bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Analysis of Non–Small Cell Lung Cancer Identifies Subsets with Different Sensitivity to Insulin-like Growth Factor I Receptor Inhibition
Authors: Gualberto Antonio , Dolled-Filhart Marisa , Gustavson Mark , Christiansen Jason , Wang Yu-Fen , Hixon Mary L. , Reynolds Jennifer , McDonald Sandra , Ang Agnes , Rimm David L. , Langer Corey J. , Blakely Johnetta , Garland Linda , Paz-Ares Luis G. , Karp Daniel D. , Lee Adrian V. 
Published: July 2010

Abstract
Purpose: This study aimed to identify molecular determinants of sensitivity of non–small cell lung cancer (NSCLC) to anti–insulin-like growth factor receptor (IGF-IR) therapy.
Experimental Design: A total of 216 tumor samples were investigated, of which 165 consisted of retrospective analyses of banked tissue and an additional 51 were from patients enrolled in a phase II study of figitumumab, a monoclonal antibody against IGF-IR, in stage IIIb/IV NSCLC. Biomarkers assessed included IGF-IR, epidermal growth factor receptor, IGF-II, IGF-IIR, insulin receptor substrate 1 (IRS-1), IRS-2, vimentin, and E-cadherin. Subcellular localization of IRS-1 and phosphorylation levels of mitogen-activated protein kinase and Akt1 were also analyzed.
Results: IGF-IR was differentially expressed across histologic subtypes (P = 0.04), with highest levels observed in squamous cell tumors. Elevated IGF-IR expression was also observed in a small number of squamous cell tumors responding to chemotherapy combined with figitumumab (P = 0.008). Because no other biomarker/response interaction was observed using classical histologic subtyping, a molecular approach was undertaken to segment NSCLC into mechanism-based subpopulations. Principal component analysis and unsupervised Bayesian clustering identified three NSCLC subsets that resembled the steps of the epithelial to mesenchymal transition: E-cadherin high/IRS-1 low (epithelial-like), E-cadherin intermediate/IRS-1 high (transitional), and E-cadherin low/IRS-1 low (mesenchymal-like). Several markers of the IGF-IR pathway were overexpressed in the transitional subset. Furthermore, a higher response rate to the combination of chemotherapy and figitumumab was observed in transitional tumors (71%) compared with those in the mesenchymal-like subset (32%; P = 0.03). Only one epithelial-like tumor was identified in the phase II study, suggesting that advanced NSCLC has undergone significant dedifferentiation at diagnosis.
Conclusion: NSCLC comprises molecular subsets with differential sensitivity to IGF-IR inhibition. Clin Cancer Res; 16(18); 4654–65. ©2010 AACR.
Monoclonal Antibodies to Fibroblast Growth Factor Receptor 2 Effectively Inhibit Growth of Gastric Tumor Xenografts
Authors: Zhao Wei-meng , Wang Lihong , Park Hangil , Chhim Sophea , Tanphanich Melanie , Yashiro Masakazu , Kim K. Jin 
Published: July 2010

Abstract
Purpose: Overexpression of fibroblast growth factor receptor 2 (FGFR2) may be a causative factor of a number of human tumors, especially gastric tumors of the poorly differentiated type. We investigated whether monoclonal antibodies (mAbs) directed against FGFR2 can inhibit the growth of tumors in xenograft models.
Experimental Design: We generated and characterized 3 mAbs that recognize different epitopes on FGFR2: GAL-FR21, GAL-FR22, and GAL-FR23. The ability of the mAbs to recognize the FGFR2IIIb and FGFR2IIIc isoforms of FGFR2 was determined, as was their ability to block binding of FGF ligands to FGFR2. The capability of the mAbs to inhibit FGF-induced FGFR2 phosphorylation and to downmodulate FGFR2 expression was also investigated. Finally, the ability of the anti-FGFR2 mAbs to inhibit tumor growth was determined by establishing xenografts of SNU-16 and OCUM-2M human gastric tumor cell lines in nude mice, treating with each mAb (0.5–5 mg/kg intraperitoneally twice weekly) and monitoring tumor size.
Results: Of the 3 mAbs, GAL-FR21 binds only the FGFR2IIIb isoform, whereas GAL-FR22 and GAL-FR23 bind to both the FGFR2IIIb and FGFR2IIIc forms, with binding regions respectively in the D3, D2-D3, and D1 domains of FGFR2. GAL-FR21 and GAL-FR22 blocked the binding of FGF2, FGF7 and FGF10 to FGFR2IIIb. GAL-FR21 inhibited FGF2 and FGF7 induced phosphorylation of FGFR2, and both mAbs downmodulated FGFR2 expression on SNU-16 cells. These mAbs effectively inhibited growth of established SNU-16 and OCUM-2M xenografts in mice.
Conclusions: Anti-FGFR2 mAbs GAL-FR21 and GAL-FR22 have potential for the treatment of gastric and other tumors. Clin Cancer Res; 16(23); 5750–58. ©2010 AACR.
The Serine Protease HtrA1 Specifically Interacts and Degrades the Tuberous Sclerosis Complex 2 Protein
Authors: Campioni Mara , Severino Anna , Manente Lucrezia , Tuduce Ioana L. , Toldo Stefano , Caraglia Michele , Crispi Stefania , Ehrmann Michael , He Xiaoping , Maguire Jacie , De Falco Maria , De Luca Antonio , Shridhar Viji , Baldi Alfonso 
Published: July 2010

