bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical Studies of Human Immunodeficiency Virus/AIDS Vaccines: Inverse Correlation between Avidity of Anti-Env Antibodies and Peak Postchallenge Viremia
Authors: Zhao Jun , Lai Lilin , Amara Rama Rao , Montefiori David C. , Villinger Francois , Chennareddi Lakshmi , Wyatt Linda S. , Moss Bernard , Robinson Harriet L. 
Published: February 2009

ABSTRACT
A major challenge for human immunodeficiency virus (HIV)/AIDS vaccines is the elicitation of anti-Env antibodies (Ab) capable of neutralizing the diversity of isolates in the pandemic. Here, we show that high-avidity, but nonneutralizing, Abs can have an inverse correlation with peak postchallenge viremia for a heterologous challenge. Vaccine studies were conducted in rhesus macaques using DNA priming followed by modified vaccinia Ankara boosting with HIV type 1 (HIV-1) immunogens that express virus-like particles displaying CCR5-tropic clade B (strain ADA) or clade C (IN98012) Envs. Rhesus granulocyte-macrophage colony-stimulating factor was used as an adjuvant for enhancing the avidity of anti-Env Ab responses. Challenge was with simian/human immunodeficiency virus (SHIV)-162P3, a CCR5-tropic clade B chimera of SIV and HIV-1. Within the groups receiving the clade B vaccine, a strong inverse correlation was found between the avidity of anti-Env Abs and peak postchallenge viremia. This correlation required the use of native but not gp120 or gp140 forms of Env for avidity assays. The high-avidity Ab elicited by the ADA Env had excellent breadth for the Envs of incident clade B but not clade C isolates, whereas the high-avidity Ab elicited by the IN98012 Env had excellent breadth for incident clade C but not clade B isolates. High-avidity Ab elicited by a SHIV vaccine with a dual-tropic clade B Env (89.6) had limited breadth for incident isolates. Our results suggest that certain Envs can elicit nonneutralizing but high-avidity Ab with broad potential for blunting incident infections of the same clade.
Optimizing Viral Protein Yield of Influenza Virus Strain A/Vietnam/1203/2004 by Modification of the Neuraminidase Gene
Authors: Adamo Joan E. , Liu Teresa , Schmeisser Falko , Ye Zhiping 
Published: February 2009

ABSTRACT
The preparation of high-yield prepandemic influenza virus H5N1 strains has presented a challenge to both researchers and vaccine manufacturers. The reasons for the relatively low yield of the H5N1 strains are not fully understood, but it might be partially dependent on the interactions between the hemagglutinin (HA) or neuraminidase (NA) surface glycoprotein and other influenza virus proteins. In this study, we have constructed chimeras between the A/Puerto Rico/8/34 (PR8) NA gene and the A/Vietnam/1203/2004 (VN1203) NA gene that have resulted in an increase in the virus yield of the reassortant viruses without a significant loss of NA activity. By combining the amino terminus of NA from the PR8 strain with the carboxy terminus of NA from VN1203, the surface epitopes unique to the H5N1 VN1203 NA glycoprotein are maintained. This reassortant virus had a higher titer and total protein yield in eggs, grew to a higher titer, produced large plaques on MDCK cells, and retained NA activity. This work describes a novel recombinant technique designed to increase the yields of vaccine candidates for the production of pandemic influenza virus vaccines. The relationship between the infectivity and protein yield of the reassortants also is discussed.
Diagnosis and treatment in inflammatory neuropathies
Authors: Lunn M P T , Willison H J 
Published: February 2009

Abstract
The inflammatory neuropathies are a large diverse group of immune-mediated neuropathies that are amenable to treatment and may be reversible. Their accurate diagnosis is essential for informing the patient of the likely course and prognosis of the disease, informing the treating physician of the appropriate therapy and informing the scientific community of the results of well-targeted, designed and performed clinical trials. With the advent of biological therapies able to manipulate the immune response more specifically, an understanding of the pathogenesis of these conditions is increasingly important. This review presents a broad overview of the pathogenesis, diagnosis and therapy of inflammatory neuropathies, concentrating on the most commonly encountered conditions.
Hand-Foot Skin Reaction Increases with Cumulative Sorafenib Dose and with Combination Anti-Vascular Endothelial Growth Factor Therapy
Authors: Azad Nilofer S. , Aragon-Ching Jeanny B. , Dahut William L. , Gutierrez Martin , Figg William D. , Jain Lokesh , Steinberg Seth M. , Turner Maria L. , Kohn Elise C. , Kong Heidi H. 
Published: February 2009

