bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Prospective, Randomized, Double‐Blinded, Placebo‐Controlled Study of Human Intravenous Immunoglobulin for the Acute Management of Presumptive Primary Immune‐Mediated Thrombocytopenia in Dogs
Authors: Bianco D. , Armstrong P.J. , Washabau R.J. 
Published: August 2009

Background:Immune‐mediated thrombocytopenia (IMT) is a common hematologic disorder in dogs. Human intravenous immunoglobulin (hIVIG) may have a beneficial effect in canine IMT.Hypothesis:A single hIVIG infusion (0.5 g/kg) in dogs with presumed primary IMT (pIMT) is a safe adjunctive emergency treatment to accelerate platelet count recovery and shorten hospitalization time without increasing the cost of patient care.Animals:Eighteen client‐owned dogs with a presumptive diagnosis of pIMT.Methods:Prospective, randomized, double‐blinded, placebo‐controlled clinical trial.Results:There were no identifiable immediate or delayed adverse reactions associated with hIVIG administration over a 6‐month period. The median platelet count recovery time for the hIVIG group was 3.5 days (mean ± SD: 3.7 ± 1.3 days; range, 2–7 days) and 7.5 days (mean ± SD: 7.8 ± 3.9 days; range, 3–12 days) for the placebo group. The median duration of hospitalization for hIVIG group was 4 days (mean ± SD: 4.2 ± 0.4 days; range, 2–8 days) and 8 days (mean ± SD: 8.3 ± 0.6 days; range, 4–12 days) for the placebo group. There was no significant difference between groups with respect to expense of initial patient care, whereas significant reduction in platelet count recovery time (P= .018) and duration of hospitalization (P= .027) were detected in the hIVIG group.Conclusions and Clinical Importance:Compared with corticosteroids alone, adjunctive emergency therapy of a single hIVIG infusion was safe and associated with a significant reduction in platelet count recovery time and duration of hospitalization without increasing the expense of medical care in a small group of dogs with presumed pIMT.
A Nanoparticle System Specifically Designed to Deliver Short Interfering RNA Inhibits Tumor Growth In vivo
Authors: Yagi Nobuhiro , Manabe Ichiro , Tottori Tsuneaki , Ishihara Atsushi , Ogata Fusa , Kim Jong Heon , Nishimura Satoshi , Fujiu Katsuhito , Oishi Yumiko , Itaka Keiji , Kato Yasuki , Yamauchi Masahiro , Nagai Ryozo 
Published: August 2009

Abstract
Use of short interfering RNA (siRNA) is a promising new approach thought to have a strong potential to lead to rapid development of gene-oriented therapies. Here, we describe a newly developed, systemically injectable siRNA vehicle, the “wrapsome” (WS), which contains siRNA and a cationic lipofection complex in a core that is fully enveloped by a neutral lipid bilayer and hydrophilic polymers. WS protected siRNA from enzymatic digestion, providing a long half-life in the systemic circulation. Moreover, siRNA/WS leaked from blood vessels within tumors into the tumor tissue, where it accumulated and was subsequently transfected into the tumor cells. Because the transcription factor KLF5 is known to play a role in tumor angiogenesis, we designed KLF5-siRNA to test the antitumor activity of siRNA/WS. KLF5-siRNA/WS exhibited significant antitumor activity, although neither WS containing control scrambled-siRNA nor saline containing KLF5-siRNA affected tumor growth. KLF5-siRNA/WS inhibited Klf5 expression within tumors at both mRNA and protein levels, significantly reducing angiogenesis, and we detected no significant acute or long-term toxicity. Our findings support the idea that siRNA/WS can be used to knock down specific genes within tumors and thereby exert therapeutic effects against cancers. [Cancer Res 2009;69(16):6531–8]
Atopic Disease and Risk of Non–Hodgkin Lymphoma: An InterLymph Pooled Analysis
Authors: Vajdic Claire M. , Falster Michael O. , de Sanjose Silvia , Martínez-Maza Otoniel , Becker Nikolaus , Bracci Paige M. , Melbye Mads , Smedby Karin Ekström , Engels Eric A. , Turner Jennifer , Vineis Paolo , Costantini Adele Seniori , Holly Elizabeth A. , Kane Eleanor , Spinelli John J. , La Vecchia Carlo , Zheng Tongzhang , Chiu Brian C-H. , Maso Luigino Dal , Cocco Pierluigi , Maynadié Marc , Foretova Lenka , Staines Anthony , Brennan Paul , Davis Scott , Severson Richard , Cerhan James R. , Breen Elizabeth C. , Birmann Brenda , Cozen Wendy , Grulich Andrew E. 
Published: August 2009

