bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ofatumumab As Single-Agent CD20 Immunotherapy in Fludarabine-Refractory Chronic Lymphocytic Leukemia
Authors: Wierda William G. , Kipps Thomas J. , Mayer Jiří , Stilgenbauer Stephan , Williams Cathy D. , Hellmann Andrzej , Robak Tadeusz , Furman Richard R. , Hillmen Peter , Trneny Marek , Dyer Martin J.S. , Padmanabhan Swami , Piotrowska Magdalena , Kozak Tomas , Chan Geoffrey , Davis Randy , Losic Nedjad , Wilms Joris , Russell Charlotte A. , Österborg Anders 
Published: March 2010

Purpose New treatments are needed for patients with fludarabine- and alemtuzumab-refractory (FA-ref) chronic lymphocytic leukemia (CLL) or patients with fludarabine-refractory CLL with bulky (> 5 cm) lymphadenopathy (BF-ref) who are less suitable for alemtuzumab treatment; these groups have poor outcomes with available salvage regimens. Ofatumumab (HuMax-CD20) is a human monoclonal antibody targeting a distinct small-loop epitope on the CD20 molecule. We conducted an international clinical study to evaluate the efficacy and safety of ofatumumab in patients with FA-ref and BF-ref CLL. Patients and Methods Patients received eight weekly infusions of ofatumumab followed by four monthly infusions during a 24-week period (dose 1 = 300 mg; doses 2 to 12 = 2,000 mg); response by an independent review committee (1996 National Cancer Institute Working Group criteria) was assessed every 4 weeks until week 24 and then every 3 months until month 24. Results This planned interim analysis included 138 treated patients with FA-ref (n = 59) and BF-ref (n = 79) CLL. The overall response rates (primary end point) were 58% and 47% in the FA-ref and BF-ref groups, respectively. Complete resolution of constitutional symptoms and improved performance status occurred in 57% and 48% of patients, respectively. Median progression-free survival and overall survival times were 5.7 and 13.7 months in the FA-ref group, respectively, and 5.9 and 15.4 months in the BF-ref group, respectively. The most common adverse events during treatment were infusion reactions and infections, which were primarily grade 1 or 2 events. Hematologic events during treatment included anemia and neutropenia. Conclusion Ofatumumab is an active, well-tolerated treatment providing clear clinical improvements for fludarabine-refractory patients with very poor-prognosis CLL.
Potential Role of Lymphadenectomy in Advanced Ovarian Cancer: A Combined Exploratory Analysis of Three Prospectively Randomized Phase III Multicenter Trials
Authors: du Bois Andreas , Reuss Alexander , Harter Philipp , Pujade-Lauraine Eric , Ray-Coquard Isabelle , Pfisterer Jacobus 
Published: March 2010

Purpose Primary surgery followed by platinum/taxane-based chemotherapy is the standard therapy in advanced ovarian cancer. The prognostic role of complete debulking has been well described; however, the impact of systematic pelvic and para-aortic lymphadenectomy and its interaction with biologic factors are still not fully defined. Methods This was an exploratory analysis of three prospective randomized trials (Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom trials 3, 5, and 7) investigating platinum/taxane-based chemotherapy regimens in advanced ovarian cancer conducted between 1995 and 2002. Results One thousand nine hundred twenty-four patients were analyzed. Lymphadenectomy was associated with superior survival in patients without gross residual disease. In patients with and without lymphadenectomy, the median survival time was 103 and 84 months, respectively, and 5-year survival rates were 67.% and 59.2%, respectively (P = .0166); multivariate analysis confirmed a significant impact of lymphadenectomy on overall survival (OS; hazard ratio [HR] = 0.74; 95% CI, 0.59 to 0.94; P = .0123). In patients with small residual tumors up to 1 cm, the effect of lymphadenectomy on OS barely reached significance (HR = 0.85; 95% CI, 0.72 to 1.00; P = .0497). For patients with small residual tumors and clinically suspect nodes, lymphadenectomy resulted in a 16% gain in 5-year OS (log-rank test, P = .0038). Conclusion Lymphadenectomy in advanced ovarian cancer might offer benefit mainly to patients with complete intraperitoneal debulking. However, this hypothesis should be confirmed in the context of a prospectively randomized trial.
Randomized Phase III Trial of Gemcitabine Plus Cisplatin Compared With Single-Agent Gemcitabine As First-Line Treatment of Patients With Advanced Pancreatic Cancer: The GIP-1 Study
Authors: Colucci Giuseppe , Labianca Roberto , Di Costanzo Francesco , Gebbia Vittorio , Cartenì Giacomo , Massidda Bruno , Dapretto Elisa , Manzione Luigi , Piazza Elena , Sannicolò Mirella , Ciaparrone Marco , Cavanna Luigi , Giuliani Francesco , Maiello Evaristo , Testa Antonio , Pederzoli Paolo , Falconi Massimo , Gallo Ciro , Di Maio Massimo , Perrone Francesco 
Published: March 2010

