bluuebunny/crossref_metadata_2025_split huggingface dataset:
KRAS Mutations As an Independent Prognostic Factor in Patients With Advanced Colorectal Cancer Treated With Cetuximab
Authors: Lièvre Astrid , Bachet Jean-Baptiste , Boige Valérie , Cayre Anne , Le Corre Delphine , Buc Emmanuel , Ychou Marc , Bouché Olivier , Landi Bruno , Louvet Christophe , André Thierry , Bibeau Fréderic , Diebold Marie-Danièle , Rougier Philippe , Ducreux Michel , Tomasic Gorana , Emile Jean-François , Penault-Llorca Frédérique , Laurent-Puig Pierre 
Published: January 2008

Purpose Cetuximab is efficient in advanced colorectal cancer (CRC). We previously showed that KRAS mutations were associated with resistance to cetuximab in 30 CRC patients. The aim of this study was to validate, in an independent larger series of 89 patients, the prognostic value of KRAS mutations on response to cetuximab and survival. Patients and Methods Eighty-nine metastatic CRC patients treated with cetuximab after treatment failure with irinotecan-based chemotherapy were analyzed for KRAS mutation by allelic discrimination on tumor DNA. The association between KRAS mutations and tumor response, skin toxicity, progression-free survival (PFS) and overall survival (OS) was analyzed. Results A KRAS mutation was present in 27% of the patients and was associated with resistance to cetuximab (0% v 40% of responders among the 24 mutated and 65 nonmutated patients, respectively; P < .001) and a poorer survival (median PFS: 10.1 v 31.4 weeks in patients without mutation; P = .0001; median OS: 10.1 v 14.3 months in patients without mutation; P = .026). When we pooled these 89 patients with patients from our previous study, the multivariate analysis showed that KRAS status was an independent prognostic factor associated with OS and PFS, whereas skin toxicity was only associated with OS. In a combined analysis, median OS times of patients with two, one, or no favorable prognostic factors (severe skin toxicity and no KRAS mutation) was of 15.6, 10.7, and 5.6 months, respectively. Conclusion These results confirm the high prognostic value of KRAS mutations on response to cetuximab and survival in metastatic CRC patients treated with cetuximab.
Randomized, Phase III Study of Weekly Paclitaxel in Combination With Carboplatin Versus Standard Every-3-Weeks Administration of Carboplatin and Paclitaxel for Patients With Previously Untreated Advanced Non–Small-Cell Lung Cancer
Authors: Belani Chandra P. , Ramalingam Suresh , Perry Michael C. , LaRocca Renato V. , Rinaldi David , Gable Preston S. , Tester William J. 
Published: January 2008

Purpose To compare the efficacy and safety of weekly paclitaxel in combination with carboplatin administered every 4 weeks to the standard regimen of paclitaxel and carboplatin administered every 3 weeks for the treatment of patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Four hundred forty-four patients with previously untreated stage IIIB/IV NSCLC were randomly assigned to either arm 1 (n = 223), paclitaxel 100 mg/m2 weekly for 3 of 4 weeks with carboplatin area under the curve (AUC) = 6 mg/mL · min on day 1 of each 4 week cycle, or arm 2 (n = 221), paclitaxel 225 mg/m2 and carboplatin AUC = 6 on day 1 of each 3-week cycle. After four cycles of therapy, patients in both treatment arms were eligible to continue weekly paclitaxel (70 mg/m2, 3 of 4 weeks) as maintenance therapy until unacceptable toxicity or disease progression. Results The objective response rate was 27.6% for arm 1 and 19.2% for arm 2. Median time to progression (TTP) was 18.4 and median survival (MS) was 38.6 weeks for arm 1. For arm 2, the median TTP and MS were 16.7 weeks and 42.9 weeks respectively. Grade 3/4 anemia was more common with arm 1, although grade 2/3 neuropathy and arthralgia were less common. The remainder of the toxicities were similar between the two arms. Conclusion All efficacy parameters were similar between the two treatment arms. The favorable nonhematologic toxicity profile of arm 1 makes this an alternative treatment option for patients with advanced NSCLC.
cT3N0 Rectal Cancer: Potential Overtreatment With Preoperative Chemoradiotherapy Is Warranted
Authors: Guillem José G. , Díaz-González Juan A. , Minsky Bruce D. , Valentini Vincenzo , Jeong Seung-Yong , Rodriguez-Bigas Miguel A. , Coco Claudio , Leon Rebecca , Hernandez-Lizoain José L. , Aristu José J. , Riedel Elyn R. , Nitti Donato , Wong W. Douglas , Pucciarelli Salvatore 
Published: January 2008

