bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of motility, invasion, and metastatic potential of squamous cell carcinoma by 1α,25‐dihydroxycholecalciferol
Authors: Ma Yingyu , Yu Wei‐Dong , Su Bing , Seshadri Mukund , Luo Wei , Trump Donald L. , Johnson Candace S.
Published: July 2012

BACKGROUND:

The active metabolite of vitamin D 1α,25‐dihydroxycholecalciferol (1,25D3) has exhibited broad‐spectrum antitumor activity in xenograft animal models. However, its activity against metastatic disease has not been extensively investigated.

METHODS:

Squamous cell carcinoma (SCC) or 1,25D3‐resistant variant SCC‐DR cells were treated with 1,25D3. Actin organization was examined by immunofluorescence assay. Cell migration was assessed by “wound” healing and chemotactic migration assays. Cell invasion was assessed by a Matrigel‐based invasion assay and in situ zymography. Matrix metalloproteinase 2 (MMP‐2) and MMP‐9 expression and secretion were examined by immunoblot analysis and an enzyme‐linked immunosorbent assay, respectively. E‐cadherin expression was assessed by flow cytometry, immunoblot analysis, and immunohistochemistry. Knockdown of E‐cadherin was achieved by small interfering RNA. An experimental metastasis mouse model was created by intravenous injection of tumor cells; and lung tumor development in the mice was assessed by magnetic resonance imaging, gross observation, and histology.

RESULTS:

SCC cellular morphology and actin organization were altered by 10 nM 1,25D3. 1,25D3 inhibited SCC cell motility and invasion, which were associated with reduced expression and secretion of MMP‐2 and MMP‐9, and 1,25D3 promoted the expression of E‐cadherin. These findings were not observed in SCC‐DR cells. Knock down of E‐cadherin rescued 1,25D3‐inhibited cell migration. Intravenous injection of SCC or SCC‐DR cells resulted in the establishment of extensive pulmonary lesions in saline‐treated C3H mice. Treatment with 1,25D3 resulted in a marked reduction in the formation of lung tumor colonies in mice that were injected with SCC cells, but not in mice that were injected with SCC‐DR cells.

CONCLUSIONS:

1,25D3 suppressed SCC cell motility, invasion, and metastasis, partially through the promotion of E‐cadherin‐mediated cell‐cell adhesion. Cancer 2013. © 2012 American Cancer Society.
Genome‐wide identification of Epstein‐Barr virus–driven promoter methylation profiles of human genes in gastric cancer cells
Authors: Zhao Junhong , Liang Qiaoyi , Cheung Kin‐Fai , Kang Wei , Lung Raymond W. M. , Tong Joanna H. M. , To Ka Fai , Sung Joseph J. Y. , Yu Jun
Published: July 2012

BACKGROUND:

Aberrant methylation of tumor‐related genes has been reported in Epstein‐Barr virus (EBV)‐associated gastric cancers. This study sought to profile EBV‐driven hypermethylation in EBV‐infected cells.

METHODS:

The EBV‐positive AGS gastric cancer cell line (AGS‐EBV) and EBV‐negative AGS cells were used in this study. DNA methyltransferase‐3b (DNMT3b) activity was assessed by EpiQuick activity assay, and genome‐wide DNA methylation profiles were assessed by methyl‐DNA immunoprecipitation microarray assay.

RESULTS:

EBV infection was confirmed in AGS‐EBV cells by EBV‐encoded RNA in situ hybridization. Expression and activity of DNA methyltransferase‐3b (DNMT3b) was significantly increased in AGS‐EBV compared to AGS. Ectopic expression of LMP2A (latent membrane protein 2A) in AGS increased activity of DNMT3b. A total of 1065 genes were differentially methylated by EBV infection (fold‐changes ≥ 2, P < .05) in AGS‐EBV compared to AGS cells. The majority of the differentially methylated genes (83.2%, 886 of 1065 genes) had cytosine‐guanine dinucleotide (CpG) hypermethylation in AGS‐EBV (fold‐changes 2.43∼65.2) versus that found in AGS cells. Gene ontology analysis revealed that hypermethylated genes were enriched in the important cancer pathways (≥ 10 genes each, P ≤ .05) including mitogen‐activated protein kinase signaling, cell adhesion molecules, wnt signaling pathway, and so forth. Six novel hypermethylated candidates (IL15RA, REC8, SSTR1, EPHB6, MDGA2, and SCARF2) were further validated. Higher levels of DNA methylation were confirmed for all these genes in AGS‐EBV cells by bisulfite genomic sequencing. Furthermore, these candidates were silenced or down‐regulated in AGS‐EBV cells, but can be restored by demethylation treatment.

CONCLUSIONS:

EBV infection in AGS cells induced aberrant CpG hypermethylation of 886 genes involving in important cancer‐related pathways. Induction of promoter methylation by EBV is regulated by up‐regulation of DNMT3b through LMP2A. Cancer 2013. © 2012 American Cancer Society.
Phase 2 trial of combined cisplatin, etoposide, gemcitabine, and methylprednisolone (PEGS) in peripheral T‐cell non‐Hodgkin lymphoma
Authors: Mahadevan Daruka , Unger Joseph M. , Spier Catherine M. , Persky Daniel O. , Young Fay , LeBlanc Michael , Fisher Richard I. , Miller Thomas P.
Published: July 2012

BACKGROUND:

Patients with peripheral T‐cell lymphomas (PTCLs) have inferior progression‐free survival (PFS) and overall survival (OS) compared with patients who have aggressive B‐cell non‐Hodgkin lymphoma. Because PTCLs over express multidrug resistance gene 1/P‐glycoprotein (MDR‐1/P‐gp), we devised platinum, etoposide, gemcitabine, and methylprednisolone (PEGS) with agents that are not substrates of the efflux pump. Gemcitabine was included because of its excellent single‐agent activity in PTCL.

