bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and validation of highly frequent CpG island hypermethylation in colorectal adenomas and carcinomas
Authors: Øster Bodil , Thorsen Kasper , Lamy Philippe , Wojdacz Tomasz K. , Hansen Lise Lotte , Birkenkamp‐Demtröder Karin , Sørensen Karina D. , Laurberg Søren , Ørntoft Torben F. , Andersen Claus L.
Published: March 2011

In our study, whole‐genome methylation arrays were applied to identify novel genes with tumor specific DNA methylation of promoter CpG islands in pre‐malignant and malignant colorectal lesions. Using a combination of Illumina HumanMethylation27 beadchips, Methylation‐Sensitive High Resolution Melting (MS‐HRM) analysis, and Exon arrays (Affymetrix) the DNA methylation pattern of ∼14,000 genes and their transcript levels were investigated in six normal mucosas, six adenomas and 30 MSI and MSS carcinomas. Sixty eight genes with tumor‐specific hypermethylation were identified (p < 0.005). Identified hypermethylated sites were validated in an independent sample set of eight normal mucosas, 12 adenomas, 40 MSS and nine MSI cancer samples. The methylation patterns of 15 selected genes, hypermethylated in adenomas and carcinomas (FLI1, ST6GALNAC5, TWIST1, ADHFE1, JAM2, IRF4, CNRIP1, NRG1 and EYA4), in carcinomas only (ABHD9, AOX1 and RERG), or in MSI but not MSS carcinomas (RAMP2, DSC3 and MLH1) were validated using MS‐HRM. Four of these genes (MLH1, AOX1, EYA4 and TWIST1) had previously been reported to be hypermethylated in CRC. Eleven genes, not previously known to be affected by CRC specific hypermethylation, were identified and validated. Inverse correlation to gene expression was observed for six of the 15 genes with Spearman correlation coefficients ranging from −0.39 to −0.60. For six of these genes the altered methylation patterns had a profound transcriptional association, indicating that methylation of these genes may play a direct regulatory role. The hypermethylation changes often occurred already in adenomas, indicating that they may be used as biomarkers for early detection of CRC.
Family history of cancer and the risk of laryngeal cancer: A case‐control study from Italy and Switzerland
Authors: Garavello Werner , Turati Federica , Bosetti Cristina , Talamini Renato , Levi Fabio , Lucenteforte Ersilia , Chiesa Fausto , Franceschi Silvia , La Vecchia Carlo , Negri Eva
Published: March 2011

Only limited data is available on the relationship between family history of laryngeal and other neoplasms and laryngeal cancer risk. We investigated the issue using data from a multicentre case‐control study conducted in Italy and Switzerland between 1992 and 2009 including 852 cases with histologically confirmed laryngeal cancer and 1970 controls admitted to hospital for acute, non neoplastic conditions. Unconditional logistic regression models adjusted for age, sex, study center, education, tobacco smoking, alcohol drinking and number of siblings were used to estimate the odds ratios (ORs) of laryngeal cancer. The multivariate OR was 2.8 (95% confidence interval [CI], 1.5–5.3) in subjects reporting a first‐degree relative with laryngeal cancer, as compared to subjects with no family history. The OR was higher when the relative was diagnosed before 60 years of age (OR = 3.5, 95% CI 1.4–8.8). As compared to subjects without family history, non‐smokers, and moderate drinkers, the OR was 37.1 (95% CI 9.9–139.4) for current smokers, heavy drinkers, with family history of laryngeal cancer. Family history of colorectal (OR = 1.5, 95% CI 1.0–2.3) and kidney (OR = 3.8, 95% CI 1.2–12.1) cancer were also associated to an increased risk of laryngeal cancer, while no significant increase in risk was found for family history of cancer at all sites, excluding the larynx (OR = 1.1).
MET inhibition in tumor cells by PHA665752 impairs homologous recombination repair of DNA double strand breaks
Authors: Medová Michaela , Aebersold Daniel M , Zimmer Yitzhak
Published: March 2011

Abnormal activation of cellular DNA repair pathways by deregulated signaling of receptor tyrosine kinase systems has broad implications for both cancer biology and treatment. Recent studies suggest a potential link between DNA repair and aberrant activation of the hepatocyte growth factor receptor Mesenchymal‐Epithelial Transition (MET), an oncogene that is overexpressed in numerous types of human tumors and considered a prime target in clinical oncology. Using the homologous recombination (HR) direct‐repeat direct‐repeat green fluorescent protein ((DR)‐GFP) system, we show that MET inhibition in tumor cells with deregulated MET activity by the small molecule PHA665752 significantly impairs in a dose‐dependent manner HR. Using cells that express MET‐mutated variants that respond differentially to PHA665752, we confirm that the observed HR inhibition is indeed MET‐dependent. Furthermore, our data also suggest that decline in HR‐dependent DNA repair activity is not a secondary effect due to cell cycle alterations caused by PHA665752. Mechanistically, we show that MET inhibition affects the formation of the RAD51‐BRCA2 complex, which is crucial for error‐free HR repair of double strand DNA lesions, presumably via downregulation and impaired translocation of RAD51 into the nucleus. Taken together, these findings assist to further support the role of MET in the cellular DNA damage response and highlight the potential future benefit of MET inhibitors for the sensitization of tumor cells to DNA damaging agents.
Brain‐derived neurotrophic factor is a potential osteoclast stimulating factor in multiple myeloma
Authors: Sun Chun‐Yan , Chu Zhang‐Bo , She Xiao‐Mei , Zhang Lu , Chen Lei , Ai Li‐Sha , Hu Yu
Published: March 2011

