bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of heterozygosity at 9p and p53 immunopositivity in surgical margins predict local relapse in head and neck squamous cell carcinoma
Authors: Graveland A. Peggy , Golusinski Pawel J. , Buijze Marijke , Douma Rinze , Sons Nanet , Kuik Dirk J. , Bloemena Elisabeth , Leemans C. René , Brakenhoff Ruud H. , Braakhuis Boudewijn J.M. 
Published: June 2010

AbstractA major problem in head and neck cancer surgery is the high rate of local relapse (LR). In at least 25% of the surgically treated head and neck squamous cell carcinoma (HNSCC) patients, a genetically defined preneoplastic lesion, also known as “field,” can be detected in the surgical margins. A remaining field may be an important cause for the development of LR. The aims of our study are (i) to investigate whether HNSCC patients with an unresected field are more likely to develop LR, and (ii) to identify molecular risk factors that predict malignant transformation of field. We retrospectively studied 35 HNSCC patients of whom 16 patients developed LR and 19 patients remained disease‐free for at least 4 years. Loss of heterozygosity (LOH) at chromosomes 3p, 9p and 17p, p53 immunostaining, Ki‐67 immunostaining and histopathological grading of all available paraffin‐embedded surgical margins was performed, and related to LR. Significant associations were determined by Kaplan‐Meier analysis and Cox‐proportional hazard models. We show that presence of field is significantly associated with LR and that LOH at 9p and p53 immunostaining have the most predictive potential (hazard ratios 3.17 and 3.46, and p values 0.027 and 0.017, respectively). The combination of LOH at 9p and/or a large p53 positive field is most predictive (hazard ratio 7.06 and p = 0.01). Presence and grade of dysplasia was not associated with LR. These data may have major impact for future diagnostic workup of surgically treated HNSCC patients.
Role for transcription factor TFII‐I in the suppression of SSeCKS/Gravin/Akap12 transcription by Src
Authors: Bu Yahao , Gao Lingqiu , Gelman Irwin H. 
Published: June 2010

AbstractThe SSeCKS/Gravin/AKAP12 gene, encoding a kinase scaffolding protein with metastasis‐suppressing activity, is transcriptionally downregulated in Src‐transformed cells through the recruitment of HDAC1 to a Src‐responsive proximal promoter site charged with Sp1, Sp3 and USF1. However, the ectopic expression of these proteins formed a suppressive complex in Src‐transformed but not in parental NIH3T3 cells, suggesting the involvement of additional repressor factors. Transcription factor II‐I (TFII‐I) [general transcription factor 2i (Gtf2i)] was identified by mass spectrometry as being associated with the SSeCKS promoter complex in NIH3T3/Src cells, and moreover, the Src‐induced tyrosine phosphorylation of TFII‐I significantly increased its binding to the SSeCKS proximal promoter. siRNA‐mediated knockdown of TFII‐I or the expression of TFII‐IY248/249F caused the derepression of SSeCKS in NIH3T3/Src cells. Taken with previous data showing that the tyrosine phosphorylation of TFII‐I facilitates its nuclear translocation, these data suggest that Src‐family kinase‐mediated phosphorylation converts a portion of TFII‐I into a transcriptional repressor.
Trends in cervical cancer incidence and mortality in the Baltic countries, Bulgaria and Romania
Authors: Arbyn Marc , Antoine Jerome , Mägi Margit , Smailyte Giedre , Stengrevics Aivars , Suteu Ofelia , Valerianova Zdravka , Bray Freddie , Weiderpass Elisabete 
Published: June 2010

