bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the genomic structure and function of regions influencing renin and angiogenesis in the SS rat
Authors: Stodola Timothy J. , de Resende Micheline M. , Sarkis Allison B. , Didier Daniela N. , Jacob Howard J. , Huebner Norbert , Hummel Oliver , Saar Kathrin , Moreno Carol , Greene Andrew S.
Published: April 2011

Impaired regulation of renin in Dahl salt-sensitive rats (SS/JRHsdMcwi, SS) contributes to attenuated angiogenesis in this strain. This study examined angiogenic function and genomic structure of regions surrounding the renin gene using subcongenic strains of the SS and BN/NHsdMcwi (BN) rat to identify important genomic variations between SS and BN involved in angiogenesis. Three candidate regions on Chr 13 were studied: two congenic strains containing 0.89 and 2.62 Mb portions of BN Chr 13 that excluded the BN renin allele and a third strain that contained a 2.02 Mb overlapping region that included the BN renin allele. Angiogenesis induced by electrical stimulation of the tibialis anterior muscle was attenuated in the SS compared with the BN. Congenics carrying the SS renin allele had impaired angiogenesis, while strains carrying the BN renin allele had angiogenesis restored. The exception was a congenic including a region of BN genome 0.4 Mb distal to renin that restored both renin regulation and angiogenesis. This suggests that there is a distant regulatory element in the BN capable of restoring normal regulation of the SS renin allele. The importance of ANG II in the restored angiogenic response was demonstrated by blocking with losartan. Sequencing of the 4.05 Mb candidate region in SS and BN revealed a total of 8,850 SNPs and other sequence variants. An analysis of the genes and their variants in the region suggested a number of pathways that may explain the impaired regulation of renin and angiogenesis in the SS rat.
A New Technique for Surgical Treatment of Vaginal Agenesis Using Combined Abdominal-Perineal Approach
Authors: Beksac Mehmet Sinan , Salman Mehmet Coskun , Dogan Nasuh Utku
Published: April 2011

Optimum therapeutic approach in vaginal agenesis has always been an area of extensive controversies. Although surgical management gained priority due to the evolution of techniques, there is currently no consensus in the literature regarding the best type of surgical approach. The most commonly preferred surgical procedure among gynecologists is McIndoe operation which involves the creation of a space between bladder and rectum, insertion of a mold covered with split-thickness skin graft into that neovaginal space, and use of postoperative vaginal dilation to avoid stenosis. However, many modifications have been introduced in time in an attempt to increase the success rates. In this paper, we describe two cases with vaginal agenesis with functioning uterus who were subjected to surgery by combined abdominal-perineal approach. The surgical technique also included the use of a specially designed vaginal mold made up of polymethyl methacrylate and use of Hyalobarrier gel which is an adhesion-preventing agent.
Drug Nanoparticle Formulation Using Ascorbic Acid Derivatives
Authors: Moribe Kunikazu , Limwikrant Waree , Higashi Kenjirou , Yamamoto Keiji
Published: April 2011

Drug nanoparticle formulation using ascorbic acid derivatives and its therapeutic uses have recently been introduced. Hydrophilic ascorbic acid derivatives such as ascorbyl glycoside have been used not only as antioxidants but also as food and pharmaceutical excipients. In addition to drug solubilization, drug nanoparticle formation was observed using ascorbyl glycoside. Hydrophobic ascorbic acid derivatives such as ascorbyl mono- and di-n-alkyl fatty acid derivatives are used either as drugs or carrier components. Ascorbyl n-alkyl fatty acid derivatives have been formulated as antioxidants or anticancer drugs for nanoparticle formulations such as micelles, microemulsions, and liposomes. ASC-P vesicles called aspasomes are submicron-sized particles that can encapsulate hydrophilic drugs. Several transdermal and injectable formulations of ascorbyl n-alkyl fatty acid derivatives were used, including ascorbyl palmitate.
Experimental and Numerical Simulations Predictions Comparison of Power and Efficiency in Hydraulic Turbine
Authors: Castro Laura , Urquiza Gustavo , Adamkowski Adam , Reggio Marcelo
Published: April 2011

On‐site power and mass flow rate measurements were conducted in a hydroelectric power plant (Mexico). Mass flow rate was obtained using Gibson′s water hammer‐based method. A numerical counterpart was carried out by using the commercial CFD software, and flow simulations were performed to principal components of a hydraulic turbine: runner and draft tube. Inlet boundary conditions for the runner were obtained from a previous simulation conducted in the spiral case. The computed results at the runner′s outlet were used to conduct the subsequent draft tube simulation. The numerical results from the runner′s flow simulation provided data to compute the torque and the turbine′s power. Power‐versus‐efficiency curves were built, and very good agreement was found between experimental and numerical data.
Subdivision Depth Computation for Tensor Product n‐Ary Volumetric Models
Authors: Mustafa Ghulam , Hashmi Muhammad Sadiq
Published: April 2011

We offer computational formula of subdivision depth for tensor
product n‐ary (n⩾2) volumetric models based on error bound evaluation technique.
This formula provides and error control tool in subdivision schemes over regular
hexahedron lattice in higher‐dimensional spaces. Moreover, the error bounds of
Mustafa et al. (2006) are special cases
of our bounds.
Is There a Metabolic Program in the Skeletal Muscle of Obese Individuals?
Authors: Houmard Joseph A. , Pories Walter J. , Dohm G. Lynis
Published: April 2011

