tbuckley/cabot-search huggingface dataset:
State of inequality in diphtheria-tetanus-pertussis immunisation coverage in low-income and middle-income countries: a multicountry study of household health surveys
Authors: Ahmad Reza Hosseinpoor, Nicole Bergen, Anne Schlotheuber, Marta Gacic-Dobo, Peter M Hansen, Kamel Senouci, Ties Boerma, Aluisio J D Barros
Journal: The Lancet Global Health (2016)

BackgroundImmunisation programmes have made substantial contributions to lowering the burden of disease in children, but there is a growing need to ensure that programmes are equity-oriented. We aimed to provide a detailed update about the state of between-country inequality and within-country economic-related inequality in the delivery of three doses of the combined diphtheria, tetanus toxoid, and pertussis-containing vaccine (DTP3), with a special focus on inequalities in high-priority countries.MethodsWe used data from the latest available Demographic and Health Surveys and Multiple Indicator Cluster Surveys done in 51 low-income and middle-income countries. Data for DTP3 coverage were disaggregated by wealth quintile, and inequality was calculated as difference and ratio measures based on coverage in richest (quintile 5) and poorest (quintile 1) household wealth quintiles. Excess change was calculated for 21 countries with data available at two timepoints spanning a 10 year period. Further analyses were done for six high-priority countries—ie, those with low national immunisation coverage and/or high absolute numbers of unvaccinated children. Significance was determined using 95% CIs.FindingsNational DTP3 immunisation coverage across the 51 study countries ranged from 32% in Central African Republic to 98% in Jordan. Within countries, the gap in DTP3 immunisation coverage suggested pro-rich inequality, with a difference of 20 percentage points or more between quintiles 1 and 5 for 20 of 51 countries. In Nigeria, Pakistan, Laos, Cameroon, and Central African Republic, the difference between quintiles 1 and 5 exceeded 40 percentage points. In 15 of 21 study countries, an increase over time in national coverage of DTP3 immunisation was realised alongside faster improvements in the poorest quintile than the richest. For example, in Burkina Faso, Cambodia, Gabon, Mali, and Nepal, the absolute increase in coverage was at least 2·0 percentage points per year, with faster improvement in the poorest quintile. Substantial economic-related inequality in DTP3 immunisation coverage was reported in five high-priority study countries (DR Congo, Ethiopia, Indonesia, Nigeria, and Pakistan), but not Uganda.InterpretationOverall, within-country inequalities in DTP3 immunisation persist, but seem to have narrowed over the past 10 years. Monitoring economic-related inequalities in immunisation coverage is warranted to reveal where gaps exist and inform appropriate approaches to reach disadvantaged populations.FundingNone.
Abstract 2288: Targeting mTOR pathway in rare and recalcitrant tumors
Authors: Veronica Rojas, Shridar Ganesan, Kim M. Hirshfield, Robert S. Dipaola, Lorna Rodriguez-Rodriguez
Journal: Cancer Research (2016)

Abstract INTRODUCTION: Genomic alterations affecting the PI3K/AKT/mTOR pathway are commonly seen among various cancer types [Kandoth 2013]. The objective of this study is to determine the clinical utility of using comprehensive genomic profiling (CGP) in the course of clinical care to identify genomic alterations affecting the PI3K/AKT/mTOR pathway in patients with either rare or refractory cancers. METHODS: CGP was performed by Foundation Medicine, Inc. Genomic alterations were reviewed by members of an institutional molecular tumor board (MTB). Consensus recommendations on genomically targeted, clinically relevant FDA-approved, on- and off-label therapies and clinical trials were sent to the treating physician for their consideration as treatment alternatives. Ninety-seven tumors with alterations in the PI3K/AKT/mTOR pathway were analyzed. RESULTS: Thirty-three patients with cancers that were either rare or refractory to standard therapy received drug targeting the PI3K/AKT/mTOR pathway. Age range was 18-78 years old. Thirteen patients were non-Hispanic White, three non-Hispanic Black, two Hispanic and one Asian. Tumors tested included 6 gynecologic, 5 renal, 2 sarcomas and one each of pancreatic, melanoma, T cell lymphoma, bladder, adrenal, and skin-not melanoma. Treatment outcomes were available for 19/33 patients (one patient died soon after presentation at the MTB and could not be treated). Seven (37%) patients derived clinical benefit from a drug targeting the PI3K/AKT/mTOR pathway; the duration of clinical benefit ranged from 90-245 days. The clinical benefit was not tumor type specific and included two endometrial tumors, 2 renal tumors, one sarcoma, one adrenal paraganglioma and one micropapillary urothelial carcinoma. Eight patients have not been started on PI3K/AKT/mTOR targeted therapy yet. CONCLUSION: These data suggest that tumors with alterations in the PI3K/AKT/mTOR pathway may respond to targeted therapy regardless of tumor of origin. Citation Format: Veronica Rojas, Shridar Ganesan, Kim M. Hirshfield, Robert S. Dipaola, Lorna Rodriguez-Rodriguez. Targeting mTOR pathway in rare and recalcitrant tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2288.
Abstract 5158: The change of EZH2 expression in development of colorectal cancer from adenoma
Authors: Mayuko Ohuchi, Yasuo Nakamoto, Ryuma Tokunaga, Kenichi Nakamura, Keisuke Kosumi, Kazuto Harada, Hironobu Shigaki, Junji Kurashige, Masaaki Iwatsuki, Yoshifumi Baba, Yuji Miyamoto, Naoya Yoshida, Hideo Baba
Journal: Cancer Research (2016)

