bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure and Function of Mammalian DNA Methyltransferases
Authors: Jurkowska Renata Zofia , Jurkowski Tomasz Piotr , Jeltsch Albert 
Published: November 2010

AbstractDNA methylation plays an important role in epigenetic signalling, having an impact on gene regulation, chromatin structure, development and disease. Here, we review the structures and functions of the mammalian DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b, including their domain structures, catalytic mechanisms, localisation, regulation, post‐translational modifications and interaction with chromatin and other proteins, summarising data obtained in genetic, cell biology and enzymatic studies. We focus on the question of how the molecular and enzymatic properties of these enzymes are connected to the dynamics of DNA methylation patterns and to the roles the enzymes play in the processes of de novo and maintenance DNA methylation. Recent enzymatic and genome‐wide methylome data have led to a new model of genomic DNA methylation patterns based on the preservation of average levels of DNA methylation in certain regions, rather than the methylation states of individual CG sites.
Supramolecular Organization of Light‐Harvesting Porphyrin Macrorings
Authors: Satake Akiharu , Azuma Shintaro , Kuramochi Yusuke , Hirota Shun , Kobuke Yoshiaki 
Published: November 2010

AbstractPorphyrin‐based supramolecular nanostructures have been produced by the self‐assembly of porphyrin macrorings with three benzoic acid groups (Acid‐R) on each side of the rings through cooperative carboxyl–carboxyl hydrogen bonds. Structures of the organized Acid‐R were analyzed by AFM, and two clear distribution peaks were observed at 3 and 27 nm in the height‐distribution histogram. From the overall assessment, the higher objects are considered to be one‐dimensional structures standing vertically on the mica substrate. The height corresponds to an 11‐mer of a unit Acid‐R. Light‐harvesting functions were examined by using fluorescence titration, whereby an energy‐acceptor molecule (Tripod 2) was employed that strongly interacted with Acid‐R units (association constant: 2.0×108 M−1), specifically from the inner pore. The titration results showed that the apparent stoichiometry [Tripod 2]/[Acid‐R] was <0.5, and that the value was concentration dependent. Titration results reasonably account for the scheme in which Tripod 2 only interacts with each terminal in the organized Acid‐R. The number of organization was fitted to a 10‐mer of Acid‐R in a 6.8×10−7 M solution, and was consistent with that estimated from the AFM results. In the composites of organized Acid‐R/Tripod 2, a singlet excitation energy transfer occurred among the Acid‐R units, and to Tripod 2. The energy‐transfer rate constants were estimated by using the decamer model, which employed kinetic parameters obtained from steady‐state and time‐resolved fluorescence experiments.
Site‐Directed Spin‐Labeling of DNA by the Azide–Alkyne ‘Click’ Reaction: Nanometer Distance Measurements on 7‐Deaza‐2′‐deoxyadenosine and 2′‐Deoxyuridine Nitroxide Conjugates Spatially Separated or Linked to a ‘dA‐dT’ Base Pair
Authors: Ding Ping , Wunnicke Dorith , Steinhoff Heinz‐Jürgen , Seela Frank 
Published: November 2010