Multiple myeloma (MM) is characterized by accumulation of monoclonal plasma cells in the bone marrow and progression of lytic bone lesions. The mechanisms of enhanced bone resorption in patients with myeloma are not fully defined. We have previously identified the role of brain‐derived neurotrophic factor (BDNF) in proliferation and migration of MM cells. In our study, we investigated whether BDNF was possibly involved in MM cell‐induced osteolysis. We showed that BDNF was elevated in MM patients and the bone marrow plasma levels of BDNF positively correlated with extent of bone disease. In osteoclast formation assay, bone marrow plasma from patients with MM increased osteoclast formation and the effect was significantly blocked by neutralizing antibody to BDNF, suggesting a critical role for BDNF in osteoclast activation. Furthermore, the direct effects of recombinant BDNF on osteoclast formation and bone resorption support the potential role of BDNF in the MM bone disease. BDNF receptor TrkB was expressed by human osteoclast precursors and a Trk inhibitor K252a markedly inhibited osteoclast formation stimulated with BDNF, demonstrating that BDNF used TrkB for its effects on osteoclast. Finally, bone marrow plasma BDNF level positively correlated with macrophage inflammatory protein‐1α and receptor activator of nuclear factor‐κB ligand, two major osteoclast stimulatory factors in MM. These results support an important role for BDNF in the development of myeloma bone disease.
Anomalous inhibition of c‐Met by the kinesin inhibitor aurintricarboxylic acid
Authors: Milanovic Mina , Radtke Simone , Peel Nick , Howell Michael , Carrière Virginie , Joffre Carine , Kermorgant Stéphanie , Parker Peter J.
Published: March 2011

c‐Met [the hepatocyte growth factor (HGF) receptor] is a receptor tyrosine kinase playing a role in various biological events. Overexpression of the receptor has been observed in a number of cancers, correlating with increased metastatic tendency and poor prognosis. Additionally, activating mutations in c‐Met kinase domain have been reported in a subset of familial cancers causing resistance to treatment. Receptor trafficking, relying on the integrity of the microtubule network, plays an important role in activation of downstream targets and initiation of signalling events. Aurintricarboxylic acid (ATA) is a triphenylmethane derivative that has been reported to inhibit microtubule motor proteins kinesins. Additional reported properties of this inhibitor include inhibition of protein tyrosine phosphatases, nucleases and members of the Jak family. Here we demonstrate that ATA prevents HGF‐induced c‐Met phosphorylation, internalisation, subsequent receptor trafficking and degradation. In addition, ATA prevented HGF‐induced downstream signalling which also affected cellular function, as assayed by collective cell migration of A549 cells. Surprisingly, the inhibitory effect of ATA on HGF‐induced phosphorylation and signallingin vivowas associated with an increase in basal c‐Met kinase activityin vitro. It is concluded that the inhibitory effects of ATA on c‐Metin vivois an allosteric effect mediated through the kinase domain of the receptor. As the currently tested adenosine triphosphate competitive tyrosine kinase inhibitors (TKIs) may lead to tumor resistance (McDermott U, et al.,Cancer Res2010;70:1625–34), our findings suggest that novel anti‐c‐Met therapies could be developed in the future for cancer treatment.
Structure–function alteration of hemoglobin in arsenicosis patients: a probable pathway to exert toxicity
Authors: Mondal Bibaswan , Chatterjee Debdutta , Bhattacharyya Maitree
Published: March 2011

Chronic arsenicosis, a major public health concern in India and Bangladesh, is mainly caused by ingestion of arsenic (As) contaminated ground water. Although this problem has been studied extensively, the mechanism of toxicity remains unknown. This paper investigates the process of trivalent arsenicals binding to hemoglobin (Hb) in chronic arsenicosis patients and consequent modification in the structure–function activity of Hb. In this work peroxidase activity, thermal denaturation profile, oxygen releasing capacity and hydrodynamic diameter have been evaluated for the Hb collected from subjects suffering with chronic arsenicosis. Increased peroxidative activity suggests altered oxidative status of Hb in the diseased state. The thermal denaturation profile indicates the Hb molecule to be more susceptible to unfolding in the pathologic state. The enhanced oxygen releasing capacity and significant reduction in hydrodynamic diameter of Hb is also observed in the diseased condition, suggesting conformational alterations in the Hb molecule. Finally, trivalent arsenic is found to bind with freshly isolated Hb from arsenicosis patients, binding affinity constant being 0.256 μM−1. The binding is positively cooperative with a Hill coefficient of +2.961 and isosbestic points at specific wavelengths. Thus, our work explores the structure–function property of Hb in chronic arsenicosis subjects and reveals that the molecule is modified in such a way that comparatively weak binding with oxygen and strong binding with arsenic occur simultaneously. This association may play a crucial role in exerting the pathway for arsenic toxicity. Copyright © 2011 John Wiley & Sons, Ltd.
Delayed response in the rat frontal lobe transcriptome to perinatal exposure to the flame retardant BDE‐47
Authors: Suvorov Alexander , Takser Larissa
Published: March 2011

BDE‐47 is the most prevalent congener of polybrominated diphenyl ethers, which are widely used flame retardants, and is known for endocrine and behavioral disrupting properties in animals. Transient effect on spontaneous motor activity in rats following perinatal exposure to BDE‐47 at low doses, relevant to human exposure, was reported in our previous study. The objective of this study was to screen for the long‐term effects on gene expression in the brain of rats perinatally exposed to BDE‐47. Wistar dams were exposed to BDE‐47 (0.002 and 0.2 mg kg−1 body weight) from gestation day 15 to postnatal day (PND) 20. Total RNA was extracted from the whole brain at PND10 and the brain frontal lobes at PND41 and hybridized to whole‐genome RNA expression microarrays. The genes, differentially expressed 1.5‐fold, were analyzed with the DAVID bioinformatics resources for cluster and gene‐term enrichment. At PND41, clusters of genes involved in nerve impulse transmission, nervous system development and functioning, and core biosynthetic process were altered, including several downregulated genes of cation channels. Representation of LINE1 RNA was decreased significantly. Altered expression of genes involved in neurodevelopment occured at least 3 weeks after the last exposure and the behavioral manifestation of low dose BDE‐47 toxicity. Copyright © 2011 John Wiley & Sons, Ltd.
Cell‐cycle phases and genetic profile of bone marrow‐derived mesenchymal stromal cells expanded in vitro from healthy donors
Authors: Achille Valentina , Mantelli Melissa , Arrigo Giulia , Novara Francesca , Avanzini Maria Antonietta , Bernardo Maria Ester , Zuffardi Orsetta , Barosi Giovanni , Zecca Marco , Maccario Rita
Published: March 2011

