bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do prostaglandins modulate renal haemodynamic effects of endothelin-1 in conscious lambs?
Authors: Ebenezar Kumar Kesavarao , Sharbaf Fatemah Ghane , Qi Wei , Smith Francine Gabriel 
Published: March 2010

To test the hypothesis that vasodilatory prostaglandins buffer the renal vasoconstrictor effects of endothelin-1 (ET-1) early in life, renal haemodynamic responses to ET-1 were measured in 2 groups of conscious, chronically instrumented lambs at 1–2 weeks of age (group I, n = 11) and 6 weeks of age (group II, n = 10). Lambs were pretreated with vehicle or 1 mg·kg–1 indomethacin, a nonselective cyclooxygenase inhibitor, and renal haemodynamic effects were measured continuously for 1 min before (control) and 5 min after intra-arterial injection of 250 ng·kg–1 ET-1. In group II lambs, there was a marked decrease in renal blood flow (RBF) and renal vascular conductance (RVC) elicited by ET-1 administration, as we have previously described. This response was not altered by vehicle or indomethacin pretreatment. In group I lambs, there was an initial increase but no decrease in RBF and RVC elicited by ET-1 administration, as we have previously described, and this response was also not altered by either vehicle or indomethacin. These results suggest that endogenously produced prostaglandins do not appear to modulate the renal haemodynamic effects of ET-1 in conscious lambs during postnatal maturation.
Competition between recolonizing wolves and resident lynx in Sweden
Authors: Wikenros Camilla , Liberg Olof , Sand Håkan , Andrén Henrik 
Published: March 2010

We studied the effect of a recolonizing wolf ( Canis lupus L., 1758) population on a resident lynx ( Lynx lynx (L., 1758)) population in south-central Sweden. Wolf and lynx share the same prey species, western roe deer ( Capreolus capreolus (L., 1758)), and the size difference between the two species suggests a strong potential for interference competition. The spatial distributions of lynx family groups (n = 378) over four winters were not significantly affected by the increase in size and range of the wolf population. Survival of lynx kittens until 9 months of age did not differ significantly inside (54%; n = 37) and outside (62%; n = 42) wolf territories, and female lynx (n = 3) selected natal den sites (n = 19) in the same local area before and after wolf establishment. Furthermore, lynx home-range size (n = 42) did not increase as a result of presence of wolves and space use by female lynx (n = 3) was not affected by wolf establishment. We found no evidence of cleptoparasitism by wolves on roe deer killed by lynx. We conclude that the intensity of interference and exploitation competition between wolves and lynx was low.
Toll-like Receptor 3–Mediated Suppression of TRAMP Prostate Cancer Shows the Critical Role of Type I Interferons in Tumor Immune Surveillance
Authors: Chin Arnold I. , Miyahira Andrea K. , Covarrubias Anthony , Teague Juli , Guo Beichu , Dempsey Paul W. , Cheng Genhong 
Published: March 2010

Abstract
Inflammation has increasingly been recognized as a critical component influencing tumor growth. Recent reports have revealed conflicting evidence for the role of Toll-like receptors (TLR) in modulating tumorigenesis. In our study, we implicate TLR3 in mediating immune surveillance with increased growth of implanted transgenic adenocarcinoma of the mouse prostate (TRAMP) tumors in TLR3−/− compared with TLR3+/+ mice. Activation of TLR3 by polyinosinic-polycytidylic acid (polyI:C) leads to induction of multiple inflammatory pathways, including NF-κB, mitogen-activated protein kinases, and interferon (IFN) regulatory factors. We explored the potential of TLR3 stimulation in prostate cancer immunotherapy and showed that treatment with polyI:C can strongly suppress both s.c. implanted TRAMP tumors in syngenic mice as well as orthotopic prostate cancers in TRAMP C57Bl6 × FvB F1 Tg+/− transgenic mice. Treated tumors remained well differentiated to moderately differentiated with increased infiltration of T lymphocytes and natural killer (NK) cells compared with poorly differentiated adenocarcinoma observed in untreated tumors. Like TLR3−/− mice, IFN-α receptor 1 (IFNAR1)−/− mice exhibited reduced tumor surveillance and impaired tumor suppression following polyI:C treatment. We observed that type I IFN–dependent induction of cytokines was responsible for NK activation, with depletion of NK cells leading to increased tumor growth as well as expansion of CD4+CD25+Foxp3+ T regulatory lymphocytes. Our study therefore delineates the importance of IFNAR-dependent functions in TLR3-mediated tumor suppression and supports the use of TLR3 agonists for prostate cancer immune-based therapies. Cancer Res; 70(7); 2595–603
CpG Island Hypermethylation in Human Astrocytomas
Authors: Wu Xiwei , Rauch Tibor A. , Zhong Xueyan , Bennett William P. , Latif Farida , Krex Dietmar , Pfeifer Gerd P. 
Published: March 2010

