bluuebunny/crossref_metadata_2025_split huggingface dataset:
High‐dose proton therapy and carbon‐ion therapy for stage I nonsmall cell lung cancer
Authors: Iwata Hiromitsu , Murakami Masao , Demizu Yusuke , Miyawaki Daisuke , Terashima Kazuki , Niwa Yasue , Mima Masayuki , Akagi Takashi , Hishikawa Yoshio , Shibamoto Yuta 
Published: March 2010

AbstractBACKGROUND:A study was undertaken to evaluate the clinical outcome of particle therapy for stage I nonsmall cell lung cancer (NSCLC).METHODS:From April 2003 to April 2007, 80 patients with stage I NSCLC were treated with proton therapy or carbon‐ion therapy (57 with proton therapy and 23 with carbon‐ion therapy) using 3 treatment protocols. In the first protocol, 80 gray equivalents (GyE) of proton therapy was given in 20 fractions, and the second proton therapy protocol used 60 GyE in 10 fractions. For carbon‐ion therapy, 52.8 GyE was given in 4 fractions. After achieving promising preliminary results for the first protocol, the authors started to use the second proton therapy protocol to shorten the overall treatment time. Carbon‐ion therapy was started in 2005, and thereafter, both proton and carbon‐ion therapy plans were made for each patient, and the 1 that appeared superior was adopted. Patient age ranged from 48 to 89 years (median, 76 years). Thirty‐seven patients were medically inoperable, and 43 refused surgery. Forty‐two patients had T1 tumors, and 38 had T2 tumors.RESULTS:The median follow‐up period for living patients was 35.5 months. For all 80 patients, the 3‐year overall survival, cause‐specific survival, and local control rates were 75% (IA: 74%; IB: 76%), 86% (IA: 84%; IB: 88%), and 82% (IA: 87%; IB: 77%), respectively. There were no significant differences in treatment results among the 3 protocols. Grade 3 pulmonary toxicity was observed in only 1 patient.CONCLUSIONS:Proton therapy and carbon‐ion therapy are safe and effective for stage I NSCLC. Further investigation of particle therapy for stage I NSCLC is warranted. Cancer 2010. © 2010 American Cancer Society.
A note from history
Authors: Hajdu Steven I. 
Published: March 2010

AbstractAntonio Benivieni, an Italian physician, Theophilus Boneti, a Swiss physician, and Giovanni Battista Mogagni, an Italian physician, pioneered postmortem examination for finding hidden causes of diseases. By correlating the results of their clinical and postmortem examinations, they established the foundation of anatomic pathology, clinical medicine, and oncology. Cancer 2010. © 2010 American Cancer Society.
A novel therapeutic combination for neuroblastoma
Authors: Zage Peter E. , Zeng Lizhi , Palla Shana , Fang Wendy , Nilsson Monique B. , Heymach John V. , Zweidler‐McKay Patrick A. 
Published: March 2010

AbstractBACKGROUND:High‐risk cases of neuroblastoma have poor survival rates, and novel therapies are needed. Vandetanib (ZD6474, Zactima) is an inhibitor of the vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection (RET) tyrosine kinases, which have each been implicated in neuroblastoma pathogenesis. The authors hypothesized that vandetanib combined with 13‐cis‐retinoic acid (CRA), a differentiating agent used in most current neuroblastoma treatment regimens, would be effective against neuroblastoma tumor models.METHODS:The authors evaluated the effects of vandetanib with and without CRA on RET phosphorylation and on the proliferation and survival of human neuroblastoma cell lines in vitro. Using a subcutaneous mouse xenograft model of human neuroblastoma, they analyzed tumors treated with CRA, vandetanib, and the combination of vandetanib plus CRA for growth, gross and histologic appearance, vascularity, and apoptosis.RESULTS:Vandetanib treatment inhibited RET phosphorylation and resulted in induction of apoptosis in the majority of neuroblastoma cell lines in vitro, whereas CRA treatment induced morphologic differentiation and cell‐cycle arrest. Treatment with vandetanib plus CRA resulted in more significant reduction in neuroblastoma cell viability than either alone. In a mouse xenograft model, the combination of vandetanib with CRA demonstrated significantly more growth inhibition than either alone, via both reduction in tumor vascularity and induction of apoptosis.CONCLUSIONS:Vandetanib induces neuroblastoma tumor cell death in vitro and reduces tumor growth and vascularity in vivo. The combination of vandetanib with CRA was more effective in reducing tumor growth than either treatment alone. The antitumor effects of vandetanib plus CRA suggest a novel combination for use in neuroblastoma patients. Cancer 2010. © 2010 American Cancer Society.
Efficacy of radiotherapy for painful bone metastases during the last 12 weeks of life
Authors: Meeuse Jan J. , van der Linden Yvette M. , van Tienhoven Geertjan , Gans Rijk O. B. , Leer Jan Willem H. , Reyners An K. L. 
Published: March 2010

