bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increasing prevalence of comorbidity in patients with colorectal cancer in the South of the Netherlands 1995–2010
Authors: van Leersum N.J. , Janssen‐Heijnen M.L.G. , Wouters M.W.J.M. , Rutten H.J.T. , Coebergh J.W. , Tollenaar R.A.E.M. , Lemmens V.E.P.P. 
Published: September 2012

AbstractComorbidity has large impact on colorectal cancer (CRC) treatment and outcomes and may increase as the population ages. We aimed to evaluate the prevalence and time trends of comorbid diseases in patients with CRC from 1995 to 2010. The Eindhoven Cancer Registry registers comorbidity in all patients with primary CRC in the South of the Netherlands. We analyzed the prevalence of serious comorbid diseases in four time frames from 1995 to 2010. Thereby, we addressed its association with age, gender and socio‐economic status (SES). The prevalence of comorbidity was registered in 27,339 patients with primary CRC. During the study period, the prevalence of comorbidity increased from 47% to 62%, multimorbidity increased from 20% to 37%. Hypertension and cardiovascular diseases were most prevalent and increased largely over time (respectively 16–29% and 12–24%). Pulmonary diseases increased in women, but remained stable in men. Average age at diagnosis increased from 68.3 to 69.5 years (p = 0.004). A low SES and male gender were associated with a higher risk of comorbidity (not changing over time). This study indicates that comorbidity among patients with CRC is common, especially in males and patients with a low SES. The prevalence of comorbidity increased from 1995 to 2010, in particular in presumably nutritional diseases. Ageing, increased life expectancy and life style changes may contribute to more comorbid diseases. Also, improved awareness among health care providers on the importance of comorbidity may have resulted in better registration. The increasing burden of comorbidity in patients with CRC emphasizes the need for more focus on individualized medicine.
Targeted imaging of breast tumor progression and therapeutic response in a human uMUC‐1 expressing transgenic mouse model
Authors: Ghosh Subrata K. , Uchida Masashi , Yoo Byunghee , Ross Alana W. , Gendler Sandra J. , Gong Jianlin , Moore Anna , Medarova Zdravka 
Published: September 2012

AbstractThe ability to monitor breast cancer initiation and progression on the molecular level would provide an effective tool for early diagnosis and therapy. In the present study, we focused on the underglycosylated MUC‐1 tumor antigen (uMUC‐1), which is directly linked to tumor progression from pre‐malignancy to advanced malignancy in breast cancer and has been identified as the independent predictor of local recurrence and tumor response to chemotherapy. We investigated whether changes in uMUC‐1 expression during tumor development and therapeutic intervention could be monitored non‐invasively using molecular imaging approach with the uMUC‐1‐specific contrast agent (MN‐EPPT) detectable by magnetic resonance and fluorescence optical imaging. This was done in mice that express human uMUC‐1 tumor antigen (MMT mice) and develop spontaneous mammary carcinoma in a stage‐wise fashion. After the injection of MN‐EPPT there was a significant reduction in average T2 relaxation times of the mammary fat pad between pre‐malignancy and cancer. In addition, T2 relaxation times were already altered at pre‐malignant state in these mice compared to non‐tumor bearing mice. This indicated that targeting uMUC‐1 could be useful for detecting pre‐malignant transformation in the mammary fat pad. We also probed changes in uMUC‐1 expression with MN‐EPPT during therapy with doxorubicin (Dox). We observed that tumor delta‐T2s were significantly reduced by treatment with Dox indicating lower accumulation of MN‐EPPT. This correlated with a lower level of MUC‐1 expression in the Dox‐treated tumors, as confirmed by immunoblotting. Our study could provide a very sensitive molecular imaging approach for monitoring tumor progression and therapeutic response.
The biological regulation of ABCE1
Authors: Tian Ye , Han Xu , Tian Da‐li 
Published: September 2012

