bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laryngeal collapse in seven brachycephalic puppies
Authors: Pink J. J. , Doyle R. S. , Hughes J. M. L. , Tobin E. , Bellenger C. R. 
Published: March 2006

Objectives:To document the histories, clinical findings, and management of seven puppies with laryngeal collapse occurring secondarily to brachycephalic airway syndrome.Methods:Seven brachycephalic puppies aged between 4·5 and six months underwent surgery for management of brachycephalic airway syndrome following presentation for exercise intolerance and increased respiratory noise and effort.Results:Stenotic nares of varying severity and an elongated soft palate were common to all dogs. All dogs had tracheal hypoplasia and this was severe in four dogs. Laryngeal collapse was present in all dogs. Two dogs had stage I, four dogs stage II, and one dog stage III laryngeal collapse. The dog with stage III laryngeal collapse and one dog with stage II laryngeal collapse died. There was no apparent association between the changes evident on thoracic radiographs or the degree of tracheal hypoplasia and postoperative outcome.ClinicalSignificance:The development of severe secondary laryngeal changes in dogs aged six months or less supports the suggestion that immature brachycephalic dogs should undergo assessment and, if indicated, surgery as soon as any clinical signs of BAS are apparent.
Inhibition of VEGFR-3 Activation with the Antagonistic Antibody More Potently Suppresses Lymph Node and Distant Metastases than Inactivation of VEGFR-2
Authors: Roberts Nicole , Kloos Bryan , Cassella Melanie , Podgrabinska Simona , Persaud Kris , Wu Yan , Pytowski Bronislaw , Skobe Mihaela 
Published: March 2006

Abstract
Lymph nodes are the first site of metastases for most types of cancer, and lymph node status is a key indicator of patient prognosis. Induction of tumor lymphangiogenesis by vascular endothelial growth factor-C (VEGF-C) has been shown to play an important role in promoting tumor metastases to lymph nodes. Here, we employed receptor-specific antagonist antibodies in an orthotopic spontaneous breast cancer metastasis model to provide direct evidence for the key role of VEGFR-3 activation in metastasis. Inhibition of VEGFR-3 activation more potently suppressed regional and distant metastases than inactivation of VEGFR-2, although VEGFR-2 blockade was more effective in inhibiting angiogenesis and tumor growth. Despite prominent proliferation, metastases were not vascularized in any of the control and treatment groups, indicating that the growth of metastases was not dependent on angiogenesis at the secondary site for the duration of the experiment. Systemic treatment with either VEGFR-2 or VEGFR-3 antagonistic antibodies suppressed tumor lymphangiogenesis, indicating that VEGFR-3 signaling affects the rate of tumor cell entry into lymphatic vessels through both lymphangiogenesis-dependent and independent mechanisms. Combination treatment with the anti-VEGFR-2 and anti-VEGFR-3 antibodies more potently decreased lymph node and lung metastases than each antibody alone. These results validate the concept of targeting the lymphatic dissemination and thereby very early steps of the metastatic process for metastasis control and suggest that a combination therapy with antiangiogenic agents may be a particularly promising approach for controlling metastases. (Cancer Res 2006; 66(5): 2650-7)
The Small Organic Compound HA14-1 Prevents Bcl-2 Interaction with Bax to Sensitize Malignant Glioma Cells to Induction of Cell Death
Authors: Manero Florence , Gautier Fabien , Gallenne Tristan , Cauquil Nicolas , Grée Danielle , Cartron Pierre-François , Geneste Olivier , Grée René , Vallette François M. , Juin Philippe 
Published: March 2006

Abstract
A functional imbalance between proapoptotic Bax and antiapoptotic Bcl-2 is likely to participate in the resistance of cancer cells to therapy. We show here that ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (HA14-1), a small organic compound recently proposed to function as an inhibitor of Bcl-2, increases the sensitivity of human glioblastoma cells to radiotherapy and chemotherapy. This sensitizing effect is lost if Bcl-2 expression, but not Bcl-xL expression, is knocked down or if cells only express a mutant of Bax that does not interact with Bcl-2. This points to a specific Bcl-2 inhibitory function of HA14-1 and implies that it selectively involves hindrance of Bcl-2 binding to Bax, which HA14-1 inhibits in cell-free assays and in cells in receipt of an apoptotic stimulation. Moreover, HA14-1, in combination with a cytotoxic treatment, slows down the growth of glioblastoma in vivo. Thus, the inhibition of Bcl-2 achieved by HA14-1 might improve treatment outcome. (Cancer Res 2006; 66(5): 2757-64)
Expression of RASSF1A, an Epigenetically Silenced Tumor Suppressor, Overcomes Resistance to Apoptosis Induction by Interferons
Authors: Reu Frederic J. , Leaman Douglas W. , Maitra Ratan R. , Bae Soo In , Cherkassky Leonid , Fox Mark W. , Rempinski Donald R. , Beaulieu Normand , MacLeod A. Robert , Borden Ernest C. 
Published: March 2006

