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  1. Infertility Research at the NICHD

    MedlinePlus

    ... in Progress: Effects of Aspirin on Gestation and Reproduction (EAGeR) Study Previous studies have suggested that some ... through the NICHD Specialized Cooperative Centers Program in Reproduction and Infertility Research (SCCPIR) recently identified a key ...

  2. NIH Institutes and Centers Served by TTC | NCI Technology Transfer Center | TTC

    Cancer.gov

    TTC services the NCI Intramural Research laboratories as well as nine other NIH institutes a range of services--NIDA, NIA, NIMHD, NICHD, NLM, CIT, NCCIH, Clinical Center, NEI. | [google6f4cd5334ac394ab.html

  3. Discover the NICHD. NIH Publication No. 13-7976

    ERIC Educational Resources Information Center

    National Institute of Child Health and Human Development (NICHD), 2013

    2013-01-01

    This four-page document provides an overview of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), a health research agency within the federal government. NICHD is a part of the National Institutes of Health in the U.S Department of Health and Human Services. This brief report describes the mission of…

  4. NCI & Division Obligations

    Cancer.gov

    Displays obligations for grants, contracts, training fellowships, intramural research, and management and support, including the number of grant awards, funding amounts, and percent of the total NCI budget.

  5. NCI Cohort Consortium Membership

    Cancer.gov

    The NCI Cohort Consortium membership is international and includes investigators responsible for more than 40 high-quality cohorts who are studying large and diverse populations in more than 15 different countries.

  6. NCI Contact Center

    Cancer.gov

    The NCI offers free, scientifically accurate, and easy-to-understand information on a range of cancer topics in English and Spanish. Get live help from compassionate information specialists at 1-800-4-CANCER.

  7. NCI Cohort Consortium

    Cancer.gov

    The NCI Cohort Consortium is an extramural-intramural partnership formed by the National Cancer Institute to address the need for large-scale collaborations to pool the large quantity of data and biospecimens necessary to conduct a wide range of cancer studies.

  8. NCI Visuals Online

    Cancer.gov

    NCI Visuals Online contains images from the collections of the National Cancer Institute's Office of Communications and Public Liaison, including general biomedical and science-related images, cancer-specific scientific and patient care-related images, and portraits of directors and staff of the National Cancer Institute.

  9. Data Sets from Major NCI Initiaves

    Cancer.gov

    The NCI Data Catalog includes links to data collections produced by major NCI initiatives and other widely used data sets, including animal models, human tumor cell lines, epidemiology data sets, genomics data sets from TCGA, TARGET, COSMIC, GSK, NCI60.

  10. NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) Trial

    Cancer.gov

    NCI's gateway for information about the NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) trial, in which patients with advanced cancer are assigned to treatment arms based on the molecular profiles of their disease.

  11. Deja Vu All Over Again: A Researcher Explains the NICHD Study. Viewpoint.

    ERIC Educational Resources Information Center

    Caldwell, Bettye M.

    2001-01-01

    Describes methods and findings of the NICHD Study of Early Child Care. Argues that media focused too heavily on one isolated finding relating quantity of day care to child aggression. Describes the conduct of a steering committee to coordinate study design. Advocates improving child care quality and examines ways to prevent aggressive behavior and…

  12. 77 FR 1705 - Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD); Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ... HUMAN SERVICES National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD); Notice of Meeting Pursuant to section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. App.), notice is hereby given of a meeting of the National Advisory...

  13. 78 FR 27408 - Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD); Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-10

    ... Child Health, and Human Development, NIH, 9000 Rockville Pike MSC 7510, Building 31, Room 2A03, Bethesda... HUMAN SERVICES National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD); Notice of Meeting Pursuant to section 10(d) of the Federal Advisory...

  14. 77 FR 29675 - Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD); Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-18

    ... Kennedy Shriver National Institute of Child Health & Human Development (NICHD); Notice of Meeting Pursuant... given of a meeting of the National Advisory Child Health and Human Development Council. The meeting will... Committee: National Advisory Child Health and Human Development Council. Date: June 7, 2012. Open: June...

  15. NCI Alliance for Nanotechnology in Cancer - NCI Alliance Bulletin

    Cancer.gov

    The NCI Alliance for Nanotechnology in Cancer Bulletin is a resource that serves to connect Alliance participants, partners, and affiliates by highlighting the innovative work of the Alliance members in their efforts to harness the power of nanotechnology to radically change the way we diagnose, treat, and prevent cancer.

  16. NCI collaborates with Multiple Myeloma Research Foundation

    Cancer.gov

    The National Cancer Institute (NCI) announced a collaboration with the Multiple Myeloma Research Foundation (MMRF) to incorporate MMRF's wealth of genomic and clinical data on the disease into the NCI Genomic Data Commons (GDC), a publicly available datab

  17. NCI Resource Room at AACR 2017

    Cancer.gov

    Researchers interested in meeting with their Program Directors should contact them ahead of AACR to arrange a time to meet at the NCI Resource Room. This space will be used for one-on-one consultations with NCI staff as well as small group meetings facilitated by the NCI.

  18. NCI-Frederick” Is Retired; Replaced with “NCI at Frederick” | Poster

    Cancer.gov

    By Andrea Frydl, Contributing Writer If you are used to using the term “NCI-Frederick” to identify your work location, please note that this name has been officially retired. This change was made to ensure consistency with the naming conventions used by other NCI locations, such as NCI at Shady Grove. Please be aware of the distinction between the terms “NCI at Frederick” and “the NCI Campus at Frederick,” as follows:

  19. Join TTC! | NCI Technology Transfer Center | TTC

    Cancer.gov

    The NCI Technology Transfer Center (TTC) offers a unique opportunity for training through the NCI TTC Fellowship program. TTC also has a unit dedicated to marketing these research opportunities and their underlying technologies to potential collaborators and licensees. | [google6f4cd5334ac394ab.html

  20. Trans-NCI Pharmacogenomics and Pharmacoepidemiology Working Group (PPWG)

    Cancer.gov

    NCI established the Trans-NCI Pharmacogenomics and Pharmacoepidemiology Working Group to support development of a comprehensive and interdisciplinary pharmacoepidemiology and pharmacogenomics cancer research program.

  1. Integration of microarray technology into prenatal diagnosis: counselling issues generated during the NICHD clinical trial.

    PubMed

    Wapner, Ronald J; Driscoll, Deborah A; Simpson, Joe Leigh

    2012-04-01

    Cytogenetic microarray analysis (CMA) in prenatal testing detects chromosome abnormalities and new genetic syndromes that would be missed by conventional cytogenetics and has the potential to significantly enhance prenatal genetic evaluation. A large Eunice Kennedy Shriver National Institute Of Child Health and Human Development (NICHD)-sponsored multicentered trial to assess the role of CMA as a primary prenatal diagnostic tool has been completed, and results will soon be available. Integration of this technology into clinical care will require thoughtful changes in patient counseling. Here, we examine four cases, all ascertained in the NICHD prenatal microarray study, to illustrate the challenges and subtleties of genetic counseling required with prenatal CMA testing. Although the specifics of each case are distinct, the underlying genetic principles of uncertainty, variable expressivity, and lack of precise genotype-phenotype correlation are well known and already part of prenatal counseling. Counselor and practitioner education will need to include both the science of interpreting array findings as well as development of improved approaches to uncertainty. A team approach to interpretation will need to be developed, as will standardized guidelines by professional organizations and laboratories. Of equal import is additional research into patient attitudes and desires, and a better understanding of the full phenotypic spectrum of copy number variants discovered in utero.

  2. NCI Holds on to Defelice Cup | Poster

    Cancer.gov

    NCI kept the Defelice Cup trophy this year after beating Leidos Biomedical Research, 15 to 9, at the 10th annual Ronald H. Defelice Golf Tournament held on Columbus Day. Sixteen players on each team battled it out at the yearly contractor vs. government tournament held at Rattlewood Golf Course in Mount Airy, Md. NCI leads the series 6–4. “The score was the highest NCI margin of victory in the 10-year series,” said Denny Dougherty, retired senior subcontracts advisor at what was formerly SAIC-Frederick. “The intensity of the annual competition has increased each year and has become...

  3. NCI at AACR 2016 | Division of Cancer Prevention

    Cancer.gov

    The National Cancer Institute (NCI) will be participating at the American Association for Cancer Research (AACR) Annual Meeting, to be held April 16-20, 2016, in New Orleans at the Ernest N. Morial Convention Center. Sessions Featuring NCI Staff An overview of the NCI-sponsored sessions and NCI experts presenting at AACR. |

  4. NCI Central Review Board Receives Accreditation

    Cancer.gov

    The Association for the Accreditation of Human Research Protection Programs has awarded the NCI Central Institutional Review Board full accreditation. AAHRPP awards accreditation to organizations demonstrating the highest ethical standards in clinical res

  5. Dinutuximab (Unituxin™) | NCI Technology Transfer Center | TTC

    Cancer.gov

    In 2010, NCI entered into a Cooperative Research and Development Agreement (CRADA) with United Therapeutics Corp., under which the company assumed responsibility for manufacturing dinutuximab and moving it through the steps required for regulatory approval.

  6. International Fellows of NCI at Frederick | Poster

    Cancer.gov

    Each year, the Employee Diversity Team (EDT) acknowledges members of the NCI at Frederick Community for their achievements and contributions towards the mission of facility.  Historically, the team has profiled the “Women of NCI at Frederick,” but this year, the team decided to instead shed light on the diverse and successful individuals who make up the international fellows community.

  7. The NCI Thesaurus quality assurance life cycle.

    PubMed

    de Coronado, Sherri; Wright, Lawrence W; Fragoso, Gilberto; Haber, Margaret W; Hahn-Dantona, Elizabeth A; Hartel, Francis W; Quan, Sharon L; Safran, Tracy; Thomas, Nicole; Whiteman, Lori

    2009-06-01

    The National Cancer Institute Enterprise Vocabulary Services (NCI EVS) uses a wide range of quality assurance (QA) techniques to maintain and extend NCI Thesaurus (NCIt). NCIt is a reference terminology and biomedical ontology used in a growing number of NCI and other systems that extend from translational and basic research through clinical care to public information and administrative activities. Both automated and manual QA techniques are employed throughout the editing and publication cycle, which includes inserting and editing NCIt in NCI Metathesaurus. NCI EVS conducts its own additional periodic and ongoing content QA. External reviews, and extensive evaluation by and interaction with EVS partners and other users, have also played an important part in the QA process. There have always been tensions and compromises between meeting the needs of dependent systems and providing consistent and well-structured content; external QA and feedback have been important in identifying and addressing such issues. Currently, NCI EVS is exploring new approaches to broaden external participation in the terminology development and QA process.

  8. NCI at Frederick Employees Honored at NCI Director’s Awards Program | Poster

    Cancer.gov

    By Nancy Parrish, Staff Writer Nineteen staff members affiliated with NCI at Frederick or the Frederick National Laboratory for Cancer Research (FNLCR) were recognized at the 2014 NCI Director’s Award Ceremony for their outstanding contributions to advancing cancer research. The ceremony, held Dec. 1, took place at the NIH Natcher Conference Center, on the main campus in Bethesda.

  9. NCI at Frederick Employees Recognized at the 2013 NCI Director’s Awards Ceremony | Poster

    Cancer.gov

    By Andrea Frydl, Contributing Writer, and Ashley DeVine, Staff Writer More than 60 NCI at Frederick government and contractor employees were recognized at the NCI Director’s Awards Ceremony on Nov. 14, held on the main NIH campus in Bethesda.

  10. Future Directions in Idiopathic Pulmonary Fibrosis Research. An NHLBI Workshop Report

    PubMed Central

    Blackwell, Timothy S.; Tager, Andrew M.; Borok, Zea; Moore, Bethany B.; Schwartz, David A.; Anstrom, Kevin J.; Bar-Joseph, Ziv; Bitterman, Peter; Blackburn, Michael R.; Bradford, William; Brown, Kevin K.; Chapman, Harold A.; Collard, Harold R.; Cosgrove, Gregory P.; Deterding, Robin; Doyle, Ramona; Flaherty, Kevin R.; Garcia, Christine Kim; Hagood, James S.; Henke, Craig A.; Herzog, Erica; Hogaboam, Cory M.; Horowitz, Jeffrey C.; King, Talmadge E.; Loyd, James E.; Lawson, William E.; Marsh, Clay B.; Noble, Paul W.; Noth, Imre; Sheppard, Dean; Olsson, Julie; Ortiz, Luis A.; O’Riordan, Thomas G.; Oury, Tim D.; Raghu, Ganesh; Roman, Jesse; Sime, Patricia J.; Sisson, Thomas H.; Tschumperlin, Daniel; Violette, Shelia M.; Weaver, Timothy E.; Wells, Rebecca G.; White, Eric S.; Kaminski, Naftali; Martinez, Fernando J.; Wynn, Thomas A.; Thannickal, Victor J.

    2014-01-01

    The median survival of patients with idiopathic pulmonary fibrosis (IPF) continues to be approximately 3 years from the time of diagnosis, underscoring the lack of effective medical therapies for this disease. In the United States alone, approximately 40,000 patients die of this disease annually. In November 2012, the NHLBI held a workshop aimed at coordinating research efforts and accelerating the development of IPF therapies. Basic, translational, and clinical researchers gathered with representatives from the NHLBI, patient advocacy groups, pharmaceutical companies, and the U.S. Food and Drug Administration to review the current state of IPF research and identify priority areas, opportunities for collaborations, and directions for future research. The workshop was organized into groups that were tasked with assessing and making recommendations to promote progress in one of the following six critical areas of research: (1) biology of alveolar epithelial injury and aberrant repair; (2) role of extracellular matrix; (3) preclinical modeling; (4) role of inflammation and immunity; (5) genetic, epigenetic, and environmental determinants; (6) translation of discoveries into diagnostics and therapeutics. The workshop recommendations provide a basis for directing future research and strategic planning by scientific, professional, and patient communities and the NHLBI. PMID:24160862

  11. Competence and psychopathology: cascade effects in the NICHD Study of Early Child Care and Youth Development.

    PubMed

    Burt, Keith B; Roisman, Glenn I

    2010-08-01

    Existing longitudinal research on the interplay between externalizing problems, internalizing problems, and academic and social competence has documented "cascading" effects from early aggressive/disruptive behavior through impairments in competence, leading to symptoms of depression and anxiety. The primary aim of the current study was to replicate such work using the NICHD Study of Early Child Care and Youth Development while also extending the developmental window of investigation of cascades back into early childhood. Participating families (N = 1,160) completed questionnaire measures of externalizing, internalizing, and social competence (maternal report), as well as individual assessment of academic achievement, spanning five time points from age 54 months through age 15 years. A series of nested structural equation models tested predicted links across various domains of competence and psychopathology. Results were consistent with prior research, demonstrating cross-domain effects from early externalizing problems through effects on both academic and social competence into later internalizing problems. Effects held across gender and were largely unaffected by inclusion of socioeconomic status, early caregiving, and early cognitive ability as covariates in the model.

  12. License Agreements | NCI Technology Transfer Center | TTC

    Cancer.gov

    Since the government cannot engage in the development, manufacture, and sale of products, the NCI Technology Transfer Center (TTC) makes its discoveries (and discoveries from nine other NIH Institutes) available to organizations that can assist in the further development and commercialization of these basic science discoveries, to convert them into public health benefits. | [google6f4cd5334ac394ab.html

  13. NCI International EBV-Gastric Cancer Consortium

    Cancer.gov

    A collaboration among NCI and extramural investigators, established by DCEG in 2006, that utilizes data and biospecimens from completed and ongoing case series and observational studies of gastric cancer to replicate and extend findings from previous studies hindered by small numbers of EBV-positive cases, and to stimulate multidisciplinary research in this area.

  14. NCI and Leidos Play Ball | Poster

    Cancer.gov

    By Carolynne Keenan, Contributing Writer The ping of an aluminum bat off a ball or the thump of a pop-up fly ball caught in a glove are two sounds familiar to baseball fans. Slow-pitch softball sounds—like those in the August game between mixed teams of NCI and Leidos Biomedical Research (formerly SAIC-Frederick) players—are similar.

  15. At NCI, Supporting the Best Science

    Cancer.gov

    Yesterday, at the AACR annual meeting, Dr. Doug Lowy spoke directly to the research community about his goals as NCI Acting Director. Dr. Lowy said that he plans to continue many of the programs launched by his predecessor, Dr. Harold Varmus, and to sharp

  16. NCI Approves Funding Plan for NCI Community Oncology Research Program (NCORP) | Division of Cancer Prevention

    Cancer.gov

    On June 24, 2014, the Scientific Program Leaders (SPL) of the National Cancer Institute (NCI) approved the funding plan for the NCI Community Oncology Research Program (NCORP), a national network of investigators, cancer care providers, academic institutions, and other organizations. NCORP will conduct multi-site cancer clinical trials and studies in diverse populations in community-based healthcare systems across the United States. The program will receive $93 million a year for five years. |

  17. NCI, NHLBI first international consensus conference on late effects after pediatric hematopoietic cell transplantation: etiology and pathogenesis of late effects after HCT performed in childhood--methodologic challenges.

    PubMed

    Bhatia, Smita; Davies, Stella M; Scott Baker, K; Pulsipher, Michael A; Hansen, John A

    2011-10-01

    Hematopoietic cell transplantation (HCT) is now a curative option for certain categories of patients with hematologic malignancies and other life-threatening illnesses. Technical and supportive care has resulted in survival rates that exceed 70% for those who survive the first 2 years after HCT. However, long-term survivors carry a high burden of morbidity, including endocrinopathies, musculoskeletal disorders, cardiopulmonary compromise, and subsequent malignancies. Understanding the etiologic pathways that lead to specific post-HCT morbidities is critical to developing targeted prevention and intervention strategies. Understanding the molecular underpinnings associated with graft-versus-host disease (GVHD), organ toxicity, relapse, opportunistic infection, and other long-term complications now recognized as health care concerns will have significant impact on translational research aimed at developing novel targeted therapies for controlling chronic GVHD, facilitating tolerance and immune reconstitution, reducing risk of relapse and secondary malignancies, minimizing chronic metabolic disorders, and improving quality of life. However, several methodological challenges exist in achieving these goals; these issues are discussed in detail in this paper.

  18. NCI, NHLBI/PBMTC First International Consensus Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: The Need for Pediatric Specific Long Term Follow-up Guidelines

    PubMed Central

    Pulsipher, Michael A.; Skinner, Roderick; McDonald, George B.; Hingorani, Sangeeta; Armenian, Saro H.; Cooke, Kenneth R.; Gracia, Clarisa; Petryk, Anna; Bhatia, Smita; Bunin, Nancy; Nieder, Michael L.; Dvorak, Christopher C.; Sung, Lillian; Sanders, Jean E.; Kurtzberg, Joanne; Baker, K. Scott

    2012-01-01

    Existing standards for screening and management of late effects occurring in children who have undergone hematopoietic cell transplantation (HCT) include recommendations from pediatric cancer networks and consensus guidelines from adult-oriented transplantation societies applicable to all recipients of HCT. While these approaches have significant merit, they are not pediatric-HCT focused and they do not address post-HCT challenges faced by children with complex non-malignant disorders. In this article we discuss the strengths and weaknesses of current published recommendations and conclude that pediatric-specific guidelines for post-HCT screening and management would be beneficial to the long-term health of these patients and would promote late-effects research in this field. Our panel of late effects experts also provides recommendations for follow up and therapy of selected post-HCT organ and endocrine complications in pediatric patients. PMID:22248713

  19. NCI, NHLBI/PBMTC First International Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation: Persistent Immune Deficiency in Pediatric Transplant Survivors

    PubMed Central

    Bunin, Nancy; Small, Trudy; Szabolcs, Paul; Baker, K. Scott; Pulsipher, Michael A.; Torgerson, Troy

    2011-01-01

    Defective immune reconstitution is a major barrier to successful hematopoietic cell transplantation (HCT), and has important implications in the pediatric population. There are many factors which affect immune recovery, including stem cell source and GVHD. Complete assessment of immune recovery, including T and B lymphocyte evaluation, innate immunity and response to neoantigens, may provide insight as to infection risk and optimal time for immunizations. The increasing use of cord blood grafts requires additional study regarding early reconstitution and impact upon survival. Immunization schedules may require modification based upon stem cell source and immune reconstitution, and this is of particular importance as many children have been incompletely immunized, or not at all, prior to school entry. Additional studies are needed in children post HCT to evaluate the impact of differing stem cell sources upon immune reconstitution, infectious risks and immunization responses. PMID:22100979

  20. Likelihood of Null Effects of Large NHLBI Clinical Trials Has Increased over Time

    PubMed Central

    Kaplan, Robert M.; Irvin, Veronica L.

    2015-01-01

    Background We explore whether the number of null results in large National Heart Lung, and Blood Institute (NHLBI) funded trials has increased over time. Methods We identified all large NHLBI supported RCTs between 1970 and 2012 evaluating drugs or dietary supplements for the treatment or prevention of cardiovascular disease. Trials were included if direct costs >$500,000/year, participants were adult humans, and the primary outcome was cardiovascular risk, disease or death. The 55 trials meeting these criteria were coded for whether they were published prior to or after the year 2000, whether they registered in clinicaltrials.gov prior to publication, used active or placebo comparator, and whether or not the trial had industry co-sponsorship. We tabulated whether the study reported a positive, negative, or null result on the primary outcome variable and for total mortality. Results 17 of 30 studies (57%) published prior to 2000 showed a significant benefit of intervention on the primary outcome in comparison to only 2 among the 25 (8%) trials published after 2000 (χ2=12.2,df= 1, p=0.0005). There has been no change in the proportion of trials that compared treatment to placebo versus active comparator. Industry co-sponsorship was unrelated to the probability of reporting a significant benefit. Pre-registration in clinical trials.gov was strongly associated with the trend toward null findings. Conclusions The number NHLBI trials reporting positive results declined after the year 2000. Prospective declaration of outcomes in RCTs, and the adoption of transparent reporting standards, as required by clinicaltrials.gov, may have contributed to the trend toward null findings. PMID:26244868

  1. Shifting Demographics among Research Project Grant Awardees at the National Heart, Lung, and Blood Institute (NHLBI)

    PubMed Central

    Oh, Young S.; Maric-Bilkan, Christine; Scott, Lindsey L.; Wu, Charles C.; Eblen, Matthew; Pearson, Katrina; Tolunay, H. Eser; Galis, Zorina S.

    2016-01-01

    The present study was initiated because of concerns expressed by NHLBI-funded mid-career investigators regarding perceived difficulties in the renewal of their grant awards. This led us to ask: “Are mid-career investigators experiencing disproportionate difficulties in the advancement of their professional careers?” Our portfolio analysis indicates that there has been a significant and evolving shift in the demographics of research project grant (RPG) awardees at NHLBI. In 1998, mid-career (ages 41–55) investigators constituted approximately 60% of all investigators with the remaining 40% being equally divided between early-stage (ages 24–40) investigators and established (ages 56 to 70 and older) investigators. However, since 1998, the proportion of established RPG awardees has been increasing in a slowly progressive and strikingly linear fashion. At the same time the proportion of early-stage awardees fell precipitously until 2006 and then stabilized. During the same period, the proportion of mid-career awardees, which had been relatively stable through 2006, began to fall significantly. In examining potential causes of these demographic shifts we have identified certain inherent properties within the RPG award system that appear to promote an increasingly more established awardee population and a persistent decrease in the proportion of mid-career investigators. A collateral result of these demographic shifts, when combined with level or declining funding, is a significant reduction in the number of RPG awards received by NHLBI mid-career investigators and a corresponding decrease in the number of independent research laboratories. PMID:27978544

  2. Clinical Research Careers: Reports from a NHLBI Pediatric Heart Network Clinical Research Skills Development Conference

    PubMed Central

    Lai, Wyman W.; Richmond, Marc; Li, Jennifer S.; Saul, J. Philip; Mital, Seema; Colan, Steven D.; Newburger, Jane W.; Sleeper, Lynn A.; McCrindle, Brain W.; Minich, L. LuAnn; Goldmuntz, Elizabeth; Marino, Bradley S.; Williams, Ismee A.; Pearson, Gail D.; Evans, Frank; Scott, Jane D.; Cohen, Meryl S.

    2013-01-01

    Background Wyman W. Lai, MD, MPH, and Victoria L. Vetter, MD, MPH. The Pediatric Heart Network (PHN), funded under the U.S. National Institutes of Health-National Heart, Lung, and Blood Institute (NIH–NHLBI), includes two Clinical Research Skills Development (CRSD) Cores, which were awarded to The Children's Hospital of Philadelphia and to the Morgan Stanley Children's Hospital of New York–Presbyterian. To provide information on how to develop a clinical research career to a larger number of potential young investigators in pediatric cardiology, the directors of these two CRSD Cores jointly organized a one-day seminar for fellows and junior faculty from all of the PHN Core sites. The participants included faculty members from the PHN and the NHLBI. The day-long seminar was held on April 29, 2009, at the NHLBI site, immediately preceding the PHN Steering Committee meeting in Bethesda, MD. Methods The goals of the seminar were 1) to provide fellows and early investigators with basic skills in clinical research 2) to provide a forum for discussion of important research career choices 3) to introduce attendees to each other and to established clinical researchers in pediatric cardiology, and 4) to publish a commentary on the future of clinical research in pediatric cardiology. Results The following chapters are compilations of the talks given at the 2009 PHN Clinical Research Skills Development Seminar, published to share the information provided with a broader audience of those interested in learning how to develop a clinical research career in pediatric cardiology. The discussions of types of clinical research, research skills, career development strategies, funding, and career management are applicable to research careers in other areas of clinical medicine as well. Conclusions The aim of this compilation is to stimulate those who might be interested in the research career options available to investigators. PMID:21167335

  3. Monoclonal Antibody Fragments for Targeting Therapeutics to Growth Plate Cartilage | NCI Technology Transfer Center | TTC

    Cancer.gov

    The NICHD seeks statements of capability or interest from parties interested in collaborative research to co-develop, evaluate, or commercialize treatment of skeletal disorders using targeting antibodies.

  4. Center for fetal monkey gene transfer for heart, lung, and blood diseases: an NHLBI resource for the gene therapy community.

    PubMed

    Tarantal, Alice F; Skarlatos, Sonia I

    2012-11-01

    The goals of the National Heart, Lung, and Blood Institute (NHLBI) Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases are to conduct gene transfer studies in monkeys to evaluate safety and efficiency; and to provide NHLBI-supported investigators with expertise, resources, and services to actively pursue gene transfer approaches in monkeys in their research programs. NHLBI-supported projects span investigators throughout the United States and have addressed novel approaches to gene delivery; "proof-of-principle"; assessed whether findings in small-animal models could be demonstrated in a primate species; or were conducted to enable new grant or IND submissions. The Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases successfully aids the gene therapy community in addressing regulatory barriers, and serves as an effective vehicle for advancing the field.

  5. NCI at Frederick Ebola Response Team | Poster

    Cancer.gov

    Editor’s note: This article was adapted from the Employee Diversity Team’s display case exhibit “Recognizing the NCI at Frederick Ebola Response Team,” in the lobby of Building 549. The Poster staff recognizes that this article does not include everyone who was involved in the response to the Ebola crisis, both at NCI at Frederick and in Africa. When the Ebola crisis broke out in 2014 in West Africa, staff members from the Frederick National Laboratory for Cancer Research responded quickly. Members of the Clinical Monitoring Research Program (CMRP) were instrumental not only in setting up the clinical trials of the vaccine in Liberia, but also in providing training, community outreach, and recruitment strategies for the trials.

  6. Efficiently Maintaining a National Resource of Historical and Contemporary Biological Collections: The NHLBI Biorepository Model

    PubMed Central

    Wagner, Elizabeth L.; Marchesani, Leah; Meagher, Kevin; Giffen, Carol

    2017-01-01

    Introduction: Reducing costs by improving storage efficiency has been a focus of the National Heart, Lung, and Blood Institute (NHLBI) Biologic Specimen Repository (Biorepository) and Biologic Specimen and Data Repositories Information Coordinating Center (BioLINCC) programs for several years. Methods: Study specimen profiles were compiled using the BioLINCC collection catalog. Cost assessments and calculations on the return on investments to consolidate or reduce a collection, were developed and implemented. Results: Over the course of 8 months, the NHLBI Biorepository evaluated 35 collections that consisted of 1.8 million biospecimens. A total of 23 collections were selected for consolidation, with a total of 1.2 million specimens located in 21,355 storage boxes. The consolidation resulted in a savings of 4055 boxes of various sizes and 10.2 mechanical freezers (∼275 cubic feet) worth of space. Conclusion: As storage costs in a biorepository increase over time, the development and use of information technology tools to assess the potential advantage and feasiblity of vial consolidation can reduce maintenance expenses. PMID:28186851

  7. NCI's Transdisciplinary High Performance Scientific Data Platform

    NASA Astrophysics Data System (ADS)

    Evans, Ben; Antony, Joseph; Bastrakova, Irina; Car, Nicholas; Cox, Simon; Druken, Kelsey; Evans, Bradley; Fraser, Ryan; Ip, Alex; Kemp, Carina; King, Edward; Minchin, Stuart; Larraondo, Pablo; Pugh, Tim; Richards, Clare; Santana, Fabiana; Smillie, Jon; Trenham, Claire; Wang, Jingbo; Wyborn, Lesley

    2016-04-01

    The Australian National Computational Infrastructure (NCI) manages Earth Systems data collections sourced from several domains and organisations onto a single High Performance Data (HPD) Node to further Australia's national priority research and innovation agenda. The NCI HPD Node has rapidly established its value, currently managing over 10 PBytes of datasets from collections that span a wide range of disciplines including climate, weather, environment, geoscience, geophysics, water resources and social sciences. Importantly, in order to facilitate broad user uptake, maximise reuse and enable transdisciplinary access through software and standardised interfaces, the datasets, associated information systems and processes have been incorporated into the design and operation of a unified platform that NCI has called, the National Environmental Research Data Interoperability Platform (NERDIP). The key goal of the NERDIP is to regularise data access so that it is easily discoverable, interoperable for different domains and enabled for high performance methods. It adopts and implements international standards and data conventions, and promotes scientific integrity within a high performance computing and data analysis environment. NCI has established a rich and flexible computing environment to access to this data, through the NCI supercomputer; a private cloud that supports both domain focused virtual laboratories and in-common interactive analysis interfaces; as well as remotely through scalable data services. Data collections of this importance must be managed with careful consideration of both their current use and the needs of the end-communities, as well as its future potential use, such as transitioning to more advanced software and improved methods. It is therefore critical that the data platform is both well-managed and trusted for stable production use (including transparency and reproducibility), agile enough to incorporate new technological advances and

  8. Obesity and Cardiovascular Disease Risk Factors in Black and White Girls: The NHLBI Growth and Health Study.

    ERIC Educational Resources Information Center

    American Journal of Public Health, 1992

    1992-01-01

    The National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study Research Group's 5-year cohort study provides basic information on the baseline cohort of 1,166 white and 1,213 African-American girls aged 9 through 10 years. Factors associated with development of obesity and cardiovascular risk factors are assessed. (SLD)

  9. METAvivor Reps Visit NCI at Frederick | Poster

    Cancer.gov

    Three representatives of METAvivor visited NCI at Frederick on April 13 to meet and tour with Balamurugan Kuppusamy, Ph.D., staff scientist in the laboratory of Esta Sterneck, Ph.D., senior investigator, Laboratory of Cell and Developmental Signaling, Center for Cancer Research.  The purpose of the visit was to learn more about Kuppusamy’s research. Kuppusamy is a recipient of a $50,000, two-year grant awarded by METAvivor to study the role of the CEBPD-FBXW7 signaling pathway in inflammatory breast cancer.

  10. NCI/DCCPS R03 Program Announcements | DCCPS/NCI/NIH

    Cancer.gov

    The Division of Cancer Control and Population Sciences funds a large portfolio of grants and contracts. The portfolio currently includes approximately 800 grants valued at nearly $450 million. Here we provide a listing of funding opportunities that are currently accepting applications. Please visit this page regularly as new funding opportunities are added upon approval by NCI.

  11. NCI/DCCPS R21 Program Announcements | DCCPS/NCI/NIH

    Cancer.gov

    The Division of Cancer Control and Population Sciences funds a large portfolio of grants and contracts. The portfolio currently includes approximately 800 grants valued at nearly $450 million. Here we provide a listing of funding opportunities that are currently accepting applications. Please visit this page regularly as new funding opportunities are added upon approval by NCI.

  12. NHLBI training workshop report: The vanishing pediatric pulmonary investigator and recommendations for recovery.

    PubMed

    Ferkol, Thomas; Zeitlin, Pamela; Abman, Steven; Blaisdell, Carol J; O'Brodovich, Hugh

    2010-01-01

    The adequacy of the pipeline of advanced pulmonary fellows to supply appropriately trained and committed researchers to enter academic careers was the major topic of a recently held National Heart Lung and Blood Institute NHLBI Workshop: Respiratory Medicine-Related Research Training for Adult and Pediatric Fellows. The special challenges and opportunities for the academic pediatric pulmonary trainee were discussed as part of this workshop and are discussed as a companion paper to the report by the full workshop. Surveys were conducted of pediatric chairs of academic departments and pediatric pulmonary training directors in the United States to examine the current status and opportunities for the pediatric pulmonary trainee. Strategies for recruitment and retention of talented young trainees and junior faculty are proposed.

  13. Combined analysis of genomewide scans for adult height: results from the NHLBI Family Blood Pressure Program.

    PubMed

    Wu, Xiaodong; Cooper, Richard S; Boerwinkle, Eric; Turner, Stephen T; Hunt, Steve; Myers, Richard; Olshen, Richard A; Curb, David; Zhu, Xiaofeng; Kan, Donghui; Luke, Amy

    2003-03-01

    A combined analysis of genome scans was performed for adult height in the NHLBI Family Blood Pressure Program. Height data were available on 6752 individuals. Linkage analysis was performed first separately for each of the eight ethnic groups in the four networks using the variance component method. To increase the power to detect the common genetic components affecting height for all the individuals, a linkage analysis was performed subsequently for the combined data set by pooling the average allele-sharing IBD () for all groups. By combining the data, we replicated evidence for a QTL influencing adult height on chromosome 7 (7q31) (LOD=2.46), which has been reported in two previous studies. Suggestive linkage (LOD>1) was found in another six regions in our combined analysis. Evidence for linkage for two of these regions (2p12, 20p11) has also been reported previously.

  14. Halaven® - eribulin mesylate (analog of halichondrin B) | NCI Technology Transfer Center | TTC

    Cancer.gov

    Under a CRADA with NCI, Eisai Co. provided eribulin for NCI's preclinical development activities and to support NCI's Phase I clinical trials. Eisai ultimately took the product, Halaven®, to licensure.

  15. NCI Community Oncology Research Program Approved | Division of Cancer Prevention

    Cancer.gov

    On June 24, 2013, the National Cancer Institute (NCI) Board of Scientific Advisors approved the creation of the NCI Community Oncology Research Program (NCORP). NCORP will bring state-of-the art cancer prevention, control, treatment and imaging clinical trials, cancer care delivery research, and disparities studies to individuals in their own communities. |

  16. The Employee Invention Report (EIR) | NCI Technology Transfer Center | TTC

    Cancer.gov

    After making such a discovery, NCI researchers should immediately contact their Laboratory or Branch Chief and inform him or her of a possible invention and consult with your NCI TTC Technology Transfer Specialist about submitting an Employee Invention Report (EIR) Form. | [google6f4cd5334ac394ab.html

  17. Double Jeopardy: Poorer Social-Emotional Outcomes for Children in the NICHD SECCYD Experiencing Home and Child-Care Environments that Confer Risk

    ERIC Educational Resources Information Center

    Watamura, Sarah Enos; Phillips, Deborah A.; Morrissey, Taryn W.; McCartney, Kathleen; Bub, Kristen

    2011-01-01

    Using data from the National Institute of Child Health and Human Development Early Child Care Research Network (NICHD SECCYD), the authors examined whether interactions between home and child-care quality affect children's social-emotional adjustment at 24, 36, and 54 months (N = 771). Triadic splits on quality of home and child care were used to…

  18. Expanding treatment options for youth with type 2 diabetes: Current problems and proposed solutions: A white paper from the NICHD Diabetes Working Group

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Best Pharmaceuticals for Children Act of 2002 mandated that the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) carries out critical reviews of the gaps in knowledge and unmet needs regarding safe and effective pharmacologic treatment of infants, children,...

  19. Mission & Role | NCI Technology Transfer Center | TTC

    Cancer.gov

    The NCI TTC serves as the focal point for implementing the Federal Technology Transfer Act to utilize patents as incentive for commercial development of technologies and to establish research collaborations and licensing among academia, federal laboratories, non-profit organizations, and industry. The TTC supports technology development activities for the National Cancer Institute and nine other NIH Institutes and Centers. TTC staff negotiate co-development agreements and licenses with universities, non-profit organizations, and pharmaceutical and biotechnology companies to ensure compliance with Federal statutes, regulations and the policies of the National Institutes of Health. TTC also reviews employee invention reports and makes recommendations concerning filing of domestic and foreign patent applications. | [google6f4cd5334ac394ab.html

  20. Tackling NCD in LMIC: Achievements and Lessons Learned From the NHLBI-UnitedHealth Global Health Centers of Excellence Program.

    PubMed

    Engelgau, Michael M; Sampson, Uchechukwu K; Rabadan-Diehl, Cristina; Smith, Richard; Miranda, Jaime; Bloomfield, Gerald S; Belis, Deshiree; Narayan, K M Venkat

    2016-03-01

    Effectively tackling the growing noncommunicable disease (NCD) burden in low- and middle-income countries (LMIC) is a major challenge. To address research needs in this setting for NCDs, in 2009, National Heart, Lung, and Blood Institute (NHLBI) and UnitedHealth Group (UHG) engaged in a public-private partnership that supported a network of 11 LMIC-based research centers and created the NHLBI-UnitedHealth Global Health Centers of Excellence (COE) Program. The Program's overall goal was to contribute to reducing the cardiovascular and lung disease burdens by catalyzing in-country research institutions to develop a global network of biomedical research centers. Key elements of the Program included team science and collaborative approaches, developing research and training platforms for future investigators, and creating a data commons. This Program embraced a strategic approach for tackling NCDs in LMICs and will provide capacity for locally driven research efforts that can identify and address priority health issues in specific countries' settings.

  1. Research opportunities for pathogen reduction/inactivation of blood components: summary of an NHLBI workshop.

    PubMed

    Klein, Harvey G; Glynn, Simone A; Ness, Paul M; Blajchman, Morris A

    2009-06-01

    In July 2008, a workshop sponsored by the Division of Blood Diseases and Resources of the National Heart, Lung, and Blood Institute (NHLBI) was convened to identify potential research opportunities that could advance our understanding of both the biologic and the clinical impact of the various available pathogen reduction/inactivation (PR/PI) methods of blood components (platelets [PLTs], red blood cells, and plasma) intended for allogeneic transfusion. These discussions resulted in consensus that, even though several PR/PI technologies have already been licensed and are being used in Europe and elsewhere for PLTs and plasma, concerns about possible side effects, particularly component quality and pulmonary toxicity, have impeded regulatory approval in North America (United States and Canada). Such concerns thus threaten to stall further development of these technologies. As a consequence, the NHLBI workshop participants focused on formulating a series of research-related recommendations to better understand, mitigate, and prevent these adverse effects. Other important issues identified included the need for a single method to inactivate pathogens in whole blood without damaging the various blood components; new ways to monitor the efficacy of treated components, including animal models to screen for safety; a better understanding of the effect of PR/PI-treated products on recipient alloimmunization, tolerance, and immune modulation; understanding the impact of PR/PI on various other noninfectious hazards of transfusion; and establishing methods to evaluate risk-benefit and cost-effectiveness, in particular with reference to emerging pathogens. The working group also discussed issues related to specific blood components, such as improving the process of clinical evaluation, investigating the impact of PR/PI on component storage lesions, understanding mechanisms that reduce component viability, and addressing the underlying resistance to the adoption of PR

  2. Auditing the NCI thesaurus with semantic web technologies.

    PubMed

    Mougin, Fleur; Bodenreider, Olivier

    2008-11-06

    Auditing biomedical terminologies often results in the identification of inconsistencies and thus helps to improve their quality. In this paper, we present a method based on Semantic Web technologies for auditing biomedical terminologies and apply it to the NCI thesaurus. We stored the NCI thesaurus concepts and their properties in an RDF triple store. By querying this store, we assessed the consistency of both hierarchical and associative relations from the NCI thesaurus among themselves and with corresponding relations in the UMLS Semantic Network. We show that the consistency is better for associative relations than for hierarchical relations. Causes for inconsistency and benefits from using Semantic Web technologies for auditing purposes are discussed.

  3. NCI at Frederick Contributes to Feds Feed Families | Poster

    Cancer.gov

    Once again, NCI at Frederick participated in the annual Feds Feed Families event, which challenges federal workers to help knock out hunger with a food drive. This year, NIH collected 26,315 pounds of non-perishable goods, beating its goal of collecting 20,000 pounds. This includes over four tons of food that was collected at satellite locations, including NCI at Frederick. The food collected at NCI at Frederick was donated locally to the Frederick Rescue Mission. These donations help feed local families in need through the holiday season.

  4. From Hot Hands to Declining Effects: The Risks of Small Numbers (News from the NHLBI)

    PubMed Central

    Lauer, Michael S

    2016-01-01

    About 25 years ago a group of researchers demonstrated that there is no such thing as the “hot hand” in professional basketball. When a player hits 5 or 7 shots in a row (or misses 10 in a row), what's at work is random variation, nothing more. However, random causes do not stop players, coaches, fans, and media from talking about and acting on “hot hands,” telling stories and making choices which ultimately are based on randomness. The same phenomenon is true in medicine. Some clinical trials with small numbers of events yield positive findings, which in turn led clinicians, academics, and government officials to talk, telling stories and sometimes making choices which were later shown to be based on randomness. I provide some cardiovascular examples, such as the use of angiotensin-receptor blockers in chronic heart failure, nesiritide in acute heart failure, and CPY2C19 genotyping in acute coronary syndrome. I also review the more general “decline effect,” by which drugs appear to yield a lower effect size over time. The “decline effect” is at least in part due to over-interpretation of small studies which are more likely to be noticed because of publication bias. As funders of research, we at NHLBI seek to support projects that will yield robust, credible evidence that will impact practice and policy in the right way. We must be alert to the risks of small numbers. PMID:22742403

  5. Multi-Ethnic Analysis of Lipid-Associated Loci: The NHLBI CARe Project

    PubMed Central

    Musunuru, Kiran; Romaine, Simon P. R.; Lettre, Guillaume; Wilson, James G.; Volcik, Kelly A.; Tsai, Michael Y.; Taylor, Herman A.; Schreiner, Pamela J.; Rotter, Jerome I.; Rich, Stephen S.; Redline, Susan; Psaty, Bruce M.; Papanicolaou, George J.; Ordovas, Jose M.; Liu, Kiang; Krauss, Ronald M.; Glazer, Nicole L.; Gabriel, Stacey B.; Fornage, Myriam; Cupples, L. Adrienne; Buxbaum, Sarah G.; Boerwinkle, Eric; Ballantyne, Christie M.; Kathiresan, Sekar; Rader, Daniel J.

    2012-01-01

    Background Whereas it is well established that plasma lipid levels have substantial heritability within populations, it remains unclear how many of the genetic determinants reported in previous studies (largely performed in European American cohorts) are relevant in different ethnicities. Methodology/Principal Findings We tested a set of ∼50,000 polymorphisms from ∼2,000 candidate genes and genetic loci from genome-wide association studies (GWAS) for association with low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) in 25,000 European Americans and 9,000 African Americans in the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe). We replicated associations for a number of genes in one or both ethnicities and identified a novel lipid-associated variant in a locus harboring ICAM1. We compared the architecture of genetic loci associated with lipids in both African Americans and European Americans and found that the same genes were relevant across ethnic groups but the specific associated variants at each gene often differed. Conclusions/Significance We identify or provide further evidence for a number of genetic determinants of plasma lipid levels through population association studies. In many loci the determinants appear to differ substantially between African Americans and European Americans. PMID:22629316

  6. Strategic plan for pediatric respiratory diseases research: an NHLBI working group report.

    PubMed

    Castro, Mario; Ramirez, Maria I; Gern, James E; Cutting, Garry; Redding, Greg; Hagood, James S; Whitsett, Jeffrey; Abman, Steve; Raj, J Usha; Barst, Robyn; Kato, Gregory J; Gozal, David; Haddad, Gabriel G; Prabhakar, Nanduri R; Gauda, Estelle; Martinez, Fernando D; Tepper, Robert; Wood, Robert E; Accurso, Frank; Teague, W Gerald; Venegas, Jose; Cole, F Sessions; Wright, Rosalind J

    2009-01-15

    The Division of Lung Diseases of the National Heart, Lung, and Blood Institute (NHLBI) recently held a workshop to identify gaps in our understanding and treatment of childhood lung diseases and to define strategies to enhance translational research in this field. Leading experts with diverse experience in both laboratory and patient-oriented research reviewed selected areas of pediatric lung diseases, including perinatal programming and epigenetic influences; mechanisms of lung injury, repair, and regeneration; pulmonary vascular disease; sleep and control of breathing; and the application of novel translational methods to enhance personalized medicine. This report summarizes the proceedings of this workshop and provides recommendations for emphasis on targeted areas for future investigation. The priority areas identified for research in pediatric pulmonary diseases included: (1) epigenetic and environmental influences on lung development that program pediatric lung diseases; (2) injury, regeneration, and repair in the developing lung; (3) pulmonary vascular disease in children; (4) development and adaptation of ventilatory responses to postnatal life; (5) nonatopic wheezing: aberrant large airway development or injury?; (6) strategies to improve assessment, diagnosis, and treatment of pediatric respiratory diseases; and (7) predictive and personalized medicine for children.

  7. Strategic plan for pediatric respiratory diseases research: an NHLBI working group report.

    PubMed

    Abman, Steve; Jobe, Alan; Chernick, Victor; Blaisdell, Carol; Castro, Mario; Ramirez, Maria I; Gern, James E; Cutting, Garry; Redding, Greg; Hagood, James S; Whitsett, Jeffrey; Abman, Steve; Raj, J Usha; Barst, Robyn; Kato, Gregory J; Gozal, David; Haddad, Gabriel G; Prabhakar, Nanduri R; Gauda, Estelle; Martinez, Fernando D; Tepper, Robert; Wood, Robert E; Accurso, Frank; Teague, W Gerald; Venegas, Jose; Cole, F Sessions; Wright, Rosalind J; Gail, Dorothy; Hamvas, Aaron; Kercsmar, Carolyn; Kiley, James; Weinmann, Gail

    2009-01-01

    The Division of Lung Diseases of the National Heart, Lung and Blood Institute (NHLBI) recently held a workshop to identify gaps in our understanding and treatment of childhood lung diseases and to define strategies to enhance translational research in this field. Leading experts with diverse experience in both laboratory and patient-oriented research reviewed selected areas of pediatric lung diseases, including perinatal programming and epigenetic influences; mechanisms of lung injury, repair, and regeneration; pulmonary vascular disease (PVD); sleep and control of breathing; and the application of novel translational methods to enhance personalized medicine. This report summarizes the proceedings of this workshop and provides recommendations for emphasis on targeted areas for future investigation. The priority areas identified for research in pediatric pulmonary diseases included: (1) epigenetic and environmental influences on lung development that program pediatric lung diseases, (2) injury, regeneration, and repair in the developing lung, (3) PVD in children, (4) development and adaptation of ventilatory responses to postnatal life, (5) nonatopic wheezing: aberrant large airway development or injury? (6) strategies to improve assessment, diagnosis, and treatment of pediatric respiratory diseases, and (7) predictive and personalized medicine for children.

  8. 2012 FRIENDS-OF-NCI-EGRP News Flashes

    Cancer.gov

    A 2012 archive of listserv announcements sent by the Epidemiology and Genetics Research Program to FRIENDS-OF-NCI-EGRP LISTSERV subscribers to communicate information about funding opportunities, grantsmanship issues, research resources, and other relevant news.

  9. 2011 FRIENDS-OF-NCI-EGRP News Flashes

    Cancer.gov

    A 2011 archive of listserv announcements sent by the Epidemiology and Genetics Research Program to FRIENDS-OF-NCI-EGRP LISTSERV subscribers to communicate information about funding opportunities, grantsmanship issues, research resources, and other relevant news.

  10. Brenda K. Edwards, PhD | DCCPS/NCI/NIH

    Cancer.gov

    Brenda K. Edwards, PhD, has been with the Surveillance Research Program (SRP) and its predecessor organizations at the National Cancer Institute (NCI) since 1989, serving as SRP’s Associate Director from 1990-2011.

  11. 2008 FRIENDS-OF-NCI-EGRP News Flashes

    Cancer.gov

    A 2008 archive of listserv announcements sent by the Epidemiology and Genetics Research Program to FRIENDS-OF-NCI-EGRP LISTSERV subscribers to communicate information about funding opportunities, grantsmanship issues, research resources, and other relevant news.

  12. Monoclonal Antibodies Targeting Tumor Growth | NCI Technology Transfer Center | TTC

    Cancer.gov

    The NCI Nanobiology Program, Protein Interaction Group is seeking parties to license or co-develop, evaluate, or commercialize monoclonal antibodies against the insulin-like growth factor for the treatment of cancer.

  13. NCI and the Precision Medicine Initiative®

    Cancer.gov

    NCI's activities related to precision medicine focuses on new and expanded precision medicine clinical trials; mechanisms to overcome drug resistance to cancer treatments; and developing a shared digital repository of precision medicine trials data.

  14. Micatu Tissue Arrayer | NCI Technology Transfer Center | TTC

    Cancer.gov

    An NCI researcher recognized a critical need to create a low-cost, easy-to-use tissue microarrayer (TMA), an instrument used by researchers and pathologists to accurately examine tissue samples from patients.

  15. 2010 FRIENDS-OF-NCI-EGRP News Flashes

    Cancer.gov

    A 2010 archive of listserv announcements sent by the Epidemiology and Genetics Research Program to FRIENDS-OF-NCI-EGRP LISTSERV subscribers to communicate information about funding opportunities, grantsmanship issues, research resources, and other relevant news.

  16. 2013 FRIENDS-OF-NCI-EGRP News Flashes

    Cancer.gov

    An archive of listserv announcements sent by the Epidemiology and Genetics Research Program to FRIENDS-OF-NCI-EGRP LISTSERV subscribers to communicate information about funding opportunities, grantsmanship issues, research resources, and other relevant news.

  17. 2014 FRIENDS-OF-NCI-EGRP News Flashes

    Cancer.gov

    An archive of listserv announcements sent by the Epidemiology and Genetics Research Program to FRIENDS-OF-NCI-EGRP LISTSERV subscribers to communicate information about funding opportunities, grantsmanship issues, research resources, and other relevant news.

  18. 2009 FRIENDS-OF-NCI-EGRP News Flashes

    Cancer.gov

    A 2009 archive of listserv announcements sent by the Epidemiology and Genetics Research Program to FRIENDS-OF-NCI-EGRP LISTSERV subscribers to communicate information about funding opportunities, grantsmanship issues, research resources, and other relevant news.

  19. GPU accelerated implementation of NCI calculations using promolecular density.

    PubMed

    Rubez, Gaëtan; Etancelin, Jean-Matthieu; Vigouroux, Xavier; Krajecki, Michael; Boisson, Jean-Charles; Hénon, Eric

    2017-03-25

    The NCI approach is a modern tool to reveal chemical noncovalent interactions. It is particularly attractive to describe ligand-protein binding. A custom implementation for NCI using promolecular density is presented. It is designed to leverage the computational power of NVIDIA graphics processing unit (GPU) accelerators through the CUDA programming model. The code performances of three versions are examined on a test set of 144 systems. NCI calculations are particularly well suited to the GPU architecture, which reduces drastically the computational time. On a single compute node, the dual-GPU version leads to a 39-fold improvement for the biggest instance compared to the optimal OpenMP parallel run (C code, icc compiler) with 16 CPU cores. Energy consumption measurements carried out on both CPU and GPU NCI tests show that the GPU approach provides substantial energy savings. © 2017 Wiley Periodicals, Inc.

  20. NCI scientists at forefront of new prostate cancer diagnostics

    Cancer.gov

    Introduction of the UroNav was the result of nearly a decade’s research and development, principally conducted at NCI. Resembling a stylized computer workstation on wheels, the system electronically fuses together pictures from magnetic resonance imaging

  1. NCI Alliance for Nanotechnology in Cancer - Alliance in the News

    Cancer.gov

    The NCI Alliance for Nanotechnology in Cancer is conducting cutting-edge research using nanotechnology to transform the diagnosis, prevention, treatment, and clinical outcomes for cancer patients. Read news stories and announcements below about the Alliance's multidisciplinary work.

  2. NCI at ASCO: A brief overview on women's cancers

    Cancer.gov

    The 2014 annual American Society of Clinical Oncology (ASCO) meeting in Chicago in June highlighted results from a number of NCI-supported and -sponsored clinical trial results in women’s cancers. Taken together, these results represent important advances

  3. Cell Lines Expressing Nuclear and/or Mitochondrial RNAse H1 | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Institute of Child Health & Human Development (NICHD), Program in Genomics of Differentiation, seeks interested parties to further co-develop small molecule inhibitors of RNase H1, especially in regards to genome instability, transcription, and translation.

  4. Invention Development Program Helps Nurture NCI at Frederick Technologies | Poster

    Cancer.gov

    The Invention Development Fund (IDF) was piloted by the Technology Transfer Center (TTC) in 2014 to facilitate the commercial development of NCI technologies. The IDF received a second round of funding from the NCI Office of the Director and the Office of Budget and Management to establish the Invention Development Program (IDP) for fiscal year 2016. The IDP is using these funds to help advance a second set of inventions.

  5. Training and retaining of underrepresented minority physician scientists - a Hispanic perspective: NICHD-AAP workshop on research in neonatology.

    PubMed

    Valcarcel, M; Diaz, C; Santiago-Borrero, P J

    2006-07-01

    In a workshop organized by NICHD and the AAP in January 2004, we addressed and discussed issues related to a Hispanic perspective in Training and Retaining of underrepresented minority physician scientists in the United States. A review of the literature related to training of underrepresented minority physicians in the United States (US) was performed, giving emphasis to those related to the Hispanic population. Success and failure in training and retention of Hispanic physician scientists and trainees was examined. An underrepresentation of Hispanic minorities in medical research workforce was found. This fact has recently resulted in efforts to increase their recruitment and there is a mandate by the National Institute of Health (NIH) for their inclusion. The Hispanic population in the US has increased rapidly, with diversity among the Hispanics in their personal and professional behavior. Significant disparities in health, health risk factors and access to health care manifested by an increased burden of illness and death have been documented. There in an undersupply of academic Hispanic neonatologist. Factors such as availability of academic employment, limited research funding in pediatrics, managed care and large debt burden of the US medical graduates interfere with recruitment of Hispanic trainees and academic physician scientist. Possible solutions, including recognition research awards, revision of NIH policies in awarding funds for neonatology, establishing strategies to improve minorities' acceptance, participation in research and increase accrual of Hispanic population in clinical trials should be given priority.

