bluuebunny/crossref_metadata_2025_split huggingface dataset:
NGALR Is Overexpressed and Regulated by Hypomethylation in Esophageal Squamous Cell Carcinoma
Authors: Cui Lei , Xu Li-Yan , Shen Zhong-Ying , Tao Qian , Gao Shu-Ying , Lv Zhuo , Du Ze-Peng , Fang Wang-Kai , Li En-Min 
Published: December 2008

Abstract
Purpose: Neutrophil gelatinase-associated lipocalin receptor (NGALR) mRNA level is reduced in isolated chronic myelogenous leukemia blasts but up-regulated in esophageal squamous cell carcinoma (ESCC). The mechanism of NGALR regulation is unknown. Here, we show the expression pattern of NGALR and examine the aberrant methylation of its gene in ESCC and esophageal carcinoma cell lines.
Experimental Design: The expression pattern of NGALR was analyzed by immunohistochemistry in 59 ESCCs and compared with noncancerous tissues. The DNA methylation status was investigated by methylation-specific PCR and by bisulfite genomic sequencing in esophageal carcinoma cell lines and surgically resected samples. Methylated cell lines were treated with a methylation inhibitor to restore NGALR expression.
Results: The expression of NGALR in ESCC was significantly higher in tumor cell membrane and cytoplasm than in normal esophageal epithelium (P &lt; 0.01). Methylated alleles were detected in three NGALR-nonexpressing cell lines but were not detected in three NGALR-expressing cell lines. Treatment of methylated cell lines with 5-aza-2′-deoxycytidine, a methylation inhibitor, restored NGALR expression. In surgically resected samples, 31 of 77 (40.3%) primary esophageal carcinomas and 46 of 77 (59.7%) paired normal tissues contained methylated NGALR alleles (P &lt; 0.05).
Conclusions: Our results suggest that NGALR hypomethylation contributes to its expression in esophageal carcinomas and that this overexpression may play a role in the pathogenesis of esophageal carcinomas.
Increased HLA-DMB Expression in the Tumor Epithelium Is Associated with Increased CTL Infiltration and Improved Prognosis in Advanced-Stage Serous Ovarian Cancer
Authors: Callahan Michael J. , Nagymanyoki Zoltan , Bonome Tomas , Johnson Michael E. , Litkouhi Babak , Sullivan Elizabeth H. , Hirsch Michelle S. , Matulonis Ursula A. , Liu Joyce , Birrer Michael J. , Berkowitz Ross S. , Mok Samuel C. 
Published: December 2008

AbstractPurpose: To evaluate the possible mechanisms influencing the infiltration of CD8 T lymphocytes into the tumor epithelium of advanced-stage serous ovarian cancers.Experimental Design: Immunohistochemical localization of CD8 T lymphocytes was done on a homogeneous population of 184 high-grade, advanced-stage serous ovarian cancer tissue specimens. Microarray analysis was done on microdissected tumor epithelium from 38 specimens to identify genes up-regulated or down-regulated in specimens with differing numbers of tumor-infiltrating CD8 T lymphocytes. Quantitative real-time PCR and immunohistochemistry were used to validate a candidate gene. Univariate and multivariate survival analyses were done combining CD8 T lymphocyte number and HLA-DMB expression with standard prognostic factors.Results: Marked CD8 T lymphocyte infiltration of the tumor epithelium is associated with a 20-month improvement in median overall survival. Additionally, when combined with cytoreduction status and age, CD8 T lymphocyte status is an independent prognostic factor for survival. Microarray analysis showed HLA-DMB, a component of the MHC II antigen presentation machinery, to be differentially expressed in specimens with an abundance of tumor-infiltrating CD8 T lymphocytes. This relationship was validated at both mRNA and protein levels. As well, high HLA-DMB expression in the tumor epithelium was associated with a significant improvement in median overall survival in both univariate and multivariate analyses.Conclusions: Tumor cell expression of HLA-DMB is associated with increased numbers of tumor-infiltrating CD8 T lymphocytes and both are associated with improved survival in advanced-stage serous ovarian cancer.
VEGF as a Marker for Outcome Among Advanced Breast Cancer Patients Receiving anti-VEGF Therapy with Bevacizumab and Vinorelbine Chemotherapy
Authors: Burstein Harold J. , Chen Yu-Hui , Parker Leroy M. , Savoie Jennifer , Younger Jerry , Kuter Irene , Ryan Paula D. , Garber Judy E. , Chen Helen , Campos Susana M. , Shulman Lawrence N. , Harris Lyndsay N. , Gelman Rebecca , Winer Eric P. 
Published: December 2008