PurposeSingle-agent gemcitabine became standard first-line treatment for advanced pancreatic cancer after demonstration of superiority compared with fluorouracil. The Gruppo Italiano Pancreas 1 randomized phase III trial aimed to compare gemcitabine plus cisplatin versus gemcitabine alone (ClinicalTrials.gov ID NCT00813696).Patients and MethodsPatients with locally advanced or metastatic pancreatic cancer, age 18 to 75 years, and Karnofsky performance status (KPS) ≥ 50, were randomly assigned to receive gemcitabine (arm A) or gemcitabine plus cisplatin (arm B). Arm A: gemcitabine 1,000 mg/m2weekly for 7 weeks, and, after a 1-week rest, on days 1, 8, and 15 every 4 weeks. Arm B: cisplatin 25 mg/m2added weekly to gemcitabine, except cycle 1 day 22. Primary end point was overall survival. To have 8% power of detecting a 0.74 hazard ratio (HR) of death, with bilateral α .05, 355 events were needed and 400 patients planned.ResultsFour hundred patients were enrolled (arm A: 199; arm B: 201). Median age was 63, 59% were male, 84% had stage IV, and 83% had KPS ≥ 80. Median overall survival was 8.3 months versus 7.2 months in arm A and B, respectively (HR, 1.10; 95% CI, 0.89 to 1.35; P = .38). Median progression-free survival was 3.9 months versus 3.8 months in arm A and B, respectively (HR, 0.97; 95% CI, 0.80 to 1.19; P = .80). The objective response rate was 10.1% in A and 12.9% in B (P = .37). Clinical benefit was experienced by 23.0% in A and 15.1% in B (P = .057). Combination therapy produced more hematologic toxicity, without relevant differences in nonhematologic toxicity.ConclusionThe addition of weekly cisplatin to gemcitabine failed to demonstrate any improvement as first-line treatment of advanced pancreatic cancer.
Large Randomized Study of Thymosin α 1, Interferon Alfa, or Both in Combination With Dacarbazine in Patients With Metastatic Melanoma
Authors: Maio Michele , Mackiewicz Andrzej , Testori Alessandro , Trefzer Uwe , Ferraresi Virginia , Jassem Jacek , Garbe Claus , Lesimple Thierry , Guillot Bernard , Gascon Pere , Gilde Katalin , Camerini Roberto , Cognetti Francesco 
Published: March 2010