Purpose Although combined-modality therapy (CMT) is the preferred treatment for T3 and/or lymph node (LN)-positive rectal cancer, the German rectal cancer study published in 2004 demonstrated that 18% of patients deemed suitable for preoperative CMT by endorectal ultrasound (ERUS) may be overstaged. Because data also suggest that LN-negative rectal cancer after total mesorectal excision may not require radiotherapy, it is reasonable to consider omitting radiotherapy for the cT3N0 subset. We therefore determined the accuracy of pre-CMT ERUS or magnetic resonance imaging (MRI) staging, to explore the validity of a nonpreoperative CMT approach for cT3N0 disease. Patients and Methods One hundred eighty-eight ERUS-/MRI-staged T3N0 rectal cancer patients received preoperative CMT (fluorouracil based and 45-50.4 Gy) followed by radical resection. Rates of pathologic complete response (pCR) and mesorectal LN involvement were determined. Results Tumors were located a median of 5 cm from the anal verge. Sphincter-preserving surgery was performed in 143 patients (76%). Overall pCR was 20%, and 41 patients (22%) had pathologically positive mesorectal LNs. The incidence of positive LNs significantly increased with T stage: ypT0, 3%; ypT1, 7%; ypT2, 20%; ypT3-4, 36% (P = .001). Conclusion The accuracy of preoperative ERUS/MRI for staging mid to distal cT3N0 rectal cancer is limited because 22% of patients have undetected mesorectal LN involvement despite CMT. Therefore, ERUS-/MRI-staged T3N0 rectal cancer patients should continue to receive preoperative CMT. Although 18% may be overstaged and therefore overtreated, our data suggest that an even larger number would be understaged and require postoperative CMT, which is associated with significantly inferior local control, higher toxicity, and worse functional outcome.
Randomized Trial Comparing Bleomycin/Etoposide/Cisplatin With Alternating Cisplatin/Cyclophosphamide/Doxorubicin and Vinblastine/Bleomycin Regimens of Chemotherapy for Patients With Intermediate- and Poor-Risk Metastatic Nonseminomatous Germ Cell Tumors: Genito-Urinary Group of the French Federation of Cancer Centers Trial T93MP
Authors: Culine Stéphane , Kramar Andrew , Théodore Christine , Geoffrois Lionel , Chevreau Christine , Biron Pierre , Nguyen Binh Bui , Héron Jean-François , Kerbrat Pierre , Caty Armelle , Delva Rémy , Fargeot Pierre , Fizazi Karim , Bouzy Jeannine , Droz Jean-Pierre 
Published: January 2008

Purpose Two chemotherapy regimens for intermediate- and poor-risk metastatic nonseminomatous germ cell tumors were compared for efficacy and toxicity. Patients and Methods From February 1994 to February 2000, 190 patients were randomly assigned between either four cycles of BEP (bleomycin 30 mg d1, d8, d15; etoposide 100 mg/m2 d1-5; cisplatin 20 mg/m2 d1-5) or four to six alternating cycles of CISCA/VB (cyclophosphamide 400 mg/m2 d1-2, doxorubicin 35 mg/m2 d1-2, cisplatin 100 mg/m2 d3/vinblastine 2.5 mg/m2 d1-5, bleomycin 25 mg/m2 d1-5). Risk was initially defined according to the Institut Gustave Roussy (Villejuif, France) prognostic model based on serum alpha-fetoprotein and human chorionic gonadotropin levels only. Patients were retrospectively assigned into the International Germ Cell Consensus Classification. Results Among 185 assessable patients, favorable responses did not differ statistically between the two arms: 49 in the CISCA/VB arm (56%; 95% CI, 45% to 66%), 57 in the BEP arm (65%; 95% CI, 55% to 75%). The CISCA/VB regimen induced more significant hematologic and mucous toxicities compared with the BEP arm. The 5-year event-free survival rates were 37% (95% CI, 27% to 47%) and 47% (95% CI, 37% to 57%) in CISCA/VB and BEP arms, respectively (hazard ratio [HR] = 0.76; 95% CI, 0.52 to 1.11; P = .15). With a median follow-up of 7.8 years, the 5-year overall survival rates were 59% (95% CI, 47% to 67%) and 69% (95% CI, 58% to 77%) in CISCA/VB and BEP arms, respectively (HR = 0.73; 95% CI, 0.46 to 1.18; P = .24). Conclusion Because of equivalent efficacy and lesser toxicity, the standard treatment for patients with intermediate- and poor-risk metastatic nonseminomatous germ cell tumors remains four cycles of BEP.
Human Immunodeficiency Virus–Associated Squamous Cell Cancer of the Anus: Epidemiology and Outcomes in the Highly Active Antiretroviral Therapy Era
Authors: Chiao Elizabeth Y. , Giordano Thomas P. , Richardson Peter , El-Serag Hashem B. 
Published: January 2008

