bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gallbladder cancer: Incidence and survival in a high‐risk area of Chile
Authors: Bertran Enriqueta , Heise Katy , Andia Marcelo E. , Ferreccio Catterina 
Published: April 2010

AbstractWe assessed population incidence rates 1998–2002 and 5‐year survival rates of 317 primary gallbladder cancer (GBC) entered in the population‐based cancer registry in Valdivia. We analyzed GBC incidence (Poisson regression) and GBC survival (Cox regression). Cases were identified by histology (69.4%), clinical work‐up (21.8%), or death certificate only (8.8%). Main symptoms were abdominal pain (82.8%), jaundice (53.6%) nausea (42.6%), and weight loss (38.2%); at diagnosis, 64% had Stage TNM IV. In the period, 4% of histopathological studies from presumptively benign cholecystectomies presented GBC. GBC cases were mainly females (76.0%), urban residents (70.3%), Hispanic (83.7%) of low schooling <4 years (64.0%). GBC standardized incidence rate per 100,000 (SIR) were all 17.5 (95%CI: 15.5–19.4), women 24.3, and men 8.6 (p < 0.00001); Mapuche 25.0, Hispanic 16.2 (p = 0.09). The highest SIRs were in Mapuche (269.2) and Hispanic women (199.6) with <4 years of schooling. Lowest SIRs were among Hispanic men (19.8) and women (21.9) with >8 years of schooling. Low schooling, female and urban residence were independent risk factors. By December 31, 2007, 6 (1.9%) cases were living, 280 (88.3%) died from GBC, 32 (10.1%) were lost of follow‐up. Kaplan Meier Global 5‐year survival was: 10.3%, 85% at stage I and 1.9% at stage IV; median survival: 3.4 months. Independent poor prognostic factors were TNM IV, jaundice and nonincidental diagnoses. Our results suggest that women of Mapuche ancestry with low schooling (>50 years) are at the highest risk of presenting and dying from GBC and should be the target for early detection programs.
De novo constitutional MLH1 epimutations confer early‐onset colorectal cancer in two new sporadic Lynch syndrome cases, with derivation of the epimutation on the paternal allele in one
Authors: Goel Ajay , Nguyen Thuy‐Phuong , Leung Hon‐Chiu E. , Nagasaka Takeshi , Rhees Jennifer , Hotchkiss Erin , Arnold Mildred , Banerji Pia , Koi Minoru , Kwok Chau‐To , Packham Deborah , Lipton Lara , Boland C. Richard , Ward Robyn L. , Hitchins Megan P. 
Published: April 2010

AbstractLynch syndrome is an autosomal dominant cancer predisposition syndrome classically caused by germline mutations of the mismatch repair genes, MLH1, MSH2, MSH6 and PMS2. Constitutional epimutations of the MLH1 gene, characterized by soma‐wide methylation of a single allele of the promoter and allelic transcriptional silencing, have been identified in a subset of Lynch syndrome cases lacking a sequence mutation in MLH1. We report two individuals with no family history of colorectal cancer who developed that disease at age 18 and 20 years. In both cases, cancer had arisen because of the de novo occurrence of a constitutional MLH1 epimutation and somatic loss‐of‐heterozygosity of the functional allele in the tumors. We show for the first time that the epimutation in one case arose on the paternally inherited allele. Analysis of 13 tumors from seven individuals with constitutional MLH1 epimutations showed eight tumors had lost the second MLH1 allele, two tumors had a novel pathogenic missense mutation and three had retained heterozygosity. Only 1 of 12 tumors demonstrated the BRAF V600E mutation and 3 of 11 tumors harbored a mutation in KRAS. The finding that epimutations can originate on the paternal allele provides important new insights into the mechanism of origin of epimutations. It is clear that the second hit in MLH1 epimutation‐associated tumors typically has a genetic not epigenetic basis. Individuals with mismatch repair–deficient cancers without the BRAF V600E mutation are candidates for germline screening for sequence or methylation changes in MLH1.
The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: Results of a prospective randomized phase II/III trial
Authors: Heiss Markus M. , Murawa Pawel , Koralewski Piotr , Kutarska Elzbieta , Kolesnik Olena O. , Ivanchenko Vladimir V. , Dudnichenko Alexander S. , Aleknaviciene Birute , Razbadauskas Arturas , Gore Martin , Ganea‐Motan Elena , Ciuleanu Tudor , Wimberger Pauline , Schmittel Alexander , Schmalfeldt Barbara , Burges Alexander , Bokemeyer Carsten , Lindhofer Horst , Lahr Angelika , Parsons Simon L. 
Published: April 2010

