bluuebunny/crossref_metadata_2025_split huggingface dataset:
An In vivo Model of Met-Driven Lymphoma as a Tool to Explore the Therapeutic Potential of Met Inhibitors
Authors: Accornero Paolo , Lattanzio Giuseppe , Mangano Tony , Chiarle Roberto , Taulli Riccardo , Bersani Francesca , Forni Paolo E. , Miretti Silvia , Scuoppo Claudio , Dastrù Walter , Christensen James G. , Crepaldi Tiziana , Ponzetto Carola 
Published: April 2008

Abstract
Purpose: Met, the tyrosine kinase receptor for hepatocyte growth factor, is frequently deregulated in human cancer. Recent evidence indicates that Met amplification may confer resistance to treatments directed toward other receptor tyrosine kinases. Thus, there is a need to develop Met inhibitors into therapeutic tools, to be used alone or in combination with other molecularly targeted drugs. Preclinical validation of Met inhibitors has thus far been done in nude mice bearing cancer cells xenogratfs. A far superior model would be a transgenic line developing spontaneous Met-driven tumors with high penetrance and short latency.
Experimental Design: To this end, we introduced into the mouse genome TPR-MET, the oncogenic form of MET. The Tpr-Met protein ensures deregulation of Met signaling because dimerization motifs in the Tpr moiety cause ligand-independent activation of the Met kinase.
Results: Here, we describe a TPR-MET transgenic line that develops thymic T-cell lymphoma with full penetrance and very short latency. In the tumors, Tpr-Met and its effectors were phosphorylated. Treatment of tumor-derived T lymphocytes with the selective Met inhibitor PHA-665752 at nanomolar concentrations abolished phosphorylation of Met and downstream effectors and led to caspase-mediated apoptosis. I.v. administration of PHA-665752 to transgenic mice bearing lymphomas in exponential growth phase led to a significant decrease in tumor growth and, in some cases, to tumor regression.
Conclusions: Our transgenic line, which within 2 months reliably develops Tpr-Met–driven T-cell lymphoma, represents a valuable tool to explore the efficacy and therapeutic potential of Met kinase inhibitors as anticancer drugs.
Pilot Randomized Phase II Study of Celecoxib in Oral Premalignant Lesions
Authors: Papadimitrakopoulou Vassiliki A. , William William N. , Dannenberg Andrew J. , Lippman Scott M. , Lee J. Jack , Ondrey Frank G. , Peterson Douglas E. , Feng Lei , Atwell Anthea , El-Naggar Adel K. , Nathan Cherie-Ann , Helman Joseph I. , Du Baoheng , Yueh Bevan , Boyle Jay O. 
Published: April 2008

Abstract
Purpose: Cyclooxygenase-2 (COX-2)–specific inhibition suppresses carcinogenesis in preclinical models and is a promising strategy for preventing oral cancer. In this pilot randomized phase II study, we evaluated the efficacy and safety of the COX-2 inhibitor celecoxib in patients with oral premalignant lesions (OPL).
Experimental Design: Patients were randomly assigned to placebo (n = 18), celecoxib 100 mg twice daily (n = 17), or celecoxib 200 mg twice daily (n = 15) for 12 weeks. Six additional patients received celecoxib (400 mg twice daily) in an unblinded extension of the study. Biopsies were obtained at baseline and week 12. All patients entering the study were required to have at least one histologically confirmed early (atypical hyperplasia, atypical hyperkeratosis, or mild dysplasia) or advanced (moderate to severe dysplasia) OPL.
Results: Forty-nine patients (46 of 50 randomized and 3 of 6 open label) were evaluable for efficacy analyses. There were no statistically significant differences between the response rates of the randomly assigned arms: placebo, 33.3% (6 of 18); celecoxib 100 mg twice daily, 41.2% (7 of 17); and celecoxib 200 mg twice daily, 20.0% (3 of 15). Two patients responded on celecoxib 400 mg twice daily. Celecoxib was generally well tolerated. Patients with higher baseline COX-2 mRNA levels had an increased risk of disease progression within 3 months.
Conclusions: Celecoxib at 100 or 200 mg twice daily was ineffective in controlling OPLs in this randomized controlled trial. This result and cardiovascular toxicity results of other (large scale) randomized controlled trials of selective COX-2 inhibitors have discouraged the continued investigation of these agents in oral cancer chemoprevention. Better methods for identifying high-risk patients and more active interventions are needed for future oral cancer chemoprevention trials.
Neoadjuvant Treatment of Colorectal Cancer with Bevacizumab: The Perioperative Angiogenic Balance Is Sensitive to Systemic Thrombospondin-1 Levels
Authors: Brostjan Christine , Gebhardt Kristina , Gruenberger Birgit , Steinrueck Verena , Zommer Halina , Freudenthaler Harald , Roka Sebastian , Gruenberger Thomas 
Published: April 2008