AbstractATP binding cassette E1 (ABCE1) protein, also named RLI or HP68, is one member of ATP binding cassette superfamily. By forming a heterodimer with RNase L, ABCE1 protein inhibits the IFN‐depended 2‐5A/RNase L system and regulates a broad range of biological functions including viral infection, tumor cell proliferation, and antiapoptosis. As a highly conserved protein, recent studies have mainly focused that ABCE1 protein is involving in the fields of HIV virus capsids assembly and important roles in translation. Our manuscript will review the studies which revealed the biological regulation of ABCE1. © 2012 IUBMB IUBMB Life, 64(10): 795–800, 2012
Copolymer cell/scaffold constructs for bone tissue engineering: Co‐culture of low ratios of human endothelial and osteoblast‐like cells in a dynamic culture system
Authors: Xing Zhe , Xue Ying , Finne‐Wistrand Anna , Yang Zhuang‐Qun , Mustafa Kamal 
Published: September 2012

AbstractThe aim of this study was to compare the effect of different ratios of human umbilical vein endothelial cells (HUVECs) on osteogenic activity of human osteoblast‐like cells (HOB) and capillary‐like structure (CLS), seeded into copolymer scaffolds in a dynamic culture system. HOB and HUVEC were co‐cultured into poly(L‐lactide)‐co‐(1,5‐dioxepan‐2‐one) [poly(LLA‐co‐DXO)] scaffolds at ratios of 5:1 (5:1 group) and 2:1 (2:1 group). Samples were collected after 5, 15, and 25 days. Cross‐sections were processed and the CLS from HUVEC was disclosed in both groups. Cell viability was determined by dsDNA assay. Cells seeded at the ratio of 5:1 had good viability. Total RNA was isolated and the reverse transcription reaction was performed. The influences on the expression of several osteogenic genes were various with regarding to different ratios of HUVEC demonstrated by the PCR array. The RT‐PCR results was in consistent with the PCR array results that several osteogenesis related genes had higher expression in the 5:1 group than in the 2:1 group, especially at day 25, such as alkaline phosphatase, insulin‐like growth factor 1 (IGF1), and so forth. ELISA showed that the production of IGF1 after 25 days of incubation were higher in cells co‐cultured at the 5:1 ratio than at the 2:1 ratio. The results show that under dynamic culture conditions, co‐culture of HOB with a low ratio of HUVEC in copolymer scaffolds results in CLS formation and significantly influenced the expression of osteogenic markers. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Periosteum, bone's “smart” bounding membrane, exhibits direction-dependent permeability
Authors: Evans Sarah F , Parent Jonathan B , Lasko Colin E , Zhen Xiaowen , Knothe Ulf R , Lemaire Thibault , Knothe Tate Melissa L 
Published: September 2012

Abstract
The periosteum serves as bone's bounding membrane, exhibits hallmarks of semipermeable epithelial barrier membranes, and contains mechanically sensitive progenitor cells capable of generating bone. The current paucity of data regarding the periosteum's permeability and bidirectional transport properties provided the impetus for the current study. In ovine femur and tibia samples, the periosteum's hydraulic permeability coefficient, k, was calculated using Darcy's Law and a custom-designed permeability tester to apply controlled, volumetric flow of phosphate-buffered saline through periosteum samples. Based on these data, ovine periosteum demonstrates mechanically responsive and directionally dependent (anisotropic) permeability properties. At baseline flow rates comparable to interstitial fluid flow (0.5 µL/s), permeability is low and does not exhibit anisotropy. In contrast, at high flow rates comparable to those prevailing during traumatic injury, femoral periosteum exhibits an order of magnitude higher permeability compared to baseline flow rates. In addition, at high flow rates permeability exhibits significant directional dependence, with permeability higher in the bone to muscle direction than vice versa. Furthermore, compared to periosteum in which the intrinsic tension (pre-stress) is maintained, free relaxation of the tibial periosteum after resection significantly increases its permeability in both flow directions. Hence, the structure and mechanical stress state of periosteum influences its role as bone's bounding membrane. During periods of homeostasis, periosteum may serve as a barrier membrane on the outer surface of bone, allowing for equal albeit low quiescent molecular communication between tissue compartments including bone and muscle. In contrast, increases in pressure and baseline flow rates within the periosteum resulting from injury, trauma, and/or disease may result in a significant increase in periosteum permeability and consequently in increased molecular communication between tissue compartments. Elucidation of the periosteum's permeability properties is key to understanding periosteal mechanobiology in bone health and healing, as well as to elucidate periosteum structure and function as a smart biomaterial that allows bidirectional and mechanically responsive fluid transport. © 2013 American Society for Bone and Mineral Research.
Role of COUP‐TFI during retinoic acid‐induced differentiation of P19 cells to endodermal cells
Authors: Pickens Brandy S. , Teets Bryan W. , Soprano Kenneth J. , Soprano Dianne Robert 
Published: September 2012

