bluuebunny/crossref_metadata_2025_split huggingface dataset:
NF-κB Activation, Dependent on Acetylation/Deacetylation, Contributes to HIF-1 Activity and Migration of Bone Metastatic Breast Carcinoma Cells
Authors: Bendinelli Paola , Matteucci Emanuela , Maroni Paola , Desiderio Maria Alfonsina 
Published: August 2009

Abstract
Here, we show that NF-κB-HIF-1 interaction contributed to breast cancer metastatic capacity by means of an incomplete epithelial/mesenchymal transition and influencing migration, as shown in 1833 (human) and 4T1 (mouse) metastatic cells after different stimuli. The 1833 and the transforming growth factor-β1–exposed 4T1 cells showed both epithelial (E-cadherins) and mesenchymal (N-cadherins and vimentin) markers, and common mechanisms contributed to the retention of certain epithelial characteristics and the control of migration. The complex NF-κB-HIF-1 reciprocal regulation and the enhanced c-Jun expression played a functional role in exacerbating the invasiveness of 1833 cells after p50/p65 transfection and of 4T1 cells exposed to transforming growth factor-β1. Twist expression seemed to exert a permissive role also regulating epithelial/mesenchymal transition markers. After c-Src wild-type (Srcwt) transfection, c-Src-signal transducer overexpression in 1833 cells increased HIF-1 transactivating activity and invasiveness, and changed E-cadherin/N-cadherin ratio versus mesenchymal phenotype. The transcription factor pattern and the motile phenotype of metastatic 1833 cells were influenced by p65-lysine acetylation and HDAC-dependent epigenetic mechanisms, which positively regulated basal NF-κB and HIF-1 activities. However, HDAC3 acted as a corepressor of NF-κB activity in parental MDA-MB231 cells, thus explaining many differences from the derived 1833 clone, including reduced HIF-1α and c-Jun expression. Invasiveness was differently affected by HDAC knockdown in 1833 and MDA-MB231 cells. We suggest that acetylation/deacetylation are critical in establishing the bone-metastatic gene signature of 1833 cells by regulating the activity of NF-κB and HIF-1, and further clarify the epigenetic control of transcription factor network in the motile phenotype of 1833 cells. (Mol Cancer Res 2009;7(8):1328–41)
Smad3 Is a Key Nonredundant Mediator of Transforming Growth Factor β Signaling in Nme Mouse Mammary Epithelial Cells
Authors: Dzwonek Joanna , Preobrazhenska Olena , Cazzola Silvia , Conidi Andrea , Schellens Ann , van Dinther Maarten , Stubbs Andrew , Klippel Anke , Huylebroeck Danny , ten Dijke Peter , Verschueren Kristin 
Published: August 2009

Abstract
Smad2 and Smad3 are intracellular mediators of transforming growth factor β (TGFβ) signaling that share various biochemical properties, but data emerging from functional analyses in several cell types indicate that these two Smad proteins may convey distinct cellular responses. Therefore, we have investigated the individual roles of Smad2 and Smad3 in mediating the cytostatic and proapoptotic effects of TGFβ as well as their function in epithelial-to-mesenchymal transition. For this purpose, we transiently depleted mouse mammary epithelial cells (Nme) of Smad2 and/or Smad3 mainly by a strategy relying on RNaseH-induced degradation of mRNA. The effect of such depletion on hallmark events of TGFβ-driven epithelial-to-mesenchymal transition was analyzed, including dissolution of epithelial junctions, formation of stress fibers and focal adhesions, activation of metalloproteinases, and transcriptional regulation of acknowledged target genes. Furthermore, we investigated the effect of Smad2 and Smad3 knockdown on the TGFβ-regulated transcriptome by microarray analysis. Our results identify Smad3 as a key factor to trigger TGFβ-regulated events and ascribe tumor suppressor as well as oncogenic activities to this protein. (Mol Cancer Res 2009;7(8):1342–53)
The Links between Transcription, β-catenin/JNK Signaling, and Carcinogenesis
Authors: Saadeddin Anas , Babaei-Jadidi Roya , Spencer-Dene Bradley , Nateri Abdolrahman Shams 
Published: August 2009

