bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychoeducational Intervention for Patients With Cutaneous Malignant Melanoma: A Replication Study
Authors: Boesen Ellen H. , Ross Lone , Frederiksen Kirsten , Thomsen Birthe L. , Dahlstrøm Karin , Schmidt Grethe , Næsted Jesper , Krag Christen , Johansen Christoffer 
Published: February 2005

PurposeIn 1993, a randomized intervention study among patients with malignant melanoma showed a significant decrease in psychological distress and increased coping capacity 6 months after the intervention and enhanced survival 6 years later. We applied a similar intervention with a few modifications in a randomized controlled trial among Danish patients with malignant melanoma and evaluated results on immediate and long-term effects on psychological distress and coping capacity.Patients and MethodsA total of 262 patients with primary cutaneous malignant melanoma were randomly assigned to the control or intervention group. Patients in the intervention group were offered six weekly sessions of 2 hours of psychoeducation, consisting of health education, enhancement of problem-solving skills, stress management, and psychological support. The participants were assessed at baseline before random assignment and 6 and 12 months after surgery. The analyses of the main effects of the intervention were based on analyses of covariance.ResultsThe patients in the intervention group showed significantly less fatigue, greater vigor, and lower total mood disturbance compared with the controls, and they used significantly more active-behavioral and active-cognitive coping than the patients in the control group. The improvements were only significant at first follow-up.ConclusionThe findings of this study support the results of an earlier intervention study among patients with malignant melanoma and indicate that a psychoeducational group intervention for such patients can decrease psychological distress and enhance effective coping. However, this effect is short term and the clinical relevance is not obvious.
[18F]Fluorodeoxyglucose Uptake by Positron Emission Tomography Predicts Outcome of Non–Small-Cell Lung Cancer
Authors: Sasaki Ryohei , Komaki Ritsuko , Macapinlac Homer , Erasmus Jeremy , Allen Pamela , Forster Kenneth , Putnam Joe B. , Herbst Roy S. , Moran Cesar A. , Podoloff Donald A. , Roth Jack A. , Cox James D. 
Published: February 2005

Purpose To determine whether the standardized uptake value (SUV) of [18F]fluorodeoxyglucose uptake by positron emission tomography could be a prognostic factor for non–small-cell lung cancer (NSCLC). Patients and Methods One hundred sixty-two patients with stage I to IIIb NSCLC were analyzed. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local-regional control (LRC) were calculated by the Kaplan-Meier method and evaluated with the log-rank test. The prognostic significance was assessed by univariate and multivariate analyses. Results There were 93 patients treated with surgery and 69 patients treated with radiotherapy. A cutoff of 5 for the SUV for the primary tumor showed the best discriminative value. The SUV for the primary tumor was a significant predictor of OS (P = .02) in both groups. Low SUVs (≤ 5.0) showed significantly better DFS rates than those with high SUVs (> 5.0; surgery group, P = .02; radiotherapy group, P = .0005). Low SUVs (≤ 5.0) indicated a significantly better DFS than those with high SUVs (> 5.0; stage I or II, P = .02; stage IIIa or IIIb, P = .004). However, using the same cutoff point of 5, the SUV for regional lymph nodes was not a significant indicator for DFS (P = .19), LRC (P = .97), or DMFS (P = .17). The multivariate analysis showed that the SUV for the primary tumor was a significant prognostic factor for OS (P = .03) and DFS (P = .001). Conclusion The SUV of the primary tumor was the strongest prognostic factor among the patients treated by curative surgery or radiotherapy.
Hyperfractionated Accelerated Chemoradiation With Concurrent Fluorouracil-Mitomycin Is More Effective Than Dose-Escalated Hyperfractionated Accelerated Radiation Therapy Alone in Locally Advanced Head and Neck Cancer: Final Results of the Radiotherapy Cooperative Clinical Trials Group of the German Cancer Society 95-06 Prospective Randomized Trial
Authors: Budach Volker , Stuschke Martin , Budach Wilfried , Baumann Michael , Geismar Dirk , Grabenbauer Gerhard , Lammert Ingrid , Jahnke Klaus , Stueben Georg , Herrmann Thomas , Bamberg Michael , Wust Peter , Hinkelbein Wolfgang , Wernecke Klaus-Dieter 
Published: February 2005