  6. Chocolate consumption and prevalence of metabolic syndrome in the NHLBI Family Heart Study

    PubMed Central

    Tokede, Oluwabunmi A.; Ellison, Curtis R.; Pankow, James S.; North, Kari E.; Hunt, Steven C.; Kraja, Aldi T.; Arnett, Donna K.; Djoussé, Luc

    2014-01-01

    SUMMARY Background & aims Previous studies have suggested that cocoa products, which are rich sources of flavonoids, may lower blood pressure, serum cholesterol, fasting blood glucose and improve endothelial function. However, it is unclear whether consumption of cocoa products including chocolate influences the risk of metabolic syndrome (MetS). In a cross-sectional design, we sought to examine the association between chocolate consumption and the prevalence of MetS. Methods We studied 4098 participants from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study aged 25–93 years. Chocolate consumption was assessed using a semi-quantitative food-frequency questionnaire. MetS was defined using the NCEP III criteria. Generalized estimating equations were used to estimate prevalence odds ratios of MetS according to frequency of chocolate intake. Results Of the 4098 participants (mean age 51.7 y) included in the analyses, 2206 (53.8%) were female. The prevalence of metabolic syndrome in our population was 30.2%. Compared with those who did not consume any chocolate, multivariate adjusted odds ratios (95% CI) for MetS were 1.26 (0.94, 1.69), 1.15 (0.85, 1.55), and 0.99 (0.66, 1.51) among women who reported chocolate consumption of 1–3 times/ month, 1–4 times/week, and 5+ times/week, respectively. Corresponding values for men were: 1.13 (0.82, 1.57), 1.02 (0.74, 1.39), and 1.21 (0.79, 1.85). Conclusion These data do not support an association between chocolate intake and the prevalence of MetS in US adult men and women. PMID:25126517

  7. An overview of the NCI precision medicine trials-NCI MATCH and MPACT.

    PubMed

    Do, Khanh; O'Sullivan Coyne, Geraldine; Chen, Alice P

    2015-09-01

    The concept of oncogene addiction was first proposed by Weinstein in 2002, postulating that tumors rely on a single dominant mutation, the oncogenic "driver", for growth and survival. We have since come to realize that the genomic landscape of tumors is heterogeneous and more complex than previously thought. Advances in biotechnology and bioinformatics over the past decade have shifted treatment paradigms with regard to the development of molecular targeted therapeutics to identify and target the presumptive dominant lesion. As such, the decision of choosing targeted treatment strategies has become increasingly more reliant on the reporting of genomic screens of patients' tumor tissue. Whether this change in treatment paradigm will translate into improved clinical benefit, remains to be seen. To this end, the United States National Cancer Institute (NCI) has launched precision-based medicine trials to address this question. NCI Molecular Analysis for Therapy Choice (MATCH), a genomic pre-screening study, was designed to explore the efficacy of using targeted agents to target specific molecular aberrations and whether these same therapies have comparable activity across different tumor subtypes. Molecular Profiling-based Assignment of Cancer Therapy (MPACT), is a smaller, provocative trial designed to address whether targeting an oncogenic "driver" would be more efficacious than one not. The Exceptional Responders' initiative further aims to evaluate patients who have derived an unexpected durable benefit to these therapies, with retrospective analysis of their tumors to delineate potential predictive biomarkers which could predict response. The results of these trials will serve to help guide the field of precision medicine and personalized care.

  8. Childhood Anxiety Trajectories and Adolescent Disordered Eating: Findings from the NICHD Study of Early Child Care and Youth Development

    PubMed Central

    Zerwas, Stephanie; Von Holle, Ann; Watson, Hunna; Gottfredson, Nisha; Bulik, Cynthia M.

    2015-01-01

    Objective The goal of the present paper was to examine whether childhood anxiety trajectories predict eating psychopathology. We predicted that girls with trajectories of increasing anxiety across childhood would have significantly greater risk of disordered eating in adolescence in comparison to girls with stable or decreasing trajectories of anxiety over childhood. Method Data were collected as part of the prospective longitudinal NICHD Study of Early Child Care and Youth Development (N=450 girls). Childhood anxiety was assessed yearly (54 months through 6th grade) via maternal report on the Child Behavior Checklist. Disordered eating behaviors were assessed at age 15 via adolescent self-report on the Eating Attitudes Test (EAT-26). We conducted latent growth mixture modeling to define girls’ childhood anxiety trajectories. Maternal sensitivity, maternal postpartum depression, maternal anxiety, and child temperament were included as predictors of trajectory membership. Results The best fitting model included three trajectories of childhood anxiety, the low-decreasing class (22.9% of girls), the high-increasing class (35.4%), and the high-decreasing class (41.6%). Mothers with more symptoms of depression and separation anxiety had girls who were significantly more likely to belong to the high-increasing anxiety trajectory. There were no significant differences in adolescent disordered eating for girls across the three childhood anxiety trajectories. Conclusions Childhood anxiety, as captured by maternal report, may not be the most robust predictor of adolescent disordered eating and may be of limited utility for prevention programs that aim to identify children in the community at greatest risk for disordered eating. PMID:24938214

  9. Providing Contemporary Access to Historical Biospecimen Collections: Development of the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC)

    PubMed Central

    Carroll, Leslie E.; Adams, John T.; Brennan, Sean P.; Coady, Sean A.; Wagner, Elizabeth L.

    2015-01-01

    The National Heart, Lung, and Blood Institute (NHLBI), within the United States' National Institutes of Health (NIH), established a Biorepository in 1976 that initially archived biospecimens from population-based blood product safety surveys. It was later expanded to biospecimens from clinical and epidemiological studies in heart, lung, and blood disorders. The NHLBI also established a Data Repository in 2000 to store and distribute study data from NHLBI-sponsored research. The NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) was established in 2008 to develop the infrastructure needed to link the contents of these two related NHLBI Repositories, facilitate access to repository resources, and streamline request processes. Three key program subcomponents were developed simultaneously: 1) the linkage of biospecimen electronic inventory records with their clinical or characterization data; 2) the development and implementation of a website with both public-facing information and private processing workspaces; and 3) the development of processes to maximize efficiency via a web-based system while maintaining workflow control, document tracking, and secure processes. The BioLINCC website was launched on October 1, 2009 with eight biospecimen collections and data from 72 research studies. By the end of the fourth online year, 38 biospecimen collections were linked and posted, and data from 108 research studies had been made available for request. The number of registered users by the end of the fourth online year approached 2600, and continues to show a trend towards an increasing rate of new users per year. BioLINCC has fulfilled 381 requests comprising 851 data collections, as well as 600 teaching dataset requests and 75 data renewal agreements. 154 biospecimen requests comprising 147,388 biospecimens were fulfilled or actively in process. We conclude that the BioLINCC program has been successful in its goal to increase the

  10. Providing Contemporary Access to Historical Biospecimen Collections: Development of the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC).

    PubMed

    Giffen, Carol A; Carroll, Leslie E; Adams, John T; Brennan, Sean P; Coady, Sean A; Wagner, Elizabeth L

    2015-08-01

    The National Heart, Lung, and Blood Institute (NHLBI), within the United States' National Institutes of Health (NIH), established a Biorepository in 1976 that initially archived biospecimens from population-based blood product safety surveys. It was later expanded to biospecimens from clinical and epidemiological studies in heart, lung, and blood disorders. The NHLBI also established a Data Repository in 2000 to store and distribute study data from NHLBI-sponsored research. The NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) was established in 2008 to develop the infrastructure needed to link the contents of these two related NHLBI Repositories, facilitate access to repository resources, and streamline request processes. Three key program subcomponents were developed simultaneously: 1) the linkage of biospecimen electronic inventory records with their clinical or characterization data; 2) the development and implementation of a website with both public-facing information and private processing workspaces; and 3) the development of processes to maximize efficiency via a web-based system while maintaining workflow control, document tracking, and secure processes. The BioLINCC website was launched on October 1, 2009 with eight biospecimen collections and data from 72 research studies. By the end of the fourth online year, 38 biospecimen collections were linked and posted, and data from 108 research studies had been made available for request. The number of registered users by the end of the fourth online year approached 2600, and continues to show a trend towards an increasing rate of new users per year. BioLINCC has fulfilled 381 requests comprising 851 data collections, as well as 600 teaching dataset requests and 75 data renewal agreements. 154 biospecimen requests comprising 147,388 biospecimens were fulfilled or actively in process. We conclude that the BioLINCC program has been successful in its goal to increase the

  11. NCI at Frederick Receives a Royal Visit | Poster

    Cancer.gov

    The Center for Cancer Research (CCR) and NCI at Frederick recently had the honor of hosting Professor Dr. Her Royal Highness Princess Chulabhorn Mahidol of Thailand. Her Royal Highness has a special interest in scientific research related to the use of natural products for treating disease. The purpose of her visit was to discuss the work on natural products being undertaken at NCI at Frederick. Her Royal Highness attended talks by researchers from both the Molecular Targets Laboratory (MTL), CCR, and the Natural Products Branch (NPB), Developmental Therapeutics Program (DTP), Division of Cancer Treatment and Diagnosis (DCTD).

  12. Robert Wiltrout Says Goodbye to NCI in 2015 | Poster

    Cancer.gov

    After 34 years at NCI, Robert Wiltrout, Ph.D., said he is looking forward to trading his I-270 commute for another type of commute: exploring the waterways of Maryland, Alaska, and Wyoming to fulfill his love of fishing. Wiltrout officially retired as director of the NCI Center for Cancer Research (CCR) on July 2 of last year. Throughout his college academic career, Wiltrout had an interest in science, but it was not until he was working on a research project for his master’s degree that he considered a career in scientific research.

  13. The NCI Digital Divide Pilot Projects: implications for cancer education.

    PubMed

    Kreps, Gary L; Gustafson, David; Salovey, Peter; Perocchia, Rosemarie Slevin; Wilbright, Wayne; Bright, Mary Anne; Muha, Cathy

    2007-01-01

    The National Cancer Institute (NCI) supported four innovative demonstration research projects, "The Digital Divide Pilot Projects," to test new strategies for disseminating health information via computer to vulnerable consumers. These projects involved active research collaborations between the NCI's Cancer Information Service (CIS) and regional cancer control researchers to field test new approaches for enhancing cancer communication in vulnerable communities. The projects were able to use computers to successfully disseminate relevant cancer information to vulnerable populations. These demonstration research projects suggested effective new strategies for using communication technologies to educate underserved populations about cancer prevention, control, and care.

  14. 78 FR 44136 - Submission for OMB review; 30-day Comment Request: National Cancer Institute (NCI) Cancer...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ... Cancer Institute (NCI) Cancer Nanotechnology Platform Partnership Scientific Progress Reports SUMMARY..., Center for Strategic Scientific Initiatives, Office of Cancer Nanotechnology Research, National Cancer... (NCI) Alliance for Nanotechnology in Cancer Platform Partnership Scientific Progress Reports,...

  15. 78 FR 27974 - Proposed Collection; 60-Day Comment Request: National Cancer Institute (NCI) Alliance for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-13

    ... Cancer Institute (NCI) Alliance for Nanotechnology in Cancer Platform Partnership Scientific Progress... for Strategic Scientific Initiatives, Office of Cancer Nanotechnology Research, National Cancer... this publication. Proposed Collection: National Cancer Institute (NCI) Alliance for Nanotechnology...

  16. 2013 NCI Alliance for Nanotechnology in Cancer Annual Bulletin

    Cancer.gov

    The NCI Alliance for Nanotechnology in Cancer Bulletin is a resource that serves to connect Alliance participants, partners, and affiliates by highlighting the innovative work of the Alliance members in their efforts to harness the power of nanotechnology to radically change the way we diagnose, treat, and prevent cancer.

  17. NCI Alliance for Nanotechnology in Cancer - Training Funding

    Cancer.gov

    The NCI Alliance for Nanotechnology in Cancer awards training grants to facilitate the training and education of the next generation of nanotechnology researchers. The grants also provide an opportunity for experienced researchers and established institutions to work together in sharing their knowledge to positively influence the future of nanotechnology.

  18. NCI Community Oncology Research Program (NCORP) | Division of Cancer Prevention

    Cancer.gov

    The NCI Community Oncology Research Program (NCORP) is a national network of cancer care investigators, providers, academia, and other organizations that care for diverse populations in health systems. View the list of publications from NCORP. | Clinical Trials network of cancer care professionals who care for diverse populations across the U.S.

  19. Creating Start-up Companies around NCI Inventions | Poster

    Cancer.gov

    By Karen Surabian, Thomas Stackhouse, and Rose Freel, Contributing Writers, and Rosemarie Truman, Guest Writer The National Cancer Institute (NCI), led by the Technology Transfer Center (TTC),  the Avon Foundation, and The Center for Advancing Innovation have partnered to create a “first-of-a-kind” Breast Cancer Start-up Challenge.

  20. Information for Our Partners | NCI Technology Transfer Center | TTC

    Cancer.gov

    CRADA PAYMENT OPTIONS: Electronic Payments by Wire Transfer via Fedwire, Mail a check to the Institute or Center, or Automated Clearing House (ACH)/Electronic Funds Transfer (ETF) payments via Pay.gov (NCI ONLY). | [google6f4cd5334ac394ab.html

  1. Apply for Cancer Control Grants | DCCPS/NCI/NIH

    Cancer.gov

    The Division of Cancer Control and Population Sciences funds a large portfolio of grants and contracts. The portfolio currently includes approximately 800 grants valued at nearly $450 million. Here we provide a listing of funding opportunities that are currently accepting applications. Please visit this page regularly as new funding opportunities are added upon approval by NCI.

  2. Russian delegation visits NIH and NCI to discuss research collaboration

    Cancer.gov

    The NCI Center for Global Health hosted a delegation from the Russian Foundation for Basic Research to discuss ongoing and future collaborations in cancer research. The delegation was accompanied by representatives from the US Embassy in Moscow and the Embassy of the Russian Federation in Washington DC.

  3. Cancer vaccines: the perspective of the Cancer Immunology Branch, NCI.

    PubMed

    Sogn, J A; Finerty, J F; Heath, A K; Shen, G L; Austin, F C

    1993-08-12

    The Cancer Immunology Branch, NCI, is supporting a great deal of exciting research relevant to cancer vaccine development. The few areas highlighted here are representative of ongoing research opportunities, but further progress depends largely on a continued infusion of investigator-initiated ideas to realize the potential of current research areas and open new ones.

  4. NCI intramural research highlighted at 2014 AACR meeting

    Cancer.gov

    This year’s American Association for Cancer Research meeting featured plenary talks by two NCI scientists, Steven Rosenberg, M.D., and Louis Staudt, M.D., Ph.D., that highlighted the challenges in developing varied and potentially synergistic treatments f

  5. Novel Method Of Preparing Vaccines | NCI Technology Transfer Center | TTC

    Cancer.gov

    This invention from the NCI Cancer and Inflammation Program describes methods to prepare vaccines for the treatment of human immunodeficiency virus (HIV) infections. The National Cancer Institute's Cancer and Inflammation Program seeks parties interested in licensing or collaborative research to further develop, evaluate, or commercialize novel methods of preparing vaccines.

  6. Summary of the NICHD-BPCA Pediatric Formulation Initiatives Workshop-Pediatric Biopharmaceutics Classification System (PBCS) Working Group

    PubMed Central

    Abdel-Rahman, Susan; Amidon, Gordon L.; Kaul, Ajay; Lukacova, Viera; Vinks, Alexander A.; Knipp, Gregory

    2012-01-01

    The Biopharmaceutics Classification System (BCS) allows compounds to be classified based on their in vitro solubility and intestinal permeability. The BCS has found widespread use in the pharmaceutical community as an enabling guide for the rational selection of compounds, formulation for clinical advancement and generic biowaivers. The Pediatric Biopharmaceutics Classification System (PBCS) working group was convened to consider the possibility of developing an analogous pediatric based classification system. Since there are distinct developmental differences that can alter intestinal contents, volumes, permeability and potentially biorelevant solubilities at the different ages, the PBCS working group focused on identifying age specific issues that would need to be considered in establishing a flexible, yet rigorous PBCS. Objective To summarize the findings of the PBCS working group and provide insights into considerations required for the development of a pediatric based biopharmaceutics classification system. Methods Through several meetings conducted both at The Eunice Kennedy Shriver National Institute of Child Health, Human Development (NICHD)-US Pediatric Formulation Initiative (PFI) workshop (November 2011) and via teleconferences, the PBCS working group considered several high level questions that were raised to frame the classification system. In addition, the PBCS working group identified a number of knowledge gaps that would need to be addressed in order to develop a rigorous PBCS. Results It was determined that for a PBCS to be truly meaningful, it would need to be broken down into several different age groups that would account for developmental changes in intestinal permeability, luminal contents, and gastrointestinal transit. Several critical knowledge gaps where identified including: 1) a lack of fully understanding the ontogeny of drug metabolizing enzymes and transporters along the gastrointestinal (GI) tract, in the liver and in the kidney; 2

  7. NCI Updates Tobacco Policies Following Re-accreditation | Poster

    Cancer.gov

    This year, NCI was re-accredited as one of nearly 200 CEO Cancer Gold Standard employers across the United States. According to its website, “the CEO Cancer Gold Standard provides a framework for employers to have a healthier workplace by focusing on cancer risk reduction, early detection, and access to clinical trials and high-quality care.” As part of this re-accreditation, NCI has updated its Tobacco-Free Policy. Part of this policy includes posting signs around campus reminding visitors and staff that NCI’s campus is tobacco-free. Therefore, the use of all tobacco products is prohibited. This includes cigarettes, cigars, pipes, e-cigarettes, and smokeless tobacco.

  8. Regular paths in SparQL: querying the NCI Thesaurus.

    PubMed

    Detwiler, Landon T; Suciu, Dan; Brinkley, James F

    2008-11-06

    OWL, the Web Ontology Language, provides syntax and semantics for representing knowledge for the semantic web. Many of the constructs of OWL have a basis in the field of description logics. While the formal underpinnings of description logics have lead to a highly computable language, it has come at a cognitive cost. OWL ontologies are often unintuitive to readers lacking a strong logic background. In this work we describe GLEEN, a regular path expression library, which extends the RDF query language SparQL to support complex path expressions over OWL and other RDF-based ontologies. We illustrate the utility of GLEEN by showing how it can be used in a query-based approach to defining simpler, more intuitive views of OWL ontologies. In particular we show how relatively simple GLEEN-enhanced SparQL queries can create views of the OWL version of the NCI Thesaurus that match the views generated by the web-based NCI browser.

  9. Like a Good Neighbor, NCI-Frederick Is There | Poster

    Cancer.gov

    The main campus of the National Cancer Institute at Frederick is an island of sorts: 68 acres of land that was once part of Fort Detrick. Accessing NCI property means passing through the Fort Detrick gates and crossing the post. While the campus is surrounded by the military installation, is protected by NIH police, and doesn’t allow the use of tobacco products, it is not a part of the military.

  10. NCI Alliance for Nanotechnology in Cancer - Tutorials and Seminar Series

    Cancer.gov

    View details about tutorials and seminars hosted by Alliance members and members of the cancer research community. These events provide a forum for sharing innovative perspectives on research and development efforts in the field of nanotechnology and their application to cancer diagnosis, treatment, and prevention. Also visit the Event Listing section to find scientific meetings and events where NCI Alliance for Nanotechnology in Cancer leaders and members are participating.

  11. Susan Koogle Marks 40+ Years at NCI at Frederick | Poster

    Cancer.gov

    By Nancy Parrish, Staff Writer In 1973, Susan Koogle commuted from Washington County to a small data processing company in Arlington, Va. When gas prices spiked from 25 to 54 cents a gallon, she began to look for a job closer to home. That’s when she came to work at NCI at Frederick, and in December 2013, she marked her 40th year with the facility.

  12. NCI at Frederick Scientific Library Reintroduces Scientific Publications Database | Poster

    Cancer.gov

    A 20-year-old database of scientific publications by NCI at Frederick, FNLCR, and affiliated employees has gotten a significant facelift. Maintained by the Scientific Library, the redesigned database—which is linked from each of the Scientific Library’s web pages—offers features that were not available in previous versions, such as additional search limits and non-traditional metrics for scholarly and scientific publishing known as altmetrics.

  13. NCI investment in nanotechnology: achievements and challenges for the future.

    PubMed

    Dickherber, Anthony; Morris, Stephanie A; Grodzinski, Piotr

    2015-01-01

    Nanotechnology offers an exceptional and unique opportunity for developing a new generation of tools addressing persistent challenges to progress in cancer research and clinical care. The National Cancer Institute (NCI) recognizes this potential, which is why it invests roughly $150 M per year in nanobiotechnology training, research and development. By exploiting the various capacities of nanomaterials, the range of nanoscale vectors and probes potentially available suggests much is possible for precisely investigating, manipulating, and targeting the mechanisms of cancer across the full spectrum of research and clinical care. NCI has played a key role among federal R&D agencies in recognizing early the value of nanobiotechnology in medicine and committing to its development as well as providing training support for new investigators in the field. These investments have allowed many in the research community to pursue breakthrough capabilities that have already yielded broad benefits. Presented here is an overview of how NCI has made these investments with some consideration of how it will continue to work with this research community to pursue paradigm-changing innovations that offer relief from the burdens of cancer.

  14. Collaboration Opportunities with the Cancer Human Biobank (caHUB) at NCI | NCI Technology Transfer Center | TTC

    Cancer.gov

    The Biorepositories and Biospecimen Research Branch (BBRB) at the National Cancer Institute has developed the Cancer Human Biobank (caHUB), which is a unique infrastructure for collecting biospecimens for the purpose of conducting biospecimen research. Biospecimens from the BPV program will be made available to collaborators with the capability to perform molecular analysis as part of a collaborative research agreement with the NCI-BBRB.

  15. Double jeopardy: poorer social-emotional outcomes for children in the NICHD SECCYD experiencing home and child-care environments that confer risk.

    PubMed

    Watamura, Sarah Enos; Phillips, Deborah A; Morrissey, Taryn W; McCartney, Kathleen; Bub, Kristen

    2011-01-01

    Using data from the National Institute of Child Health and Human Development Early Child Care Research Network (NICHD SECCYD), the authors examined whether interactions between home and child-care quality affect children's social-emotional adjustment at 24, 36, and 54 months (N = 771). Triadic splits on quality of home and child care were used to examine children in specific ecological niches, with a focus on those who experience the double jeopardy of poor quality home and child-care environments. Children in this niche exhibited the highest levels of mother-reported problem behavior and the lowest levels of prosocial behavior. However, there was evidence that children from lower quality home environments were able to benefit from the compensatory influence of high-quality child care. These results suggest policies aimed at the cross-context influences of protective and risky settings.

  16. NCI Scientists Awarded National Medal of Technology and Innovation by President Obama | Poster

    Cancer.gov

    Two NCI scientists received the National Medal of Technology and Innovation, the nation’s highest honor for technological achievement. The award was announced by President Obama in October. The honorees, John Schiller, Ph.D., Laboratory of Cellular Oncology (LCO), Center for Cancer Research, NCI, and Douglas Lowy, M.D., also from LCO and NCI deputy director, received their medals at a White House ceremony on Nov. 20.

  17. Vaccines for HIV | NCI Technology Transfer Center | TTC

    Cancer.gov

    The development of an effective HIV vaccine has been an ongoing area of research. The high variability in HIV-1 virus strains has represented a major challenge in successful development. Ideally, an effective candidate vaccine would provide protection against the majority of clades of HIV. Two major hurdles to overcome are immunodominance and sequence diversity. This vaccine utilizes a strategy for overcoming these two issues by identifying the conserved regions of the virus and exploiting them for use in a targeted therapy. NCI seeks licensees and/or research collaborators to commercialize this technology, which has been validated in macaque models.

  18. Before You Collaborate, You Should Partner with NCI TTC | Poster

    Cancer.gov

    By Karen Surabian, Thomas Stackhouse, and Jeffrey W. Thomas, Contributing Writers As the fall and winter seasons progress, you may be attending more scientific conferences, where you may find a number of opportunities for research collaborations. To assist your lab in reaching its research goals through collaborations, the staff of the National Cancer Institute Technology Transfer Center (NCI TTC) can guide you through a tool box of agreements you may need for protecting your intellectual property (IP) and effectively managing your collaboration. 

  19. NCI at Frederick Employees Sew for Cancer | Poster

    Cancer.gov

    By Carolynne Keenan, Contributing Writer The R&W Club Frederick hosted a sewing party on Feb. 18 to give employees a chance to help sew pillowcases for children hospitalized for illnesses and cancer treatments. The nonprofit organization ConKerr Cancer provides the pillowcases to children across the country. Melissa Porter, administrative manager, Office of Scientific Operations, NCI at Frederick, and vice chair of the R&W Club Frederick, said the event went well. While the turnout was lower than expected, 27 pillowcases were completed, she said.

  20. New Phone System Coming to NCI Campus at Frederick | Poster

    Cancer.gov

    By Travis Fouche and Trent McKee, Guest Writers Beginning in September, phones at the NCI Campus at Frederick will begin to be replaced, as the project to upgrade the current phone system ramps up. Over the next 16 months, the Information Systems Program (ISP) will be working with Facilities Maintenance and Engineering and Computer & Statistical Services to replace the current Avaya phone system with a Cisco Unified Communications phone system. The Cisco system is already in use at the Advanced Technology Research Facility (ATRF).

  1. Guidelines for Large-Scale Sequence-Based Complex Trait Association Studies: Lessons Learned from the NHLBI Exome Sequencing Project.

    PubMed

    Auer, Paul L; Reiner, Alex P; Wang, Gao; Kang, Hyun Min; Abecasis, Goncalo R; Altshuler, David; Bamshad, Michael J; Nickerson, Deborah A; Tracy, Russell P; Rich, Stephen S; Leal, Suzanne M

    2016-10-06

    Massively parallel whole-genome sequencing (WGS) data have ushered in a new era in human genetics. These data are now being used to understand the role of rare variants in complex traits and to advance the goals of precision medicine. The technological and computing advances that have enabled us to generate WGS data on thousands of individuals have also outpaced our ability to perform analyses in scientifically and statistically rigorous and thoughtful ways. The past several years have witnessed the application of whole-exome sequencing (WES) to complex traits and diseases. From our analysis of NHLBI Exome Sequencing Project (ESP) data, not only have a number of important disease and complex trait association findings emerged, but our collective experience offers some valuable lessons for WGS initiatives. These include caveats associated with generating automated pipelines for quality control and analysis of rare variants; the importance of studying minority populations; sample size requirements and efficient study designs for identifying rare-variant associations; and the significance of incidental findings in population-based genetic research. With the ESP as an example, we offer guidance and a framework on how to conduct a large-scale association study in the era of WGS.

  2. Birth cohorts in asthma and allergic diseases: Report of a NIAID, NHLBI, MeDALL joint workshop

    PubMed Central

    Bousquet, J; Gern, JE; Martinez, FD; Anto, JM; Johnson, CC; Holt, PG; Lemanske, RF; Le Souef, PN; Tepper, R; von Mutius, ERM; Arshad, SH; Bacharier, LB; Becker, A; Belanger, K; Bergstrom, A; Bernstein, D; Cabana, MD; Carroll, KN; Castro, M; Cooper, PJ; Gillman, MW; Gold, DR; Henderson, J; Heinrich, J; S-J, Hong; Jackson, DJ; Keil, T; Kozyrskyj, AL; Lodrup-Carlsen, K; Miller, RL; Momas, I; Morgan, WJ; Noel, P; Ownby, DR; Pinart, M; Ryan, P; Schwaninger, JM; Sears, MR; Simpson, A; Smit, HA; Stern, D; Subbarao, P; Valenta, R; Wang, X; Weiss, ST; Wood, R; Wright, AL; Wright, RJ; Togias, A; Gergen, PJ

    2014-01-01

    Population-based birth cohorts on asthma and allergies increasingly provide new insights into the development and natural history of the diseases. Over 130 birth cohorts focusing on asthma and allergy have been initiated in the last 30 years. A NIAID (National Institute of Allergy and Infectious Diseases), NHLBI (National Heart Lung and Blood Institute), MeDALL (Mechanisms of the Development of Allergy, Framework Programme 7 of the European Commission) joint workshop was held in Bethesda, MD, USA September 11–12, 2012 with 3 objectives (1) documenting the knowledge that asthma/allergy birth cohorts have provided, (2) identifying the knowledge gaps and inconsistencies and (3) developing strategies for moving forward, including potential new study designs and the harmonization of existing asthma birth cohort data. The meeting was organized around the presentations of 5 distinct workgroups: (1) clinical phenotypes, (2) risk factors, (3) immune development of asthma and allergy, (4) pulmonary development and (5) harmonization of existing birth cohorts. This manuscript presents the workgroup reports and provides web links (AsthmaBirthCohorts.niaid.nih.gov or www.medall-fp7.eu) where the reader will find tables describing the characteristics of the birth cohorts included in this report, type of data collected at differing ages, and a selected bibliography provided by the participating birth cohorts. PMID:24636091

  3. Human Monoclonal Antibodies Targeting Glypican-2 in Neuroblastoma | NCI Technology Transfer Center | TTC

    Cancer.gov

    Researchers at the National Cancer Institute’s Laboratory of Molecular Biology (NCI LMB) have developed and isolated several single domain monoclonal human antibodies against GPC2. NCI seeks parties interested in licensing or co-developing GPC2 antibodies and/or conjugates.

  4. 75 FR 46945 - Proposed Collection; Comment Request; the Drug Accountability Record (Form NIH 2564) (NCI)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-04

    ... Accountability Record (Form NIH 2564) (NCI) SUMMARY: In compliance with the requirement of Section 3506(c)(2)(A... collection projects, the National Cancer Institute (NCI), the National Institutes of Health (NIH) will... (OMB) for review and approval. Proposed Collection Title: The Drug Accountability Record (Form NIH...

  5. 75 FR 4827 - Submission for OMB Review; Comment Request Clinical Trials Reporting Program (CTRP) Database (NCI)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-29

    ... Reporting Program (CTRP) Database (NCI) Summary: Under the provisions of Section 3507(a)(1)(D) of the Paperwork Reduction Act of 1995, the National Cancer Institute (NCI), the National Institutes of Health (NIH... cancer trials. On January 6, 2010, the same commenter sent a subsequent comment concerning corruption...

  6. 78 FR 2678 - Proposed Collection; Comment Request (60-Day FRN): The National Cancer Institute (NCI...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-14

    ... National Cancer Institute (NCI) SmokefreeTXT (Text Message) Program Evaluation (NCI) SUMMARY: In compliance... memorandum. This study seeks to assess the efficacy of the SmokefreeTXT program, a text message smoking... text- messaging service and a series of web-based surveys. All web-based survey data will be...

  7. 76 FR 14034 - Proposed Collection; Comment Request; NCI Cancer Genetics Services Directory Web-Based...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-15

    ... HUMAN SERVICES National Institutes of Health Proposed Collection; Comment Request; NCI Cancer Genetics... Management and Budget (OMB) for review and approval. Proposed Collection: Title: NCI Cancer Genetics Services... application form and the Web-based update mailer is to collect information about genetics professionals to...

  8. Rep. Delaney Learns about Breast Cancer Research at NCI at Frederick | Poster

    Cancer.gov

    By Andrea Frydl, Contributing Writer Rep. John Delaney (D-Md., 6th District) visited the NCI Campus at Frederick on October 21 to learn more about the research that scientists at NCI at Frederick are doing on breast cancer. October is Breast Cancer Awareness month.

  9. Chocolate Consumption is Inversely Associated with Calcified Atherosclerotic Plaque in the Coronary Arteries: The NHLBI Family Heart Study

    PubMed Central

    Djoussé, Luc; Hopkins, Paul N.; Arnett, Donna K.; Pankow, James S.; Borecki, Ingrid; North, Kari E.; Ellison, R. Curtis

    2010-01-01

    Background and Aims While a diet rich in anti-oxidant has been favorably associated with coronary disease and hypertension, limited data have evaluated the influence of such diet on subclinical disease. Thus, we sought to examine whether chocolate consumption is associated with calcified atherosclerotic plaque in the coronary arteries (CAC). Methods In a cross-sectional design, we studied 2,217 participants of the NHLBI Family Heart Study. Chocolate consumption was assessed by a semi-quantitative food-frequency questionnaire and CAC was measured by cardiac CT. We defined prevalent CAC using an Agatston score of at least 100 and fitted generalized estimating equations to calculate prevalence odds ratios of CAC. Results There was an inverse association between frequency of chocolate consumption and prevalent CAC. Odds ratios (95% CI) for CAC were 1.0 (reference), 0.94 (0.66-1.35), 0.78 (0.53-1.13), and 0.68 (0.48-0.97) for chocolate consumption of 0, 1-3 times per month, once per week, and 2+ times per week, respectively (p for trend 0.022), adjusting for age, sex, energy intake, waist-hip ratio, education, smoking, alcohol consumption, ratio of total-to-HDL-cholesterol, non-chocolate candy, and diabetes mellitus. Controlling for additional confounders did not alter the findings. Exclusion of subjects with coronary heart disease or diabetes mellitus did not materially change the odds ratio estimates but did modestly decrease the overall significance (p = 0.07). Conclusions These data suggest that chocolate consumption might be inversely associated with prevalent CAC. PMID:20655129

  10. Association of egg consumption and calcified atherosclerotic plaque in the coronary arteries: the NHLBI Family Heart Study

    PubMed Central

    Robbins, Jeremy M.; Petrone, Andrew B.; Ellison, R. Curtis; Hunt, Steven C.; Carr, J. Jeffrey; Heiss, Gerardo; Arnett, Donna K.; Gaziano, J. Michael; Djoussé, Luc

    2015-01-01

    Background and Aims Eggs are a ubiquitous and important source of dietary cholesterol and nutrients, yet their relationship to coronary heart disease (CHD) remains unclear. While some data have suggested a positive association between egg consumption and CHD, especially among diabetic subjects, limited data exist on the influence of egg consumption on subclinical disease. Thus, we sought to examine whether egg consumption is associated with calcified atherosclerotic plaques in the coronary arteries. Methods In a cross-sectional design, we studied 1848 participants of the NHLBI Family Heart Study without known CHD. Egg consumption was assessed by a semi-quantitative food frequency questionnaire and coronary-artery calcium (CAC) was measured by cardiac CT. We defined prevalent CAC using an Agatston score of at least 100 and fitted generalized estimating equations to calculate prevalence odds ratios of CAC. Results Mean age was 56.5 years and 41% were male. Median consumption of eggs was 1/week. There was no association between frequency of egg consumption and prevalent CAC. Odds ratios (95% CI) for CAC were 1.0 (reference), 0.95 (0.66-1.38), 0.94 (0.63-1.40), and 0.90 (0.57-1.42) for egg consumption of almost never, 1-3 times per month, once per week, and 2+ times per week, respectively (p for trend 0.66), adjusting for age, sex, BMI, smoking, alcohol, physical activity, income, field center, total calories, and bacon. Additional control for hypertension and diabetes mellitus, or restricting the analysis to subjects with diabetes mellitus or fasting glucose >126 mg/dL did not alter the findings. Conclusions These data do not provide evidence for an association between egg consumption and prevalent CAC in adult men and women. PMID:25642410

  11. Softball Games Bring NCI and Leidos Biomed Employees Together | Poster

    Cancer.gov

    NCI and Leidos Biomed employees took to the fields at Nallin Pond for the third annual slow-pitch softball games on August 26. The series attracted 54 employees who were divided into four teams, Red, Blue, Gray, and White, and they were cheered on by about 40 enthusiastic spectators. In the first set of games, the Gray team defeated the Blue team, 15–8, and the White team pulled out a win against the Red team, 17–15. After a brief rest, the two winning teams and the two losing teams faced each other in a second set of games. On Field 1, the “winners” match-up of the Gray and White teams was a nail biter, with a close score throughout the game. Daylight was a factor, however, and the team captains decided to call the game for safety reasons. With a lead of 15 to 13, the Gray team was declared the overall winner.

  12. P30 Cancer Center Support Grant Administrative Supplements to support NCI Approved Clinical Trial Proposals from NCI-designated Cancer Centers not affiliated with the NCI Experimental Therapeutics Clinical Trials Network (ETCTN) for Investigator-Initiated Trials Utilizing CTEP IND agents in the ETCTN

    Cancer.gov

    P30 Cancer Center Support Grant Administrative Supplements to support NCI Approved Clinical Trial Proposals from NCI-designated Cancer Centers not affiliated with the NCI Experimental Therapeutics Clinical Trials Network (ETCTN) for Investigator-Initiated Trials Utilizing CTEP IND agents in the ETCTN

  13. Risks and Outcomes Associated with Disorganized/Controlling Patterns of Attachment at Age Three in the NICHD Study of Early Child Care and Youth Development

    PubMed Central

    O’Connor, Erin; Bureau, Jean-Francois; McCartney, Kathleen; Lyons-Ruth, Karlen

    2011-01-01

    Disorganized/controlling attachment in preschool has been found to be associated with maternal and child maladjustment, making it of keen interest in the study of psychopathology. Additional work is needed, however, to better understand disorganized/controlling attachment occurring as early as age three. The primary aims of this study were to evaluate risk factors and outcomes associated with disorganized/controlling behavior at age three and to evaluate the risk factors and outcomes differentiating the four subtypes of disorganized/controlling attachment. Analyses were conducted with the first two phases of the NICHD Study of Early Child Care and Youth Development, a prospective study of 1,364 children from birth. At 36 months of age, across the attachment-relevant domains of maternal well-being, mother-child interactions, and child social adaptation, the disorganized/controlling group evidenced the most maladaptive patterns in comparison to both secure and insecure-organized groups. At 54 months of age, the disorganized/controlling group displayed the highest levels of internalizing and externalizing behavior problems, as rated by mothers and teachers, and the lowest quality relationships with teachers. Significant differences found among the disorganized/controlling subtypes indicated that the behaviorally disorganized and controlling-punitive subtypes had more maladaptive patterns across variables than did the controlling-caregiving and controlling-mixed subtypes. PMID:21799549

  14. NCI Takes Back the Defelice Cup at Ninth Annual Golf Tournament | Poster

    Cancer.gov

    By Ashley DeVine, Staff Writer After being down by a point in the morning, NCI reclaimed the Defelice Cup trophy from Leidos Biomedical Research, with a final score of 12 ½ to 11 ½, at the ninth annual Ronald H. Defelice Golf Tournament, held Oct. 13. “The tightest matches in the nine-year history of this cup competition resulted in a narrow victory for NCI and allowed NCI to take a 5–4 victory total,” said Denny Dougherty, one of the team captains for Leidos Biomed and a retired senior subcontracts advisor at what was formerly SAIC-Frederick.

  15. Experimental studies of the Universal Chemical Key (UCK) algorithm on the NCI database of chemical compounds.

    PubMed

    Grossman, Robert; Kasturi, Pavan; Hamelberg, Donald; Liu, Bing

    2003-01-01

    We have developed an algorithm called the Universal Chemical Key (UCK) algorithm that constructs a unique key for a molecular structure. The molecular structures are represented as undirected labeled graphs with the atoms representing the vertices of the graph and the bonds representing the edges. The algorithm was tested on 236,917 compounds obtained from the National Cancer Institute (NCI) database of chemical compounds. In this paper we present the algorithm,some examples and the experimental results on the NCI database. On the NCI database, the UCK algorithm provided distinct unique keys for chemicals with different molecular structures.

  16. NHLBI state of the science symposium in therapeutic apheresis: Knowledge gaps and research opportunities in the area of hematology-oncology.

    PubMed

    Karafin, Matthew S; Sachais, Bruce S; Connelly-Smith, Laura; Field, Joshua J; Linenberger, Michael L; Padmanabhan, Anand

    2016-02-01

    The National Heart Lung and Blood Institute (NHLBI) hosted a two-day state of the science symposium on therapeutic apheresis in Bethesda, MD on November 28th-29th, 2012. The purpose of the symposium was multifaceted, and included the following aims: (a) To discuss this state of research and key scientific questions in apheresis medicine; (b) To identify gaps in knowledge for relevant cardiovascular diseases, hematological and oncological diseases, infectious diseases and sepsis, renal diseases, and neurological diseases where there may be strong therapeutic rationale for the application of apheresis treatments; (c) To explore ways of coordinating therapeutic apheresis with other medical disciplines and treatment modalities; (d) To identify and prioritize the most important research questions to be answered in apheresis medicine; and (e) To offer NHLBI suggestions on how a structured research approach can be applied to the therapeutic apheresis research agenda in future years. The following document summarizes three such key proposals presented at the meeting for evaluating apheresis therapy for the treatment of pain in sickle cell disease, heparin induced thrombocytopenia, and leukostasis from acute myeloid leukemia. The challenges and limitations regarding apheresis therapy for each disease are discussed, and avenues for future investigation for each disease are outlined.

  17. National Medal of Technology Awarded to NCI Drs. Lowy and Schiller

    Cancer.gov

    President Obama announced that two NCI scientists would be recipients of the National Medal of Technology and Innovation -- the nation's highest honor for technological achievement. The honorees, John Schiller, Ph.D., Laboratory of Cellular Oncology (LCO)

  18. NCI Requests Targets for Monoclonal Antibody Production and Characterization - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution.

  19. 76 FR 66932 - The National Cancer Institute (NCI) Announces the Initiation of a Public Private Industry...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-28

    ... Initiation of a Public Private Industry Partnership on Translation of Nanotechnology in Cancer (TONIC) To Promote Translational Research and Development Opportunities of Nanotechnology-Based Cancer Solutions AGENCY: National Cancer Institute (NCI), Office of Cancer Nanotechnology Research (OCNR),...

  20. Craig Reynolds, Ph.D., to Retire as NCI Associate Director for Frederick | Poster

    Cancer.gov

    On December 2, Craig Reynolds, Ph.D., director, Office of Scientific Operations, and NCI associate director for Frederick, will put the finishing touches on a 37-year career with the National Cancer Institute.

  1. Ratio Based Biomarkers for the Prediction of Cancer Survival | NCI Technology Transfer Center | TTC

    Cancer.gov

    The NCI seeks licensees or co-development partners for this technology, which describes compositions, methods and kits for identifying, characterizing biomolecules expressed in a sample that are associated with the presence, the development, or progression of cancer.

  2. Gardasil® and Cervarix® | NCI Technology Transfer Center | TTC

    Cancer.gov

    Vaccine for human papilloma virus (HPV) to protect from cancers Key elements of the technology for Gardasil® and Cervarix originated from the HPV research of the laboratory of Drs. Douglas Lowy and John Schiller of the NCI.

  3. NCI Launches Proteomics Assay Portal - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    In a paper recently published by the journal Nature Methods, Investigators from the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (NCI-CPTAC) announced the launch of a proteomics Assay Portal for multiple reaction monitoring-mass

  4. NCI and the Chinese Academy of Medical Sciences Sign Statement of Intent

    Cancer.gov

    Today the National Cancer Institute (NCI) and the Cancer Institute/Hospital of the Chinese Academy of Medical Sciences (CICAMS) signed a statement of intent to share an interest in fostering collaborative biomedical research in oncology and a common goal

  5. Identification of a new restriction endonuclease R.NciII, from Neisseria cinerea.

    PubMed

    Piekarowicz, A

    1994-01-01

    Site-specific restriction endonuclease R. Nci II has been purified from Neisseria cinerea strain 32615. The enzyme recognizes the sequence 5' GATC 3' and its activity is inhibited by the presence of methylated adenine residue within the recognition sequence.

  6. NCI at Frederick Team Receives 2014 HHS Green Champions Award | Poster

    Cancer.gov

    A team of NCI and Leidos Biomedical Research employees at NCI at Frederick received the Energy and Fleet Management Award, one of the 2014 Department of Health and Human Services (HHS) Green Champions Awards, for comparing the costs and energy usage of two -80°C freezer technologies. This was the first scientific study to be jointly conducted by Leidos Biomedical Research’s Applied and Developmental Research Directorate (ADRD) and Facilities Maintenance and Engineering Directorate (FME).  

  7. The effect of jet and DBD plasma on NCI-78 blood cancer cells

    NASA Astrophysics Data System (ADS)

    Kaushik, Nagendra K.; Kaushik, Neha; Choi, Eun Ha

    2013-06-01

    In this study we describe the effects of a nonthermal jet and dielectric barrier discharge (DBD) plasma on the T98G brain cancer cell line. The results of this study reveal that the jet and DBD plasma inhibits NCI-78 blood cancer cells growth efficiently with the loss of metabolic viability of cells. The main goal of this study is to induce cell death in NCI-78 blood cancer cells by the toxic effect of jet and DBD plasma.

  8. Screening of Menkes Disease in Newborns that are likely to Benefit from Copper Treatment | NCI Technology Transfer Center | TTC

    Cancer.gov

    The Eunice Kennedy Shriver National Institute of Child Health and Human Development's (NICHD) Molecular Medicine Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, or evaluate on a large-scale, population-based newborn screening for Menkes disease (also known as kinky hair disease).

  9. Building a platform for translational research in chronic noncommunicable diseases to address population health: lessons from NHLBI supported CRONICAS in Peru.

    PubMed

    Miranda, J Jaime; Bernabé-Ortiz, Antonio; Diez-Canseco, Francisco; Málaga, Germán; Cardenas, María K; Carrillo-Larco, Rodrigo M; Pesantes, M Amalia; Araya, Ricardo; Boggio, Oscar; Checkley, William; García, Patricia J; León-Velarde, Fabiola; Lescano, Andrés G; Montori, Victor; Pan, William; Rivera-Chira, Maria; Sacksteder, Katherine; Smeeth, Liam; García, Héctor H; Gilman, Robert H

    2015-03-01

    The CRONICAS Centre of Excellence in Chronic Diseases, based at Universidad Peruana Cayetano Heredia, was created in 2009 with support from the U.S. National Heart, Lung, and Blood Institute (NHLBI). The vision of CRONICAS is to build a globally recognized center of excellence conducting quality and innovative research and generating high-impact evidence for health. The center's identity is embedded in its core values: generosity, innovation, integrity, and quality. This review has been structured to describe the development of the CRONICAS Centre, with a focus on highlighting the ongoing translational research projects and capacity-building strategies. The CRONICAS Centre of Excellence is not a risk-averse organization: it benefits from past experiences, including past mistakes, and improves upon them and thus challenges traditional research approaches. This ethos and environment are key to fostering innovation in research.

  10. Characterization of osimertinib (AZD9291)-resistant non-small cell lung cancer NCI-H1975/OSIR cell line.

    PubMed

    Tang, Zheng-Hai; Jiang, Xiao-Ming; Guo, Xia; Fong, Chi Man Vivienne; Chen, Xiuping; Lu, Jin-Jian

    2016-12-06

    Osimertinib (OSI, also known as AZD9291) is the newest FDA-approved epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor for non-small cell lung cancer (NSCLC) patients with EGFR T790M mutation. However, resistance to OSI is likely to progress and the study of potential OSI-resistant mechanisms in advanced is necessary. Here, the OSI-resistant NCI-H1975/OSIR cells were established. After cells developed resistance to OSI, cell proliferation was decreased while cell migration and invasion were increased. The NCI-H1975/OSIR cells exhibited more resistance to gefitinib, erlotinib, afatinib, rociletinib, doxorubicin, and fluorouracil, meanwhile showing higher sensitivity to paclitaxel, when compared with NCI-H1975 cells. In addition, the NCI-H1975/OSIR cells did not display multidrug resistance phenotype. The activation and expression of EGFR were decreased after cells exhibited resistance. Compared with NCI-H1975 cells, the activation of ERK and AKT in NCI-H1975/OSIR cells could not be significantly inhibited by OSI treatment. Navitoclax (ABT-263)-induced cell viability inhibition and apoptosis were more significant in NCI-H1975/OSIR cells than that in NCI-H1975 cells. Moreover, these effects of navitoclax in NCI-H1975/OSIR cells could be reversed by pretreatment of Z-VAD-FMK. Collectively, loss of EGFR could pose as one of the OSI-resistant mechanisms and navitoclax might be the candidate drug for OSI-resistant NSCLC patients.

  11. NIH and NCI grant-related changes during fiscal years 2014 and 2015

    NASA Astrophysics Data System (ADS)

    Wong, Rosemary S. L.

    2015-03-01

    The 2014 fiscal year (FY) continued to be a challenging one for all federal agencies despite the many Congressional strategies proposed to address the U.S. budget deficit. The Bipartisan Budget Act of 2013 passed by the House and Senate in December 2013 approved a two-year spending bill which cancelled the FY2014 and FY2015 required sequestration cuts (i.e., 4-5% National Institute of Health (NIH)/National Cancer Institute (NCI) budget reduction initiated on March 1, 2013), but extended the sequestration period through FY2023. This bill passage helped minimize any further budget reductions and resulted in a final FY2014 NIH budget of 29.9 billion and a NCI budget of 4.9 billion. Both NIH and NCI worked hard to maintain awarding the same number of NIH/NCI investigator-initiated R01 and exploratory R21 grants funded in FY2014 and similar to the level seen in FY2013 and previous years (see Tables 1 and 2). Since Congress only recently passed the 2015 spending bill in December 16, 2014, the final NIH and NCI budget appropriations for FY2015 remains unknown at this time and most likely will be similar to the FY2014 budget level. The NCI overall success and funding rates for unsolicited investigator-initiated R01 applications remained at 15%, while the success rate for exploratory R21 applications was 12% in FY2014 with similar rates seen in FY2013 (see Tables 1 and 2). The success rate for biomedical research applications in the Photodynamic Therapy and laser research field will be provided for the past few years. NIH provides numerous resources to help inform the extramural biomedical research community of new and current grant applicants about new grant policy changes and the grant submission and review processes.

  12. EHS and FME Lend Their Expertise to NCI Campus Refurbishment Project | Poster

    Cancer.gov

    In October 2015, the NCI executive officer and the director of NCI’s Office of Space and Facilities Management (OSFM) announced a wide-ranging refurbishment plan for NCI at Frederick. Since then, a project team comprising members from the Office of Scientific Operations, the Management Operations Support Branch, OSFM, the Center for Cancer Research, the Environment, Health, and Safety (EHS) directorate, and the Facilities Maintenance and Engineering (FME) directorate have met regularly with the laboratory groups affected by the refurbishment plan. Read more...

  13. Connecting Genomic Alterations to Cancer Biology with Proteomics: The NCI Clinical Proteomic Tumor Analysis Consortium

    SciTech Connect

    Ellis, Matthew; Gillette, Michael; Carr, Steven A.; Paulovich, Amanda G.; Smith, Richard D.; Rodland, Karin D.; Townsend, Reid; Kinsinger, Christopher; Mesri, Mehdi; Rodriguez, Henry; Liebler, Daniel

    2013-10-03

    The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium is applying the latest generation of proteomic technologies to genomically annotated tumors from The Cancer Genome Atlas (TCGA) program, a joint initiative of the NCI and the National Human Genome Research Institute. By providing a fully integrated accounting of DNA, RNA, and protein abnormalities in individual tumors, these datasets will illuminate the complex relationship between genomic abnormalities and cancer phenotypes, thus producing biologic insights as well as a wave of novel candidate biomarkers and therapeutic targets amenable to verifi cation using targeted mass spectrometry methods.

  14. Diagnostic Marker for Improving Treatment Outcomes of Hepatitis C | NCI Technology Transfer Center | TTC

    Cancer.gov

    NCI Researchers have discovered Interferon-lambda 4 (IFNL4), a protein found through analysis of genomic data. Preliminary studies indicate that this protein may play a role in the clearance of HCV and may be a new target for diagnosing and treating HCV infection. The National Cancer Institute (NCI) Division of Cancer Epidemiology and Genetics (DCEG) Immunoepidemiology Branch is seeking statements of capability or interest from parties interested in in-licensing or collaborative research to further co-develop a gene-based diagnostic for Hepatitis C virus (HepC, HCV).

  15. 76 FR 28439 - Submission for OMB Review; Comment Request; NCI Cancer Genetics Services Directory Web-Based...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-17

    ... Genetics Services Directory Web-Based Application Form and Update Mailer Summary: Under the provisions of... Collection: Title: NCI Cancer Genetics Services Directory Web-based Application Form and Update Mailer. Type... collect information about genetics professionals to be included in the NCI Cancer Genetics...

  16. NCI's Physician Data Query (PDQ®) cancer information summaries: history, editorial processes, influence, and reach.

    PubMed

    Manrow, Richard E; Beckwith, Margaret; Johnson, Lenora E

    2014-03-01

    In the National Cancer Act of 1971, the Director of the National Cancer Institute (NCI) was given a mandate to "Collect, analyze, and disseminate all data useful in the prevention, diagnosis, and treatment of cancer, including the establishment of an International Cancer Research Data Bank (ICRDB) to collect, catalog, store, and disseminate insofar as feasible the results of cancer research undertaken in any country for the use of any person involved in cancer research in any country" (National Cancer Act of 1971, S 1828, 92nd Congress, 1st Sess (1971)). In subsequent legislation, the audience for NCI's information dissemination activities was expanded to include physicians and other healthcare professionals, patients and their families, and the general public, in addition to cancer researchers. The Institute's response to these legislative requirements was to create what is now known as the Physician Data Query (PDQ®) cancer information database. From its beginnings in 1977 as a database of NCI-sponsored cancer clinical trials, PDQ has grown to include extensive information about cancer treatment, screening, prevention, supportive and palliative care, genetics, drugs, and more. Herein, we describe the history, editorial processes, influence, and global reach of one component of the PDQ database, namely its evidence-based cancer information summaries for health professionals. These summaries are widely recognized as important cancer information and education resources, and they further serve as foundational documents for the development of other cancer information products by NCI and other organizations.

  17. Reducing Friction: An Update on the NCIP Open Development Initiative - NCI BioMedical Informatics Blog

    Cancer.gov

    NCIP has migrated 132 repositories from the NCI subversion repository to our public NCIP GitHub channel with the goal of facilitating third party contributions to the existing code base. Within the GitHub environment, we are advocating use of the GitHub “fork and pull” model.

  18. Treatment of Prostate Cancer using Anti-androgen Small Molecules | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute seeks parties interested in collaborative research to co-develop and commercialize a new class of small molecules for the treatment of prostate cancer. General information on co-development research collaborations, can be found on our web site (http://ttc.nci.nih.gov/forms).

  19. HIV Conference to Be Held on October 21 at NCI at Frederick | Poster

    Cancer.gov

    By Anne Arthur, Guest Writer The HIV Drug Resistance Program Conference on “Virus Structure: Putting the Pieces Together” will be held at NCI at Frederick on October 21, 2014, from 1:00 to 5:45 p.m. in the Conference Center auditorium, Building 549.

  20. (Update) HIV Conference to Be Held on February 25 at NCI at Frederick | Poster

    Cancer.gov

    By Anne Arthur, Guest Writer The HIV Drug Resistance Program (HIV DRP), Center for Cancer Research (CCR), will hold a conference on “Host Factors and Cofactors in HIV Infection” at the National Cancer Institute (NCI) campus in Frederick, Md., on Feb. 25, from 1:00 to 5:35 p.m.

  1. NCI at Frederick Employees Receive Awards at the Spring Research Festival | Poster

    Cancer.gov

    NCI and Frederick National Laboratory staff members were among those honored at the Spring Research Festival Awards Ceremony on May 28. The ceremony was the culmination of the festival, which was sponsored by the National Interagency Confederation for Biological Research (NICBR), May 4–7. Maj. Gen. Brian Lein, commanding general, U.S. Army Medical Research and Materiel Command (USAMRMC), presented the awards.

  2. NCI and the Chinese National Cancer Center pursue new collaborations in cancer research

    Cancer.gov

    CGH Director, Dr. Ted Trimble, and East Asia Program Director, Dr. Ann Chao, traveled to Beijing with Mr. Matthew Brown from the Department of Health and Human Services Office of Global Affairs to attend the Joint Meeting of the NCC and the U.S. NCI.

  3. Caveolin-1 knockdown is associated with the metastasis and proliferation of human lung cancer cell line NCI-H460.

    PubMed

    Song, Yang; Xue, Liyan; Du, Sha; Sun, Mingzhong; Hu, Jun; Hao, Lihong; Gong, Linlin; Yeh, Dongmei; Xiong, Hai; Shao, Shujuan

    2012-09-01

    Caveolin-1 (CAV-1), one component of caveolae, involves in multiple cellular processes and signal transductions. We previously showed that the expression of CAV-1 gene in NCI-H446 cells inhibited cell proliferation and promoted cell metastasis. Here we explore the function of CAV-1 on tumor growth and metastasis by using NCI-H460 in vitro. First, we established NCI-H460 cell line, which CAV-1 was stably knockdown. Then we investigated the effects of CAV-1 on the morphology, proliferation, cell cycle and metastasis potential for NCI-H460 cell by crystal violet stains, CCK-8, colony formation, flow cytometry, scratch-wound assay and transwell assay. Western blot was used to examine the expression changes of cyclin D1, PCNA, E-cadherin and β-catenin. Our results showed stable knockdown of CAV-1 inhibited the proliferation of NCI-H460 cells. Cell cycle of the transfected cells was arrested in G1/S phase and the expressions of cyclin D1 and PCNA protein were downregulated. Downregulation of CAV-1 promoted the migration and invasion abilities of NCI-H460 cells in vitro. The expression of β-catenin increased and the level of E-cadherin decreased. In summary, our findings provide experimental evidence that CAV-1 may function as a proproliferative and antimetastatic gene in NCI-H460 cell line.

  4. Accelerating Scientific Advancement for Pediatric Rare Lung Disease Research. Report from a National Institutes of Health-NHLBI Workshop, September 3 and 4, 2015.