Abstract
Background: Anti-vascular endothelial growth factor therapy (VEGF) is an important new treatment modality in oncology. We sought to determine the efficacy and safety of the humanized monoclonal anti-VEGF antibody, bevacizumab, and vinorelbine as treatment for refractory breast cancer and to explore the role of plasma VEGF as a predictor of treatment outcome.
Experimental Design: Eligible patients had received one or two prior chemotherapy regimens for metastatic breast cancer or recurred within 12 months of adjuvant therapy and had measurable disease and adequate end-organ function. Patients received bevacizumab 10 mg/kg every 2 weeks, and vinorelbine each week, until tumor progression or prohibitive toxicity. Plasma VEGF was measured at baseline.
Results: Among 56 women treated on protocol, bevacizumab and vinorelbine yielded a 34% response rate (95% confidence interval, 22-48%) and median time to progression of 5.5 months. Activity was observed regardless of tumor hormone receptor status or type or extent of prior chemotherapy. Side effects included uncomplicated neutropenia, hypertension, nasal congestion/epistaxis, and neuropathy, consistent with well-described side effects of the respective agents. Three patients had impaired wound healing following surgical procedures. There were only rare instances of thrombosis or clinically significant proteinuria. Lower levels of baseline VEGF were associated with longer time to progression.
Conclusions: Bevacizumab and vinorelbine are well tolerated and effective as treatment for refractory breast cancer. Plasma VEGF warrants further evaluation as a prognostic marker for treatment outcome in advanced breast cancer patients receiving anti-VEGF therapy.
Prognostic Factors and Survival in 324 Patients with Pancreatic Endocrine Tumor Treated at a Single Institution
Authors: Ekeblad Sara , Skogseid Britt , Dunder Kristina , Öberg Kjell , Eriksson Barbro 
Published: December 2008

Abstract
Purpose: Unequivocal pathologic markers for the prognosis of pancreatic endocrine tumors are often lacking. Suggestions for prognostic guidance include the WHO classification. Recently, a tumor-node-metastasis (TNM) staging system was proposed. We evaluate this system, as well as assess other potential prognostic factors such as tumor Ki67, size, endocrine syndrome, heredity, body mass index (BMI), and plasma chromogranin A, in a large patient material treated at a single institution.
Experimental Design: A total of 324 patients with pancreatic endocrine tumor, consecutively diagnosed and treated at a tertiary referral center, were retrospectively evaluated. Median follow-up was 54 months (range, 1-423 months). Patient and tumor data were extracted from medical records. Univariate and multivariate analyses were done to recognize factors of prognostic value.
Results: The median overall survival was 99 months (95% confidence interval, 81-117). Five- and 10-year survival rates were 64% and 44%, respectively. In univariate analysis, TNM stage, radical surgery, WHO classification, nonfunctioning tumor, Ki67 ≥2%, chromogranin A ≥3 times the upper normal limit, BMI &lt;20 kg/m2, sporadic tumor, tumor size, and referral from our primary uptake area had a significant prognostic effect. In multivariate analysis, TNM stage, WHO classification, radical surgery, and Ki67 ≥2% retained their significance. Having a nonfunctioning tumor was not an independent marker of poor prognosis and neither was heredity.
Conclusions: The recently suggested TNM staging system emerged as a useful clinical tool.
HER-2 Gene Amplification, HER-2 and Epidermal Growth Factor Receptor mRNA and Protein Expression, and Lapatinib Efficacy in Women with Metastatic Breast Cancer
Authors: Press Michael F. , Finn Richard S. , Cameron David , Di Leo Angelo , Geyer Charles E. , Villalobos Ivonne E. , Santiago Angela , Guzman Roberta , Gasparyan Armen , Ma Yanling , Danenberg Kathy , Martin Anne Marie , Williams Lisa , Oliva Cristina , Stein Steven , Gagnon Robert , Arbushites Michael , Koehler Maria T. 
Published: December 2008