METHODS:

Patients who had PTCL with stage II bulky disease, stage III or IV disease with extra‐nodal, nodal, and transformed cutaneous presentations were eligible. Patients received intravenous cisplatin 25 mg/m2 on days 1 through 4, etoposide 40 mg/m2 on days 1 through 4, gemcitabine 1000 mg/m2 on day 1, and methylprednisolone 250 mg on days 1 through 4 of a 21‐day cycle for 6 cycles.

RESULTS:

In total, 34 patients were enrolled, 33 were eligible, and 79% were newly diagnosed. Histologic types were PTCL not otherwise specified (n = 15), anaplastic lymphoma kinase (ALK)‐negative anaplastic large cell lymphoma (n = 4), angioimmunoblastic T‐cell lymphoma (n = 6), or other T‐cell non‐Hodgkin lymphomas (n = 8). Adverse events included 1 grade 5 infection with grade 3 or 4 neutropenia and 9 grade 4 hematologic toxicities. The overall response rate was 39% (47% in PTCL not otherwise specified, 33% in angioimmunoblastic T‐cell lymphoma, 25% in ALK‐negative and 38% in other T‐cell non‐Hodgkin lymphomas). The PFS rate at 2 years was 12% (95% confidence interval, 0.1%‐31%), and the median PFS was 7 months. The OS rate at 2 years was 30% (95% confidence interval, 8%‐54%), and the median OS was 17 months. Immunohistochemical analysis of P‐gp expression revealed strong positivity in a subset of lymphoma cells (n = 6) and tumor endothelium (n = 25).

CONCLUSIONS:

Overall, PEGS was well tolerated, but OS was not considered promising given the design‐specified targets. These results may serve as a benchmark for future comparisons for non‐CHOP regimens. Cancer 2013. © 2012 American Cancer Society.
Phase 2 trial of linifanib (ABT‐869) in patients with unresectable or metastatic hepatocellular carcinoma
Authors: Toh Han Chong , Chen Pei‐Jer , Carr Brian I. , Knox Jennifer J. , Gill Sharlene , Ansell Peter , McKeegan Evelyn M. , Dowell Barry , Pedersen Michelle , Qin Qin , Qian Jiang , Scappaticci Frank A. , Ricker Justin L. , Carlson Dawn M. , Yong Wei Peng
Published: July 2012

BACKGROUND:

The efficacy and safety of linifanib (ABT‐869), a selective inhibitor of vascular endothelial growth factor and platelet‐derived growth factor receptor tyrosine kinases, were assessed in this phase 2, single‐arm, open‐label, multicenter trial.

METHODS:

Eligible patients had unresectable or metastatic hepatocellular carcinoma and had received ≤ 1 prior systemic therapy. Patients received oral linifanib at a fasting dose of 0.25 mg/kg,. The primary endpoint was the progression‐free rate at 16 weeks. Tumor response was assessed every 8 weeks. Secondary endpoints included the time to disease progression, overall survival, and objective response rate. Safety was also assessed.

RESULTS:

Of the 44 patients enrolled, the majority were Asian (89%), had received no prior systemic therapy (82%), had Child‐Pugh class A hepatic function (86%), and had hepatitis B virus infection (61%). The estimated progression‐free rate at 16 weeks was 31.8% (34.2% for patients with Child‐Pugh class A hepatic function), the estimated objective response rate was 9.1% (10.5% for patients with Child‐Pugh class A hepatic function), the median time to disease progression was 3.7 months (3.7 months for patients with Child‐Pugh class A hepatic function), and the median overall survival was 9.7 months (10.4 months for patients with Child‐Pugh class A hepatic function). The most common linifanib‐related adverse events were diarrhea (55%) and fatigue (52%). The most common linifanib‐related grade 3/4 adverse events were hypertension (25%) and fatigue (14%). Serum levels of biomarkers cancer antigen (CA) 125, cytokeratin fragment (CYFRA)21.1, and protein induced by vitamin K absence or antagonist II (PIVKA) demonstrated potential as prognostic indicators of patient response or outcome.

CONCLUSIONS:

Single‐agent linifanib was found to be clinically active in patients with advanced hepatocellular carcinoma, with an acceptable safety profile. Cancer 2013. © 2012 American Cancer Society.
Cost analysis of a patient navigation system to increase screening colonoscopy adherence among urban minorities
Authors: Jandorf Lina , Stossel Lauren M. , Cooperman Julia L. , Graff Zivin Joshua , Ladabaum Uri , Hall Diana , Thélémaque Linda D. , Redd William , Itzkowitz Steven H.
Published: July 2012

BACKGROUND:

Patient navigation (PN) is being used increasingly to help patients complete screening colonoscopy (SC) to prevent colorectal cancer. At their large, urban academic medical center with an open‐access endoscopy system, the authors previously demonstrated that PN programs produced a colonoscopy completion rate of 78.5% in a cohort of 503 patients (predominantly African Americans and Latinos with public health insurance). Very little is known about the direct costs of implementing PN programs. The objective of the current study was to perform a detailed cost analysis of PN programs at the authors' institution from an institutional perspective.

METHODS:

In 2 randomized controlled trials, average‐risk patients who were referred for SC by primary care providers were recruited for PN between May 2008 and May 2010. Patients were randomized to 1 of 4 PN groups. The cost of PN and net income to the institution were determined in a cost analysis.

RESULTS:

Among 395 patients who completed colonoscopy, 53.4% underwent SC alone, 30.1% underwent colonoscopy with biopsy, and 16.5% underwent snare polypectomy. Accounting for the average contribution margins of each procedure type, the total revenue was $95,266.00. The total cost of PN was $14,027.30. Net income was $81,238.70. In a model sample of 1000 patients, net incomes for the institutional completion rate (approximately 80%), the historic PN program (approximately 65%), and the national average (approximately 50%) were compared. The current PN program generated additional net incomes of $35,035.50 and $44,956.00, respectively.

