bluuebunny/crossref_metadata_2025_split huggingface dataset:
Broad Antitumor Activity in Breast Cancer Xenografts by Motesanib, a Highly Selective, Oral Inhibitor of Vascular Endothelial Growth Factor, Platelet-Derived Growth Factor, and Kit Receptors
Authors: Coxon Angela , Bush Tammy , Saffran Douglas , Kaufman Stephen , Belmontes Brian , Rex Karen , Hughes Paul , Caenepeel Sean , Rottman James B. , Tasker Andrew , Patel Vinod , Kendall Richard , Radinsky Robert , Polverino Anthony 
Published: December 2008

Abstract
Purpose: Angiogenesis plays a critical role in breast cancer development and progression. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that regulates endothelial cell proliferation and survival. We investigated the effects of motesanib, a novel, oral inhibitor of VEGF receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit receptor, on the growth of xenografts representing various human breast cancer subtypes.
Experimental Design: Athymic nude mice were implanted with MCF-7 (luminal) or MDA-MB-231 (mesenchymal) tumor fragments or Cal-51 (mixed/progenitor) tumor cells. Once tumors were established, animals were randomized to receive increasing doses of motesanib alone or motesanib plus cytotoxic chemotherapy (docetaxel, doxorubicin, or tamoxifen).
Results: Across all three xenograft models, motesanib treatment resulted in significant dose-dependent reductions in tumor growth, compared with vehicle-treated controls, and in marked reductions in viable tumor fraction and blood vessel density. No significant effect on body weight was observed with compound treatment compared with control-treated animals. Motesanib did not affect the proliferation of tumor cells in vitro. There was a significantly greater reduction in xenograft tumor growth when motesanib was combined with docetaxel (MDA-MB-231 tumors) or with the estrogen receptor modulator tamoxifen (MCF-7 tumors), compared with either treatment alone, but not when combined with doxorubicin (Cal-51 tumors).
Conclusions: Treatment with motesanib alone or in combination with chemotherapy inhibits tumor growth in vivo in various models of human breast cancer. These data suggest that motesanib may have broad utility in the treatment of human breast cancer.
SCG3 Transcript in Peripheral Blood Is a Prognostic Biomarker for REST-Deficient Small Cell Lung Cancer
Authors: Moss Adrian C. , Jacobson Gregory M. , Walker Lauren E. , Blake Neil W. , Marshall Ernie , Coulson Judy M. 
Published: December 2008

Abstract
Purpose: Specific markers of circulating tumor cells may be informative in managing lung cancer. Because the RE-1 silencing transcription factor (REST/NRSF) is a transcriptional repressor that is inactivated in neuroendocrine lung cancer, we identified REST-regulated transcripts (CHGA, CHGB, SCG3, VGF, and PCSK1) for evaluation as biomarkers in peripheral blood.
Experimental Design: Transcripts were screened across lung cancer and normal cell lines. Candidates were assessed by reverse transcription-PCR and hybridization of RNA extracted from the peripheral blood of 111 lung cancer patients obtained at clinical presentation and from 27 cancer-free individuals.
Results: Expression profiling revealed multiple chromogranin transcripts were readily induced on REST depletion, most notably SCG3 was induced &gt;500-fold. The SCG3 transcript was also overexpressed by 12,000-fold in neuroendocrine compared with nonneuroendocrine lung cancer cells. In peripheral blood of lung cancer patients and cancer-free individuals, we found that SCG3 was more tumor-specific and more sensitive than other chromogranin transcripts as a biomarker of circulating tumor cells. Overall, 36% of small cell lung cancer (SCLC) and 16% of non-SCLC patients scored positively for normalized SCG3 transcript. This correlated with worse survival among SCLC patients with limited disease (n = 33; P = 0.022) but not extensive disease (n = 29; P = 0.459). Interestingly, the subcohort of 6 SCLC patients with resistance to platinum/etoposide chemotherapy all scored positively for peripheral blood SCG3 transcript (P = 0.022).
Conclusions: SCG3 mRNA, a component of the REST-dependent neurosecretory transcriptional profile, provides a sensitive prognostic biomarker for noninvasive monitoring of neuroendocrine lung cancer.
In vivo Knockdown of the Androgen Receptor Results in Growth Inhibition and Regression of Well-Established, Castration-Resistant Prostate Tumors
Authors: Snoek Robert , Cheng Helen , Margiotti Katia , Wafa Latif A. , Wong Charmaine A. , Wong Erica Chan , Fazli Ladan , Nelson Colleen C. , Gleave Martin E. , Rennie Paul S. 
Published: December 2008