Human mesenchymal stromal cells (MSCs) expanded in vitro for cell therapy approaches need to be carefully investigated for genetic stability, by employing both molecular and conventional karyotyping. Reliability of cytogenetic analysis may be hampered in some MSC samples by the difficulty of obtaining an adequate number of metaphases. In an attempt to overcome this problem, a methodology apt to evaluate the cell‐cycle structure on synchronous MSCs was optimised. Results obtained in five independent experiments by comparing cell‐cycle analysis of synchronous and asynchronous MSC populations evaluated at early and late culture passages documented that in synchronous MSCs, 30% of cells entered G2/M phase after about 27–28 h of culture, while in asynchronous MSCs only 8% of cells in G2/M phase could be observed at the same time point. Cytogenetic analysis on synchronous MSCs allowed us to obtain 20–25 valuable metaphases/slide, whereas only 0–4 metaphases/slide were detectable in asynchronous preparations. J. Cell. Biochem. 112: 1817–1821, 2011. © 2011 Wiley‐Liss, Inc.
Removal of methylene blue from coloured effluents by adsorption onto SBA‐15
Authors: Dong Yanling , Lu Bin , Zang Shuying , Zhao Jingxiang , Wang Xiaoguang , Cai Qinghai
Published: March 2011

Adsorption has been proven to be the most efficient method for quickly lowering the concentration of dissolved dyes in an effluent. In this regard, activated carbon is the most widely used adsorbent for removal of dyes from aqueous solution. However, the high cost of production and regeneration make it uneconomical. Therefore, inorganic adsorbents (e.g. zeolites) with high surface areas have been used as alternatives to carbon adsorbents. Microporous zeolites ZSM‐5, NH4‐Beta, MCM‐22 and mesoporous materials MCM‐41 have been investigated for the removal of dyes from aqueous solutions and they show effective adsorption performance. SBA‐15 possesses a larger pore size and pore wall thickness than MCM‐41. As a result, SBA‐15 has greater potential for the adsorption of methylene blue with larger molecule size and higher hydrothermal stability than the M41S family. SBA‐15 is an excellent adsorbent for methylene blue (MB), exhibiting 280 mg g−1 adsorption capacity and about 100% fading rate for MB. The adsorptive process is so fast that adsorption equilibrium is achieved in 5 min. In addition, SBA‐15 can be effectively recovered by calcination and reused 10 times without significant loss in removal of MB from aqueous solution. The efficient adsorption of MB molecules onto SBA‐15 was ascribed to MB adsorbed into the pore channels of SBA‐15, which was confirmed by nitrogen physisorption analysis of the adsorbent before and after adsorption. The long reuse life of the adsorbent suggests a high potential for application in industry. Copyright © 2010 Society of Chemical Industry
Yeast‐mediated stereo‐selective reduction of estrone by continuous cell culture with dual stirred tanks for product yield improvement
Authors: Cheng Cheanyeh , Tsai Hsiang‐Rong
Published: March 2011

BACKGROUND: β‐Estradiol is an important hormone for the treatment of breast cancer and osteoporosis. β‐Estradiol can be produced via Saccharomyces cerevisiae mediated reduction of estrone. However, substrate inhibition and low production yield have been observed in the batch cell culture.

RESULTS: An innovative continuous cell culture with dual stirred tanks in series was designed to solve the above problems. The growth medium was fed continuously to the incubation tank where the cells were incubated aerobically; the viable cells were then supplied continuously to the reaction tank in which the yeast‐mediated anaerobic reduction of estrone was performed with continuous feed of the substrate medium and continuous withdawal of the reaction cell culture. Thus, an increase in cell productivity from about 3‐fold to 7‐fold was obtained when compared with the batch cell culture. The β‐estradiol yield was improved to 64.8% on the second reaction day, accompanied by an accumulation of 12.9 mg β‐estradiol on the third reaction day. The yield was about 10% more and the accumulated recovery of β‐estradiol was 4.3‐fold better than with the batch cell culture. The diastereomeric excess value (%de) of β‐estradiol was more than 99%.

CONCLUSION: A high product yield with excellent stereo‐selectivity was achieved in a short reaction period with the developed continuous cell culture and the dual stirred tank. Copyright © 2010 Society of Chemical Industry
Article alerts: Items from 2009, Part II
Authors: Hafdahl Adam R.
Published: March 2011

This second installment of the ‘Article Alerts’ feature section more than doubles the collection's number of items. The print and archive versions now include 200 and 2579 items, respectively. Remarks are offered on inclusion criteria, anticipated growth of the archive version, and a related resource. Copyright 2011 John Wiley & Sons, Ltd.
‘Cross hairs’ plots for diagnostic meta‐analysis
Authors: Phillips Bob , Stewart Lesley A. , Sutton Alex J.
Published: March 2011

