bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ATPase Activity of Reptin Is Required for Its Effects on Tumor Cell Growth and Viability in Hepatocellular Carcinoma
Authors: Grigoletto Aude , Neaud Véronique , Allain-Courtois Nathalie , Lestienne Patrick , Rosenbaum Jean 
Published: December 2012

Abstract
Reptin is overexpressed in most human hepatocellular carcinomas. Reptin is involved in chromatin remodeling, transcription regulation, or supramolecular complexes assembly. Its silencing leads to growth arrest and apoptosis in cultured hepatocellular carcinoma cells and stops hepatocellular carcinoma progression in xenografts. Reptin has an ATPase activity linked to Walker A and B domains. It is unclear whether every Reptin function depends on its ATPase activity. Here, we expressed Walker B ATPase-dead mutants (D299N or E300G) in hepatocellular carcinoma cells in the presence of endogenous Reptin. Then, we silenced endogenous Reptin and substituted it with siRNA-resistant wild-type (WT) or Flag-Reptin mutants. There was a significant decrease in cell growth when expressing either mutant in the presence of endogenous Reptin, revealing a dominant negative effect of the ATPase dead mutants on hepatocellular carcinoma cell growth. Substitution of endogenous Reptin by WT Flag-Reptin rescued cell growth of HuH7. On the other hand, substitution by Flag-Reptin D299N or E300G led to cell growth arrest. Similar results were seen with Hep3B cells. Reptin silencing in HuH7 cells led to an increased apoptotic cell death, which was prevented by WT Flag-Reptin but not by the D299N mutant. These data show that Reptin functions relevant for cancer are dependent on its ATPase activity, and suggest that antagonists of Reptin ATPase activity may be useful as anticancer agents. Mol Cancer Res; 11(2); 133–9. ©2012 AACR.
Dietary Immunosuppressants Do Not Enhance UV-Induced Skin Carcinogenesis, and Reveal Discordance between p53-Mutant Early Clones and Carcinomas
Authors: Voskamp Pieter , Bodmann Carolien A , Koehl Gudrun E , Rebel Heggert G. , Van Olderen Marjolein G.E. , Gaumann Andreas , El Ghalbzouri Abdoel , Tensen Cornelis P. , Bavinck Jan N. Bouwes , Willemze Rein , Geissler Edward K. , De Gruijl Frank R. 
Published: December 2012

AbstractImmunosuppressive drugs are thought to cause the dramatically increased risk of carcinomas in sun-exposed skin of organ transplant recipients. These drugs differ in local effects on skin. We investigated whether this local impact is predictive of skin cancer risk and may thus provide guidance on minimizing the risk. Immunosuppressants (azathioprine, cyclosporine, tacrolimus, mycophenolate mofetil, and rapamycin) were assessed on altering the UV induction of apoptosis in human skin models and of p53 mutant cell clones (putative tumor precursors) and ensuing skin carcinomas (with mutant p53) in the skin of hairless mice. Rapamycin was found to increase apoptosis (three-fold), whereas cyclosporine decreased apoptosis (three-fold). Correspondingly, a 1.5- to five-fold reduction (P = 0.07) or a two- to three-fold increase (P &lt; 0.001) was found in cell clusters overexpressing mutant p53 in chronically UV-exposed skin of mice that had been fed rapamycin or cyclosporine, respectively. Deep sequencing showed, however, that the allelic frequency (∼5%) of the hotspot mutations in p53 (codons 270 and 275) remained unaffected. The majority of cells with mutated p53 seemed not to overexpress the mutated protein. Unexpectedly, none of the immunosuppressants admixed in high dosages to the diet accelerated tumor development, and cyclosporine even delayed tumor onset by approximately 15% (P &lt; 0.01). Thus, in contrast to earlier findings, the frequency of p53-mutant cells was not predictive of the incidence of skin carcinoma. Moreover, the lack of any accelerative effect on tumor development suggests that immunosuppressive medication is not the sole cause of the dramatic increase in skin cancer risk in organ transplant recipients. Cancer Prev Res; 6(2); 129–38. ©2012 AACR.
Smoking, Smoking Cessation, and Risk of Sudden Cardiac Death in Women
Authors: Sandhu Roopinder K. , Jimenez Monik C. , Chiuve Stephanie E. , Fitzgerald Kathryn C. , Kenfield Stacey A. , Tedrow Usha B. , Albert Christine M. 
Published: December 2012

Background—
Few prospective studies have examined quantitative cigarette consumption and smoking cessation on sudden cardiac death (SCD) risk with long-term follow-up.