AbstractRetinoic acid (RA) is a positive regulator of P19 cell differentiation. Silencing of pre‐B cell leukemia transcription factors (PBXs) expression in P19 cells (AS cells) results in a failure of these cells to differentiate to endodermal cells upon RA treatment. Chicken Ovalbumin Upstream Promoter Transcription Factor I (COUP‐TFI) is an orphan member of the steroid‐thyroid hormone superfamily. RA treatment of wild type P19 cells results in a dramatic increase in the expression of COUP‐TFI; however, COUP‐TFI mRNA levels fail to be elevated upon RA treatment of AS cells indicating that PBX expression is required for elevation in COUP‐TFI expression. To study the role of COUP‐TFI during RA‐dependent differentiation of P19 cells, AS cells that inducibly express various levels of COUP‐TFI were prepared. Exogenous expression of COUP‐TFI in AS cells, in a dose‐dependent fashion, leads to growth inhibition, modest cell cycle disruption, and early apoptosis. Furthermore, AS cells can overcome the blockage in RA‐dependent differentiation to endodermal cells when either pharmacological levels of COUP‐TFI are expressed or a combination of both the expression of physiological levels of COUP‐TFI and RA treatment. Additionally, the mRNA level of several pluripotency associated genes including OCT‐4, DAX‐1, and SF‐1 in the COUP‐TFI expressing AS cells are reduced. Moreover, analysis of the expression of primary RA response genes indicates that COUP‐TFI is involved in the regulatory modulation of the expression of at least two genes, CYP26A1 and HoxA1. These studies demonstrate that COUP‐TFI functions as a physiologically relevant regulator during RA‐mediated endodermal differentiation of P19 cells. J. Cell. Physiol. 228: 791–800, 2013. © 2012 Wiley Periodicals, Inc.
p53 regulates epithelial–mesenchymal transition induced by transforming growth factor β
Authors: Termén Stefan , Tan E‐Jean , Heldin Carl‐Henrik , Moustakas Aristidis 
Published: September 2012