Abstract
Purpose: Sorafenib, a vascular endothelial growth factor (VEGF) receptor-2 and RAF kinase inhibitor, commonly causes skin toxicity. We retrospectively analyzed dermatologic toxicity in patients receiving combined antiangiogenic therapy involving sorafenib and bevacizumab.
Experimental Design: Castration-resistant prostate cancer and metastatic non-small cell lung cancer patients were accrued to phase II studies, receiving sorafenib 400 mg twice daily. A phase I study explored sorafenib 200 to 400 mg twice daily with bevacizumab 5 to 10 mg/kg every 2 weeks in patients with advanced solid tumors. The probability of development of maximum grade of dermatologic toxicity as a function of the cumulative dose of sorafenib was determined. Additional analyses compared extent of toxicity, pharmacokinetics, and patient risk factors.
Results: Ninety-six patients were enrolled: 54 received sorafenib and 42 received bevacizumab/sorafenib. Hand-foot skin reaction (HFSR) was observed in 50 of 96 (52%) patients. Grade 2 to 3 HFSR developed in 16 of 54 (30%) sorafenib patients and 24 of 42 (57%) bevacizumab/sorafenib patients (P = 0.012) and was associated with cumulative sorafenib exposure (P = 0.0008). Twenty-four of 42 phase I patients randomized to start with bevacizumab had increased risk of grade 2 to 3 HFSR than those starting with sorafenib (P = 0.013) after adjusting for association between HFSR risk and hypertension (P = 0.01), which was the only toxicity associated with HFSR. There was no association between HFSR and baseline history of neuropathy, prior taxane/platinum treatment, or systemic sorafenib levels.
Conclusions: Sorafenib-related HFSR is associated with increasing cumulative sorafenib dose. HFSR is increased in patients treated with bevacizumab/sorafenib combination anti-VEGF therapy, and this finding is not explained by pharmacokinetic interaction between the two agents. Our results suggest that the pathophysiology of HFSR may be related to VEGF inhibition.
Molecular Mechanisms of Tamoxifen Therapy for Cholangiocarcinoma: Role of Calmodulin
Authors: Pawar Pritish , Ma Liping , Byon Chang Hyun , Liu Hui , Ahn Eun-Young , Jhala Nirag , Arnoletti Juan P. , McDonald Jay M. , Chen Yabing 
Published: February 2009

Abstract
Purpose: Cholangiocarcinoma is a fatal tumor with limited therapeutic options. We have reported that calmodulin antagonists tamoxifen and trifluoperazine induced apoptosis in cholangiocarcinoma cells. Here, we determined the effects of tamoxifen on tumorigenesis and the molecular mechanisms of tamoxifen-induced apoptosis.
Experimental Design: Nude mice xenograft model of cholangiocarcinoma was used and tamoxifen was given i.p. and intratumorally. Cholangiocarcinoma cells were used to characterize molecular mechanisms of tamoxifen-induced apoptosis in vitro.
Results: I.p. or intratumoral injection of tamoxifen decreased cholangiocarcinoma tumorigenesis by 40% to 80% in nude mice. In cells isolated from tumor xenografts, tamoxifen inhibited phosphorylation of AKT (pAKT) and cellular FLICE like inhibitory protein (c-FLIP). Immunohistochemical analysis further showed that pAKT was identified in all nontreated tumors but was absent in tamoxifen-treated tumors. In vitro, tamoxifen activated caspase-8 and caspase-10, and their respective inhibitors partially blocked tamoxifen-induced apoptosis. Overexpression of c-FLIP inhibited tamoxifen-induced apoptosis and enhanced tumorigenesis of cholangiocarcinoma cells in nude mice, whereas deletion of the calmodulin-binding domain on c-FLIP restored the sensitivity to tamoxifen and inhibited tumorigenesis. With two additional cholangiocarcinoma cell lines, we confirmed that the expression of FLIP is an important factor in mediating spontaneous and tamoxifen-induced apoptosis.
Conclusions: Thus, tamoxifen inhibits cholangiocarcinoma tumorigenesis in nude mice. Tamoxifen-induced apoptosis is partially dependent on caspases, inhibition of pAKT, and FLIP expression. Further, calmodulin-FLIP binding seems to be important in FLIP-mediated resistance to tamoxifen. Therefore, the present studies support the concept that tamoxifen may be used as a therapy for cholangiocarcinoma and possibly other malignancies in which the calmodulin targets AKT and c-FLIP play important roles in the tumor pathogenesis.
Antitumor Activity of an Oncolytic Adenoviral-CD40 Ligand (CD154) Transgene Construct in Human Breast Cancer Cells
Authors: Gomes Erica M. , Rodrigues Margret S. , Phadke Anagha P. , Butcher Lindsay D. , Starling Cherry , Chen Salina , Chang Dongkun , Hernandez-Alcoceba Ruben , Newman Joseph T. , Stone Marvin J. , Tong Alex W. 
Published: February 2009