AbstractThe burden of cervical cancer varies considerably in the European Union (EU). In this article, we describe trends in incidence of and mortality from this cancer in the two most affected areas: the Baltic countries (Estonia, Latvia and Lithuania) and Southeast Europe (Bulgaria and Romania). Incidence data were obtained from the national cancer registries. Data on population and number of deaths from uterine cancers were extracted from the World Health Organization mortality database. Mortality rates were corrected for inaccuracies in the death certification of not otherwise specified uterine cancer. Joinpoint regression was used to study the annual variation of corrected and standardized incidence and mortality rates. Changes were assessed by calendar period and age group, whereas the evolution by birth cohort was synthesized by computing standardized cohort incidence/mortality ratios. Joinpoint regression revealed rising trends of incidence (in Lithuania, Bulgaria and Romania) and of mortality (in Latvia, Lithuania, Bulgaria and Romania). In Estonia, rates were rather stable. Women born between 1940 and 1960 were at continuously increasing risk of both incidence of and mortality from cervical cancer. Although some quality issues in the registration of cancer and causes of death cannot be ignored, the trends indicate increased exposure to human papillomavirus infection and absence of effective screening programs. Rising trends of cervical cancer in the most affected EU member states reveal a worrying pattern that warrants urgent preventive actions.
Multiple antimelanoma potential of dry olive leaf extract
Authors: Mijatovic Sanja A. , Timotijevic Gordana S. , Miljkovic Djordje M. , Radovic Julijana M. , Maksimovic‐Ivanic Danijela D. , Dekanski Dragana P. , Stosic‐Grujicic Stanislava D. 
Published: June 2010

AbstractVarious constituents of the olive tree (Olea europaea) have been traditionally used in the treatment of infection, inflammation, prevention of chronic diseases, cardiovascular disorders and cancer. The anticancer potential of dry olive leaf extract (DOLE) represents the net effect of multilevel interactions between different biologically active compounds from the extract, cancer cells and conventional therapy. In this context, it was of primary interest to evaluate the influence of DOLE on progression of the highly malignant, immuno‐ and chemoresistant type of skin cancer—melanoma. DOLE significantly inhibited proliferation and subsequently restricted clonogenicity of the B16 mouse melanoma cell line in vitro. Moreover, late phase tumor treatment with DOLE significantly reduced tumor volume in a syngeneic strain of mice. DOLE‐treated B16 cells were blocked in the G0/G1 phase of the cell cycle, underwent early apoptosis and died by late necrosis. At the molecular level, the dying process started as caspase dependent, but finalized as caspase independent. In concordance, overexpression of antiapoptotic members of the Bcl‐2 family, Bcl‐2 and Bcl‐XL, and diminished expression of their natural antagonists, Bim and p53, were observed. Despite molecular suppression of the proapoptotic process, DOLE successfully promoted cell death mainly through disruption of cell membrane integrity and late caspase‐independent fragmentation of genetic material. Taken together, the results of this study indicate that DOLE possesses strong antimelanoma potential. When DOLE was applied in combination with different chemotherapeutics, various outcomes, including synergy and antagonism, were observed. This requires caution in the use of the extract as a supplementary antitumor therapeutic.
Abnormal microarchitecture and reduced stiffness at the radius and tibia in postmenopausal women with fractures
Authors: Stein Emily M , Liu X Sherry , Nickolas Thomas L , Cohen Adi , Thomas Valerie , McMahon Donald J , Zhang Chiyuan , Yin Perry T , Cosman Felicia , Nieves Jeri , Guo X Edward , Shane Elizabeth 
Published: June 2010

Abstract
Measurement of areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA) has been shown to predict fracture risk. High-resolution peripheral quantitative computed tomography (HR-pQCT) yields additional information about volumetric BMD (vBMD), microarchitecture, and strength that may increase understanding of fracture susceptibility. Women with (n = 68) and without (n = 101) a history of postmenopausal fragility fracture had aBMD measured by DXA and trabecular and cortical vBMD and trabecular microarchitecture of the radius and tibia measured by HR-pQCT. Finite-element analysis (FEA) of HR-pQCT scans was performed to estimate bone stiffness. DXA T-scores were similar in women with and without fracture at the spine, hip, and one-third radius but lower in patients with fracture at the ultradistal radius (p &lt; .01). At the radius fracture, patients had lower total density, cortical thickness, trabecular density, number, thickness, higher trabecular separation and network heterogeneity (p &lt; .0001 to .04). At the tibia, total, cortical, and trabecular density and cortical and trabecular thickness were lower in fracture patients (p &lt; .0001 to .03). The differences between groups were greater at the radius than at the tibia for inner trabecular density, number, trabecular separation, and network heterogeneity (p &lt; .01 to .05). Stiffness was reduced in fracture patients, more markedly at the radius (41% to 44%) than at the tibia (15% to 20%). Women with fractures had reduced vBMD, microarchitectural deterioration, and decreased strength. These differences were more prominent at the radius than at the tibia. HR-pQCT and FEA measurements of peripheral sites are associated with fracture prevalence and may increase understanding of the role of microarchitectural deterioration in fracture susceptibility. © 2010 American Society for Bone and Mineral Research.
Decreasing incidence and changing pattern of childhood fractures: A population-based study
Authors: Mäyränpää Mervi K , Mäkitie Outi , Kallio Pentti E 
Published: June 2010