Abstract
Purpose: Progression to the castration-resistant state is the incurable and lethal end stage of prostate cancer, and there is strong evidence that androgen receptor (AR) still plays a central role in this process. We hypothesize that knocking down AR will have a major effect on inhibiting growth of castration-resistant tumors.
Experimental Design: Castration-resistant C4-2 human prostate cancer cells stably expressing a tetracycline-inducible AR-targeted short hairpin RNA (shRNA) were generated to directly test the effects of AR knockdown in C4-2 human prostate cancer cells and tumors.
Results: In vitro expression of AR shRNA resulted in decreased levels of AR mRNA and protein, decreased expression of prostate-specific antigen (PSA), reduced activation of the PSA-luciferase reporter, and growth inhibition of C4-2 cells. Gene microarray analyses revealed that AR knockdown under hormone-deprived conditions resulted in activation of genes involved in apoptosis, cell cycle regulation, protein synthesis, and tumorigenesis. To ensure that tumors were truly castration-resistant in vivo, inducible AR shRNA expressing C4-2 tumors were grown in castrated mice to an average volume of 450 mm3. In all of the animals, serum PSA decreased, and in 50% of them, there was complete tumor regression and disappearance of serum PSA.
Conclusions: Whereas castration is ineffective in castration-resistant prostate tumors, knockdown of AR can decrease serum PSA, inhibit tumor growth, and frequently cause tumor regression. This study is the first direct evidence that knockdown of AR is a viable therapeutic strategy for treatment of prostate tumors that have already progressed to the castration-resistant state.
Intracellular Clusterin Inhibits Mitochondrial Apoptosis by Suppressing p53-Activating Stress Signals and Stabilizing the Cytosolic Ku70-Bax Protein Complex
Authors: Trougakos Ioannis P. , Lourda Magda , Antonelou Marianna H. , Kletsas Dimitris , Gorgoulis Vassilis G. , Papassideri Issidora S. , Zou Yonglong , Margaritis Lukas H. , Boothman David A. , Gonos Efstathios S. 
Published: December 2008

AbstractPurpose: Secretory clusterin (sCLU)/apolipoprotein J is an extracellular chaperone that has been functionally implicated in DNA repair, cell cycle regulation, apoptotic cell death, and tumorigenesis. It exerts a prosurvival function against most therapeutic treatments for cancer and is currently an antisense target in clinical trials for tumor therapy. However, the molecular mechanisms underlying its function remained largely unknown.Experimental Design: The molecular effects of small interfering RNA-mediated sCLU depletion in nonstressed human cancer cells were examined by focusing entirely on the endogenously expressed sCLU protein molecules and combining molecular, biochemical, and microscopic approaches.Results: We report here that sCLU depletion in nonstressed human cancer cells signals stress that induces p53-dependent growth retardation and high rates of endogenous apoptosis. We discovered that increased apoptosis in sCLU-depleted cells correlates to altered ratios of proapoptotic to antiapoptotic Bcl-2 protein family members, is amplified by p53, and is executed by mitochondrial dysfunction. sCLU depletion-related stress signals originate from several sites, because sCLU is an integral component of not only the secretory pathway but also the nucleocytosolic continuum and mitochondria. In the cytoplasm, sCLU depletion disrupts the Ku70-Bax complex and triggers Bax activation and relocation to mitochondria. We show that sCLU binds and thereby stabilizes the Ku70-Bax protein complex serving as a cytosol retention factor for Bax.Conclusions: We suggest that elevated sCLU levels may enhance tumorigenesis by interfering with Bax proapoptotic activities and contribute to one of the major characteristics of cancer cells, that is, resistance to apoptosis.
Reoxygenation of Hypoxic Glioblastoma Multiforme Cells Potentiates the Killing Effect of an Interleukin-13-Based Cytotoxin
Authors: Liu Tie Fu , Cai Jiaozhong , Gibo Denise M. , Debinski Waldemar 
Published: December 2008

