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.

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

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.

NCI-MATCH Trial Links Targeted Drugs to Mutations

Cancer.gov

Investigators for the nationwide trial, NCI-MATCH: Molecular Analysis for Therapy Choice, announced that the trial will seek to determine whether targeted therapies for people whose tumors have specific gene mutations will be effective regardless of their cancer type. NCI-MATCH will incorporate more than 20 different study drugs or drug combinations, each targeting a specific gene mutation, in order to match each patient in the trial with a therapy that targets a molecular abnormality in their tumor.

NCI Contact Center

Cancer.gov

The NCI Contact Center (formerly the Cancer Information Service) provides accurate, up-to-date, and reliable information on cancer that is easy to understand. Trained information specialists provide personalized responses to a range of cancer questions.

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.

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.

CRADA Payment Options | NCI Technology Transfer Center | TTC

Cancer.gov

NCI TTC 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).

NCI-MATCH trial releases new findings

Cancer.gov

The NCI-MATCH precision medicine clinical trial has reached a milestone with the release of results from several study treatment arms. Findings from three arms were released at the 2018 ASCO annual meeting, adding to findings from one arm released in 2017.

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.

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.

The NCI All Ireland Cancer Conference.

PubMed

Johnston; Daly; Liu

1999-01-01

education and training and also promote clinical trials and cancer epidemiology programs. Major components of the NCI Ireland Agreement will include some of the following: EDUCATION AND EXCHANGE OF SCHOLARS: Education will form one of the major platforms of this agreement through the support of educational programs for medical, nursing and scientific staff. These will include the exchange of scholars, including Ph.D., M.D. and nursing students. Particular emphasis will be given to the exchange of medical and nursing trainees focused on clinical research. This will have an immediate clinical impact and will naturally extend the support that has already been given to the training of medical and scientific trainees from the Island of Ireland. Further exchanges would include Ph.D. students, laboratory-based M.D.s in training, clinical visiting professors and investigators from the U.S. wishing to extend their studies in Ireland. CLINICAL TRIALS: Another major area for partnership will be the enhancement of a clinical trials infrastructure and clinical trial development. Modernization of cancer care requires that delivery of care should be in the context of evidence-based medicine. This requires a vigorous and contemporary clinical trials infrastructure which would center around the clinical trials infrastructure already established at the Northern Ireland Cancer Centre and the Irish Clinical Oncology Research Group (ICORG) in the Republic of Ireland. The NCI has already commissioned the development of a new Clinical Trials Information System (CTIS) which seeks as its goal to set international standards in the clinical trials process, and it has already committed significant resources to its implementation. The outcome of this element of partnership will be that clinical trials performed in Irish institutions will immediately be compatible for collation, analysis and presentation with studies performed in the U.S. Moreover, this system will allow participating centers to

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.

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

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

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

NCI ALMANAC Tool for Research on Cancer Drug Combinations

Cancer.gov

A Cancer Currents blog post on the NCI ALMANAC, a new resource that provides data showing how well pairs of FDA-approved cancer drugs performed in killing tumor cells from NCI-60 Human Tumor Cell Lines.

NCI support for particle therapy: past, present, future.

PubMed

Deye, James A

2012-11-01

In light of the rising worldwide interest in particle therapy, and proton therapy specifically in the United States, the National Cancer Institute (NCI) is being asked more often about funding for such research and facilities. Many of the questions imply that NCI is naive to the exciting possibilities inherent in particle therapies, and thus they wish to encourage NCI to initiate and underwrite such programs. In fact, NCI has a long track record of support for the translation of hadrons from the physics laboratory to the therapy clinic by way of technology development and scientific investigations of physical and biological processes as well as clinical outcomes. Early work has included continuous funding since 1961 of proton treatments for more than 15,000 patients and facility construction at the Harvard/Massachusetts General Hospital (MGH) site; treatment of 227 patients with the pi-meson facility at Los Alamos between 1974 and 1981; funding of more than $69M for seven neutron therapy centers between 1971 and 1989; many funded projects in boron neutron capture radiation therapy through the present time; and numerous radiobiology projects over the past 50 y. NCI continues to play an active role in the incorporation of protons into randomized clinical trials through the Children's Oncology Group, Radiation Therapy Oncology Group, and the Program Project Grant (P01), which is co-directed by the MGH and MD Anderson Cancer Center. This has required funding development and implementation of guidelines that enable intercomparison of dosimetry and treatment between facilities. NCI has also funded recent efforts to develop new physical processes for the production of particles such as protons. With regard to the future, while it is true that there are no specific funding opportunity announcements directed to particle therapy research, it is also true that NCI remains open to reviewing any research that is compatible with an established mechanism. However, given the very

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.

Auditing the NCI Thesaurus with Semantic Web Technologies

PubMed Central

Mougin, Fleur; Bodenreider, Olivier

2008-01-01

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. PMID:18999265

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.

Comprehensive List of Cancer-Related Genetic Variations of the NCI-60 Panel | Center for Cancer Research

Cancer.gov

The NCI-60 cell lines are the most frequently studied human tumor cell lines in cancer research. The panel of cell lines represents nine different types of cancer: breast, ovary, prostate, colon, lung, kidney, brain, leukemia, and melanoma. Originally developed to screen anticancer compounds by the NCI Developmental Therapeutics Program (DTP), the NCI-60 panel has generated

GPU accelerated implementation of NCI calculations using promolecular density.

PubMed

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

2017-05-30

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. © 2017 Wiley Periodicals, Inc.

76 FR 2253 - TRICARE; Coverage of National Cancer Institute (NCI) Sponsored Phase I Studies

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-13

... works. Phase II studies usually focus on a particular type of cancer. A Phase III trial tests a new drug... Secretary, DoD. ACTION: Final rule. SUMMARY: This final rule adds coverage of National Cancer Institute (NCI... evaluate how a new drug should be given (by mouth, injected into the blood, or injected into the muscle...

Sharpless Outlines His Plans for NCI During Spring Town Hall | Poster

Cancer.gov

At the National Cancer Institute (NCI) Spring Town Hall, new director Norman E. “Ned” Sharpless, M.D., summarized his goals for NCI’s role in cancer research. The event, which was held at NCI Shady Grove and livestreamed to eight other major NCI locations, was Sharpless’ first town hall since his six-month “listening and learning tour” concluded.

NCI Pediatric Preclinical Testing Consortium

Cancer.gov

NCI has awarded grants to five research teams to participate in its Pediatric Preclinical Testing Consortium, which is intended to help to prioritize which agents to pursue in pediatric clinical trials.

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.

Direct cortical hemodynamic mapping of somatotopy of pig nostril sensation by functional near-infrared cortical imaging (fNCI).

PubMed

Uga, Minako; Saito, Toshiyuki; Sano, Toshifumi; Yokota, Hidenori; Oguro, Keiji; Rizki, Edmi Edison; Mizutani, Tsutomu; Katura, Takusige; Dan, Ippeita; Watanabe, Eiju

2014-05-01

Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique for the noninvasive monitoring of human brain activation states utilizing the coupling between neural activity and regional cerebral hemodynamics. Illuminators and detectors, together constituting optodes, are placed on the scalp, but due to the presence of head tissues, an inter-optode distance of more than 2.5cm is necessary to detect cortical signals. Although direct cortical monitoring with fNIRS has been pursued, a high-resolution visualization of hemodynamic changes associated with sensory, motor and cognitive neural responses directly from the cortical surface has yet to be realized. To acquire robust information on the hemodynamics of the cortex, devoid of signal complications in transcranial measurement, we devised a functional near-infrared cortical imaging (fNCI) technique. Here we demonstrate the first direct functional measurement of temporal and spatial patterns of cortical hemodynamics using the fNCI technique. For fNCI, inter-optode distance was set at 5mm, and light leakage from illuminators was prevented by a special optode holder made of a light-shielding rubber sheet. fNCI successfully detected the somatotopy of pig nostril sensation, as assessed in comparison with concurrent and sequential somatosensory-evoked potential (SEP) measurements on the same stimulation sites. Accordingly, the fNCI system realized a direct cortical hemodynamic measurement with a spatial resolution comparable to that of SEP mapping on the rostral region of the pig brain. This study provides an important initial step toward realizing functional cortical hemodynamic monitoring during neurosurgery of human brains. Copyright © 2014. Published by Elsevier Inc.

Determinants of NCI Cancer Center attendance in Medicare patients with lung, breast, colorectal, or prostate cancer.

PubMed

Onega, Tracy; Duell, Eric J; Shi, Xun; Demidenko, Eugene; Goodman, David

2009-02-01

Geographic access to NCI-Cancer Centers varies by region, race/ethnicity, and place of residence, but utilization of these specialized centers has not been examined at the national level in the U.S. This study identified determinants of NCI-Cancer Center attendance in Medicare cancer patients. SEER-Medicare (Surveillance Epidemiology and End Results) data were used to identify individuals with an incident cancer of the breast, lung, colon/rectum, or prostate from 1998-2002. NCI-Cancer Center attendance was determined based on utilization claims from 1998-2003. Demographic, clinical, and geographic factors were examined in multilevel models. We performed sensitivity analyses for the NCI-Cancer Center attendance definition. Overall, 7.3% of this SEER-Medicare cohort (N = 211,048) attended an NCI-Cancer Center. Travel-time to the nearest NCI-Cancer Center was inversely related to attendance, showing 11% decreased likelihood of attendance for every 10 minutes of additional travel-time (OR = 0.89, 95%CI 0.88-0.90). Receiving predominantly generalist care prior to diagnosis was associated with a lower likelihood of attendance (OR = 0.79, 95%CI 0.77-0.82). The other factors associated with greater NCI-Cancer attendance were later stage at diagnosis, fewer comorbidities, and urban residence in conjunction with African-American race. Attendance at NCI-Cancer Centers is low among Medicare beneficiaries, but is strongly influenced by proximity and general provider care prior to diagnosis. Other patient factors are predictive of NCI-Cancer Center attendance and may be important in better understanding cancer care utilization.

The NCI Alliance for Nanotechnology in Cancer: achievement and path forward.

PubMed

Ptak, Krzysztof; Farrell, Dorothy; Panaro, Nicholas J; Grodzinski, Piotr; Barker, Anna D

2010-01-01

Nanotechnology is a 'disruptive technology', which can lead to a generation of new diagnostic and therapeutic products, resulting in dramatically improved cancer outcomes. The National Cancer Institute (NCI) of National Institutes of Health explores innovative approaches to multidisciplinary research allowing for a convergence of molecular biology, oncology, physics, chemistry, and engineering and leading to the development of clinically worthy technological approaches. These initiatives include programmatic efforts to enable nanotechnology as a driver of advances in clinical oncology and cancer research, known collectively as the NCI Alliance for Nanotechnology in Cancer (ANC). Over the last 5 years, ANC has demonstrated that multidisciplinary approach catalyzes scientific developments and advances clinical translation in cancer nanotechnology. The research conducted by ANC members has improved diagnostic assays and imaging agents, leading to the development of point-of-care diagnostics, identification and validation of numerous biomarkers for novel diagnostic assays, and the development of multifunctional agents for imaging and therapy. Numerous nanotechnology-based technologies developed by ANC researchers are entering clinical trials. NCI has re-issued ANC program for next 5 years signaling that it continues to have high expectations for cancer nanotechnology's impact on clinical practice. The goals of the next phase will be to broaden access to cancer nanotechnology research through greater clinical translation and outreach to the patient and clinical communities and to support development of entirely new models of cancer care.

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

PubMed Central

Guo, Xia; Fong, Chi Man Vivienne; Chen, Xiuping; Lu, Jin-Jian

2016-01-01

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. PMID:27835594

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.

Quality Assurance of NCI Thesaurus by Mining Structural-Lexical Patterns

PubMed Central

Abeysinghe, Rashmie; Brooks, Michael A.; Talbert, Jeffery; Licong, Cui

2017-01-01

Quality assurance of biomedical terminologies such as the National Cancer Institute (NCI) Thesaurus is an essential part of the terminology management lifecycle. We investigate a structural-lexical approach based on non-lattice subgraphs to automatically identify missing hierarchical relations and missing concepts in the NCI Thesaurus. We mine six structural-lexical patterns exhibiting in non-lattice subgraphs: containment, union, intersection, union-intersection, inference-contradiction, and inference union. Each pattern indicates a potential specific type of error and suggests a potential type of remediation. We found 809 non-lattice subgraphs with these patterns in the NCI Thesaurus (version 16.12d). Domain experts evaluated a random sample of 50 small non-lattice subgraphs, of which 33 were confirmed to contain errors and make correct suggestions (33/50 = 66%). Of the 25 evaluated subgraphs revealing multiple patterns, 22 were verified correct (22/25 = 88%). This shows the effectiveness of our structurallexical-pattern-based approach in detecting errors and suggesting remediations in the NCI Thesaurus. PMID:29854100

Employees Honored at NCI Director’s Awards & Appreciation Ceremony | Poster

Cancer.gov

The NCI Director’s Awards & Appreciation Ceremony began with a video of NCI employees talking about their roles, whether in transportation, nursing, IT, or research. Many spoke of family members who have or had cancer, and all were proud to be able to contribute to NCI’s mission.

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

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

Find an NCI-Designated Cancer Center

Cancer.gov

Find the locations of NCI-designated cancer centers by area, region, state, or name that includes contact information to help health care providers and cancer patients with referrals to clinical trials.

Senator John McCain Thanks NCI | Division of Cancer Prevention

Cancer.gov

Senator John McCain (R-AZ) made remarks on the Senate on October 31 thanking and praising all of the professionals and administrators at NCI, for both treating his brain cancer and for supporting cancer research around the country. Source: https://www.c-span.org/video/?c4689292/sen-mccain-thanks-nci |

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

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

Keeping NCI at Frederick Pest-Free—Doug Vaughn | Poster

Cancer.gov

Nuisance critters and creepy crawlers aren’t a problem at the National Cancer Institute (NCI) at Frederick, and that’s largely thanks to the efforts of Douglas Vaughn, the institution’s pest controller. Endearingly known to some staff as “Doug the Bug Guy,” Vaughn has been doing pest control for 39 years, 22 of which have been at NCI at Frederick. However, he doesn’t just

Evaluation & Validation of the DHQ | EGRP/DCCPS/NCI/NIH

Cancer.gov

Learn about the evaluation and validation studies of the National Cancer Institute's (NCI) original Diet History Questionnaire (DHQ I) and why they are relevant to the second and third versions of the DHQ food frequency questionnaire, DHQ II and DHQ III.

NCI and the Cancer Community: Focus on Patients Through Innovative Research

Cancer.gov

At the 2018 AACR Annual Meeting , NCI Director Norman Sharpless describes the key focus areas where NCI can be particularly important to the cancer research enterprise on advancing progress and explains how addressing the challenges of the cancer research landscape requires innovative thinking.

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.

Diesel Exhaust Particles Enhance MUC4 Expression in NCI-H292 Cells and Nasal Epithelial Cells via the p38/CREB Pathway.

