bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Simultaneous Knockdown of HER2 and PTK6 on Malignancy and Tumor Progression in Human Breast Cancer Cells
Authors: Ludyga Natalie , Anastasov Natasa , Rosemann Michael , Seiler Jana , Lohmann Nadine , Braselmann Herbert , Mengele Karin , Schmitt Manfred , Höfler Heinz , Aubele Michaela 
Published: January 2013

Abstract
Breast cancer is the most common malignancy in women of the Western world. One prominent feature of breast cancer is the co- and overexpression of HER2 and protein tyrosine kinase 6 (PTK6). According to the current clinical cancer therapy guidelines, HER2-overexpressing tumors are routinely treated with trastuzumab, a humanized monoclonal antibody targeting HER2. Approximately, 30% of HER2-overexpressing breast tumors at least initially respond to the anti-HER2 therapy, but a subgroup of these tumors develops resistance shortly after the administration of trastuzumab. A PTK6-targeted therapy does not yet exist. Here, we show for the first time that the simultaneous knockdown in vitro, compared with the single knockdown of HER2 and PTK6, in particular in the trastuzumab-resistant JIMT-1 cells, leads to a significantly decreased phosphorylation of crucial signaling proteins: mitogen-activated protein kinase 1/3 (MAPK 1/3, ERK 1/2) and p38 MAPK, and (phosphatase and tensin homologue deleted on chromosome ten) PTEN that are involved in tumorigenesis. In addition, dual knockdown strongly reduced the migration and invasion of the JIMT-1 cells. Moreover, the downregulation of HER2 and PTK6 led to an induction of p27, and the dual knockdown significantly diminished cell proliferation in JIMT-1 and T47D cells. In vivo experiments showed significantly reduced levels of tumor growth following HER2 or PTK6 knockdown. Our results indicate a novel strategy also for the treatment of trastuzumab resistance in tumors. Thus, the inhibition of these two signaling proteins may lead to a more effective control of breast cancer. Mol Cancer Res; 11(4); 381–92. ©2013 AACR.
Alpha-CaMKII Plays a Critical Role in Determining the Aggressive Behavior of Human Osteosarcoma
Authors: Daft Paul G. , Yuan Kaiyu , Warram Jason M. , Klein Michael J. , Siegal Gene P. , Zayzafoon Majd 
Published: January 2013

Abstract
Osteosarcoma is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. Despite improvements in osteosarcoma treatment, more specific molecular targets are needed as potential therapeutic options. One target of interest is α-Ca2+/calmodulin-dependent protein kinase II (α-CaMKII), a ubiquitous mediator of Ca2+-linked signaling, which has been shown to regulate tumor cell proliferation and differentiation. Here, we investigate the role of α-CaMKII in the growth and tumorigenicity of human osteosarcoma. We show that α-CaMKII is highly expressed in primary osteosarcoma tissue derived from 114 patients, and is expressed in varying levels in different human osteosarcoma (OS) cell lines [MG-63, N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)/HOS, and 143B). To examine whether α-CaMKII regulates osteosarcoma tumorigenic properties, we genetically inhibited α-CaMKII in two osteosarcoma cell lines using two different α-CaMKII shRNAs delivered by lentiviral vectors and overexpressed α-CaMKII by retrovirus. The genetic deletion of α-CaMKII by short hairpin RNA (shRNA) in MG-63 and 143B cells resulted in decreased proliferation (50% and 41%), migration (22% and 25%), and invasion (95% and 90%), respectively. The overexpression of α-CaMKII in HOS cells resulted in increased proliferation (240%), migration (640%), and invasion (10,000%). Furthermore, α-CaMKII deletion in MG-63 cells significantly reduced tumor burden in vivo (65%), whereas α-CaMKII overexpression resulted in tumor formation in a previously nontumor forming osteosarcoma cell line (HOS). Our results suggest that α-CaMKII plays a critical role in determining the aggressive phenotype of osteosarcoma, and its inhibition could be an attractive therapeutic target to combat this devastating adolescent disease. Mol Cancer Res; 11(4); 349–59. ©2013 AACR.
Defining the Role of Histone Deacetylases in the Inhibition of Mammary Carcinogenesis by Dietary Energy Restriction (DER): Effects of Suberoylanilide Hydroxamic Acid (SAHA) and DER in a Rat Model
Authors: Zhu Zongjian , Jiang Weiqin , McGinley John N. , Thompson Henry J. 
Published: January 2013