Abstract
Resistance of human renal cell carcinoma (RCC) and melanoma to the apoptosis-inducing effects of IFNs was postulated to result from epigenetic silencing of genes by DNA methylation, a common feature of human cancers. To reverse silencing, 5-AZA-deoxycytidine (5-AZA-dC) or selective depletion of DNA methyltransferase 1 (DNMT1) by phosphorothioate oligonucleotide antisense (DNMT1 AS) were employed in cells resistant (&lt;5% terminal deoxynucleotidyl transferase–mediated nick-end labeling positive) to apoptosis induction by IFN-α2 and IFN-β (ACHN, SK-RC-45, and A375). 5-AZA-dC and DNMT1 AS similarly depleted available DNMT1 protein and, at doses that did not cause apoptosis alone, resulted in apoptotic response to IFNs. The proapoptotic tumor suppressor RASSF1A was reactivated by DNMT1 inhibitors in all three cell lines. This was associated with demethylation of its promoter region. IFNs augmented RASSF1A protein expression after reactivation by DNMT1 inhibition. In IFN-sensitive WM9 melanoma cells, expression of RASSF1A was constitutive but also augmented by IFNs. RASSF1A small interfering RNA reduced IFN-induced apoptosis in WM9 cells and in DNMT1-depleted ACHN cells. Conversely, lentiviral expression of RASSF1A but not transduction with empty virus enabled IFN-induced apoptosis. IFN induced tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and TRAIL-neutralizing antibody inhibited apoptotic response to IFN in RASSF1A-expressing ACHN cells. Accordingly, RASSF1A markedly sensitized to recombinant TRAIL. Normal kidney epithelial cells, although expressing RASSF1A, did not undergo apoptosis in response to IFN or TRAIL but had &gt;400-fold higher TRAIL decoy receptor 1 expression than transduced ACHN cells (real-time reverse transcription-PCR). Results identified RASSF1A as regulated by IFNs and participating in IFN-induced apoptosis at least in part by sensitization to TRAIL. (Cancer Res 2006; 66(5): 2785-93)
Proteolytic Release of Soluble UL16-Binding Protein 2 from Tumor Cells
Authors: Waldhauer Inja , Steinle Alexander 
Published: March 2006

Abstract
The MHC class I–related ligands of the immunoreceptor NKG2D are frequently expressed by tumor cells and stimulate tumor immunity mediated by CD8 T cells and natural killer (NK) cells. In humans, NKG2D ligands (NKG2DL) are encoded by the MHC-encoded MIC and non–MHC-encoded UL16-binding protein (ULBP) families of proteins. Recently, we and others showed that tumor cells release soluble MICA (sMICA), thereby counteracting NKG2D-mediated tumor immunosurveillance. Here, we now report that ULBP2 molecules are likewise released from tumor cells in a processed soluble form, and that soluble ULBP2 (sULBP2) can be detected in sera of some patients with hematopoietic malignancies. Tumor cell–derived sULBP2 as opposed to cell-bound ULBP2 does not down-regulate NKG2D on NK cells. Unexpectedly, the glycosylphosphatidylinositol-anchored ULBP2 molecules are not released by phospholipases but by the action of metalloproteases. Proteolytic shedding of both NKG2D ligands MICA and ULBP2 by tumor cells was strongly enhanced after phorbol 12-myristate 13-acetate treatment and paralleled by a markedly reduced susceptibility to NKG2D-mediated cytotoxicity. Shedding of MICA and ULBP2 can be blocked by the same inhibitors, suggesting the involvement of related metalloproteases. Thus, our data suggest that reducing NKG2DL surface densities is due to a common cleavage process executed by metalloproteases that promotes escape of tumors from NKG2D-mediated immunosurveillance. (Cancer Res 2006; 66(5): 2520-6)
Pharmacogenomic Identification of Novel Determinants of Response to Chemotherapy in Colon Cancer
Authors: Boyer John , Allen Wendy L. , McLean Estelle G. , Wilson Peter M. , McCulla Andrea , Moore Stephen , Longley Daniel B. , Caldas Carlos , Johnston Patrick G. 
Published: March 2006

