bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of medium composition on oxygen transfer rate in animal cell culture
Authors: Toye D. , Galifi A. , Salmon T. , Marchot P. , Verdin E. , Crine M. 
Published: June 2010

AbstractExperiments were conducted in a 0.25 m diameter bubble column to investigate the effect of medium composition on oxygen transfer rate. Aqueous solutions, the composition of which mimics a mammalian cell culture medium, are used. The effect on oxygen transfer rate of additives used to protect cells against local hydrodynamic stresses induced by bubble coalescence and bursting is addressed, in the range of operating conditions (aeration rates) met in animal cell cultures.The mass transfer coefficient, the liquid viscosity and surface tension, and the bubble size distribution are measured as a function of liquid composition and of gas superficial velocity, allowing to decouple the effects of the different additive on kL and on a.
Epidermal growth factor receptor mutations detected by denaturing high‐performance liquid chromatography in nonsmall cell lung cancer
Authors: Cohen Victor , Agulnik Jason S. , Ang Celina , Kasymjanova Goulnar , Batist Gerald , Small David , Brandao Guilherme , Chong George , Miller Wilson H. 
Published: June 2010

AbstractBACKGROUND:Somatic mutations in the epidermal growth factor receptor (EGFR) kinase domain are associated with sensitivity to EGFR‐tyrosine kinase inhibitors (EGFR‐TKI) in patients with nonsmall cell lung cancer (NSCLC).METHODS:The authors tested the possibility that nucleotide sequencing may be poorly suited for detection of mutations in tumor samples and found that denaturing high‐performance liquid chromatography (dHPLC) was an efficient and more sensitive method for screening.RESULTS:These results suggested that some reports based on standard DNA sequencing techniques may have underestimated mutation rates. In the present report, the authors examined the relationship between the presence and type of EGFR mutations detected by dHPLC and various clinicopathologic features of NSCLC, including response to therapy with EGFR‐TKI. Among 251 patients with advanced disease, 100 individuals received EGFR‐TKI. Those whose tumors harbored a detectable EGFR kinase mutation were much more likely to have a partial response (PR) or stable disease (SD) with EGFR‐TKI therapy than patients whose tumor contained no mutation (80% vs 35%; P = .001). Among the individual genotype subgroups, the frequency of a PR or SD was significantly different between patients with an exon 19 deletion compared with those with no detectable mutation (86% vs 35%; P < .001). Furthermore, patients whose tumors expressed an exon 19 mutant EGFR isoform exhibited a trend toward better EGFR‐TKI response (86% vs 67%; P = .171) and improved survival compared with patients whose tumors expressed an exon 21 mutation.CONCLUSIONS:Our findings warrant confirmation in large prospective trials and exploration of the biological mechanisms of the differences between mutation types. Cancer 2010. © 2010 American Cancer Society.
Efficacy and safety of the combination of rituximab, fludarabine, and mitoxantrone for rituximab‐naive, recurrent/refractory follicular non‐Hodgkin lymphoma with high tumor burden
Authors: Morschhauser Franck , Mounier Nicolas , Sebban Catherine , Brice Pauline , Solal‐Celigny Phillippe , Tilly Herve , Feugier Pierre , Fermé Christophe , Copin Marie Christine , Lamy Thierry 
Published: June 2010

AbstractBACKGROUND:This phase 2 trial was undertaken to evaluate the efficacy and safety of rituximab combined with intravenous fludarabine and mitoxantrone (R‐FM) for patients with recurrent/refractory follicular lymphoma who had high tumor burden according to Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria.METHODS:Fifty patients were enrolled who had received a maximum of 2 previous regimens, including 1 cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)/CHOP‐like regimen but no previous exposure to rituximab, fludarabine, or mitoxantrone. At baseline, 58% of patients had bulky disease (lesion >7cm), 56% had high‐risk Follicular Lymphoma International Prognostic Index (FLIPI) scores (range, 3‐5), and 22% were refractory. Treatment consisted of 4 courses of R‐FM (rituximab 375 mg/m2 intravenously on Day 1, fludarabine 25 mg/m2 intravenously on Days 2 through 4, and mitoxantrone 10 mg/m2 intravenously on Day 2, recycling at Day 28) and consolidation with 2 courses of fludarabine and mitoxantrone (the same regimen without rituximab).RESULTS:The best response (84% overall response rate including 68% complete response/complete response unconfirmed) was achieved after 4 courses of R‐FM. Response rates were high regardless of age, refractoriness to last previous therapy, and FLIPI score. After a median follow‐up of 4 years, the 3‐year progression‐free survival rate was 47%, the event‐free survival rate was 41%, and the 3‐year overall survival rate was 66%. Grade ≥3 neutropenia and infections were the most common toxicities and occurred in 72% and 14% of patients, respectively.CONCLUSIONS:Cytoreduction with 4 courses of R‐FM was safe and highly efficient in patients with recurrent/refractory follicular lymphoma who had high tumor burden; however, better consolidation than FM is needed to further improve outcome. Cancer 2010. © 2010 American Cancer Society.
Insurance status and survival disparities among nonelderly rectal cancer patients in the National Cancer Data Base
Authors: Robbins Anthony S. , Chen Amy Y. , Stewart Andrew K. , Staley Charles A. , Virgo Katherine S. , Ward Elizabeth M. 
Published: June 2010

