bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 3 study of induction treatment with concurrent chemoradiotherapy versus chemotherapy before surgery in patients with pathologically confirmed N2 stage IIIA nonsmall cell lung cancer (WJTOG9903)
Authors: Katakami Nobuyuki , Tada Hirohito , Mitsudomi Tetsuya , Kudoh Shinzoh , Senba Hiroshi , Matsui Kaoru , Saka Hideo , Kurata Takayasu , Nishimura Yasumasa , Fukuoka Masahiro 
Published: June 2012

AbstractBACKGROUND:This study sought to ascertain whether induction‐concurrent radiotherapy added to chemotherapy could improve the survival of patients undergoing surgery for stage IIIA N2 nonsmall cell lung cancer (NSCLC).METHODS:Patients with pathologically proven N2 disease were randomized to receive either induction chemotherapy (docetaxel 60 mg/m2 and carboplatin AUC [area under the receiver operating characteristic curve] = 5 for 2 cycles) plus concurrent radiation therapy (40 Gy) followed by surgery (CRS arm) or induction chemotherapy followed by surgery (CS arm). They subsequently underwent pulmonary resection when possible.RESULTS:Sixty patients were randomly assigned between December 2000 and August 2005. The study was prematurely terminated in January 2006 because of slow accrual. The most common toxicity was grade 3 or 4 leukopenia in 92.9% of patients in the CRS arm and 46.4% in the CS arm. Induction therapy was generally well tolerated, and there were no treatment‐related deaths in either arm. Downstaging in the CS arm and CRS arm was 21% and 40%, respectively. The progression‐free survival (PFS) and overall survival (OS) in the CS arm were 9.7 months and 29.9 months (PFS, hazard ratio [HR] = 0.68, P = .187), and those in the CRS arm were 12.4 months and 39.6 months (OS, HR = 0.77, P = .397), respectively. The PFS with and without downstaging was 55.0 and 9.4 months, respectively (HR = 3.39, P = .001). The OS with and without downstaging was 63.3 and 29.5 months, respectively (HR = 2.62, P = .021).CONCLUSIONS:The addition of radiotherapy to induction chemotherapy conferred better local control without significant adverse events. Tumor downstaging is important for prolonging the OS in patients with stage IIIA (N2) NSCLC. Cancer 2012. © 2012 American Cancer Society.
Safety, pharmacokinetics, and activity of EZN‐2208, a novel conjugate of polyethylene glycol and SN38, in patients with advanced malignancies
Authors: Kurzrock Razelle , Goel Sanjay , Wheler Jennifer , Hong David , Fu Siqing , Rezai Keyvan , Morgan‐Linnell Sonia K. , Urien Saik , Mani Sridhar , Chaudhary Imran , Ghalib Mohammed H. , Buchbinder Aby , Lokiec François , Mulcahy Mary 
Published: June 2012

AbstractBACKGROUND:EZN‐2208 is a water‐soluble, polyethylene glycol drug conjugate of SN38, which is the active moiety of irinotecan. In this study, the authors evaluated the tolerability, pharmacokinetics (PK), and activity of EZN‐2208 in adult patients with advanced solid tumors.METHODS:Patients in sequential cohorts (3 + 3 design) received intravenous EZN‐2208 at doses between 1.25 mg/m2 and 25 mg/m2 once every 21 days.RESULTS:Thirty‐nine patients received EZN‐2208. The median number of prior therapies was 2 (range, 0‐10 prior therapies). Seventeen patients received prior irinotecan. Two maximum tolerated doses (MTDs) were defined: EZN‐2208 with (16.5 mg/m2) and without (10 mg/m2) granulocyte‐colony–stimulating factor (G‐CSF). The dose‐limiting toxicity (DLT) was febrile neutropenia. Two of 19 patients who were heterozygous for a polymorphism in the uridine diphosphate glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) gene (UGT1A1*28) developed DLTs (dose, 25 mg/m2 with G‐CSF), and 2 patients who were homozygous for UGT1A1*28 were treated without DLTs (dose, 5 mg/m2). PK analysis indicated a mean terminal half‐life of 19.4 ± 3.4 hours. Sixteen patients (41%) achieved stable disease, including 6 of 39 patients (15%) who had stable disease that lasted ≥4 months. One patient with cholangiocarcinoma (no prior irinotecan) achieved a short‐lived 32% tumor regression. Among 6 patients who had stable disease that lasted for ≥4 months, 3 had received prior irinotecan, and 1 had KRAS‐positive colorectal cancer.CONCLUSIONS:EZN‐2208 was well tolerated and produced stable disease that lasted for ≥4 months/unconfirmed partial responses in 7 of 39 heavily pretreated patients (18%) with advanced solid tumors, including those who had failed prior irinotecan therapy. Cancer 2012. © 2012 American Cancer Society.
Identification of polymorphisms in ultraconserved elements associated with clinical outcomes in locally advanced colorectal adenocarcinoma
Authors: Lin Moubin , Eng Cathy , Hawk Ernest T. , Huang Maosheng , Lin Jie , Gu Jian , Ellis Lee M. , Wu Xifeng 
Published: June 2012