Purpose To evaluate and determine predictors of squamous cell carcinoma of the anus (SCCA) outcomes in the highly active antiretroviral therapy (HAART) era for HIV-positive and -negative individuals using large national Veterans Affairs (VA) Administration databases. Patients and Methods We used the VA administrative databases to perform a retrospective cohort study in 1,184 veterans diagnosed with SCCA between 1998 and 2004. We calculated HIV infection rates and used logistic regression to identify epidemiologic factors that were associated with HIV infection. Kaplan-Meier curves and Cox proportional hazards models were calculated to compare survival between HIV-positive and HIV-negative veterans. Results In our cohort, 175 patients (15%) were HIV positive. The median age of the HIV-negative and -positive patients was 63 and 49 years, respectively (P < .001). Individuals with HIV were eight times more likely to be male (P = .01) and three times more likely to be African American (P < .001). There were no differences between HIV-positive and HIV-negative individuals in the receipt of treatment. The 2-year observed survival rates were 77% and 75% among HIV-positive and HIV-negative individuals, respectively. In multivariate Cox analysis, significant predictors of survival were age, sex, metastasis at diagnosis, and comorbidity score. HIV infection did not affect survival. Conclusion A noteworthy proportion of individuals with SCCA in the VA system are HIV positive. HIV-associated SCCA seems mainly to be a disease among younger men. Survival of SCCA is equivalent between HIV-positive and HIV-negative individuals in the HAART era. Treatment should not be withheld or deintensified based on HIV status.
6-STEPPPs: A Modular Tool to Facilitate Clinician Participation in Fair Decisions for Funding New Cancer Drugs
Authors: Browman George P. , Manns Braden , Hagen Neil , Chambers Carole R. , Simon Anita , Sinclair Shane 
Published: January 2008

Purpose: To design a tool to assist clinician participation with cancer drug funding decisions. Public policy-makers and insurers are struggling with funding decisions regarding increasingly expensive new cancer drugs. Increasingly, oncologists are contributing to the process of review that leads to such decisions. We were asked to design a system for ranking new cancer drugs for priority-based funding decisions. Methods: The “Accountability for Reasonableness” framework informed the design of a six-module multistakeholder decision process blending evidence-based traditional technology assessment methods with individual and cultural values elicitation. The tool was piloted in three settings: (1) videotaped simulated multistakeholder deliberation sessions; (2) clinical oncology leaders; and (3) a regional (Canadian provincial) pharmacy and therapeutics committee making formulary decisions. The modules involve: decision clarification, drug eligibility screening (filtering), clinical performance scoring index, cost modeling, data integration and values clarification, and process evaluation. Results: The tool was feasible to use, acceptable to participants, and able to rank candidate drugs. The pharmacy and therapeutics committee with whom it was tested used the tool as a part of their deliberations, and the tumor group leaders requested its incorporation into organization-based decision making. Conclusion: The decision tool can facilitate priority-based cancer drug funding decisions that meet the conditions of fairness as perceived by participants, including oncologists.
Antioxidant and antibacterial activity of two compounds (forsythiaside and forsythin) isolated from Forsythia suspensa
Authors: Qu Huanhuan , Zhang Yongmin , Wang Yan , Li Baixue , Sun Wenji 
Published: January 2008

Abstract
Forsythia suspensa (Thunb.) Vahl. has been widely used in traditional medicines in Asia to treat gonorrhoea, erysipelas, inflammation, pyrexia, ulcer and other diseases. Recently the investigation has been focused on the antioxidant and antibacterial activity of this plant. However, limited scientifically proven information is available. We isolated two compounds (forsythiaside and forsythin) from this plant. The aims of this investigation, therefore, were to assay antioxidant activity and antibacterial properties of the two main and distinctive compounds isolated and to exploit antioxidants and antibacterial agents from natural compounds. The antioxidant activity was estimated using the 1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity method and the in-vitro antimicrobial activity was evaluated by microtitre plate method. Forsythiaside was found to possess strong antioxidant and antibacterial activity but forsythin was much weaker. Owing to these properties, the study can be further extended to exploit the possible application of forsythiaside as an alternative antioxidant and antibacterial agent of natural origin.
Potential relationships between transaminase abnormality and valproic acid clearance or serum carnitine concentrations in Japanese epileptic patients
Authors: Goto Shuji , Seo Takayuki , Hagiwara Takashi , Ueda Kentaro , Yamauchi Tsuyuko , Nagata Shiro , Ando Yukio , Ishitsu Takateru , Nakagawa Kazuko 
Published: January 2008

