bluuebunny/crossref_metadata_2025_split huggingface dataset:
Connective Tissue Growth Factor Acts as a Therapeutic Agent and Predictor for Peritoneal Carcinomatosis of Colorectal Cancer
Authors: Lin Been-Ren , Chang Cheng-Chi , Chen Robert Jeen-Chen , Jeng Yung-Ming , Liang Jin-Tung , Lee Po-Huang , Chang King-Jen , Kuo Min-Liang 
Published: May 2011

Abstract
Purpose: Here, we aimed to investigate the role of connective tissue growth factor (CTGF) in peritoneal carcinomatosis (PC) associated with colorectal cancer (CRC) and to characterize the underlying mechanism of CTGF mediating adhesion.
Experimental Design: A cohort of 136 CRC patient specimens was analyzed in this study. CRC cell lines were used for in vitro adhesion assay and in vivo peritoneal dissemination experiment. Recombinant CTGF protein treatment, transfection of CTGF expression plasmids, and knockdown of CTGF expression in CRC cells were utilized to evaluate the integrin α5, which served as a target of CTGF in inhibiting peritoneal seeding.
Results: The analysis of CRC tissues revealed an inverse correlation between CTGF expression and prevalence of PC. Lower CTGF level in CRC patients was associated with higher peritoneal recurrence rate after surgery. Inducing CTGF expression in cancer cells resulted in decreased incidence of PC and increased rate of mice survival. The mice received intraperitoneal injection of recombinant CTGF protein simultaneously with cancer cells or following tumor formation; in both cases, peritoneal tumor dissemination was found to be effectively inhibited in the mouse model. Functional assay revealed that CTGF significantly decreased the CRC cell adhesion ability, and integrin α5 was confirmed by reverse transcriptase PCR and functional blocking assay as a downstream effector in the CTGF-mediated inhibition of CRC cell adhesion.
Conclusions: CTGF acts as a molecular predictor of PC and could be a potential therapeutic target for the chemoprevention and treatment of PC in CRC patients. Clin Cancer Res; 17(10); 3077–88. ©2011 AACR.
Recommendations from the iSBTc-SITC/FDA/NCI Workshop on Immunotherapy Biomarkers
Authors: Butterfield Lisa H. , Palucka A. Karolina , Britten Cedrik M. , Dhodapkar Madhav V. , Håkansson Leif , Janetzki Sylvia , Kawakami Yutaka , Kleen Thomas-Oliver , Lee Peter P. , Maccalli Cristina , Maecker Holden T. , Maino Vernon C. , Maio Michele , Malyguine Anatoli , Masucci Giuseppe , Pawelec Graham , Potter Douglas M. , Rivoltini Licia , Salazar Lupe G. , Schendel Dolores J. , Slingluff Craig L. , Song Wenru , Stroncek David F. , Tahara Hideaki , Thurin Magdalena , Trinchieri Giorgio , van Der Burg Sjoerd H. , Whiteside Theresa L. , Wigginton Jon M. , Marincola Francesco , Khleif Samir , Fox Bernard A. , Disis Mary L. 
Published: May 2011

AbstractPurpose: To facilitate development of innovative immunotherapy approaches, especially for treatment concepts exploiting the potential benefits of personalized therapy, there is a need to develop and validate tools to identify patients who can benefit from immunotherapy. Despite substantial effort, we do not yet know which parameters of antitumor immunity to measure and which assays are optimal for those measurements.Experimental Design: The iSBTc-SITC (International Society for Biological Therapy of Cancer-Society for Immunotherapy of Cancer), FDA (Food and Drug Administration), and NCI (National Cancer Institute) partnered to address these issues for immunotherapy of cancer. Here, we review the major challenges, give examples of approaches and solutions, and present our recommendations.Results and Conclusions: Although specific immune parameters and assays are not yet validated, we recommend following standardized (accurate, precise, and reproducible) protocols and use of functional assays for the primary immunologic readouts of a trial; consideration of central laboratories for immune monitoring of large, multi-institutional trials; and standardized testing of several phenotypic and functional potential potency assays specific to any cellular product. When reporting results, the full QA (quality assessment)/QC (quality control) should be conducted and selected examples of truly representative raw data and assay performance characteristics should be included. Finally, to promote broader analysis of multiple aspects of immunity, and gather data on variability, we recommend that in addition to cells and serum, RNA and DNA samples be banked (under standardized conditions) for later testing. We also recommend that sufficient blood be drawn to allow for planned testing of the primary hypothesis being addressed in the trial, and that additional baseline and posttreatment blood is banked for testing novel hypotheses (or generating new hypotheses) that arise in the field. Clin Cancer Res; 17(10); 3064–76. ©2011 AACR.
Molecular Markers in Low-Grade Gliomas: Predictive or Prognostic?
Authors: Hartmann Christian , Hentschel Bettina , Tatagiba Marcos , Schramm Johannes , Schnell Oliver , Seidel Clemens , Stein Robert , Reifenberger Guido , Pietsch Torsten , von Deimling Andreas , Loeffler Markus , Weller Michael 
Published: May 2011