PubMed

Park, Il-Ho; Kang, Ju-Hyung; Kim, Jin Ah; Shin, Jae-Min; Lee, Heung-Man

2016-01-01

Diesel exhaust particles (DEPs), the major contributors to air pollution, induce inflammatory responses in the nasal epithelium. Overproduction of airway mucins is an important pathogenic finding in inflammatory airway diseases. The aims of the present study were to determine the effect of DEPs on the expression of the mucin gene MUC4 and to investigate the underlying mechanism of DEP-induced MUC4 expression in NCI-H292 cells and primary nasal epithelial cells (PNECs). NCI-H292 cells were stimulated for 24 h with DEPs. Messenger RNA (mRNA) and protein expression of MUC4 was determined by real-time reverse transcription (RT) polymerase chain reaction (PCR) and Western blotting. NCI-H292 cells were exposed to 3 mitogen-activated protein kinase inhibitors (U0126, SB203580, and SP600125) and a CREB (cAMP response element-binding protein) inhibitor prior to stimulation with DEPs, and MUC4 expression was examined by RT-PCR and Western blotting. PNECs were pretreated with a p38 inhibitor and CREB inhibitor prior to stimulation with DEPs, and MUC4 expression was then determined by RT-PCR and/or Western blotting. DEPs significantly increased the expression of MUC4 mRNA and protein. MUC4 mRNA and protein expression was inhibited by pretreatment with p38 and CREB inhibitors in NCI-H292 stimulated with DEPs. p38 and CREB inhibitors also blocked the expression of MUC4 mRNA and protein in DEP-stimulated PNECs. We demonstrated that DEPs stimulated the expression of MUC4 via the p38/CREB pathway in NCI-H292 cells and PNECs. The results of the present study pave the way for further studies on the role of MUC4 in DEP-induced hypersecretion in airway epithelium. © 2017 S. Karger AG, Basel.

Selected Publications by the NCI Director

Cancer.gov

Dr. Norman Sharpless's written work on cancer research appears in many leading scientific journals, as well as a variety of other publications. This page lists some of the articles published by Dr. Sharpless since becoming NCI director.

Micro-Dose Calibrator for Pre-clinical Radiotracer Assays | NCI Technology Transfer Center | TTC

Cancer.gov

Pre-clinical radiotracer biomedical research involves the use of compounds labeled with radioisotopes, including cell binding studies, immune cell labeling techniques, and radio-ligand bio-distribution studies. Before this Micro-Dose Calibrator, measurement of pre-clinical level dosage for small animal studies was inaccurate and unreliable. This dose calibrator is a prototype ready for manufacturing. It is designed to accurately measure radioactive doses in the range of 50 nCi (1.8 kBq) to 100 µCi (3.7 MBq) with 1% precision. The NCI seeks co-development or licensing to commercialize it. Alternative uses will be considered.

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

Keeping NCI at Frederick Pest-Free—Doug Vaughn | Poster

Cancer.gov

Nuisance critters and creepy crawlers aren’t a problem at the National Cancer Institute (NCI) at Frederick, and that’s largely thanks to the efforts of Douglas Vaughn, the institution’s pest controller. Endearingly known to some staff as “Doug the Bug Guy,” Vaughn has been doing pest control for 39 years, 22 of which have been at NCI at Frederick. However, he doesn’t just handle bugs, and he isn’t the average exterminator.

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).

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.

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.

Emergency Services at NCI at Frederick | Poster

Cancer.gov

Despite precautions and preventive techniques, injuries and emergencies can happen at NCI at Frederick. When they occur, employees should call the same number as they would when they are off-campus: 911.

Life Outside NCI | Cancer Prevention Fellowship Program

Cancer.gov

The CPFP Office is located at the NCI facilities in Rockville, Maryland, near the Nation’s Capital. With the convenient Metro subway reaching throughout the metropolitan area, transportation is within easy reach.

About TTC | NCI Technology Transfer Center | TTC

Cancer.gov

The TTC facilitates licensing and co-development partnerships between biomedical industry, academia, and government agencies and the research laboratories of the NCI and nine other institutes and centers of NIH.

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.

Comprehensive List of Cancer-Related Genetic Variations of the NCI-60 Panel | Center for Cancer Research

Cancer.gov

The NCI-60 cell lines are the most frequently studied human tumor cell lines in cancer research. The panel of cell lines represents nine different types of cancer: breast, ovary, prostate, colon, lung, kidney, brain, leukemia, and melanoma. Originally developed to screen anticancer compounds by the NCI Developmental Therapeutics Program (DTP), the NCI-60 panel has generated the most extensive cancer pharmacology database worldwide. The 60 cell lines have also been extensively analyzed for their gene and microRNA expression levels, DNA mutation status, and DNA copy number variations. These findings have provided the groundwork for research centered on increasing our understanding of tumor biology and drug activity.

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

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.

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.

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.

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.

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

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.

NCI-CONNECT - Comprehensive Oncology Network Evaluating Rare CNS Tumors | Center for Cancer Research

Cancer.gov

NCI-CONNECT:  Comprehensive Oncology Network Evaluating Rare CNS Tumors Purpose NCI-CONNECT aims to advance the understanding of rare adult central nervous system (CNS) cancers by establishing and fostering patient-advocacy-provider partnerships and networks to improve approaches to care and treatment.

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.

TEAM Webinar Series | EGRP/DCCPS/NCI/NIH

Cancer.gov

View archived webinars from the Transforming Epidemiology through Advanced Methods (TEAM) Webinar Series, hosted by NCI's Epidemiology and Genomics Research Program. Topics include participant engagement, data coordination, mHealth tools, sample selection, and instruments for diet & physical activity assessment.

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,

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).

NCI designated cancer center funding not influenced by organizational structure.

PubMed

Wolfe, Margaret E; Yagoda, Daniel; Thurman, Paul W; Luna, Jorge M; Figg, William Douglas

2009-05-01

National Cancer Institutes (NCI) designated cancer centers use one of three organizational structures. The hypothesis of this study is that there are differences in the amount of annual NCI funding per faculty member based on a cancer center's organizational structure. The study also considers the impact of secondary factors (i.e., the existence of a clinical program, the region and the size of the city in which the cancer center is located) on funding and the number of Howard Hughes Medical Institute (HHMI) investigators at each cancer center. Of the 63 cancer centers, 44 use a matrix structure, 16 have a freestanding structure, and three have a Department of Oncology structure. Kruskal-Wallis tests reveal no statistically significant differences in the amount of funding per faculty member or the number of HHMI investigators between centers with a matrix, freestanding or Department of Oncology structure. Online research and telephone interviews with each cancer center were used to gather information, including: organizational structure, the presence of a clinical program, the number of faculty members, and the number of Howard Hughes Medical Institute investigators. Statistical tests were used to assess the impact which organizational structure has on the amount of funding per faculty member and number of HHMI investigators. While the results seem to suggest that the organizational structure of a given cancer center does not impact the amount of NCI funding or number of HHMI investigators which it attracts, the existence of this relationship is likely masked by the small sample size in this study. Further studies may be appropriate to examine the effect organizational structure has on other measurements which are relevant to cancer centers, such as quality and quantity of research produced.

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.

College Graduate with NCI Internship Gains Experience, Carries Chemistry into Medicine | Poster

Cancer.gov

For Jennifer Marshall, the skills learned through an internship at the National Cancer Institute (NCI) at Frederick have prepared her for the next step of her life—medical school. Marshall, who will be attending the West Virginia University School of Medicine in the fall, spent three summers in NCI at Frederick’s Summer Internship Program expanding her love and passion for

The generalizability of NCI-sponsored clinical trials accrual among women with gynecologic malignancies.

PubMed

Mishkin, Grace; Minasian, Lori M; Kohn, Elise C; Noone, Anne-Michelle; Temkin, Sarah M

2016-12-01

Enrollment of a representative population to cancer clinical trials ensures scientific reliability and generalizability of results. This study evaluated the similarity of patients enrolled in NCI-supported group gynecologic cancer trials to the incident US population. Accrual to NCI-sponsored ovarian, uterine, and cervical cancer treatment trials between 2003 and 2012 were examined. Race, ethnicity, age, and insurance status were compared to the analogous US patient population estimated using adjusted SEER incidence data. There were 18,913 accruals to 156 NCI-sponsored gynecologic cancer treatment trials, ovarian (56%), uterine (32%), and cervical cancers (12%). Ovarian cancer trials included the least racial, ethnic and age diversity. Black women were notably underrepresented in ovarian trials (4% versus 11%). Hispanic patients were underrepresented in ovarian and uterine trials (4% and 5% versus 18% and 19%, respectively), but not in cervical cancer trials (14 versus 11%). Elderly patients were underrepresented in each disease area, with the greatest underrepresentation seen in ovarian cancer patients over the age of 75 (7% versus 29%). Privately insured women were overrepresented among accrued ovarian cancer patients (87% versus 76%), and the uninsured were overrepresented among women with uterine or cervical cancers. These patterns did not change over time. Several notable differences were observed between the patients accrued to NCI funded trials and the incident population. Improving representation of racial and ethnic minorities and elderly patients on cancer clinical trials continues to be a challenge and priority. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

NCI Expands Repository of Cancer Research Models

Cancer.gov

NCI is expanding its Patient-Derived Models Repository (PDMR), which generates and distributes models like patient-derived xenografts and organoids. In this Cancer Currents Q&A with Drs. Yvonne Evrard and James Doroshow, learn how the expansion can help cancer researchers make more rapid progress.

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.

Vaccine for BK Polyomavirus-associated Infections in Transplant Recipients | NCI Technology Transfer Center | TTC

Cancer.gov

NCI researches identified a BK polyomavirus (BKV) virulent strain that causes chronic urinary tract infections, and the development of vaccine and therapeutic methods that would block BKV pathogenesis. The NCI Laboratory of Cellular Oncology, seek parties to license or co-develop this technology.

Published Research - NCI Alliance for Nanotechnology in Cancer

Cancer.gov

The NCI Alliance for Nanotechnology in Cancer has published much exciting and impactful research over the years. Find here a list of all of these listed in PubMed and others across the field of Cancer Nanotechnology.

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.

NCI and FDA to Study Cancer Proteogenomics Together | Office of Cancer Clinical Proteomics Research

Cancer.gov

The National Cancer Institute (NCI) Office of Cancer Clinical Proteomics Research (OCCPR), part of the National Institutes of Health, and the U.S. Food and Drug Administration (FDA) has signed a Memorandum of Understanding (MOU) in proteogenomic regulatory science.  This will allow the agencies to share information that will accelerate the development of proteogenomic technologies and biomarkers, as it relates to precision medicine in cancer.

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

NCI Core Open House Shines Spotlight on Supportive Science and Basic Research | Poster

Cancer.gov

The lobby of Building 549 at NCI at Frederick bustled with activity for two hours on Tuesday, May 1, as several dozen scientists and staff gathered for the NCI Core Open House. The event aimed to encourage discussion and educate visitors about the capabilities of the cores, laboratories, and facilities that offer support to NCI’s Center for Cancer Research.

A Qualitative Study of Motivations for Minority Recruitment in Cancer Clinical Trials Across Five NCI-Designated Cancer Centers.

PubMed

Simoni, Zachary R; Martin, Michelle; Wenzel, Jennifer A; Cook, Elise D; Konety, Badrinath; Vickers, Selwyn M; Chen, Moon S; Foaud, Mona N; Durant, Raegan W

2016-11-08

Minority enrollment in cancer clinical trials is traditionally low. In light of this fact, numerous studies have investigated barriers to recruitment and retention within minority populations. However, very little research has investigated the importance of clinicians' and researchers' motivations for minority recruitment in cancer clinical trials. Therefore, we sought to examine motivations for minority recruitment across four professional stakeholder groups (principal investigators, clinicians, research staff, and Cancer Center leaders) at five National Cancer Institute (NCI)-designated Comprehensive Cancer Centers. This study is based on the data from 91 qualitative interviews conducted across the five NCI-designated Comprehensive Cancer Centers to investigate stakeholders' motivations for minority recruitment in cancer clinical trials. Emergent themes include (a) minority recruitment increases generalizability of cancer clinical trials, (b) minority recruitment is motivated by social justice, (c) some institutions promote minority recruitment through the use of supplemental financial support, (d) federal funding requirements for minority inclusion in clinical research motivate investigators to focus on minority recruitment, and (e) some stakeholders favor a more race-neutral approach to participant recruitment rather than an emphasis on targeted minority recruitment. The perspectives of clinical and research stakeholders potentially inform the assessment of existing strategies and the development of new strategies to increase motivation for minority recruitment in cancer clinical trials.

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.

NCI Director Norman Sharpless’s ASCO 2018 Remarks

Cancer.gov

In this video, NCI Director Dr. Norman E. Sharpless discusses the future of cancer research at the 2018 American Society of Clinical Oncology (ASCO) annual meeting in Chicago. Learn more about his focus on basic science, workforce development, big data, and clinical trials.

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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...

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. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

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

Multivalent Immunogenic Vaccines for Treating Prostate and Breast Cancer | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the NCI have developed a treatment for prostate and breast cancer using multivalent peptides derived from TARP, the T cell receptor gamma alternate reading frame protein. These immunogenic peptides from TARP elicit an immune response, triggering T cells to kill only the cancer cells within a patient. NCI seeks licensees or co-development partners to commercialize this invention.

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

Pharmacologically directed strategies in academic anticancer drug discovery based on the European NCI compounds initiative.

PubMed

Hendriks, Hans R; Govaerts, Anne-Sophie; Fichtner, Iduna; Burtles, Sally; Westwell, Andrew D; Peters, Godefridus J

2017-07-11

The European NCI compounds programme, a joint initiative of the EORTC Research Branch, Cancer Research Campaign and the US National Cancer Institute, was initiated in 1993. The objective was to help the NCI in reducing the backlog of in vivo testing of potential anticancer compounds, synthesised in Europe that emerged from the NCI in vitro 60-cell screen. Over a period of more than twenty years the EORTC-Cancer Research Campaign panel reviewed ∼2000 compounds of which 95 were selected for further evaluation. Selected compounds were stepwise developed with clear go/no go decision points using a pharmacologically directed programme. This approach eliminated quickly compounds with unsuitable pharmacological properties. A few compounds went into Phase I clinical evaluation. The lessons learned and many of the principles outlined in the paper can easily be applied to current and future drug discovery and development programmes. Changes in the review panel, restrictions regarding numbers and types of compounds tested in the NCI in vitro screen and the appearance of targeted agents led to the discontinuation of the European NCI programme in 2017 and its transformation into an academic platform of excellence for anticancer drug discovery and development within the EORTC-PAMM group. This group remains open for advice and collaboration with interested parties in the field of cancer pharmacology.

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

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UNC Cancer Center Director to Lead NCI.

PubMed

2017-08-01

President Donald Trump has selected Norman "Ned" Sharpless, MD, director of the University of North Carolina Lineberger Comprehensive Cancer Center, to lead the NCI. The news was met with widespread approval among cancer researchers, who view Sharpless as a strong communicator who can ably represent the needs of the cancer community in the face of proposed funding cuts. ©2017 American Association for Cancer Research.

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.

NCI Partners with VA, DoD for Cancer Research

Cancer.gov

Partnerships and collaborations are an important component of NCI’s success. In this Cancer Currents blog post, NCI Director Dr. Norman Sharpless describes three efforts made possible by a memorandum of agreement with three US military institutions: the APOLLO network, NAVIGATE, and BD-STEP.

Help NCI at Frederick “Knock Out Hunger” | Poster

Cancer.gov

NCI at Frederick is once again participating in the Feds Feed Families initiative, an annual food drive that addresses severe shortages of non-perishable items in food banks across D.C., Maryland, and Virginia during the summer months, when giving is at its lowest.

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. Copyright © 2016 John Wiley & Sons, Ltd.