AbstractNucleobase‐directed spin‐labeling by the azide‐alkyne ‘click’ (CuAAC) reaction has been performed for the first time with oligonucleotides. 7‐Deaza‐7‐ethynyl‐2′‐deoxyadenosine (1) and 5‐ethynyl‐2′‐deoxyuridine (2) were chosen to incorporate terminal triple bonds into DNA. Oligonucleotides containing 1 or 2 were synthesized on a solid phase and spin labeling with 4‐azido‐2,2,6,6‐tetramethylpiperidine 1‐oxyl (4‐azido‐TEMPO, 3) was performed by post‐modification in solution. Two spin labels (3) were incorporated with high efficiency into the DNA duplex at spatially separated positions or into a ‘dA‐dT’ base pair. Modification at the 5‐position of the pyrimidine base or at the 7‐position of the 7‐deazapurine residue gave steric freedom to the spin label in the major groove of duplex DNA. By applying cw and pulse EPR spectroscopy, very accurate distances between spin labels, within the range of 1–2 nm, were measured. The spin–spin distance was 1.8±0.2 nm for DNA duplex 17(dA*7,10)⋅11 containing two spin labels that are separated by two nucleotides within one individual strand. A distance of 1.4±0.2 nm was found for the spin‐labeled ‘dA‐dT’ base pair 15(dA*7)⋅16(dT*6). The ‘click’ approach has the potential to be applied to all four constituents of DNA, which indicates the universal applicability of the method. New insights into the structural changes of canonical or modified DNA are expected to provide additional information on novel DNA structures, protein interaction, DNA architecture, and synthetic biology.
Simultaneous analysis of tramadol, O‐desmethyltramadol, and N‐desmethyltramadol enantiomers in rat plasma by high‐performance liquid chromatography‐tandem mass spectrometry: Application to pharmacokinetics
Authors: Godoy Ana Leonor Pardo Campos , De Moraes Natália Valadares , Martinez Edson Zangiacomi , Carvalho Teresa Maria De Jesus Ponte , Marques Maria Paula , Lanchote Vera Lucia 
Published: November 2010

AbstractTramadol (T) is available as a racemic mixture of (+)‐trans‐T and (−)‐trans‐T. The main metabolic pathways are O‐demethylation and N‐demethylation, producingtrans‐O‐desmethyltramadol (M1) andtrans‐N‐desmethyltramadol (M2) enantiomers, respectively. The analgesic effect of T is related to the opioid activity of (+)‐trans‐T and (+)‐M1and to the monoaminergic action of (+/−)‐trans‐T. This is the first study using tandem mass spectrometry as a detection system for the simultaneous analysis oftrans‐T,M1, andM2enantiomers. The analytes were resolved on a Chiralpak® AD column using hexane:ethanol (95.5:4.5, v/v) plus 0.1% diethylamine as the mobile phase. The quantitation limits were 0.5 ng/ml fortrans‐T andM1and 0.1 ng/ml forM2. The method developed and validated here was applied to a pharmacokinetic study in rats. Male Wistar rats (n= 6 at each time point) received a single oral dose of 20 mg/kg racemictrans‐T. Blood samples were collected up to 12 h after drug administration. The kinetic disposition oftrans‐T andM2was enantioselective (AUC(+)/(−)ratio = 4.16 and 6.36, respectively). The direction and extent of enantioselectivity in the pharmacokinetics oftrans‐T andM2in rats were comparable to data previously reported for healthy volunteers, suggesting that rats are a suitable model for enantioselective studies oftrans‐T pharmacokinetics. Chirality, 2011. © 2010 Wiley‐Liss, Inc.
Phase II study of belotecan, a camptothecin analogue, in combination with carboplatin for the treatment of recurrent ovarian cancer
Authors: Choi Chel Hun , Lee Yoo‐Young , Song Tae‐Jong , Park Hwang‐Shin , Kim Min Kyu , Kim Tae‐Joong , Lee Jeong‐Won , Lee Je‐Ho , Bae Duk‐Soo , Kim Byoung‐Gie 
Published: November 2010