AbstractBACKGROUND:Ultraconserved elements (UCEs) are noncoding genomic sequences that completely identical among human, mouse, and rat species and harbor critical biologic functions. The authors hypothesized that single nucleotide polymorphisms (SNPs) within UCEs are associated with clinical outcomes in patients with colorectal cancer (CRC).METHODS:Forty‐eight SNPs within UCEs were genotyped in 662 patients with stage I through III CRC. The associations between genotypes and recurrence and survival were analyzed in patients with stage II or III CRC who received fluoropyrimidine‐based adjuvant chemotherapy using a training and validation design. The training set included 115 patients with stage II disease and 170 patients with stage III disease, and the validation set included 88 patients with stage II disease and 112 patients with stage III disease.RESULTS:Eight SNPs were associated with clinical outcomes stratified by disease stage. In particular, for patients with stage II CRC who had at least 1 variant allele of reference SNP sequence 7849 (rs7849), a consistent association with increased recurrence risk was observed in the training set (hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.04‐5.52), in the replication set (HR, 3.70; 95% CI, 1.42‐9.64), and in a meta‐analysis (HR, 2.89; 95% CI, 1.54‐5.41). Several other SNPs were significant in the training set but not in the validation set. These included rs2421099, rs16983007, and rs10211390 for recurrence and rs6590611 for survival in patients with stage II disease; and SNPs rs6124509 and rs11195893 for recurrence in patients with stage III disease. In addition, a significant cumulative effect was observed of multiple risk genotypes and potential gene‐gene interactions on recurrence risk.CONCLUSIONS:To the authors' knowledge, this is the first study to evaluate the association between SNPs within UCEs and clinical outcome in patients with CRC. The results suggested that SNPs within UCEs may be valuable prognostic biomarkers for patients with locally advanced CRC who receive 5‐fluorouracil–based chemotherapy. Cancer 2012. © 2012 American Cancer Society.
The quantitative Gleason score improves prostate cancer risk assessment
Authors: Reese Adam C. , Cowan Janet E. , Brajtbord Jonathan S. , Harris Catherine R. , Carroll Peter R. , Cooperberg Matthew R. 
Published: June 2012

AbstractBACKGROUND:In the current study, the authors propose the quantitative Gleason score (qGS), a modification of the current Gleason grading system for prostate cancer, based on the weighted average of Gleason patterns present in the pathology specimen. They hypothesize that the qGS can improve prostate cancer risk stratification and help prevent the overtreatment of patients with clinically indolent tumors.METHODS:The qGS was applied to patients in the University of California San Francisco urologic oncology database with tumors determined to have a GS of 7 on prostate biopsy or final pathology after radical prostatectomy (RP). Using multivariable logistic regression, Cox proportional hazards regression, receiver operating characteristic (ROC), and decision curve analyses, the ability of qGS to predict pathological GS and the risk of disease recurrence after RP was assessed.RESULTS:A total of 225 men were included in the analysis of biopsy specimens and 618 men were included in the assessment of RP specimens. Compared with traditional Gleason scoring, the qGS improved concordance between biopsy and pathological GS on decision curve and ROC analyses (area under the curve ROC curve, 0.79 vs 0.71). On regression analysis, the qGS of biopsy specimens was found to be significantly associated with pathological grade after RP (hazard ratio [HR], 1.78; 95% confidence interval [95% CI], 1.49‐2.12) and the qGS of RP specimens was significantly associated with the risk of biochemical disease recurrence after RP (HR, 1.13; 95% CI, 1.04‐1.24).CONCLUSIONS:The qGS, a simple modification of the current Gleason system, appears to improve the correlation between biopsy and pathological GS, as well as the prediction of biochemical disease recurrence after RP. This scoring system may allow more men to pursue active surveillance, thereby avoiding the morbidity of prostate cancer treatment modalities. Cancer 2012. © 2012 American Cancer Society.
Value of cytologic Papanicolaou smears and polymerase chain reaction screening for human papillomavirus DNA in detecting anal intraepithelial neoplasia
Authors: Etienney Isabelle , Vuong Sarra , Si‐Mohamed Ali , Fléjou Jean‐François , Atienza Patrick , Bauer Pierre ,   and the Cytological Diaconesses Group
Published: June 2012