Phenethyl Isothiocyanate Induces Apoptotic Cell Death Through the Mitochondria-dependent Pathway in Gefitinib-resistant NCI-H460 Human Lung Cancer Cells In Vitro.

PubMed

Hsia, Te-Chun; Huang, Yi-Ping; Jiang, Yi-Wen; Chen, Hsin-Yu; Cheng, Zheng-Yu; Hsiao, Yung-Ting; Chen, Cheng-Yen; Peng, Shu-Fen; Chueh, Fu-Shin; Chou, Yu-Cheng; Chung, Jing-Gung

2018-04-01

Some lung cancer patients treated with gefitinib develop resistance to this drug resulting in unsatisfactory treatment outcomes. Phenethyl isothiocyanate (PEITC), present in our common cruciferous vegetables, exhibits anticancer activities in many human cancer cell lines. Currently, there is no available information on the possible modification of gefitinib resistance of lung cancer in vitro by PEITC. Thus, the effects of PEITC on gefitinib resistant lung cancer NCI-H460 cells were investigated in vitro. The total cell viability, apoptotic cell death, production of reactive oxygen species (ROS) and Ca 2+ , levels of mitochondria membrane potential (ΔΨ m ) and caspase-3, -8 and -9 activities were measured by flow cytometry assay. PEITC induced chromatin condensation was examined by DAPI staining. PEITC-induced cell morphological changes, decreased total viable cell number and induced apoptotic cell death in NCI-H460 and NCI-H460/G cells. PEITC decreased ROS production in NCI-H460 cells, but increased production in NCI-H460/G cells. PEITC increased Ca 2+ production, decreased the levels of ΔΨ m and increased caspase-3, -8 and -9 activities in both NCI-H460 and NCI-H460/G cells. Western blotting was used to examine the effect of apoptotic cell death associated protein expression in NCI-H460 NCI-H460/G cells after exposure to PEITC. Results showed that PEITC increased expression of cleaved caspase-3, PARP, GADD153, Endo G and pro-apoptotic protein Bax in NCI-H460/G cells. Based on these results, we suggest that PEITC induces apoptotic cell death via the caspase- and mitochondria-dependent pathway in NCI-H460/G cells. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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.

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.

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.

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

Differences Between DHQ II & DHQ III | EGRP/DCCPS/NCI/NIH

Cancer.gov

Learn about the changes to the food questions that were added or modified, and dietary supplement changes, from the National Cancer Institute's (NCI) Diet History Questionnaire II (DHQ II) to the third version of this food frequency questionnaire, DHQ III.

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. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

A multiple phase transitioning peptide hydrogel for use in vascular a | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the National Cancer Institute (NCI), in collaboration with surgical specialists from Johns Hopkins University, have developed hydrogel compositions and methods to suture blood vessels with the hydrogels during microsurgery. These hydrogels are particularly beneficial for surgeons in whole tissue transplant procedures. The NCI researchers seek licensing and/or co-development research collaborations for further development of this technology.

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,

How You Can Partner with NIH | NCI Technology Transfer Center | TTC

Cancer.gov

NCI Technology Transfer Center (TTC) provides an array of agreements to support the National Cancer Institute's partnering. Deciding which type of agreement to use can be a challenge: CRADA, MTA, collaboration, agreement, CTA, Materials-CRADA

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.

History of the Diet History Questionnaire (DHQ) | EGRP/DCCPS/NCI/NIH

Cancer.gov

Learn about the evolution of the Diet History Questionnaire (DHQ), developed by the National Cancer Institute (NCI) initially in 2001, to the DHQ II in 2010, up to the present version, DHQ III, launched in 2018.

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)

NIH Employee Invention Report (EIR) | NCI Technology Transfer Center | TTC

Cancer.gov

NIH researchers must immediately contact their Laboratory or Branch Chief and inform him or her of a possible invention, and then consult with your NCI TTC Technology Transfer Manager about submitting an Employee Invention Report (EIR) Form. | [google6f4cd5334ac394ab.html

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.

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

PubMed

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

2017-02-18

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.

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

CellMiner Companion: an interactive web application to explore CellMiner NCI-60 data.

PubMed

Wang, Sufang; Gribskov, Michael; Hazbun, Tony R; Pascuzzi, Pete E

2016-08-01

The NCI-60 human tumor cell line panel is an invaluable resource for cancer researchers, providing drug sensitivity, molecular and phenotypic data for a range of cancer types. CellMiner is a web resource that provides tools for the acquisition and analysis of quality-controlled NCI-60 data. CellMiner supports queries of up to 150 drugs or genes, but the output is an Excel file for each drug or gene. This output format makes it difficult for researchers to explore the data from large queries. CellMiner Companion is a web application that facilitates the exploration and visualization of output from CellMiner, further increasing the accessibility of NCI-60 data. The web application is freely accessible at https://pul-bioinformatics.shinyapps.io/CellMinerCompanion The R source code can be downloaded at https://github.com/pepascuzzi/CellMinerCompanion.git ppascuzz@purdue.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Evaluation of the UF/NCI hybrid computational phantoms for use in organ dosimetry of pediatric patients undergoing fluoroscopically guided cardiac procedures

NASA Astrophysics Data System (ADS)

Marshall, Emily L.; Borrego, David; Tran, Trung; Fudge, James C.; Bolch, Wesley E.

2018-03-01

Epidemiologic data demonstrate that pediatric patients face a higher relative risk of radiation induced cancers than their adult counterparts at equivalent exposures. Infants and children with congenital heart defects are a critical patient population exposed to ionizing radiation during life-saving procedures. These patients will likely incur numerous procedures throughout their lifespan, each time increasing their cumulative radiation absorbed dose. As continued improvements in long-term prognosis of congenital heart defect patients is achieved, a better understanding of organ radiation dose following treatment becomes increasingly vital. Dosimetry of these patients can be accomplished using Monte Carlo radiation transport simulations, coupled with modern anatomical patient models. The aim of this study was to evaluate the performance of the University of Florida/National Cancer Institute (UF/NCI) pediatric hybrid computational phantom library for organ dose assessment of patients that have undergone fluoroscopically guided cardiac catheterizations. In this study, two types of simulations were modeled. A dose assessment was performed on 29 patient-specific voxel phantoms (taken as representing the patient’s true anatomy), height/weight-matched hybrid library phantoms, and age-matched reference phantoms. Two exposure studies were conducted for each phantom type. First, a parametric study was constructed by the attending pediatric interventional cardiologist at the University of Florida to model the range of parameters seen clinically. Second, four clinical cardiac procedures were simulated based upon internal logfiles captured by a Toshiba Infinix-i Cardiac Bi-Plane fluoroscopic unit. Performance of the phantom library was quantified by computing both the percent difference in individual organ doses, as well as the organ dose root mean square values for overall phantom assessment between the matched phantoms (UF/NCI library or reference) and the patient

NCI Scientists Create New Assay, Identify Novel Therapeutic Compounds, and Take Places on Front Lines of Cancer Research | Poster

Cancer.gov

A team of scientists and specialists from NCI at Frederick, NCI at Bethesda, the Frederick National Laboratory for Cancer Research, and Data Management Services, Inc., has developed the first method for identifying natural products that could increase the effectiveness of camptothecin-based cancer treatments.

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

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.

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.

NCI at Frederick's Wye Oak Moves Down the Street | Poster

Cancer.gov

One of NCI at Frederick’s two offspring of the Wye Oak tree that lived for nearly 500 years in Talbot County, Maryland, has found a new home on campus. The move was necessitated by upgrades to Chiller Plant #5 and the associated water piping routes on the west side of building 560.

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

Improving global data infrastructures for more effective and scalable analysis of Earth and environmental data: the Australian NCI NERDIP Approach

NASA Astrophysics Data System (ADS)

Evans, Ben; Wyborn, Lesley; Druken, Kelsey; Richards, Clare; Trenham, Claire; Wang, Jingbo; Rozas Larraondo, Pablo; Steer, Adam; Smillie, Jon

2017-04-01

different disciplines and research communities to invoke new forms of analysis and discovery in an increasingly complex data-rich environment. Driven by the heterogeneity of Earth and environmental datasets, NCI developed a Data Quality/Data Assurance Strategy to ensure consistency is maintained within and across all datasets, as well as functionality testing to ensure smooth interoperability between products, tools, and services. This is particularly so for collections that contain data generated from multiple data acquisition campaigns, often using instruments and models that have evolved over time. By implementing the NCI Data Quality Strategy we have seen progressive improvement in the integration and quality of the datasets across the different subject domains, and through this, the ease by which the users can access data from this major data infrastructure. By both adhering to international standards and also contributing to extensions of these standards, data from the NCI NERDIP platform can be federated with data from other globally distributed data repositories and infrastructures. The NCI approach builds on our experience working with the astronomy and climate science communities, which have been internationally coordinating such interoperability standards within their disciplines for some years. The results of our work so far demonstrate more could be done in the Earth science, solid earth and environmental communities, particularly through establishing better linkages between international/national community efforts such as EPOS, ENVRIplus, EarthCube, AuScope and the Research Data Alliance.

Studies demonstrate modified T cells effective in treating blood-borne cancers

Cancer.gov

At the 2013 American Society of Hematology meeting in Dec. 2013, James Kochenderfer, M.D., NCI, presented findings from two clinical trials evaluating the use of genetically modified immune system T cells as cancer therapy. These reports represent import

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

Best Performers Announced for the NCI-CPTAC DREAM Proteogenomics Computational Challenge | Office of Cancer Clinical Proteomics Research

Cancer.gov

The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) is pleased to announce that teams led by Jaewoo Kang (Korea University), and Yuanfang Guan with Hongyang Li (University of Michigan) as the best performers of the NCI-CPTAC DREAM Proteogenomics Computational Challenge. Over 500 participants from 20 countries registered for the Challenge, which offered $25,000 in cash awards contributed by the NVIDIA Foundation through its Compute the Cure initiative.

Comparison of the NCI open database with seven large chemical structural databases.

PubMed

Voigt, J H; Bienfait, B; Wang, S; Nicklaus, M C

2001-01-01

Eight large chemical databases have been analyzed and compared to each other. Central to this comparison is the open National Cancer Institute (NCI) database, consisting of approximately 250 000 structures. The other databases analyzed are the Available Chemicals Directory ("ACD," from MDL, release 1.99, 3D-version); the ChemACX ("ACX," from CamSoft, Version 4.5); the Maybridge Catalog and the Asinex database (both as distributed by CamSoft as part of ChemInfo 4.5); the Sigma-Aldrich Catalog (CD-ROM, 1999 Version); the World Drug Index ("WDI," Derwent, version 1999.03); and the organic part of the Cambridge Crystallographic Database ("CSD," from Cambridge Crystallographic Data Center, 1999 Version 5.18). The database properties analyzed are internal duplication rates; compounds unique to each database; cumulative occurrence of compounds in an increasing number of databases; overlap of identical compounds between two databases; similarity overlap; diversity; and others. The crystallographic database CSD and the WDI show somewhat less overlap with the other databases than those with each other. In particular the collections of commercial compounds and compilations of vendor catalogs have a substantial degree of overlap among each other. Still, no database is completely a subset of any other, and each appears to have its own niche and thus "raison d'être". The NCI database has by far the highest number of compounds that are unique to it. Approximately 200 000 of the NCI structures were not found in any of the other analyzed databases.

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

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.

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

Cancer Immunotherapy Using Virus-like Particles | NCI Technology Transfer Center | TTC

Cancer.gov

A considerable effort has been devoted to identifying and targeting specific extracellular cancer markers using antibody based therapies. However, diminished access to new cancer cell surface markers has limited the development of corresponding antibodies. NCI Technology Transfer Center is seeking to license cancer immunotherapy using virus-like particles.

Connecting genomic alterations to cancer biology with proteomics: the NCI Clinical Proteomic Tumor Analysis Consortium.

PubMed

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

2013-10-01

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 verification using targeted mass spectrometry methods. ©2013 AACR.

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

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.

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.

NCI's Proteome Characterization Centers Announced | Office of Cancer Clinical Proteomics Research

Cancer.gov

The National Cancer Institute (NCI), part of the National Institutes of Health, announces the launch of a Clinical Proteomic Tumor Analysis Consortium (CPTAC). CPTAC is a comprehensive, coordinated team effort to accelerate the understanding of the molecular basis of cancer through the application of robust, quantitative, proteomic technologies and workflows.

March 2018 Cancer Epidemiology Matters E-News | EGRP/DCCPS/NCI/NIH

Cancer.gov

March 2018 issue of Cancer Epidemiology Matters E-News, published by NCI’s Epidemiology and Genomics Research Program, features sessions for epidemiologists at the American Association for Cancer Research Annual Meeting, new NCI funding opportunities in epidemiologic research on emerging risk factors and liver cancer susceptibility, upcoming events, and more.

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

The NCI Community Oncology Research Program: what every clinician needs to know.

PubMed

McCaskill-Stevens, Worta; Lyss, Alan P; Good, Marge; Marsland, Thomas; Lilenbaum, Rogerio

2013-01-01

Research in the community setting is essential for the translation of advances in cancer research into practice and improving cancer care for all populations. The National Cancer Institute is proposing a new community-based program, NCI Community Oncology Research Program (NCORP), which is the alignment of two existing programs, the Community Clinical Oncology Program, Minority-Based Community Clinical Oncology Program, and their Research Bases, and the National Cancer Institute's Community Cancer Centers Program. NCROP will support cancer control, prevention, treatment, and screening clinical trials and expand its research scope to include cancer care delivery research. Cancer disparities research will be integrated into studies across the continuum of NCORP research. Input from current NCI-funded community investigators provides critical insight into the challenges faced by oncology practices within various organizational structures. Furthermore, these investigators identify the resources, both administrative and clinical, that will be required in the community setting to support cancer care delivery research and to meet the requirements for a new generation of clinical research. The American Society for Clinical Oncology (ASCO) has initiated a forum to focus on the conduct of clinical research in the community setting. Resources are being developed to help practices in managing cancer care in community settings.

NCI-FDA Interagency Oncology Task Force Workshop Provides Guidance for Analytical Validation of Protein-based Multiplex Assays | Office of Cancer Clinical Proteomics Research

Cancer.gov

An NCI-FDA Interagency Oncology Task Force (IOTF) Molecular Diagnostics Workshop was held on October 30, 2008 in Cambridge, MA, to discuss requirements for analytical validation of protein-based multiplex technologies in the context of its intended use. This workshop developed through NCI's Clinical Proteomic Technologies for Cancer initiative and the FDA focused on technology-specific analytical validation processes to be addressed prior to use in clinical settings. In making this workshop unique, a case study approach was used to discuss issues related to

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-15

... Request; NCI Cancer Genetics Services Directory Web-Based Application Form and Update Mailer Summary: In... Cancer Genetics Services Directory Web-based Application Form and Update Mailer. [[Page 14035

Frederick National Laboratory Advisory Committee Welcomes New FNL, NCI Leaders | Poster

Cancer.gov

The Frederick National Laboratory Advisory Committee recently met to discuss the future of several high-profile Frederick National Lab initiatives in a meeting that included a chance to meet the new NCI and FNLCR leaders. Here is a look at a few of the highlights from the last of the 2017 FNLAC meetings.