AbstractWe performed a pooled analysis of data on atopic disease and risk of non–Hodgkin lymphoma (NHL) from 13 case-control studies, including 13,535 NHL cases and 16,388 controls. Self-reported atopic diseases diagnosed 2 years or more before NHL diagnosis (cases) or interview (controls) were analyzed. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were computed in two-stage random-effects or joint fixed-effects models, and adjusted for age, sex, and study center. When modeled individually, lifetime history of asthma, hay fever, specific allergy (excluding hay fever, asthma, and eczema), and food allergy were associated with a significant reduction in NHL risk, and there was no association for eczema. When each atopic condition was included in the same model, reduced NHL risk was only associated with a history of allergy (OR, 0.80; 95% CI, 0.68–0.94) and reduced B-cell NHL risk was associated with history of hay fever (OR, 0.85; 95% CI, 0.77–0.95) and allergy (OR, 0.84; 95% CI, 0.76–0.93). Significant reductions in B-cell NHL risk were also observed in individuals who were likely to be truly or highly atopic—those with hay fever, allergy, or asthma and at least one other atopic condition over their lifetime. The inverse associations were consistent for the diffuse large B-cell and follicular subtypes. Eczema was positively associated with lymphomas of the skin; misdiagnosis of lymphoma as eczema is likely, but progression of eczema to cutaneous lymphoma cannot be excluded. This pooled study shows evidence of a modest but consistent reduction in the risk of B-cell NHL associated with atopy. [Cancer Res 2009;69(16):6482–9]
A Loss-of-Function Polymorphism in the Propeptide Domain of the LOX Gene and Breast Cancer
Authors: Min Chengyin , Yu Ziyang , Kirsch Kathrin H. , Zhao Yingshe , Vora Siddharth R. , Trackman Philip C. , Spicer Douglas B. , Rosenberg Lynn , Palmer Julie R. , Sonenshein Gail E. 
Published: August 2009

Abstract
The lysyl oxidase (LOX) gene reverted Ras transformation of NIH 3T3 fibroblasts and tumor formation by gastric cancer cells, which frequently carry mutant RAS genes. The secreted lysyl oxidase proenzyme is processed to a propeptide (LOX-PP) and a functional enzyme (LOX). Unexpectedly, the tumor suppressor activity mapped to the LOX-PP domain, which inhibited tumor formation and the invasive phenotype of NF639 breast cancer cells driven by human epidermal growth factor receptor-2/neu, which signals via Ras. A single-nucleotide polymorphism, G473A (rs1800449), resulting in an Arg158Gln substitution in a highly conserved region within LOX-PP, occurs with an average 473A allele carrier frequency of 24.6% in the HapMap database, but was present in many breast cancer cell lines examined. Here, we show that the Arg-to-Gln substitution profoundly impairs the ability of LOX-PP to inhibit the invasive phenotype and tumor formation of NF639 cells in a xenograft model. LOX-PP Gln displayed attenuated ability to oppose the effects of LOX, which promoted a more invasive phenotype. In a case-control study of African American women, a potential association of the Gln-encoding A allele was seen with increased risk of estrogen receptor (ER)-α–negative invasive breast cancer in African American women. Consistently, LOX gene expression was higher in ER-negative versus ER-positive primary breast cancers, and LOX-PP Gln was unable to inhibit invasion by ER-negative cell lines. Thus, these findings identify for the first time genetic polymorphism as a mechanism of impaired tumor suppressor function of LOX-PP and suggest that it may play an etiologic role in ER-negative breast cancer. [Cancer Res 2009;69(16):6685–93]
Migratory and Antigen Presentation Functions of IFN-Producing Killer Dendritic Cells
Authors: Himoudi Nourredine , Yan Mengyong , Bouma Gerben , Morgenstern Daniel , Wallace Rebecca , Seddon Ben , Buddle Jo , Eddaoudi Ayad , Howe Steven J. , Cooper Nichola , Anderson John 
Published: August 2009

