bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histogenesis of Clear Cell Adenocarcinoma in the Urinary Tract: Evidence of Urothelial Origin
Authors: Sung Ming-Tse , Zhang Shaobo , MacLennan Gregory T. , Lopez-Beltran Antonio , Montironi Rodolfo , Wang Mingsheng , Tan Puay-Hoon , Cheng Liang 
Published: April 2008

Abstract
Purpose: Clear cell adenocarcinoma in the urinary tract is a rare entity with an appearance resembling its counterpart in the female genital tract. Although several theories have been proposed about its origin, its exact histogenesis has remained uncertain.
Experimental Design: We integrated molecular genetic evaluation by fluorescence in situ hybridization and X-chromosome inactivation with conventional morphologic and immunohistochemical analyses in 12 patients with clear cell adenocarcinomas in the urinary tract.
Results: Concurrent urothelial carcinoma or urothelial carcinoma in situ was present in six cases (50%) and foci of cystitis glandularis were observed in four cases (33%). Neither intestinal metaplasia nor Müllerian component was identified in any case. Cytoplasmic expression of α-methylacyl-CoA racemase was demonstrable in 10 of 12 tumors (83%). Moderate to diffuse immunostaining for cytokeratin 7 was identified in all 12 tumors (100%), whereas only 3 of 12 (25%) tumors showed positive immunostaining for cytokeratin 20. Focal uroplakin III staining was seen in 6 of 12 tumors (50%). In five cases (42%), focal to moderate CD10 immunoreactivity was observed. Immunostains for OCT4 and CDX2 were completely negative in all tumors. In UroVysion fluorescence in situ hybridization assays, all tumors displayed chromosomal alterations similar to those commonly found in urothelial carcinoma. Identical patterns of nonrandom X-chromosome inactivation in concurrent clear cell adenocarcinoma and urothelial neoplasia were identified in two informative female cases.
Conclusions: Our findings support an urothelial origin for most clear cell adenocarcinomas of the urinary tract, despite their morphologic resemblance to certain Müllerian-derived tumors of the female genital tract.
Lupeol Inhibits Growth of Highly Aggressive Human Metastatic Melanoma Cells In vitro and In vivo by Inducing Apoptosis
Authors: Saleem Mohammad , Maddodi Nityanand , Abu Zaid Mohammad , Khan Naghma , bin Hafeez Bilal , Asim Mohammad , Suh Yewseok , Yun Jung-Mi , Setaluri Vijayasaradhi , Mukhtar Hasan 
Published: April 2008

Abstract
Purpose: Poor prognosis of metastatic melanoma mandates the development of novel strategies for its treatment and prevention. In this study, the effect of lupeol, a diet-based triterpene, was determined on the growth and tumorigenicity of human melanoma cells in vitro and in vivo.
Experimental Design: Normal human melanocytes, and human metastatic (451Lu) and nonmetastatic (WM35) cells were treated with lupeol; its effect on growth, proliferation, and apoptosis were evaluated. Further athymic nude mice bearing 451Lu cell–originated tumors were administered with lupeol thrice a week, and its effect on tumor growth and surrogate biomarkers was evaluated.
Results: Lupeol significantly decreased the viability of 451Lu and WM35 melanoma cells but had only a marginal effect on normal human melanocyte cells at similar doses. Lupeol treatment of 451Lu cells caused (a) G1-S phase cell cycle arrest and apoptosis; (b) down-regulation of Bcl2 and up-regulation of Bax; (c) activation of caspase-3 and induction of poly(ADP)ribose polymerase cleavage; (d) decreased expression of cyclin D1, cyclin D2, and cdk2; and (e) increased expression of p21 protein. Next, lupeol significantly reduced 451Lu tumor growth in athymic nude mice and modulated the expression of proliferation markers, apoptotic markers, and cell cycle regulatory molecules in tumor xenografts.
Conclusion: Our findings showed the anticancer efficacy of lupeol with mechanistic rationale against metastatic human melanoma cells. We suggest that lupeol, alone or as an adjuvant to current therapies, could be useful for the management of human melanoma.
In vivoOptical Coherence Tomography Imaging of Preinvasive Bronchial Lesions
Authors: Lam Stephen , Standish Beau , Baldwin Corisande , McWilliams Annette , leRiche Jean , Gazdar Adi , Vitkin Alex I. , Yang Victor , Ikeda Norihiko , MacAulay Calum 
Published: April 2008

