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  • 1
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 43 ( 2014-10-28), p. 15544-15549
    Abstract: Previous studies have established that a subset of head and neck tumors contains human papillomavirus (HPV) sequences and that HPV-driven head and neck cancers display distinct biological and clinical features. HPV is known to drive cancer by the actions of the E6 and E7 oncoproteins, but the molecular architecture of HPV infection and its interaction with the host genome in head and neck cancers have not been comprehensively described. We profiled a cohort of 279 head and neck cancers with next generation RNA and DNA sequencing and show that 35 (12.5%) tumors displayed evidence of high-risk HPV types 16, 33, or 35. Twenty-five cases had integration of the viral genome into one or more locations in the human genome with statistical enrichment for genic regions. Integrations had a marked impact on the human genome and were associated with alterations in DNA copy number, mRNA transcript abundance and splicing, and both inter- and intrachromosomal rearrangements. Many of these events involved genes with documented roles in cancer. Cancers with integrated vs. nonintegrated HPV displayed different patterns of DNA methylation and both human and viral gene expressions. Together, these data provide insight into the mechanisms by which HPV interacts with the human genome beyond expression of viral oncoproteins and suggest that specific integration events are an integral component of viral oncogenesis.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
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  • 2
    In: Ecology and Evolution, Wiley, Vol. 4, No. 24 ( 2014-12), p. 4701-4735
    Abstract: Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local‐scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – https://www.nhm.ac.uk/our-science/our-work/biodiversity/predicts.html ). We make site‐level summary data available alongside this article. The full database will be publicly available in 2015.
    Type of Medium: Online Resource
    ISSN: 2045-7758 , 2045-7758
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2014
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  • 3
    In: Cancer Immunology, Immunotherapy, Springer Science and Business Media LLC, Vol. 60, No. 7 ( 2011-7), p. 919-929
    Type of Medium: Online Resource
    ISSN: 0340-7004 , 1432-0851
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2011
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  • 4
    In: Central Nervous System Agents in Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 11, No. 3 ( 2011-09-01), p. 223-227
    Type of Medium: Online Resource
    ISSN: 1871-5249
    Language: English
    Publisher: Bentham Science Publishers Ltd.
    Publication Date: 2011
    SSG: 15,3
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  • 5
    In: Endocrinology, The Endocrine Society, Vol. 152, No. 6 ( 2011-06-01), p. 2164-2173
    Abstract: The IGF axis has been implicated in the risk of various cancers. We previously reported a potential role of tissue-derived IGF in lung tumor formation and progression. However, the role of IGF-binding protein (IGFBP)-3, a major IGFBP, on the activity of tissue-driven IGF in lung cancer development is largely unknown. Here, we show that IGF-I, but not IGF-II, protein levels in non-small-cell lung cancer (NSCLC) were significantly higher than those in normal and hyperplastic bronchial epithelium. We found that IGF-I and IGFBP-3 levels in NSCLC tissue specimens were significantly correlated with phosphorylated IGF-IR (pIGF-IR) expression. We investigated the impact of IGFBP-3 expression on the activity of tissue-driven IGF-I in lung cancer development using mice carrying lung-specific human IGF-I transgene (Tg), a germline-null mutation of IGFBP-3, or both. Compared with wild-type (BP3+/+) mice, mice carrying heterozygous (BP3+/−) or homozygous (BP3−/−) deletion of IGFBP-3 alleles exhibited decreases in circulating IGFBP-3 and IGF-I. Unexpectedly, IGFTg mice with 50% of physiological IGFBP-3 (BP3+/−; IGFTg) showed higher levels of pIGF-IR/IR and a greater degree of spontaneous or tobacco carcinogen [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]-induced lung tumor development and progression than did the IGFTg mice with normal (BP3+/+;IGFTg) or homozygous deletion of IGFBP-3 (BP3−/−; IGFTg). These data show that IGF-I is overexpressed in NSCLC, leading to activation of IGF-IR, and that IGFBP-3, depending on its expression level, either inhibits or potentiates IGF-I actions in lung carcinogenesis.