Abstract
Astrocytomas are common and lethal human brain tumors. We have analyzed the methylation status of over 28,000 CpG islands and 18,000 promoters in normal human brain and in astrocytomas of various grades using the methylated CpG island recovery assay. We identified 6,000 to 7,000 methylated CpG islands in normal human brain. Approximately 5% of the promoter-associated CpG islands in the normal brain are methylated. Promoter CpG island methylation is inversely correlated whereas intragenic methylation is directly correlated with gene expression levels in brain tissue. In astrocytomas, several hundred CpG islands undergo specific hypermethylation relative to normal brain with 428 methylation peaks common to more than 25% of the tumors. Genes involved in brain development and neuronal differentiation, such as BMP4, POU4F3, GDNF, OTX2, NEFM, CNTN4, OTP, SIM1, FYN, EN1, CHAT, GSX2, NKX6-1, PAX6, RAX, and DLX2, were strongly enriched among genes frequently methylated in tumors. There was an overrepresentation of homeobox genes and 31% of the most commonly methylated genes represent targets of the Polycomb complex. We identified several chromosomal loci in which many (sometimes more than 20) consecutive CpG islands were hypermethylated in tumors. Seven such loci were near homeobox genes, including the HOXC and HOXD clusters, and the BARHL2, DLX1, and PITX2 genes. Two other clusters of hypermethylated islands were at sequences of recent gene duplication events. Our analysis offers mechanistic insights into brain neoplasia suggesting that methylation of the genes involved in neuronal differentiation, in cooperation with other oncogenic events, may shift the balance from regulated differentiation towards gliomagenesis. Cancer Res; 70(7); 2718–27
An Optimized Telomerase-Specific Lentivirus for Optical Imaging of Tumors
Authors: Yu Song-Tao , Yang Yin-Bing , Liang Guang-Ping , Li Chuan , Chen Ling , Shi Chun-Meng , Tang Xu-Dong , Li Chang-Zhu , Li Ling , Wang Guo-Zheng , Wu Yu-Yun , Yang Shi-Ming , Fang Dian-Chun 
Published: March 2010

Abstract
Advances in medical imaging techniques, such as ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography, have made great progress in detecting tumors. However, these imaging techniques are unable to differentiate malignant tumors from benign ones. Recently developed optical imaging of tumors in small animals provides a useful method to distinguish malignant tumors from their surrounding normal tissues. Human telomerase reverse transcriptase (hTERT) is normally inactivated in most somatic cells, whereas it is commonly reactivated in many cancer cells. In this study, we constructed a lentiviral vector that expresses green fluorescent protein (GFP) driven by an optimized hTERT promoter to create a noninvasive tumor-specific imaging methodology. The activity of this optimized hTERT promoter was found to be equal to the activity of SV40 and cytomegalovirus promoters. In vitro experiments showed that GFP was only expressed in telomerase-positive tumor cells infected with this lentivirus, whereas there was no GFP expression in telomerase-negative tumor cells or normal somatic cells. We also found that subcutaneous telomerase-positive tumors could be visualized 24 hours after an intratumoral injection with this lentivirus by using a charge-coupled device (CCD) camera. In contrast, telomerase-negative tumors could not be imaged after an intratumoral injection even for 30 days. These results suggest that infection with lentivirus containing this optimized hTERT promoter might be a useful diagnostic tool for the real-time visualization of macroscopically invisible tumor tissues using a highly sensitive CCD imaging system. Cancer Res; 70(7); 2585–94
A Small Interfering RNA Screen of Genes Involved in DNA Repair Identifies Tumor-Specific Radiosensitization by POLQ Knockdown
Authors: Higgins Geoff S. , Prevo Remko , Lee Yin-Fai , Helleday Thomas , Muschel Ruth J. , Taylor Steve , Yoshimura Michio , Hickson Ian D. , Bernhard Eric J. , McKenna W. Gillies 
Published: March 2010