Abstract
The CD11cint B220+ NK1.1+ CD49+ subset of cells has recently been described as IFN-producing killer dendritic cells (IKDC), which share phenotypic and functional properties with both dendritic cells and natural killer cells. We have previously shown that IKDCs within murine bone marrow–derived DC preparations are essential for the antitumor activity of unpulsed DCs. Here we show that bone marrow–derived IKDCs (BM-IKDC) migrate in vivo into tumors and thence to tumor draining lymph nodes, where they highly express MHC class II and costimulatory molecules. In vitro, freshly isolated BM-IKDCs, fluorescence-activated cell sorted to homogeneity, have no intrinsic antigen presentation function unless cocultured with tumor target cells. On killing of target cells, they can cross-present antigens to stimulate antigen-primed CD8 T cells and can also present antigens to antigen-primed CD4 cells. In vivo, in mice lacking class I–restricted antigen-presenting cell function, robust proliferation of antigen-specific T cells is achieved after adoptive transfer of BM-IKDCs at an injection site distant to the tumor site. Therefore, BM-IKDCs are capable of cytotoxic killing of tumor targets and also of potent antigen presentation after encountering antigen in the context of a viable target cell. [Cancer Res 2009;69(16):6598–606]
Proteasome Inhibition Causes Regression of Leukemia and Abrogates BCR-ABL–Induced Evasion of Apoptosis in Part through Regulation of Forkhead Tumor Suppressors
Authors: Jagani Zainab , Song Keli , Kutok Jeffery L. , Dewar M. Rajan , Melet Armelle , Santos Tanya , Grassian Alexandra , Ghaffari Saghi , Wu Catherine , Ren Ruibao , Rodin Heather Yeckes , Miller Kenneth , Khosravi-Far Roya 
Published: August 2009

Abstract
BCR-ABL plays an essential role in the pathogenesis of chronic myeloid leukemia (CML) and some cases of acute lymphocytic leukemia (ALL). Although ABL kinase inhibitors have shown great promise in the treatment of CML, the persistence of residual disease and the occurrence of resistance have prompted investigations into the molecular effectors of BCR-ABL. Here, we show that BCR-ABL stimulates the proteasome-dependent degradation of members of the forkhead family of tumor suppressors in vitro, in an in vivo animal model, and in samples from patients with BCR-ABL–positive CML or ALL. As several downstream mediators of BCR-ABL are regulated by the proteasome degradation pathway, we also show that inhibition of this pathway, using bortezomib, causes regression of CML-like disease. Bortezomib treatment led to inhibition of BCR-ABL–induced suppression of FoxO proteins and their proapoptotic targets, tumor necrosis factor–related apoptosis-inducing ligand and BIM, thereby providing novel insights into the molecular effects of proteasome inhibitor therapy. We additionally show sensitivity of imatinib-resistant BCR-ABL T315I cells to bortezomib. Our data delineate the involvement of FoxO proteins in BCR-ABL–induced evasion of apoptosis and provide evidence that bortezomib is a candidate therapeutic in the treatment of BCR-ABL–induced leukemia. [Cancer Res 2009;69(16):6546–55]
Tissue Selectivity in Multiple Endocrine Neoplasia Type 1-Associated Tumorigenesis
Authors: Gracanin Ana , Dreijerink Koen M. A. , van der Luijt Rob B. , Lips Cornelis J. M. , Höppener Jo W. M. 
Published: August 2009

