bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced 4-Hydroxynonenal Resistance inKEAP1Silenced Human Colon Cancer Cells
Authors: Jung Kyeong-Ah , Kwak Mi-Kyoung
Published: May 2013

Nuclear factor erythroid 2-related factor 2 (NRF2) is the transcription factor that regulates an array of antioxidant/detoxifying genes for cellular defense. The conformational changes of Kelch-like ECH-associated protein 1 (KEAP1), a cytosolic repressor protein of NRF2, by various stimuli result in NRF2 liberation and accumulation in the nucleus. In the present study, we aimed to investigate the effect ofKEAP1knockdown on NRF2 target gene expression and its toxicological implication using human colon cancer cells. The stableKEAP1-knockdown HT29 cells exhibit elevated levels of NRF2 and its target gene expressions. In particular, the mRNA levels of aldo-keto reductases (AKR1C1, 1C2, 1C3, 1B1, and 1B10) were substantially increased inKEAP1silenced HT29 cells. These differential AKRs expressions appear to contribute to protection against oxidative stress. TheKEAP1-knockdown cells were relatively more resistant to hydrogen peroxide (H2O2) and 4-hydroxynonenal (4HNE) compared to the control cells. Accordantly, we observed accumulation of 4HNE protein adducts in H2O2- or 4HNE-treated control cells, whereasKEAP1-knockdown cells did not increase adduct formation. The treatment ofKEAP1-silenced cells with AKR1C inhibitor flufenamic acid increased 4HNE-induced cellular toxicity and protein adduct formation. Taken together, these results indicate that AKRs, which are NRF2-dependent highly inducible gene clusters, play a role in NRF2-mediated cytoprotection against lipid peroxide toxicity.
Suture Granuloma Showing False-Positive Findings on FDG-PET
Authors: Takahara Kohei , Kakinoki Hiroaki , Ikoma Saya , Udo Kazuma , Tobu Shohei , Satoh Yuji , Tokuda Yuji , Noguchi Mitsuru , Aoki Shigehisa , Uozumi Jiro
Published: May 2013

We report a case of a 33-year-old male with a mixed germ-cell testicular tumor. Postoperative follow-up FDG-PET revealed concentration of FDG in the left inguinal area which is not tumor metastasis or local recurrence but suture reactivity granuloma. In this paper, we reviewed suture granulomas associated with false-positive findings on FDG-PET after surgery. If FDG-PET will be used more frequently in the future, it will be necessary to refrain from using silk thread in order to prevent any unnecessary surgery.
Simulation of Formation Damage after Long-Term Water Flooding
Authors: He Liu , Yang Gao , Guoxin Li , Yiliang Li
Published: May 2013

Water flooding is a commonly used technology for enhancing oil recovery. Its main mechanism is to maintain higher pressure to sweep oil towards production wells. However, the strong water flooding will cause higher compression pressure around the injection wellbore. This high pressure in the reservoir causes stress redistribution and higher stress near the wellbore which induces material damage and permeability change. We developed a fluid-solid coupling finite element model to simulate and quantitatively analyze the pressure evolution in the reservoir as well as damage and permeability change in the formation during long-term water flooding process. The obtained results offer theoretical understanding of the benefits (pore pressure increase in the simulation domain), rock damage, permeability change of long-term water flooding, and the insights of how to detect and prevent wellbore failure and collapse due to water flooding.
Chess-Like Games May Have No Uniform Nash Equilibria Even in Mixed Strategies
Authors: Boros Endre , Gurvich Vladimir , Yamangil Emre
Published: May 2013

Recently, it was shown that Chess-like games may have no uniform (subgame perfect) Nash equilibria in pure positional strategies. Moreover, Nash equilibria may fail to exist already in two-person games in which all infinite plays are equivalent and ranked as the worst outcome by both players. In this paper, we extend this negative result further, providing examples that are uniform Nash equilibria free, even in mixed or independently mixed strategies. Additionally, in case of independently mixed strategies we consider two different definitions for effective payoff: the Markovian and the a priori realization.
C-Band Polarimetric Coherences and Ratios for Discriminating Sea Ice Roughness
Authors: Gupta Mukesh , Scharien Randall K. , Barber David G.
Published: May 2013

The rapid decline of sea ice in the Arctic has resulted in a variable sea ice roughness that necessitates improved methods for efficient observation using high-resolution spaceborne radar. The utility of C-band polarimetric backscatter, coherences, and ratios as a discriminator of ice surface roughness is evaluated. An existing one-dimensional backscatter model has been modified to two-dimensions (2D) by considering deviation in the orientation (i.e., the slopes) in azimuth and range direction of surface roughness simultaneously as an improvement in the model. It is shown theoretically that the circular coherence (ρRRLL) decreases exponentially with increasing surface roughness. The crosspolarized coherence (ρHHVH) is found to be less sensitive to surface roughness, whereas the copolarized coherence (ρVVHH) decreases at far-range incidence angles for all ice types. A complete validation of the adapted 2D model using direct measurements of surface roughness is suggested as an avenue for further research.
Inpatient Treatment of Community-Acquired Pneumonias with Integrative Medicine
Authors: Geyer Ulrich , Diederich Klas , Kusserow Maria , Laubersheimer Andreas , Kramer Klaus
Published: May 2013