Severe obesity (BMI ≥ 40 kg/m2) is associated with multiple defects in skeletal muscle which contribute to insulin resistance and a reduction in fatty acid oxidation (FAO) in this tissue. These metabolic derangements are retained in human skeletal muscle cells raised in culture. Together, these findings are indicative of a dysfunctional global metabolic program with severe obesity which is of an epigenetic or genetic origin. Weight loss via gastric bypass surgery can “turn off” and/or correct components of this metabolic program as insulin sensitivity is restored; however, the impairment in FAO in skeletal muscle remains evident. Physical activity can improve FAO and insulin action, indicating that this patient population is not exercise resistant and that exercise offers a pathway to circumvent the abnormal program. Findings presented in this review will hopefully increase the understanding of and aid in preventing and/or treating the severely obese condition.
Early Years Policy
Authors: Waldfogel Jane , Washbrook Elizabeth
Published: April 2011

We analyze the role that early years policy might play in narrowing educational attainment gaps. We begin by examining gaps in school readiness between low-, middle-, and high-income children, drawing on data from new large and nationally representative birth cohort studies in the USA and UK. We find that sizable income-related gaps in school readiness are present in both countries before children enter school and then decompose these gaps to identify the factors that account for the poorer scores of low-income children. We then consider what role early years policy could play in tackling these gaps, drawing on the best available evidence to identify promising programs.
Electronic Absorption Spectra of Some Triazolopyrimidine Derivatives
Authors: Moustafa Hussein , Shibl M. F. , Hilal Rifaat , Ali Laila I. , Abdel Halim Sheimaa
Published: April 2011

The electronic absorption spectra of triazolo pyrimidine and some of its derivatives were measured in polar as well as nonpolar solvents. Assignment of the observed transitions is facilitated via molecular orbital calculations. Charge density distributions, dipole moments, and the extent of delocalization of the MOS were used to interpret the observed solvent effects. The observed transitions are assigned as charge transfer (CT), localized, and delocalized according to the contribution of the various configurations in the CI‐states. The correspondence between the calculated and experimental transition energies is satisfactory.
Selective Interactions of Valeriana officinalis Extracts and Valerenic Acid with [3H]Glutamate Binding to Rat Synaptic Membranes
Authors: Del Valle-Mojica Lisa M. , Ayala-Marín Yoshira M. , Ortiz-Sanchez Carmen M. , Torres-Hernández Bianca A. , Abdalla-Mukhaimer Safa , Ortiz José G.
Published: April 2011

Although GABA neurotransmission has been suggested as a mechanism for Valeriana officinalis effects, CNS depression can also be evoked by inhibition of ionotropic (iGluR) and metabotropic glutamate receptors (mGluR). In this study, we examined if aqueous valerian extract interacted with glutamatergic receptors. Freshly prepared aqueous valerian extract was incubated with rat cortical synaptic membranes in presence of 20 nM [3H]Glutamate. Aqueous valerian extract increased [3H]Glutamate binding from 1 × 10−7 to 1 × 10−3 mg/mL. In the presence of (2S,1′S,2′S)‐2‐(Carboxycyclopropyl)glycine (LCCG‐I) and (2S,2′R,3′R)‐2‐(2′,3′‐Dicarboxycyclopropyl)glycine (DCG‐IV), Group II mGluR agents, valerian extract markedly decreased [3H]Glutamate binding, while (2S)‐2‐amino‐3‐(3,5‐dioxo‐1,2,4‐oxadiazolidin‐2‐yl) propanoic acid) (quisqualic acid, QA), Group I mGluR agonist, increased [3H]Glutamate binding. At 0.05 mg/mL aqueous valerian extract specifically interacted with kainic acid NMDA and AMPA receptors. Valerenic acid, a marker compound for Valeriana officinalis, increased the [3H]Glutamate binding after 1.6 × 10−2 mg/mL, and at 0.008 mg/mL it interacted only with QA (Group I mGluR). The selective interactions of valerian extract and valerenic acid with Group I and Group II mGluR may represent an alternative explanation for the anxiolytic properties of this plant.
The Intensity Model for Pricing Credit Securities with Jump Diffusion and Counterparty Risk
Authors: Hao Ruili , Ye Zhongxing
Published: April 2011

We present an intensity‐based model with counterparty risk. We assume
the default intensity of firm depends on the stochastic interest rate driven by the jump‐diffusion
process and the default states of counterparty firms. Furthermore, we make use
of the techniques in Park (2008) to compute the conditional distribution of default times
and derive the explicit prices of bond and CDS. These are extensions of the models in
Jarrow and Yu (2001).
Examination of Strength Modeling Reliability of Physical Tests on Structural Concrete Columns
Authors: Mirza Sher Ali
Published: April 2011

Comparisons and analyses of strengths from selected computational procedures were undertaken of more than 500 physical tests of rectangular, tied, structural concrete columns reported in the published literature. The computational procedures compared with the physical tests and with each other include a commercially available nonlinear finite element modeling software and the Canadian Standards Association (CSA) Standard A23.3-04. The requirements of the American Concrete Institute (ACI) 318-08 are very similar to those of the CSA A23.3-04, and hence, strength comparisons and analyses reported here are also applicable to ACI 318-08. The physical tests used for comparison were conducted on columns that were braced and pinned at both ends and were constructed using normal-density concrete with a compressive strength between approximately 17 and 57 MPa. The columns were subjected to short-term loads producing pure axial force, axial force combined with symmetrical single-curvature bending, or pure bending. Major variables included the concrete strength, the end eccentricity ratio, the slenderness ratio, the longitudinal reinforcing steel index for reinforced concrete or the structural steel index for composite columns, and the transverse reinforcement (tie/hoop) volumetric ratio. The study provides an examination of the reliability of the computational methods examined.
Current Surgical Treatment of Knee Osteoarthritis
Authors: Rönn Karolin , Reischl Nikolaus , Gautier Emanuel , Jacobi Matthias
Published: April 2011