Purpose To report the results and corresponding acute and late reactions of a prospective, randomized, clinical study in locally advanced head and neck cancer comparing concurrent fluorouracil (FU) and mitomycin (MMC) chemotherapy and hyperfractionated accelerated radiation therapy (C-HART; 70.6 Gy) to hyperfractionated accelerated radiation therapy alone (HART; 77.6 Gy). Patients and Methods Three hundred eighty-four stage III (6%) and IV (94%) oropharyngeal (59.4%), hypopharyngeal (32.3%), and oral cavity (8.3%) cancer patients were randomly assigned to receive either 30 Gy (2 Gy every day) followed by 1.4 Gy bid to a total of 70.6 Gy concurrently with FU (600 mg/m2, 120 hours continuous infusion) days 1 through 5 and MMC (10 mg/m2) on days 5 and 36 (C-HART) or 14 Gy (2 Gy every day) followed by 1.4 Gy bid to a total dose of 77.6 Gy (HART). The data were analyzed on an intent-to-treat basis. Results At 5 years, the locoregional control and overall survival rates were 49.9% and 28.6% for C-HART versus 37.4% and 23.7% for HART, respectively (P = .001 and P = .023, respectively). Progression-free and freedom from metastases rates were 29.3% and 51.9% for C-HART versus 26.6% and 54.7% for HART, respectively (P = .009 and P = .575, respectively). For C-HART, maximum acute reactions of mucositis, moist desquamation, and erythema were lower than with HART, whereas no differences in late reactions and overall rates of secondary neoplasms were observed. Conclusion C-HART (70.6 Gy) is superior to dose-escalated HART (77.6 Gy) with comparable or less acute reactions and equivalent late reactions, indicating an improvement of the therapeutic ratio.
Randomized Trial of 30 Versus 20 Gy in the Adjuvant Treatment of Stage I Testicular Seminoma: A Report on Medical Research Council Trial TE18, European Organisation for the Research and Treatment of Cancer Trial 30942 (ISRCTN18525328)
Authors: Jones William G. , Fossa Sophie D. , Mead Graham M. , Roberts J. Trevor , Sokal Michael , Horwich Alan , Stenning Sally P. 
Published: February 2005

PurposeTo assess the possibility of reducing radiotherapy doses without compromising efficacy in the management of patients with stage I seminoma.Patients and MethodsPatients were randomly assigned 20 Gy/10 fractions over 2 weeks or 30 Gy/15 fractions during 3 weeks after orchidectomy. They completed a symptom diary card during treatment and quality-of-life forms pre- and post-treatment. The trial was powered to exclude absolute differences in 2-year relapse rates of 3% to 4% (α = .05 [one sided]; 90% power).ResultsFrom 1995 to 1998, 625 patients were randomly assigned to treatment. Four weeks after starting radiotherapy, significantly more patients receiving 30 Gy reported moderate or severe lethargy (20% v 5%) and an inability to carry out their normal work (46% v 28%). However, by 12 weeks, levels in both groups were similar. With a median follow-up of 61 months, 10 and 11 relapses, respectively, have been reported in the 30- and 20-Gy groups (hazard ratio, 1.11; 90% CI, 0.54 to 2.28). The absolute difference in 2-year relapse rates is 0.7%; the lower 90% confidence limit is 2.9%. Only one patient has died from seminoma (allocated to the 20-Gy treatment group).ConclusionTreatment with 20 Gy in 10 fractions is unlikely to produce relapse rates more than 3% higher than for standard 30 Gy radiation therapy, and data on an additional 469 patients randomly assigned in a subsequent trial support and strengthen these results. Reductions in morbidity enable patients to return to work more rapidly. Prolonged follow-up is required before any inference can be made about any impact of allocated treatment on new primary cancer diagnoses.
First and Subsequent Cycle Use of Pegfilgrastim Prevents Febrile Neutropenia in Patients With Breast Cancer: A Multicenter, Double-Blind, Placebo-Controlled Phase III Study
Authors: Vogel Charles L. , Wojtukiewicz Marek Z. , Carroll Robert R. , Tjulandin Sergei A. , Barajas-Figueroa Luis Javier , Wiens Brian L. , Neumann Theresa A. , Schwartzberg Lee S. 
Published: February 2005