Purpose Thymosin α 1 (Tα1) is an immunomodulatory polypeptide that enhances effector T-cell responses. In this large randomized study, we evaluated the efficacy and safety of combining Tα1 with dacarbazine (DTIC) and interferon alfa (IFN-α) in patients with metastatic melanoma. Patients and Methods Four hundred eighty-eight patients were randomly assigned to five treatment groups: DTIC+IFN-α+Tα1 (1.6 mg); DTIC+IFN-α+Tα1 (3.2 mg); DTIC+IFN-α+Tα1 (6.4 mg); DTIC+Tα1 (3.2 mg); DTIC+IFN-α (control group). The primary end point was best overall response at study end (12 months). Secondary end points included duration of response, overall survival (OS), and progression-free survival (PFS). Patients were observed for up to 24 months. Results Ten and 12 tumor responses were observed in the DTIC+IFN-α+Tα1 (3.2 mg) and DTIC+Tα1 (3.2 mg) groups, respectively, versus four in the control group, which was sufficient to reject the null hypothesis that P0 ≤ .05 (expected response rate of standard therapy) in these two arms. Duration of response ranged from 1.9 to 23.2 months in patients given Tα1 and from 4.4 to 8.4 months in the control group. Median OS was 9.4 months in patients given Tα1 versus 6.6 months in the control group (hazard ratio = 0.80; 9% CI, 0.63 to 1.02; P = .08). An increase in PFS was observed in patients given Tα1 versus the control group (hazard ratio = 0.80; 95% CI, 0.63 to 1.01; P = .06). Addition of Tα1 to DTIC and IFN-α did not lead to any additional toxicity. Conclusion These results suggest Tα1 has activity in patients with metastatic melanoma and provide rationale for further clinical evaluation of this agent.
Imatinib Mesylate in Advanced Dermatofibrosarcoma Protuberans: Pooled Analysis of Two Phase II Clinical Trials
Authors: Rutkowski Piotr , Van Glabbeke Martine , Rankin Cathryn J. , Ruka Wlodzimierz , Rubin Brian P. , Debiec-Rychter Maria , Lazar Alexander , Gelderblom Hans , Sciot Raf , Lopez-Terrada Dolores , Hohenberger Peter , van Oosterom Allan T. , Schuetze Scott M. 
Published: March 2010

PurposeDermatofibrosarcoma protuberans (DFSP) is a dermal sarcoma typically carrying a translocation between chromosomes 17 and 22 that generates functional platelet-derived growth factor B (PDGFB).Patients and MethodsTwo distinct phase II trials of imatinib (400 to 800 mg daily) in patients with locally advanced or metastatic DFSP were conducted and closed prematurely, one in Europe (European Organisation for Research and Treatment of Cancer [EORTC]) with 14-week progression-free rate as the primary end point and the other in North America (Southwest Oncology Group [SWOG]) with confirmed objective response rate as the primary end point. In the EORTC trial, confirmation of PDGFB rearrangement was required, and surgery was undertaken after 14 weeks if feasible. The SWOG study confirmed t(17;22) after enrollment.ResultsSixteen and eight patients were enrolled onto the EORTC and SWOG trials, respectively. Tumor size ranged from 1.2 to 49 cm. DFSP was located on head/neck, trunk, and limb in seven, 11, and six patients, respectively, and was classic, pigmented, and fibrosarcomatous DFSP in 13, one, and nine patients, respectively. Metastases were present in seven patients (lung involvement was present six patients). Eleven patients (4%) had partial response as best response, and four patients had progressive disease as best response. Median time to progression (TTP) was 1.7 years. Imatinib was stopped in 11 patients because of progression, one patient because of toxicity, and two patients after complete resection of disease. Median overall survival (OS) time has not been reached; 1-year OS rate was 87.5%.ConclusionImatinib is active in DFSP harboring t(17;22) including fibrosarcomatous DFSP, with objective response rate approaching 50%. Response rates and TTP did not differ between patients taking 400 mg daily versus 400 mg twice a day.
Tracking of Bone Mass and Density during Childhood and Adolescence
Authors: Kalkwarf Heidi J. , Gilsanz Vicente , Lappe Joan M. , Oberfield Sharon , Shepherd John A. , Hangartner Thomas N. , Huang Xangke , Frederick Margaret M. , Winer Karen K. , Zemel Babette S. 
Published: March 2010