AbstractEpithelial plasticity characterizes embryonic development and diseases such as cancer. Epithelial–mesenchymal transition (EMT) is a reversible and guided process of plasticity whereby embryonic or adult epithelia acquire mesenchymal properties. Multiple signaling pathways control EMT, and the transforming growth factor β (TGFβ) pathway plays a central role as its inducer. Here, we analyzed the role of the tumor suppressor protein p53 in TGFβ‐induced EMT in a well‐established mammary epithelial cell model. We found that diploid NMuMG mammary cells bi‐allelically express a wild type and a missense mutant (R277C) form of p53. Global reduction of both forms of p53 led to an enhanced EMT response to TGFβ. Conversely, stabilization of wild type p53 using the compound nutlin had a negative impact on EMT. After silencing both p53 forms, rescue experiments using either wild type or R277C mutant p53 revealed that wild type p53 inhibited, whereas the R277C mutant did not significantly affect, the TGFβ‐driven EMT response. Under serum‐free culture conditions, silencing of total p53 levels led to higher numbers of mammospheres characterized by larger size. Rescue of the silenced endogenous p53 with R277C mutant p53, in contrast, suppressed both size and numbers of the mammospheres. This work proposes that wild type p53 controls the efficiency by which mammary epithelial cells undergo EMT in response to TGFβ. J. Cell. Physiol. 228: 801–813, 2013. © 2012 Wiley Periodicals, Inc.
Functional coupling of TRPC2 cation channels and the calcium‐activated anion channels in rat thyroid cells: Implications for iodide homeostasis
Authors: Viitanen Tero M. , Sukumaran Pramod , Löf Christoffer , Törnquist Kid 
Published: September 2012

AbstractThe initial step in a synthesis of thyroid hormones is the uptake of iodide from the circulation. Iodide (I−) is transported into thyroid cells via a Na+/I− symporter (NIS), which is electrogenic and thus sensitive to alterations in membrane potential (Vm). I− is then released to the lumen of thyroid follicles where the hormones are synthesised and stored. The mechanisms of I− release to follicle lumen are poorly characterised. Our whole‐cell voltage clamp recordings revealed the presence of a Ca2+ activated Cl− current (CaCC) in Fisher rat thyroid cell line 5 (FRTL‐5). Transcripts of anoctamin 1 (ANO1) and anoctamin 10 (ANO10), putative molecular constituents of CaCC, were detected. The anion channels underlying CaCC are highly permeable to I−. Both niflumic acid (NFA) and 2‐aminoethyl diphenylborinate (2‐APB), antagonists of CaCC and transient receptor potential channels, respectively, inhibited CaCC. Canonical transient receptor potential channel 2 (TRPC2) is the only TRPC member present in FRTL‐5 cells. The activation rate of CaCC was markedly slower in shTRPC2 knock‐down cells, indicating that Ca2+ entry via TRPC2 contributes to CaCC activation. The uptake of iodide was enhanced and the resting Vm was more depolarised in TRPC2 knock‐down cells. We suggest that the interplay between TRPC2 and ANO1 may have dual effects on iodide transport, modulating I− release via ANO channels and I− uptake via the Vm sensitive NIS. J. Cell. Physiol. 228: 814–823, 2013. © 2012 Wiley Periodicals, Inc.
Effects of acute exercise over heart proteome from monogenic obese (ob/ob) mice
Authors: Petriz Bernardo A. , Cunha Verusca N. , Villeth Gabriela R.C. , Mehta Ângela , Rocha Luiz A.O. , Silva Osmar N. , Almeida Jeeser A. , Morais Pamella K. , Simões Herbert G. , Franco Octávio L. 
Published: September 2012

AbstractExercise is recognized to prevent and attenuate several metabolic and cardiovascular disorders. Obesity is commonly related to cardiovascular diseases, frequently resulting in heart failure and death. To elucidate the effects of acute exercise in heart tissue from obese animals, 12‐week‐old C57BL6/J obese (ob/ob) and non‐obese (ob/OB) mice were submitted to a single bout of swimming and had their hearts analyzed by proteomic techniques. Mice were divided into three groups: control (ob/ob, n = 3; ob/OB, n = 3); a moderate intensity consisting of 20 min of swimming around 90% of Maximal Lactate Steady State (ob/ob, n = 3; ob/OB, n = 3), and a high intensity exercise performed as an incremental overload test (ob/ob, n = 3; ob/OB, n = 3). Obesity modulations were analyzed by comparing ob/ob and ob/OB control groups. Differential 2‐DE analysis revealed that single session of exercise was able to up‐regulate: myoglobin (ob/ob), aspartate aminotransferase (ob/OB) and zinc finger protein (ob/OB) and down‐regulate: nucleoside diphosphate kinase B (ob/OB), mitochondrial aconitase (ob/ob and ob/OB) and fatty acid binding protein (ob/ob). Zinc finger protein and α‐actin were up‐regulated by the effect of obesity on heart proteome. These data demonstrate the immediate response of metabolic and stress‐related proteins after exercise so as contractile protein by obesity modulation on heart proteome. J. Cell. Physiol. 228: 824–834, 2013. © 2012 Wiley Periodicals, Inc.
Mitochondrial‐targeted nitroxides disrupt mitochondrial architecture and inhibit expression of peroxiredoxin 3 and FOXM1 in malignant mesothelioma cells
Authors: Cunniff Brian , Benson Kira , Stumpff Jason , Newick Kheng , Held Paul , Taatjes Douglas , Joseph Joy , Kalyanaraman Balaraman , Heintz Nicholas H. 
Published: September 2012