AbstractBACKGROUND:Radiotherapy is an effective treatment for painful bone metastases. Whether this applies also in patients with limited survival remains to be investigated. This study analyzed the effect of radiotherapy for painful bone metastases in patients with a survival ≤12 weeks.METHODS:In the Dutch Bone Metastasis Study, 1157 patients with painful bone metastases were randomized to single fraction (1 × 8 grays [Gy]) or multiple fraction (6 × 4 Gy) radiotherapy. Patients who died within 12 weeks after randomization were included in this analysis. Patients were classified as responders or nonresponders, based on their pain response to radiotherapy. This response was calculated considering changes in pain intensity (measured with an 11‐point numeric rating scale) and analgesic usage. Cox proportional hazards models were used to analyze pain response and survival.RESULTS:Two hundred seventy‐4 patients were included in this analysis. At randomization, the mean pain intensity score (±standard deviation) was 7 (±2). The proportion showing a pain response did not differ between the single fraction and multiple fraction groups. Toward death, pain intensity score decreased to 5 (±3) in responders (45%), whereas in nonresponders (55%) no change was observed. Despite the benefit in responders, in 60% of all patients pain intensity remained 5 after randomization.CONCLUSIONS:Pain responded in about half of the patients who survived ≤12 weeks after randomization into the Dutch Bone Metastasis Study. When considering radiotherapy, single fraction should be preferred. Additional palliative measures remain essential for adequate pain control. Cancer 2010. © 2010 American Cancer Society.
Association ofp53codon 72 polymorphism with risk of second primary malignancy in patients with squamous cell carcinoma of the head and neck
Authors: Li Fanglin , Sturgis Erich M. , Chen Xingming , Zafereo Mark E. , Wei Qingyi , Li Guojun 
Published: March 2010

AbstractBACKGROUND:p53 plays a critical role in cellular anticancer mechanisms, and has been correlated with second primary malignancy (SPM) development. A common polymorphism in codon 72 ofp53results in an amino acid substitution and could influence p53 function. The authors hypothesized thatp53codon 72 polymorphism may be associated with risk of SPMs and SPM‐free survival among patients with squamous cell carcinoma of the head and neck (SCCHN).METHODS:A total of 1271 patients, who were diagnosed with incident SCCHN between May 1995 and January 2007, were genotyped and observed for SPM development. Log‐rank test and Cox proportional hazard models were used to compare SPM‐free survival and SPM risk between the different genotype groups.RESULTS:The authors found significantly reduced SPM‐free survival for patients with variant proline (Pro) 72 allele compared with patients with arginine (Arg) 72 homozygous genotype (log‐rank test,P= .005). Compared with SCCHN patients with thep5372Arg/Arg genotype, there was a significantly greater risk of SPM associated with thep5372Arg/Pro genotype (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.17‐2.61) and combinedp5372Arg/Pro + Pro/Pro (HR, 1.58; 95% CI, 1.07‐2.34). Furthermore, stratification analyses showed that the risk of SPM associated withp53variant genotypes (Arg/Pro + Pro/Pro) was more pronounced in several subgroups.CONCLUSIONS:p53codon 72 polymorphism could be a risk marker for genetic susceptibility to SPM in patients with primary SCCHN. Cancer 2010. © 2010 American Cancer Society.
Weekly alternating therapy with irinotecan plus cisplatin and etoposide plus cisplatin in the treatment of patients with extensive small cell lung carcinoma
Authors: William William N. , Uyeki James , Johnson Faye M. , Feng Lei , Peeples Beverly O. , Fossella Frank V. , Karp Daniel D. , Blumenschein George R. , Stewart David J. , Glisson Bonnie S. 
Published: March 2010