A Gene-Based Prognostic for Hepatocellular Carcinoma Patient Response to Adjuvant Transcatheter Arterial Chemoembolization | NCI Technology Transfer Center | TTC

Cancer.gov

The gold standard of care for hepatocellular carcinoma patients with intermediate- to locally advanced tumors is transcatheter arterial chemoembolization (TACE), a procedure whereby the tumor is targeted both with local chemotherapy and restriction of local blood supply. NCI scientists have identified a 14-gene signature predictive of response to TACE, and NCI seeks licensees or co-development partners to develop the technology toward commercialization.

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.

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.

It’s Easy to Recycle at NCI at Frederick | Poster

Cancer.gov

From 2013 through the first quarter of 2018, NCI at Frederick has recycled over 1,667 tons of material, while incinerating or landfilling over 4,273 tons of trash. This earns us a recycling rate close to 28 percent, which is below the national average of 32 percent, according to the Environmental Protection Agency, and well below our goal of 50 percent. (These numbers only

77 FR 2734 - Proposed Collection; Comment Request: Solar Cell: A Mobile UV Manager for Smart Phones (NCI)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-19

... Request: Solar Cell: A Mobile UV Manager for Smart Phones (NCI) SUMMARY: In compliance with the... Management and Budget (OMB) for review and approval. Proposed Collection: Title: Solar Cell: A Mobile UV... Collection: The overall goal of the study is to design a smart phone application, Solar Cell, which uses...

Transcriptional profiling of NCI/ADR-RES cells unveils a complex network of signaling pathways and molecular mechanisms of drug resistance

PubMed Central

Vert, Anna; Castro, Jessica; Ribó, Marc; Vilanova, Maria; Benito, Antoni

2018-01-01

Background Ovarian cancer has the highest mortality rate among all the gynecological cancers. This is mostly due to the resistance of ovarian cancer to current chemotherapy regimens. Therefore, it is of crucial importance to identify the molecular mechanisms associated with chemoresistance. Methods NCI/ADR-RES is a multidrug-resistant cell line that is a model for the study of drug resistance in ovarian cancer. We carried out a microarray-derived transcriptional profiling analysis of NCI/ADR-RES to identify differentially expressed genes relative to its parental OVCAR-8. Results Gene-expression profiling has allowed the identification of genes and pathways that may be important for the development of drug resistance in ovarian cancer. The NCI/ADR-RES cell line has differential expression of genes involved in drug extrusion, inactivation, and efficacy, as well as genes involved in the architectural and functional reorganization of the extracellular matrix. These genes are controlled through different signaling pathways, including MAPK–Akt, Wnt, and Notch. Conclusion Our findings highlight the importance of using orthogonal therapies that target completely independent pathways to overcome mechanisms of resistance to both classical chemotherapeutic agents and molecularly targeted drugs. PMID:29379303

NCI Director Norman E. Sharpless on the Future of Cancer Research | Poster

Cancer.gov

Last week, Director Norman E. “Ned” Sharpless spoke with Paul Goldberg, editor and publisher of The Cancer Letter, regarding his six-month “listening tour,” a project he embarked on after being named the new director, as well as his vision for the National Cancer Institute (NCI).

Program Spotlight: Ground Broken for NCI-supported Cancer Treatment Center in Puerto Rico

Cancer.gov

Dr. Sanya A. Springfield represented NCI at the groundbreaking ceremonies for the University of Puerto Rico (UPR) cancer hospital. In her remarks, she acknowledged the driving force behind this development is the UPR and the MD Anderson Cancer Center partnership.

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

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.

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. Copyright © 2013 Elsevier Ltd. All rights reserved.

Small Molecule Inhibitors of Drug Resistant Forms of HIV-1 Integrase | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the National Cancer Institute discovered small-molecule compounds containing 1-hydroxy-2-oxo-1,8-naphthyridine moieties whose activity against HIV-1 integrase mutants confer resistance to currently approved INSTIs. Preliminary rodent efficacy, metabolic, and pharmacokinetic studies have been completed by the NCI researchers. The National Cancer Institute seeks partners to commercialize this class of compounds through licensing or co-development.

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

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.

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.

A Novel Growth Factor and Anti-Apoptotic Agent for Promoting Lung Development and Treating Lung Disease | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the NCI have developed a new therapeutic strategy for lung cancer using secretoglobin family 3A member 2 (SCGB3A2), as a cell proliferative and anti-apoptotic agent. SCGB3A2 can be used to inhibit lung damage that results from treatment with anti-cancer agents. NCI seeks parties to license or co-develop this technology.

A New Class of Stable Heptamethine Cyanine Fluorophores and Biomedical Applications Thereof | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the National Cancer Institute (NCI) have developed an improved class of heptamethine cyanine fluorophore dyes useful for imaging applications in the near-IR range (750-850 nm). A new chemical reaction has been developed that provides easy access to novel molecules with improved properties. Specifically, the dyes display greater resistance to thiol nucleophiles, and are more robust while maintaining excellent optical properties. The dyes have been successfully employed in various in vivo imaging applications and in vitro labeling and microscopy applications. The NCI seek co-development or licensees to develop them as targetable agents for optical-guided surgical interventions.

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.

Adoptive Immunotherapy with T Lymphocytes Engineered for Enhanced Survival | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the NCI have developed a method of genetically engineering lymphocytes to expressed elevated levels of cytokine proteins. This technology is useful for improving cellular adoptive immunotherapies to treat a range of infectious diseases and cancers.

NCI Helps Children’s Hospital of Philadelphia to Identify and Treat New Target in Pediatric Cancer | Poster

Cancer.gov

There may be a new, more effective method for treating high-risk neuroblastoma, according to scientists at the Children’s Hospital of Philadelphia and collaborators in the Cancer and Inflammation Program at NCI at Frederick. Together, the groups published a study describing a previously unrecognized protein on neuroblastoma cells, called GPC2, as well as the creation of a

Human antibodies and fusion proteins as HIV-1 therapeutic | NCI Technology Transfer Center | TTC

Cancer.gov

Available for licensing from the NCI are novel human anti-HIV-1 domain antibodies and their fusion proteins for anti-HIV-1 antibodies and anti-retroviral as therapeutics and/or preventatives for infection by different HIV-1 strains.

Academic Surgical Oncologists' Productivity Correlates with Gender, Grant Funding, and Institutional NCI Comprehensive Cancer Center Affiliation.

PubMed

Nguyen, Vi; Marmor, Rebecca A; Ramamoorthy, Sonia L; Blair, Sarah L; Clary, Bryan M; Sicklick, Jason K

2018-07-01

A scholar's h-index is defined as the number of h papers published, each of which has been cited at least h times. We hypothesized that the h-index strongly correlates with the academic rank of surgical oncologists. We utilized the National Cancer Institute (NCI) website to identify NCI-designated Comprehensive Cancer Centers (CCC) and Doximity to identify the 50 highest-ranked general surgery residency programs with surgical oncology divisions. Demographic data of respective academic surgical oncologists were collected from departmental websites and Grantome. Bibliometric data were obtained from Web of Science. We identified 544 surgical oncologists from 64 programs. Increased h-index was associated with academic rank (p < 0.001), male gender (p < 0.001), number of National Institutes of Health (NIH) grants (p < 0.001), and affiliation with an NCI CCC (p = 0.018) but not number of additional degrees (p = 0.661) or Doximity ranking (p = 0.102). H-index was a stronger predictor of academic rank (r = 0.648) than total publications (r = 0.585) or citations (r = 0.450). This is the first report to assess the h-index within academic surgical oncology. H-index is a bibliometric predictor of academic rank that correlates with NIH grant funding and NCI CCC affiliation. We also highlight a previously unexpected and unappreciated gender disparity in the academic productivity of US surgical oncologists. When academic rank was accounted for, female surgical oncologists had lower h-indices compared with their male colleagues. Evaluation of the etiologies of this gender disparity is needed to address barriers to academic productivity faced by female surgical oncologists as they progress through their careers.

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

Conserved Elements Vaccine for HIV | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the National Cancer Institute (NCI) developed a DNA vaccine using conserved elements of HIV-1 Gag, administered in a prime-boost vaccination protocol. Two of the HIV Gag CE DNA vectors have been tested in a rhesus macaque model. Priming with the Gag CE vaccine and boosting with full length Gag DNA showed increased immune responses when compared to vaccination with Gag alone. Researchers seek licensing and/or co-development research collaborations for development this DNA vaccine.

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

Silica-Coated Nanodiamonds for Imaging and Delivery of Therapeutic Agents | NCI Technology Transfer Center | TTC

Cancer.gov

The NCI Radiation Oncology Branch and the NHLBI Laboratory of Single Molecule Biophysics seek parties to co-develop fluorescent nanodiamonds for use as in vivo and in vitro optical tracking probes toward commercialization.

VIG Seminar March 1, 2018 Alex Compton NCI-Frederick | Center for Cancer Research

Cancer.gov

Please join us for the Virology Interest Group Seminar on Thursday, March 1st, from 2:30 until 3:30 in Bethesda, Building 50, Room 2328. The seminar will also be broadcasted to Frederick, Building 549, Conference Room A. This seminar will be presented by Alex Compton, NCI-Frederick.

Enhanced Missing Proteins Detection in NCI60 Cell Lines Using an Integrative Search Engine Approach.

PubMed

Guruceaga, Elizabeth; Garin-Muga, Alba; Prieto, Gorka; Bejarano, Bartolomé; Marcilla, Miguel; Marín-Vicente, Consuelo; Perez-Riverol, Yasset; Casal, J Ignacio; Vizcaíno, Juan Antonio; Corrales, Fernando J; Segura, Victor

2017-12-01

The Human Proteome Project (HPP) aims deciphering the complete map of the human proteome. In the past few years, significant efforts of the HPP teams have been dedicated to the experimental detection of the missing proteins, which lack reliable mass spectrometry evidence of their existence. In this endeavor, an in depth analysis of shotgun experiments might represent a valuable resource to select a biological matrix in design validation experiments. In this work, we used all the proteomic experiments from the NCI60 cell lines and applied an integrative approach based on the results obtained from Comet, Mascot, OMSSA, and X!Tandem. This workflow benefits from the complementarity of these search engines to increase the proteome coverage. Five missing proteins C-HPP guidelines compliant were identified, although further validation is needed. Moreover, 165 missing proteins were detected with only one unique peptide, and their functional analysis supported their participation in cellular pathways as was also proposed in other studies. Finally, we performed a combined analysis of the gene expression levels and the proteomic identifications from the common cell lines between the NCI60 and the CCLE project to suggest alternatives for further validation of missing protein observations.

Enhanced Missing Proteins Detection in NCI60 Cell Lines Using an Integrative Search Engine Approach

PubMed Central

2017-01-01

The Human Proteome Project (HPP) aims deciphering the complete map of the human proteome. In the past few years, significant efforts of the HPP teams have been dedicated to the experimental detection of the missing proteins, which lack reliable mass spectrometry evidence of their existence. In this endeavor, an in depth analysis of shotgun experiments might represent a valuable resource to select a biological matrix in design validation experiments. In this work, we used all the proteomic experiments from the NCI60 cell lines and applied an integrative approach based on the results obtained from Comet, Mascot, OMSSA, and X!Tandem. This workflow benefits from the complementarity of these search engines to increase the proteome coverage. Five missing proteins C-HPP guidelines compliant were identified, although further validation is needed. Moreover, 165 missing proteins were detected with only one unique peptide, and their functional analysis supported their participation in cellular pathways as was also proposed in other studies. Finally, we performed a combined analysis of the gene expression levels and the proteomic identifications from the common cell lines between the NCI60 and the CCLE project to suggest alternatives for further validation of missing protein observations. PMID:28960077

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 spectrometry (MRM-MS) assays.  This community web-based repository for well-characterized quantitative proteomic assays currently consists of 456 unique peptide assays to 282 unique proteins and ser

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. Submissions will be accepted through July 9, 2012.

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.

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

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

...The Alliance for Nanotechnology in Cancer of the National Cancer Institute (NCI) is initiating a public private industry partnership called TONIC (Translation Of Nanotechnology In Cancer) to promote translational research and development opportunities of nanotechnology-based cancer solutions. An immediate consequence of this effort will be the formation of a consortium involving government and pharmaceutical, and biotechnology companies. This consortium will evaluate promising nanotechnology platforms and facilitate their successful translation from academic research to clinical environment, resulting in safe, timely, effective and novel diagnosis and treatment options for cancer patients. The purpose of this notice is to inform the community about the Alliance for Nanotechnology in Cancer of NCI's intention to form the consortium and to invite eligible companies (as defined in last paragraph) to participate.

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

Cancer.gov

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

NCI Requests Cancer 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, the National Cancer Institute (NCI) Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution.

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. Submissions will be accepted through February 5, 2016.

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. Submissions will be accepted through July 12, 2013.

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.

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).

It’s Easy to Recycle at NCI at Frederick | Poster

Cancer.gov

From 2013 through the first quarter of 2018, NCI at Frederick has recycled over 1,667 tons of material, while incinerating or landfilling over 4,273 tons of trash. This earns us a recycling rate close to 28 percent, which is below the national average of 32 percent, according to the Environmental Protection Agency, and well below our goal of 50 percent. (These numbers only include operational wastes and not construction debris.) To help improve our rates, please read the following refresher on our recycling program.

Determination of betamethasone and triamcinolone acetonide by GC-NCI-MS in excreta of treated animals and development of a fast oxidation procedure for derivatisation of corticosteroids.

PubMed

Courtheyn, D; Vercammen, J; Logghe, M; Seghers, H; De Wasch, K; De Brabander, H

1998-12-01

The use of corticosteroids in combination with other hormonal substances has long been known to result in increased mass gain with bovines. Practice has demonstrated, however, that even the single use of a glucocorticoid may result in growth promoting effects. In addition to the popular dexamethasone, more recently other corticosteroids have also been misused for fattening purposes. The first part of this study deals with the detection of two of them, namely betamethasone and triamcinolone acetonide. Betamethasone was administered orally to a cow at a dose of 50 mg d-1 for 5 d, then later the same cow was injected intramuscularly with a dose of 50 mg of betamethasone dipropionate. Excretion in urine and faeces was followed with both HPLC-enzyme immunoassay and a previously described method based on negative chemical ionization mass spectrometry (NCI-MS) after oxidation. For the triamcinolone acetonide study a cow was treated with 50 mg d-1 of the drug during a 7 d period. Excretion in faeces was followed with GC-NCI-MS. As triamcinolone acetonide is resistant to the previously described oxidation procedure, however, a hydrolysis step had to be introduced prior to oxidation. In addition to this specific modification necessary for triamcinolone acetonide, in a subsequent part of this study the original oxidation procedure with pyridinium chlorochromate was re-investigated especially to shorten the procedure. With the introduction of potassium dichromate the reaction time could be decreased from 3 h to 10 min.

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).

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

... Request; the Drug Accountability Record (Form NIH 2564) (NCI) SUMMARY: In compliance with the requirement... Management and Budget (OMB) for review and approval. Proposed Collection Title: The Drug Accountability... agent accountability. In order to fulfill these requirements, a standard Investigational Drug...

NCI Director Norman Sharpless’s ASCO 2018 Remarks-The Power and Promise of Cancer Research

Cancer.gov

NCI Director Dr. Norman E. Sharpless discusses the future of cancer research at the 2018 American Society of Clinical Oncology (ASCO) annual meeting in Chicago. Learn more about his focus on basic science, workforce development, big data, and clinical trials.