CONCLUSIONS:

PN among minority patients with mostly public health insurance generated additional income to the institution, mainly because of increased colonoscopy completion rates. Cancer 2013. © 2012 American Cancer Society.
Cytologic features of triple‐negative breast carcinoma
Authors: Bonzanini Mariella , Morelli Luca , Bonandini Elena Maria , Leonardi Elena , Pertile Riccardo , Dalla Palma Paolo
Published: July 2012

BACKGROUND:

Triple‐negative breast cancer (TNBC) is distinct from other breast cancers, because the tumor cells lack estrogen and progesterone receptors (hormone receptors) and also are negative for human epidermal growth factor receptor 2 (HER2). They comprise a heterogeneous group of tumors with various histologic features and clinical behaviors. High‐grade, invasive ductal carcinoma not otherwise specified is the most frequent type, and a substantial fraction of TNBCs belongs to the basal‐like tumor type. The purpose of this study was to determine whether some cytologic features could predict the triple phenotype of breast carcinoma.

METHODS:

Fine‐needle aspiration cytology samples of 62 TNBCs were compared with samples of 82 hormone receptor‐positive, high‐grade, invasive carcinomas (HRBC) and with samples of 33 hormone receptor‐negative, HER2 positive, invasive carcinomas (HER2BC) for the following cytomorphologic features: cellularity, necrosis, lymphocytes, syncytial clusters, tubular/ductal‐like clusters, large bare nuclei, streaming within the clusters, and calcifications. Moreover, single cell features, such as cellular borders, cytoplasm, cytoplasmic vacuoles, nuclear pleomorphism, nucleoli, and type of chromatin pattern, were evaluated. Descriptive analyses and 2 multivariate regression models were performed to compare TNBC, HRBC, and HER2BC and to identify the cytologic factors that were associated with tumor type.

RESULTS:

TNBCs were more likely to have an abundant necrotic background, many lymphocytes, many syncytial clusters, and ill defined cell borders than non‐TNBCs. A tubular/ductal pattern was observed only rarely in TNBCs. Multivariate logistic analysis indicated a 90.8% probability of identifying TNBC versus HRBC by the following cytologic variables: lymphocytes, ill defined cell borders and syncytial clusters, tubular/ductal clusters, cytoplasmic vacuoles, and cellular pleomorphism; whereas there was a 77.5% probability of identifying TNBC rather than HER2BC by the following variables: cellularity, ill defined cellular borders and syncytial clusters, and tubular/ductal clusters.

CONCLUSIONS:

Although TNBCs embrace a heterogeneous group of tumors, in this study, they exhibited some common cytologic features that can help to distinguish them from other high‐grade breast carcinomas in daily practice. Cancer (Cancer Cytopathol) 2012;. © 2012 American Cancer Society.
The majority of CD1d‐sulfatide‐specific T cells in human blood use a semiinvariant Vδ1 TCR
Authors: Bai Li , Picard Damien , Anderson Brian , Chaudhary Vinod , Luoma Adrienne , Jabri Bana , Adams Erin J. , Savage Paul B. , Bendelac Albert
Published: July 2012

αβ T‐cell lines specific for sulfatide, an abundant myelin glycosphingolipid presented by various CD1 molecules, have been previously derived from PBMCs of patients with demyelinating diseases such as multiple sclerosis (MS) but also from healthy subjects. Using an unbiased tetramer‐based MACS enrichment method to enrich for rare antigen‐specific cells, we confirmed the presence of CD1d‐sulfatide‐specific T cells in all healthy individuals examined. Surprisingly, the great majority of fresh sulfatide‐specific T cells belonged to the γδ lineage. Furthermore, these cells used the Vδ1 TCR variable segment, which is uncommon in the blood but predominates in tissues such as the gut and specifically accumulates in MS lesions. Recombinant Vδ1 TCRs from different individuals were shown to bind recombinant CD1d‐sulfatide complexes in a sulfatide‐specific manner. These results provide the first direct demonstration of MHC‐like‐restricted, antigen‐specific recognition by γδ TCRs. Together with previous reports, they support the notion that human Vδ1 T cells are enriched in CD1‐specific T cells and suggest that the Vδ1 T‐cell population that accumulates in MS lesions might be enriched in CD1‐sulfatide‐specific cells.
Special Electronic Structure and Extended Supramolecular Oligomerization of Anionic 1,4‐Dicorannulenylbenzene
Authors: Eisenberg David , Quimby Jennifer M. , Ho Derrick , Lavi Ronit , Benisvy Laurent , Scott Lawrence T. , Shenhar Roy
Published: July 2012

The chemistry of oligocorannulenes (compounds composed of two or more corannulenyl moieties) arises from the properties of each corannulenyl and from the interactions between them. Varying the linkage between the corannulenyl moieties can influence the interaction and give rise to new properties in these carbon‐rich compounds. This work describes the synthesis and reduction of 1,4‐dicorannulenylbenzene in which a rigid aromatic benzene spacer leads to new electronic and supramolecular behavior, as shown by NMR, EPR, and UV/Vis spectroscopy, as well as DFT calculations. Structural and energy analyses of the dianion revealed that the benzene ring modifies the electronic communication between the two bowls. To preserve the aromatic character of the benzene, conjugation between the bowls is minimized and the benzene assumes a biradical bonding pattern rather than a quinoidal one. At the octaanionic stage, self‐diffusion NMR experiments revealed extended supramolecular polymerization through charged polyarene stacking. The highly charged supramolecular oligomers are composed of up to 11 monomers per chain, significantly longer than the first (bicorannulenyl) oligomers of this type. This observation constitutes a proof‐of‐principle for controlling this novel type of polymer through modification of the intercorannulenyl spacer.
Ligated Regioselective PdII Catalysis to Access β‐Aryl‐Bearing Aldehydes, Ketones, and β‐Keto Esters
Authors: Vellakkaran Mari , Andappan Murugaiah M. S. , Kommu Nagaiah
Published: July 2012