Introduction.The aim of the presented observational case series was to evaluate the experience in treating patients with community-acquired pneumonia (CAP) within integrative medicine, particularly anthroposophic medicine in a well-experienced and specialized unit.Patients and Methods.Patients with proven CAP were evaluated (CAP-study group) based on a retrospective chart review. To estimate the severity of pneumonia, the pneumonia severity index (PSI) was applied. Treatment efficacy was evaluated regarding body temperature, CRP level, leukocytes blood count, the need to be treated on ICU, and mortality. Results were compared with the inpatient data of the Pneumonia PORT Validation Cohort.Results.15/18 patients of the CAP-study group belonged to risk class groups I–III (low and moderate risk), 2 patients to risk class IV, and one patient to risk class V (severe pneumonia). 16/18 patients were treated with anthroposophic medicine only and 2/18 got additionally antibiotic therapy (both of risk class IV). A significant reduction of body temperature, CRP level, and leukocytes blood count has been obtained by applying anthroposophic medicine, while neither complications nor pneumonia-related death occurred. Compared with the control group there was no significant difference in mortality rate, whereby no patient had to be treated on the ICU, but the duration of hospital stay was significantly longer in the presented series.Conclusion.Inpatient treatment of CAP with anthroposophic medicine without the use of antibiotics may achieve reasonable results in selected cases. Additional larger sized prospective controlled trials should further clarify the role of AM in the treatment of CAP.
Analytical Particular Solutions of Multiquadrics Associated with Polyharmonic Operators
Authors: Tsai Chia-Cheng
Published: May 2013

We derive two- and three-dimensional analytical particular solutions of multiquadrics (MQ) associated with the polyharmonic operators, named as the polyharmonic multiquadrics (PMQs). The methods of undetermined coefficients are constructed by observing the first few orders of the PMQs which are obtained by the symbolic software,Mathematica. By expanding the PMQs into the Laurent series, the unknown coefficients of the PMQs can be determined. The homogeneous parts of the PMQs are suitably arranged so that the PMQs are hierarchically unique and infinitely differentiable.Mathematicacodes are provided for obtaining the PMQs of arbitrary orders. The derived PMQs are validated by numerical solutions for Poisson’s equation. Numerical results indicate that the solutions obtained by the PMQs are more accurate than those by the MQ.
Hepatic Iron Quantification on 3 Tesla (3 T) Magnetic Resonance (MR): Technical Challenges and Solutions
Authors: Anwar Muhammad , Wood John , Manwani Deepa , Taragin Benjamin , Oyeku Suzette O. , Peng Qi
Published: May 2013

MR has become a reliable and noninvasive method of hepatic iron quantification. Currently, most of the hepatic iron quantification is performed on 1.5 T MR, and the biopsy measurements have been paired withR2andR2*values for 1.5 T MR. As the use of 3 T MR scanners is steadily increasing in clinical practice, it has become important to evaluate the practicality of calculating iron burden at 3 T MR. Hepatic iron quantification on 3 T MR requires a better understanding of the process and more stringent technical considerations. The purpose of this work is to focus on the technical challenges in establishing a relationship betweenT2*values at 1.5 T MR and 3 T MR for hepatic iron concentration (HIC) and to develop an appropriately optimized MR protocol for the evaluation ofT2*values in the liver at 3 T magnetic field strength. We studied 22 sickle cell patients using multiecho fast gradient-echo sequence (MFGRE) 3 T MR and compared the results with serum ferritin and liver biopsy results. Our study showed that the quantification of hepatic iron on 3 T MRI in sickle cell disease patients correlates well with clinical blood test results and biopsy results. 3 T MR liver iron quantification based on MFGRE can be used for hepatic iron quantification in transfused patients.
On the Successive Linearisation Approach to the Flow of Reactive Third-Grade Liquid in a Channel with Isothermal Walls
Authors: Motsa S. S. , Makinde O. D. , Shateyi S.
Published: May 2013

The nonlinear differential equations modeling flow of a reactive third-grade liquid between two parallel isothermal plates is investigated using a novel hybrid of numerical-analytical scheme known as the successive linearization method (SLM). Numerical and graphical results obtained show excellence in agreement with the earlier results reported in the literature. A comparison with numerical results generated using the inbuilt MATLAB boundary value solverbvp4cdemonstrates that the new SLM approach is a very efficient technique for tackling highly nonlinear differential equations of the type discussed in this paper.
Comparative Studies on Cellular Behaviour of Carnation (Dianthus caryophyllus Linn. cv. Grenadin) Grown In Vivo and In Vitro for Early Detection of Somaclonal Variation
Authors: Yaacob Jamilah Syafawati , Taha Rosna Mat , Khorasani Esmaeili Arash
Published: May 2013

The present study deals with the cytological investigations on the meristematic root cells of carnation (Dianthus caryophyllus Linn.) grown in vivo and in vitro. Cellular parameters including the mitotic index (MI), chromosome count, ploidy level (nuclear DNA content), mean cell and nuclear areas, and cell doubling time (Cdt) were determined from the 2 mm root tip segments of this species. The MI value decreased when cells were transferred from in vivo to in vitro conditions, perhaps due to early adaptations of the cells to the in vitro environment. The mean chromosome number was generally stable (2n = 2x = 30) throughout the 6‐month culture period, indicating no occurrence of early somaclonal variation. Following the transfer to the in vitro environment, a significant increase was recorded for mean cell and nuclear areas, from 26.59 ± 0.09 μm2 to 35.66 ± 0.10 μm2 and 142.90 ± 0.59 μm2 to 165.05 ± 0.58 μm2, respectively. However, the mean cell and nuclear areas of in vitro grown D. caryophyllus were unstable and fluctuated throughout the tissue culture period, possibly due to organogenesis or rhizogenesis. Ploidy level analysis revealed that D. caryophyllus root cells contained high percentage of polyploid cells when grown in vivo and maintained high throughout the 6‐month culture period.
Alternative Splicing for Diseases, Cancers, Drugs, and Databases
Authors: Tang Jen-Yang , Lee Jin-Ching , Hou Ming-Feng , Wang Chun-Lin , Chen Chien-Chi , Huang Hurng-Wern , Chang Hsueh-Wei
Published: May 2013