Abstract
Purpose: Biomarkers from two randomized phase III trials were analyzed to optimize selection of patients for lapatinib therapy.
Experimental Design: In available breast cancer tissue from EGF30001 (paclitaxel ± lapatinib in HER-2-negative/unknown metastatic breast cancer, n = 579) and EGF100151 (capecitabine ± lapatinib in HER-2-positive metastatic breast cancer, n = 399), HER-2 gene amplification by fluorescence in situ hybridization (FISH), HER-2 mRNA by reverse transcription-PCR (RT-PCR), HER-2 protein expression by HercepTest immunohistochemistry (IHC), epidermal growth factor receptor (EGFR) mRNA level by RT-PCR, and EGFR protein by IHC were analyzed and compared with clinical outcome. HER-2 was determined by FISH in an academic reference/research laboratory and in a large, high-volume commercial reference laboratory.
Results: The HER-2 gene was amplified in 47% (344 of 733) and IHC was 3+ in 35% (279 of 798), with significant correlation (P &lt; 0.01) between FISH and IHC. Positive EGFR immunostaining (IHC 1+, 2+, or 3+) in 28% (213 of 761) correlated with EGFR mRNA levels by RT-PCR (r = 0.59; P &lt; 0.01). HER-2 gene amplification/overexpression was associated with improved clinical outcomes (progression-free survival; P &lt; 0.001) in both trials. A significant improvement in outcome was seen in FISH-positive and IHC 0, 1+, or 2+ patients. HER-2 mRNA expression correlated with HER-2 FISH (r = 0.83) and IHC status (r = 0.72; n = 138). No correlation was found between EGFR expression (IHC or mRNA) and responsiveness to lapatinib regardless of HER-2 status. Although a significant correlation with lapatinib responsiveness was observed among “HER-2-negative” breast cancer patients in the large, high-volume commercial reference laboratory, this was not confirmed in the academic reference/research laboratory.
Conclusions: Women with HER-2-positive metastatic breast cancer benefit from lapatinib, whereas women with HER-2-negative metastatic breast cancer derive no incremental benefit from lapatinib.
Genome-Wide Loss of Heterozygosity and Uniparental Disomy in BRCA1/2-Associated Ovarian Carcinomas
Authors: Walsh Christine S. , Ogawa Seishi , Scoles Daniel R. , Miller Carl W. , Kawamata Norihiko , Narod Steven A. , Koeffler H. Phillip , Karlan Beth Y. 
Published: December 2008

AbstractPurpose: The importance of the BRCA gene products in maintaining genomic stability led us to hypothesize that BRCA-associated and sporadic ovarian cancers would have distinctive genetic profiles despite similarities in histologic appearance.Experimental Design: A whole-genome copy number analysis of fresh, frozen, papillary serous ovarian cancer DNA was done using the Affymetrix 50K Xba Mapping Array using each patient's normal genomic DNA as the matched control. Loss of heterozygosity and copy number abnormalities were summarized to define regions of amplification, deletion, or uniparental disomy (UPD), defined as loss of one allele and duplication of the remaining allele. Genomic abnormalities were compared between BRCA-associated and sporadic tumors.Results: We compared 6 BRCA-associated with 14 sporadic papillary serous ovarian carcinomas. Genetic instability, measured by percentage of genome altered, was more pronounced in BRCA-associated tumors (median, 86.6%; range, 54-100%) than sporadic tumors (median, 43.6%; range, 2-83%; P = 0.009). We used frequency plots to show the proportion of cases affected by each type abnormality at each genomic region. BRCA-associated tumors showed genome-wide loss of heterozygosity primarily due to the occurrence of UPD rather than deletion. UPD was found in 100% of the BRCA-associated and 50% of the sporadic tumors profiled.Conclusions: This study reports on a previously underappreciated genetic phenomenon of UPD, which occurs frequently in ovarian cancer DNA. We observed distinct genetic patterns between BRCA-associated and sporadic ovarian cancers, suggesting that these papillary serous tumors arise from different molecular pathways.
Constitutive Activation of Signal Transducer and Activator of Transcription 5 Contributes to Tumor Growth, Epithelial-Mesenchymal Transition, and Resistance to Epidermal Growth Factor Receptor Targeting
Authors: Koppikar Priya , Lui Vivian Wai Yan , Man David , Xi Sichuan , Chai Raymond Liu , Nelson Elizabeth , Tobey Allison B.J. , Grandis Jennifer Rubin 
Published: December 2008