AbstractMalignant mesothelioma (MM) is an intractable tumor of the peritoneal and pleural cavities primarily linked to exposure to asbestos. Recently, we described an interplay between mitochondrial‐derived oxidants and expression of FOXM1, a redox‐responsive transcription factor that has emerged as a promising therapeutic target in solid malignancies. Here we have investigated the effects of nitroxides targeted to mitochondria via triphenylphosphonium (TPP) moieties on mitochondrial oxidant production, expression of FOXM1 and peroxiredoxin 3 (PRX3), and cell viability in MM cells in culture. Both Mito‐carboxy‐proxyl (MCP) and Mito‐TEMPOL (MT) caused dose‐dependent increases in mitochondrial oxidant production that was accompanied by inhibition of expression of FOXM1 and PRX3 and loss of cell viability. At equivalent concentrations TPP, CP, and TEMPOL had no effect on these endpoints. Live cell ratiometric imaging with a redox‐responsive green fluorescent protein targeted to mitochondria (mito‐roGFP) showed that MCP and MT, but not CP, TEMPOL, or TPP, rapidly induced mitochondrial fragmentation and swelling, morphological transitions that were associated with diminished ATP levels and increased production of mitochondrial oxidants. Mdivi‐1, an inhibitor of mitochondrial fission, did not rescue mitochondria from fragmentation by MCP. Immunofluorescence microscopy experiments indicate a fraction of FOXM1 coexists in the cytoplasm with mitochondrial PRX3. Our results indicate that MCP and MT inhibit FOXM1 expression and MM tumor cell viability via perturbations in redox homeostasis caused by marked disruption of mitochondrial architecture, and suggest that both compounds, either alone or in combination with thiostrepton or other agents, may provide credible therapeutic options for the management of MM. J. Cell. Physiol. 228: 835–845, 2013. © 2012 Wiley Periodicals, Inc.
Why imatinib remains an exception of cancer research
Authors: Horne Steven D. , Stevens Joshua B. , Abdallah Batoul Y. , Liu Guo , Bremer Steven W. , Ye Christine J. , Heng Henry H.Q. 
Published: September 2012

AbstractThe archetype driving the drug targeting approach to cancer therapy is the success of imatinib against chronic phase chronic myeloid leukemia (CML‐CP). Molecular targeting success of this magnitude has yet to be repeated for most solid tumors. To answer why imatinib remains an exception of cancer research, we summarize key features and patterns of evolution that contrast CML‐CP from prostate cancer, an example of a solid tumor that also shares a signature fusion gene. Distinctive properties of CML‐CP include: a large cell population size that is not geographically constrained, a highly penetrant dominant oncogene that sweeps the entire cell population, subsequent progressive and ordered clonal genetic changes, and the effectiveness of molecular targeting within the chronic phase, which is comparable to the benign phase of solid tumors. CML‐CP progression resembles a clonal, stepwise model of evolution, whereas the pattern of solid tumor evolution is highly dynamic and stochastic. The distinguishing features and evolutionary pattern of CML‐CP support why the success of imatinib does not carry over to most solid tumors. Changing the focus of cancer research from a gene‐based view to a genome‐based theory will provide insight into solid tumor evolutionary dynamics. J. Cell. Physiol. 228: 665–670, 2013. © 2012 Wiley Periodicals, Inc.
EGFR through STAT3 modulates ΔN63α expression to sustain tumor‐initiating cell proliferation in squamous cell carcinomas
Authors: Ripamonti Francesca , Albano Luisa , Rossini Anna , Borrelli Serena , Fabris Sonia , Mantovani Roberto , Neri Antonino , Balsari Andrea , Magnifico Alessandra , Tagliabue Elda 
Published: September 2012

