bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDH1‐related hereditary diffuse gastric cancer syndrome: Clinical variations and implications for counseling
Authors: Kluijt Irma , Siemerink Ester J.M. , Ausems Margreet G.E.M. , van Os Theo A.M. , de Jong Daphne , Simões‐Correia Joana , van Krieken J. Han , Ligtenberg Marjolijn J. , Figueiredo Joana , van Riel Els , Sijmons Rolf H. , Plukker John T.M. , van Hillegersberg Richard , Dekker Evelien , Oliveira Carla , Cats Annemieke , Hoogerbrugge Nicoline ,   on behalf of the Dutch Working Group on Hereditary Gastric Cancer
Published: September 2011

AbstractCDH1 mutation carriers have a strongly increased risk of developing gastric cancer (GC) and lobular breast cancer (LBC). Clinical data of GC cases and surgical and histological data of prophylactic gastrectomies and mastectomies of all 10 Dutch CDH1 mutation families were collected. In vitro functional assays were performed to analyze the nature of the newly found missense mutation c.1748T>G (p.Leu583Arg). Ten different CDH1 mutations were found. Functional assays gave strong arguments for the pathogenic nature of the p.Leu583Arg mutation. The pedigrees comprised 36 GC cases (mean age 40 years, range 20–72 years) and one LBC case. Twenty‐nine/37 carriers alive, aged 18–61 years, underwent prophylactic gastrectomy. Invasive GC‐foci and premalignant abnormalities were detected in 2 and 25 patients, respectively. In four patients GC/signetring cell (SRC) foci were diagnosed at preoperative gastroscopy. Long‐standing presence of SRCs without progression to invasive carcinoma was shown in two others. Multifocal LBC/LCIS was found in the two prophylactic mastectomy specimens. Clefts of lip and/or palate (CL/P) were reported in seven individuals from three families. The age at onset and aggressiveness of GC is highly variable, which has to be included in counseling on planning prophylactic gastrectomies. The incidence of LBC is expected to increase and prophylactic mastectomy needs to be considered. The relationship between CL/P and CDH1 needs further study to inform future parents from hereditary diffuse gastric cancer (HDGC) families adequately.
Regulation of neuroendocrine differentiation by AKT/hnRNPK/AR/β‐catenin signaling in prostate cancer cells
Authors: Ciarlo Monica , Benelli Roberto , Barbieri Ottavia , Minghelli Simona , Barboro Paola , Balbi Cecilia , Ferrari Nicoletta 
Published: September 2011

AbstractCurrent diagnostic tools cannot predict clinical failure and androgen‐independent disease progression for patients with prostate cancer (PC). The survival signaling pathways of prostate cells play a central role in the progression of tumors to a neuroendocrine (NE) phenotype. NE cells demonstrate attributes that suggest that they are an integral part of the signaling cascade leading to castration‐resistant PC. In this study, making use of in vitro neuroendocrine differentiation (NED) of human LNCaP and mouse TRAMP‐C2 cells after androgen withdrawal, and of the transgenic adenocarcinoma of mouse prostate (TRAMP) model, we characterized a sequence of molecular events leading to NED and identified a number of markers that could be detectable by routine analyses not only in castration resistant PC but also in hormone naïve PC at the time of initial diagnosis. We found that NED associates with AKT activation that in turn regulates heterogeneous nuclear ribonucleoprotein K (hnRNP K), androgen receptor (AR) and β‐catenin levels. Addition of molecules targeting membrane‐bound receptors and protein kinases blocks NE differentiation in LNCaP and TRAMP‐C2 cells. The extent of AKT phosphorylation and hnRNP K, AR and β‐catenin levels may have a potential value as prognostic indicators discriminating between androgen‐responsive and unresponsive cells and could be used as molecular targets to monitor the anti‐tumor action of new therapeutic protocols based on antireceptor agents and/or neuroendocrine hormone antagonists.
Sustained proliferation and resistance to apoptosis after a cytotoxic insult are early alterations in rat colon carcinogenesis
Authors: Femia Angelo Pietro , Salvianti Francesca , Luceri Cristina , Dolara Piero , Salvadori Maddalena , Pinzani Pamela , Caderni Giovanna 
Published: September 2011