Abstract
Context: Whether a child with low bone mineral density (BMD) at one point in time will continue to have low BMD, despite continued growth and maturation, is important clinically. The stability of a characteristic during growth is referred to as “tracking.”
Objective: We examined the degree of tracking in bone mineral content (BMC) and BMD during childhood and adolescence and investigated whether tracking varied according to age, sexual maturation, and changes in growth status.
Design: We conducted a longitudinal study with measurements at baseline and annually for 3 yr.
Setting: The Bone Mineral Density in Childhood Study was conducted at five clinical centers in the United States.
Study Participants: A total of 1554 girls and boys, ages 6–16 yr at baseline, participated in the study.
Main Outcome Measures: Whole body, spine, hip, and forearm BMC and BMD were measured by dual-energy x-ray absorptiometry, and age-, sex-, and race-specific Z-scores were calculated. Deviation from tracking was calculated as the Z-score at yr 3 minus baseline.
Results: Correlations between Z-scores at baseline and yr 3 ranged from 0.76–0.88. Among children with a Z-score below −1.5 at baseline, 72–87% still had a Z-score below −1 after 3 yr. Age, sexual maturation, and deviations in growth status (P &lt; 0.01) were associated with deviation from tracking; however, tracking was strongly evident even after adjusting for the effects of age, maturation, and growth.
Conclusions: Bone density showed a high degree of tracking over 3 yr in children and adolescents. Healthy children with low bone density will likely continue to have low bone density unless effective interventions are instituted.
Comparison of Competitive Radioimmunoassays and Two-Site Sandwich Assays for the Measurement and Interpretation of Plasma Ghrelin Levels
Authors: Prudom Catherine , Liu Jianhua , Patrie James , Gaylinn Bruce D. , Foster-Schubert Karen E. , Cummings David E. , Thorner Michael O. , Geysen H. Mario 
Published: March 2010

Abstract
Context: Ghrelin, an endogenous ligand for the GH secretagogue receptor, is an orexigenic peptide hormone produced primarily by the stomach. Recent studies suggest significant differences in the specificity of currently available ghrelin assays.
Objective: The aim of the study was to compare four ghrelin assays (two commercially available and two developed by our group) of differing specificity, each used on the same set of more than 800 plasma samples from a human study.
Design: Thirteen volunteers were sampled every 20 min for 6 h after consumption of one of three isocaloric drinks consisting of either 80% fat, 80% carbohydrate, or 80% protein. The samples were assayed by RIA for total and active ghrelin, as well as by sandwich assays for acyl and des-acyl ghrelin. The ghrelin profiles for each individual were smoothed using a statistical algorithm to lessen the effects of pulsatility and noise.
Results: The sandwich assays for acyl and des-acyl ghrelin yielded ghrelin values that were lower than those from the corresponding RIAs. The ghrelin profiles after nutrient ingestion were similar, yet key differences among the four assays were apparent; in particular, percentage changes were significantly greater in the sandwich assays.
Conclusions: The lower levels and greater relative changes in ghrelin values reported by the sandwich assays are consistent with greater assay specificity. When applied to the nutrient study, the sandwich assays were better able to distinguish the different responses to different nutrients than were the RIAs.
Association of Lipoprotein-Associated Phospholipase A2 with Coronary Artery Disease in African-Americans and Caucasians
Authors: Anuurad Erdembileg , Ozturk Zeynep , Enkhmaa Byambaa , Pearson Thomas A. , Berglund Lars 
Published: March 2010

