bluuebunny/crossref_metadata_2025 huggingface dataset:
Morbidity and mortality in gynecological cancers among first‐ and second‐generation immigrants in Sweden
Authors: Mousavi Seyed Mohsen , Sundquist Kristina , Hemminki Kari
Published: September 2011

We studied the effect of new environment on the risk in and mortality of gynecological cancers in first‐ and second‐generation immigrants in Sweden. We used the nationwide Swedish Family‐Cancer Database to calculate standardized incidence/mortality ratios (SIRs/SMRs) of cervical, endometrial and ovarian cancers among immigrants in comparison to the native Swedes. Risk of cervical cancer increased among first‐generation immigrants with Danish (SIR = 1.64), Norwegian (1.33), former Yugoslavian (1.21) and East European (1.35) origins, whereas this risk decreased among Finns (0.88) and Asians (SIRs varies from 0.11 in Iranians to 0.54 in East Asians). Risk of endometrial (SIRs varies from 0.28 in Africans to 0.86 in Finns) and ovarian (SIRs varies from 0.23 in Chileans to 0.82 in Finns) cancers decreased in first‐generation immigrants. The overall gynecological cancer risk for the second‐generation immigrants, independent of the birth region, was almost similar to that obtained for the first generations. The birth region‐specific SMRs of gynecological cancers in first‐ and second‐generation immigrants co‐varied with the SIRs. Risk of gynecological cancers among the first‐generation immigrants is similar to that in their original countries, except for cervical cancer among Africans and endometrial cancer among North Americans and East Europeans. Our findings show that risk and mortality of gynecological cancers observed in the first‐generation immigrants remain in the second generation. We conclude that the risk and protective factors of gynecological cancers are preserved upon immigration and through generations, suggesting a role for behavioral factors or familial aggregation in the etiology of these diseases.
mTOR as a therapeutic target in patients with gastric cancer
Authors: Al‐Batran Salah‐Eddin , Ducreux Michel , Ohtsu Atsushi
Published: September 2011

The poor long‐term outcomes associated with current chemotherapy treatment of patients with advanced gastric cancer suggest a need for novel targeted agents that may confer a better survival benefit. Evidence of mammalian target of rapamycin (mTOR) activation has been demonstrated in patient‐derived gastric cancer cells and tumors. This review explores the relevance of the mTOR pathway to gastric cancer pathogenesis and its potential as a therapeutic target in patients with gastric cancer as well as presenting the first available clinical data on mTOR inhibitors in this disease setting. Preclinical data suggest that suppression of the mTOR pathway inhibited the proliferation of gastric cancer cells and delayed tumor progression in in vitro and animal models. In the clinical setting, the mTOR inhibitor everolimus has been active and well tolerated in phase I/II studies of patients with chemotherapy‐refractory metastatic gastric cancer. Based on these promising results, everolimus currently is being investigated as a monotherapy or in combination with chemotherapeutic agents in ongoing phase II/III clinical studies.
Validation of tumor‐associated macrophage ferritin light chain as a prognostic biomarker in node‐negative breast cancer tumors: A multicentric 2004 national PHRC study
Authors: Jézéquel Pascal , Campion Loïc , Spyratos Frédérique , Loussouarn Delphine , Campone Mario , Guérin‐Charbonnel Catherine , Joalland Marie‐Pierre , André Jean , Descotes Françoise , Grenot Catherine , Roy Pascal , Carlioz Antoine , Martin Pierre‐Marie , Chassevent Agnès , Jourdan Marie‐Lise , Ricolleau Gabriel
Published: September 2011