Abstract
Dietary energy restriction (DER) inhibits experimentally induced mammary cancer, an effect accompanied by elevated levels of silent information regulator 2 (SIRT1), a class III histone deacetylase (HDAC). However, the effect of DER on targets of other classes of HDACs has not been reported, a highly relevant issue given evidence that HDAC induction favors the development of cancer and tumor growth. Experiments were carried out to determine whether suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor with broad activity, would affect the anti-cancer activity of DER. Female Sprague Dawley rats (n = 30/group) were injected with 1-methyl-1-nitrosourea (50 mg/kg) at 21 days of age and 7 days thereafter were randomized to groups fed: (i) control diet (AIN-93G), (ii) 0.1% SAHA (w/w), (iii) 40% DER, or (iv) 0.1% SAHA + 40% DER. An additional group was fed 0.1% SAHA + 40%DER for 5 weeks and released to control diet for 3 weeks. DER significantly reduced mammary cancer incidence, multiplicity, and cancer burden and prolonged cancer latency (P &lt; 0.01). Cancer inhibition was maintained in SAHA + DER, despite evidence that histone (H2ALys9, H2BLys5, and H4Lys5/8/12/16, but not H3Lys9; P &lt; 0.001) and non-histone protein deacetylation (p53Lys373 and p53Lys382; P &lt; 0.001) induced by DER was reversed by SAHA. This indicates that the inhibition of DER of cancer is not dependent on HDAC induction. After releasing rats from DER + SAHA, cancer multiplicity remained lower than control (P &lt; 0.05), consistent with apoptosis-mediated cell deletion. These findings support further investigation of the hypothesis that HDAC induction by DER blunts its anti-carcinogenic impact. Cancer Prev Res; 6(4); 290–8. ©2013 AACR.
Disruption of components of vascular endothelial growth factor angiogenic signalling system in metabolic syndrome
Authors: Akter Shamima , Rahman Md. Mizanur , Islam Md. Majedul , Islam A. M. Shahidul , Sultana Sayeeda N. , Mowa Chishimba N. , Yamaguchi Naoto , Okazaki Osamu , Satoru Kawano , Kimura Sosuke , Hiroe Michiaki , Mizutani Taro , Moroi Masao , Jesmin Subrina 
Published: January 2013

SummaryMetabolic syndrome (MetS) is associated with impaired angiogenesis, a process that is chiefly regulated by vascular endothelial growth factor (VEGF) upon binding to its specific receptors, VEGF-R1 and VEGF-R2. The purpose of the present study was to assess trends or patterns in plasma levels of VEGF and its soluble receptors in subjects with (MetS) or without (non-MetS) MetS; and further examine their association with clinical or metabolic parameters using a subpopu-lation of South Asian country. A total of 1,802 rural Bangladeshi women aged ≥15 years were studied using a population-based cross-sectional survey. Plasma levels of VEGF were found to be significantly increased (MetS vs. non-MetS: 483.9 vs. 386.9, p<0.001), whereas, the soluble forms of VEGF receptors, sVEGF-R1 and sVEGF-R2, were significantly decreased in subjects with Mets (sVEGF-R1, MetS vs. non-MetS: 512.5 vs. 631.3, p<0.001; sVEGF-R2, MetS vs. non-MetS: 9,302.8 vs. 9,787.4, p=0.004). After adjustment for age and all potential variables, multiple regression analysis revealed that plasma levels of VEGF had significant positive association with blood glucose (p = 0.019) and body mass index (p = 0.007). We also found that mean plasma levels of VEGF increased in direct proportion to levels of MetS components. The present study is the first ever to demonstrate a positive association between trends in levels of plasma VEGF and MetS using a large sample size from South Asia. The association between plasma VEGF and MetS needs further investigations in order to clearly decipher the clinical predictive value and accuracy of plasma VEGF in MetS.
Serum levels of anti-apolipoprotein A-1 auto-antibodies and myeloperoxidase as predictors of major adverse cardiovascular events after carotid endarterectomy
Authors: Spinella Giovanni , Pagano Sabrina , Bertolotto Maria , Pane Bianca , Pende Aldo , Galan Katia , Roux-Lombard Pascale , Combescure Christophe , Dallegri Franco , Vuilleumier Nicolas , Montecucco Fabrizio , Mach François , Palombo Domenico 
Published: January 2013