Methods and Results—

We prospectively examined the association between cigarette smoking and smoking cessation on the risk of SCD among 101 018 women participating in the Nurses’ Health Study without known coronary heart disease, stroke, and cancer at baseline 1980. During 30 years of follow-up, we identified 351 SCD events. Compared with never smokers, current smokers had a 2.44-fold (95% CI, 1.80–3.31) increased risk of SCD after controlling for coronary risk factors. In multivariable analyses, quantity of cigarettes smoked daily (
P
value for trend, <0.0001) and smoking duration (
P
value for trend, <0.0001) were linearly associated with SCD risk among current smokers. Small-to-moderate amounts of cigarette consumption (1–14 per day) were associated with a significant 1.84-fold (95% CI, 1.16–2.92) increase in SCD risk and every 5 years of continued smoking was associated with an 8% increase in SCD risk (hazard ratio, 1.08; 95% CI, 1.05–1.12;
P
<0.0001). The SCD risk linearly decreased over time after quitting and was equivalent to that of a never smoker after 20 years of cessation (
P
value for trend, <0.0001).

Conclusions—
In this large prospective cohort of women without coronary heart disease at baseline, a strong dose–response relationship between cigarette smoking and SCD risk was observed, and smoking cessation significantly reduced and eventually eliminated excess SCD risk. This suggests efforts to prevent SCD among women should include aggressive strategies for smoking cessation.
Upper-Troposphere MM5 and WRF Temperature Error and Vertical Velocity Coupling
Authors: Soich Kelly , Rappenglueck Bernhard 
Published: December 2012

AbstractThe fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5) and the Weather Research and Forecasting Model (WRF) have been employed to predict troposphere temperatures for atmospheric study and operational decision making with positive results. Temperature bias in MM5 and WRF has been noted in previous troposphere studies through radiosonde vertical profile comparison; however, long-range horizontal in situ temperature observations have never been utilized to assess MM5 and WRF upper-troposphere temperature prediction. This study investigates upper-troposphere temperature forecasting of MM5 and WRF utilizing long-range in situ observations linking temperature error to forecast vertical velocity within the upper troposphere over surface elevation changes and different surface types. Temperature observations were taken during flights over North America, Europe, and southwest Asia between 6000 and 7600 m above sea level and compared with MM5 and WRF upper-troposphere forecasts. Regression analysis indicated MM5 and WRF upper-troposphere temperature forecast errors were related to changes in forecast vertical velocities within 100 km laterally of the modeled flight tracks between 39° and 59°N latitude. Temperature error and forecast vertical velocity coupling occurred in MM5 and WRF forecasts over land, while no evidence of temperature error and forecast vertical velocity coupling in MM5 or WRF forecasts was found over water. Evaluation of MM5 and WRF forecasts displayed varying results of temperature error and forecast vertical velocity coupling between specific surface elevations above sea level, vegetative cover, and urban influences.
Discoidin domain receptor 2 regulates neutrophil chemotaxis in 3D collagen matrices
Authors: Afonso Philippe V. , McCann Colin P. , Kapnick Senta M. , Parent Carole A. 
Published: December 2012

Key Points
DDR2 regulates the directional migration of neutrophils in 3D collagen matrices, but not on 2D surfaces. DDR2 regulates directionality through increased metalloproteinase secretion and generation of collagen-derived chemotactic peptide gradients.
MTH1 and RGT1 demonstrate combined haploinsufficiency in regulation of the hexose transporter genes in Saccharomyces cerevisiae
Authors: Dietzel Kevin L , Ramakrishnan Vidhya , Murphy Erin E , Bisson Linda F 
Published: December 2012