AbstractBACKGROUND:Irinotecan has significant activity in small‐cell lung cancer (SCLC). The authors' previous phase 1 study of alternating weekly therapy with irinotecan/cisplatin (IP), etoposide/cisplatin (EP), and granulocyte–colony‐stimulating factor (G‐CSF) support was well tolerated and active in patients with SCLC. A phase 2 trial was conducted to estimate the efficacy of this regimen in previously untreated patients with extensive SCLC.METHODS:A total of 33 patients were treated between June 2002 and July 2007. Patients received 12 weeks of therapy with cisplatin (20 mg/m2) on Day 1 and irinotecan (100 mg/m2) on Day 1 and G‐CSF on Days 2 to 5 (Weeks 1, 3, 5, 7, 9, and 11) followed by cisplatin (20 mg/m2) on Day 1 and etoposide (60 mg/m2) on Days 1 to 3 with G‐CSF on Days 4 to 7 (Weeks 2, 4, 6, 8, 10, and 12). The primary endpoint was 1‐year survival rate.RESULTS:Grade 4 neutropenia (toxicities were determined using the National Cancer Institute Common Toxicity Criteria [version 2.0]) was noted in 5 (1.5%) of 343 courses with neutropenic fever in only 5 (1%) of 343 courses. One patient died of neutropenic sepsis. Nonhematologic toxicities grade ≥2 were observed in 15 (4%) of 343 courses and were limited to fatigue, hyponatremia, and diarrhea. The overall objective response rate was 89% in 28 assessable patients (no complete responses and 25 partial responses). The median progression‐free and overall survivals were 6.0 months and 10.9 months, respectively. The 1‐year survival rate was 33%.CONCLUSIONS:Weekly therapy with IP alternating with EP and G‐CSF support was well tolerated in patients with extensive SCLC, but did not demonstrate improved progression‐free or overall survival when compared with historical controls at the study institution. Cancer 2010. © 2010 American Cancer Society.
Detection of chromosomal anomalies in endometrial atypical hyperplasia and carcinoma by using fluorescence in situ hybridization
Authors: Qian Junqi , Weber Deena , Cochran Richard , Hossain Deloar , Bostwick David G. 
Published: March 2010