Osteoathritis (OA) of the knee is common, and the chances of suffering from OA increase with age. Its treatment should be initially nonoperative—and requires both pharmacological and nonpharmacological treatment modalities. If conservative therapy fails, surgery should be considered. Surgical treatments for knee OA include arthroscopy, cartilage repair, osteotomy, and knee arthroplasty. Determining which of these procedures is most appropriate depends on several factors, including the location, stage of OA, comorbidities on the one side and patients suffering on the other side. Arthroscopic lavage and débridement is often carried out, but does not alter disease progression. If OA is limited to one compartment, unicompartmental knee arthroplasty or unloading osteotomy can be considered. They are recommended in young and active patients in regard to the risks and limited durability of total knee replacement. Total arthroplasty of the knee is a common and safe method in the elderly patients with advanced knee OA. This paper summarizes current surgical treatment strategies for knee OA, with a focus on the latest developments, indications and level of evidence.
Comparison of 111In Leakage from Labeled Endocardial and Epicardial Cells: Impact on Modeling Viability of Cells to Be Transplanted into Myocardium
Authors: Blackwood Kimberley J. , Sykes Jane , Deans Lela , Wisenberg Gerald , Prato Frank S.
Published: April 2011

Introduction. Previously we proposed a cellular imaging technique to determine the surviving fraction of transplanted cells in vivo. Epicardial kinetics using Indium-111 determined the Debris Impulse Response Function (DIRF) and leakage coefficient parameters. Convolution-based modeling which corrected for these signal contributions indicated that 111In activity was quantitative of cell viability with half-lives within 20 hrs to 37 days. We determine if the 37-day upper limit remains valid for endocardial injections by comparing previous epicardial cell leakage parameter estimates to those for endocardial cells. Methods. Normal canine myocardium was injected (111In-tropolone) epicardially (9 injections) or endocardially (10 injections). Continuous whole body and SPECT scans for 5 hours were acquired with three weekly follow-up imaging sessions up to 20–26 days. Time-activity curves evaluated each injection type. Results. The epicardial and endocardial kinetics were not significantly different (Epi: 1286±253; Endo: 1567±470 hours P=.62).
Conclusion. The original epicardial estimate of leakage kinetics has been validated for use in endocardial injections.
Possible Roles of Ectophosphatases in Host-Parasite Interactions
Authors: Gomes Marta T. , Lopes Angela H. , Meyer-Fernandes José Roberto
Published: April 2011

The interaction and survival of pathogens in hostile environments and in confrontation with host immune responses are important mechanisms for the establishment of infection. Ectophosphatases are enzymes localized at the plasma membrane of cells, and their active sites face the external medium rather than the cytoplasm. Once activated, these enzymes are able to hydrolyze phosphorylated substrates in the extracellular milieu. Several studies demonstrated the presence of surface-located ecto-phosphatases in a vast number of pathogenic organisms, including bacteria, protozoa, and fungi. Little is known about the role of ecto-phosphatases in host-pathogen interactions. The present paper provides an overview of recent findings related to the virulence induced by these surface molecules in protozoa and fungi.
The Numerical Method for Solving Differential Equations of Lane‐Emden Type by Padé Approximation
Authors: Yiğider Muhammed , Tabatabaei Khatereh , Çelik Ercan
Published: April 2011

Numerical solution differential equation of Lane‐Emden type is considered by Padé approximation. We apply these method to two examples. First differential equation of Lane‐Emden type has been converted to power series by one‐dimensional differential transformation, then the numerical solution of equation was put into Padé series form. Thus, we have obtained numerical solution differential equation of Lane‐Emden type.
On Maximal Subsemigroups of Partial Baer‐Levi Semigroups
Authors: Singha Boorapa , Sanwong Jintana
Published: April 2011

Suppose that X is an infinite set with |X | ≥ q ≥ ℵ0 and I(X) is the symmetric inverse semigroup defined on X. In 1984, Levi and Wood determined a class of maximal subsemigroups MA (using certain subsets A of X) of the Baer‐Levi semigroup BL(q) = {α ∈ I(X): dom α = X and |X∖Xα| = q}. Later, in 1995, Hotzel showed that there are many other classes of maximal subsemigroups of BL(q), but these are far more complicated to describe. It is known that BL(q) is a subsemigroup of the partial Baer‐Levi semigroup PS(q) = {α ∈ I(X) : |X∖Xα| = q}. In this paper, we characterize all maximal subsemigroups of PS(q) when |X | > q, and we extend MA to obtain maximal subsemigroups of PS(q) when |X | = q.
Integrability of the Bakirov System: A Zero‐Curvature Representation
Authors: Sakovich Sergei
Published: April 2011

For the Bakirov system, which is known to possess only one higher‐order local generalized symmetry, we explicitly find a zero‐curvature
representation containing an essential parameter.
Versatile Implementation in Angle‐Resolved Optical Microscopy: Its Application to Local Spectrometry of Microcavities with PIC‐J‐Aggregates
Authors: Obara Yuki , Saitoh Keita , Oda Masaru , Tani Toshiro
Published: April 2011