AbstractPurpose: Optical coherence tomography (OCT) is an optical imaging method that can visualize cellular and extracellular structures at and below tissue surface. The objective of the study was to determine if OCT could characterize preneoplastic changes in the bronchial epithelium identified by autofluorescence bronchoscopy.Experimental Design: A 1.5-mm fiberoptic probe was inserted via a bronchoscope into the airways of 138 volunteer heavy smokers participating in a chemoprevention trial and 10 patients with lung cancer to evaluate areas that were found to be normal or abnormal on autofluorescence bronchoscopy. Radial scanning of the airways was done to generate OCT images in real time. Following OCT imaging, the same sites were biopsied for pathologic correlation.Results: A total of 281 OCT images and the corresponding bronchial biopsies were obtained. The histopathology of these areas includes 145 normal/hyperplasia, 61 metaplasia, 39 mild dysplasia, 10 moderate dysplasia, 6 severe dysplasia, 7 carcinoma in situ, and 13 invasive carcinomas. Quantitative measurement of the epithelial thickness showed that invasive carcinoma was significantly different than carcinoma in situ (P = 0.004) and dysplasia was significantly different than metaplasia or hyperplasia (P = 0.002). In addition, nuclei of the cells corresponding to histologic results became more discernible in lesions that were moderate dysplasia or worse compared with lower-grade lesions.Conclusion: Preliminary data suggest that autofluorescence bronchoscopy–guided OCT imaging of bronchial lesions is technically feasible. OCT may be a promising nonbiopsy tool for in vivo imaging of preneoplastic bronchial lesions to study their natural history and the effect of chemopreventive intervention.
Direct Visualization of Heterogeneous Extravascular Distribution of Trastuzumab in Human Epidermal Growth Factor Receptor Type 2 Overexpressing Xenografts
Authors: Baker Jennifer H.E. , Lindquist Kirstin E. , Huxham Lynsey A. , Kyle Alastair H. , Sy Jonathan T. , Minchinton Andrew I. 
Published: April 2008

Abstract
Purpose: The high molecular weight and binding affinity of trastuzumab, a monoclonal antibody in use for treatment of breast cancers overexpressing human epidermal growth factor receptor type 2 (HER2), in combination with microenvironmental factors, may limit its distribution and efficacy. We assessed and mapped the distribution of systemically given, unlabeled trastuzumab at micrometer resolution in tumor xenografts using immunohistochemistry.
Experimental Design: Mice bearing MDA-435/LCC6HER2 xenografts were given single doses of 4 or 20 mg/kg unlabeled trastuzumab with tumor harvest at various time points thereafter; bound trastuzumab was imaged directly in tumor cryosections using fluorescently tagged antihuman secondary antibodies. Combinations of additional markers, including HER2, 5-bromo-2-deoxyuridine, CD31, DioC7(3), desmin, and collagen IV were also mapped on the same tumor sections.
Results: Distribution of trastuzumab in MDA-435/LCC6HER2 tumors is found to be heterogeneous, with tumor margins saturating more thoroughly in doses and times analyzed. Considerable intervessel heterogeneity is also seen. For example, in unsaturated tissues, there remain perfused vessels without any trastuzumab in addition to vessels with a few layers of positively stained perivascular cells, in addition to vessels with bound drug up to 150 μm away. This heterogeneity is independent of HER2 expression, microvessel density, and perfusion. A slightly greater proportion of vessels were associated with pericytes in sections with greater trastuzumab saturation, but this would not adequately account for observed heterogeneous trastuzumab distribution.
Conclusions: Complete penetration of trastuzumab in tumor tissue was not seen in our study, leaving the possibility that inadequate distribution may represent a mechanism for resistance to trastuzumab.
Endoglin (CD105): A Marker of Tumor Vasculature and Potential Target for Therapy
Authors: Dallas Nikolaos A. , Samuel Shaija , Xia Ling , Fan Fan , Gray Michael J. , Lim Sherry J. , Ellis Lee M. 
Published: April 2008