Purpose We evaluated the efficacy of pegfilgrastim to reduce the incidence of febrile neutropenia associated with docetaxel in breast cancer patients. Patients and Methods Patients were randomly assigned to either placebo or pegfilgrastim 6 mg subcutaneously on day 2 of each 21-day chemotherapy cycle of 100 mg/m2 docetaxel. The primary end point was the percentage of patients developing febrile neutropenia (defined as body temperature ≥ 38.2°C and neutrophil count < 0.5 × 109/L on the same day of the fever or the day after). Secondary end points were incidence of hospitalizations associated with a diagnosis of febrile neutropenia, intravenous (IV) anti-infectives required for febrile neutropenia, and the ability to maintain planned chemotherapy dose on time. Patients with febrile neutropenia were converted to open-label pegfilgrastim in subsequent cycles. Results Nine hundred twenty-eight patients received placebo (n = 465) or pegfilgrastim (n = 463). Patients receiving pegfilgrastim, compared with patients receiving placebo, had a lower incidence of febrile neutropenia (1% v 17%, respectively; P < .001), febrile neutropenia–related hospitalization (1% v 14%, respectively; P < .001), and use of IV anti-infectives (2% v 10%, respectively; P < .001). The percentage of patients receiving the planned dose on time was similar between patients receiving pegfilgrastim and patients who initially received placebo (80% and 78%, respectively), as would be expected of the study design. Pegfilgrastim was generally well tolerated and safe, and the adverse events reported were typical of this patient population. Conclusion First and subsequent cycle use of pegfilgrastim with a moderately myelosuppressive chemotherapy regimen markedly reduced febrile neutropenia, febrile neutropenia–related hospitalizations, and IV anti-infective use.
Phase I Trial of 17-Allylamino-17-Demethoxygeldanamycin in Patients With Advanced Cancer
Authors: Goetz Matthew P. , Toft David , Reid Joel , Ames Matthew , Stensgard Bridget , Safgren Stephanie , Adjei Araba A. , Sloan Jeff , Atherton Pamela , Vasile Vlad , Salazaar Sandra , Adjei Alex , Croghan Gary , Erlichman Charles 
Published: February 2005

Purpose We determined the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLT) of 17-allylamino-17-demethoxygeldanamycin (17-AAG) when infused on days 1, 8, and 15 of a 28-day cycle in advanced solid tumor patients. We also characterized the pharmacokinetics of 17-AAG, its effect on chaperone and client proteins, and whether cytochrome P450 (CYP) 3A5 and NAD(P)H:quinone oxidoreductase 1 (NQO1) polymorphisms affected 17-AAG disposition or toxicity. Patients and Methods An accelerated titration design was used. Biomarkers were measured in peripheral-blood mononuclear cells (PBMCs) at baseline and on days 1 and 15, and pharmacokinetic analysis was performed on day 1 of cycle 1. CYP3A5*3 and NQO1*2 genotypes were determined and correlated with pharmacokinetics and toxicity. Results Twenty-one patients received 52 courses at 11 dose levels. DLTs at 431 mg/m2 were grade 3 bilirubin (n = 1), AST (n = 1), anemia (n = 1), nausea (n = 1), vomiting (n = 1), and myalgias (n = 1). No tumor responses were seen. 17-AAG consistently increased heat shock protein (Hsp) 70 levels in PBMCs. At the MTD, the clearance and half-life (t1/2) of 17-AAG were 11.6 L/h/m2 and 4.15 hours, respectively; whereas the active metabolite 17-aminogeldanamycin had a t1/2 of 7.63 hours. The CYP3A5*3 and NQO1*2 polymorphisms were not associated with 17-AAG toxicity. The CYP3A5*3 polymorphism was associated with higher 17-AAG clearance. Conclusion The MTD of weekly 17-AAG is 308 mg/m2. 17-AAG induced Hsp70 in PBMCs, indicating that Hsp90 has been affected. Further evaluation of 17-AAG is ongoing using a twice-weekly regimen, and this schedule of 17-AAG is being tested in combination with chemotherapy.
Role of the Second-Messenger Cyclic-Adenosine 5′-Diphosphate-Ribose on Adrenocorticotropin Secretion from Pituitary Cells
Authors: Soares Sandra M. , Thompson Michael , Chini Eduardo N. 
Published: February 2005