Abstract
The effectiveness of radiotherapy treatment could be significantly improved if tumor cells could be rendered more sensitive to ionizing radiation (IR) without altering the sensitivity of normal tissues. However, many of the key therapeutically exploitable mechanisms that determine intrinsic tumor radiosensitivity are largely unknown. We have conducted a small interfering RNA (siRNA) screen of 200 genes involved in DNA damage repair aimed at identifying genes whose knockdown increased tumor radiosensitivity. Parallel siRNA screens were conducted in irradiated and unirradiated tumor cells (SQ20B) and irradiated normal tissue cells (MRC5). Using γH2AX foci at 24 hours after IR, we identified several genes, such as BRCA2, Lig IV, and XRCC5, whose knockdown is known to cause increased cell radiosensitivity, thereby validating the primary screening end point. In addition, we identified POLQ (DNA polymerase θ) as a potential tumor-specific target. Subsequent investigations showed that POLQ knockdown resulted in radiosensitization of a panel of tumor cell lines from different primary sites while having little or no effect on normal tissue cell lines. These findings raise the possibility that POLQ inhibition might be used clinically to cause tumor-specific radiosensitization. Cancer Res; 70(7); 2984–93
An Unexpectedly Large Polyclonal Repertoire of HPV-Specific T Cells Is Poised for Action in Patients with Cervical Cancer
Authors: de Vos van Steenwijk Peggy J. , Heusinkveld Moniek , Ramwadhdoebe Tamara H. , Löwik Margriet J. , van der Hulst Jeanette M. , Goedemans Renske , Piersma Sytse J. , Kenter Gemma G. , van der Burg Sjoerd H. 
Published: March 2010

AbstractThe diversity and extent of the local tumor-specific T-cell response in a given individual is largely unknown. We have performed an in-depth study of the local T-cell repertoire in a selected group of patients with cervical cancer, by systematic analyses of the proportion, breadth, and polarization of human papillomavirus (HPV) E6/E7-specific T cells within the total population of tumor-infiltrating lymphocytes (TIL) and tumor-draining lymph node cells (TDLNC). Isolated T cells were stimulated with sets of overlapping E6 and E7 peptides and analyzed by multiparameter flow cytometry with respect to activation, cytokine production, and T-cell receptor Vβ usage. HPV-specific CD4+ and CD8+ T-cell responses were detected in TIL and TDLNC and their relative contribution varied between &lt;1% and 66% of all T cells. In general, these HPV-specific responses were surprisingly broad, aimed at multiple E6 and E7 epitopes and involved multiple dominant and subdominant T-cell receptor Vβs per single peptide-epitope. In most patients, only few IFNγ-producing T cells were found and the amount of IFNγ produced was low, suggesting that these are poised T cells, rendered functionally inactive within the tumor environment. Importantly, stimulation of the TIL and TDLNC with cognate antigen in the presence of commonly used Toll-like receptor ligands significantly enhanced the effector T-cell function. In conclusion, our study suggests that within a given patient with HPV-specific immunity many different tumor-specific CD4+ and CD8+ T cells are locally present and poised for action. This vast existing local T-cell population is awaiting proper stimulation and can be exploited for the immunotherapy of cancer. Cancer Res; 70(7); 2707–17
DNA Copy Numbers Profiles in Affinity-Purified Ovarian Clear Cell Carcinoma
Authors: Kuo Kuan-Ting , Mao Tsui-Lien , Chen Xu , Feng Yuanjian , Nakayama Kentaro , Wang Yue , Glas Ruth , Ma M. Joe , Kurman Robert J. , Shih Ie-Ming , Wang Tian-Li 
Published: March 2010