AbstractBACKGROUND:Endometrial cancer is the most common pelvic gynecological malignancy. The diagnosis of well‐differentiated endometrial adenocarcinoma, atypical hyperplasia, and hyperplasia is often challenging. The authors sought to investigate the utility of chromosomal anomalies for the detection of endometrial hyperplasia and carcinoma using multitarget fluorescence in situ hybridization (FISH).METHODS:Samples were collected by endometrial Tao brush and processed by liquid‐based cytological preparation protocol from consecutive cases to include 50 benign, 50 hyperplasia without atypia, 47 atypical hyperplasia, and 53 endometrial cancers. Each was hybridized using fluorescence‐labeled DNA probes to chromosomes 1, 8, and 10. The FISH signals were enumerated in 100 cells per case, and the chromosomal anomalies were correlated with pathologic findings, including histologic diagnoses on matched endometrial tissue samples.RESULTS:Numeric chromosomal anomalies were found in 0% (0 of 50) of benign, 20% (10 of 50) of hyperplasia, 74% (35 of 47) of atypical hyperplasia, and 87% (46 of 53) of carcinoma specimens. The mean percentage of cells with chromosomal changes was 55% in cancer specimens, which was significantly higher than that in hyperplasia without atypia (13%, P < .0001) and atypical hyperplasia (32%, P = .003). The most frequent chromosomal anomaly was gain of chromosome 1. FISH anomalies had an overall sensitivity of 81% and specificity of 90% for the detection of atypical hyperplasia and/or endometrial carcinoma. There was no association with grade of endometrial carcinoma.CONCLUSIONS:Multitarget FISH appears to be useful for the differential diagnosis of hyperplasia, atypical hyperplasia, and endometrial adenocarcinoma, with a high level of sensitivity and specificity. It is also a potential tool for the early detection of neoplastic cells in endometrial cytology specimens. Endometrial hyperplasia with FISH‐detected chromosomal anomalies may represent a clinically significant subset of cases that warrant close clinical follow‐up. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.
A process‐oriented architecture for complex system modelling
Authors: Ritson C. G. , Welch P. H. 
Published: March 2010

AbstractA fine‐grained massively parallel and process‐oriented architecture for the modelling of complex systems is presented. We propose that the concurrency in the model simplifies its design and construction by directly reflecting the processes in the natural world. The architecture is based on CSP, extended with mechanisms for process mobility from the pi‐calculus; implementations are presented using the occam‐pi language. A case study, modelling platelets (possibly artificial) within a blood vessel, is described. The aim for this model is to engineer emergent behaviour: the clotting of platelets in response to a wound in the blood vessel wall and the staunching of blood loss. A three‐dimensional model is constructed, along with mechanisms for visualization and interaction. Its expressiveness and efficiency relies strongly on the dynamic and mobile capabilities of occam‐pi. General principles for the design of large and complex system models are drawn. The described case study runs to millions of processes engaged in ever‐changing communication topologies. It is free from deadlock, livelock, race hazards and starvation by design, employing a small set of synchronization patterns for which we have proven safety theorems. Compiled occam‐π codes automatically and efficiently exploit all cores in a shared‐memory multiprocessor system. They are also straightforward to distribute over standard cluster architectures. Copyright © 2007 CG Ritson & PH Welch.
Urinary biomarkers involved in type 2 diabetes: a review
Authors: Matheson Agnès , Willcox Mark D. P. , Flanagan Judith , Walsh Bradley J. 
Published: March 2010

AbstractDiabetes mellitus is one of the most challenging health concerns of the 21st century. With at least 30% of the diabetic population remaining undiagnosed, effective and early diagnosis is of critical concern. Development of a diagnostic test, more convenient and reliable than those currently used, would therefore be highly beneficial. Urine as a diagnostic medium allows for non‐invasive detection of biomarkers, including some associated with type 2 diabetes and its complications. This review provides a synopsis of those urinary biomarkers that potentially may provide a basis for the development of improved diagnostic tests. Three main pathways for the sourcing of potential makers are identified: kidney damage, oxidative stress and low‐grade inflammation including atherosclerosis/vascular damage. This review briefly presents each pathway and some of the most relevant urinary biomarkers that may be used to monitor the development or progression of diabetes and its complications. In particular, biomarkers of renal dysfunction such as transferrin, type IV collagen and N‐acetyl‐β‐D‐glucosaminidase might prove to be more sensitive than urinary albumin, the current gold standard, in the detection of incipient nephropathy and risk assessment of cardiovascular disease. Inflammatory markers including orosomucoid, tumour necrosis factor‐α, transforming growth factor‐β, vascular endothelial growth factor and monocyte chemoattractant protein‐1, as well as oxidative stress markers such as 8‐hydroxy‐2′deoxyguanosine may also be useful biomarkers for diagnosis or monitoring of diabetic complications, particularly kidney disease. However, the sensitivity of these markers compared with albumin requires further investigation. Copyright © 2010 John Wiley & Sons, Ltd.
Relationship between insulin resistance, inflammation and liver cell apoptosis in patients with severe obesity
Authors: Civera M. , Urios A. , Garcia‐Torres M. L. , Ortega J. , Martinez‐Valls J. , Cassinello N. , del Olmo J. A. , Ferrandez A. , Rodrigo J. M. , Montoliu C. 
Published: March 2010

