bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-ordination of generalist care for patients towards the end of life: a literature review
Authors: Mason B L , Barclay S , Dale J , Daveson B , Donaldson A , Epiphaniou E , Harding R , Higginson I J , Munday D , Nanton V , Shipman C , Murray S A 
Published: May 2011

AbstractIntroduction and aimIncreased coordination and collaboration have been highlighted as improving the provision of health and social care for people at the end of life. We aimed to review the literature concerning coordination or collaboration of care to determine whether coordination and collaboration improves the quality of care delivered by generalists towards the end of life.MethodsSearches in PUBMED and ISI Web of Knowledge for the stems ‘coordinat-‘ or ‘collaborat-‘ in the context of the stem ‘palliat-‘ or the phrase ‘terminal care.’ Search of Web of Knowledge for the categories ‘generalist health care’ and ‘palliative.’ Search of PUBMED MeSH terms ‘palliative care admin and organisation’, ‘terminal care admin and organisation’ and ‘Cooperative Behavior.’ Electronic searches were supplemented by hand searches of leading palliative care journals (2008–2010).Results1672 articles initially identified as requiring further screening, and 55 eligible studies identified. Different approaches/terminology to enabling coordination and collaboration were identified including networks, integrated care pathways, partnerships, frameworks, programmes and ‘collaboratives’. Lack of coordination and/or collaboration was routinely identified as a barrier to good palliative care.ConclusionApproaches to enabling coordination and collaboration are evident in the literature but no metrics to measure coordination or collaboration were uncovered so it is impossible to determine whether a particular intervention increased coordination or collaboration. Therefore more research to determine whether collaboration and coordination improves quality of care is needed. Management or organisational theory as well as robust evaluation of models of co-ordination is indicated to guide current policy developments. This will require increased conceptual clarity regarding the terms collaboration and coordination in this context.
Development of guidelines for the management of cancer related fatigue
Authors: Eng S , Velikova G 
Published: May 2011

AbstractIntroductionCancer related fatigue (CRF) is a common symptom that is neither formally assessed not actively addressed. Despite a plethora of tools available for measuring fatigue, there is a lack of a clear pathway for its management.AimsTo develop guidelines for management of fatigue to be used together with a computerised touch screen system for patients to report fatigue.MethodA literature review was conducted on management of CRF. This was followed by a series of individual meetings with physiotherapists (3), dieticians (2) sleep physicians (2), sleep nurse (1), providers of complementary therapists (4) to ascertain referral criteria and types of local services available for cancer patients with fatigue. Informal meetings with SHOs (2), consultant oncologists (2) and nurses (11) helped ascertain current management strategies.ResultsThere is a paucity of knowledge surrounding the management of CRF, and a lack of awareness of available services. A local guideline was developed as anaide memoirefor medical oncologists and nurses. Information is presented in sections with assessment questions to determine the level of fatigue, prompts for biologic assessments and its corresponding management. A traffic light system is used to represent severity of fatigue, matching it with available services and information, contact details, referral criteria and structured advice on diet, exercise and sleep.ConclusionThe guidelines will be used as part of a resource package for training doctors and will be available in outpatient clinics.
Factors influencing exercise capacity in people with thoracic cancer
Authors: Maddocks M , England R , Manderson C , Wilcock A 
Published: May 2011

AbstractIntroduction and aimsPatients with thoracic cancer often complain of a reduced exercise capacity which can impede levels of independence and quality of life. Several factors may be responsible but there is little formal study in this group. We have explored how various physiological and psychological factors relate to performance in a test of exercise capacity.MethodsInspiratory muscle strength, peripheral muscle power, lung function and mastery over breathlessness were assessed using sniff nasal inspiratory pressure, leg extensor power, simple spirometry and the mastery domain of the Chronic Respiratory Disease Questionnaire respectively. Exercise capacity was assessed using the Incremental Shuttle walk Test (ISWT) during which patients wore a K4 b2 system allowing continuous measurement of heart rate, minute ventilation (VE) and oxygen uptake (VO2). Relationships between ISWT distance and independent factors were determined using Pearson's correlation coefficient and β regressions coefficients.Results41 patients (21 male, mean (SD) age 64 (8) years) took part. They walked a median (IQR) 320 (250–430) m and reached 76 (10)%, 48 (14)% and 77 (25)% of their predicted maximal heart rate, VE and VO2 respectively. Exercise capacity was significantly associated only with inspiratory muscle strength (r=0.42, p<0.01) and peripheral muscle power (r=0.39, p=0.01). These factors were also significant determinants of exercise capacity (β coefficients (95% CI) 1.77 (0.53 to 3.01) and 1.22 (0.31 to 2.14)).ConclusionsBoth inspiratory and peripheral muscle performance appear to influence exercise capacity in people with thoracic cancer. Interventions aimed at maintaining or slowing down the decline in exercise capacity should include components targeting muscular performance.
Resolving tensions: optimising the role of primary care in lung cancer follow-up care
Authors: Highet G , Murray S A , Campbell C , Kendall M , Rainey P , Neal R , Rose P , Anandan C , Amoakwa E , Weller D 
Published: May 2011