AbstractWe examined the role of the second-messenger cyclic-ADP-ribose (cADPR) on the regulation of ACTH secretion using AtT20 corticotroph tumor cell line. We found that the cADPR antagonist, 8-Br-cADPR, substantially diminished the secretion of ACTH induced by CRH and potassium in these cells, whereas xestospongin C, an inositol 1,4,5-triphosphate receptor antagonist, had no effect. In addition, the cADPR agonist, 3-deaza-cADPR, augmented ACTH secretion. The presence of the components of the cADPR system, namely ryanodine receptor, CD38, and cADPR itself, was determined in AtT20 cells. Furthermore, we observed that antagonists of the ryanodine channel and cADPR system can decrease the potassium-induced Ca2+ transients in these cells. These results suggest that cADPR is a second messenger in pituitary cells and regulates ACTH secretion by a mechanism dependent on activation of the ryanodine channel by extracellular Ca2+.
Insulin Receptor Substrate-1 Is Required for Bone Anabolic Function of Parathyroid Hormone in Mice
Authors: Yamaguchi Masayuki , Ogata Naoshi , Shinoda Yusuke , Akune Toru , Kamekura Satoru , Terauchi Yasuo , Kadowaki Takashi , Hoshi Kazuto , Chung Ung-Il , Nakamura Kozo , Kawaguchi Hiroshi 
Published: February 2005

Abstract
Bone anabolic action of PTH has been suggested to be mediated by induction of IGF-I in osteoblasts; however, little is known about the molecular mechanism by which IGF-I leads to bone formation under the PTH stimulation. This study initially confirmed in mouse osteoblast cultures that PTH treatment increased IGF-I mRNA and protein levels and alkaline phosphatase activity, which were accompanied by phosphorylations of IGF-I receptor, insulin receptor substrate (IRS)-1 and IRS-2, essential adaptor molecules for the IGF-I signaling. To learn the involvement of IRS-1 and IRS-2 in the bone anabolic action of PTH in vivo, IRS-1−/− and IRS-2−/− mice and their respective wild-type littermates were given daily injections of PTH (80 μg/kg) or vehicle for 4 wk. In the wild-type mice, the PTH injection increased bone mineral densities of the femur, tibia, and vertebrae by 10–20% without altering the serum IGF-I level. These stimulations were similarly seen in IRS-2−/− mice; however, they were markedly suppressed in IRS-1−/− mice. Although the PTH anabolic effects were stronger on trabecular bones than on cortical bones, the stimulations on both bones were blocked in IRS-1−/− mice but not in IRS-2−/− mice. Histomorphometric and biochemical analyses showed an increased bone turnover by PTH, which was also blunted by the IRS-1 deficiency, though not by the IRS-2 deficiency. These results indicate that the PTH bone anabolic action is mediated by the activation of IRS-1, but not IRS-2, as a downstream signaling of IGF-I that acts locally as an autocrine/paracrine factor.
Functional Expression of β-Chemokine Receptors in Osteoblasts: Role of Regulated upon Activation, Normal T Cell Expressed and Secreted (RANTES) in Osteoblasts and Regulation of Its Secretion by Osteoblasts and Osteoclasts
Authors: Yano Shozo , Mentaverri Romuald , Kanuparthi Deepthi , Bandyopadhyay Sanghamitra , Rivera Alicia , Brown Edward M. , Chattopadhyay Naibedya 
Published: February 2005