Abstract
Fractures are common in children, and some studies suggest an increasing incidence. Data on population-based long-term trends are scarce. In order to establish fracture incidence and epidemiologic patterns, we carried out a population-based study in Helsinki, Finland. All fractures in children aged 0 to 15 years were recorded from public health care institutions during a 12-month period in 2005. Details regarding patient demographics, fracture site, and trauma mechanism were collected. All fractures were confirmed from radiographs. Similar data from 1967, 1978, and 1983 were used for comparison. In 2005, altogether 1396 fractures were recorded, 63% in boys. The overall fracture incidence was 163 per 10,000. Causative injuries consisted of mainly falls when running or walking or from heights less than 1.5 m. Fracture incidence peaked at 10 years in girls and 14 years in boys. An increase in fracture incidence was seen from 1967 to 1983 (24%, p &lt; .0001), but a significant decrease (18%, p &lt; .0001) was seen from 1983 to 2005. This reduction was largest in children between the ages of 10 and 13 years. Despite the overall decrease and marked decrease in hand (−39%, p &lt; .0001) and foot (−48%, p &lt; .0001) fractures, the incidence of forearm and upper arm fractures increased significantly by 31% (p &lt; .0001) and 39% (p = .021), respectively. Based on these findings, the overall incidence of childhood fractures has decreased significantly during the last two decades. Concurrently, the incidence of forearm and upper arm fractures has increased by one-third. The reasons for these epidemiologic changes remain to be elucidated in future studies. © 2010 American Society for Bone and Mineral Research.
The role of estrogen receptor α in growth plate cartilage for longitudinal bone growth
Authors: Börjesson Anna E , Lagerquist Marie K , Liu Chen , Shao Ruijin , Windahl Sara H , Karlsson Camilla , Sjögren Klara , Movérare-Skrtic Sofia , Antal Maria Christina , Krust Andrée , Mohan Subburaman , Chambon Pierre , Sävendahl Lars , Ohlsson Claes 
Published: June 2010

Abstract
Estrogens enhance skeletal growth during early sexual maturation, whereas high estradiol levels during late puberty result in growth plate fusion in humans. Although the growth plates do not fuse directly after sexual maturation in rodents, a reduction in growth plate height is seen by treatment with a high dose of estradiol. It is unknown whether the effects of estrogens on skeletal growth are mediated directly via estrogen receptors (ERs) in growth plate cartilage and/or indirectly via other mechanisms such as the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis. To determine the role of ERα in growth plate cartilage for skeletal growth, we developed a mouse model with cartilage-specific inactivation of ERα. Although mice with total ERα inactivation displayed affected longitudinal bone growth associated with alterations in the GH/IGF-1 axis, the skeletal growth was normal during sexual maturation in mice with cartilage-specific ERα inactivation. High-dose estradiol treatment of adult mice reduced the growth plate height as a consequence of attenuated proliferation of growth plate chondrocytes in control mice but not in cartilage-specific ERα−/− mice. Adult cartilage-specific ERα−/− mice continued to grow after 4 months of age, whereas growth was limited in control mice, resulting in increased femur length in 1-year-old cartilage-specific ERα−/− mice compared with control mice. We conclude that during early sexual maturation, ERα in growth plate cartilage is not important for skeletal growth. In contrast, it is essential for high-dose estradiol to reduce the growth plate height in adult mice and for reduction of longitudinal bone growth in elderly mice. © 2010 American Society for Bone and Mineral Research.
A longitudinal HR-pQCT study of alendronate treatment in postmenopausal women with low bone density: Relations among density, cortical and trabecular microarchitecture, biomechanics, and bone turnover
Authors: Burghardt Andrew J , Kazakia Galateia J , Sode Miki , de Papp Anne E , Link Thomas M , Majumdar Sharmila 
Published: June 2010