Abstract
Purpose: Colorectal cancer patients receiving neoadjuvant treatment with bevacizumab, a monoclonal antibody neutralizing vascular endothelial growth factor (VEGF), may suffer from wound healing complications after surgery as the antibody persists in patient blood. We characterized the systemic angiogenic balance in the perioperative period to evaluate its effect on physiologic angiogenesis.
Experimental Design: Nineteen patients receiving combination chemotherapy and bevacizumab for six neoadjuvant cycles were compared with 14 patients receiving chemotherapy without bevacizumab. Plasma from perioperative days −1, +1, +7, and +21 was analyzed for VEGF, thrombospondin-1 (TSP-1), and PD-ECGF concentrations. The angiogenic capacity was further tested in an in vitro assay of endothelial cell proliferation and migration.
Results: On day +1, the onset of wound healing was reflected in a change of balance, i.e., an increase of proangiogenic factors VEGF and platelet-derived endothelial cell growth factor compared with low TSP-1 inhibitor levels in both treatment groups. Patients with bevacizumab therapy showed significantly higher blood levels of total VEGF throughout the evaluation period. However, most VEGF molecules were inactive, i.e., complexed with antibody. Nevertheless, the capacity to stimulate endothelial growth was higher for these plasma samples and was reflected in low TSP-1 levels and an altered TSP-1 sensitivity. When purified TSP-1 protein was added, plasma samples of the bevacizumab but not the chemotherapy group showed reduced endothelial growth.
Conclusions: Feedback mechanisms of bevacizumab therapy are not restricted to VEGF expression but seem to involve additional factors, such as TSP-1, which influences the systemic angiogenic balance and permits endothelial growth.
A Severe Combined Immunodeficient–hu In vivo Mouse Model of Human Primary Mantle Cell Lymphoma
Authors: Wang Michael , Zhang Liang , Han Xiaohong , Yang Jing , Qian Jianfei , Hong Sungyoul , Lin Pei , Shi Yuankai , Romaguera Jorge , Kwak Larry W. , Yi Qing 
Published: April 2008

Abstract
Purpose: To establish a severe combined immunodeficient (SCID)-hu in vivo mouse model of human primary mantle cell lymphoma (MCL) for the study of the biology and novel therapy of human MCL.
Experimental Design: Primary MCL cells were isolated from spleen, lymph node, bone marrow aspirates, or peripheral blood of six different patients and injected respectively into human bone chips, which had been s.c. implanted in SCID-hu. Circulating human β2-microglobulin in mouse serum was used to monitor the engraftment and growth of patient's MCL cells. H&E staining and immunohistochemical staining with anti-human CD20 and cyclin D1 antibodies were used to confirm the tumor growth and migration.
Results: Increasing levels of circulating human β2-microglobulin in mouse serum indicated that the patient's MCL cells were engrafted successfully into human bone chip of SCID-hu mice. The engraftment and growth of patient's MCL cells were dependent on human bone marrow microenvironment. Immunohistochemical staining with anti-human CD20 and cyclin D1 antibodies confirmed that patient's MCL cells were able to not only survive and propagate in the bone marrow microenvironment of the human fetal bone chips, but also similar to the human disease, migrate to lymph nodes, spleen, bone marrow, and gastrointestinal tract of host mice. Treatment of MCL-bearing SCID-hu mice with atiprimod, a novel antitumor compound against the protection of bone marrow stromal cells, induced tumor regression.
Conclusion: This is the first human primary MCL animal model that should be useful for the biological and therapeutic research on MCL.
Pharmacology of the Novel Antiangiogenic Peptide ATN-161 (Ac-PHSCN-NH2): Observation of a U-Shaped Dose-Response Curve in Several Preclinical Models of Angiogenesis and Tumor Growth
Authors: Doñate Fernando , Parry Graham C. , Shaked Yuval , Hensley Harvey , Guan Xiaojun , Beck Ivy , Tel-Tsur Ziva , Plunkett Marian L. , Manuia Mari , Shaw David E. , Kerbel Robert S. , Mazar Andrew P. 
Published: April 2008