Abstract
Interactions between transcription and signaling are fundamentally important for understanding both the structure and function of genetic pathways and their role in diseases such as cancer. The finding that β-catenin/TCF4 and JNK/c-Jun cooperate has important implications in carcinogenesis. Previously, we found that binding of c-Jun and β-catenin/TCF4 to the c-jun promoter is dependent upon JNK activity, thus one role for this complex is to contribute to the repression and/or activation of genes that may mediate cell maintenance, proliferation, differentiation, and death, whereas deregulation of these signals may contribute to carcinogenesis. Here we address the functional links reported between activated β-catenin/JNK signaling pathways, their component genes, and their common targets, and discuss how alterations in the properties of these genes lead to the development of cancer. (Mol Cancer Res 2009;7(8):1189–96)
Roles of MKK1/2-ERK1/2 and Phosphoinositide 3-Kinase–AKT Signaling Pathways in Erlotinib-Induced Rad51 Suppression and Cytotoxicity in Human Non–Small Cell Lung Cancer Cells
Authors: Ko Jen-Chung , Ciou Shih-Ci , Jhan Jhih-Yuan , Cheng Chao-Min , Su Ying-Jhen , Chuang Show-Mei , Lin Szu-Ting , Chang Chia-Che , Lin Yun-Wei 
Published: August 2009

Abstract
Erlotinib (Tarceva) is a selective epidermal growth factor receptor tyrosine kinase inhibitor in the treatment of human non–small cell lung cancer (NSCLC). In this study, we investigated the roles of ERK1/2 and AKT signaling pathways in regulating Rad51 expression and cytotoxic effects in different NSCLC cell lines treated with erlotinib. Erlotinib decreased cellular levels of phosphorylated ERK1/2, phosphorylated AKT, Rad51 protein, and mRNA in erlotinib-sensitive H1650, A549, and H1869 cells, leading to cell death via apoptosis, but these results were not seen in erlotinib-resistant H520 and H1703 cells. Erlotinib decreased Rad51 protein levels by enhancing Rad51 mRNA and protein instability. Enforced expression of constitutively active MKK1 or AKT vectors could restore Rad51 protein levels, which were inhibited by erlotinib, and decrease erlotinib-induced cytotoxicity. Knocking down endogenous Rad51 expression by si-Rad51 RNA transfection significantly enhanced erlotinib-induced cytotoxicity. In contrast, overexpression of Rad51 by transfection with Rad51 vector could protect the cells from cytotoxic effects induced by erlotinib. Blocking the activations of ERK1/2 and AKT by MKK1/2 inhibitor (U0126) and phosphoinositide 3-kinase inhibitor (wortmannin) suppressed the expression of Rad51 and enhanced the erlotinib-induced cell death in erlotinib-resistant cells. In conclusion, suppression of Rad51 may be a novel therapeutic modality in overcoming drug resistance of erlotinib in NSCLC. (Mol Cancer Res 2009;7(8):1378–89)
Differential Influence of Normal and Cancer-Associated Fibroblasts on the Growth of Human Epithelial Cells in an In vitro Cocultivation Model of Prostate Cancer
Authors: Paland Nicole , Kamer Iris , Kogan-Sakin Ira , Madar Shalom , Goldfinger Naomi , Rotter Varda 
Published: August 2009

Abstract
The prostate is composed of a number of different cell populations. The interaction between them is crucial for the development and proper function of the prostate. However, the effect of the molecular cross talk between these cells in the course of carcinogenesis is still unclear. Employing an approach wherein immortalized epithelial cells and immortalized human fibroblasts were cocultured, we show that normal associated fibroblasts (NAF) and cancer-associated fibroblasts (CAF) differentially influenced the growth and proliferation of immortalized human prostate epithelial cells. Whereas NAFs inhibited the growth of immortalized epithelial cells but promoted the growth of metastatic PC-3 cells, CAFs promoted the growth of immortalized epithelial cells but not of PC-3. Cytokine arrays revealed that NAFs secreted higher levels of tumor necrosis factor-α compared with CAFs whereas CAFs secreted higher levels of interleukin-6 (IL-6) compared with NAFs. The growth-inhibiting effects of NAFs were counteracted by the addition of IL-6, and the growth-promoting effects exerted by the CAFs were counteracted by tumor necrosis factor-α. Furthermore, CAFs induced the migration of endothelial cells in an IL-6–dependent manner. Here, we show that normal fibroblast cells have a protective function at very early stages of carcinogenesis by preventing immortalized epithelial cells from proliferating and forming new blood vessels whereas CAFs aid immortalized epithelial cells to further develop. (Mol Cancer Res 2009;7(8):1212–23)
Functional Role of Cell Surface CUB Domain-Containing Protein 1 in Tumor Cell Dissemination
Authors: Deryugina Elena I. , Conn Erin M. , Wortmann Andreas , Partridge Juneth J. , Kupriyanova Tatyana A. , Ardi Veronica C. , Hooper John D. , Quigley James P. 
Published: August 2009