AbstractTo study the early alterations in carcinogenesis, we determined apoptosis and proliferation in rat mucin depleted foci (MDF), precancerous lesions in the colon under basal conditions and 24 h after treatment with 1,2‐dimethylhydrazine (DMH), which induces apoptosis in the colon. Spontaneous apoptosis in MDF was higher than in normal mucosa (Apoptotic Index was 1.61 ± 0.30 and 0.21 ± 0.02 in MDF and normal mucosa, respectively, mean ± SE, p < 0.05). DMH (30 and 75 mg/kg) increased apoptosis in both normal mucosa and MDF (up to 20 times higher compared to basal levels in normal mucosa, but only two times in MDF). MDF had a higher and deregulated pattern of proliferation along the crypt compared to normal mucosa. After DMH, proliferation in normal mucosa was significantly depressed, but it did not vary in MDF. Survivin‐Birc5 regulating apoptosis and proliferation was significantly over‐expressed (RT‐qPCR and immunohistochemistry experiments) in MDF vs. normal mucosa, but did not vary in response to DMH. The expression of the pro‐apoptotic protein Bak did not vary in normal mucosa and MDF. Since inflammation is present in MDF, which may hamper apoptosis, we studied the effect of pre‐treatment with aspirin (600 ppm in the diet for 10 days). No significant effects of aspirin were observed. In conclusion, MDF had a higher spontaneous apoptosis and proliferation coupled with a reduced response to apoptotic stimuli from cytotoxic compounds. Survivin over‐expression in MDF indicates that this is an early event in colon carcinogenesis and suggests that down‐regulation of Survivin may represent a strategy for cancer prevention.
Transarterial chemoembolization in the treatment of patients with unresectable cholangiocarcinoma: Results and prognostic factors governing treatment success
Authors: Vogl Thomas J. , Naguib Nagy N.N. , Nour‐Eldin Nour‐Eldin A. , Bechstein Wolf O. , Zeuzem Stefan , Trojan Jörg , Gruber‐Rouh Tatjana 
Published: September 2011

AbstractThe aim of the study was to evaluate the effectiveness of transarterial chemoembolization (TACE) with four chemotherapeutic protocols in terms of local tumor control and survival of patients with unresectable cholangiocarcinoma (CCC) and to identify the prognostic factors governing treatment success. In the single‐centre study, 115 patients (mean ages = 60.4 years) with unresectable CCC were repeatedly treated with TACE. In total, 819 chemoembolization sessions were performed in 4 week intervals with a mean of 7.1 (range, 3–30) sessions per patient. The chemotherapeutic used was Mitomycin C only in 20.9% of patients, Gemcitabine only in 7%, Mitomycin C with Gemcitabine in 47% and combination of Gemcitabine, Mitomycin C and Cisplatin in 25.1%. Local tumor response was evaluated by MRI according to RECIST. Survival data were calculated according to the Kaplan–Meier method. Prognostic factors for patient's survival were evaluated using log‐rank‐test. The local tumor controls were: partial response 8.7%, stable disease 57.4% and progressive disease 33.9% of patients. The median and mean survival times from the start of TACE were 13 and 20.8 months. Survival rate from the start of TACE was 52% after 1‐year, 29% after 2‐years and 10% after 3‐years. Initial tumor response, high tumor vascularity and Child‐Pugh class A were statistically significant factors for patient's survival. No statistically significant difference between patients treated with different chemotherapy protocols was noted. In conclusion, TACE is a palliative and safe treatment option for patients with unresectable CCC. Child Pugh class B, tumor hypovascularity and initially progressive disease were poor prognostic factors for patient survival.
Femtosecond laser nanosurgery of sub‐cellular structures in HeLa cells by employing Third Harmonic Generation imaging modality as diagnostic tool
Authors: Tserevelakis George J. , Psycharakis Stylianos , Resan Bojan , Brunner Felix , Gavgiotaki Evagelia , Weingarten Kurt , Filippidis George 
Published: September 2011