Abstract
Endoglin (CD105) is an accessory protein of the transforming growth factor-β receptor system expressed on vascular endothelial cells. Mutation of the endoglin gene is associated with hereditary hemorrhagic telangiectasias, or Osler-Weber-Rendu syndrome, and has been studied extensively in the context of this disease. The expression of endoglin is elevated on the endothelial cells of healing wounds, developing embryos, inflammatory tissues, and solid tumors. Endoglin is a marker of activated endothelium, and its vascular expression is limited to proliferating cells. Recent studies identified endoglin expression in several solid tumor types, with the level of expression correlating with various clinicopathologic factors including decreased survival and presence of metastases. Attempts to target endoglin and the cells that express this protein in tumor-bearing mice have yielded promising results.
Intratumoral Epiregulin Is a Marker of Advanced Disease in Non–Small Cell Lung Cancer Patients and Confers Invasive Properties onEGFR-Mutant Cells
Authors: Zhang Jie , Iwanaga Kentaro , Choi Kuicheon C. , Wislez Marie , Raso Maria Gabriela , Wei Wei , Wistuba Ignacio I. , Kurie Jonathan M. 
Published: April 2008

AbstractNon–small cell lung cancer (NSCLC) cells with activating epidermal growth factor receptor (EGFR) somatic mutations have unique biological properties, including high expression of the ErbB ligand epiregulin; however, the biological role of epiregulin in these cells has not been elucidated. To examine its role, we used an immunohistochemical approach to detect epiregulin expression in NSCLC biopsy samples and pharmacologic and genetic approaches to inhibit epiregulin in cultured NSCLC cells. In NSCLC biopsy samples, epiregulin was detected in 237 of 366 (64.7%) tumors, which correlated with nodal metastasis and a shorter duration of survival. In EGFR-mutant NSCLC cell lines, treatment with a small-molecule EGFR tyrosine kinase inhibitor diminished mRNA levels of the gene encoding epiregulin (EREG). The ability of EGFR-mutant NSCLC cells to invade through Matrigel in vitro was inhibited by treatment with an anti-epiregulin neutralizing antibody or by transfection with an EREG short hairpin RNA. Collectively, these findings show that epiregulin expression correlated with advanced disease, was EGFR dependent, and conferred invasive properties on NSCLC cells. Additional studies are warranted in NSCLC patients to evaluate whether epiregulin expression predicts the metastatic potential of primary tumors and whether anti-epiregulin treatment strategies are efficacious in the prevention of metastasis.
Targeting the Activator Protein 1 Transcription Factor for the Prevention of Estrogen Receptor–Negative Mammary Tumors
Authors: Shen Qiang , Uray Ivan P. , Li Yuxin , Zhang Yun , Hill Jamal , Xu Xiao-Chun , Young Matthew R. , Gunther Edward J. , Hilsenbeck Susan G. , Colburn Nancy H. , Chodosh Lewis A. , Brown Powel H. 
Published: April 2008

Abstract
The oncogene erbB2 is overexpressed in 20% to 30% human breast cancers and is most commonly overexpressed in estrogen receptor (ER)–negative breast cancers. Transgenic mice expressing erbB2 develop ER-negative mammary tumors, mimicking human breast carcinogenesis. Previously, we have shown that activator protein 1 (AP-1) regulates proliferation of ER-negative breast cancer cells. We hypothesized that blockade of AP-1 in mouse mammary epithelial cells will suppress ER-negative tumorigenesis induced by erbB2. Trigenic erbB2 mice were generated by crossing a bigenic pUHD-Tam67/MMTV-rtTA mouse to a MMTV-erbB2 mouse. The resulting trigenic mice develop tumors and express a doxycycline-inducible c-Jun dominant negative mutant (Tam67) in the mammary glands. In vivo AP-1 blockade by Tam67 expression started delayed mammary tumor formation in MMTV-erbB2 mice by more than 11 weeks. By 52 weeks of age, 100% (18 of 18) of the untreated animals had developed mammary tumors, whereas 56% (9 of 16) of the doxycycline-treated trigenic mice developed tumors. In addition, the tumors that arose in the AP-1–blocked erbB2 mice failed to express Tam67. Twenty-five percent of the doxycycline-treated MMTV-erbB2 mice survived more than 72 weeks of age without developing mammary tumors. Examination of normal-appearing mammary glands from these mice showed that AP-1 blockade by Tam67 also significantly prevents the development of premalignant lesions in these glands. The expression of erbB2 either in normal mammary tissue or in mammary tumors was not altered. Our results show that blocking the AP-1 signaling in mammary cells suppresses erbB2-induced transformation, and show that the AP-1 transcription factor is a critical transducer of erbB2. These results provide a scientific rationale to develop targeted drugs that inhibit AP-1 to prevent the development of ER-negative breast cancer.
Cardiovascular Risk of Celecoxib in 6 Randomized Placebo-Controlled Trials
Authors: Solomon Scott D. , Wittes Janet , Finn Peter V. , Fowler Robert , Viner Jaye , Bertagnolli Monica M. , Arber Nadir , Levin Bernard , Meinert Curtis L. , Martin Barbara , Pater Joseph L. , Goss Paul E. , Lance Peter , Obara Stefanie , Chew Emily Y. , Kim Jonghyeon , Arndt Gretchen , Hawk Ernest 
Published: April 2008