SummaryWe aimed at challenging the prognostic accuracies of myeloperoxidase (MPO) and antibodies anti-apolipoprotein A-1 (anti-apoA-1 IgG), alone or in combination, for major adverse cardiovascular events (MACE) prediction, one year after carotid endarterectomy (CEA). In this prospective single centre study, 178 patients undergoing elective CEA were included. Serum anti-apoA-1 IgG and MPO were assessed by enzyme-linked immunosorbent assay prior to the surgery. Post-hoc determination of the MPO cut-off was performed by receiver operating characteristics (ROC) analyses. MACE was defined by the occurrence of fatal or non-fatal acute coronary syndromes or stroke during one year follow-up. Prognostic accuracy of anti-apoA-1 IgG was assessed by ROC curve analyses, survival analyses and reclassification statistics. During follow-up, 5% (9/178) of patients presented a MACE, and 29% (52/178) were positive for anti-apoA-1 IgG. Patients with MACE had higher median MPO and anti-apoA-1 IgG levels at admission (p=0.01), but no difference for the 10-year global Framingham risk score (FRS) was observed (p=0.22). ROC analyses indicated that both MPO and anti-apoA-1 IgG were significant predictors of subsequent MACE (area under the curve [AUC]: 0.75, 95% confidence interval [95%CI]: 0.61–0.89, p=0.01; and 0.74, 95%CI: 0.59–90; p=0.01), but combining anti-apoA-1 IgG positivity and MPO>857 ng/ml displayed the best predictive accuracy (AUC: 0.78, 95%CI: 0.65–0.91; p=0.007). It was associated with a poorer MACE-free survival (98.2% vs. 57.1%; p<0.001, LogRank), with a positive likelihood ratio of 13.67, and provided incremental predictive ability over FRS. In conclusion, combining the assessment of anti-apoA-1 IgG and MPO appears as a promising risk stratification tool in patients with severe carotid stenosis.
Diet of the Eurasian badger (Meles meles) in the Western Carpathians and its implications for species conservation in Poland
Authors: Mysłajek Robert W. , Nowak Sabina , Rożen Anna , Jędrzejewska Bogumiła 
Published: January 2013

Food composition of the Eurasian badger Meles meles was studied in the mountain zone and foothills of the Western Carpathians (Southern Poland). The diet, obtained by scat analysis, was compared with availability of earthworms, fruits, amphibians, rodents and ground nesting birds (capercaillie Tetrao urogallus and hazel grouse Bonasa bonasia) within both altitudinal zones. Earthworms and fruits were the most abundant food source in the foothills, while amphibians were scarce and rodents were equally available in both altitudinal zones. Capercaillie and hazel grouse occurred in the forests above 560 m a.s.l. In the foothills, vegetable matter (mainly fruits), constituted 56.3%, and earthworms 39.6%, of the biomass consumed, while mammals were supplementary resources (2.9%). In the mountains, the importance of vegetable matter was smaller (47.9%). Earthworms and insects had a similar share (37.8% and 1.8%, respectively), but mammals were eaten much more intensively (13.9%). Birds (exclusively domestic hen) were taken by badgers only in the foothills (0.6%). There was a seasonal variation in badger diet composition in both altitudinal zones, as earthworms dominated in spring, while fruits were eaten mainly in summer and autumn. The composition of the badgers’ diet only slightly differed between foothills and mountains. This was probably caused by regular movement of badgers between elevational zones during foraging. We conclude that the present hunting regulation, which allows year-round hunting on badgers in areas inhabited by capercaillie, is not justified.
Training Haptic Stiffness Discrimination
Authors: Teodorescu Kinneret , Bouchigny Sylvain , Korman Maria 
Published: January 2013

Objective: In this study, we explored the time course of haptic stiffness discrimination learning and how it was affected by two experimental factors, the addition of visual information and/or knowledge of results (KR) during training. Background: Stiffness perception may integrate both haptic and visual modalities. However, in many tasks, the visual field is typically occluded, forcing stiffness perception to be dependent exclusively on haptic information. No studies to date addressed the time course of haptic stiffness perceptual learning. Method: Using a virtual environment (VE) haptic interface and a two-alternative forced-choice discrimination task, the haptic stiffness discrimination ability of 48 participants was tested across 2 days. Each day included two haptic test blocks separated by a training block. Additional visual information and/or KR were manipulated between participants during training blocks. Results: Practice repetitions alone induced significant improvement in haptic stiffness discrimination. Between days, accuracy was slightly improved, but decision time performance was deteriorated. The addition of visual information and/or KR had only temporary effects on decision time, without affecting the time course of haptic discrimination learning. Conclusion: Learning in haptic stiffness discrimination appears to evolve through at least two distinctive phases: A single training session resulted in both immediate and latent learning. This learning was not affected by the training manipulations inspected. Application: Training skills in VE in spaced sessions can be beneficial for tasks in which haptic perception is critical, such as surgery procedures, when the visual field is occluded. However, training protocols for such tasks should account for low impact of multisensory information and KR.
Functional Outcomes and Patient Satisfaction After Fasciotomy for Chronic Exertional Compartment Syndrome
Authors: Packer Jonathan D. , Day Michael S. , Nguyen Joseph T. , Hobart Sarah J. , Hannafin Jo A. , Metzl Jordan D. 
Published: January 2013

