bluuebunny/crossref_metadata_2025_split huggingface dataset:
The efficacy and safety of bortezomib and dexamethasone as a maintenance therapy in patients with advanced multiple myeloma who are responsive to salvage bortezomib‐containing regimens
Authors: Benevolo Giulia , Larocca Alessandra , Gentile Massimo , Pregno Patrizia , Gay Francesca , Botto Barbara , Frairia Chiara , Evangelista Andrea , Morabito Fortunato , Boccadoro Mario , Vitolo Umberto , Palumbo Antonio 
Published: November 2010

AbstractBACKGROUND:Although treatment for multiple myeloma (MM) has considerably improved in the past decade, MM continues to be an incurable hematological malignancy that causes most patients to eventually relapse and die from their illness. Thus, the identification of effective salvage strategies remains a priority.METHODS:In this trial, the authors evaluated the safety and efficacy of bortezomib and dexamethasone [V: on days 1 and 15 (1.3 mg/mq); D: on days 1‐2 and 15‐16, every 28‐day cycle until progression (20 mg/d)] as maintenance therapy (MT) in patients with advanced MM who responded to salvage therapy that used a bortezomib‐containing regimen.RESULTS:Forty‐nine MM patients were enrolled in this study between October of 2004 and April of 2008. All patients who were included in this study were responsive to a prior salvage therapy with bortezomib and had a measurable disease. The bortezomib and dexamethasone MT improved the quality of responses to complete remission in 4 patients and very good partial response in 3 patients. In addition, 10 patients experienced at least a 50% improvement in their symptoms. The median time to progression (TTP) was 16 months with a progression‐free survival of 61% after 1 year. The overall response after 1 year was 76%, and the cumulative incidence of death due to disease progression, which was adjusted for competitive risk events, was 14%. Non‐dose‐limiting toxicities included neuropathy (predominantly grade 1), herpes zoster reactivation, pneumonia, and gastrointestinal affections (constipation and diarrhea). Three patients developed grade 2 neuropathy, which required a bortezomib dose reduction to 1.0 mg/mq. No grade 3 or 4 toxicities were recorded.CONCLUSIONS:The use of bortezomib and dexamethasone as MT in advanced MM was effective and well tolerated. The twice‐monthly bortezomib infusion appeared to reduce the incidence of grade 3 and 4 neuropathies in comparison to similar experiences in other settings. Cancer 2011. © 2010 American Cancer Society.
Progression‐free survival as a predictor of overall survival in metastatic renal cell carcinoma treated with contemporary targeted therapy
Authors: Heng Daniel Y. C. , Xie Wanling , Bjarnason Georg A. , Vaishampayan Ulka , Tan Min‐Han , Knox Jennifer , Donskov Frede , Wood Lori , Kollmannsberger Christian , Rini Brian I. , Choueiri Toni K. 
Published: November 2010

AbstractBACKGROUND.The majority of metastatic renal cell carcinoma (mRCC) clinical trials that examined targeted agents used progression‐free survival (PFS) as the primary endpoint. Whether PFS can be used as a predictor of overall survival (OS) is unknown.METHODS.Patients from 12 cancer centers who received targeted therapy for mRCC were identified. Landmark analyses for progression at 3 months and 6 months after drug initiation were performed to minimize lead‐time bias. A proportional hazards model was used to assess the utility of PFS for predicting OS.RESULTS.In total, 1158 patients were included. The median follow‐up was 30.6 months, the median age was 60 years, and the median Karnofsky performance status was 80%. For the entire cohort, the median PFS was 7.6 months, and the median OS was 19.7 months. In the landmark analysis, the median OS for patients who progressed at 3 months was 7.8 months compared with 23.6 months for patients who did not progress (log‐rank test; P < .0001). Similarly, for patients who progressed at 6 months, the median OS was 8.6 months compared with 26 months for patients who did not progress (P < .0001). Compared with those who did not progress, for the patients who progressed at 3 months and at 6 months, the hazard ratios for death adjusted for adverse prognostic factors were 3.05 (95% confidence interval, 2.42‐3.84) and 2.96 (95% confidence interval, 2.39‐3.67), respectively. Similar results were demonstrated with landmark analyses at 9 months and at 12 months and in the bootstrap validation. Kendall tau rank correlation and a Fleischer model demonstrated a statistically significant dependent correlation.CONCLUSIONS.PFS at 3 months and at 6 months predicted OS, and the current results indicated that PFS may be a meaningful intermediate endpoint for OS in patients with mRCC who receive treatment with novel agents. Cancer 2011;. © 2010 American Cancer Society.
Regulatory T cells predict the time to initial treatment in early stage chronic lymphocytic leukemia
Authors: Weiss Lukas , Melchardt Thomas , Egle Alexander , Grabmer Christoph , Greil Richard , Tinhofer Inge 
Published: November 2010