Abstract
Purpose: Advanced ovarian clear cell carcinoma (CCC) is one of the most aggressive ovarian malignancies, in part because it tends to be resistant to platinum-based chemotherapy. At present, little is known about the molecular genetic alterations in CCCs except that there are frequent activating mutations in PIK3CA. The purpose of this study is to comprehensively define the genomic changes in CCC based on DNA copy number alterations.
Experimental Design: We performed 250K high-density single nucleotide polymorphism array analysis in 12 affinity-purified CCCs and 10 CCC cell lines. Discrete regions of amplification and deletion were also analyzed in additional 21 affinity-purified CCCs using quantitative real-time PCR.
Results: The level of chromosomal instability in CCC as defined by the extent of DNA copy number changes is similar to those previously reported in low-grade ovarian serous carcinoma but much less than those in high-grade serous carcinoma. The most remarkable region with DNA copy number gain is at chr20, which harbors a potential oncogene, ZNF217. This discrete amplicon is observed in 36% of CCCs but rarely detected in serous carcinomas regardless of grade. In addition, homozygous deletions are detected at the CDKN2A/2B and LZTS1 loci. Interestingly, the DNA copy number changes observed in fresh CCC tissues are rarely detected in the established CCC cell lines.
Conclusions: This study provides the first high resolution, genome-wide view of DNA copy number alterations in ovarian CCC. The findings provide a genomic landscape for future studies aimed at elucidating the pathogenesis and developing new target-based therapies for CCCs. Clin Cancer Res; 16(7); 1997–2008. ©2010 AACR.
Transcriptional Profiles Predict Disease Outcome in Patients with Cutaneous T-Cell Lymphoma
Authors: Litvinov Ivan V. , Jones David A. , Sasseville Denis , Kupper Thomas S. 
Published: March 2010

Abstract
Purpose: Average survival of cutaneous T-cell lymphoma (CTCL) is associated with clinical stage at diagnosis, where stage I has a favorable survival prognosis, whereas patients with more advanced stages succumb to their disease within 5 years. Although the majority of patients present with an early-stage CTCL, 15% to 20% of them will inevitably progress. Current state-of-the-art clinical criteria cannot identify individuals with stage I disease who are at risk of progression. The purpose of the current work is to gain novel molecular insight into the pathophysiology of CTCL to be able to identify patients with poor versus favorable prognosis. Our previous work used microarray analysis of skin biopsies from 62 CTCL patients to perform an unsupervised analysis of gene expression, which revealed three distinct transcription profile clusters.
Experimental Design: In the present study, we used reverse transcription-PCR to confirm gene expression levels for a subset of representative genes in each cluster. We also performed a Kaplan-Meier analysis of survival and disease progression based on the 6 years of clinical follow-up.
Results: Our reverse transcription-PCR results confirmed the upregulation of representative genes for each cluster, whereas clinical analysis documents that all stage I cases that progressed to stage II and beyond were in poor and intermediate prognosis clusters 1 and 3 and none were in favorable prognosis cluster 2. This analysis also identified certain genes that were preferentially expressed in favorable (e.g., WIF-1) versus poor (e.g., IL-17F) prognosis clusters.
Conclusion: This work suggests that it may be possible to stratify CTCL patients into low-risk, intermediate-risk, and high-risk groups based on gene expression. Clin Cancer Res; 16(7); 2106–14. ©2010 AACR.
Bcl2 and Human Papilloma Virus 16 as Predictors of Outcome following Concurrent Chemoradiation for Advanced Oropharyngeal Cancer
Authors: Nichols Anthony C. , Finkelstein Dianne M. , Faquin William C. , Westra William H. , Mroz Edmund A. , Kneuertz Peter , Begum Shahnaz , Michaud William A. , Busse Paul M. , Clark John R. , Rocco James W. 
Published: March 2010

Abstract
Purpose: Oropharyngeal squamous cell carcinoma (OPSCC) associated with human papilloma virus (HPV) is rapidly growing in incidence. Despite better prognosis than OPSCC associated with traditional risk factors, treatment failure still occurs in a significant proportion of patients. We had identified the antiapoptotic protein Bcl2 as a marker for poor outcome in advanced OPSCC treated with concurrent chemoradiation. To determine whether Bcl2 and HPV together might further characterize treatment response, we examined whether the prognostic value of Bcl2 was independent of HPV status.
Experimental Design: Pretreatment tumor biopsies from 68 OPSCC patients were tested for HPV by in situ hybridization and were immunostained for Bcl2 to evaluate relations with disease-free (DFS) and overall survival following platin-based concurrent chemoradiation. Median follow-up among surviving patients was 47 months (range, 10-131 months).
Results: Bcl2 and HPV independently predicted DFS and overall survival. Hazard ratios (with 95% confidence interval) for positive versus negative status in bivariate Cox proportional hazard analysis of DFS were 6.1 (1.8-21) for Bcl2 and 0.11 (0.035-0.37) for HPV. Only 1 of 32 HPV-positive/Bcl2-negative tumors recurred. Pretreatment Bcl2 expression was specifically associated with distant metastasis; five of six distant metastases occurred in the &lt;40% of patients whose primary tumors were Bcl2 positive.
Conclusions: Independent of HPV status, pretreatment Bcl2 expression identifies a subset of OPSCC patients having increased risk of treatment failure, particularly through distant metastasis, after concurrent chemoradiation. Considering HPV and Bcl2 together should help in devising better personalized treatments for OPSCC. Clin Cancer Res; 16(7); 2138–46. ©2010 AACR.
Gene Signatures for the Prediction of Response to Bacillus Calmette-Guérin Immunotherapy in Primary pT1 Bladder Cancers
Authors: Kim Yong-June , Ha Yun-Sok , Kim Seon-Kyu , Yoon Hyung Yoon , Lym Min Su , Kim Min-Ju , Moon Sung-Kwon , Choi Yung Hyun , Kim Wun-Jae 
Published: March 2010