AbstractBACKGROUND:Belotecan (CKD602; Camtobell, Chong Keun Dang Corp., Seoul, Korea) is a recently developed camptothecin derivative with antitumor properties. This phase II study was designed to evaluate the toxicity and efficacy of belotecan combined with carboplatin in patients with recurrent epithelial ovarian cancer (EOC).METHODS:Thirty‐eight patients with recurrent EOC were treated with belotecan 0.3 mg/m2/day (days 1‐5) and carboplatin AUC 5 (day 5) every 3 weeks for 6 cycles. The primary objective was to determine the response rate as defined by Response Evaluation Criteria in Solid Tumors and CA‐125 response. Other end points included toxicities and progression‐free survival (PFS).RESULTS:All 38 patients were assessed for toxicity, and 35 patients were assessed for response. The overall response rate was 57.1%; there were 7 complete responses (20.0%), 13 partial responses (37.1%), 6 patients with stable disease (17.1%), and 9 patients with progressive disease (25.7%). Grades 3 and 4 hematologic toxicities included neutropenia (28.8%), thrombocytopenia (19.8%), and anemia (14.4%), and there were 2 episodes of febrile neutropenia. Median PFS was 7 months, with a median follow‐up of 12 months.CONCLUSIONS:The newly developed topoisomerase I inhibitor belotecan (CKD‐602) combined with carboplatin is a well‐tolerated regimen with activity in recurrent EOC. Further testing of this regimen is warranted to further characterize efficacy and indications for use. Cancer 2011. © 2010 American Cancer Society.
Radiation‐induced osteosarcomas of the calvarium and skull base
Authors: Patel Akash J. , Rao Vikas Y. , Fox Benjamin D. , Suki Dima , Wildrick David M. , Sawaya Raymond , DeMonte Franco 
Published: November 2010

AbstractBACKGROUND:Although a rare complication of ionizing radiation, radiation‐induced osteosarcoma is now more frequently recognized as radiation therapy has become common and cancer survival has increased. To date, publications on radiation‐induced osteosarcoma of the cranium are limited to a few small series and case reports.METHODS:Data from 175 patients with a history of sarcoma of the head at The University of Texas M. D. Anderson Cancer Center from 1975 to 2007 were reviewed to identify patients with radiation‐induced osteosarcoma. The diagnostic criteria were: 1) osteosarcoma arose within the previously irradiated field; 2) new sarcoma was histologically distinct from the original neoplasm; 3) no evidence of new sarcoma at the time of radiation; and 4) distinct latency period could be recognized. Frequencies and descriptive statistics were obtained for the various characteristics under study.RESULTS:The authors identified 16 patients with radiation‐induced osteosarcoma of the cranium at their institution. The average age at diagnosis was 35 years. The median latency period was 12.5 years. Nine patients had skull base tumors, and 7 had calvarial tumors. Of the 14 patients treated surgically, 86% developed local recurrence. The median survival time was 29 months, and the 5‐year survival rate was 29.6%.CONCLUSIONS:The authors report the largest series of cranial radiation‐induced osteosarcoma. Although radiation‐induced osteosarcoma is an uncommon but dire complication of radiotherapy, its incidence will probably increase in the future as the frequency of radiation treatment and cancer survival increase. These tumors are locally aggressive, and despite aggressive surgical and medical management, they have a high rate of local recurrence and mortality. Cancer 2011. © 2010 American Cancer Society.
Metabolic surgery and cancer
Authors: Ashrafian Hutan , Ahmed Kamran , Rowland Simon P. , Patel Vanash M. , Gooderham Nigel J. , Holmes Elaine , Darzi Ara , Athanasiou Thanos 
Published: November 2010