Abstract
Purpose: Hypoxia is a cause for resistance to cancer therapies. Molecularly targeted recombinant cytotoxins have shown clinical efficacy in the treatment of patients with primary brain tumors, glioblastoma multiforme, but it is not known whether hypoxia influences their antitumor effect.
Experimental Design: We have exposed glioblastoma multiforme cells, such as U-251 MG, U-373 MG, SNB-19, and A-172 MG, to either anoxia or hypoxia and then reoxygenated them while treating with an interleukin (IL)-13-based diphtheria toxin (DT)-containing cytotoxin, DT-IL13QM. We measured the levels of immunoreactive IL-13Rα2, a receptor that mediates IL-13-cytotoxin cell killing, and the levels of active form of furin, a protease that activates the bacterial toxin portion in a cytotoxin.
Results: We found that anoxia/hypoxia significantly alters the responsiveness of glioblastoma multiforme cells to DT-IL13QM. Interestingly, bringing these cells back to normoxia caused them to become even more susceptible to the cytotoxin than the cells maintained under normoxia. Anoxia/hypoxia caused a highly prominent decrease in the immunoreactive levels of both IL-13R and active forms of furin, and reoxygenation not only restored their levels but also became higher than that in normoxic glioblastoma multiforme cells.
Conclusions: Our results show that a recombinant cytotoxin directed against glioblastoma multiforme cells kills these cells much less efficiently under anoxic/hypoxic conditions. The reoxygenation brings unexpected additional benefit of making glioblastoma multiforme cells even more responsive to the killing effect of a cytotoxin.
How to attract and retain the best in government
Authors: Pan Suk Kim  
Published: December 2008

The purpose of this article is to discuss challenges and strategies of attracting and retaining the best in government, particularly from the perspective of government in developing countries or transitional economies. This article will first touch briefly on the technical and practical issues of how to attract and retain the best, followed by an elaboration of current trends in human resource management (HRM). It will also look at a case of the Korean experience on HRM, followed by discussion of the theoretical and policy implications on HRM. Various kinds of best practices and new ideas are available through diverse venues around the world, but it is difficult to determine what really works for whom and how. It is not feasible to apply the same reform strategy to all countries. The challenge is, therefore, to find out what is applicable to the specific country; and how things can be applied while minimizing negative consequences. Points for the practitioners Under rapidly changing circumstances around the world with increasing pressure on performance and innovation in government, old-fashioned personnel management must be significantly transformed, in order to attract and retain the best in government as well as to win the war for talent. Thus HR managers should initiate far-reaching, much needed change in talent management in terms of how they source, attract, select, train, develop, retain, promote, and move employees through the organization. In order to make government the model employer of choice, HR managers need to make a new Copernican transition in finding a new way of human resource management.
Tsunami engulfs Sri Lankan governance
Authors: Samaratunge Ramanie , Coghill Ken , Herath H.M.A. 
Published: December 2008

The features of governance during the provision of relief immediately following the 2004 tsunami, the restoration of key services and facilities, and the longer term rebuilding of damaged/destroyed infrastructure, in the Galle District of Sri Lanka, are investigated in this case study. Interview data revealed that recovery attempts were significantly weakened by the lack of collaboration among key players at the central and the district level. In particular, at the district level, interactions among key stakeholders have lacked focus and were ad hoc. We argue that despite the growing recognition of the advantages of the integration of the actions of various state and non-state actors in such governance, government appears to be reluctant to move away from the existing `command and control mode' of governance. As a result, transaction costs of governance were excessive, and the resources allocated for reconstruction were either misused or left underutilized. Points for practitioners Following a major disaster there is enormous goodwill, with willingness to overlook previous divisions and partisan interests. However, this is fragile and easily dissipated. It must be deliberately preserved and built on. Practitioners should seize the opportunity to build collaborative relationships and to reform administrative processes to facilitate the delivery of supplies and services, giving priority according to need. Advice to the political executive must emphasize the urgency and public interest in drawing on all available human, financial and physical resources through collaborative arrangements involving all sources, including the public service at each level of government, business and non-government organizations.
Reversing the tuberculosis upwards trend: a success story in Romania
Authors: Marica C. , Didilescu C. , Galie N. , Chiotan D. , Zellweger J. P. , Sotgiu G. , D'Ambrosio L. , Centis R. , Ditiu L. , Migliori G. B. 
Published: December 2008