Abstract
Purpose: To investigate whether TP53 mutation, 1p/19q codeletions, O6-methylguanylmethyltransferase (MGMT) promoter methylation, and isocitrate dehydrogenase 1 (IDH1) mutation predict natural course of disease or response to radiotherapy or chemotherapy or both in low-grade glioma patients.
Experimental Design: Cohort A consisted of 89 patients with diffuse astrocytoma World Health Organization (WHO) grade II (n = 40), oligoastrocytoma (n = 23), or oligodendroglioma (n = 26) who did not receive radiotherapy or chemotherapy after first operation and were monitored until progression [progressive disease (PD); n = 59] and beyond or until the end of follow-up (n = 30). Cohort B consisted of 50 patients with WHO grade II gliomas who received radiotherapy or chemotherapy at diagnosis. Tumors were analyzed for TP53 mutations, 1p/19q codeletions, MGMT promoter methylation, and IDH1 mutations.
Results: Median progression-free survival (PFS) in cohort A was 4.1 years (95% CI: 3.1–5.1). No molecular marker was prognostic for PFS after surgery alone, using multivariate adjustment for histology, age, and extent of resection. IDH1 mutations were associated with prolonged survival from the diagnosis of PD in oligoastrocytomas (OA II)/oligodendrogliomas (O II) and with overall survival (OS) in all tumors. 1p/19q codeletion and IDH1 mutation were prognostic for PFS and OS in cohort B.
Conclusions: None of the parameters are sensitive prognostic biomarkers in WHO grade II glioma patients who do not receive radiotherapy or chemotherapy after surgery. Limitations of this study include the selection of patients with favorable outcome, the nonrandomized allocation of treatment, and the insufficient sample size to distinguish between effects of radiotherapy versus chemotherapy. Regardless of histology, IDH1 mutation status is the strongest prognostic marker for OS. Clin Cancer Res; 17(13); 4588–99. ©2011 AACR.
Instability of Foxp3 Expression Limits the Ability of Induced Regulatory T Cells to Mitigate Graft versus Host Disease
Authors: Beres Amy , Komorowski Richard , Mihara Masahiko , Drobyski William R. 
Published: May 2011

AbstractPurpose: Graft versus host disease (GVHD) is the major complication of allogeneic bone marrow transplantation (BMT) and limits the therapeutic efficacy of this modality. Although the role of natural T-regulatory cells (nTreg) in attenuating GVHD has been extensively examined, the ability of induced T-regulatory cells (iTreg) to mitigate GVHD is unknown. The purpose of this study was to examine the ability of in vitro and in vivo iTregs to abrogate GVHD.Experimental Design: We examined the ability of in vitro differentiated and in vivo iTregs to reduce the severity of GVHD in a clinically relevant mouse model of BMT. The effect of blockade of interleukin (IL) 6 signaling on the efficacy of these Treg populations was also studied.Results: In vitro differentiated iTregs fail to protect mice from lethal GVHD even when administered at high Treg:effector T-cell ratios. Lack of GVHD protection was associated with loss of Foxp3 expression and in vivo reversion of these cells to a proinflammatory phenotype characterized by secretion of IFN-γ. Phenotypic reversion could not be abrogated by blockade of IL-6 signaling or by in vitro exposure of iTregs to all-trans retinoic acid. In contrast, the in vivo induction of iTregs was significantly augmented by IL-6 blockade and this resulted in reduced GVHD.Conclusion: Instability of Foxp3 expression limits the utility of adoptively transferred iTregs as a source of cellular therapy for the abrogation of GVHD. Blockade of IL-6 signaling augments the ability of in vivo iTregs to prevent GVHD but has no effect on in vitro differentiated iTregs. Clin Cancer Res; 17(12); 3969–83. ©2011 AACR.
Targeting Superficial or Nodular Basal Cell Carcinoma with Topically Formulated Small Molecule Inhibitor of Smoothened
Authors: Tang Tracy , Tang Jean Y. , Li Dongwei , Reich Mike , Callahan Christopher A. , Fu Ling , Yauch Robert L. , Wang Frank , Kotkow Karen , Chang Kris S. , Shpall Elana , Wu Angela , Rubin Lee L. , Marsters James C. , Epstein Ervin H. , Caro Ivor , de Sauvage Frederic J. 
Published: May 2011