AbstractIntroductionThere is a little consensus on how to manage the supportive and palliative care needs of people with lung cancer once they have completed initial treatment. We aimed to gain insights into the perspectives of clinicians and service users as to how primary care could provide better care in collaboration with lung cancer specialists.MethodsWe conducted a qualitative study encompassing (a) telephone interviews (84) with healthcare professionals from four UK healthcare authorities, recruited through primary care research networks and other professional contacts and working in primary, secondary and palliative care, and (b) focus groups (4) with lung cancer patients and carers recruited through the Roy Castle Foundation. Interviews and focus groups were digitally recorded, transcribed and entered into NVivo for thematic analysis, initially from different perspectives and then synthesised across the whole data set.ResultsLung cancer care is currently ‘shared’ rather than ‘integrated’ across heath care sectors. Debates about follow-up care tend to make a distinction between clinical care (provided in hospital by specialists) and supportive care (provided in the community by generalists) and there are contested ideas about where best to follow-up lung cancer patients who are relatively ‘stable’. Psycho-social support, support for carers and communication between primary and secondary care were identified as potential areas for development.ConclusionLung cancer follow-up care is characterised by a range of tensions which must be resolved if primary care is to play an optimum role in providing follow-up care and support for lung cancer patients and their carers.
NONLINEAR FRACTURE SIGNAL ANALYSIS USING MULTIFRACTAL APPROACH COMBINED WITH WAVELETS
Authors: AOUIT D. AIT , OUAHABI A. 
Published: May 2011

Based on the continuous Wavelet Transform Modulus Maxima method (WTMM), a multifractal analysis was introduced to discriminate the irregular fracture signals of materials. This method provides an efficient numerical technique to characterize statistically the local regularity of fractures. The results obtained by this nonlinear analysis suggest that multifractal parameters such as the capacity dimension D0, the average singularity strength α0, the aperture of the left side (α0 - α min ) and the total width (α max - α min ) of the D(α) spectra allow a better fit for the characterization of the different fracture stages. Discriminating the three principal stages of the fracture namely the fracture initiation, the fracture propagation and the final rupture, provides a powerful diagnostic tool to identify the crack initiation site, and thus delineates the causes of the cracking of the material.
Contribution of Abcc10 (Mrp7) to In Vivo Paclitaxel Resistance as Assessed in Abcc10−/− Mice
Authors: Hopper-Borge Elizabeth A. , Churchill Timothy , Paulose Chelsy , Nicolas Emmanuelle , Jacobs Joely D. , Ngo Olivia , Kuang Yehong , Grinberg Alex , Westphal Heiner , Chen Zhe-Sheng , Klein-Szanto Andres J. , Belinsky Martin G. , Kruh Gary D. 
Published: May 2011

Abstract
Recently, we reported that the ATP-binding cassette transporter 10 (ABCC10), also known as multidrug resistance protein 7 (MRP7), is able to confer resistance to a variety of anticancer agents, including taxanes. However, the in vivo functions of the pump have not been determined to any extent. In this study, we generated and analyzed Abcc10−/− mice to investigate the ability of Abcc10 to function as an endogenous resistance factor. Mouse embryo fibroblasts derived from Abcc10−/− mice were hypersensitive to docetaxel, paclitaxel, vincristine, and cytarabine (Ara-C) and exhibited increased cellular drug accumulation, relative to wild-type controls. Abcc10−/− null mice treated with paclitaxel exhibited increased lethality associated with neutropenia and marked bone marrow toxicity. In addition, toxicity in spleen and thymus was evident. These findings indicate that Abcc10 is dispensable for health and viability and that it is an endogenous resistance factor for taxanes, other natural product agents, and nucleoside analogues. This is the first demonstration that an ATP-binding cassette transporter other than P-glycoprotein can affect in vivo tissue sensitivity toward taxanes. Cancer Res; 71(10); 3649–57. ©2011 AACR.
HDAC4-Regulated STAT1 Activation Mediates Platinum Resistance in Ovarian Cancer
Authors: Stronach Euan A. , Alfraidi Albandri , Rama Nona , Datler Christoph , Studd James B. , Agarwal Roshan , Guney Tankut G. , Gourley Charlie , Hennessy Bryan T. , Mills Gordon B. , Mai Antonello , Brown Robert , Dina Roberto , Gabra Hani 
Published: May 2011

