bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three Phase II Cytokine Working Group Trials of gp100 (210M) Peptide Plus High-Dose Interleukin-2 in Patients With HLA-A2–Positive Advanced Melanoma
Authors: Sosman Jeffrey A. , Carrillo Carole , Urba Walter J. , Flaherty Lawrence , Atkins Michael B. , Clark Joseph I. , Dutcher Janet , Margolin Kim A. , Mier James , Gollob Jarod , Kirkwood John M. , Panka David J. , Crosby Nancy A. , O'Boyle Kevin , LaFleur Bonnie , Ernstoff Marc S. 
Published: May 2008

PurposeHigh-dose interleukin-2 (IL-2) induces responses in 15% to 20% of patients with advanced melanoma; 5% to 8% are durable complete responses (CRs). The HLA-A2–restricted, modified gp100 peptide (210M) induces T-cell immunity in vivo and has little antitumor activity but, combined with high-dose IL-2, reportedly has a 42% (13 of 31 patients) response rate (RR). We evaluated 210M with one of three different IL-2 schedules to determine whether a basis exists for a phase III trial.Patients and MethodsIn three separate phase II trials, patients with melanoma received 210M subcutaneously during weeks 1, 4, 7, and 10 and standard high-dose IL-2 during weeks 1 and 3 (trial 1), weeks 7 and 9 (trial 2), or weeks 1, 4, 7, and 10 (trial 3). Immune assays were performed on peripheral-blood mononuclear cells collected before and after treatment.ResultsFrom 1998 to 2003, 131 patients with HLA-A2–positive were enrolled. With 60-month median follow-up time, the overall RR for 121 assessable patients was 16.5% (95% CI, 10% to 26%); the RRs were 23.8% in trial 1 (42 patients), 12.5% in trial 2 (40 patients), and 12.8% in trial 3 (39 patients). There were 11 CRs (9%) and nine partial responses (7%), with 11 patients (9%) progression free at ≥ 30 months. Immune studies including assays of CD3-ζ expression and numbers of CD4+/CD25+/FoxP3+regulatory T cells, CD15+/CD11b+/CD14–immature myeloid-derived cells, and CD8+gp100 tetramer-positive cells in the blood did not correlate with clinical benefit.ConclusionThe results again demonstrate efficacy of high-dose IL-2 in advanced melanoma but did not demonstrate the promising clinical activity reported with vaccine and high-dose IL-2 in any of three phase II trials.
Phase II Study of Extended-Dose Temozolomide in Patients With Melanoma
Authors: Rietschel Petra , Wolchok Jedd D. , Krown Susan , Gerst Scott , Jungbluth Achim A. , Busam Klaus , Smith Katherine , Orlow Irene , Panageas Katherine , Chapman Paul B. 
Published: May 2008

Purpose We conducted a phase II trial of extended-dose temozolomide (TMZ) in patients with melanoma to test the hypothesis that the approximately 30% response rate observed in patients treated with extended-dose TMZ with antiangiogenic agents was caused by TMZ alone. We hypothesized that expression of methylguanine methyltransferase (MGMT) in the tumor would correlate with drug resistance to TMZ. Patients and Methods Patients with stage IV or unresectable stage III melanoma were treated with TMZ 75 mg/m2/d for 6 weeks followed by a 2-week rest period. Cycles were repeated until progression. Patients were stratified by M1c disease or not. The primary end point was objective response proportion. MGMT expression was assessed by methylation-specific pyrosequencing of the promoter and by immunohistochemistry. Results Forty-nine patients (25 with M1c disease) were assessable. Three patients (12.5%) in each cohort experienced partial responses; there were no complete responses. Ten patients (21%) had stable disease lasting more than 24 weeks. Median time to progression was 3.3 months. Median survival was 10.1 months; survival was similar in the two cohorts. The estimated 18-month survival was 27%. There was no correlation between response and either immunohistochemistry staining for MGMT or for MGMT promoter methylation. Seventy-five percent of patients developed CD4+ lymphopenia after three cycles. Conclusion Extended-dose TMZ therapy did not result in a 30% responses rate, which has been observed using extended-dose TMZ with antiangiogenic agents. Response did not correlate with MGMT expression or promoter methylation as a continuous variable, suggesting that other resistance mechanisms are important.
Prognostic Factors in Metastatic Rhabdomyosarcomas: Results of a Pooled Analysis From United States and European Cooperative Groups
Authors: Oberlin Odile , Rey Annie , Lyden Elizabeth , Bisogno Gianni , Stevens Michael C.G. , Meyer William H. , Carli Modesto , Anderson James R. 
Published: May 2008