AbstractThe expression and functions of receptors for the β-chemokine, regulated upon activation, normal T cell expressed, and secreted (RANTES)/CCL5, were investigated in osteoblasts. Both primary osteoblasts and the MC3T3-E1 osteoblast cell line express the RANTES receptors, CCR1, 3, 4, and 5 (by RT-PCR), which encode functional receptors in osteoblasts as shown by [125I]-RANTES binding followed by Scatchard analysis. Expression of all four RANTES receptor mRNAs in osteoblast is in contrast to the reports of expression of CCR1 being the only RANTES receptor expressed by osteoclasts. Exogenous RANTES elicits chemotaxis of osteoblasts and promotes cell survival via phosphatidylinositol 3-kinase with attendant phosphorylation of Akt. Osteoclastic RANTES, obtained from the conditioned medium of receptor activator of nuclear factor-κB ligand-differentiated RAW264.7 cells also induces chemotaxis of MC3T3-E1 cells. Incubating the conditioned medium with an anti-RANTES neutralizing antibody attenuated this effect. RANTES secretion from osteoblast is inhibited by differentiation promoting hormones, e.g. 1,25 (OH)2D3 and dexamethasone, whereas macrophage inflammatory protein-1α (but not macrophage inflammatory protein-1β) and elevated calcium induce it. Elevated calcium also stimulated RANTES secretion by osteoclasts. Therefore, RANTES is an osteoblast chemoattractant and a survival-promoting molecule whose regulation in osteoblast is varied. Furthermore, RANTES secreted from osteoclasts induces osteoblast chemotaxis. Therefore, expression of RANTES and its receptors in both osteoblasts and osteoclasts could enable this chemokine to act in autocrine/paracrine modes.
Thyroid Transcription Factor 1 Rescues PAX8/p300 Synergism Impaired by a Natural PAX8 Paired Domain Mutation with Dominant Negative Activity
Authors: Grasberger Helmut , Ringkananont Usanee , LeFrancois Paule , Abramowicz Marc , Vassart Gilbert , Refetoff Samuel 
Published: February 2005

AbstractMutations in the paired domain transcription factor PAX8 are a rare cause of congenital hypothyroidism due to thyroid dysgenesis. We identified a novel and unique PAX8 mutation segregating in seven affected members of a three-generations family. The mutation replaces an invariant serine residue within helix 2 of the paired DNA-binding domain for phenylalanine. The mutant protein (PAX8-S48F) does not induce the thyroglobulin promoter in nonthyroid cells, but displays almost half of wild-type PAX8 activity in thyroid cells. PAX8-S48F shows no defect in expression, nuclear targeting, or DNA binding and retains the ability to synergize with thyroid transcription factor 1 (TTF-1, NKX2.1). However, we found that in nonthyroid cells, the acetylation-independent synergism with the general transcriptional adaptor p300 is completely abrogated, suggesting that PAX8-S48F may be unable to efficiently recruit p300. Reconstitution experiments in nonthyroid cells reveal that TTF-1 can partially rescue PAX8-S48F/p300 synergism and thus reproduce the situation in thyroid cells. These functional characteristics result in a dominant negative effect of PAX8-S48F on coexpressed wild-type PAX8 activity, which is not observed in paired domain mutations with DNA binding defect. Our results describe the first dominant negative missense mutation in a paired domain and provide evidence for a crucial role of the p300 coactivator in mediating the functional synergism between PAX8 and TTF-1 in thyroid-specific gene expression.
Negative Interference in Cardiac Troponin I Immunoassays by Circulating Troponin Autoantibodies
Authors: Eriksson Susann , Halenius Heidi , Pulkki Kari , Hellman Jukka , Pettersson Kim 
Published: February 2005