AbstractFemtosecond laser assisted nanosurgery of microscopic biological specimens is a relatively new technique which allows the selective disruption of sub‐cellular structures without causing any undesirable damage to the surrounding regions. The targeted structures have to be stained in order to be clearly visualized for the nanosurgery procedure. However, the validation of the final nanosurgery result is difficult, since the targeted structure could be simply photobleached rather than selectively destroyed. This fact comprises a main drawback of this technique. In our study we employed a multimodal system which integrates non‐linear imaging modalities with nanosurgery capabilities, for the selective disruption of sub‐cellular structures in HeLa cancer cells. Third Harmonic Generation (THG) imaging modality was used as a tool for the identification of structures that were subjected to nanosurgery experiments. No staining of the biological samples was required, since THG is an intrinsic property of matter. Furthermore, cells' viability after nanosurgery processing was verified via Two Photon Excitation Fluorescence (TPEF) measurements. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Runx2 contributes to murine Col10a1 gene regulation through direct interaction with its cis-enhancer
Authors: Li Feifei , Lu Yaojuan , Ding Ming , Napierala Dobrawa , Abbassi Sam , Chen Yuqing , Duan Xiangyun , Wang Siying , Lee Brendan , Zheng Qiping 
Published: September 2011

Abstract
We have recently shown that a 150-bp Col10a1 distal promoter (−4296 to −4147 bp) is sufficient to direct hypertrophic chondrocyte-specific reporter (LacZ) expression in vivo. More recently, through detailed sequence analysis we identified two putative tandem-repeat Runx2 binding sites within the 3′-end of this 150-bp region (TGTGGG-TGTGGC, −4187 to −4176 bp). Candidate electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation, and transfection studies demonstrate that these putative Runx2 sites bind Runx2 and mediate upregulated Col10a1/reporter activity in vitro. Transgenic studies using the 5′-sequence without Runx2 sites were not able to drive the cell-specific LacZ reporter activity, suggesting the in vivo requirement of the Runx2 sites located in the 3′-end in mediating Col10a1/reporter expression. Indeed, mutating the Runx2 sites in the context of the 150-bp promoter abolishes its capacity to drive hypertrophic chondrocyte-specific reporter expression in transgenic mice. We have also generated multiple transgenic mouse lines using only the 3′-sequence containing the Runx2 sites to drive the LacZ gene. Interestingly, no hypertrophic chondrocyte-specific blue staining was observed in these transgenic mice. Together, our data support that Runx2 directly interacts with murine Col10a1 cis-enhancer. This interaction is required but not sufficient for cell-specific Col10a1 promoter activity in vivo. Additional cooperative/repressive elements within the 5′- or 3′-sequences of this 150-bp promoter are needed to work with Runx2 together to mediate cell-specific Col10a1 expression. Further delineation of these elements/factors has the potential to identify novel therapeutic targets for multiple skeletal disorders, including osteoarthritis, that show abnormal Col10a1 expression and altered chondrocyte maturation. © 2011 American Society for Bone and Mineral Research
In silico evaluation of proposed biosynthetic pathways for the unique dithiolate ligand of the H‐cluster of [FeFe]‐hydrogenase
Authors: Grigoropoulos Alexios , Szilagyi Robert K. 
Published: September 2011