Abstract
Purpose: Inappropriate activation of the Hedgehog (Hh) signaling pathway in skin is critical for the development of basal cell carcinomas (BCC). We have investigated the anti-BCC efficacy of topically-applied CUR61414, an inhibitor of the Hh signal transduction molecule Smoothened.
Experimental Design: In preclinical studies, we used a depilatory model to evaluate the ability of topical formulations of CUR61414 to repress Hh responsive cells found at the base of hair follicles in normal skin. We also tested the in vivo effects of topical CUR61414 on murine BCCs developed in Ptch1 +/− K14-CreER2 p53 fl/fl mice. In a phase I clinical study, we evaluated the safety, tolerability, and efficacy of a multidose regimen of CUR61414 (0.09%, 0.35%, 1.1%, and 3.1%) applied topically to human superficial or nodular BCCs for up to 28 days.
Results: In mice, topical CUR61414 significantly inhibited skin Hh signaling, blocked the induction of hair follicle anagen, and shrank existing BCCs. However, we observed no clinical activity of this formulation in human superficial or nodular BCCs in a phase I clinical study.
Conclusions: Our data highlight some of the challenges of translating preclinical experience into successful human results for a topical anticancer agent. Clin Cancer Res; 17(10); 3378–87. ©2011 AACR.
Toll-Like Receptor-Mediated Inflammatory Signaling Reprograms Cardiac Energy Metabolism by Repressing Peroxisome Proliferator-Activated Receptor γ Coactivator-1 Signaling
Authors: Schilling Joel , Lai Ling , Sambandam Nandakumar , Dey Courtney E. , Leone Teresa C. , Kelly Daniel P. 
Published: May 2011

Background—
Currently, there are no specific therapies available to treat cardiac dysfunction caused by sepsis and other chronic inflammatory conditions. Activation of toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) is an early event in Gram-negative bacterial sepsis, triggering a robust inflammatory response and changes in metabolism. Peroxisome proliferator–activated receptor-γ coactivator-1 (PGC-1) α and β serve as critical physiological regulators of energy metabolic gene expression in heart.

Methods and Results—
Injection of mice with LPS triggered a myocardial fuel switch similar to that of the failing heart: reduced mitochondrial substrate flux and myocyte lipid accumulation. The LPS-induced metabolic changes were associated with diminished ventricular function and suppression of the genes encoding PGC-1α and β, known transcriptional regulators of mitochondrial function. This cascade of events required TLR4 and nuclear factor-κB activation. Restoration of PGC-1β expression in cardiac myocytes in culture and in vivo in mice reversed the gene regulatory, metabolic, and functional derangements triggered by LPS. Interestingly, the effects of PGC-1β overexpression were independent of the upstream inflammatory response, highlighting the potential utility of modulating downstream metabolic derangements in cardiac myocytes as a novel strategy to prevent or treat sepsis-induced heart failure.

Conclusions—
LPS triggers cardiac energy metabolic reprogramming through suppression of PGC-1 coactivators in the cardiac myocyte. Reactivation of PGC-1β expression can reverse the metabolic and functional derangements caused by LPS-TLR4 activation, identifying the PGC-1 axis as a candidate therapeutic target for sepsis-induced heart failure.
The Unrecognized Burden of Osteoporosis-Related Vertebral Fractures in Patients With Heart Failure
Authors: Lyons Kristin J. , Majumdar Sumit R. , Ezekowitz Justin A. 
Published: May 2011

Background—
Heart failure (HF) is associated with several factors that contribute to both reduced bone mineral density and increased risk of osteoporosis-related fractures. Our objectives were to describe the prevalence and predictors of the most common osteoporotic fracture, vertebral compression fractures (VCF), in patients with HF.

