Caroli-Bosc, Estelle Cauchin, Nicolas Regenet, Tamara Matysiak-Budnik, Yann Touchefeu
OBJECTIVE: Temozolomide (TMZ) is an alkylating agent frequently used in well-differentiated metastatic pancreatic neuroendocrine tumors (PNETs) with very variable responses. O-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme whose loss of expression has been suggested to be predictive of response to TMZ in various human tumors. We evaluated the predictive value of MGMT status, assessed by immunohistochemistry (IHC) and methylation-specific PCR (MS-PCR), in well-differentiated metastatic PNETs treated by a TMZ-based chemotherapy...
March 21, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28322566/o6-corona-6-arenes-with-expanded-cavities-for-specific-complexation-with-c70
#4
Yao Lu, Zhan-Da Fu, Qing-Hui Guo, Mei-Xiang Wang
O6-Corona[3]arene[3]tetrazines with expanded cavities were synthesized by one-pot SNAr reaction between 3,6-dichlorotetrazine and aromatic diols. The macrocycle-to-macrocycle transformation involving IEDDA of tetrazine moieties with an enamine followed by denitrogenative aromatization afforded O6-corona[3]arene[3]pyridazines. O6-Corona[6]arenes adopted coronary conformations yielding hexagonal cavities of varied sizes. While O6-corona[3]arene[3]pyridazines complexed both C60 and C70 in a virtually nonselective manner, O6-corona[3]arene[3]tetrazines behaved as selective receptors to complex C70 with K1:1 values up to (3...
March 21, 2017: Organic Letters
https://www.readbyqxmd.com/read/28321994/detection-and-imaging-of-chrome-yellow-lead-chromate-in-latent-prints-solid-residues-and-minerals-by-laser-desorption-ionization-mass-spectrometry-ldi-ms
#5
Zhaoyu Zheng, Julius Pavlov, Athula B Attygalle
In the past, Chrome Yellow (lead chromate, PbCrO4 ), a bright orange-red substance, has been widely used as an inorganic pigment in the production of paints, coatings, and plastics. Herein, we demonstrate that laser desorption/ionization mass spectrometry (LDI-MS) is a powerful tool for the detection of lead chromate in solid residues. In fact, lead chromate in trace amounts is easily detectable by LDI-MS even from residues left as latent prints. For example, a latent print obtained by stamping the exposed laterally cut surface of a pencil over 50 years old on an acetonitrile-moistened paper, was successfully imaged for both lead and chromate using a Synapt G2 HDMS mass spectrometer...
March 21, 2017: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/28316806/crystal-structure-of-the-solid-solution-ba8-35pb0-65-b3o6-6
#6
Wenwu Zhao
Single crystals of lead barium borate, Ba8.35Pb0.65(B3O6)6, octabarium lead(II) hexa-kis-(triborate), have been obtained by spontaneous nucleation from a high-temperature melt. Its three-dimensional structure is constructed on the basis of a BaO9 polyhedron, a (Pb/Ba)O6 octa-hedron (occupancy ratio Pb:Ba = 0.216:0.784) and a condensed B3O6 ring anion. In the crystal, the planar B3O6 anions are stacked in an alternating fashion with Ba and (Pb/Ba) atoms along [001]. A comparison is made with the structures of related solid solutions in the system Ba/Pb/B/O...
March 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28316805/new-mixed-aluminium-chromium-diarsenate
#7
Mohamad Alem Bouhassine, Habib Boughzala
Potassium chromium aluminium diarsenate, KCr1/4Al3/4As2O7, was prepared by solid-state reaction. The structure consists of (Cr1/4/Al3/4)O6 octa-hedra and As2O7 diarsenate groups sharing corners to build up a three-dimensional anionic framework. The potassium cations are located in wide channels running along the c-axis direction. The crystal structure is isostructural with the triclinic A(I)M(III)X2O7 (A(I) = alkali metal; M(III) = Al, Cr, Fe; X = As, P) compounds. However, the M(III) octa-hedrally coordinated site is 25% partially occupied by chromium and 75% by aluminium...