Novel prognostic biomarkers are imperatively needed to help direct treatment decisions by typing subgroups of node‐negative breast cancer patients. Large screening of different biological compartments, such as the proteome, by means of high throughput techniques may greatly help scientists to find such markers. The present retrospective multicentric study included 268 node‐negative breast cancer patients. We used a proteomic approach of SELDI‐TOF‐MS screening to identify differentially expressed cytosolic proteins with prognostic impact. The screening cohort was composed of 198 patients. Seventy supplementary patients were included for validation. Immunohistochemistry (IHC) and immunoassay (IA) were run to confirm the prognostic role of the marker identified by SELDI‐TOF‐MS screening. IHC was also used to explore links between selected marker and epithelial‐mesenchymal transition (EMT)‐like, proliferation and macrophage markers. Ferritin light chain (FTL) was identified as an independent prognostic marker (HR = 1.30–95% CI: 1.10–1.50, p = 0.001). Validation step by means of IHC and IA confirmed the prognostic value of FTL level. CD68 IHC showed that FTL was stored in tumor‐associated macrophages (TAM), which exhibit an M2‐like phenotype. We report here, first, the validation of FTL as a breast tumor prognostic biomarker in node‐negative patients, and second, the fact that FTL is stored in TAM.
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

CDH1 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

Current 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

To 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

The 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

Femtosecond 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

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

The 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

Understanding 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

The 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

A 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

A 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

This 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

Background

The purpose of this study was to evaluate the effect of a video on patient understanding of basic breast cancer concepts.

Methods

An 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.

Results

Eighty‐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.

Conclusions

Implementation 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

Background and Objectives

We 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.

Methods

The association between the hypermethylation of RUNX3 and clinicopathological characteristics of 186 NMIBC samples was analyzed using methylation‐specific polymerase chain reaction (MS‐PCR).

Results

RUNX3 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].

Conclusions

RUNX3 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

This 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.
Alterations in affective processing of attack images following September 11, 2001
Authors: Tso Ivy F. , Chiu Pearl H. , King‐Casas Brooks R. , Deldin Patricia J.
Published: September 2011

The events of September 11, 2001 created unprecedented uncertainty about safety in the United States and created an aftermath with significant psychological impact across the world. This study examined emotional information encoding in 31 healthy individuals whose stress response symptoms ranged from none to a moderate level shortly after the attacks as assessed by the Impact of Event Scale‐Revised. Participants viewed attack‐related, negative (but attack‐irrelevant), and neutral images while their event‐related brain potentials (ERPs) were recorded. Attack images elicited enhanced P300 relative to negative and neutral images, and emotional images prompted larger slow waves than neutral images did. Total symptoms were correlated with altered N2, P300, and slow wave responses during valence processing. Specifically, hyperarousal and intrusion symptoms were associated with diminished stimulus discrimination between neutral and unpleasant images; avoidance symptoms were associated with hypervigilance, as suggested by reduced P300 difference between attack and other images and reduced appraisal of attack images as indicated by attenuated slow wave. The findings in this minimally symptomatic sample are compatible with the alterations in cognition in the posttraumatic stress disorder (PTSD) literature and are consistent with a dimensional model of PTSD.
A postdeployment expressive writing intervention for military couples: A randomized controlled trial
Authors: Baddeley Jenna L. , Pennebaker James W.
Published: September 2011

The current study tested the effectiveness of a brief expressive writing intervention on the marital adjustment of 102 military couples recently reunited following a deployment to Iraq or Afghanistan. Active duty soldiers and their spouses were randomly assigned to write about either their relationship or a nonemotional topic on 3 occasions on a single day. The resulting design included 4 couple‐level writing topic conditions: soldier‐expressive/spouse‐expressive, soldier‐expressive/spouse‐control, soldier‐control/spouse‐expressive, and soldier‐control/spouse‐control. Participants completed marital adjustment measures before writing, 1 month, and 6 months after writing. When soldiers, but not spouses, did expressive writing, couples increased in marital satisfaction over the next month, particularly if the soldier had had high combat exposure.
Kinetic studies on the metal(II) tartarate–peroxomonosulfate reaction
Authors: Shailaja Sivasubramonian , Ramachandran Murugian Shanmugam
Published: September 2011