AbstractThe worldwide epidemic of obesity and the global incidence of cancer are both increasing. There is now epidemiological evidence to support a correlation between obesity, weight gain, and some cancers. Metabolic or bariatric surgery can provide sustained weight loss and reduced obesity‐related mortality. These procedures can also improve the metabolic profile to decrease cardiovascular risk and resolve diabetes in morbidly obese patients. The operations offer several physiological steps, the so‐called BRAVE effects: 1) bile flow alteration, 2) reduction of gastric size, 3) anatomical gut rearrangement and altered flow of nutrients, 4) vagal manipulation and 5) enteric gut hormone modulation. Metabolic operations are also associated with a significant reduction of cancer incidence and mortality. The cancer‐protective role of metabolic surgery is strongest for female obesity‐related tumors; however, the underlying mechanisms may involve both weight‐dependent and weight‐independent effects. These include the improvement of insulin resistance with attenuation of the metabolic syndrome as well as decreased oxidative stress and inflammation in addition to the beneficial modulation of sex steroids, gut hormones, cellular energetics, immune system, and adipokines. Elucidating the precise metabolic mechanisms of cancer prevention by metabolic surgery can increase our understanding of how obesity, diabetes, and metabolic syndrome are associated with cancer. It may also offer novel treatment strategies in the management of tumor generation and growth. Cancer 2011. © 2010 American Cancer Society.
Concomitant ABCG2 overexpression and FLT3‐ITD mutation identify a subset of acute myeloid leukemia patients at high risk of relapse
Authors: Tiribelli Mario , Geromin Antonella , Michelutti Angela , Cavallin Margherita , Pianta Annalisa , Fabbro Dora , Russo Domenico , Damante Giuseppe , Fanin Renato , Damiani Daniela 
Published: November 2010

AbstractBACKGROUND:ABCG2 protein overexpression and FLT3 internal tandem duplication (ITD) correlate with higher relapse rate and shorter disease‐free survival (DFS) in acute myeloid leukemia (AML), but no data are available on the possible effect of concomitant presence of these 2 factors.METHODS:The authors analyzed the outcome of 166 cases of adult AML patients who were homogeneously treated with a fludarabine‐based induction therapy.RESULTS:ABCG2 overexpression and FLT3‐ITD were detected in 83 (50%) and 47 (28%) patients, respectively. A significant correlation was found between ABCG2 positivity and FLT3 mutation, with 33 (40%) ITD in 83 ABCG2‐positive patients compared with 14 (17%) ITD in 83 ABCG2‐negative patients (P = .002). Complete remission (CR) after induction therapy was achieved in 95 (57%) patients. Neither ABCG2 overexpression nor FLT3‐ITD had any impact on achievement of CR. Relapse occurred in 42 of 95 (44%) patients at a median time of 28 months. Time to relapse was shortened in patients overexpressing ABCG2 (P = .0004). DFS was not affected by FLT3‐ITD alone, but FLT3 mutation significantly worsened long‐term outcome of ABCG2‐positive patients. DFS at 1 and 3 years in patients with overexpression of both ABCG2 and FLT3‐ITD was only 36% and 28%, respectively; in ABCG2‐positive/FLT3‐negative patients, DFS at 1 and 3 years was 65% and 48%, respectively; and in ABCG2‐negative cases (regardless of FLT3 status), DFS at 1 and 3 years was greater than 85% and 75%.CONCLUSIONS:Concomitant overexpression of ABCG2 and FLT3‐ITD is relatively frequent and identifies a subgroup of AML patients with a significantly worse prognosis. The possible interactions between these 2 prognostic factors need to be defined. Cancer 2011. © 2010 American Cancer Society.
Clinicopathologic factors of the recurrent tumor predict outcome in patients with ipsilateral breast tumor recurrence
Authors: Panet‐Raymond Valerie , Truong Pauline T. , Alexander Cheryl , Lesperance Mary , McDonald Rachel E. , Watson Peter H. 
Published: November 2010