Abstract
Purpose: CD40 ligand (CD40L, CD154) plays a central role in immunoregulation and also directly modulates epithelial cell growth and differentiation. We previously showed that the CD40 receptor is commonly expressed in primary breast cancer tissues. In this proof-of-principle study, we examined the breast cancer growth–regulatory activities of an oncolytic adenoviral construct carrying the CD40L transgene (AdEHCD40L).
Experimental Design: In vitro and in vivo evaluations were carried out on AdEHCD40L to validate selective viral replication and CD40L transgene activity in hypoxia inducing factor-1α and estrogen receptor–expressing human breast cancer cells.
Results: AdEHCD40L inhibited the in vitro growth of CD40+ human breast cancer lines (T-47D, MDA-MB-231, and BT-20) by up to 80% at a low multiplicity of infection of 1. Incorporation of the CD40L transgene reduced the effective dose needed to achieve 50% growth inhibition (ED50) by ∼10-fold. In contrast, viral and transgene expression of AdEHCD40L, as well its cytotoxicity, was markedly attenuated in nonmalignant cells. Intratumoral injections with AdEHCD40L reduced preexisting MDA-MB-231 xenograft growth in severe combined immunodeficient mice by &gt;99% and was significantly more effective (P &lt; 0.003) than parental virus AdEH (69%) or the recombinant CD40L protein (49%). This enhanced antitumor activity correlated with cell cycle blockade and increased apoptosis in AdEHCD40L-infected tumor cells.
Conclusions: These novel findings, together with the previously known immune-activating features of CD40L, support the potential applicability of AdEHCD40L for experimental treatment of human breast cancer.
Role of ADAMs in Cancer Formation and Progression
Authors: Duffy Michael J. , McKiernan Eadaoin , O'Donovan Norma , McGowan Patricia M. 
Published: February 2009

Abstract
The ADAMs (a disintegrin and metalloproteinase) comprise a family of multidomain transmembrane and secreted proteins. One of their best-established roles is the release of biologically important ligands, such as tumor necrosis factor–α, epidermal growth factor, transforming growth factor–α, and amphiregulin. Because these ligands have been implicated in the formation and progression of tumors, it might be expected that the specific ADAMs involved in their release would also be involved in malignancy. Consistent with this hypothesis, emerging data from model systems suggest that ADAMs, such as ADAM-9, ADAM-12, ADAM-15, and ADAM-17, are causally involved in tumor formation/progression. In human cancer, specific ADAMs are up-regulated, with levels generally correlating with parameters of tumor progression and poor outcome. In preclinical models, selective ADAM inhibitors against ADAM-10 and ADAM-17 have been shown to synergize with existing therapies in decreasing tumor growth. The ADAMs are thus a new family of potential targets for the treatment of cancer, especially malignancies that are dependent on human epidermal growth factor receptor ligands or tumor necrosis factor–α.
Angiopoietin-2 Levels Are Associated with Disease Progression in Metastatic Malignant Melanoma
Authors: Helfrich Iris , Edler Lutz , Sucker Antje , Thomas Markus , Christian Sven , Schadendorf Dirk , Augustin Hellmut G. 
Published: February 2009