The kinetics of oxidation of tartaric acid (TAR) by peroxomonosulfate (PMS) in the presence of Cu(II) and Ni(II) ions was studied in the pH range 4.05–5.20 and also in alkaline medium (pH ∼12.7). The rate was calculated by measuring the [PMS] at various time intervals. The metal ions concentration range used in the kinetic studies was 2.50 × 10−5 to 1.00 × 10−4 M [Cu(II)], 2.50 × 10−4 to 2.00 × 10−3M [Ni(II)], 0.05 to 0.10 M [TAR], and µ = 0.15 M. The metal(II) tartarates, not TAR/tartarate, are oxidized by PMS. The oxidation of copper(II) tartarate at the acidic pH shows an appreciable induction period, usually 30–60 min, as in classical autocatalysis reaction. The induction period in nickel(II) tartarate is small. Analysis of the [PMS]–time profile shows that the reactions proceed through autocatalysis. In alkaline medium, the Cu(II) tartarate–PMS reaction involves autocatalysis whereas Ni(II) tartarate obeys simple first‐order kinetics with respect to [PMS]. The calculated rate constants for the initial oxidation (k1) and catalyzed oxidation (k2) at [TAR] = 0.05 M, pH 4.05, and 31°C are Cu(II) (1.00 × 10−4 M): k1 = 4.12 × 10−6 s−1, k2 = 7.76 × 10−1 M−1s−1 and Ni(II) (1.00 × 10−3 M): k1 = 5.80 × 10−5 s−1, k2 = 8.11 × 10−2 M−1 s−1. The results suggest that the initial reaction is the oxidative decarboxylation of the tartarate to an aldehyde. The aldehyde intermediate may react with the alpha hydroxyl group of the tartarate to give a hemi acetal, which may be responsible for the autocatalysis. © 2011 Wiley Periodicals, Inc. Int J Chem Kinet 43: 620–630, 2011
The role of TNF‐α in inflammatory olfactory loss
Authors: Sultan Babar , May Lindsey A. , Lane Andrew P.
Published: September 2011

Background:

Despite the significant health impact of olfactory loss in chronic rhinosinusitis (CRS), the underlying pathophysiology is incompletely understood. A transgenic mouse model of olfactory inflammation induced by tumor necrosis factor‐alpha (TNF‐α) has provided new insights into the cellular and molecular basis of inflammatory olfactory loss. Here, we utilize systemic corticosteroids to suppress downstream cytokine expression, in order to study the direct role of TNF‐α in CRS‐associated olfactory dysfunction.

Methods:

Transgenic mice were induced to express TNF‐α in the olfactory epithelium for 6 weeks. In a subset of mice, 1 mg/kg prednisolone was administered concurrently to inhibit downstream inflammatory responses. The olfactory epithelium (OE) was analyzed by histology and electro‐olfactogram (EOG) recordings.

Results:

Treatment with prednisolone successfully prevented inflammatory infiltration over significant regions of the OE. In areas where significant subepithelial inflammation was present, a corresponding loss of olfactory neurons was observed. In contrast, areas without major inflammatory changes had normal olfactory neuron layers, despite chronic local expression of TNF‐α. Prednisolone partially reversed the complete loss of olfaction in the mouse model, preserving odorant responses that were significantly diminished compared to controls, but not absent.

Conclusions:

The addition of prednisolone to the transgenic model of olfactory inflammation isolates the direct effects of induced TNF‐α expression on the OE. The finding that prednisolone treatment prevents neuronal loss in some regions of the OE suggests that TNF‐α does not directly cause neuronal apoptosis—rather, that subepithelial inflammation or other downstream mediators may be responsible. At the same time, EOG results imply that TNF‐α directly causes physiologic dysfunction of olfactory neurons, independent of the inflammatory state. An understanding of the role of TNF‐α and other inflammatory cytokines may suggest novel therapeutic strategies for CRS‐associated olfactory loss.
Mammalian Cell Viability in Electrospun Composite Nanofiber Structures
Authors: Fatih Canbolat Mehmet , Tang Christina , Bernacki Susan H. , Pourdeyhimi Behnam , Khan Saad
Published: September 2011