Background—Observational studies and randomized trials have reported increased cardiovascular risk associated with cyclooxygenase-2 inhibitors. Prior placebo-controlled randomized studies had limited ability to assess the relationship of either celecoxib dose or pretreatment cardiovascular status to risk associated with celecoxib. Our aim was to assess the cardiovascular risk associated with celecoxib in 3 dose regimens and to assess the relationship between baseline cardiovascular risk and effect of celecoxib on cardiovascular events.Methods and Results—We performed a patient-level pooled analysis of adjudicated data from 7950 patients in 6 placebo-controlled trials comparing celecoxib with placebo for conditions other than arthritis with a planned follow-up of at least 3 years. Patients were administered celecoxib in 3 dose regimens: 400 mg QD, 200 mg BID, or 400 mg BID. From the pooled data, we calculated a hazard ratio for all dose regimens combined and individual hazard ratios for each dose regimen and examined whether celecoxib-related risk was associated with baseline cardiovascular risk. The primary end point was the combination of cardiovascular death, myocardial infarction, stroke, heart failure, or thromboembolic event. With 16 070 patient-years of follow-up, the hazard ratio for the composite end point combining the tested doses was 1.6 (95% CI, 1.1 to 2.3). The risk, which increased with dose regimen (P=0.0005), was lowest for the 400-mg-QD dose (hazard ratio, 1.1; 95% CI, 0.6 to 2.0), intermediate for the 200-mg-BID dose (hazard ratio, 1.8; 95% CI, 1.1 to 3.1), and highest for the 400-mg-BID dose (hazard ratio, 3.1; 95% CI, 1.5 to 6.1). Patients at highest baseline risk demonstrated disproportionately greater risk of celecoxib-related adverse events (Pfor interaction=0.034).Conclusions—We observed evidence of differential cardiovascular risk as a function of celecoxib dose regimen and baseline cardiovascular risk. By further clarifying the extent of celecoxib-related cardiovascular risk, these findings may help guide treatment decisions for patients who derive clinical benefit from selective cyclooxygenase-2 inhibition.
Heterosexism and the Interpretation of Romans 1:18-32
Authors: Martin Dale B. 
Published: April 2008

AbstractThis article, concentrating on two articles by Richard Hays, critiques recent interpretations of Rom. 1:18-32. Modern interpreters, influenced more by particularly modern forms of heterosexism and its construction of homosexuality, desire, and "nature" than by a straightforward historical-critical reading of Paul's letter, portray Paul as referring to the "Fall" of Genesis 1-3 in Romans 1. Paul, it is assumed, takes homosexuality to be a sign of "humanity's fallen state." These interpreters, therefore, inscribe homosexual desire into universal fallen humanity in a way that Paul does not do. For one thing, Paul is referring not to the Fall in Romans 1 but to the invention of idolatry and polytheism by the Gentiles; homosexual intercourse is therefore not a symptom of "the Fall" but of Gentile polytheism. For another, Paul is not giving an etiology of homosexual desire, which for him as for most ancients was not different from heterosexual desire, but an etiology of homosexual intercourse. Furthermore, modern scholars misconstrue Paul's references to "nature" and acts "contrary to nature" because they import into Paul's discourse particularly modern notions of "natural" and "unnatural" not available in the ancient world. Heterosexist scholars interpret Paul the way they do not because they are simply and objectively "reading the text," as they claim, but because of their implication in homophobia, a particularly modern ideological system that constructs desire, "nature," and sexuality in particular ways.
At the Beginning: the Status of Women in Neolithic and Shang China*
Authors: Keightley David N. 
Published: April 2008