AbstractBackgroundTheSNF3gene in the yeastSaccharomyces cerevisiaeencodes a low glucose sensor that regulates expression of an important subset of the hexose transporter (HXT) superfamily. Null mutations ofsnf3result in a defect in growth on low glucose concentrations due to the inability to relieve repression of a subset of theHXTgenes. Thesnf3null mutation phenotype is suppressed by the loss of either one of the downstream co-repressor proteins Rgt1p or Mth1p. The relief of repression allows expression ofHXTtransporter proteins, the resumption of glucose uptake and therefore of growth in the absence of a functional Snf3 sensor.ResultsStrains heterozygous for both theRGT1andMTH1genes (RGT1/rgt1Δ MTH1/mth1Δ snf3Δ/snf3Δ) but homozygous for thesnf3∆ were found to grow on low glucose. Since null alleles in the heterozygous state lead to suppression,MTH1andRGT1display the phenomenon of combined haploinsufficiency. This observed haploinsufficiency is consistent with the finding of repressor titration as a mechanism of suppression ofsnf3. Mutants of theSTD1homolog ofMTH1did not display haploinsufficiency singly or in combination with mutations inRGT1.HXTgene reporter fusion assays indicated that the presence of heterozygosity at theMTH1andRGT1alleles leads to increased expression of theHXT2gene. Deletion of theHXT2gene in a heterozygous diploid,RGT1/rgt1Δ MTH1/mth1Δ snf3Δ/snf3Δ hxt2Δ/hxt2Δ,prevented the suppression ofsnf3Δ.ConclusionsThese findings support the model of relief of repression as the mechanism of restoration of growth on low glucose concentrations in the absence of functional Snf3p. Further, the observation thatHXT2is the gene responsible for restoration of growth under these conditions suggests that the numbers of repressor binding domains found in the regulatory regions of members of theHXTfamily may have biological relevance and enable differential regulation.
Comparative study comparing endoscopic thyroidectomy using the axillary approach and open thyroidectomy for papillary thyroid microcarcinoma
Authors: Lee Hayemin , Lee Jina , Sung Ki Young 
Published: December 2012

Abstract

Background
Endoscopic thyroidectomy has been applied prudently to malignant thyroid tumors. The purpose of our study was to compare the surgical outcomes of endoscopic thyroidectomy (ET) and conventional open thyroidectomy (COT) for micropapillary thyroid carcinoma.

Methods
From October 2002 to December 2008, 78 patients underwent unilateral lobectomy and isthmectomy with central lymph node dissection for papillary thyroid microcarcinoma. Of these, 37 patients underwent ET and 41patients COT. Surgical outcomes, including operation time, number of retrieved lymph nodes, postoperative complication rate and patients’ satisfaction with the cosmetic results, were analyzed.

Results
The mean age of the patients was 42.3 ± 7.6 years in the ET group and 49.0 ± 10.8 years in the OT group (P = 0.003). The operation time was shorter in the COT group (112.3 ± 14min) than in the ET group (138.4 ± 36.9 min, P< 0.01). However, there were no significant differences in tumor size (0.5 ± 0.231vs. 0.41 ± 0.264cm, P = 0.116), number of retrieved lymph nodes (3.63 ± 2.1vs. 3.82 ± 3.28, P = 0.78) or postoperative hospital stay (3.35 ± 0.94vs. 3.17 ± 1.16 days, P = 0.457). Patients in the ET group experienced more pain than those in the COT group at 1 and 7 days after the operation as evaluated by a visual analog scale (P = 0.037, 0.026). Cosmetically, patients in the ET group were very satisfied with the operative procedure according to the questionnaire we used (1.43 ± 0.55vs. 3.21 ± 0.72, P< 0.001). The mean follow-up period was 54.3 months in the ET group and 47.4 months in the COT group, and each group exhibited one case of tumor recurrence detected at the other thyroid lobe within 2 years.

Conclusions
Large series of prospective studies and long-term follow-up are needed, but the results of ET using the axillary approach for micropapillary thyroid carcinoma were not inferiortothose using COT, and it might be a safe and feasible procedure with good cosmetic results.
Enhanced antibacterial activity of roxithromycin loaded pegylated poly lactide-co-glycolide nanoparticles
Authors: Koopaei Mona Noori , Maghazei Mohamad Shahab , Mostafavi Seyed Hossein , Jamalifar Hossein , Samadi Nasrin , Amini Mohsen , Malek Soheyl Jafari , Darvishi Behrad , Atyabi Fatemeh , Dinarvand Rassoul 
Published: December 2012

Abstract

Background and the purpose of the study
The purpose of this study was to prepare pegylated poly lactide-co-glycolide (PEG-PLGA) nanoparticles (NPs) loaded with roxithromycin (RXN) with appropriate physicochemical properties and antibacterial activity. Roxithromycin, a semi-synthetic derivative of erythromycin, is more stable than erythromycin under acidic conditions and exhibits improved clinical effects.