Alternative splicing is a major diversification mechanism in the human transcriptome and proteome. Several diseases, including cancers, have been associated with dysregulation of alternative splicing. Thus, correcting alternative splicing may restore normal cell physiology in patients with these diseases. This paper summarizes several alternative splicing‐related diseases, including cancers and their target genes. Since new cancer drugs often target spliceosomes, several clinical drugs and natural products or their synthesized derivatives were analyzed to determine their effects on alternative splicing. Other agents known to have modulating effects on alternative splicing during therapeutic treatment of cancer are also discussed. Several commonly used bioinformatics resources are also summarized.
Emergence in Elderly Patient Undergoing General Anesthesia with Xenon
Authors: Sanfilippo Maria , Wefki Abdelgawwad Shousha Ahmed Abdelgawwad , Paparazzo Antonella
Published: May 2013

Introduction. It is a consensus that the postoperative cognitive function is impaired in elderly patients after general anaesthesia, and such category patient takes more time to recover. Xenon is a noble gas with anesthetic properties mediated by antagonism of N-methyl-D-aspartate receptors. With a minimum alveolar concentration of 0.63, xenon is intended for maintaining hypnosis with 30% oxygen. The fast recovery after xenon anaesthesia was hypothesized to be advantageous in this scenario.Case Presentation. We report the case of 99-year-old woman who underwent sigmoid colon carcinoma resection with colorectal anastomosis. We carried out the induction phase by propofol, oxygen, fentanil, and rocuronium bromide, and then we proceeded to a rapid sequence endotracheal intubation consequently. The patient was monitored by IBP, NIBP, ECG, cardiac frequency, respiratory rate, capnometry, TOF Guard, blood gas analysis, and BIS. For maintenance we administrated oxygen, remifentanil, rocuronium bromide, and xenon gas 60–65%. Shortly after the end of surgery the patients started an autonomous respiratory activity, and a high BIS level was also recorded. Decision was made by our team to proceed into the emergence phase. The residual neuromuscular block was antagonized by sugammadex, modified Aldrete score was implicated, and we got our patient fully awake without any cognitive dysfunction or delirium.Conclusion. The rapid emergence to full orientation in very elderly patient who had been anesthetized by xenon shows concordance to the high BIS values and the clinical signs of the depth of anesthesia.
Role of Cone Beam Computed Tomography in Rehabilitation of a Traumatised Deficient Maxillary Alveolar Ridge Using Symphyseal Block Graft Placement
Authors: Arora Shipra , Lamba Arundeep Kaur , Faraz Farrukh , Tandon Shruti , Ahad Abdul
Published: May 2013

Deficiencies in the alveolar ridges cause multiple problems in achieving aesthetic and functional outcome of implant therapy and are commonly restored by using onlay graft from intraoral source. Careful assessment of the recipient as well as the donor site using cone beam computed tomography (CBCT) is a prerequisite to ideal treatment planning. This paper highlights the critical role of CBCT in planning a successful rehabilitation of traumatised deficient anterior maxillary alveolar ridge using autogenous block graft from mandibular symphysis, followed by implant placement. A 21-year-old male reported with missing right maxillary lateral incisor due to traumatic avulsion 6 months back. A concavity was found on the labial aspect of edentulous area. Serial transplanar images on CBCT revealed gross irregular radiolucency in place of labial cortical plate. Using CBCT, size of the required block was estimated, and mandibular symphyseal area was evaluated for the feasibility of harvesting a graft of suitable dimension. Onlay block graft was harvested from mandibular symphysis and placed at the edentulous site to augment the alveolar ridge. Implants were placed 5 months later and loaded successfully after osseointegration. After 1 year of followup, implant-based prosthesis is working well, without any complications.
The Effect of Food Hardness on the Development of Dental Caries in Alloxan-Induced Diabetic Rats
Authors: Nakahara Yutaka , Sano Tomoya , Kodama Yasushi , Ozaki Kiyokazu , Matsuura Tetsuro
Published: May 2013

We have previously shown that dental caries may be produced in diabetic rodent models fed with noncariogenic standard diets; however, many studies usually add large amounts of sugar to the diet to induce dental caries. Moreover, the physical properties of cariogenic diets have been reported as an important factor in the formation of caries. The aim of this study was to clarify the effect of the hardness of non-cariogenic diets on the development of dental caries in diabetic rodents. Seven-week-old female F344 rats were divided into 4 groups: intact rats fed with a standard pelletized or powdered diet and alloxan-induced diabetic rats fed with a standard pelletized or powdered diet. All of the rats were sacrificed at 52 weeks of age for morphological examinations on their dental tissue. Dental caries had developed and extended to all the molars in the diabetic rats that were fed with both the pelletized and powdered diets. Moreover, the lesion was significantly enhanced in the powdered diet group compared to that in the pelletized diet group. In conclusion, food hardness is an important factor influencing the development of dental caries in diabetic rats.
Major Components of Energy Drinks (Caffeine, Taurine, and Guarana) Exert Cytotoxic Effects on Human Neuronal SH-SY5Y Cells by Decreasing Reactive Oxygen Species Production
Authors: Zeidán-Chuliá Fares , Gelain Daniel Pens , Kolling Eduardo Antônio , Rybarczyk-Filho José Luiz , Ambrosi Priscilla , Resende Terra Silvia , Pires André Simões , da Rocha João Batista Teixeira , Antônio Behr Guilherme , Fonseca Moreira José Cláudio
Published: May 2013