Understanding diagnostic test accuracy (DTA) data, especially meta‐analysis of this information, can be challenging for researchers and clinicians. The use of plots of receiver‐operator curve (ROC) space showing individual studies and summary estimates of diagnostic accuracy has become common but can be difficult to interpret. The assessment of heterogeneity in sensitivity and specificity across studies can be particularly difficult. In this paper, we review the key concepts of assessing DTA, starting at the level of individual studies and progressing to the setting of research synthesis. We explore the standard displays of this information and then propose and explain an alternative approach to summarizing key data. These ‘cross‐hairs’ plots display the individual studies in ROC space with paired confidence intervals representing sensitivity and specificity, and allow for the results of meta‐analysis to be overlaid on the plot. We suggest that these plots are more easily interpreted, and are a more informative graphical form than common approaches. Copyright © 2011 John Wiley & Sons, Ltd.
The total number of resected lymph node is not a prognostic factor for recurrence in esophageal squamous cell carcinoma patients undergone transthoracic esophagectomy
Authors: Hsu Po‐Kuei , Wang Bing‐Yen , Chou Teh‐Ying , Huang Chien‐Sheng , Wu Yu‐Chung , Hsu Wen‐Hu
Published: March 2011

Background

The total number of resected lymph nodes (TLN) has been shown to predict survival in esophageal cancer, but its relationship with recurrence has been rarely reported. We aim to study the prognostic factors in esophageal squamous cell carcinoma (ESCC) patients, with a particular focus on the role of TLN.

Methods

Two hundred sixty‐eight ESCC patients who underwent transthoracic esophagectomy were selected for the study. A Cox regression model was used to identify prognostic factors.

Results

Recurrence occurred in 115 of 268 patients. The median time to recurrence was 10 months (range, 1–58). The recurrence‐free survival at 1, 3, and 5 years was 62.3%, 32.1%, and 28.5%, respectively. Multivariate analysis identified age (P = 0.001), N stage (N1–3 vs. N0, P = 0.001), tumor length (P = 0.019), and development of recurrence (P < 0.001) as independent prognostic factors for overall survival, whereas T (T3/4 vs. T1/2, P = 0.029) and N stage (N1–3 vs. N0, P = 0.017) were independent prognostic factors for recurrence. TLN was a significant factor only when predicting overall survival in N0 patients (HR, 0.976; 95% CI, 0.953–0.999; P = 0.042).

Conclusion

The TLN is not a prognostic factor for recurrence in ESCC patients undergone transthoracic esophagectomy. J. Surg. Oncol. 2011; 103:416–420. © 2011 Wiley‐Liss, Inc.
Prognostic analysis of familial gastric cancer in Chinese population
Authors: Ye Yan‐Wei , Dong Rui‐Zheng , Zhou Ye , Du Chun‐Yan , Wang Chun‐Meng , Fu Hong , Shi Ying‐Qiang
Published: March 2011

Background

The aim of this study was firstly to elucidate the prognosis of familial gastric cancer (FGC) in Chinese population.

Methods

A total of 162 patients were recruited, including 81 patients with FGC and 81 patients with sporadic gastric cancer (SGC), who underwent gastrectomy between 1996 and 2007. Paraffin‐embedded tumor specimens were obtained from tissue bank of Cancer Hospital, Fudan University. The expression of epidermal growth factor receptor (EGFR), P53, C‐myc, and proliferating cell nuclear antigen (PCNA) were detected by immunohistochemical method.

Results

There were significant differences in tumor size, vessel invasion, EGFR, and P53 expression between FGC and SGC patients. The 5‐year survival rates were 48% and 57% in FGC and SGC patients, respectively (P = 0.033). Subgroup analysis showed that the 5‐year survival rates were worse in FGC patients with nerve invasion, high PCNA expression, negative expression of EGFR, and positive expression of P53 than those in SGC group. Multivariate analysis showed that AJCC stage, tumor size, and nerve invasion were independent prognostic factors in all patients. Furthermore, AJCC stage and P53 expression dramatically affected the prognosis of FGC patients.

Conclusions

The prognosis of FGC patients might be worse than those of SGC patients. AJCC stage and P53 expression are independent prognostic factors in FGC patients.

J. Surg. Oncol. 2011;104:76–82. © 2011 Wiley‐Liss, Inc.
A reconstruction with extracorporeal irradiated autograft in osteosarcoma around the knee
Authors: Kim Jae‐Do , Lee Gun Woo , Chung So Hak
Published: March 2011

Background and Objectives

An extracorporeal irradiated (ECI) autograft was first reported in Israel in 1968 for the treatment of primary malignant bone tumor. However, subsequent reports covered mostly short‐term follow up results, and the reported results of reconstruction vary from study to study. We analyze the long‐term follow up results of reconstruction using an extracorporeal irradiated (ECI) autograft in osteosarcoma around the knee.

Methods

We retrospectively reviewed 23 osteosarcoma patients who underwent reconstruction with ECI between December 1995 and April 2005. The 15 males and 8 females had a mean age of 21 years (range: 7–74) and a mean follow‐up of 127 months(range: 57–170). Tumors were located in the distal femur in 14 cases, and the proximal tibia in 9 cases. Pathological types were conventional in 22 cases, and parosteal in 1 case. Resection methods were osteoarticular in 18 cases and total joint in 5 cases. Eighteen cases were reconstructed with the ECI autograft and five with ECI autograft‐prosthesis composite (APC). The Musculoskeletal Tumor Society (MSTS) score was used for functional evaluation. The overall survival rate, local recurrence, complications were analyzed.

Results

The overall survival rate was 82.6%, and the disease‐free survival rate was 69.5%. We found 20 complications, including 6 nonunions, 5 deep infections, 4 joint instabilities, 2 fractures, 1 limb‐length discrepancy (LLD), 1 epiphyseal collapse, and 1 vessel occlusion. The average MSTS functional score was 62.6%.