    Type of Medium: Online Resource
    ISSN: 0013-7227 , 1945-7170
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2011
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  • 6
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 3744-3744
    Abstract: Recent evidence indicates that both PI3K-Akt-mTOR signaling pathway and HDAC are validated targets in hematological cancers. In order to overcome primary resistance and prevent secondary resistance resulting from compensatory/feedback mechanisms in cancer cells, CUDC-907 was designed to inhibit all isoforms of Class I PI3K and Class I and II HDAC, based on previous observations that synergistic effects can be achieved by inhibition of both HDAC and PI3K in cancer cells. In cell proliferation assays, this compound displays potent anti-proliferation activity in hematological cancer cell lines including non-Hodgkin's lymphoma (NHL), and multiple myeloma (MM). Mechanistically, CUDC-907 is able to simultaneously suppress PI3K-Akt-mTOR as well as other essential signaling pathways due to epigenetic modifications via HDAC inhibition. CUDC-907 is orally bio-available in dogs, has a long half-life in murine tumors, induces apoptosis and inhibits cancer cell proliferation in xenograft tumors. In efficacy studies in NHL and MM models, CUDC-907 is more efficacious than either a single-agent PI3K or HDAC inhibitor reference compound or a combination of the two agents given at maximally tolerated doses (MTD). Furthermore, CUDC-907 is more efficacious than the PI3Kα-selective inhibitor CAL-101 when dosed at MTD doses. These observations are related to our findings that, all isoforms of PI3K are expressed in most hematological cancer models. Therefore, the efficacy of isoform selective PI3K inhibitors may be limited only to those cancers driven by a specific PI3K subtype. In addition, a synergistic antitumor effect can be achieved in efficacy studies when CUDC-907 is combined with standard of care agents in both NHL and MM models. In conclusion, through broad network disruption, CUDC-907 may offer a greater therapeutic benefit than isoform-specific PI3K inhibitors as a novel anti-cancer treatment of hematological malignancies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3744. doi:1538-7445.AM2012-3744
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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  • 7
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 21, No. 10_Supplement ( 2012-10-01), p. A88-A88
    Abstract: Background: Perceived discrimination among the US population has been associated with lower utilization of cancer screening tests. Data from the Hispanic Community Health Study / Study of Latinos (HCHS/SOL) Socio-cultural Ancillary Study were analyzed to determine if perceived discrimination was associated with adherence to breast, cervical and colorectal cancer screening tests. Methods: Respondents included 5,313 participants from Bronx NY, Chicago IL, Miami FL, and San Diego CA recruited using a 2-stage area household probability design. Of these, 3,083 women aged 18-74 and 840 men aged 50-74 were included in the analysis. Cancer screening behaviors, income, health insurance status, and having a usual source of healthcare were assessed via self-report. Perceived discrimination was measured using the Perceived Ethnic Discrimination Questionnaire (PEDQ). Acculturation was measured using the Short Acculturation Scale for Hispanics. Adherence to cervical and breast cancer screening tests was defined as receipt of a Pap smear within the last 2 years (in women 18-74) and receipt of a mammogram within the last 2 years (in women 40-74), respectively. In all participants 50-74, adherence to fecal occult blood testing (FOBT) was defined as having FOBT within the 1 year; adherence to colonscopy/sigmoidoscopy was defined as having had either test in the last 5 years. Chi-square tests were used to test for differences between groups. Multivariate polytomous logistic regression models were fit to assess the association between perceived discrimination and cancer screening adherence. Models were adjusted for income, health insurance status, having a usual source of care, location, and acculturation. Results: Among women, 72.1% were adherent to cervical cancer screening and 54.2% were adherent to breast cancer screening. In participants aged 50-74, 23.5% of women and 27.2% of men were adherent to FOBT; 36.9% of women and 30.0% of men were adherent to colonscopy/sigmoidoscopy. After adjustment for covariates, men in the highest quartiles of perceived discrimination were more likely be non-adherent to FOBT compared to men