Scope. To elucidate the morphological and biochemicalin vitroeffects exerted by caffeine, taurine, and guarana, alone or in combination, since they are major components in energy drinks (EDs).Methods and Results. On human neuronal SH-SY5Y cells, caffeine (0.125–2 mg/mL), taurine (1–16 mg/mL), and guarana (3.125–50 mg/mL) showed concentration-dependent nonenzymatic antioxidant potential, decreased the basal levels of free radical generation, and reduced both superoxide dismutase (SOD) and catalase (CAT) activities, especially when combined together. However, guarana-treated cells developed signs of neurite degeneration in the form of swellings at various segments in a beaded or pearl chain-like appearance and fragmentation of such neurites at concentrations ranging from 12.5 to 50 mg/mL. Swellings, but not neuritic fragmentation, were detected when cells were treated with 0.5 mg/mL (or higher doses) of caffeine, concentrations that are present in EDs. Cells treated with guarana also showed qualitative signs of apoptosis, including membrane blebbing, cell shrinkage, and cleaved caspase-3 positivity. Flow cytometric analysis confirmed that cells treated with 12.5–50 mg/mL of guarana and its combinations with caffeine and/or taurine underwent apoptosis.Conclusion. Excessive removal of intracellular reactive oxygen species, to nonphysiological levels (or “antioxidative stress”), could be a cause ofin vitrotoxicity induced by these drugs.
Maximum Likelihood Estimation of the VAR(1) Model Parameters with Missing Observations
Authors: Mouriño Helena , Barão Maria Isabel
Published: May 2013

Missing-data problems are extremely common in practice. To achieve reliable inferential results, we need to take into account this feature of the data. Suppose that the univariate data set under analysis has missing observations. This paper examines the impact of selecting an auxiliary complete data set—whose underlying stochastic process is to some extent interdependent with the former—to improve the efficiency of the estimators for the relevant parameters of the model. The Vector AutoRegressive (VAR) Model has revealed to be an extremely useful tool in capturing the dynamics of bivariate time series. We propose maximum likelihood estimators for the parameters of the VAR(1) Model based on monotone missing data pattern. Estimators’ precision is also derived. Afterwards, we compare the bivariate modelling scheme with its univariate counterpart. More precisely, the univariate data set with missing observations will be modelled by an AutoRegressive Moving Average (ARMA(2,1)) Model. We will also analyse the behaviour of the AutoRegressive Model of order one, AR(1), due to its practical importance. We focus on the mean value of the main stochastic process. By simulation studies, we conclude that the estimator based on the VAR(1) Model is preferable to those derived from the univariate context.
Mixed Static and Dynamic Optimization of Four-Parameter Functionally Graded Completely Doubly Curved and Degenerate Shells and Panels Using GDQ Method
Authors: Tornabene Francesco , Ceruti Alessandro
Published: May 2013

This study deals with a mixed static and dynamic optimization of four-parameter functionally graded material (FGM) doubly curved shells and panels. The two constituent functionally graded shell consists of ceramic and metal, and the volume fraction profile of each lamina varies through the thickness of the shell according to a generalized power-law distribution. The Generalized Differential Quadrature (GDQ) method is applied to determine the static and dynamic responses for various FGM shell and panel structures. The mechanical model is based on the so-called First-order Shear Deformation Theory (FSDT). Three different optimization schemes and methodologies are implemented. The Particle Swarm Optimization, Monte Carlo and Genetic Algorithm approaches have been applied to define the optimum volume fraction profile for optimizing the first natural frequency and the maximum static deflection of the considered shell structure. The optimization aim is in fact to reach the frequency and the static deflection targets defined by the designer of the structure: the complete four-dimensional search space is considered for the optimization process. The optimized material profile obtained with the three methodologies is presented as a result of the optimization problem solved for each shell or panel structure.
Recent Strategy of Biodiesel Production from Waste Cooking Oil and Process Influencing Parameters: A Review
Authors: Gnanaprakasam A. , Sivakumar V. M. , Surendhar A. , Thirumarimurugan M. , Kannadasan T.
Published: May 2013

Cost of biodiesel produced from virgin vegetable oil through transesterification is higher than that of fossil fuel, because of high raw material cost. To minimize the biofuel cost, in recent days waste cooking oil was used as feedstock. Catalysts used in this process are usually acids, base, and lipase. Since lipase catalysts are much expensive, the usage of lipase in biodiesel production is limited. In most cases, NaOH is used as alkaline catalyst, because of its low cost and higher reaction rate. In the case of waste cooking oil containing high percentage of free fatty acid, alkaline catalyst reacts with free fatty acid and forms soap by saponification reaction. Also, it reduces the biodiesel conversions. In order to reduce the level of fatty acid content, waste cooking oil is pretreated with acid catalyst to undergo esterification reaction, which also requires high operating conditions. In this review paper, various parameters influencing the process of biofuel production such as reaction rate, catalyst concentration, temperature, stirrer speed, catalyst type, alcohol used, alcohol to oil ratio, free fatty acid content, and water content have been summarized.
Superficial Siderosis and Sudden Sensorineural Hearing Loss: A Case Report and Review of the Literature
Authors: Lee Kirsti S. V. , Sritharan Niranjan , Forrest Allan
Published: May 2013