March 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28290677/molecular-insights-into-the-translesion-synthesis-of-benzyl-guanine-from-molecular-dynamics-simulations-structural-evidence-of-mutagenic-and-nonmutagenic-replication
#8
Katie A Wilson, Stacey D Wetmore
DNA can be damaged by many compounds in our environment, and the resulting damaged DNA is commonly replicated by translesion synthesis (TLS) polymerases. Because the mechanism and efficiency of TLS are affected by the type of DNA damage, obtaining information for a variety of DNA adducts is critical. However, there is no structural information for the insertion of a dNTP opposite an O6-dG adduct, which is a particularly harmful class of DNA lesions. We used molecular dynamics (MD) simulations to investigate structural and energetic parameters that dictate preferred dNTP insertion opposite O6-benzyl-guanine (Bz-dG) by DNA polymerase IV, a prototypical TLS polymerase...
March 24, 2017: Biochemistry
https://www.readbyqxmd.com/read/28284130/adsorption-of-cd-ii-and-pb-ii-by-in-situ-oxidized-fe3o4-membrane-grafted-on-316l-porous-stainless-steel-filter-tube-and-its-potential-application-for-drinking-water-treatment
#9
Mengfei Zhu, Li Zhu, Jianlong Wang, Tianli Yue, Ronghua Li, Zhonghong Li
Removing heavy metal ions from aqueous solutions is one of the most challenging separations. In situ oxidized Fe3O4 membranes using 316L porous stainless steel filter tube have shown great potential for removing anion Cr(VI). Here we report the performances of the in situ oxidized Fe3O4 membranes for removing two toxic cations Cd(II) and Pb(II) commonly existing in water and their potential applications for drinking water purification. The membranes exhibited high removal efficiency: 97% at pH 9.0 for Cd(II) of 1...
March 8, 2017: Journal of Environmental Management
https://www.readbyqxmd.com/read/28278076/adenovirus-based-strategies-enhance-antitumor-capability-through-p53-mediated-downregulation-of-mgmt-in-uveal-melanoma
#10
Xun Li, Ling Yuan, Jianfeng Zhao, Hui Yang, Yunzhi Yang, Yanfei Zhang, Biyun Cun
Uveal melanoma (UM) is an intractable disease with a low survival rates, despite adequate local treatment, as a result of its metastatic characteristics. Thus, new therapeutic strategies, including combinations of novel gene therapy and traditional chemotherapy, are under investigation to improve long-term prognosis. Dacarbazine or DTIC, an alkylating agent which results in DNA methylation, is most commonly used to treat melanoma but the response is very limited. The O6-methylguanine DNA methyl transferase (MGMT), a DNA repair protein, is involved in chemoresistance in DTIC treatment...
February 21, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28266716/the-prognostic-value-of-mgmt-promoter-methylation-in-glioblastoma-a-meta-analysis-of-clinical-trials
#11
Maryam Moradi, Afsane Bahrami, Soodabeh ShahidSales, Marjan Joodi, Mona Joudi Mashhad, Seyed Mahdi Hassanian, Kazem Anvari, Amir Avan
The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) is suggested to be associated with resistance to alkylating agents such as Temozolomide which is being used in treatment of patients with glioblastoma (GBM). Therefore we evaluated the associations between MGMT promoter methylation and prognosis of patients with glioblastoma (GBM). Data were extracted from publications in Embase, PubMed, and the Cochrane Library. Data on overall survival (OS), progression-free survival (PFS), and MGMT methylation status were obtained and 4097 subjects were enrolled...
March 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28239795/antiproliferative-activity-of-a-new-nitrosyl-iron-complex-with-cysteamine-in-human-tumor-cells-in-vitro
#12
O S Zhukova, Z S Smirnova, I O Chikileva, M V Kiselevskii
We studied cytotoxic activity of a new NO-releasing tetranitrosyl binuclear iron complex with cysteamine (CysAm) for human tumor cells, the relationship between the expression of O6-methylguanine-DNA methyltransferase (MGMT) and cell sensitivity to CysAm, and apoptosis-inducing capacity of this preparation. It was found that histogenetically different cell lines are characterized by different sensitivity to CysAm, and this parameter correlated with the basal level of MGMT. CysAm induced apoptosis via activation of caspases 3 and 7...