    PubMed

    Young, Lisa R; Trapnell, Bruce C; Mandl, Kenneth D; Swarr, Daniel T; Wambach, Jennifer A; Blaisdell, Carol J

    2016-12-01

    Pediatric rare lung disease (PRLD) is a term that refers to a heterogeneous group of rare disorders in children. In recent years, this field has experienced significant progress marked by scientific discoveries, multicenter and interdisciplinary collaborations, and efforts of patient advocates. Although genetic mechanisms underlie many PRLDs, pathogenesis remains uncertain for many of these disorders. Furthermore, epidemiology and natural history are insufficiently defined, and therapies are limited. To develop strategies to accelerate scientific advancement for PRLD research, the NHLBI of the National Institutes of Health convened a strategic planning workshop on September 3 and 4, 2015. The workshop brought together a group of scientific experts, intramural and extramural investigators, and advocacy groups with the following objectives: (1) to discuss the current state of PRLD research; (2) to identify scientific gaps and barriers to increasing research and improving outcomes for PRLDs; (3) to identify technologies, tools, and reagents that could be leveraged to accelerate advancement of research in this field; and (4) to develop priorities for research aimed at improving patient outcomes and quality of life. This report summarizes the workshop discussion and provides specific recommendations to guide future research in PRLD.

  5. Training and Capacity Building in LMICs for Research in Heart and Lung Diseases: The NHLBI-UnitedHealth Global Health Centers of Excellence Program

    PubMed Central

    Bloomfield, Gerald S.; Xavier, Denis; Belis, Deshirée; Alam, Dewan; Davis, Patricia; Dorairaj, Prabhakaran; Ghannem, Hassen; Gilman, Robert H.; Kamath, Deepak; Kimaiyo, Sylvester; Levitt, Naomi; Martinez, Homero; Mejicano, Gabriela; Miranda, J. Jaime; Koehlmoos, Tracey Perez; Rabadán-Diehl, Cristina; Ramirez-Zea, Manuel; Rubinstein, Adolfo; Sacksteder, Katherine A.; Steyn, Krisela; Tandon, Nikhil; Vedanthan, Rajesh; Wolbach, Tracy; Wu, Yangfeng; Yan, Lijing L.

    2016-01-01

    Stemming the tide of noncommunicable diseases (NCDs) worldwide requires a multi-pronged approach. Although much attention has been paid to disease control measures, there is relatively little consideration of the importance of training the next generation of health-related researchers to play their important role in this global epidemic. The lack of support for early stage investigators in low- and middle-income countries interested in the global NCD field has resulted in inadequate funding opportunities for research, insufficient training in advanced research methodology and data analysis, lack of mentorship in manuscript and grant writing and meager institutional support for developing, submitting and administering research applications and awards. To address this unmet need, the NHLBI-UnitedHealth Collaborating Centers of Excellence initiative created a Training Subcommittee that coordinated and developed an intensive, mentored health-related research experience for a number of early stage investigators from the 11 Centers of Excellence around the world. We describe the challenges faced by early stage investigators in low- and middle-income countries, the organization and scope of the Training Subcommittee, training activities, early outcomes of the early stage investigators (foreign and domestic) and training materials that have been developed by this program that are available to the public. By investing in the careers of individuals in a supportive global NCD network, we demonstrate the impact that an investment in training individuals from low- and middle-income countries can have on the preferred future of or current efforts to combat NCDs. PMID:27102019

  6. Common and rare von Willebrand factor (VWF) coding variants, VWF levels, and factor VIII levels in African Americans: the NHLBI Exome Sequencing Project.

    PubMed

    Johnsen, Jill M; Auer, Paul L; Morrison, Alanna C; Jiao, Shuo; Wei, Peng; Haessler, Jeffrey; Fox, Keolu; McGee, Sean R; Smith, Joshua D; Carlson, Christopher S; Smith, Nicholas; Boerwinkle, Eric; Kooperberg, Charles; Nickerson, Deborah A; Rich, Stephen S; Green, David; Peters, Ulrike; Cushman, Mary; Reiner, Alex P

    2013-07-25

    Several rare European von Willebrand disease missense variants of VWF (including p.Arg2185Gln and p.His817Gln) were recently reported to be common in apparently healthy African Americans (AAs). Using data from the NHLBI Exome Sequencing Project, we assessed the association of these and other VWF coding variants with von Willebrand factor (VWF) and factor VIII (FVIII) levels in 4468 AAs. Of 30 nonsynonymous VWF variants, 6 were significantly and independently associated (P < .001) with levels of VWF and/or FVIII. Each additional copy of the common VWF variants encoding p.Thr789Ala or p.Asp1472His was associated with 6 to 8 IU/dL higher VWF levels. The VWF variant encoding p.Arg2185Gln was associated with 7 to 13 IU/dL lower VWF and FVIII levels. The type 2N-related VWF variant encoding p.His817Gln was associated with 17 IU/dL lower FVIII level but normal VWF level. A novel, rare missense VWF variant that predicts disruption of an O-glycosylation site (p.Ser1486Leu) and a rare variant encoding p.Arg2287Trp were each associated with 30 to 40 IU/dL lower VWF level (P < .001). In summary, several common and rare VWF missense variants contribute to phenotypic differences in VWF and FVIII among AAs.

  7. NCI QuitPal, an App from the National Cancer Institute | NIH MedlinePlus the Magazine

    MedlinePlus

    ... turn Javascript on. NCI QuitPal, an App from the National Cancer Institute Past Issues / Winter 2013 Table ... Institutes of Health National Cancer Institute What if the tools you need to quit smoking were as ...

  8. Jean C. Zenklusen, M.S., Ph.D., Discusses the NCI Genomics Data Commons at AACR 2014 - TCGA

    Cancer.gov

    At the AACR 2014 meeting, Dr. Jean C. Zenklusen, Director of The Cancer Genome Atlas Program Office, highlights the Genomics Data Commons, a harmonized data repository that will allow simultaneous access and analysis of NCI genomics data, including The Ca

  9. CGH and OCC Announce a New, Two-Year Funding Opportunity for NCI-designated Cancer Centers

    Cancer.gov

    CGH and OCC announce a new funding opportunity available from CGH for cancer prevention and control (CPC) researchers at NCI-designated cancer centers: Administrative Supplements to Promote Cancer Prevention and Control Research in Low and Middle Income Countries.

  10. Molecular mechanism of antiproliferation potential of Acacia honey on NCI-H460 cell line.

    PubMed

    Aliyu, Muhammad; Odunola, Oyeronke A; Farooq, Ahsana D; Rasheed, Huma; Mesaik, Ahmed M; Choudhary, Muhammad I; Channa, Iffat S; Khan, Salman A; Erukainure, Ochuko L

    2013-01-01

    Lung cancer is one of the leading causes of death worldwide. We investigated the molecular mechanism of antiproliferation potential of Acacia honey on NCI-H460 cells by cell cycle, viability, cytokines, calcium ion and gene expression analysis. Acacia honey inhibited cells proliferation, arrested G0/G1 phase, stimulated cytokines, calcium ion release as well as suppressed p53 and Bcl-2 expression in a dose-dependent manner. We proposed that the molecular mechanism of the antiproliferation potential of Acacia honey on NCI-H460 cell line is due to cell cycle arrest, stimulation of cytokines and calcium ion as well as downregulation of Bcl-2 and p53 genes.

  11. 2007 EORTC-NCI-ASCO annual meeting: molecular markers in cancer.

    PubMed

    Lukan, C

    2008-01-01

    The recent EORTC-NCI-ASCO Annual Meeting on 'Molecular Markers in Cancer' was held on 15-17 November 2007 in Brussels, Belgium. It was the largest meeting to date and marked the first year in which the American Association of Clinical Oncology (ASCO) joined in the efforts of the European Organisation for Research and Treatment of Cancer (EORTC) and the National Cancer Institute (NCI) in organizing this annual event. More than 300 clinicians, pathologists, laboratory scientists and representatives from regulatory agencies and the pharmaceutical industry came together for three days of intense discussion, debate and reflection on the latest biomarker therapeutic discoveries, strategies and clinical applications. The poster discussion sessions featured 79 research abstracts. The three most outstanding abstracts, all authored by young female researchers, were selected for presentation during the main meeting sessions. Highlights of each scientific session are presented.

  12. Puerto Rico NCI Community Oncology Research Program Minority/Underserved | Division of Cancer Prevention

    Cancer.gov

    DESCRIPTION (provided by applicant): The Puerto Rico NCI Community Oncology Research Program (PRNCORP) will be the principal organization in the island that promotes cancer prevention, control and screening/post-treatment surveillance clinical trials. It will conduct cancer care delivery research and will provide access to treatment and imaging clinical trials conducted under the reorganization of the National Clinical Trials Network (NCTN). It will evaluate disparity issues and outcomes in cancer care delivery and treatments. |

  13. Analysis of Maryland Cancer Patient Participation in NCI Supported Cancer Treatment Clinical Trials

    PubMed Central

    Baquet, Claudia R.; Ellison, Gary L.; Mishra, Shiraz I.

    2013-01-01

    Purpose We examined the relationship of sociodemographic factors, urban/rural residence, and countylevel socioeconomic factors on accrual of Maryland patients with cancer to National Cancer Institute (NCI)-sponsored cancer treatment clinical trials. Patients and Methods Data were analyzed for the period 1999 to 2002 for 2,240 Maryland patients with cancer accrued onto NCI-sponsored treatment trials. The extent to which Maryland patients with cancer and patients residing in lower socioeconomic and/or rural areas were accrued to cancer trials and were representative of all patients with cancer in Maryland was determined. Data were obtained from several sources, including NCI’s Cancer Therapy Evaluation Program for Maryland patients with cancer in Cooperative Group therapeutic trials, Maryland Cancer Registry data on cancer incidence, and United States Census and the Department of Agriculture. Results For Maryland patients with cancer accrued onto NCI-sponsored treatment trials between 1999 and 2002, subgroups accrued at a higher rate included pediatric and adolescent age groups, white patients, female patients (for sex-specific tumors), patients with private health insurance, and patients residing in the Maryland National Capitol region. Moreover, between 1999 and 2002, there was an estimated annual decline (8.9% per year; P < .05) in the percentage of black patients accrued onto cancer treatment trials. Logistic regression models uncovered different patterns of accrual for female patients and male patients on county-level socioeconomic factors. Conclusion Results highlight disparities in the accrual of Maryland patients with cancer onto NCI-sponsored treatment trials based on patient age, race/ethnicity, geography of residence, and county-level socioeconomic factors. Findings provide the basis for development of innovative tailored and targeted educational efforts to improve trial accrual, particularly for the underserved. PMID:18612153

  14. Analysis of Maryland Cancer Patient Participation in NCI Supported Cancer Treatment Clinical Trials

    PubMed Central

    Baquet, Claudia R.; Ellison, Gary L.; Mishra, Shiraz I.

    2013-01-01

    Purpose We examined the relationship of sociodemographic factors, urban/rural residence, and countylevel socioeconomic factors on accrual of Maryland patients with cancer to National Cancer Institute (NCI)-sponsored cancer treatment clinical trials. Patients and Methods Data were analyzed for the period 1999 to 2002 for 2,240 Maryland patients with cancer accrued onto NCI-sponsored treatment trials. The extent to which Maryland patients with cancer and patients residing in lower socioeconomic and/or rural areas were accrued to cancer trials and were representative of all patients with cancer in Maryland was determined. Data were obtained from several sources, including NCI’s Cancer Therapy Evaluation Program for Maryland patients with cancer in Cooperative Group therapeutic trials, Maryland Cancer Registry data on cancer incidence, and United States Census and the Department of Agriculture. Results For Maryland patients with cancer accrued onto NCI-sponsored treatment trials between 1999 and 2002, subgroups accrued at a higher rate included pediatric and adolescent age groups, white patients, female patients (for sex-specific tumors), patients with private health insurance, and patients residing in the Maryland National Capitol region. Moreover, between 1999 and 2002, there was an estimated annual decline (8.9% per year; P < .05) in the percentage of black patients accrued onto cancer treatment trials. Logistic regression models uncovered different patterns of accrual for female patients and male patients on county-level socioeconomic factors. Conclusion Results highlight disparities in the accrual of Maryland patients with cancer onto NCI-sponsored treatment trials based on patient age, race/ethnicity, geography of residence, and county-level socioeconomic factors. Findings provide the basis for development of innovative tailored and targeted educational efforts to improve trial accrual, particularly for the underserved. PMID:19711497

  15. 3D Models of the NCI60 Cell Lines for Screening Oncology Compounds.

    PubMed

    Selby, Mike; Delosh, Rene; Laudeman, Julie; Ogle, Chad; Reinhart, Russell; Silvers, Thomas; Lawrence, Scott; Kinders, Robert; Parchment, Ralph; Teicher, Beverly A; Evans, David M

    2017-03-01

    The NCI60 cell line panel screen includes 60 human tumor cell lines derived from nine tumor types that has been used over the past 20+ years to screen small molecules, biologics, and natural products for activity. Cells in monolayer culture in 96-well plates are exposed to compounds for 48 h, and Sulforhodamine B is used to determine cell viability. Data analysis tools such as COMPARE allow classification of compounds based on the pattern of cell line response. However, many compounds highly active in monolayer cell culture fail to show efficacy in vivo. Therefore, we explored 3D culture of the NCI60 panel as a strategy to improve the predictive accuracy of the screen. 3D cultures more closely resemble tumors than monolayer cultures with tighter cell-cell contact and nutrient and oxygen gradients between the periphery and the center. We optimized the NCI60 cell line panel for generating 3D spheroids of a prespecified diameter (300-500 µm) in ultra-low attachment (ULA) plates. Spheroids were classified into four categories based on imaging, and concentration response of select agents in 2D and 3D models is presented.

  16. Comparison of Long-Term Safety and Efficacy Outcomes after Drug-Eluting and Bare-Metal Stent Use across Racial Groups: insights from NHLBI Dynamic Registry

    PubMed Central

    Olafiranye, Oladipupo; Vlachos, Helen; Mulukutla, Suresh R.; Marroquin, Oscar; Selzer, Faith; Kelsey, Sheryl F.; Williams, David O.; Strollo, Patrick J.; Reis, Steven E.; Lee, Joon S.; Smith, AJ. Conrad

    2015-01-01

    Background Long-term data on outcomes after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) and bare-metal stent (BMS) across racial groups are limited, and minorities are under-represented in existing clinical trials. Whether DES has better long-term clinical outcomes compared to BMS across racial groups remains to be established. Accordingly, we assessed whether longer-term clinical outcomes are better with DES compared to BMS across racial groups. Methods Using the multicenter National Heart, Lung, and Blood Institute (NHLBI)-sponsored Dynamic Registry, 2-year safety (death, MI) and efficacy (repeat revascularization) outcomes of 3,326 patients who underwent PCI with DES versus BMS were evaluated. Results With propensity-score adjusted analysis, the use of DES, compared to BMS, was associated with a lower risk for death or MI at 2 years for both blacks (adjusted Hazard Ratio (aHR)=0.41, 95% CI 0.25–0.69, p<0.001) and whites (aHR=0.67, 95% CI 0.51–0.90, p=0.007). DES use was associated with a significant 24% lower risk of repeat revascularization in whites (aHR=0.76, 95% CI 0.60–0.97, p=0.03) and with nominal 34% lower risk in blacks (aHR=0.66, 95% CI 0.39–1.13, p=0.13). Conclusion Use of DES in PCI was associated with better long-term safety outcomes across racial groups. Compared to BMS, DES was more effective in reducing repeat revascularization in whites and blacks, but this benefit was attenuated after statistical adjustment in blacks. These findings indicate that DES is superior to BMS in all patients regardless of race. Further studies are needed to determine long-term outcomes across racial groups with newer generation stents. PMID:25697874

  17. Ardipusilloside I purified from Ardisia pusilla competitively binds VEGFR and induces apoptosis in NCI-H460 cells.

    PubMed

    Zhang, Yanmin; Qu, Youle; Zhang, Jie; Wang, Xiaojuan

    2010-06-01

    The present study was to evaluate the effects of Ardipusilloside I isolated from Ardisia pusilla on the growth, vascular endothelial growth factor receptor (VEGFR) expression and apoptosis of NCI-H460 cell line by MTT, ELISA and flow cytometer, respectively. The docking assay between Ardipusilloside I and VEGFR was studied by Sybyl/Sketch module. The change of microstructure was observed by transmission electron microscope (TEM). DNA fragmentation was visualized by agarose gel electrophoresis. The protein expression of Bax and Bcl-2 was detected by immunohistochemistry (IHC). A series of changes were observed in NCI-H460 cell treated by Ardipusilloside I, including microstructure, DNA fragmentation, protein expression of VEGFR, Bax and Bcl-2. The results showed Ardipusilloside I had a good docking with VEGFR and could inhibit growth and induce apoptosis of NCI-H460 cell in a dose-dependent manner. Cell cycle was significantly stopped at the G(1) phase. Under electronic microscope, the morphology of NCI-H460 cell treated with Ardipusilloside I showed nuclear karyopycnosis, chromatin agglutination and typical apoptotic body. VEGFR and Bcl-2 expression were decreased and Bax expression was increased. In conclusion, all these results demonstrate that Ardipusilloside I has a good docking with VEGFR and has an inhibitory effect on growth of NCI-H460 cell and can induce its apoptosis.

  18. Chemical data mining of the NCI human tumor cell line database.

    PubMed

    Wang, Huijun; Klinginsmith, Jonathan; Dong, Xiao; Lee, Adam C; Guha, Rajarshi; Wu, Yuqing; Crippen, Gordon M; Wild, David J

    2007-01-01

    The NCI Developmental Therapeutics Program Human Tumor cell line data set is a publicly available database that contains cellular assay screening data for over 40 000 compounds tested in 60 human tumor cell lines. The database also contains microarray assay gene expression data for the cell lines, and so it provides an excellent information resource particularly for testing data mining methods that bridge chemical, biological, and genomic information. In this paper we describe a formal knowledge discovery approach to characterizing and data mining this set and report the results of some of our initial experiments in mining the set from a chemoinformatics perspective.

  19. Former WHK Intern Returns to NCI at Frederick as Earl-Stadtman Investigator | Poster

    Cancer.gov

    The Laboratory of Cell and Developmental Signaling (LCDS) recently welcomed John Brognard, Ph.D., as the new Earl-Stadtman Investigator. While Brognard is new to this role, he is not new to NCI at Frederick. In high school, Brognard was a Werner H. Kirsten Student Intern in what was formerly known as the ABL research program, where he worked under Bob Moschel, Ph.D., senior investigator, and Gary Pauly, Ph.D., currently a staff scientist in the Chemical Biology Laboratory.

  20. Microsoft Office 365 Deployment Continues through June at NCI at Frederick | Poster

    Cancer.gov

    The latest Microsoft suite, Office 365 (O365), is being deployed to all NCI at Frederick computers during the months of May and June to comply with federal mandates. The suite includes the latest versions of Word, Excel, Outlook, PowerPoint, and Skype for Business, along with cloud-based capabilities. These cloud-based capabilities will help meet the federal mandates that require all Health and Human Services operating divisions to migrate e-mail to the cloud by the end of 2016.

  1. NCI Workshop Report: Clinical and Computational Requirements for Correlating Imaging Phenotypes with Genomics Signatures

    PubMed Central

    Colen, Rivka; Foster, Ian; Gatenby, Robert; Giger, Mary Ellen; Gillies, Robert; Gutman, David; Heller, Matthew; Jain, Rajan; Madabhushi, Anant; Madhavan, Subha; Napel, Sandy; Rao, Arvind; Saltz, Joel; Tatum, James; Verhaak, Roeland; Whitman, Gary

    2014-01-01

    The National Cancer Institute (NCI) Cancer Imaging Program organized two related workshops on June 26–27, 2013, entitled “Correlating Imaging Phenotypes with Genomics Signatures Research” and “Scalable Computational Resources as Required for Imaging-Genomics Decision Support Systems.” The first workshop focused on clinical and scientific requirements, exploring our knowledge of phenotypic characteristics of cancer biological properties to determine whether the field is sufficiently advanced to correlate with imaging phenotypes that underpin genomics and clinical outcomes, and exploring new scientific methods to extract phenotypic features from medical images and relate them to genomics analyses. The second workshop focused on computational methods that explore informatics and computational requirements to extract phenotypic features from medical images and relate them to genomics analyses and improve the accessibility and speed of dissemination of existing NIH resources. These workshops linked clinical and scientific requirements of currently known phenotypic and genotypic cancer biology characteristics with imaging phenotypes that underpin genomics and clinical outcomes. The group generated a set of recommendations to NCI leadership and the research community that encourage and support development of the emerging radiogenomics research field to address short-and longer-term goals in cancer research. PMID:25389451

  2. NCI Awards 18 Grants to Continue the Early Detection Research Network (EDRN) Biomarkers Effort | Division of Cancer Prevention

    Cancer.gov

    The NCI has awarded 18 grants to continue the Early Detection Research Network (EDRN), a national infrastructure that supports the integrated development, validation, and clinical application of biomarkers for the early detection of cancer. The awards fund 7 Biomarker Developmental Laboratories, 8 Clinical Validation Centers, 2 Biomarker Reference Laboratories, and a Data Management and Coordinating Center (DMCC). |

  3. Dysregulation of FURIN by prostaglandin-endoperoxide synthase 2 in lung epithelial NCI-H292 cells.

    PubMed

    Brant, Kelly A; Leikauf, George D

    2014-03-01

    Because proprotein convertases (PCSKs) activate growth factors and matrix metalloproteinase, these enzymes have been implicated in non-small cell lung cancer tumor progression and aggressiveness. Previous studies indicate that one PCSK member, FURIN is overexpressed in NSCLC, but little is known regarding the mechanisms driving PCSKs expression during malignant change. We sought to determine whether prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (PTGS2) (aka COX2), whose expression is also frequently increased in NSCLC, differentially regulates PCSK expression and activity between normal (NHBE) and NSCLC epithelial cells (NCI-H292, NCI-H441, A549). NSCLC cells exhibit significantly greater cell-associated and secreted PCSK activity as compared with NHBE. The heightened activity is consistent with increased FURIN, PCSK4, and PCSK6 protein in the NCSLC cells. Inhibition of PTGS2 activity using NS-398 and siRNA decreased FURIN mRNA, protein, activity along with cell proliferation in NCI-H292 cells but not NHBE cells. NSCLC also expressed elevated levels of the transcription factor E2F1. When NCI-H292 cells were transfected with E2F1 siRNA, both PTGS2 expression and PCSK activity were attenuated, arguing a pivotal role for E2F1 in the differential regulation of PCSKs by PTGS2. Our results highlight a novel role for PTGS2 in NSCLC and may provide a mechanism, whereby PTGS2 inhibitors suppress lung cancer cell growth.

  4. Trading places. Vendors walk the floor while hospital executives man booths at unusual purchasing exhibit in Florida hosted by NCI.

    PubMed

    Becker, Cinda

    2003-10-20

    Vendors truly had a captive audience at the ninth annual IDN Summit & Expo, as providers' cubicles were swarmed by company representatives offering powerful sales pitches on everything from high-tech fabrics to breast implants. NCI's open forum provided a rare view of how healthcare supplies are bought in this country. Elizabeth Duncan-Hawker, left, fielded pitches at Sentara Healthcare's booth.

  5. Screening and identification of a peptide specifically targeted to NCI-H1299 from a phage display peptide library.

    PubMed

    Zang, Linquan; Shi, Lei; Guo, Jiao; Pan, Qin; Wu, Wei; Pan, Xuediao; Wang, Junye

    2009-08-18

    In this study, a NCI-H1299 (Non-Small Cell Lung Cancer, NSCLC) and a normal lung cell line (Small Airway Epithelial Cells, SAEC) were used for the subtractive screening in vitro with a phage display-12 peptide library. After three rounds of panning, there was an obvious enrichment for the phages specifically binding to the NCI-H1299 cells, and the output/input ratio of phages increased about 875-fold (from 0.4x10(4) to 3.5x10(6)). A group of peptides being capable of binding specifically to the NCI-H1299 cells were obtained, and the affinity of these peptides to bind to the targeted cells and tissues was studied. Through a cell-based ELISA, immunocytochemical staining, immunohistochemical staining, and immunofluorescence, a M13 phage isolated and identified from the above screenings, and a synthetic peptide ZS-1 (sequence EHMALTYPFRPP) corresponded to the sequence of the surface protein of the M13 phage were demonstrated to be capable of binding to the tumor cell surfaces of NCI-H1299 and A549 cell lines and biopsy specimens, but not to normal lungs tissue samples, other different cancer cells, or nontumor surrounding lung tissues. In conclusion, the peptide ZS-1 may be a potential candidate of biomarker ligands used for targeted drug delivery in therapy of lung cancer.

  6. New NCI-N87-derived human gastric epithelial line after human telomerase catalytic subunit over-expression

    PubMed Central

    Saraiva-Pava, Kathy; Navabi, Nazanin; Skoog, Emma C; Lindén, Sara K; Oleastro, Mónica; Roxo-Rosa, Mónica

    2015-01-01

    AIM: To establish a cellular model correctly mimicking the gastric epithelium to overcome the limitation in the study of Helicobacter pylori (H. pylori) infection. METHODS: Aiming to overcome this limitation, clones of the heterogenic cancer-derived NCI-N87 cell line were isolated, by stably-transducing it with the human telomerase reverse-transcriptase (hTERT) catalytic subunit gene. The clones were first characterized regarding their cell growth pattern and phenotype. For that we measured the clones’ adherence properties, expression of cell-cell junctions’ markers (ZO-1 and E-cadherin) and ability to generate a sustained transepithelial electrical resistance. The gastric properties of the clones, concerning expression of mucins, zymogens and glycan contents, were then evaluated by haematoxylin and eosin staining, Periodic acid Schiff (PAS) and PAS/Alcian Blue-staining, immunocytochemistry and Western blot. In addition, we assessed the usefulness of the hTERT-expressing gastric cell line for H. pylori research, by performing co-culture assays and measuring the IL-8 secretion, by ELISA, upon infection with two H. pylori strains differing in virulence. RESULTS: Compared with the parental cell line, the most promising NCI-hTERT-derived clones (CL5 and CL6) were composed of cells with homogenous phenotype, presented higher relative telomerase activities, better adhesion properties, ability to be maintained in culture for longer periods after confluency, and were more efficient in PAS-reactive mucins secretion. Both clones were shown to produce high amounts of MUC1, MUC2 and MUC13. NCI-hTERT-CL5 mucins were shown to be decorated with blood group H type 2 (BG-H), Lewis-x (Lex), Ley and Lea and, in a less extent, with BG-A antigens, but the former two antigens were not detected in the NCI-hTERT-CL6. None of the clones exhibited detectable levels of MUC6 nor sialylated Lex and Lea glycans. Entailing good gastric properties, both NCI-hTERT-clones were found to produce

  7. NCI's High Performance Computing (HPC) and High Performance Data (HPD) Computing Platform for Environmental and Earth System Data Science

    NASA Astrophysics Data System (ADS)

    Evans, Ben; Allen, Chris; Antony, Joseph; Bastrakova, Irina; Gohar, Kashif; Porter, David; Pugh, Tim; Santana, Fabiana; Smillie, Jon; Trenham, Claire; Wang, Jingbo; Wyborn, Lesley

    2015-04-01

    The National Computational Infrastructure (NCI) has established a powerful and flexible in-situ petascale computational environment to enable both high performance computing and Data-intensive Science across a wide spectrum of national environmental and earth science data collections - in particular climate, observational data and geoscientific assets. This paper examines 1) the computational environments that supports the modelling and data processing pipelines, 2) the analysis environments and methods to support data analysis, and 3) the progress so far to harmonise the underlying data collections for future interdisciplinary research across these large volume data collections. NCI has established 10+ PBytes of major national and international data collections from both the government and research sectors based on six themes: 1) weather, climate, and earth system science model simulations, 2) marine and earth observations, 3) geosciences, 4) terrestrial ecosystems, 5) water and hydrology, and 6) astronomy, social and biosciences. Collectively they span the lithosphere, crust, biosphere, hydrosphere, troposphere, and stratosphere. The data is largely sourced from NCI's partners (which include the custodians of many of the major Australian national-scale scientific collections), leading research communities, and collaborating overseas organisations. New infrastructures created at NCI mean the data collections are now accessible within an integrated High Performance Computing and Data (HPC-HPD) environment - a 1.2 PFlop supercomputer (Raijin), a HPC class 3000 core OpenStack cloud system and several highly connected large-scale high-bandwidth Lustre filesystems. The hardware was designed at inception to ensure that it would allow the layered software environment to flexibly accommodate the advancement of future data science. New approaches to software technology and data models have also had to be developed to enable access to these large and exponentially

  8. NIOSH/NCI study of exposure to diesel exhaust in underground mines -- An industry perspective

    SciTech Connect

    Pritchard, C.J.

    1999-07-01

    In 1992, the National Institute for Occupational Safety and Health (NIOSH) initiated a study, funded by the National Cancer Institute (NCI), to evaluate the health effects, if any, involving underground miners exposure to diesel exhaust. An industry organization, the Methane Awareness Research Group (MARG) already in place to respond to gassy mine related issues, was redirected to work with diesel concerns. In 1995, NIOSH released a draft protocol and feasibility assessment, indicating its intent to initiate a study at 14 underground mines, some of which were operated by MARG members. After considerable debate on the study protocol, in-mine industrial hygiene studies were begun in December, 1997 and expected to end in early 1999.

  9. (Updated) NCI Fiscal 2016 Bypass Budget Proposes $25 Million for Frederick National Lab | Poster

    Cancer.gov

    By Nancy Parrish, Staff Writer; image by Richard Frederickson, Staff Photographer The additional funding requested for Frederick National Laboratory for Cancer Research (FNLCR) in the Fiscal 2016 Bypass Budget was $25 million, or approximately 3.5 percent of the total additional funding request of $715 million. Officially called the Professional Judgment Budget, the Bypass Budget is a result of the National Cancer Act of 1971, which authorizes NCI to submit a budget directly to the president, to send to Congress. With a focus on NCI’s research priorities and areas of cancer research with potential for investment, the Bypass Budget specifies additional funding, over and above the current budget, that is needed to advance

  10. Integrating constitutive gene expression and chemoactivity: mining the NCI60 anticancer screen.

    PubMed

    Covell, David G

    2012-01-01

    Studies into the genetic origins of tumor cell chemoactivity pose significant challenges to bioinformatic mining efforts. Connections between measures of gene expression and chemoactivity have the potential to identify clinical biomarkers of compound response, cellular pathways important to efficacy and potential toxicities; all vital to anticancer drug development. An investigation has been conducted that jointly explores tumor-cell constitutive NCI60 gene expression profiles and small-molecule NCI60 growth inhibition chemoactivity profiles, viewed from novel applications of self-organizing maps (SOMs) and pathway-centric analyses of gene expressions, to identify subsets of over- and under-expressed pathway genes that discriminate chemo-sensitive and chemo-insensitive tumor cell types. Linear Discriminant Analysis (LDA) is used to quantify the accuracy of discriminating genes to predict tumor cell chemoactivity. LDA results find 15% higher prediction accuracies, using ∼30% fewer genes, for pathway-derived discriminating genes when compared to genes derived using conventional gene expression-chemoactivity correlations. The proposed pathway-centric data mining procedure was used to derive discriminating genes for ten well-known compounds. Discriminating genes were further evaluated using gene set enrichment analysis (GSEA) to reveal a cellular genetic landscape, comprised of small numbers of key over and under expressed on- and off-target pathway genes, as important for a compound's tumor cell chemoactivity. Literature-based validations are provided as support for chemo-important pathways derived from this procedure. Qualitatively similar results are found when using gene expression measurements derived from different microarray platforms. The data used in this analysis is available at http://pubchem.ncbi.nlm.nih.gov/andhttp://www.ncbi.nlm.nih.gov/projects/geo (GPL96, GSE32474).

  11. NCI's national environmental research data collection: metadata management built on standards and preparing for the semantic web

    NASA Astrophysics Data System (ADS)

    Wang, Jingbo; Bastrakova, Irina; Evans, Ben; Gohar, Kashif; Santana, Fabiana; Wyborn, Lesley

    2015-04-01

    National Computational Infrastructure (NCI) manages national environmental research data collections (10+ PB) as part of its specialized high performance data node of the Research Data Storage Infrastructure (RDSI) program. We manage 40+ data collections using NCI's Data Management Plan (DMP), which is compatible with the ISO 19100 metadata standards. We utilize ISO standards to make sure our metadata is transferable and interoperable for sharing and harvesting. The DMP is used along with metadata from the data itself, to create a hierarchy of data collection, dataset and time series catalogues that is then exposed through GeoNetwork for standard discoverability. This hierarchy catalogues are linked using a parent-child relationship. The hierarchical infrastructure of our GeoNetwork catalogues system aims to address both discoverability and in-house administrative use-cases. At NCI, we are currently improving the metadata interoperability in our catalogue by linking with standardized community vocabulary services. These emerging vocabulary services are being established to help harmonise data from different national and international scientific communities. One such vocabulary service is currently being established by the Australian National Data Services (ANDS). Data citation is another important aspect of the NCI data infrastructure, which allows tracking of data usage and infrastructure investment, encourage data sharing, and increasing trust in research that is reliant on these data collections. We incorporate the standard vocabularies into the data citation metadata so that the data citation become machine readable and semantically friendly for web-search purpose as well. By standardizing our metadata structure across our entire data corpus, we are laying the foundation to enable the application of appropriate semantic mechanisms to enhance discovery and analysis of NCI's national environmental research data information. We expect that this will further

  12. Performance Observations of Scanner Qualification of NCI-Designated Cancer Centers: Results From the Centers of Quantitative Imaging Excellence (CQIE) Program

    PubMed Central

    Rosen, Mark; Kinahan, Paul E.; Gimpel, James F.; Opanowski, Adam; Siegel, Barry A.; Hill, G. Craig; Weiss, Linda; Shankar, Lalitha

    2016-01-01

    We present an overview of the Centers for Quantitative Imaging Excellence (CQIE) program, which was initiated in 2010 to establish a resource of clinical trial-ready sites within the National Cancer Institute (NCI)-designated Cancer Centers (NCI-CCs) network. The intent was to enable imaging centers in the NCI-CCs network capable of conducting treatment trials with advanced quantitative imaging end points. We describe the motivations for establishing the CQIE, the process used to initiate the network, the methods of site qualification for positron emission tomography, computed tomography, and magnetic resonance imaging, and the results of the evaluations over the subsequent 3 years. PMID:28395794

  13. Why Should There Be an NICHD?

    PubMed Central

    2011-01-01

    In its nearly 5 decades of existence, the Eunice Kennedy Shriver National Institute of Child Health and Human Development has expended $23 billion in conducting and supporting research and translating discoveries to practice. The resulting dramatic impact on peoples' lives and improved health for children and families, chronicled herein, are a testament to the benefits of having this institute at the National Institutes of Health. PMID:21199851

  14. Qualification of NCI-Designated Cancer Centers for Quantitative PET/CT Imaging in Clinical Trials.

    PubMed

    Scheuermann, Joshua S; Reddin, Janet S; Opanowski, Adam; Kinahan, Paul E; Siegel, Barry A; Shankar, Lalitha K; Karp, Joel S

    2017-03-02

    The National Cancer Institute (NCI) developed the Centers for Quantitative Imaging Excellence (CQIE) initiative in 2010 to pre-qualify imaging facilities at all of the NCI-designated Comprehensive and Clinical Cancer Centers for oncology trials using advanced imaging techniques, including positron emission tomography (PET). This paper reviews the CQIE PET/CT (Computed Tomography) scanner qualification process and results in detail. Methods: Over a period of approximately 5 years, sites were requested to submit a variety of phantom, including uniform and ACR (American College of Radiology) phantoms, PET/CT images, as well as examples of clinical images. Submissions were divided into 3 distinct time points: initial submission (T0), followed by two requalification submissions (T1 and T2). Images were analyzed using standardized procedures and scanners received a pass or fail designation. Sites had the opportunity to submit new data for failed scanners. Quantitative results were compared: across scanners within a given time point and across time points for a given scanner. Results: 65 unique PET/CT scanners across 42 sites were submitted for CQIE T0 qualification, with 64 passing qualification. 44 (68%) of the scanners from T0 had data submitted for T2. From T0 to T2 the percentage of scanners passing the CQIE qualification on the first attempt rose from 38% in T1 to 67% in T2. The most common reasons for failure were: standardized uptake value (SUV) out of specifications, incomplete data submission and uniformity issues. Uniform phantom and ACR phantom results between scanner manufacturers are similar. Conclusion: The results of the CQIE process show that periodic requalification may decrease the frequency of deficient data submissions. The CQIE project also highlighted the concern within imaging facilities about the burden of maintaining different qualifications and accreditations. Finally, we note that for quantitative imaging-based trials the relationships between

  15. Concentration of endogenous estrogens and estrogen metabolites in the NCI-60 human tumor cell lines

    PubMed Central

    2012-01-01

    Background Endogenous estrogens and estrogen metabolites play an important role in the pathogenesis and development of human breast, endometrial, and ovarian cancers. Increasing evidence also supports their involvement in the development of certain lung, colon and prostate cancers. Methods In this study we systemically surveyed endogenous estrogen and estrogen metabolite levels in each of the NCI-60 human tumor cell lines, which include human breast, central nerve system, colon, ovarian, prostate, kidney and non-small cell lung cancers, as well as melanomas and leukemia. The absolute abundances of these metabolites were measured using a liquid chromatography-tandem mass spectrometry method that has been previously utilized for biological fluids such as serum and urine. Results Endogenous estrogens and estrogen metabolites were found in all NCI-60 human tumor cell lines and some were substantially elevated and exceeded the levels found in well known estrogen-dependent and estrogen receptor-positive tumor cells such as MCF-7 and T-47D. While estrogens were expected to be present at high levels in cell lines representing the female reproductive system (that is, breast and ovarian), other cell lines, such as leukemia and colon, also contained very high levels of these steroid hormones. The leukemia cell line RMPI-8226 contained the highest levels of estrone (182.06 pg/106 cells) and 17β-estradiol (753.45 pg/106 cells). In comparison, the ovarian cancer cell line with the highest levels of these estrogens contained only 19.79 and 139.32 pg/106 cells of estrone and 17β-estradiol, respectively. The highest levels of estrone and 17β-estradiol in breast cancer cell lines were only 8.45 and 87.37 pg/106 cells in BT-549 and T-47D cells, respectively. Conclusions The data provided evidence for the presence of significant amounts of endogenous estrogens and estrogen metabolites in cell lines not commonly associated with these steroid hormones. This broad discovery of

  16. Metformin synergistically enhances antiproliferative effects of cisplatin and etoposide in NCI-H460 human lung cancer cells*

    PubMed Central

    Teixeira, Sarah Fernandes; Guimarães, Isabella dos Santos; Madeira, Klesia Pirola; Daltoé, Renata Dalmaschio; Silva, Ian Victor; Rangel, Leticia Batista Azevedo

    2013-01-01

    OBJECTIVE: To test the effectiveness of combining conventional antineoplastic drugs (cisplatin and etoposide) with metformin in the treatment of non-small cell lung cancer in the NCI-H460 cell line, in order to develop new therapeutic options with high efficacy and low toxicity. METHODS: We used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and calculated the combination index for the drugs studied. RESULTS: We found that the use of metformin as monotherapy reduced the metabolic viability of the cell line studied. Combining metformin with cisplatin or etoposide produced a synergistic effect and was more effective than was the use of cisplatin or etoposide as monotherapy. CONCLUSIONS: Metformin, due to its independent effects on liver kinase B1, had antiproliferative effects on the NCI-H460 cell line. When metformin was combined with cisplatin or etoposide, the cell death rate was even higher. PMID:24473757

  17. Ongoing Use of Data and Specimens from NCI Sponsored Cancer Prevention Clinical Trials in the Community Clinical Oncology Program

    PubMed Central

    Minasian, Lori; Tangen, Catherine M.; Wickerham, D. Lawrence

    2015-01-01

    Large cancer prevention trials provide opportunities to collect a wide array of data and biospecimens at study entry and longitudinally, for a healthy, aging population without cancer. This provides an opportunity to use pre-diagnostic data and specimens to evaluate hypotheses about the initial development of cancer. This paper reports on strides made by, and future possibilities for, the use of accessible biorepositories developed from precisely annotated samples obtained through large-scale National Cancer Institute (NCI)-sponsored cancer prevention clinical trials conducted by the NCI Cooperative Groups. These large cancer prevention studies, which have enrolled over 80,000 volunteers, continue to contribute to our understanding of cancer development more than 10 years after they were closed. PMID:26433556

  18. Matrine suppresses invasion and metastasis of NCI-H1299 cells by enhancing microRNA-133a expression

    PubMed Central

    Liao, Hehe; Zhao, Xixi; Qu, Jinkun; Zhang, Jia; Cai, Hui

    2015-01-01

    Matrine has been proved to inhibit proliferation and induce apoptosis of human lung cancer cells. However, less studies involved in evaluating the effects and mechanism of matrine in cell migration and invasion of lung cancer. This study was aim to investigate the involvement of miR-133a in matrine’s anti-invasion and anti-metastasis in lung cancer. MTT assay was used to assess the inhibition of proliferation effects of matrine in NCI-H1299 cells. Migration and invasion abilities of NCI-H1299 cells were investigated by Transwell assays. Expression of miR-133a was detected by real-time PCR. Anti-miR technique was applied to inhibit miR-133a in matrine treated HCI-H1299 cells. Real-time PCR and Western blotting were performed to evaluate the activation of EGFR/Akt/MMP-9 pathway. As results, matrine treatment significantly inhibited proliferation, migration and invasion of NCI-H1299 cells in a concentration-dependent manner, accompanied by significantly elevation of miR-133a expression. However, matrine failed to inhibit the metastatic ability when cells transfected with anti-miR-133a. Matrine treatment also suppressed activation of EGFR/Akt/MMP-9 pathway. The inhibitory effects of matrine on activation of EGFR pathway were also reversed by anti-miR-133a transfection in NCI-H1299 cells. In conclusion, matrine inhibited the invasion and metastasis of lung cancer cell by elevating expression of miR-133a which further suppressed activation of EGFR/Akt/MMP-9 pathway. PMID:26379863

  19. Screening and identification of a peptide specifically targeted to NCI-H1299 cells from a phage display peptide library.

    PubMed

    Tu, Xiangan; Zang, Linquan; Lan, Daiyan; Liang, Weican

    2009-01-01

    Ligands that are capable of binding to tumor cell surface biomarkers specifically used in the early diagnosis of cancer and targeted drug delivery in cancer chemotherapy have been extensively investigated. Phage display technology has been demonstrated to be a powerful tool in this field. In this study, the non-small cell lung cancer NCI-H1299 and the normal lung small airway epithelial cell lines were used for subtractive screening in vitro with a phage display 12-peptide library. After three rounds of panning, there was an obvious enrichment in the phages specifically binding to the NCI-H1299 cells, and the output/input ratio of phages increased approximately 875-fold (from 0.4x104 to 3.5x106). A group of peptides capable of binding specifically to the NCI-H1299 cells was obtained, and the affinity of these peptides to bind to the targeted cells and tissues was studied. Through cell-based ELISA, immunocytochemical staining, immunohistochemical staining and immunofluorescence, an M13 phage was isolated and identified from the above screenings, and a synthetic peptide, ZT-1 (sequence QQMHLMSYAPGP), corresponding to the sequence of the surface protein of the M13 phage, was demonstrated to be capable of binding to the tumor cell surfaces of NCI-H1299 and A549 cells and biopsy specimens, but not to normal lung tissue samples, other cancer cells, or non-tumor adjacent lung tissues. In conclusion, the peptide ZT-1 may be a potential candidate biomarker ligand that can be used for targeted drug delivery in lung cancer therapy.

  20. Matrine suppresses invasion and metastasis of NCI-H1299 cells by enhancing microRNA-133a expression.

    PubMed

    Liao, Hehe; Zhao, Xixi; Qu, Jinkun; Zhang, Jia; Cai, Hui

    2015-01-01

    Matrine has been proved to inhibit proliferation and induce apoptosis of human lung cancer cells. However, less studies involved in evaluating the effects and mechanism of matrine in cell migration and invasion of lung cancer. This study was aim to investigate the involvement of miR-133a in matrine's anti-invasion and anti-metastasis in lung cancer. MTT assay was used to assess the inhibition of proliferation effects of matrine in NCI-H1299 cells. Migration and invasion abilities of NCI-H1299 cells were investigated by Transwell assays. Expression of miR-133a was detected by real-time PCR. Anti-miR technique was applied to inhibit miR-133a in matrine treated HCI-H1299 cells. Real-time PCR and Western blotting were performed to evaluate the activation of EGFR/Akt/MMP-9 pathway. As results, matrine treatment significantly inhibited proliferation, migration and invasion of NCI-H1299 cells in a concentration-dependent manner, accompanied by significantly elevation of miR-133a expression. However, matrine failed to inhibit the metastatic ability when cells transfected with anti-miR-133a. Matrine treatment also suppressed activation of EGFR/Akt/MMP-9 pathway. The inhibitory effects of matrine on activation of EGFR pathway were also reversed by anti-miR-133a transfection in NCI-H1299 cells. In conclusion, matrine inhibited the invasion and metastasis of lung cancer cell by elevating expression of miR-133a which further suppressed activation of EGFR/Akt/MMP-9 pathway.

  1. Bisdemethoxycurcumin induces DNA damage and inhibits DNA repair associated protein expressions in NCI-H460 human lung cancer cells.

    PubMed

    Yu, Chien-Chih; Yang, Su-Tso; Huang, Wen-Wen; Peng, Shu-Fen; Huang, An-Cheng; Tang, Nou-Ying; Liu, Hsin-Chung; Yang, Mei-Due; Lai, Kuang-Chi; Chung, Jing-Gung

    2015-08-30

    Nonsmall cell lung carcinoma (NSCLC) is a devastating primary lung tumor resistant to conventional therapies. Bisdemethoxycurcumin (BDMC) is one of curcumin derivate from Turmeric and has been shown to induce NSCLC cell death. Although there is one report to show BDMC induced DNA double strand breaks, however, no available information to show BDMC induced DNA damage action with inhibited DNA repair protein in lung cancer cells in detail. In this study, we tested BDMC-induced DNA damage and condensation in NCI-H460 cells by using Comet assay and DAPI staining examinations, respectively and we found BDMC induced DNA damage and condension. Western blotting was used to examine the effects of BDMC on protein expression associated with DNA damage and repair and results indicated that BDMC suppressed the protein levels associated with DNA damage and repair, such as 14-3-3σ (an important checkpoint keeper of DDR), O6-methylguanine-DNA methyltransferase, DNA repair proteins breast cancer 1, early onset, mediator of DNA damage checkpoint 1 but activate phosphorylated p53 and p-H2A.X (phospho Ser140) in NCI-H460 cells. Confocal laser systems microscopy was used for examining the protein translocation and results show that BDMC increased the translocation of p-p53 and p-H2A.X (phospho Ser140) from cytosol to nuclei in NCI-H460 cells. In conclusion, BDMC induced DNA damage and condension and affect DNA repair proteins in NCI-H460 cells in vitro. © 2015 Wiley Periodicals, Inc. Environ Toxicol, 2015.

  2. Curcumin induces apoptosis in human non-small cell lung cancer NCI-H460 cells through ER stress and caspase cascade- and mitochondria-dependent pathways.

    PubMed

    Wu, Shin-Hwar; Hang, Liang-Wen; Yang, Jai-Sing; Chen, Hung-Yi; Lin, Hui-Yi; Chiang, Jo-Hua; Lu, Chi-Cheng; Yang, Jiun-Long; Lai, Tung-Yuan; Ko, Yang-Ching; Chung, Jing-Gung

    2010-06-01

    It has been reported that curcumin inhibited various types of cancer cells in vitro and in vivo. However, mechanisms of curcumin-inhibited cell growth and -induced apoptosis in human non-small cell lung cancer cells (NCI-H460) still remain unclear. In this study, NCI-H460 cells were treated with curcumin to determine its anticancer activity. Different concentrations of curcumin were used for different durations in NCI-H460 cells and the subsequent changes in the cell morphology, viability, cell cycle, mRNA and protein expressions were determined. Curcumin induced apoptotic morphologic changes in NCI-H460 cells in a dose-dependent manner. After curcumin treatment, BAX and BAD were up-regulated, BCL-2, BCL-X(L) and XIAP were down-regulated. In addition, reactive oxygen species (ROS), intracellular Ca(2+) and endoplasmic reticulum (ER) stress were increased in NCI-H460 cells after exposure to curcumin. These signals led to a loss of mitochondrial membrane potential (Delta Psi(m)) and culminated in caspase-3 activation. Curcumin-induced apoptosis was also stimulated through the FAS/caspase-8 (extrinsic) pathway and ER stress proteins, growth arrest- and DNA damage-inducible gene 153 (GADD153) and glucose-regulated protein 78 (GRP78) were activated in the NCI-H460 cells. Apoptotic cell death induced by curcumin was significantly reversed by pretreatment with ROS scavenger or caspase-8 inhibitor. Furthermore, the NCI-H460 cells tended to be arrested at the G(2)/M cell cycle stage after curcumin treatment and down-regulation of cyclin-dependent kinase 1 (CDK1) may be involved. In summary, curcumin exerts its anticancer effects on lung cancer NCI-H460 cells through apoptosis or cell cycle arrest.

  3. Highlights of recent developments and trends in cancer nanotechnology research--view from NCI Alliance for Nanotechnology in Cancer.

    PubMed

    Hull, L C; Farrell, D; Grodzinski, P

    2014-01-01

    Although the incidence of cancer and cancer related deaths in the United States has decreased over the past two decades due to improvements in early detection and treatment, cancer still is responsible for a quarter of the deaths in this country. There is much room for improvement on the standard treatments currently available and the National Cancer Institute (NCI) has recognized the potential for nanotechnology and nanomaterials in this area. The NCI Alliance for Nanotechnology in Cancer was formed in 2004 to support multidisciplinary researchers in the application of nanotechnology to cancer diagnosis and treatment. The researchers in the Alliance have been productive in generating innovative solutions to some of the central issues of cancer treatment including how to detect tumors earlier, how to target cancer cells specifically, and how to improve the therapeutic index of existing chemotherapies and radiotherapy treatments. Highly creative ideas are being pursued where novelty in nanomaterial development enables new modalities of detection or therapy. This review highlights some of the innovative materials approaches being pursued by researchers funded by the NCI Alliance. Their discoveries to improve the functionality of nanoparticles for medical applications includes the generation of new platforms, improvements in the manufacturing of nanoparticles and determining the underlying reasons for the movement of nanoparticles in the blood.

  4. Spergularia marina Induces Glucagon-Like Peptide-1 Secretion in NCI-H716 Cells Through Bile Acid Receptor Activation

    PubMed Central

    Kim, Kyong; Lee, Yu Mi; Rhyu, Mee-Ra

    2014-01-01

    Abstract Spergularia marina Griseb. (SM) is a halophyte that grows in mud flats. The aerial portions of SM have been eaten as vegetables and traditionally used to prevent chronic diseases in Korea. However, there has been no scientific report that demonstrates the pharmacological effects of SM. Glucagon-like peptide-1 (GLP-1) is important for the maintenance of glucose and energy homeostasis through acting as a signal in peripheral and neural systems. To discover a functional food for regulating glucose and energy homeostasis, we evaluated the effect of an aqueous ethanolic extract (AEE) of SM on GLP-1 release from enteroendocrine NCI-H716 cells. In addition, we explored the Takeda G-protein-coupled receptor 5 (TGR5) agonist activity of AEE-SM in Chinese hamster ovary (CHO)-K1 cells transiently transfected with human TGR5. As a result, treatment of NCI-H716 cells with AEE-SM increased GLP-1 secretion and intracellular Ca2+ and cyclic AMP (cAMP) levels in a dose-dependent manner. Transfection of NCI-H716 cells with TGR5-specific small interference RNA inhibited AEE-SM-induced GLP-1 secretion and the increase in Ca2+ and cAMP levels. Moreover, AEE-SM showed that the TGR5 agonist activity in CHO-K1 cells transiently transfected with TGR5. The results suggest that AEE-SM might be a candidate for a functional food to regulate glucose and energy homeostasis. PMID:25260089

  5. Rationale, Procedures, and Response Rates for the 2015 Administration of NCI's Health Information National Trends Survey: HINTS-FDA 2015.

    PubMed

    Blake, Kelly D; Portnoy, David B; Kaufman, Annette R; Lin, Chung-Tung Jordan; Lo, Serena C; Backlund, Eric; Cantor, David; Hicks, Lloyd; Lin, Amy; Caporaso, Andrew; Davis, Terisa; Moser, Richard P; Hesse, Bradford W

    2016-12-01

    The National Cancer Institute (NCI) developed the Health Information National Trends Survey (HINTS) to monitor population trends in cancer communication practices, information preferences, health risk behaviors, attitudes, and cancer knowledge. The U.S. Food and Drug Administration (FDA) recognized HINTS as a unique data resource for informing its health communication endeavors and partnered with NCI to field HINTS-FDA 2015. HINTS-FDA 2015 was a self-administered paper instrument sent by mail May 29 to September 8, 2015, using a random probability-based sample of U.S. postal addresses stratified by county-level smoking rates, with an oversampling of high and medium-high smoking strata to increase the yield of current smokers responding to the survey. The response rate for HINTS-FDA 2015 was 33% (N = 3,738). The yield of current smokers (n = 495) was lower than expected, but the sampling strategy achieved the goal of obtaining more former smokers (n = 1,132). Public-use HINTS-FDA 2015 data and supporting documentation have been available for download and secondary data analyses since June 2016 at http://hints.cancer.gov . NCI and FDA encourage the use of HINTS-FDA for health communication research and practice related to tobacco-related communications, public knowledge, and behaviors as well as beliefs and actions related to medical products and dietary supplements.

  6. Automatic segmentation of pulmonary nodules on CT images by use of NCI lung image database consortium

    NASA Astrophysics Data System (ADS)

    Tachibana, Rie; Kido, Shoji

    2006-03-01

    Accurate segmentation of small pulmonary nodules (SPNs) on thoracic CT images is an important technique for volumetric doubling time estimation and feature characterization for the diagnosis of SPNs. Most of the nodule segmentation algorithms that have been previously presented were designed to handle solid pulmonary nodules. However, SPNs with ground-glass opacity (GGO) also affects a diagnosis. Therefore, we have developed an automated volumetric segmentation algorithm of SPNs with GGO on thoracic CT images. This paper presents our segmentation algorithm with multiple fixed-thresholds, template-matching method, a distance-transformation method, and a watershed method. For quantitative evaluation of the performance of our algorithm, we used the first dataset provided by NCI Lung Image Database Consortium (LIDC). In the evaluation, we employed the coincident rate which was calculated with both the computerized segmented region of a SPN and the matching probability map (pmap) images provided by LIDC. As the result of 23 cases, the mean of the total coincident rate was 0.507 +/- 0.219. From these results, we concluded that our algorithm is useful for extracting SPNs with GGO and solid pattern as well as wide variety of SPNs in size.

  7. NCI Funding Trends and Priorities in Physical Activity and Energy Balance Research Among Cancer Survivors.

    PubMed

    Alfano, Catherine M; Bluethmann, Shirley M; Tesauro, Gina; Perna, Frank; Agurs-Collins, Tanya; Elena, Joanne W; Ross, Sharon A; O'Connell, Mary; Bowles, Heather R; Greenberg, Deborah; Nebeling, Linda

    2016-01-01

    There is considerable evidence that a healthy lifestyle consisting of physical activity, healthy diet, and weight control is associated with reduced risk of morbidity and mortality after cancer. However, these behavioral interventions are not widely adopted in practice or community settings. Integrating heath behavior change interventions into standard survivorship care for the growing number of cancer survivors requires an understanding of the current state of the science and a coordinated scientific agenda for the future with focused attention in several priority areas. To facilitate this goal, this paper presents trends over the past decade of the National Cancer Institute (NCI) research portfolio, fiscal year 2004 to 2014, by funding mechanism, research focus, research design and methodology, primary study exposures and outcomes, and study team expertise and composition. These data inform a prioritized research agenda for the next decade focused on demonstrating value and feasibility and creating desire for health behavior change interventions at multiple levels including the survivor, clinician, and healthcare payer to facilitate the development and implementation of appropriately targeted, adaptive, effective, and sustainable programs for all survivors.

  8. CRC/EORTC/NCI Joint Formulation Working Party: experiences in the formulation of investigational cytotoxic drugs.

    PubMed Central

    Beijnen, J. H.; Flora, K. P.; Halbert, G. W.; Henrar, R. E.; Slack, J. A.