AbstractBACKGROUND:The role of clinicopathologic characteristics of the recurrent tumor in determining survival in a cohort of patients with ipsilateral breast tumor recurrence (IBTR) was investigated.METHODS:Among 6020 women with pT1‐T2, pN0‐1, M0 treated with breast‐conserving surgery from 1989 to 1999, 269 developed isolated IBTR. Ten‐year Kaplan‐Meier breast cancer‐specific survival (BCSS) and overall survival (OS), calculated from date of IBTR, were analyzed according to clinicopathologic characteristics.RESULTS:Factors that were associated with diminished OS and BCSS on univariate analysis were: time to IBTR ≤48 months, lymphovascular invasion positive status, estrogen receptor (ER) negative status, high grade, clinical IBTR detection, biopsy alone, and close/positive margins (all P < .05). On multivariate analysis, time to IBTR ≤48 months (hazard ratio [HR], 1.87, P = .012), lymphovascular invasion positive status (HR, 2.46; P < .001), ER negative status (HR, 2.08; P = .013), high‐grade recurrent disease (HR, 1.88; P = .013), and close/positive margins after surgery for IBTR (HR, 1.94; P = .013) retained significance for prediction of diminished OS. When stratified according to number of adverse prognostic features, 10‐year OS was 70.4% in patients with 1 factor, 35.8% with 2 factors, and 19.9% with 3 or more factors (P < .001).CONCLUSIONS:Time to recurrence ≤48 months, lymphovascular invasion positive status, ER negative status, high‐grade histology, and close/positive margins in association with the recurrent tumor are independent prognostic factors for survival after IBTR. The presence of 2 or more of these features at recurrence is significantly associated with poor OS. These criteria can be used to prognosticate and guide clinical decisions after recurrence. Cancer 2011. © 2010 American Cancer Society.
Lysyl oxidase: A lung adenocarcinoma biomarker of invasion and survival
Authors: Wilgus May‐Lin , Borczuk Alain C. , Stoopler Mark , Ginsburg Mark , Gorenstein Lyall , Sonett Joshua R. , Powell Charles A. 
Published: November 2010

AbstractBACKGROUND:Lung adenocarcinoma invasion and metastasis arises from autocrine and paracrine signaling events between tumor epithelial cells and the stromal microenvironment that is mediated in part by transforming growth factor‐β (TGF‐β) signaling. The copper‐dependent amine oxidase lysyl oxidase (LOX) plays a role in extracellular matrix structure and is up‐regulated in invasive type II TGF‐β receptor‐deficient cells. The authors hypothesized that LOX expression is associated with extent of invasion and survival in patients with lung adenocarcinoma.METHODS:LOX immunohistochemical staining was examined in 166 surgically resected lung adenocarcinomas and results were correlated with clinicopathological features and survival.RESULTS:High‐intensity LOX staining was found to be associated with the linear extent of invasion (Spearman correlation coefficient = 0.2; P = .01). There was an association between high LOX staining and decreased 5‐year survival observed within the entire cohort (log‐rank P < .001) and among the patients with stage I disease (n = 119; P < .001). Cox proportional hazards regression analysis confirmed that LOX was a significant prognostic indicator of increased risk of 5‐year mortality for all patients (hazard ratio [HR], 2.55; 95% confidence interval [95% CI], 1.51‐4.30 [P < .001]) and for patients with Stage I disease (HR, 3.51; 95% CI, 1.77‐6.99 [P < .001]). LOX expression was found to be independently associated with risk of death after adjustment for relevant covariates (HR, 2.29; 95% CI, 1.33‐3.94 [P = .003]).CONCLUSIONS:Higher expression of LOX is associated with invasion and is an independent predictor of poor prognosis in patients with early stage lung adenocarcinoma. Cancer 2011. © 2010 American Cancer Society.
Genomic differences between estrogen receptor (ER)‐positive and ER‐negative human breast carcinoma identified by single nucleotide polymorphism array comparative genome hybridization analysis
Authors: Fang Min , Toher Jessica , Morgan Martin , Davison Jerry , Tannenbaum Susan , Claffey Kevin 
Published: November 2010