Versatile novel implementations in microspectroscopy are developed, which can provide angle‐resolved optical spectroscopy at local sample areas almost in diffraction limit. By selecting focus position of light flux incident within the back focal plane of the objective lens radially from the position of the optical axis of the microscope with employing off‐centered pinhole, we can obtain parallel beam with oblique incidence and its angle tuning at the sample surface. In this paper, we describe our specific optical setup and its practical working principle in detail. We report, as a demonstration of its performance, our latest studies on optical properties of cavity polariton states in the so‐called quantum microcavity structures, which contain molecular J‐aggregates of pseudoisocyanine (PIC) dye as active working materials. By using the microscope technique, we obtain a fair amount of improvement in the linewidth observation of cavity polariton spectra.
Effects of Environmental Temperature on the Dynamics of Ichthyophoniasis in Juvenile Pacific Herring (Clupea pallasii)
Authors: Gregg Jake L. , Vollenweider Johanna J. , Grady Courtney A. , Heintz Ron A. , Hershberger Paul K.
Published: April 2011

The effects of temperature and infection byIchthyophonuswere examined in juvenile Pacific herring (Clupea pallasii) maintained under simulated overwinter fasting conditions. In addition to defining parameters for a herring bioenergetics model (discussed in Vollenweider et al. this issue), these experiments provided new insights into factors influencing the infectivity and virulence of the parasiteIchthyophonus. In groups of fish with established disease, temperature variation had little effect on disease outcome.Ichthyophonusmortality outpaced that resulting from starvation alone. In newly infected fish, temperature variation significantly changed the mortality patterns related to disease. Both elevated and lowered temperatures suppressed disease-related mortality relative to ambient treatments. When parasite exposure dose decreased, an inverse relationship between infection prevalence and temperature was detected. These findings suggest interplay between temperature optima for parasite growth and host immune function and have implications for our understanding of howIchthyophonusinfections are established in wild fish populations.
Autologous Peripheral Blood Mononuclear Cell Recognition of Autologous Proliferating Tumor Cells in the Context of a Patient‐Specific Vaccine Trial
Authors: Cornforth A. N. , Lee G. , Dillman R. O.
Published: April 2011

Metastatic melanoma patients who were treated with patient‐specific vaccines consisting of dendritic cells loaded with autologous tumor cells had a 5‐year survival of over 50%. Enzyme‐linked immunospot (ELISPOT) has been used to detect antigen reactive T cells as a means of determining immune response. We wished to determine whether IFN‐gamma secretion in an ELISPOT assay was prognostic or predictive for survival following treatment. Peripheral blood mononuclear cells (PBMCs) collected at weeks 0 and 4 were evaluated by ELISPOT assay for response to autologous tumor cells. Overall, there was slight increase in the number of tumor reactive lymphocytes from week 0 to week 4. Using >5 spots/100 K PBMC as the cutoff, a log‐rank analysis revealed only a slight statistical significance in overall survival for patients who lacked tumor reactive PBMCs at week 4. The sensitivity of ELISPOT in the context of patient‐specific cellular vaccines is unclear.
Natural Killer Cells in Human Cancer: From Biological Functions to Clinical Applications
Authors: Levy Estrella Mariel , Roberti María Paula , Mordoh José
Published: April 2011

Natural killer (NK) cells are central components of the innate immunity. In murine models, it has been shown that NK cells can control both local tumor growth and metastasis due to their ability to exert direct cellular cytotoxicity without prior sensitization and to secrete immunostimulatory cytokines like IFN‐γ. The latter participates in cancer elimination by inhibiting cellular proliferation and angiogenesis, promoting apoptosis, and stimulating the adaptive immune system, and it is instrumental for enhancing Ag processing and presentation. Nevertheless, NK cells display impaired functionality and capability to infiltrate tumors in cancer patients. Also, NK cells are feasible targets of stimulation to participate in immunotherapeutic approaches like antibody‐based strategies and adoptive cell transfer. Thus, multiple attempts currently aim to manipulate NK for utilization in the immunotherapy of cancer.
The Immunomodulatory Effects of AlbuminIn VitroandIn Vivo
Authors: Wheeler Derek S. , Giuliano John S. , Lahni Patrick M. , Denenberg Alvin , Wong Hector R. , Zingarelli Basilia
Published: April 2011

Albumin appears to have proinflammatory effectsin vitro. We hypothesized that albumin would induce a state of tolerance to subsequent administration of lipopolysaccharide (LPS)in vitroandin vivo. RAW264.7 and primary peritoneal macrophages were treated with increasing doses of bovine serum albumin (BSA) and harvested for NF-κB luciferase reporter assay or TNF-αELISA. In separate experiments, RAW264.7 cells were preconditioned with 1 mg/mL BSA for 18 h prior to LPS (10 μg/mL) treatment and harvested for NF-κB luciferase reporter assay or TNF-αELISA. Finally, C57Bl/6 mice were preconditioned with albumin via intraperitoneal administration 18 h prior to a lethal dose of LPS (60 mg/kg body wt). Blood was collected at 6 h after LPS administration for TNF-αELISA. Albumin produced a dose-dependent and TLR-4-dependent increase in NF-κB activation and TNF-αgene expressionin vitro. Albumin preconditioning abrogated the LPS-mediated increase in NF-κB activation and TNF-αgene expressionin vitroandin vivo. The clinical significance of these findings remains to be elucidated.
Quantifying Tumor Vascular Heterogeneity with Dynamic Contrast‐Enhanced Magnetic Resonance Imaging: A Review
Authors: Yang Xiangyu , Knopp Michael V.
Published: April 2011