AbstractBackgroundIn obesity, insulin resistance appears frequently after activation of proinflammatory molecules. Caspase‐generated cytokeratin‐18 (CK‐18) fragments are produced during the apoptosis of hepatic cells. The main objective in the present study is to investigate the relationship between insulin resistance and caspase‐generated CK‐18 fragments in patients with severe obesity.MethodsSixty‐two patients selected for bariatric surgery were clinically studied (sex, age, weight, waist diameter, body mass index, arterial pressure and type 2 diabetes mellitus) and analytic parameters were measured in blood (glucose concentration, cholesterol, triglycerides, insulin, glycosylated hemoglobin, aspartate aminotransferase, alanine aminotransferase, high‐sensitivity C‐reactive protein, adiponectin, interleukin 6, interleukin 18 and CK‐18 fragments). Patient group division was based on 70th percentile of insulin resistance as measured by homeostasis model asssessment (HOMA) and also according to liver histology.ResultsPatients with greater insulin resistance (percentile > 70th) showed higher values of CK‐18 fragments, interleukin 6 and transaminases. A positive correlation between the HOMA score, value of CK‐18 fragments and triglyceride level was found. A correlation between CK‐18 fragments with interleukin 6, triglycerides and transaminases was also observed. HOMA score and value of CK‐18 fragments correlated with the degree of liver fibrosis.ConclusionsGreater degree of insulin resistance induces apoptosis of hepatic cells as measured by the serum levels of CK‐18 fragments. Copyright © 2010 John Wiley & Sons, Ltd.
Proteomics analysis of the temporal changes in axonal proteins during maturation
Authors: Yamatani Hitoshi , Kawasaki Takahiko , Mita Sakura , Inagaki Naoyuki , Hirata Tatsumi 
Published: March 2010

AbstractAfter the initial primary projection, axons undergo various structural and functional changes to establish mature neural circuits. The changes in protein expression associated with this maturation were investigated in lateral olfactory tract axons using two‐dimensional gel electrophoresis. The most prominent group upregulated during the period consisted of calcium‐dependent membrane‐binding proteins including VILIP1, neurocalcin δ, copine 6, and annexin A6 from three structurally different families. During maturation of primary cultured neurons, annexin A6 gradually became concentrated on the axon initial segment, and its overexpression significantly enhanced axon branching. On the other hand, overexpression of VILIP1 and neurocalcin δ reduced axon outgrowth and branching. The second group upregulated during axon maturation comprised tubulin‐ and microtubule‐binding proteins including CRMP2, guanine deaminase, MAP1B, and fibronectin type3 SPRY domain‐containing protein. Because the maturation of lateral olfactory axons involves massive extension of secondary collateral branches, the augmentation of these proteins during these stages may underlie the drastic restructuring of the axon cytoskeleton. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70:523–537, 2010
Determination of 13C/12C ratios of urinary excreted boldenone and its main metabolite 5β‐androst‐1‐en‐17β‐ol‐3‐one
Authors: Piper Thomas , Geyer Hans , Gougoulidis Vassilios , Flenker Ulrich , Schänzer Wilhelm 
Published: March 2010