Abstract
The function of CUB domain-containing protein 1 (CDCP1), a recently described transmembrane protein expressed on the surface of hematopoietic stem cells and normal and malignant cells of different tissue origin, is not well defined. The contribution of CDCP1 to tumor metastasis was analyzed by using HeLa carcinoma cells overexpressing CDCP1 (HeLa-CDCP1) and a high-disseminating variant of prostate carcinoma PC-3 naturally expressing high levels of CDCP1 (PC3-hi/diss). CDCP1 expression rendered HeLa cells more aggressive in experimental metastasis in immunodeficient mice. Metastatic colonization by HeLa-CDCP1 was effectively inhibited with subtractive immunization-generated, CDCP1-specific monoclonal antibody (mAb) 41-2, suggesting that CDCP1 facilitates relatively late stages of the metastatic cascade. In the chick embryo model, time- and dose-dependent inhibition of HeLa-CDCP1 colonization by mAb 41-2 was analyzed quantitatively to determine when and where CDCP1 functions during metastasis. Quantitative PCR and immunohistochemical analyses indicated that CDCP1 facilitated tumor cell survival soon after vascular arrest. Live cell imaging showed that the function-blocking mechanism of mAb 41-2 involved enhancement of tumor cell apoptosis, confirmed by attenuation of mAb 41-2–mediated effects with the caspase inhibitor z-VAD-fmk. Under proapoptotic conditions in vitro, CDCP1 expression conferred HeLa-CDCP1 cells with resistance to doxorubicin-induced apoptosis, whereas ligation of CDCP1 with mAb 41-2 caused additional enhancement of the apoptotic response. The functional role of naturally expressed CDCP1 was shown by mAb 41-2–mediated inhibition of both experimental and spontaneous metastasis of PC3-hi/diss. These findings confirm that CDCP1 functions as an antiapoptotic molecule and indicate that during metastasis CDCP1 facilitates tumor cell survival likely during or soon after extravasation. (Mol Cancer Res 2009;7(8):1197–211)
Clinical errors, nursing shortage and moral distress: The situation in Jordan
Authors: Mrayyan Majd T , Hamaideh Shaher H 
Published: August 2009

Abstract In the current healthcare arena, clinical errors are receiving much attention. Unintentionally, nurses commit errors, which require guiding ethical principles. This replicated study aimed to assess Jordanian Registered Nurses’ (RNs) perceptions of clinical errors they had committed over the past year: assess nurses’ perceptions of clinical errors committed by other nurses’ detect if these errors were related to the nursing shortage and assess whether or not nurses felt any moral distress. The studied phenomena were compared across different hospitals as well as in various units and wards. A survey was used to collect data from 420 nurses from 13 hospitals. A considerable percentage of RNs reported that they omitted to give medication/treatment or gave medication/treatment at the wrong time, and also indicated that other nurses gave incorrect medication or incorrectly administered treatments; practice issues which were related to the nursing shortage and causing moral distress. RNs perceived that clinical errors/untoward clinical incidents that they and other nurses experienced occurred largely because of the nursing shortage and resulted in moral distress. Moreover, a considerable percentage of RNs perceived that other nurses made clinical errors and/or experienced untoward clinical incidents related to the nursing shortage more frequently than the RNs themselves. Across different types of hospitals, nurses were not different in regard to clinical errors and their treatments, and the resultant moral distress. Nurses in units were slightly higher than nurses in wards in reporting clinical errors, treating them when they occurred, relating these errors to the nursing shortage, and thus were experiencing more moral distress. Aggravated by the nursing shortage, moral distress that occurs as a result of clinical errors is increasing, thus nurse managers should assess the contributing factors of moral distress and find ways to eliminate them.
Differences of hospitals’ organisational climates and nurses’ intent to stay: Nurses’ perspectives
Authors: Mrayyan Majd T 
Published: August 2009