By employing ligands in the PdII‐mediated arylative isomerization of allyl alcohols, a milder and regioselective access to the versatile building blocks β‐aryl aldehydes and ketones was developed. This new and chelation‐controlled protocol enabled the compatibility of wide range of functionalities to generate dihydrochalcones, α‐benzyl‐α′‐alkyl acetones, dihydrocinnamaldehydes, and α‐benzyl β‐keto esters (from Baylis–Hillman adducts). A practical multigram synthesis of an intermediate for Propafenone was also demonstrated.
Functional analysis of promoter variants in KU70 and their role in cancer susceptibility
Authors: Ouimet Manon , Cassart Pauline , Larivière Mathieu , Kritikou Ekaterini A. , Simard Jacques , Sinnett Daniel
Published: July 2012

KU70 is involved in the DNA double‐strand break repair pathway, which plays a critical role in maintaining genomic stability and preventing cancer. Genetic variation within the KU70 gene has been shown to be associated with increased risk of several types of cancers including breast cancer. Here, we used gene reporter and gel shift assays combined with site‐directed mutagenesis to characterize genetic variation within the KU70 proximal promoter region and investigate the putative functional role of regulatory variation and altered KU70 expression in modulating an individual's susceptibility to disease. We show that the variant rs2267437C>G significantly influences KU70 transcriptional activity in an allele‐ specific manner and alters DNA–protein complex formation in breast cancer cell lines. Our data provide a possible molecular explanation for the associations observed between the KU70 regulatory variant rs2267437 and breast cancer risk. © 2012 Wiley Periodicals, Inc.
PROX1 overexpression inhibits protein kinase C beta II transcription through promoter DNA methylation
Authors: Hagiwara Kazumi , Ito Hiromi , Murate Takashi , Miyata Yasuhiko , Ohashi Haruhiko , Nagai Hirokazu
Published: July 2012

Prospero‐related homeobox 1 (PROX1) is important for embryonic organ formation and differentiation, and changes in PROX1 activity were recently associated with cancer. To address the PROX1 roles in tumorigenesis, we established cells stably overexpressing PROX1 using the human cervical cancer cell line, HeLa. Overexpression of PROX1 reduced cell proliferation and the rate of tumor formation as compared with controls. Comparison of gene expression profiles between PROX1‐overexpressing and mock‐transfected cells revealed that the expression of protein kinase C βII (PRKCB2) is down‐regulated in PROX1‐overexpressing cells. A PRKCB inhibitor suppressed cell growth of control cells more than PROX1‐expressing cells. Analysis of the 5′‐promoter of PRKCB revealed that a region between −110 bp and the first exon contains two Sp1 binding sites and is important for transcriptional regulation of PRKCB. The inhibition of Sp1 transcription factor resulted in down‐regulation of PRKCB2 protein levels. Treatment with a demethylating agent, 5‐aza‐2′‐deoxycytidine, restored PRKCB2 mRNA expression in PROX1‐expressing cells, suggesting that the 5′‐promoter of PRKCB is methylated in these cells. Actually, it was found that a CpG island in this region, in particular a CpG site overlapping with the distal Sp1 site, was hypermethylated and direct Sp1 binding to this region was inhibited in PROX1‐overexpressing cells. Thus, the suppressive effect of PROX1 on cell growth and tumor formation might be partially mediated by PRKCB2 via altered methylation of its promoter. © 2012 Wiley Periodicals, Inc.
Effect of bedrock flow on catchment rainfall‐runoff characteristics and the water balance in forested catchments in Tanzawa Mountains, Japan
Authors: Oda Tomoki , Suzuki Masakazu , Egusa Tomohiro , Uchiyama Yoshimi
Published: July 2012

In this paper, we examined the role of bedrock groundwater discharge and recharge on the water balance and runoff characteristics in forested headwater catchments. Using rigorous observations of catchment precipitation, discharge and streamwater chemistry, we quantified net bedrock flow rates and contributions to streamwater runoff and the water balance in three forested catchments (second‐order to third‐order catchments) underlain by uniform bedrock in Japan. We found that annual rainfall in 2010 was 3130 mm. In the same period, annual discharge in the three catchments varied from 1800 to 3900 mm/year. Annual net bedrock flow rates estimated by the chloride mass balance method at each catchment ranged from −1600 to 700 mm/year. The net bedrock flow rates were substantially different in the second‐order and third‐order catchments. During baseflow, discharge from the three catchments was significantly different; conversely, peak flows during large storm events and direct runoff ratios were not significantly different. These results suggest that differences in baseflow discharge rates, which are affected by bedrock flow and intercatchment groundwater transfer, result in the differences in water balance among the catchments. This study also suggests that in these second‐order to third‐order catchments, the drainage area during baseflow varies because of differences between the bedrock drainage area and surface drainage area, but that the effective drainage area during storm flow approaches the surface drainage area. Copyright © 2012 John Wiley & Sons, Ltd.
CHASING WATER: DIVERGING FARMERS' STRATEGIES TO COPE WITH THE GROUNDWATER CRISIS IN THE COASTAL CHAOUIA REGION IN MOROCCO
Authors: Berahmani Adnane , Faysse Nicolas , Errahj Mostafa , Gafsi Mohamed
Published: July 2012