Conclusions

Reconstruction with an extracorporeal irradiated is not recommended for osteosarcoma around the knee. J. Surg. Oncol. 2011;104:187–191. © 2011 Wiley‐Liss, Inc.
Monolith as a new sample preparation material: Recent devices and applications
Authors: Namera Akira , Nakamoto Akihiro , Saito Takeshi , Miyazaki Shota
Published: March 2011

Monolith was first used as a material for chromatographic separation two decades ago and solid‐phase extraction over 10 years, and since then, separation science has undergone a dramatic change owing to advancements in analytical technology. Recently, monolith has been modified to suit various devices for the extraction and enrichment of analytes in any matrices of environmental, food, and biological analyses. This approach has contributed to miniaturization and automation for sample preparation, and it can reduce the time and cost requirements of sample preparation. Recently, numerous applications have been demonstrated for online and inline preconcentration coupled with monolith, and many kinds of devices have been designed and developed for offline devices. In this review, these applications and devices are listed and discussed in reference to other fields.
Clinical features, health‐related quality of life, and adult voice in juvenile‐onset recurrent respiratory papillomatosis
Authors: Ilmarinen Taru , Nissilä Heljä , Rihkanen Heikki , Roine Risto P , Pietarinen‐Runtti Petra , Pitkäranta Anne , Aaltonen Leena‐Maija
Published: March 2011

Objectives/Hypothesis:

To determine clinical features, health‐related quality of life, and adult voice in patients with a history of juvenile‐onset recurrent respiratory papillomatosis (JORRP).

Study Design:

Case‐control study.

Methods:

All 32 patients with JORRP treated at Helsinki University Hospital between 1975 and 1994 were invited to an outpatient visit in spring 2008, and 18 of them (56%) entered the study. Each patient had an age‐ and gender‐matched control subject with similar smoking habits. Videolaryngostroboscopy was performed and voice quality determined by acoustic and perceptual analysis. Voice‐quality characteristics of the whole patient group and the recurrence‐free patients were examined separately. Subjective voice‐related disability was studied with voice handicap index (VHI) and health‐related quality of life with a 15D questionnaire.

Results:

Acoustic analysis showed that patients had statistically significantly higher values in percent jitter, percent shimmer, and noise‐to‐harmonics ratio. Perceptual analysis indicated higher scores for patients in overall grade, roughness, breathiness, and strain. Acoustic and perceptual values for recurrence‐free patients (n = 14) were also significantly higher than those for their matched paired controls. No statistically significant differences emerged for handicap related to voice or to health‐related quality of life. Four study patients (22%) had undergone tracheotomy, indicating severity of juvenile‐onset disease.

Conclusions:

JORRP is a risk factor for permanent laryngeal pathology and voice‐disturbances in adulthood. Laryngoscope, 2011
The Use of Poly(L‐lactide‐co‐caprolactone) as a Scaffold for Adipose Stem Cells in Bone Tissue Engineering: Application in a Spinal Fusion Model
Authors: Vergroesen Pieter‐Paul A. , Kroeze Robert‐Jan , Helder Marco N. , Smit Theodoor H.
Published: March 2011

Since the early 1990s, tissue engineering has been heralded as a strategy that may solve problems associated with bone grafting procedures. The original concept of growing bone in the laboratory, however, has proven illusive due to biological, logistic, and regulatory problems. Fat‐derived stem cells and synthetic polymers open new, more practicable routes for bone tissue engineering. In this paper, we highlight the potential of poly(L‐lactide‐co‐caprolactone) (PLCL) to serve as a radiolucent scaffold in bone tissue engineering. It appears that PLCL quickly and preferentially binds adipose stem cells (ASCs), which proliferate rapidly and eventually differentiate into the osteogenic phenotype. An in vivo spinal fusion study in a goat model provides a preclinical proof‐of‐concept for a one‐step surgical procedure with ASCs in bone tissue engineering.

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Construction of a Hyperbranched Supramolecular Polymer as a Bifunctional Antioxidative Enzyme Model
Authors: Yu Shuangjiang , Zhang Wei , Zhu Junyan , Yin Yanzhen , Jin Haiyan , Zhou Lipeng , Luo Quan , Xu Jiayun , Liu Junqiu
Published: March 2011

A HBSP has been designed as a novel bifunctional enzyme model with SOD and GPx activity by host/guest‐directed self‐assembly of MnTPyP‐M‐Ad and 6‐Te‐diCD. The structure of the host/guest complex was elucidated by 1H NMR spectra, and the HBSP was characterized by SEM, DLS and measurement of catalytic properties. In the bifunctional enzyme model, the Mn(III) porphyrins act as efficient SOD active sites and the tellurol moieties endow GPx activity. The SOD‐like activity (IC50) of this new supramolecular catalyst was found to be 1.05 × 10−7 M, which corresponds to 2.82% of the activity of the native SOD enzyme. Besides this, the hyperbranched supramolecular polymer also shows a higher GPx activity (ν0 = 21.7 × 10−6 M · min−1) than other supramolecular enzyme models.

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Sharp trace inequalities on fractional Sobolev spaces
Authors: Pak Hee Chul , Park Young Ja
Published: March 2011

The best constant and extremal functions for Sobolev trace inequalities on fractional Sobolev spaces are achieved by a simple argument. © 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim
Azide‐based Cross‐Linking of Polymers of Intrinsic Microporosity (PIMs) for Condensable Gas Separation
Authors: Du Naiying , Cin Mauro M. Dal‐ , Pinnau Ingo , Nicalek Andrzej , Robertson Gilles P. , Guiver Michael D.
Published: March 2011

Cross‐linked polymers of intrinsic microporosity (PIM)s for gas separation membranes, were prepared by a nitrene reaction from a representative PIM in the presence of two different diazide cross‐linkers. The reaction temperature was optimized using TGA. The homogenous membranes were cast from THF solutions of different ratios of PIM to azides. The resulting cross‐linked structures of the PIMs membranes were formed at 175 °C after 7.5 h and confirmed by TGA, XPS, FT‐IR spectroscopy and gel content analysis. These resulting cross‐linked polymeric membranes showed excellent gas separation performance and can be used for O2/N2 and CO2/N2 gas pairs, as well as for condensable gases, such as CO2/CH4, propylene/propane separation. Most importantly, and differently from typical gas separation membranes derived from glassy polymers, the crosslinked PIMs showed no obvious CO2 plasticization up to 20 atm pressure of pure CO2 and CO2/CH4 mixtures.