Abstract
Purpose: Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy is effective in the prevention of recurrence and progression in many cases of nonmuscle invasive bladder cancer, but many patients fail to respond. The aim of this study was to identify gene sets of markers that could predict the response to BCG immunotherapy in primary pT1 bladder cancer using microarray gene expression profiling.
Experimental Design: We used 80 patients with primary pT1 bladder cancer treated with BCG immunotherapy as training (48) and test (32) sets. Microarray gene expression profiling was done in the training set to identify genes differentially expressed between responder and nonresponder to BCG immunotherapy according to the events (recurrence or progression). Using a real-time reverse-transcriptase PCR, our findings were validated in the test set.
Results: In the training set, 424 and 287 genes were significantly associated with recurrence- and progression-free survival, respectively. Functional annotation of these genes included cell-mediated immune response, inflammatory response, cellular growth, and proliferation. From these predictive gene signatures, 24 genes (12 in recurrence and 12 in progression) with the highest score of expression ratio were extracted for validation in the test set. In multivariate regression analyses, predictive gene signatures were the only independent predictors of recurrence (hazard ratio, 3.38; P = 0.048) or progression (hazard ratio, 10.49; P = 0.048) in the test set.
Conclusions: Predictive gene signatures have diagnostic value for determining the response to intravesical BCG immunotherapy in primary pT1 bladder cancer. Clin Cancer Res; 16(7); 2131–7. ©2010 AACR.
Weight Loss via Exercise with Controlled Dietary Intake May Affect Phospholipid Profile for Cancer Prevention in Murine Skin Tissues
Authors: Ouyang Ping , Jiang Yu , Doan Hieu M. , Xie Linglin , Vasquez David , Welti Ruth , Su Xiaoyu , Lu Nanyan , Herndon Betty , Yang Shie-Shien , Jeannotte Richard , Wang Weiqun 
Published: March 2010

Abstract
Exercise has been linked to a reduced cancer risk in animal models. However, the underlying mechanisms are unclear. This study assessed the effect of exercise with dietary consideration on the phospholipid profile in 12-O-tetradecanoylphorbol-13-acetate (TPA)–induced mouse skin tissues. CD-1 mice were randomly assigned to one of the three groups: ad libitum–fed sedentary control; ad libitum–fed treadmill exercise at 13.4 m/min for 60 min/d, 5 d/wk (Ex+AL); and treadmill-exercised but pair-fed with the same amount as the control (Ex+PF). After 14 weeks, Ex+PF but not Ex+AL mice showed ∼25% decrease in both body weight and body fat when compared with the controls. Of the total 338 phospholipids determined by electrospray ionization–tandem mass spectrometry, 57 were significantly changed, and 25 species could distinguish effects of exercise and diet treatments in a stepwise discriminant analysis. A 36% to 75% decrease of phosphatidylinositol (PI) levels in Ex+PF mice occurred along with a significant reduction of PI 3-kinase in TPA-induced skin epidermis, as measured by both Western blotting and immunohistochemistry. In addition, ∼2-fold increase of the long-chain polyunsaturated fatty acids, docosahexaenoic and docosapentaenoic acids, in phosphatidylcholines, phosphatidylethanolamines, and lysophosphatidylethanolamines was observed in the Ex+PF group. Microarray analysis indicated that the expression of fatty acid elongase-1 increased. Taken together, these data indicate that exercise with controlled dietary intake, but not exercise alone, significantly reduced body weight and body fat as well as modified the phospholipid profile, which may contribute to cancer prevention by reducing TPA-induced PI 3-kinase and by enhancing ω-3 fatty acid elongation. Cancer Prev Res; 3(4); 466–77