In many developing countries where agricultural groundwater use led to aquifer overexploitation, direct control over farmers' groundwater use is difficult to implement. This calls for the setting up, at least in the short term, of indirect policies, the efficiency of which will depend on farmers' strategies. The different strategies adopted by farmers to cope with the groundwater crisis are analysed in the Chaouia region in Morocco, where intensive agricultural groundwater use for the past 50 years has led to seawater intrusion in the seashore part and falling groundwater levels further inland. First, strategies may be based on ‘chasing’ groundwater, by deepening boreholes, bringing fresh water in sufficient quantity to the farms or renting fields in areas with sufficient fresh groundwater, so as to maintain a water‐intensive farming system. Second, strategies that may be designated as adaptive, entail adapting the farming system to the water available on‐farm given existing hydraulic infrastructures. These strategies may be considered as more sustainable with regard to water resources. Most of analysed strategies were not at the same time economically and environmentally sustainable. Possible policies to achieve economically and environmentally sustainable activities differ not only in the difficulty of implementing them, but also in the types of farms likely to benefit from them. Copyright © 2012 John Wiley & Sons, Ltd.
Concurrent improvement in biocompatibility and bioinertness of diamond‐like carbon films with nitrogen doping
Authors: Liao Wen‐Hsiang , Lin Chii‐Ruey , Wei Da‐Hua , Shen You‐Ruey , Li Yi‐Chieh , Lee Jen‐Ai , Liang Chia‐Yao
Published: July 2012

The surfaces of implantable biomaterials improving biocompatibility and bioinertness are critical for new application of bioimplantable devices. Diamond‐like carbon (DLC) film is a promising biomaterial with use for coating bioimplantable devices because of its good biocompatibility, bioinertness, and mechanical properties. In this study, concurrent improvement in biocompatibility and bioinertness of DLC films has been achieved using N‐incorporation technique. The N doping degree was found to play an important role in affecting the biocompatibility and bioinertness of N‐doped DLC films. The results indicated that the N‐doped DLC films deposited at N2 concentration of 5% could help to create suitable condition of surface/structure/adhesion combination of DLC films in the both affinity of the L929 mouse fibroblasts and electrochemical inertness in the Hank's balanced salt solutions (simulating human body fluids). N doping supports the attachment and proliferation of cells and prevents the permeation of electrolyte solutions, thereby simultaneity improved the biocompatibility and bioinertness of DLC films. This finding is useful for the fabrication and encapsulation of in vivo devices without induced immune response in the human body. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A:3151–3156, 2012.
Development of a chemically extracted acellular muscle scaffold seeded with amniotic epithelial cells to promote spinal cord repair
Authors: Xue Hui , Zhang Xiu‐Ying , Liu Jia‐Mei , Song Yu , Li Yi‐Fan , Chen Dong
Published: July 2012

Bridging strategies are essential for spinal cord repair in order to provide a physical substrate allowing axons to grow across the site of spinal cord lesions. In this study, we have evaluated the therapeutic effects of adding amniotic epithelial cells to a unidirectionally oriented acellular muscle scaffold and have compared this with the effect of a scaffold alone. Chemically extracted acellular muscles, with or without amniotic epithelial cells, were implanted into the lateral hemisected adult rat thoracic spinal cord. Control rats were similarly injured. After 4 weeks, the acellular muscle scaffolds were found to be well integrated with the host tissue. The chemically extracted acellular muscle scaffold seeded with amniotic epithelial cells promoted axonal growth in a distinctly organized and linear fashion, induced sprouting of calcitonin gene‐related peptide positive axons, and was not associated with an astrocyte response. Compared with acellular muscle scaffolds alone, the addition of amniotic epithelial cells further promoted the remyelination of nerve fibers, sprouting of 5‐hydroxytryptamine nerve fibers, relays of cortical motor‐evoked potential and cortical somatosensory‐evoked potential, and functional recovery. All these data together suggest that co‐implantation of chemically extracted acellular muscle with amniotic epithelial cells may constitute a valuable approach to study and/or develop therapies for spinal cord injury. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A:145–156, 2013.
Biodegradable balloon‐expandable self‐locking polycaprolactone stents as buckling explants for the treatment of retinal detachment: An in vitro and in vivo study
Authors: Peng Yi‐Jie , Lu Yu‐Ting , Liu Kuo‐Sheng , Liu Shih‐Jung , Fan Ling , Huang Wen‐Cheng
Published: July 2012

The purpose of this report was to develop biodegradable balloon‐expandable self‐locking poly(ε‐caprolactone) (PCL) stents for the treatment of retinal detachment. To create the biodegradable stents, polycaprolactone components were first fabricated by a laboratory‐scale microinjection molding machine. The components were then assembled into mesh‐like stents of 6 and 8 mm in diameter. A special geometry of the components was designed to self‐lock the assembled stents after being expanded by balloons. Characterization of the biodegradable PCL stents was carried out. PCL stents exhibited comparable mechanical properties with that of silicone sponge. Neither significant amount of collapse pressure reduction nor weight loss of the stents was observed after being submerged in phosphate buffered saline for 30 days. In addition, the stents were also implanted in the episcleral space of 10 New Zealand white rabbits. The stents were placed in radial direction and left unsutured after balloon expansion. The stents achieved an efficient buckling effect in echographic and fundus photographic examinations. The ocular pressure was significantly elevated after stent implantation and gradually normalized after the second week. The computed tomography studies verified the hypothesis of minimal migration of the PCL stents. The in vivo result suggests that balloon‐expandable biodegradable stents can potentially serve as an ideal indenting biomaterial in retinal detachment surgery. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A:167–175, 2013.
High mineral affinity of polyphosphoester ionomer–phospholipid vesicles
Authors: Ikeuchi Ryota , Iwasaki Yasuhiko
Published: July 2012