Abstract
The goal of this study was to characterize longitudinal changes in bone microarchitecture and function in women treated with an established antifracture therapeutic. In this double-blind, placebo-controlled pilot study, 53 early postmenopausal women with low bone density (age = 56 ± 4 years; femoral neck T-score = −1.5 ± 0.6) were monitored by high-resolution peripheral quantitative computed tomography (HR-pQCT) for 24 months following randomization to alendronate (ALN) or placebo (PBO) treatment groups. Subjects underwent annual HR-pQCT imaging of the distal radius and tibia, dual-energy X-ray absorptiometry (DXA), and determination of biochemical markers of bone turnover (BSAP and uNTx). In addition to bone density and microarchitecture assessment, regional analysis, cortical porosity quantification, and micro-finite-element analysis were performed. After 24 months of treatment, at the distal tibia but not the radius, HR-pQCT measures showed significant improvements over baseline in the ALN group, particularly densitometric measures in the cortical and trabecular compartments and endocortical geometry (cortical thickness and area, medullary area) (p &lt; .05). Cortical volumetric bone mineral density (vBMD) in the tibia alone showed a significant difference between treatment groups after 24 months (p &lt; .05); however, regionally, significant differences in Tb.vBMD, Tb.N, and Ct.Th were found for the lateral quadrant of the radius (p &lt; .05). Spearman correlation analysis revealed that the biomechanical response to ALN in the radius and tibia was specifically associated with changes in trabecular microarchitecture (|ρ| = 0.51 to 0.80, p &lt; .05), whereas PBO progression of bone loss was associated with a broad range of changes in density, geometry, and microarchitecture (|ρ| = 0.56 to 0.89, p &lt; .05). Baseline cortical geometry and porosity measures best predicted ALN-induced change in biomechanics at both sites (ρ &gt; 0.48, p &lt; .05). These findings suggest a more pronounced response to ALN in the tibia than in the radius, driven by trabecular and endocortical changes. © 2010 American Society for Bone and Mineral Research.
Reactive oxygen and nitrogen species during meiotic resumption from diplotene arrest in mammalian oocytes
Authors: Pandey Ashutosh N. , Tripathi Anima , PremKumar Karuppanan V. , Shrivastav Tulsidas G. , Chaube Shail K. 
Published: June 2010

AbstractMammalian ovary is metabolically active organ and generates by‐products such as reactive oxygen species (ROS) and reactive nitrogen species (RNS) on an extraordinary scale. Both follicular somatic cells as well as oocyte generate ROS and RNS synchronously and their effects are neutralized by intricate array of antioxidants. ROS such as hydrogen peroxide (H2O2) and RNS such as nitric oxide (NO) act as signaling molecules and modulate various aspects of oocyte physiology including meiotic cell cycle arrest and resumption. Generation of intraoocyte H2O2 can induce meiotic resumption from diplotene arrest probably by the activation of adenosine monophosphate (AMP)‐activated protein kinase A (PRKA)—or Ca2+‐mediated pathway. However, reduced intraoocyte NO level may inactivate guanylyl cyclase‐mediated pathway that results in the reduced production of cyclic 3′,5′‐guanosine monophosphate (cGMP). The reduced level of cGMP results in the activation of cyclic 3′,5′‐adenosine monophosphate (cAMP)‐phosphodiesterase 3A (PDE3A), which hydrolyses cAMP. The reduced intraoocyte cAMP results in the activation of maturation promoting factor (MPF) that finally induces meiotic resumption. Thus, a transient increase of intraoocyte H2O2 level and decrease of NO level may signal meiotic resumption from diplotene arrest in mammalian oocytes. J. Cell. Biochem. 111: 521–528, 2010. © 2010 Wiley‐Liss, Inc.
Activated α2 macroglobulin induces matrix metalloproteinase 9 expression by low‐density lipoprotein receptor‐related protein 1 through MAPK‐ERK1/2 and NF‐κB activation in macrophage‐derived cell lines
Authors: Cáceres Leandro C. , Bonacci Gustavo R. , Sánchez María C. , Chiabrando Gustavo A. 
Published: June 2010