    1995-01-01

    The pharmaceutical formulation of a new anti-tumour agent has often been perceived as the bottleneck in anti-cancer drug development. In order to increase the speed of this essential development step, the Cancer Research Campaign (CRC), the European Organization for Research and Treatment of Cancer (EORTC) and the National Cancer Institute (NCI) agreed in 1987 to form the Joint Formulation Working Party (JFWP). The main goal of the JFWP is to facilitate the rapid progress of a new drug through pharmaceutical developmental to preclinical toxicology and subsequently to phase I clinical trial. Under the auspices of the JFWP around 50 new agents have been developed or are currently in development. In this report we present our formulation experiences since the establishment of the JFWP with a selected number of agents: aphidicolin glycinate, bryostatin 1, carmethizole, carzelesin, combretastatin A4, dabis maleate, disulphonated aluminium phthalocyanine, E.O.9, 4-hydroxyanisole, pancratistatin, rhizoxin, Springer pro-drug, SRI 62-834, temozolomide, trimelamol and V489. The approaches used and problems presented may be of general interest to scientists in related fields and those considering submitting agents for development. PMID:7599054

  9. Unravelling Protein-DNA Interactions at Molecular Level: A DFT and NCI Study.

    PubMed

    González, J; Baños, I; León, I; Contreras-García, J; Cocinero, E J; Lesarri, A; Fernández, J A; Millán, J

    2016-02-09

    Histone-DNA interactions were probed computationally at a molecular level, by characterizing the bimolecular clusters constituted by selected amino acid derivatives with polar (asparagine and glutamine), nonpolar (alanine, valine, and isoleucine), and charged (arginine) side chains and methylated pyrimidinic (1-methylcytosine and 1-methylthymine) and puric (9-methyladenine and 9-methylguanine) DNA bases. The computational approach combined different methodologies: a molecular mechanics (MMFFs forced field) conformational search and structural and vibrational density-functional calculations (M06-2X with double and triple-ζ Pople's basis sets). To dissect the interactions, intermolecular forces were analyzed with the Non-Covalent Interactions (NCI) analysis. The results for the 24 different clusters studied show a noticeable correlation between the calculated binding energies and the propensities for protein-DNA base interactions found in the literature. Such correlation holded even for the interaction of the selected amino acid derivatives with Watson and Crick pairs. Therefore, the balance between hydrogen bonds and van der Waals interactions (specially stacking) in the control of the final shape of the investigated amino acid-DNA base pairs seems to be well reproduced in dispersion-corrected DFT molecular models, reinforcing the idea that the specificity between the amino acids and the DNA bases play an important role in the regulation of DNA.

  10. PANCREATITIS - DIABETES - PANCREATIC CANCER: Summary of an NIDDK-NCI Workshop

    PubMed Central

    Andersen, Dana K.; Andren-Sandberg, Åke; Duell, Eric J.; Goggins, Michael; Korc, Murray; Petersen, Gloria M.; Smith, Jill P.; Whitcomb, David C.

    2013-01-01

    A workshop sponsored by the NIDDK and the NCI on “Pancreatitis-Diabetes-Pancreatic Cancer” focused on the risk factors of chronic pancreatitis (CP) and diabetes mellitus (DM) on the development of pancreatic ductal adenocarcinoma (PDAC). Sessions were held on a) an overview of the problem of PDAC, b) CP as a risk factor for PDAC, c) DM as a risk factor for PDAC, d) pancreatogenic, or type 3c DM (T3cDM), e) genomic associations of CP, DM, and PDAC, f) surveillance of high-risk populations and early detection of PDAC, and g) effects of DM treatment on PDAC. Recent data and current understandings of the mechanisms of CP- and DM-associated factors on PDAC development were discussed, and a detailed review of the possible risks of DM treatment on the development of PDAC was provided by representatives from academia, industry, and the Food and Drug Administration. The current status of possible biomarkers of PDAC and surveillance strategies for high-risk populations were discussed, and the gaps in knowledge and opportunities for further research were elucidated. A broad spectrum of expertise of the speakers and discussants provided an unusually productive workshop, the highlights of which are summarized in the accompanying article. PMID:24152948

  11. Deoxypodophyllotoxin triggers necroptosis in human non-small cell lung cancer NCI-H460 cells.

    PubMed

    Wu, Meijuan; Jiang, Zhenzhou; Duan, Huaqin; Sun, Lixin; Zhang, Shuang; Chen, Mi; Wang, Yun; Gao, Qin; Song, Yuming; Zhu, Xiong; Zhang, Luyong

    2013-10-01

    Deoxypodophyllotoxin (DPT), a naturally occurring microtubule destabilizer, inhibits tubulin polymerization and causes cell cycle arrest at G2/M phase in tumor cells. However, the anti-tumor effect and specific mechanism of DPT in non-small cell lung cancer (NSCLC) are still poorly understood. In this study, we determined the anti-tumor effect and potential mechanism of DPT in the NSCLC cell line, NCI-H460 (H460). First, we demonstrated that DPT significantly inhibits the proliferation of H460 cells in vitro and the growth of H460 xenografts in vivo. In further studies, DPT triggered necroptosis in H460 cells with the following characteristics: (I) necrotic cell death morphology; (II) autophagy; (III) loss of plasma membrane integrity; (IV) loss of mitochondria membrane potential; (V) elevation of reactive oxygen species levels; and (VI) specific inhibition of necroptosis via a small molecule, necrostatin-1. This study also revealed that DPT has a similar effect towards the drug-sensitive cancer cell line, H460, and the drug-resistant cell line, H460/Bcl-xL. To our knowledge, this is the first report to document the induction of necroptosis by a microtubule-targeting agent to circumvent cancer drug resistance, thereby providing a new potential choice for clinical cancer therapy, especially drug-resistant cancer therapy.

  12. CXCL14 enhances proliferation and migration of NCI-H460 human lung cancer cells overexpressing the glycoproteins containing heparan sulfate or sialic acid.

    PubMed

    Park, Cho Rong; You, Dong-Joo; Kim, Dong-Kyu; Moon, Mi Jin; Lee, Cheolju; Oh, Seung-Hyun; Ahn, Curie; Seong, Jae Young; Hwang, Jong-Ik

    2013-05-01

    CXCL14 is a chemokine family member that is involved in various cellular responses in addition to immune cell activation. Although constitutive CXCL14 expression in normal epithelial cells may help protect against infection by activating immune systems, its expression in cancer cells has raised controversy regarding its possible role in tumorigenesis. However, the underlying mechanisms for this disparity remain unknown. Investigation of cellular CXCL14 binding properties might increase our understanding of the peptide's roles in tumorigenesis. In the present study, we found that CXCL14 binds to various cell types. Interestingly, binding to NCI-H460 cells was prevented by heparan sulfate and N-acetyl neuraminic acid. Next, we examined effect of CXCL14 binding in NCI-H460 and NCI-H23. CXCL14 enhanced proliferation and migration in NCI-H460 but had no effect on NCI-H23. A reporter gene assay with various transcription factor response elements revealed that only nuclear factor-κB (NF-κB) signaling was activated by CXCL14 in NCI-H460 cells, which was blocked by BAPTA-AM, TPCA-1, and brefeldin A. Exogenous expression of some glycoproteins such as syndecan-4, podoplanin, and CD43 in these cells enhanced CXCL14 binding and NF-κB activity. Collectively, these results demonstrate that CXCL14 binding to glycoproteins harboring heparan sulfate proteoglycans and sialic acids leads proliferation and migration of some cancer cells.

  13. Recommendations from the iSBTc-SITC/FDA/NCI Workshop on Immunotherapy Biomarkers

    PubMed Central

    Butterfield, Lisa H.; Palucka, A. Karolina; Britten, Cedrik M.; Dhodapkar, Madhav V.; Håkansson, Leif; Janetzki, Sylvia; Kawakami, Yutaka; Kleen, Thomas-Oliver; Lee, Peter P.; Maccalli, Cristina; Maecker, Holden T.; Maino, Vernon C.; Maio, Michele; Malyguine, Anatoli; Masucci, Giuseppe; Pawelec, Graham; Potter, Douglas M.; Rivoltini, Licia; Salazar, Lupe G.; Schendel, Dolores J.; Slingluff, Craig L.; Song, Wenru; Stroncek, David F.; Tahara, Hideaki; Thurin, Magdalena; Trinchieri, Giorgio; van Der Burg, Sjoerd H.; Whiteside, Theresa L.; Wigginton, Jon M.; Marincola, Francesco; Khleif, Samir; Fox, Bernard A.; Disis, Mary L.

    2011-01-01

    Purpose To facilitate development of innovative immunotherapy approaches, especially for treatment concepts exploiting the potential benefits of personalized therapy, there is a need to develop and validate tools to identify patients who can benefit from immunotherapy. Despite substantial effort, we do not yet know which parameters of anti-tumor immunity to measure and which assays are optimal for those measurements. Experimental Design The iSBTc-SITC, FDA and NCI partnered to address these issues for immunotherapy of cancer. Here, we review the major challenges, give examples of approaches and solutions and present our recommendations. Results and Conclusions While specific immune parameters and assays are not yet validated, we recommend following standardized (accurate, precise and reproducible) protocols and use of functional assays for the primary immunologic readouts of a trial; consideration of central laboratories for immune monitoring of large, multi-institutional trials; and standardized testing of several phenotypic and functional potential potency assays specific to any cellular product. When reporting results, the full QA/QC performed, selected examples of truly representative raw data and assay performance characteristics should be included. Lastly, to promote broader analysis of multiple aspects of immunity, and gather data on variability, we recommend that in addition to cells and serum, that RNA and DNA samples be banked (under standardized conditions) for later testing. We also recommend that sufficient blood be drawn to allow for planned testing of the primary hypothesis being addressed in the trial, and that additional baseline and post-treatment blood is banked for testing novel hypotheses (or generating new hypotheses) that arise in the field. PMID:21558394

  14. Deciphering causal and statistical relations of molecular aberrations and gene expressions in NCI-60 cell lines

    PubMed Central

    2011-01-01

    Background Cancer cells harbor a large number of molecular alterations such as mutations, amplifications and deletions on DNA sequences and epigenetic changes on DNA methylations. These aberrations may dysregulate gene expressions, which in turn drive the malignancy of tumors. Deciphering the causal and statistical relations of molecular aberrations and gene expressions is critical for understanding the molecular mechanisms of clinical phenotypes. Results In this work, we proposed a computational method to reconstruct association modules containing driver aberrations, passenger mRNA or microRNA expressions, and putative regulators that mediate the effects from drivers to passengers. By applying the module-finding algorithm to the integrated datasets of NCI-60 cancer cell lines, we found that gene expressions were driven by diverse molecular aberrations including chromosomal segments' copy number variations, gene mutations and DNA methylations, microRNA expressions, and the expressions of transcription factors. In-silico validation indicated that passenger genes were enriched with the regulator binding motifs, functional categories or pathways where the drivers were involved, and co-citations with the driver/regulator genes. Moreover, 6 of 11 predicted MYB targets were down-regulated in an MYB-siRNA treated leukemia cell line. In addition, microRNA expressions were driven by distinct mechanisms from mRNA expressions. Conclusions The results provide rich mechanistic information regarding molecular aberrations and gene expressions in cancer genomes. This kind of integrative analysis will become an important tool for the diagnosis and treatment of cancer in the era of personalized medicine. PMID:22051105

  15. Computational Environments and Analysis methods available on the NCI High Performance Computing (HPC) and High Performance Data (HPD) Platform

    NASA Astrophysics Data System (ADS)

    Evans, B. J. K.; Foster, C.; Minchin, S. A.; Pugh, T.; Lewis, A.; Wyborn, L. A.; Evans, B. J.; Uhlherr, A.

    2014-12-01

    The National Computational Infrastructure (NCI) has established a powerful in-situ computational environment to enable both high performance computing and data-intensive science across a wide spectrum of national environmental data collections - in particular climate, observational data and geoscientific assets. This paper examines 1) the computational environments that supports the modelling and data processing pipelines, 2) the analysis environments and methods to support data analysis, and 3) the progress in addressing harmonisation of the underlying data collections for future transdisciplinary research that enable accurate climate projections. NCI makes available 10+ PB major data collections from both the government and research sectors based on six themes: 1) weather, climate, and earth system science model simulations, 2) marine and earth observations, 3) geosciences, 4) terrestrial ecosystems, 5) water and hydrology, and 6) astronomy, social and biosciences. Collectively they span the lithosphere, crust, biosphere, hydrosphere, troposphere, and stratosphere. The data is largely sourced from NCI's partners (which include the custodians of many of the national scientific records), major research communities, and collaborating overseas organisations. The data is accessible within an integrated HPC-HPD environment - a 1.2 PFlop supercomputer (Raijin), a HPC class 3000 core OpenStack cloud system and several highly connected large scale and high-bandwidth Lustre filesystems. This computational environment supports a catalogue of integrated reusable software and workflows from earth system and ecosystem modelling, weather research, satellite and other observed data processing and analysis. To enable transdisciplinary research on this scale, data needs to be harmonised so that researchers can readily apply techniques and software across the corpus of data available and not be constrained to work within artificial disciplinary boundaries. Future challenges will

  16. LPS Cooperates with Poly-L-Arginine to Promote IL-6 and IL-8 Release via the JNK Signaling Pathway in NCI-H292 Cells

    PubMed Central

    Zhang, Ling-Ling; Chen, Bing; Wu, Sha-Sha; Zhang, Sheng-Quan; Wu, Hui-Mei

    2016-01-01

    Objective. Herein, we aimed to study the mechanism whereby poly-L-arginine (PLA) and lipopolysaccharide (LPS) can synergistically induce the release of interleukin-6 (IL-6) and IL-8 in NCI-H292 cells. Methods. NCI-H292 cells were divided into control, PLA, LPS, and PLA+LPS groups. At various time points, the phosphorylation of JNK in each group was measured by western blotting. Additionally, the productions of IL-6 and IL-8 were assessed using an enzyme-linked immunosorbent assay (ELISA). The effects of SP600125, an inhibitor of the JNK pathway, on the increase of p-JNK, IL-6, and IL-8 were also studied. Results. Our results showed that either PLA or LPS treatment alone can significantly increase the phosphorylation level of JNK in NCI-H292 cells. Of interest was the combined use of PLA and LPS that has a synergistic effect on the phosphorylation of JNK, as well as synergistically inducing the release of IL-6 and IL-8 in NCI-H292 cells. Furthermore, SP600125 significantly inhibited the activation of JNK signal, as well as reducing the productions of IL-6 and IL-8 in response to PLA+LPS stimulation. Conclusions. The JNK signaling pathway contributes to the release of IL-6 and IL-8, which is stimulated by the synergistic actions of PLA+LPS in NCI-H292 cells. PMID:28116315

  17. NCI Researchers Discover Exceptionally Potent Antibodies with Potential for Prophylaxis and Therapy of MERS-Coronavirus Infections | Poster

    Cancer.gov

    By Andrea Frydl, Contributing Writer In a recent article published in the Journal of Virology, Tianlei Ying, Ph.D., Dimiter Dimitrov, Ph.D., and their colleagues in the Laboratory of Experimental Immunology (LEI), Cancer and Inflammation Program, NCI Center for Cancer Research, reported the identification of three human monoclonal antibodies (m336, m337, and m338) that target the part of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) that is responsible for binding to its receptor. These antibodies are exceptionally potent inhibitors of MERS-CoV infection and also provide a basis for creating a future MERS-CoV vaccine.

  18. NCI-60 Whole Exome Sequencing and Pharmacological CellMiner Analyses

    PubMed Central

    Reinhold, William C.; Varma, Sudhir; Sousa, Fabricio; Sunshine, Margot; Abaan, Ogan D.; Davis, Sean R.; Reinhold, Spencer W.; Kohn, Kurt W.; Morris, Joel; Meltzer, Paul S.; Doroshow, James H.; Pommier, Yves

    2014-01-01

    Exome sequencing provides unprecedented insights into cancer biology and pharmacological response. Here we assess these two parameters for the NCI-60, which is among the richest genomic and pharmacological publicly available cancer cell line databases. Homozygous genetic variants that putatively affect protein function were identified in 1,199 genes (approximately 6% of all genes). Variants that are either enriched or depleted compared to non-cancerous genomes, and thus may be influential in cancer progression and differential drug response were identified for 2,546 genes. Potential gene knockouts are made available. Assessment of cell line response to 19,940 compounds, including 110 FDA-approved drugs, reveals ≈80-fold range in resistance versus sensitivity response across cell lines. 103,422 gene variants were significantly correlated with at least one compound (at p<0.0002). These include genes of known pharmacological importance such as IGF1R, BRAF, RAD52, MTOR, STAT2 and TSC2 as well as a large number of candidate genes such as NOM1, TLL2, and XDH. We introduce two new web-based CellMiner applications that enable exploration of variant-to-compound relationships for a broad range of researchers, especially those without bioinformatics support. The first tool, “Genetic variant versus drug visualization”, provides a visualization of significant correlations between drug activity-gene variant combinations. Examples are given for the known vemurafenib-BRAF, and novel ifosfamide-RAD52 pairings. The second, “Genetic variant summation” allows an assessment of cumulative genetic variations for up to 150 combined genes together; and is designed to identify the variant burden for molecular pathways or functional grouping of genes. An example of its use is provided for the EGFR-ERBB2 pathway gene variant data and the identification of correlated EGFR, ERBB2, MTOR, BRAF, MEK and ERK inhibitors. The new tools are implemented as an updated web-based Cell

  19. mRNA and microRNA expression profiles of radioresistant NCI-H520 non-small cell lung cancer cells

    PubMed Central

    GUO, WEI; XIE, LI; ZHAO, LONG; ZHAO, YUEHUAN

    2015-01-01

    To elucidate the mechanism of radioresistance in non-small cell lung cancer (NSCLC) cells and to identify key molecules conferring radioresistance, the radioresistant subclone NCI-H520/R, derived from the NCI-H520 NSCLC cell line, was established with eight rounds of sublethal irradiation. The radioresistant features were subsequently assessed using a clonogenic assay, analysis of apoptosis and an MTT assay, the gene expression levels were examined using an Agilent Whole Human Genome 4×44 k Oligo microarray and Agilent Human miRCURY™ LNA array, and confirmed by reverse transcription-quantitative polymerase chain reaction. Pathway analysis and Gene Ontology (GO) analysis were performed to determine the biological functions of the subset of differentially expressed genes. miRNA-mRNA correlation analysis between the expression levels of each miRNA and all its predicted target genes was performed to further understand the radioresistance in the NCI-H520 cells. Following eight rounds of sublethal irradiation, a total of 2,862 mRNAs were significantly differentially expressed in the NCI-H520/R cells, including 893 upregulated genes and 1,969 downregulated genes. A total of 162 upregulated miRNAs and 274 downregulated miRNAs were significantly deregulated in the NCI-H520/R cells. Multiple core regulatory processes and signaling pathways were identified as being of likely relevance to radioresistance in NCI-H520/R cells, including the mitogen-activated protein kinase signaling pathway and neurotrophin signaling pathway. The expression of genes associated with radioresistance reflects the complex biological processes involved in clinical cancer cell eradication and requires further investigation for future enhancement of therapy. PMID:25873351

  20. Effects of Cx43 gene modification on the proliferation and migration of the human lung squamous carcinoma cell line NCI-H226.

    PubMed

    Zang, J-P; Wei, R

    2015-10-27

    In this study, the human lung squamous carcinoma cell line NCI-H226 was transfected with the recombinant plasmid pBudCE4.1_Cx43 to explore the role of the Cx43 gene in cell growth, cell cycle, and tumor migration. pBudCE4.1-Cx43 was transfected into human lung squamous carcinoma NCI-H226 cells using Lipofectamine TM2000. The mRNA and protein expressions of Cx43 in the transfected cells were detected by reverse transcriptase polymerase chain reaction and western blot analysis. The cell-cell communication was detected using the scratch dye tracer method and the cell cycle was detected by flow cytometry. The CCK-8 proliferation, scratch healing, and cell invasion assays were performed to evaluate the effect of the Cx43 gene transfection on the proliferation, migration, and invasive abilities of NCI-H226 cells. Cx43 mRNA and protein expressions and the fluorescence intensity in the scratch healing test were significantly higher in the experimental group than those in the control and blank groups (P < 0.05 and < 0.01, respectively). The CCK-8 proliferation assay and the scratch healing experiment revealed significantly inhibited NCI-H226 cell proliferation (especially 72 h after incubation) and cell migration, respectively, in the experimental group, compared to the control and blank groups (P < 0.001 and <0.05, respectively). The transwell chamber test showed a statistically significant decrease in the invasive ability of NCI-H226 cells in the experimental group (P < 0.05). Therefore, Cx43 gene transfection could inhibit the migration of human lung squamous carcinoma cell line NCI-H226, thereby inhibiting tumor cell proliferation.

  1. Cantharidin induces DNA damage and inhibits DNA repair-associated protein levels in NCI-H460 human lung cancer cells.

    PubMed

    Hsia, Te-Chun; Lin, Ju-Hwa; Hsu, Shu-Chun; Tang, Nou-Ying; Lu, Hsu-Feng; Wu, Shin-Hwar; Lin, Jaung-Geng; Chung, Jing-Gung

    2015-09-01

    Cantharidin is one of the major compounds from mylabris and it has cytotoxic effects in many different types of human cancer cells. Previously, we found that cantharidin induced cell death through cell cycle arrest and apoptosis induction in human lung cancer NCI-H460 cells. However, cantharidin-affected DNA damage, repair, and associated protein levels in NCI-H460 cells have not been examined. In this study, we determined whether cantharidin induced DNA damage and condensation and altered levels of proteins in NCI-H460 cells in vitro. Incubation of NCI-H460 cells with 0, 2.5, 5, 10, and 15 μM of cantharidin caused a longer DNA migration smear (comet tail). Cantharidin also increased DNA condensation. These effects were dose-dependent. Cantharidin (5, 10, and 15 μM) treatment of NCI-H460 cells reduced protein levels of ataxia telangiectasia mutated (ATM), breast cancer 1, early onset (BRCA-1), 14-3-3 proteins sigma (14-3-3σ), DNA-dependent serine/threonine protein kinase (DNA-PK), O(6) -methylguanine-DNA methyltransferase (MGMT), and mediator of DNA damage checkpoint protein 1 (MDC1). Protein translocation of p-p53, p-H2A.X (S140), and MDC1 from cytoplasm to nucleus was induced by cantharidin in NCI-H460 cells. Taken together, this study showed that cantharidin caused DNA damage and inhibited levels of DNA repair-associated proteins. These effects may contribute to cantharidin-induced cell death in vitro.

  2. An anthraquinone derivative from Luffa acutangula induces apoptosis in human lung cancer cell line NCI-H460 through p53-dependent pathway.

    PubMed

    Vanajothi, Ramar; Srinivasan, Pappu

    2016-01-01

    The current study was designed to evaluate the in vitro antiproliferative activity of 1,8-dihydroxy-4-methylanthracene-9,10-dione (DHMA) isolated from the Luffa acutangula against human non-small cell lung cancer cell line (NCI-H460). Induction of apoptosis and reactive oxygen species (ROS) generation was determined through fluorescence microscopic technique. Quantitative real-time PCR and western blotting analysis was carried out to detect the expression of pro-apoptotic (p53, p21, caspase-3, Bax, GADD45A, and ATM) and anti-apoptotic (NF-κB) proteins in NCI-H460 cell line. In silico studies also performed to predict the binding mechanism of DHMA with MDM2-p53 protein. The DHMA inhibited the cell viability of NCI-H460 cells in a dose-dependent manner with an IC(50) of about 50 µg/ml. It significantly reduced cell viability correlated with induction of apoptosis, which was associated with ROS generation. The apoptotic cell death was further confirmed through dual staining and DNA fragmentation assay. DHMA significantly increased the expression of anti-apoptotic protein such as p53, p21, Bax, and caspase-3 but downregulated the expression of NF-κB in NCI-H460 cell line. In silico studies demonstrate that DHMA formed hydrogen bond interaction with key residues Trp26, Phe55 and Lys24 by which it disrupt the binding of p53 with MDM2 receptor. These findings suggested that DHMA induces apoptosis in NCI-H460 via a p53-dependent pathway. This the first study on cytotoxic and apoptosis inducing activity of DHMA from L. acutangula against NCI-H460 cell line. Therefore, DHMA has therapeutic potential for lung cancer treatment.

  3. A1E inhibits proliferation and induces apoptosis in NCI-H460 lung cancer cells via extrinsic and intrinsic pathways.

    PubMed

    Bak, Yesol; Ham, Sunyoung; Baatartsogt, O; Jung, Seung Hyun; Choi, Kang-Duk; Han, Tae-Young; Han, Il-Young; Yoon, Do-Young

    2013-07-01

    It has been reported that extracts from Asian traditional/medical herbs possess therapeutic agents against cancers, metabolic diseases, inflammatory diseases, and other intractable diseases. In this study, we assessed the molecular mechanisms involved in the anticancer effects of A1E, the extract of Korean medicinal herbs. We examined the role of the cytotoxic and apoptotic pathways in the cancer chemopreventive activity in non-small-cell lung cancer (NSCLC) cell lines NCI-H460 and NCI-H1299. A1E inhibited the proliferation of NCI-H460 more efficiently than NCI-H1299 (p53(-/-)) cells. The apoptosis was detected by nuclear morphological changes, annexin V-FITC/PI staining, cell cycle analysis, western blot, RT-PCR, and measurement of mitochondrial membrane potential. A1E induced cellular morphological changes and nuclear condensation at 24 h in a dose-dependent manner. A1E also perturbed cell cycle progression at the sub-G1 stage and altered cell cycle regulatory factors in NCI-H460 cells. Furthermore, A1E inhibited the PI3K/Akt and NF-κB survival pathways, and it activated apoptotic intrinsic and extrinsic pathways. A1E increased the expression levels of members of the extrinsic death receptor complex FasL and FADD. In addition, A1E treatment induced cleavage of caspase-8, caspase-9, caspase-3, and poly ADP-ribose polymerase (PARP), whereas the expression levels of Bcl-2 and Bcl-xl were downregulated. A1E induced mitochondrial membrane potential collapse and cytochrome C release. Our results suggest that A1E induces apoptosis via activation of both extrinsic and intrinsic pathways and inhibition of PI3K/Akt survival signaling pathways in NCI-H460 cells. In conclusion, these data demonstrate the potential of A1E as a novel chemotherapeutic agent in NSCLC.

  4. Are we winning or losing the war on cancer? Deciphering the propaganda of NCI's 33-year war.

    PubMed

    Howe, Genevieve K; Clapp, Richard W

    2004-01-01

    The National Cancer Institute (NCI) and collaborating agencies have proclaimed great progress in the U.S. "war on cancer," while at the same time presenting more reasons for concern than celebration. We reviewed various documents and data files and found that incidence and mortality rates for all cancer sites combined remain higher than they were when the "war on cancer" was declared in 1971, despite very recent, modest decreases. The burden of the disease has risen from three million to nearly ten million people. Black Americans, men of all races, and other segments of the population disproportionately bear the burden of cancer. We also looked at data for malignant breast cancer and found that incidence rates increased 36% from 1973 to 2000, while mortality for all population groups combined declined slightly. Breast cancer mortality is 34% higher among black women than among white women, even though white women are generally more likely to get the disease. The $50 billion spent on the "war on cancer" over the last 33 years has yielded few gains. The NCI's resources must be refocused on preventing cancers we know how to prevent.

  5. Comparison of the ISU, NCI, MSM, and SPADE Methods for Estimating Usual Intake: A Simulation Study of Nutrients Consumed Daily.

    PubMed

    Laureano, Greice H C; Torman, Vanessa B L; Crispim, Sandra P; Dekkers, Arnold L M; Camey, Suzi A

    2016-03-15

    Various methods are available for estimating usual dietary intake distributions. Hence, there is a need for simulation studies to compare them. The methods Iowa State University (ISU), National Cancer Institute (NCI), Multiple Source Method (MSM) and Statistical Program to Assess Dietary Exposure (SPADE) were previously compared in another study, but some results were inconclusive due to the small number of replications used in the simulation. Seeking to overcome this limitation, the present study used 1000 simulated samples for 12 different scenarios to compare the accuracy of estimates yielded by the aforementioned methods. The focus is on scenarios that exhibited the most uncertainty in the conclusions of the mentioned study above, i.e., scenarios with small sample sizes, skewed intake distributions, and large ratios of the between- and within-person variances. Bias was used as a measure of accuracy. For scenarios with small sample sizes (n = 150), the ISU, MSM and SPADE methods generally achieved more accurate estimates than the NCI method, particularly for the 10th and 90th percentiles. The differences between methods became smaller with larger sample sizes (n = 300 and n = 500). With few exceptions, the methods were found to perform similarly.

  6. Pediatric Terminology

    Cancer.gov

    The National Institute of Child Health and Human Development (NICHD) is working with NCI Enterprise Vocabulary Services (EVS) to provide standardized terminology for coding pediatric clinical trials and other resea

  7. Time, Concentration, and pH-Dependent Transport and Uptake of Anthocyanins in a Human Gastric Epithelial (NCI-N87) Cell Line

    PubMed Central

    Atnip, Allison A.; Sigurdson, Gregory T.; Bomser, Joshua; Giusti, M. Mónica

    2017-01-01

    Anthocyanins are the largest class of water soluble plant pigments and a common part of the human diet. They may have many potential health benefits, including antioxidant, anti-inflammatory, anti-cancer, and cardioprotective activities. However, anthocyanin metabolism is not well understood. Studies suggest that anthocyanins absorption may occur in the stomach, in which the acidic pH favors anthocyanin stability. A gastric epithelial cell line (NCI-N87) has been used to study the behavior of anthocyanins at a pH range of 3.0–7.4. This work examines the effects of time (0–3 h), concentration (50–1500 µM), and pH (3.0, 5.0, 7.4) on the transport and uptake of anthocyanins using NCI-N87 cells. Anthocyanins were transported from the apical to basolateral side of NCI-N87 cells in time and dose dependent manners. Over the treatment time of 3 h the rate of transport increased, especially with higher anthocyanin concentrations. The non-linear rate of transport may suggest an active mechanism for the transport of anthocyanins across the NCI-N87 monolayer. At apical pH 3.0, higher anthocyanin transport was observed compared to pH 5.0 and 7.4. Reduced transport of anthocyanins was found to occur at apical pH 5.0. PMID:28218720

  8. Purine analogs sensitize the multidrug resistant cell line (NCI-H460/R) to doxorubicin and stimulate the cell growth inhibitory effect of verapamil.

    PubMed

    Pesić, Milica; Podolski, Ana; Rakić, Ljubisa; Ruzdijić, Sabera

    2010-08-01

    The resistant cell line NCI-H460/R and its counterpart NCI-H460 were used to investigate the ability of purine analogs to overcome multidrug resistance (MDR) that seriously limit the efficacy of lung cancer regimens with chemotherapeutic agents. Two purine analogs, sulfinosine (SF) and 8-Cl-cAMP, exerted dose-dependent effects on cell growth in both parental and resistant cell lines. They significantly decreased mdr1 expression in NCI-H460/R cells. Low concentrations (1 microM) of SF and 8-Cl-cAMP in combination with doxorubicin (DOX) exerted synergistic growth inhibition in both cell lines. Pretreatment with SF and 8-Cl-cAMP improved the sensitivity to DOX more than verapamil (VER), the standard modulator of MDR. The increased accumulation of DOX observed after the treatment with SF and 8-Cl-cAMP was consistent with the results obtained with VER. VER stimulated the effect of 8-Cl-cAMP on DOX cytotoxicity and mdr1 expression. Combinations of either SF or 8-Cl-cAMP with VER at clinically acceptable concentrations exhibited synergistic effects on cell growth inhibition in the resistant cell line. SF and 8-Cl-cAMP modulated MDR in NCI-H460/R cells, especially when applied before DOX administration. This feature, together with their ability to reverse MDR, renders the purine analogs (in combination with VER) as potential candidates for improving the clinical activity of existing lung cancer therapeutics.

  9. Lipid-soluble ginseng extract induces apoptosis and G0/G1 cell cycle arrest in NCI-H460 human lung cancer cells.

    PubMed

    Kang, Moo Rim; Kim, Hwan Mook; Kang, Jong Soon; Lee, Kiho; Lee, Sung Dong; Hyun, Dong-Hoon; In, Man-Jin; Park, Song-Kyu; Kim, Dong Chung

    2011-06-01

    This study was performed to elucidate the anticancer mechanism of a lipid-soluble ginseng extract (LSGE) by analyzing induction of apoptosis and arrest of cell cycle progression using the NCI-H460 human lung cancer cell line. Proliferation of NCI-H460 cells was potently inhibited by LSGE in a dose-dependent manner. The cell cycle arrest at the G0/G1 phase in NCI-H460 cells was induced by LSGE. The percentage of G0/G1 phase cells significantly increased, while that of S phase cells decreased after treatment with LSGE. The expression levels of cyclin-dependent kinase2 (CDK2), CDK4, CDK6, cyclin D3 and cyclin E related to G0/G1 cells progression were also altered by LSGE. In addition, LSGE-induced cell death occurred through apoptosis, which was accompanied by increasing the activity of caspases including caspase-8, caspase-9 and caspase-3. Consistent with enhancement of caspase activity, LSGE increased protein levels of cleaved caspase-3, caspase-8, caspase-9, and poly-ADP-ribose polymerase (PARP). These apoptotic effects of LSGE were inhibited by the pan-caspase inhibitor Z-VAD-fmk. These findings indicate that LSGE inhibits NCI-H460 human lung cancer cell growth by cell cycle arrest at the G0/G1 phase and induction of caspase-mediated apoptosis.

  10. An Aqueous Extract of Tuberaria lignosa Inhibits Cell Growth, Alters the Cell Cycle Profile, and Induces Apoptosis of NCI-H460 Tumor Cells.

    PubMed

    Pereira, Joana M; Lopes-Rodrigues, Vanessa; Xavier, Cristina P R; Lima, M João; Lima, Raquel T; Ferreira, Isabel C F R; Vasconcelos, M Helena

    2016-05-06

    Tuberaria lignosa (Sweet) Samp. is found in European regions, and has antioxidant properties due to its composition in ascorbic acid and phenolic compounds. Given its traditional use and antioxidant properties, the tumor cell growth inhibitory potential of aqueous extracts from T. lignosa (prepared by infusion and decoction) was investigated in three human tumor cell lines: MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), and HCT-15 (human colorectal adenocarcinoma). Both extracts inhibited the growth of these cell lines; the most potent one being the T. lignosa extract obtained by infusion in the NCI-H460 cells (GI50 of approximately 50 μg/mL). Further assays were carried out with this extract in NCI-H460 cells. At 100 μg/mL or 150 μg/mL it caused an increase in the percentage of cells in the G0/G1 phase and a decrease of cells in S phase of the cell cycle. Additionally, these concentrations caused an increase in the percentage of apoptotic cells. In agreement, a decrease in total poly (ADP-ribose) polymerase (PARP) and pro-caspase 3 levels was found. In conclusion, the T. lignosa extract obtained by infusion was more potent in NCI-H460 cells, altering the cell cycle progression and inducing apoptosis. This work highlights the importance of T. lignosa as a source of bioactive compounds with tumor cell growth inhibitory potential.

  11. Demethoxycurcumin-induced DNA Damage Decreases DNA Repair-associated Protein Expression Levels in NCI-H460 Human Lung Cancer Cells.

    PubMed

    Ko, Yang-Ching; Lien, Jin-Cherng; Liu, Hsin-Chung; Hsu, Shu-Chun; Lin, Hui-Yi; Chueh, Fu-Shin; Ji, Bin-Chuan; Yang, Mei-Due; Hsu, Wu-Huei; Chung, Jing-Gung

    2015-05-01

    Demethoxycurcumin (DMC) is a key component of Chinese medicine (Turmeric) and has been proven effective in killing various cancer cells. Its role in inducing cytotoxic effects in many cancer cells has been reported, but its role regarding DNA damage on lung cancer cells has not been studied in detail. In the present study, we demonstrated DMC-induced DNA damage and condensation in NCI-H460 cells by using the Comet assay and DAPI staining examinations, respectively. Western blotting indicated that DMC suppressed the protein levels associated with DNA damage and repair, such as 14-3-3σ (an important checkpoint keeper of DNA damage response), DNA repair proteins breast cancer 1, early onset (BRCA1), O6-methylguanine-DNA methyltransferase (MGMT), mediator of DNA damage checkpoint 1 (MDC1), and p53 (tumor suppressor protein). DMC activated phosphorylated p53 and p-H2A.X (phospho Ser140) in NCI-H460 cells. Furthermore, we used confocal laser systems microscopy to examine the protein translocation. The results showed that DMC promotes the translocation of p-p53 and p-H2A.X from the cytosol to the nuclei in NCI-H460 cells. Taken together, DMC induced DNA damage and affected DNA repair proteins in NCI-H460 cells in vitro.

  12. Integration of GC/EI-MS and GC/NCI-MS for simultaneous quantitative determination of opiates, amphetamines, MDMA, ketamine, and metabolites in human hair.

    PubMed

    Wu, Ya-Hsueh; Lin, Keh-Liang; Chen, Su-Chin; Chang, Yan-Zin

    2008-07-15

    In this paper, the possibility of using a multiple ionization mode approach of GC/MS was developed for the simultaneous hair testing of common drugs of abuse in Asia, including amphetamines (amphetamine, AP; methamphetamine, MA; methylenedioxy amphetamine, MDA; methylenedioxy methamphetamine, MDMA; methylenedioxy ethylamphetamine, MDEA), ketamine (ketamine, K; norketamine, NK), and opiates (morphine, MOR; codeine, COD; 6-acetylmorphine, 6-AM). This strategy integrated the characteristics of gas chromatography-mass spectrometry (GC-MS) using electron impact ionization (EI) and negative chemical ionization (NCI). Hair samples (25 mg) were washed, cut, and incubated overnight at 25 degrees C in methanol-trifluoroacetic acid (methanol-TFA). The samples were extracted by solid phase extraction (SPE) procedure, derivatized using heptafluorobutyric acid anhydride (HFBA) at 70 degrees C for 30 min, and the derivatives analyzed by GC-MS with EI and NCI. The limit of detection (LOD) with GC/EI-MS analysis obtained were 0.03 ng/mg for AP, MA, MDA, MDMA, and MDEA; 0.05 ng/mg for K, NK, MOR, and COD; and 0.08 ng/mg for 6-AM. The LOD of GC/NCI-MS analysis was much lower than GC/EI-MS analysis. The LOD obtained were 30 pg/mg for AP and MDA in GC/EI-MS and 2 pg/mg in GC/NCI-MS. Therefore, the sensitivity of AP and MDA in GC/NCI-MS was improved from 15-fold compared with EI. The sensitivity of AP, MA, MDA, MDMA, MDEA, MOR, and COD was improved from 15- to 60-fold compared with EI. In addition, the sensitivity of 6-AM increased 8-fold through selection of m/z 197 for the quantitative ion. Moreover, K and NK could dramatically improve their sensitivity at 200- and 2000-fold. The integration of GC/EI-MS and GC/NCI-MS can obtain the high sensitivity and complementary results of drugs of abuse in hair. Six hair samples from known drug abusers were examined by this new strategy. These results show that integrating the characteristics of GC/EI-MS and GC/NCI-MS were not only enhancement of

  13. Identification of four potential epigenetic modulators from the NCI structural diversity library using a cell-based assay.

    PubMed

    Best, Anne M; Chang, Jianjun; Dull, Angie B; Beutler, John A; Martinez, Elisabeth D

    2011-01-01

    Epigenetic pathways help control the expression of genes. In cancer and other diseases, aberrant silencing or overexpression of genes, such as those that control cell growth, can greatly contribute to pathogenesis. Access to these genes by the transcriptional machinery is largely mediated by chemical modifications of DNA or histones, which are controlled by epigenetic enzymes, making these enzymes attractive targets for drug discovery. Here we describe the characterization of a locus derepression assay, a fluorescence-based mammalian cellular system which was used to screen the NCI structural diversity library for novel epigenetic modulators using an automated imaging platform. Four structurally unique compounds were uncovered that, when further investigated, showed distinct activities. These compounds block the viability of lung cancer and melanoma cells, prevent cell cycle progression, and/or inhibit histone deacetylase activity, altering levels of cellular histone acetylation.

  14. Combined anticancer activity of osthole and cisplatin in NCI-H460 lung cancer cells in vitro.

    PubMed

    Xu, Xiao-Man; Zhang, Yi; Qu, Dan; Liu, Hong-Bo; Gu, Xiu; Jiao, Guang-Yu; Zhao, Li

    2013-03-01

    Drug combination therapies are common practice in the treatment of cancer. Cisplatin is the most active chemotherapeutic agent for lung cancer treatment. Osthole is a natural compound extracted from a number of medicinal plants. To determine whether osthole enhances the anticancer effect of cisplatin in human lung cancer, we treated NCI-H460 cells with osthole alone or in combination with cisplatin and evaluated cell growth and apoptosis using 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and fluorescence microscopy. The results showed that, in comparison with single agent treatment, the combination of osthole and cisplatin resulted in greater efficacy in growth inhibition and apoptosis induction. Western blot analysis revealed that the combination effect of osthole and cisplatin was due to regulation of the Bcl-2 family proteins. Findings of this investigation suggested that osthole combined with cisplatin is a potential clinical chemotherapeutic approach in human lung cancer.

  15. Alterations of DNA repair genes in the NCI-60 cell lines and their predictive value for anticancer drug activity

    PubMed Central

    Sousa, Fabricio G.; Matuo, Renata; Tang, Sai-Wen; Rajapakse, Vinodh N.; Luna, Augustin; Sander, Chris; Varma, Sudhir; Simon, Paul H.G.; Doroshow, James H.; Reinhold, William C.; Pommier, Yves

    2015-01-01

    Loss of function of DNA repair (DNAR) genes is associated with genomic instability and cancer predisposition; it also makes cancer cells reliant on a reduced set of DNAR pathways to resist DNA-targeted therapy, which remains the core of the anticancer armamentarium. Because the landscape of DNAR defects across numerous types of cancers and its relation with drug activity have not been systematically examined, we took advantage of the unique drug and genomic databases of the US National Cancer Institute cancer cell lines (the NCI-60) to characterize 260 DNAR genes with respect to deleterious mutations and expression down-regulation; 169 genes exhibited a total of 549 function-affecting alterations, with 39 of them scoring as putative knockouts across 31 cell lines. Those mutations were compared to tumor samples from 12 studies of The Cancer Genome Atlas (TCGA) and The Cancer Cell Line Encyclopedia (CCLE). Based on this compendium of alterations, we determined which DNAR genomic alterations predicted drug response for 20,195 compounds present in the NCI-60 drug database. Among 242 DNA damaging agents, 202 showed associations with at least one DNAR genomic signature. In addition to SLFN11, the Fanconi anemia-scaffolding gene SLX4 (FANCP/BTBD12) stood out among the genes most significantly related with DNA synthesis and topoisomerase inhibitors. Depletion and complementation experiments validated the causal relationship between SLX4 defects and sensitivity to raltitrexed and cytarabine in addition to camptothecin. Therefore, we propose new rational uses for existing anticancer drugs based on a comprehensive analysis of DNAR genomic parameters. PMID:25758781

  16. Synergistic effects of the purine analog sulfinosine and curcumin on the multidrug resistant human non-small cell lung carcinoma cell line (NCI-H460/R).

    PubMed

    Andjelkovic, Tijana; Pesic, Milica; Bankovic, Jasna; Tanic, Nikola; Markovic, Ivanka D; Ruzdijic, Sabera

    2008-07-01

    Multidrug resistance (MDR) is the main obstacle to a successful chemotherapy of lung cancer. We tested the potential of sulfinosine and curcumin, alone and in combination, for modulating MDR in the human resistant, non-small cell lung carcinoma cell line (NCI-H460/R). First, we determined the mutational status of the p53 gene in NCI-H460/R cells by PCR-SSCP and DNA sequencing and identified mutations which could at least partially contribute to the development of the MDR phenotype. The effects of sulfinosine and curcumin were studied, both separately and in combination, at the level of cytotoxicity, cell cycle distribution and gene expression. Sulfinosine displayed dose-dependent growth inhibition in both resistant and control sensitive cell lines, whereas curcumin considerably inhibited their growth only at relatively high doses. When sulfinosine was combined with a low dose of curcumin the drugs exerted a synergistic cytotoxic effect in NCI-H460/R cells. The expression of MDR-related genes mdr1, gst-pi and topo IIalpha, was altered by sulfinosine and curcumin. The most pronounced effect was observed when the agents were applied together. Sulfinosine and curcumin caused perturbations in cell cycle distribution in the NCI-H460/R cell line. The combination of the two drugs induced a more pronounced cell cycle arrest in S and G(2)/M in NCI-H460/R cells. Our results show that sulfinosine and curcumin overcome MDR in non-small cell lung carcinoma cell line (NSCLC), especially in combination despite the presence of a mutated p53 gene.

  17. NHLBI: A Partner in School Health Education.

    ERIC Educational Resources Information Center

    Jacobs, Jane A.

    1982-01-01

    The National Heart, Lung, and Blood Institute, a federal biomedical research agency, contributes to school health education by means of information dissemination and cooperation with schools and other agencies to apply research findings to health education programs. (CJ)

  18. Non-small-cell lung cancer cell lines A549 and NCI-H460 express hypoxanthine guanine phosphoribosyltransferase on the plasma membrane

    PubMed Central

    Townsend, Michelle H; Anderson, Michael D; Weagel, Evita G; Velazquez, Edwin J; Weber, K Scott; Robison, Richard A; O’Neill, Kim L

    2017-01-01

    In both males and females, lung cancer is one of the most lethal cancers worldwide and accounts for >30% of cancer-related deaths. Despite advances in biomarker analysis and tumor characterization, there remains a need to find suitable biomarker antigen targets for treatment in late-stage lung cancer. Previous research on the salvage pathway enzyme TK1 shows a unique relationship with cancer patients as serum levels are raised according to cancer grade. To expand this analysis, the other salvage pathway enzymes were evaluated for possible upregulation within lung cancer. Adenine phosphoribosyltransferase, deoxycytidine kinase, and hypoxanthine guanine phosphoribosyltransferase (HPRT) were assessed for their presentation on two non-small-cell lung cancer cell lines NCI-H460 and A549. In the present study, we show that deoxycytidine kinase and adenine phosphoribosyltransferase have no significant relationship with the membrane of NCI-H460 cells. However, we found significant localization of HPRT to the membrane of NCI-H460 and A549 cells. When treated with anti-HPRT antibodies, the average fluorescence of the cell population increased by 24.3% and 12.9% in NCI-H460 and A549 cells, respectively, in comparison with controls. To ensure that expression was not attributed to cytoplasmic HPRT, confocal microscopy was performed to visualize HPRT binding on the plasma membrane. After staining NCI-H460 cells treated with both fluorescent antibodies and a membrane-specific dye, we observed direct overlap between HPRT and the membrane of the cancer cells. Additionally, gold-conjugated antibodies were used to label and quantify the amount of HPRT on the cell surface using scanning electron microscopy and energy-dispersive analysis X-ray. Further confirming HPRT presence, the gold weight percentage of the sample increased significantly when NCI-H460 cells were exposed to HPRT antibody (P=0.012) in comparison with isotype controls. Our results show that HPRT is localized on the

  19. MO-E-BRF-01: Research Opportunities in Technology for Innovation in Radiation Oncology (Highlight of ASTRO NCI 2013 Workshop)

    SciTech Connect

    Hahn, S; Jaffray, D; Chetty, I; Benedict, S

    2014-06-15

    Radiotherapy is one of the most effective treatments for solid tumors, in large part due to significant technological advances associated with, for instance, the ability to target tumors to very high levels of accuracy (within millimeters). Technological advances have played a central role in the success of radiation therapy as an oncologic treatment option for patients. ASTRO, AAPM and NCI sponsored a workshop “Technology for Innovation in Radiation Oncology” at the NCI campus in Bethesda, MD on June 13–14, 2013. The purpose of this workshop was to bring together expert clinicians and scientists to discuss the role of disruptive technologies in radiation oncology, in particular with regard to how they are being developed and translated to clinical practice in the face of current and future challenges and opportunities. The technologies discussed encompassed imaging and delivery aspects, along with methods to enable/facilitate application of them in the clinic. Measures for assessment of the performance of these technologies, such as techniques to validate quantitative imaging, were reviewed. Novel delivery technologies, incorporating efficient and safe delivery mechanisms enabled by development of tools for process automation and the associated field of oncology informatics formed one of the central themes of the workshop. The discussion on disruptive technologies was grounded in the need for evidence of efficacy. Scientists in the areas of technology assessment and bioinformatics provided expert views on different approaches toward evaluation of technology efficacy. Clinicians well versed in clinical trials incorporating disruptive technologies (e.g. SBRT for early stage lung cancer) discussed the important role of these technologies in significantly improving local tumor control and survival for these cohorts of patients. Recommendations summary focused on the opportunities associated with translating the technologies into the clinic and assessing their

  20. Demethoxycurcumin induces the apoptosis of human lung cancer NCI-H460 cells through the mitochondrial-dependent pathway.

    PubMed

    Ko, Yang-Ching; Lien, Jin-Cherng; Liu, Hsin-Chung; Hsu, Shu-Chun; Ji, Bin-Chuan; Yang, Mei-Due; Hsu, Wu-Huei; Chung, Jing-Gung

    2015-05-01

    Lung cancer is the most common cause of cancer-related mortality in the US as well as other regions of the world. Curcumin, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) are the major components of Curcuma longa L. It has been reported that curcumin inhibits the growth of various types of cancer cells in vitro and in vivo. However, the mechanisms involved in the inhibition of cell growth and induced apoptosis by DMC in human lung cancer cells remain unclear. In the present study, we investigated the effect of DMC on cell death via the induction of apoptosis in NCI-H460 human lung cancer cells. Flow cytometric assay was used to examine the total percentage of viable cells, the population of cells in the sub-G1 phase of the cell cycle, the level of reactive oxygen species (ROS), Ca²⁺ production, mitochondrial membrane potential (ΔΨm) and caspase activity. Western blotting was used to examine the changes in the expression of cell cycle- and apoptosis-associated proteins. Confocal microscopy was used to examine the translocation of apoptosis-associated proteins. The results indicated that DMC significantly induced cell morphological changes and decreased the percentage of viable NCI-H460 cells and DMC induced apoptosis based on the cell distribution in the sub-G1 phase. Moreover, DMC promoted ROS and Ca²⁺ production and decreased the level of ΔΨm and promoted the activities of caspase-3, -8 and -9. The Western blotting results showed that DMC promoted the expression of AIF, Endo G and PARP. The levels of Fas ligand (Fas L) and Fas were also upregulated. Furthermore, DMC promoted expression of ER stress-associated proteins such as GRP78, GADD153, IRE1β, ATF-6α, ATF-6β and caspase-4. Based on the findings, we suggest that DMC may be used as a novel anticancer agent for the treatment of lung cancer in the future.

  1. P30 Cancer Center Support Grant Administrative Supplements to NCI-designated Cancer Centers not affiliated with the Experimental Therapeutics Clinical Trials Network (ETCTN) to support participation in the ETCTN

    Cancer.gov

    P30 Cancer Center Support Grant Administrative Supplements to NCI-designated Cancer Centers not affiliated with the Experimental Therapeutics Clinical Trials Network (ETCTN) to support participation in the ETCTN

  2. Complex modes of bonding: NCI/ELI-D vs. DORI surface analyses of hapticities and hydrogen-hydrogen contacts in zincocene related compounds

    NASA Astrophysics Data System (ADS)

    Mebs, Stefan

    2016-05-01

    Atoms-in-molecules (AIM) topology is prone to wrong/ambiguous bond assignments (lacking bond critical points) in areas of low electron densities (ED), e.g. for hydrogen-hydrogen contacts, and flat density gradients, e.g. for metal-ring contacts (hapticities), both in experimental and computed ED. Within this study, two ED-derived bonding indicators are applied to a set of zincocene related compounds: non-covalent interactions (NCI) surfaces are combined with electron localizability indicator (ELI-D) surfaces and compared to density overlap regions indicator (DORI) surfaces. Both methods (NCI/ELI-D, DORI) result in spatial deconvolution of covalent and non-covalent interactions and unravel weak interactions not observed in the AIM topology.

  3. Anticancer activity of SAHA, a potent histone deacetylase inhibitor, in NCI-H460 human large-cell lung carcinoma cells in vitro and in vivo.

    PubMed

    Zhao, Yanxia; Yu, Dandan; Wu, Hongge; Liu, Hongli; Zhou, Hongxia; Gu, Runxia; Zhang, Ruiguang; Zhang, Sheng; Wu, Gang

    2014-02-01

    Suberoylanilide hydroxamic acid (SAHA), a potent pan-histone deacetylase (HDAC) inhibitor, has been clinically approved for the treatment of cutaneous T-cell lymphoma (CTCL). SAHA has also been shown to exert a variety of anticancer activities in many other types of tumors, however, few studies have been reported in large-cell lung carcinoma (LCC). Our study aimed to investigate the potential antitumor effects of SAHA on LCC cells. Here, we report that SAHA was able to inhibit the proliferation of the LCC cell line NCI-H460 in a dose- and time-dependent manner, induced cell apoptosis and G2/M cell cycle arrest, decreased AKT and ERK phosphorylation, inhibited the expression of pro-angiogenic factors (VEGF, HIF-1α) in vitro, and suppressed tumor progression in an NCI-H460 cell nude mouse xenograft model in vivo. These results indicate that SAHA can exert its strong antitumor effects in LCC patient.

  4. TBMS1 exerts its cytotoxicity in NCI-H460 lung cancer cells through nucleolar stress-induced p53/MDM2-dependent mechanism, a quantitative proteomics study.

    PubMed

    Lin, Yingying; Xie, Guobin; Xia, Ji; Su, Dan; Liu, Jie; Jiang, Fuquan; Xu, Yang

    2016-02-01

    Tubeimoside-1 (TBMS1) exerts its anticancer effects by inducing G2/M arrest and apoptosis of cancer cells. However, the precise molecular mechanism of its anti-tumor effects has not been fully elucidated, especially the signaling pathways involved in the early stage of TBMS1 stimulation. In this study, we employed stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics approach and identified 439 proteins that exhibit significant differential expressions in NCI-H460 lung cancer cells upon exposure to TBMS1. Gene ontology and network analysis using DAVID and STRING on-line tools revealed that several nucleolar stress (ribosomal biogenesis) response proteins were differentially regulated by TBMS1. Functional validation demonstrated that TBMS1-induced NCI-H460 cell cytotoxicity involved nucleolar stress-induced p53/murine double minute clone 2 (MDM2), mTOR, and NF-κB signaling pathways.

  5. Cantharidin Impairs Cell Migration and Invasion of Human Lung Cancer NCI-H460 Cells via UPA and MAPK Signaling Pathways.

    PubMed

    Hsia, Te-Chun; Yu, Chien-Chih; Hsiao, Yung-Ting; Wu, Shin-Hwar; Bau, DA-Tian; Lu, Hsu-Feng; Huang, Yi-Ping; Lin, Jaung-Geng; Chang, Shu-Jen; Chung, Jing-Gung

    2016-11-01

    Cantharidin (CTD), a component of natural mylabris (Mylabris phalerata Pallas), has been shown to have biological activities and induce cell death in many human cancer cells. In the present study, we investigated the effect of CTD on cell migration and invasion of NCI-H460 human lung cancer cells. Cell viability was examined and results indicated that CTD decreased the percentage of viable cells in dose-dependent manners. CTD inhibited cell migration and invasion in dose-dependent manners. Gelatin zymography analysis was used to measure the activities of matrix metalloproteinases (MMP-2/-9) and the results indicated that CTD inhibited the enzymatic activities of MMP-2/-9 of NCI-H460 cells. Western blotting was used to examine the protein expression of NCI-H460 cells after incubation with CTD and the results showed that CTD decreased the expression of MMP-2/-9, focal adhesion kinase (FAK), Ras homolog gene family, member A (Rho A), phospho-protein kinase B (AKT) (Thr308)(p-AKT(308)), phospho-extracellular signal-regulated kinase1/2 (p-ERK1/2), phospho-p38 mitogen-activated protein (MAP) kinase (p-p38), phospho c-Jun N-terminal kinase 1/2 (p-JNK1/2), nuclear factor-κB (NF-κB) and urokinase plasminogen activator (UPA). Furthermore, confocal laser microscopy was used to confirm that CTD suppressed the expression of NF-κB p65, but did not significantly affect protein kinase C (PKC) translocation in NCI-H460 cells. Based on those observations, we suggest that CTD may be used as a novel anticancer metastasis agent for lung cancer in the future.

  6. Analysis Plan: Study to Measure the Cost of CHAMPUS-Eligible Participants in Southwest Oncology Group NCI Cooperative Program Cancer Clinical Trials 1988-1996: Technical Report No. 1.

    DTIC Science & Technology

    2007-11-02

    The National Cancer Institute’s Division of Cancer Treatment , Diagnosis, and Centers (DCTDC) has initiated effort to expand clinical trial...Defense (DOD) to allow patients who are beneficiaries of TRICAKE/CHAMPUS to participate in, and be reimbursed for, NCI-sponsored clinical cancer ... treatment trials. This study is a cancer demonstration project pilot study to evaluate the potential cost impact of the NCI/DOD agreement. The initial

  7. Decursin in Angelica gigas Nakai (AGN) Enhances Doxorubicin Chemosensitivity in NCI/ADR-RES Ovarian Cancer Cells via Inhibition of P-glycoprotein Expression.