AbstractBACKGROUND:Among patients with colorectal cancer, insurance status is associated with disparities in survival as well as differences in stage and treatment. The role of stage and treatment differences in these survival disparities is not clear because insurance status is also strongly correlated with race/ethnicity, socioeconomic status, and other factors.METHODS:The authors used data from the National Cancer Data Base, a national hospital‐based cancer registry, to examine insurance status and other factors related to survival among 19,154 rectal cancer patients aged 18 to 64 years. The authors examined the impact of 10 factors on 5‐year survival: age, sex, race/ethnicity, histologic grade, histologic subtype, neighborhood education and income levels, facility type, stage, and treatment.RESULTS:Adjusted only for age, the hazard ratio (HR) for death at 5 years was 1.00 (referent) among privately insured patients, 2.05 (95% confidence interval [CI], 1.89‐2.23) among Medicaid‐insured patients, and 2.01 (95% CI, 1.84‐2.19) among uninsured patients. After adjustment for all factors other than stage and treatment, the HRs were 1.88 (95% CI, 1.722.04) for Medicaid‐insured patients and 1.84 (95% CI, 1.69‐2.01) for uninsured patients. After further adjustment for stage and treatment, the HRs were 1.34 (95% CI, 1.22‐1.46) for Medicaid‐insured patients and 1.29 (95% CI, 1.18‐1.42) for uninsured patients.CONCLUSIONS:After adjustment for age, further adjustment for 9 other factors reduced the excess mortality among rectal cancer patients without private insurance by approximately 70%. Disparities in stage and treatment accounted for approximately 53% of the excess mortality, whereas factors other than stage and treatment accounted for approximately 17%. Cancer 2010. © 2010 American Cancer Society.
Expression of Concern: Adenovirus‐mediated expression of truncated E2F‐1 suppresses tumor growth in vitro and in vivo
Authors: Gomez‐Gutierrez Jorge G. , Garcia‐Garcia Aracely , Hao Hongying , Rao Xiao‐Mei , Montes de Oca‐Luna Roberto , Zhou Heshan S. , McMasters Kelly M. 
Published: June 2010

AbstractBACKGROUND:Adenovirus (Ad)‐mediated E2F‐1 gene transfer induces apoptosis in cancer cells in vitro and in vivo, but clinical application of E2F‐1 in cancer gene therapy remains controversial because of the oncogenic potential of E2F‐1. This barrier can be circumvented by using the truncated form of the E2F‐1 gene (E2Ftr) (amino acids 1 through 375), which lacks the E2F‐1 transactivation domain and cell cycle‐promoting effects.METHODS:The authors constructed 3 adenoviral vectors that expressed E2Ftr under regulation of the tetracycline (Tet)‐off system (AdTet‐E2Ftr1, AdTet‐E2Ftr2, and AdTet‐E2Ftr3). These vectors were compared for E2Ftr expression and apoptosis induction in cancer cells and normal cells. E2Ftr antitumor activity in vivo also was assessed in a melanoma xenograft model.RESULTS:One of the 3 vectors, AdTet‐E2Ftr3, had the highest E2Ftr protein expression levels, which were correlated with the greatest induction of apoptosis and inhibition of cancer cell growth. E2Ftr induced apoptosis in a variety of cancer cell lines independent of p53 status with little cytotoxicity in normal cell lines. In a mouse melanoma xenograft model, AdTet‐E2Ftr3 exhibited an approximately 80% decrease in tumor size compared with controls in vivo.CONCLUSIONS:The current results indicated that AdTet‐E2Ftr3 is a novel anticancer agent that has significant therapeutic activity in vitro and in vivo. Cancer 2010. © 2010 American Cancer Society.
Dendritic cells erase bad memory
Authors: Kurts Christian 
Published: June 2010