Abstract
The phenotype of the multiple endocrine neoplasia type 1 (MEN1) syndrome cannot be explained solely by the expression pattern of the predisposing gene MEN1 and its encoded protein, menin. This review addresses putative factors determining MEN1-associated tissue-selective tumorigenesis. Menin's interaction with mixed-lineage leukemia protein-containing histone methyl transferase (MLL-HMT) complex mediates tissue-selective tumor-suppressing and tumor-promoting effects of menin, and as such could be decisive for the predisposition of individual tissues to MEN1-associated tumorigenesis. In tissues in which menin acts as a tumor suppressor, tumorigenesis could depend on the inability of such tissues to adequately compensate for MEN1 gene loss, whereas the variable clinical presentation of MEN1 in individual patients could be a reflection of additional epigenetic factors and/or modifier genes. Further research on this topic may facilitate development of novel therapeutic strategies that could prevent or delay the onset of MEN1-associated tumorigenesis. [Cancer Res 2009;69(16):6371–4]
Functional Restoration of BRCA2 Protein by SecondaryBRCA2Mutations inBRCA2-Mutated Ovarian Carcinoma
Authors: Sakai Wataru , Swisher Elizabeth M. , Jacquemont Céline , Chandramohan Kurapaty Venkatapoorna , Couch Fergus J. , Langdon Simon P. , Wurz Kaitlyn , Higgins Jake , Villegas Emily , Taniguchi Toshiyasu 
Published: August 2009

AbstractAcquired platinum resistance is a serious problem in the treatment of ovarian carcinomas. However, the mechanism of the drug resistance has not been elucidated. Here, we show functional significance of restoration of BRCA2 protein by secondary BRCA2 mutations in acquired drug resistance of BRCA2-mutated ovarian carcinoma. Three ovarian cancer cell lines (PEO1, PEO4, and PEO6) were derived from a BRCA2 mutation [5193C&gt;G (Y1655X)] carrier with ovarian carcinoma with acquired cisplatin resistance and a secondary BRCA2 mutation [5193C&gt;T (Y1655Y)] that canceled the inherited mutation. PEO1 was BRCA2 deficient and sensitive to cisplatin and a poly(ADP-ribose) polymerase inhibitor, AG14361, whereas PEO4 was resistant. PEO4 and PEO6, derived from ascites at the time of relapse with cisplatin resistance, had the secondary mutation and were BRCA2 proficient. In vitro cisplatin/AG14361 selection of PEO1 led to restoration of BRCA2 due to another secondary BRCA2 mutation. BRCA2 depletion sensitized BRCA2-restored PEO1 clones and PEO4 to cisplatin/AG14361. Thus, restoration of BRCA2 due to secondary BRCA2 mutation is involved in acquired drug resistance of BRCA2-mutated ovarian carcinoma. [Cancer Res 2009;69(16):6381–6]
Up-regulation of miR-200 and let-7 by Natural Agents Leads to the Reversal of Epithelial-to-Mesenchymal Transition in Gemcitabine-Resistant Pancreatic Cancer Cells
Authors: Li Yiwei , VandenBoom Timothy G. , Kong Dejuan , Wang Zhiwei , Ali Shadan , Philip Philip A. , Sarkar Fazlul H. 
Published: August 2009