    PubMed

    Choi, Hyeong Sim; Cho, Sung-Gook; Kim, Min Kyoung; Kim, Min Soo; Moon, Seung Hee; Kim, Il Hwan; Ko, Seong-Gyu

    2016-12-01

    Angelica gigas Nakai (AGN, Korean Dang-gui) is traditionally used for the treatment of various diseases including cancer. Here, we investigated multidrug-resistant phenotype-reversal activities of AGN and its compounds (decursin, ferulic acid, and nodakenin) in doxorubicin-resistant NCI/ADR-RES ovarian cancer cells. Our results showed that a combination of doxorubicin with either AGN or decursin inhibited a proliferation of NCI/ADR-RES cells. These combinations increased the number of cells at sub-G1 phase when cells were stained with Annexin V-fluorescein isothiocyanate. We also found that these combinations activated caspase-9, caspase-8, and caspase-3 and increased cleaved PARP level. Moreover, an inhibition of P-glycoprotein expression by either AGN or decursin resulted in a reduction of its activity in NCI/ADR-RES cells. Therefore, our data demonstrate that decursin in AGN inhibits doxorubicin-resistant ovarian cancer cell proliferation and induces apoptosis in the presence of doxorubicin via blocking P-glycoprotein expression. Therefore, AGN would be a potentially novel treatment option for multidrug-resistant tumors by sensitizing to anticancer agents. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Cytotoxic Activities of Physalis minima L. Chloroform Extract on Human Lung Adenocarcinoma NCI-H23 Cell Lines by Induction of Apoptosis

    PubMed Central

    Leong, Ooi Kheng; Muhammad, Tengku Sifzizul Tengku; Sulaiman, Shaida Fariza

    2011-01-01

    Physalis minima L. is reputed for having anticancer property. In this study, the chloroform extract of this plant exhibited remarkable cytotoxic activities on NCI-H23 (human lung adenocarcinoma) cell line at dose- and time-dependent manners (after 24, 48 and 72 h of incubation). Analysis of cell-death mechanism demonstrated that the extract exerted apoptotic programed cell death in NCI-H23 cells with typical DNA fragmentation, which is a biochemical hallmark of apoptosis. Morphological observation using transmission electron microscope (TEM) also displayed apoptotic characteristics in the treated cells, including clumping and margination of chromatins, followed by convolution of the nuclear and budding of the cells to produce membrane-bound apoptotic bodies. Different stages of apoptotic programed cell death as well as phosphatidylserine externalization were confirmed using annexin V and propidium iodide staining. Furthermore, acute exposure to the extract produced a significant regulation of c-myc, caspase-3 and p53 mRNA expression in this cell line. Due to its apoptotic effect on NCI-H23 cells, it is strongly suggested that the extract could be further developed as an anticancer drug. PMID:19541726

  9. Comparison of HeLa-I, HEp-2 and NCI-H292 cell lines for the isolation of human respiratory syncytial virus (HRSV).

    PubMed

    Perini, Ana Priscila; Barbosa, Maria Luisa; Botosso, Viviane Fongaro; de Moraes, Claudia Trigo Pedroso; Gillio, Alfredo E; Hens, Noeli; Stewien, Klaus E; Durigon, Edison L

    2007-12-01

    Generally, laboratory diagnosis of viral respiratory infections utilizes virus isolation in cell culture and immunofluorescence assays. In this study, three cell lines (HEp-2, NCI-H292 and HeLa-I) were used for HRSV isolation of strains obtained from patients admitted at HU-USP with respiratory tract disease. HRSV was isolated in 46% (37) of 80 specimens inoculated in HeLa-I, 48% (39) in HEp-2, and 36.3% (29) in NCI-H292. Immunofluorescence was considered the gold standard and yielded 53% positive (43). The results from both methods combined had better sensitivity (73.2%) compared to either method alone. Comparing results between the cell lines with HEp-2 cells as the benchmark, the greatest sensitivity (72.2%) was observed in HeLa-I. This data shows that HeLa-I is adequate for HRSV isolation, giving results similar to the HEp-2 cells. The combined use of the HEp-2, HeLa-I and NCI-H292 cells improve the detection of HRSV.

  10. Cytotoxic Activities of Physalis minima L. Chloroform Extract on Human Lung Adenocarcinoma NCI-H23 Cell Lines by Induction of Apoptosis.

    PubMed

    Leong, Ooi Kheng; Muhammad, Tengku Sifzizul Tengku; Sulaiman, Shaida Fariza

    2011-01-01

    Physalis minima L. is reputed for having anticancer property. In this study, the chloroform extract of this plant exhibited remarkable cytotoxic activities on NCI-H23 (human lung adenocarcinoma) cell line at dose- and time-dependent manners (after 24, 48 and 72 h of incubation). Analysis of cell-death mechanism demonstrated that the extract exerted apoptotic programed cell death in NCI-H23 cells with typical DNA fragmentation, which is a biochemical hallmark of apoptosis. Morphological observation using transmission electron microscope (TEM) also displayed apoptotic characteristics in the treated cells, including clumping and margination of chromatins, followed by convolution of the nuclear and budding of the cells to produce membrane-bound apoptotic bodies. Different stages of apoptotic programed cell death as well as phosphatidylserine externalization were confirmed using annexin V and propidium iodide staining. Furthermore, acute exposure to the extract produced a significant regulation of c-myc, caspase-3 and p53 mRNA expression in this cell line. Due to its apoptotic effect on NCI-H23 cells, it is strongly suggested that the extract could be further developed as an anticancer drug.

  11. Role of autophagy in apoptosis induction by methylene chloride extracts of Mori cortex in NCI-H460 human lung carcinoma cells.

    PubMed

    Park, Shin-Hyung; Chi, Gyoo Yong; Eom, Hyun Sup; Kim, Gi-Young; Hyun, Jin Won; Kim, Wun-Jae; Lee, Su-Jae; Yoo, Young Hyun; Choi, Yung Hyun

    2012-06-01

    The root of Mori cortex has traditionally been used in Korea for the treatment of cutaneous inflammation, pulmonary asthma, and congestion for thousands of years. The present study was designed to validate the anticancer effects of methylene chloride extracts of the M. cortex root (MEMC) in NCI-H460 human lung carcinoma cells. Exposure to MEMC was found to result in growth inhibition by the induction of caspase‑dependent apoptosis in NCI-H460 cells, which correlated with upregulated expression of death receptor (DR)4, DR5 and FasL, downregulation of anti-apoptotic Bcl-2 and Bcl-xL expression, cleavage of Bid, and loss of mitochondrial membrane potential. In addition, autophagosomes, a characteristic finding of autophagy, and markers of autophagy, conversion of microtubule-associated protein light chain-3 (LC3)-I to LC3-II and increased beclin-1 accumulation, were observed in MEMC-treated NCI-H460 cells. Inhibition of autophagy by 3-methyladenine or LC3B small interfering (siRNA) resulted in enhanced apoptotic cell death, suggesting that MEMC-induced autophagy functions as a suppressor of apoptosis. MEMC-induced autophagy was also blocked by N-acetyl-cysteine (NAC) and catalase, indicating that H2O2 can regulate autophagy. Our data demonstrate that MEMC triggers both ROS-mediated autophagy and caspase-dependent apoptosis, and that autophagy plays a protective role against apoptotic cell death.

  12. Synergistic anti-tumor effects of the combination of a benzofuroxan derivate and sorafenib on NCI-H460 human large cell lung carcinoma cells.

    PubMed

    Teixeira, Sarah Fernandes; Alexandre de Azevedo, Ricardo; Salomon, Maria Alejandra Clavijo; Jorge, Salomão Dória; Levy, Débora; Bydlowski, Sérgio Paulo; Rodrigues, Cecília Pessoa; Pizzo, Célia Regina; Barbuto, José Alexandre Marzagão; Ferreira, Adilson Kleber

    2014-10-01

    Lung cancer is the most frequent and lethal human cancer in the world. Because is still an unsolved health issue, new compounds or therapeutic strategies are urgently needed. Furoxans are presented as potentials candidates for lung cancer treatment. Accordingly, we evaluated the efficacy of a benzofuroxan derivative, BFD-22, alone and combined with sorafenib against NCI-H460 cell line. We showed that BFD-22 has cytotoxic effects on the NCI-H460 cells. Importantly, the Combination Index (CI) evaluation revels that BFD-22 combined with sorafenib has a stronger cytotoxic effect. In addition, the combination induces apoptosis through extrinsic pathway, leading to TRAIL-R1/DR4-triggered apoptosis. Furthermore, BFD-22 combined with sorafenib increases ROS production and simultaneously reduces perlecan expression in the NCI-H460 cells. In accordance, tumor cells were arrested in the S-phase, and these anti-proliferative effects also inhibit cell migration. This is the first study reporting an advantage of BFD-22 combined with sorafenib as a new therapeutic strategy in the fight against lung cancer.

  13. Induction of DNA damage by deguelin is mediated through reducing DNA repair genes in human non-small cell lung cancer NCI-H460 cells.

    PubMed

    Ji, Bin-Chuan; Yu, Chien-Chih; Yang, Su-Tso; Hsia, Te-Chun; Yang, Jai-Sing; Lai, Kuang-Chi; Ko, Yang-Ching; Lin, Jen-Jyh; Lai, Tung-Yuan; Chung, Jing-Gung

    2012-04-01

    It has been shown that deguelin, one of the compounds of rotenoids from flavonoid family, induced cytotoxic effects through induction of cell cycle arrest and apoptosis in many types of human cancer cell lines, but deguelin-affected DNA damage and repair gene expression (mRNA) are not clarified yet. We investigated the effects of deguelin on DNA damage and associated gene expression in human lung cancer NCI-H460 cells in vitro. DNA damage was assayed by using the comet assay and DNA gel electrophoresis and the results indicated that NCI-H460 cells treated with 0, 50, 250 and 500 nM deguelin led to a longer DNA migration smear based on the single cell electrophoresis and DNA fragmentation occurred based on the examination of DNA gel electrophoresis. DNA damage and repair gene expression (mRNA) were evaluated by using real-time PCR assay and the results indicated that 50 and 250 nM deguelin for a 24-h exposure in NCI-H460 cells, decreased the gene levels of breast cancer 1, early onset (BRCA1), DNA-dependent serine/threonine protein kinase (DNA-PK), O6-methylguanine-DNA methyltransferase (MGMT), p53, ataxia telangiectasia mutated (ATM) and ataxia-telangiectasia and Rad3-related (ATR) mRNA expressions. Collectively, the present study showed that deguelin caused DNA damage and inhibited DNA damage and repair gene expressions, which might be due to deguelin-inhibited cell growth in vitro.

  14. Facilitating informed decision making about breast cancer risk and genetic counseling among women calling the NCI's Cancer Information Service.

    PubMed

    Miller, Suzanne M; Fleisher, Linda; Roussi, Pagona; Buzaglo, Joanne S; Schnoll, Robert; Slater, Elyse; Raysor, Susan; Popa-Mabe, Melania

    2005-01-01

    Despite increased interest among the public in breast cancer genetic risk and genetic testing, there are limited services to help women make informed decisions about genetic testing. This study, conducted with female callers (N = 279) to the National Cancer Institute's (NCI's) Atlantic Region Cancer Information Service (CIS), developed and evaluated a theory-based, educational intervention designed to increase callers' understanding of the following: (a) the kinds of information required to determine inherited risk; (b) their own personal family history of cancer; and (c) the benefits and limitations of genetic testing. Callers requesting information about breast/ovarian cancer risk, risk assessment services, and genetic testing were randomized to either: (1) standard care or (2) an educational intervention. Results show that the educational intervention reduced intention to obtain genetic testing among women at average risk and increased intention among high-risk women at 6 months. In addition, high monitors, who typically attend to and seek information, demonstrated greater increases in knowledge and perceived risk over the 6-month interval than low monitors, who typically are distracted from information. These findings suggest that theoretically designed interventions can be effective in helping women understand their cancer risk and appropriate risk assessment options and can be implemented successfully within a service program like the CIS.

  15. Proteomic profiling of NCI-60 extracellular vesicles uncovers common protein cargo and cancer type-specific biomarkers

    PubMed Central

    Liu, Xia; Singh, Rakesh K.; Meckes, David G.

    2016-01-01

    Packed with biological information, extracellular vesicles (EVs) offer exciting promise for biomarker discovery and applications in therapeutics and non-invasive diagnostics. Currently, our understanding of EV contents is confined by the limited cells from which vesicles have been characterized utilizing the same enrichment method. Using sixty cell lines from the National Cancer Institute (NCI-60), here we provide the largest proteomic profile of EVs in a single study, identifying 6,071 proteins with 213 common to all isolates. Proteins included established EV markers, and vesicular trafficking proteins such as Rab GTPases and tetraspanins. Differentially-expressed proteins offer potential for cancer diagnosis and prognosis. Network analysis of vesicle quantity and proteomes identified EV components associated with vesicle secretion, including CD81, CD63, syntenin-1, VAMP3, Rab GTPases, and integrins. Integration of vesicle proteomes with whole-cell molecular profiles revealed similarities, suggesting EVs provide a reliable reflection of their progenitor cell content, and are therefore excellent indicators of disease. PMID:27894104

  16. Drug Transporter Protein Quantification of Immortalized Human Lung Cell Lines Derived from Tracheobronchial Epithelial Cells (Calu-3 and BEAS2-B), Bronchiolar-Alveolar Cells (NCI-H292 and NCI-H441), and Alveolar Type II-like Cells (A549) by Liquid Chromatography-Tandem Mass Spectrometry.

    PubMed

    Sakamoto, Atsushi; Matsumaru, Takehisa; Yamamura, Norio; Suzuki, Shinobu; Uchida, Yasuo; Tachikawa, Masanori; Terasaki, Tetsuya

    2015-09-01

    Understanding the mechanisms of drug transport in the human lung is an important issue in pulmonary drug discovery and development. For this purpose, there is an increasing interest in immortalized lung cell lines as alternatives to primary cultured lung cells. We recently reported the protein expression in human lung tissues and pulmonary epithelial cells in primary culture, (Sakamoto A, Matsumaru T, Yamamura N, Uchida Y, Tachikawa M, Ohtsuki S, Terasaki T. 2013. J Pharm Sci 102(9):3395-3406) whereas comprehensive quantification of protein expressions in immortalized lung cell lines is sparse. Therefore, the aim of the present study was to clarify the drug transporter protein expression of five commercially available immortalized lung cell lines derived from tracheobronchial cells (Calu-3 and BEAS2-B), bronchiolar-alveolar cells (NCI-H292 and NCI-H441), and alveolar type II cells (A549), by liquid chromatography-tandem mass spectrometry-based approaches. Among transporters detected, breast cancer-resistance protein in Calu-3, NCI-H292, NCI-H441, and A549 and OCTN2 in BEAS2-B showed the highest protein expression. Compared with data from our previous study,(Sakamoto A, Matsumaru T, Yamamura N, Uchida Y, Tachikawa M, Ohtsuki S, Terasaki T. 2013. J Pharm Sci 102(9):3395-3406) NCI-H441 was the most similar with primary lung cells from all regions in terms of protein expression of organic cation/carnitine transporter 1 (OCTN1). In conclusion, the protein expression profiles of transporters in five immortalized lung cell lines were determined, and these findings may contribute to a better understanding of drug transport in immortalized lung cell lines.

  17. Spatial-temporal analysis of non-Hodgkin lymphoma in the NCI-SEER NHL case-control study

    PubMed Central

    2011-01-01

    Background Exploring spatial-temporal patterns of disease incidence through cluster analysis identifies areas of significantly elevated or decreased risk, providing potential clues about disease risk factors. Little is known about the etiology of non-Hodgkin lymphoma (NHL), or the latency period that might be relevant for environmental exposures, and there are no published spatial-temporal cluster studies of NHL. Methods We conducted a population-based case-control study of NHL in four National Cancer Institute (NCI)-Surveillance, Epidemiology, and End Results (SEER) centers: Detroit, Iowa, Los Angeles, and Seattle during 1998-2000. Using 20-year residential histories, we used generalized additive models adjusted for known risk factors to model spatially the probability that an individual had NHL and to identify clusters of elevated or decreased NHL risk. We evaluated models at five different time periods to explore the presence of clusters in a time frame of etiologic relevance. Results The best model fit was for residential locations 20 years prior to diagnosis in Detroit, Iowa, and Los Angeles. We found statistically significant areas of elevated risk of NHL in three of the four study areas (Detroit, Iowa, and Los Angeles) at a lag time of 20 years. The two areas of significantly elevated risk in the Los Angeles study area were detected only at a time lag of 20 years. Clusters in Detroit and Iowa were detected at several time points. Conclusions We found significant spatial clusters of NHL after allowing for disease latency and residential mobility. Our results show the importance of evaluating residential histories when studying spatial patterns of cancer. PMID:21718483

  18. Impact of the 2010 Consensus Recommendations of the Clinical Trial Design Task Force of the NCI Investigational Drug Steering Committee.

    PubMed

    Seymour, Lesley; Groshen, Susan; Rosner, Gary L; Sullivan, Daniel M; Spriggs, David R; Reeves, Steven; Gravell, Amy; Ivy, S Percy; Ratain, Mark J

    2015-11-15

    Oncology phase III trials have a high failure rate, leading to high development costs. The Clinical Trials Design Task Force of the Investigational Drug Steering Committee of the NCI Cancer Therapy and Evaluation Program developed Recommendations regarding the design of phase II trials. We report here on the results of a Concordance Group review charged with documenting whether concordance rates improved after the publication of the Recommendations. One hundred and fifty-five trials were reviewed. Letter of Intents (LOI) from the post-Recommendation period were more likely to be randomized (44% vs. 34%) and biomarker selected (19% vs. 10%). Single-arm studies using time-to-event endpoints (benchmarked against historical data) were similar, as was the type of tumor. There was a significant improvement in the rate of concordance, with 74% of LOIs scored as concordant compared with 58% before the Recommendations (P = 0.042). This included a marked decrease in the use of single-arm designs to evaluate the activity of drug combinations (19% vs. 5%, P = 0.009). There were areas for which clarification was warranted, including the need for protocols to include further development plans, the use of realistic benchmarks, the careful evaluation of historical controls, and the use of a standard treatment option as a control. Ongoing critical evaluation of current trial design methodology and the development of new Guidelines when appropriate will continue to improve drug development ensuring that safe and effective cancer therapeutics are made available to our patients as quickly and efficiently as possible.

  19. Inhibition of protein kinase C α/βII and activation of c-Jun NH2-terminal kinase mediate glycyrrhetinic acid induced apoptosis in non-small cell lung cancer NCI-H460 cells.

    PubMed

    Song, Junho; Ko, Hyun-suk; Sohn, Eun Jung; Kim, Bonglee; Kim, Jung Hyo; Kim, Hee Jeong; Kim, Chulwoo; Kim, Jai-eun; Kim, Sung-Hoon

    2014-02-15

    Though glycyrrhetinic acid (GA) from Glycyrrhiza glabra was known to exert antioxidant, antifilarial, hepatoprotective, anti-inflammatory and anti-tumor effects, the antitumor mechanism of GA was not clearly elucidated in non-small cell lung cancer cells (NSCLCCs). Thus, in the present study, the underlying apoptotic mechanism of GA was examined in NCI-H460 NSCLCCs. GA significantly suppressed the viability of NCI-H460 and A549 non-small lung cancer cells. Also, GA significantly increased the sub G1 population by cell cycle analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells in a concentration dependent manner in NCI-H460 non-small lung cancer cells. Consistently, GA cleaved poly (ADP-ribosyl) polymerase (PARP), caspase 9/3, attenuated the expression of Bcl-XL, Bcl-2, Cyclin D1 and Cyclin E in NCI-H460 cells. Interestingly, GA attenuated the phosphorylation of protein kinase C (PKC) α/βII and extracellular activated protein kinase (ERK) as well as activated the phosphorylation of PKC δ and c-Jun NH2-terminal kinase in NCI-H460 cells. Conversely, PKC promoter phorbol 12-myristate 13-acetate (PMA) and JNK inhibitor SP600125 reversed the cleavages of caspase 3 and PARP induced by GA in NCI-H460 cells. Overall, our findings suggest that GA induces apoptosis via inhibition of PKC α/βII and activation of JNK in NCI-H460 non-small lung cancer cells as a potent anticancer candidate for lung cancer treatment.

  20. Estradiol and progesterone-mediated regulation of P-gp in P-gp overexpressing cells (NCI-ADR-RES) and placental cells (JAR).

    PubMed

    Coles, Lisa D; Lee, Insong J; Voulalas, Pamela J; Eddington, Natalie D

    2009-01-01

    The effect of progesterone and estrogen treatment on the expression and function of P-glycoprotein (P-gp) was evaluated in JAR cells and a P-gp overexpressing cell line, NCI-ADR-RES. Western blot analysis and real-time Q-PCR were used to evaluate P-gp protein and MDR1 mRNA expression respectively in the cells following incubation with progesterone (P4) and/or beta-estradiol (E2). Cellular uptake studies of the P-gp substrates, saquinavir and paclitaxel, were performed to evaluate function. Treatment with either E2 or P4 resulted in a significant increase in P-gp protein levels in the NCI-ADR-RES cells at concentrations of or greater than 100 nM or 10 nM, respectively. JAR cells also had increased levels of P-gp with 100 nM of P4 but were much more sensitive to E2 showing increased P-gp at a concentration of 1 nM. Furthermore, E2 or P4 treatment resulted in a significant decrease in cellular uptake of the P-gp substrates tested in these cells lines. Based on mRNA quantitation, a transient increase (2-fold) in MDR1 levels was observed at 8 h postincubation with either E2 or P4, while MDR1 levels remained high in the JAR cells treated with E2 for 72 h postincubation. The addition of actinomycin D, a transcription inhibitor negated the increase in P-gp by P4 and E2. P4 and E2 increase P-gp expression and function in NCI-ADR-RES and JAR cells with the ERalpha-expressing cells (JAR) much more sensitive to E2. Furthermore, transcriptional regulation by E2 and P4 likely contributes to the modulation of P-gp levels.

  1. The NCI High Performance Computing (HPC) and High Performance Data (HPD) Platform to Support the Analysis of Petascale Environmental Data Collections

    NASA Astrophysics Data System (ADS)

    Evans, B. J. K.; Pugh, T.; Wyborn, L. A.; Porter, D.; Allen, C.; Smillie, J.; Antony, J.; Trenham, C.; Evans, B. J.; Beckett, D.; Erwin, T.; King, E.; Hodge, J.; Woodcock, R.; Fraser, R.; Lescinsky, D. T.

    2014-12-01

    The National Computational Infrastructure (NCI) has co-located a priority set of national data assets within a HPC research platform. This powerful in-situ computational platform has been created to help serve and analyse the massive amounts of data across the spectrum of environmental collections - in particular the climate, observational data and geoscientific domains. This paper examines the infrastructure, innovation and opportunity for this significant research platform. NCI currently manages nationally significant data collections (10+ PB) categorised as 1) earth system sciences, climate and weather model data assets and products, 2) earth and marine observations and products, 3) geosciences, 4) terrestrial ecosystem, 5) water management and hydrology, and 6) astronomy, social science and biosciences. The data is largely sourced from the NCI partners (who include the custodians of many of the national scientific records), major research communities, and collaborating overseas organisations. By co-locating these large valuable data assets, new opportunities have arisen by harmonising the data collections, making a powerful transdisciplinary research platformThe data is accessible within an integrated HPC-HPD environment - a 1.2 PFlop supercomputer (Raijin), a HPC class 3000 core OpenStack cloud system and several highly connected large scale and high-bandwidth Lustre filesystems. New scientific software, cloud-scale techniques, server-side visualisation and data services have been harnessed and integrated into the platform, so that analysis is performed seamlessly across the traditional boundaries of the underlying data domains. Characterisation of the techniques along with performance profiling ensures scalability of each software component, all of which can either be enhanced or replaced through future improvements. A Development-to-Operations (DevOps) framework has also been implemented to manage the scale of the software complexity alone. This ensures that

  2. Rubus coreanus Miquel extract causes apoptosis of doxorubicin-resistant NCI/ADR-RES ovarian cancer cells via JNK phosphorylation.

    PubMed

    Kim, Min Kyoung; Choi, Hyeong Sim; Cho, Sung-Gook; Shin, Yong Cheol; Ko, Seong-Gyu

    2016-05-01

    Cancer cells can acquire an anticancer, drug-resistant phenotype following chemotherapy, which is tightly linked to cancer malignancy and patient survival rates. Therefore, the identification of options to treat chemotherapy‑resistant cancer cells is an urgent requirement. Rubus coreanus Miquel (RCM) has long been used as a source of food. In addition, it has been reported that RCM has effective functions against particular diseases, including cancer and inflammation. In the present study, it was demonstrated that RCM extract caused the apoptotic cell death of doxorubicin‑resistant NCI/ADR‑RES ovarian cancer cells by phosphorylating c‑Jun N‑terminal kinase (JNK). The RCM‑mediated reduction of cell viability showed no synergism with doxorubicin. In addition, ellagic acid and quercetin, which are phytochemicals found in RCM, also caused apoptosis of the NCI/ADR‑RES cells. In subsequent investigations of the RCM‑altered signaling pathway, RCM extract, ellagic acid and quercetin were found to commonly induce the phosphorylation of JNK and AKT. Additionally, the inhibition of JNK with SP600125 repressed the apoptotic cell death induced by RCM extract, ellagic acid and quercetin, and the inhibition of JNK appeared to switch apoptosis to necrosis. JNK inhibition also reduced the phosphorylation of AKT, which was induced by RCM extract, ellagic acid and quercetin, suggesting that the phosphorylation of JNK is required for AKT phosphorylation in RCM‑, ellagic acid‑ or quercetin‑induced apoptotic cell death. Therefore, the data obtained in the present study led to the conclusion that RCM caused apoptosis of doxorubicin‑resistant NCI/ADR-RES ovarian cancer cells via JNK phosphorylation, and suggested that RCM may be effective in the treatment of chemotherapy‑resistant cancer cells.

  3. Inactivated Tianjin strain, a novel genotype of Sendai virus, induces apoptosis in HeLa, NCI-H446 and Hep3B cells.

    PubMed

    Chen, Jun; Han, Han; Wang, Bin; Shi, Liying

    2016-07-01

    The Sendai virus strain Tianjin is a novel genotype of the Sendai virus. In previous studies, ultraviolet-inactivated Sendai virus strain Tianjin (UV-Tianjin) demonstrated antitumor effects on human breast cancer cells. The aim of the present study was to investigate the in vitro antitumor effects of UV-Tianjin on the human cervical carcinoma HeLa, human small cell lung cancer NCI-H446 and human hepatocellular carcinoma Hep 3B cell lines, and the possible underlying mechanisms of these antitumor effects. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay revealed that UV-Tianjin treatment inhibited the proliferation of HeLa, NCI-H446 and Hep 3B cells in a dose- and time-dependent manner. Hoechst and Annexin V-fluorescein isothiocyanate/propidium iodide double staining indicated that UV-Tianjin induced dose-dependent apoptosis in all three cell lines with the most significant effect observed in the HeLa cell line. In the HeLa cell line, UV-Tianjin-induced apoptosis was further confirmed by the disruption of the mitochondria membrane potential and the activation of caspases, as demonstrated by fluorescent cationic dye and colorimetric assays, respectively. In addition, western blot analysis revealed that UV-Tianjin treatment resulted in significant upregulation of cytochrome c, apoptosis protease activating factor-1, Fas, Fas ligand and Fas-associated protein with death domain, and activated caspase-9, -8 and -3 in HeLa cells. Based on these results, it is hypothesized that UV-Tianjin exhibits anticancer activity in HeLa, NCI-H446 and Hep 3B cell lines via the induction of apoptosis. In conclusion, the results of the present study indicate that in the HeLa cell line, intrinsic and extrinsic apoptotic pathways may be involved in UV-Tianjin-induced apoptosis.

  4. Bufalin Inhibits NCI-H460 Human Lung Cancer Cell Metastasis In Vitro by Inhibiting MAPKs, MMPs, and NF-κB Pathways.

    PubMed

    Wu, Shin-Hwar; Hsiao, Yung-Ting; Kuo, Chao-Lin; Yu, Fu-Shun; Hsu, Shu-Chun; Wu, Ping-Ping; Chen, Jaw-Chyun; Hsia, Te-Chun; Liu, Hsin-Chung; Hsu, Wu-Huei; Chung, Jing-Gung

    2015-01-01

    Bufalin, a component of Chan Su (a traditional Chinese medicine), has been known to have antitumor effects for thousands of years. In this study, we investigated its anti-metastasis effects on NCI-H460 lung cancer cells. Under sub-lethal concentrations (from 25 up to 100 nM), bufalin significantly inhibits the invasion and migration nature of NCI-H460 cells that were measured by Matrigel Cell Migration Assay and Invasion System. Bufalin also suppressed the enzymatic activity of matrix metalloproteinase (MMP)-9, which was examined by gelatin zymography methods. Western blotting revealed that bufalin depressed several key metastasis-related proteins, such as NF-κB, MMP-2, MMP-9, protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3-K), phosphorylated Akt, growth factor receptor-bound protein 2 (GRB2), phosphorylated extracellular signal-regulated kinase (ERK), phosphorylated p38, and phosphorylated c-Jun NH2-terminal kinase (JNK). As evidenced by immunostaining and the electrophoretic mobility shift assay (EMSA), bufalin induced not only a decreased cytoplasmic NF-κB production, but also decreased its nuclear translocation. Several metastasis-related genes, including Rho-associated (Rho A), coiled-coil-containing protein kinase 1 (ROCK1), and focal adhesion kinase (FAK), were down-regulated after bufalin treatment. In conclusion, bufalin is effective in inhibiting the metastatic nature of NCI-H460 cells in low, sub-lethal concentrations. Such an effect involves many mechanisms including MMPs, mitogen-activated protein kinases (MAPKs) and NF-κB systems. Bufalin has a potential to evolve into an anti-metastasis drug for human lung cancer in the future.

  5. Synthesis and in vitro characterization of platinum(II) anticancer coordinates using FTIR spectroscopy and NCI COMPARE: A fast method for new compound discovery.

    PubMed

    Berger, Gilles; Leclercqz, Hélène; Derenne, Allison; Gelbcke, Michel; Goormaghtigh, Erik; Nève, Jean; Mathieu, Véronique; Dufrasne, François

    2014-07-01

    Platinum-based drugs have been used for several decades to treat various cancers successfully. Cisplatin is the original compound in this class; it cross-links DNA, resulting in cell cycle arrest and cell death via apoptosis. Cisplatin is effective against several tumor types but exhibits toxic side effects; in addition, tumors often develop resistance. An original in vitro approach is proposed to determine whether platinum-based research compounds are good candidates for further study by comparing them to marketed drugs using FTIR spectroscopy and the COMPARE analysis from the NCI. Both methods can produce fingerprints and highlight differences between the compounds, classifying the candidates and revealing promising derivatives.

  6. AACR-NCI-EORTC - 27th International Symposium - Molecular Targets and Cancer Therapeutics (November 5-9, 2015 - Boston, Massachusetts, USA).

    PubMed

    Carceller, V

    2015-11-01

    The 27th joint meeting of the European Organization for Research and Treatment of Cancer, National Cancer Institute and the American Association of Cancer Research (EORTC-NCI-AACR) International Conference on Molecular Targets and Cancer Therapeutics was held this year in Boston. Approximately 3,000 international academics, scientists and pharmaceutical industry representatives discussed new discoveries in the field of molecular biology of cancer and presented the latest information on drug discovery, preclinical research, clinical research and target selection in oncology. This report summarizes data on advances in cancer drug discovery.

  7. Cytotoxicity and cell death mechanisms induced by a novel bisnaphthalimidopropyl derivative against the NCI-H460 non-small lung cancer cell line.

    PubMed

    Lima, Raquel T; Barron, Gemma A; Grabowska, Joanna A; Bermano, Giovanna; Kaur, Simranjeet; Roy, Nilanjan; Vasconcelos, M Helena; Lin, Paul K T

    2013-03-01

    Some polyamine derivatives, namely the bisnaphthalimidopropyl polyamines (BNIPPs) may have potential as anticancer drugs. Indeed, previous work from some of us had shown that the ability of these molecules to bind to DNA may contribute to their cytotoxicity. However, their precise mode of action has not been fully understood. In the present work, we report for the first time the effect of the previously synthesised compounds, BNIPDaCHM and NPA, together with a new BNIP derivative (BNIP-3,4-DaDPM) in the in vitro growth of a non-small cell lung cancer cell line (NCI-H460). In addition, for the most potent compound (BNIPDaCHM), its activity as sirtuin inhibitor was investigated in vitro and further confirmed in silico. Results in the NCI-H460 cells showed that, from the compounds tested, BNIPDaCHM was the most potent (GI50 of 1.3 μM). In addition, a concentration-dependent alteration in the normal NCI-H460 cell cycle profile was observed following treatment with BNIPDaCHM as well as an increase in the sub-G1 peak (suggestive of apoptotis). This effect was further supported by Annexin V/PI staining and by analysing the expression of proteins related to apoptosis (cleaved PARP and Caspase-3) by Western blot. It was also observed that BNIPDaCHM inhibited the activity of SIRT2 in vitro, but not of SIRT1. Accordingly, this compound also caused a small increase in tubulin acetylation in NCI-H460 cells. To determine the binding potential of BNIPDaCHM on hSIRT2 and to further validate its inhibitory action, in silico docking studies were carried out, which revealed that BNIPDaCHM is composed of an entirely new SIRT2- inhibiting structural scaffold. In conclusion, this study indicates that BNIP derivatives with a novel structural backbone, such as BNIPDaCHM, may have potential as building blocks for novel antitumour agents which might selectively bind to hSIRT-2.

  8. NCI will no longer support investigator-initiated phase III clinical trials through R01 and P01s grants | Division of Cancer Prevention

    Cancer.gov

    The NCI has traditionally provided support for all phases of clinical trials and interventions via grants and cooperative agreements (including the R03, R21, R01, P01, U01, U10, and UM1 mechanisms). Historically, the majority of early phase trials have been conducted under R03, R21, R01, P01, U01, and UM1 activity codes, whereas most Phase III clinical trials have been conducted under the U10 activity code, with a limited number of Phase III clinical trials performed under the R01, P01, and U01 activity codes... |

  9. Low inter-rater reliability in grading of rectal bleeding using NCI CTC and RTOG toxicity scales: a survey of radiation oncologists

    PubMed Central

    Huynh-Le, Minh-Phuong; Zhang, Zhe; Tran, Phuoc T.; DeWeese, Theodore L.; Song, Danny Y.

    2014-01-01

    Purpose/Objective(s) Rectal bleeding is one of the most common toxicities following prostate radiotherapy (RT), and both NCI CTC and RTOG grading scales are frequently used to report outcomes. We measured concordance among genitourinary radiation oncologists in using these scales to grade rectal bleeding. Methods and Materials From 6/2013–1/2014, a web-based survey was sent to 250 American and Canadian academic radiation oncologists who treat prostate cancer. Participants were provided 4 case vignettes where patients received RT and developed rectal bleeding and were asked for management plans and to rate the bleeding according to NCI CTC v.4 and RTOG late toxicity grading (scales provided). In 2 cases, participants were also asked if they would send the patient for colonoscopy. A multilevel, random intercept modeling approach was used to assess sources of variation (case, respondent) in toxicity grading to calculate the intraclass correlation coefficient (ICC). Agreement on a dichotomous grading scale (low grades 1–2 vs. high grades 3–4) was also assessed, using kappa statistic for multiple respondents. Results Seventy-two radiation oncologists (28%) completed the survey. Forty-seven (65%) reported having either written or been principal investigator on a study using these scales. Agreement between respondents was moderate (ICC=0.52, 95% CI 0.47–0.58) when using NCI CTC and fair using the RTOG scale (ICC=0.28, 95% CI 0.20–0.40). Respondents who chose an invasive management were more likely to select a higher toxicity grade (p<0.0001). Using the dichotomous scale, we observed moderate agreement (kappa=0.42, 95% CI 0.40–0.44) with the NCI CTC scale, but only slight agreement with the RTOG scale (kappa=0.19, 95% CI 0.17–0.21). Conclusion Low inter-rater reliability was observed among radiation oncologists grading rectal bleeding using two common scales. Clearer definitions of late rectal bleeding toxicity should be constructed to reduce this variability

  10. Analysis of Environmental Chemical Mixtures and Non-Hodgkin Lymphoma Risk in the NCI-SEER NHL Study

    PubMed Central

    Czarnota, Jenna; Gennings, Chris; Colt, Joanne S.; De Roos, Anneclaire J.; Cerhan, James R.; Severson, Richard K.; Hartge, Patricia; Ward, Mary H.

    2015-01-01

    , Wheeler DC. 2015. Analysis of environmental chemical mixtures and non-Hodgkin lymphoma risk in the NCI-SEER NHL Study. Environ Health Perspect 123:965–970; http://dx.doi.org/10.1289/ehp.1408630 PMID:25748701

  11. NCI SRK Award

    Cancer.gov

    The SRK Fellowship is a highly competitive, unpaid, and annual, one-year program that provides additional mentoring opportunities, networking, seminars, and workshops to help prepare NCI’s female postdoctoral fellows for the competitive nature of the job market and help them remain in a biomedical research career.

  12. Research Advocacy at NCI

    Cancer.gov

    The patient perspective research advocates brings into NCI’s research enterprise helps to inform research focus and support the dissemination of results that lead to new and better cancer prevention, detection, and treatment methods.

  13. NCI Designated Cancer Centers

    MedlinePlus

    ... disseminate evidence-based findings into communities that can benefit from these findings, but the centers can also, through the experience of working with those patients, help inform national research and ...

  14. [99mTc-octreotide receptor scintigraphy in NCI-H446 small cell lung cancer nude mice model].

    PubMed

    Li, Chao; Zuo, Shuyao; Wang, Xufu; Liu, Xinfeng; Wang, Guoming; Wu, Fengyu

    2015-01-01

    背景与目的 小细胞肺癌恶性程度高,早期诊断对其预后有重要价值,目前的检查方法比较局限,传统影像学方法特异性差,而PET/CT价格昂贵,难于推广应用。小细胞肺癌属神经内分泌肿瘤,高表达生长抑素受体,是其早期进行分子影像诊断的理论基石。本实验旨在观察99mTc-octreotide在正常裸鼠体内的分布、代谢及荷人NCI-H446小细胞肺癌裸鼠模型体内显像变化,为临床小细胞肺癌早期诊断奠定基础。方法 建立人小细胞肺癌的裸鼠肿瘤模型,正常裸鼠及荷瘤鼠静脉注射99mTc-octreotide显像剂后行动态及延迟显像。运用感兴趣区(region of interest, ROI)技术勾画各时相裸鼠各脏器、肿瘤(T)及肿瘤对侧对应部位(N)放射性计数,计算相应T/N比值,并建立30 min内各ROI的时间-放射性(A-T)曲线。结果 ①正常裸鼠的肾脏、肝脏内99mTc-octreotide分布最多,肺部、心脏部位分布较低,头部放射性分布最少,99mTc-octreotide主要通过泌尿系统排泄;各脏器30 min内A-T曲线显示放射性分布随时间延迟呈逐渐下降趋势。②5例荷瘤裸鼠的肿瘤显像均呈阳性;静脉注射99mTc-octreotide后肿瘤部位在3 h显像最清楚,整个检查时间内肝脏放射性强度明显高于肿瘤组织,肺部放射性与肿瘤部位较相近。半定量分析结果显示,静脉注射99mTc-octreotide后肿瘤组织与对侧肢体肌肉的T/N比值在0.5 h、2 h、 3 h、4 h分别为1.163±0.03、2.08±0.12、3.03±0.23、2.689±0.31;各时相T/N比值差异有统计学意义(F=51.69, P<0.000,1);通过两两比较发现,静脉注射显像剂后3 h的T/N比值与其他各时相差异均有统计学意义(P<0.05);不同检查时间肝脏部位的放射性平均计数高于肿瘤部位,肺部的平均计数与肿瘤相近。肿瘤部位A-T曲线显示,注射99mTc-octreotide后2 min-3 min出现一过性

  15. Estimation of the Mechanism of Adrenal Action of Endocrine-Disrupting Compounds Using a Computational Model of Adrenal Steroidogenesis in NCI-H295R Cells

    PubMed Central

    Saito, Ryuta; Terasaki, Natsuko; Yamazaki, Makoto; Masutomi, Naoya; Tsutsui, Naohisa; Okamoto, Masahiro

    2016-01-01

    Adrenal toxicity is one of the major concerns in drug development. To quantitatively understand the effect of endocrine-active compounds on adrenal steroidogenesis and to assess the human adrenal toxicity of novel pharmaceutical drugs, we developed a mathematical model of steroidogenesis in human adrenocortical carcinoma NCI-H295R cells. The model includes cellular proliferation, intracellular cholesterol translocation, diffusional transport of steroids, and metabolic pathways of adrenal steroidogenesis, which serially involve steroidogenic proteins and enzymes such as StAR, CYP11A1, CYP17A1, HSD3B2, CYP21A2, CYP11B1, CYP11B2, HSD17B3, and CYP19A1. It was reconstructed in an experimental dynamics of cholesterol and 14 steroids from an in vitro steroidogenesis assay using NCI-H295R cells. Results of dynamic sensitivity analysis suggested that HSD3B2 plays the most important role in the metabolic balance of adrenal steroidogenesis. Based on differential metabolic profiling of 12 steroid hormones and 11 adrenal toxic compounds, we could estimate which steroidogenic enzymes were affected in this mathematical model. In terms of adrenal steroidogenic inhibitors, the predicted action sites were approximately matched to reported target enzymes. Thus, our computer-aided system based on systems biological approach may be useful to understand the mechanism of action of endocrine-active compounds and to assess the human adrenal toxicity of novel pharmaceutical drugs. PMID:27057163

  16. From Mice and Men to Earth and Space: Joint NASA-NCI Workshop on Lung Cancer Risk Resulting from Space and Terrestrial Radiation

    PubMed Central

    Shay, Jerry W.; Cucinotta, Francis A.; Sulzman, Frank M.; Coleman, C. Norman; Minna, John D.

    2011-01-01

    On June 27–28, 2011 scientists from the National Cancer Institute (NCI), NASA, and academia met in Bethesda to discuss major lung cancer issues confronting each organization. For NASA – available data suggest lung cancer is the largest potential cancer risk from space travel for both men and women and quantitative risk assessment information for mission planning is needed. In space the radiation risk is from high energy and charge (HZE) nuclei (such as Fe) and high energy protons from solar flares and not from gamma radiation. By contrast the NCI is endeavoring to estimate the increased lung cancer risk from the potential wide-spread implementation of computed tomography (CT) screening in individuals at high risk for developing lung cancer based on the National Lung Cancer Screening Trial (NLST). For the latter, exposure will be x-rays from CT scans from the screening (which uses “low dose” CT scans) and also from follow-up scans used to evaluate abnormalities found during initial screening. Topics discussed included the risk of lung cancer arising after HZE particle, proton, and low dose Earth radiation exposure. The workshop examined preclinical models, epidemiology, molecular markers, “omics” technology, radiobiology issues, and lung stem cells (LSC) that relate to the development of lung cancer. PMID:21900398

  17. From mice and men to earth and space: joint NASA-NCI workshop on lung cancer risk resulting from space and terrestrial radiation.

    PubMed

    Shay, Jerry W; Cucinotta, Francis A; Sulzman, Frank M; Coleman, C Norman; Minna, John D

    2011-11-15

    On June 27-28, 2011, scientists from the National Cancer Institute (NCI), NASA, and academia met in Bethesda to discuss major lung cancer issues confronting each organization. For NASA, available data suggest that lung cancer is the largest potential cancer risk from space travel for both men and women and quantitative risk assessment information for mission planning is needed. In space, the radiation risk is from high energy and charge (HZE) nuclei (such as Fe) and high-energy protons from solar flares and not from gamma radiation. In contrast, the NCI is endeavoring to estimate the increased lung cancer risk from the potential widespread implementation of computed tomographic (CT) screening in individuals at high risk for developing lung cancer based on the National Lung Cancer Screening Trial (NLST). For the latter, exposure will be X-rays from CT scans from the screening (which uses "low-dose" CT scans) and also from follow-up scans used to evaluate abnormalities found during initial screening. Topics discussed included the risk of lung cancer arising after HZE particle, proton, and low-dose exposure to Earth's radiation. The workshop examined preclinical models, epidemiology, molecular markers, "omics" technology, radiobiology issues, and lung stem cells that relate to the development of lung cancer.

  18. Demethoxycurcumin alters gene expression associated with DNA damage, cell cycle and apoptosis in human lung cancer NCI-H460 cells in vitro.

    PubMed

    Ko, Yang-Ching; Hsu, Shu-Chun; Liu, Hsin-Chung; Hsiao, Yung-Ting; Hsia, Te-Chun; Yang, Su-Tso; Hsu, Wu-Huei; Chung, Jing-Gung

    2015-01-01

    Lung cancer is the leading cause of cancer-related deaths and new lung cancer cases are continuously emerging around the globe; however, treatment of lung cancer remains unsatisfactory. Demethoxycurcumin (DMC) has been shown to exert cytotoxic effects in human cancer cells via induction of apoptosis. However, the effects of DMC on genetic mechanisms associated with these actions have not been yet elucidated. Human lung cancer NCI-H460 cells were incubated with or without 35 μM of DMC for 24 h and total RNA was extracted for cDNA synthesis labeling and microarray hybridization, followed by fluor-labeled cDNA hybridization on chip. Expression Console software with default Robust Multichip Analysis (RMA) parameters were used for detecting and quantitating the localized concentrations of fluorescent molecules. The GeneGo software was used for investigating key genes involved and their possible interaction pathways. Genes associated with DNA damage and repair, cell-cycle check point and apoptosis could be altered by DMC; in particular, 144 genes were found up-regulated and 179 genes down-regulated in NCI-H460 cells after exposure to DMC. In general, DMC-altered genes may offer information to understand the cytotoxic mechanism of this agent at the genetic level since gene alterations can be useful biomarkers or targets for the diagnosis and treatment of human lung cancer in the future.

  19. Analysis of agricultural residues on tea using d-SPE sample preparation with GC-NCI-MS and UHPLC-MS/MS.

    PubMed

    Zhang, Xian; Mobley, Nicole; Zhang, Jiugen; Zheng, Xiaomin; Lu, Ling; Ragin, Oscar; Smith, Christopher J

    2010-11-24

    This study presents new sample preparation and analytical procedures for the quantification of pesticides on processed tea leaves. The new method includes tea extraction and dispersive solid phase extraction (d-SPE) to prepare gas chromatography (GC) and ultrahigh-performance liquid chromatography (UHPLC)-ready samples, providing a fast and cost-effective solution for time-sensitive industrial analysis to fulfill regulatory requirements. Both GC-negative chemical ionization mass spectrometry (GC-NCI-MS) and UHPLC-tandem mass spectrometry (UHPLC-MS/MS) were employed to produce highly sensitive and reproducible data. Excellent limits of detection (typically below 1 μg/kg for GC and 10 μg/kg for UHPLC), wide linearity ranges, and good recoveries (mostly >70%) were achieved on the selected pesticides. Twenty-seven tea samples purchased from local grocery stores were analyzed using the newly developed methods. Among the pesticides analyzed, endosulfan sulfate and kelthane were the most frequently detected by GC-NCI-MS and imidacloprid and acetamiprid by UHPLC-MS/MS in these teas. The samples were found to be relatively clean, with <1 mg/kg of total pesticide residues. The organic-labeled teas were significantly cleaner than nonorganic ones. The cost per gram of tea did not correlate with pesticide residue levels detected.

  20. Nano neodymium oxide induces massive vacuolization and autophagic cell death in non-small cell lung cancer NCI-H460 cells.

    PubMed

    Chen, Yong; Yang, Lisong; Feng, Chao; Wen, Long-Ping

    2005-11-11

    Neodymium, a rare earth element, was known to exhibit cytotoxic effects and induce apoptosis in certain cancer cells. Here we show that nano-sized neodymium oxide (Nano Nd2O3) induced massive vacuolization and cell death in non-small cell lung cancer NCI-H460 cells at micromolar equivalent concentration range. Cell death elicited by Nano Nd2O3 was not due to apoptosis and caspases were not involved. Electron microscopy and acridine orange staining revealed extensive autophagy in the cytoplasm of the cells treated by Nano Nd2O3. Autophagy induced by Nano Nd2O3 was accompanied by S-phase cell cycle arrest, mild disruption of mitochondrial membrane potential, and inhibition of proteasome activity. Bafilomycin A1, but not 3-MA, induced apoptosis while inhibiting autophagy. Our results revealed a novel biological function for Nano Nd2O3 and may have implications for the therapy of non-small cell lung cancer.

  1. The Tumor Microenvironment at a Turning Point Knowledge Gained Over the Last Decade, and Challenges and Opportunities Ahead: A White Paper from the NCI TME Network.

    PubMed

    DeClerck, Yves A; Pienta, Kenneth J; Woodhouse, Elisa C; Singer, Dinah S; Mohla, Suresh

    2017-03-01

    Over the past 10 years, the Tumor Microenvironment Network (TMEN), supported by the NCI (Bethesda, MD), has promoted collaborative research with the explicit goal of fostering multi-institutional and transdisciplinary groups that are capable of addressing complex issues involving the tumor microenvironment. The main goal of the TMEN was to generate novel information about the dynamic complexity of tumor-host interactions in different organ systems with emphasis on using human tissues and supplemented by experimental models. As this initiative comes to a close, members of the TMEN took time to examine what has been accomplished by the Network and importantly to identify the challenges and opportunities ahead. This consensus document summarizes for the broader scientific community discussions that occurred at the two final meetings of the TMEN in 2015 and 2016. Cancer Res; 77(5); 1051-9. ©2017 AACR.

  2. High Resolution Copy Number Variation Data in the NCI-60 Cancer Cell Lines from Whole Genome Microarrays Accessible through CellMiner

    PubMed Central

    Varma, Sudhir; Pommier, Yves; Sunshine, Margot; Weinstein, John N.; Reinhold, William C.

    2014-01-01

    Array-based comparative genomic hybridization (aCGH) is a powerful technique for detecting gene copy number variation. It is generally considered to be robust and convenient since it measures DNA rather than RNA. In the current study, we combine copy number estimates from four different platforms (Agilent 44 K, NimbleGen 385 K, Affymetrix 500 K and Illumina Human1Mv1_C) to compute a reliable, high-resolution, easy to understand output for the measure of copy number changes in the 60 cancer cells of the NCI-DTP (the NCI-60). We then relate the results to gene expression. We explain how to access that database using our CellMiner web-tool and provide an example of the ease of comparison with transcript expression, whole exome sequencing, microRNA expression and response to 20,000 drugs and other chemical compounds. We then demonstrate how the data can be analyzed integratively with transcript expression data for the whole genome (26,065 genes). Comparison of copy number and expression levels shows an overall medium high correlation (median r = 0.247), with significantly higher correlations (median r = 0.408) for the known tumor suppressor genes. That observation is consistent with the hypothesis that gene loss is an important mechanism for tumor suppressor inactivation. An integrated analysis of concurrent DNA copy number and gene expression change is presented. Limiting attention to focal DNA gains or losses, we identify and reveal novel candidate tumor suppressors with matching alterations in transcript level. PMID:24670534

  3. A Micro-Grid Simulator Tool (SGridSim) using Effective Node-to-Node Complex Impedance (EN2NCI) Models

    SciTech Connect

    Udhay Ravishankar; Milos manic

    2013-08-01

    This paper presents a micro-grid simulator tool useful for implementing and testing multi-agent controllers (SGridSim). As a common engineering practice it is important to have a tool that simplifies the modeling of the salient features of a desired system. In electric micro-grids, these salient features are the voltage and power distributions within the micro-grid. Current simplified electric power grid simulator tools such as PowerWorld, PowerSim, Gridlab, etc, model only the power distribution features of a desired micro-grid. Other power grid simulators such as Simulink, Modelica, etc, use detailed modeling to accommodate the voltage distribution features. This paper presents a SGridSim micro-grid simulator tool that simplifies the modeling of both the voltage and power distribution features in a desired micro-grid. The SGridSim tool accomplishes this simplified modeling by using Effective Node-to-Node Complex Impedance (EN2NCI) models of components that typically make-up a micro-grid. The term EN2NCI models means that the impedance based components of a micro-grid are modeled as single impedances tied between their respective voltage nodes on the micro-grid. Hence the benefit of the presented SGridSim tool are 1) simulation of a micro-grid is performed strictly in the complex-domain; 2) faster simulation of a micro-grid by avoiding the simulation of detailed transients. An example micro-grid model was built using the SGridSim tool and tested to simulate both the voltage and power distribution features with a total absolute relative error of less than 6%.

  4. Mitotane exhibits dual effects on steroidogenic enzymes gene transcription under basal and cAMP-stimulating microenvironments in NCI-H295 cells.

    PubMed

    Lin, Chia-Wen; Chang, Yen-Hwa; Pu, Hsiao-Fung

    2012-08-16

    Adrenocortical carcinoma (ACC) is an extremely rare and aggressive endocrine malignancy with a poor prognosis. The most common symptom of ACC is hypercortisolism (Cushing's syndrome), which has the highest mortality. Mitotane is used as a steroidogenesis inhibitor for Cushing's syndrome or as a chemical adrenalectomy drug for ACC. Mitotane induces adrenal cortex necrosis, mitochondrial membrane impairment, and irreversible binding to CYP proteins. In this study, we explored the molecular effect of mitotane on steroidogenesis in human adrenocortical cancer NCI-H295 cells. Mitotane (10-40μM) inhibited basal and cAMP-induced cortisol secretion but did not cause cell death. Mitotane exhibited an inhibitory effect on the basal expression of StAR and P450scc protein. Furthermore, 40μM of mitotane significantly diminished StAR, CYP11A1 and CYP21 mRNA expression. HSD3B2 and CYP17 seem to be insensitive to mitotane. The stimulatory effects of mitotane on CYP11B1 were more remarkable than its inhibitory effects. In contrast, the activation of cAMP signaling strongly elevated the expression of all these genes. Mitotane (40μM) almost completely neutralized this positive effect and returned 8-Br-cAMP-induced StAR, CYP11A1, CYP17 and CYP21 mRNA to control levels. After cAMP activation, mitotane did not change the levels of CYP11B1 mRNA. The present study demonstrates that mitotane can inhibit cortisol biosynthesis due to a non-specific interference with the gene transcription of steroidogenic enzymes under both basal and 8-Br-cAMP-activated conditions in NCI-H295 cells. We also identified that StAR and CYP11A1 key enzymes that participate in the rate-limiting step of steroidogenesis, were more sensitive to mitotane. In addition, the biphasic effect of mitotane on CYP11B1 was also elucidated.

  5. Bufalin alters gene expressions associated DNA damage, cell cycle, and apoptosis in human lung cancer NCI-H460 cells in vitro.

    PubMed

    Wu, Shin-Hwar; Hsiao, Yung-Ting; Chen, Jaw-Chyum; Lin, Ju-Hwa; Hsu, Shu-Chun; Hsia, Te-Chun; Yang, Su-Tso; Hsu, Wu-Huei; Chung, Jing-Gung

    2014-05-13

    Lung cancer is the leading cause of cancer related death and there is no effective treatment to date. Bufalin has been shown effective in inducing apoptosis and DNA damage in lung cancer cells. However, the genetic mechanisms underlying these actions have not been elucidated yet. Cultured NCI-H460 cells were treated with or without 2 μM of bufalin for 24 h. The total RNA was extracted from each treatment for cDNA synthesis and labeling, microarray hybridization, and then followed by flour-labeled cDNA hybridized on chip. The localized concentrations of fluorescent molecules were detected and quantitated and analyzed by Expression Console software (Affymetrix) with default RMA parameters. The key genes involved and their possible interaction pathways were mapped by GeneGo software. About 165 apoptosis-related genes were affected. CASP9 was up-regulated by 5.51 fold and THAP1 by 2.75-fold while CCAR1 was down-regulated by 2.24 fold. 107 genes related to DNA damage/repair were affected. MDC1 was down-regulated by 2.22-fold, DDIT4 by 2.52 fold while GADD45B up-regulated by 3.72 fold. 201 genes related to cell cycles were affected. CCPG1 was down-regulated by 2.11 fold and CDCA7L by 2.71 fold. Many genes about apoptosis, cell cycle regulation and DNA repair are changed significantly following bufalin treatment in NCI-H460 cells. These changes provide an in depth understanding of cytotoxic mechanism of bufalin in genetic level and also offer many potentially useful biomarkers for diagnosis and treatment of lung cancer in future.