Abstract
This study tested the hypothesis that the determinants of mild liver injury are prerequisites for more severe idiosyncratic hepatotoxicity. This study verified whether the possible risk factors for rare idiosyncratic valproic acid (VPA)-induced hepatotoxicity, VPA clearance and/or serum carnitine concentrations are common to those for a mild elevation in transaminases in VPA-treated patients. VPA clearance was calculated in 172 Japanese patients with epilepsy, using a non-linear mixed-effects regression program. Carnitine concentrations were determined in a subset of 60 patients. The relationships between VPA clearance, carnitine concentration and levels of transaminases and ammonia were evaluated by Pearson's correlation coefficients. The final model of VPA apparent clearance (CL/F) was as follows: CL/F (L h−1) = 0.012 × (BW/40)0.34 × dose0.55 × 0.90gender × 1.32PHT × 1.11CBZ × 1.12PB, where BW = total body weight (kg); gender = 1 if female, 0 if male; PHT/CBZ/PB = 1 if phenytoin, carbamazepine, or phenobarbital, respectively, is coadministrated, otherwise 0. Either a higher VPA clearance or acyl/free carnitine ratio and a lower total and/or free carnitine concentration, but not VPA concentration, were associated with the mild elevation in transaminases or ammonia. These results support the initial hypothesis, while also helping to clarify the mechanism of severe idiosyncratic hepatotoxicity with VPA.
Reference Intervals for Serum Creatinine Concentrations: Assessment of Available Data for Global Application
Authors: Ceriotti Ferruccio , Boyd James C , Klein Gerhard , Henny Joseph , Queraltó Josep , Kairisto Veli , Panteghini Mauro ,   the IFCC Committee on Reference Intervals and Decision Limits (C-RIDL)
Published: January 2008

AbstractBackground: Reference intervals for serum creatinine remain relevant despite the current emphasis on the use of the estimated glomerular filtration rate for assessing renal function. Many studies on creatinine reference values have been published in the last 20 years. Using criteria derived from published IFCC documents, we sought to identify universally applicable reference intervals for creatinine via a systematic review of the literature.Methods: Studies were selected for inclusion in the systematic review only if the following criteria were met: (a) reference individuals were selected using an “a priori” selection scheme, (b) preanalytical conditions were adequately described; (c) traceability of the produced results to the isotope dilution–mass spectrometry (IDMS) reference method was demonstrated experimentally, and (d) the collected data received adequate statistical treatment.Results: Of 37 reports dealing specifically with serum creatinine reference values, only 1 report with pediatric data and 5 reports with adult data met these criteria. The primary reason for exclusion of most papers was an inadequate demonstration of measurement traceability. Based on the data of the selected studies, we have collated recommended reference intervals for white adults and children.Conclusion: Laboratories using methods producing traceable results to IDMS can apply the selected reference intervals for serum creatinine in evaluating white individuals.
Human Fertility Increases With Marital Radius
Authors: Labouriau Rodrigo , Amorim António 
Published: January 2008

Abstract
We report a positive association between marital radius (distance between mates' birthplaces) and fertility detected in a large population. Spurious association due to socioeconomic factors is discarded by a conditional analysis involving income, education, and urbanicity. Strong evidence of consanguinity's deleterious effects affecting an entire human population is provided.
Genetic Design and Statistical Power of Nested Association Mapping in Maize
Authors: Yu Jianming , Holland James B , McMullen Michael D , Buckler Edward S 
Published: January 2008