Abstract
Purpose: Signal transducer and activator of transcription 5 (STAT5) is activated in squamous cell carcinoma of the head and neck (SCCHN), where targeting of STAT5 inhibits tumor growth in vitro and in vivo. The role of STAT5 activation in carcinogenesis, tumor progression, and response to therapy remains incompletely understood. In this study, we investigated the effects of STAT5 activation on squamous epithelial carcinogenesis and response to therapy.
Experimental Design: The functional consequences of STAT5 activation in squamous epithelial carcinogenesis were examined using cells derived from normal (Het-1A) and transformed mucosal epithelial cells engineered to express constitutive-active mutants of STAT5.
Results: The growth rate of stable clones derived from both normal and transformed squamous epithelial cells expressing the constitutive-active STAT5 was increased. In SCCHN xenografts, tumor volumes were increased in constitutive-active STAT5 mutant cells compared with vector-transfected controls. Constitutive activation of STAT5 significantly increased cell migration and invasion through Matrigel, as well as the transforming efficiency of SCCHN cells in vitro, as assessed by soft agar assays. The constitutive-active STAT5 clones derived from SCCHN cells showed changes consistent with an epithelial-mesenchymal transition including decreased expression of E-cadherin and increased vimentin in comparison with control transfectants. In these cells, STAT5 activation was associated with resistance to cisplatin-mediated apoptosis and growth inhibition induced by the epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib.
Conclusions: These results suggest that constitutive STAT5 signaling enhances tumor growth, invasion, and epithelial-to-mesenchymal transition in squamous epithelial carcinogenesis and may contribute to resistance to epidermal growth factor receptor tyrosine kinase inhibitor and chemotherapy.
The Challenge of Herbal Therapies for Prostate Cancer
Authors: Bhatt Rupal S. , Bubley Glenn J. 
Published: December 2008

Abstract
The paper by Singh et al. shows that silibinin inhibits prostate cancer growth in the TRAMP mouse model. Among its other properties, silibinin inhibits the progression of prostate cancer by decreasing angiogenesis and tumor invasion. Identification of the biological effects of herbal remedies such as silibinin is critical for their development as anticancer treatments.
Pragmatism, Piety, and Environmental Ethics
Authors: Minteer Ben 
Published: December 2008

AbstractThe rise of pragmatism in environmental ethics in the 1990s was driven by several factors, including dissatisfaction with the field's dominant nonanthropocentrism and the desire to increase the political and policy influence of environmental ethics. Yet despite an emphasis on human experience as the foundation of environmental values and action, environmental pragmatists have paid little attention to the religious dimensions of human-nature interactions. In this paper I attempt to address this neglect by exploring the religious thought of John Dewey, arguably the most significant pragmatist philosopher of the classical period. I suggest that Dewey's understanding of religiosity—in particular, his concept of "natural piety"—instructs us to respect nonhuman nature as a source of human imaginative experience and self-unification. Although Dewey's naturalized approach to religious experience retains a broadly instrumentalist view toward nature, it is an instrumentality that supports a humble and appreciative attitude toward the environment and a sense of caution regarding the modification of nature for human purposes. I conclude by arguing that the recovery of Dewey's attitude of natural piety provides an important constraint on more aggressively anthropocentric approaches to human-nature relations, including those promoting sustainability as an alternative to traditional limits-based environmentalism.
Sacrifice and Sustainability
Authors: Chapple Christopher Key 
Published: December 2008