  6. 2β, 3β, 23-trihydroxy-urs-12-ene-28-olic acid (TUA) isolated from Actinidia chinensis Radix inhibits NCI-H460 cell proliferation by decreasing NF-κB expression.

    PubMed

    Cheng, Qi-Lai; Li, Hong-Liang; Huang, Zhi-Qin; Chen, Yi-Jian; Liu, Ta-Si

    2015-10-05

    A natural ursolic compound, 2β, 3β, 23-trihydroxy-urs-12-ene-28-olic acid (TUA) was isolated from the root of Actinidia chinensis Planch (A. chinensis Radix). Since a large number of triterpenoid compound has marked anticancer effects toward various types of cancer cell lines in vitro, this study was carried out to investigate the anticancer effect of TUA in non-small cell lung cancer cells (NSCLCCs) and the underlying apoptotic mechanism of TUA was examined in NCI-H460 cell lines. Cell proliferation, apoptosis and cell cycle were measured using a cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The activity of transcription factor NF-κB was determined by EMSA method. The expression of apoptosis- and proliferation-related proteins was determined by western blotting. The effect of TUA on NF-κB mRNA expression in NCI-H460 cells was detected by RT-PCR. TUA significantly suppressed the viability of NCI-H460 cells. Also, TUA significantly increased the sub G1 population by cell cycle analysis and in a concentration dependent manner in NCI-H460 cells. Such an effect was accompanied by p65 (NF-κB subunit) inactivation by an inhibition of IκBα phosphorylation, and by inhibition of p65 mRNA expressions. Consistently Overall, our findings suggest that TUA induces apoptosis via inhibition of NF-κB (p65) expression level and activation of IκBα in NCI-H460 cells as a potent anticancer candidate for lung cancer treatment.

  7. Diallyl Trisulfide Inhibits Growth of NCI-H460 in Vitro and in Vivo, and Ameliorates Cisplatin-Induced Oxidative Injury in the Treatment of Lung Carcinoma in Xenograft Mice

    PubMed Central

    Jiang, Xiaoyan; Zhu, Xiaosong; Liu, Na; Xu, Hongya; Zhao, Zhongxi; Li, Siying; Li, Shanzhong; Cai, Jianhua; Cao, Jimin

    2017-01-01

    Diallyl trisulfide (DATS), an organosulfuric component of garlic oil, exhibits potential anticancer and chemopreventive effects. Cisplatin (DDP), a common chemotherapeutic agent, has provided great therapeutic contributions to treating solid tumors, but with serious side effects. Here, we verified the anti-tumor properties of DATS on lung cancer in vitro and in vivo, and evaluated synergistic effects of DATS combined with DDP on the NCI-H460 xenograft model. Significantly decreased cell viabilities, cell cycle G1 arrest, and apoptosis induction were observed in DATS treated NCI-H460 cells (p<0.05). And injection of DATS (30 or 40 mg/kg) to female Balb/c mice significantly inhibited the growth of human NCI-H460 cell tumor xenograft (p<0.001). Moreover, DATS in combination with DDP exhibited enhanced anti-tumor activity via induction of apoptosis. Apoptosis pathways were confirmed by modulation of p53, Bcl-2 family members; induction of active caspase-3/8/9 and activation of JNK- and p38-MAPK pathways. Interestedly, DATS+DDP administration exerted fewer side effects, such as suppressing the weight loss and ameliorating DDP-induced oxidative injury, especially in renal parenchyma. In addition, increased E-cadherin and decreased MMP-9 expression levels were observed in DATS-treated tumor tissues. These studies provide supports that DATS might be a potential candidate for combination with DDP in cancer treatment. PMID:28255269

  8. Diallyl Trisulfide Inhibits Growth of NCI-H460 in Vitro and in Vivo, and Ameliorates Cisplatin-Induced Oxidative Injury in the Treatment of Lung Carcinoma in Xenograft Mice.

    PubMed

    Jiang, Xiaoyan; Zhu, Xiaosong; Liu, Na; Xu, Hongya; Zhao, Zhongxi; Li, Siying; Li, Shanzhong; Cai, Jianhua; Cao, Jimin

    2017-01-01

    Diallyl trisulfide (DATS), an organosulfuric component of garlic oil, exhibits potential anticancer and chemopreventive effects. Cisplatin (DDP), a common chemotherapeutic agent, has provided great therapeutic contributions to treating solid tumors, but with serious side effects. Here, we verified the anti-tumor properties of DATS on lung cancer in vitro and in vivo, and evaluated synergistic effects of DATS combined with DDP on the NCI-H460 xenograft model. Significantly decreased cell viabilities, cell cycle G1 arrest, and apoptosis induction were observed in DATS treated NCI-H460 cells (p<0.05). And injection of DATS (30 or 40 mg/kg) to female Balb/c mice significantly inhibited the growth of human NCI-H460 cell tumor xenograft (p<0.001). Moreover, DATS in combination with DDP exhibited enhanced anti-tumor activity via induction of apoptosis. Apoptosis pathways were confirmed by modulation of p53, Bcl-2 family members; induction of active caspase-3/8/9 and activation of JNK- and p38-MAPK pathways. Interestedly, DATS+DDP administration exerted fewer side effects, such as suppressing the weight loss and ameliorating DDP-induced oxidative injury, especially in renal parenchyma. In addition, increased E-cadherin and decreased MMP-9 expression levels were observed in DATS-treated tumor tissues. These studies provide supports that DATS might be a potential candidate for combination with DDP in cancer treatment.

  9. The Side Population in Human Lung Cancer Cell Line NCI-H460 Is Enriched in Stem-Like Cancer Cells

    PubMed Central

    Shi, Yang; Fu, Xuelian; Hua, Yong; Han, Yang; Lu, Ying; Wang, Junchen

    2012-01-01

    Lung cancer is among the most lethal malignancies with a high metastasis and recurrence rate. Recent studies indicate that tumors contain a subset of stem-like cancer cells that possess certain stem cell properties. Herein, we used Hoechst 33342 dye efflux assay and flow cytometry to isolate and characterize the side population (SP) cells from human lung cancer cell line NCI-H460 (H460). We show that the H460 SP cells harbor stem-like cells as they can readily form anchorage-independent floating spheres, possess great proliferative potential, and exhibit enhanced tumorigenicity. Importantly, the H460 SP cells were able to self-renew both in vitro and in vivo. Finally, we show that the H460 SP cells preferentially express ABCG2 as well as SMO, a critical mediator of the Hedgehog (HH) signaling, which seems to play an important role in H460 lung cancer cells as its blockage using Cyclopamine greatly inhibits cell-cycle progression. Collectively, our results lend further support to the existence of lung cancer stem cells and also implicate HH signaling in regulating large-cell lung cancer (stem) cells. PMID:22428030

  10. Comparison of Intracellular Stress Response of NCI-H526 Small Cell Lung Cancer (SCLC) Cells to Platinum(II) Cisplatin and Platinum(IV) Oxoplatin

    PubMed Central

    Hamilton, Gerhard

    2014-01-01

    In attempts to develop an orally applicable platinum-based drug, platinum(IV) drugs which exhibit higher in vivo stability compared to the platinum(II) drug cisplatin were formulated. The first such chemotherapeutic agent, namely satraplatin, failed to receive approval. In the present work, we checked the initial cellular stress response of the chemosensitive NCI-H526 small cell lung cancer (SCLC) cells by determination of the relative phosphorylation of 46 specific phosphorylation sites of 38 selected proteins in a six hours response to cisplatin (platinum(II)) or oxoplatin (platinum(IV)), respectively. Oxoplatin is considered as prodrug of cisplatin, although several findings point to differences in intracellular effects. Cisplatin induced hyperphosphorylation of p38α MAPK and AMPKα1, whereas oxoplatin treatment resulted in increased phosphorylation of a large number of signaling proteins involved in stress response/drug resistance, including JNK, GSK-3α, AMPKα1, src kinases, STATs, CHK-2 and especially focal adhesion kinase (FAK). Cisplatin exerts markedly higher cytotoxicity upon four hours short-term exposure in comparison to oxoplatin and, correspondingly, the extended initial stress response to the platinum(IV) drug oxoplatin thus is expected to increase clinical drug resistance. Induction of a substantial stress response to any prodrug of a platinum-based compound may likewise limit the effectivity of its active metabolite(s), such contributing to the failure of selected derivatized platinum complexes. PMID:25006835

  11. Multiplexed specific label-free detection of NCI-H358 lung cancer cell line lysates with silicon based photonic crystal microcavity biosensors.

    PubMed

    Chakravarty, Swapnajit; Lai, Wei-Cheng; Zou, Yi; Drabkin, Harry A; Gemmill, Robert M; Simon, George R; Chin, Steve H; Chen, Ray T

    2013-05-15

    We experimentally demonstrate label-free photonic crystal (PC) microcavity biosensors in silicon-on-insulator (SOI) to detect the epithelial-mesenchymal transition (EMT) transcription factor, ZEB1, in minute volumes of sample. Multiplexed specific detection of ZEB1 in lysates from NCI-H358 lung cancer cells down to an estimated concentration of 2 cells per micro-liter is demonstrated. L13 photonic crystal microcavities, coupled to W1 photonic crystal waveguides, are employed in which resonances show high Q in the bio-ambient phosphate buffered saline (PBS). When the sensor surface is derivatized with a specific antibody, the binding of the corresponding antigen from a complex whole-cell lysate generates a change in refractive index in the vicinity of the photonic crystal microcavity, leading to a change in the resonance wavelength of the resonance modes of the photonic crystal microcavity. The shift in the resonance wavelength reveals the presence of the antigen. The sensor cavity has a surface area of ∼11μm(2). Multiplexed sensors permit simultaneous detection of many binding interactions with specific immobilized antibodies from the same bio-sample at the same instant of time. Specificity was demonstrated using a sandwich assay which further amplifies the detection sensitivity at low concentrations. The device represents a proof-of-concept demonstration of label-free, high throughput, multiplexed detection of cancer cells with specificity and sensitivity on a silicon chip platform.

  12. Virtual Screening of Specific Insulin-Like Growth Factor 1 Receptor (IGF1R) Inhibitors from the National Cancer Institute (NCI) Molecular Database

    PubMed Central

    Fan, Cong; Huang, Yan-Xin; Bao, Yong-Li; Sun, Lu-Guo; Wu, Yin; Yu, Chun-Lei; Zhang, Yu; Song, Zhen-Bo; Zheng, Li-Hua; Sun, Ying; Wang, Guan-Nan; Li, Yu-Xin

    2012-01-01

    Insulin-like growth factor 1 receptor (IGF1R) is an attractive drug target for cancer therapy and research on IGF1R inhibitors has had success in clinical trials. A particular challenge in the development of specific IGF1R inhibitors is interference from insulin receptor (IR), which has a nearly identical sequence. A few potent inhibitors that are selective for IGF1R have been discovered experimentally with the aid of computational methods. However, studies on the rapid identification of IGF1R-selective inhibitors using virtual screening and confidence-level inspections of ligands that show different interactions with IGF1R and IR in docking analysis are rare. In this study, we established virtual screening and binding-mode prediction workflows based on benchmark results of IGF1R and several kinase receptors with IGF1R-like structures. We used comprehensive analysis of the known complexes of IGF1R and IR with their binding ligands to screen specific IGF1R inhibitors. Using these workflows, 17 of 139,735 compounds in the NCI (National Cancer Institute) database were identified as potential specific inhibitors of IGF1R. Calculations of the potential of mean force (PMF) with GROMACS were further conducted for three of the identified compounds to assess their binding affinity differences towards IGF1R and IR. PMID:23242155

  13. Aquated cisplatin and heparin-pluronic nanocomplexes exhibiting sustainable release of active platinum compound and NCI-H460 lung cancer cell antiproliferation.

    PubMed

    Tong, Nhat-Anh N; Nguyen, Thi Phuong; Cuu Khoa, Nguyen; Tran, Ngoc Quyen

    2016-01-01

    In recent decades, platinum compounds have been many contributions in medicine. Development of new drugs from the active platinum compounds as well as nanocarriers for targeted delivery and reducing side effects of the drugs has paid much attention. In the study, nanocomplexes were prepared from aquated species of cisplatin and pluronic-conjugated heparin which distributed in the range of 80-100 nm by Transmission Electron Microscopy and 134 nm by Dynamic light scattering (DLS). Formation of the complex was confirmed by FTIR and DLS. The nanocomplexes exhibited high drug-loading capacity (approximately 42.5% wt/wt at 37 °C and 37.5% wt/wt at 25 °C). In vitro, drug-loaded nanogels showed much slower release profiles of cisplatin CDDP in pH 7.4 (physiological pH) compared with pH 5.5 condition at 37 °C. Moreover, the cytotoxicity assay results also indicated that Hep-F127 was cytocompatible; meanwhile, CDDP-loaded nanocomplex was able to reduce the cytotoxic ability of free CDDP (IC50 = 5.68 ± 0.73 μg/ml), which still maintain a significantly antiproliferative activity on NCI-H460 lung cancer cell. The in vitro preliminarily obtained results indicate that the nanocomplex is a candidate for CDDP delivery which can be studied further in cancer therapy.

  14. Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3)

    PubMed Central

    Ahn, Jiyoung; Schumacher, Fredrick R.; Berndt, Sonja I.; Pfeiffer, Ruth; Albanes, Demetrius; Andriole, Gerald L.; Ardanaz, Eva; Boeing, Heiner; Bueno-de-Mesquita, Bas; Chanock, Stephen J.; Clavel-Chapelon, Françoise; Diver, W. Ryan; Feigelson, Heather Spencer; Gaziano, J. Michael; Giovannucci, Edward; Haiman, Christopher A.; Henderson, Brian E.; Hoover, Robert N.; Kolonel, Laurence N.; Kraft, Peter; Ma, Jing; Le Marchand, Loïc; Overvad, Kim; Palli, Domenico; Stattin, Pär; Stampfer, Meir; Stram, Daniel O.; Thomas, Gilles; Thun, Michael J.; Travis, Ruth C.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Weinstein, Stephanie J.; Yeager, Meredith; Kaaks, Rudolf; Hunter, David J.; Hayes, Richard B.

    2009-01-01

    Twin studies suggest a heritable component to circulating sex steroid hormones and sex hormone-binding globulin (SHBG). In the NCI-Breast and Prostate Cancer Cohort Consortium, 874 SNPs in 37 candidate genes in the sex steroid hormone pathway were examined in relation to circulating levels of SHBG (N = 4720), testosterone (N = 4678), 3α-androstanediol-glucuronide (N = 4767) and 17β-estradiol (N = 2014) in Caucasian men. rs1799941 in SHBG is highly significantly associated with circulating levels of SHBG (P = 4.52 × 10−21), consistent with previous studies, and testosterone (P = 7.54 × 10−15), with mean difference of 26.9 and 14.3%, respectively, comparing wild-type to homozygous variant carriers. Further noteworthy novel findings were observed between SNPs in ESR1 with testosterone levels (rs722208, mean difference = 8.8%, P = 7.37 × 10−6) and SRD5A2 with 3α-androstanediol-glucuronide (rs2208532, mean difference = 11.8%, P = 1.82 × 10−6). Genetic variation in genes in the sex steroid hormone pathway is associated with differences in circulating SHBG and sex steroid hormones. PMID:19574343

  15. Evaluation of cytotoxic effect of the combination of a pyridinyl carboxamide derivative and oxaliplatin on NCI-H1299 human non-small cell lung carcinoma cells.

    PubMed

    Teixeira, Sarah Fernandes; de Azevedo, Ricardo Alexandre; Silva, Arthur Carvalho; Braga, Rodolpho Campos; Jorge, Salomão Dória; Barbuto, José Alexandre Marzagão; Andrade, Carolina Horta; Ferreira, Adilson Kleber

    2016-12-01

    Even with all improvements in both diagnostic and therapeutic techniques, lung cancer remains as the most lethal and prevalent cancer in the world. Therefore, new therapeutic drugs and new strategies of drug combination are necessary to provide treatments that are more efficient. Currently, standard therapy regimen for lung cancer includes platinum drugs, such as cisplatin, oxaliplatin, and carboplatin. Besides of the better toxicity profile of oxaliplatin when compared with cisplatin, peripheral neuropathy remains as a limitation of oxaliplatin dose. This study presents LabMol-12, a new pyridinyl carboxamide derivative with antileishmanial and antichagasic activity, as a new hit for lung cancer treatment, which induces apoptosis dependent of caspases in NCI-H1299 lung cancer cells both in monolayer and 3D culture. Moreover, LabMol-12 allows a reduction of oxaliplatin dose when they are combined, thereby, it is a relevant strategy for reducing the side effects of oxaliplatin with the same response. Molecular modeling studies corroborated the biological findings and suggested that the combined therapy can provide a better therapeutically profile effects against NSCLC. All these findings support the fact that the combination of oxaliplatin and LabMol-12 is a promising drug combination for lung cancer.

  16. The side population in human lung cancer cell line NCI-H460 is enriched in stem-like cancer cells.

    PubMed

    Shi, Yang; Fu, Xuelian; Hua, Yong; Han, Yang; Lu, Ying; Wang, Junchen

    2012-01-01

    Lung cancer is among the most lethal malignancies with a high metastasis and recurrence rate. Recent studies indicate that tumors contain a subset of stem-like cancer cells that possess certain stem cell properties. Herein, we used Hoechst 33342 dye efflux assay and flow cytometry to isolate and characterize the side population (SP) cells from human lung cancer cell line NCI-H460 (H460). We show that the H460 SP cells harbor stem-like cells as they can readily form anchorage-independent floating spheres, possess great proliferative potential, and exhibit enhanced tumorigenicity. Importantly, the H460 SP cells were able to self-renew both in vitro and in vivo. Finally, we show that the H460 SP cells preferentially express ABCG2 as well as SMO, a critical mediator of the Hedgehog (HH) signaling, which seems to play an important role in H460 lung cancer cells as its blockage using Cyclopamine greatly inhibits cell-cycle progression. Collectively, our results lend further support to the existence of lung cancer stem cells and also implicate HH signaling in regulating large-cell lung cancer (stem) cells.

  17. Nano neodymium oxide induces massive vacuolization and autophagic cell death in non-small cell lung cancer NCI-H460 cells

    SciTech Connect

    Chen Yong; Yang Lisong; Feng Chao; Wen Longping . E-mail: lpwen@ustc.edu.cn

    2005-11-11

    Neodymium, a rare earth element, was known to exhibit cytotoxic effects and induce apoptosis in certain cancer cells. Here we show that nano-sized neodymium oxide (Nano Nd{sub 2}O{sub 3}) induced massive vacuolization and cell death in non-small cell lung cancer NCI-H460 cells at micromolar equivalent concentration range. Cell death elicited by Nano Nd{sub 2}O{sub 3} was not due to apoptosis and caspases were not involved. Electron microscopy and acridine orange staining revealed extensive autophagy in the cytoplasm of the cells treated by Nano Nd{sub 2}O{sub 3}. Autophagy induced by Nano Nd{sub 2}O{sub 3} was accompanied by S-phase cell cycle arrest, mild disruption of mitochondrial membrane potential, and inhibition of proteasome activity. Bafilomycin A1, but not 3-MA, induced apoptosis while inhibiting autophagy. Our results revealed a novel biological function for Nano Nd{sub 2}O{sub 3} and may have implications for the therapy of non-small cell lung cancer.

  18. Bioassay-guided isolation and identification of bioactive compound from aerial parts of Luffa acutangula against lung cancer cell line NCI-H460.

    PubMed

    Vanajothi, Ramar; Srinivasan, Pappu

    2015-01-01

    Luffa acutangula (Cucurbitaceae) is widely used as a traditional medicine in India and was reported to possess various pharmacological activities including its anti-proliferative effects. In this study, the bioactive compound of ethanolic extract of L. acutangula (LA) was isolated using bioassay-guided approach. Five major fractions were collected and evaluated for their anti-proliferative activity against non-small cell lung cancer cells (NCI-H460). Among the test fractions, the fraction LA/FII effectively decreased the growth of cancer cells with IC50 values of 10 µg/ml concentration. Furthermore, it significantly increased intracellular reactive oxygen species and decreased the mitochondrial membrane potential. The apoptogenic activity of fraction LA/FII was confirmed by cell shrinkage, membrane blebbing and formation of apoptotic bodies. A single bioactive compound was isolated from the active faction, LA/FII and subsequently identified as 1,8 dihydroxy-4-methylanthracene 9,10-dione (compound 1) by comparing its spectral data [Ultraviolet (UV), Infrared (IR), Nuclear magnetic resonance (NMR) and Electrospray Ionization-Mass Spectroscopy (ESI-MS)] with literature values. This is the first report on the isolation of compound 1 from this plant.

  19. Investigation by microarray analysis of effects of cigarette design characteristics on gene expression in human lung mucoepidermoid cancer cells NCI-H292 exposed to cigarette smoke.

    PubMed

    Sekine, Takashi; Sakaguchi, Chikako; Fukano, Yasuo

    2015-02-01

    The effects of tobacco leaf types and the presence or absence of charcoal in the cigarette filters on gene expression were investigated using cigarette prototypes made of either flue-cured (FC) leaf or burley (BLY) leaf and Kentucky Reference 2R4F as a representative blend cigarette with cellulose acetate filters or charcoal filters. NCI-H292, human lung mucoepidermoid carcinoma cell line, was exposed to the total particulate matter (TPM) and gas/vapor phase (GVP) from each prototype for 8h and then the changes in gene expression from microarray data were analyzed. A number of genes associated with oxidative stress, inflammation, DNA damage and xenobiotic response were modified by the two fractions, TPM and GVP, from the three prototypes with cellulose acetate filters. Both TPM and GVP fractions strongly enhanced the gene expression of HMOX1, which is encoding the limiting enzyme in heme degradation and a key regulator of oxidative stress and inflammatory process. Comparing the effects of TPM and GVP fraction, TPM strongly activated Nrf2 pathway-mediated anti-oxidative stress reaction, whereas GVP caused notable DNA damage response. In comparison of FC and BLY, TPM from FC more strongly induced the expression of histone family proteins than that from BLY. GVP from FC markedly induced gene expression associated with HSP70-mediated inflammation relative to that from BLY. Charcoal included in the filter strongly reduced the effects of GVP from each cigarette on gene expression. However, charcoal did not modified the effects of TPM. As a whole, charcoal is a useful material for reducing the biological effects of GVP.

  20. Insulin-like growth factor pathway genes and blood concentrations, dietary protein and risk of prostate cancer in the NCI Breast and Prostate Cancer Cohort Consortium (BPC3).

    PubMed

    Tsilidis, Konstantinos K; Travis, Ruth C; Appleby, Paul N; Allen, Naomi E; Lindström, Sara; Albanes, Demetrius; Ziegler, Regina G; McCullough, Marjorie L; Siddiq, Afshan; Barricarte, Aurelio; Berndt, Sonja I; Bueno-de-Mesquita, H Bas; Chanock, Stephen J; Crawford, E David; Diver, W Ryan; Gapstur, Susan M; Giovannucci, Edward; Gu, Fangyi; Haiman, Christopher A; Hayes, Richard B; Hunter, David J; Johansson, Mattias; Kaaks, Rudolf; Kolonel, Laurence N; Kraft, Peter; Le Marchand, Loic; Overvad, Kim; Polidoro, Silvia; Riboli, Elio; Schumacher, Fredrick R; Stevens, Victoria L; Trichopoulos, Dimitrios; Virtamo, Jarmo; Willett, Walter C; Key, Timothy J

    2013-07-15

    It has been hypothesized that a high intake of dairy protein may increase prostate cancer risk by increasing the production of insulin-like growth factor 1 (IGF-1). Several single nucleotide polymorphisms (SNPs) have been weakly associated with circulating concentrations of IGF-1 and IGF binding protein 3 (IGFBP-3), but none of these SNPs was associated with risk of prostate cancer. We examined whether an association between 16 SNPs associated with circulating IGF-1 or IGFBP-3 concentrations and prostate cancer exists within subgroups defined by dietary protein intake in 5,253 cases and 4,963 controls of European ancestry within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). The BPC3 includes nested case-control studies within large North-American and European cohorts. Per-allele odds ratios for prostate cancer for the SNPs were compared across tertiles of protein intake, which was expressed as the percentage of energy derived from total, animal, dairy or plant protein sources, using conditional logistic regression models. Total, animal, dairy and plant protein intakes were significantly positively associated with blood IGF-1 (p < 0.01), but not with IGFBP-3 concentrations (p > 0.10) or with risk of prostate cancer (p > 0.20). After adjusting for multiple testing, the SNP-prostate cancer associations did not differ by intakes of protein, although two interactions by intake of plant protein were of marginal statistical significance [SSTR5 (somatostatin receptor 5)-rs197056 (uncorrected p for interaction, 0.001); SSTR5-rs197057 (uncorrected p for interaction, 0.002)]. We found no strong evidence that the associations between 16 IGF pathway SNPs and prostate cancer differed by intakes of dietary protein.

  1. The ROS-induced cytotoxicity of ascorbate is attenuated by hypoxia and HIF-1alpha in the NCI60 cancer cell lines.

    PubMed

    Sinnberg, Tobias; Noor, Seema; Venturelli, Sascha; Berger, Alexander; Schuler, Paul; Garbe, Claus; Busch, Christian

    2014-03-01

    Intravenous application of high-dose ascorbate is used in complementary palliative medicine to treat cancer patients. Pharmacological doses of ascorbate in the mM range induce cytotoxicity in cancer cells mediated by reactive oxygen species (ROS), namely hydrogen peroxide and ascorbyl radicals. However, little is known about intrinsic or extrinsic factors modulating this ascorbate-mediated cytotoxicity. Under normoxia and hypoxia, ascorbate IC50 values were determined on the NCI60 cancer cells. The cell cycle, the influence of cobalt chloride-induced hypoxia-inducible factor-1α (HIF-1α) and the glucose transporter 1 (GLUT-1) expression (a pro-survival HIF-1α-downstream-target) were analysed after ascorbate exposure under normoxic and hypoxic conditions. The amount of ascorbyl radicals increased with rising serum concentrations. Hypoxia (0.1% O2 ) globally increased the IC50 of ascorbate in the 60 cancer cell lines from 4.5 ± 3.6 mM to 10.1 ± 5.9 mM (2.2-fold increase, P < 0.001, Mann-Whitney t-test), thus inducing cellular resistance towards ascorbate. This ascorbate resistance depended on HIF-1α-signalling, but did not correlate with cell line-specific expression of the ascorbate transporter GLUT-1. However, under normoxic and hypoxic conditions, ascorbate treatment at the individual IC50 reduced the expression of GLUT-1 in the cancer cells. Our data show a ROS-induced, HIF-1α- and O2 -dependent cytotoxicity of ascorbate on 60 different cancer cells. This suggests that for clinical application, cancer patients should additionally be oxygenized to increase the cytotoxic efficacy of ascorbate.

  2. The UF/NCI family of hybrid computational phantoms representing the current US population of male and female children, adolescents, and adults—application to CT dosimetry

    NASA Astrophysics Data System (ADS)

    Geyer, Amy M.; O'Reilly, Shannon; Lee, Choonsik; Long, Daniel J.; Bolch, Wesley E.

    2014-09-01

    Substantial increases in pediatric and adult obesity in the US have prompted a major revision to the current UF/NCI (University of Florida/National Cancer Institute) family of hybrid computational phantoms to more accurately reflect current trends in larger body morphometry. A decision was made to construct the new library in a gridded fashion by height/weight without further reference to age-dependent weight/height percentiles as these become quickly outdated. At each height/weight combination, circumferential parameters were defined and used for phantom construction. All morphometric data for the new library were taken from the CDC NHANES survey data over the time period 1999-2006, the most recent reported survey period. A subset of the phantom library was then used in a CT organ dose sensitivity study to examine the degree to which body morphometry influences the magnitude of organ doses for patients that are underweight to morbidly obese in body size. Using primary and secondary morphometric parameters, grids containing 100 adult male height/weight bins, 93 adult female height/weight bins, 85 pediatric male height/weight bins and 73 pediatric female height/weight bins were constructed. These grids served as the blueprints for construction of a comprehensive library of patient-dependent phantoms containing 351 computational phantoms. At a given phantom standing height, normalized CT organ doses were shown to linearly decrease with increasing phantom BMI for pediatric males, while curvilinear decreases in organ dose were shown with increasing phantom BMI for adult females. These results suggest that one very useful application of the phantom library would be the construction of a pre-computed dose library for CT imaging as needed for patient dose-tracking.

  3. Insulin-like growth factor pathway genes and blood concentrations, dietary protein, and risk of prostate cancer in the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)

    PubMed Central

    Tsilidis, Konstantinos K; Travis, Ruth C; Appleby, Paul N; Allen, Naomi E; Lindström, Sara; Albanes, Demetrius; Ziegler, Regina G; McCullough, Marjorie L; Siddiq, Afshan; Barricarte, Aurelio; Berndt, Sonja I; Bueno-de-Mesquita, H Bas; Chanock, Stephen J; Crawford, E David; Diver, W Ryan; Gapstur, Susan M; Giovannucci, Edward; Gu, Fangyi; Haiman, Christopher A; Hayes, Richard B; Hunter, David J; Johansson, Mattias; Kaaks, Rudolf; Kolonel, Laurence N; Kraft, Peter; Le Marchand, Loic; Overvad, Kim; Polidoro, Silvia; Riboli, Elio; Schumacher, Fredrick R; Stevens, Victoria L; Trichopoulos, Dimitrios; Virtamo, Jarmo; Willett, Walter C; Key, Timothy J

    2013-01-01

    It has been hypothesized that a high intake of dairy protein may increase prostate cancer risk by increasing the production of insulin-like growth factor 1 (IGF-1). Several single nucleotide polymorphisms (SNPs) have been weakly associated with circulating concentrations of IGF-1 and IGF binding protein 3 (IGFBP-3), but none of these SNPs was associated with risk of prostate cancer. We examined whether an association between 16 SNPs associated with circulating IGF-1 or IGFBP-3 concentrations and prostate cancer exists within subgroups defined by dietary protein intake in 5,253 cases and 4,963 controls of European ancestry within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). The BPC3 includes nested case-control studies within large North-American and European cohorts. Per allele odds ratios for prostate cancer for the SNPs were compared across tertiles of protein intake, which was expressed as the percentage of energy derived from total, animal, dairy or plant protein sources, using conditional logistic regression models. Total, animal, dairy and plant protein intakes were significantly positively associated with blood IGF-1 (P<0.01), but not with IGFBP-3 concentrations (P>0.10) or with risk of prostate cancer (P>0.20). After adjusting for multiple testing, the SNP-prostate cancer associations did not differ by intakes of protein, although two interactions by intake of plant protein were of marginal statistical significance (SSTR5 (somatostatin receptor 5) -rs197056 [uncorrected P for interaction, 0.001]; SSTR5-rs197057 [uncorrected P for interaction, 0.002]). We found no strong evidence that the associations between 16 IGF pathway SNPs and prostate cancer differed by intakes of dietary protein. PMID:23341348

  4. Analysis of the DNA damage produced by a platinum-acridine antitumor agent and its effects in NCI-H460 lung cancer cells.

    PubMed

    Qiao, Xin; Zeitany, Alexandra E; Wright, Marcus W; Essader, Amal S; Levine, Keith E; Kucera, Gregory L; Bierbach, Ulrich

    2012-07-01

    High-performance liquid chromatography in conjunction with electrospray mass spectrometry (LC-ESMS) was used to structurally characterize the adducts formed by the platinum-acridine agent [PtCl(en)(N-(2-(acridin-9-ylamino)ethyl)-N-methylpropionimidamide)](NO(3))(2) (compound 1) in cell-free DNA. Compound 1 forms monofunctional adducts exclusively with guanine, based on the fragments identified in enzymatic digests (dG*, dGMP*, dApG*, and dTpG*, where the asterisk denotes bound drug). The time course of accumulation and DNA adduct formation of compound 1 and the clinical drug cisplatin in NCI-H460 lung cancer cells at physiologically relevant drug concentrations (0.1 μM) was studied by inductively-coupled plasma mass spectrometry (ICP-MS). Compound 1 accumulates rapidly in cells and reaches intracellular levels of up to 60-fold higher than those determined for cisplatin. The hybrid agent shows unusually high DNA binding levels: while cisplatin adducts form at a maximum frequency of 5 adducts per 10(6) nucleotides, compound 1 produces 25 adducts per 10(6) nucleotides after only 3 h of continuous incubation with the lung cancer cells. The high overall levels of compound 1 in the cells and in cellular DNA over the entire 12-h treatment period translate into a rapid decrease in cell viability. Possible implications of these findings for the mechanism of action of compound 1 and the agent's potential to overcome tumor resistance to cisplatin are discussed.

  5. Common genetic variants in prostate cancer risk prediction – Results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)

    PubMed Central

    Lindström, Sara; Schumacher, Fredrick R.; Cox, David; Travis, Ruth C.; Albanes, Demetrius; Allen, Naomi E.; Andriole, Gerald; Berndt, Sonja I.; Boeing, Heiner; Bueno-de-Mesquita, H. Bas; Crawford, E. David; Diver, W. Ryan; Ganziano, J. Michael; Giles, Graham G.; Giovannucci, Edward; Gonzalez, Carlos A.; Henderson, Brian; Hunter, David J.; Johansson, Mattias; Kolonel, Laurence N.; Ma, Jing; Le Marchand, Loic; Pala, Valeria; Stampfer, Meir; Stram, Daniel O.; Thun, Michael J.; Tjonneland, Anne; Trichopoulos, Dimitrios; Virtamo, Jarmo; Weinstein, Stephanie J.; Willett, Walter C.; Yeager, Meredith; Hayes, Richard B.; Severi, Gianluca; Haiman, Christopher A.; Chanock, Stephen J.; Kraft, Peter

    2012-01-01

    Background One of the goals of personalized medicine is to generate individual risk profiles that could identify individuals in the population that exhibit high risk. The discovery of more than two-dozen independent SNP markers in prostate cancer has raised the possibility for such risk stratification. In this study, we evaluated the discriminative and predictive ability for prostate cancer risk models incorporating 25 common prostate cancer genetic markers, family history of prostate cancer and age. Methods We fit a series of risk models and estimated their performance in 7,509 prostate cancer cases and 7,652 controls within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). We also calculated absolute risks based on SEER incidence data. Results The best risk model (C-statistic=0.642) included individual genetic markers and family history of prostate cancer. We observed a decreasing trend in discriminative ability with advancing age (P=0.009), with highest accuracy in men younger than 60 years (C-statistic=0.679). The absolute ten-year risk for 50-year old men with a family history ranged from 1.6% (10th percentile of genetic risk) to 6.7% (90th percentile of genetic risk). For men without family history, the risk ranged from 0.8% (10th percentile) to 3.4% (90th percentile). Conclusions Our results indicate that incorporating genetic information and family history in prostate cancer risk models can be particularly useful for identifying younger men that might benefit from PSA screening. Impact Although adding genetic risk markers improves model performance, the clinical utility of these genetic risk models is limited. PMID:22237985

  6. Computational analysis of liquid chromatography-tandem mass spectrometric steroid profiling in NCI H295R cells following angiotensin II, forskolin and abiraterone treatment.

    PubMed

    Mangelis, Anastasios; Dieterich, Peter; Peitzsch, Mirko; Richter, Susan; Jühlen, Ramona; Hübner, Angela; Willenberg, Holger S; Deussen, Andreas; Lenders, Jacques W M; Eisenhofer, Graeme

    2016-01-01

    Adrenal steroid hormones, which regulate a plethora of physiological functions, are produced via tightly controlled pathways. Investigations of these pathways, based on experimental data, can be facilitated by computational modeling for calculations of metabolic rate alterations. We therefore used a model system, based on mass balance and mass reaction equations, to kinetically evaluate adrenal steroidogenesis in human adrenal cortex-derived NCI H295R cells. For this purpose a panel of 10 steroids was measured by liquid chromatographic-tandem mass spectrometry. Time-dependent changes in cell incubate concentrations of steroids - including cortisol, aldosterone, dehydroepiandrosterone and their precursors - were measured after incubation with angiotensin II, forskolin and abiraterone. Model parameters were estimated based on experimental data using weighted least square fitting. Time-dependent angiotensin II- and forskolin-induced changes were observed for incubate concentrations of precursor steroids with peaks that preceded maximal increases in aldosterone and cortisol. Inhibition of 17-alpha-hydroxylase/17,20-lyase with abiraterone resulted in increases in upstream precursor steroids and decreases in downstream products. Derived model parameters, including rate constants of enzymatic processes, appropriately quantified observed and expected changes in metabolic pathways at multiple conversion steps. Our data demonstrate limitations of single time point measurements and the importance of assessing pathway dynamics in studies of adrenal cortical cell line steroidogenesis. Our analysis provides a framework for evaluation of steroidogenesis in adrenal cortical cell culture systems and demonstrates that computational modeling-derived estimates of kinetic parameters are an effective tool for describing perturbations in associated metabolic pathways.

  7. Depletion of Bcl-2 by an antisense oligonucleotide induces apoptosis accompanied by oxidation and externalization of phosphatidylserine in NCI-H226 lung carcinoma cells.

    PubMed

    Koty, Patrick P; Tyurina, Yulia Y; Tyurin, Vladimir A; Li, Shang-Xi; Kagan, Valerian E

    2002-01-01

    Oxidant-induced apoptosis involves oxidation of many different and essential molecules including phospholipids. As a result of this non-specific oxidation, any signaling role of a particular phospholipid-class of molecules is difficult to elucidate. To determine whether preferential oxidation of phosphatidylserine (PS) is an early event in apoptotic signaling related to PS externalization and is independent of direct oxidant exposure, we chose a genetic-based induction of apoptosis. Apoptosis was induced in the lung cancer cell line NCI-H226 by decreasing the amount of Bcl-2 protein expression by preventing the translation of bcl-2 mRNA using an antisense bcl-2 oligonucleotide. Peroxidation of phospholipids was assayed using a fluorescent technique based on metabolic integration of an oxidation-sensitive and fluorescent fatty acid, cis-parinaric acid (PnA), into cellular phospholipids and subsequent HPLC separation of cis-PnA-labeled phospholipids. We found a decrease in Bcl-2 was associated with a selective oxidation of PS in a sub-population of the cells with externalized PS. No significant difference in oxidation of cis-PnA-labeled phospholipids was observed in cells treated with medium alone or a nonsense oligonucleotide. Treatment with either nonsensc or antisense bcl-2 oligonucleotides was not associated with changes in the pattern of individual phospholipid classes as determined by HPTLC. These metabolic and topographical changes in PS arrangement in plasma membrane appear to be early responses to antisense bcl-2 exposure that trigger a PS-dependent apoptotic signaling pathway. This observed externalization of PS may facilitate the 'labeling' of apoptotic cells for recognition by macrophage scavenger receptors and subsequent phagocytic clearance.

  8. Replication of five prostate cancer loci identified in an Asian population – Results from the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)

    PubMed Central

    Lindstrom, Sara; Schumacher, Fredrick R.; Campa, Daniele; Albanes, Demetrius; Andriole, Gerald; Berndt, Sonja I.; Bueno-de-Mesquita, H. Bas; Chanock, Stephen J.; Diver, W. Ryan; Ganziano, J. Michael; Gapstur, Susan M.; Giovannucci, Edward; Haiman, Christopher A.; Henderson, Brian; Hunter, David J; Johansson, Mattias; Kolonel, Laurence N.; Le Marchand, Loic; Ma, Jing; Stampfer, Meir; Stevens, Victoria L.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Willett, Walter C.; Yeager, Meredith; Hsing, Ann W.; Kraft, Peter

    2011-01-01

    Background A recent Genome-Wide Association Study (GWAS) of prostate cancer in a Japanese population identified five novel regions not previously discovered in other ethnicities. In this study, we attempt to replicate these five loci in a series of nested prostate cancer case-control studies of European ancestry. Methods We genotyped five SNPs: rs13385191 (chromosome 2p24), rs12653946 (5p15), rs1983891 (6p21), rs339331 (6p22) and rs9600079 (13q22), in 7,956 prostate cancer cases and 8,148 controls from a series of nested case-control studies within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). We tested each SNP for association with prostate cancer risk and assessed if associations differed with respect to disease severity and age of onset. Results Four SNPs (rs13385191, rs12653946, rs1983891 and rs339331) were significantly associated with prostate cancer risk (p-values ranging from 0.01 to 1.1×10-5). Allele frequencies and odds ratios were overall lower in our population of European descent compared to the discovery Asian population. SNP rs13385191 (C2orf43) was only associated with low-stage disease (p=0.009, case-only test). No other SNP showed association with disease severity or age of onset. We did not replicate the 13q22 SNP, rs9600079 (p=0.62). Conclusions Four SNPs associated with prostate cancer risk in an Asian population are also associated with prostate cancer risk in men of European descent. Impact This study illustrates the importance of evaluation of prostate cancer risk markers across ethnic groups. PMID:22056501

  9. Identification of a novel potent, selective and cell permeable inhibitor of protein kinase CK2 from the NIH/NCI Diversity Set Library.

    PubMed

    Guerra, Barbara; Hochscherf, Jennifer; Jensen, Nina Bjelkerup; Issinger, Olaf-Georg

    2015-08-01

    The anti-apoptotic protein kinase CK2 increasingly becomes an attractive target in cancer research with great therapeutic potential. Here, we have performed an in vitro screening of the Diversity Set III of the DTP program from the NCI/NIH, comprising 1600 compounds. We have identified 1,3-Dichloro-6-[(E)-((4-methoxyphenyl)imino)methyl] dibenzo(b,d) furan-2,7-diol (referred to as D11) to be a potent and selective inhibitor of protein kinase CK2. The D11 compound was tested against 354 eukaryotic protein kinases. By setting the threshold for inhibition to <2% remaining kinase activity, only DYRK1B, IRAK1 and PIM3 were inhibited to an extent as the tetrameric CK2 holoenzyme and its catalytic subunits α and α'. The IC50 values for the CK2α and CK2α' were on average 1-2 nM in comparison to the DYRK1B, IRAK1 and PIM3 kinases, which ranged from 18 to 49 nM. Cell permeability and efficacy of D11 were tested with cells in culture. In MIA PaCa-2 cells (human pancreatic carcinoma cell line), the phosphorylation of the CK2 biomarker CDC37 at S13 was almost completely inhibited in the presence of D11. This was observed both under normoxia and hypoxia. In the case of the human non-small cell lung carcinoma cell line, H1299, increasing amounts of D11 led to an inhibition of S380/T382/383 phosphorylation in PTEN, another biomarker for CK2 activity.

  10. Inhibition of proliferation, VEGF secretion of human neuroendocrine tumor cell line NCI-H727 by an antagonist of growth hormone-releasing hormone (GH-RH) in vitro.

    PubMed

    Sacewicz, Małgorzata; Lawnicka, Hanna; Siejka, Agnieszka; Stepień, Tomasz; Krupiński, Roman; Komorowski, Jan; Stepień, Henryk

    2008-09-08

    Growth hormone-releasing hormone (GH-RH) can stimulate not only growth hormone (GH) secretion by anterior pituitary gland but also proliferation of many cancer cell lines in vitro and in xenografts tumor models in vivo. Several antagonists of GH-RH have been shown to inhibit several cancer growths, but the role of GH-RH antagonists in the regulation of neuroendocrine cancers cell proliferation and tumor progression remains obscure. The aim of the study was to evaluate the influence of JV-1-36 (synthetic GH-RH antagonist) on proliferation and VEGF secretion by human neuroendocrine lung non-small cell carcinoma (NCI-H727) using cell culture model. The in vitro effect of JV-1-36 on the proliferation of NCI-H727 cells was assessed by the measurement of BrdU incorporation by colorimetric immunoassay. The presence of VEGF and membrane GH-RH receptors on the surface of H727 cells were visualized by immunocytochemistry using specific anti-GH-RH receptor antibody directed to the carboxy-terminal region. VEGF secretion to the cell cultures supernatants was assessed by ELISA methods. Immunoreactive cell membrane GH-RH receptors and VEGF-immunopositive cytoplasmatic granules were clearly confined on the surface of nearly all cancer cells. JV-1-36 at the concentration of 10(-6)-10(-10)M significantly inhibited growth of H727 cells, compared with untreated controls. In H727 cells, the antiproliferative JV-1-36 effect was associated with a dose-dependent reduction of VEGF secretion. In conclusion, our findings demonstrate the strong evidence for the antiproliferative action of GH-RH antagonist JV-1-36 for the NCI-H727 cells. In addition the suppression of VEGF secretion by H727 cells might contribute, at least in part, to the antitumor action of GH-RH antagonists.

  11. CREM confers cAMP responsiveness in human steroidogenic acute regulatory protein expression in NCI-H295R cells rather than SF-1/Ad4BP.

    PubMed

    Sugawara, Teruo; Sakuragi, Noriaki; Minakami, Hisanori

    2006-10-01

    Steroidogenic acute regulatory (StAR) protein plays a critical role in steroid hormone synthesis. Tropic hormones induce human StAR gene expression by a cAMP-dependent pathway. Steroidogenic factor-1/adrenal-4-binding protein (SF-1/Ad4BP) plays an important role in the expression of human StAR gene. We investigated the mechanism of cAMP responsiveness in human StAR gene expression in NCI-H295R cells. The StAR promoter activity and protein levels in cells subjected to various treatments were examined. Anti-SF-1/Ad4BP IgG transfection treatment resulted in decreases in the basal StAR promoter activity and StAR protein levels, but did not affect cAMP-stimulated promoter activity and protein levels. The basal and cAMP-stimulated StAR promoter activity levels were reduced in SF-1/Ad4BP mutant (G35E)-transfected cells, but the cAMP induction of StAR promoter activity in response to 1 mM 8-Br-cAMP was not inhibited when G35E SF-1/Ad4BP mutant expression vectors were co-transfected with cAMP-response element-binding (CREB) expression vectors. Although the basal StAR mRNA expression and protein levels were decreased by SF-1/Ad4BP-siRNA treatment, the cAMP-stimulated StAR mRNA expression and protein levels did not change. The basal StAR promoter activity level was not decreased by cAMP-response element modulator (CREM)-siRNA treatment, but the cAMP-stimulated StAR promoter activity level, the magnitude of cAMP induction of StAR promoter, and the cAMP-stimulated StAR protein level were decreased. The cAMP induction of StAR promoter activity in cells was inhibited when S117ACREM mutant expressionvectors were transfected. We conclude that inhibition of the function of SF-1/Ad4BP does not reduce the cAMP induction of StAR promoter activity and protein level. CREM is needed to confer cAMP responsiveness in human StAR protein expression.

  12. Curcumin alters gene expression-associated DNA damage, cell cycle, cell survival and cell migration and invasion in NCI-H460 human lung cancer cells in vitro.

    PubMed

    Chiang, I-Tsang; Wang, Wei-Shu; Liu, Hsin-Chung; Yang, Su-Tso; Tang, Nou-Ying; Chung, Jing-Gung

    2015-10-01

    Lung cancer is the most common cause of cancer mortality and new cases are on the increase worldwide. However, the treatment of lung cancer remains unsatisfactory. Curcumin has been shown to induce cell death in many human cancer cells, including human lung cancer cells. However, the effects of curcumin on genetic mechanisms associated with these actions remain unclear. Curcumin (2 µM) was added to NCI-H460 human lung cancer cells and the cells were incubated for 24 h. Total RNA was extracted from isolated cells for cDNA synthesis, labeling, microarray hybridization and flour‑labeled cDNA hybridized on chip. Localized concentrations of fluorescent molecules were detected and quantified using Expression Console software (Affymetrix) with default RMA parameters. GeneGo software was used for the key genes involved and their possible interaction pathways. The results showed that ~170 genes were significantly upregulated and 577 genes were significantly downregulated in curcumin‑treated cells. Specifically, the up‑ and downregulated genes included CCNE2, associated with DNA damage; ID3, associated with cell survival and 146 genes with a >2- to 3-fold change including the TP53INP1 gene, associated with DNA damage; CDC6, CDCA5, TAKMIP2, CDK14, CDK5, CDCA76, CDC25A, CDC5L and SKP2, associated with cell cycle; the CARD6, ID1 and ID2 genes, associated with cell survival and the BRMS1L, associated with cell migration and invasion. Additionally, 59 downregulated genes exhibited a >4-fold change, including the DDIT3 gene, associated with DNA damage; while 97 genes had a >3- to 4-fold change including the DDIT4 gene, associated with DNA damage; the CCPG1 gene, associated with cell cycle and 321 genes with a >2- to 3-fold including the GADD45A and CGREF1 genes, associated with DNA damage; the CCPG1 gene, associated with cell cycle, the TNFRSF10B, GAS5, TSSC1 and TNFRSF11B gene, associated with cell survival and the ARHAP29 and CADM2 genes, associated with cell migration

  13. The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel

    PubMed Central

    2010-01-01

    Background Drinking water contaminated with inorganic arsenic is associated with increased risk for different types of cancer. Paradoxically, arsenic trioxide can also be used to induce remission in patients with acute promyelocytic leukemia (APL) with a success rate of approximately 80%. A comprehensive study examining the mechanisms and potential signaling pathways contributing to the anti-tumor properties of arsenic trioxide has not been carried out. Methods Here we applied a systems biology approach to identify gene biomarkers that underlie tumor cell responses to arsenic-induced cytotoxicity. The baseline gene expression levels of 14,500 well characterized human genes were associated with the GI50 data of the NCI-60 tumor cell line panel from the developmental therapeutics program (DTP) database. Selected biomarkers were tested in vitro for the ability to influence tumor susceptibility to arsenic trioxide. Results A significant association was found between the baseline expression levels of 209 human genes and the sensitivity of the tumor cell line panel upon exposure to arsenic trioxide. These genes were overlayed onto protein-protein network maps to identify transcriptional networks that modulate tumor cell responses to arsenic trioxide. The analysis revealed a significant enrichment for the oxidative stress response pathway mediated by nuclear factor erythroid 2-related factor 2 (NRF2) with high expression in arsenic resistant tumor cell lines. The role of the NRF2 pathway in protecting cells against arsenic-induced cell killing was validated in tumor cells using shRNA-mediated knock-down. Conclusions In this study, we show that the expression level of genes in the NRF2 pathway serve as potential gene biomarkers of tumor cell responses to arsenic trioxide. Importantly, we demonstrate that tumor cells that are deficient for NRF2 display increased sensitivity to arsenic trioxide. The results of our study will be useful in understanding the mechanism of

  14. Downregulation of HIF-1α inhibits the proliferation and invasion of non-small cell lung cancer NCI-H157 cells

    PubMed Central

    QIAN, JIALIN; BAI, HAO; GAO, ZHIQIANG; DONG, YU; PEI, JUN; MA, MEILI; HAN, BAOHUI

    2016-01-01

    Lung cancer, specifically non-small cell lung cancer (NSCLC), is the leading cause of cancer-associated mortality in the world. In previous years, almost no significant advancements have been made towards the molecular characterization of NSCLC, which highlights the requirement for novel target genes. Hypoxia inducible factor-1α (HIF-1α) is known to be essential in tumorigenesis, as it regulates the expression of numerous factors that are involved in angiogenesis, cellular proliferation and apoptosis. However, no direct association between HIF-1α and NSCLC treatment has previously been established. The aim of the present study was to characterize the effect of HIF-1α on NSCLC and to explore the possible mechanism. Additionally, HIF-1α small interfering (si)RNA and diamminedichloroplatinum (DDP) were used in combination to explore the combined effects on NSCLC cells. Lung carcinoma NCI-H157 cells were treated with HIF-1α small interfering (si)RNA, 5 µg/ml DDP or a combination of the two, and the proliferation, apoptosis and invasion ability of the cells were detected using a cell counting kit-8 assay, Annexin V/propidium iodide staining and a Transwell assay, respectively. In addition, the protein levels of caspase-3/9, anti-apoptotic protein B-cell lymphoma-2 (Bcl-2), vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), phosphoinositide 3-kinase (PI3K), phosphorylated (p-)PI3K, protein kinase B (AKT), p-AKT, extracellular signal-regulated kinase (ERK) and p-ERK were detected using western blot analysis. Similar to DPP treatment, HIF-1α siRNA treatment may reduce cell proliferation and the invasiveness of tumor cells while promoting apoptosis. Additionally, HIF-1α siRNA may increase the levels of the apoptotic proteins caspases 3 and 9 and inhibit the expression of Bcl-2. These anti-tumor effects may be acting through the VEGF/PEDF, PI3K/AKT and Raf/mitogen-activated protein kinase kinase/ERK signaling pathways. The effects

  15. NCI Cancer Research Data Ecosystem

    Cancer.gov

    An infographic explaining NCI’s present and future efforts to promote a culture of sharing data—clinical, genomic, proteomic, imaging, patient histories, and outcomes data—among stakeholders to impact cancer care.

  16. Step 4: NCI Funding Determinations

    Cancer.gov

    Funding determinations are made around Oct. 1 each federal fiscal year. These decisions take into account several factors, including Congressional mandates, new scientific opportunities and program priorities when deciding which grants receive funding.

  17. NCI: DCTD: Biometric Research Program

    Cancer.gov

    The Biometric Research Program (BRP) is the statistical and biomathematical component of the Division of Cancer Treatment, Diagnosis and Centers (DCTDC). Its members provide statistical leadership for the national and international research programs of the division in developmental therapeutics, developmental diagnostics, diagnostic imaging and clinical trials.

  18. NCI: DCTD: Biometric Research Branch

    Cancer.gov

    The Biometric Research Branch (BRB) is the statistical and biomathematical component of the Division of Cancer Treatment, Diagnosis and Centers (DCTDC). Its members provide statistical leadership for the national and international research programs of the division in developmental therapeutics, developmental diagnostics, diagnostic imaging and clinical trials.

  19. NCI: DCTD: Biometric Research Branch

    Cancer.gov

    The Biometric Research Branch (BRP) is the statistical and biomathematical component of the Division of Cancer Treatment, Diagnosis and Centers (DCTDC). Its members provide statistical leadership for the national and international research programs of the division in developmental therapeutics, developmental diagnostics, diagnostic imaging and clinical trials.

  20. NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute’s Technology Transfer Center (TTC) facilitates partnerships between the NIH research laboratories and external partners. With specialized teams, TTC guides the interactions of our partners from the point of discovery to patenting, from invention development to licensing. We play a key role in helping to accelerate development of cutting-edge research by connecting our partners to NIH’s world-class researchers, facilities, and knowledge.

  1. NCI: DCTD: Biometric Research Program

    Cancer.gov

    The Biometric Research Program (BRB) is the statistical and biomathematical component of the Division of Cancer Treatment, Diagnosis and Centers (DCTDC). Its members provide statistical leadership for the national and international research programs of the division in developmental therapeutics, developmental diagnostics, diagnostic imaging and clinical trials.

  2. NCI Dictionary of Genetics Terms

    Cancer.gov

    A dictionary of more than 150 genetics-related terms written for healthcare professionals, developed to support the comprehensive, evidence-based, peer-reviewed PDQ cancer genetics information summaries.

  3. NCI R25T Award

    Cancer.gov

    Institutional award for predoctoral or postdoctoral candidates or mentored junior faculty who are pursuing careers in cancer prevention, control, behavioral, and population sciences or transdisciplinary sciences.

  4. Regimen-related toxicity following reduced-intensity stem-cell transplantation (RIST): comparison between Seattle criteria and National Cancer Center Common Toxicity Criteria (NCI-CTC) version 2.0.

    PubMed

    Sakiyama, M; Kami, M; Hori, A; Imataki, O; Hamaki, T; Murashige, N; Kobayashi, K; Kishi, Y; Kojima, R; Kim, S-W; Kusumi, E; Yuji, K; Miyakoshi, S; Mori, S; Tanosaki, R; Taniguchi, S; Takaue, Y

    2004-11-01

    Acute regimen-related toxicity (RRT) is minimal in reduced-intensity stem-cell transplantation (RIST). However, the Seattle RRT grading (Bearman et al), developed in the context of conventional-intensity transplantation, is frequently applied to RIST. We compared the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0 with the Seattle criteria after RIST in 86 patients. RRT within 30 days of transplant graded by both sets of criteria were significantly associated with the outcome confirming the predictive value of both the systems. A total of 15 patients died of disease progression, and 12 of transplant-related mortality: RRT (n = 2), graft-versus-host disease (GVHD) (n = 7), infection (n = 1), and others (n = 2). GVHD-related deaths primarily resulted from infections after steroid treatment (n = 6) and bronchiolitis obliterans (n = 1). This study shows that NCI-CTC is appropriate in toxicity evaluation of RIST, and that its application to RIST enables a toxicity comparison between RIST and other types of cancer treatments. Since GVHD is a significant problem in RIST, modifications are required to evaluate immunological complications following RIST.