Tumor microvasculature possesses a high degree of heterogeneity in its structure and function. These features have been demonstrated to be important for disease diagnosis, response assessment, and treatment planning. The exploratory efforts of quantifying tumor vascular heterogeneity with DCE‐MRI have led to promising results in a number of studies. However, the methodological implementation in those studies has been highly variable, leading to multiple challenges in data quality and comparability. This paper reviews several heterogeneity quantification methods, with an emphasis on their applications on DCE‐MRI pharmacokinetic parametric maps. Important methodological and technological issues in experimental design, data acquisition, and analysis are also discussed, with the current opportunities and efforts for standardization highlighted.
FPGA Acceleration of Communication-Bound Streaming Applications: Architecture Modeling and a 3D Image Compositing Case Study
Authors: Schumacher Tobias , Süß Tim , Plessl Christian , Platzner Marco
Published: April 2011

Reconfigurable computers usually provide a limited number of different memory resources, such as host memory, external memory, and on-chip memory with different capacities and communication characteristics. A key challenge for achieving high-performance with reconfigurable accelerators is the efficient utilization of the available memory resources. A detailed knowledge of the memories' parameters is key for generating an optimized communication layout. In this paper, we discuss a benchmarking environment for generating such a characterization. The environment is built on IMORC, our architectural template and on-chip network for creating reconfigurable accelerators. We provide a characterization of the memory resources available on the XtremeData XD1000 reconfigurable computer. Based on this data, we present as a case study the implementation of a 3D image compositing accelerator that is able to double the frame rate of a parallel renderer.
A New Framework of Multiphase Segmentation and Its Application to Partial Volume Segmentation
Authors: Chen Fuhua , Chen Yunmei , Tagare Hemant D.
Published: April 2011

We proposed a novel framework of multiphase segmentation
based on stochastic theory and phase transition theory. Our main
contribution lies in the introduction of a constructed function so that its
composition with phase function forms membership functions. In this way,
it saves memory space and also avoids the general simplex constraint problem
for soft segmentations. The framework is then applied to partial volume
segmentation. Although the partial volume segmentation in this paper is focused
on brain MR image, the proposed framework can be applied to any
segmentation containing partial volume caused by limited resolution and
overlapping.
Cytotoxicity Effects of Amoora rohituka and chittagonga on Breast and Pancreatic Cancer Cells
Authors: Chan Leo L. , George Sherine , Ahmad Irfan , Gosangari Saujanya L. , Abbasi Atiya , Cunningham Brian T. , Watkin Kenneth L.
Published: April 2011

Chemotherapeutic agents for cancer are highly toxic to healthy tissues and hence alternative medicine avenues are widely researched. Majority of the recent studies on alternative medicine suggested that Amoora rohituka possesses considerable antitumor and antibacterial properties. In this work, rohituka and chittagonga, fractionated with petroleum ether, dichloromethane, and ethanol, were explored for their anticancer potential against two breast cancer (MCF‐7 and HTB‐126) and three pancreatic cancer (Panc‐1, Mia‐Paca2, and Capan1). The human foreskin fibroblast, Hs68, was also included. Cytotoxicity of each extract was analyzed using the MTT assay and label‐free photonic crystal biosensor assay. A concentration series of each extract was performed on the six cell lines. For MCF‐7 cancer cells, the chittagonga (Pet‐Ether and CH2Cl2) and rohituka (Pet‐Ether) extracts induced cytotoxicity; the chittagonga (EtoAC) and rohituka (MeOH) extracts did not induce cytotoxicity. For HTB126, Panc‐1, Mia‐Paca2, and Capan‐1 cancer cells, only the chittagonga CH2Cl2 extract showed a significant cytotoxic effect. The extracts were not cytotoxic to normal fibroblast Hs68 cells, which may be correlated to the specificity of Amoora extracts in targeting cancerous cells. Based on these results, further examination of the potential anticancer properties Amoora species and the identification of the active ingredients of these extracts is warranted.
Approximation Order for MultivariateDurrmeyer Operators with Jacobi Weights
Authors: Wang Jianjun , Yang Chan-Yun , Duan Shukai
Published: April 2011

Using the equivalence relation between K‐functional and modulus of smoothness, we
establish a strong direct theorem and an inverse theorem of weak type for multivariate
Bernstein‐Durrmeyer operators with Jacobi weights on a simplex in this paper. We
also obtain a characterization for multivariate Bernstein‐Durrmeyer operators with Jacobi
weights on a simplex. The obtained results not only generalize the corresponding ones for
Bernstein‐Durrmeyer operators, but also give approximation order of Bernstein‐Durrmeyer
operators.
Technical Progress in Single-Incision Laparoscopic Cholecystectomy in Our Initial Experience
Authors: Adachi Tomohiko , Okamoto Tatsuya , Ono Shinichiro , Kanematsu Takashi , Kuroki Tamotsu
Published: April 2011

Single-incision laparoscopic cholecystectomy (SILC) has rapidly spread throughout the world because of its low invasiveness and because it is a scarless procedure. Various surgical methods of performing SILC are present in each institute; however, it is necessary to develop a standardized procedure that we can perform safely, such as the conventional 4-port laparoscopic cholecystectomy (LC). The SILC experiment in our institute was started by use of the commercial SILS Port and changed from a 3-port method via an umbilicus to a 2-port method to improve some problems. Although none of the conversions to conventional 4-port LC and also none of the complications such as bile duct injury occurred in each method, the 2-port method functioned best and was also economical. However, it is most important to adopt strict criteria and select the patients suitable for SILC to demonstrate SILC safety same as 4-port LC.
Targeted Methylation of Two Tumor Suppressor Genes Is Sufficient to Transform Mesenchymal Stem Cells into Cancer Stem/Initiating Cells
Authors: Teng I-Wen , Hou Pei-Chi , Lee Kuan-Der , Chu Pei-Yi , Yeh Kun-Tu , Jin Victor X. , Tseng Min-Jen , Tsai Shaw-Jenq , Chang Yu-Sun , Wu Chi-Sheng , Sun H. Sunny , Tsai Kuen-daw , Jeng Long-Bin , Nephew Kenneth P. , Huang Tim H.-M. , Hsiao Shu-Huei , Leu Yu-Wei
Published: April 2011