Abstract
Context: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is bound predominately to low-density lipoprotein and has been implicated as a risk factor for coronary artery disease (CAD).
Objective: We investigated the association between Lp-PLA2 and CAD in a biethnic African-American and Caucasian population.
Design: Lp-PLA2 mass, activity, and index, an integrated measure of mass and activity, and other cardiovascular risk factors were determined in 224 African-Americans and 336 Caucasians undergoing coronary angiography.
Main Outcome Measures: We assessed the distribution of Lp-PLA2 levels and determined the predictive role of Lp-PLA2 as a risk factor for CAD.
Results: Levels of Lp-PLA2 mass and activity were higher among Caucasians compared with African-Americans (293 ± 75 vs. 232 ± 76 ng/ml, P &lt; 0.001 for mass and 173 ± 41 vs. 141 ± 39 nmol/min/ml, P &lt; 0.001 for activity, respectively). However, Lp-PLA2 index was similar in the two groups (0.61 ± 0.17 vs. 0.64 ± 0.19, P = NS). In both ethnic groups, Lp-PLA2 activity and index was significantly higher among subjects with CAD. African-American subjects with CAD had significantly higher Lp-PLA2 index than corresponding Caucasian subjects (0.69 ± 0.20 vs. 0.63 ± 0.18, P = 0.028). In multivariate regression analyses, after adjusting for other risk factors, Lp-PLA2 index was independently (odds ratio 6.7, P = 0.047) associated with CAD in African-Americans but not Caucasians.
Conclusions: Lp-PLA2 activity and index was associated with presence of CAD among African-Americans and Caucasians undergoing coronary angiography. The findings suggest an independent impact of vascular inflammation among African-Americans as contributory to CAD risk and underscore the importance of Lp-PLA2 as a cardiovascular risk factor.
Decision criteria for rational selection of homogeneous genotyping platforms for pharmacogenomics testing in clinical diagnostics
Authors: Di Francia Raffaele , Frigeri Ferdinando , Berretta Massimiliano , Cecchin Erika , Orlando Claudio , Pinto Antonio , Pinzani Pamela 
Published: March 2010

Abstract

Background: Genotyping is crucial for the identification of genetic markers underlying the development of neoplastic diseases and for determining individual variations in response to specific drugs. Technologies which can accurately identify genetic polymorphisms will dramatically affect routine diagnostic processes and future therapeutic developments in personalized medicine. However, such methods need to fulfill the principles of analytical validation to determine their suitability to assess nucleotide polymorphisms in target genes.

Approach: This article reviews recent developments in homogeneous technologies for the genotyping of single nucleotide polymorphisms. Here, homogeneous methods essentially refer to “single-tube” assays performed in a liquid phase. For the appropriate choice of any method, several criteria must be considered: 1) detection of known genetic variations; 2) analytical performance including specificity, sensitivity and robustness of the method; 3) availability of large platforms and required equipment; 4) suitability of platforms and tests for routine diagnostics; 5) suitability for high throughput implementation.

Content: This review is intended to provide the reader with an understanding of these various technologies for pharmacogenomic testing in the routine clinical laboratory. A brief overview is provided on the available technologies for the detection of known mutations, a specific description of the homogeneous platforms currently employed in genotyping analysis, and considerations regarding the proper assessment of the analytical performance of these methods. Based on the criteria proposed here, potential users may evaluate advantages and limitations of the various analytical platforms and identify the most appropriate platform according to their specific setting and diagnostic needs.
Clin Chem Lab Med 2010;48:447–59.
UGT2B17 and SULT1A1 gene copy number variation (CNV) detection by LabChip microfluidic technology
Authors: Gaedigk Andrea , Gaedigk Roger , Leeder J. Steven 
Published: March 2010

Abstract

Background: Gene copy number variations (CNVs) are increasingly recognized to play important roles in the expression of genes and hence on their respective enzymatic activities. This has been demonstrated for a number of drug metabolizing genes, such as UDP-glucuronosyltransferases 2B17 (UGT2B17) and sulfotransferase 1A1 (SULT1A1), which are subject to genetic heterogeneity, including CNV. Quantitative assays to assess gene copy number are therefore becoming an integral part of accurate genotype assessment and phenotype prediction.

Methods: In this study, we evaluated a microfluidics-based system, the Bio-Rad Experion system, to determine the power and utility of this platform to detect UGT2B17 and SULT1A1 CNV in DNA samples derived from blood and tissue. UGT2B17 is known to present with 0, 1 or 2 and SULT1A1 with up to 5 gene copies.