Methods
RXN was loaded in pegylated PLGA NPs in different drug;polymer ratios by solvent evaporation technique and characterized for their size and size distribution, surface charge, surface morphology, drug loading, in vitro drug release profile, and in vitro antibacterial effects on S. aureus, B. subtilis, and S. epidermidis.

Results and conclusion
NPs were spherical with a relatively mono-dispersed size distribution. The particle size of nanoparticles ranged from 150 to 200 nm. NPs with entrapment efficiency of up to 80.0±6.5% and drug loading of up to 13.0±1.0% were prepared. In vitro release study showed an early burst release of about 50.03±0.99% at 6.5 h and then a slow and steady release of RXN was observed after the burst release. In vitro antibacterial effects determined that the minimal inhibitory concentration (MIC) of RXN loaded PEG-PLGA NPs were 9 times lower on S. aureus, 4.5 times lower on B. subtilis, and 4.5 times lower on S. epidermidis compared to RXN solution. In conclusion it was shown that polymeric NPs enhanced the antibacterial efficacy of RXN substantially.
Molecular sexing of threatened Gyps vultures: an important strategy for conservation breeding and ecological studies
Authors: Ghorpade Prabhakar B , Gupta Praveen K , Prakash Vibhu , Cuthbert Richard J , Kulkarni Mandar , Prakash Nikita , Das Asit , Sharma Anil K , Saini Mohini 
Published: December 2012

Abstract
During the last two decades populations of three resident species of Gyps vulture have declined dramatically and are now threatened with extinction in South Asia. Sex identification of vultures is of key importance for the purpose of conservation breeding as it is desirable to have an equal sex ratio in these monogamous species which are housed together in large colony aviaries. Because vultures are monomorphic, with no differences in external morphology or plumage colour between the sexes, other methods are required for sex identification. Molecular methods for sex identification in birds rely on allelic length or nucleotide sequence discrimination of the chromohelicase-DNA binding (CHD) gene located on male and female chromosomes ZZ and ZW, respectively. We characterized the partial sequences of CHD alleles from Gyps indicus, Gyps bengalensis, Gyps himalayensis and Aegypius monachus and analysed the applicability of five molecular methods of sex identification of 46 individual vultures including 26 known-sex G. bengalensis and G. indicus. The results revealed that W-specific PCR in combination with ZW-common PCR is a quick, accurate and simple method, and is ideal for sex identification of vultures. The method is also suitable to augment ecological studies for identifying sex of these endangered birds during necropsy examinations especially when gonads are not apparent, possibly due to regression during non-breeding seasons.
Effects of a polyphenol present in olive oil, oleuropein aglycone, in a murine model of intestinal ischemia/reperfusion injury
Authors: Campolo Michela , Di Paola Rosanna , Impellizzeri Daniela , Crupi Rosalia , Morittu Valeria Maria , Procopio Antonio , Perri Enzo , Britti Domenico , Peli Angelo , Esposito Emanuela , Cuzzocrea Salvatore 
Published: December 2012

AbstractOleuropein aglycone reduces damage in SAO-shocked mice.Dietary olive oil supplementation and more recently, olive oil phenols have been recommended as important therapeutic interventions in preventive medicine. Ole has several pharmacological properties, including antioxidant, anti-inflammatory, antiatherogenic, anticancer, antimicrobial, and antiviral and for these reasons, is becoming an important subject of study in recent years. The aim of this study was to investigate the effects of Ole aglycone on the modulation of the secondary events in mice subjected to intestinal IRI. This was induced in mice by clamping the superior mesenteric artery and the celiac trunk for 30 min, followed by release of the clamp, allowing reperfusion for 1 h. After 60 min of reperfusion, animals were killed for histological examination of the ileum tissue and immunohistochemical localization of proinflammatory cytokines (TNF-α and IL-1β) and adhesion molecules (ICAM-1 and P-sel); moreover, by Western blot analysis, we investigated the activation of NF-κB and IκBα. In addition, we evaluated the apoptosis process, as shown by TUNEL staining and Bax/Bcl-2 expressions. The results obtained by the histological and molecular examinations showed in Ole aglycone-treated mice, a decrease of inflammation and apoptosis pathway versus SAO-shocked mice. In conclusion, we propose that the olive oil compounds, in particular, the Ole aglycone, could represent a possible treatment against secondary events of intestinal IRI.
Phase III Randomized Intergroup Trial of CHOP Plus Rituximab Compared With CHOP Chemotherapy Plus131Iodine-Tositumomab for Previously Untreated Follicular Non-Hodgkin Lymphoma: SWOG S0016
Authors: Press Oliver W. , Unger Joseph M. , Rimsza Lisa M. , Friedberg Jonathan W. , LeBlanc Michael , Czuczman Myron S. , Kaminski Mark , Braziel Rita M. , Spier Catherine , Gopal Ajay K. , Maloney David G. , Cheson Bruce D. , Dakhil Shaker R. , Miller Thomas P. , Fisher Richard I. 
Published: December 2012