Although DNA hypermethylation within promoter CpG islands is highly correlated with tumorigenesis, it has not been established whether DNA hypermethylation within a specific tumor suppressor gene (TSG) is sufficient to fully transform a somatic stem cell. In this study, we addressed this question using a novel targeted DNA methylation technique to methylate the promoters of HIC1 and RassF1A, two well-established TSGs, along with a two-component reporter system to visualize successful targeting of human bone marrow–derived mesenchymal stem cells (MSC) as a model cell system. MSCs harboring targeted promoter methylations of HIC1/RassF1A displayed several features of cancer stem/initiating cells including loss of anchorage dependence, increased colony formation capability, drug resistance, and pluripotency. Notably, inoculation of immunodeficient mice with low numbers of targeted MSC resulted in tumor formation, and subsequent serial xenotransplantation and immunohistochemistry confirmed the presence of stem cell markers and MSC lineage in tumor xenografts. Consistent with the expected mechanism of TSG hypermethylation, treatment of the targeted MSC with a DNA methyltransferase inhibitor reversed their tumorigenic phenotype. To our knowledge, this is the first direct demonstration that aberrant TSG hypermethylation is sufficient to transform a somatic stem cell into a fully malignant cell with cancer stem/initiating properties. Cancer Res; 71(13); 4653–63. ©2011 AACR.
HER2 Overexpression Elicits a Proinflammatory IL-6 Autocrine Signaling Loop That Is Critical for Tumorigenesis
Authors: Hartman Zachary C. , Yang Xiao-Yi , Glass Oliver , Lei Gangjun , Osada Takuya , Dave Sandeep S. , Morse Michael A. , Clay Timothy M. , Lyerly Herbert K.
Published: April 2011

HER2 overexpression occurs in approximately 25% of breast cancers, where it correlates with poor prognosis. Likewise, systemic inflammation in breast cancer correlates with poor prognosis, although the process is not understood. In this study, we explored the relationship between HER2 and inflammation, comparing the effects of overexpressing wild-type or mutated inactive forms of HER2 in primary human breast cells. Wild-type HER2 elicited a profound transcriptional inflammatory profile, including marked elevation of interleukin-6 (IL-6) expression, which we established to be a critical determinant of HER2 oncogenesis. Mechanistic investigations revealed that IL-6 secretion induced by HER2 overexpression activated Stat3 and altered gene expression, enforcing an autocrine loop of IL-6/Stat3 expression. Both mouse and human in vivo models of HER2-amplified breast carcinoma relied critically on this HER2–IL-6–Stat3 signaling pathway. Our studies offer the first direct evidence linking HER2 to a systemic inflammatory mechanism that orchestrates HER2-mediated tumor growth. We suggest that the HER2–IL-6–STAT3 signaling axis we have defined in breast cancer could prompt new therapeutic or prevention strategies for treatment of HER2-amplified cancers. Cancer Res; 71(13); 4380–91. ©2011 AACR.
Targeted Nanogels: A Versatile Platform for Drug Delivery to Tumors
Authors: Murphy Eric A. , Majeti Bharat K. , Mukthavaram Rajesh , Acevedo Lisette M. , Barnes Leo A. , Cheresh David A.
Published: April 2011

Although nanoparticle-based drug delivery formulations can improve the effectiveness and safety of certain anticancer drugs, many drugs, due to their chemical composition, are unsuitable for nanoparticle loading. Here, we describe a targeted nanogel drug delivery platform that can (i) encapsulate a wide range of drug chemotypes, including biological, small molecule, and cytotoxic agents; (ii) display targeting ligands and polymeric coatings on the surface; (iii) enhance drug retention within the nanogel core after photo-cross-linking; and (iv) retain therapeutic activity after lyophilization allowing for long-term storage. For therapeutic studies, we used integrin αvβ3–targeted lipid-coated nanogels with cross-linked human serum albumin in the core for carrying therapeutic cargoes. These particles exhibited potent activity in tumor cell viability assays with drugs of distinct chemotype, including paclitaxel, docetaxel, bortezomib, 17-AAG, sorafenib, sunitinib, bosutinib, and dasatinib. Treatment of orthotopic breast and pancreas tumors in mice with taxane-loaded nanogels produced a 15-fold improvement in antitumor activity relative to Abraxane by blocking both primary tumor growth and spontaneous metastasis. With a modifiable surface and core, the lipid-coated nanogel represents a platform technology that can be easily adapted for specific drug delivery applications to treat a wide range of malignant diseases. Mol Cancer Ther; 10(6); 972–82. ©2011 AACR.
ATM and p53 Regulate FOXM1 Expression via E2F in Breast Cancer Epirubicin Treatment and Resistance
Authors: Millour Julie , de Olano Natalia , Horimoto Yoshiya , Monteiro Lara J. , Langer Julia K. , Aligue Rosa , Hajji Nabil , Lam Eric W.-F.
Published: April 2011