Abstract
Hamartin and tuberin are products of the tumor suppressor genes TSC1 and TSC2, respectively. Mutations affecting either gene result in the tuberous sclerosis syndrome, a neurologic genetic disorder characterized by the formation of multiple benign tumors or hamartomas. In this study, we report the identification of TSC2, but not TSC1, as a substrate of HtrA1, a member of the human HtrA family proteins of serine proteases. We show the direct interaction and colocalization in the cytoplasm of HtrA1 and TSC2 and that HtrA1 cleaves TSC2 both in vitro and in vivo. Finally, we show that alterations in HtrA1 expression cause modifications in phosphorylation status of two downstream targets of TSC2: 4E-BP1 and S6K. Our data suggest that, under particular physiologic or pathologic conditions, HtrA1 degrades TSC2 and activates the downstream targets. Considering that HtrA1 levels are significantly increased during embryogenesis, we speculate that one of the targets of HtrA1 activity during fetal development is the TSC2-TSC1 pathway. Mol Cancer Res; 8(9); 1248–60. ©2010 AACR.
High-Density Lipoprotein Induces Proliferation and Migration of Human Prostate Androgen–Independent Cancer Cells by an ABCA1-Dependent Mechanism
Authors: Sekine Yoshitaka , Demosky Steve J. , Stonik John A. , Furuya Yosuke , Koike Hidekazu , Suzuki Kazuhiro , Remaley Alan T. 
Published: July 2010

Abstract
Androgen deprivation therapy for prostate cancer leads to a significant increase of high-density lipoprotein (HDL), which is generally viewed as beneficial, particularly for cardiovascular disease, but the effect of HDL on prostate cancer is unknown. In this study, we investigated the effect of HDL on prostate cancer cell proliferation, migration, intracellular cholesterol levels, and the role of cholesterol transporters, namely ABCA1, ABCG1, and SR-BI in these processes. HDL induced cell proliferation and migration of the androgen-independent PC-3 and DU145 cells by a mechanism involving extracellular signal-regulated kinase (ERK) 1/2 and Akt, but had no effect on the androgen-dependent LNCaP cell, which did not express ABCA1 unlike the other cell lines. Treatment with HDL did not significantly alter the cholesterol content of the cell lines. Knockdown of ABCA1 but not ABCG1 or SR-BI by small interfering RNA (siRNA) inhibited HDL-induced cell proliferation, migration, and ERK1/2 and Akt signal transduction in PC-3 cells. Moreover, after treatment of LNCaP cells with charcoal-stripped fetal bovine serum, ABCA1 was induced ∼10-fold, enabling HDL to induce ERK1/2 activation, whereas small interfering RNA knockdown of ABCA1 inhibited HDL-induced ERK1/2 activation. Simvastatin, which inhibited ABCA1 expression in PC-3 and DU145 cells, attenuated HDL-induced PC-3 and DU145 cell proliferation, migration, and ERK1/2 and Akt phosphorylation. In human prostate biopsy samples, ABCA1 mRNA expression was ∼2-fold higher in the androgen deprivation therapy group than in subjects with benign prostatic hyperplasia or pretreatment prostate cancer groups. In summary, these results suggest that HDL by an ABCA1-dependent mechanism can mediate signal transduction, leading to increased proliferation and migration of prostate cancer cells. Mol Cancer Res; 8(9); 1284–94. ©2010 AACR.
Increased Risk of Stroke Associated With Nonsteroidal Anti-Inflammatory Drugs
Authors: Chang Chia-Hsuin , Shau Wen-Yi , Kuo Chuei-Wen , Chen Shu-Ting , Lai Mei-Shu 
Published: July 2010