AbstractOvarian cancer frequently acquires resistance to platinum chemotherapy, representing a major challenge for improving patient survival. Recent work suggests that resistant clones exist within a larger drug-sensitive cell population prior to chemotherapy, implying that resistance is selected for rather than generated by treatment. We sought to compare clinically derived, intrapatient paired models of initial platinum response and subsequent resistant relapse to define molecular determinants of evolved resistance. Transcriptional analysis of a matched cell line series from three patients with high-grade serous ovarian cancer before and after development of clinical platinum resistance (PEO1/PEO4/PEO6, PEA1/PEA2, PEO14/PEO23) identified 91 up- and 126 downregulated genes common to acquired resistance. Significantly enhanced apoptotic response to platinum treatment in resistant cells was observed following knockdown of histone deacetylase (HDAC) 4, FOLR2, PIK3R1, or STAT1 (P &lt; 0.05). Interestingly, HDAC4 and STAT1 were found to physically interact. Acetyl-STAT1 was detected in platinum-sensitive cells but not in HDAC4 overexpressing platinum-resistant cells from the same patient. In resistant cells, STAT1 phosphorylation/nuclear translocation was seen following platinum exposure, whereas silencing of HDAC4 increased acetyl-STAT1 levels, prevented platinum-induced STAT1 activation, and restored cisplatin sensitivity. Conversely, matched sensitive cells were refractory to STAT1 phosphorylation on platinum treatment. Analysis of 16 paired tumor biopsies taken before and after development of clinical platinum resistance showed significantly increased HDAC4 expression in resistant tumors [n = 7 of 16 (44%); P = 0.04]. Therefore, clinical selection of HDAC4-overexpressing tumor cells upon exposure to chemotherapy promotes STAT1 deacetylation and cancer cell survival. Together, our findings identify HDAC4 as a novel, therapeutically tractable target to counter platinum resistance in ovarian cancer. Cancer Res; 71(13); 4412–22. ©2011 AACR.
Cancer Cell–Associated MT1-MMP Promotes Blood Vessel Invasion and Distant Metastasis in Triple-Negative Mammary Tumors
Authors: Perentes Jean Y. , Kirkpatrick Nathaniel D. , Nagano Satoshi , Smith Eve Y. , Shaver Christine M. , Sgroi Dennis , Garkavtsev Igor , Munn Lance L. , Jain Rakesh K. , Boucher Yves 
Published: May 2011

Abstract
Functional roles for the cancer cell–associated membrane type I matrix metalloproteinase (MT1-MMP) during early steps of the metastatic cascade in primary tumors remain unresolved. In an effort to determine its significance, we determined the in vivo effects of RNAi-mediated downregulation in mammary cancer cells on the migration, blood and lymphatic vessel invasion (LVI), and lymph node and lung metastasis. We also correlated the expression of cancer cell MT1-MMP with blood vessel invasion (BVI) in 102 breast cancer biopsies. MT1-MMP downregulation in cancer cells decreased lung metastasis without affecting primary tumor growth. The inhibition of lung metastasis correlated with reduced cancer cell migration and BVI. Furthermore, cancer cell–expressed MT1-MMP upregulated the expression of MT1-MMP in vascular endothelial cells, but did not affect MT1-MMP expression in lymphatic endothelial cells, LVI, or lymph node metastasis. Of clinical importance, we observed that elevated MT1-MMP expression correlated with BVI in biopsies from triple-negative breast cancers (TNBC), which have a poor prognosis and high incidence of distant metastasis, relative to other breast cancer subtypes. Together, our findings established that MT1-MMP activity in breast tumors is essential for BVI, but not LVI, and that MT1-MMP should be further explored as a predictor and therapeutic target of hematogenous metastasis in TNBC patients. Cancer Res; 71(13); 4527–38. ©2011 AACR.
RECQL1 and WRN Proteins Are Potential Therapeutic Targets in Head and Neck Squamous Cell Carcinoma
Authors: Arai Akihito , Chano Tokuhiro , Futami Kazunobu , Furuichi Yasuhiro , Ikebuchi Kaichiro , Inui Takuma , Tameno Hitosuke , Ochi Yasuko , Shimada Taketoshi , Hisa Yasuo , Okabe Hidetoshi 
Published: May 2011