AbstractThe biosynthesis of the active site of the [FeFe]‐hydrogenases (H‐cluster) remains a tantalizing puzzle due to its unprecedented and complex ligand environment. It contains a [2Fe] cluster ([2Fe]H) bearing cyanide and carbon monoxide ligands attached to low‐valence Fe ions and an abiological dithiolate ligand (SCH2XCH2S)2− that bridges the two iron centers. Various experimentally testable hypotheses have already been put forward regarding the precursor molecule and the biosynthetic mechanism that leads to the formation of the dithiolate ligand. In this work, we report a density functional theory‐based theoretical evaluation of these hypotheses. We find preference for a mechanistically simple and energetically favorable pathway that includes known radical‐SAM (S‐adenosylmethionine) catalyzed reactions. We modeled this pathway using a long alkyl chain precursor molecule that leads to the formation of pronanadithiolate (X = CH2). However, the same pathway can be readily adopted for the biosynthesis of the dithiomethylamine (X = NH) or the dithiomethylether (X = O) analog, provided that the proper precursor molecule is available. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Development and characterization of an organotypic model of Barrett's esophagus
Authors: Kosoff Rachelle E. , Gardiner Kristin L. , Merlo Lauren M.F. , Pavlov Kirill , Rustgi Anil K. , Maley Carlo C. 
Published: September 2011

AbstractUnderstanding the molecular and cellular processes underlying the development, maintenance, and progression of Barrett's esophagus (BE) presents an empirical challenge because there are no simple animal models and standard 2D cell culture can distort cellular processes. Here we describe a three‐dimensional (3D) cell culture system to study BE. BE cell lines (CP‐A, CP‐B, CP‐C, and CP‐D) and esophageal squamous keratinocytes (EPC2) were cultured on a matrix consisting of esophageal fibroblasts and collagen. Comparison of growth and cytokeratin expression in the presence of all‐trans retinoic acid or hydrochloric acid was made by immunohistochemistry and Alcian Blue staining to determine which treatments produced a BE phenotype of columnar cytokeratin expression in 3D culture. All‐trans retinoic acid differentially affected the growth of BE cell lines in 3D culture. Notably, the non‐dyplastic metaplasia‐derived cell line (CP‐A) expressed reduced squamous cytokeratins and enhanced columnar cytokeratins upon ATRA treatment. ATRA altered the EPC2 squamous cytokeratin profile towards a more columnar expression pattern. Cell lines derived from patients with high‐grade dysplasia already expressed columnar cytokeratins and therefore did not show a systematic shift toward a more columnar phenotype with ATRA treatment. ATRA treatment, however, did reduce the squamoid‐like multilayer stratification observed in all cell lines. As the first study to demonstrate long‐term 3D growth of BE cell lines, we have determined that BE cells can be cultured for at least 3 weeks on a fibroblast/collagen matrix and that the use of ATRA causes a general reduction in squamous‐like multilayered growth and an increase in columnar phenotype with the specific effects cell‐line dependent. J. Cell. Physiol. 227: 2654–2659, 2012. © 2011 Wiley Periodicals, Inc.
List Colorings of K5‐Minor‐Free Graphs With Special List Assignments
Authors: Cranston Daniel W. , Pruchnewski Anja , Tuza Zsolt , Voigt Margit 
Published: September 2011

AbstractThe following question was raised by Bruce Richter. Let G be a planar, 3‐connected graph that is not a complete graph. Denoting by d(v) the degree of vertex v, is G L‐list colorable for every list assignment L with |L(v)| = min{d(v), 6} for all v∈V(G)? More generally, we ask for which pairs (r, k) the following question has an affirmative answer. Let r and k be the integers and let G be a K5‐minor‐free r‐connected graph that is not a Gallai tree (i.e. at least one block of G is neither a complete graph nor an odd cycle). Is G L‐list colorable for every list assignment L with |L(v)| = min{d(v), k} for all v∈V(G)? We investigate this question by considering the components of G[Sk], where Sk: = {v∈V(G)|d(v)8k} is the set of vertices with small degree in G. We are especially interested in the minimum distance d(Sk) in G between the components of G[Sk]. © 2011 Wiley Periodicals, Inc. J Graph Theory 71:18–30, 2012
Maximum Δ‐edge‐colorable subgraphs of class II graphs
Authors: Mkrtchyan Vahan V. , Steffen Eckhard 
Published: September 2011