AbstractBACKGROUND:The performance of cytologic screening and its correlation with histology and polymerase chain reaction (PCR) detection of human papillomavirus (HPV) DNA have not been evaluated in populations with a low prevalence of anal intraepithelial neoplasia (AIN). The objective of the current study was to analyze the significance of abnormal smears relative to the histology and PCR detection of HPV DNA.METHODS:A cytologic smear and a viral sample were taken in 300 consecutive patients undergoing surgery (Milligan‐Morgan hemorrhoidectomy and/or fissurectomy) who gave their informed consent.RESULTS:The cytologic smear was normal in 216 of 290 patients (74.5%). Four high‐grade and 19 low‐grade intraepithelial neoplastic lesions were identified. In 5 patients, high‐grade lesions could not be excluded, 30 lesions were of undetermined significance, and there were 16 cellular modifications with a non‐neoplastic appearance. The PCR test for HPV was positive in 18.7% of patients, and a high‐risk genotype was identified in 63.6% of positive samples. Histologic examination of the surgical samples was normal in 92.3% of patients. The 23 AIN samples were distributed as follows: 13 grade 1 AIN (AIN1), 6 AIN2, and 4 AIN3. The sensitivity of cytologic smears and PCR for detecting AIN was 56% and 60.8%, respectively, and specificity was 77% and 84.5%, respectively. Combining the 2 tests increased sensitivity to 78% but decreased specificity to 68%.CONCLUSIONS:Compared with a large surgical sample, anal cytologic Papanicolaou smears and HPV PCR exhibited sensitivity and specificity that varied, depending on the risk of HPV infection and AIN. Positive HPV DNA screening increased with AIN grade, and high‐risk HPV testing was particularly helpful. Cancer 2012. © 2012 American Cancer Society.
Primary cancers before and after prostate cancer diagnosis
Authors: Van Hemelrijck Mieke , Drevin Linda , Holmberg Lars , Garmo Hans , Adolfsson Jan , Stattin Pär 
Published: June 2012

AbstractBACKGROUND:The occurrence of multiple cancers may indicate common etiology; and, although some studies have investigated the risk of second primary cancers after prostate cancer (PCa), there are no studies on cancers before PCa.METHODS:The PCBaSe Sweden database is based on the National Prostate Cancer Register (NPCR), which covers >96% of PCa cases. The authors estimated the prevalence and cumulative incidence of different cancers before and after PCa diagnosis in 72,613 men according to PCa treatment and disease stage in PCBaSe and their matched comparison cohort of men who were free of PCa.RESULTS:In total, 6829 men were diagnosed with another primary cancer before their PCa diagnosis, including 138 men at the time of PCa diagnosis and 5230 men were diagnosed after PCa diagnosis. Cancer of the bladder or colon and nonmelanoma of the skin were the 3 most frequently observed cancers before and after PCa diagnosis. At the time of PCa diagnosis, the prevalence of these 3 cancers was 1.94% for bladder cancer, 1.08% for colon cancer, and 1.08% for nonmelanoma skin cancer, compared with 1.30%, 0.96%, and 1.03%, respectively, for the matched comparison cohort. Five years after PCa diagnosis, the difference in incidence proportion between PCa men and their comparison cohort was 7‰ (95% CI, 5.6‰‐8.5‰), 1.3‰ (0‰‐2.6‰), and 1.6‰ (0.6‰‐2.6‰) for these 3 cancers, respectively. From a uro‐oncologic point of view, it is interesting to note that the prevalence of kidney cancer at the time of PCa diagnosis was 0.42% compared with 0.28% for the matched comparison cohort.CONCLUSIONS:Approximately 17% of all PCa occurred in combination with another primary cancer (before or after PCa diagnosis). Detection bias probably explains part of this observation, but further investigations are required to assess possible underlying mechanisms. Cancer 2012. © 2012 American Cancer Society.
Corrosion behavior of solid solution (Ti, Al) N as a function of Al concentration
Authors: Larijani M. M. , Manouchehrian M. , Seyedi H. , Yari M. 
Published: June 2012