This case report highlights an unusual case of sudden sensorineural hearing loss related to superficial siderosis (SS). Our patient had a craniotomy for medulloblastoma 23 years earlier, and this may represent a delayed complication related to this procedure. Magnetic resonance imaging (MRI) remains the key diagnostic investigation to illustrate the imaging features of superficial siderosis and exclude other pathologies. Increased awareness of progressive and sudden hearing complications caused by SS is important in the otolaryngologic community to expedite management and better counsel patients during the consent process.
Prognostic Value of Complete Blood Count and Electrolyte Panel during Emergency Department Evaluation for Acute Ischemic Stroke
Authors: Ganti Latha , Gilmore Rachel M. , Weaver Amy L. , Brown Robert D.
Published: May 2013

Objective. To determine whether routine laboratory parameters are predictors of early mortality after acute ischemic stroke (AIS).
Methods. The cohort consisted of 522 consecutive patients with AIS presenting to the emergency department (ED) at a
tertiary referral center during a 27-month period, residing within the surrounding ten counties. Serum laboratory
values were obtained for all patients and categorized according to whether the levels were low, normal, or high.
These laboratory results were evaluated as potential predictors of 90-day mortality using Cox proportional
hazards models. The associations were summarized by calculating risk ratios (RRs) and 95% confidence
intervals (CI). Results. The presence of elevated white blood cell count (RR 2.2, 95% CI 1.5–3.4), low bicarbonate (RR 4.2, 95% CI 2.6–6.7), low calcium (RR 2.9, 95% CI 1.4–5.9), and high glucose (RR 1.3, 95% 1.1–1.6) were each univariately associated with significantly higher mortality within the first 90 days. Based on fitting a multivariate Cox regression model, elevated white blood cell count, low bicarbonate, and high glucose were each identified as being jointly associated with early mortality ().
Conclusion. Early leukocytosis, acidosis, and hyperglycemia and hypocalcemia in AIS appear to be associated with early
mortality. Whether addressing these factors will impact survival remains to be investigated.
VEGF-C and VEGF-D Blockade Inhibits Inflammatory Skin Carcinogenesis
Authors: Alitalo Annamari K. , Proulx Steven T. , Karaman Sinem , Aebischer David , Martino Stefania , Jost Manuela , Schneider Nicole , Bry Maija , Detmar Michael
Published: May 2013

VEGF-C and VEGF-D were identified as lymphangiogenic growth factors and later shown to promote tumor metastasis, but their effects on carcinogenesis are poorly understood. Here, we have studied the effects of VEGF-C and VEGF-D on tumor development in the murine multistep chemical carcinogenesis model of squamous cell carcinoma by using a soluble VEGF-C/VEGF-D inhibitor. After topical treatment with a tumor initiator and repeated tumor promoter applications, transgenic mice expressing a soluble VEGF-C/VEGF-D receptor (sVEGFR-3) in the skin developed significantly fewer squamous cell tumors with a delayed onset when compared with wild-type mice or mice expressing sVEGFR-3 lacking the ligand-binding site. Epidermal proliferation was reduced in the carcinogen-treated transgenic skin, whereas epidermal keratinocyte proliferation in vitro was not affected by VEGF-C or VEGF-D, indicating indirect effects of sVEGFR-3 expression. Importantly, transgenic mouse skin was less sensitive to tumor promoter–induced inflammation, with reduced angiogenesis and blood vessel leakage. Cutaneous leukocytes, especially macrophages, were reduced in transgenic skin without major changes in macrophage polarization or blood monocyte numbers. Several macrophage-associated cytokines were also reduced in transgenic papillomas, although the dermal macrophages themselves did not express VEGFR-3. These findings indicate that VEGF-C/VEGF-D are involved in shaping the inflammatory tumor microenvironment that regulates early tumor progression. Our results support the use of VEGF-C/VEGF-D–blocking agents not only to inhibit metastatic progression, but also during the early stages of tumor growth. Cancer Res; 73(14); 4212–21. ©2013 AACR.
Circulating Adipokine Levels and Endometrial Cancer Risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Authors: Luhn Patricia , Dallal Cher M. , Weiss Jocelyn M. , Black Amanda , Huang Wen-Yi , Lacey James V. , Hayes Richard B. , Stanczyk Frank Z. , Wentzensen Nicolas , Brinton Louise A.
Published: May 2013

Background: Circulating adipokine levels may be associated with endometrial cancer risk, yet few studies have evaluated these markers prospectively.

Methods: We conducted a nested case–control study of postmenopausal women in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (n = 78,216), including 167 incident endometrial cancer cases and 327 controls that were matched on age, study center, race, study year of diagnosis, year of blood draw, time of day of blood draw, and menopausal hormone therapy (MHT) use. Adipokine and estradiol levels were categorized into tertiles (T). ORs and 95% confidence intervals (CIs) for the associations of adiponectin, leptin, and visfatin with endometrial cancer risk were estimated by conditional logistic regression, adjusting for known endometrial cancer risk factors, including body mass index (BMI) and circulating estradiol levels.

Results: Adiponectin levels were inversely associated with risk of endometrial cancer [ORT3vsT1 = 0.48; 95% CI, 0.29–0.80); Ptrend < 0.01], whereas elevated leptin levels showed a positive association [2.77 (1.60–4.79); Ptrend < 0.01]. These results remained significant after adjustment for estradiol, but not after further adjustment for BMI. When analyses were restricted to non-MHT users, associations of adiponectin and leptin were stronger and remained significant after adjustment for estradiol and BMI [0.25 (0.08–0.75); Ptrend = 0.01 and 4.72 (1.15–19.38); Ptrend = 0.02, respectively]. Nonsignificant positive associations were observed for visfatin.

Conclusion: Adipokines may influence endometrial cancer risk through pathways other than estrogen-mediated cell growth in postmenopausal women not currently on MHT.