AbstractBACKGROUND:Estrogen receptor (ER) remains one of the most important biomarkers for breast cancer subtyping and prognosis, and comparative genome hybridization has greatly contributed to the understanding of global genetic imbalance. The authors used single‐nucleotide polymorphism (SNP) arrays to compare overall copy number aberrations (CNAs) as well as loss of heterozygosity (LOH) of the entire human genome in ER‐positive and ER‐negative breast carcinomas.METHODS:DNA was extracted from frozen tumor sections of 21 breast carcinoma specimens and analyzed with a proprietary 50K XbaI SNP array. Copy number and LOH probability values were derived for each sample. Data were analyzed using bioinformatics and computational software, and permutation tests were used to estimate the significance of these values.RESULTS:There was a global increase in CNAs and LOH in ER‐negative relative to ER‐positive cancers. Gain of the long arm of chromosome 1 (1q) and 8q were the most obvious changes common in both subtypes: An increase in the chromosome 1 short arm (1p)/1q ratio was observed in ER‐negative samples, and an increased 16p/16q ratio was observed in ER‐positive samples. Significant CNAs (adjusted P<.05) in ER‐negative relative to ER‐positive tumors included 5q deletion, loss of 15q, and gain of 2p and 21q. Copy‐neutral LOH (cnLOH) common to both ER‐positive and ER‐negative samples included 9p21, the p16 tumor suppressor locus, and 4q13, the RCHY1 (ring finger and CHY zinc finger domain‐containing 1) oncogene locus. Of particular interest was an enrichment of 17q LOH among the ER‐negative tumors, potentially suggesting breast cancer 1 gene (BRCA1) mutations.CONCLUSIONS:SNP array detected both genetic imbalances and cnLOH and was capable of discriminating ER‐negative breast cancer from ER‐positive breast cancer. Cancer 2011. © 2010 American Cancer Society.
Arrival times for the wave equation
Authors: McLaughlin Joyce R. , Yoon Jeong‐Rock 
Published: November 2010

AbstractWe establish a definition of arrival time of a wavefront for a propagating wave in anisotropic media that is initially at rest and where the governing partial differential equation is the anisotropic wave equation. This definition of arrival time is not the same as the one in [8, 12]; it eliminates pathological discontinuities that can occur with the older definition and is still consistent with physical intuition. What is substantively new here is that we show that the newly defined arrival time is locally Lipschitz‐continuous. Then following the method in [8, 12] we establish that it satisfies the eikonal equation. Furthermore, in the isotropic case we establish that the arrival time, as defined here, is the unique viscosity solution of the eikonal equation. Our motivation for this work is to use this arrival time at points in the interior of a physical or biological material, which is estimated from displacement measurements, to determine properties of the medium that are represented as functions in the eikonal equation; see [8, 10, 11, 12]. © 2010 Wiley Periodicals, Inc.
Aluminophosphates for CO2 Separation
Authors: Liu Qingling , Cheung Ngo Chuen Ocean , Garcia‐Bennett Alfonso E. , Hedin Niklas 
Published: November 2010

AbstractThe pressure‐swing adsorption method for carbon dioxide capture would ideally be facilitated by adsorbents with a high capacity and a high selectivity for CO2. Several aluminophosphates with 8‐ring window apertures (AlPO4‐17, AlPO4‐18, AlPO4‐53, and AlPO4‐25) were synthesized by hydrothermal crystallization, calcined, and their CO2 uptake and CO2/N2 selectivity were studied. CO2 and N2 uptake was determined for pressures up to 101 kPa at 273 and 293 K. Langmuir and Toth adsorption models were used to describe the adsorption isotherms. The CO2 and N2 uptakes strongly indicated that the squeezed 8‐ring windows of certain aluminophosphates can sieve CO2 from a CO2 and N2 gas mixture. Both AlPO4‐53 and AlPO4‐25 exhibited a remarkably higher uptake of CO2 compared to N2. The hydrophilicity of the AlPO4 materials was investigated by means of water adsorption, and the results showed that all of the tested aluminophosphates were less water sensitive than a benchmark zeolite (13X). In particular, AlPO4‐53 and AlPO4‐25 showed a very low degree of water uptake with up to 20–30 % relative humidity. Determination of cyclic adsorption and desorption confirmed the relatively hydrophobic nature of the aluminophosphates, which render them less energy costly for the regeneration of adsorbents.