Abstract
Pancreatic cancer is the fourth most common cause of cancer death in the United States, and the aggressiveness of pancreatic cancer is in part due to its intrinsic and extrinsic drug resistance characteristics, which are also associated with the acquisition of epithelial-to-mesenchymal transition (EMT). Emerging evidence also suggests that the processes of EMT are regulated by the expression status of many microRNAs (miRNA), which are believed to function as key regulators of various biological and pathologic processes during tumor development and progression. In the present study, we compared the expression of miRNAs between gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer cells and investigated whether the treatment of cells with “natural agents” [3,3′-diindolylmethane (DIM) or isoflavone] could affect the expression of miRNAs. We found that the expression of miR-200b, miR-200c, let-7b, let-7c, let-7d, and let-7e was significantly down-regulated in gemcitabine-resistant cells, which showed EMT characteristics such as elongated fibroblastoid morphology, lower expression of epithelial marker E-cadherin, and higher expression of mesenchymal markers such as vimentin and ZEB1. Moreover, we found that reexpression of miR-200 by transfection studies or treatment of gemcitabine-resistant cells with either DIM or isoflavone resulted in the down-regulation of ZEB1, slug, and vimentin, which was consistent with morphologic reversal of EMT phenotype leading to epithelial morphology. These results provide experimental evidence, for the first time, that DIM and isoflavone could function as miRNA regulators leading to the reversal of EMT phenotype, which is likely to be important for designing novel therapies for pancreatic cancer. [Cancer Res 2009;69(16):6704–12]
Serum Insulin-like Growth Factor-I and Mammary Tumor Development inAd libitum–Fed, Chronic Calorie–Restricted, and Intermittent Calorie–Restricted MMTV-TGF-α Mice
Authors: Rogozina Olga P. , Bonorden Melissa J.L. , Grande Joseph P. , Cleary Margot P. 
Published: August 2009

AbstractThe effect of chronic (CCR) and intermittent (ICR) caloric restriction on serum insulin-like growth factor (IGF)-I levels and mammary tumor (MT) development was investigated. Ten-week-old MMTV-TGF-α female mice were assigned to ad libitum–fed (AL; AIN-93M diet), ICR [3-week 50% caloric restriction using AIN-93M-mod diet, 2× protein, fat, vitamins, and minerals followed by 3 weeks of daily 100% AL consumption of AIN-93M (∼75% of AL for each 6-week cycle)], and CCR (calorie and nutrient intake matched for each 6-week ICR cycle) groups. Half of the mice from each group were sacrificed at 79 (end of restriction) or 82 (end of refeeding) weeks of age. Serum was obtained at euthanasia and in cycles 1, 3, 5, 8, and 11. MT incidence was 71.0%, 35.4%, and 9.1% for AL, CCR, and ICR mice. ICR-Restricted mice had significantly lower terminal serum IGF-I and IGF-I/IGF binding protein-3 (IGFBP-3) ratio than CCR, ICR-Refed, and AL mice. There were no differences in terminal IGFBP-3. Final body, internal, and mammary fat pad weights correlated positively with IGF-I and negatively with IGFBP-3. Few changes were found for protein expression of IGF-IRα and IGFBP-3 in mammary tissue and MTs. During the study, IGF-I levels of ICR-Restricted mice were reduced, whereas refeeding allowed partial recovery. For all groups, elevated IGF-I levels preceded MT detection, although not all values were significant versus mice without MTs. However, the specific role of IGF-I in the protective effect of calorie restriction remains to be determined. These results confirm that ICR prevents MT development to a greater extent than CCR.
Macronutrient Intake and Cancer: How Does Dietary Restriction Influence Tumor Growth and Why Should We Care?
Authors: Pollak Michael 
Published: August 2009

Abstract
This perspective on the report by Rogozina and colleagues (beginning on page 712 in this issue of the journal) reviews mechanisms that may underlie inhibitory effects of dietary restriction on tumor growth in the mouse mammary tumor virus transforming growth factor alpha (MMTV-TGF-alpha) breast cancer model and comments on the potential clinical relevance of these mechanisms. The inhibitory effect of caloric restriction on carcinogenesis and tumor growth in rodent models is a classic finding that is receiving increasing attention. In some experimental models, the magnitude of the effect is significant, rivaling what can be achieved by pharmacologic approaches to cancer prevention or treatment. Major challenges include defining the underlying mechanisms and determining the clinical relevance of laboratory models of caloric restriction.
Paul's Reversal of Jews Calling Gentiles 'Dogs' (Philippians 3:2): 1600 Years of an Ideological Tale Wagging an Exegetical Dog?
Authors: Nanos Mark 
Published: August 2009