Impact: Understanding how adipokines influence endometrial cancer risk may help to elucidate biological mechanisms important for the observed obesity–endometrial cancer association. Cancer Epidemiol Biomarkers Prev; 22(7); 1304–12. ©2013 AACR.
Deubiquitinase Inhibition of 19S Regulatory Particles by 4-Arylidene Curcumin Analog AC17 Causes NF-κB Inhibition and p53 Reactivation in Human Lung Cancer Cells
Authors: Zhou Binhua , Zuo Yinglin , Li Baojian , Wang Hao , Liu Hao , Wang Xianfeng , Qiu Xu , Hu Yun , Wen Shijun , Du Jun , Bu Xianzhang
Published: May 2013

Proteasome inhibitors have been suggested as potential anticancer agents in many clinical trials. Recent evidence indicates that proteasomal deubiquitinase (DUB) inhibitors, bearing a different mechanism from that of traditional proteasome inhibitors, would be appropriate candidates for new anticancer drug development. In the present study, we describe the deubiquitinase inhibition of 19S regulatory particles (19S RP) by AC17, a 4-arylidene curcumin analog synthesized in our laboratory. Although 4-arylidene curcumin analogs were reported to act as inhibitory κB (IκB) kinase (IKK) inhibitors, AC17 instead induced a rapid and marked accumulation of ubiquitinated proteins without inhibiting proteasome proteolytic activities. In contrast to its parent compound, curcumin, which is a proteasome proteolytic inhibitor, AC17 serves as an irreversible deubiquitinase inhibitor of 19S RP, resulting in inhibition of NF-κB pathway and reactivation of proapoptotic protein p53. In addition, in a murine xenograft model of human lung cancer A549, treatment with AC17 suppresses tumor growth in a manner associated with proteasome inhibition, NF-κB blockage, and p53 reactivation. These results suggest that 4-arylidene curcumin analogs are novel 19S deubiquitinase inhibitors with great potential for anticancer drug development. Mol Cancer Ther; 12(8); 1381–92. ©2013 AACR.
DNA Methylation Biomarkers for Noninvasive Diagnosis of Colorectal Cancer
Authors: Carmona F. Javier , Azuara Daniel , Berenguer-Llergo Antonio , Fernández Agustin F. , Biondo Sebastiano , de Oca Javier , Rodriguez-Moranta Francisco , Salazar Ramón , Villanueva Alberto , Fraga Mario F. , Guardiola Jordi , Capellá Gabriel , Esteller Manel , Moreno Victor
Published: May 2013

DNA methylation biomarkers for noninvasive diagnosis of colorectal cancer (CRC) and precursor lesions have been extensively studied. Different panels have been reported attempting to improve current protocols in clinical practice, although no definite biomarkers have been established.

In the present study, we have examined patient biopsies starting from a comprehensive analysis of DNA methylation differences between paired normal and tumor samples in known cancer-related genes aiming to select the best performing candidates informative for CRC diagnosis in stool samples.

Five selected markers were considered for subsequent analyses in independent biologic cohorts and in silico data sets. Among the five selected genes, three of them (AGTR1, WNT2 and SLIT2) were validated in stool DNA of affected patients with a detection sensitivity of 78% [95% confidence interval (CI), 56%–89%]. As a reference, DNA methylation of VIM and SEPT9 was evaluated in a subset of stool samples yielding sensitivities of 55% and 20%, respectively. Moreover, our panel may complement histologic and endoscopic diagnosis of inflammatory bowel disease (IBD)-associated neoplasia, as it was also efficient detecting aberrant DNA methylation in non-neoplastic tissue samples from affected patients.

This novel panel of specific methylation markers can be useful for early diagnosis of CRC using stool DNA and may help in the follow-up of high-risk patients with IBD. Cancer Prev Res; 6(7); 656–65. ©2013 AACR.
Longitudinal Transmission Pathways of Borderline Personality Disorder Symptoms: From Mother to Child?
Authors: Reinelt Eva , Stopsack Malte , Aldinger Maren , Ulrich Ines , Grabe Hans Jörgen , Barnow Sven
Published: May 2013

Background: There is evidence that the borderline symptomatology of the mother longitudinally predicts the number of borderline criteria met by the children. However, possible underlying mechanisms have rarely been examined. In line with transactional models of borderline personality disorder (BPD), we analyzed a broad concept of maladaptive mother-child interactions of mothers with BPD symptoms towards their children, including insensitive parenting and mother-child discrepancies, in reporting the child's psychopathological behavior. Sampling/Methods: The sample was drawn from the population-based Greifswald Family Study and consisted of 295 children and their biological mothers. Both were examined at two points in time, first when the children were about 15 years old (T₀) and again 5 years later (T1), using path analyses. Results: Maladaptive mother-child interactions (especially an overprotective and rejecting parenting style and high discrepancies regarding internalizing problems) mediate the longitudinal transmission of borderline symptoms from mother to child. Furthermore, our data revealed that this result is consistent for various youth symptoms which are associated with BPD such as impulsivity or dissociation. Conclusion: The data of the current study imply that the transmission of borderline symptoms from mother to child is mediated by maladaptive mother-child interactions. For this reason early and professional support may be useful to prevent these children from developing severe psychopathology.
Management of Twin Anemia-Polycythemia Sequence Using Intrauterine Blood Transfusion for the Donor and Partial Exchange Transfusion for the Recipient
Authors: Genova L. , Slaghekke F. , Klumper F.J. , Middeldorp J.M. , Steggerda S.J. , Oepkes D. , Lopriore E.
Published: May 2013