AbstractMalignant ascites is a common manifestation of advanced cancers, and treatment options are limited. The trifunctional antibody catumaxomab (anti‐epithelial cell‐adhesion molecule x anti‐CD3) represents a targeted immunotherapy for the intraperitoneal (i.p.) treatment of malignant ascites secondary to epithelial cancers. In this phase II/III trial (EudraCT 2004‐000723‐15; NCT00836654), cancer patients (n = 258) with recurrent symptomatic malignant ascites resistant to conventional chemotherapy were randomized to paracentesis plus catumaxomab (catumaxomab) or paracentesis alone (control) and stratified by cancer type (129 ovarian and 129 nonovarian). Catumaxomab was administered as an i.p. infusion on Days 0, 3, 7 and 10 at doses of 10, 20, 50 and 150 μg, respectively. The primary efficacy endpoint was puncture‐free survival. Secondary efficacy parameters included time to next paracentesis, ascites signs and symptoms and overall survival (OS). Puncture‐free survival was significantly longer in the catumaxomab group (median 46 days) than the control group (median 11 days) (hazard ratio = 0.254: p < 0.0001) as was median time to next paracentesis (77 versus 13 days; p < 0.0001). In addition, catumaxomab patients had fewer signs and symptoms of ascites than control patients. OS showed a positive trend for the catumaxomab group and, in a prospectively planned analysis, was significantly prolonged in patients with gastric cancer (n = 66; 71 versus 44 days; p = 0.0313). Although adverse events associated with catumaxomab were frequent, they were manageable, generally reversible and mainly related to its immunologic mode of action. Catumaxomab showed a clear clinical benefit in patients with malignant ascites secondary to epithelial cancers, especially gastric cancer, with an acceptable safety profile.
Clinicopathological significance of cell cycle regulation markers in a large series of genetically confirmed Ewing's Sarcoma Family of Tumors
Authors: López‐Guerrero José Antonio , Machado Isidro , Scotlandi Katia , Noguera Rosa , Pellín Antonio , Navarro Samuel , Serra Massimo , Calabuig‐Fariñas Silvia , Picci Piero , Llombart‐Bosch Antonio 
Published: April 2010

AbstractMore than 90% of all Ewing's Sarcoma Family of Tumors (ESFT) exhibit specific chromosomal rearrangements between theEWSgene on chromosome 22 and various members of theETSgene family of transcription factors. The gene fusion type and other secondary genetic alterations, mainly involving cell cycle regulators, have been shown to be of prognostic relevance in ESFT. However, no conclusive results have been reported. We analyzed the clinicopathological significance of relevant cell cycle regulators in genetically confirmed ESFT. A total of 324 cases were analyzed for the immunohistochemical expression of p53, p21Waf1/Cip1, p27Kip1and Ki67 and the chromosomal alterations of thep53and9p21locus by fluorescent in situ hybridization. We observed that expression of p53 (p= 0.025), p21Waf1/Cip1(p= 0.015) and p27Kip1(p= 0.013) was higher in disseminated than in localized disease. Furthermore, a cohort of 217 patients with localized disease was considered for studying the prognosis involvement of these factors on patient follow‐up. The median follow‐up was 39 months (range: 0.17–452) with an overall survival (OS) of 55%. Ki67 was expressed in 34% of cases and constituted an independent prognostic factor for progression free survival and OS independently of the type of treatment [hazard ratio of 2.0 (95% CI: 1.3–3.1;p= 0.003) and 1.9 (95% IC: 1.3–2.9;p= 0.007) for progression free survival and OS, respectively, being especially relevant in the group of patients which incorporated radiotherapy in their regimen schedules. In conclusion, this study demonstrates that Ki67 expression constitutes a valuable indicator of poor prognosis in localized ESFT.
Antioxidant intake and risk of endometrial cancer: Results from the Nurses' Health Study
Authors: Cui Xiaohui , Rosner Bernard , Willett Walter C. , Hankinson Susan E. 
Published: April 2010