AbstractMany squamous cell carcinomas (SCCs) are characterized by high levels of EGFR and by overexpression of the ΔNp63α isoform. Here, we investigated the regulation of ΔNp63α expression upon EGFR activation and the role of the EGFR–ΔNp63α axis in proliferation of SCC tumor‐initiating cells (TICs). SCC cell lines A‐431, Cal‐27, and SCC‐25 treated with EGF showed a time‐dependent increase in ΔNp63α expression at the protein and mRNA levels, which was blocked by the tyrosine kinase inhibitor (TKI) Lapatinib. RNA interference experiments suggested the role of STAT3 in regulating ΔNp63α expression downstream of EGFR. Inactivation of EGFR by the monoclonal antibody Cetuximab and RNA interference against STAT3 or ΔNp63α impaired the TICs ability to grow under non‐differentiating conditions. Radiation treatment, which triggers EGFR activation, induced ΔNp63α accumulation without affecting TICs proliferation, whereas the combination Cetuximab plus radiation significantly reduced TICs growth under non‐differentiating conditions. Together, our findings provide evidence that ΔNp63α expression is regulated by EGFR activation through STAT3 and that the EGFR–ΔNp63α axis is crucial for proliferation of TICs present in SCCs. J. Cell. Physiol. 228: 871–878, 2013. © 2012 Wiley Periodicals, Inc.
HOX and TALE signatures specify human stromal stem cell populations from different sources
Authors: Picchi Jacopo , Trombi Luisa , Spugnesi Laura , Barachini Serena , Maroni Giorgia , Brodano Giovanni Barbanti , Boriani Stefano , Valtieri Mauro , Petrini Mario , Magli Maria Cristina 
Published: September 2012

AbstractHuman stromal stem cell populations reside in different tissues and anatomical sites, however a critical question related to their efficient use in regenerative medicine is whether they exhibit equivalent biological properties. Here, we compared cellular and molecular characteristics of stromal stem cells derived from the bone marrow, at different body sites (iliac crest, sternum, and vertebrae) and other tissues (dental pulp and colon). In particular, we investigated whether homeobox genes of the HOX and TALE subfamilies might provide suitable markers to identify distinct stromal cell populations, as HOX proteins control cell positional identity and, together with their co‐factors TALE, are involved in orchestrating differentiation of adult tissues. Our results show that stromal populations from different sources, although immunophenotypically similar, display distinct HOX and TALE signatures, as well as different growth and differentiation abilities. Stromal stem cells from different tissues are characterized by specific HOX profiles, differing in the number and type of active genes, as well as in their level of expression. Conversely, bone marrow‐derived cell populations can be essentially distinguished for the expression levels of specific HOX members, strongly suggesting that quantitative differences in HOX activity may be crucial. Taken together, our data indicate that the HOX and TALE profiles provide positional, embryological and hierarchical identity of human stromal stem cells. Furthermore, our data suggest that cell populations derived from different body sites may not represent equivalent cell sources for cell‐based therapeutical strategies for regeneration and repair of specific tissues. J. Cell. Physiol. 228: 879–889, 2013. © 2012 Wiley Periodicals, Inc.