AbstractIn this work, a series of (Ti, Al) N coatings with different Al contents were deposited on 304 stainless steel substrates by Hollow Cathode Discharge (HCD) method. The coatings were grown on 304 stainless steel substrates at 400 °C. The coatings were characterized using energy dispersive X‐ray spectroscopy (EDX), X‐ray diffraction (XRD), atomic force microscopy (AFM), and microhardness test. The XRD confirmed the transition from TiN phase to (Ti, Al) N phase and then to AlN phase with increasing Al concentration in the solid solution. It was found that with increasing Al concentration the hardness of the coatings initially increased up to a maximum value of about 30 GPa at around 32 at.% of Al and then the coating hardness decreased rapidly with further increase of Al content (Al > 32 at.%). The potentiodynamic polarization analysis was carried out in 3.5 wt.% NaCl solutions to study the corrosion resistance of the coatings. From the corrosion test it can be inferred that the amount of Al atoms in the coatings plays an important role for reducing the corrosion.
Malaria Intervention Policies and Pharmaceutical Nanotechnology as a Potential Tool for Malaria Management
Authors: Kuntworbe Noble , Martini Nataly , Shaw John , Al‐Kassas Raida 
Published: June 2012

Abstract

Strategy, Management and Health Policy

Enabling Technology, Genomics, Proteomics
Preclinical Research
Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics
Clinical Development Phases I‐III Regulatory, Quality, Manufacturing
Postmarketing Phase IV

In order to better understand the persistence of malaria, it is timely to reflect on the various approaches toward its eradication and to consider what is being done well and to identify what needs to be improved. This review explores currently available tools and policies designed to eradicate malaria and the potential difficulties associated with each. We have also considered pharmaceutical nanotechnology as a possible tool in the fight against malaria. Each policy, ranging from the adaption of combination drug therapy to the deployment of insecticide‐treated nets was considered to be laudable. The implementation and coverage of policies, however, exposed many gaps with persistence of the disease. Some of the challenges identified include misdiagnosis, production and distribution of fake and substandard antimalarial drugs, misapplication of insecticides, poor infrastructure, lack of sociopolitical will, and conflicts leading to displacement of people. Failure of malaria eradication has been attributed to the development of multiple drug resistance and the side effects associated with the use of conventional antimalarial chemotherapy. The review identified nanotechnology as a formulation strategy that has the potential to improve the safety and efficacy of drug therapy and help the cause of malaria eradication. In conclusion, this review is expected to provide a better understanding of the policies on malaria eradication and challenges associated with each of them. It also suggests that nanotechnology has the potential to reduce side effects of antimalarial drugs and improve their efficacy and should be given serious attention.
Triptolide‐Induced Apoptosis of Androgen‐Independent Prostatic Cancer (AIPC) via Modulation of Histone Methylation
Authors: Zhao Kailiang , Wang Weixing , Yu Xiaohui , Zhou Xing , Shi Qiao , Hu Yunfei 
Published: June 2012

Abstract

Strategy, Management and Health Policy

Enabling Technology, Genomics, Proteomics
Preclinical Research
Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics
Clinical Development Phases I‐III Regulatory, Quality, Manufacturing
Postmarketing Phase IV

Triptolide is the principal active ingredient in extracts from the Chinese herb, Tripterygium wilfordii Hook.F (TwHF) and has various biological functions including immunosuppression, anti‐inflammatory, antiviral, and antitumor properties. Triptolide has antitumor activity in a variety of tumors, and numerous studies have attempted to elucidate the potential antitumor mechanism. Triptolide can modulate histone methylation, suggesting that epigenetic mechanisms may play an important role in its antitumor activity. The present study assessed the association between the antitumor effects of triptolide in androgen‐independent prostatic cancer and the regulation of histone methylation. Triptolide inhibited the proliferation of the androgen‐independent prostatic cancer cell line, Du145 and induced apoptosis in a time‐ and dose‐dependent manner. Triptolide decreased histone H3K27me3 methylation via downregulation of histone methyltransferase enhancer of zeste 2, which may represent the antitumor mechanism of triptolide.
Germ cell survival in C. elegans and C. remanei is affected when the dead box rna helicases Vbh‐1 or Cre‐VBH‐1 are silenced
Authors: Salinas Laura S. , Franco‐Cea Ari , Láscarez‐Lagunas Laura I. , Villanueva‐Chimal Emmanuel , Maldonado Ernesto , Navarro Rosa E. 
Published: June 2012