Incorporation of mammalian cells into nanofibers (cell electrospinning) and multilayered cell‐nanofiber structures (cell layering) via electrospinning are promising techniques for tissue engineering applications. We investigate the viability of 3T3‐L1 mouse fibroblasts after incorporation into poly(vinyl alcohol) nanofibers and multilayering with poly(caprolactone) nanofibers and analyze the possible factors that affect cell viability. We observe that cells do not survive cell electrospinning but survive cell layering. Assessing the factors involved in cell electrospinning, we find that dehydration and fiber stretching are the main causes of cell death. In cell layering, the choice of solvent is critical, as residual solvent in the electrospun fibers could be detrimental to the cells.

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Computational Approaches for Studying the Granular Dynamics of Continuous Blending Processes, 2 – Population Balance and Data‐Based Methods
Authors: Boukouvala Fani , Dubey Atul , Vanarase Aditya , Ramachandran Rohit , Muzzio Fernando J. , Ierapetritou Marianthi
Published: September 2011

The application of computationally inexpensive modeling methods for a predictive study of powder mixing is discussed. A multidimensional population balance model is formulated to track the evolution of the distribution of a mixture of particle populations with respect to position and time. Integrating knowledge derived from a discrete element model, this method can be used to predict residence time distribution, mean and relative standard deviation of the API concentration in a continuous mixer. Low‐order statistical models, including response surface methods, kriging, and high‐dimensional model representations are also presented. Their efficiency for design optimization and process design space identification with respect to operating and design variables is illustrated.

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Flexible Polymer/Clay Nanocomposite Films as Oxygen Supply Materials
Authors: Stefanescu Eduard A. , Stefanescu Cristina
Published: September 2011

PIB/MMT nanocomposite films containing UHP are fabricated and characterized for potential applications in wounded‐skin oxygen delivery and/or tooth cleaning. The UHP acts as a source of oxygen, whereas MMT creates a pathway for water molecules penetrating the film in order to generate a controlled release of H2O2 molecules. Most UHP particles are uniformly dispersed throughout the entire thickness of the films. DMA measurements indicate that the material retains most of its structural characteristics when exposed to water. SEM measurements show that no interface exists between individually spread multilayers. SAXS measurements indicate that the clay platelets are predominantly exfoliated and randomly oriented within the film. Controlled release of H2O2 is found over a period of ≈90–100 min.

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Synthesis, Characterization and Properties of New Semifluorinated Poly(arylene ether phosphine oxide)s
Authors: Ghosh Anindita , Bera Debaditya , Wang De‐Yi , Komber Hartmut , Mohanty Aruna Kumar , Banerjee Susanta , Voit Brigitte
Published: September 2011

Bis(4‐fluoro‐3‐trifluoromethylphenyl)phenylphosphine oxide is synthesized and six new poly(arylene ether)s are prepared by nucleophilic displacement of the fluorine atom on the benzene ring by several diphenols under basic conditions. The products show very high glass transition temperatures of up to 252 °C and very good thermal stabilities of up to 490 °C for 5% weight loss. The polymers display very low heat release rates in the microscale combustion calorimeter test, suggesting good flame retardance. All polymers are soluble in a wide range of organic solvents. Transparent thin films cast from dichloromethane exhibit tensile strengths up to 54 MPa, a modulus of elasticity up to 0.97 GPa and elongation at break up to 47% depending on their exact repeating unit structures.

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Effect of Boehmite Alumina Nanofiller Incorporation on the Morphology and Thermal Properties of Functionalized Poly(propylene)/Polyamide 12 Blends
Authors: Ogunniran Elijah Soba , Sadiku Rotimi , Sinha Ray Suprakas , Luruli Nyambeni
Published: September 2011

A composite of boehmite alumina nanoparticles and a PP/PA12 blend is prepared. WAXD and SEM suggest that a low filler loading enhances the coalescence of PA12, whereas a higher loading reverses the situation. DSC, DMA and TGA reveal that the final properties of the blend composites such as crystallization temperatures, flexural storage moduli, or thermal degradation temperatures improve with increasing nanoparticle loading. The data are compared with the neat polymers and the compatibilized blend, and the results show that the compatibility increases only at high nanoparticle loading, and most of the thermal properties improve with increasing nanoparticle content in the blends. The presence of interfacial interactions between the polymer matrices and the filler was confirmed via FTIR.