AbstractBackground: There are numerous potential sources of interference in immunoassays. Our aim was to identify the blood component that causes negative interference in cardiac troponin I (cTnI) immunoassays based on antibodies against the central part of cTnI.Methods: We isolated an interfering factor (IF) from a sample with low recovery of added cTnI, using several consecutive purification steps: caprylic acid precipitation, ammonium sulfate precipitation, and purification on Cibacron Blue gel and protein G columns. Purified IF was identified by gel electrophoresis and mass spectrometric analysis of protein bands. For the direct detection of human antibodies to cardiac troponin in serum samples, we developed immunoassays using three different anti-human immunoglobulin antibodies and measured troponin antibodies in samples with low and normal cTnI recovery.Results: Treatment with caprylic acid did not precipitate IF, but IF precipitated at 40% ammonium sulfate saturation. IF bound to a Cibacron Blue gel column, from which it was eluted with a linear salt gradient; it also bound to protein G. Gel electrophoresis of purified IF showed two major bands with molecular masses corresponding to the heavy (∼50 kDa) and light chains (∼25 kDa) of immunoglobulin, and their identities were confirmed by mass spectrometry. The presence of troponin-specific autoantibodies was confirmed in samples with low recoveries of cTnI by three different immunoassays. The median signals were significantly higher in 10 samples with low recovery than in 10 samples with normal recovery of cTnI (P ≤ 0.007).Conclusions: Circulating autoantibodies to cTnI or other proteins of the troponin complex can be a source of negative interference in cTnI immunoassays.
Comparison of Cardiac Troponin I Immunoassays Variably Affected by Circulating Autoantibodies
Authors: Eriksson Susann , Ilva Tuomo , Becker Charlotte , Lund Juha , Porela Pekka , Pulkki Kari , Voipio-Pulkki Liisa-Maria , Pettersson Kim 
Published: February 2005

AbstractBackground: We recently provided evidence that circulating autoantibodies against cardiac troponin I (cTnI) or the troponin complex cause negative interference in cTnI immunoassays. By comparing three cTnI immunoassays, we further explored the phenomenon of circulating autoantibodies and their consequences in patient samples.Methods: We developed a cTnI immunoassay with a novel assay design using three antibodies, two of which bind epitopes outside the stable, central part of cTnI. Samples from 541 chest pain patients were measured with the new cTnI assay and with a first-generation cTnI assay (Innotrac Aio cTnI) using a conventional midfragment assay design. Using another sample cohort, we also compared the new assay with a second-generation cTnI assay (Access AccuTnI).Results: The analytical detection limit of the new cTnI assay was 0.012 μg/L, and the lowest concentration giving a total imprecision (CV) of 10% was 0.060 μg/L. The mean difference (95% limits of agreement) between the new cTnI and Aio cTnI assays was larger in admission samples (21.0%; −107.8% to 149.7%) than in samples taken 6–12 h (12.8%; −61.5% to 87.2%) and 24 h after admission (3.0%; −71.3% to 77.4%; P &lt;0.001). With the lowest concentrations giving 10% CV (0.22 μg/L for Aio cTnI) used as cutoffs, 14.3% (n = 76) of admission samples were positive only with the new assay, whereas 13.5% (n = 72) were positive with both assays. Of samples taken at 6–12 and 24 h, 10.2% (n = 31) and 8.3% (n = 29) were positive only with the new assay. ROC curve analysis of admission samples showed a significantly higher area under the curve for the new cTnI assay (0.940) than for the Aio cTnI assay (0.846; P &lt;0.001). The new cTnI assay gave generally lower results than the AccuTnI assay; the mean (95% limits of agreement) differences were −58.9% (−151.8% to 34.0%) in admission samples. In samples with severe interference from autoantibodies, median ratios between the new assay and AccuTnI were higher than in samples with no apparent troponin autoantibodies (0.875 vs 0.481; P&lt;0.001).Conclusions: The new cTnI assay, which is based on a novel antibody combination different from the conventional midfragment antibody approach, offers improved detection of cTnI in samples containing troponin autoantibodies.