Abstract [Background]Colorectal cancer has been revealed to develop from adenoma through mutation and deletion of various genes such as FAP, KRAS, DCC and p53 in the process called adenoma-carcinoma sequence. Furthermore, proteins of the polycomb repressive complex 2 (PRC2) function as transcriptional repressors by trimethylating histone H3 at lysine 27, and this complex's activity is essential for cell proliferation and differentiation. The histone methyltransferase enhancer zeste homolog 2 (EZH2), a key member of PRC2, is associated with transcriptional repression of tumor suppressor gene. In our previous study, EZH2 expression was reported to increase as pathology worsened in pancreatic IPMN. Thus EZH2 expression was hypothesized to increase in the adenoma-carcinoma sequence as well.[Purpose]The purpose of this study was to investigate the change of EZH2 expression in progressing colorectal cancer. [Materials and Methods]63 patients with colorectal adenoma, 24 patients with carcinoma in adenoma and 14 patients with colorectal carcinoma who underwent surgical or endoscopic resection were enrolled in this study. The normal lesions of the clinical specimens were also examined. We evaluated the association between EZH2 expression, pathology and expression of tumor suppressor gene. Immunohistochemistry of EZH2, Ki-67, p21, p27 and p16 was performed.[Results]The Ki-67 expression increased parallel to the worsening of pathological findings (p = 0.009), and EZH2 expression showed a significantly positive association with Ki-67 expression (p = 0.02). There was a significant increase of EZH2 expression between normal and colorectal adenoma and carcinoma in adenoma. However, no significance between carcinoma in adenoma and colorectal cancer in EZH2 expression could be identified. Conversely, p21 expression decreased significantly between normal and adenoma lesion; however, p16 and p27 expression showed no major change. [Conclusion]EZH2 expression considerately increased parallel to pathological worsening and p21 expression showed a decrease between normal and colorectal adenoma. Thus EZH2 can contribute to development of colorectal cancer from adenoma via p21 suppression. Citation Format: Mayuko Ohuchi, Yasuo Nakamoto, Ryuma Tokunaga, Kenichi Nakamura, Keisuke Kosumi, Kazuto Harada, Hironobu Shigaki, Junji Kurashige, Masaaki Iwatsuki, Yoshifumi Baba, Yuji Miyamoto, Naoya Yoshida, Hideo Baba. The change of EZH2 expression in development of colorectal cancer from adenoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5158.
Regulation of tumor cell PD-L1 expression by microRNA-200 and control of lung cancer metastasis.
Authors: Don Lynn Gibbons, Limo Chen, Sangeeta Goswami, Maria Angelica Cortez, Young-Ho Ahn, Lauren Averett Byers, Wei Lin, Lixia Diao, Jing Wang, Jonathon Roybal, Christin Ungewiss, Scott Joseph Antonia, Melanie Mediaville-Varela, Milind B. Suraokar, James Welsh, Lieping Chen, Ignacio Ivan Wistuba, John Heymach, Jonathan M. Kurie, Frank Xiao-Feng Qin
Journal: Journal of Clinical Oncology (2014)