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Electrochemical Fluorescence Switching from a Patternable Poly(1,3,4‐oxadiazole) Thin Film
Authors: Seo Seogjae , Kim Yuna , You Jungmok , Sarwade Bhimrao D. , Wadgaonkar Prakash P. , Menon Shamal K. , More Arvind S. , Kim Eunkyoung
Published: March 2011

A highly soluble poly(1,3,4‐oxadiazole) (POD) substituted with long alkyl chains was examined for electrochemical fluorescence switching. The high solubility of the polymers enabled a simple fabrication of an electrochemical cell, which showed reversible fluorescence switching between dark (n‐doping) and bright (neutral) states with a maximum on/off ratio of 2.5 and a cyclability longer than 1 000 cycles. Photochemical cleavage of the oxadiazole in POD allowed photo‐patterning of the POD film upon exposure to UV source. The patterned POD films displayed patterned image reversibly under a step potential of +1.8/−1.8 V.

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Application of Alkyne‐TCNQ Addition Reaction to Polymerization
Authors: Washino Yusuke , Michinobu Tsuyoshi
Published: March 2011

The polymerization using a high‐yielding addition reaction between electron‐rich alkynes and 7,7,8,8‐tetracyanoquinodimethane (TCNQ) derivatives is described. The bifunctional monomer containing two TCNQ moieties and the counter comonomer bearing two dialkylaniline (DAA)‐substituted alkynes are reacted in 1,2‐dichloroethane under mild heating conditions. At the high monomer concentrations, high molecular weight linear polymers are obtained, while the reaction at the low monomer concentrations produces a significant amount of the cyclic compounds. A clear relationship between the monomer concentration and the cyclic compound amount is demonstrated. The obtained polymers feature a sufficient thermal stability with the decomposition temperature exceeding 300 °C as well as strong charge‐transfer (CT) bands and redox activities ascribed to the produced donor–acceptor moieties. These features are also used to optimize the polymerization conditions and to estimate the chemical structures.

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The Development of Proton Conducting Polymer Membranes for Fuel Cells Using Sulfonated Carbon Nanofibres
Authors: Barroso‐Bujans F. , Verdejo R. , Arroyo M. , Lopez‐Gonzalez M. M. , Riande E. , Lopez‐Manchado M. A.
Published: March 2011

The Development of Proton Conducting Polymer Membranes for Fuel Cells Using Sulfonated Carbon Nanofibres (Macromol. Rapid Commun. 2008, 29, 234–238) Macromol. Rapid Commun. 2011, 32, ((page))
Studies of cyclization reactions of linear cumulenes and heterocumulenes using the neutralization–reionization procedure and/or ab initio calculations
Authors: Wang Tianfang , Bowie John H.
Published: March 2011

A number of linear cumulenes and heterocumulenes have been made by charge stripping of anions of known bond connectivity in the source of a mass spectrometer. Some of these reactive molecules have been identified in interstellar molecular clouds. The structures of these neutrals may be investigated by reionization to a decomposing positive ion [the neutralization–reionization technique (−NR+)], and/or by ab initio calculations. Energized linear cumulenes and heterocumulenes may undergo cyclization to form stable cyclic isomers. To cite a selection of the examples described in this review: (i) four‐atom systems CCCC and some heterocumulenes CCCX (X = B, N, Al, Si, P) involve the formation of stable four‐membered ring rhombic (also called kite and fan) structures. One of the cyclic molecules, cyclo‐C3Si, has been detected in interstellar molecular clouds, (ii) five‐atom cumulene and heterocumulene systems are more complex. Linear CCCCC rearranges the carbon skeleton by forming a C substituted rhomboid system, CCCCO forms a three‐membered cyclic isomer, while nitrogen containing five‐atom cumulenes effect nitrile to isonitrile interconversion via three‐centered cyclized intermediates, and (iii) CCCCCC and CCCCBO cyclize to give unique six‐membered ring systems. © 2010 Wiley Periodicals, Inc., Mass Spec Rev 30:1225–1241, 2011
From reticulate doped to nanostructural polymeric systems
Authors: Kryszewski Marian
Published: March 2011

Preparation of very small or nanoscopic crystallites applying wet techniques and their properties are discussed. It is shown that controlled evaporation of the solvent from the solution containing low molecular weight CT complexes and polymers leads to formation of continuous networks of microcrystallites, which are responsible for the magnetic, optical and particularly electrical properties of the obtained systems (isotropic, surface or anisotropic conductivity). Using a variation of this method one can obtain very small crystals of CT complex salts or other substances showing nonlinear optical properties. Application of the so‐called “droplet technique” results in formation of the emulsion of the crystallizable compounds. The crystallization in small droplets leads to very small crystals which show, because of their nanoscopic size, different properties than bigger single crystals of these compounds.
Functional characterization of peroxisome proliferator‐activated receptor‐β/δ expression in colon cancer
Authors: Foreman Jennifer E. , Chang Wen‐Chi L. , Palkar Prajakta S. , Zhu Bokai , Borland Michael G. , Williams Jennie L. , Kramer Lance R. , Clapper Margie L. , Gonzalez Frank J. , Peters Jeffrey M.
Published: March 2011