Background: Patients with chronic exertional compartment syndrome who have failed nonoperative treatment are evaluated with pre-exertion and postexertion compartment pressure testing and may be treated with fasciotomy. Failure rates of up to 20% have been reported and may be related to factors such as age, sex, postexertion compartment pressures, compartment(s) released, and duration of symptoms. Hypothesis: Higher preoperative postexertion compartment pressures are correlated with higher success and patient satisfaction rates after fasciotomy. Study Design: Cohort study; Level of evidence, 3. Methods: From 1999 to 2008, patients with clinical symptoms of chronic exertional compartment syndrome with failed nonoperative management underwent standardized pre-exertion and postexertion compartment pressure measurements. Patients were then offered continued nonoperative treatment or referral to an orthopaedic surgeon for compartment release. Patients with a minimum 2-year follow-up were given a telephone questionnaire describing their pretreatment and posttreatment conditions including quality and duration of symptoms, analog pain scale, symptomatic and functional responses to treatment, and satisfaction with treatment. Medical records and operative reports were reviewed. Results: The mean follow-up period for the nonoperative treatment group (n = 27) was 5.6 years (range, 2.1-10.6) and for the operative group (n = 73) was 5.2 years (range, 2.0-11.3). The operative group had a higher success rate (81%) compared with the nonoperative group (41%) ( P < .001), and the operative group had a higher patient satisfaction rate (81%) compared with the nonoperative group (56%) ( P = .011). There was no significant correlation between compartment pressures and patient outcomes. Patients with combined anterior and lateral compartment releases had an increased failure rate compared with isolated anterior release (31% vs 0%, respectively; P = .035). Surgical patients who were post-college had a lower satisfaction rate (66%) compared with high school (89%) and college patients (94%) ( P = .017). Conclusion: High school and college patients (age <23 years) and isolated anterior compartment release (compared with anterior/lateral release) were factors associated with improved subjective function and satisfaction after fasciotomy. We recommend the avoidance of lateral release unless symptoms or postexertion compartment pressures are clearly indicative of lateral compartment involvement.
Responses of Portulaca oleracea Linn. to selenium exposure
Authors: Prabha D , Sivakumar S , Subbhuraam CV , Son HK 
Published: January 2013

The present study was investigated to evaluate the uptake and accumulation of selenium (Se) by the stem cuttings of Portulaca oleracea L. grown in alfisol amended with various concentrations of Se. P. oleracea accumulated a maximum of 63.4 µg g−1 dry weight in a short growth period of 42 days. The order of accumulation of Se among the plant parts was leaves (31.5 μg g−1) > stems (16.4 μg g−1) > roots (15.5 μg g−1). The accumulation potential was fourfold higher than the plant available concentration of 15.2 μg g−1 of Se g−1 of soil (diethylenetriaminepentaacetic acid extracted). Although the plant was able to accumulate Se in their tissues, increase in Se concentrations in soil caused a concentration-dependent decrease in the growth rate of plants (regeneration of leaves, number of leaves, number of roots, root length, stem length and biomass).
Multiorgan System Dysfunction in the Chylomicronemia Syndrome
Authors: Argula Rahul G. , Strange Charlie , Budisavljevic Milos N. 
Published: January 2013

Objective: To describe an extreme presentation of the chylomicronemia syndrome resulting in multiorgan system dysfunction. Patient: A 40-year-old African American male with no past medical history presented with multiorgan system dysfunction manifested by acute respiratory failure and acute kidney injury. He was noted to have very-high triglyceride levels (>5000 mg/dL) at admission. Interventions: An echocardiogram showed normal cardiac function. Amylase and lipase were normal. We confirmed the chylomicronemia syndrome with a triglyceride assay. The associated hyperviscosity was treated with plasmapheresis to reduce the plasma triglyceride level. Results: After 3 sessions of plasmapheresis, his triglyceride levels were significantly reduced, his oxygenation improved, and his acute kidney injury resolved. He was successfully extubated on day 7 of the intensive care unit stay. His diabetes and hypertriglyceridemia were newly diagnosed and drug therapy was instituted with home discharge on day 14. Conclusions: Severe chylomicronemia can cause multiorgan system dysfunction related to hyperviscosity. Early institution of plasmapheresis to reduce the triglyceride-rich lipoproteins can improve tissue perfusion and prevent further organ damage.
Preparation and properties of quartz cloth–reinforced Xylok composites fabricated by vacuum bag only process
Authors: Yang Guang , Gao Longfei , Cheng Kai 
Published: January 2013