Background and Purpose—Limited studies assessed cerebrovascular safety of individual nonsteroidal anti-inflammatory drugs (NSAIDs). We evaluated the risk of ischemic and hemorrhagic stroke associated with short-term use of selective and nonselective NSAIDs in a Chinese population with a high incidence of stroke.Methods—A retrospective case–crossover study was conducted by analyzing the Taiwan National Health Insurance Database. We identified all ischemic and hemorrhagic stroke patients in 2006, aged ≥20 years, based on International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes from inpatient claims and defined the index date as the date of hospitalization. For each patient, we defined case period as 1 to 30 days before the index date and control period as 91 to 120 days before the index date. A pharmacy prescription database was searched for NSAID use during the case and control periods. We calculated adjusted ORs and their 95% CIs with a conditional logistic regression model.Results—A total of 28 424 patients with ischemic stroke and 9456 patients with hemorrhagic stroke were included. For ischemic stroke, a modest increased risk was evident for all oral NSAIDs with adjusted ORs (95% CI) ranging from1.20 (1.00 to 1.44) for celecoxib to 1.90 (1.39 to 2.60) for ketorolac. For hemorrhagic stroke, oral ketorolac was associated with a significantly higher risk with OR of 2.69 (1.56 to 4.66). Significantly increased risk was found for parenteral NSAIDs, in particular ketorolac, with an OR of 3.92 (3.25 to 4.72) for ischemic stroke and 5.98 (4.40 to 8.13) for hemorrhagic stroke.Conclusions—Use of selective and nonselective NSAIDs was associated with an increased risk of both ischemic and hemorrhagic stroke, strikingly high for parenteral ketorolac.
The Birth of Esotericism from the Spirit of Protestantism La naissance de l'ésotérisme à partir de l'esprit du protestantisme
Authors: Hanegraaff Wouter 
Published: July 2010

AbstractCet article traite de l'émergence et du développement historiques des manières dont nous entendons actuellement l'“ésotérisme occidental” compris comme domaine relativement autonome de la recherche universitaire. Il en traite en explorant un certain nombre de moments possibles de sa “naissance”, en partant du présent et, à partir de là, en remontant dans le temps. Déterminantes pour l'émergence de l'ésotérisme occidental en tant que concept sont les années 1992 (L'ésotérisme, d'Antoine Faivre), 1965 (création de la première chaire d'Histoire de l'ésotérisme occidental, à l'E.P.H.E. [Paris]), 1933 (le début des conférences Eranos), et 1828 (l'Histoire critique du gnosticisme, de Jacques Matter). L'auteur pose qu'en définissant l'ésotérisme en termes de prétention à la connaissance (recherche de connaissance secrète, cachée, dissimulée, supérieure, plus profonde, ou intérieure), les approches traditionnelles, religionistes, aussi bien que les approches discursives contemporaines de l'ésotérisme finissent par en faire un concept théorique aux applications potentiellement universelles et, du même coup, risquent de faire perdre de vue sa spécificité historique. A l'encontre de ces perspectives, l'auteur défend la manière dont Faivre conçoit l'ésotérisme, c'est-à-dire, comme une série de courants historiques ayant donné lieu à un corpus référentiel de textes. Il poursuit en posant que ce que ces courants et ces textes ont en commun n'est pas, comme le dit Faivre, leur participation à une “forme de pensée”, mais leur exclusion, à caractère polémique, de la part d'un discours “anti-apologétique” dans le Protestantisme du 17ème siècle.
Meals and Politics in the Yaad: A Reconsideration
Authors: Eckhardt Benedikt 
Published: July 2010

AbstractThe “Rule of the Community” (1QS) prescribes the organization of meals in a short and not very informative way, which has led to widespread speculations about the cultic significance and/or the political character of meals held in the Yaad. This analysis seeks to show that there is nothing in the Qumran texts which justifies the designation of the meal as either “holy” or “political” in the sense usually given to that term. No anti-Hellenistic attitude is apparent. The meals are political in a different sense, designed to visualize hierarchies and to inscribe them into daily practice. Strategies employed for securing the status of priests make the use of semantics potentially associated with the cult understandable as the attempt to create a frame of reference which makes acceptance of priestly status in the community unavoidable.
Jubilees 46:6‐47:1 and 4QVisions of Amram
Authors: VanderKam James C. 
Published: July 2010

AbstractThe present paper explores the ways in which the authors of the Hebrew Book of Jubilees and the Aramaic Visions of Amram used the motif of a Canaanite-Egyptian war as they labored with the issues raised by the accounts at the end of Genesis and the beginning of Exodus. There is no clear indication that either writer used the work of the other; rather the war in question seems to have been a motif that was available to both when they composed their works and that each adopted and adapted independently.
A Forgotten Reference to Divine Procreation? Psalm 2:6 in Light of Egyptian Royal Ideology
Authors: Granerød Gard 
Published: July 2010