Abstract
Purpose: ATN-161 (Ac-PHSCN-NH2) is an integrin-binding peptide that is currently in phase II trials in cancer patients. This peptide has been shown to have antitumor activity in a number of different preclinical models.
Experimental Design: In this study, we examined the binding, biodistribution, and dose and biomarker response of ATN-161 in several animal models.
Results: ATN-161 bound to the β subunit of a number of different integrins implicated in tumor growth and progression, which depended on its cysteine thiol. The peptide had antiangiogenic activity in the Matrigel plug model, and this activity could be reversed by inhibitors of protein kinase A, an effector of α5β1-dependent angiogenesis. A labeled analogue of ATN-161, ATN-453, localized to neovessels but not to preexisting vasculature in vivo. The half-life of the peptide when localized to a tumor was much longer than in plasma. Dose-response studies in the Matrigel plug model of angiogenesis or a Lewis lung carcinoma model of tumor growth showed a U-shaped dose-response curve with 1 to 10 mg/kg given thrice a week, being the optimal dose range of ATN-161. Two additional pharmacodynamic models of angiogenesis (dynamic contrast-enhanced magnetic resonance imaging and measurement of endothelial cell progenitors) also revealed U-shaped dose-response curves.
Conclusions: The presence of a U-shaped dose-response curve presents a significant challenge to identifying a biologically active dose of ATN-161. However, the identification of biomarkers of angiogenesis that also exhibit this same U-shaped response should allow the translation of those biomarkers to the clinic, allowing them to be used to identify the active dose of ATN-161 in phase II studies.
Impact of Smoking Cessation on Global Gene Expression in the Bronchial Epithelium of Chronic Smokers
Authors: Zhang Li , Lee J. Jack , Tang Hongli , Fan You-Hong , Xiao Lianchun , Ren Hening , Kurie Jonathan , Morice Rodolfo C. , Hong Waun Ki , Mao Li 
Published: April 2008

AbstractCigarette smoke is the major cause of lung cancer and can interact in complex ways with drugs for lung cancer prevention or therapy. Molecular genetic research promises to elucidate the biological mechanisms underlying divergent drug effects in smokers versus nonsmokers and to help in developing new approaches for controlling lung cancer. The present study compared global gene expression profiles (determined via Affymetrix microarray measurements in bronchial epithelial cells) between chronic smokers, former smokers, and never smokers. Smoking effects on global gene expression were determined from a combined analysis of three independent data sets. Differential expression between current and never smokers occurred in 591 of 13,902 measured genes (P &lt; 0.01 and &gt;2-fold change; pooled data)—a profound effect. In contrast, differential expression between current and former smokers occurred in only 145 of the measured genes (P &lt; 0.01 and &gt;2-fold change; pooled data). Nine of these 145 genes showed consistent and significant changes in each of the three data sets (P &lt; 0.01 and &gt;2-fold change), with eight being down-regulated in former smokers. Seven of the eight down-regulated genes, including CYP1B1 and three AKR genes, influence the metabolism of carcinogens and/or therapeutic/chemopreventive agents. Our data comparing former and current smokers allowed us to pinpoint the genes involved in smoking-drug interactions in lung cancer prevention and therapy. These findings have important implications for developing new targeted and dosing approaches for prevention and therapy in the lung and other sites, highlighting the importance of monitoring smoking status in patients receiving oncologic drug interventions.
Increased Susceptibility of Nrf2 Knockout Mice to Colitis-Associated Colorectal Cancer
Authors: Khor Tin Oo , Huang Mou-Tuan , Prawan Auemduan , Liu Yue , Hao Xingpei , Yu Siwang , Cheung William Ka Lung , Chan Jefferson Y. , Reddy Bandaru S. , Yang Chung S. , Kong Ah-Ng 
Published: April 2008

Abstract
The nuclear factor-erythroid 2-related factor 2 (Nrf2) plays a critical role in protecting various tissues against inflammation, which is a potential risk factor for colorectal and other cancers. Our previously published mouse model work showed that Nrf2 helps protect against dextran sulfate sodium (DSS)–induced colitis/inflammation, and others have shown that Nrf2 helps protect against inflammation-associated colorectal carcinogenesis (aberrant crypt foci). The present study extended these important earlier findings by exploring the role of Nrf2 in colitis-associated colorectal cancer in a mouse model involving azoxymethane/DSS–induced colorectal carcinogenesis in Nrf2 knockout mice. Azoxymethane/DSS–treated Nrf2 knockout mice had increased incidence, multiplicity, and size of all colorectal tumors, including adenomas, versus treated wild-type (WT) mice, and the proportion of tumors that were adenocarcinoma was much higher in knockout (80%) versus WT (29%) mice. Compared with WT mice, knockout mice also had increased markers of inflammation in tumor tissue (cyclooxygenase-2 and 5-lipoxygenase expressions and prostaglandin E2 and leukotriene B4 levels) and in inflamed colonic mucosa (nitrotyrosine expression), supporting the association of knockout mouse tumor formation with inflammation. The phase II detoxifying/antioxidant enzymes NAD(P)H-quinone reductase 1 and UDP-glucurosyltransferase 1A1 were elevated in the normal mucosa of WT, but not Nrf 2 knockout, mice treated with azoxymethane/DSS. Our findings show that Nrf2 plays a critical role in protecting against inflammation-associated colorectal cancer.
How We Know Early Hadīth Critics Did Matn Criticism and Why It's So Hard to Find
Authors: Brown Jonathan 
Published: March 2008