  5. DT-13, a saponin monomer 13 of the Dwarf lilyturf tuber, synergized with vinorelbine to induce mitotic arrest via activation of ERK signaling pathway in NCI-H1299 cells.

    PubMed

    Li, Hongyang; Sun, Li; Li, Hang; Lv, Xiaodan; Semukunzi, Herve; Li, Ruiming; Yu, Jun; Yuan, Shengtao; Lin, Sensen

    2017-03-16

    Vinorelbine (NVB) is a semi-synthetic vinca alkaloid that is approved for the clinical therapy of lung cancer. However, the clinical application of NVB was limited because of the acquisition of resistance and inacceptable toxicity. Therefore, it is of great interest to develop low-cytotoxic drugs that can synergize with NVB. DT-13, a saponin monomer 13 of the Dwarf lilyturf tuber, showed inhibitory effects on tumor metastasis and angiogenesis in the previous studies. Here, we found that DT-13 combined with NVB exhibited synergistic effect to inhibit the cell proliferation in human lung cancer NCI-H1299 cells rather than human embryonic lung fibroblasts WI-38. The combination of DT-13 and NVB significantly inhibited the colony formation, induced cellular and nuclear morphological changes, and triggered cell cycle arrest at mitotic phase. Furthermore, MAPK signaling pathway was activated by the combination treatment, and the activation of ERK was required for the induction of mitotic arrest. Taken together, DT-13 combined with NVB exhibited synergistic anticancer effect in NCI-H1299 cells, and DT-13 may be a candidate agent for adjuvant chemotherapy of NVB in lung cancer.

  6. Danusertib, a potent pan-Aurora kinase and ABL kinase inhibitor, induces cell cycle arrest and programmed cell death and inhibits epithelial to mesenchymal transition involving the PI3K/Akt/mTOR-mediated signaling pathway in human gastric cancer AGS and NCI-N78 cells.

    PubMed

    Yuan, Chun-Xiu; Zhou, Zhi-Wei; Yang, Yin-Xue; He, Zhi-Xu; Zhang, Xueji; Wang, Dong; Yang, Tianxing; Pan, Si-Yuan; Chen, Xiao-Wu; Zhou, Shu-Feng

    2015-01-01

    Gastric cancer is the second leading cause of cancer-related death worldwide, with a poor response to current chemotherapy. Danusertib is a pan-inhibitor of the Aurora kinases and a third-generation Bcr-Abl tyrosine kinase inhibitor with potent anticancer effects, but its antitumor effect and underlying mechanisms in the treatment of human gastric cancer are unknown. This study aimed to investigate the effects of danusertib on cell growth, apoptosis, autophagy, and epithelial to mesenchymal transition and the molecular mechanisms involved in human gastric cancer AGS and NCI-N78 cells. The results showed that danusertib had potent growth-inhibitory, apoptosis-inducing, and autophagy-inducing effects on AGS and NCI-N78 cells. Danusertib arrested AGS and NCI-N78 cells in G2/M phase, with downregulation of expression of cyclin B1 and cyclin-dependent kinase 1 and upregulation of expression of p21 Waf1/Cip1, p27 Kip1, and p53. Danusertib induced mitochondria-mediated apoptosis, with an increase in expression of proapoptotic protein and a decrease in antiapoptotic proteins in both cell lines. Danusertib induced release of cytochrome c from the mitochondria to the cytosol and triggered activation of caspase 9 and caspase 3 in AGS and NCI-N78 cells. Further, danusertib induced autophagy, with an increase in expression of beclin 1 and conversion of microtubule-associated protein 1A/1B-light chain 3 (LC3-I) to LC3-II in both cell lines. Inhibition of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein kinase pathways as well as activation of 5' AMP-activated protein kinase contributed to the proautophagic effect of danusertib in AGS and NCI-N78 cells. SB202191 and wortmannin enhanced the autophagy-inducing effect of danusertib in AGS and NCI-N78 cells. In addition, danusertib inhibited epithelial to mesenchymal transition with an increase in expression of E-cadherin and a decrease in expression of

  7. Danusertib, a potent pan-Aurora kinase and ABL kinase inhibitor, induces cell cycle arrest and programmed cell death and inhibits epithelial to mesenchymal transition involving the PI3K/Akt/mTOR-mediated signaling pathway in human gastric cancer AGS and NCI-N78 cells

    PubMed Central

    Yuan, Chun-Xiu; Zhou, Zhi-Wei; Yang, Yin-Xue; He, Zhi-Xu; Zhang, Xueji; Wang, Dong; Yang, Tianxing; Pan, Si-Yuan; Chen, Xiao-Wu; Zhou, Shu-Feng

    2015-01-01

    Gastric cancer is the second leading cause of cancer-related death worldwide, with a poor response to current chemotherapy. Danusertib is a pan-inhibitor of the Aurora kinases and a third-generation Bcr-Abl tyrosine kinase inhibitor with potent anticancer effects, but its antitumor effect and underlying mechanisms in the treatment of human gastric cancer are unknown. This study aimed to investigate the effects of danusertib on cell growth, apoptosis, autophagy, and epithelial to mesenchymal transition and the molecular mechanisms involved in human gastric cancer AGS and NCI-N78 cells. The results showed that danusertib had potent growth-inhibitory, apoptosis-inducing, and autophagy-inducing effects on AGS and NCI-N78 cells. Danusertib arrested AGS and NCI-N78 cells in G2/M phase, with downregulation of expression of cyclin B1 and cyclin-dependent kinase 1 and upregulation of expression of p21 Waf1/Cip1, p27 Kip1, and p53. Danusertib induced mitochondria-mediated apoptosis, with an increase in expression of proapoptotic protein and a decrease in antiapoptotic proteins in both cell lines. Danusertib induced release of cytochrome c from the mitochondria to the cytosol and triggered activation of caspase 9 and caspase 3 in AGS and NCI-N78 cells. Further, danusertib induced autophagy, with an increase in expression of beclin 1 and conversion of microtubule-associated protein 1A/1B-light chain 3 (LC3-I) to LC3-II in both cell lines. Inhibition of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein kinase pathways as well as activation of 5′ AMP-activated protein kinase contributed to the proautophagic effect of danusertib in AGS and NCI-N78 cells. SB202191 and wortmannin enhanced the autophagy-inducing effect of danusertib in AGS and NCI-N78 cells. In addition, danusertib inhibited epithelial to mesenchymal transition with an increase in expression of E-cadherin and a decrease in expression

  8. Three centered hydrogen bonds of the type C=O···H(N)···X-C in diphenyloxamide derivatives involving halogens and a rotating CF3 group: NMR, QTAIM, NCI and NBO studies.

    PubMed

    Lakshmipriya, A; Rama Chaudhari, Sachin; Shahi, Abhishek; Arunan, E; Suryaprakash, N

    2015-03-21

    The existence of three centered C=O···H(N)···X-C hydrogen bonds (H-bonds) involving organic fluorine and other halogens in diphenyloxamide derivatives has been explored by NMR spectroscopy and quantum theoretical studies. The three centered H-bond with the participation of a rotating CF3 group and the F···H-N intramolecular hydrogen bonds, a rare observation of its kind in organofluorine compounds, has been detected. It is also unambiguously established by a number of one and two dimensional NMR experiments, such as temperature perturbation, solvent titration, (15)N-(1)H HSQC, and (19)F-(1)H HOESY, and is also confirmed by theoretical calculations, such as quantum theory of atoms in molecules (QTAIM), natural bond orbital (NBO) and non-covalent interaction (NCI).

  9. Molecular Mechanism of Cinnamomum verum Component Cuminaldehyde Inhibits Cell Growth and Induces Cell Death in Human Lung Squamous Cell Carcinoma NCI-H520 Cells In Vitro and In Vivo.

    PubMed

    Yang, Shu-Mei; Tsai, Kuen-Daw; Wong, Ho-Yiu; Liu, Yi-Heng; Chen, Ta-Wei; Cherng, Jonathan; Hsu, Kwang-Ching; Ang, Yao-Uh; Cherng, Jaw-Ming

    2016-01-01

    Cinnamomum verum is used to make the spice cinnamon and has been used as a traditional Chinese herbal medicine. We evaluated the effects and the molecular mechanisms of cuminaldehyde (CuA), a constituent of the bark of Cinnamomum verum, on human lung squamous cell carcinoma NCI-H520 cells. Specifically, cell viability was evaluated by colorimetric assay; cytotoxicity by LDH release; apoptosis was determined by Western blotting, and morphological analysis with, acridine orange and neutral red stainings and comet assay; topoisomerase I activity was assessed using assay based upon DNA relaxation and topoisomerase II by DNA relaxation plus decatentation of kinetoplast DNA; lysosomal vacuolation and volume of acidic compartments (VAC) were evaluated with neutral red staining. The results show that CuA suppressed proliferation and induced apoptosis as indicated by an up-regulation of pro-apoptotic bax and bak genes and a down-regulation of anti-apoptotic bcl-2 and bcl-XL genes, mitochondrial membrane potential loss, cytochrome c release, activation of caspase 3 and 9, and morphological characteristics of apoptosis, including blebbing of the plasma membrane, nuclear condensation, fragmentation, apoptotic body formation, and comet with elevated tail intensity and moment. In addition, CuA also induced lysosomal vacuolation with increased VAC, cytotoxicity, as well as suppressions of both topoisomerase I and II activities in a dose-dependent manner. Further study revealed the growth-inhibitory effect of CuA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of CuA against NCI-H520 cells is accompanied by downregulations of proliferative control involving apoptosis and both topoisomerase I and II activities, and upregulation of lysosomal with increased VAC and cytotoxicity. Similar effects were found in other cell lines, including human lung adenocarcinoma A549 cells and colorectal adenocarcinoma COLO 205 (results not

  10. Hair analysis for delta(9)-THC, delta(9)-THC-COOH, CBN and CBD, by GC/MS-EI. Comparison with GC/MS-NCI for delta(9)-THC-COOH.

    PubMed

    Baptista, Maria João; Monsanto, Paula Verâncio; Pinho Marques, Estela Gouveia; Bermejo, Ana; Avila, Sofia; Castanheira, Alice Martelo; Margalho, Cláudia; Barroso, Mário; Vieira, Duarte Nuno

    2002-08-14

    A sensitive analytical method was developed for quantitative analysis of delta(9)-tetrahydrocannabinol (delta(9)-THC), 11-nor-delta(9)-tetrahydrocannabinol-carboxylic acid (delta(9)-THC-COOH), cannabinol (CBN) and cannabidiol (CBD) in human hair. The identification of delta(9)-THC-COOH in hair would document Cannabis use more effectively than the detection of parent drug (delta(9)-THC) which might have come from environmental exposure. Ketamine was added to hair samples as internal standard for CBN and CBD. Ketoprofen was added to hair samples as internal standard for the other compounds. Samples were hydrolyzed with beta-glucuronidase/arylsulfatase for 2h at 40 degrees C. After cooling, samples were extracted with a liquid-liquid extraction procedure (with chloroform/isopropyl alcohol, after alkalinization, and n-hexane/ethyl acetate, after acidification), which was developed in our laboratory. The extracts were analysed before and after derivatization with pentafluoropropionic anhydride (PFPA) and pentafluoropropanol (PFPOH) using a Hewlett Packard gas chromatographer/mass spectrometer detector, in electron impact mode (GC/MS-EI). Derivatized delta(9)-THC-COOH was also analysed using a Hewlett Packard gas chromatographer/mass spectrometer detector, in negative ion chemical ionization mode (GC/MS-NCI) using methane as the reagent gas. Responses were linear ranging from 0.10 to 5.00 ng/mg hair for delta(9)-THC and CBN, 0.10-10.00 ng/mg hair for CBD, 0.01-5.00 ng/mg for delta(9)-THC-COOH (r(2)>0.99). The intra-assay precisions ranged from <0.01 to 12.40%. Extraction recoveries ranged from 80.9 to 104.0% for delta(9)-THC, 85.9-100.0% for delta(9)-THC-COOH, 76.7-95.8% for CBN and 71.0-94.0% for CBD. The analytical method was applied to 87 human hair samples, obtained from individuals who testified in court of having committed drug related crimes. Quantification of delta(9)-THC-COOH using GC/MS-NCI was found to be more convenient than GC/MS-EI. The latter may give rise

  11. Blockade of T-type voltage-dependent Ca2+ channels by benidipine, a dihydropyridine calcium channel blocker, inhibits aldosterone production in human adrenocortical cell line NCI-H295R.

    PubMed

    Akizuki, Osamu; Inayoshi, Atsushi; Kitayama, Tetsuya; Yao, Kozo; Shirakura, Shiro; Sasaki, Katsutoshi; Kusaka, Hideaki; Matsubara, Masahiro

    2008-04-28

    Benidipine, a long-lasting dihydropyridine calcium channel blocker, is used for treatment of hypertension and angina. Benidipine exerts pleiotropic pharmacological features, such as renoprotective and cardioprotective effects. In pathophysiological conditions, the antidiuretic hormone aldosterone causes development of renal and cardiovascular diseases. In adrenal glomerulosa cells, aldosterone is produced in response to extracellular potassium, which is mainly mediated by T-type voltage-dependent Ca2+ channels. More recently, it has been demonstrated that benidipine inhibits T-type Ca2+ channels in addition to L-type Ca2+ channels. Therefore, effect of calcium channel blockers, including benidipine, on aldosterone production and T-type Ca2+ channels using human adrenocortical cell line NCI-H295R was investigated. Benidipine efficiently inhibited KCl-induced aldosterone production at low concentration (3 and 10 nM), with inhibitory activity more potent than other calcium channel blockers. Patch clamp analysis indicated that benidipine concentration-dependently inhibited T-type Ca2+ currents at 10, 100 and 1000 nM. As for examined calcium channel blockers, inhibitory activity for T-type Ca2+ currents was well correlated with aldosterone production. L-type specific calcium channel blockers calciseptine and nifedipine showed no effect in both assays. These results indicate that inhibition of T-type Ca2+ channels is responsible for inhibition of aldosterone production in NCI-H295R cells. Benidipine efficiently inhibited KCl-induced upregulation of 11-beta-hydroxylase mRNA and aldosterone synthase mRNA as well as KCl-induced Ca2+ influx, indicating it as the most likely inhibition mechanism. Benidipine partially inhibited angiotensin II-induced aldosterone production, plus showed additive effects when used in combination with the angiotensin II type I receptor blocker valsartan. Benidipine also partially inhibited angiotensin II-induced upregulation of the above m

  12. Tumorigenicity, invasion and metastasis of the small cell lung cancer cell line NCI-H69 and two derivative lines MOG-H69V and MOG-H69VZ.

    PubMed

    Khan, M Z; McNicol, A M; Freshney, R I

    1996-01-01

    Two adherent cell lines MOG-H69V and MOG-H69VZ have been isolated from a continuous cell line, NCI-H69, derived from human small cell lung cancer by Carney et al, [1987]. They have been established and characterised morphologically, biochemically, and for growth characteristics in vitro Khan et al (19). In the present study both the parental and the derivative lines have been investigated for invasiveness in vitro and in vivo. The parental line showed an early invasiveness compared with both the derivative cell lines. All cell lines formed tumours in nude mice with 100% take rate. Xenograft histology of all the cell lines revealed pleomorphic tumours, however the derivative lines showed areas of focal, large, spindle cells containing both acidic and neutral mucin, and spaces between the cells were found filled with alcianophilic, amorphous material. The parental line was invasive and metastatic. Tumours of both the derivative lines were non-metastatic under similar conditions. They were also investigated for neuroendocrine-cell marker expression. These data show that while the behaviour of the parental line was compatible with small cell lung cancer, that of the derivative lines was more indicative of non-small cell lung cancer, both in vitro and in vivo. As previous data suggested a common origin of the parental and the derivative lines, probably from a stem cell subpopulation present in the parental line, these lines represent a useful model for the study of phenotypic changes in lung cancer.

  13. Infant Child Care and Attachment Security: Results of the NICHD Study of Early Child Care.

    ERIC Educational Resources Information Center

    National Inst. of Child Health and Human Development (NIH), Bethesda, MD. Early Child Care Network.

    A longitudinal study explored the effects of different aspects of child care on infants' attachment security. Child care variables examined included age of entry; the quality, amount, stability, and type of care; and mother's sensitivity to the child's needs. When the validity of the Strange Situation was tested by comparing children with low and…

  14. 77 FR 52338 - Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD); Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-29

    ... attendance limited to space available. A portion of this meeting will be closed to the public in accordance..., including taxis, hotel, and airport shuttles, will be inspected before being allowed on campus....

  15. NICHD Research Networks Help Piece Together the Puzzle of Polycystic Ovary Syndrome

    MedlinePlus

    ... Behavior Branch (CDBB) Contraception Research Branch (CRB) Developmental Biology and Structural Variation Branch (DBSVB) Fertility and Infertility ( ... Basic Mechanisms of Genome Regulation Bone and Matrix Biology in Development and Disease Cell and Structural Biology ...

  16. 77 FR 10759 - Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Notice...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-23

    ... of Child Health and Human Development. Dates and Times: March 7, 2012, at 3 p.m. Place: American...., Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Office of Program... National Institute of Child Health and Human Development, National Institutes of Health. BILLING CODE...

  17. Mental Retardation and Developmental Disabilities (MRDD) Branch. NICHD Report to the NACHHD Council

    ERIC Educational Resources Information Center

    National Institute of Child Health and Human Development (NICHD), 2005

    2005-01-01

    This document is the quadrennial report of the Mental Retardation and Developmental Disabilities (MRDD) Branch to the National Advisory Child Health and Human Development (NACHHD) Council. The MRDD Branch is a vital, evolving entity within the Center for Developmental Biology and Perinatal Medicine (CDBPM) at the National Institute of Child …

  18. Mental Retardation and Developmental Disabilities Branch (NICHD) Report to the NACHHD Council.

    ERIC Educational Resources Information Center

    National Inst. of Child Health and Human Development (NIH), Bethesda, MD. Mental Retardation and Developmental Disabilities Branch.

    This report highlights some of the projects supported by the Mental Retardation and Developmental Disabilities (MRDD) Branch of the Center for Research for Mothers and Children at the National Institute of Child Health and Human Development since its last report in January 1997. The MRDD Branch provides support for research, research training,…

  19. 78 FR 50425 - Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD); Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-19

    ... Health and Human Development Council. The meeting will be open to the public as indicated below, with... Human Development Council. Date: September 19, 2013. Open: September 19, 2013, 8:00 a.m. to 12:00 p.m... order to facilitate public attendance at the open session of Council in the main meeting...

  20. Molecular structure, hydrogen-bonding patterns and topological analysis (QTAIM and NCI) of 5-methoxy-2-nitroaniline and 5-methoxy-2-nitroaniline with 2-amino-5-nitropyridine (1:1) co-crystal

    NASA Astrophysics Data System (ADS)

    Hernández-Paredes, Javier; Carrillo-Torres, Roberto C.; López-Zavala, Alonso A.; Sotelo-Mundo, Rogerio R.; Hernández-Negrete, Ofelia; Ramírez, José Zeferino; Alvarez-Ramos, Mario E.

    2016-09-01

    In this work, we report an analysis of the molecular structure and the hydrogen-bonding patterns in the crystal structures of 5-methoxy-2-nitroaniline (1) and 5-methoxy-2-nitroaniline with 2-amino-5-nitropyridine (1:1) co-crystal (2). X-ray single crystal diffraction experiments were carried out to analyse the intermolecular forces in terms of geometrical criteria. These intermolecular interactions were also investigated through topological analysis of the electron density (ρ) employing QTAIM and NCI methods. Additionally, Raman spectroscopy was employed to analyse the vibrational characteristics of the entitled materials. The supramolecular structure of (1) is produced by crosslinked chains, which are primarily dominated by N-H···O hydrogen bonds. However, C-H···O interactions reinforce this connectivity. Furthermore, the molecules in (1) are connected through two-centre instead of the three-centre hydrogen-bonding interactions between the -NH2 and -NO2 groups commonly observed in nitroanilines. The asymmetric unit of (2) contains two symmetry-independent molecules of 5-methoxy-2-nitroaniline (5M2NA) and two symmetry-independent molecules of 2-amino-5-nitropyridine (2A5NP). The supramolecular structure of (2) is developed not only for N-H···O but also N-H···N and supportive C-H···O hydrogen bonds. The two symmetry-independent 2A5NP molecules bound to each other through two-centre hydrogen bonds between the -NH2 and -NO2 groups forming C22(16) chains. 5M2NA molecules bound to these chains forming R22 9 and R22(8) synthons. Experimental and theoretical results obtained in this work suggest that C-H···O interactions play an important role in the stabilization of these supramolecular structures.

  1. Success Stories | NCI Technology Transfer Center | TTC

    Cancer.gov

    NIH’s world-class facilities, resources, and discoveries. Some of our partnerships have resulted in the commercialization of therapeutics, vaccines, diagnostics, medical devices and research tools that benefit patients worldwide. TTC is proud to share a few examples of our successful partnerships. | [google6f4cd5334ac394ab.html

  2. Patents | NCI Technology Transfer Center | TTC

    Cancer.gov

    Timely reporting of discoveries is critical, because patent protection may be lost if an invention is publicly disclosed prior to filing a patent application. A public disclosure may include Talks, presentations, posters; Publications, including titles and abstracts posted on websites; Internet postings; Graduate student theses, job interviews; andDiscussions with non-NIH personnel without a Confidential Disclosure Agreement (CDA) in place. | [google6f4cd5334ac394ab.html

  3. Women of NCI at Frederick | Poster

    Cancer.gov

    By Andrea Frydl, Contributing Writer Editor’s note: This article has been updated since it was originally posted on August 22, 2013 Each year, the Employee Diversity Team (EDT) acknowledges a group of women for their great achievements and contributions towards the mission of the National Cancer Institute at Frederick.  Details of their achievements and unique personalities were on display in Building 549 in March, and we present a brief summary of each below:

  4. Research Initiatives | DCCPS/NCI/NIH

    Cancer.gov

    This page provides detailed information about currently funded RFA initiatives both led by DCCPS, and those led by other NIH Institutes and Centers (I/Cs) that include DCCPS as a partner. Each initiative includes a table of funded grants and a map that shows the location of funded institutions.

  5. Lowy Named Acting NCI Director April 2015

    Cancer.gov

    Douglas Lowy, M.D., today was officially named the National Cancer Institute’s Acting Director. Dr. Lowy, a cancer researcher for more than 40 years, received the National Medal of Technology and Innovation from President Obama in 2014 for his research th

  6. Vision and Mission | DCCPS/NCI/NIH

    Cancer.gov

    The Division of Cancer Control and Population Sciences both generates new knowledge and seeks to ensure that the products of cancer control research are effectively applied in all segments of the population.

  7. About TTC | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute’s Technology Transfer Center (TTC) facilitates partnerships between the NIH research laboratories and external partners, and helping to accelerate development of cutting-edge research by connecting our partners to NIH’s world-class facilities, resources, and discoveries. Contact us to learn more. | [google6f4cd5334ac394ab.html

  8. Biological Semiconductors | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute's Cancer Diagnostic Program and the Food and Drug Administration's Center for Devices and Radiological Health is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize biological semiconductors as diagnostic sensors.

  9. Who We Are | DCCPS/NCI/NIH

    Cancer.gov

    DCCPS was organized in 1997 to lead NCI’s efforts in cancer control research. Since that time, the division has grown and evolved to become a stronghold of NCI’s campaign to eliminate suffering and death from cancer.

  10. SEER Statistics | DCCPS/NCI/NIH

    Cancer.gov

    The Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute works to provide information on cancer statistics in an effort to reduce the burden of cancer among the U.S. population.

  11. Search Technologies | NCI Technology Transfer Center | TTC

    Cancer.gov

    Our team of technology transfer specialists has specialized training in invention reporting, patenting, patent strategy, executing technology transfer agreements and marketing. TTC is comprised of professionals with diverse legal, scientific, and business/marketing expertise. Most of our staff hold doctorate-level technical and/or legal training.

  12. Available Technologies | NCI Technology Transfer Center | TTC

    Cancer.gov

    Our team of technology transfer specialists has specialized training in invention reporting, patenting, patent strategy, executing technology transfer agreements and marketing. TTC is comprised of professionals with diverse legal, scientific, and business/marketing expertise. Most of our staff hold doctorate-level technical and/or legal training.

  13. NCI Dictionary | Cancer Trends Progress Report

    Cancer.gov

    The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

  14. Provocative Questions in Cancer: NCI Seminar

    Cancer.gov

    science writers' seminar to discuss various aspects of one of NCI’s signature efforts -- the Provocative Questions project. Discussion will focus on the scientific research that surrounds some of these questions.

  15. Key Collaborations | DCCPS/NCI/NIH

    Cancer.gov

    DCCPS builds bridges across NIH and with other organizations by fostering partnerships on initiatives that emphasize and promote transdisciplinary team science, stretching across multiple disciplines and levels of analysis.

  16. Asthma: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases

    PubMed Central

    Hartert, Tina V.; Martinez, Fernando D.; Weiss, Scott T.; Fahy, John V.

    2014-01-01

    Asthma is a common disease with enormous public health costs, and its primary prevention is an ambitious and important goal. Understanding of how host and environmental factors interact to cause asthma is incomplete, but persistent questions about mechanisms should not stop clinical research efforts aimed at reducing the prevalence of childhood asthma. Achieving the goal of primary prevention of asthma will involve integrated and parallel sets of research activities in which mechanism-oriented studies of asthma inception proceed alongside clinical intervention studies to test biologically plausible prevention ideas. For example, continued research is needed, particularly in young children, to uncover biomarkers that identify asthma risk and provide potential targets of intervention, and to improve understanding of the role of microbial factors in asthma risk and disease initiation. In terms of clinical trials that could be initiated now or in the near future, we recommend three interventions for testing: (1) preventing asthma through prophylaxis against respiratory syncytial virus and human rhinovirus infections of the airway; (2) immune modulation, using prebiotics, probiotics, and bacterial lysates; and (3) prevention of allergen sensitization and allergic inflammation, using anti-IgE. These interventions should be tested while other, more universal prevention measures that may promote lung health are also investigated. These potential universal lung health measures include prevention of preterm delivery; reduced exposure of the fetus and young infant to environmental pollutants, including tobacco smoke; prevention of maternal and child obesity; and management of psychosocial stress. PMID:24754822

  17. The Sports Guide: NHLBI Planning Guide for Cardiovascular Risk Reduction Projects at Sporting Events.

    ERIC Educational Resources Information Center

    National Heart, Lung, and Blood Inst. (DHHS/NIH), Bethesda, MD.

    The most recent national surveys of public awareness and knowledge of treatment and control of cardiovascular disease (CVD) show that health initiatives targeting specific populations are effective ways to support health promotion and disease prevention. Projects and activities outlined in this guide are directed to spectators at sporting events,…

  18. Bronchopulmonary dysplasia: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases.

    PubMed

    McEvoy, Cindy T; Jain, Lucky; Schmidt, Barbara; Abman, Steven; Bancalari, Eduardo; Aschner, Judy L

    2014-04-01

    Bronchopulmonary dysplasia (BPD) is the most common complication of extreme preterm birth. Infants who develop BPD manifest aberrant or arrested pulmonary development and can experience lifelong alterations in cardiopulmonary function. Despite decades of promising research, primary prevention of BPD has proven elusive. This workshop report identifies current barriers to the conduct of primary prevention studies for BPD and causal pathways implicated in BPD pathogenesis. Throughout, we highlight promising areas for research to improve understanding of normal and aberrant lung development, distinguish BPD endotypes, and ascertain biomarkers for more targeted therapeutic approaches to prevention. We conclude with research recommendations and priorities to accelerate discovery and promote lung health in infants born preterm.

  19. Progress and new directions in genetics of tuberculosis: an NHLBI working group report.

    PubMed

    Smith, Issar; Nathan, Carl; Peavy, Hannah H

    2005-12-15

    Tuberculosis (TB), along with AIDS and malaria, is one of the three major killers among infectious diseases. New approaches to preventing, diagnosing, and curing TB are needed, which depend on a better understanding of Mycobacterium tuberculosis and the host. The National Heart, Lung, and Blood Institute convened a working group to develop recommendations for future TB research, including genetic aspects of the disease. The following areas were identified: (1) animal model research to improve understanding of persistence, reactivation, and granulomatous reactions; (2) preclinical studies aimed at shortening treatment of TB; (3) new resources for manipulating and characterizing the M. tuberculosis genome, proteome chips for more specific diagnoses, and studies of genes that appear to be essential but whose functions are not known; (4) prospective studies associated with clinical trials in populations with or at risk of TB to advance development of diagnostics and prognostics; (5) new quantitative and bioinformatic approaches to study the interaction between M. tuberculosis and the infected host and how this influences the infection process; (6) molecular characterization of M. tuberculosis genome diversity and phylogenetic analysis; (7) coordinated studies of human genome scans; (8) genetic epidemiology studies; (9) activities to foster knowledge dissemination, education, and training; and (10) coordination between the National Institutes of Health, the Gates Foundation, the Global Alliance for Tuberculosis Drug Development, and other organizations.

  20. Red blood cell fatty acid composition and the metabolic syndrome: NHLBI GOLDN study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Different fatty acids may vary in their effect on the metabolic syndrome (MetS). We tested whether fatty acid classes measured in red blood cells (RBC) are associated with the MetS or its components. Included were men (n=497, 49+/-16 y) and women (n=539, 48+/-16 y) from 187 families in the Genetics ...

  1. Perspectives from NHLBI Global Health Think Tank Meeting for Late Stage (T4) Translation Research.

    PubMed

    Engelgau, Michael M; Peprah, Emmanuel; Sampson, Uchechukwu K A; Mishoe, Helena; Benjamin, Ivor J; Douglas, Pamela S; Hochman, Judith S; Ridker, Paul M; Brandes, Neal; Checkley, William; El-Saharty, Sameh; Ezzati, Majid; Hennis, Anselm; Jiang, Lixin; Krumholz, Harlan M; Lamourelle, Gabrielle; Makani, Julie; Narayan, K M Venkat; Ohene-Frempong, Kwaku; Straus, Sharon E; Stuckler, David; Chambers, David A; Belis, Deshirée; Bennett, Glen C; Boyington, Josephine E; Creazzo, Tony L; de Jesus, Janet M; Krishnamurti, Chitra; Lowden, Mia R; Punturieri, Antonello; Shero, Susan T; Young, Neal S; Zou, Shimian; Mensah, George A

    2016-07-21

    Almost three-quarters (74%) of all the noncommunicable disease burden is found within low- and middle-income countries. In September 2014, the National Heart, Lung, and Blood Institute held a Global Health Think Tank meeting to obtain expert advice and recommendations for addressing compelling scientific questions for late stage (T4) research-research that studies implementation strategies for proven effective interventions-to inform and guide the National Heart, Lung, and Blood Institute's global health research and training efforts. Major themes emerged in two broad categories: 1) developing research capacity; and 2) efficiently defining compelling scientific questions within the local context. Compelling scientific questions included how to deliver inexpensive, scalable, and sustainable interventions using alternative health delivery models that leverage existing human capital, technologies and therapeutics, and entrepreneurial strategies. These broad themes provide perspectives that inform an overarching strategy needed to reduce the heart, lung, blood, and sleep disorders disease burden and global health disparities.

  2. Family Structure, Psychosocial Factors, and Cardiovascular Risk Factors in the NHLBI CARDIA Study

    DTIC Science & Technology

    2013-11-21

    Additionally, familial stressors originating from both spouses and children are associated with angina pectoris (37) and worsened CAD outcomes (57). Besides...negative aspects of social relations predictive of angina pectoris ? a 6-year follow-up study of middle-aged Danish women and men. J. of Epid. and

  3. Serum Urate Is Not Associated with Coronary Artery Calcification: The NHLBI Family Heart Study

    PubMed Central

    NEOGI, TUHINA; TERKELTAUB, ROBERT; ELLISON, R. CURTIS; HUNT, STEVEN; ZHANG, YUQING

    2011-01-01

    Objective Urate may have effects on vascular remodeling and atherosclerosis. We had shown an association between serum uric acid (SUA) and carotid atherosclerotic plaques. Inflammation and vascular remodeling in atherosclerosis promote coronary artery calcification (CAC), a preclinical marker for atherosclerosis. Here, we examined whether SUA is associated with CAC, using the same study sample and methods as for our previous carotid atherosclerosis study. Methods The National Heart, Lung, and Blood Institute Family Heart Study is a multicenter study designed to assess risk factors for heart disease. Participants were recruited from population-based cohorts in the US states of Massachusetts, North Carolina, Minnesota, Utah, and Alabama. CAC was assessed with helical computed tomography (CT). We conducted sex-specific and family-cluster analyses, as well as additional analyses among persons without risk factors related to both cardiovascular disease and hyperuricemia, adjusting for potential confounders as we had in the previous study of carotid atherosclerosis. Results For the CAC study, 2412 subjects had both SUA and helical CT results available (55% women, age 58 ± 13 yrs, body mass index 27.6 ± 5.3). We found no association of SUA with CAC in men or women [OR in men: 1.0, 1.11, 0.86, 0.90; women: 1.0, 0.83, 1.00, 0.87 for increasing categories of SUA: < 5 (referent group), 5 to < 6, 6 to < 6.8, ≥ 6.8 mg/dl, respectively], nor in subgroup analyses. Conclusion Replicating the methods used to demonstrate an association of SUA with carotid atherosclerosis did not reveal any association between SUA and CAC, suggesting that SUA likely does not contribute to atherosclerosis through effects on arterial calcification. The possibility that urate has divergent pathophysiologic effects on atherosclerosis and artery calcification merits further study. PMID:20889594

  4. Outcome of Extremely Low Birth Weight Infants with Congenital Heart Defects in the Eunice Kennedy Shriver NICHD Neonatal Research Network

    PubMed Central

    Pappas, Athina; Shankaran, Seetha; Hansen, Nellie I.; Bell, Edward F.; Stoll, Barbara J.; Laptook, Abbot R.; Walsh, Michele C.; Das, Abhik; Bara, Rebecca; Hale, Ellen C.; Newman, Nancy S.; Boghossian, Nansi S.; Murray, Jeffrey C.; Cotten, C. Michael; Adams-Chapman, Ira; Hamrick, Shannon; Higgins, Rosemary D.

    2013-01-01

    Little is known about the outcomes of extremely low birth weight (ELBW) preterm infants with congenital heart defects (CHDs). The aim of this study was to assess the mortality, morbidity, and early childhood outcomes of ELBW infants with isolated CHD compared with infants with no congenital defects. Participants were 401–1,000 g infants cared for at National Institute of Child Health and Human Development Neonatal Research Network centers between January 1, 1998 and December 31, 2005. Neonatal morbidities and 18–22 months’ corrected age outcomes were assessed. Neurodevelopmental impairment (NDI) was defined as moderate to severe cerebral palsy, Bayley II mental or psychomotor developmental index < 70, bilateral blindness, or hearing impairment requiring aids. Poisson regression models were used to estimate relative risks for outcomes while adjusting for gestational age, small for gestational-age status, and other variables. Of 14,457 ELBW infants, 110 (0.8 %) had isolated CHD, and 13,887 (96 %) had no major birth defect. The most common CHD were septal defects, tetralogy of Fallot, pulmonary valve stenosis, and coarctation of the aorta. Infants with CHD experienced increased mortality (48 % compared with 35 % for infants with no birth defect) and poorer growth. Surprisingly, the adjusted risks of other short-term neonatal morbidities associated with prematurity were not significantly different. Fifty-seven (52 %) infants with CHD survived to 18–22 months’ corrected age, and 49 (86 %) infants completed follow-up. A higher proportion of surviving infants with CHD were impaired compared with those without birth defects (57 vs. 38 %, p = 0.004). Risk of death or NDI was greater for ELBW infants with CHD, although 20% of infants survived without NDI. PMID:22644414

  5. Physical nature of interactions in Zn(II) complexes with 2,2'-bipyridyl: quantum theory of atoms in molecules (QTAIM), interacting quantum atoms (IQA), noncovalent interactions (NCI), and extended transition state coupled with natural orbitals for chemical valence (ETS-NOCV) comparative studies.

    PubMed

    Cukrowski, Ignacy; de Lange, Jurgens H; Mitoraj, Mariusz

    2014-01-23

    In the present account factors determining the stability of ZnL, ZnL2, and ZnL3 complexes (L = bpy, 2,2′-bipyridyl) were characterized on the basis of various techniques: the quantum theory of atoms in molecules (QTAIM), energy decomposition schemes based on interacting quantum atoms (IQA), and extended transition state coupled with natural orbitals for chemical valence (ETS-NOCV). Finally, the noncovalent interactions (NCI) index was also applied. All methods consistently indicated that the strength of the coordination bonds, Zn–O and Zn–N, decreases from ZnL to ZnL3. Importantly, it has been identified that the strength of secondary intramolecular heteropolar hydrogen bonding interactions, CH···O and CH···N, increases when going from ZnL to ZnL3. A similar trend appeared to be valid for the π-bonding as well as electrostatic stabilization. In addition to the above leading bonding contributions, all techniques suggested the existence of very subtle, but non-negligible additional stabilization from the CH···HC electronic exchange channel; these interactions are the weakest among all considered here. From IQA it was found that the local diatomic interaction energy, Eint(H,H), amounts at HF to −2.5, −2.7, and −2.9 kcal mol(–1) for ZnL, ZnL2, and ZnL3, respectively (−2.1 kcal mol(–1) for ZnL at MP2). NOCV-based deformation density channels showed that formation of CH--HC contacts in Zn complexes causes significant polarization of σ(C–H) bonds, which accordingly leads to charge accumulation in the CH···HC bay region. Charge depletion from σ(C–H) bonds was also reflected in the calculated spin–spin (1)J(C–H) coupling constants, which decrease from 177.06 Hz (ZnL) to 173.87 Hz (ZnL3). This last result supports our findings of an increase in the local electronic CH···HC stabilization from ZnL to ZnL3 found from QTAIM, IQA, and ETS-NOCV. Finally, this work unites for the first time the results from four methods that are widely

  6. CGH’s Third Year with NCI: Progress, Partnerships, & Possibilities

    Cancer.gov

    The Center for Global Health is embarking on its third year within the National Cancer Institute, and I am pleased with the extraordinary progress and achievements made in this time by our dedicated staff members.  CGH has established new, and strengthened ongoing, initiatives and programs with great success, including the regional Leadership Forums for Cancer Control Planning, the United States – Latin America Cancer Research Network, and the regional Grant Writing Workshops.  CGH has also developed several funding opportunities in collaboration with partners across NIH and our stakeholders.

  7. Mouse Xenograft Model for Mesothelioma | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute is seeking parties interested in collaborative research to co-develop, evaluate, or commercialize a new mouse model for monoclonal antibodies and immunoconjugates that target malignant mesotheliomas. Applications of the technology include models for screening compounds as potential therapeutics for mesothelioma and for studying the pathology of mesothelioma.

  8. NIH Patent Policy | NCI Technology Transfer Center | TTC

    Cancer.gov

    The Public Health Service (PHS) may determine that it is necessary to seek patent protection on its inventions, when doing so would facilitate the commercial development of products or services that will benefit the public health, or when a patent will advance another PHS objective. | [google6f4cd5334ac394ab.html

  9. Linking cancer genome to proteome: NCI's investment into proteogenomics.

    PubMed

    Rivers, Robert C; Kinsinger, Christopher; Boja, Emily S; Hiltke, Tara; Mesri, Mehdi; Rodriguez, Henry

    2014-12-01

    Advances in both targeted and unbiased MS-based proteomics are now at a mature stage for comprehensively and reproducibly characterizing a large part of the cancer proteome. These developments combined with the extensive genomic characterization of several cancer types by large-scale initiatives such as the International Cancer Genome Consortium and Cancer Genome Atlas Project have paved the way for proteogenomic analysis of omics datasets and integration methods. The advances serve as the basis for the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium and this article highlights its current work and future steps in the area of proteogenomics.

  10. 2015 New Grantee Workshop Overview | DCCPS/NCI/NIH

    Cancer.gov

    At the 2015 New Grantee Workshop, the Division of Cancer Control & Population Sciences (DCCPS) brought together approximately forty new investigators who received their first R01 in 2012 and 2013 to build a strong and vibrant cancer control research program and to help advance their careers.

  11. CRADAs: They're Not Just for NCI Anymore | Poster

    Cancer.gov

    By Karen Surabian, Thomas Stackhouse, and Jeffrey Thomas, Contributing Writers, and Bruce Crise, Guest Writer Advancing scientific discovery is increasingly dependent on diverse and innovative partnerships, and the Cooperative Research and Development Agreement (CRADA) is an essential tool for establishing partnerships. CRADAs allow a federal laboratory to enter into collaborative research and development (R&D) projects with outside parties (commercial or nonprofit).

  12. Working with TTC | NCI Technology Transfer Center | TTC

    Cancer.gov

    There are many ways that inventors of the National Institutes of Health and the National Cancer Institute may contribute to the development and commercialization of their inventions | [google6f4cd5334ac394ab.html

  13. Fall Events at the NCI Campus at Frederick | Poster

    Cancer.gov

    Take a Hike Day – September 19 Occupational Health Services and the R&W Club teamed up again to hold Take a Hike Day on September 19. About 45 employees walked or jogged the 1.3-mile course around Fort Detrick during their lunch hours. The event is designed to encourage employees to engage in physical activity, according to Sarah Hooper, RN, manager of OHS. Sports pouch kits that included a water bottle, sunscreen, and an exercise band were given out as prizes to those employees who correctly answered walking trivia questions. The next Take a Hike Day will be held in the spring.

  14. DCCPS Organization and Leadership | DCCPS/NCI/NIH

    Cancer.gov

    The organizational units that make up the DCCPS represent dedicated scientists, professionals, and support staff who work as a team in bringing the best cancer control research activities to the public.

  15. Engineered Biological Pacemakers | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Institute on Aging's Cellular Biophysics Section is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize biological pacemakers.

  16. NCI Director Harold Varmus to address National Press Club

    Cancer.gov

    The barriers that impede greater and faster progress against cancer include the inherent biological properties of tumors; the difficulties of developing new ways to prevent, diagnose and treat cancers; and economic and social factors that slow the nation’

  17. NCI and the Republic of Peru Sign Statement of Intent

    Cancer.gov

    The U.S. National Cancer Institute and the Republic of Peru signed a statement of intent to share an interest in fostering collaborative biomedical research in oncology and a common goal in educating and training the next generation of cancer research sci

  18. Co-Development Agreements | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute's TTC uses three different co-development agreements to help industry and academia interact and partner with National Institutes of Health laboratories and scientists to support technology development activities. | [google6f4cd5334ac394ab.html

  19. Renal Cancer Biomarkers | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute's Laboratory of Proteomics and Analytical Technologies is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize diagnostic, therapeutic and prognostic cancer biomarkers from clinical specimens.

  20. Nitroxyl (HNO) Releasing Therapeutics | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute''s Laboratory of Comparative Carcinogenesis is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize agents that generate HNO in physiological media for therapeutic benefit.

  1. Immunotherapeutics for Pediatric Solid Tumors | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute’s Pediatric Oncology Branch seeks partners interested in licensing or collaborative research to co-develop new immunotherapeutic agents based on chimeric antigen receptor (CARs) for the treatment of pediatric solid tumors.

  2. Reforms speed initiation of NCI-sponsored clinical trials

    Cancer.gov

    The process of opening a cancer clinical trial for patient accrual often takes years, and research has shown that trials which are slow to register patients often fail to finish. Following a thorough review, NCI’s Operational Efficiency Working Group prod

  3. Cancer Control Framework and Synthesis Rationale | DCCPS/NCI/NIH

    Cancer.gov

    Cancer control science is the conduct of basic and applied research in the behavioral, social, and population sciences to create or enhance interventions that, independently or in combination with biomedical approaches, reduce cancer risk, incidence, morbidity and mortality, and improve quality of life.

  4. Usual Dietary Intakes: SAS Macros for the NCI Method

    Cancer.gov

    SAS macros are currently available to facilitate modeling of a single dietary component, whether consumed daily or episodically; ratios of two dietary components that are consumed nearly every day; multiple dietary components, whether consumed daily or episodically.

  5. NCI at Frederick Surpasses Feds Feed Families Goal | Poster

    Cancer.gov

    The 2016 Feds Feed Families campaign recently concluded, with the numbers released earlier this week. A grand total of 33,447 pounds of food were donated in less than three months, surpassing the goal of 28,000 pounds.

  6. Angiogenesis-Based Cancer Therapeutic | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute's Urologic Oncology Branch seeks interested parties to co-develop antagonists to VEGF-A and hepatocyte growth factor (HGF) that block signal transduction and associated cellular responses.

  7. Novel Therapeutic for Inflammatory Disorders | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute's Frederick National Lab's Molecular Targets Laboratory is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize a novel inhibitor of the NF-kappa B signal transduction pathway, which leads to many inflammatory disorders.

  8. Obesity and cardiovascular disease risk factors in black and white girls: the NHLBI Growth and Health Study.

    PubMed Central

    1992-01-01

    OBJECTIVES. Obesity may be a possible explanation for the higher cardiovascular disease mortality in Black women compared with White women. The National Heart, Lung, and Blood Institute Growth and Health Study (NGHS) is designed to assess factors associated with the development of obesity in Black and White preadolescent girls and its effects on major cardiovascular-disease risk factors. METHODS. NGHS is a 5-year cohort study of 2379 girls, aged 9 through 10 years at entry. Anthropometry, blood pressure, and maturation staging are measured annually, and blood lipids biannually. Information on education, income, and family composition is also obtained from parents. RESULTS. At baseline, compared with White girls, Black girls were slightly older, biologically more mature, taller, heavier, and had higher Quetelet Indices, skinfolds, and blood pressures. Black girls had lower triglycerides and higher HDL cholesterol than White girls. Total cholesterol and LDL cholesterol were similar in the two groups. CONCLUSIONS. Baseline descriptive characteristics of the NGHS cohort showed that, in subjects aged 9 and 10 years, racial differences in obesity and blood pressure were already present. PMID:1456335

  9. Reducing Health Inequities in the U.S.: Recommendations From the NHLBI's Health Inequities Think Tank Meeting.

    PubMed

    Sampson, Uchechukwu K A; Kaplan, Robert M; Cooper, Richard S; Diez Roux, Ana V; Marks, James S; Engelgau, Michael M; Peprah, Emmanuel; Mishoe, Helena; Boulware, L Ebony; Felix, Kaytura L; Califf, Robert M; Flack, John M; Cooper, Lisa A; Gracia, J Nadine; Henderson, Jeffrey A; Davidson, Karina W; Krishnan, Jerry A; Lewis, Tené T; Sanchez, Eduardo; Luban, Naomi L; Vaccarino, Viola; Wong, Winston F; Wright, Jackson T; Meyers, David; Ogedegbe, Olugbenga G; Presley-Cantrell, Letitia; Chambers, David A; Belis, Deshirée; Bennett, Glen C; Boyington, Josephine E; Creazzo, Tony L; de Jesus, Janet M; Krishnamurti, Chitra; Lowden, Mia R; Punturieri, Antonello; Shero, Susan T; Young, Neal S; Zou, Shimian; Mensah, George A

    2016-08-02

    The National, Heart, Lung, and Blood Institute convened a Think Tank meeting to obtain insight and recommendations regarding the objectives and design of the next generation of research aimed at reducing health inequities in the United States. The panel recommended several specific actions, including: 1) embrace broad and inclusive research themes; 2) develop research platforms that optimize the ability to conduct informative and innovative research, and promote systems science approaches; 3) develop networks of collaborators and stakeholders, and launch transformative studies that can serve as benchmarks; 4) optimize the use of new data sources, platforms, and natural experiments; and 5) develop unique transdisciplinary training programs to build research capacity. Confronting health inequities will require engaging multiple disciplines and sectors (including communities), using systems science, and intervening through combinations of individual, family, provider, health system, and community-targeted approaches. Details of the panel's remarks and recommendations are provided in this report.

  10. 77 FR 14531 - Proposed Collection; Comment Request; Web-Based Assessment of the NHLBI Clinical Studies Support...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-12

    ... HUMAN SERVICES National Institutes of Health Proposed Collection; Comment Request; Web-Based Assessment... and Budget (OMB) for review and approval. Proposed Collection: Title: Web-Based Assessment of the...-person meetings, Web conferences, and teleconferences; managing distribution of adverse...

  11. Harnessing the Power of Integrated Mitochondrial Biology and Physiology: A Special Report on the NHLBI Mitochondria in Heart Diseases Initiative.

    PubMed

    Ping, Peipei; Gustafsson, Åsa B; Bers, Don M; Blatter, Lothar A; Cai, Hua; Jahangir, Arshad; Kelly, Daniel; Muoio, Deborah; O'Rourke, Brian; Rabinovitch, Peter; Trayanova, Natalia; Van Eyk, Jennifer; Weiss, James N; Wong, Renee; Schwartz Longacre, Lisa

    2015-07-17

    Mitochondrial biology is the sum of diverse phenomena from molecular profiles to physiological functions. A mechanistic understanding of mitochondria in disease development, and hence the future prospect of clinical translations, relies on a systems-level integration of expertise from multiple fields of investigation. Upon the successful conclusion of a recent National Institutes of Health, National Heart, Lung, and Blood Institute initiative on integrative mitochondrial biology in cardiovascular diseases, we reflect on the accomplishments made possible by this unique interdisciplinary collaboration effort and exciting new fronts on the study of these remarkable organelles.

  12. Harnessing the Power of Integrated Mitochondrial Biology and Physiology: A Special Report on the NHLBI Mitochondria in Heart Diseases Initiative

    PubMed Central

    Ping, Peipei; Gustafsson, Åsa B.; Bers, Don M.; Blatter, Lothar; Cai, Hua; Jahangir, Arshad; Kelly, Daniel; Muoio, Deborah; O'Rourke, Brian; Rabinovitch, Peter; Trayanova, Natalia; Van Eyk, Jennifer; Weiss, James N.; Wong, Renee; Longacre, Lisa Schwartz

    2015-01-01

    Summary Mitochondrial biology is the sum of diverse phenomena from molecular profiles to physiological functions. A mechanistic understanding of mitochondria in disease development, and hence the future prospect of clinical translations, relies on a systems-level integration of expertise from multiple fields of investigation. Upon the successful completion of a recent National Institutes of Health, National Heart, Lung, and Blood Institute initiative on integrative mitochondrial biology in cardiovascular diseases, we reflect on the accomplishments made possible by this unique interdisciplinary collaboration effort and exciting new fronts on the study of these remarkable organelles. PMID:26185209

  13. Emerging Research Directions in Adult Congenital Heart Disease: A Report From an NHLBI/ACHA Working Group.

    PubMed

    Gurvitz, Michelle; Burns, Kristin M; Brindis, Ralph; Broberg, Craig S; Daniels, Curt J; Fuller, Stephanie M P N; Honein, Margaret A; Khairy, Paul; Kuehl, Karen S; Landzberg, Michael J; Mahle, William T; Mann, Douglas L; Marelli, Ariane; Newburger, Jane W; Pearson, Gail D; Starling, Randall C; Tringali, Glenn R; Valente, Anne Marie; Wu, Joseph C; Califf, Robert M

    2016-04-26

    Congenital heart disease (CHD) is the most common birth defect, affecting about 0.8% of live births. Advances in recent decades have allowed >85% of children with CHD to survive to adulthood, creating a growing population of adults with CHD. Little information exists regarding survival, demographics, late outcomes, and comorbidities in this emerging group, and multiple barriers impede research in adult CHD. The National Heart, Lung, and Blood Institute and the Adult Congenital Heart Association convened a multidisciplinary working group to identify high-impact research questions in adult CHD. This report summarizes the meeting discussions in the broad areas of CHD-related heart failure, vascular disease, and multisystem complications. High-priority subtopics identified included heart failure in tetralogy of Fallot, mechanical circulatory support/transplantation, sudden cardiac death, vascular outcomes in coarctation of the aorta, late outcomes in single-ventricle disease, cognitive and psychiatric issues, and pregnancy.

  14. State of the science of cardioprotection: Challenges and opportunities--proceedings of the 2010 NHLBI Workshop on Cardioprotection.

    PubMed

    Kloner, Robert A; Schwartz Longacre, Lisa

    2011-01-01

    The National Heart, Lung, and Blood Institute convened a Workshop on September 20-21, 2010, "New Horizons in Cardioprotection," to identify future research directions for cardioprotection against ischemia and reperfusion injury. Since the early 1970s, there has been evidence that the size of a myocardial infarction could be altered by various interventions. Early coronary artery reperfusion has been an intervention that consistently reduces myocardial infarct size in animal models as well as humans. Most cardiologists agree that the best way to treat acute ST-segment elevation myocardial infarction is to reperfuse the infarct artery as soon as possible and to keep the infarct artery patent. In general, stenting is superior to angioplasty, which is superior to thrombolysis. There is no accepted adjunctive therapy to acutely limit myocardial infarct size along with reperfusion that is routinely used in clinical practice. In the Kloner experimental laboratory, some adjunctive therapies have reproducibly limited infarct size (regional hypothermia, preconditioning, cariporide, combinations of the above, remote preconditioning, certain adenosine agonists, and late sodium current blockade). In clinical trials, a host of pharmacologic adjunctive therapies have failed to either reduce infarct size or improve clinical outcome. Potential reasons for the failure of these trials are discussed. However, some adjunctive therapies have shown promise in data subanalyses or subpopulations of clinical trials (adenosine, therapeutic hypothermia, and hyperoxemic reperfusion) or in small clinical trials (atrial natriuretic peptide, ischemic postconditioning, and cyclosporine, the mitochondrial permeability transition pore inhibitor). A recent clinical trial with remote conditioning induced by repetitive inflation of a brachial artery cuff begun prior to hospitalization showed promise in improving myocardial salvage and there are several reports in the cardiothoracic literature, suggesting that remote preconditioning protects hearts during surgery. Thus, in 2011, there is hope that applying some of the body's own conditioning mechanisms may provide protection against ischemic damage.

  15. Early Child Care and Children's Development in the Primary Grades: Follow-Up Results from the NICHD Study of Early Child Care

    ERIC Educational Resources Information Center

    American Educational Research Journal, 2005

    2005-01-01

    Associations between early child care and children's functioning though the end of third grade were examined. Some of the relations that had been detected before children's school entry were maintained. Higher-quality child care continued to be linked to higher scores in math, reading, and memory. More time spent in center care was associated with…

  16. Do effects of early child care extend to age 15 years? Results from the NICHD study of early child care and youth development.

    PubMed

    Vandell, Deborah Lowe; Belsky, Jay; Burchinal, Margaret; Steinberg, Laurence; Vandergrift, Nathan

    2010-01-01

    Relations between nonrelative child care (birth to 4(1/2) years) and functioning at age 15 were examined (N = 1,364). Both quality and quantity of child care were linked to adolescent functioning. Effects were similar in size as those observed at younger ages. Higher quality care predicted higher cognitive-academic achievement at age 15, with escalating positive effects at higher levels of quality. The association between quality and achievement was mediated, in part, by earlier child-care effects on achievement. High-quality early child care also predicted youth reports of less externalizing behavior. More hours of nonrelative care predicted greater risk taking and impulsivity at age 15, relations that were partially mediated by earlier child-care effects on externalizing behaviors.

  17. Is the Prediction of Adolescent Outcomes from Early Child Care Moderated by Later Maternal Sensitivity? Results from the NICHD Study of Early Child Care and Youth Development

    ERIC Educational Resources Information Center

    Burchinal, Margaret R.; Lowe Vandell, Deborah; Belsky, Jay

    2014-01-01

    Longitudinal data are used to examine whether effects of early child care are amplified and/or attenuated by later parenting. Analyses tested these interactions using parenting as both a categorical and continuous variable to balance power and flexibility in testing moderation. The most consistent finding was that maternal sensitivity during…

  18. Examining the Black-White achievement gap among low-income children using the NICHD study of early child care and youth development.

    PubMed

    Burchinal, Margaret; McCartney, Kathleen; Steinberg, Laurence; Crosnoe, Robert; Friedman, Sarah L; McLoyd, Vonnie; Pianta, Robert

    2011-01-01

    The Black-White achievement gap in children's reading and mathematics school performance from 4½ years of age through fifth grade was examined in a sample of 314 lower income American youth followed from birth. Differences in family, child care, and schooling experiences largely explained Black-White differences in achievement, and instructional quality was a stronger predictor for Black than White children. In addition, the achievement gap was detected as young as 3 years of age. Taken together, the findings suggest that reducing the Black-White achievement gap may require early intervention to reduce race gaps in home and school experiences during the infant and toddler years as well as during the preschool and school years.