Twin anemia-polycythemia sequence (TAPS) is a rare condition which may occur either spontaneously in uncomplicated monochorionic twin pregnancies or may develop after laser treatment in twin-twin transfusion syndrome. TAPS is characterized by a large intertwin discordance in hemoglobin levels without discordance in amniotic fluid levels, and may lead to severe complications including fetal hydrops, hematological morbidity and perinatal mortality. Several treatments have been proposed including intrauterine transfusion, laser surgery, elective delivery and expectant management. The optimal treatment remains unclear. In this case series we report 3 TAPS cases managed recently at our center with a combination of intrauterine blood transfusion for the anemic twin and intrauterine partial exchange transfusion for the polycythemic twin. In 1 case, the donor was found to have severe cerebral injury on neuroimaging examination. We propose etiologic mechanisms for cerebral injury in TAPS, discuss the rationale behind this treatment alternative, and evaluate the pros and cons of the various management options.
Anemic Nevus in Neurofibromatosis Type 1
Authors: Tadini G. , Brena M. , Pezzani L. , Gelmetti C. , Santagada F. , Boldrini M.P.
Published: May 2013

Anemic nevus (AN) is a congenital-vascular anomaly of the skin. Although it is a benign and asymptomatic lesion, it could be a frequent ‘cutaneous finding' in neurofibromatosis type 1 (NF1). We performed a retrospective analysis to detect the prevalence of AN in all children with a presumptive diagnosis of NF1 treated in our center.
A Randomized Controlled Trial on Cognitive Restructuring and Imagery Modification to Reduce the Feeling of Being Contaminated in Adult Survivors of Childhood Sexual Abuse Suffering from Posttraumatic Stress Disorder
Authors: Jung Kerstin , Steil Regina
Published: May 2013

Background: The feeling of being contaminated (FBC) is a common phenomenon in survivors of childhood sexual abuse (CSA) suffering from posttraumatic stress disorder (PTSD). Thus far, this symptom has been neglected in research and therapy. For this reason, we developed Cognitive Restructuring and Imagery Modification (CRIM), a two-session treatment (lasting 90 and 50 min) that specifically targets the FBC. The present study examined the efficacy of the treatment. Methods: Thirty-four women with CSA-related PTSD (mean age = 37 years) were randomized to either the CRIM group or a waitlist control group. Primary outcomes were intensity, vividness, and uncontrollability of the FBC, associated distress, and PTSD symptoms, which were assessed using the Clinician-Administered PTSD Scale and the Posttraumatic Diagnostic Scale. Outcomes were measured pre- and posttreatment, and at the 4-week follow-up. (M)ANOVAs were used to compare improvements across conditions. Results: All FBC scores yielded a greater reduction in the CRIM group than the waitlist control (WL) group. Between-group effect sizes at follow-up were large and highly significant (intensity: d = 1.52, p < 0.001; vividness: d = 1.28, p < 0.001; uncontrollability: d = 1.77, p < 0.001; distress: d = 1.80, p < 0.001). PTSD symptoms also yielded a greater reduction in the CRIM group than the WL group, with large between-group effect sizes (Clinician-Administered PTSD Scale: d = 0.93, p < 0.001). Conclusions: Our findings support the efficacy of the newly developed CRIM in reducing the FBC and PTSD symptoms in adult survivors of CSA.
Is a Dexamethasone-Sparing Strategy Capable of Preventing Acute and Delayed Emesis Caused by Combined Doxorubicin and Paclitaxel for Breast Cancer? Analysis of a Phase II Trial
Authors: Damian Silvia , Celio Luigi , De Benedictis Elena , Mariani Paola , Agustoni Francesco , Ricchini Francesca , De Braud Filippo
Published: May 2013

Objective: The effectiveness of palonosetron without delayed dexamethasone dosing against emesis was investigated in patients scheduled to receive the corticosteroid-containing combination of doxorubicin and paclitaxel (AT) for 3 cycles. Methods: Chemo-naïve women with breast cancer receiving doxorubicin (60 mg/m2) and paclitaxel (200 mg/m2) were eligible. Patients received palonosetron 0.25 mg intravenously before chemotherapy, however, all patients also received a premedication consisting of prednisone (25 mg orally the evening before therapy) and hydrocortisone (250 mg intravenously just before paclitaxel). The primary end point was complete control (CC; no vomiting, no rescue anti-emetics, and no more than mild nausea) during the overall phase (days 1-5) following cycle 1. Results: Seventy-six patients were enrolled and evaluable (median age 50 years). Fifty-six patients (74%; 95% CI 62-83%) achieved overall CC. Acute (day 1) and delayed (days 2-5) CC rates were 78 and 74%, respectively. No vomiting rates for the acute, delayed and overall phases were 85, 85 and 83%, respectively. An exploratory analysis showed only a small decrease in the probability of achieving CC between cycle 1 (74%) and cycle 3 (66%). Conclusion: The dexamethasone-sparing strategy prevented emesis in more than 70% of breast cancer patients receiving their initial cycle of AT chemotherapy.
Soluble Human Leukocyte Antigen G Molecule Expression in Allogeneic Hematopoietic Stem Cell Transplantation: Good Predictor of Acute Graft-versus-Host Disease
Authors: Liu Hui , Chen Yinkui , Xuan Li , Wu Xiuli , Zhang Yu , Fan Zhiping , Huang Fen , Zhang Xian , Jiang Qianli , Sun Jing , Liu Qifa
Published: May 2013