Methods and Results—

We conducted a cross-sectional study in a random sample of patients attending a tertiary care HF Clinic in Edmonton, Alberta, Canada. We collected sociodemographic, clinical, medication, and chest radiograph information. Primary outcome was board-certified radiologist–documented VCF on chest radiographs. Multivariable logistic regression was used to determine independent correlates of VCF. Overall, 623 patients with HF were included; 32% were over 75 years of age, 31% were women, 65% had ischemic cardiomyopathy, and 38% had atrial fibrillation. Prevalence of VCF was 77 of 623 (12%; 95% confidence interval, 10% to 15%), and 42 of 77 (55%) patients had multiple fractures. Only 15% of those with VCF were treated for osteoporosis. In multivariable analyses adjusted for age, female sex, weight, and medications, the only remaining predictors independently associated with fracture were atrial fibrillation (present in 42 of 77 [55%] of those with VCF versus 197 of 540 [36%] of those without; adjusted odds ratio, 2.1; 95% confidence interval, 1.2 to 3.6;
P
=0.009) and lipid-lowering drugs (used by 36 of 77 [47%] of those with VCF versus 342 of 540 [63%] of those without; adjusted odds ratio, 0.2; 95% confidence interval, 0.1 to 0.9;
P
=0.03).

Conclusions—
About one-tenth of HF patients had a chest radiograph–documented VCF, and half of those with VCF had multiple fractures; most (85%) were not receiving an osteoporosis-specific therapy. A previously unrecognized risk factor—atrial fibrillation—was found to be independently associated with VCF. Chest radiograph reports may represent an important case-finding tool for osteoporosis-specific VCF, particularly in HF patients with atrial fibrillation.
Downtime of in-use water pump installations for high-rise residential buildings
Authors: Mui KW , Wong LT , Hui KW 
Published: May 2011

This study examines the fresh and flushing water pump installations for high-rise residential buildings in Hong Kong in terms of system availability, mean time to failure, mean time between failures and restoration time. Together with some reliability data published elsewhere, it applies Bayesian analysis to improve our understanding of the downtime characteristics of water pump installations. For three consecutive years (2005–2007), water pump failures in 46 typical high-rise residential buildings were recorded to determine the component failure rates. In order to study the failure patterns, Monte Carlo simulations were performed for the operations of 100 parallel pump sets over a period of 10 years. The mean time to failure, total downtime, failure counts and system availability estimated for the fresh water pump installations were 1.24 years, 8990 h, 709 and 90% while those estimated for the flushing seawater pump installations were 0.46 years, 4049 h, 2081 and 78%, respectively. The results are useful in the calculation of water supply availability for high-rise residential buildings while keeping the balance between maintenance cost and system reliability. This study also demonstrates a method for reliability modelling of water supply for high-rise residential buildings. Practical applications: This study demonstrates a method for reliability modelling of building services systems. With the use of Bayesian analysis, example estimates of the mean time to failure, total downtime, failure counts and system availability were determined for the fresh and flushing water pump installations for high-rise residential buildings in Hong Kong.
Transfusions during cardiopulmonary bypass: better when triggered by venous oxygen saturation and oxygen extraction rate
Authors: Ranucci M. , Castelvecchio S. , Ditta A. , Brozzi S. , Boncilli A. , Baryshnikova E. ,   Surgical and Clinical Outcome Research (SCORE) group
Published: May 2011

During cardiopulmonary bypass (CPB), red blood cell transfusions may be required to correct dilutional anemia. The decision-making process for transfusions is usually based on the level of hemoglobin.This study investigates the hypothesis that oxygen-derived variables (mixed venous oxygen saturation, SvO2, and oxygen extraction rate, O2ER) may be more reliable predictors of the efficacy of the transfusion. Thirty-six patients for 41 transfusion episodes during CPB were retrospectively analyzed. For each patient, oxygen-derived variables, including SvO2 and O2ER, were measured before and after the transfusion. No changes in pump flow were allowed between the two measurements. The efficacy of transfusion was defined as an increase in SvO2 of at least 5%. We identified 11 transfusion episodes leading to an efficacious SvO 2 increase. Factors associated with the efficacy of the transfusion were a low SvO2 and a high O2ER. No association was found with hemoglobin values, unless for a trend for efficacy of transfusion in patients with very low (<6 g/dL) hemoglobin values. Cut-off values of 68% for SvO2 and 39% for O2ER were predictive for the efficacy of red blood cell transfusions, with a high accuracy (c-statistics 0.856 and 0.848, respectively) and negative and positive predictive values exceeding 82%. In conclusion, SvO2 and O2ER are better than the hemoglobin value for guiding the decision-making process of red blood cell transfusions to correct hemodilutional anemia during CPB.
Safety and quality assurance of chemotherapeutic preparations in a hospital production unit: Acceptance sampling plan and economic impact
Authors: Paci A , Borget I , Mercier L , Azar Y , Desmaris RP , Bourget P 
Published: May 2011