A Rapid Method of Isolating Neoantigen-specific T Cell Receptor Sequences | NCI Technology Transfer Center | TTC

Cancer.gov

Recent research has demonstrated that neoantigen-specific T-cell receptors (TCRs) can be isolated from a cancer patient’s lymphocytes. These TCRs may be used to engineer populations of tumor-reactive T cells for cancer immunotherapies. Obtaining sequences of these functional TCRs is a critical initial step in preparing this type of personalized cancer treatment; however, current methods are time-consuming and labor-intensive. Scientists at the National Cancer Institute (NCI) have developed a rapid and robust method of isolating the sequences of mutation-specific TCRs to alleviate these issues; they seek licensing and/or co-development research collaborations for the development of a method for isolating the sequences of tumor-reactive TCRs. For collaboration opportunities, please contact Steven A. Rosenberg, M.D., Ph.D. at sar@nih.gov.

Pharmacokinetics and Safety of Bortezomib in Patients with Advanced Malignancies and Varying Degrees of Liver Dysfunction: Phase 1 NCI Organ Dysfunction Working Group Study NCI-6432

PubMed Central

LoRusso, Patricia M; Venkatakrishnan, Karthik; Ramanathan, Ramesh K; Sarantopoulos, John; Mulkerin, Daniel; Shibata, Stephen I; Hamilton, Anne; Dowlati, Afshin; Mani, Sridhar; Rudek, Michelle A; Takimoto, Chris H; Neuwirth, Rachel; Esseltine, Dixie-Lee; Ivy, Percy

2013-01-01

Purpose The proteasome inhibitor bortezomib undergoes oxidative hepatic metabolism. This study (NCI-6432; NCT00091117) was conducted to evaluate bortezomib pharmacokinetics and safety in patients with varying degrees of hepatic impairment, to inform dosing recommendations in these special populations. Methods Patients received bortezomib on days 1, 4, 8, and 11 of 21-day cycles. Patients were assigned to four hepatic function groups based on the National Cancer Institute Organ Dysfunction Working Group classification. Those with normal function received bortezomib at the 1.3 mg/m2 standard dose. Patients with severe, moderate, and mild impairment received escalating doses from 0.5, 0.7, and 1.0 mg/m2, respectively, up to a 1.3 mg/m2 maximum. Serial blood samples were collected for 24 hours post-dose on days 1 and 8, cycle 1, for bortezomib plasma concentration measurements. Results Sixty-one patients were treated, including 14 with normal hepatic function and 17, 12, and 18 with mild, moderate, and severe impairment, respectively. Mild hepatic impairment did not alter dose-normalized bortezomib exposure (AUC0-tlast) or Cmax compared with patients with normal function. Mean dose-normalized AUC0-tlast was increased by approximately 60% on day 8 in patients with moderate or severe impairment. Conclusions Patients with mild hepatic impairment do not require a starting dose adjustment of bortezomib. Patients with moderate or severe hepatic impairment should be started at a reduced dose of 0.7 mg/m2. PMID:22394984

Activated Dual Specificity Lymphocytes and Their Methods of Use | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the NCI have developed a method of using genetic modifications to generate leukocytes with multiple specificities. This technology represents a potential therapy for a wide variety of malignancies, and because of the genetic modification used, this therapy will be applicable to patients of any MHC type.

Evaluation of Bortezomib-Induced Neuropathy Using Total Neuropathy Score (Reduced and Clinical Versions) and NCI CTCAE v4.0 in Newly Diagnosed Patients With Multiple Myeloma Receiving Bortezomib-Based Induction.

PubMed

Lakshman, Arjun; Modi, Manish; Prakash, Gaurav; Malhotra, Pankaj; Khadwal, Alka; Jain, Sanjay; Kumari, Savita; Varma, Neelam; Varma, Subhash

2017-08-01

Bortezomib-induced peripheral neuropathy (BiPN) is a dose-limiting adverse effect of bortezomib-based therapy for multiple myeloma (MM). The reporting of BiPN is variable because of the use of different neuropathy scales. Most investigators use the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). We prospectively evaluated the incidence of BiPN in treatment-naive patients with MM receiving weekly cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in 28-day cycles using 3 neuropathy scores: Total Neuropathy Score-reduced (TNSr) and -clinical (TNSc), and NCI CTCAE v4.0. Twenty-six patients received CyBorD. Twenty patients completed follow-up. The rates of occurrence of BiPN were as follows: TNSr - 55% (n = 11), TNSc - 40% (n = 8), and NCI CTCAE - 45% (n = 9). All 3 scales showed worsening after treatment (P < .01). When compared to BiPN by TNSr, sensitivities for NCI CTCAE and TNSc were 77.8% and 88.9%, respectively. Specificity was 63.3% for both NCI CTCAE and TNSc. Among 12 patients who did not have BiPN by NCI CTCAE scale, 41.7% (n = 5) and 16.7% (n = 2) patients satisfied the criteria for BiPN by TNSr and TNSc, respectively. The higher detection rate of neuropathy by TNSr and TNSc is probably due to increment in scores that are allotted for increase in anatomic extent of sensorimotor involvement, unlike the NCI CTCAE scale, which requires functional limitation for increase in grade. NCI CTCAE may be suboptimal in comparison to TNSr and TNSc in assessment of BiPN because it may miss worsening neuropathy without functional limitation. Copyright © 2017 Elsevier Inc. All rights reserved.

(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.

NCI Requests Cancer 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. Submissions will be accepted through July 11, 2014.

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. © 2013.

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Photoactivatable Lipid-based Nanoparticles as a Vehicle for Dual Agent Delivery | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the National Cancer Institute (NCI) RNA Biology Laboratory have developed nanoparticles that can deliver an agent (i.e., therapeutic or imaging) and release the agent upon targeted photoactivation allowing for controlled temporal and localized release of the agent.

Evaluation of the Impact of NCI Summer Curriculum on Cancer Prevention’s on Participants from Low- and Middle Income Countries

PubMed Central

Williams, Makeda J.; Otero, Isabel V.; Harford, Joe B.

2013-01-01

The NCI Summer Curriculum on Cancer Prevention provides scientists and health care professionals training in principles and practices of cancer prevention and control, and molecular biology and genetics of cancer. Originally intended for U.S. scientists, the Curriculum’s enrollment of international scientists has increased steadily. The objective of the current study was to evaluate the Curriculum’s impact on knowledge, skills and career accomplishments of the international participants from low- and middle-income countries (LMIC). International participants from 1998 to 2009 completed questionnaires regarding knowledge, overall experience and accomplishments directly associated with the Curriculum. Almost all respondents agreed the Curriculum enhanced their knowledge and skills, prepared them to contribute to cancer control activities in their home countries and addressed specific needs and achieve research goals. The NCI Summer Curriculum on Cancer Prevention gives international participants a unique opportunity to enhance their knowledge and effectively contribute to cancer control activities in their home country. PMID:23355281

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

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.

Near-IR Light-Cleavable Antibody Conjugates and Conjugate Precursors | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the National Cancer Institute (NCI) developed novel groups of cyanine (Cy) based antibody-drug conjugate (ADC) chemical linkers that undergo photolytic cleavage upon irradiation with near-IR light. By using the fluorescent properties of the Cy linker to monitor localization of the ADC, and subsequent near-IR irradiation of cancerous tissue, drug release could be confined to the tumor microenvironment.

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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

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

PubMed

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

2014-10-01

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.

A New Series of Thalidomide Analogs That Have Potent Anti-Angiogenic Properties | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the National Cancer Institute (NCI) have synthesized novel thalidomide derivatives that have therapeutic potential for a broad spectrum of cancer related diseases alone, or in combination with existing therapies. The compounds can also be useful for the treatment of autoimmune diseases.

Chimeric Antigen Receptors that Recognize Mesothelin for Cancer Immunotherapy | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the NCI have developed chimeric antigen receptors (CARs) with a high affinity for mesothelin to be used as an immunotherapy to treat pancreatic cancer, ovarian cancer, and mesothelioma. Cells that express CARs, most notably T cells, are highly reactive against their specific tumor antigen in an MHC-unrestricted manner to generate an immune response that promotes robust tumor cell elimination when infused into cancer patients.

NCI Statement on the U.S. Surgeon General's "Call to Action to Prevent Skin Cancer"

Cancer.gov

As the Federal Government's principal agency for cancer research and training, the National Cancer Institute (NCI) endorses the U.S. Surgeon General’s “Call to Action to Prevent Skin Cancer,” which provides a comprehensive evaluation of the current state of skin cancer prevention efforts in the United States and recommends actions for improvement in the future.

NCI Helps Children’s Hospital of Philadelphia to Identify and Treat New Target in Pediatric Cancer | Poster

Cancer.gov

There may be a new, more effective method for treating high-risk neuroblastoma, according to scientists at the Children’s Hospital of Philadelphia and collaborators in the Cancer and Inflammation Program at NCI at Frederick. Together, the groups published a study describing a previously unrecognized protein on neuroblastoma cells, called GPC2, as well as the creation of a novel antibody-drug conjugate, a combination of a human antibody and a naturally occurring anticancer drug, that locates and binds to GPC2 in a highly efficient way.

Immunogenic Peptides (Vaccines) for the Treatment of Prostate and Breast Cancer | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the NCI have developed a novel treatment for prostate and breast cancer using synthetic peptides derived from TARP, the T cell receptor gamma alternate reading frame protein. These immunogenic peptides from TARP elicit an immune response, triggering T cells to kill only the cancer cells within a patient.

Reminder: NCI Requests Cancer Targets for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

Cancer.gov

In an effort to improve rigor and reproducibility, the National Cancer Institute (NCI) Antibody Characterization Program requests cancer-related protein targets for monoclonal antibody production and distribution to the scientific community. The program from The Office of Cancer Clinical Proteomics Research provides well-characterized

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.

A SNP-based blood test for predicting breast cancer survival and determining treatment strategies | NCI Technology Transfer Center | TTC

Cancer.gov

The NCI seeks licensing of methods that provide significant improvements in examining additional SNPs for improved prognostics and to evaluate whether the SNP signature is associated with overall cancer incidence or effective treatment strategies.

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.

A Rabbit Anti-pT1989 ATR Monoclonal Antibody for Use in Immunoassays | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the National Cancer Institute (NCI) have developed a monoclonal antibody against ataxia telangiectasia-mutated and Rad3-related (ATR) kinase phosphorylated at threonine 1989. The antibody can be used for pharmacodynamic assays to quantify drug action on the ATR target.

NCI HPC Scaling and Optimisation in Climate, Weather, Earth system science and the Geosciences

NASA Astrophysics Data System (ADS)

Evans, B. J. K.; Bermous, I.; Freeman, J.; Roberts, D. S.; Ward, M. L.; Yang, R.

2016-12-01

The Australian National Computational Infrastructure (NCI) has a national focus in the Earth system sciences including climate, weather, ocean, water management, environment and geophysics. NCI leads a Program across its partners from the Australian science agencies and research communities to identify priority computational models to scale-up. Typically, these cases place a large overall demand on the available computer time, need to scale to higher resolutions, use excessive scarce resources such as large memory or bandwidth that limits, or in some cases, need to meet requirements for transition to a separate operational forecasting system, with set time-windows. The model codes include the UK Met Office Unified Model atmospheric model (UM), GFDL's Modular Ocean Model (MOM), both the UK Met Office's GC3 and Australian ACCESS coupled-climate systems (including sea ice), 4D-Var data assimilation and satellite processing, the Regional Ocean Model (ROMS), and WaveWatch3 as well as geophysics codes including hazards, magentuellerics, seismic inversions, and geodesy. Many of these codes use significant compute resources both for research applications as well as within the operational systems. Some of these models are particularly complex, and their behaviour had not been critically analysed for effective use of the NCI supercomputer or how they could be improved. As part of the Program, we have established a common profiling methodology that uses a suite of open source tools for performing scaling analyses. The most challenging cases are profiling multi-model coupled systems where the component models have their own complex algorithms and performance issues. We have also found issues within the current suite of profiling tools, and no single tool fully exposes the nature of the code performance. As a result of this work, international collaborations are now in place to ensure that improvements are incorporated within the community models, and our effort can be targeted

A review of NCI's extramural grant portfolio: identifying opportunities for future research in genes and environment in cancer.

PubMed

Ghazarian, Armen A; Simonds, Naoko I; Bennett, Kelly; Pimentel, Camilla B; Ellison, Gary L; Gillanders, Elizabeth M; Schully, Sheri D; Mechanic, Leah E

2013-04-01

Genetic and environmental factors jointly influence cancer risk. The NIH has made the study of gene-environment (GxE) interactions a research priority since the year 2000. To assess the current status of GxE research in cancer, we analyzed the extramural grant portfolio of the National Cancer Institute (NCI) from Fiscal Years 2007 to 2009. Publications attributed to selected grants were also evaluated. From the 1,106 research grants identified in our portfolio analysis, a random sample of 450 grants (40%) was selected for data abstraction; of these, 147 (33%) were considered relevant. The most common cancer type was breast (20%, n = 29), followed by lymphoproliferative (10%, n = 14), colorectal (9%, n = 13), melanoma/other skin (9%, n = 13), and lung/upper aerodigestive tract (8%, n = 12) cancers. The majority of grants were studies of candidate genes (68%, n = 100) compared with genome-wide association studies (GWAS) (8%, n = 12). Approximately one-third studied environmental exposures categorized as energy balance (37%, n = 54) or drugs/treatment (29%, n = 43). From the 147 relevant grants, 108 publications classified as GxE or pharmacogenomic were identified. These publications were linked to 37 of the 147 grant applications (25%). The findings from our portfolio analysis suggest that GxE studies are concentrated in specific areas. There is room for investments in other aspects of GxE research, including, but not limited to developing alternative approaches to exposure assessment, broadening the spectrum of cancer types investigated, and conducting GxE within GWAS. This portfolio analysis provides a cross-sectional review of NCI support for GxE research in cancer.

BHD Tumor Cell Line and Renal Cell Carcinoma Line | NCI Technology Transfer Center | TTC

Cancer.gov

Scientists at the National Cancer Institute  have developed a novel renal cell carcinoma (RCC) cell line designated UOK257, which was derived from the surgical kidney tissue of a patient with hereditary Birt-Hogg-Dube''''(BHD) syndrome and companion cell line UOK257-2 in which FLCN expression has been restored by lentivirus infection. The NCI Urologic Oncology Branch seeks parties interested in licensing or collaborative research to co-develop, evaluate, or commercialize kidney cancer tumor cell lines.

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 utilization of websites for fundraising by NCI-designated cancer centers: Examining the capacity for dialogic communication with prospective donors.

PubMed

Erwin, Cathleen O; Dias, Ashley M

2016-01-01

The study employs a dialogic public relations framework to explore the utilization of the Internet for fundraising by nonprofit health care organizations-specifically, NCI-designated cancer centers. Cancer centers have been noted for effective websites and for being highly engaged in fundraising, which is characterized as relationship marketing. Results indicate all but one cancer center use websites and social media for fundraising but are limited in capacity for two-way symmetrical dialogue. Results are discussed and recommendations are made for future research.

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

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.

Genetic Assay for Transcription Errors: Methods to Monitor Treatments or Chemicals that Increase the Error Rate of RNA synthesis | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the National Cancer Institute (NCI) developed a genetic assay for detecting transcription errors in RNA synthesis. This new assay extends the familiar concept of an Ames test which monitors DNA damage and synthesis errors to the previously inaccessible issue of RNA synthesis fidelity. The FDA requires genetic DNA focused tests for all drug approval as it assesses the in vivo mutagenic and carcinogenic potential of a drug. The new assay will open an approach to monitoring the impact of treatments on the accuracy of RNA synthesis. Errors in transcription have been hypothesized to be a component of aging and age-related diseases. The National Cancer Institute (NCI) seeks licensing partners for the genetic assay.