AbstractWestern scholars generally agree that early hadīth critics limited their authentication of hadīths to examining isnāds. The argument that these critics took the matn into account has relied on material of dubious reliability or on works produced after the formative period of the Sunni hadīth tradition. By providing examples of matn criticism from the 3rd/9th and 4th/10th centuries, I prove that Sunni hadīth critics did in fact engage in matn criticism; and I argue that these critics consciously manufactured the image of exclusive focus on the isnād in an effort to ward off attacks by rationalist opponents. By demonstrating a high correlation between the hadīths found in early books of transmitter criticism and those found in later books of forged hadīth with explicit matn criticism, I show that early critics engaged in matn criticism far more often than appears to have been the case, disguising this activity in the language of isnād criticism.
The Students' Representative in the Law Colleges of 14th-Century Damascus
Authors: Stewart Devin 
Published: March 2008

AbstractThis study examines two fatwās issued by Taqī al-Dīn al-Subkī in the mid-14-century regarding the Shāmīyah Madrasah of Damascus. Both texts refer to the position of "representative of the law students" (nāib al-fuqahā) and state that the position had become customary at the Shāmīyah Madrasah and other madrasahs in Damascus during that period. The existence of the post, which has not been noted in scholarship on pre-modern Islamic education to date, shows that madrasah students were more organized in this context than has been realized and raises questions about the institutional character of the madrasah.
The Construction of Madhhab Authority: Ibn Taymiyya's Interpretation of Juristic Preference (Istihsān)
Authors: Opwis Felicitas 
Published: March 2008

AbstractThis essay analyzes Ibn Taymiyya's discussion of juristic preference (istihsān) as a valid method of law-finding. Ibn Taymiyya rejects the interpretation of leading Hanbalīs of juristic preference as contrary to analogy and explains it instead as specification of the ratio legis (takhsīs al-'illa). His changed understanding of juristic preference leads him to re-interpret several of Ibn Hanbal's rulings that are based on this legal principle. How Ibn Taymiyya does this is illustrated with Ibn Hanbal's ruling on usurpation of agricultural land. Ibn Taymiyya does not question the actual ruling but rather rejects the rationalization adduced for it by previous Hanbalīs, such as Abū Ya'lā and Ibn 'Aqīl. By attributing his own position to Ibn Hanbal, Ibn Taymiyya undermines the authority of earlier prominent Hanbalīs, increases the authority of the eponym of the school, and enhances his own position as the living heir of Ibn Hanbal.
A Statistical Portrait of the Resistance to Logic by Sunni Muslim Scholars Based on the Works of Jalāl al-Dīn al-Suyūtī (849-909/1448-1505)
Authors: Ali Mufti 
Published: March 2008

AbstractOn the basis of my analysis of four works composed by al-Suyūtī, I argue that hostility to logic was a predominant feature of Sunni scholarship, especially during the 13th, 14th, and 15th centuries. Logic was condemned by distinguished Sunni scholars in Valencia, Fez, Aleppo, Iraq, and Mecca, but especially in Egypt and Syria. This conclusion confirms Goldziher's argument that resistance to logic started already in the 2nd/8th century and increased in the 13th and 14th centuries; and disconfirms al-Rouayheb's argument that opposition to logic was never predominant among Muslim Sunni scholars.
(2 Sam. xiii 32): Lot (šiāmu/šâmu/šīmtu)?
Authors: Joo Samantha 
Published: March 2008

AbstractTwo distinct proposals have been suggested for the meaning of. The present author adopts an alternative reading based on an Akkadian cognate, šiāmu/šâmu/šīmtu, to capture the gravity of one's disposition in guiding one's actions.
Ezekiel, P, and the Priestly School
Authors: Haran Menahem 
Published: March 2008