AbstractRECQL1 and WRN proteins are RecQ DNA helicases that participate in suppression of DNA hyper-recombination and repair. In this study, we report evidence supporting their candidacy as cancer therapeutic targets. In hypopharyngeal carcinomas, which have the worst prognosis among head and neck squamous cell carcinomas (HNSCC) that are rapidly rising in incidence, we found that RECQL1 and WRN proteins are highly expressed and that siRNA-mediated silencing of either gene suppressed carcinoma cell growth in vitro. Similarly, siRNA administration in a murine xenograft model of hypopharyngeal carcinoma markedly inhibited tumor growth. Moreover, combining either siRNA with cis-platinum (II) diammine dichloride significantly augmented the in vivo anticancer effects of this drug that is used commonly in HNSCC treatment. Notably, we observed no recurrence of some tumors following siRNA treatment in this model. Our findings offer a preclinical proof of concept for RECQL1 and WRN proteins as novel therapeutic targets to treat aggressive HNSCC and perhaps other cancers. Cancer Res; 71(13); 4598–607. ©2011 AACR.
Trastuzumab and Pertuzumab Produce Changes in Morphology and Estrogen Receptor Signaling in Ovarian Cancer Xenografts Revealing New Treatment Strategies
Authors: Faratian Dana , Zweemer Annelien J.M. , Nagumo Yoko , Sims Andrew H. , Muir Morwenna , Dodds Michael , Mullen Peter , Um Inhwa , Kay Charlene , Hasmann Max , Harrison David J. , Langdon Simon P. 
Published: May 2011

Abstract
Purpose: The aim of this study was to investigate the antitumor effects of HER2-directed combination therapy in ovarian cancer xenograft models to evaluate their potential. The combinations of trastuzumab and pertuzumab, and trastuzumab and aromatase inhibitor therapy were investigated.
Experimental Design: The effects of trastuzumab, pertuzumab, and letrozole on growth response, apoptosis, morphology, and gene and protein expression were evaluated in the SKOV3 ovarian cancer cell line xenograft and a panel of five human ovarian xenografts derived directly from clinical specimens.
Results: The combination of HER2-directed antibodies showed enhanced antitumor activity compared with single antibody therapy in the SKOV3 xenograft model. Apoptosis, morphology, and estrogen-regulated gene expression were modulated by these antibodies in both spatial and temporal manners. A panel of ovarian cancer xenografts showed differential growth responses to the combination of trastuzumab and pertuzumab. High HER2 expression and increasing HER3 protein expression on treatment were associated with growth response. In trastuzumab-treated SKOV3 tumors, there was a change in tumor morphology, with a reduction in frequency of estrogen receptor alpha (ERα)-negative clear cell areas. Trastuzumab, but not pertuzumab, increased expression of ERα in SKOV3 xenografts when analyzed by quantitative immunofluorescence. ERα and downstream signaling targets were modulated by trastuzumab alone and in combination. Trastuzumab enhanced the responsiveness of SKOV3 xenografts to letrozole when given in combination.
Conclusions: These data suggest that trastuzumab in combination with pertuzumab could be an effective approach in high HER2-expressing ovarian cancers and could also enhance sensitivity to endocrine therapy in ERα-positive ovarian cancer. Clin Cancer Res; 17(13); 4451–61. ©2011 AACR.
KL1 Internal Repeat Mediates Klotho Tumor Suppressor Activities and Inhibits bFGF and IGF-I Signaling in Pancreatic Cancer
Authors: Abramovitz Lilach , Rubinek Tamar , Ligumsky Hagai , Bose Shikha , Barshack Iris , Avivi Camila , Kaufman Bella , Wolf Ido 
Published: May 2011