AbstractDNA microarray analysis was used to analyze the transcriptional profile of HCT116 colorectal cancer cells that were treated with 5-fluorouracil (5-FU) or oxaliplatin and selected for resistance to these agents. Bioinformatic analyses identified sets of genes that were constitutively dysregulated in drug-resistant cells and transiently altered following acute exposure of parental cells to drug. We propose that these genes may represent molecular signatures of sensitivity to 5-FU and oxaliplatin. Using real-time reverse transcription-PCR (RT-PCR), the robustness of our microarray data was shown with a strong overall concordance of expression trends for ≥82% (oxaliplatin) and ≥85% (5-FU) of a representative subset of genes. Furthermore, strong correlations between the microarray and real-time RT-PCR measurements of average fold changes in gene expression were observed for both the 5-FU (R2 ≥ 0.73) and oxaliplatin gene sets (R2 ≥ 0.63). Functional analysis of three genes identified in the microarray study [prostate-derived factor (PDF), calretinin, and spermidine/spermine N1-acetyl transferase (SSAT)] revealed their importance as novel regulators of cytotoxic drug response. These data show the power of this novel microarray-based approach to identify genes which may be important markers of response to treatment and/or targets for therapeutic intervention. (Cancer Res 2006; 66(5): 2765-77)
Matrix Metalloproteinase 26 Proteolysis of the NH2-Terminal Domain of the Estrogen Receptor β Correlates with the Survival of Breast Cancer Patients
Authors: Savinov Alexei Y. , Remacle Albert G. , Golubkov Vladislav S. , Krajewska Maryla , Kennedy Susan , Duffy Michael J. , Rozanov Dmitri V. , Krajewski Stan , Strongin Alex Y. 
Published: March 2006

Abstract
Estrogens have many cellular functions, including their interactions with estrogen receptors α and β (ERα and ERβ). Earlier, we determined that the estrogen-ER complex stimulates the transcriptional activity of the matrix metalloproteinase 26 (MMP-26) gene promoter. We then determined that ERβ is susceptible to MMP-26 proteolysis whereas ERα is resistant to the protease. MMP-26 targets the NH2-terminal region of ERβ coding for the divergent NH2-terminal A/B domain that is responsible for the ligand-independent transactivation function. As a result, MMP-26 proteolysis generates the COOH-terminal fragments of ERβ. Immunohistochemical analysis of tissue microarrays derived from 121 cancer patients corroborated these data and revealed an inverse correlation between the ERα-dependent expression of MMP-26 and the levels of the intact ERβ in breast carcinomas. MMP-26 is not expressed in normal mammary epithelium. The levels of MMP-26 are strongly up-regulated in ductal carcinoma in situ (DCIS). In the course of further disease progression through stages I to III, the expression of MMP-26 decreases. In contrast to many tumor-promoting MMPs, the expression of MMP-26 in DCIS correlated with a longer patient survival. Our data suggest the existence of an MMP-26–mediated intracellular pathway that targets ERβ and that MMP-26, a novel and valuable cancer marker, contributes favorably to the survival of the ERα/β–positive cohort of breast cancer patients. (Cancer Res 2006; 66(5): 2716-24)
Hypoxia-Inducible Factor-1-Dependent Repression of E-cadherin in von Hippel-Lindau Tumor Suppressor–Null Renal Cell Carcinoma Mediated by TCF3, ZFHX1A, and ZFHX1B
Authors: Krishnamachary Balaji , Zagzag David , Nagasawa Hideko , Rainey Karin , Okuyama Hiroaki , Baek Jin H. , Semenza Gregg L. 
Published: March 2006