AbstractMacrophages under certain stimuli induce matrix metalloproteinase 9 (MMP‐9) expression and protein secretion through the activation of MAPK‐ERK and NF‐κB signaling pathways. Previously, we demonstrated that activated α2‐macroglulin (α2M*) through the interaction with its receptor low‐density lipoprotein receptor‐related protein 1 (LRP1) induces macrophage proliferation mediated by the activation of MAPK‐ERK1/2. In the present work, we examined whether α2M*/LRP1interaction could induce the MMP‐9 production in J774 and Raw264.7 macrophage‐derived cell lines. It was shown that α2M* promoted MMP‐9 expression and protein secretion by LRP1 in both macrophage‐derived cell lines, which was mediated by the activation of MAPK‐ERK1/2 and NF‐κB. Both intracellular signaling pathways activated by α2M* were effectively blocked by calphostin‐C, suggesting involvement of PKC. In addition, we demonstrate that α2M* produced extracellular calcium influx via LRP1. However, when the intracellular calcium mobilization was inhibited by BAPTA‐AM, the α2M*‐induced MAPK‐ER1/2 activation was fully blocked in both macrophage cell lines. Finally, using specific pharmacological inhibitors for PKC, Mek1, and NF‐κB, it was shown that the α2M*‐induced MMP‐9 protein secretion was inhibited, indicating that the MMP production promoted by the α2M*/LRP1 interaction required the activation of both signaling pathways. These findings may prove useful in the understanding of the macrophage LRP1 role in the vascular wall during atherogenic plaque progression. J. Cell. Biochem. 111: 607–617, 2010. © 2010 Wiley‐Liss, Inc.
Cancer hallmarks in induced pluripotent cells: New insights
Authors: Malchenko Sergey , Galat Vasiliy , Seftor Elisabeth A. , Vanin Elio F. , Costa Fabricio F. , Seftor Richard E.B. , Soares Marcelo B. , Hendrix Mary J.C. 
Published: June 2010

AbstractStudies are beginning to emerge that demonstrate intriguing differences between human‐induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs). Here, we investigated the expression of key members of the Nodal embryonic signaling pathway, critical to the maintenance of pluripotency in hESCs. Western blot and real‐time RT‐PCR analyses reveal slightly lower levels of Nodal (a TGF‐β family member) and Cripto‐1 (Nodal's co‐receptor) and a dramatic decrease in Lefty (Nodal's inhibitor and TGF‐β family member) in hiPSCs compared with hESCs. The noteworthy drop in hiPSC's Lefty expression correlated with an increase in the methylation of Lefty B CpG island. Based on these findings, we addressed a more fundamental question related to the consequences of epigenetically reprogramming hiPSCs, especially with respect to maintaining a stable ESC phenotype. A global comparative analysis of 365 microRNAs (miRs) in two hiPSC versus four hESC lines ultimately identified 10 highly expressed miRs in hiPCSs with >10‐fold difference, which have been shown to be cancer related. These data demonstrate cancer hallmarks expressed by hiPSCs, which will require further assessment for their impact on future therapies. J. Cell. Physiol. 225: 390–393, 2010. © 2010 Wiley‐Liss, Inc.
Synthetic strategies in the construction of chromones
Authors: Li Nian‐Guang , Shi Zhi‐Hao , Tang Yu‐Ping , Ma Hong‐Yue , Yang Jian‐Ping , Li Bao‐Quan , Wang Zhen‐Jiang , Song Shu‐Lin , Duan Jin‐Ao 
Published: June 2010

Abstract
magnified image
Because of important biological applications of chromones, some synthetic strategies leading to more complex derivatives have been widely explored in the past years. Thus, the purpose of this review is to report some recent improvements of the classical synthetic methods and of some nonclassical methods to obtain simple oxygenated chromones. The strategies for synthesis of heterocycle analogs containing phosphorus, nitrogen, and sulfur are also summarized. J. Heterocyclic Chem., (2010).
Disability measures as an indicator of poverty: A case study from Viet Nam
Authors: Palmer Michael G. , Thuy Nguyen Thi Minh , Quyen Quach Thi Ngoc , Duy Dang Sy , Van Huynh Hoang , Berry Helen L. 
Published: June 2010

AbstractThis paper examines the relationship between disability and poverty at a health‐demographic surveillance site in Viet Nam using alternative measures of disability severity. Analysis of the site population (n = 65 400) is combined with interviews of 27 households containing members with disabilities. Results show that disability severity is positively associated with poverty. Results support recent efforts of the Vietnamese government to extend programmes of social protection for households containing members with severe disabilities. However, a higher level of disability targeting is required, both in terms of eligibility and of benefit levels. Copyright © 2010 John Wiley & Sons, Ltd.