In this report, we investigated the role and regulation of forkhead box M1 (FOXM1) in breast cancer and epirubicin resistance. We generated epirubicin-resistant MCF-7 breast carcinoma (MCF-7-EPIR) cells and found FOXM1 protein levels to be higher in MCF-7-EPIR than in MCF-7 cells and that FOXM1 expression is downregulated by epirubicin in MCF-7 but not in MCF-7-EPIR cells. We also established that there is a loss of p53 function in MCF-7-EPIR cells and that epirubicin represses FOXM1 expression at transcription and gene promoter levels through activation of p53 and repression of E2F activity in MCF-7 cells. Using p53−/− mouse embryo fibroblasts, we showed that p53 is important for epirubicin sensitivity. Moreover, transient promoter transfection assays showed that epirubicin and its cellular effectors p53 and E2F1 modulate FOXM1 transcription through an E2F-binding site located within the proximal promoter region. Chromatin immunoprecipitation analysis also revealed that epirubicin treatment increases pRB (retinoblastoma protein) and decreases E2F1 recruitment to the FOXM1 promoter region containing the E2F site. We also found ataxia-telangiectasia mutated (ATM) protein and mRNA to be overexpressed in the resistant MCF-7-EPIR cells compared with MCF-7 cells and that epirubicin could activate ATM to promote E2F activity and FOXM1 expression. Furthermore, inhibition of ATM in U2OS cells with caffeine or depletion of ATM in MCF-7-EPIR with short interfering RNAs can resensitize these resistant cells to epirubicin, resulting in downregulation of E2F1 and FOXM1 expression and cell death. In summary, our data show that ATM and p53 coordinately regulate FOXM1 via E2F to modulate epirubicin response and resistance in breast cancer. Mol Cancer Ther; 10(6); 1046–58. ©2011 AACR.
B7-H3 Silencing Increases Paclitaxel Sensitivity by Abrogating Jak2/Stat3 Phosphorylation
Authors: Liu Hao , Tekle Christina , Chen Yih-Wen , Kristian Alexandr , Zhao Yuhua , Zhou Ming , Liu Zixing , Ding Yan , Wang Bin , Mælandsmo Gunhild Mari , Nesland Jahn Marthin , Fodstad Oystein , Tan Ming
Published: April 2011

In many types of cancer, the expression of the immunoregulatory protein B7-H3 has been associated with poor prognosis. Previously, we observed a link between B7-H3 and tumor cell migration and invasion, and in present study, we have investigated the role of B7-H3 in chemoresistance in breast cancer. We observed that silencing of B7-H3, via stable short hairpin RNA or transient short interfering RNA transfection, increased the sensitivity of multiple human breast cancer cell lines to paclitaxel as a result of enhanced drug-induced apoptosis. Overexpression of B7-H3 made the cancer cells more resistant to the drug. Next, we investigated the mechanisms behind B7-H3–mediated paclitaxel resistance and found that the level of Stat3 Tyr705 phosphorylation was decreased in B7-H3 knockdown cells along with the expression of its direct downstream targets Mcl-1 and survivin. The phosphorylation of Janus kinase 2 (Jak2), an upstream molecule of Stat3, was also significantly decreased. In contrast, reexpression of B7-H3 in B7-H3 knockdown and low B7-H3 expressing cells increased the phosphorylation of Jak2 and Stat3. In vivo animal experiments showed that B7-H3 knockdown tumors displayed a slower growth rate than the control xenografts. Importantly, paclitaxel treatment showed a strong antitumor activity in the mice with B7-H3 knockdown tumors, but only a marginal effect in the control group. Taken together, our data show that in breast cancer cells, B7-H3 induces paclitaxel resistance, at least partially by interfering with Jak2/Stat3 pathway. These results provide novel insight into the function of B7-H3 and encourage the design and testing of approaches targeting this protein and its partners. Mol Cancer Ther; 10(6); 960–71. ©2011 AACR.
Proteomic Analysis Reveals an Elevated Expression of Heat Shock Protein 27 in Preeclamptic Placentas
Authors: Shin Jeong-Kyu , Baek Jong-Chul , Kang Min-Young , Park Ji-Kwon , Lee Soon-Ae , Lee Jong-Hak , Choi Wan-Sung , Paik Won-Young
Published: April 2011

Aim: The purpose of this study was to identify the placental proteins that are associated with preeclampsia by performing proteomic analysis. Methods: To identify the proteins associated with preeclampsia, we performed two-dimensional electrophoresis (2-DE), followed by silver staining. The overexpressed proteins were identified by performing matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS), followed by peptide mass fingerprinting, a protein database search and Western blot analysis. Immunohistochemical staining was performed to determine the localization of the overexpressed Hsp27. Results: By use of 2-DE and MALDI-TOF-MS analysis, twelve differentially expressed proteins were identified, of which four proteins were upregulated and eight proteins were downregulated. One of the upregulated spots was identified as Hsp27. Immunohistochemical analysis showed that Hsp27 was mainly located in the trophoblasts. The Western blot analysis showed that the expression of Hsp27 in the tissues of the preeclampsia placenta was significantly increased. Conclusions: Our study confirmed that four proteins are upregulated and eight proteins are downregulated in preeclampsia. These differentially expressed proteins include signal transduction protein and molecular chaperon protein, in which Hsp27 is upregulated. We suggest that the increased expression level of Hsp27 might be correlated with the pathophysiology of preeclampsia.
Vaginal Cuff Closure: A Comparison between the Vaginal Route and Laparoscopic Suture in Patients Undergoing Total Laparoscopic Hysterectomy
Authors: Hwang Jong Ha , Lee Jae Kwan , Lee Nak Woo , Lee Kyu Wan
Published: April 2011