Xylok resin was synthesized from 1,4-bis(methoxymethyl)-benzene and phenol through a condensation reaction catalyzed by p-toluenesulfonic acid. The effects of molar ratio of phenol to 1,4-bis(methoxymethyl)-benzene, reaction time and washing process on the properties of Xylok resin were investigated. Xylok composite laminates reinforced by quartz cloth were fabricated by vacuum bag only (VBO) process. Softening point of Xylok resin and volatile content of prepreg and voids in composites were also studied to better control process defects in composite laminates. Void content was measured by image analysis and calculating parameters. Experimental results showed that the Xylok composite laminates manufactured by VBO process had good thermal and dielectric properties. The flexural strength and flexural modulus of laminates could be 733 MPa and 23 GPa, respectively.
Hallux Valgus in Males—Part 2
Authors: Nery Caio , Coughlin Michael J. , Baumfeld Daniel , Ballerini Flávio José , Kobata Silvia 
Published: January 2013

Background: In an early report on this patient cohort, we concluded that a hallux valgus deformity in males is frequently hereditary in nature. An increase in the distal metatarsal articular angle (DMAA) was observed to be the major defining characteristic of hallux valgus in males. In this follow-up study, our goal was to evaluate the effectiveness of surgical treatment for this cohort of male patients. Methods: Data from 50 feet of male patients with hallux valgus who were surgically treated by the same surgeon between 1985 and 2005 were retrospectively analyzed. The technique was algorithmically chosen according to the severity and complexity of the deformity. Thus, 10 chevron osteotomies, 9 biplanar chevron osteotomies, 12 Mitchell osteotomies, 9 scarf osteotomies, and 10 basilar first metatarsal osteotomies were performed. The average follow-up was 10 years (range, 2-20). Results: After analyzing the angular radiological parameters, sesamoid subluxation, and the articular congruency, most procedures proved to have achieved adequate correction of the angular deformities. When examining each of the procedures separately, 4 of the 5 procedures had similar corrective capacities; the scarf osteotomy however had decidedly inferior results. The improvement in the postoperative American Orthopaedic Foot and Ankle Society (AOFAS) score demonstrated the clinical and functional improvement. Conclusions: The algorithm was based mainly upon the presence of increased DMAA and increased severity of angular deformities. We conclude that hallux valgus deformities in males were adequately corrected with the selected techniques. Greater difficulty or resistance to surgical treatment could not be detected when we contrasted our results to females. The scarf osteotomy proved to have an inferior corrective capacity compared to the other techniques used in this series. Level of Evidence: Level III, retrospective comparative series.
High risk of cardiovascular diseases after diagnosis of multiple sclerosis
Authors: Jadidi Elham , Mohammadi Mohammad , Moradi Tahereh 
Published: January 2013

Background: Studies of the risk of cardiovascular diseases (CVDs) in patients with multiple sclerosis (MS) have the potential to improve our understanding of the etiology of and the heterogeneity of prognosis and outcomes. Objectives: To investigate the risk of myocardial infarction (MI), stroke, heart failure (HF), and atrial fibrillation (AF) or Flutter in MS patients with different ethnicity, both female and male. Methods: Using Poisson regression, we performed a nationwide study in Sweden to investigate the association between the diagnosis of MS and the risk of MI, stroke, HF, or AF/Flutter in 8281 patients who were hospitalized due to MS from 1987 through 2009, plus 76,640 matched control individuals. We performed stratified analyses by sex, age at follow-up and country of birth. Results: Among MS patients, the incidence rate ratio for MI was 1.85 (95% confidence interval (CI) 1.59 to 2.15), for stroke was 1.71 (95% CI 1.46 to 2.00), for HF was 1.97 (95% CI 1.52 to 2.56) and for AF/Flutter was 0.63 (95% CI 0.46 to 0.87), as compared with individuals without MS. The increased risks were particularly prominent for women. These associations remained after stratification by sex, age and country of birth. Conclusion: We recommend careful surveillance and preventive CVDs measures among MS patients, particularly among the women.