AbstractDC not only activate CD4 T (Th) cell and cytotoxic CD8 T cell (CTL) responses against pathogens, but they also tolerize autoreactive T cells in order to avoid autoimmunity. Previous studies have demonstrated that steady‐state DC can tolerize naïve CTL, naïve Th cells and memory CTL. A study in this issue of the European Journal of Immunology demonstrates that DC also tolerize memory Th cells. This is arguably most critical for developing therapies against autoimmune disease; first, because Th cells are the central regulators of all adaptive immune responses, and second because memory, rather than naïve T cells are the clinically relevant cells in established autoimmune diseases. This study fosters hope that DC‐based specific immunotherapies for common autoimmune diseases are possible.
Microglia promote colonization of brain tissue by breast cancer cells in a Wnt‐dependent way
Authors: Pukrop Tobias , Dehghani Faramarz , Chuang Han‐Ning. , Lohaus Raphaela , Bayanga Kathrin , Heermann Stephan , Regen Tommy , Rossum Denise Van , Klemm Florian , Schulz Matthias , Siam Laila , Hoffmann Anja , Trümper Lorenz , Stadelmann Christine , Bechmann Ingo , Hanisch Uwe‐Karsten , Binder Claudia 
Published: June 2010

AbstractAlthough there is increasing evidence that blood‐derived macrophages support tumor progression, it is still unclear whether specialized resident macrophages, such as brain microglia, also play a prominent role in metastasis formation. Here, we show that microglia enhance invasion and colonization of brain tissue by breast cancer cells, serving both as active transporters and guiding rails. This is antagonized by inactivation of microglia as well as by the Wnt inhibitor Dickkopf‐2. Proinvasive microglia demonstrate altered morphology, but neither upregulation of M2‐like cytokines nor differential gene expression. Bacterial lipopolysacharide shifts tumor‐educated microglia into a classical M1 phenotype, reduces their proinvasive function, and unmasks inflammatory and Wnt signaling as the most strongly regulated pathways. Histological findings in human brain metastases underline the significance of these results. In conclusion, microglia are critical for the successful colonization of the brain by epithelial cancer cells, suggesting inhibition of proinvasive microglia as a promising antimetastatic strategy. © 2010 Wiley‐Liss, Inc.
MicroRNA‐125b suppresses the development of bladder cancer by targeting E2F3
Authors: Huang Li , Luo Junhua , Cai Qingqing , Pan Qiuhui , Zeng Hong , Guo Zhenghui , Dong Wen , Huang Jian , Lin Tianxin 
Published: June 2010

AbstractIncreasing evidence has suggested that dysregulation of certain microRNAs (miRNAs) may contribute to tumorigenesis. microRNA‐125b (miR‐125b) was implicated to have close relationship with cell proliferation and differentiation, and downregulation of miR‐125b was observed in various types of cancers. However, the biological function of miR‐125b in bladder tumorigenesis is still unknown. In our study, we showed that the expression of miR‐125b was significantly decreased in bladder cancer tissues and four bladder cancer cell lines. Moreover, miR‐125b could suppress bladder cancer cells to form colonies in vitro and to develop tumors in nude mice. E2F3, which was critical for G1/S transition and was overexpressed in most of poor‐differentiated bladder cancers, was identified as a target of miR‐125b by luciferase assay. The E2F3 mRNA and protein expression levels were detected in bladder cancer tissues and cell lines, and interestingly, inverse correlations between miR‐125b and E2F3 protein level were found in bladder cancer tissues and four E2F3 nonamplified cell lines. Introduction of miR‐125b could reduce the expression of E2F3 protein but not the E2F3 mRNA. In addition, we observed that transfection of miR‐125b could inhibit the expression of Cyclin A2, one of the E2Fs‐responsive genes involved in G1/S transition. These results suggest that miR‐125b may regulate G1/S transition through the E2F3–Cyclin A2 signaling pathway. Taken together, miR‐125b may act as a tumor suppressor in bladder urothelium, and downregulation of miR‐125b may contribute to the tumorigenesis of bladder cancer.
β‐amino acid substitution to investigate the recognition of angiotensin II (AngII) by angiotensin converting enzyme 2 (ACE2)
Authors: Clayton Daniel , Hanchapola Iresha , Hausler Nicholas , Unabia Sharon , Lew Rebecca A. , Widdop Robert E. , Smith Alexander I. , Perlmutter Patrick , Aguilar Marie‐Isabel 
Published: June 2010