Abstract
Purpose: The blood vessel-destabilizing Tie2 ligand angiopoietin-2 (Ang-2) acts in concert with the vascular endothelial growth factor/vascular endothelial growth factor receptor system to control vessel assembly during tumor progression. We hypothesized that circulating soluble Ang-2 (sAng-2) may be involved in melanoma progression.
Experimental Design: Serum samples (n = 98) from melanoma patients (American Joint Committee on Cancer stages I-IV), biopsies of corresponding patients, and human melanoma cell lines were analyzed for expression of Ang-2 and S100β. Multiple sera of a subcohort of 33 patients were tested during progression from stage III to IV. Small interfering RNA-based loss-of-function experiments were done to assess effects of Ang-2 on melanoma cells.
Results: Circulating levels of sAng-2 correlate with tumor progression in melanoma patients (P &lt; 0.0001) and patient survival (P = 0.007). Analysis of serum samples during the transition from stage III to IV identified an increase of sAng-2 up to 400%. Comparative analyses revealed a 56% superiority of sAng-2 as predictive marker over the established marker S100β. Immunohistochemistry and reverse transcription-PCR confirmed the prominent expression of Ang-2 by tumor-associated endothelial cells but identified Ang-2 also as a secreted product of melanoma cells themselves. Corresponding cellular experiments revealed that human melanoma-isolated tumor cells were Tie2 positive and that Ang-2 acted as an autocrine regulator of melanoma cell migration and invasion.
Conclusions: The experiments establish sAng-2 as a biomarker of melanoma progression and metastasis correlating with tumor load and overall survival. The identification of an autocrine angiopoietin/Tie loop controlling melanoma migration and invasion warrants further functional experiments and validate the angiopoietin/Tie system as a promising therapeutic target for human melanomas.
The Combined Therapeutic Effects of Bortezomib and Fenretinide on Neuroblastoma Cells Involve Endoplasmic Reticulum Stress Response
Authors: Pagnan Gabriella , Di Paolo Daniela , Carosio Roberta , Pastorino Fabio , Marimpietri Danilo , Brignole Chiara , Pezzolo Annalisa , Loi Monica , Galietta Luis J.V. , Piccardi Federica , Cilli Michele , Nico Beatrice , Ribatti Domenico , Pistoia Vito , Ponzoni Mirco 
Published: February 2009

Abstract
Purpose: The proteasome inhibitor bortezomib inhibited cell growth and angiogenesis in neuroblastoma. Bortezomib has been shown to induce synergistic activity when combined with other antineoplastic agents. Here we have investigated the antitumor activity of bortezomib in combination with fenretinide, a synthetic retinoid, against neuroblastoma cells.
Experimental Design: Different neuroblastoma cell lines were tested for sensitivity to bortezomib and fenretinide, given alone or in different dose-dependent and time-dependent combination schedules. Cell proliferation, cell viability, and apoptosis were evaluated by measuring 3H-thymidine incorporation, trypan blue staining, DNA fragmentation, and western blot analysis. Angiogenesis was assessed by the chick embryo chorioallantoic membrane assay. An orthotopic neuroblastoma mouse model was used to examine in vivo sensitivity.
Results: Each compound alone was able to induce a dose-dependent inhibition of cell proliferation, with a significant enhanced antiproliferative effect for the drugs used in combination. This inhibition was characterized by marked G2-M and G1 cell cycle arrest with nearly complete depletion of S phase. Bortezomib and fenretinide in association triggered an increased apoptosis through activation of specific genes of the endoplasmic reticulum stress compared with either drug tested alone. Tumor-bearing mice treated with bortezomib plus fenretinide lived statistically significantly longer than mice treated with each drug alone. Histologic evaluation and chorioallantoic membrane analysis of primary tumors showed that the combined therapeutic activity of bortezomib and fenretinide rested upon antitumor and antiangiogenic mechanisms.
Conclusions: These findings provide the rationale for the development of a new therapeutic strategy for neuroblastoma based on this pharmacologic combination.
Turmeric and Green Tea: A Recipe for the Treatment of B-Chronic Lymphocytic Leukemia
Authors: Angelo Laura S. , Kurzrock Razelle 
Published: February 2009

Abstract
Two naturally occurring compounds, curcumin, the active ingredient in the spice turmeric, and the green tea extract epigallocatechin-3-gallate, have marked effects on the apoptotic machinery in chronic lymphocytic leukemia. These results provide a preclinical foundation for future clinical use of these compounds in this disease.
Fragments of a Global Past: Ceramics Manufacture in Song-Yuan-Ming Jingdezhen
Authors: Gerritsen Anne 
Published: February 2009