AbstractBACKGROUND:Early stage chronic lymphocytic leukemia is characterized by a highly variable course of disease. Because it is believed that regulatory T cells (Tregs) are potent suppressors of antitumor immunity, the authors hypothesized that increased Tregs may favor disease progression.METHODS:Treg levels (cluster of differentiation 3 [CD3]‐positive, [CD4]‐positive, CD25‐positive, and CD127‐negative) in peripheral blood from 102 patients were analyzed by flow cytometry. Statistical analysis was used to evaluate correlations with clinical data.RESULTS:The relative Treg numbers in CD4‐positive T cells were significantly greater in patients with chronic lymphocytic leukemia compared with the numbers in a control group of 170 healthy individuals (P = .001). Patients were divided into 2 groups using a median Treg value of 9.7% (the percentage of CD4‐positive T cells). Patients with higher Treg levels had a significantly shorter time to initial treatment (median, 5.9 years) compared with patients who had lower Treg levels (median, 11.7 years; log‐rank P = .019). Furthermore, Treg levels (the percentage of CD4‐positive T cells) had significant prognostic power to predict the time to initial treatment in univariate analysis (P = .023) and in multivariate Cox regression analysis that included the variables Rai stage, immunoglobulin heavy‐chain variable region gene mutational status, chromosomal aberrations, and CD38 expression (P = .028).CONCLUSIONS:Higher Treg levels had significant and independent prognostic power for predicting the time to initial treatment in patients with low to intermediate stage chronic lymphocytic leukemia. Cancer 2011. © 2010 American Cancer Society.
Cancer‐related chronic pain
Authors: Green Carmen R. , Hart‐Johnson Tamera , Loeffler Deena R. 
Published: November 2010

AbstractBACKGROUND:Disparities in cancer survival and pain rates negatively impact quality of life (QOL). This study examines cancer‐related chronic pain (CP) and its impact on QOL in diverse cancer survivors.METHODS:This survey study focused on current and past pain, health, and QOL in black and white cancer survivors. Participants with breast, colorectal, lung, and prostate cancer and multiple myeloma were recruited through the Michigan State Cancer Registry. Analysis of variance was used to examine outcome differences by pain status, race, and sex. Hierarchical regressions explored predictors for experiencing pain.RESULTS:The subjects (N = 199) were 31% black, 49% female, and 57 to 79 years old; 19.5% experienced current pain, and 42.6% reported pain since diagnosis. Women experience more pain (P < .001) and greater pain severity (P = .04) than men. Blacks experienced more pain interference and disability (P < .05). Experiencing pain is related to greater depressive symptoms, poorer functioning, and more symptoms. In hierarchical regressions, female sex predicted pain since diagnosis; pain severity for pain since diagnosis was predicted by black race and female sex.CONCLUSIONS:The authors extend the literature by showing that 20% of diverse cancer survivors had cancer‐related CP, and 43% had experienced pain since diagnosis, revealing racial and sex disparities in cancer‐related CP's incidence and impact on QOL. Having pain was related to poorer QOL in several domains and was more frequently experienced by women. Although black race was not related to pain prevalence, it was related to greater severity. This study reveals an unaddressed cancer survivorship research, clinical, and policy issue. Cancer 2011. © 2010 American Cancer Society.
Neoadjuvant therapy is associated with improved survival in resectable pancreatic adenocarcinoma
Authors: Artinyan Avo , Anaya Daniel A. , McKenzie Shaun , Ellenhorn Joshua D. I. , Kim Joseph 
Published: November 2010