Background: Graft-versus-host disease (GVHD) remains a main complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Human leukocyte antigen G (HLA-G) is a non-classical class I molecule exerting multiple immunoregulatory functions. The aim of this study was to explore the relationship between soluble HLA-G (sHLA-G) and GVHD after allo-HSCT. Methods: The sHLA-G levels were examined using enzyme-linked immunosorbent assay in patients with hematological malignancies (n = 106) before transplantation, on days +15 and +30 after transplantation, as well as healthy volunteers (n = 10). Results: The levels of sHLA-G5, sHLA-G6 and sHLA-G7 in patients on days +15 and +30 after transplantation were all significantly higher than those before transplantation (all p ≤ 0.001). The increased levels of sHLA-G5 on days +15 and +30 after transplantation were both significantly higher in patients with grade 0-I acute GVHD (aGVHD) compared to those with grade II-IV aGVHD (both p < 0.001). The increased levels of sHLA-G5 on days +15 and +30 after transplantation were both negatively correlated with the severity of aGVHD (both p < 0.001). Conclusion: sHLA-G5 might be a predictor of the occurrence and severity of aGVHD, which may help to establish individual prophylaxis against aGVHD and improve the survival for patients after allo-HSCT.
Indices of Insulin Resistance and Dyslipidemia Are Correlated with Lymphocyte Proneness to Apoptosis in Obese or Overweight Low Birth Weight Children
Authors: Barg Ewa , Szopa Jan , Pesz Karolina A. , Gąsiorowski Kazimierz
Published: May 2013

Aims: Our aim was to study the relationship between markers of cell proneness to apoptosis and indices of insulin resistance and dyslipidemia in children born with low birth weight (LBW). Methods: The study comprised 177 prepubertal children stratified by birth weight and their nutritional status into LBW (n = 138) and normal birth weight (NBW; n = 39) groups. We analyzed DNA from peripheral blood lymphocytes, separated by pulsed-field gel electrophoresis (PFGE), as well as the serum levels of cholesterol, HDL-cholesterol, triglycerides, fasting insulin and glucose, caspase 3, and BCL2. Results: LBW children with a BMI SDS >1.55 demonstrated increased content of the large fragments of the lymphocyte DNA [300-500 kb (DNA300-500 kb)] in electrophoretic slides (a marker of decreased chromatin stability and susceptibility of cells to apoptosis) compared to the NBW group. In these children the level of DNA300-500 kb exhibited a strong negative correlation with the serum level of antiapoptotic protein of BCL2 (r = -0.901). DNA300-500 kb significantly correlated with calculated indices of insulin resistance: HOMA-IR and QUICKI as well as with the indices of lipid homeostasis (Castelli and AIP). Conclusions: Increased susceptibility of lymphocytes to apoptosis correlated with a higher risk of insulin resistance and lipid disturbance in overweight or obese LBW children. A comprehensive study of the proneness of cells to apoptosis should be implemented to further investigate the pathomechanism of the metabolic syndrome in these children.
Experience in Integrating ALK Testing and Crizotinib into the Routine Treatment of Patients with Non-Small Cell Lung Cancer
Authors: Gautschi Oliver , Schefer Hubert , Riklin Christian , Strobel Klaus , Diebold Joachim
Published: May 2013

Background: Crizotinib, an inhibitor of the anaplastic lymphoma kinase (ALK), is approved since 2012 in Switzerland for use in ALK-rearranged advanced pretreated non-small cell lung cancer (NSCLC). Patients and Methods: Here we describe our own experience with crizotinib and ALK testing via fluorescence in-situ hybridization (FISH) in the first 10 ALK-positive patients who were treated in central Switzerland in 2011 on a compassionate use basis. Results: We have demonstrated that FISH testing for ALK can be performed simultaneously with other diagnostic procedures, providing oncologists with results in a timely manner to make informed decisions about patient treatment. The majority of our patients treated with crizotinib had a clinical benefit, and the drug was tolerated well. Conclusion: The clinical development of crizotinib has been extremely rapid. Nonetheless, by the time crizotinib was approved, many centers including our own had local testing in place and clinical experience with the drug. This emphasizes the importance of broad clinical studies and compassionate use programs in oncology.
Multiple Low-Grade Fibromyxoid Sarcoma on the Upper Arms with Atypical Histological Presentation
Authors: Furudate Sadanori , Fujimura Taku , Kambayashi Yumi , Tsukada Akira , Numata Yukikazu , Aiba Setsuya
Published: May 2013

Low-grade fibromyxoid sarcoma (LGFMS) is a rare variant of spindle cell tumor that is composed of collagen-rich and myxoid parts. We describe the case of a 61-year-old Japanese patient with multiple, recurrent LGFMS on the upper arms with atypical histological presentation. In the present case, we resected the tumor several times with a minimal surgical margin, as in Moh's microsurgery. However, this can frequently lead to local recurrence of the tumor. Our case suggested that, regarding mesenchymal tumors with potential of malignancy in the skin, an initial wide excision is indispensable for complete remission of the tumor, even for low-grade malignancy such as LGFMS.
Adult Intestinal Intussusception Caused by an Inflammatory Myofibroblastic Tumor
Authors: Ida Satoshi , Matsuzaki Hosei , Kawashima Shinichi , Watanabe Masayuki , Akiyama Yasuhiro , Baba Hideo
Published: May 2013

Inflammatory myofibroblastic tumor (IMT), which usually affects young adults and children, is a solid neoplastic mesenchymal proliferation composed of myofibroblastic spindle cells admixed with inflammatory infiltrates. Numerous extrapulmonary sites of these tumors have been found, but intestinal IMT is rare, especially in elderly patient. Its diagnosis is recognized as difficult because the patients usually do not have a specific symptom. Here, we present the case of a 79-year-old man with an IMT that caused small intestinal intussusception, which was diagnosed by abdominal ultrasonography. We review the literature on IMT and specially focus on the diagnostic modalities for this disease.