Purpose To identify risk factors associated with outcome in children with metastatic rhabdomyosarcoma in a large cohort of patients Patients and Methods Pooled data were obtained from 788 patients treated in nine studies performed by European and American cooperative groups. Clinical factors, including age, histology, site of primary, and site(s) and number of sites of metastatic disease, were correlated with event-free survival (EFS) and overall survival (OS). Results Seven hundred eighty-eight patients were eligible for analysis. The 3-year OS and EFS were 34% (SE, 1.7) and 27% (SE, 1.6), respectively. By univariate analysis, 3-year EFS was significantly and adversely influenced by age, alveolar histology, location of primary tumor in unfavorable site (defined as extremity and “other” sites), presence of three or more sites of metastatic disease, and the presence of bone or bone marrow involvement. By multivariate analysis, EFS was strongly correlated to all factors except histology. Relative risks were 1.6 for age younger than 1 year or at least 10 years, 1.4 for unfavorable site of primary tumor, 1.4 for bone or bone marrow involvement, 1.4 for three or more metastatic sites. EFS was 50% for patients without any of these four adverse factors and was respectively 42%, 18%, 12%, and 5% in patients with one, two, three, or four factors (P < .0001). Conclusion This analysis identified subsets of patients with metastatic rhabdomyosaroma with different outcomes to current therapy and offers a strategy to define patient candidates for experimental approaches to treatment.
Tailored Chemotherapy Information Faxed to General Practitioners Improves Confidence in Managing Adverse Effects and Satisfaction With Shared Care: Results From a Randomized Controlled Trial
Authors: Jefford Michael , Baravelli Carl , Dudgeon Paul , Dabscheck Adrian , Evans Melanie , Moloney Michael , Schofield Penelope 
Published: May 2008

Purpose General practitioners (GPs) play a critical role in the treatment of patients with cancer; yet often lack information for optimal care. We developed standardized information for GPs about chemotherapy (CT). In a randomized controlled trial we assessed the impact of sending, by fax, information tailored to the particular patient's CT regimen. Primary end points were: confidence treating patients who were receiving CT (confidence), knowledge of adverse effects and reasons to refer the patient to the treatment center (knowledge), and satisfaction with information and shared care of patients (satisfaction). Methods Focus group work informed the development of the CT information which focused on potential adverse effects and recommended management strategies. GPs of patients due to commence CT were randomly assigned to receive usual correspondence with or without the faxed patient/regimen-specific information. Telephone questionnaire at baseline and 1 week postintervention assessed knowledge, confidence, and satisfaction. Results Ninety-seven GPs managed 97 patients receiving 23 types of CT. Eighty-one (83.5%) completed the follow-up questionnaire. GPs in the intervention group demonstrated a significantly greater increase in confidence (mean difference, 0.28; 95% CI, 0.10 to 0.47) and satisfaction (mean difference, 0.57; 95% CI, 0.27 to 0.88) compared with usual care, reflecting a 7.1% and 10.5% difference in score, respectively. No differences were detected for knowledge. GPs receiving the CT sheet found correspondence significantly more useful (P < .001) and instructive (P < .001) than GPs who received standard correspondence alone. Conclusion Information about CT faxed to GPs is a simple, inexpensive intervention that increases confidence managing CT adverse effects and satisfaction with shared care. This intervention could have widespread application.
Interventions for Alleviating Cancer-Related Dyspnea: A Systematic Review
Authors: Ben-Aharon Irit , Gafter-Gvili Anat , Paul Mical , Leibovici Leonard , Stemmer Salomon M. 
Published: May 2008