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Magnetic Organosilica Nanoparticles for Localized Polymer Surface Modification
Authors: Gu Hongyan , Faucher Santiago , Zhu Shiping
Published: September 2011

Magnetic organosilica nanoparticles are synthesized by grafting MPB‐POSS/MMA‐based block copolymers from magnetic iron nanoparticles via surface‐initiated ATRP. The hybrid nanoparticles consist of a magnetic iron core and a PMMA/POSS composite shell. A small amount of the nanoparticles is added as “smart additive” in casting PMMA sheets for localized surface modification. It is demonstrated that the particles are readily brought to the surface of the cast piece by applying a magnet field to the molding. At 1 wt% loading, the sample has a 50‐time higher particle content in a 100 µm‐thick surface layer than in the bulk. The indentation hardness of the modified surface is increased by 30%.

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Mechanical Investigations on Agar Gels Using Atomic Force Microscopy: Effect of Deuteration
Authors: Grant Colin A. , Twigg Peter C. , Savage Michael D. , Woon W. Hong , Greig Denis
Published: September 2011

The isotopic effect of exchanging deuterium with hydrogen on the mechanical and surface properties of agar gel is examined. The elastic modulus of the D2O gels obtained by AFM nanoindentation is significantly higher (factor of ≈1.5–2) than the modulus found in H2O agar gels. Furthermore, the modulus is independent of loading rate. Surface imaging reveals that the surface roughness gets progressively smaller with increasing agar concentration. All these data suggest that the isotopic replacement of deuterium enhances the mechanical properties of the agar gel, with significant advantages in its use as a biphasic scaffold.

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Thermally Tunable Surface Wettability of Electrospun Fiber Mats: Polystyrene/Poly(N‐isopropylacrylamide) Blended versus Crosslinked Poly[(N‐isopropylacrylamide)‐co‐(methacrylic acid)]
Authors: Muthiah Palanikkumaran , Hoppe Sarah M. , Boyle Timothy J. , Sigmund Wolfgang
Published: September 2011

This work reports on thermally tunable surface wettability of electrospun fiber mats of: polystyrene (PS)/poly(N‐isopropylacrylamide) (PNIPA) blended (bl‐PS/PNIPA) and crosslinked poly[(N‐isopropylacrylamide)‐co‐[methacrylic acid)] (PNIPAMAA) (xl‐NIPAMAA). Both the bl‐PS/PNIPA and xl‐PNIPAMAA fiber mats demonstrate reversibly switchable surface wettability, with the bl‐PS/PNIPA fiber mats approaching superhydrophobic ≥150° and superhydrophilic contact angle (CA) values at extreme temperatures. Weight loss studies carried out at 10 °C indicate that the crosslinked PNIPAMAA fiber mats had better structural integrity than the bl‐PS/PNIPA fiber mats. PNIPA surface chemistry and the Cassie–Baxter model were used to explain the mechanism behind the observed extreme wettability.

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Loss of Trp53 promotes medulloblastoma development but not skin tumorigenesis in Sufu heterozygous mutant mice
Authors: Heby‐Henricson Karin , Bergström Åsa , Rozell Björn , Toftgård Rune , Teglund Stephan
Published: September 2011