AbstractTo investigate the associations between antioxidant intake and risk of endometrial cancer, the authors analyzed data from the prospective Nurses' Health Study. From 1980 to 2006, 669 invasive adenocarcinoma cases were identified over 1.3 million person‐years of follow‐up. Information on dietary intake was collected in 1980 and updated every 2–4 years. Cox proportional hazard models were used to calculate the multivariate relative risks (RR), controlling for total energy and potential risk factors for endometrial cancer. Overall, the authors found no association between intakes of vitamins A, C, E or carotenoids from foods or supplements and cancer risk. The RR and 95% confidence intervals (CI) for the highest vs. lowest quintiles of vitamins A, C, E and total carotenoids were 1.09 (95% CI: 0.85–1.39), 0.98 (95% CI: 0.76–1.25), 1.07 (95% CI: 0.83–1.38) and 1.12 (95% CI: 0.86–1.45), respectively. Similarly, the use of multivitamins or specific vitamins A, C or E supplements was unassociated with risk. In subgroup analyses, several associations seemed to vary by postmenopausal hormone use. Our results suggest that there is no overall association between dietary antioxidant intake or use of antioxidant supplements with risk of endometrial cancer.
Pancreatic cancer incidence and outcome in relation to ABO blood groups among Han Chinese patients: A case–control study
Authors: Ben Qiwen , Wang Kaixuan , Yuan Yaozong , Li Zhaoshen 
Published: April 2010

AbstractThe aim of the current study was to determine the association between ABO blood group and the risk and progression of pancreatic ductal adenocarcinoma (PDAC) in the Han Chinese ethnic group. During the period of 2000–2009, 1,431 patients with PDAC and 1,449 age‐ and sex‐matched controls were recruited in two university‐affiliated hospitals. An unconditional multivariable logistic regression analysis was used to estimate adjusted odds ratios (ORs). The relationship between patient ABO blood group and clinicopathologic features was also analyzed. Compared with subjects having blood group O, a modestly higher risk was observed among cases with blood group A or AB with adjusted ORs (95% confidence interval) of 1.368 (1.127–1.661) and 1.391 (1.053–1.838), respectively. The TNM stages of tumors in patients with non‐O blood groups (A, B or AB) were more highly advanced than in patients with blood group O (p < 0.001). Among patients who underwent a potentially curative operation, the median survival time of patients with blood group O was significantly longer than that of patients with non‐O blood groups (16.0 months vs. 11.0 months, p = 0.001, log‐rank test). This study shows evidence of an association between blood group type and risk for development and progression of PDAC. These findings merit further confirmation in a large population‐based prospective study in patients of the Han Chinese ethnic group.
Trafficking and signaling in mammalian autophagy
Authors: Tooze Sharon A. , Jefferies Harold B. J. , Kalie Eyal , Longatti Andrea , Mcalpine Fiona E. , Mcknight Nicole C. , Orsi Andrea , Polson Hannah E. J. , Razi Minoo , Robinson Deborah J. , Webber Jemma L. 
Published: April 2010

AbstractMacroautophagy, here called autophagy, is literally a “self‐eating” catabolic process, which is evolutionarily conserved. Autophagy is initiated by cellular stress pathways, resulting in the sequestration or engulfment of cytosolic proteins, membranes, and organelles in a double membrane structure that fuses with endosomes and lysosomes, thus delivering the sequestered material for degradation. Autophagy is implicated in a number of human diseases, many of which can either be characterized by an imbalance in protein, organelle, or cellular homeostasis, ultimately resulting in an alteration of the autophagic response. Here, we will review the recent progress made in understanding the induction of autophagy, with emphasis on the contributions from our laboratory. © 2010 IUBMB IUBMB Life 62(7): 503–508, 2010
Species and strain identification of lactic acid bacteria using FTIR spectroscopy and artificial neural networks
Authors: Wenning Mareike , Büchl Nicole R. , Scherer Siegfried 
Published: April 2010

AbstractLactic acid bacteria (LAB) are a heterogeneous group of micro‐organisms with high relevance for fermented food and beverages as well as human and animal health. Identification of LAB is complicated by species richness, a high degree of heterogeneity between species and the presence of very closely related species at the same time. In the present study we developed identification systems based on FTIR spectra and artificial neural networks (ANNs) for species identification of 92 LAB species out of nine genera and strain identification of probiotic and environmental Enterococcus faecium strains used as additives for animal feed. The reference databases established in this work permit reliable identification of LAB with accuracies of 93.2% at species and 97.1% at strain level for Ec. faecium, demonstrating the excellent suitability of FTIR spectroscopy as a technique applicable for simultaneous species and strain identification. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The effect of the association of near infrared laser therapy, bone morphogenetic proteins, and guided bone regeneration on tibial fractures treated with internal rigid fixation: A Raman spectroscopic study
Authors: Lopes Cibele B. , Pacheco Marcos T. T. , Silveira Landulfo , Cangussú Maria Cristina T. , Pinheiro Antonio L. B. 
Published: April 2010