Purpose Dyspnea is one of the most distressing symptoms experienced by terminally ill cancer patients. This study aimed to evaluate the role of interventions for the palliation of dyspnea. Methods We conducted a systematic review of randomized controlled trials assessing all pharmacologic and nonpharmacologic interventions for dyspnea palliation in cancer patients, and searched the Cochrane Library, MEDLINE, conference proceedings, and references. Two reviewers independently appraised the quality of trials and extracted data. Results Our search yielded 18 trials. Fourteen evaluated pharmacologic interventions: seven assessing opioids (a total of 256 patients), five assessing oxygen (137 patients), one assessing helium-enriched air, and one assessing furosemide. Four trials evaluated nonpharmacologic interventions (403 patients). The administration of subcutaneous morphine resulted in a significant reduction in dyspnea Visual Analog Scale (VAS) compared with placebo. No difference was observed in dyspnea VAS score when nebulized morphine was compared with subcutaneous morphine, although patients preferred the nebulized route. The addition of benzodiazepines to morphine was significantly more effective than morphine alone, without additional adverse effects. Oxygen was not superior to air for alleviating dyspnea, except for patients with hypoxemia. Nursing-led interventions improved breathlessness. Acupuncture was not beneficial. Conclusion Our review supports the use of opioids for dyspnea relief in cancer patients. The use of supplemental oxygen to alleviate dyspnea can be recommended only in patients with hypoxemia. Nursing-led nonpharmacologic interventions seem valuable. Only a few studies addressing this question were performed. Thus, further studies evaluating interventions for alleviating dyspnea are warranted.
Survival Following Recurrence in Stage II and III Colon Cancer: Findings From the ACCENT Data Set
Authors: O'Connell Michael J. , Campbell Megan E. , Goldberg Richard M. , Grothey Axel , Seitz Jean-François , Benedetti Jacqueline K. , André Thierry , Haller Daniel G. , Sargent Daniel J. 
Published: May 2008

Purpose This study was undertaken to examine five possible prognostic factors in patients with recurrent stage II and III colon cancer: time from randomization on an adjuvant therapy clinical trial to tumor recurrence (< 1 year, 1 to 2 years, 2 to 3 years, 3 to 4 years, > 4 years), initial stage (II v III), initial adjuvant treatment (fluorouracil [FU]-based v surgery alone), the era in which the patient entered an adjuvant therapy clinical trial (1978 to 1985, 1986 to 1992, 1993 to 1999), and patient age at recurrence. Methods The Adjuvant Colon Cancer End Points (ACCENT) data set was analyzed using univariate and multivariate Cox proportional hazards models, stratified by study. Results 5,722 (32.9%) of 17,381 patients experienced recurrence. Median survival following recurrence was 13.3 months. Time from randomization to recurrence was highly prognostic of survival following recurrence (P < .0001). Longer survival following recurrence was seen in patients with initial stage II versus III disease (P < .0001; 14.3% 6-year overall survival after recurrence in initial stage II patients), patients entered more recently onto trials (P < .0001), and patients initially treated with surgery alone versus FU adjuvant treatment (P = .0005). All relationships were maintained in multivariate models. Conclusion Time from initial treatment to recurrence and initial stage are important prognostic factors in patients with recurrent colon cancer. Survival following recurrence increased modestly from 1978 to 1999. Patients who had a recurrence following adjuvant therapy had poorer prognosis than those who progressed after surgery alone. These prognostic factors may be useful for clinical trial design and treatment decisions in patients with recurrent colon cancer.
Comparing results of digital photoplethysmography in two groups of chronic obstructive pulmonary disease patients with and without high pulmonary artery pressure
Authors: Sharif-Kashani B , Behzadnia N , Shahabi P 
Published: May 2008

Background Digital photoplethysmography (D-PPG) is a newly introduced method of optical screening of deep vein thrombosis (DVT) by recording changes in the size of limb due to tissue fluid. Objectives The objective of this study is to assess the effect of high pulmonary artery pressure (PAP) and consequently increased venous system pressure on D-PPG test results. Methods Forty-five patients with and 45 patients without PAP pressure were enrolled in the study and divided into two groups. All the patients had a history of chronic obstructive pulmonary disease (COPD). D-PPG test was performed for both legs of all the patients and the results of the two groups were compared. Also, all patients underwent duplex sonography for ruling out DVT. Results Using venous refilling time (RT) of <22 s as the optimal cut-off point, it was found that 32 (35%) legs of patients with and 39 (43%) legs of patients without high PAP had positive D-PPG test. Although the rate of positive D-PPG test was higher in patients with high PAP, this was not statistically significant ( P = 0.28). Moreover, overall correlation between RT and venous pump detected by D-PPG and PAP was r = −0.11 ( P = 0.2) and r = −0.01 ( P = 0.6), respectively. Conclusion Our results showed that the rate of positive D-PPG test results is slightly higher in patients with pulmonary hypertension, but this difference is not statistically significant. Therefore, increased PAP could be excluded as a confounding factor of D-PPG test.
SMAD3 Functions as a Transcriptional Repressor of Acid-Sensing Ion Channel 3 (ASIC3) in Nucleus Pulposus Cells of the Intervertebral Disc
Authors: Uchiyama Yoshiyasu , Guttapalli Asha , Gajghate Sachin , Mochida Joji , Shapiro Irving M , Risbud Makarand V 
Published: May 2008