  19. Early Child Care and Adolescent Functioning at the End of High School: Results from the NICHD Study of Early Child Care and Youth Development

    ERIC Educational Resources Information Center

    Vandell, Deborah Lowe; Burchinal, Margaret; Pierce, Kim M.

    2016-01-01

    Relations between early child care and adolescent functioning at the end of high school (EOHS; M age = 18.3 years) were examined in a prospective longitudinal study of 1,214 children. Controlling for extensive measures of family background, early child care was associated with academic standing and behavioral adjustment at the EOHS. More…

  20. Maternal employment and child cognitive outcomes in the first three years of life: the NICHD Study of Early Child Care. National Institute of Child Health and Human Development.

    PubMed

    Brooks-Gunn, Jeanne; Han, Wen-Jui; Waldfogel, Jane

    2002-01-01

    With increased numbers of women employed in their children's first year of life and with increased attention being paid by parents and policy makers to the importance of early experiences for children, establishing the links that might exist between early maternal employment and child cognitive outcomes is more important than ever. Negative associations between maternal employment during the first year of life and children's cognitive outcomes at age 3 (and later ages) have been reported using data from the National Longitudinal Survey of Youth-Child Supplement. However, it was not known whether these findings would be replicated in another study, nor whether these results were due to features of child care (e.g., quality, type), home environment (e.g., provision of learning), and/or parenting (e.g., sensitivity). This study explored these issues using data on 900 European American children from the National Institute of Child Health and Human Development Study of Early Child Care, which provides information on child cognitive scores at 15, 24, and 36 months, as well as data about the home environment (as assessed by the Home Observation of the Measurement of the Environment Scale), parental sensitivity, and child-care quality and type over the first 3 years of life. Maternal employment by the ninth month was found to be linked to lower Bracken School Readiness scores at 36 months, with the effects more pronounced when mothers were working 30 hr or more per week and with effects more pronounced for certain subgroups (i.e., children whose mothers were not sensitive, boys, and children with married parents). Although quality of child care, home environment, and maternal sensitivity also mattered, the negative effects of working 30 hr or more per week in the first 9 months were still found, even when controlling for child-care quality, the quality of the home environment, and maternal sensitivity. Implications for policy are also discussed.

  1. 42 CFR 68c.1 - What is the scope and purpose of the National Institute of Child Health and Human Development...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Institute of Child Health and Human Development (NICHD) Contraception and Infertility Research Loan... purpose of the National Institute of Child Health and Human Development (NICHD) Contraception and... payments under the National Institute of Child Health and Human Development (NICHD) Contraception...

  2. 42 CFR 68c.1 - What is the scope and purpose of the National Institute of Child Health and Human Development...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Institute of Child Health and Human Development (NICHD) Contraception and Infertility Research Loan... purpose of the National Institute of Child Health and Human Development (NICHD) Contraception and... payments under the National Institute of Child Health and Human Development (NICHD) Contraception...

  3. 42 CFR 68c.1 - What is the scope and purpose of the National Institute of Child Health and Human Development...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Institute of Child Health and Human Development (NICHD) Contraception and Infertility Research Loan... purpose of the National Institute of Child Health and Human Development (NICHD) Contraception and... payments under the National Institute of Child Health and Human Development (NICHD) Contraception...

  4. Stroke: Overview

    MedlinePlus

    ... News and Spotlights Selected NICHD Research Advances of 2016 Getting to Know the New NICHD Director Boosting Mobility and Independence from Infant to Adult All related news ... NIH...Turning Discovery Into Health ® Printed from the NICHD Web Site

  5. Infant Care and Infant Health

    MedlinePlus

    ... science-focused interviews Multimedia Audio briefings, videos & podcasts related to NICHD research About NICHD Institute Overview Mission, founding & history, accomplishments of NICHD Organization Organization chart, offices, divisions, centers, branches & labs Budget & Appropriations State, ...

  6. Extreme Temperatures May Increase Risk for Low Birth Weight at Term

    MedlinePlus

    ... Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Low birth weight refers to infants weighing ... Kennedy Shriver National Institute of Child Health and Human Development (NICHD) : NICHD conducts and supports research in the ...

  7. What Are the Treatments for Pregnancy Loss/Miscarriage?

    MedlinePlus

    ... Training, Education, & Career Development Support for Training at Universities & Other Institutions Training at NICHD Other Training, Education, & Career Development Programs News & Media Join NICHD Listservs ...

  8. Phenylketonuria (PKU)

    MedlinePlus

    ... Disorder (ASD) Intellectual and Developmental Disabilities (IDDs) Newborn Screening NICHD News and Spotlights Getting to Know the New NICHD Director Neuroscience Research Resources NIH Scientists Combine ...

  9. Clinical Utility of Echocardiography for the Diagnosis and Prognosis in Children with Bronchopulmonary Dsyplasia

    PubMed Central

    Choi, Young Earl; Cho, Hwa Jin; Song, Eun Song; Jeong, In Seok; Yoon, Namsik; Choi, Young Youn; Ma, Jae Sook

    2016-01-01

    Background Bronchopulmonary dysplasia (BPD) may result in chronic pulmonary artery hypertension and right ventricular (RV) dysfunction. Various echocardiographic assessments of RV dysfunction have been used to determine whether echocardiographic measurements of premature infants with BPD could provide sensitive measures of RV function that correlates with BPD severity. Methods Twenty-eight control subjects without BPD (non BPD group), 28 patients with mild BPD, 11 patients with moderate BPD, and six patients with severe BPD underwent echocardiograms with standard measurement such as ejection fraction by M-mode, tricuspid regurgitation pressure gradient, myocardial performance index (MPI) derived from pulse Doppler, and tissue Doppler imaging (TDI) measurements. BPD severity was classified by the NICHD/NHLBI/ORD workshop rating scale. Twenty-eight control subjects without BPD (non BPD group), 28 patients with mild BPD, 11 patients with moderate BPD, and six patients with severe BPD underwent echocardiograms with standard measurement such as ejection fraction by M-mode, tricuspid regurgitation pressure gradient, myocardial performance index (MPI) derived from pulse Doppler, and TDI measurements. BPD severity was classified by the NICHD/NHLBI/ORD workshop rating scale. Results None of the standard echocardiographic findings was significantly different between the control group and BPD groups. However, mean septal TDI-MPI of the severe BPD group (0.68 ± 0.06) was significantly (p < 0.01) higher than that of the non-BPD (0.58 ± 0.10) or the mild BPD group (0.59 ± 0.12). In addition, mean RV TDI-MPI of the severe BPD group (0.71 ± 0.13) was significantly (p < 0.05) higher than that of the non-BPD group (0.56 ± 0.08) or the mild BPD group (0.60 ± 0.125). Linear regression showed a good correlation between the severity of BPD and RV TDI-MPI (p = 0.01, R = 0.30) or septal TDI-MPI (p = 0.04, R = 0.24). Conclusion Echocardiographic evaluation of RV function based on an

  10. TIMI Frame Count and Adverse Events in Women with No Obstructive Coronary Disease: A Pilot Study from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE)

    PubMed Central

    Petersen, John W.; Johnson, B. Delia; Kip, Kevin E.; Anderson, R. David; Handberg, Eileen M.; Sharaf, Barry; Mehta, Puja K.; Kelsey, Sheryl F.; Merz, C. Noel Bairey; Pepine, Carl J.

    2014-01-01

    Background TIMI frame count (TFC) predicts outcomes in patients with obstructive coronary artery disease (CAD); it remains unclear whether TFC predicts outcomes in patients without obstructive CAD. Methods TFC was determined in a sample of women with no obstructive CAD enrolled in the Women's Ischemia Syndrome Evaluation (WISE) study. Because TFC is known to be higher in the left anterior descending artery (LAD), TFC determined in the LAD was divided by 1.7 to provide a corrected TFC (cTFC). Results A total of 298 women, with angiograms suitable for TFC analysis and long-term (6–10 year) follow up data, were included in this sub-study. Their age was 55±11 years, most were white (86%), half had a history of smoking, and half had a history of hypertension. Higher resting cTFC was associated with a higher rate of hospitalization for angina (34% in women with a cTFC >35, 15% in women with a cTFC ≤35, P<0.001). cTFC provided independent prediction of hospitalization for angina after adjusting for many baseline characteristics. In this cohort, resting cTFC was not predictive of major events (myocardial infarction, heart failure, stroke, or all-cause death), cardiovascular events, all-cause mortality, or cardiovascular mortality. Conclusions In women with signs and symptoms of ischemia but no obstructive CAD, resting cTFC provides independent prediction of hospitalization for angina. Larger studies are required to determine if resting TFC is predictive of major events in patients without obstructive coronary artery disease. PMID:24800739

  11. Training and Capacity Building in LMIC for Research in Heart and Lung Diseases: The NHLBI-UnitedHealth Global Health Centers of Excellence Program.

    PubMed

    Bloomfield, Gerald S; Xavier, Denis; Belis, Deshirée; Alam, Dewan; Davis, Patricia; Dorairaj, Prabhakaran; Ghannem, Hassen; Gilman, Robert H; Kamath, Deepak; Kimaiyo, Sylvester; Levitt, Naomi; Martinez, Homero; Mejicano, Gabriela; Miranda, J Jaime; Koehlmoos, Tracey Perez; Rabadán-Diehl, Cristina; Ramirez-Zea, Manuel; Rubinstein, Adolfo; Sacksteder, Katherine A; Steyn, Krisela; Tandon, Nikhil; Vedanthan, Rajesh; Wolbach, Tracy; Wu, Yangfeng; Yan, Lijing L

    2016-03-01

    Stemming the tide of noncommunicable diseases (NCDs) worldwide requires a multipronged approach. Although much attention has been paid to disease control measures, there is relatively little consideration of the importance of training the next generation of health-related researchers to play their important role in this global epidemic. The lack of support for early stage investigators in low- and middle-income countries interested in the global NCD field has resulted in inadequate funding opportunities for research, insufficient training in advanced research methodology and data analysis, lack of mentorship in manuscript and grant writing, and meager institutional support for developing, submitting, and administering research applications and awards. To address this unmet need, The National Heart, Lung, and Blood Institute-UnitedHealth Collaborating Centers of Excellence initiative created a Training Subcommittee that coordinated and developed an intensive, mentored health-related research experience for a number of early stage investigators from the 11 Centers of Excellence around the world. We describe the challenges faced by early stage investigators in low- and middle-income countries, the organization and scope of the Training Subcommittee, training activities, early outcomes of the early stage investigators (foreign and domestic) and training materials that have been developed by this program that are available to the public. By investing in the careers of individuals in a supportive global NCD network, we demonstrate the impact that an investment in training individuals from low- and middle-income countries can have on the preferred future of or current efforts to combat NCDs.

  12. Cardiac Effects of Antiretroviral Therapy in HIV-Negative Infants Born to HIV-Positive Mothers: The NHLBI CHAART-1 Cohort Study

    PubMed Central

    Lipshultz, Steven E.; Shearer, William T.; Thompson, Bruce; Rich, Kenneth C.; Cheng, Irene; Orav, E. John; Kumar, Sulekha; Pignatelli, Ricardo H.; Bezold, Louis I.; LaRussa, Philip; Starc, Thomas J.; Glickstein, Julie S.; O'Brien, Sharon; Cooper, Ellen R.; Wilkinson, James D.; Miller, Tracie L.; Colan, Steven D.

    2011-01-01

    Objective To investigate the possible effects of antiretroviral therapy (ART) in utero on cardiac development and function in HIV-negative children. Background ART reduces vertical HIV transmission. Long-term cardiotoxicity after in utero exposure to ART is unknown in children but has occurred in young animals. Methods Using a prospective multi-site cohort study design, we compared echocardiograms taken between birth and 24 months in two groups of HIV-negative infants of HIV-positive mothers: 136 infants exposed to ART (ART+) and 216 unexposed infants (ART−). Results Mean LV mass Z-scores were consistently lower in ART+ girls than in ART− girls: differences in mean Z-scores were −0.46 at birth (P=0.005), −1.02 at 6 months (P<0.001), −0.74 at 12 months (P<0.001), and −0.79 at 24 months (P<0.001). Corresponding differences in Z-scores for boys were smaller: 0.13 at 1 month (P=0.42), −0.44 at 6 months (P=0.01), −0.15 at 12 months (P=0.37), and −0.21 at 24 months (P=0.21). Septal wall thickness and LV dimension were smaller than expected in ART+ infants, but LV contractility was consistently about 1 SD higher at all ages (P<0.001). In ART+ infants, LV fractional shortening was higher than in ART− infants; girls showed a greater difference. Conclusion Fetal exposure to ART is associated with reduced LV mass, LV dimension, and septal wall thickness Z-scores and increased LV fractional shortening and contractility up to age 2 years. These effects are more pronounced in girls than in boys. Fetal ART exposure may impair myocardial growth while improving depressed LV function. PMID:21185505

  13. NHLBI Smoking Education Program. Planning Workshop for Professional and Patient Education (Silver Spring, Maryland, January 29-30, 1985). Summary Report.

    ERIC Educational Resources Information Center

    National Heart, Lung, and Blood Inst. (DHHS/NIH), Bethesda, MD.

    The workshop reported in this document focused on professional and patient smoking education. First, high priority clinical opportunities for smoking intervention were identified. Second, topically-oriented small groups met to plan activities in each of the following priority areas: (1) initiation of smoking cessation/maintaining non-smoking…

  14. Autosomal and X Chromosome Structural Variants Are Associated with Congenital Heart Defects in Turner Syndrome: The NHLBI GenTAC Registry

    PubMed Central

    Prakash, Siddharth K.; Bondy, Carolyn A.; Maslen, Cheryl L.; Silberbach, Michael; Lin, Angela E.; Perrone, Laura; Limongelli, Giuseppe; Michelena, Hector I.; Bossone, Eduardo; Citro, Rodolfo; Lemaire, Scott A.; Body, Simon C.; Milewicz, Dianna M.

    2016-01-01

    Turner Syndrome (TS) is a developmental disorder caused by partial or complete loss of one sex chromosome. Bicuspid aortic valve and other left-sided congenital heart lesions (LSL), including thoracic aortic aneurysms and acute aortic dissections, are 30-50 times more frequent in TS than in the general population. In 454 TS subjects, we found that LSL are significantly associated with reduced dosage of Xp genes and increased dosage of Xq genes. We also showed that genome-wide copy number variation is increased in TS and identify a common copy number variant (CNV) in chromosome 12p13.31 that is associated with LSL with an odds ratio of 3.7. This CNV contains three protein-coding genes (SLC2A3, SLC2A14 and NANOGP1) and was previously implicated in congenital heart defects in the 22q11 deletion syndrome. In addition, we identified a subset of rare and recurrent CNVs that are also enriched in non-syndromic BAV cases. These observations support our hypothesis that X chromosome and autosomal variants affecting cardiac developmental genes may interact to cause the increased prevalence of LSL in TS. PMID:27604636

  15. Autosomal and X chromosome structural variants are associated with congenital heart defects in Turner syndrome: The NHLBI GenTAC registry.

    PubMed

    Prakash, Siddharth K; Bondy, Carolyn A; Maslen, Cheryl L; Silberbach, Michael; Lin, Angela E; Perrone, Laura; Limongelli, Giuseppe; Michelena, Hector I; Bossone, Eduardo; Citro, Rodolfo; Lemaire, Scott A; Body, Simon C; Milewicz, Dianna M

    2016-12-01

    Turner Syndrome (TS) is a developmental disorder caused by partial or complete loss of one sex chromosome. Bicuspid aortic valve and other left-sided congenital heart lesions (LSL), including thoracic aortic aneurysms and acute aortic dissections, are 30-50 times more frequent in TS than in the general population. In 454 TS subjects, we found that LSL are significantly associated with reduced dosage of Xp genes and increased dosage of Xq genes. We also showed that genome-wide copy number variation is increased in TS and identify a common copy number variant (CNV) in chromosome 12p13.31 that is associated with LSL with an odds ratio of 3.7. This CNV contains three protein-coding genes (SLC2A3, SLC2A14, and NANOGP1) and was previously implicated in congenital heart defects in the 22q11 deletion syndrome. In addition, we identified a subset of rare and recurrent CNVs that are also enriched in non-syndromic BAV cases. These observations support our hypothesis that X chromosome and autosomal variants affecting cardiac developmental genes may interact to cause the increased prevalence of LSL in TS. © 2016 Wiley Periodicals, Inc.

  16. Genome-wide association study of triglyceride response to a high-fat meal among participants of the NHLBI genetics of lipid lowering drugs and diet network (GOLDN)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: The triglyceride (TG) response to a high-fat meal (postprandial lipemia, PPL) affects cardiovascular disease risk and is influenced by genes and environment. Genes involved in lipid metabolism have dominated genetic studies of PPL TG response. We sought to elucidate common genetic variant...

  17. Heterogeneity of Severe Asthma in Childhood: Confirmation by Cluster Analysis of Children in the NIH/NHLBI Severe Asthma Research Program (SARP)

    PubMed Central

    Fitzpatrick, Anne M.; Teague, W. Gerald; Meyers, Deborah A.; Peters, Stephen P.; Li, Xingnan; Li, Huashi; Wenzel, Sally E.; Aujla, Shean; Castro, Mario; Bacharier, Leonard B.; Gaston, Benjamin M.; Bleecker, Eugene R.; Moore, Wendy C.

    2011-01-01

    Background Asthma in children is a heterogeneous disorder with many phenotypes. Although unsupervised cluster analysis is a useful tool for identifying phenotypes, it has not been applied to school-age children with persistent asthma across a wide range of severities. Objectives This study determined how children with severe asthma are distributed across a cluster analysis and how well these clusters conform to current definitions of asthma severity. Methods Cluster analysis was applied to 12 continuous and composite variables from 161 children at 5 centers enrolled in the Severe Asthma Research Program (SARP). Results Four clusters of asthma were identified. Children in Cluster 1 (n = 48) had relatively normal lung function and less atopy, while children in Cluster 2 (n = 52) had slightly lower lung function, more atopy, and increased symptoms and medication usage. Cluster 3 (n = 32) had greater co-morbidity, increased bronchial responsiveness and lower lung function. Cluster 4 (n = 29) had the lowest lung function and the greatest symptoms and medication usage. Predictors of cluster assignment were asthma duration, the number of asthma controller medications, and baseline lung function. Children with severe asthma were present in all clusters, and no cluster corresponded to definitions of asthma severity provided in asthma treatment guidelines. Conclusions Severe asthma in children is highly heterogeneous. Unique phenotypic clusters previously identified in adults can also be identified in children, but with important differences. Larger validation and longitudinal studies are needed to determine the baseline and predictive validity of these phenotypic clusters in the larger clinical setting. PMID:21195471

  18. GENOME-WIDE ASSOCIATION STUDY OF TRIGLYCERIDE RESPONSE TO A HIGH-FAT MEAL AMONG PARTICIPANTS OF THE NHLBI GENETICS OF LIPID LOWERING DRUGS AND DIET NETWORK (GOLDN)

    PubMed Central

    Wojczynski, M.K.; Parnel, L.D.; Pollin, T.I.; Lai, C.Q.; Feitosa, M.F.; O’Connell, J.R.; Frazier-Wood, A.C.; Gibson, Q.; Aslibekyan, S.; Ryan, K.A.; Province, M.A.; Tiwari, H.K.; Ordovas, J.M.; Shuldiner, A.R.; Arnett, D.K.; Borecki, I.B.

    2015-01-01

    Objective The triglyceride (TG) response to a high-fat meal (postprandial lipemia, PPL) affects cardiovascular disease risk and is influenced by genes and environment. Genes involved in lipid metabolism have dominated genetic studies of PPL TG response. We sought to elucidate common genetic variants through a genome-wide association (GWA) study in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). Methods The GOLDN GWAS discovery sample consisted of 872 participants within families of European ancestry. Genotypes for 2,543,887 variants were measured or imputed from HapMap. Replication of our top results was performed in the Heredity and Phenotype Intervention (HAPI) Heart Study (n=843). PPL TG response phenotypes were constructed from plasma TG measured at baseline (fasting, 0 hour), 3.5 and 6 hours after a high-fat meal, using a random coefficient regression model. Association analyses were adjusted for covariates and principal components, as necessary, in a linear mixed model using the kinship matrix; additional models further adjusted for fasting TG were also performed. Meta-analysis of the discovery and replication studies (n=1,715) was performed on the top SNPs from GOLDN. Results GOLDN revealed 111 suggestive (p<1E-05) associations, with two SNPs meeting GWA significance level (p<5E-08). Of the two significant SNPs, rs964184 demonstrated evidence of replication (p=1.20E-03) in the HAPI Heart Study and in a joint analysis, was GWA significant (p=1.26E-09). Rs964184 has been associated with fasting lipids (TG and HDL) and is near ZPR1 (formerly ZNF259), close to the APOA1/C3/A4/A5 cluster. This association was attenuated upon additional adjustment for fasting TG. Conclusion This is the first report of a genome-wide significant association with replication for a novel phenotype, namely PPL TG response. Future investigation into response phenotypes is warranted using pathway analyses, or newer genetic technologies such as metabolomics. PMID:26256467

  19. Anginal Symptoms, Coronary Artery Disease, and Adverse Outcomes in Black and White Women: The NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study

    PubMed Central

    Johnson, B. Delia; Rutledge, Thomas; Bittner, Vera; Whittaker, Kerry S.; Krantz, David S.; Cornell, Carol E.; Eteiba, Wafia; Handberg, Eileen; Vido, Diane; Bairey Merz, C. Noel

    2013-01-01

    Abstract Background Black women are less likely to be evaluated and treated for anginal symptoms, despite a higher premature cardiac mortality rate compared to white women. Our objective was to compare angina symptoms in black versus white women regarding (1) angina symptoms characterization; (2) relationship with obstructive coronary artery disease (CAD); and (3) relationship with subsequent mortality. Methods A cohort of 466 women (69 black and 397 white) undergoing coronary angiography for suspected ischemia and without prior history of CAD completed symptom checklists. Four symptom clusters (CHEST, UPPER, STOMACH, and TYPICAL TRIGGERS) were derived by factor analysis. All angiograms were analyzed by core lab. Mortality data over 10 years were obtained from National Death Index. Results (1) Black women had lower mean CHEST cluster scores (0.60±0.30 vs. 0.73±30, p=0.002), but higher STOMACH scores (0.41±0.25 vs. 0.30±0.25, p=0.011) than white women. (2) Prevalence and severity of CAD did not differ in black and white women and was not predicted by symptom cluster scores. (3) All-cause mortality rates were 24.9% in blacks versus 14.5% in whites, p=0.007; and cardiovascular mortality 22.5% vs.8.8%, p=0.001. Symptom clusters were not predictive of adverse events in white women. However, black women with a low TYPICAL score had significantly higher mortality compared to those with a high TYPICAL score (43% vs. 10%, p=0.006). Conclusions Among women undergoing coronary angiography, black women report fewer chest-related and more stomach-related symptoms, regardless of presence or severity of CAD, and these racial symptom presentation differences are linked with the more adverse prognosis observed in the black women. Atypical symptom presentation may be a barrier to appropriate and timely diagnosis and treatment and contribute to poorer outcomes for black women. PMID:23992103

  20. Synthesis and Characterization of Silyldichloramines, Their Reactions with F- Ions, Stability of N2CI2 and NCI2(-), and Formation of NCI3 (Postprint)

    DTIC Science & Technology

    2007-01-01

    synthesis of the former was successfully repeated, and its structure was established by single crystal X-ray diffraction and vibrational spectroscopy... structure was established by single-crystal X-ray diffraction and vibrational spectroscopy. Attempts to prepare (CH3)3SiNCl2 were unsuccessful; however, a...Tetramethylammonium fluoride tet- rahydrate (Aldrich, 98%) was dehydrated by a literature method.16 Crystal Structure Determination of Ph3SiNCl2. (a

  1. Oral Contraceptives and Cancer Risk

    MedlinePlus

    ... NCI NCI Overview History Contributing to Cancer Research Leadership Director's Page Previous NCI Directors NCI Organization Advisory ... History of NCI Contributing to Cancer Research Senior Leadership Director Previous Directors NCI Organization Divisions, Offices & Centers ...

  2. HPV and Cancer

    MedlinePlus

    ... NCI NCI Overview History Contributing to Cancer Research Leadership Director's Page Previous NCI Directors NCI Organization Advisory ... History of NCI Contributing to Cancer Research Senior Leadership Director Previous Directors NCI Organization Divisions, Offices & Centers ...

  3. General Information about Vaginal Cancer

    MedlinePlus

    ... NCI NCI Overview History Contributing to Cancer Research Leadership Director's Page Previous NCI Directors NCI Organization Advisory ... History of NCI Contributing to Cancer Research Senior Leadership Director Previous Directors NCI Organization Divisions, Offices & Centers ...

  4. Cervical Cancer Prevention

    MedlinePlus

    ... NCI NCI Overview History Contributing to Cancer Research Leadership Director's Page Previous NCI Directors NCI Organization Advisory ... History of NCI Contributing to Cancer Research Senior Leadership Director Previous Directors NCI Organization Divisions, Offices & Centers ...

  5. Nausea and Vomiting (PDQ)

    MedlinePlus

    ... NCI NCI Overview History Contributing to Cancer Research Leadership Director's Page Previous NCI Directors NCI Organization Advisory ... History of NCI Contributing to Cancer Research Senior Leadership Director Previous Directors NCI Organization Divisions, Offices & Centers ...

  6. Diethylstilbestrol (DES) and Cancer

    MedlinePlus

    ... NCI NCI Overview History Contributing to Cancer Research Leadership Director's Page Previous NCI Directors NCI Organization Advisory ... History of NCI Contributing to Cancer Research Senior Leadership Director Previous Directors NCI Organization Divisions, Offices & Centers ...

  7. 75 FR 79009 - Proposed Collection; Comment Request; Questionnaire Cognitive Interview and Pretesting (NCI)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-17

    ... publish periodic summaries of proposed projects to be submitted to the Office of Management and Budget... agencies, as well as by academic and commercial survey organizations. There are no costs to respondents other than their time. The total estimated annualized burden hours are 600. Frequency of Response:...

  8. Cancer Inhibitors Isolated from an African Plant | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute's Molecular Targets Development Program is seeking parties interested in collaborative research to further develop, evaluate, or commercialize cancer inhibitors isolated from the African plant Phyllanthus englerii. The technology is also available for exclusive or non-exclusive licensing.

  9. Mouse Model for the Preclinical Study of Metastatic Disease | NCI Technology Transfer Center | TTC

    Cancer.gov

    The Laboratory of Cancer Biology and Genetics, National Cancer Institute seeks partners for collaborative research to co-develop a mouse model that shows preclinical therapeutic response of residual metastatic disease.

  10. TU-FG-207B-04: NCI Funding Opportunities in Imaging and Image-Guided Therapy.

    PubMed

    Farahani, K

    2016-06-01

    Up-to-date knowledge about federal funding opportunities related to medical physics research, as well as obtaining skills for writing effective grant proposals are critical for academic and entrepreneurial medical physicists. In this symposium, program directors from key federal research funding agencies, including the National Cancer Institute, the National Institute of Biomedical Imaging and Bioengineering, and the National Science Foundation, will present information about current funding opportunities relevant to the field of medical physics. They will also provide insight to issues that applicants should pay special attention to when crafting their research grant proposals. In addition, the symposium will include presentations on research funding for small business concerns, and the results of an independent AAPM study of the National Institutes of Health funding of AAPM members from 2002-2015.

  11. TU-FG-207B-03: NCI Small Business Funding Opportunities.

    PubMed

    Narayanan, D

    2016-06-01

    Up-to-date knowledge about federal funding opportunities related to medical physics research, as well as obtaining skills for writing effective grant proposals are critical for academic and entrepreneurial medical physicists. In this symposium, program directors from key federal research funding agencies, including the National Cancer Institute, the National Institute of Biomedical Imaging and Bioengineering, and the National Science Foundation, will present information about current funding opportunities relevant to the field of medical physics. They will also provide insight to issues that applicants should pay special attention to when crafting their research grant proposals. In addition, the symposium will include presentations on research funding for small business concerns, and the results of an independent AAPM study of the National Institutes of Health funding of AAPM members from 2002-2015.

  12. 75 FR 49938 - Proposed Collection; Comment Request; NIH NCI Central Institutional Review Board (CIRB...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-16

    ... publish periodic summaries of proposed projects to be submitted to the Office of Management and Budget.... The annual reporting burden is estimated at 2221 hours (see Table below for the estimated time burden... operating costs of $150,637. Table A.12-1--Estimates of Annual Burden Hours Number of Frequency of...

  13. 76 FR 22714 - Proposed Collection; Comment Request; Health Information National Trends Survey 4 (HINTS 4) (NCI)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-22

    ... publish periodic summaries of proposed projects to be submitted to the Office of Management and Budget... the table below. There are no Capital Costs, Operating Costs, and/or Maintenance Costs to...

  14. 75 FR 61763 - Submission of OMB Review; Comment Request; Drug Accountability Record (Form NIH 2564) (NCI)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-06

    ... accountability record will be used to keep track of the dispensing of investigational anticancer agents to... technological collection techniques or other forms of information technology. Direct Comments to OMB: Written... public burden and associated response times, should be directed to the Attention: NIH Desk...

  15. Best Practices in Cancer Nanotechnology – Perspective from NCI Nanotechnology Alliance

    PubMed Central

    Zamboni, William C.; Torchilin, Vladimir; Patri, Anil; Hrkach, Jeff; Stern, Stephen; Lee, Robert; Nel, Andre; Panaro, Nicholas J.; Grodzinski, Piotr

    2014-01-01

    Historically, treatment of patients with cancer using chemotherapeutic agents has been associated with debilitating and systemic toxicities, poor bioavailability, and unfavorable pharmacokinetics. Nanotechnology-based drug delivery systems, on the other hand, can specifically target cancer cells while avoiding their healthy neighbors, avoid rapid clearance from the body, and be administered without toxic solvents. They hold immense potential in addressing all of these issues which has hampered further development of chemotherapeutics. Furthermore, such drug delivery systems will lead to cancer therapeutic modalities which are not only less toxic to the patient but also significantly more efficacious. In addition to established therapeutic modes of action, nanomaterials are opening up entirely new modalities of cancer therapy, such as photodynamic and hyperthermia treatments. Furthermore, nanoparticle carriers are also capable of addressing several drug delivery problems which could not be effectively solved in the past and include overcoming formulation issues, multi-drug-resistance phenomenon and penetrating cellular barriers that may limit device accessibility to intended targets such as the blood-brain-barrier. The challenges in optimizing design of nanoparticles tailored to specific tumor indications still remain; however, it is clear that nanoscale devices carry a significant promise towards new ways of diagnosing and treating cancer. This review focuses on future prospects of using nanotechnology in cancer applications and discusses practices and methodologies used in the development and translation of nanotechnology-based therapeutics. PMID:22669131

  16. inteferon Gamma as a Therapeutic to Treat Ocular Diseases | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Eye Institute's Section on Epithelial and Retinal Physiology and Disease (SERPD) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize therapeutics for ocular diseases caused by accumulation of sub-retinal fluid.

  17. 78 FR 53763 - Proposed Collection; 60-day Comment Request Cancer Trials Support Unit (CTSU) (NCI)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-30

    ... trials program. Currently guided by the efforts of the Clinical Trials Working Group (CTWG) and the... survey is in place for the Oncology Patient Enrollment Network (OPEN). User satisfaction surveys...

  18. NCI's Dr. Barry Kramer on PBS NewsHour | Division of Cancer Prevention

    Cancer.gov

    Talking about New Cancer Definitions to Avoid Unnecessary Treatments. A panel of doctors and scientists proposed a change to the definition of cancer, in hopes of shifting the way we think about and treat the disease. Gwen Ifill discusses the recommendation with Dr. Barnett Kramer of the National Cancer Institute and Dr. Larry Norton of the Memorial Sloan-Kettering Cancer Center... |

  19. 75 FR 70268 - Submission for OMB Review; Comment Request; NIH NCI Central Institutional Review Board (CIRB...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-17

    .... Frequency of Response: Once, except for the SAE Reviewer Worksheet. Affected Public: Includes the Federal... Members CIRB SAE Reviewer Worksheet 10 15 30/60 (.5 hour) 75 (Attachment 6K). Total 4,904 2,209...

  20. 75 FR 26266 - National Cancer Institute (NCI); National Institute of Allergy and Infectious Diseases (NIAID...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-11

    ..., an agency of the Department of Health and Human Services, in collaboration with the Lupus Foundation of America, Washington, DC, will hold a scientific conference. Title: ``Systemic Lupus Erythematosus... research scientists working on models of autoimmune disease relevant to lupus together with...

  1. Active NCI Community Oncology Research Program Grants | Division of Cancer Prevention

    Cancer.gov

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  2. In Vivo Imaging of Tissue Physiological Function using EPR Spectroscopy | NCI Technology Transfer Center | TTC

    Cancer.gov

    Electron paramagnetic resonance (EPR) is a technique for studying chemical species that have one or more unpaired electrons.  The current invention describes Echo-based Single Point Imaging (ESPI), a novel EPR image formation strategy that allows in vivo imaging of physiological function.  The National Cancer Institute's Radiation Biology Branch is seeking statements of capability or interest from parties interested in in-licensing an in vivo imaging using Electron paramagnetic resonance (EPR) to measure active oxygen species.

  3. UOK 268 Cell Line for Hereditary Leiomyomatosis and Renal Cell Carcinoma | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute’s Urologic Oncology Branch seeks parties to co-develop the UOK 262 immortalized cell line as research tool to study aggressive hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated recurring kidney cancer.

  4. Treatment of Glioma, Glioblastoma, and Astrocytoma | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Institute on Aging, Laboratory of Clinical Investigation is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of fenoterol and fenoterol analogs in the front line and adjuvant treatment of CNS tumors and other B2 AR expressing tumors.

  5. Biomarkers For Breast Cancer Based On Genetic Instability | NCI Technology Transfer Center | TTC

    Cancer.gov

    It is difficult to establish a prognosis for breast cancer because the clinical course and survival times of patients with the disease vary greatly.  The National Cancer Institute's Genetics Branch is seeking statements of capability or interest from parties interested in in-licensing or collaborative research to co-develop, evaluate, or commercialize prognostic tests for breast cancer based on a 12-gene expression signature.

  6. Assay for Arf GTP-binding Proteins | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute's Laboratory of Cellular and Molecular Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize an antibody-based proteomics assay.

  7. Colon Cancer Biomarkers To Identify Patients Suitable For Therapeutic Intervention | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute's Laboratory of Human Carcinogenesis is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize cancer biomarkers and therapeutic targets.

  8. BODIPY-FL Nilotinib (Tasigna) for Use in Cancer Research | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute''s Laboratory of Cell Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize bodipy conjugated tyrosine kinase inhibitors that are currently used in the clinic for the treatment of CML or gastric cancers.

  9. Detection of THCCOOH in hair by MSD-NCI after HPLC clean-up.

    PubMed

    Sachs, H; Dressler, U

    2000-01-10

    Regular consumption of cannabis can easily be detected by examination of hair for tetrahydrocannabinol, cannabinol, and cannabidiol. Although several studies have demonstrated that after contamination with smoke or treatment with THC containing shampoos THC is not detectable, or only in small traces, the detection of 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (THCCOOH) should be offered to prove the consumption and metabolisation of THC. Up to now this confirmation was only available using tandem MS techniques combined with negative chemical ionisation. A new method using a normal quadrupole GC/MS is described. The lack of expensive instruments has to be paid for by a costly and time consuming extraction and clean-up. After the sample has been digested by 2 M NaOH at 95 degrees C and the neutralised liquid has been extracted with a mixture of n-hexane and ethyl acetate the dried residue is reconstituted in acetonitrile-methanol-0.01 M sulfuric acid (49:21:30, v/v/v) and the cannabinoids separated by HPLC. Each fraction is collected over 1 min. Another extraction with n-hexane-ethyl acetate is followed by evaporation, derivatisation, and GC/MS determination. The calibration with THCCOOH spiked hair led to a LOD of 0.3 pg/mg and a LOQ of 1.1 pg/mg.

  10. Diabetes, Obesity, and Other Insulin-Related Diseases | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute’s Urologic Oncology Branch seeks partners interested in collaborative research to co-develop small molecule epoxy-guaiane derivative englerin A and related compounds for diseases associated with insulin resistance.

  11. Application Period Open for NCI Biospecimen Use | Division of Cancer Prevention

    Cancer.gov

    The application period for investigators interested in obtaining biospecimens and data from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial re-opened June 1. A separate application for obtaining biospecimens and data with research funding is also open. |

  12. NCI Community Oncology Research Program Clinical Trials | Division of Cancer Prevention

    Cancer.gov

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  13. Improved Antibodies Against ERBB4/HER4 | NCI Technology Transfer Center | TTC

    Cancer.gov

    The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Section on Molecular Neurobiology is seeking statements of capability or interest from parties interested in collaborative research to further evaluate or commercialize specific rabbit monoclonal antibodies generated against the ErbB4 receptor (also known as HER4) that have been validated for specificity using tissue sections and extracts from ErbB4 knockout mice.

  14. Human Antibodies Against Middle East Respiratory Syndrome Coronavirus | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute is seeking statements of capability or interest from parties interested in collaborative research to co-develop antibody-based therapeutic against MERS-CoV, including animal studies, cGMP manufacturing, and clinical trials.

  15. Jeffrey Strathern Retires After More Than Three Decades at NCI | Poster

    Cancer.gov

    Jeffrey Strathern, Ph.D., has hung up his lab coat and donned a sailor’s cap after 32 years of advancing science in areas such as genetics and genomics, chromosome biology, molecular biology, and biochemistry.

  16. Automated Tools for Clinical Research Data Quality Control using NCI Common Data Elements.

    PubMed

    Hudson, Cody L; Topaloglu, Umit; Bian, Jiang; Hogan, William; Kieber-Emmons, Thomas

    2014-01-01

    Clinical research data generated by a federation of collection mechanisms and systems often produces highly dissimilar data with varying quality. Poor data quality can result in the inefficient use of research data or can even require the repetition of the performed studies, a costly process. This work presents two tools for improving data quality of clinical research data relying on the National Cancer Institute's Common Data Elements as a standard representation of possible questions and data elements to A: automatically suggest CDE annotations for already collected data based on semantic and syntactic analysis utilizing the Unified Medical Language System (UMLS) Terminology Services' Metathesaurus and B: annotate and constrain new clinical research questions though a simple-to-use "CDE Browser." In this work, these tools are built and tested on the open-source LimeSurvey software and research data analyzed and identified to contain various data quality issues captured by the Comprehensive Research Informatics Suite (CRIS) at the University of Arkansas for Medical Sciences.

  17. Method for Targeted Therapeutic Delivery of Proteins into Cells | NCI Technology Transfer Center | TTC

    Cancer.gov

    The Protein Expression Laboratory at the National Cancer Institute in Frederick, MD is seeking statements of capability or interest from parties interested in collaborative research to further develop a platform technology for the targeted intra-cellular delivery of proteins using virus-like particles (VLPs).

  18. OLIGODEOXYNUCLEOTIDES AS ANTI-CANCER THERAPEUTICS AND DIAGNOSTICS | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute Laboratory of Experimental Immunology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize anti-cancer oligodeoxynucleotides.  

  19. Novel Tumor-Associated Antigen for Cancer Diagnostics and Therapeutics | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Institute on Aging's Laboratory of Immunology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of SPANX-B-based therapeutic approaches to combat cancers.

  20. Oncologists’ Perspectives on Concurrent Palliative Care in an NCI-designated Comprehensive Cancer Center

    PubMed Central

    Bakitas, Marie; Lyons, Kathleen Doyle; Hegel, Mark T.; Ahles, Tim

    2013-01-01

    Purpose To understand oncology clinicians’ perspectives about the care of advanced cancer patients following the completion of the ENABLE II (Educate, Nurture, Advise, Before Life Ends) randomized clinical trial (RCT) of a concurrent oncology palliative care model. Methods Qualitative interview study of 35 oncology clinicians about their approach to patients with advanced cancer and the effect of the ENABLE II RCT. Results Oncologists believed that integrating palliative care at the time of an advanced cancer diagnosis enhanced patient care and complemented their practice. Self-assessment of their practice with advanced cancer patients comprised four themes: 1) treating the whole patient, 2) focusing on quality versus quantity of life, 3) “some patients just want to fight”, and 4) helping with transitions; timing is everything. Five themes comprised oncologists’ views on the complementary role of palliative care: 1) “refer early and often”, 2) referral challenges: “Palliative” equals hospice; “Heme patients are different”, 3) palliative care as consultants or co-managers, 4) palliative care “shares the load”, and 5) ENABLE II facilitated palliative care integration. Conclusions Oncologists described the RCT as holistic and complementary, and as a significant factor in adopting concurrent care as a standard of care. PMID:23040412

  1. Optimizing pain care delivery in outpatient facilities: experience in NCI, Cairo, Egypt.

    PubMed

    Hameed, Khaled Abdel

    2011-04-01

    As a result of increasing waiting lists of patients attending National Cancer Institute of Cairo, we are faced to provide high-quality pain care service through our outpatient pain clinic. The program description presented here shows the capacity of a 24 hours/7 days outpatient cancer pain management service to provide rapidly accessible, high-quality care to patients with complex pain and palliative care symptom burdens. In addition, this model avoids inpatient hospital admissions. Pain clinics of cancer are committed to helping patients and families identify and implement the treatments necessary to achieve optimum functional ability and the best possible quality of life. These clinics also help to communicate and work with the family physician, surgeon, and other physicians associated with patient treatment. Cancer pain is complex in its causes, and affects all parts of the body. It involves the tissues, body systems , and the mind. Being multidimensional, it is never adequately addressed with unidimensional treatment. Pain management must extend beyond physical approaches to include the psychological, social, and even spiritual aspects of the patient. Effective integrated treatment fosters self awareness and teaches appropriate and effective self care. With time, complex issues are managed, pain is reduced, and the patient moves toward peak physical and psychological functioning. These goals can be achieved by providing the highest quality pain management services. Patients attending the clinic get treated medically for their physical ailments. Their emotional and psychological problems also need to be attended with an atmosphere of love and care. The mission of the highest quality service is to obtain customer satisfaction with reduction of cost in a multidisciplinary (or better interdisciplinary) approach. This can be reached by proper identification of the customers either internal or external, assessing their needs, and implementing plans for their satisfaction. In addition, monitoring the improvement of such plans is an integral part of the quality process. Importantly, the facility provides comprehensive care with professionals available 24 hours/7 days. On-call teams assigned to manage pain and other treatment modalities comprises of staff supervised by the primary cancer clinicians; this arrangement facilitates reaching this goal. This study will illustrate our experience through 25 years, trying to provide the highest care of patients with cancer pain on an outpatient basis.

  2. 78 FR 19496 - Submission for OMB Review; 30-day Comment Request; The National Cancer Institute (NCI...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-01

    ... designed for young adult smokers ages 18 to 29. The SmokefreeTXT program is a component of a larger series... (DHHS). The study seeks to recruit a large sample of adult smokers to examine how exposure to the... hours) hours Adults Aged 18 to 29 Screener/ 10,620 1 5/60 885 recruitment. Baseline........ 2,124 1...

  3. Diagnosis of Age-Related Cardiovascular Disorders | NCI Technology Transfer Center | TTC

    Cancer.gov

    Researchers at the NIH, National Institute on Aging, Cardiovascular Biology Unit-Vascular Group have discovered a method for the diagnosis and prognosis of cardiovascular aging, and is seeking parties interested in in-licensing or collaborative research to co-develop, evaluate, or commercialize novel methods for diagnosing age-related cardiovascular disorders.

  4. User Committees Give NCI and Frederick National Lab Employees a Voice | Poster

    Cancer.gov

    Do you want a wider selection of food options at the Discovery Cafeteria? Do you wish Purchasing and Logistics would enhance the current software for more efficient processing? Maybe you’d like to see better defined service availability times at Occupational Health Services (OHS). Whatever your suggestion, you can make your voice heard by contacting the appropriate user committee online.

  5. Chimeric Antigen Receptors to CD276 for Treating Cancer | NCI Technology Transfer Center | TTC

    Cancer.gov

    This licensing opportunity from the National Cancer Institute concerns the development of CARs comprising an antigen-binding fragment derived from the MGA271 antibody. The resulting CARs can be used in adoptive cell therapy treatment for neuroblastoma and other tumors that express CD276.

  6. Improved Vaccines for the Treatment of Prostate and Breast Cancer | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute’s Vaccine Branch seeks partners interested in collaborative research to continue clinical development and/or license a multi-epitope therapeutic cancer vaccine. The research is in early-stage clinical evaluation, with in vitro and in vivo (animal and human) data available.

  7. Virus-Like Particles That Can Deliver Proteins and RNA | NCI Technology Transfer Center | TTC

    Cancer.gov

    The present invention describes novel virus-like particles (VLPs) that are capable of binding to and replicating within a target mammalian cell, including human cells. The claimed VLPs are safer than viral delivery because they are incapable of re-infecting target cells. The National Cancer Institute's Protein Expression Laboratory seeks parties interested in licensing the novel delivery of RNA to mammalian cells using virus-like particles.

  8. Synergistic Combination Agent for Cancer Therapy | NCI Technology Transfer Center | TTC

    Cancer.gov

    The Nanotechnology Characterization Laboratory of the Frederick National Laboratory for Biomedical Research seeks parties interested in collaborative research to co-develop a ceramide and vinca alkaloid combination therapy for treatment of cancer.

  9. Anti-Mesothelin Monoclonal Antibodies for the Treatment of Cancer | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute, Laboratory of Molecular Biology is seeking parties interested in collaborative research to further co-develop monoclonal antibodies for the treatment of mesothelin-expressing cancers.

  10. Description of the research conducted by the infections and immunoepidemiology branch of NCI

    Cancer.gov

    The research mission of the Infections and Immunoepidemiology Branch is to discover infectious causes of cancer, to elucidate the determinants of malignancy for established oncogenic infections, to uncover novel infection-cancer associations, and to clarify how alterations in immunity and inflammation relate to cancer risk.

  11. T Cell Receptors that Recognize the Tyrosinase Tumor Antigen | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute, Surgery Branch, Tumor Immunology Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize T Cells Attacking Cancer: T Cell Receptors that Recognize the Tyrosinase Tumor Antigen

  12. NCI study finds extreme obesity may shorten life expectancy up to 14 years

    Cancer.gov

    Extremely obese people have increased risks of dying from cancer and many other causes including heart disease, stroke, diabetes, and kidney and liver diseases, according to results of an analysis of data pooled from 20 large studies of people from three

  13. NCI-supported facility to conduct cancer trials breaks ground in Puerto Rico

    Cancer.gov

    The Puerto Rican government has allocated $196 million dollars to build a 287,000 sq. ft., 96-bed, cancer hospital in San Juan. The new hospital, which will provide cancer treatment and conduct clinical trials, is the first of its kind in the Caribbean.

  14. Ketamine Metabolites for the Treatment of Depression and Pain | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Institute on Aging, Laboratory of Clinical Investigation, is seeking parties interested in collaborative research to co-develop ketamine metabolites for the treatment of different forms of depression and for alleviating pain.

  15. Biomimetic tissue-engineered systems for advancing cancer research: NCI Strategic Workshop report.

    PubMed

    Schuessler, Teresa K; Chan, Xin Yi; Chen, Huanhuan Joyce; Ji, Kyungmin; Park, Kyung Min; Roshan-Ghias, Alireza; Sethi, Pallavi; Thakur, Archana; Tian, Xi; Villasante, Aranzazu; Zervantonakis, Ioannis K; Moore, Nicole M; Nagahara, Larry A; Kuhn, Nastaran Z

    2014-10-01

    Advanced technologies and biomaterials developed for tissue engineering and regenerative medicine present tractable biomimetic systems with potential applications for cancer research. Recently, the National Cancer Institute convened a Strategic Workshop to explore the use of tissue biomanufacturing for development of dynamic, physiologically relevant in vitro and ex vivo biomimetic systems to study cancer biology and drug efficacy. The workshop provided a forum to identify current progress, research gaps, and necessary steps to advance the field. Opportunities discussed included development of tumor biomimetic systems with an emphasis on reproducibility and validation of new biomimetic tumor models, as described in this report.

  16. 76 FR 2253 - TRICARE; Coverage of National Cancer Institute (NCI) Sponsored Phase I Studies

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-13

    ..., injected into the blood, or injected into the muscle), how often, and what dose is safe. DATES: Effective... evaluate how a new drug should be given (by mouth, injected into the blood, or injected into the muscle... evaluate how well the new drug works. Phase II studies usually focus on a particular type of cancer....

  17. Former NCI Researcher, George Vande Woude, Receives AAAS Fellowship Award | Poster

    Cancer.gov

    Editor’s Note: This article was adapted from a press release and biographical information from the Van Andel Research Institute’s website: http://www.vai.org/en/NewsRoom/press-release-01-28-14.aspx.

  18. Virus-Free Human Placental Cell Lines To Study Genetic Functions | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Institute of Child Health and Human Development's Section on Cellular Differentiation is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize immortalized virus-free human placental cell lines.The National Institute of Child Health and Human Development's Section on Cellular Differentiation is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize immortalized virus-free human placental cell lines.

  19. NCI Scientists Solve Structure of Protein that Enables MERS Virus to Spread | Poster

    Cancer.gov

    Scientists at the Frederick National Lab have produced three crystal structures that reveal a specific part of a protein that can be targeted to fight the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes an emerging viral respiratory illness. Senior Investigator David Waugh, Ph.D., Macromolecular Crystallography Laboratory, has solved the structure of an enzyme known as the 3C-like protease (3CLpro), which, if blocked, can prevent the virus from replicating...

  20. 78 FR 52204 - Proposed Collection; 60-day Comment Request: NIH NCI Central Institutional Review Board (CIRB...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-22

    ... project, contact: CAPT Michael Montello, Pharm. D., MBA, Cancer Therapy Evaluation Program, Operations and... review. The benefits to the National Clinical Trials Network and Experimental Therapy-Clinical...

  1. The Effects of Infant Child Care on Infant-Mother Attachment Security: Results of the NICHD [National Institute of Child Health and Human Development] Study of Early Child Care.

    ERIC Educational Resources Information Center

    NICHD Early Child Care Research Network

    1997-01-01

    Examined validity of Strange Situation attachment classifications for infants with and without extensive child-care experience and the association of early child-care experience with attachment security. Found that infants were less likely to be secure when low maternal sensitivity was combined with poor quality child care, more than minimal…

  2. Oncofertility: A New Medical Specialty Helping Young Cancer Patients Have Children

    MedlinePlus

    ... Feature: Oncofertility: A Revolution in Childbearing Oncofertility: A New Medical Specialty Helping Young Cancer Patients Have Children ... NICHD). Photo courtesy of: NICHD "Oncofertility" is a new term that addresses an old problem: the fertility ...

  3. Treatments for Diseases That Cause Infertility

    MedlinePlus

    ... its symptoms is available from the NICHD PCOS topic page . Treatments for infertility in women with PCOS include ... this topic can be found on the NICHD topic page on endometriosis . Treatments for the infertility that can ...

  4. Federal Report Shows Drop in Proportion of Children in US Population

    MedlinePlus

    ... by such factors as child care, home educational environment, teachers’ instructional practices, and class size. About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): The NICHD sponsors research on development, before ...

  5. What Health Problems Can Develop during Pregnancy?

    MedlinePlus

    ... Who is at risk for complications? How does stress affect pregnancy? NICHD Research Information Research Goals Activities and Advances ... Who is at risk for complications? How does stress affect pregnancy? NICHD Research Information Clinical Trials Resources and Publications ...

  6. What Preconception Tests Might I Need?

    MedlinePlus

    ... Who is at risk for complications? How does stress affect pregnancy? NICHD Research Information Research Goals Activities and Advances ... Who is at risk for complications? How does stress affect pregnancy? NICHD Research Information Clinical Trials Resources and Publications ...

  7. Preconception Care and Prenatal Care

    MedlinePlus

    ... Who is at risk for complications? How does stress affect pregnancy? NICHD Research Information Research Goals Activities and Advances ... Who is at risk for complications? How does stress affect pregnancy? NICHD Research Information Clinical Trials Resources and Publications ...

  8. Who Is at Increased Risk of Health Problems during Pregnancy?

    MedlinePlus

    ... Who is at risk for complications? How does stress affect pregnancy? NICHD Research Information Research Goals Activities and Advances ... Who is at risk for complications? How does stress affect pregnancy? NICHD Research Information Clinical Trials Resources and Publications ...

  9. How Are My Newborn's Screening Results Used?

    MedlinePlus

    ... newborn screening device Selected NICHD Research Advances of 2016 All related news Home Contact Accessibility Web Policies and Notices FOIA Facebook Twitter Pinterest YouTube RSS NIH...Turning Discovery Into Health ® Printed from the NICHD Web Site

  10. NIH Quickfinder and NIH Medline Plus Advisory Group | NIH MedlinePlus the Magazine

    MedlinePlus

    ... Kennedy Shriver National Institute of Child Health and Human Development (NICHD) www.nichd.nih.gov/Pages/index.aspx ... Ph.D., National Institute of Child Health and Human Development Naomi Miller, National Library of Medicine (ex-officio) ...

  11. NIH Quickfinder | NIH MedlinePlus the Magazine

    MedlinePlus

    ... Kennedy Shriver National Institute of Child Health and Human Development (NICHD) www.nichd.nih.gov/Pages/index.aspx ... Ph.D., National Institute of Child Health and Human Development Naomi Miller, National Library of Medicine (ex-officio) ...

  12. How Many People Are Affected by or at Risk of Adrenal Gland Disorders?

    MedlinePlus

    ... NICHD Research Information Research Goals Activities and Advances Scientific Articles Clinical Trials More Information Other FAQs Resources Search ... NICHD Research Information Research Goals Activities and Advances Scientific Articles Clinical Trials More Information Other FAQs Resources Grants & ...

  13. Clinical Research and Clinical Trials

    MedlinePlus

    ... Youth NCMHEP NICHD Publications Data Sharing and Other Resources Research The Human Placenta Project Research and Funding Frequently Asked Questions (FAQs) Meetings Related News and Media The National Children's ... & Selected Staff Profiles Multimedia About NICHD Institute ...

  14. What Are the Common Treatments for Necrotizing Enterocolitis?

    MedlinePlus

    ... it? » Related A-Z Topics Breastfeeding and Breast Milk Infant Care and Infant Health Infant Mortality All related topics NICHD News and Spotlights NICHD scientists decipher how group of proteins regulate immune cell development in mice Getting to ...

  15. Vulvodynia

    MedlinePlus

    ... NICHD Research Information Research Goals Activities and Advances Scientific Articles Clinical Trials More Information Other FAQs Resources Search ... NICHD Research Information Research Goals Activities and Advances Scientific Articles Clinical Trials More Information Other FAQs Resources Grants & ...

  16. Restoring Bone Density in Women with Ovarian Disorder

    MedlinePlus

    ... Kennedy Shriver National Institute of Child Health and Human Development (NICHD) tested the effects of hormone replacement therapy ... Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and Procter & Gamble. Search NIH Research Matters ...

  17. NIH Quickfinder and NIH MedlinePlus Advisory Group

    MedlinePlus

    ... 451-6772 National Institute of Child Health and Human Development (NICHD) www.nichd.nih.gov/Pages/index.aspx ... Ph.D. , National Institute of Child Health and Human Development Gregory Roa , National Institute on Alcohol Abuse and ...

  18. Drug Improves Birth Rates for Women with Ovary Disorder

    MedlinePlus

    ... Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and National Center for Advancing Translational Sciences ( ... Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and National Center for Advancing Translational Sciences ( ...

  19. NIH Quickfinder and NIH MedlinePlus Advisory Group - Winter 2010 | NIH MedlinePlus the Magazine

    MedlinePlus

    ... Kennedy Shriver National Institute of Child Health and Human Development (NICHD) www.nichd.nih.gov/Pages/index.aspx ... Ph.D., National Institute of Child Health and Human Development Naomi Miller, National Library of Medicine (ex-officio) ...

  20. NIH Quickfinder and NIH MedlinePlus Advisory Group - Winter 2011

    MedlinePlus

    ... Kennedy Shriver National Institute of Child Health and Human Development (NICHD) www.nichd.nih.gov/Pages/index.aspx ... Ph.D., National Institute of Child Health and Human Development Naomi Miller, National Library of Medicine (ex-officio) ...