in the lowest quartile of perceived discrimination (Q3 vs. Q1, OR: 2.3 [1.1-4.7]; Q4 vs. Q1, OR: 4.4 [2.0-9.7] ). We observed no association between perceived discrimination, and breast or cervical cancer screening, or colonoscopy/sigmoidoscopy. Not having health insurance was a significant independent predictor of non-adherence to breast, cervical, and colorectal cancer screening (breast cancer, OR: 2.5 [1.7-3.5]; cervical cancer, OR: 1.7 [1.2-2.4] ; FOBT in women, OR: 2.6 [1.3-4.9]; colonoscopy/sigmoidoscopy in women, OR: 5.5[2.7-11.3] ; in men, OR: 3.4 [1.5-7.4]). Greater degree of acculturation to the dominant US culture was associated with non-adherence to cervical and colorectal cancer screening in women (cervcal cancer, OR: 1.4 [1.1-1.8] ; FOBT, OR: 2.0 [1.3-3.2]; colonscopy/sigmoidoscopy, OR: 1.7 [1.1-2.8] ). Conclusions: For breast, cervical and colorectal cancer screening behaviors, not having health insurance and being more acculturated to US culture were significant predictors of lower rates of cancer screening; perceived discrimination was not significantly related. The finding that higher levels of discrimination are associated to non-adherence to FOBT among men warrants further research. Citation Format: Cristina Valdovinos, Carmen Isasi, Molly Jung, Heather Greenlee, Robert Kaplan, Frank J. Penedo, Rebeca A. Espinoza, Patricia Gonzalez, Vanessa L. Malcarne, Krista Perreira, Hugo Salgado, Melissa A. Simon, Lisa M. Wruck. Perceived discrimination and cancer screening behaviors in U.S. Hispanics: Preliminary results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary Study. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A88.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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  • 8
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2010
    In:  Clinical Cancer Research Vol. 16, No. 1 ( 2010-01-01), p. 34-44
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 16, No. 1 ( 2010-01-01), p. 34-44
    Abstract: Purpose: To identify the pattern of interleukin-1 receptor–associated kinase (IRAK-1) protein expression in non–small cell lung carcinoma (NSCLC) and corresponding preneoplastic lesions. Experimental Design: Archived tissue from NSCLC (adenocarcinoma and squamous cell carcinoma; n = 306) and adjacent bronchial epithelial specimens (n = 315) were analyzed for the immunohistochemical expression of IRAK-1, and the findings were correlated with patients' clinicopathologic features. Furthermore, we investigated the correlation between IRAK-1 expression and expression of NF-κB and IL-1α in tumor specimens. Results: NSCLC tumors showed significantly higher cytoplasmic and lower nuclear IRAK-1 expression than normal epithelium. Squamous dysplasias had significantly higher cytoplasmic IRAK-1 expression than normal epithelium. In tumors, a significant positive correlation was detected between IRAK-1 expression (nuclear and cytoplasmic; P = 0.011) and IL-1α cytoplasmic expression (P & lt; 0.0001). The correlation between the expression of the markers and patients' clinicopathologic features varied according to tumor histologic type and sex. High IRAK-1 cytoplasmic expression correlated with worse recurrence-free survival in women with NSCLC [hazard ratio (HR), 2.204; P = 0.033], but not in men. In adenocarcinoma, combined low level of expression of nuclear IRAK-1 and NF-κB correlated significantly with worse overall (HR, 2.485; P = 0.007) and recurrence-free (HR, 3.058; P = 0.006) survivals in stage I/II patients. Conclusions: IRAK-1 is frequently expressed in NSCLC tissue specimens, and this expression is an early phenomenon in the sequential development of lung cancer. IRAK-1 is a novel inflammation-related marker and a potential target for lung cancer chemopreventive strategies. Clin Cancer Res; 16(1); 34–44
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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  • 9
    Online Resource
    Online Resource
    Informa UK Limited ; 2010
    In:  Molecular and Cellular Biology Vol. 30, No. 11 ( 2010-06-01), p. 2681-2692
    In: Molecular and Cellular Biology, Informa UK Limited, Vol. 30, No. 11 ( 2010-06-01), p. 2681-2692
    Type of Medium: Online Resource
    ISSN: 1098-5549
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2010
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  • 10
    In: Chemosphere, Elsevier BV, Vol. 83, No. 1 ( 2011-3), p. 76-82
    Type of Medium: Online Resource
    ISSN: 0045-6535
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2011
    detail.hit.zdb_id: 1496851-4
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