Basal cell carcinoma of the skin typically carries genetic alterations in components of the hedgehog (HH) signaling pathway. Previously, we generated a knockout mouse with a loss‐of‐function mutation in suppressor of fused (Sufu), an essential repressor of the pathway downstream of Hh ligand cell surface reception. Mice heterozygous for the mutated Sufu allele develop a skin phenotype that includes lesions similar to basaloid follicular hamartomas. The purpose of the current study was to test the possibility that the simultaneous loss of the tumor suppressor gene, transformation related protein 53 (Trp53), would aggravate the Sufu skin phenotype since Trp53 loss is known to enhance the growth of other Hh‐driven tumors. Consistent with previous reports, medulloblastomas and rhabdomyosarcomas developed in Sufu+/−;Trp53−/− mice. However, the characteristic Sufu+/− skin phenotype was not altered in the absence of Trp53, and showed no changes in latency, multiplicity, cellular phenotype, or proliferative capacity of the basaloid lesions. This finding was both novel and intriguing and demonstrated a differential, tissue‐specific sensitivity to Sufu and Trp53 tumor suppressor gene loss, which may be linked to developmental stage and the degree of proliferative activity in specific cell types. © 2011 Wiley Periodicals, Inc.
Cognitive impairment in nondemented Parkinson's disease
Authors: Barone Paolo , Aarsland Dag , Burn David , Emre Murat , Kulisevsky Jaime , Weintraub Daniel
Published: September 2011

A substantial percentage of patients with newly diagnosed Parkinson's disease without dementia are reported to be affected by cognitive impairment (CI). In practice, however, CI is underrecognized, as the signs may not be apparent in early‐stage disease and many routine assessment tools lack the sensitivity to detect subtle cognitive dysfunction. Patients with PD and mild CI (MCI) may have a higher risk of developing dementia than cognitively intact PD patients; however, it is not currently known which patients with CI are at increased risk of developing dementia. This review summarizes current knowledge about CI in nondemented PD; it discusses the structural and functional changes associated with CI and addresses areas of unmet needs. We focus on questions that should be addressed in future studies to achieve consensus on its characteristics and definition, pathophysiology, epidemiology, diagnosis and assessment, and treatment and management. © 2011 Movement Disorder Society
Safety and efficacy of botulinum toxin type B for treatment of sialorrhea in Parkinson's disease: A prospective double‐blind trial
Authors: Chinnapongse Robert , Gullo Kristen , Nemeth Paul , Zhang Yuxin , Griggs Lynn
Published: September 2011

Sialorrhea (drooling) is a common symptom of Parkinson's disease (PD) that can significantly impair a patient's health and quality of life. Fifty‐four PD subjects with troublesome sialorrhea were enrolled using a multicenter, randomized, double‐blind, sequential‐dose escalation design in which subjects received a single intraglandular treatment with botulinum toxin type B (doses of 1,500 Units [0.3 mL]; 2,500 Units [0.5 ml]; or 3,500 Units [0.7 ml]) or placebo. Postinjection, subjects were followed acutely for 4 weeks and long‐term for up to 20 weeks. Safety/tolerability, as assessed by adverse events, was the primary outcome measure. Efficacy, as assessed by the Drooling Frequency and Severity Scale and unstimulated salivary flow rate, was secondary. Gastrointestinal‐related adverse events occurred more frequently in the active groups versus placebo group (31% vs 7%), with dry mouth being most common (15%). There were no serious adverse events attributed to botulinum toxin type B or discontinuations due to adverse events from treatment. At 4 weeks postinjection, Drooling Frequency and Severity Scale scores significantly improved versus placebo (−1.3 ± 1.3) in a dose‐related manner (−2.1 ± 1.2, P = 0.0191; −3.3 ± 1.4, P < 0.0001; −3.5 ± 1.1, P < 0.0001, respectively) and unstimulated salivary flow rates significantly decreased in all active groups versus placebo (P ≤ 0.0009). Furthermore, treated subjects appeared to have more sustained improvement in sialorrhea than placebo subjects. We conclude that intraglandular injection of botulinum toxin type B was safe, tolerable, and efficacious in treating sialorrhea in PD patients. Additional studies are warranted to further confirm the drug's robust efficacy, as well as evaluate its effect with repeated dosing. © 2011 Movement Disorder Society