Abstract This research studied the differences of hospitals’ organisational climates and nurses’ intent to stay at different types of Jordanian hospitals and investigated the relationship between the two concepts, from the point views of nurses. In 2005, using convenience sampling technique, a survey was used to collect the data. A total of 361 nurses were recruited; 190 nurses from governmental hospitals, 107 nurses from teaching hospitals and 64 nurses from private hospitals. Comparisons were performed using the total scores and the individual items of scales. Farley’s Nursing Practice Environment Scale (NPES) was used to assess the organisational climates (Farly, MJ, Nyberg, J (1990) Nurs Health Care11: 532–535). McCain’s Behavioral Commitment Scale (1990) was used to measure nurses’ intent to stay (McCloskey, JC (1990) Image J Nurs Sch22: 140–143). Nurses ‘somewhat disagree’ about the organisational climates of their hospitals. Quality of care and professionalism were the most important variables that influence hospitals’ organisational climates. There were some significant differences between nurses at different types of hospitals in their perceptions about hospitals’ organisational climates. Nurses were neutral in reporting their intent to stay; but there were no statistically significant differences. Although, nurses plan to stay at their jobs for at least 2–3 years and as long as possible, some nurse reported that they will not stay at their jobs to the end of their careers. Nurse administrators have to create supportive organisational climates that would encourage nurses to stay at their jobs to the end of their careers. This would influence positively the quality of patient care and nurses’ professionalism. These outcomes could be achieved if nurse administrators use supportive leadership styles in organisations that are adaptive to change and professionals’ needs.
A thousand words paint a picture: The use of storyline in grounded theory research
Authors: Birks Melanie , Mills Jane , Francis Karen , Chapman Ysanne 
Published: August 2009

Abstract This paper explores the use of storyline in grounded theory research and potentially other research methodologies that seek to explain phenomena. Storyline as a research strategy has had limited discussion in the literature. Although stories have been used as both a source of data and a means of reporting research findings, the use of storyline is underutilised and undeveloped as a method of constructing and conveying grounded theory. Construction of a theory that is grounded in the data and not influenced by external concepts is possible through the use of storyline. In presenting grounded theory in the form of a storyline, the nurse researcher is able to explain and describe the theoretical contribution in the context of nursing knowledge. Theoretical precedence, variation, limited gaps, the use of evidence and appropriate style are characteristics of an effective storyline. As both a means and an end in itself, storyline enhances the development, presentation and comprehension of the outcomes of grounded theory research in nursing.
Caring for persons with Parkinson’s disease in care homes: Perceptions of residents and their close relatives, and an associated review of residents’ care plans
Authors: Armitage Gerry , Adams Jenny , Newell Robert , Coates David , Ziegler Lucy , Hodgson Ian 
Published: August 2009

Abstract Through qualitative in-depth interviews, we collected the views of persons with Parkinson’s disease (pwPD) and their close relatives in care homes to establish their collective views of the effectiveness of care. We also reviewed the corresponding care plans. Drawing on these two forms of data collection, we compared similarities and differences between the qualitative interview data and the care plan analysis to elaborate on the experience of residential care for pwPD. Close relatives of care home residents can be a fruitful source of information for care home staff, throughout the care planning process, especially in relation to the specific needs of a pwPD. Although health and social policy advocate active collaboration between people with long-term conditions, their families, and their formal carers, there is limited evidence of such collaboration in the data examined here. There is an apparent shortfall in the knowledge and understanding of PD among care home staff. There are important pragmatic (e.g. drug administration) as well as psycho-social reasons for flexibility in routine care provision to meet the dynamic needs of pwPD. The findings here support the need for further, larger scale research into the quality of care for pwPD who are care home residents.
Comparative analysis of NLN NCLEX-RN readiness exam performance: BSN versus ADN
Authors: Simon Elizabeth , Augustus Lois 
Published: August 2009