At present, no published evidence is available on the effectiveness of the DOTS (directly observed treatment, short-course) strategy in reducing the incidence of tuberculosis (TB) within a country in the European “hot spots”. The present study aimed to demonstrate the effectiveness of the strategy implementation in reversing the epidemiological TB trend in Romania based on programmatic data analysis.Key programme indicators were analysed from 1998 to 2007, and included DOTS coverage, case-detection rate, treatment success and overall incidence of notified cases. Internationally agreed definitions were used.The key programme indicators began declining and the World Health Assembly targets were reached (79% case-detection of new sputum-smear positive cases and 85.5% success rate in new culture-positive TB cases), 7 yrs after initiation of the DOTS expansion.The success story in Romania suggests that other middle-income, high-incidence countries (i.e.those belonging to the former Soviet Union) might be able to reach the World Health Assembly Targets and curb the burden of tuberculosis.
WSSV ie1 promoter is more efficient than CMV promoter to express H5 hemagglutinin from influenza virus in baculovirus as a chicken vaccine
Authors: He Fang , Ho YuenFern , Yu Li , Kwang Jimmy 
Published: December 2008

Abstract

Background
The worldwide outbreak of influenza A (H5N1) viruses among poultry species and humans highlighted the need to develop efficacious and safe vaccines based on efficient and scaleable production.

Results
White spot syndrome virus (WSSV) immediate-early promoter one (ie1) was shown to be a stronger promoter for gene expression in insect cells compared with Cytomegalovirus immediate-early (CMV) promoter in luciferase assays. In an attempt to improve expression efficiency, a recombinant baculovirus was constructed expressing hemagglutinin (HA) of H5N1 influenza virus under the control of WSSV ie1 promoter. HA expression in SF9 cells increased significantly with baculovirus under WSSV ie1 promoter, compared with CMV promoter based on HA contents and hemagglutination activity. Further, immunization with baculovirus under WSSV ie1 promoter in chickens elicited higher level anti-HA antibodies compared to CMV promoter, as indicated in hemagglutination inhibition, virus neutralization and enzyme-linked immunosorbent assays. By immunohistochemistry, strong HA antigen expression was observed in different chicken organs with vaccination of WSSV ie1 promoter controlled baculovirus, confirming higher efficiency in HA expression by WSSV ie1 promoter.

Conclusion
The production of H5 HA by baculovirus was enhanced with WSSV ie1 promoter, especially compared with CMV promoter. This contributed to effective elicitation of HA-specific antibody in vaccinated chickens. This study provides an alternative choice for baculovirus based vaccine production.
Diagnosis of foot-and mouth disease by real time reverse transcription polymerase chain reaction under field conditions in Brazil
Authors: Paixão Tatiane A , Neta Alcina V Carvalho , Paiva Naimes O , Reis Jorge R , Barbosa Meirivan S , Serra Claudia V , Silva René R , Beckham Tammy R , Martin Barbara M , Clarke Neville P , Adams L Garry , Santos Renato L 
Published: December 2008

Abstract

Background
Foot-and-mouth disease (FMD) is an economically important and highly contagious viral disease that affects cloven-hoofed domestic and wild animals. Virus isolation and enzyme-linked immunosorbent assay (ELISA) are the gold standard tests for diagnosis of FMD. As these methods are time consuming, assays based on viral nucleic acid amplification have been developed.

Results
A previously described real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay with high sensitivity and specificity under laboratorial and experimental conditions was used in the current study. To verify the applicability of this assay under field conditions in Brazil, 460 oral swabs from cattle were collected in areas free of FMD (n = 200) and from areas with outbreaks of FMD (n = 260). Three samples from areas with outbreaks of FMD were positive by real-time RT-PCR, and 2 of those samples were positive by virus isolation and ELISA. Four other samples were considered inconclusive by real-time RT-PCR (threshold cycle [Ct] > 40); whereas all 200 samples from an area free of FMD were real-time RT-PCR negative.