Bone‐specific drug delivery is important for the treatment of osteoporosis and osseous metastases. However, there have been limitations in the design of drug carriers having bone affinity. We synthesized amphiphilic polyphosphoester ionomers (CH‐PHE) and modified them to 1,2‐dioleoyl‐sn‐glycero‐3‐phosphocholine (DOPC) vesicles. The ζ‐potential of the vesicles was decreased by immobilization of CH‐PHE; the amount was influenced by the structure and fraction of CH‐PHE. The release rate of 5‐carboxyfluorescein from the vesicles could be controlled by changing the fraction of DOPC and CH‐PHE. In particular, the release of CF from DOPC vesicles containing 3% CH‐PHE was most reduced. In addition, the enzymatic degradation of DOPC was reduced by immobilization with polyphosphoester ionomers; enzyme tolerance was increased with an increase in the molar fraction of polyphosphoester ionomers. Hemolytic activity of the phospholipid vesicles bearing CH‐PHE was infrequently observed and was similar to that of the DOPC vesicles. Although a decrease in the viability of mouse osteoblastic cells (MC3T3‐E1) in contact with the vesicles bearing CH‐PHE was observed when the DOPC concentration of the vesicles bearing 20 mol % CH‐PHE with highly ionized units was greater than 200 μM, the cytotoxicity was diminished by sodium salt formation of the CH‐PHE. The affinity of the vesicles to calcium deposits generated by MC3T3‐E1 cells was significantly improved by the immobilization polyphosphoesters. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Novel frameshift mutation in the p16/INK4A tumor suppressor gene in canine breast cancer alters expression from the p16/INK4A/p14ARF locus
Authors: Lutful Kabir Farruk M. , Agarwal Payal , DeInnocentes Patricia , Zaman Jishan , Bird Allison Church , Bird R. Curtis
Published: July 2012

The INK4 family of cyclin‐dependent kinase inhibitors (CKI) encode important cell cycle regulators that tightly control cell cycle during G1 to S phase. These related genes are considered tumor suppressors as loss of function contributes to the malignant phenotype. Expression of CKIs p16, p14ARF, or p15 were defective in six different canine mammary tumor (CMT) cell lines compared to normal thoracic canine fibroblasts. This suggests CKI defects are frequently responsible for neoplastic transformation in canine mammary carcinomas. p16 and p14ARF are two alternatively spliced products derived from the canine p16/INK4A/p14ARF gene locus. Despite omissions in the published p16 transcript and canine genome and the presence of GC‐rich repeats, we determined the complete coding sequence of canine p16 revealing a deletion and frameshift mutation in p16 exon 1α in CMT28 cells. In addition, we determined canine p14ARF mRNA and protein sequences. Mapping of these mutations uncovered important aspects of p16 and p14ARF expression and defects in CMT28 cells shifting the p16 reading frame into p14ARF making a fusion protein that was predicted to be truncated, unstable and devoid of structural and functional integrity. This data describes an important neoplastic mechanism in the p16/INK4A/p14ARF locus in a spontaneous canine model of breast cancer. J. Cell. Biochem. 114: 56–66, 2012. © 2012 Wiley Periodicals, Inc.
Thrombin induces slug‐mediated E‐cadherin transcriptional repression and the parallel Up‐regulation of N‐cadherin by a transcription‐independent mechanism in RPE cells
Authors: Palma‐Nicolás José Prisco , López‐Colomé Ana María
Published: July 2012

The proliferation, directional migration to the vitreous and epithelial–mesenchymal transition (EMT) of quiescent, differentiated retinal pigment epithelium (RPE) cells is a major feature in the development of proliferative vitreoretinopathy (PVR) following exposure of the immuno‐privileged eye niche to serum components, thrombin among them. We have previously documented thrombin induction of RPE cell proliferation and migration. We here analyzed the effect of thrombin on the E/N cadherin switch, a hallmark of EMT. Results show that thrombin induces the specific repression of epithelial E‐cadherin gene transcription, alongside with the up‐regulation of mesenchymal N‐cadherin protein in RPE cells. We demonstrate, for the first time, that thrombin induces E‐cadherin repression by stimulating snail‐2 (SLUG) transcription factor expression, and the concomitant up‐regulation of N‐cadherin through the transcription‐independent increase in protein translation promoted by PI3K/PKC‐ζ/mTOR signaling. Our present findings suggest that the activation of protease‐activated receptor‐1 (PAR‐1) by thrombin induces EMT of RPE cells, further supporting a central role for thrombin in PVR pathogenesis. J. Cell. Physiol. 228: 581–589, 2013. © 2012 Wiley Periodicals, Inc.
Non‐Critical Vertices and Long Circuits in Strong Tournaments of Order n and Diameter d
Authors: Savchenko S. V.
Published: July 2012

Let T be a strong tournament of order with diameter . A vertex w in T is non‐critical if the subtournament is also strong. In the opposite case, it is a critical vertex. In the present article, we show that T has at most critical vertices. This fact and Moon's vertex‐pancyclic theorem imply that for , it contains at least circuits of length . We describe the class of all strong tournaments of order with diameter for which this lower bound is achieved and show that for , the minimum number of circuits of length in a tournament of this class is equal to . In turn, the minimum among all strong tournaments of order with diameter 2 grows exponentially with respect to n for any given . Finally, for , we select a strong tournament of order n with diameter d and conjecture that for any strong tournament T of order n whose diameter does not exceed d, the number of circuits of length ℓ in T is not less than that in for each possible ℓ. Moreover, if these two numbers are equal to each other for some given , where , then T is isomorphic to either or its converse . For , this conjecture was proved by Las Vergnas. In the present article, we confirm it for the case . In an Appendix, some problems concerning non‐critical vertices are considered for generalizations of tournaments.
What does “Getting to ZeroTM Through the Power of One” mean to you?
Authors: Hilliard Mary Anne
Published: July 2012