Abstract
A critical event in the pathogenesis of invasive and metastatic cancer is E-cadherin loss of function. Renal clear cell carcinoma (RCC) is characterized by loss of function of the von Hippel-Lindau tumor suppressor (VHL), which negatively regulates hypoxia-inducible factor-1 (HIF-1). Loss of E-cadherin expression and decreased cell-cell adhesion in VHL-null RCC4 cells were corrected by enforced expression of VHL, a dominant-negative HIF-1α mutant, or a short hairpin RNA directed against HIF-1α. In human RCC biopsies, expression of E-cadherin and HIF-1α was mutually exclusive. The expression of mRNAs encoding TCF3, ZFHX1A, and ZFHX1B, which repress E-cadherin gene transcription, was increased in VHL-null RCC4 cells in a HIF-1–dependent manner. Thus, HIF-1 contributes to the epithelial-mesenchymal transition in VHL-null RCC by indirect repression of E-cadherin. (Cancer Res 2006; 66(5): 2725-31)
Caspase Recruitment Domain-Containing Protein 15 Mutations in Patients with Colorectal Cancer
Authors: Roberts Rebecca L. , Gearry Richard B. , Allington Melanie D.E. , Morrin Helen R. , Robinson Bridget A. , Frizelle Frank A. 
Published: March 2006

Abstract
The caspase recruitment domain-containing protein 15 (CARD15) plays a crucial role in mediating the innate immune response. Mutations within this protein have been shown to be independent risk factors for the development of Crohn's disease in Caucasians. As Crohn's disease patients are at increased risk of developing sporadic colorectal cancer, it is conceivable that genetic variability within CARD15 may also play a role in determining susceptibility to this gastrointestinal malignancy in individuals without Crohn's disease. This hypothesis is supported by the findings of two case-control studies that found the frequencies of CARD15 mutations were significantly elevated in Polish and Greek colorectal cancer patients. Given the results of these previous studies, we examined whether the high incidence of sporadic colorectal cancer observed in New Zealand Caucasians was due to mutations within CARD15. To answer this question, we genotyped 133 colorectal cancer patients and 201 Caucasian controls for R702W, G908R, 1007fs, and P268S. χ2 Testing found that the combined frequency of R702W, G908R, and 1007fs was significantly elevated in colorectal cancer patients compared with controls (P = 0.001; odds ratio, 2.8; 95% confidence interval, 1.5-5.4), but no association was detected between tumor behavior or age of disease onset and CARD15 mutations in our colorectal cancer cohort. This study is the first to explore the link between CARD15 mutations and colorectal cancer in New Zealand Caucasians. Our results strongly suggest that CARD15 influences susceptibility to colorectal cancer, but we have found no evidence to indicate that CARD15 mutations predict the clinicopathologic characteristics of this disease. (Cancer Res 2006; 66(5): 2532-5)
Conversion And The Religious Market: A Theological Perspective
Authors: Houtepen Anton 
Published: March 2006

AbstractThis article wants first of all to describe, which historical-theological factors contributed to an important shift of meaning of the concept of conversion from the 18th and 19th century onwards. A more communal and covenantal, theocentric and ecclesial understanding of religious belonging has gradually shifted towards an individual personal, experiential, anthropocentric and charismatic interpretation. Evangelicals and Pentecostals share the idea of 'heartfelt religion', interpreting conversion as a sudden and momentous event, usually after a personal crisis. The historical churches rather stress the lifelong challenge of conversion, related to participation in church life, the liturgy and the sacraments.The second part deals with a series of Roman Catholic-Pentecostal ecumenical dialogues about the problems arising between these rather opposite ideas of Christian conversion. Different ecclesiological and pneumatological points of view are at stake here. Major problems arise when people from the older churches are invited to change their affiliation and want to renew their baptismal votes with the 'baptism in the Holy Spirit'. Dialogue partners tend to avoid all forms of proselytism, but common evangelisation and common witness, let alone ecumenical cooperation toward church unity or ecclesial communion still seem to be a bridge too far.
Exorcism And Conversion To African Pentecostalism
Authors: Anderson Allan 
Published: March 2006

AbstractThe rapid growth of Pentecostal forms of Christianity in Africa in recent years can partly be attributed to the prevalent practice of exorcism or 'deliverance' that characterises it. This essay considers the phenomenon from the perspective of the African popular religious spirit world, where spirits and 'demons' abound. It begins with a discussion of the 'translation' of pre-modern African religious ideas into Christian discourse, and gives several case studies from West Africa and especially from Southern Africa. It concludes that Pentecostal Christianity with its offer of 'deliverance' from evil powers fulfils a felt need and therefore produces a 'product' that is attractive in Africa's religious market, resulting in multiple conversions.
A review of acute effects of 3,4-methylenedioxymethamphetamine in healthy volunteers
Authors: Dumont G. J. H. , Verkes R. J. 
Published: March 2006