NCI's Distributed Geospatial Data Server

NASA Astrophysics Data System (ADS)

Larraondo, P. R.; Evans, B. J. K.; Antony, J.

2016-12-01

Earth systems, environmental and geophysics datasets are an extremely valuable source of information about the state and evolution of the Earth. However, different disciplines and applications require this data to be post-processed in different ways before it can be used. For researchers experimenting with algorithms across large datasets or combining multiple data sets, the traditional approach to batch data processing and storing all the output for later analysis rapidly becomes unfeasible, and often requires additional work to publish for others to use. Recent developments on distributed computing using interactive access to significant cloud infrastructure opens the door for new ways of processing data on demand, hence alleviating the need for storage space for each individual copy of each product. The Australian National Computational Infrastructure (NCI) has developed a highly distributed geospatial data server which supports interactive processing of large geospatial data products, including satellite Earth Observation data and global model data, using flexible user-defined functions. This system dynamically and efficiently distributes the required computations among cloud nodes and thus provides a scalable analysis capability. In many cases this completely alleviates the need to preprocess and store the data as products. This system presents a standards-compliant interface, allowing ready accessibility for users of the data. Typical data wrangling problems such as handling different file formats and data types, or harmonising the coordinate projections or temporal and spatial resolutions, can now be handled automatically by this service. The geospatial data server exposes functionality for specifying how the data should be aggregated and transformed. The resulting products can be served using several standards such as the Open Geospatial Consortium's (OGC) Web Map Service (WMS) or Web Feature Service (WFS), Open Street Map tiles, or raw binary arrays under

15kD Granulysin for Monocyte Differentiation: A New Immunotherapeutic for Both in vivo and ex vivo Applications | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the NCI have developed a method of enhancing immune response in patients by using 15 kD granulysin. Granulysin, a proinflammatory molecule, is broadly applicable for the treatment of several diseases.

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

Oncofertility resources at NCI-designated comprehensive cancer centers.

PubMed

Clayman, Marla L; Harper, Maya M; Quinn, Gwendolyn P; Reinecke, Joyce; Shah, Shivani

2013-12-01

NCI-designated comprehensive cancer centers (CCCs) set the standard for providing exemplary patient care. Quality cancer care includes discussions about fertility and referrals to fertility specialists for patients at risk for sterility. This study sought to determine what fertility preservation (FP) resources are available in CCCs and how well those are integrated into patient care. Leaders at each CCC received a letter requesting a short telephone interview with individuals who could provide information about the institution's FP resources. A semi-structured interview guide was used and responses were audio-recorded. Data were analyzed using content and thematic analysis. Interviews were conducted with 30 of the 39 CCCs that see adult patients (77%). The remaining institutions included 4 nonresponders, 3 that referred the interviewers to childhood cancer survivorship clinics, 1 that refused, and 1 that could not identify any FP resources. Participants were primarily affiliated with reproductive endocrinology (n=15) or hematology/oncology divisions (n=10). Institutional policies regarding consistent provision of FP information were rare (n=4), although most sites (n=20) either had some services on-site or had referral programs (n=8). However, only 13 had some experimental services, such as ovarian tissue cryopreservation. Respondents reported barriers to provision of FP, including oncologists' identification of patients at risk, low referral rates, and perceptions of patient prognosis. Only 8 (27%) sites had staff with time dedicated to FP. CCCs vary widely in implementing FP-recommended practice to their patients. CCCs are positioned to provide exemplary oncofertility care, but most need to better integrate FP information and referral into practice.

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

Ternary copper(II) complex: NCI60 screening, toxicity studies, and evaluation of efficacy in xenograft models of nasopharyngeal carcinoma.

PubMed

Ahmad, Munirah; Suhaimi, Shazlan-Noor; Chu, Tai-Lin; Abdul Aziz, Norazlin; Mohd Kornain, Noor-Kaslina; Samiulla, D S; Lo, Kwok-Wai; Ng, Chew-Hee; Khoo, Alan Soo-Beng

2018-01-01

Copper(II) ternary complex, [Cu(phen)(C-dmg)(H2O)]NO3 was evaluated against a panel of cell lines, tested for in vivo efficacy in nasopharyngeal carcinoma xenograft models as well as for toxicity in NOD scid gamma mice. The Cu(II) complex displayed broad spectrum cytotoxicity against multiple cancer types, including lung, colon, central nervous system, melanoma, ovarian, and prostate cancer cell lines in the NCI-60 panel. The Cu(II) complex did not cause significant induction of cytochrome P450 (CYP) 3A and 1A enzymes but moderately inhibited CYP isoforms 1A2, 2C9, 2C19, 2D6, 2B6, 2C8 and 3A4. The complex significantly inhibited tumor growth in nasopharyngeal carcinoma xenograft bearing mice models at doses which were well tolerated without causing significant or permanent toxic side effects. However, higher doses which resulted in better inhibition of tumor growth also resulted in toxicity.

Methods for the analysis of organophosphorus flame retardants-Comparison of GC-EI-MS, GC-NCI-MS, LC-ESI-MS/MS, and LC-APCI-MS/MS.

PubMed

Tokumura, Masahiro; Miyake, Yuichi; Wang, Qi; Nakayama, Hayato; Amagai, Takashi; Ogo, Sayaka; Kume, Kazunari; Kobayashi, Takeshi; Takasu, Shinji; Ogawa, Kumiko

2018-04-16

Organophosphorus flame retardants (PFRs) are extensively used as alternatives to banned polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD). In this study, we analyzed 14 PFRs by means of four mass-spectrometry-based methods: gas chromatography combined with electron-impact mass spectrometry (GC-EI-MS) or negative-chemical-ionization mass spectrometry (GC-NCI-MS) and liquid chromatography combined with tandem mass spectrometry using electrospray ionization (LC-ESI-MS/MS) or atmospheric pressure chemical ionization (LC-APCI-MS/MS). The limits of quantification (LOQs) for LC-ESI-MS/MS and LC-APCI-MS/MS (0.81-970 pg) were 1-2 orders of magnitude lower than the LOQs for GC-EI-MS and GC-NCI-MS (2.3-3900 pg). LC-APCI-MS/MS showed the lowest LOQs (mean = 41 pg; median = 3.4 pg) for all but two of the PFRs targeted in this study. For LC-APCI-MS/MS, the lowest LOQ was observed for tributyl phosphate (TBP) (0.81 pg), and the highest was observed for tris(butoxyethyl) phosphate (TBOEP) (36 pg). The results of this study indicate that LC-APCI-MS/MS is the optimum analytical method for the target PFRs, at least in terms of LOQ.

75 FR 20606 - The Agricultural Health Study: A Prospective Cohort Study of Cancer and Other Disease Among Men...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-20

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health The Agricultural Health Study: A Prospective Cohort Study of Cancer and Other Disease Among Men and Women in Agriculture (NCI... Study of Cancer and Other Disease Among Men and Women in Agriculture (NCI)'' was submitted with errors...

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.

NCI Releases Video: Proteogenomics Research - On the Frontier of Precision Medicine | Office of Cancer Clinical Proteomics Research

Cancer.gov

The Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI), part of the National Institutes of Health, announces the release of an educational video titled “Proteogenomics Research: On the Frontier of Precision Medicine."  Launched at the HUPO2017 Global Leadership Gala Dinner, catalyzed in part by the Cancer Moonshot initiative and featuring as keynote speaker the 47th Vice President of the United States of America Joseph R.

Salt-responsive lytic polysaccharide monooxygenases from the mangrove fungus Pestalotiopsis sp. NCi6.

PubMed

Patel, Ilabahen; Kracher, Daniel; Ma, Su; Garajova, Sona; Haon, Mireille; Faulds, Craig B; Berrin, Jean-Guy; Ludwig, Roland; Record, Eric

2016-01-01

Lytic polysaccharide monooxygenases (LPMOs) belong to the "auxiliary activities (AA)" enzyme class of the CAZy database. They are known to strongly improve the saccharification process and boost soluble sugar yields from lignocellulosic biomass, which is a key step in the efficient production of sustainable economic biofuels. To date, most LPMOs have been characterized from terrestrial fungi, but novel fungal LPMOs isolated from more extreme environments such as an estuary mangrove ecosystem could offer enzymes with unique properties in terms of salt tolerance and higher stability under harsh condition. Two LPMOs secreted by the mangrove-associated fungus Pestalotiopsis sp. NCi6 (PsLPMOA and PsLPMOB) were expressed in the yeast Pichia pastoris and produced in a bioreactor with >85 mg L(-1) for PsLPMOA and >260 mg L(-1) for PsLPMOB. Structure-guided homology modeling of the PsLPMOs showed a high abundance of negative surface charges, enabling enhanced protein stability and activity in the presence of sea salt. Both PsLPMOs were activated by a cellobiose dehydrogenase (CDH) from Neurospora crassa, with an apparent optimum of interaction at pH 5.5. Investigation into their regioselective mode of action revealed that PsLPMOA released C1- and C4-oxidized cello-oligosaccharide products, while PsLPMOB released only C4-oxidized products. PsLPMOA was found to cleave polymeric cellulose in the presence of up to 6 % sea salt, which emphasizes the use of sea water in the industrial saccharification process with improved ecological footprints. Two new LPMOs from the mangrove fungus Pestalotiopsis sp. NCi6 were found to be fully reactive against cellulose. The combined hydrolytic activities of these salt-responsive LPMOs could therefore facilitate the saccharification process using sea water as a reaction medium for large-scale biorefineries.

Validation of Immunohistochemical Assays for Integral Biomarkers in the NCI-MATCH EAY131 Clinical Trial.

PubMed

Khoury, Joseph D; Wang, Wei-Lien; Prieto, Victor G; Medeiros, L Jeffrey; Kalhor, Neda; Hameed, Meera; Broaddus, Russell; Hamilton, Stanley R

2018-02-01

Biomarkers that guide therapy selection are gaining unprecedented importance as targeted therapy options increase in scope and complexity. In conjunction with high-throughput molecular techniques, therapy-guiding biomarker assays based upon immunohistochemistry (IHC) have a critical role in cancer care in that they inform about the expression status of a protein target. Here, we describe the validation procedures for four clinical IHC biomarker assays-PTEN, RB, MLH1, and MSH2-for use as integral biomarkers in the nationwide NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) EAY131 clinical trial. Validation procedures were developed through an iterative process based on collective experience and adaptation of broad guidelines from the FDA. The steps included primary antibody selection; assay optimization; development of assay interpretation criteria incorporating biological considerations; and expected staining patterns, including indeterminate results, orthogonal validation, and tissue validation. Following assay lockdown, patient samples and cell lines were used for analytic and clinical validation. The assays were then approved as laboratory-developed tests and used for clinical trial decisions for treatment selection. Calculations of sensitivity and specificity were undertaken using various definitions of gold-standard references, and external validation was required for the PTEN IHC assay. In conclusion, validation of IHC biomarker assays critical for guiding therapy in clinical trials is feasible using comprehensive preanalytic, analytic, and postanalytic steps. Implementation of standardized guidelines provides a useful framework for validating IHC biomarker assays that allow for reproducibility across institutions for routine clinical use. Clin Cancer Res; 24(3); 521-31. ©2017 AACR . ©2017 American Association for Cancer Research.

Vectors to Increase Production Efficiency of Inducible Pluripotent Stem Cell (iPSC) | NCI Technology Transfer Center | TTC

Cancer.gov

This invention describes the discovery that specific p53 isoform increase the number of inducible pluripotent stem cells (iPS). It is known that the activity of p53 regulates the self-renewal and pluripotency of normal and cancer stem cells, and also affects re-programming efficiency of iPS cells. This p53 isoform-based technology provides a more natural process of increasing iPS cell production than previous methods of decreasing p53. NCI seeks licensees for this technology.

Usual Intake Distribution of Vitamins and Prevalence of Inadequacy in a Large Sample of Iranian At-Risk Population: Application of NCI Method.

PubMed

Heidari, Zahra; Feizi, Awat; Azadbakht, Leila; Sarrafzadegan, Nizal

2016-01-01

This study provides an assessment of usual intake distribution of vitamins and estimating prevalence of inadequacy and excess among a large representative sample of middle-aged and elderly people in central regions of Iran. A cross-sectional study that is a second follow-up to the Isfahan Cohort Study (ICS). The study setting included urban and rural areas from 3 cities (Isfahan, Najafabad, and Arak) in central regions of Iran. Subjects included 1922 people aged 40 years and older, with a mean age of 55.9 ± 10.6; 50.4% were male and the majority (79.3%) were urban. Dietary intakes were collected using a 24-hour recall and 2 food records. Distribution of vitamins intake was estimated using traditional and national cancer institute (NCI) methods. The proportion of subjects at risk of vitamin intake inadequacy or excess was estimated using the estimated average requirement (EAR) cut-point method and the tolerable upper intake levels (UL) index. There were differences between values obtained from traditional and NCI methods, particularly in the lower and upper percentiles of the intake distribution. High prevalence of inadequacies for vitamins A, D, E, B2, B3 (especially among females), and B9 was observed. Significant gender differences were found in terms of inadequate intakes for vitamins A, B1, B2, B3, B6, B9, B12, and C (p < 0.05). Imbalanced vitamin intake was observed in the middle-aged and elderly Iranian population. Nutritional interventions particularly through population-based educational programs in order to improve diet variety and consume nutrient supplements may be necessary.

75 FR 9902 - Proposed Collection; Comment Request; The Agricultural Health Study: A Prospective Cohort Study...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-04

... and Women in Agriculture (NCI) SUMMARY: In compliance with the requirement of Section 3506(c)(2)(A) of... Study of Cancer and Other Disease Among Men and Women in Agriculture (NCI) (OMB : 0925-0406). Type of... exposure information as well as medical history information for respondents enrolled in the Agriculture...

The Pitfalls of Thesaurus Ontologization – the Case of the NCI Thesaurus

PubMed Central

Schulz, Stefan; Schober, Daniel; Tudose, Ilinca; Stenzhorn, Holger

2010-01-01

Thesauri that are “ontologized” into OWL-DL semantics are highly amenable to modeling errors resulting from falsely interpreting existential restrictions. We investigated the OWL-DL representation of the NCI Thesaurus (NCIT) in order to assess the correctness of existential restrictions. A random sample of 354 axioms using the someValuesFrom operator was taken. According to a rating performed by two domain experts, roughly half of these examples, and in consequence more than 76,000 axioms in the OWL-DL version, make incorrect assertions if interpreted according to description logics semantics. These axioms therefore constitute a huge source for unintended models, rendering most logic-based reasoning unreliable. After identifying typical error patterns we discuss some possible improvements. Our recommendation is to either amend the problematic axioms in the OWL-DL formalization or to consider some less strict representational format. PMID:21347074

(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

Focusing X-ray free-electron laser pulses using Kirkpatrick-Baez mirrors at the NCI hutch of the PAL-XFEL.