AbstractThe commentary tradition on Philippians 3:2 (and on Matt. 15 and Mark 7 too) has been claiming at least since Chrysostom that Jews commonly called Gentiles dogs, thereby legitimating a pattern of calling Jews dogs. Contemporary commentaries indicate no awareness of the harmful legacy or the continued implications of the polemic to which it contributes when perpetuating this invective. Moreover, evidence of this supposed common prejudice is often not provided, and when it is, usually consists of sayings attributed to Jesus and the Syro-Phoenician or Canaanite woman—thus available to us only in documents that post-date Paul, representing early "Christian" polemic. In addition to being anachronistic and not likely known to Paul's audience in Philippi, upon examination, it is also not clear that these Gospel sayings provide the proof supposed. Sometimes an appeal is made to Psalm 22 and other Jewish texts, but under examination, none of these substantiate the claim. Likewise, the many supposed cases in rabbinic literature—which could only provide anachronistic evidence at best—do not in fact substantiate that Jews ever called Gentiles dogs, much less that Jews commonly did so, even long after Christians habitually called Jews dogs. This essay examines the texts and challenges the interpretive tradition's claims, as well as its failure to exhibit hermeneutical distance when repeating this supposed invective against Jews and Judaism. Having exposed this ideological tale, several exegetical options worth exploring are noted.
The Sweet Scent of the Gospel in the Didache and in Second Corinthians: Some Comments on Two Recent Interpretations of the Stinoufi Prayer in the Coptic Did. 10.8
Authors: Kurek-Chomycz Dominika 
Published: August 2009

AbstractThe Coptic Didache excerpt, and the so called stinoufi prayer in particular, remain a contentious issue. In this essay two of the interpretations that have been proposed, by Joseph Ysebaert and Alistair Stewart-Sykes, respectively, are reassessed. I argue that not only the stinoufi prayer, but also 2 Cor 2:14-16 is best understood against the sapiential tradition of associating Wisdom with fragrance. In Did. 10.8, like in the Pauline passage, the notion of the aroma most likely refers to the gospel. Thus even though it may not be possible to establish a direct dependence, some relationship between the Pauline metaphor and the stinoufi prayer cannot be excluded.
The Latin Patristic Reception of the Book of Canticles in the Hexapla
Authors: Ceulemans Reinhart 
Published: August 2009

AbstractAlthough Hexaplaric studies tend to limit themselves to Greek exegesis only, the Latin Fathers, too, are quite valuable for our understanding of Origen's Hexapla. This article discusses two examples, both concerning the book of Canticles, which illustrate the contribution of Latin patristic exegesis to one's understanding of each of the Hexapla's two main features. Firstly, Jerome adds to our knowledge of the Hexaplaric recension of the LXX text, since he revised the Old Latin text on the basis of that recension. Secondly, the readings of α′ and σ′, which Ambrose provides throughout his exegesis, are of direct relevance for the establishment of a new edition of the Hexaplaric fragments, since they were unnoticed by previous editors. An appendix opens new perspectives by asking the question (and providing some steps towards answering it) of the provenance of these variants provided by Ambrose.
The Organization of Augustine's Psalmus contra Partem Donati
Authors: Nodes Daniel 
Published: August 2009

AbstractAugustine of Hippo writes in the Retractations that he composed his Psalmus contra Partem Donati (393) as a retort to the rhymed "psalms" which Donatist congregations chanted, and that he had intended his own Psalm for chanting in his congregation. Instead of a lyrical hymn, however, Augustine composed a brilliant defense of the catholic understanding of the nature and mission of the Christian community in the world. The piece was meant for his congregation to sing according to individual capacity but was structured and delivered as a homily rather than a hymn. To produce his didactic, polemical sung sermon, Augustine employed not only the standard rhetorical elements like repetition, anaphora, and even prosopopoeia, which readers have recognized, he also used the organizational pattern of forensic oratory: exordium, narratio, refutatio, confirmatio, and peroratio, which has not been commented on. The form of the Psalmus also has no sources in Latin but it reflects the pattern of other verse sermons of the era, such as those abundantly represented in the Greek East.