This review of the literature aims to identify the acute effects of MDMA (ecstasy) in healthy volunteers. The wide range of relevant but methodologically diverse tests was .rst grouped into clusters to allow an evaluation of tests that would otherwise have been excluded due to their low frequency of utilization. The following three types of tests were evaluated: (1) functional tests quantifying executive, attention, visual, motor, visuomotor and auditory functions, (2) phenomenological tests assessing personal, subjective experiences, and (3) physiological measures re.ecting neurophysiological, endocrine and physiological parameters.MDMA showed robust effects on most of the phenomenological and physiological tests. Functional tests were scarce, preventing any meaningful conclusions to be drawn from their evaluation other than that these tests should be incorporated into future acute-effect studies.A striking doseñresponse relationship appeared for cardiovascular effects. At doses below 1.0 mg/kg MDMA no change was observed relative to placebo while above this dose all studies reported signi.cant increases. Furthermore, pupil size, plasma cortisol and plasma prolactin levels proved responsive to MDMA administration. The reported subjective effects of MDMA matched the entactogenic profile.Although interest in the action of MDMA is considerable, the existing knowledge about the cognitive effects of MDMA in humans is still rather limited and further research into the drug's effects is recommended, also in view of potential therapeutic uses of the drug.
Activity of subcutaneous interleukin-12 in AIDS-related Kaposi sarcoma
Authors: Little Richard F. , Pluda James M. , Wyvill Kathleen M. , Rodriguez-Chavez Isaac R. , Tosato Giovanna , Catanzaro Andrew T. , Steinberg Seth M. , Yarchoan Robert 
Published: March 2006

AbstractInterleukin-12 (IL-12) enhances Th1-type T-cell responses and exerts antiangiogenic effects. We initiated a phase 1 pilot study of IL-12 in 32 patients with acquired immunodeficiency syndrome (AIDS)–related Kaposi sarcoma (KS) whose KS was progressing while on antiretroviral therapy. Fifteen patients had poor prognosis T1S1 disease. IL-12 was administered subcutaneously twice weekly at doses from 100 to 625 ng/kg. The maximum tolerated dose was 500 ng/kg, and the principal toxicities were flulike symptoms, transaminase or bilirubin elevations, neutropenia, hemolytic anemia, and depression. No tumor responses were seen at the lowest dose (100 ng/kg), but 17 of 24 evaluable patients at the higher doses had partial or complete responses (response rate, 71%; 95% confidence interval, 48%-89%). Only 3 of 17 patients had a change in antiretroviral therapy before responding, and there were no significant differences between responders and nonresponders with regard to changes in CD4 counts or viral loads. Patients had increases in their serum IL-12, interferon-γ, and inducible protein-10 (IP-10) after the first dose, and increases above baseline persisted after week 4. These results provide preliminary evidence that IL-12 has substantial activity against AIDS-related KS with acceptable toxicity and warrants further investigation for this indication.
Quantitative proteomics reveals posttranslational control as a regulatory factor in primary hematopoietic stem cells
Authors: Unwin Richard D. , Smith Duncan L. , Blinco David , Wilson Claire L. , Miller Crispin J. , Evans Caroline A. , Jaworska Ewa , Baldwin Stephen A. , Barnes Kay , Pierce Andrew , Spooncer Elaine , Whetton Anthony D. 
Published: March 2006

AbstractThe proteome is determined by rates of transcription, translation, and protein turnover. Definition of stem cell populations therefore requires a stem cell proteome signature. However, the limit to the number of primary cells available has restricted extensive proteomic analysis. We present a mass spectrometric method using an isobaric covalent modification of peptides for relative quantification (iTRAQ), which was employed to compare the proteomes of approximately 1 million long-term reconstituting hematopoietic stem cells (Lin–Sca+Kit+; LSK+) and non–long-term reconstituting progenitor cells (Lin–Sca+Kit–; LSK–), respectively. Extensive 2-dimensional liquid chromatography (LC) peptide separation prior to mass spectrometry (MS) enabled enhanced proteome coverage with relative quantification of 948 proteins. Of the 145 changes in the proteome, 54% were not seen in the transcriptome. Hypoxia-related changes in proteins controlling metabolism and oxidative protection were observed, indicating that LSK+ cells are adapted for anaerobic environments. This approach can define proteomic changes in primary samples, thereby characterizing the molecular signature of stem cells and their progeny.