AbstractA graph G is class II, if its chromatic index is at least Δ + 1. Let H be a maximum Δ‐edge‐colorable subgraph of G. The paper proves best possible lower bounds for |E(H)|/|E(G)|, and structural properties of maximum Δ‐edge‐colorable subgraphs. It is shown that every set of vertex‐disjoint cycles of a class II graph with Δ≥3 can be extended to a maximum Δ‐edge‐colorable subgraph. Simple graphs have a maximum Δ‐edge‐colorable subgraph such that the complement is a matching. Furthermore, a maximum Δ‐edge‐colorable subgraph of a simple graph is always class I. © 2011 Wiley Periodicals, Inc. J Graph Theory
Synthesis of 10‐amino‐9‐aryl‐2,3,4,5,6,7,9,10‐octahydroacridine‐1,8‐dione derivatives
Authors: Han Guang‐Fan , Cui Bin , Chen Li‐Zhuang , Hu Xiao‐Lei 
Published: September 2011

AbstractA series of novel 10‐amino‐9‐aryl‐2,3,4,5,6,7,9,10‐octahydroacridine‐1,8‐dione derivatives 4 were synthesized by hydrazine or phenylhydrazine and 9‐aryl‐1,8‐dioxo‐2,3,4,5,6,7,9‐heptahydroxanthene derivatives 3, which were prepared by 5‐substituted‐1,3‐cyclohexanedione 1 and aromatic aldehydes 2 in the presence of concentrated H2SO4 as a catalyst in water. The structures of all compounds were characterized by IR, MS, 1H‐NMR, and elemental analysis, and the title compounds possess good fluorescence properties. J. Heterocyclic Chem., (2012).
10Be and 26Al exposure‐age dating of bedrock surfaces on the Aran ridge, Wales: evidence for a thick Welsh Ice Cap at the Last Glacial Maximum
Authors: Glasser Neil F. , Hughes Philip D. , Fenton Cassandra , Schnabel Christoph , Rother Henrik 
Published: September 2011

AbstractThis paper presents results of the analysis of paired cosmogenic isotopes (10Be and 26Al) from eight quartz‐rich samples collected from ice‐moulded bedrock on the Aran ridge, the highest land in the British Isles south of Snowdon. On the Aran ridge, comprising the summits of Aran Fawddwy (905 m a.s.l.) and Aran Benllyn (885 m a.s.l.), 26Al and 10Be ages indicate complete ice coverage and glacial erosion at the global Last Glacial Maximum (LGM). Six samples from the summit ridge above 750–800 m a.s.l. yielded paired 10Be and 26Al ages ranging from 17.2 to 34.4 ka, respectively. Four of these samples are very close in age (10Be ages of 17.5 ± 0.6, 17.5 ± 0.7, 19.7 ± 0.8 and 20.0 ± 0.7 ka) and are interpreted as representing the exposure age of the summit ridge. Two other summit samples are much older (10Be ages of 27.5 ± 1.0 and 33.9 ± 1.2 ka) and these results may indicate nuclide inheritance. The 26Al/10Be ratios for all samples are indistinguishable within one‐sigma uncertainty from the production rate ratio line, indicating that there is no evidence for a complex exposure history. These results indicate that the last Welsh Ice Cap was thick enough to completely cover the Aran ridge and achieve glacial erosion at the LGM. However, between c. 20 and 17 ka ridge summits were exposed as nunataks at a time when glacial erosion at lower elevations (below 750–800 m a.s.l.) was achieved by large outlet glaciers in the valleys surrounding the mountains. Copyright © 2011 John Wiley & Sons, Ltd.
Implementation of educational video improves patient understanding of basic breast cancer concepts in an undereducated county hospital population
Authors: Bouton Marcia E. , Shirah Gina R. , Nodora Jesse , Pond Erika , Hsu Chiu‐Hsieh , Klemens Anne E. , Martinez Maria Elena , Komenaka Ian K. 
Published: September 2011