AbstractFractures have different etiology and treatment and may be associated or not to bone losses. Laser light has been shown to improve bone healing. We aimed to assess, through Raman spectroscopy, the level of CHA (∼958 cm−1) on complete fractures animals treated with IRF treated or not with Low Level Laser Therapy—LLLT and associated or not to BMPs and GBR. Complete tibial fractures were created on 15 animals that were divided into five groups. LLLT (Laser Unit, Kondortech, São Carlos, SP, Brazil, λ790 nm, 4 J/cm2/point, 40 mW, ϕ ∼ 0.5 cm2, 16 J/cm2 session) started immediately after surgery and repeated at 48 h interval (2 weeks). Animal death occurred after 30 days. Raman spectroscopy was performed at the surface of the fracture. Our results showed significant differences between the groups IRF + BL /IRF_NBL (p = 0.05); between all experimental groups and untreated bone; bone/IRF + BL; IRF + BL + Bio + GBR; IRF + BL + LLLT; IRF + BL + Bio + GBR + LLLT; IRF_NBL (p < 0.001, all); IRF_NBL/IRF + BL + LLLT (p = 0.03); IRF_NBL/IRF + BL + Bio + GBR + LLLT (p = 0.02); IRF + BL/IRF + BL + LLLT (p = 0.04); IRF + BL/IRF + BL + Bio + GBR + LLLT (p = 0.002); IRF + BL + Bio + GBR/IRF + BL + Bio + GBR + LLLT (p = 0.05). It is concluded that the use of NIR LLLT associated to BMPs and GBR was effective in improving bone healing on fractured bones due to increased levels of CHA. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
A comparison of imaging methodologies for 3D tissue engineering
Authors: Smith Louise E. , Smallwood Rod , Macneil Sheila 
Published: April 2010

AbstractImaging of cells in two dimensions is routinely performed within cell biology and tissue engineering laboratories. When biology moves into three dimensions imaging becomes more challenging, especially when multiple cell types are used. This review compares imaging techniques used regularly in our laboratory in the culture of cells in both two and three dimensions. The techniques reviewed include phase contrast microscopy, fluorescent microscopy, confocal laser scanning microscopy, electron microscopy, and optical coherence tomography. We compare these techniques to the current “gold standard” for imaging three‐dimensional tissue engineered constructs, histology. Microsc. Res. Tech. 73:1123–1133, 2010. © 2010 Wiley‐Liss, Inc.
Confocal microscopy for the analysis of siRNA delivery by polymeric nanoparticles
Authors: Portis Amanda M. , Carballo Georgina , Baker Gregory L. , Chan Christina , Walton S. Patrick 
Published: April 2010

AbstractClinical applications of genetic therapies, including delivery of short, interfering RNAs (siRNAs) for RNA interference (RNAi), are limited due to the difficulty of delivering nucleic acids to specific cells of interest while at the same time minimizing toxicity and immunogenicity. The use of cationic polymers to deliver nucleic acid therapeutics has the potential to address these complex issues but is currently limited by low‐delivery efficiencies. Although cell culture studies have shown that some polymers can be used to deliver siRNAs and achieve silencing, it is still not clear what physical or chemical properties are needed to ensure that the polymers form active polymer‐siRNA complexes. In this study, we used multicolor fluorescence confocal microscopy to analyze the cellular uptake of siRNAs delivered by novel propargyl glycolide polymeric nanoparticles (NPs). Delivery by these vehicles was compared with delivery by linear polyethyleneimine (LPEI) and Lipofectamine 2000 (LF2K), which are both known as effective delivery vehicles for siRNAs. Our results showed that when LF2K and LPEI were used, large quantities of siRNA were delivered rapidly, presumably overwhelming the basal levels of mRNA to initiate silencing. In contrast, our novel polymeric NPs showed delivery of siRNAs but at concentrations that were initially too low to achieve silencing. Nonetheless, the exceptionally low cytotoxicity of our NPs, and the simplicity with which they can be modified, makes them good candidates for further study to optimize their delivery profiles and, in turn, achieve efficient silencing. Microsc. Res. Tech. 73:878–885, 2010. © 2010 Wiley‐Liss, Inc.
Multiphoton fluorescence lifetime imaging of 3D‐stem cell spheroids during differentiation
Authors: König Karsten , Uchugonova Aisada , Gorjup Erwin 
Published: April 2010