This study critically examined the role of PPARβ/δ in colon cancer models. Expression of PPARβ/δ mRNA and protein was lower and expression of CYCLIN D1 protein higher in human colon adenocarcinomas compared to matched non‐transformed tissue. Similar results were observed in colon tumors from Apc+/Min‐FCCC mice compared to control tissue. Dietary administration of sulindac to Apc+/Min‐FCCC mice had no influence on expression of PPARβ/δ in normal colon tissue or colon tumors. Cleaved poly (ADP‐ribose) polymerase (PARP) was either increased or unchanged, while expression of 14‐3‐3ε was not influenced in human colon cancer cell lines cultured with the PPARβ/δ ligand GW0742 under conditions known to increase apoptosis. While DLD1 cells exhibited fewer early apoptotic cells after ligand activation of PPARβ/δ following treatment with hydrogen peroxide, this change was associated with an increase in late apoptotic/necrotic cells, but not an increase in viable cells. Stable over‐expression of PPARβ/δ in human colon cancer cell lines enhanced ligand activation of PPARβ/δ and inhibition of clonogenicity in HT29 cells. These studies are the most quantitative to date to demonstrate that expression of PPARβ/δ is lower in human and Apc+/Min‐FCCC mouse colon tumors than in corresponding normal tissue, consistent with the finding that increasing expression and activation of PPARβ/δ in human colon cancer cell lines inhibits clonogenicity. Because ligand‐induced attenuation of early apoptosis can be associated with more late, apoptotic/necrotic cells, but not more viable cells, these studies illustrate why more comprehensive analysis of PPARβ/δ‐dependent modulation of apoptosis is required in the future. © 2011 Wiley Periodicals, Inc.
Role of androgen receptor and associated lysine‐demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer
Authors: Kauffman Eric C. , Robinson Brian D. , Downes Martin J. , Powell Leagh G. , Lee Ming Ming , Scherr Douglas S. , Gudas Lorraine J. , Mongan Nigel P.
Published: March 2011

Bladder cancer is approximately three times more common in men as compared to women. We and others have previously investigated the contribution of androgens and the androgen receptor (AR) to bladder cancer. JMJD2A and LSD1 are recently discovered AR coregulator proteins that mediate AR‐dependent transcription via recently described histone lysine‐demethylation (KDM) mechanisms. We used immunohistochemistry to examine JMJD2A, LSD1, and AR expression in 72 radical cystectomy specimens, resulting in evaluation of 129 tissue samples (59 urothelial carcinoma, 70 benign). We tested levels of these proteins for statistical association with clinicopathologic variables and patient survival. Expression of these markers was also assessed in human bladder cancer cell lines. The effects of pharmacological inhibition of LSD1 on the proliferation of these bladder cancer cells was determined. JMJD2A and AR levels were significantly lower in malignant versus benign urothelium, while increased LSD1 levels were observed in malignant urothelium relative to benign. A significant reduction in all three proteins occurred with cancer stage progression, including muscle invasion (JMJD2A/LSD1/AR), extravesical extension (JMJD2A/LSD1), and lymph node metastasis (JMJD2A/AR). Lower JMJD2A intensity correlated with additional poor prognostic features, including lymphovascular invasion, concomitant carcinoma in situ and tobacco usage, and predicted significantly worse overall survival. Pharmacological inhibition of LSD1 suppressed bladder cancer cell proliferation and androgen‐induced transcription. Our results support a novel role for the AR–KDM complex in bladder cancer initiation and progression, identify JMJD2A as a promising prognostic biomarker, and demonstrate targeting of the KDM activity as an effective potential approach for bladder cancer growth inhibition. © 2011 Wiley Periodicals, Inc.
Effect of polymorphisms of IL‐1β and TNF‐α genes on CpG island hyper methylation (CIHM) in the nonneoplastic gastric mucosa
Authors: Tahara Tomomitsu , Shibata Tomoyuki , Nakamura Masakatsu , Yamashita Hiromi , Yoshioka Daisuke , Okubo Masaaki , Yonemura Joh , Kamiya Yoshio , Ishizuka Takamitsu , Hirata Ichiro , Arisawa Tomiyasu
Published: March 2011

CpG island hyper methylation (CIHM) is one of the major events in gastric carcinogenesis. To evaluate the influence of host genetic factors in CIHM related carcinogenesis, we investigated the association between common polymorphisms in IL‐1β and TNF‐α genes, with CIHM status in the nonneoplastic gastric mucosa. Polymorphisms in the IL‐1β gene (‐31T>C and ‐511C>T) and the TNF‐α gene (‐857C>T) were genotyped in 385 cancer‐free subjects. CIHM of four candidate genes: p16 (INK4a), p14 (ARF), E‐cadherin (CDH1), and death‐associated protein kinase (DAP‐kinase), were determined by methylation‐specific‐polymerase chain reaction (MSP). CIHM high was defined as two or more CpG islands methylated. CIHM of all four genes and CIHM high were significantly associated with Helicobacter pylori infection status. In over all, significant marginal association was found between IL‐1β‐511 TT genotype and reduced susceptibility to CIHM of DAP‐kinase (adjusted OR = 0.48, 95% CI = 0.29–0.78) and CIHM high (adjusted OR = 0.53, 95% CI = 0.32–0.86). This association was more enhanced in subjects 65 yr or younger age. We also found positive association between TNF‐α‐857T carrier and increased susceptibility to CIHM of CDH (adjusted OR = 1.78, 95% CI = 1.01–3.16), and CIHM high (adjusted OR = 1.86, 95% CI = 1.04–3.33) in the same generation. The mean number of CIHM was lower in subjects with IL‐1β‐511TT genotype, while the mean number was higher in subjects with TNF‐α‐857 T carrier especially in subjects 65 yr and younger patients. IL‐1β‐511 TT genotype is associated with reduced susceptibility to CIHM especially in younger generation. Furthermore, the TNF‐α‐857T carrier is associated with increased susceptibility of CIHM in the same generation. © 2011 Wiley Periodicals, Inc.
5′‐Nitro‐indirubinoxime inhibits epidermal growth factor‐ and phorbol ester‐induced AP‐1 activity and cell transformation through inhibition of phosphorylation of Pin1
Authors: Khanal Prem , Choi Hoo‐Kyun , Namgoong Gwang Mo , Ahn Sang‐Gun , Yoon Jung‐Hoon , Sohn Honglae , Choi Hong Seok
Published: March 2011