Results: Distinct clustering (p<0.001) into copy number groups was achieved for both genes. DNA samples derived from blood exhibited less inter-run variability compared to DNA samples obtained from liver tissue. This variability may be caused by tissue-specific PCR inhibitors as it could be overcome by using DNA from another tissue, or after the DNA had undergone whole genome amplification.

Conclusions: This method produced results comparable to those reported for other quantitative test platforms.
Clin Chem Lab Med 2010;48:627–33.
Somme 1916 und Normandie 1944. Zwei Erinnerungslandschaften der Weltkriegsepoche zwischen Geschichte, Politik und Tourismus
Authors: Mütter Bernd 
Published: March 2010

Zusammenfassung
Der Beitrag geht aus vom Eindruck des heutigen deutschen Besuchers der beiden Weltkriegsschlachtfelder (1). Nach einer vergleichenden analytischen Skizze der beiden Schlachten (2) wird die westalliierte Inszenierung der Erinnerung (Kriegsspuren, Soldatenfriedhöfe, Denkmäler, Museen) untersucht (3). Schließlich stellt sich die Frage, wie die Erinnerung vor Ort auf dem Hintergrund der europäischen Verständigung ehemaliger Weltkriegsgegner und des anstehenden Generationswechsels zukunftsfähig gestaltet werden kann (4).
The role of maternal gut hormones in normal pregnancy: fasting plasma active glucagon-like peptide 1 level is a negative predictor of fetal abdomen circumference and maternal weight change
Authors: Valsamakis Georgios , Margeli Alexandra , Vitoratos Nikolaos , Boutsiadis Anastassios , Sakkas Evangelos G , Papadimitriou George , Al-Daghri Nasser M , Botsis Dimitrios , Kumar Sudhesh , Papassotiriou Ioannis , Creatsas George , Mastorakos George 
Published: March 2010

AbstractObjectiveMaternal weight in pregnancy contributes to a glycemic environment that affects fetal growth. Gut peptides (glucagon-like peptide 1 (GLP1), glucose-dependent insulinotropic peptide (GIP), ghrelin, and peptide YY (PYY)) have been related to insulin sensitivity and secretion, weight control, and adipose tissue metabolism. This study aimed at examining the associations of gut hormones during pregnancy with maternal glucose homeostasis, maternal weight, and fetal growth.MethodsA total of 55 pregnant nonobese, nondiabetic Caucasian women were examined during the three trimesters of pregnancy, and anthropometric measurements, evaluation of fasting maternal plasma GLP1 (active), ghrelin (active), total PYY, total GIP, and a 75-g oral glucose tolerance test were done in them. Homeostasis model assessment (HOMA-R), insulin sensitivity index (ISI), and indices of insulin secretion were calculated. Fetal growth was estimated by ultrasound.ResultsFasting GLP1 increased significantly from the second to the third trimester (P<0.05). Fasting GLP1 correlated positively with high-density lipoprotein cholesterol (r=0.52,P=0.04). At the second trimester, fasting GLP1 levels correlated negatively with fetal abdomen circumference (r=−0.55,P=0.034), birth weight (r=−0.50,P=0.040), HOMA-R (r=−0.65,P=0.001), insulin secretion, and triglycerides. At the first trimester, fasting ghrelin levels correlated negatively with HOMA-R and insulin secretion, and positively with ISI. In backward multiple regression analysis, the first trimester GLP1 levels were the best negative predictors of the second trimester fetal abdomen circumference (β=−0.96,P=0.009). In longitudinal regression model, maternal fat and HOMA-R were the positive predictors of maternal weight change during pregnancy, and fasting GLP1 levels were the negative predictors of maternal weight change during pregnancy.ConclusionsDuring pregnancy, maternal GLP1 might be involved in mechanisms that compensate for the pregnancy-related increase in glycemia and insulin resistance, suggesting a role of this peptide in maternal metabolism and weight and fetal growth.