February 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28222788/antimicrobial-resistance-and-genomic-rep-pcr-fingerprints-of-pseudomonas-aeruginosa-strains-from-animals-on-the-background-of-the-global-population-structure
#13
Isa Serrano, Manuela Oliveira, José Pedro Santos, Florence Bilocq, Alexandre Leitão, Luis Tavares, Jean-Paul Pirnay, Daniel De Vos
BACKGROUND: Pseudomonas aeruginosa is an important human opportunistic pathogen responsible for fatal nosocomial infections worldwide, and has emerged as a relevant animal pathogen. Treatment options are dramatically decreasing, due to antimicrobial resistance and the microorganism's large versatile genome. Antimicrobial resistance profiles, serotype frequency and genomic profile of unrelated P. aeruginosa isolates of veterinary origin (n = 73), including domesticated, farm, zoo and wild animals mainly from Portugal were studied...
February 21, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28219079/light-induced-structural-changes-and-the-site-of-o-o-bond-formation-in-psii-caught-by-xfel
#14
Michihiro Suga, Fusamichi Akita, Michihiro Sugahara, Minoru Kubo, Yoshiki Nakajima, Takanori Nakane, Keitaro Yamashita, Yasufumi Umena, Makoto Nakabayashi, Takahiro Yamane, Takamitsu Nakano, Mamoru Suzuki, Tetsuya Masuda, Shigeyuki Inoue, Tetsunari Kimura, Takashi Nomura, Shinichiro Yonekura, Long-Jiang Yu, Tomohiro Sakamoto, Taiki Motomura, Jing-Hua Chen, Yuki Kato, Takumi Noguchi, Kensuke Tono, Yasumasa Joti, Takashi Kameshima, Takaki Hatsui, Eriko Nango, Rie Tanaka, Hisashi Naitow, Yoshinori Matsuura, Ayumi Yamashita, Masaki Yamamoto, Osamu Nureki, Makina Yabashi, Tetsuya Ishikawa, So Iwata, Jian-Ren Shen
Photosystem II (PSII) is a huge membrane-protein complex consisting of 20 different subunits with a total molecular mass of 350 kDa for a monomer. It catalyses light-driven water oxidation at its catalytic centre, the oxygen-evolving complex (OEC). The structure of PSII has been analysed at 1.9 Å resolution by synchrotron radiation X-rays, which revealed that the OEC is a Mn4CaO5 cluster organized in an asymmetric, 'distorted-chair' form. This structure was further analysed with femtosecond X-ray free electron lasers (XFEL), providing the 'radiation damage-free' structure...
March 2, 2017: Nature
https://www.readbyqxmd.com/read/28217330/crystal-structure-of-tris-4-7-13-16-21-24-hexa-oxa-1-10-di-aza-bicyclo-8-8-8-hexa-cosane-%C3%AE%C2%BA-8-n2-o6-rubidium-rubidium-nona-stannide
#15
Wilhelm Klein, Haiyan He, Thomas F Fässler
The crystal structure of the title compound, [Rb(C18H36N2O6)]3RbSn9, consists of deltahedral [Sn9](4-) cluster anions, Rb(+) cations and cryptand mol-ecules, which partially sequester the cations. Those cations, which are not coordinated by cryptand mol-ecules, are neighboured directly to the [Sn9](4-) clusters and inter-connect them to form ∞(1)[RbSn9](3-) chains. These chains extend parallel to [001] and are arranged in a pseudo-hexa-gonal rod packing, separated by the Rb-cryptand complex cations.