AbstractIn spite of the important role of angiotensin converting enzyme 2 (ACE2) in the cardiovascular system, little is known about the substrate structural requirements of the AngII–ACE2 interaction. Here we investigate how changes in angiotensin II (AngII) structure affect binding and cleavage by ACE2. A series of C3 β‐amino acid AngII analogs were generated and their secondary structure, ACE2 inhibition, and proteolytic stability assessed by circular dichroism (CD), quenched fluorescence substrate (QFS) assay, and LC‐MS analysis, respectively. The β‐amino acid‐substituted AngII analogs showed differences in secondary structure, ACE2 binding and proteolytic stability. In particular, three different subsets of structure‐activity profiles were observed corresponding to substitutions in the N‐terminus, the central region and the C‐terminal region of AngII. The results show that β‐substitution can dramatically alter the structure of AngII and changes in structure correlated with ACE2 inhibition and/or substrate cleavage. β‐amino acid substitution in the N‐terminal region of AngII caused little change in structure or substrate cleavage, while substitution in the central region of AngII lead to increased β‐turn structure and enhanced substrate cleavage. β‐amino acid substitution in the C‐terminal region significantly diminished both secondary structure and proteolytic processing by ACE2. The β‐AngII analogs with enhanced or decreased proteolytic stability have potential application for therapeutic intervention in cardiovascular disease. Copyright © 2010 John Wiley & Sons, Ltd.
Introduction of axial chirality in a planar aromatic ligand results in chiral recognition with DNA
Authors: Dubois Marc‐André , Grandbois Alain , Collins Shawn K. , Schmitzer Andreea R. 
Published: June 2010

AbstractDimerization of a hydroxycarbazole produces an axially chiral biaryl, BICOL (2). One enantiomer (R)‐2, is capable of enantioselective binding to different polymorphs of DNA. The biaryl (R)‐2 was shown by fluorescence and circular dichroism to induce a shift of Z‐DNA to B‐DNA. The opposite enantiomer (S)‐2 shows no specific binding. The significant difference in behaviour between the two enantiomers (S)‐2 and (R)‐2 is in line with molecular modelling studies which show two very different binding geometries between the enantiomers with each polymorph of DNA. Copyright © 2010 John Wiley & Sons, Ltd.
Determination of eight fatty acid ethyl esters in meconium samples by headspace solid‐phase microextraction and gas chromatography–mass spectrometry
Authors: Roehsig Marli , de Paula Daniela Mendes Louzada , Moura Sidnei , de Albuquerque Diniz Edna Maria , Yonamine Mauricio 
Published: June 2010

AbstractA number of fatty acid ethyl esters (FAEEs) have recently been detected in meconium samples. Several of these FAEEs have been evaluated as possible biomarkers for in utero ethanol exposure. In the present study, a method was optimized and validated for the simultaneous determination of eight FAEEs (ethyl laurate, ethyl myristate, ethyl palmitate, ethyl palmitoleate, ethyl stearate, ethyl oleate, ethyl linoleate and ethyl arachidonate) in meconium samples. FAEEs were extracted by headspace solid‐phase microextraction. Analyte detection and quantification were carried out using GC‐MS operated in chemical ionization mode. The corresponding D5‐ethyl esters were synthesized and used as internal standards. The LOQ and LOD for each analyte were <150 and <100 ng/g, respectively. The method showed good linearity (r2>0.98) in the concentration range studied (LOQ – 2000 ng/g). The intra‐ and interday imprecision, given by the RSD of the method, was lower than 15% for all FAEEs studied. The validated method was applied to 63 authentic specimens. FAEEs could be detected in alcohol‐exposed newborns (>600 ng/g cumulative concentration). Interestingly, FAEEs could also be detected in some non‐exposed newborns, although the concentrations were much lower than those measured in exposed cases.
Alternatives to amino acid analysis for the purity control of pharmaceutical grade L‐alanine
Authors: Holzgrabe Ulrike , Nap Cees‐Jan , Beyer Tanja , Almeling Stefan 
Published: June 2010