AbstractBoldenone (androsta–1,4–dien–17β–ol–3–one, Bo) is an anabolic steroid known to have been used in cattle breeding or equine sport as a doping agent for many years. Although not clinically approved for human application, Bo or its main metabolite 5β‐androst‐1‐en‐17β‐ol‐3‐one (BM1) were detected in several doping control samples. For more than 15 years the possibility of endogenous Bo production in human beings has been discussed. This is a challenging issue for doping control laboratories as Bo belongs to the list of prohibited substances of the World Anti‐Doping Agency and therefore the chance for false positive testing is significant. By GC/C/IRMS (gas chromatography/combustion/isotope ratio mass spectrometry) it should be possible to analyze the 13C/12C ratio of either Bo or BM1 and to distinguish whether their source is endogenous or exogenous. Therefore a method was developed to determine the 13C/12C ratios of Bo, BM1, pregnanediol, androsterone, etiocholanolone, and testosterone from a single urine specimen. The validity of the method was ensured by repeated processing of urine fortified with 2–50 ng/mL Bo and BM1. The specificity of the method was ensured by gas chromatography/mass spectrometry determinations. Out of 23 samples investigated throughout the last four years, 11 showed 13C/12C ratios of Bo or BM1 inconsistent with an exogenous origin. Two of these samples were collected from the same athlete within a one‐month interval, strongly indicating the chance of endogenous Bo production by this athlete. Copyright © 2010 John Wiley & Sons, Ltd.
Expanded‐Ring and Backbone‐Functionalised N‐Heterocyclic Carbenes
Authors: Iglesias Manuel , Beetstra Dirk J. , Cavell Kingsley J. , Dervisi Athanasia , Fallis Ian A. , Kariuki Benson , Harrington Ross W. , Clegg William , Horton Peter N. , Coles Simon J. , Hursthouse Michael B. 
Published: March 2010

AbstractAn unsaturated seven‐membered amidinium salt 7 decomposes in the presence of metal salts under basic conditions. However, 7 readily forms a Diels–Alder cycloadduct with CpH from which the RhI complexes may be prepared. Thus, structurally elaborate, sterically crowded carbene ligand complexes bearing peripheral unsaturated functionality are available in a short versatile synthesis.
Non‐Oxido Mixed‐Valence MnII6MnIII4 Cluster with Benzoate, Triethanolamine and Phosphonate Bridging Ligands
Authors: Dendrinou‐Samara Catherine , Muryn Christopher A. , Tuna Floriana , Winpenny Richard E. P. 
Published: March 2010

AbstractThe synthesis, structure and magnetic properties of a new non‐oxido mixed‐valence decanuclear heterometallic manganese cluster [K3Mn10(PhCOO)10(PhPO3)2(Htea)6](PhCOO)·6MeCN}n (1), where Htea2– is the dianion of triethanolamine, is reported. Compound 1 can be regarded as an analogue of 24‐metallacrown‐10, acting as a host for three potassium ions. The resulting {Mn10} cage crystallises as a cation; benzoate anions link the cages into a 1D polymer within the crystal. Direct current magnetic susceptibility measurements were collected at temperatures between 1.8 and 300 K and applied magnetic fields of 1 and 10 kG. The room‐temperature value is very close to the spin‐only value of 38.25 cm3 mol–1 K expected for an Mn10‐cage repeat unit comprising six MnII and four MnIII ions. At 2 K and 70 kG the magnetisation reaches a value of 19.5 NμB, suggesting a ground state larger than S = 10.
Efficient Synthesis of Biaryls through the Kumada Reaction Catalyzed by Carbene Adducts of Cyclopalladated Ferrocenylimine
Authors: Ren Gerui , Cui Xiuling , Wu Yangjie 
Published: March 2010

AbstractA series of carbene adducts of cyclopalladated ferrocenylimine were prepared and evaluated in the cross‐coupling reaction of aryl halides with Grignard reagents (the Kumada reaction). Complex d exhibited high catalytic activity for the coupling of aryl chlorides with sterically hindered Grignard reagents and the reaction tolerated various functional groups. A wide range of biaryls were efficiently obtained in good to excellent yields in the presence of 0.5 mol‐% catalyst under mild reaction conditions.