AbstractWe investigated the genetic and statistical properties of the nested association mapping (NAM) design currently being implemented in maize (26 diverse founders and 5000 distinct immortal genotypes) to dissect the genetic basis of complex quantitative traits. The NAM design simultaneously exploits the advantages of both linkage analysis and association mapping. We demonstrated the power of NAM for high-power cost-effective genome scans through computer simulations based on empirical marker data and simulated traits with different complexities. With common-parent-specific (CPS) markers genotyped for the founders and the progenies, the inheritance of chromosome segments nested within two adjacent CPS markers was inferred through linkage. Genotyping the founders with additional high-density markers enabled the projection of genetic information, capturing linkage disequilibrium information, from founders to progenies. With 5000 genotypes, 30–79% of the simulated quantitative trait loci (QTL) were precisely identified. By integrating genetic design, natural diversity, and genomics technologies, this new complex trait dissection strategy should greatly facilitate endeavors to link molecular variation with phenotypic variation for various complex traits.
Hitchhiking Mapping Reveals a Candidate Genomic Region for Natural Selection in Three-Spined Stickleback Chromosome VIII
Authors: Mäkinen Hannu S , Shikano Takahito , Cano José Manuel , Merilä Juha 
Published: January 2008

Abstract
Identification of genes and genomic regions under directional natural selection has become one of the major goals in evolutionary genetics, but relatively little work to this end has been done by applying hitchhiking mapping to wild populations. Hitchhiking mapping starts from a genome scan using a randomly spaced set of molecular markers followed by a fine-scale analysis in the flanking regions of the candidate regions under selection. We used the hitchhiking mapping approach to narrow down a selective sweep in the genomic region flanking a candidate locus (Stn90) in chromosome VIII in the three-spined stickleback (Gasterosteus aculeatus). Twenty-four microsatellite markers were screened in an ∼800-kb region around the candidate locus in three marine and four freshwater populations. The patterns of genetic diversity and differentiation in the candidate region were compared to those of a putatively neutral set of markers. The Bayesian FST-test indicated an elevated genetic differentiation, deviating significantly from neutral expectations, at a continuous region of ∼20 kb upstream from the candidate locus. Furthermore, a method developed for an array of microsatellite markers rejected neutrality in a region of ∼90 kb flanking the candidate locus supporting the selective sweep hypothesis. Likewise, the genomewide pattern of genetic diversity differed from the candidate region in a bottleneck analysis suggesting that selection, rather than demography, explains the reduced genetic diversity at the candidate interval. The neutrality tests suggest that the selective sweep had occurred mainly in the Lake Pulmanki population, but the results from bottleneck analyses indicate that selection might have operated in other populations as well. These results suggest that the narrow interval around locus Stn90 has likely been under directional selection, but the region contains several predicted genes, each of which can be the actual targets of selection. Understanding of the functional significance of this genomic region in an ecological context will require a more detailed sequence analysis.
Investigations of CHD1 Function in Transcription and Development of Drosophila melanogaster
Authors: McDaniel Ivy E , Lee Jennifer M , Berger Matthew S , Hanagami Cori K , Armstrong Jennifer A 
Published: January 2008

Abstract
In this report we describe chd1 mutant alleles and show that the CHD1 chromatin-remodeling factor is important for wing development and fertility. While CHD1 colocalizes with elongating RNA polymerase II (Pol II) on polytene chromosomes, elongating Pol II can persist on chromatin in the absence of CHD1. These results clarify the roles of chromatin remodelers in transcription and provide novel insights into CHD1 function.
Mitochondrial DNA Transfer to the Nucleus Generates Extensive Insertion Site Variation in Maize
Authors: Lough Ashley N , Roark Leah M , Kato Akio , Ream Thomas S , Lamb Jonathan C , Birchler James A , Newton Kathleen J 
Published: January 2008

AbstractMitochondrial DNA (mtDNA) insertions into nuclear chromosomes have been documented in a number of eukaryotes. We used fluorescence in situ hybridization (FISH) to examine the variation of mtDNA insertions in maize. Twenty overlapping cosmids, representing the 570-kb maize mitochondrial genome, were individually labeled and hybridized to root tip metaphase chromosomes from the B73 inbred line. A minimum of 15 mtDNA insertion sites on nine chromosomes were detectable using this method. One site near the centromere on chromosome arm 9L was identified by a majority of the cosmids. To examine variation in nuclear mitochondrial DNA sequences (NUMTs), a mixture of labeled cosmids was applied to chromosome spreads of ten diverse inbred lines: A188, A632, B37, B73, BMS, KYS, Mo17, Oh43, W22, and W23. The number of detectable NUMTs varied dramatically among the lines. None of the tested inbred lines other than B73 showed the strong hybridization signal on 9L, suggesting that there is a recent mtDNA insertion at this site in B73. Different sources of B73 and W23 were examined for NUMT variation within inbred lines. Differences were detectable, suggesting either that mtDNA is being incorporated or lost from the maize nuclear genome continuously. The results indicate that mtDNA insertions represent a major source of nuclear chromosomal variation.