Objective: The opportunity to apply a sampling plan was evaluated. Costs were computed by a microcosting study. Setting: In 2003, a sampling plan was defined to reduce the number of chemotherapy quality controls while preserving the same level of quality. Recent qualitative and quantitative changes led us to define a second sampling plan supplemented by an economic evaluation to determine the cost and cost-savings of quality control. Methods: The study considers preparation produced during four semesters classified into three groups. The first one includes drugs produced below 200 batches a semester. Group 2, those for which the lot of preparation lots would have been rejected twice among these four semesters. Group 3, those would have been accepted (≥3 ‘acceptable lot’). A single sampling plan by attributes was applied to this group with an acceptance quality level of 1.65% and a lot tolerance percent defective below 5%. A micro-costing study was conducted on quality control, from the sampling to the validation of the results. Results: Among 39 cytotoxic drugs, 11 were sampled which enabled to avoid a mean of 17,512 control assays per year. Each batch of the 28 non-sampled drugs was however analyzed. Costs were estimated at 2.98€ and 5.25€ for control assays depending of the analytical method. The savings from the application of the sampling plans was 153,207€ in 6 years. Conclusion: The sampling plan allowed maintaining constancy in number of controls and the level of quality with significant costsavings, despite a substantial increase in drugs to assay and in the number of preparations produced.
Report of an evaluation of a Nurse-led Dementia Outreach Service for people with the behavioural and psychological symptoms of dementia living in residential aged care facilities
Authors: Borbasi Sally , Emmanuel Elizabeth , Farrelly Brona , Ashcroft Jayne 
Published: May 2011

Background: This paper describes the implementation and evaluation of a Dementia Outreach Service (DEMOS). The service is led by the first Nurse Practitioner in Dementia Care in the State of Queensland in Australia and is highly innovative in terms of its mode of delivery. The evaluation took place due to a perception that new models such as the DEMOS often fail to gain momentum due to a lack of data on their effectiveness and efficiency. Method: The parameters of the project were to evaluate the extent to which the DEMOS met its key deliverables, focusing specifically on outcomes for residential aged care facilities (RACF) residents and staff. The study involved both quantitative and qualitative data collection. Qualitative data was collected through interviews, focus groups and reflective journals. A survey which was administered at three stages of the 12 months of the study was the main source of quantitative data. Additional statistical data was collected from relevant healthcare providers. Findings: Twenty RACFs within a specific health service district participated in the study. This included an intervention group of 7 facilities (which received the service) and a control group of 13. A total of 320 RACF staff participated in Stage 1 of the study, although due to staff attrition this had reduced to 153 (54.6%) at Stage 3. Attrition rates were much lower in the 7 intervention facilities, with 67.9% of the original sample remaining at Stage 3. To augment the quantitative data collected as above, drawing on a range of qualitative techniques the researchers canvassed the perceptions, thoughts and opinions of differing stakeholders. The qualitative data proved extremely valuable in confirming the success of DEMOS. Key Success Areas: Increased self-confidence among staff in dealing with residents with dementia; reduced stress among staff; reductions in the instances of difficult behaviours; reduced referrals to acute sector services; high levels of satisfaction among RACF management regarding DEMOS; and a process of continuous improvement of DEMOS based on stakeholder feedback. Implications for Practice: Recommendations for the future directions of the service include: ◆ The continued support and expansion of DEMOS; ◆ An increase in the DEMOS service portfolio to actively assist facilities to change the culture of care amongst RACF carers; and ◆ Showcasing of DEMOS as an example of ‘best practice’ in dementia care to argue the need for provision of additional Nurse Practitioners specializing in dementia care.