AbstractBACKGROUND:Neoadjuvant therapy has been used to improve survival in operable pancreatic cancer. The authors' objective was to compare long‐term outcomes in patients receiving neoadjuvant versus adjuvant therapy for resectable pancreatic adenocarcinoma.METHODS:The California Cancer Surveillance Program for Los Angeles County retrospectively identified 458 patients with nonmetastatic pancreatic adenocarcinoma who underwent definitive pancreatic resection and received systemic chemotherapy between 1987 and 2006. The cohort was grouped by timing of systemic therapy—neoadjuvant or adjuvant. Clinicopathologic characteristics and overall survival were compared. Multivariate Cox regression analysis was used to determine the benefit of neoadjuvant therapy, independent of other significant factors.RESULTS:Of the 458 patients, 39 (8.5%) received neoadjuvant therapy, and 419 (91.5%) received adjuvant therapy. There was a significantly lower rate of lymph node positivity in the neoadjuvant group (45% vs 65%; P = .011) despite a higher rate of extrapancreatic tumor extension. On Kaplan‐Meier analysis, the neoadjuvant group had significantly better overall survival compared with the adjuvant group (median survival, 34 vs 19 months; P = .003). Overall survival was also improved in the neoadjuvant therapy patients with extrapancreatic disease (median survival, 31 vs 19 months; P = .018). On multivariate Cox regression analysis, neoadjuvant therapy was an independent predictor of improved survival (hazard ratio, 0.57; 95% confidence interval, 0.37‐0.89; P = .013).CONCLUSIONS:This is the first population‐based study to compare neoadjuvant versus adjuvant treatment strategies in resectable pancreatic cancer. Neoadjuvant therapy is associated with a lower rate of lymph node positivity and improved overall survival and should be considered an acceptable alternative to the surgery‐first paradigm in operable pancreatic cancer. Cancer 2011. © 2010 American Cancer Society
Direct preparation of K0.5Na0.5NbO3 powders
Authors: Jiang Heng , Su Ting Ting , Gong Hong , Zhai Yu Chun 
Published: November 2010

AbstractK0.5Na0.5NbO3 powders have been directly synthesized by an alternative solid–state method. Stoichimometric mixture of ammonium niobium oxalate and C4H4O6KNa·4H2O were calcined in temperature range from 500 to 800 °C for 3 h. The precursor and calcination products were characterized with respect to stoichiometry, purity, crystalline structure, particle size and powder morphology using X–ray diffraction (XRD), X‐ray fluorescence (XRF) spectrometer, scanning electron microscope (SEM), Fourier transform infrared (FTIR) spectra, thermogravimetric (TG) analysis, differential scanning calorimetry (DSC) and UV–Vis diffuse reflectance (UV–Vis) spectroscopy. XRD and XRF results reveal that stoichiometric K0.5Na0.5NbO3 powders could be synthesized by the method. The particle size is about 68 nm for the precursor calcined at 500 °C according to XRD data, which is in good agreement with SEM data. The average band gap energy is estimated to be 3.18 eV by UV–vis diffuse reflectance spectra. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The building blocks of mammalian lung development
Authors: Rawlins Emma L. 
Published: November 2010

AbstractProgress has recently been made in identifying progenitor cell populations in the embryonic lung. Some progenitor cell types have been definitively identified by lineage‐tracing studies. However, others are not as well characterized and their existence is inferred on the basis of lung morphology, or mutant phenotypes. Here, I focus on lung development after the specification of the initial lung primordium. The evidence for various lung embryonic progenitor cell types is discussed and future experiments are suggested. The regulation of progenitor proliferation in the embryonic lung, and its coordinate control with morphogenesis, is also discussed. In addition, the relationship between embryonic and adult lung progenitors is considered. Developmental Dynamics 240:463–476, 2011. © 2010 Wiley‐Liss, Inc.
Migration of dorsal aorta mesenchymal stem cells induced by mouse embryonic circulation
Authors: Yan Xin‐Long , Lan Yu , Wang Xiao‐Yan , He Wen‐Yan , Yao Hui‐Yu , Chen Dong‐Bo , Xiong Jia‐Xiang , Gao Jiao , Li Zhuan , Yang Guan , Li Xiu‐Sen , Liu Yuan‐Lin , Zhang Ji‐Yan , Liu Bing , Mao Ning 
Published: November 2010

AbstractMesenchymal stem cells (MSCs) represent powerful tools for regenerative medicine for their differentiation and migration capacity. However, ontogeny and migration of MSCs in mammalian mid‐gestation conceptus is poorly understood. We identified canonical MSCs in the mouse embryonic day (E) 11.5 dorsal aorta (DA). They possessed homogenous immunophenotype (CD45−CD31−Flk‐1−CD44+CD29+), expressed perivascular markers (α‐SMA+NG2+PDGFRβ+PDGFRα+), and had tri‐lineage differentiation potential (osteoblasts, adipocytes, and chondrocytes). Of interest, MSCs were also detected in E12.5–E13.5 embryonic circulation, 24 hr later than in DA, suggesting migration like hematopoietic stem cells. Functionally, E12.5 embryonic blood could trigger efficient migration of DA‐MSCs through platelet‐derived growth factor (PDGF) receptor‐, transforming growth factor‐beta receptor‐, but not basic fibroblast growth factor receptor‐mediated signaling. Moreover, downstream JNK and AKT signaling pathway played important roles in embryonic blood‐ or PDGF‐mediated migration of DA‐derived MSCs. Taken together, these results revealed that clonal MSCs developed in the mouse DA. More importantly, the embryonic circulation, in addition to its conventional transporting roles, could modulate migration of MSC during early embryogenesis. Developmental Dynamics, 2011. © 2010 Wiley‐Liss, Inc.
Three‐dimensional localisation of NANOG, OCT4, and E‐cadherin in porcine pre‐ and peri‐implantation embryos
Authors: Wolf Xenia Asbæk , Serup Palle , Hyttel Poul 
Published: November 2010