PubMed

Kim, Jangwoo; Kim, Hyo Yun; Park, Jaehyun; Kim, Sangsoo; Kim, Sunam; Rah, Seungyu; Lim, Jun; Nam, Ki Hyun

2018-01-01

The Pohang Accelerator Laboratory X-ray Free-Electron Laser (PAL-XFEL) is a recently commissioned X-ray free-electron laser (XFEL) facility that provides intense ultrashort X-ray pulses based on the self-amplified spontaneous emission process. The nano-crystallography and coherent imaging (NCI) hutch with forward-scattering geometry is located at the hard X-ray beamline of the PAL-XFEL and provides opportunities to perform serial femtosecond crystallography and coherent X-ray diffraction imaging. To produce intense high-density XFEL pulses at the interaction positions between the X-rays and various samples, a microfocusing Kirkpatrick-Baez (KB) mirror system that includes an ultra-precision manipulator has been developed. In this paper, the design of a KB mirror system that focuses the hard XFEL beam onto a fixed sample point of the NCI hutch, which is positioned along the hard XFEL beamline, is described. The focusing system produces a two-dimensional focusing beam at approximately 2 µm scale across the 2-11 keV photon energy range. XFEL pulses of 9.7 keV energy were successfully focused onto an area of size 1.94 µm × 2.08 µm FWHM.

NCI Program for Natural Product Discovery: A Publicly-Accessible Library of Natural Product Fractions for High-Throughput Screening.

PubMed

Thornburg, Christopher C; Britt, John R; Evans, Jason R; Akee, Rhone K; Whitt, James A; Trinh, Spencer K; Harris, Matthew J; Thompson, Jerell R; Ewing, Teresa L; Shipley, Suzanne M; Grothaus, Paul G; Newman, David J; Schneider, Joel P; Grkovic, Tanja; O'Keefe, Barry R

2018-06-13

The US National Cancer Institute's (NCI) Natural Product Repository is one of the world's largest, most diverse collections of natural products containing over 230,000 unique extracts derived from plant, marine, and microbial organisms that have been collected from biodiverse regions throughout the world. Importantly, this national resource is available to the research community for the screening of extracts and the isolation of bioactive natural products. However, despite the success of natural products in drug discovery, compatibility issues that make extracts challenging for liquid handling systems, extended timelines that complicate natural product-based drug discovery efforts and the presence of pan-assay interfering compounds have reduced enthusiasm for the high-throughput screening (HTS) of crude natural product extract libraries in targeted assay systems. To address these limitations, the NCI Program for Natural Product Discovery (NPNPD), a newly launched, national program to advance natural product discovery technologies and facilitate the discovery of structurally defined, validated lead molecules ready for translation will create a prefractionated library from over 125,000 natural product extracts with the aim of producing a publicly-accessible, HTS-amenable library of >1,000,000 fractions. This library, representing perhaps the largest accumulation of natural-product based fractions in the world, will be made available free of charge in 384-well plates for screening against all disease states in an effort to reinvigorate natural product-based drug discovery.

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

Small Molecule Anti-cancer Agents that Stabilize the MYC-G-Quadruplex | NCI Technology Transfer Center | TTC

Cancer.gov

The proto-oncogene c-Myc is deregulated and overexpressed in ~70% of all cancers. Thus, c-Myc is an attractive therapeutic target. Beyond cancer, Myc is also a positive effector of tissue inflammation, and its function has been implicated in the pathophysiology of heart failure. Researchers at the National Cancer Institute (NCI) developed novel small molecules that target c-Myc at the transcriptional level, thus enabling a potential pan-cancer therapeutic. Specifically, these compounds stabilize the transcription repressing quadruplex in the c-Myc gene promoter region. The National Cancer Institute seeks parties interested in licensing or collaborative research to co-develop these therapeutic targets.'

Think Tank: Identifying and Creating the Next Generation of Community-Based Cancer Prevention Studies | Division of Cancer Prevention

Cancer.gov

In late 2015, the NCI Division of Cancer Prevention convened cancer prevention research experts and stakeholders to discuss the current state of cancer prevention research, identify key prevention research priorities for the NCI, and identify studies that could be conducted within the NCI Community Oncology Research Program. Read the Cancer Prevention Research journal article

Multisite concordance of apparent diffusion coefficient measurements across the NCI Quantitative Imaging Network.

PubMed

Newitt, David C; Malyarenko, Dariya; Chenevert, Thomas L; Quarles, C Chad; Bell, Laura; Fedorov, Andriy; Fennessy, Fiona; Jacobs, Michael A; Solaiyappan, Meiyappan; Hectors, Stefanie; Taouli, Bachir; Muzi, Mark; Kinahan, Paul E; Schmainda, Kathleen M; Prah, Melissa A; Taber, Erin N; Kroenke, Christopher; Huang, Wei; Arlinghaus, Lori R; Yankeelov, Thomas E; Cao, Yue; Aryal, Madhava; Yen, Yi-Fen; Kalpathy-Cramer, Jayashree; Shukla-Dave, Amita; Fung, Maggie; Liang, Jiachao; Boss, Michael; Hylton, Nola

2018-01-01

Diffusion weighted MRI has become ubiquitous in many areas of medicine, including cancer diagnosis and treatment response monitoring. Reproducibility of diffusion metrics is essential for their acceptance as quantitative biomarkers in these areas. We examined the variability in the apparent diffusion coefficient (ADC) obtained from both postprocessing software implementations utilized by the NCI Quantitative Imaging Network and online scan time-generated ADC maps. Phantom and in vivo breast studies were evaluated for two ([Formula: see text]) and four ([Formula: see text]) [Formula: see text]-value diffusion metrics. Concordance of the majority of implementations was excellent for both phantom ADC measures and in vivo [Formula: see text], with relative biases [Formula: see text] ([Formula: see text]) and [Formula: see text] (phantom [Formula: see text]) but with higher deviations in ADC at the lowest phantom ADC values. In vivo [Formula: see text] concordance was good, with typical biases of [Formula: see text] to 3% but higher for online maps. Multiple b -value ADC implementations were separated into two groups determined by the fitting algorithm. Intergroup mean ADC differences ranged from negligible for phantom data to 2.8% for [Formula: see text] in vivo data. Some higher deviations were found for individual implementations and online parametric maps. Despite generally good concordance, implementation biases in ADC measures are sometimes significant and may be large enough to be of concern in multisite studies.

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.

Evaluation of permeability alteration and epithelial-mesenchymal transition induced by transforming growth factor-β1 in A549, NCI-H441, and Calu-3 cells: Development of an in vitro model of respiratory epithelial cells in idiopathic pulmonary fibrosis.

PubMed

Togami, Kohei; Yamaguchi, Kotaro; Chono, Sumio; Tada, Hitoshi

2017-07-01

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease, which is accompanied by changes in lung structure. With regard to treatment, aerosolized drugs administered intrapulmonarily are rapidly distributed into the plasma and do not remain in the lungs due to damage to the alveolar epithelium that occurs from pulmonary fibrosis. In this study, we sought to develop an in vitro model of respiratory epithelial cells in IPF for the evaluation of the intrapulmonary distribution of aerosolized drugs. We investigated transforming growth factor (TGF)-β 1 -induced epithelial-mesenchymal transition (EMT) and permeability alteration in A549, NCI-H441, and Calu-3 cell monolayers. After TGF-β 1 treatment of A549, NCI-H441, and Calu-3 cells, EMT markers including E-cadherin and vimentin and tight junction proteins including claudins-1, -3, and -5 were stained using immunofluorescence methods and detected using immunoblotting methods. Transport experiments were performed using TGF-β 1 -treated cell monolayers and fluorescein isothiocyanate dextrans (FD; 4.4, 10, and 70kDa). In addition, TGF-β 1 -induced apoptosis and necrosis were evaluated by flow cytometry using Annexin V and ethidium homodimer III, respectively. In NCI-H441 cells, incomplete EMT, destruction of claudins-1 and -3, and enhancement of FD permeability were caused by TGF-β 1 treatment. In A549 cells, complete EMT occurred but was not adequate for transport experiments because of low transepithelial electrical resistance. Whereas in Calu-3 cells, no changes were observed. TGF-β 1 -induced apoptosis and necrosis were not observed in any of the cell lines. Incomplete EMT and permeability enhancement were observed in the alveolar epithelium of IPF. Therefore, our results indicate that TGF-β 1 -treated NCI-H441 cell monolayers may serve as a useful in vitro model of respiratory epithelial cells for IPF. Copyright © 2017 Elsevier Inc. All rights reserved.

Consensus Report of a Joint NCI Thoracic Malignancies Steering Committee: FDA Workshop on Strategies for Integrating Biomarkers into Clinical Development of New Therapies for Lung Cancer Leading to the Inception of “Master Protocols” in Lung Cancer

PubMed Central

Pazdur, Richard; Abrams, Jeffrey S.; Socinski, Mark A.; Sause, William T.; Harpole, David H.; Welch, John J.; Korn, Edward L.; Ullmann, Claudio Dansky; Hirsch, Fred R.

2014-01-01

On February 2, 2012, the National Cancer Institute (NCI) sponsored a 2-day workshop with the NCI Thoracic Malignancies Steering Committee and the Food and Drug Administration to bring together leading academicians, clinicians, industry and government representatives to identify challenges and potential solutions in the clinical development of novel targeted therapies for lung cancer. Measures of success are rapidly evolving from a scientific and regulatory perspective and the objectives of this workshop were to achieve initial consensus on a high priority biomarker-driven clinical trial designed to rapidly assess the activity of targeted agents in molecularly defined lung cancer subsets and to facilitate generation of data leading to approval of these new therapies. Additionally, the meeting focused on identification of the barriers to conduct such a trial and the development of strategies to overcome those barriers. The “Lung Master Protocols” recently launched by NCI were the direct outcome of this workshop. PMID:25521397

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fully Human Antibodies and Antibody Drug Conjugates Targeting CD276 (B7-H3) for the Treatment of Cancer | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the National Cancer Institute (NCI) seek research collaborations or licensees for a monoclonal antibody targeting CD276, also known as B7-H3, and related conjugates. The antibody and antibody drug conjugates (ADC) containing the antibody of the current invention were tested in vivo and have potential for use in cancer immunotherapy.

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

A Novel Carbohydrate Antibody to GalNac1-3Gal and Its Application for Cancer Diagnostic and Prognosis | NCI Technology Transfer Center | TTC

Cancer.gov

The National Cancer Institute (NCI) seeks licensees for a monoclonal antibody specific to the GalNAc1-3Gal antigen that is present in human carcinomas. The antibody can be used as a research tool for a variety of purposes, including immunohistochemical staining of various human carcinomas. The antibody may also be useful as a prognostic marker for cervical cancer.

Ab initio calculations, structure, NBO and NCI analyses of Xsbnd H⋯π interactions

NASA Astrophysics Data System (ADS)

Wu, Qiyang; Su, He; Wang, Hongyan; Wang, Hui

2018-02-01

The performance of ab initio methods (MP2, DFT/B3LYP, random-phase approximation (RPA), CCSD(T) and QCISD(T)) in predicting interaction energy of Xsbnd H⋯π (Xsbnd H = HCCH, HCl, HF; π = C2H2, C2H4, C6H6) hydrogen complexes are assessed systematically. The CCSD(T)/CBS benchmarks of interaction energy are reported. It is found that RPA agrees well with CCSD(T)/CBS benchmarks and experimental results. CCSD(T) and QCISD(T) perform the best only when compared with CCSD(T)/CBS benchmarks, MP2 performs well only for experimental data. B3LYP provides the worst accuracy. Additionally, the equilibrium structure, interaction type of Xsbnd H⋯π hydrogen complexes are investigated by the natural bond orbital (NBO) and the non-covalent interaction index (NCI).

The effect of Nullomer-derived peptides 9R, 9S1R and 124R on the NCI-60 panel and normal cell lines.

PubMed

Alileche, Abdelkrim; Hampikian, Greg

2017-08-09

Nullomer peptides are the smallest sequences absent from databases of natural proteins. We first began compiling a list of absent 5-amino acid strings in 2006 (1). We report here the effects of Nullomer-derived peptides 9R, 9S1R and 124R on the NCI-60 panel, derived from human cancers of 9 organs (kidney, ovary, skin melanoma, lung, brain, lung, colon, prostate and the hematopoietic system), and four normal cell lines (endothelial HUVEC, skin fibroblasts BJ, colon epithelial FHC and normal prostate RWPE-1). NCI-60 cancer cell panel and four normal cell lines were cultured in vitro in RPMI1640 supplemented with 10% Hyclone fetal bovine serum and exposed for 48 h to 5 μM, 25 μM and 50 μM of peptides 9R, 9S1R and 124R. Viability was assessed by CCK-8 assay. For peptide ATP depletion effects, one cell line representing each organ in the NCI-60 panel, and four normal cell lines were exposed to 50 μM of peptides 9R, 9S1R and 124R for 3 h. The ATP content was assessed in whole cells, and their supernatants. Peptides 9S1R and 9R are respectively lethal to 95 and 81.6% of the 60 cancer cell lines tested. Control peptide 124R has no effect on the growth of these cells. Especially interesting the fact that peptides 9R and 9S1R are capable of killing drug-resistant and hormone-resistant cell lines, and even cancer stem cells. Peptides 9R and 9S1R have a broader activity spectrum than many cancer drugs in current use, can completely deplete cellular ATP within 3 h, and are less toxic to 3 of the 4 normal cell lines tested than they are to several cancers. Nullomer peptides 9R and 9S1R have a large broad lethal effect on cancer cell lines derived from nine organs represented in the NCI-60 panel. This broad activity crosses many of the categorical divisions used in the general classification of cancers: solid vs liquid cancers, drug sensitive vs drug resistant, hormone sensitive vs hormone resistant, cytokine sensitive vs cytokine non sensitive, slow growing vs rapid

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

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. ©2011 AACR

Growth of Integrative Medicine at Leading Cancer Centers Between 2009 and 2016: A Systematic Analysis of NCI-Designated Comprehensive Cancer Center Websites.

PubMed

Yun, Hyeongjun; Sun, Lingyun; Mao, Jun J

2017-11-01

Cancer centers have increasingly offered integrative medicine therapies in response to their patients' unmet needs. We evaluated the growth of integrative medicine in leading academic cancer centers in the United States as reflected by their public-facing websites. We performed a systematic review of 45 National Cancer Institute (NCI)-designated comprehensive cancer center websites. Two researchers independently evaluated whether the websites provided information regarding integrative medicine modalities and, if so, whether the services were provided in the same health system. They compared the proportion of cancer centers providing the information on each modality in 2016 with the data from the prior study in 2009. The most common integrative medicine therapies mentioned on the 45 NCI-designated comprehensive cancer center websites were exercise (97.8%) and acupuncture and meditation (88.9% each), followed by yoga (86.7%), massage (84.4%), and music therapy (82.2%). The majority of the websites also provided information on nutrition (95.6%), dietary supplements (93.3%), and herbs (88.9%). The most common therapies offered in the health systems were acupuncture/massage (73.3% each), meditation/yoga (68.9% each), and consultations about nutrition (91.1%), dietary supplements (84.4%), and herbs (66.7%). Compared with 2009, there was a statistically significant increase in the number of websites mentioning acupuncture, dance therapy, healing touch, hypnosis, massage, meditation, Qigong, and yoga (all P < .05). Leading US cancer centers increasingly present integrative medicine content on their websites, and the majority of them provide these services to patients in the same health systems. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 SGridSimmore » 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%.« less

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. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

Detecting Role Errors in the Gene Hierarchy of the NCI Thesaurus

PubMed Central

Min, Hua; Cohen, Barry; Halper, Michael; Oren, Marc; Perl, Yehoshua

2008-01-01

Gene terminologies are playing an increasingly important role in the ever-growing field of genomic research. While errors in large, complex terminologies are inevitable, gene terminologies are even more susceptible to them due to the rapid growth of genomic knowledge and the nature of its discovery. It is therefore very important to establish quality-assurance protocols for such genomic-knowledge repositories. Different kinds of terminologies oftentimes require auditing methodologies adapted to their particular structures. In light of this, an auditing methodology tailored to the characteristics of the NCI Thesaurus’s (NCIT’s) Gene hierarchy is presented. The Gene hierarchy is of particular interest to the NCIT’s designers due to the primary role of genomics in current cancer research. This multiphase methodology focuses on detecting role-errors, such as missing roles or roles with incorrect or incomplete target structures, occurring within that hierarchy. The methodology is based on two kinds of abstraction networks, called taxonomies, that highlight the role distribution among concepts within the IS-A (subsumption) hierarchy. These abstract views tend to highlight portions of the hierarchy having a higher concentration of errors. The errors found during an application of the methodology are reported. Hypotheses pertaining to the efficacy of our methodology are investigated. PMID:19221606

NCI Think Tank Concerning the Identifiability of Biospecimens and “-Omic” Data

PubMed Central

Weil, Carol J.; Mechanic, Leah E.; Green, Tiffany; Kinsinger, Christopher; Lockhart, Nicole C.; Nelson, Stefanie A.; Rodriguez, Laura L.; Buccini, Laura D.