AbstractDespite the local and frequently disparate nature of the evidence, both archaeological and inscriptional, and despite the difficulties involved in interpreting that evidence, the study of particular topics-such as secondary burial, following-in-death, sex ratios, marriage patterns, childbearing, Shang royal consorts, Shang ancestresses, and lineage terminology-permits the general conclusion that from at least the Late Neolithic until the Late Shang the political and economic status of most women in China, as represented in burial practices and recorded religious beliefs, was, despite some significant exceptions, inferior to that of most men. The present article provides an initial exploration of how such status distinctions emerged and how they functioned.
Anat-Yahu, Some Other Deities, and the Jews of Elephantine
Authors: Van Der Toorn Karel 
Published: April 2008

AbstractThis contribution discusses the problem of the origin of the goddess Anat-Yahu and the related issue of the cultural background of the Jewish colony at Elephantine. It is argued that Anat-Yahu has been modeled after Anat-Bethel. Contrary to a current opinion, neither Bethel nor Anat-Bethel can be regarded as Phoenician gods. They are late Aramaean gods whose cult is confined to North Syria. Anat-Yahu must be regarded as an Aramaean creation, elicited by the identification of Yahu with Bethel. The latter identification was one of the results of the Aramaean migration to Samaria, either enforced or voluntary, at the end of the 8th century. The theory here proposed assumes that the Jews and Aramaeans of the colonies at Elephantine and Syene originated predominantly from Northern Israel. The ultimate origins of the Aramaean settlers go back to North Syria. The Jewish character of the Elephantine colony is secondary. It can be accounted for by the Judaean transit of Israelite colonists on their way to Egypt and the secondary influx of actual Judaeans. Yet, despite the common designation of the Elephantine colony as "Jewish", its religion is in fact Israelite.
Attitudes toward Animals: Species Ratings
Authors: Driscoll Janis Wiley 
Published: April 2008

AbstractA questionnaire was used to assess people's attitudes toward 33 species of animals on six dimensions (useful-useless, smart-stupid, responsive-unresponsive, lovable-unlovable, safe-dangerous, and important-unimportant). A cluster analysis resulted in five groups of animals with similar ratings on these dimensions. Respondents were also asked about their attitudes toward hunting, fishing, and medical, scientific and product-testing research using animals.
Pet Ownership and Adults' Views on the Use of Animals
Authors: Hepper Peter G. , Wells Deborah L. 
Published: April 2008

AbstractFour hundred and twenty-two adults completed a postal questionnaire in which they provided information regarding pet ownership and their attitudes toward 13 issues involving the use of animals. Over 63% of the sample owned a household pet, with the dog being the most common. Household pets were more commonly owned by respondents who were married, younger than 65 years of age, living in detached houses, or with a child/children present in the home. Most concern was expressed toward those types of animal uses which lead to death or injury, especially dog fighting. Females expressed more disagreement than males with most of the uses o f animals examined. Dog owners expressed more approval offox-hunting and hare-coursing than non-dog owners, and horse owners expressed more approval offox-hunting than non-horse owners. This study reveals that some of the ways in which people use animals are considered more acceptable than others, and suggests that it is incorrect to group different kinds of animal use into one broad category. The authors argue that future years may see a shift in the way society uses animals, from manipulation toward care for their well-being.
Health Correlates of Compatibility and Attachment in Human-Companion Animal Relationships
Authors: George Ross St. , Jones Boyd , Spicer John , Claire Budge R. 
Published: April 2008

AbstractThe relationship between animal ownership and owners' health has received increasing attention in the recent human-companion animal literature. This article considers a new aspect of the human-companion animal relationship, that of compatibility between pet and owner. Compatibility is viewed as the fit between the animal and the owner on physical, behavioral, and psychological dimensions. A postal survey was used to test the hypothesis that compatibility has influences on physical and mental health that are independent of those due to owners' level ofpet attachment and human social support. A sample group of 176 pet owners completed a questionnaire containing a new measure of compatibility as well as standard measures of pet attachment, human social support, and mental and physical health. Results of multiple regression analyses indicated that people who are relatively more compatible with their pets report better mental health overall and fewer physical symptoms. Social support was positively associated with mental health. Pet attachment was also positively associated with mental health, but negatively with physical health.