AbstractThe expression patterns of NANOG and OCT4 have previously been reported to differ markedly between mammalian species indicating distinct species‐specific roles during development. We investigate the three‐dimensional expression pattern of NANOG and OCT4 in porcine pre‐ and peri‐implantation embryos. The expression of NANOG differed remarkably from that reported in other species. NANOG was not detected in the inner cell mass of hatched porcine blastocysts, but later appeared in the epiblast and hypoblast of spherical blastocysts where Rauber's layer had disintegrated. In pre‐gastrulating, filamentous embryos NANOG was localised to nuclei in a minor portion of the epiblast cells in which E‐CADHERIN seemed to be up‐regulated and OCT4 down‐regulated. Later NANOG was restricted to the potential PGCs. OCT4 was detected in inner cell mass, epiblast, and mesoderm, and we found that OCT4 expression, in contrast to earlier speculations, at least in hatched blastocysts, resembles the expression pattern in the mouse embryo. Developmental Dynamics, 2011. © 2010 Wiley‐Liss, Inc.
Characterization of Pitx2c expression in the mouse heart using a reporter transgene
Authors: Furtado Milena B. , Biben Christine , Shiratori Hidetaka , Hamada Hiroshi , Harvey Richard P. 
Published: November 2010

AbstractTo aid in detection and tracking of cells targeted by the left‐right (LR) pathway in the heart throughout morphogenesis, expression from a Pitx2c‐lacZ transgene (P2Ztg) was analysed in detail. β‐galactosidase expression from P2Ztg was robust, allowing reliable visualisation of low‐level Pitx2c expression, and was virtually entirely dependent upon NODAL signalling in the heart. P2Ztg showed expression in trabecular and septal, as well as non‐trabecular, myocardium, and a strong expression bias in myocardium associated with individual endocardial cushions of the atrioventricular canal and outflow tract, which are essential for cardiac septation. Expression on the ventral surface of the outflow tract evolved to a specific stripe that could be used to track the future aorta during outflow tract spiralling and remodelling. Our data show that the P2Ztg transgene is a useful resource for detection of molecular disturbances in the LR cascade, as well as morphogenetic defects associated with other cardiac congenital disorders. Developmental Dynamics, 2011. © 2010 Wiley‐Liss, Inc.
Cell autonomous requirement of endocardial Smad4 during atrioventricular cushion development in mouse embryos
Authors: Song Langying , Zhao Mei , Wu Bingruo , Zhou Bin , Wang Qin , Jiao Kai 
Published: November 2010

AbstractAtrioventricular (AV) cushions are the precursors of AV septum and valves. In this study, we examined roles of Smad4 during AV cushion development using a conditional gene inactivation approach. We found that endothelial/endocardial inactivation of Smad4 led to the hypocellular AV cushion defect and that both reduced cell proliferation and increased apoptosis contributed to the defect. Expression of multiple genes critical for cushion development was down‐regulated in mutant embryos. In collagen gel assays, the number of mesenchymal cells formed is significantly reduced in mutant AV explants compared to that in control explants, suggesting that the reduction of cushion mesenchyme formation in mutants is unlikely secondary to their gross vasculature abnormalities. Using a previously developed immortal endocardial cell line, we showed that Smad4 is required for BMP signaling‐ stimulated upregulation of Tbx20 and Gata4. Therefore, our data collectively support the cell‐autonomous requirement of endocardial Smad4 in regulating AV cushion development. Developmental Dynamics, 2011. © 2010 Wiley‐Liss, Inc.
A process for the production of a diacylglycerol‐based milk fat analogue
Authors: Lubary Marta , Hofland Gerard W. , ter Horst Joop H. 
Published: November 2010