Hopefully by now you've heard the mantra and are now aware of ASHRM's initiative of “Getting to ZeroTM Through the Power of One.” But what does that mean to you? And how can you forward the message on to your colleagues and coworkers? It's as simple as looking at it this way: “Everyone is a risk manager.”
Stop the escalation before it begins by using the pediatric Behavior Response Team protocol
Authors: Adkins‐Bley Karen , Shaw Barbara K. , Smith Josh , McMyler Eileen
Published: July 2012

In today's world, clinicians need to be prepared to care for challenging patients and families that are struggling with the stress of illness and hospitalization and have inadequate coping skills. The University of Michigan Health System (UMHS) has developed a protocol identifying a team with representatives from psychiatry, security, and risk management to provide a rapid response in situations that historically have resulted in, at worst, sentinel/adverse events and at best, service disasters.

The pediatric BRT protocol formalizes the purpose of the team, how staff should access them, and the expectation for involved staff to debrief about the interventions at identified times. It has proven to be an effective intervention and allows clinicians to provide needed care to the patients.
Disclosure and documentation of reported unanticipated medical events or outcomes: Need for healthcare provider education
Authors: Singh Vinita , Cunningham Christopher J. L. , Panda Mukta , Hetzler Dale C. , Stanley Daniel
Published: July 2012

In 2001 the Joint Commission on Accreditation of Healthcare Organizations added “requirement to disclose unanticipated outcomes” to accreditation standards. Full disclosure increases patient satisfaction and trust in physicians. Though studies suggest elements of complete disclosure, there are no national standards.
The A to Z of healthcare data breaches
Authors: Kobus III Theodore J.
Published: July 2012

There currently exists a myriad of privacy laws that impact a healthcare entity, including more than 47 notification laws that require notification when a data breach occurs, as well as the breach notification requirements of the Health Information Technology for Economic and Clinical Health Act. Given the plethora of issues a healthcare entity faces, there are certain principles that can be built into an organization's philosophy that will comply with the law and help protect it from reputational harm.
Patterns of covariation in the masticatory apparatus of hystricognathous rodents: Implications for evolution and diversification
Authors: Hautier Lionel , Lebrun Renaud , Cox Philip G.
Published: July 2012

The mammalian masticatory apparatus is a highly plastic region of the skull. In this study, a quantification of shape variation, the separation of phylogeny from ecology in the genesis of shape brings new insights on the relationships between morphological changes in the cranium, mandible, and muscle architecture. Our study focuses on the Ctenohystrica, a clade that is remarkably diverse and exemplifies a rich evolutionary history in the Old and New World. Current and past rodent diversity brings out the limitations of the qualitative descriptive approach and highlights the need for using integrative quantitative methods. We present here the first descriptive comparison of the whole masticatory apparatus within the Ctenohystrica, by combining geometric morphometric approaches with a noninvasive method of dissection in 3D, iodine‐enhanced microcomputed tomography. We used these methods to explore the patterns of covariation between the cranium and the mandible, and the interspecific morphological variation of the skull with regard to several factors such as phylogeny, activity period, type of habitat, and diet. Our study revealed strong phylogenetic and ecological imprints on the morphological traits associated with masticatory mechanics. We showed that, despite a high diversification of lineages, the evolutionary history of Ctenohystrica comprises only a small number of morphotypes for the skull and mandible. The position of the eye was suggested as a key factor determining morphological evolution of the masticatory apparatus by limiting the number of possible pathways and promoting convergent evolution toward new habitats and diets between different clades. J. Morphol. 2012. © 2012 Wiley Periodicals, Inc.
Conformational energies of silacyclohexanes C5H10SiHMe, C5H10SiH(CF3) and C5H10SiCl(SiCl3) from variable temperature Raman spectra
Authors: Kern Thomas , Hölbling Margit , Dzambaski Ana , Flock Michaela , Hassler Karl , Wallevik Sunna Ó. , Arnason Ingvar , Bjornsson Ragnar
Published: July 2012

From variable temperature vibrational Raman spectra, the axial/equatorial enthalpy differences for the substituted silacyclohexanes C5H10SiHMe, C5H10SiH(CF3) and C5H10SiCl(SiCl3) were determined. The pure liquids and solutions in various solvents were investigated. Preferred conformations are equatorial for methylsilacyclohexane and axial for trifluoromethylsilacyclohexane, consistent with earlier results from nuclear magnetic resonance experiments and ab initio calculations. For C5H10SiCl(SiCl3) an enthalpy difference close to zero was found, which is supported by high‐level which is supported by high‐level quantum chemical calculations at the second‐order Møller‐Plesset (MP2) and coupled cluster with single, double, and perturbative triple excitations (CCSD(T)) levels, which employed various basis sets. A novel synthesis for C5H10SiCl(SiCl3) was developed using ClMg(CH2)5MgCl instead of BrMg(CH2)5MgBr as a starting material. The procedure avoids the formation of partially brominated products, facilitating the purification of the compound. 1H, 13C and 29Si nuclear magnetic resonance data are reported. Copyright © 2012 John Wiley & Sons, Ltd.
Self‐assembly and structure formation in liquid crystalline phthalocyanine thin films studied by Raman spectroscopy and AFM
Authors: Latteyer Florian , Savu Sabine , Peisert Heiko , Chassé Thomas
Published: July 2012