AbstractBackgroundThe purpose of this study was to evaluate the effect of a video on patient understanding of basic breast cancer concepts.MethodsAn 11 item tool of breast cancer concepts was devised. A previous study obtained baseline information on patient knowledge. Subsequently an 8 min video was designed to facilitate the understanding of these concepts. The next 40 consecutive patients who saw the video were then administered the same 11 item questionnaire.ResultsEighty‐one women agreed to participate in the study, 41 before and 40 after the implementation of the video. Fifty‐one percent had less than a high school education. The group who saw the video had a higher mean number of questions correct (6.7 vs. 8.9, P = 0.0007). Interestingly 90% of all respondents correctly answered the question on the value of screening mammography, however, only 37% of these patients underwent screening mammograms. A multiple linear regression model adjusting for years of education, language, and seeing the video, revealed that having seen the video (P = 0.0029) and years of education (P = 0.0002) remained significantly associated with higher score.ConclusionsImplementation of an educational video significantly improved understanding of breast cancer concepts in an undereducated population. J. Surg. Oncol. 2012; 105:48–54. © 2011 Wiley Periodicals, Inc.
RUNX3 methylation as a predictor for disease progression in patients with non‐muscle‐invasive bladder cancer
Authors: Yan Chunri , Kim Young‐Won , Ha Yun‐Sok , Kim Isaac Yi , Kim Yong‐June , Yun Seok‐Joong , Moon Sung‐Kwon , Bae Suk‐Chul , Kim Wun‐Jae 
Published: September 2011

AbstractBackground and ObjectivesWe have previously reported that RUNX3 inactivation by promoter hypermethylation correlated with advanced disease and poor clinical outcome in bladder cancer. In this study, we examined primary tumors from non‐muscle‐invasive bladder cancer (NMIBC) patients in order to investigate the relationship between RUNX3 methylation and disease progression.MethodsThe association between the hypermethylation of RUNX3 and clinicopathological characteristics of 186 NMIBC samples was analyzed using methylation‐specific polymerase chain reaction (MS‐PCR).ResultsRUNX3 methylation was associated with increased tumor stage, grade, and number of tumors (each P < 0.05). Kaplan–Meier estimates revealed significant differences in time to recurrence and progression based on RUNX3 methylation status (P = 0.043 and 0.006, respectively). RUNX3 methylation was an independent predictor of NMIBC progression on univariate and multivariate analysis. Combining tumor grade and RUNX3 methylation status demonstrated that patients with G3 tumors with RUNX3 methylation had a worse progression‐free survival compared with the patients with lower‐grade or unmethylated tumors [hazard ratio (HR), 19.450].ConclusionsRUNX3 methylation status predicted the risk of NMIBC progression independently of tumor stage. In conjunction with tumor grade, RUNX3 methylation status in patients with NMIBC strongly predicts disease progression. J. Surg. Oncol. 2012;105:425–430. © 2011 Wiley Periodicals, Inc.
Predictors of the impact of the September 11th terrorist attacks on victims of intimate partner violence
Authors: Franz Victoria A. , Arnkoff Diane B. , Glass Carol R. , Mete Mihriye , Dutton Mary Ann 
Published: September 2011

AbstractThis study examined the role of several hypothesized predictors of the impact of a potentially traumatic event, the terrorist attacks of September 11, 2001 (9/11), on a sample of women experiencing intimate partner violence (IPV) and related posttraumatic stress symptoms (PTSS). We found that IPV‐related PTSS mediated the relationship between IPV and 9/11‐related PTSS, confirming the hypothesis that severity of symptoms related to prior trauma plays a role in the development and severity of PTSS related to subsequent potentially traumatic events. Media exposure and threat appraisal were significantly positively associated with 9/11‐related PTSS, whereas social support was significantly negatively associated with 9/11‐related PTSS, with none of these variables serving as moderators of the relationship between IPV‐related and 9/11‐related PTSS. Our results suggest that trauma‐related psychiatric history is an important factor in the development of PTSS subsequent to an additional potentially traumatic event, even after adjusting for relevant variables occurring at the time of that event.