AbstractWe propose a novel process for the production of a DAG‐rich acylglycerol mixture derived from milk fat. This product has potentially interesting nutritional properties, derived from both its high content of DAG and of short‐chain fatty acids (FAs). The proposed process consists of three steps: lipase‐catalysed partial ethanolysis of milk fat, extraction of the by‐product fatty acid ethyl esters (FAEEs) using supercritical carbon dioxide (SC‐CO2) and isomerization of DAG to increase the proportion of 1,3‐DAG. The experimental investigation of the process steps was done using milk fat and trilaurin. Several lipases were tested for maximizing the percentage of DAG in the acylglycerol mixture produced by ethanolysis. The selectivity of the chosen lipase was such that the produced AG mixture was enriched in short‐chain FAs in relation to the original milk fat. FAEEs were completely extracted from the ethanolysis mixture by SC‐CO2. In the final process step, we explored the reaction conditions for facilitating acyl migration in the DAG mixture, so that the equilibrium proportion of 1,3‐DAG (∼64%) was attained. Our results set the basis for the development of a simple process for the production of a DAG‐rich milk fat analogue.
Lipase‐catalyzed synthesis of partial acylglycerols of acetoacetate
Authors: Haas Michael J. , Fox Pamela S. , Foglia Thomas A. 
Published: November 2010

AbstractImmobilized Rhizomucor miehei lipase (Lipozyme RMIM) was employed in the synthesis of partial acylglycerols of acetoacetate (C4H6O3, 3‐oxobutanoic acid). Both 1(3)‐sn‐monoacetoacetyl glycerol (MAcG) and 1,3‐sn‐diacetoacetyl glycerol (DAcG) resulting from esterification of glycerol with ethylacetoacetate were isolated and identified by 1H and 13C NMR. An HPLC method for the separation and quantitation of these species was developed. The effects on product yield of coordinate variations in the amounts of enzyme, water, ethyl acetoacetate, and the ratio of immobilizing silica to glycerol were explored. This allowed creation of predictive equations relating these variables to product yield. Reaction conditions were thereby identified and validated under which maximum yields of MAcG and/or DAcG or total ester were predicted. The production of both MAcG and DAcG was markedly sensitive to water, with optimal yields obtained within a narrow range of added water contents. Substantial excesses of ethylacetoacetate ameliorated the inhibitory effect of water. MAcG was effectively produced with the lowest amount of RMIM investigated. It was necessary to use larger amounts of lipase to achieve high yields of DAcG, and even then actual yields were only 30% of theoretical maximum. In the absence of silica only MAcG was produced.Practical applications: Aceotacetyl esters of glycerol are potential prochiral building blocks for further chemical synthesis and exhibit the chemical reactivity of both the acetoacetyl moiety and of glycerol. They are thus of potential use in, for example, the production of biopolymers exhibiting any of a variety of features and functionalities. The use of enzymatic catalysis rather than chemical synthesis for their production offers advantages of reduced degradation and contamination due to the gentler reaction conditions characteristic of enzymatic catalysis, as well as a potential reduction in the costs to procure and dispose of catalyst.
Relationships between the transcriptome and physiological indicators of reproduction in female rainbow trout over an annual cycle
Authors: Hook Sharon E , Nagler James J , Cavileer Tim , Verducci Joseph , Liu Yushi , Hayton William , Schultz Irvin R 
Published: November 2010

Abstract
Normal transcriptomic patterns along the brain-pituitary-gonad-liver (BPGL) axis should be better characterized if endocrine-disrupting compound–induced changes in gene expression are to be understood. Female rainbow trout were studied over a complete year-long reproductive cycle. Tissue samples from pituitary, ovary, and liver were collected for microarray analysis using the 16K Genomic Research on Atlantic Salmon Project (GRASP) microarray and for quantitative polymerase chain reaction measures of estrogen receptor (ER) isoform messenger RNA (mRNA) levels. Plasma was collected to determine levels of circulating estradiol-17β (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). As an a priori hypothesis, changes in gene expression were correlated to either circulating levels of E2, FSH, and LH, or ER mRNAs quantified by quantitative polymerase chain reaction. In the liver, most transcriptomic patterns correlated to levels of either E2, LH, or ERs. Fewer ovarian transcripts could be correlated to levels of E2, ERα, or FSH. No significant associations were obvious in the pituitary. As a post hoc hypothesis, changes in transcript abundance were compared with microarray features with known roles in gonadal maturation. Many altered transcripts in the ovary correlated to transcript levels of estradiol 17-beta-dehydrogenase 8 or 17 B HSD12, or to glycoprotein alpha chain 1 or 2. In the pituitary, genes involved with the growth axis (e.g., growth hormone, insulin-related growth factor binding protein) correlated with the most transcripts. These results suggest that transcriptional networks along the BPGL axis may be regulated by factors other than circulating steroid hormones. Environ. Toxicol. Chem. 2011;30:309–318. © 2010 SETAC