Abstract Nursing schools are committed to improving the passing rate of the National Council Licensure Examination for Registered Nurses (NCLEX-RN) and to remain above acceptable levels. Therefore, the National League for Nursing (NLN) readiness exam taken before graduation can be used as a diagnostic test. The NLN scores are used to investigate which clinical course grade has the highest correlation with the readiness exam and ultimately with the NCLEX. With that knowledge, educators could strengthen particular courses in order to ultimately enhance a higher NCLEX-RN passing rate. To investigate the relationship among nursing clinical course grades, foundational science courses, and NCLEX-RN readiness exam scores, the initial study in 2004 on BSN performance was compared to a follow-up study on ADN students in 2007 in another college within the same university. Stepwise regression and Pearson moment correlation analysed the data. The first nursing course, adult health nursing and maternal child health nursing, truly appears foundational for the NCLEX readiness exam. These results were consistent in both BSN and ADN programs. As adult learning theory suggests, the first nursing course may provide an overview into which the facts and skills of later courses are integrated.
The regulatory T-cell response during acute retroviral infection is locally defined and controls the magnitude and duration of the virus-specific cytotoxic T-cell response
Authors: Zelinskyy Gennadiy , Dietze Kirsten K. , Hüsecken Yvonne P. , Schimmer Simone , Nair Savita , Werner Tanja , Gibbert Kathrin , Kershaw Olivia , Gruber Achim D. , Sparwasser Tim , Dittmer Ulf 
Published: August 2009

AbstractCytotoxic CD8+ T cells control acute viremia in many viral infections. However, most viruses that establish chronic infections evade destruction by CD8+ T cells, and regulatory T cells (Treg) are thought to be involved in this immune evasion. We have infected transgenic mice, in which Treg can be selectively depleted, with Friend retrovirus (FV) to investigate the influence of Treg on pathogen-specific CD8+ T-cell responses in vivo. We observed that Treg expansion during acute infection was locally defined to organs with high viral loads and massive activation of virus-specific effector CD8+ T cells. Experimental ablation of Treg resulted in a significant increase of peak cytotoxic CD8+ T-cell responses against FV. In addition, it prevented the development of functional exhaustion of CD8+ T cells and significantly reduced FV loads in lymphatic organs. Surprisingly, despite the massive virus-specific CD8+ T-cell response after temporary Treg depletion, no evidence of immunopathology was found. These results demonstrate the important role of Treg in controlling acute retrovirus-specific CD8+ T-cell responses, and suggest that temporary manipulation of Treg might be a possible therapeutic approach in chronic infectious diseases.
Evaluation of bone marrow reticulin formation in chronic immune thrombocytopenia patients treated with romiplostim
Authors: Kuter David J. , Mufti Ghulam J. , Bain Barbara J. , Hasserjian Robert P. , Davis Wende , Rutstein Mark 
Published: August 2009

AbstractRomiplostim is a thrombopoietin receptor agonist that increases platelet counts in patients with chronic immune thrombocytopenia (ITP). Thrombopoietin receptor agonists are reported to increase the risk for reticulin fiber deposition within bone marrow. This report describes bone marrow findings from romiplostim-treated rats, a retrospective analysis of reticulin observed in romiplostim ITP clinical trials, and a prospective clinical study of the effects of romiplostim on bone marrow morphology. In rats, romiplostim produced a dose-dependent increase in bone marrow fibrosis that resolved after treatment withdrawal. Of 271 ITP patients in romiplostim clinical trials, 10 were reported to have reticulin deposition; reticulin grade was increased in 4 of 5 patients with both pretreatment and on-treatment bone marrow results. Reticulin grade often decreased soon after romiplostim discontinuation. In the prospective study, reticulin grade during romiplostim treatment remained within the normal range for all patients and was increased in only 1 of 6 patients with pretreatment and on-treatment bone marrow results. This report suggests that romiplostim produces reversible, dose-dependent bone marrow changes in rats and produces modest increases in bone marrow reticulin in some ITP patients that decrease when therapy is discontinued. These studies were registered at www.clinicaltrials.gov as #NCT00102323, #NCT00102336, #NCT00861224, and #NCT00116688.