5′‐Nitro‐indirubinoxime (5′‐NIO), a derivative of indirubin, exhibits anti‐cancer activity in a variety of human cancer cells. However, the underlying molecular mechanisms and molecular target(s) of the chemopreventive activities of 5′‐NIO remain unknown. Here, we report that 5′‐NIO inhibited the epidermal growth factor (EGF) or 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced neoplastic cell transformation of JB6 Cl41 mouse skin epidermal cells without any cytotoxic effects. Western blot analysis revealed that 5'‐NIO inhibited activities of Raf‐1 (S338), MEK1/2, ERK1/2, JNK, and c‐Jun induced by EGF or TPA, respectively, whereas it did not affect autophosphorylation of epidermal growth factor receptor (EGFR) induced by EGF or TPA. In addition, 5′‐NIO exerted strong inhibitory effects on the EGF‐ or TPA‐induced c‐fos or c‐jun transcriptional activity, and thereby inhibited the associated activator protein‐1 (AP‐1) transactivation activity induced by EGF or TPA. Importantly, 5'‐NIO inhibited Pin1 phosphorylation at serine 16 induced by EGF or TPA, respectively, resulted in the inhibition of interaction between Pin1 and Raf‐1. Immunoprecipitation/immunoblot analysis revealed that 5'‐NIO bound with Pin1. Together, these findings suggest that 5'‐NIO might act as an anticarcinogene in EGF‐ or TPA‐induced carcinogenesis through the inhibition of interaction between Pin1 and Raf‐1. © 2011 Wiley Periodicals, Inc.
β‐Escin sodium inhibits inducible nitric oxide synthase expression via downregulation of the JAK/STAT pathway in A549 cells
Authors: Ji Deng Bo , Xu Bo , Liu Jing Tao , Ran Fu Xiang , Cui Jing Rong
Published: March 2011

β‐escin, a triterpene saponin, is one of the major active compounds extracted from horse chestnut (Aesculus hippocastanum) seed. Previous work has found that β‐escin sodium has antiinflammatory and antitumor effects. In the present study, we investigated its effect on cell proliferation and inducible nitric‐oxide synthase (iNOS) expression in human lung carcinoma A549 cells. β‐escin sodium (5–40 µg/mL) inhibited cytokine mixture (CM)‐induced nitric oxide (NO) production in A549 cells by reducing the expression of iNOS. β‐escin sodium suppressed phosphorylation and nuclear translocation of STAT1 (Tyr701) and STAT3 (Tyr705) induced by CM but did not affect the activation of c‐Jun and NF‐κB. β‐escin sodium inhibited the activation of protein tyrosine kinase JAK2. Pervanadate treatment reversed the β‐escin sodium‐induced downregulation of STAT3 and STAT1. β‐escin sodium treatment enhanced an activating phosphorylation of the phosphatase SHP2. Small interfering RNA‐mediated knockdown of SHP2 inhibited β‐escin sodium‐induced phospho‐STAT dephosphorylation. Moreover β‐escin sodium reduced the activation of p38 MAPK. Finally, β‐escin sodium inhibited the proliferation of A549 cells, did not change the cell membrane's permeability, nuclear morphology and size and the mitochondria's transmembrane potential of A549 cells. Taken together, these results demonstrate that β‐escin sodium could downregulate iNOS expression through inhibiting JAK/STAT signaling and p38 MAPK activation in A549 cells. β‐escin sodium has a marked antiproliferative effect on A549 cells at least in part by inhibiting the JAK/STAT signaling pathway, but not by a cytotoxic effect. β‐escin sodium would be useful as a chemopreventive agent or a therapeutic against inflammatory‐associated tumor. © 2011 Wiley Periodicals, Inc.
Resection and free tissue reconstruction of locally advanced oral cancer: Avoidance of lip split
Authors: Myers Larry L , Sumer Baran D , Truelson John M , Ahn Chul , Leach Joseph L
Published: March 2011

The purpose of this study is to report the outcomes of patients with locally advanced (T3–T4) oral cancers undergoing surgical resection and free tissue reconstruction without the lower lip‐split procedure. In this retrospective chart review, we analyzed 86 consecutive patients presenting between July 2000 and December 2009 at our university‐based, tertiary care medical center. The oral site distribution was: 73 (86%) oral cavity, 10 (12%) oropharynx, and 3 (2%) combined. The average specimen volume was 240.3 cm3 (range 17.5–3718 cm3). Sixty‐seven patients (78%) had widely clear histopathologic margins. Performing mandibulectomy had no advantage over maintaining mandible continuity to achieve clear margins (P = 0.97). Nineteen patients (22%) had focally involved microscopic margins; 10 (53%) soft tissue, seven (37%) bone, and two (10%) both. Thirty patients (35%) had postoperative complications, and 16 patients (19%) had a salivary fistula. The flaps used were: 39 fibula (45%), 25 radial forearm (29%), eight anterolateral thigh (9%), eight rectus abdominus (9%), three scapula (4%), and three iliac crest (4%). The average length of bone used was 9 cm (range 5–16 cm). The average soft tissue area was 99.7 cm2 (range 24–300 cm2). Nine patients (10%) had either partial or total flap loss. The lower lip‐split procedure for surgical exposure is unnecessary for both oncologic resection and reconstruction for locally advanced oral cancers. Clear margins, relatively facile flap inset with high success rates, and acceptable complication rates can be safely achieved in this patient population. © 2011 Wiley‐Liss, Inc. Microsurgery 2011.