AbstractThe author discusses whether or not MT Ps 2:6 (in particular the verb ) reflects Egyptian royal ideology as the one evident in “Ptah’s Decree to Ramesses”. He tentatively concludes that the verse historically reflects a concept where the god procreates the human king. Semantically, the verb might originally have denoted the emission of semen, either after the model of or at least in a way comparable to “Ptah’s Decree to Ramesses” (c. 13th-11th centuries BCE). The common translation by means of a legal term “to install” etc. reflects the LXX. LXX Ps 2:6 might represent a theological correction of what the translators considered to be a case of an intolerable anthropomorphism in the Hebrew text.
Short Note
Authors: Waite Jerry 
Published: July 2010

AbstractThis paper shows that the use of the Hebrew word ‘lp as a troop gives the army size consistent with the Israelite population calculated for the average family, each having three males. The mathematical approach of C. J. Humphreys encounters problems because his assumption about the first-born gives the average Israelite family having 8.7 sons. A possible solution to the census of the 30-50 year old Levites is presented.
The Politics of Ritual Rhetoric: A Proposed Sociopolitical Context for the Redaction of Leviticus 1-16
Authors: Leuchter Mark 
Published: July 2010

AbstractRecent studies have indicated the rhetorical purpose of Leviticus 1-16 as reification for the ritual authority of the Aaronide priesthood. In the present study, it is suggested that the literary shaping of these chapters was a response to external stimuli that threatened the priesthood. After weighing a variety of historical and socio-political contexts in which such a threat might have emerged, the tenure of Nehemiah as governor is considered as an example of the type of competing leadership typology that encroached upon the priesthood, and the rhetorical features of the Nehemiah Memoir are reconsidered in this light. The redaction of Leviticus 1-16 provides a sacral counter argument to administrative agents such as Nehemiah and his supporters, supporting an ideology where national survival was ensured not through interaction with Persia but through the integrity of Temple ritual entrusted solely to the Aaronide priests.
Amuletic Inscriptions and the Background of YHWH as Guardian and Protector in Psalm 12
Authors: Smoak Jeremy D. 
Published: July 2010

AbstractThe last three verses of Psalm 12 have long posed a variety of problems for interpreters. As a result, a number of studies have argued that certain textual emendations should be made to clarify their meaning. The present study argues that the MT reading should be retained and in fact makes good sense in light of the larger message of the Psalm. In particular, the following contends that the enigmatic phrase blyl in verse 7 should be understood as a reference to the types of Iron Age smelting furnaces, which were partially sunk into the ground. Moreover, the use of the dyad “guard” (šmr) and “protect” (nr) in the following verse is reminiscent of several amulets, which contain these two verbs inscribed on their surfaces. The occurrence of these two verbs on the amulets indicates that they formed a stock protective formula during the Iron Age. As a result, I argue below that the reference to the smelting furnace in verse 7 and the use of the dyad in the following verse allows for a conclusion that the imagery in these verses may have originated from the practice of forming and inscribing metal amulets.
Profanität und Sakralisierung der Beschneidung im Alten Testament
Authors: Wagner Volker 
Published: July 2010

AbstractUntil after the era of exile, (male) circumcision was not widely practiced in Israel nor did it possess any religious or specific cultic significance. Only in very late texts of the Old Testament, dating to the end of the first millennium BC, a theologization and, especially, a sacralisation are attested. This development led to a comprehensive dissemination of the practice of circumcision in Judaism (and Islam).
Royal Recreation: Ivan the Terrible Goes Hunting
Authors: Halperin Charles J. 
Published: July 2010

AbstractIvan the Terrible loved hunting but between 1548 and 1564 he seems not to have indulged his favorite pastime. An anonymous English account written 1556-1558 says that Ivan had given hunting up for religious reasons. Three Russian texts written between 1550 and 1563, an entry in the Nikon Chronicle for 1556-1557 which praises Ivan for abstaining from hunting to become a true pastor of his flock, the Domostroi, a book of household management, and two vitae in the Stepennaia kniga tsarskogo rodosloviia (Book of Degrees of Imperial Genealogy), contain diatribes against the cruelty and immorality of hunting. These texts echo a minority anti-hunting tradition in medieval and early modern Europe. As in Europe hunting continued unabated, but in Muscovy it is possible that the anti-hunting animus of these texts inspired at least one temporary convert, Ivan the Terrible himself.
News and Views
Authors: Pawliczak Jakub , Bosek Leszek 
Published: July 2010