AbstractLong‐term high‐resolution multiphoton imaging of nonlabeled human salivary gland stem cell spheroids has been performed with submicron spatial resolution, 10.5‐nm spectral resolution, and picosecond temporal resolution. In particular, the two‐photon‐excited coenzyme NAD(P)H and flavins have been detected by time‐correlated single photon counting (TCSPC). Stem cells increased their autofluorescence lifetimes and decreased their total fluorescence intensity during the adipogenic‐differentiation process. In addition, the onset of the biosynthesis of lipid vacuoles was monitored over a period of several weeks in stem‐cell spheroids. Time‐resolved multiphoton autofluorescence imaging microscopes may become a promising tool for marker‐free stem‐cell characterization and cell sorting. Microsc. Res. Tech. 74:9‐17, 2011. © 2010 Wiley‐Liss, Inc.
Abnormal human chondrocyte morphology is related to increased levels of cell‐associated IL‐1β and disruption to pericellular collagen type VI
Authors: Murray Dianne H. , Bush Peter G. , Brenkel Ivan J. , Hall Andrew C. 
Published: April 2010

AbstractEarly osteoarthritis (OA) is poorly understood, but abnormal chondrocyte morphology might be important. We studied IL‐1β and pericellular collagen type VI in morphologically normal and abnormal chondrocytes. In situ chondrocytes within explants from nondegenerate (grade 0/1) areas of human tibial plateaus (n = 21) were fluorescently labeled and visualized [2‐photon laser scanning microscopy (2PLSM)]. Normal chondrocytes exhibited a “smooth” membrane surface, whereas abnormal cells were defined as demonstrating ≥1 cytoplasmic process. Abnormal chondrocytes were further classified by number and average length of cytoplasmic processes/cell. IL‐1β or collagen type VI associated with single chondrocytes were visualized by fluorescence immuno‐histochemistry and confocal laser scanning microscopy (CLSM). Fluorescence was quantified as the number of positive voxels (i.e., 3D pixels with fluorescence above baseline)/cell. IL‐1β‐associated fluorescence increased between normal and all abnormal cells in the superficial (99.7 ± 29.8 [11 (72)] vs. 784 ± 382 [15 (132)]; p = 0.04, positive voxels/cell) and deep zones (66.5 ± 29.4 [9 (64)] vs. 795 ± 224 [9 (56)]; p = 0.006). There was a correlation (r2 = 0.988) between the number of processes/cell (0–5) and IL‐1β, and an increase particularly with short processes (≤5 µm; p = 0.022). Collagen type VI coverage and thickness decreased (p < 0.001 and p = 0.005, respectively) with development of processes. Abnormal chondrocytes in macroscopically nondegenerate cartilage demonstrated a marked increase in IL‐1β and loss of pericellular type VI collagen, changes that could lead to cartilage degeneration. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1507–1514, 2010
Mechanical activation of β‐catenin regulates phenotype in adult murine marrow‐derived mesenchymal stem cells
Authors: Case Natasha , Xie Zhihui , Sen Buer , Styner Maya , Zou Minxu , O'Conor Chris , Horowitz Mark , Rubin Janet 
Published: April 2010

AbstractRegulation of skeletal remodeling appears to influence the differentiation of multipotent mesenchymal stem cells (MSC) resident in the bone marrow. As murine marrow cultures are contaminated with hematopoietic cells, they are problematic for studying direct effects of mechanical input. Here we use a modified technique to isolate marrow‐derived MSC (mdMSC) from adult mice, yielding a population able to differentiate into adipogenic and osteogenic phenotypes that is devoid of hematopoietic cells. In pure mdMSC populations, a daily strain regimen inhibited adipogenic differentiation, suppressing expression of PPARγ and adiponectin. Strain increased β‐catenin and inhibition of adipogenesis required this effect. Under osteogenic conditions, strain activated β‐catenin signaling and increased expression of WISP1 and COX2. mdMSC were also generated from mice lacking caveolin‐1, a protein known to sequester β‐catenin: caveolin‐1(−/−) mdMSC exhibited retarded differentiation along both adipogenic and osteogenic lineages but retained mechanical responses that involved β‐catenin activation. Interestingly, caveolin‐1(−/−) mdMSC failed to express bone sialoprotein and did not form mineralized nodules. In summary, mdMSC from adult mice respond to both soluble factors and mechanical input, with mechanical activation of β‐catenin influencing phenotype. As such, these cells offer a useful model for studies of direct mechanical regulation of MSC differentiation and function. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1531–1538, 2010