Conclusion
real-time RT-PCR is a powerful technique for reliable detection of FMDV in a fraction of the time required for virus isolation and ELISA. However, it is noteworthy that lack of infrastructure in certain areas with high risk of FMD may be a limiting factor for using real-time RT-PCR as a routine diagnostic tool.
Laparoscopic-assisted small bowel resection for treatment of adult small bowel intussusception: a case report
Authors: Stewart Donald , Hughes Michael , Hope William W 
Published: December 2008

Abstract

Background
Intussuception is a rare cause of intestinal obstruction in adults. Diagnosis is often difficult due to the variable and sometimes episodic nature of symptoms. Surgery is the recommended treatment option in adults if the diagnosis is proven.

Case presentation
We present a case of a 33 year old Caucasian female admitted with a small bowel obstruction and no history of previous abdominal surgery. Patient did not improve with medical management consisting of bowel rest and nasogastric tube decompression. Surgery was consulted and patient was taken to the operating room for a laparoscopic-assisted small bowel resection for a small bowel intussusception caused by a submucosal fibroma.

Conclusion
Our case highlights the feasibility and potential benefits of laparoscopy in assisting the diagnosis and treatment of small bowel obstructions.
Malignant melanoma associated with a blue naevus: a case report
Authors: Mellone Pasquale , Bianchi Alexander , Dragonetti Emanuele , Murace Raffaele , Persichetti Paolo , Baldi Alfonso 
Published: December 2008

Abstract

Introduction
Combined malignant naevi are characterised pathologically by the association of a melanoma with one or more different types of benign melanocytic naevi in a single lesion.

Case Presentation
We show here a case of malignant combined naevus made up of a blue naevus and a melanoma, presenting as a slowly progressing and asymptomatic pigmented lesion on the trunk of a 35-year-old man. Dermoscopic examination was not conclusive for a malignant lesion, showing only an atypical brown pigment network. The definitive diagnosis was reached only at the hystopathological examination.

Conclusion
This finding suggests that combined naevi should be always excised and histologically examined to achieve a correct diagnosis and avoid risk of misclassification.
Influence ofSlc11a1(formerlyNramp1) on DSS-induced colitis in mice
Authors: Jiang Hui-Rong , Gilchrist Derek S , Popoff Jean-Francois , Jamieson Sarra E , Truscott Martha , White Jacqueline K , Blackwell Jenefer M 
Published: December 2008

AbstractMultiple genetic studies in humans indicate a role for solute carrier family 11a member 1 [SLC11A1; formerly natural resistance-associated macrophage protein 1 (NRAMP1)] in autoimmune disease susceptibility, including ulcerative colitis. Murine Slc11a1 has many pleiotropic effects on macrophage activation and proinflammatory responses. To determine which of these are important in ulcerative colitis, we established a phenotype for oral dextran sulfate sodium (DSS)-induced acute colitis in congenic Slc11a1 wild-type (wt) and mutant (mt) mice on a B10 background. For over 7 days of treatment with 2% DSS in the drinking water, Slc11a1 wt mice showed enhanced acute ulcerative colitis, as demonstrated by significantly greater body weight loss and reduction in colon length, as well as a marked increase in monocyte/macrophage inflammatory infiltrates and histopathology changes in the colon. This was accompanied by a clear, inverse relationship between IFN-γ and IL-10 responses in Slc11a1 wt compared with mt mice, resulting in a significantly higher ratio of IFN-γ:IL-10 in wt compared with mt mice in lymph node and splenic T cells. RNase protection assays confirmed the presence of significantly higher IFN-γ at the RNA level in the colons of wt compared with mt mice at Day 7 of treatment. Interestingly this was accompanied by significantly enhanced RNA levels for the acute-phase protein IL-6, which is known to inhibit the generation of forkhead box P3+ regulatory T cells and help to drive the differentiation of Th17 from naive T cells and not by differences in RNA for IL-12p35 or IL-12p40 molecules that dimerize to form the Th1-inducing cytokine IL-12.