Abstract
The goal of this investigation was to study the regulation of acid-sensing ion channel (ASIC)3 expression by TGFβ in the nucleus pulposus cells of the intervertebral disc. Analysis of human nucleus pulposus tissue indicated decreased ASIC3 and elevated TGFβ expression in the degenerate state. In a parallel study, treatment of nucleus pulposus cells with TGFβ resulted in decreased expression of ASIC3 mRNA and protein. Suppression of ASIC3 promoter activity was evident when the nucleus pulposus cells were treated with TGFβ or co-transfected with the constitutively active ALK5 or a smad3 construct. On the other hand, co-transfection of dominant negative smad3 or smad7 restored ASIC3 promoter activity. We validated the role of smad3 in controlling ASIC3 expression using cells derived from smad3-null mice. ASIC3 promoter activity in the null cells was 2- to 3-fold higher than the wildtype cells. Moreover, expression of smad3 in null cells decreased ASIC3 promoter activity by almost 50%. Further studies using deletion constructs and trichostatin A treatment showed that the full-length smad3 was necessary, and the suppression involved recruitment of histone deacetylase to the promoter. To determine the mechanism, we evaluated the rat ASIC3 promoter sequence and noted the presence of two smad interacting CAGA box motifs. Gel-shift and supershift analysis indicated that smad3 protein was bound to this motif. Chromatin immunoprecipitation analysis confirmed that smad3 bound both the CAGA elements. Results of these studies clearly show that TGFβ is highly expressed in the degenerate disc and through smad3 serves as a negative regulator of ASIC3 expression.
A Missense T(Brachyury) Mutation Contributes to Vertebral Malformations
Authors: Ghebranious Nader , Blank Robert D , Raggio Cathleen L , Staubli Justin , McPherson Elizabeth , Ivacic Lynn , Rasmussen Kristen , Jacobsen F Stig , Faciszewski Thomas , Burmester James K , Pauli Richard M , Boachie-Adjei Oheneba , Glurich Ingrid , Giampietro Philip F 
Published: May 2008

Abstract
No major susceptibility genes for sporadically occurring congenital vertebral malformations (CVM) in humans have been identified to date. Body patterning genes whose mutants cause axial skeletal anomalies in mice are candidates for human CVM susceptibility. T (also known as Brachyury) and TBX6 are critical genes needed to establish mesodermal identity. We hypothesized that mutations in T and/or TBX6 contribute to the pathogenesis of human CVMs. The complete T and TBX6 coding regions, splice junctions, and proximal 500 bp of the promoters were sequenced in 50 phenotyped patients with CVM. Three unrelated patients with sacral agenesis, Klippel-Feil syndrome, and multiple cervical and thoracic vertebral malformations were heterozygous for a c.1013C&gt;T substitution, resulting in a predicted Ala338Val missense alteration in exon 8. A clinically unaffected parent of each patient also harbored the substitution, but the variant did not occur in an ethnically diverse, 443-person reference population. The c.1013C&gt;T variant is significantly associated with CVM (p &lt; 0.001). Alanine 338 shows moderate conservation across species, and valine at this position has not been reported in any species. A fourth patient harbored a c.908–8C&gt;T variant in intron 7. This previously unreported variant was tested in 347 normal control subjects, and 11 heterozygotes and 2 T/T individuals were found. No TBX6 variants were identified. We infer that the c.1013C&gt;T substitution is pathogenic and represents the first report of an association between a missense mutation in the T gene and the occurrence of sporadic CVMs in humans. It is uncertain whether the splice junction variant increases CVM risk. TBX6 mutations do not seem to be associated with CVM. We hypothesize that epistatic interactions between T and other developmental genes and the environment modulate the phenotypic consequences of T variants.
Drift Dynamics of Larval Pallid Sturgeon and Shovelnose Sturgeon in a Natural Side Channel of the Upper Missouri River, Montana
Authors: Braaten Patrick J. , Fuller David B. , Holte Landon D. , Lott Ryan D. , Viste William , Brandt Tyrel F. , Legare Robert G. 
Published: May 2008