AbstractThe Act of 6 November 2008 on Patients’ Rights and the Commissioner for Patients’ Rights collect and safeguard patients’ basic rights as well as provide, for the first time in Poland, an original concept for patients’ collective rights. In addition, the new Act stipulates the specific mechanism for protecting patients’ rights by the newly established body called the Commissioner for Patients’ Rights. Polish reform of medical law will undoubtedly contribute to the expected ratification of the Convention on Human Rights and Biomedicine. However, the nature of codified rights is relatively abstract, and the Act cannot be read without reference to legislation related to physicians and health care institutions.
1903-1914
Authors: Confino Michael 
Published: July 2010

AbstractFrom the first years after 1900, the Russian anarchists debated the “question of the organization,” and examined how they should organize the movement so that they may carry on its political activities and secure freedom of expression and of spontaneous action both for its members and for the masses. Opposed as they were to all kind of hierarchic, centralized, and pyramidal types of organization, most of the Russian anarchists preferred the creation of independent and autonomous groups whose members would be linked by a community of ideas and feelings. (The first groups appeared in Russia in 1903.) Under the influence of classical anarchist thinkers like Bakunin, Kropotkin, and Malatesta, some of them saw in anarchism not only an ideology, but a way of life, and tried to create cells in the image of the future society. Everyday realities compelled many of them to adopt more efficient and practical solutions. The most frequent terms used in their vocabulary (and examined here) reveal their state of mind and ways of action, terms such as self-rule, initiative, autonomous action, independence, creativity, and free activity. Their groups were usually homogenous in terms of their social, educational, and national or ethnic composition. They rejected the practice of collecting members' fees or donations. As a result they faced the problem of how to finance their activities. A major debate ensued whether or not to use “expropriations” (eksy), armed attacks on state institutions or private enterprises, for gathering funds, and how such actions were viewed by the masses. The Revolution of 1905, in which the anarchists participated actively, had important repercussions on their views and ways of organizing.
Black Monks and White Gold The Solovetskii Monastery's Prosperous Salt Trade during the Time of Troubles of the Early Seventeenth Century
Authors: Gruber Isaiah 
Published: July 2010

AbstractThis article represents a study of extant business records of the Vologda podvor'e of the Solovotskii Monastery from the Time of Troubles (1598-1613). The archival records show that the monastery continued to take in impressive sums from its salt trade during this period of crisis, and in fact was able to increase its revenue during the first two thirds of the Troubles. The study additionally demonstrates that both prices and sales volume oscillated (rose and fell) in a yearly pattern. However, over the longer term, volume remained constant while prices rose, thus producing the increase in net income. The detailed records of prices also enable a comparison to the late Prof. Hellie's data set in The Ecomomy and Material Culture of Russia. The Solovki salt prices recorded at Vologda manifest distinct price levels and behavior and thus significantly enhance Hellie's charts for the Time of Troubles period. The study as a whole illustrates that the Time of Troubles exerted quite an uneven effect on the population of Muscovy, with the wealthy monasteries often economically unaffected or at least less affected than the general population. It also reveals the extent to which economic profit remained a principal driving force of the monasterial “corporation” at this time.
“National Identity in Premodern Rus”
Authors: Halperin Charles 
Published: July 2010

AbstractThis article is a commentary on some of the conclusions of Serhii Plokhy's The Origin of the Slavic Nations. Premodern Identities in Russia, Ukraine and Belarus. Plokhy addressed ethnocultural (national) identities and national identity projects from the tenth to the early eighteenth century. This essay is concerned with Kievan Rus', the Mongol impact on the East Slavs, and Muscovite history from the fourteenth to the sixteenth century. It offers alternative interpretations both of the historical background which Plokhy outlines for the evolution of East Slavic peoples and of Plokhy's interpretations of various historical, political, religious and literary texts. The chronology of the translatio of the myth of the Rus' Land from Kievan Rus' to Moscow is still a matter of contention. In synthesizing the views of such historians as Edward Keenan and Donald Ostrowski, Plokhy has attributed too much influence to the Mongols on Russian institutional and cultural history. Plokhy has failed to be consistent in his application of Keenan's criticism of sources and Keenan's concept of sixteenth-century Muscovite society and culture. Finally, Plokhy somewhat oversimplifies the cultural heterogeneity of Ivan the Terrible and Ivan the Terrible's Muscovy. These criticisms are a tribute to Plokhy's challenging but inspiring monograph.