AbstractThis essay explores textual genres related to the production of ceramics in Jingdezhen, including maps, literati collections, the literature of connoisseurship, local gazetteers, and merchant manuals. An analysis of these genres brings the Chinese textual record of ceramics into sharper focus and reveals what has remained unwritten. Whereas European writings on Chinese ceramics from the seventeenth and eighteenth centuries dwell on modes of manufacture in a global context, Chinese writers generally ignore matters of technology and commerce beyond the confines of the Chinese realm. These omissions emerge in part from the peculiarities of the genres within which these writings have been transmitted. Cet essai examine les différents genres de textes qui ont trait à la production de la céramique dans Jingdezhen. Parmi ces textes, il se trouve des cartes géographiques, des collections d'écrits de 'literati', des monographies locales et des manuels de commerce. L'analyse de ces genres permet d'approfondir notre compréhension de la tradition écrite au sujet de la céramique, tout en révélant en même temps, ce qui reste implicite en ces textes. Les auteurs chinois ne s'attardent pas aux questions de technologie, ni au commerce au-delà des confins de l'Empire chinois. Le présent essai suggère que ces omissions s'expliquent par les conventions des genres auxquels ces écrits appartiennent.
Regulating Corporate Social and Human Rights Responsibilities at the UN Plane: Institutionalising New Forms of Law and Law-making Approaches?
Authors: Buhmann Karin 
Published: February 2009

AbstractGlobalisation's unprecedented growth and transborder activities of business coupled with increasing awareness of the impact of business on societies and human rights has resulted in demands for the international society to regulate corporate social and human rights responsibilities. This not only challenges traditional notions of duty bearers under international law, but also calls for novel approaches for the United Nations (UN) to implement central parts of the Charter's human rights aims and to address corporate behaviour in a state-centred international law-making order that lacks the willingness of States to regulate business. This article explores recent UN responses and argues that in the absence of States acting through ordinary international law-making, the UN as an intergovernmental organisation draws on participatory modes of law-making and new forms of law in order to normatively influence businesses' impact on human rights. The pattern of using these forms suggests an institutionalisation of reflexive regulation as a regulatory process drawing on public-private regulation, and of an emerging UN based 'Global Administrative Law' in order to meet regulatory challenges in living up to the human rights aims embodied in the UN Charter under the conditions posed by globalisation of the economy and emergence of strong transnational non-state actors. The analysis is based on the UN Global Compact, the draft Norms on the Responsibilities of Transnational Corporations and Other Business Enterprises with regard to Human Rights and the process of the Special Representative of the Secretary General on the issue of human rights and transnational corporations and business (SRSG).
'Territorial Non-Application' of the European Convention on Human Rights
Authors: Larsen Kjetil Mujezinović 
Published: February 2009

AbstractThis article examines the issue of when a State can be considered not to exercise jurisdiction under Article 1 of the European Convention on Human Rights in parts of its own territory. The starting point is that the notion of jurisdiction in the Convention is primarily territorial, and that a State is presumed to exercise jurisdiction throughout the entire territory. The presumption can be rebutted in exceptional circumstances. The author argues that this can happen only if the State is prevented from exercising authority and control in parts of the territory, and that the lack of authority and control must be caused by the influence of another State. Even if the State is considered to be in this position, the State retains a "reduced jurisdiction", and is under a positive obligation to take measures to protect the human rights of the population. The article examines the issue with particular reference to the Assanidze and Ilaşcu cases from the European Court of Human Rights, and illustrates the issue by reviewing briefly the current situation in four regions in the Caucasus.
Group Rights and Conflicts in Africa: A Critical Reflection on Ife-Modakeke, Nigeria
Authors: Akanji Olajide 
Published: February 2009

AbstractThe issue of group rights is indubitably an issue that concerns both minority and majority groups. Notwithstanding, minorities are quicker to claim the rights than the dominant groups. But the fact that group rights are a set of rights, though distinguishable from individual rights, within the general framework of fundamental human rights, shows that both minority and majority groups can exercise and enjoy them. The thrust of this article, however, is to fill the lacuna in extant literature on the need to appraise the role and place of group rights in the generation, transformation and sustenance of conflicts in Nigeria. The paper uses the age-long, protracted Ife-Modakeke conflict as a case study. Nigeria, being a plural society, the paper infers, is indeed susceptible to conflicts that border on issues of the collective rights of ethnic, sub-ethnic and religious groups. The article, nonetheless, argues that it is the non-recognition and respect of the rights of groups, both minority and majority, through the non-provision of adequate and appropriate measures by successive governments, contrary to international standards to which the country is a signatory, that often heightened tension and fractured inter-group relations in the country.