AbstractThe Vasa family of proteins comprises several conserved DEAD box RNA helicases important for mRNA regulation whose exact function in the germline is still unknown. In Caenorhabditis elegans, there are six known members of the Vasa family, and all of them are associated with P granules. One of these proteins, VBH‐1, is important for oogenesis, spermatogenesis, embryo development, and the oocyte/sperm switch in this nematode. We decided to extend our previous work in C. elegans to sibling species Caenorhabditis remanei to understand what is the function of the VBH‐1 homolog in this gonochoristic species. We found that Cre‐VBH‐1 is present in the cytoplasm of germ cells and it remains associated with P granules throughout the life cycle of C. remanei. Several aspects between VBH‐1 and Cre‐VBH‐1 function are conserved like their role during oogenesis, spermatogenesis, and embryonic development. However, Cre‐vbh‐1 silencing in C. remanei had a stronger effect on spermatogenesis and spermatid activation than in C. elegans. An unexpected finding was that silencing of vbh‐1 in the C. elegans caused a decrease in germ cell apoptosis in the hermaphrodite gonad, while silencing of Cre‐vbh‐1 in C. remanei elicited germ cell apoptosis in the male gonad. These data suggest that VBH‐1 might play a role in germ cell survival in both species albeit it appears to have an opposite role in each one. genesis 1–18 2012. © 2012 Wiley Periodicals, Inc.
The role of water quality in large mammal migratory behaviour in the Serengeti
Authors: Strauch Ayron M. 
Published: June 2012

ABSTRACTSurface water resources are important components of savanna landscapes, supplying large populations of wildlife with drinking water critical for thermoregulation and digestion. However, little is known about the behavioural or physiological influence of water quality on wildlife health. East African savannas are well known for their migrating populations of ungulates coinciding with seasonal and spatial patterns of forage. In the Serengeti ecosystem, seasonal rainfall, high wildlife abundance and spatially variable soil composition result in temporal and spatial differences in surface water quality. Furthermore, nutrient enrichment from dissolved minerals and animal waste transported in runoff drive bacterial and algal blooms. Previous studies have suggested that water quality may be a factor in the migratory behaviour of wildebeest as poor quality water can have significant health consequences for ungulates, including depressed milk production and reduced food conversion. This paper examines the hypothesis that water quality in the southern Serengeti plains exceeds expected maximum tolerance limits at the end of the wet season – when migratory wildlife move northward, away from this region. Data collected during the migration's movement over 3 years are examined to determine if regional differences in water quality are physiologically meaningful and how the consumption of poor quality water may influence wildebeest nutrient intake. With increased demand for surface water resources from human populations, growing climatic uncertainty and significant changes in land cover outside of protected areas, the influence of water quality on animal behaviour needs to be considered for future management strategies. Copyright © 2012 John Wiley & Sons, Ltd.
Contrasting water‐uptake and growth responses to drought in co‐occurring riparian tree species
Authors: Singer Michael Bliss , Stella John C. , Dufour Simon , Piégay Hervé , Wilson Rob J.S. , Johnstone Laura 
Published: June 2012

ABSTRACTGrowth responses of riparian trees to changes in water availability are poorly understood, thereby limiting understanding of regional drought implications in river corridors. We used dendrochronological methods to develop growth series and analysed oxygen isotopic ratios (δ18O) in α‐cellulose from individual tree rings for two co‐occurring riparian species, Fraxinus excelsior and Populus nigra. Trees were sampled along the Ain River (France) to assess growth and annual source water availability, inferred from tree‐ring δ18O, compared with variations in streamflow and precipitation. Both species exhibited decreased growth during drought years, but F. excelsior demonstrated less variation in annual growth across sites compared with P. nigra. The latter species expressed a smaller range of δ18O among individuals and years, but greater δ18O sensitivity to river discharge, indicating a more consistent hyporheic water source. P. nigra also suffered more growth inhibition than F. excelsior in dry years when water tables were suppressed. These differences suggest contrasting patterns of water use, wherein F. excelsior uses primarily water from the vadose zone to maintain moderate growth rates, and P. nigra demonstrates more consistent phreatic water usage and suffers in drought years when water tables are suppressed. These observations are consistent with data on floodplain rooting depths, which show that F. excelsior maintains its roots above the gravel layer, whereas P. nigra generally roots deeply into phreatic zone gravels. These results indicate that surprisingly, poplars may be more sensitive to drought than ash trees and may be vulnerable to climate changes affecting water availability in riparian corridors. Copyright © 2012 John Wiley & Sons, Ltd.