This work presents an investigation of films prepared by doctor blade casting, the formation of self‐assembled microstructures of a liquid crystalline phthalocyanine with highly oriented molecules. Raman Spectroscopy in combination with atomic force microscopy is applied to study the structures within the films. By keeping the substrate at room temperature or at 353 K during coating, different geometric structures namely rods and islands form. Rod‐like structures are growing in coating direction, whereas directional growth of the islands is not observed. The distribution of the rod lengths varies widely, whereas the width appears more uniform. Annealing of the samples shows a different behavior of the two textures. Islands tend to melt, and rods smooth their structural form, which is extracted from Raman imaging in combination with atomic force microscopy. Additionally, Raman imaging gives insight into laterally different relative crystallinity. These observations are discussed in the context of the molecular orientation as probed by polarized Raman spectroscopy. These polarized Raman spectra indicate azimuthal alignment of the molecules within the rods (edge on alignment). This alignment occurs along and also perpendicular to the growth direction. In contrast to the alignment in the rods, the molecules inside the islands occurring at higher temperature do not show preferential molecular orientation. After annealing, no preferential molecular orientation is observed in rods because of the loss of anisotropy, too. Copyright © 2012 John Wiley & Sons, Ltd.
Incidence of occult cervical metastasis in head and neck carcinomas: Development over time
Authors: Psychogios Georgios , Mantsopoulos Konstantinos , Bohr Christopher , Koch Michael , Zenk Johannes , Iro Heinrich
Published: July 2012

Background

With the development of imaging techniques in diagnostics of head and neck carcinomas, especially computed tomography and ultrasonogaphy, one might expect that the incidence of occult metastases would be reduced. The aim of this study was to determine the rate of occult metastases in a large population cohort and explore its changes with improvement of imaging techniques over the last 30 years.

Methods

All patients between 1980 and 2010 with head and neck carcinoma and cN0 neck status were retrospectively evaluated. Six hundred thirty‐six patients with cN0 neck who received an elective neck dissection as part of a definitive surgical treatment were included.

Results

The overall rate of occult metastases was 24.8% (158/636). The rate was 26.5% (80/302) between 1980 and 1995 and 23.4% (78/334) between 1995 and 2010. Only pT1–2 glottic carcinomas had an occult metastases rate of less than 10%. All other pT1–2 carcinomas had an incidence of occult metastases between 19.1% and 42.5%. pT3–4 tumors showed an occult metastases rate of 24.5–53.3%.

Conclusion

The occult metastases rate showed only a marginal improvement over the last 30 years and is still above the 20% margin. All but pT1–2 glottic carcinomas should be considered for elective treatment of the neck. J. Surg. Oncol. 2013;107:384–387. © 2012 Wiley Periodicals, Inc.
Sorafenib reduces hepatic infiltrated regulatory T cells in hepatocellular carcinoma patients by suppressing TGF‐beta signal
Authors: Wang Quanrongzi , Yu Tongfu , Yuan Yifeng , Zhuang Haiwen , Wang Zhaojing , Liu Xisheng , Feng Min
Published: July 2012

Background and Objectives

Sorafenib has been shown to improve survival rate of hepatocellular carcinoma (HCC) patients significantly. Decline of tumor infiltrated regulatory T cells (TITs) may account for the activity of sorafenib partially. In this study, the underlying mechanism of sorafenib reducing TITs was investigated.

Methods

Tumor infiltrated mononuclear cells (TIMs), which were isolated form 19 HCC patients with or without sorafenib therapy, were analyzed by flow cytometry. TGF‐β signal pathways were analyzed by immunoblotting. In vitro test, naïve T cells were induced to regulatory T cells (Tregs) with or without sorafenib. After 3 days of culture, percentage of Tregs from CD4+ cells and TGF‐β signal pathways were analyzed. Meanwhile, TIMs from HCC patients without sorafenib treatment were cultured in the presence of sorafenib, and then the percentage of Foxp3 expressing cells from TIMs was analyzed.

Results

TITs were increased in HCC patients compared with controls. However, after sorafenib therapy, TITs were decreased significantly and TGF‐β signal pathways were down‐regulated. Additionally, in the presence of sorafenib, induction of Tregs was inhibited and TGF‐β signal pathways in resulting cells were down‐regulated. However, sorafenib treatment did not affect the percentage of Foxp3 expressing cells from TIMs in vitro.

Conclusions

Sorafenib reducing TITs in HCC patients are associated with down‐regulation of TGF‐β signal. This finding may help us for better understanding the activity of sorafenib in HCC patients. J. Surg. Oncol. 2013;107:422–427. © 2012 Wiley Periodicals, Inc.
Peritraumatic and persistent dissociation as predictors of PTSD symptoms in a female cohort
Authors: Werner Kimberly B. , Griffin Michael G.
Published: July 2012

Recent research has investigated peritraumatic and persistent dissociation as a possible predictive factor for posttraumatic stress disorder (PTSD). The current study aimed to add to this literature by examining dissociative responses in female assault survivors (N = 92 at initial assessment; n = 62 at follow‐up). Dissociative symptoms experienced at 3 time points were assessed: peritraumatic dissociation (PD), persistent dissociation–initial (M = 28.2 days posttrauma) and follow‐up (M = 224.9 days posttrauma), as well as initial and follow‐up PTSD symptoms. We hypothesized that PD and persistent dissociative symptoms would predict chronic PTSD symptoms at the follow‐up assessment with initial PTSD symptoms and assault type in the model. Hierarchical regression resulted in a significant model predicting 39% of the variance in follow‐up PTSD symptom scores (p < .001). Both peritraumatic and follow‐up persistent dissociative symptoms significantly and uniquely added to the variance explained in follow‐up PTSD symptom score contributing 4% (p = .05) and 8% (p = .008) of the variance, respectively. Results support the predictive value of peritraumatic and persistent dissociative symptoms, and the findings suggest that persistent dissociation may contribute to the development and continuation of PTSD symptoms. We discuss the implications for assessment and possible treatment of PTSD as well as future directions.