8063 Background: Tumor cell regulation of the activity of diverse inflammatory cells creates an immunosuppressive microenvironment that favors tumor growth and metastasis. However, the mechanistic basis of how tumor cells trigger intra-tumoral immunosuppression has not been fully defined. Here we show that metastasis-prone lung adenocarcinoma cells suppress the proliferation and activity of intra-tumoral CD8+T cells through a PD-L1 dependent mechanism and that PD-L1 expression is regulated by microRNA-200 (miR-200), a known mediator of tumor cell EMT. Methods: Publically available TCGA datasets were analyzed, along with a large MDACC cohort of resected tumors. Experimentally we utilized genetic and syngeneic mouse models of metastatic lung adenocarcinoma. Results: In lung adenocarcinomas from The Cancer Genome Atlas (TCGA) (n=230) and a large MDACC cohort of resected tumors (N>150), those with a mesenchymal gene expression signature displayed repression of the miR-200 family and higher levels of PD-L1. These findings were confirmed experimentally in human and murine NSCLC cell lines. In vivo experiments with a Kras/p53 mutant mouse model of lung adenocarcinoma showed that decreased miR-200 led to increased tumor cell expression of PD-L1, causing profound CD8+ T cell suppression. Upon suppression of CD8+T cell activity tumors acquired a growth advantage and became metastatic. Confirmation of these results with the Lewis lung cancer model in PD-L1 knockout mice also demonstrated that PD-L1 expression on the tumor cells, rather than other cells in the tumor microenvironment, was critical to tumor immunity and metastastic ability. Genetic and pharmacologic blockade of PD-L1 suppressed metastasis. Conclusions: Our findings demonstrate a novel biological role for miR-200 in cancer cells by simultaneous control of the cell-intrinsic EMT program and the cell-non-autonomous PD-L1-mediated immune evasion. These findings support the conclusion that EMT-associated immunosuppression promotes metastasis and the potential use of EMT-related biomarkers to select immunomodulatory therapies.
Safety and Efficacy Of Imatinib In Elderly Patients With Chronic-Phase Chronic Myeloid Leukemia: Analysis Of Outcome For &lt; 60 Years Versus ≥ 60 Years
Authors: Young-Woong Won, DongWook Kim, Sung-Eun Lee, Soo Young Choi, Soo-Hyun Kim, Eun-Jung Jang
Journal: Blood (2013)
Adult acute myeloid leukemia with trisomy 11 as the sole abnormality is characterized by the presence of five distinct gene mutations: MLL-PTD, DNMT3A, U2AF1, FLT3-ITD and IDH2
Authors: A-K Eisfeld, J Kohlschmidt, K Mrózek, J S Blachly, D Nicolet, K Kroll, S Orwick, A J Carroll, R M Stone, A de la Chapelle, J C Byrd, C D Bloomfield
Journal: Leukemia (2016)
Stem-loop binding protein is a multifaceted cellular regulator of HIV-1 replication
Authors: Ming Li, Lynne D. Tucker, John M. Asara, Collins K. Cheruiyot, Huafei Lu, Zhijin J. Wu, Michael C. Newstein, Mark S. Dooner, Jennifer Friedman, Michelle A. Lally, Bharat Ramratnam
Journal: Journal of Clinical Investigation (2016)

A rare subset of HIV-1-infected individuals is able to maintain plasma viral load (VL) at low levels without antiretroviral treatment. Identifying the mechanisms underlying this atypical response to infection may lead to therapeutic advances for treating HIV-1. Here, we developed a proteomic analysis to compare peripheral blood cell proteomes in 20 HIV-1-infected individuals who maintained either high or low VL with the aim of identifying host factors that impact HIV-1 replication. We determined that the levels of multiple histone proteins were markedly decreased in cohorts of individuals with high VL. This reduction was correlated with lower levels of stem-loop binding protein (SLBP), which is known to control histone metabolism. Depletion of cellular SLBP increased promoter engagement with the chromatin structures of the host gene high mobility group protein A1 (HMGA1) and viral long terminal repeat (LTR), which led to higher levels of HIV-1 genomic integration and proviral transcription. Further, we determined that TNF-α regulates expression of SLBP and observed that plasma TNF-α levels in HIV-1-infected individuals correlated directly with VL levels and inversely with cellular SLBP levels. Our findings identify SLBP as a potentially important cellular regulator of HIV-1, thereby establishing a link between histone metabolism, inflammation, and HIV-1 infection.
Transcriptomic/proteomic identification of allergens in the mite <i>Tyrophagus putrescentiae</i>
Authors: Y. Cui, L. Yu, F. Teng, C. Zhang, N. Wang, L. Yang, Y. Zhou
Journal: Allergy (2016)