PurposeAdvanced follicular lymphomas (FL) are considered incurable with conventional chemotherapy and there is no consensus on the best treatment approach. Southwest Oncology Group (SWOG) and Cancer and Leukemia Group B compared the safety and efficacy of two immunochemotherapy regimens for FL in a phase III randomized intergroup protocol (SWOG S0016) that enrolled 554 patients with previously untreated, advanced-stage FL between March 1, 2001, and September 15, 2008.Patients and MethodsPatients were eligible for the study if they had advanced-stage (bulky stage II, III, or IV) evaluable FL of any grade (1, 2, or 3) and had not received previous therapy. In one arm of the study, patients received six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy at 3-week intervals with six doses of rituximab (CHOP-R). In another arm of the study, patients received six cycles of CHOP followed by consolidation with tositumomab/iodine I-131 tositumomab radioimmunotherapy (RIT).ResultsAfter a median follow-up period of 4.9 years, the 2-year estimate of progression-free survival (PFS) was 76% on the CHOP-R arm and 80% on the CHOP-RIT arm (P = .11). The 2-year estimate of overall survival (OS) was 97% on the CHOP-R arm and 93% on the CHOP-RIT arm (P = .08).ConclusionThere was no evidence of a significant improvement in PFS comparing CHOP-RIT with CHOP-R. However, PFS and OS were outstanding on both arms of the study. Future studies are needed to determine the potential benefits of combining CHOP-R induction chemotherapy with RIT consolidation and/or extended rituximab maintenance therapy.
EMA/CO for High-Risk Gestational Trophoblastic Neoplasia: Good Outcomes With Induction Low-Dose Etoposide-Cisplatin and Genetic Analysis
Authors: Alifrangis Constantine , Agarwal Roshan , Short Delia , Fisher Rosemary A. , Sebire Neil J. , Harvey Richard , Savage Philip M. , Seckl Michael J. 
Published: December 2012

Purpose Patients with high-risk (International Federation of Gynecology and Obstetrics score ≥ 7) gestational trophoblastic neoplasia (GTN) frequently receive etoposide, methotrexate, and dactinomycin alternating weekly with cyclophosphamide and vincristine (EMA/CO). Between 1979 and 1995, overall survival (OS) with this regimen at our institute was 85.4% with a significant proportion of early deaths (< 4 weeks). Here, we determine whether survival rates have improved in a more recent patient cohort (1995 to 2010). Patients and Methods Patients receiving EMA/CO were identified using the Charing Cross GTN database. Genetic analysis identified nongestational trophoblastic tumors (nGTTs). The use of induction low-dose etoposide 100 mg/m2 and cisplatin 20 mg/m2 (EP; days 1 and 2 every 7 days) since 1995 to reduce early deaths before commencing EMA/CO was noted. Results Four hundred thirty-eight patients received EMA/CO between 1995 and 2010. Six patients had nGTTs, 140 had high-risk disease, and 250 had relapsed/resistant low-risk GTN. OS was 94.3% in high-risk patients (90.4% including nGTTs) and 99.6% in the low-risk group, with a median follow-up time of 4.2 years. All patients with nGTT and seven patients with high-risk GTNs died as a result of drug-resistant disease. EP induction chemotherapy was given to 23.1% of high-risk patients (33 of 140 patients) with a large disease burden, and the early death rate was only 0.7% (n = 1; 95% CI, 0.1% to 3.7%) compared with 7.2% (n = 11 of 151 patients; 95% CI, 4.1% to 12.6%) in the pre-1995 cohort. Conclusion OS after EMA/CO for high-risk GTN has increased by nearly 9%. This reflects a more accurate estimate of OS by excluding nGTTs (3.9%) in patients with atypical presentations using genetic diagnosis. Low-dose induction EP in selected individuals also allows near complete elimination of early deaths. The latter should be considered routinely in high-risk GTN.