February 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28199478/evaluation-of-o6-benzylguanine-potentiated-topical-carmustine-for-mycosis-fungoides-a-phase-1-2-clinical-trial
#16
Joselin D Tacastacas, Derek V Chan, Sean Carlson, Stanton L Gerson, Afshin Dowlati, Pingfu Fu, Kurt Lu, Sarah Groft, Julie Rosenjack, Kord Honda, Thomas McCormick, Kevin D Cooper
Importance: In a phase 1 trial, single-dose O6-benzylguanine with topical carmustine for patients with early stage (stage IA through stage IIA) cutaneous T-cell lymphoma, mycosis fungoides (MF) type, resulted in clinical responses proportional to inhibition of O6-alkylguanine DNA alkyltransferase activity, but a maximum tolerated dose (MTD) was not reached. Objective: To determine whether dose escalation of carmustine in combination with dual-dose O6-benzylguanine to prolong alkyltransferase inhibition could reach an MTD...
February 15, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28197617/mechanistic-insights-on-the-electronic-properties-and-electronic-atomic-structure-aspects-in-orthorhombic-srvo3-thin-films-xanes-exafs-study
#17
Aditya Sharma, Mayora Varshney, Weon Cheol Lim, Hyun-Joon Shin, Jitendra Pal Singh, Sung Ok Won, Keun Hwa Chae
Correlations among the B-O6 octahedra distortions, existing polymorphous phases, band structures and electronic conductivities of ABO3 perovskites are matters for debate and require a deep understanding of their local atomic/electronic structures and diverse assets. In this study, to illustrate the distortion in V-O6 octahedra and its implication on the band structure and electronic properties, spectroscopic investigations on the RF-sputtering grown insulating SrVO3 thin films were employed using X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS)...
February 15, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28195901/prognostic-molecular-and-imaging-biomarkers-in-primary-glioblastoma
#18
Edit Bosnyák, Sharon K Michelhaugh, Neil V Klinger, David O Kamson, Geoffrey R Barger, Sandeep Mittal, Csaba Juhász
PURPOSE: Several molecular glioma markers (including isocitrate dehydrogenase 1 [IDH1] mutation, amplification of the epidermal growth factor receptor [EGFR], and methylation of the O6-methylguanine-DNA methyltransferase [MGMT] promoter) have been associated with glioblastoma survival. In this study, we examined the association between tumoral amino acid uptake, molecular markers, and overall survival in patients with IDH1 wild-type (primary) glioblastoma. PATIENTS AND METHODS: Twenty-one patients with newly diagnosed IDH1 wild-type glioblastomas underwent presurgical MRI and PET scanning with alpha[C-11]-L-methyl-tryptophan (AMT)...
February 14, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28195711/impact-of-mn-ii-manganese-oxide-reactions-on-ni-and-zn-speciation
#19
Margaret A G Hinkle, Katherine G Dye, Jeffrey G Catalano
Layered Mn oxide minerals (phyllomanganates) often control trace metal fate in natural systems. The strong uptake of metals such as Ni and Zn by phyllomanganates results from adsorption on or incorporation into vacancy sites. Mn(II) also binds to vacancies and subsequent comproportionation with structural Mn(IV) may alter sheet structures by forming larger and distorted Mn(III)O6 octahedra. Such Mn(II)-phyllomanganate reactions may thus alter metal uptake by blocking key reactive sites. Here we investigate the effect of Mn(II) on Ni and Zn binding to phyllomanganates of varying initial vacancy content (δ-MnO2, hexagonal birnessite, and triclinic birnessite) at pH 4 and 7 under anaerobic conditions...
March 1, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28191940/thorium-chemistry-in-oxo-tellurium-system-under-extreme-conditions
#20
Bin Xiao, Philip Kegler, Dirk Bosbach, Evgeny V Alekseev
Through the use of a high-temperature/high-pressure synthesis method, four thorium oxo-tellurium compounds with different tellurium valence states were isolated. The novel inorganic phases illustrate the intrinsic complexity of the actinide tellurium chemistry under extreme conditions of pressure and temperature. Th2Te3O11 is the first instance of a mixed-valent oxo-tellurium compound, and at the same time, Te exhibits three different coordination environments (Te(IV)O3, Te(IV)O4, and Te(VI)O6) within a single structure...
February 13, 2017: Inorganic Chemistry
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