AbstractSeeing that Ezekiel, with his law code of chaps. xl-xlviii, is connected with P in many characteristics, while, at the same time, they contradict each other in almost any tangible aspect, it is the author's contention that the two are independent manifestation of the same school, of which P is its authentic expression whereas Ezekiel is its loose and later extension. It is out of the question to argue, as was done recently, that Ezekiel saw P and modified it at will. The relationship between P and Ezekiel comprises two aspects, the first of which is the common literary language they share, which in itself calls for explanation. The lack of agreement between the two is the second aspect demanding an explanation, but only if it is assumed that, when formulating his code, Ezekiel had direct access to P. Since Ezekiel used the priestly style as his own, he should have acquired it, after the practice of the Ancient Near East, over the course of many years of training, beginning in childhood and ending up in maturity. This implies that Ezekiel received his training in Jerusalem, while upon his arrival in Babylonia he was already a qualified priestly scribe, and it was there that he became a prophet. It is a vexed question whether the P scrolls were obtainable at all in Tel Abib by the river Chebar.
Das Tag YHWHs-Verständnis von Zephanja iii
Authors: Beck Martin 
Published: March 2008

AbstractZeph. iii 6-8ab proclaims anew, in post-exilic times, the Day of YHWH as a disastrous event for Jerusalem. Various updatings in Zeph. iii 14-20 add to this image the idea of a forgiving God whose primary will aims at the wellbeing of his people. The Day of YHWH is understood in the sense of a comprehensive final judgment (iii 8b). Zeph. iii 11-13 points to a distinction between pious people and sinners in Jerusalem as a means of salvation, whereas iii 9-10 the nations (seen as a rest) are presented as taking part in the salvation.
Pain and Production in Eden: Some Philological Reflections on Genesis iii 16
Authors: Novick Tzvi 
Published: March 2008

AbstractGenesis iii 16, which describes the unhappy consequences for Eve of her decision to eat from the forbidden fruit, is one of the most historically and theologically significant verses in the Hebrew Bible. Scholars have long debated certain cruces in the verse, among them the meaning of the phrase. I review various positions on the latter and then offer a new proposal.
The Ryukyu Islands Feng Shui Village Landscape
Authors: Chen Bixia , Kurima Gengi , Nakama Yuei 
Published: March 2008

AbstractIn a typical Ryukyu "Feng Shui" village, a forest belt, known as village Ho:go, was planted to curve in the front and extend to the east and the west to embrace the village along with preserved forest on the rear hill. Lines of Fukugi trees (Garcinia subelliptica) were planted to embrace the houses. Compared to the more symbolic existence of Feng Shui trees in China and other regions in East Asia, tree planting on a large scale was used as a practical means to repair defective topography with little protection from the strict natural condition on Ryuku's flat islands. This study focuses on village layout, forest composition in the front forest belt, habitat embracing trees, and forest plantations on the back hill. Garcinia subelliptica and Calophyllum inophyllum are the predominant species in the upper storey in the forest belt. A large number of species are also found in the under storey vegetation in the preserved forest. Thus, a Ryukyu Feng Shui village landscape, which embodies a symbiosis of the nature and human intervention, provides an ideal village landscape pattern in the Ryukyu Islands.
The Anonymity of the New Testament History Books: A Stylistic Device in the Context of Greco-Roman and Ancient Near Eastern Literature
Authors: Baum Armin 
Published: April 2008

AbstractThe anonymity of the NT historical books should not be regarded as peculiar to early Christian literature nor should it be interpreted in the context of Greco-Roman historiography. The striking fact that the NT Gospels and Acts do not mention their authors' names has its literary counterpart in the anonymity of the OT history books, whereas OT anonymity itself is rooted in the literary conventions of the Ancient Near East. Just as in the OT, where the authors of books that belonged to the genre of wisdom and prophetic literature were usually named while historical works were written anonymously, only the NT letters and the Apocalypse were published under their authors' names while the narrative literature of the NT remained anonymous. The authorial intent of the Gospels' anonymity can also be deduced from its ancient Near Eastern and OT background. Unlike the Greek or Roman historian who, among other things, wanted to earn praise and glory for his literary achievements from both his contemporaries and posterity, the history writer in the Ancient Near East sought to disappear as much as possible behind the material he presented and to become its invisible mouthpiece. By adopting the stylistic device of anonymity from OT historiography the Evangelists of the NT implied that they regarded themselves as comparatively insignificant mediators of a subject matter that deserved the full attention of the readers. The anonymity of the Gospels is thus rooted in a deep conviction concerning the ultimate priority of their subject matter.