Background: To compare the vaginal route and laparoscopic suture for vaginal cuff closure (VCC) in patients undergoing a total laparoscopic hysterectomy (TLH). Methods: A total of 471 women who required hysterectomy were allocated to two groups. 261 women had TLH via VCC by the vaginal route and 210 women had TLH via VCC by laparoscopic suture. All TLHs were performed by the same laparoscopic surgeon. Results: The cuff-related complications included vaginal disruption (3.4%), dehiscence (1.27%), vaginal vault bleeding (1.91%), vaginal spotting (19.32%), granulation (1.27%), cuff infection (1.49%), and yellowish vaginal discharge (6.16%). No difference in vaginal cuff complications was found between the laparoscopic and vaginal approach. The median operation time was significantly shorter for the laparoscopic suture (76.74 min, range 40–220; 95% CI 74.84–83.45) than the vaginal route for VCC (85.77 min, range 45–290; 95% CI 86.87–95.36) after hysterectomy (p < 0.001). Conclusion: For VCC with TLH, laparoscopic suture was a safe and less time-consuming procedure. The cuff-related complications were similar in the two groups.
Endometriosis Cost Assessment (the EndoCost Study): A Cost-of-Illness Study Protocol
Authors: Simoens Steven , Hummelshoj Lone , Dunselman Gerard , Brandes Iris , Dirksen Carmen , D’Hooghe Thomas ,   EndoCost Consortium
Published: April 2011

Aims: The EndoCost study aims to calculate the costs of endometriosis from a societal perspective. Methods: This multicentre, prevalence-based cost-of-illness analysis aggregates data on endometriosis costs and quality of life from a prospective hospital questionnaire and from both retrospective and prospective patient questionnaires. The EndoCost study comprises 12 representative tertiary care centres involved in the care of women with endometriosis in 10 countries. The sample includes patients with a laparoscopic and/or histological diagnosis of endometriosis and with at least 1 patient contact related to endometriosis during 2008. The EndoCost study measures direct healthcare costs (e.g. costs of medication, physician visits), direct non-healthcare costs (e.g. transportation costs), and indirect costs of productivity loss. Cost questions are developed specifically for the purpose of the EndoCost study. Quality of life is measured using the EuroQol-5D and relevant parts of the Global Study of Women’s Health instruments. Both aggregate analyses and country-specific analyses are planned for total costs per patient. Costs are broken down into cost drivers and into the various payers that incur costs. Conclusions: The cost estimates provided by the EndoCost cost-of-illness analysis may be used to justify the prioritisation of future research in endometriosis.
The Difference of the Impacts of Surgical Approaches on Cellular Immunity in Patients with Uterine Malignancies: A Comparative Study of Laparoscopy and Laparotomy Surgery
Authors: Zhang Nawei , Liu Haiyan , Zhang Zhenyu , Wang Shuzhen , Guo Shuli
Published: April 2011

Objective: To explore the impact of laparoscopy and laparotomy surgery on cellular immunity in patients with malignant uterine tumors. Methods: Thirty-eight women with uterine malignancies were enrolled in a prospective nonrandomized cohort study. Either laparoscopy or laparotomy was performed according to the patients’ choice. The frequency of CD3+, CD4+, CD8+ T cells and natural killer cells derived from peripheral venous blood was evaluated by flow cytometry. Results: (1) Postoperatively, there was a decrease in the number of lymphocyte counts, especially after laparotomy, on the first postoperative day (p < 0.01). (2) Compared with preoperative levels, the frequencies of CD3+ and CD4+ cells and the CD4+/CD8+ ratio were declined both in the laparoscopy and laparotomy groups on postoperative day 1 (p < 0.01). (3) The frequencies of CD3+ and CD4+ cells and the ratio of CD4+ to CD8+ cells were less depressed in the laparoscopy group on the first postoperative day (p < 0.05). (4) The frequency of natural killer cells increased, both in the laparoscopy and laparotomy groups on the first postoperative day (p < 0.01), but there were no significant differences between the two groups (p > 0.05). Conclusion: Cellular immunity was temporally depressed in patients with uterine malignancy after surgical treatment, but laparoscopic surgery depressed the immunity less than laparotomy.
Term Delivery Rate after Hysteroscopic Metroplasty in Patients with Recurrent Spontaneous Abortion and T-Shaped, Arcuate and Septate Uterus
Authors: Giacomucci Evaldo , Bellavia Emanuela , Sandri Fabrizio , Farina Antonio , Scagliarini Giorgio
Published: April 2011

Background: To evaluate the improvement of the term delivery rate after uterine surgery in various uterine malformations. Methods: 170 patients were eligible for the present retrospective case series study. Data were weighted for the number of pregnancies observed (n = 218) after surgical intervention, stratified to the number of previous abortions (at least 2) and type of malformation. Results: Before surgery, the overall term delivery rate was 5.5%. After surgery, the overall term delivery rate was 59% (absolute benefit increase, ABI, was 54.5) and correlated with the number of previous abortions (69.7% ABI = 64.2, 56.5% ABI = 51 and 26.3% ABI = 20.8 for 2, 3–4 and >4 abortions, respectively; p = 0.0008, log-rank test). Data stratified according to uterine malformations yielded the following term delivery rate: 66.7% for T-shaped uterus, 62.8% for septum/partial septum and 55.6% for arcuate uterus (NS, log-rank test). The number of previous abortions and maternal age also affected the term delivery rate. Their effect upon the term delivery rate, expressed as an odds ratio, was 1.73 (95% CI: 1.20–2.49) and 1.11 (95% CI: 1.05–1.18), respectively. Conclusion: The term delivery rate was about 10-fold higher after surgery. T-shaped uterus surgery yielded the best term delivery rate.