While a number of allergens from house dust mites have been described, much remains to be discovered about allergens from storage mites. Here, next-generation sequencing was combined with MS/MS shotgun proteomics to identify proteins, especially potential allergens from Tyrophagus putrescentiae, commonly found in stored food products, especially flour. cDNAs of suspected allergens were cloned and expressed from bacterial cells, and recombinant allergens were tested for binding to IgE in sera from T. putrescentiae-sensitive patients. These analyses identified three previously uncharacterized allergens, Tyr p 28, Tyr p 35, and Tyr p 36, which have been officially assigned by the WHO/IUIS Allergen Nomenclature Sub-committee. Recombinant proteins rTyr p 28, rTyr p 35, and rTyr p 36 bound with 47.1%, 82.4%, and 70.6% of T. putrescentiae-sensitive sera. We provide here a new method to identify allergens by the combination of transcriptomic and proteomic approaches.
Abstract 412: RNA-Seq provides cost-effective alternative for typing self-identifying antigens in immunotherapy patients
Authors: Kimberly Robasky, Jason Powers, Donald Trapolsi, Jeff Jasper, Chad Brown
Journal: Cancer Research (2016)

Abstract The excitement surrounding immunotherapy is being driven by results in the clinic. Currently, autoimmunity is an unfortunate side-effect for a large fraction of those treated. Consequently, understanding how self-antigens are recognized is nearly as important as characterizing the immune repertoire for efficacious delivery of these promising new therapies. One approach to measuring the tumor immune environment is with RNA-Seq assays. Here we show that the genes responsible for presenting self-antigens (HLA Class I and Class II) can also be ascertained from RNA-Seq on total RNA. We present the detailed results from standard RNA-Seq pipeline analysis for 40 lymphoblastoid cell lines to achieve 91.3% overall concordance with “gold standard” typings. These samples were sequenced with 50bp paired-ends and approximately 30M reads. We additionally present RNA-Seq analysis results from calling HLA alleles on 15 replicate pairs of FFPE hepatic tumor samples, finding 88.33% overall replicate concordance with 2-digit precision, and 90% for Class I alleles. Finally, we present HLA-types on triplicates from 2 common breast cancer cell lines, MCF7 and T47D for loci HLA-A,-B,-C,-DRB1,-DQB1, with 90% overall replicate concordance. Emerging targeted DNA-Seq assays aimed at high-throughput clinical trials require high quality whole-blood samples that yield larger amounts of assay input material. Alternatively, the analyses presented here do not require HLA-region enrichment and thus can also be performed on legacy RNA-Seq data. Notably, the data here are generated from sample types and amounts that are more typical to a clinical oncology setting, and because it does not rely on targeted capture as do DNA-Seq assays, these analyses hold greater promise for assembling rare alleles and fusions. Citation Format: Kimberly Robasky, Jason Powers, Donald Trapolsi, Jeff Jasper, Chad Brown. RNA-Seq provides cost-effective alternative for typing self-identifying antigens in immunotherapy patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 412.
Abstract 3904: Overcoming resistance to HER2 inhibitors through cell based screening
Authors: Chris J. Novotny, Sirkku Pollari, Jin H. Park, Mark A. Lemmon, Peter G. Schultz, Weijun Shen, Kevan M. Shokat
Journal: Cancer Research (2016)

Abstract Signaling from the human epidermal growth factor receptor (HER) family of proteins is dependent on a well-orchestrated series of interactions between family members to form either homo- or heterodimers. The heterodimeric complex formed by HER2 and HER3 is a particularly potent oncogenic signaling unit that can act as a driver of cancer growth and has also been shown to rescue a large number of cancers from a variety of targeted agents. The currently available therapies targeting HER2, such as Lapatinib or ado-trastuzumab emtansine, have dramatically improved patient outcomes in the clinic but preferentially target the protein in its monomeric state. Because of this, increasing the concentration of the HER2/HER3 heterodimer, either by growth factors or increasing the concentrations of HER2 and HER3 at the membrane, significantly diminishes their activity. In order to find a next generation inhibitor of the active HER2/HER3 oncogenic complex we screened 1 million small molecules against an engineered Ba/F3 cell line dependent on ligand stimulated HER2/HER3 signaling for survival. The removal of non-selective inhibitors using alternative Ba/F3 cell lines resulted in the identification of a single core scaffold hit. A medicinal chemistry campaign enabled by a co-crystal structure of a hit compound complexed to EGFR led to the development of a molecule capable of inhibiting the active state of HER2. As a result, this next generation HER2 inhibitor is capable of inhibiting growth factor stimulated HER2/HER3 heterodimers and mutationally activated forms of HER2, which are resistant to current clinical small molecule HER2 inhibitors. Citation Format: Chris J. Novotny, Sirkku Pollari, Jin H. Park, Mark A. Lemmon, Peter G. Schultz, Weijun Shen, Kevan M. Shokat. Overcoming resistance to HER2 inhibitors through cell based screening. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3904.
Effect of Wuchereria bancrofti infection on HIV incidence in southwest Tanzania: a prospective cohort study
Authors: Inge Kroidl, Elmar Saathoff, Lucas Maganga, Williams H Makunde, Achim Hoerauf, Christof Geldmacher, Petra Clowes, Leonard Maboko, Michael Hoelscher
Journal: The Lancet (2016)
Lipid peroxidation and protein oxidation are related to the severity of OSAS
Authors: E. Hopps, B. Canino, V. Calandrino, M. Montana, R. Lo Presti, G. Caimi
Journal: European Respiratory Journal (2014)

OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) is associated with ele - vated cardiovascular morbidity and mortality. Considering that oxidative stress is involved in endothelial dysfunction and atherosclerosis de - velopment, our aim was to examine lipid peroxi- dation and protein oxidation, two parameters of oxidative status, in a group of subjects with OSAS. PATIENTS AND METHODS: We consecutively enrolled 48 patients (36 men and 12 women; mean age 49.7±14.6 yrs) with OSAS, subse - quently subdivided according to the apnea/hy - popnea index (AHI) value in two subgroups: Low (L= 21 subjects with AHI 30). We examined lipid peroxidation, expressed asTBARS, and protein oxidation, measured as carbonyl groups in plasmasamplesfromfastingvenousblood. RESULTS: We observed that TBARS and car - bonyl groups were significantly higher in sub - jectswithAHI>30incomparisonwiththeLsub - group and the whole group of OSAS subjects. In addition, we found that these parameters were positivelycorrelatedwithneckandwaistcircum - ference, with the AHI value and with the oxygen desaturation index, and negatively correlated withthemeanoxygensaturation. CONCLUSIONS: Lipid peroxidation and pro - tein oxidation in OSAS patients are significant - lycorrelatedwiththeseverityofthedisease.
Abstract 2740: Mechanistic basis of Palbociclib combinatorial activity in ER+ breast cancer and non-breast indications
Authors: Stephen Dann, Jing Yuan, John Chionis, Chaoting Liu, Tao Xie, Nathan V. Lee, Enhong Chen, Ping Wei, Paul A. Rejto, David J. Shields, Todd VanArsdale
Journal: Cancer Research (2016)

Abstract Phosphorylation of the retinoblastoma protein (Rb) by cyclin-dependent kinases 4 and 6 (CDK4/6) is a critical checkpoint for G1/S cell cycle progression and commitment to cellular proliferation. Human malignancies often subvert these control mechanisms through a range of genetic and biochemical adaptations. Accordingly, tumors that depend on CDK4/6 activity for proliferation and survival are particularly sensitive to inhibition of this pathway by palbociclib (IbranceTM), a highly selective inhibitor of CDK4/6 kinase activities. Treatment regimen of palbociclib with letrozole significantly improved progression-free survival in a randomized phase 2 study of women with advanced estrogen receptor-positive (ER+), HER2-negative breast cancer. Likewise, in ER+ breast cancer models palbociclib and estrogen antagonists combine for greater anti-proliferative activity, increased hallmarks of cellular senescence and prolonged durability of response following drug removal. Dual inhibition of CDK4/6 and ER signaling demonstrated robust anti-tumor activity in xenograft studies. The addition of Palbociclib to other targeted therapeutics elicits improved activity in pre-clinical models of several non-breast indications and these effects also manifest through modulation of cellular proliferation, senescence and growth arrest. Data will be presented on the molecular basis of combination benefit with Palbociclib in ER+ breast and other oncology indications. Citation Format: Stephen Dann, Jing Yuan, John Chionis, Chaoting Liu, Tao Xie, Nathan V. Lee, Enhong Chen, Ping Wei, Paul A. Rejto, David J. Shields, Todd VanArsdale. Mechanistic basis of Palbociclib combinatorial activity in ER+ breast cancer and non-breast indications. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2740.
Vegf and bFGF Single-Nucleotide Polymorphisms In Chronic Lymphocytic Leukemia: Impact On Susceptibility
Authors: Sandra Ballester, Begoña Pineda, Eduardo Tormo, Blanca Navarro, Ariadna Perez, Anabel Teruel, Mª José Terol, Carlos Solano, Pilar Eroles
Journal: Blood (2013)