Abstract
Purpose: Klotho is a transmembrane protein which can be shed, act as a circulating hormone and modulate the insulin-like growth factor (IGF)-I and the fibroblast growth factor (FGF) pathways. We have recently identified klotho as a tumor suppressor in breast cancer. Klotho is expressed in the normal pancreas and both the IGF-I and FGF pathways are involved in pancreatic cancer development. We, therefore, undertook to study the expression and activity of klotho in pancreatic cancer.
Experimental Design: Klotho expression was studied using immunohistochemistry and quantitative RT-PCR. Effects of klotho on cell growth were assessed in the pancreatic cancer cells Panc1, MiaPaCa2, and Colo357, using colony and MTT assays and xenograft models. Signaling pathway activity was measured by Western blotting.
Results: Klotho expression is downregulated in pancreatic adenocarcinoma. Overexpression of klotho, or treatment with soluble klotho, reduced growth of pancreatic cancer cells in vitro and in vivo, and inhibited activation of the IGF-I and the bFGF pathways. KL1 is a klotho subdomain formed by cleavage or alternative splicing. Compared with the full-length protein, KL1 showed similar growth inhibitory activity but did not promote FGF23 signaling. Thus, its administration to mice showed favorable safety profile.
Conclusions: These studies indicate klotho as a potential tumor suppressor in pancreatic cancer, and suggest, for the first time, that klotho tumor suppressive activities are mediated through its KL1 domain. These results suggest the use of klotho or KL1 as potential strategy for the development of novel therapeutic interventions for pancreatic cancer. Clin Cancer Res; 17(13); 4254–66. ©2011 AACR.
EFEMP1 as a Novel DNA Methylation Marker for Prostate Cancer: Array-Based DNA Methylation and Expression Profiling
Authors: Kim Yong-June , Yoon Hyung-Yoon , Kim Seon-Kyu , Kim Young-Won , Kim Eun-Jung , Kim Isaac Yi , Kim Wun-Jae 
Published: May 2011

Abstract
Purpose: Abnormal DNA methylation is associated with many human cancers. The aim of the present study was to identify novel methylation markers in prostate cancer (PCa) by microarray analysis and to test whether these markers could discriminate normal and PCa cells.
Experimental Design: Microarray-based DNA methylation and gene expression profiling was carried out using a panel of PCa cell lines and a control normal prostate cell line. The methylation status of candidate genes in prostate cell lines was confirmed by real-time reverse transcriptase-PCR, bisulfite sequencing analysis, and treatment with a demethylation agent. DNA methylation and gene expression analysis in 203 human prostate specimens, including 106 PCa and 97 benign prostate hyperplasia (BPH), were carried out. Further validation using microarray gene expression data from the Gene Expression Omnibus (GEO) was carried out.
Results: Epidermal growth factor–containing fibulin-like extracellular matrix protein 1 (EFEMP1) was identified as a lead candidate methylation marker for PCa. The gene expression level of EFEMP1 was significantly higher in tissue samples from patients with BPH than in those with PCa (P &lt; 0.001). The sensitivity and specificity of EFEMP1 methylation status in discriminating between PCa and BPH reached 95.3% (101 of 106) and 86.6% (84 of 97), respectively. From the GEO data set, we confirmed that the expression level of EFEMP1 was significantly different between PCa and BPH.
Conclusion: Genome-wide characterization of DNA methylation profiles enabled the identification of EFEMP1 aberrant methylation patterns in PCa. EFEMP1 might be a useful indicator for the detection of PCa. Clin Cancer Res; 17(13); 4523–30. ©2011 AACR.
Response of Human Prostate Cancer Cells and Tumors to Combining PARP Inhibition with Ionizing Radiation
Authors: Barreto-Andrade Juan Camilo , Efimova Elena V. , Mauceri Helena J. , Beckett Michael A. , Sutton Harold G. , Darga Thomas E. , Vokes Everett E. , Posner Mitchell C. , Kron Stephen J. , Weichselbaum Ralph R. 
Published: May 2011

Abstract
Radiation therapy remains a promising modality for curative treatment of localized prostate cancer, but dose-limiting toxicities significantly limit its effectiveness. Agents that enhance efficacy at lower radiation doses might have considerable value in increasing tumor control without compromising organ function. Here, we tested the hypothesis that the PARP inhibitor ABT-888 (veliparib) can enhance the response of prostate cancer cells and tumors to ionizing radiation (IR). Following exposure of DU-145 and PC-3 prostate cancer cell lines to the combination of 10 μmol/L ABT-888 and 6 Gy, we observed similar persistence between both cell lines of DNA damage foci and in vitro radiosensitization. We have previously observed that persistent DNA damage foci formed after ABT-888 plus IR efficiently promote accelerated cell senescence, but only PC-3 cells displayed the expected senescent response of G2–M arrest, induction of p21 and β-galactosidase expression, and accumulation as large flat cells. In turn, combining ABT-888 with 6 Gy resulted in delayed tumor regrowth compared with either agent alone only in PC-3 xenograft tumors, whereas DU-145 tumors continued to grow. By 7 days after treatment with ABT-888 plus IR, PC-3 tumors contained abundant senescent cells displaying persistent DNA damage foci, but no evidence of senescence was noted in the DU-145 tumors. That equivalent radiosensitization by ABT-888 plus IR in vitro failed to predict comparable results with tumors in vivo suggests that the efficacy of PARP inhibitors may partially depend on a competent senescence response to accumulated DNA damage. Mol Cancer Ther; 10(7); 1185–93. ©2011 AACR.