Abstract
The drift dynamics of larval shovelnose sturgeon Scaphirhynchus platorynchus (1, 2, 6, and 10 d posthatch (dph)) and pallid sturgeon S. albus (1, 2, 5, 9, 11, and 17 dph) were examined in a natural side channel of the Missouri River to quantify the vertical drift location of larvae in the water column, determine the drift velocity of larvae relative to water velocity, and simulate the cumulative distance (km) drifted by larvae during ontogenetic development. Larvae were released at the side-channel inlet and sampled at points 100, 500, 900, and 1,300 m downstream. Larvae drifted primarily near the riverbed, as 58–79% of recaptured shovelnose sturgeon and 63–89% of recaptured pallid sturgeon were sampled in the lower 0.5 m of the water column. The transition from the drifting to the benthic life stage was initiated at 6 dph (mean length, 15.6 mm) for shovelnose sturgeon and at 11–17 dph (mean length, 18.1–20.3 mm) for pallid sturgeon. Across ages, the drift rates of larval shovelnose sturgeon averaged 0.09–0.16 m/s slower than the mean water column velocity. The drift rates of pallid sturgeon were similar to or slightly slower (0.03–0.07 m/s) than the mean water column velocity for 1–11-dph larvae. Conversely, 17-dph larval pallid sturgeon dispersed downstream at a much slower rate (mean, 0.20 m/s slower than the mean water column velocity) owing to their transition to benthic habitats. Drift simulations indicated that the average larval shovelnose sturgeon may drift from 94 to 250 km and the average larval pallid sturgeon may drift from 245 to 530 km, depending on water velocity. Differences in larval drift dynamics between species provide a possible explanation for differences in recruitment between shovelnose sturgeon and pallid sturgeon in the upper Missouri River.
Modeling effects of herbicide drift on the competitive interactions between weeds
Authors: Damgaard Christian , Mathiassen Solvejg Kopp , Kudsk Per 
Published: May 2008

Abstract
Herbicides may drift onto road verges or natural areas adjacent to arable fields and affect nontarget plants. The effect of low doses of mecoprop-P on the competitive interactions and plant community dynamics was investigated in a model system using Capsella bursa-pastoris and Geranium dissectum as test plants. Dose–response experiments on single species showed that compared to G. dissectum, C. bursa-pastoris was more affected by mecoprop-P. Consequently, we expected that G. dissectum would outcompete C. bursa-pastoris when mecoprop-P was applied at a low dose in the competition experiment. Indeed, mecoprop-P had a significant effect on the interspecific competitive ability of both C. bursa-pastoris and G. dissectum. Our previous expectation, however, was not met: The interspecific competitive ability of both species increased significantly with the dose of the herbicide, and it was predicted that C. bursa-pastoris and G. dissectum are more likely to coexist in natural habitats with low concentrations of the herbicide compared to natural habitats with relatively high concentrations. The results from the dose–response experiments on the single species and the more laborious competition experiment approach, which is assumed to mimic the dynamics of plant communities more closely, show considerable discrepancies even though the experiments were performed at the same time and in the same greenhouse. This finding generally reduces the credibility of using single-species tests in ecological risk assessment of herbicide use.
Responses of zooplankton in lufenuron-stressed experimental ditches in the presence or absence of uncontaminated refuges
Authors: López-Mancisidor Patricia , Van den Brink Paul J , Crum Steven J.H , Maund Steve J , Carbonell Gregoria , Brock Theo C.M 
Published: May 2008

AbstractOutdoor experimental ditches were used to evaluate the influence of untreated refuges on the recovery of zooplankton communities following treatment with the fast-dissipating insecticide lufenuron. Each experimental ditch was divided into three sections of the same surface area. The treatments differed in the proportion of ditch (0, 33, 67, and 100% of the surface area) to which the insecticide was applied at the same nominal treatment (3 μg/L). During the first week postapplication, a barrier was placed between treated and untreated ditch sections. The untreated sections were included to provide a source of organisms for recovery of affected zooplankton populations in the treated sections of the ditch after the removal of the barrier. Cyclopoida were the most affected by lufenuron treatment, followed by Daphnia gr. galeata. These and other direct effects of treatment on larvae of the phantom midge Chaoborus spp. resulted in clear indirect effects on populations of Calanoida, Ceriodaphnia, and Rotifera. Overall, faster recovery of the zooplankton community was observed in the treated sections of ditches that were sprayed for a smaller proportion of their surface area. Nevertheless, individual zooplankton populations showed considerable differences in rate of recovery. Cyclopoida showed a relatively slow rate of recovery even in the partially treated ditches. Daphnia gr. galeata recovered more rapidly in treated ditch sections in the presence of unsprayed ditch sections, illustrating the potential influence of unexposed refuges. Furthermore, the presence of refuges most likely dampened the magnitude and duration of indirect effects in the ditches treated with lufenuron.