AbstractSacrifice in the Jewish, Hellenistic, and Christian traditions involves a giving up, a surrendering of something for the sake of a greater good. Sacrifice in times past took the form of a bloody offering. In Christianity this has been replaced with the Eucharist, which promotes human conscience and adherence to a moral code. Sacrifice in the ancient Vedic traditions of India entailed the offering of an animal or the symbolic offering of a human being that correlated bodily parts to functions of society and the cosmos. Sacrifice in India in rare instances still includes the killing of animals. Ritual throughout India, known as Puja, celebrates the body, the senses, and their connection with the physical world through offerings of fruits, flowers, incense, and other ritual objects.The contemporary challenge presented by the need to develop sustainable lifestyles can draw from both traditions of sacrifice. The Mediterranean model urges people to do with less for the sake of a greater good. The Indic model encourages people to recognize the web of relations among humans, nature, and animals and develop sensitivity to the need for the protection of the earth. Both models of sacrifice can serve as inspiration for the development of reasonable patterns for resource management.
The Greening of China: The Constructive Postmodern Movement in Contemporary China
Authors: McDaniel Jay 
Published: December 2008

AbstractWhen China's economy began to grow in the 1980's, many people throughout the world, including many people in China, hoped that China might offer the world a unique model of development. Many Chinese carry this hope even today, and some among them are turning to Whiteheadian or process thought for guidance. Of course Whitehead is a Western philosopher, but they see in his ideas deep similarities with Chinese ways of thinking, enabling Chinese to articulate traditional points of view in a modern setting. With help from Whitehead they are developing what they call a "Constructively Postmodern" approach to China's future. This essay introduces this movement, its core ideas, and some of its key figures, linking them with the theme of religion and sustainability.
Nollywood Films and the Cultural Imperialism Hypothesis
Authors: Akpabio Eno , Mustapha-Lambe Kayode 
Published: December 2008

Abstract
From the viewpoint of the cultural imperialism hypothesis and its complications, the overall aim of this study was to find out if foreign films still had a stranglehold on Nigerian audience members. The findings indicate that a majority of respondents watch and have a favorable attitude towards Nigerian home video films. However, in terms of preference between local and foreign films, a small percentage indicated preference for the former. The study concludes that the high quality of production of American films accounts for the favorable views held by respondents, even though it is apparent that these and other foreign productions no longer have a captive market in Nigeria.
Between Magic and Logic: Globalization and the Challenge of Medical Collaboration in Ngugi's Wizard Of The Crow
Authors: Olaoluwa Senayon 
Published: December 2008

AbstractPerhaps one of the ways by which the Third World, especially Africa, may negotiate its position in the unfolding global politics is through what has been described as the necessary "fusion of ideas and cultures" (Anyidoho 2006:158), along an intellectual axis for Africa's developmental goals. Therefore, this paper seeks to explore one of the areas of such intellectual contributions through a reading and analysis of the developmental angle of Ngugi wa Thiong'o's latest novel Wizard of the Crow (2006). Although the novel has been aptly described as a novel that reflects "on Africa's dysfunctions… and possibilities" (Reed Business Information 2006) in the age of globalization, this paper seeks to transcend the overwhelming concern about unbridled African despotism caught in the mesh of global politics, which the author critiques in the novel and which many a reviewer has commented upon in order to consider the developmental rays of hope that fire through the narrative simultaneously. By so doing, the paper is concerned with one of the "possibilities" in the positive sense of the word along the line of the reinvention of autochthonous African medical practice, otherwise derogatorily designated as magic and sorcery. The reason is that it is obvious in the novel that there is a possibility of investing the indigenous medical practice with a logical modern appeal to the extent of finding collaboration with Western medical practice in order to earn better reception across global spatial boundaries. In the process of this exploration, I also engage the notion of modernity.
From Drops of Blood: Charisma and Political Legitimacy in the translatio of the 'Uthmānic Codex of al-Andalus
Authors: Zadeh Travis 
Published: December 2008

AbstractThe account of the 'Uthmānic mushaf of Córdoba, which passed from generation to generation across the western shores of Islam, has played a prominent role in the history of al-Andalus and the Maghrib. The prized codex appears throughout historiographical and literary discourses, stretching from the Hispano-Umayyad caliphate to the dynasty of the Banū Marīn in North Africa. Brought into battle against Christians and fellow Muslims, decorated with ornate coverings, and made into the object of countless panegyrics, the 'Uthmānic codex of al-Andalus offers a glimpse into a sustained network of meaning and power. The codex came symbolically to align successive Muslim dynasties to the early history of Islam. Drawing attention to the parallel phenomena of the furta sacra and the translatio of relics in medieval Christian tradition, this article explores the broader political, religious, and literary dimensions which silhouette the veneration toward the 'Uthmānic codex.