AbstractThe quality control of drugs is important for safety of patients and consumers. International pharmacopoeias mostly employed HPLC with UV detection for this purpose. This is always a problem when the drugs, such as most amino acids, are lacking a chromophor. Instead of UV detection, the impurity control of alanine was performed using charged aerosol detector, evaporative light‐scattering detector, nano quantity analyte detector, MS detector, and as an orthogonal method, quantitative NMR spectroscopy. The charged aerosol detector, MS detector, and quantitative NMR spectroscopy provided similar and precise results, whereas the evaporative light‐scattering detector and nano quantity analyte detector revealed some problems regarding sensitivity, linearity, and robustness.
Telomere/telomerase interplay in virus‐driven and virus‐independent lymphomagenesis: pathogenic and clinical implications
Authors: Dolcetti Riccardo , De Rossi Anita 
Published: June 2010

AbstractTelomerase is a ribonucleoprotein complex critically involved in extending and maintaining telomeres. Unlike the majority of somatic cells, in which hTERT and telomerase activity are generally silent, normal lymphocytes show transient physiological hTERT expression and telomerase activity according to their differentiation/activation status. During lymphomagenesis, induction of persistent telomerase expression and activity may occur before or after telomere shortening, as a consequence of the different mechanisms through which transforming factors/agents may activate telomerase. Available data indicate that the timing of telomerase activation may allow the distinction of two different lymphomagenetic models: (i) an early activation of telomerase via exogenous regulators of hTERT, along with an increased lymphocyte growth and a subsequent selection of cells with increased transforming potential may characterize several virus‐related lymphoid malignancies; (ii) a progressive shortening of telomeres, leading to genetic instability which favors a subsequent activation of telomerase via endogenous regulators may occur in most virus‐unrelated lymphoid tumors. These models may have clinically relevant implications, particularly for the tailoring of therapeutic strategies targeting telomerase. © 2010 Wiley Periodicals, Inc. Med Res Rev
The possible role of regenerating axons in pain persistence after brachial plexus grafting
Authors: Bertelli Jayme Augusto , Ghizoni Marcos Flávio 
Published: June 2010

AbstractWe tested the hypothesis that chronic pain in patients with grafted brachial plexus injuries stems from regenerating axons. Eight patients who had undergone brachial plexus grafting still reported persistent pain 24 months after surgery, and were followed for an additional 6months. After recording each patient's self‐reported pain severity using a 10‐point verbal analogue scale, a tourniquet was inflated in the injured arm for 90 seconds. Then, patients were asked again to rate their pain. Finally, anesthetic blocks were administered to the nonavulsed C5 root. After tourniquet application to the injured limb, pain significantly decreased by 85% (P < 0.001) in all grafted patients. Anesthetic blocks yielded at least 90% pain reduction. Our findings suggest that pain after brachial plexus injury arises from nonavulsed rather than avulsed roots. After grafting, regenerating axons which have attained the periphery might be responsible for pain maintenance. © 2010 Wiley‐Liss, Inc. Microsurgery 30:532–536, 2010.
Latissimus dorsi muscle flap for lower extremity reconstruction in children
Authors: Namdar Thomas , Stollwerck Peter L. , Stang Felix H. , Lange Thomas , Mailänder Peter , Siemers Frank 
Published: June 2010

AbstractComplete loss of free latissimus dorsi muscle flaps to the leg is frequently reported. The purpose of this study is to analyze the outcome of latissimus dorsi muscle flaps to the lower extremity in children. Patients and methods. This retrospective analysis includes 11 children treated with a free latissimus dorsi muscle flap after severe trauma to the lower leg and foot. Results. Fourteen free latissimus dorsi muscle flaps were performed in 11 children with a mean age of 13 ± 4 years. The injuries were caused by traffic accidents, lawnmower accidents, and a crush trauma. Thirteen (92.8%) flaps needed surgical revision. Three complete flap losses and 1 partial flap loss were registered. Conclusions. Free latissimus dorsi muscle flaps seem to be a useful technique for lower extremity salvage after severe injury, but there is a relevant flap failure risk in children. © 2010 Wiley‐Liss, Inc. Microsurgery 30:537–540, 2010.