2014-01-01

On June 11 and 12, 2012, the National Cancer Institute (NCI) hosted a think tank concerning the identifiability of biospecimens and “omic” Data in order to explore challenges surrounding this complex and multifaceted topic. The think tank brought together forty-six leaders from several fields, including cancer genomics, bioinformatics, human subject protection, patient advocacy, and commercial genetics. The first day involved presentations regarding the state of the science of re-identification; current and proposed regulatory frameworks for assessing identifiability; developments in law, industry and biotechnology; and the expectations of patients and research participants. The second day was spent by think tank participants in small break-out groups designed to address specific sub-topics under the umbrella issue of identifiability, including considerations for the development of best practices for data sharing and consent, and targeted opportunities for further empirical research. We describe the outcomes of this two day meeting, including two complimentary themes that emerged from moderated discussions following the presentations on Day 1, and ideas presented for further empirical research to discern the preferences and concerns of research participants about data sharing and individual identifiability. PMID:23579437

Developing Cancer Informatics Applications and Tools Using the NCI Genomic Data Commons API.

PubMed

Wilson, Shane; Fitzsimons, Michael; Ferguson, Martin; Heath, Allison; Jensen, Mark; Miller, Josh; Murphy, Mark W; Porter, James; Sahni, Himanso; Staudt, Louis; Tang, Yajing; Wang, Zhining; Yu, Christine; Zhang, Junjun; Ferretti, Vincent; Grossman, Robert L

2017-11-01

The NCI Genomic Data Commons (GDC) was launched in 2016 and makes available over 4 petabytes (PB) of cancer genomic and associated clinical data to the research community. This dataset continues to grow and currently includes over 14,500 patients. The GDC is an example of a biomedical data commons, which collocates biomedical data with storage and computing infrastructure and commonly used web services, software applications, and tools to create a secure, interoperable, and extensible resource for researchers. The GDC is (i) a data repository for downloading data that have been submitted to it, and also a system that (ii) applies a common set of bioinformatics pipelines to submitted data; (iii) reanalyzes existing data when new pipelines are developed; and (iv) allows users to build their own applications and systems that interoperate with the GDC using the GDC Application Programming Interface (API). We describe the GDC API and how it has been used both by the GDC itself and by third parties. Cancer Res; 77(21); e15-18. ©2017 AACR . ©2017 American Association for Cancer Research.

Quality evaluation of value sets from cancer study common data elements using the UMLS semantic groups

PubMed Central

Solbrig, Harold R; Chute, Christopher G

2012-01-01

Objective The objective of this study is to develop an approach to evaluate the quality of terminological annotations on the value set (ie, enumerated value domain) components of the common data elements (CDEs) in the context of clinical research using both unified medical language system (UMLS) semantic types and groups. Materials and methods The CDEs of the National Cancer Institute (NCI) Cancer Data Standards Repository, the NCI Thesaurus (NCIt) concepts and the UMLS semantic network were integrated using a semantic web-based framework for a SPARQL-enabled evaluation. First, the set of CDE-permissible values with corresponding meanings in external controlled terminologies were isolated. The corresponding value meanings were then evaluated against their NCI- or UMLS-generated semantic network mapping to determine whether all of the meanings fell within the same semantic group. Results Of the enumerated CDEs in the Cancer Data Standards Repository, 3093 (26.2%) had elements drawn from more than one UMLS semantic group. A random sample (n=100) of this set of elements indicated that 17% of them were likely to have been misclassified. Discussion The use of existing semantic web tools can support a high-throughput mechanism for evaluating the quality of large CDE collections. This study demonstrates that the involvement of multiple semantic groups in an enumerated value domain of a CDE is an effective anchor to trigger an auditing point for quality evaluation activities. Conclusion This approach produces a useful quality assurance mechanism for a clinical study CDE repository. PMID:22511016

A Smartphone App to Screen for HIV-Related Neurocognitive Impairment.

PubMed

Robbins, Reuben N; Brown, Henry; Ehlers, Andries; Joska, John A; Thomas, Kevin G F; Burgess, Rhonda; Byrd, Desiree; Morgello, Susan

2014-02-01

Neurocognitive Impairment (NCI) is one of the most common complications of HIV-infection, and has serious medical and functional consequences. However, screening for it is not routine and NCI often goes undiagnosed. Screening for NCI in HIV disease faces numerous challenges, such as limited screening tests, the need for specialized equipment and apparatuses, and highly trained personnel to administer, score and interpret screening tests. To address these challenges, we developed a novel smartphone-based screening tool, NeuroScreen , to detect HIV-related NCI that includes an easy-to-use graphical user interface with ten highly automated neuropsychological tests. To examine NeuroScreen's : 1) acceptability among patients and different potential users; 2) test construct and criterion validity; and 3) sensitivity and specificity to detect NCI. Fifty HIV+ individuals were administered a gold-standard neuropsychological test battery, designed to detect HIV-related NCI, and NeuroScreen . HIV+ test participants and eight potential provider-users of NeuroScreen were asked about its acceptability. There was a high level of acceptability of NeuroScreen by patients and potential provider-users. Moderate to high correlations between individual NeuroScreen tests and paper-and-pencil tests assessing the same cognitive domains were observed. NeuroScreen also demonstrated high sensitivity to detect NCI. NeuroScreen, a highly automated, easy-to-use smartphone-based screening test to detect NCI among HIV patients and usable by a range of healthcare personnel could help make routine screening for HIV-related NCI feasible. While NeuroScreen demonstrated robust psychometric properties and acceptability, further testing with larger and less neurocognitively impaired samples is warranted.

Metuzumab enhanced chemosensitivity and apoptosis in non-small cell lung carcinoma

PubMed Central

Feng, Fei; Wang, Bin; Sun, Xiuxuan; Zhu, Yumeng; Tang, Hao; Nan, Gang; Wang, Lijuan; Wu, Bo; Huhe, Muren; Liu, Shuangshuang; Diao, Tengyue; Hou, Rong; Zhang, Yang; Zhang, Zheng

2017-01-01

ABSTRACT Targeted therapeutics is used as an alternative treatment of non-small cell lung cancer (NSCLC); however, treatment effect is far from being satisfactory, and therefore identification of new targets is needed. We have previously shown that metuzumab inhibit tumor growth in vivo. The present study was performed to investigate the anti-tumor efficacy of metuzumab combined with gemcitabine and cisplatin (GP), paclitaxel and cisplatin (TP) or navelbine and cisplatin (NP) regimens in multiple NSCLC cell lines. Our results demonstrate that, in comparison to single agent metuzumab or GP treated cells, metuzumab combined with GP display inhibitory effects on tumor growth. Furthermore, we found that metuzumab elevated the sensitivity of cell lines to gemcitabine, which was identified by MTT assay. Flow cytometric analysis showed that metuzumab combined with gemcitabine (GEM) treatment led to an obvious G1 arrest and an elevated apoptosis in A549, NCI-H460 and NCI-H520 cells. Western blot analysis also demonstrated a significantly reduced level of cyclin D1, Bcl-2, and an obviously increase level of Bax and full-length caspase-3 in A549, NCI-H460 and NCI-H520 cells treated with metuzumab/gemcitabine combination in comparison with single agent treated cells. In addition, metuzumab/gemcitabine treated A549, NCI-H460 and NCI-H520 cells also demonstrated a significantly increase in deoxycytidine kinase (dCK) protein level compared with single agent metuzumab or gemcitabine treated cells. Xenograft models also demonstrated that this metuzumab/gemcitabine combination led to upregulation of dCK. Taken together, the mechanisms of metuzumab combined with GP repress tumor growth were that the combined treatment significantly inhibited the tumor cell proliferation, apoptosis and cell cycle in vitro and in vivo and at least partially by induction of dCK expression. Our results suggested that metuzumab could significantly enhance chemosensitivity of human NSCLC cells to

Anti-bacterial Treatments Using Peptide-Based Inhibitors of the STAT3-IL10 Pathway | NCI Technology Transfer Center | TTC

Cancer.gov

Tuberculosis (TB) is an infectious disease that typically affects the lungs. Current therapies include a panel of antibiotics given over a range of 6-9 months. As a result of the expense of treatment, the extended timeframe needed for effective treatment, and the scarcity of medicines in some developing countries, patient compliance with TB treatment is very low and results in multi-drug resistant TB (MDR-TB). There remains a need for a faster, more effective treatment for TB. NCI researchers seek licensing and/or co-development of peptide inhibitors of STAT3 and IL-10 developed to treat bacterial infections such as tuberculosis. See aslo: NIH inventions E-164-2007 and E-167-2010

Intermolecular interaction in nucleobases and dimethyl sulfoxide/water molecules: A DFT, NBO, AIM and NCI analysis.

PubMed

Venkataramanan, Natarajan Sathiyamoorthy; Suvitha, Ambigapathy; Kawazoe, Yoshiyuki

2017-11-01

This study aims to cast light on the physico-chemical nature and energetics of interactions between the nucleobases and water/DMSO molecules which occurs through the non-conventional CH⋯O/N-H bonds using a comprehensive quantum-chemical approach. The computed interaction energies do not show any appreciable change for all the nucleobase-solvent complexes, conforming the experimental findings on the hydration enthalpies. Compared to water, DMSO form complexes with high interaction energies. The quantitative molecular electrostatic potentials display a charge transfer during the complexation. NBO analysis shows the nucleobase-DMSO complexes, have higher stabilization energy values than the nucleobase-water complexes. AIM analysis illustrates that the in the nucleobase-DMSO complexes, SO⋯H-N type interaction have strongest hydrogen bond strength with high E HB values. Furthermore, the Laplacian of electron density and total electron density were negative indicating the partial covalent nature of bonding in these systems, while the other bonds are classified as noncovalent interactions. EDA analysis indicates, the electrostatic interaction is more pronounced in the case of nucleobase-water complexes, while the dispersion contribution is more dominant in nucleobase-DMSO complexes. NCI-RDG analysis proves the existence of strong hydrogen bonding in nucleobase-DMSO complex, which supports the AIM results. Copyright © 2017 Elsevier Inc. All rights reserved.

A Smartphone App to Screen for HIV-Related Neurocognitive Impairment

PubMed Central

Robbins, Reuben N.; Brown, Henry; Ehlers, Andries; Joska, John A.; Thomas, Kevin G.F.; Burgess, Rhonda; Byrd, Desiree; Morgello, Susan

2014-01-01

Background Neurocognitive Impairment (NCI) is one of the most common complications of HIV-infection, and has serious medical and functional consequences. However, screening for it is not routine and NCI often goes undiagnosed. Screening for NCI in HIV disease faces numerous challenges, such as limited screening tests, the need for specialized equipment and apparatuses, and highly trained personnel to administer, score and interpret screening tests. To address these challenges, we developed a novel smartphone-based screening tool, NeuroScreen, to detect HIV-related NCI that includes an easy-to-use graphical user interface with ten highly automated neuropsychological tests. Aims To examine NeuroScreen’s: 1) acceptability among patients and different potential users; 2) test construct and criterion validity; and 3) sensitivity and specificity to detect NCI. Methods Fifty HIV+ individuals were administered a gold-standard neuropsychological test battery, designed to detect HIV-related NCI, and NeuroScreen. HIV+ test participants and eight potential provider-users of NeuroScreen were asked about its acceptability. Results There was a high level of acceptability of NeuroScreen by patients and potential provider-users. Moderate to high correlations between individual NeuroScreen tests and paper-and-pencil tests assessing the same cognitive domains were observed. NeuroScreen also demonstrated high sensitivity to detect NCI. Conclusion NeuroScreen, a highly automated, easy-to-use smartphone-based screening test to detect NCI among HIV patients and usable by a range of healthcare personnel could help make routine screening for HIV-related NCI feasible. While NeuroScreen demonstrated robust psychometric properties and acceptability, further testing with larger and less neurocognitively impaired samples is warranted. PMID:24860624

A critique of the exposure assessment in the epidemiologic study of benzene-exposed workers in China conducted by the Chinese Academy of Preventive Medicine and the US National Cancer Institute.

PubMed

Wong, O

1999-12-01

As reviewed in some detail in the present paper, workers employed in a wide variety of industries were included in the Chinese benzene study, and were exposed to not only benzene but also a wide range of other industrial chemicals. To attribute any or all health effects observed in the exposed cohort to benzene without examining other concomitant exposures is not appropriate. Although it was stated that one of the major objectives of the expanded study was to examine the effects of other risk factors, no such examination was made in any of the analyses in the expanded CAPM-NCI study. The CAPM-NCI study suffered from a number of limitations. One of the most serious limitations of the study involved the exposure estimates developed by the US NCI team. Comparing the assumptions used in the development of estimates and the exposure estimates themselves to actual data reported previously by the Chinese investigators revealed numerous inconsistencies and, in many cases, large discrepancies. It appeared that the exposure estimates were consistently lower than the actual exposure data. The so-called indirect validation conducted by the NCI team served no useful purpose, since by definition it could not validate the absolute values of the estimates. NCI was fully aware of some of the inadequacies of its exposure estimates. Although in a 1994 paper, the NCI team recognized that little confidence could be attached to the estimated (e.g., only 2% of the estimates for the time interval 1949-1959 and only 6% of the estimates prior to 1975 were rated in the high confidence category), the inadequacy of the estimates was never mentioned or discussed in any subsequent analyses or in the latest report (Hayes et al., 1998). Instead, the exposure of the workers was hailed as "well characterized" (Hayes et al., 1998). In conclusion both CAPM and NCI have made substantial efforts in studying the relationship between benzene exposure and various malignancies. Unfortunately, there were

The Use of Demonstrative Pronoun and Demonstrative Determiner "This" in Upper-Level Student Writing: A Case Study

ERIC Educational Resources Information Center

Rustipa, Katharina

2015-01-01

Demonstrative "this" is worthy to investigate because of the role of "this" as a common cohesive device in academic writing. This study attempted to find out the variables underlying the realization of demonstrative "this" in graduate-student writing of Semarang State University, Indonesia. The data of the study were…

Advanced Demonstration and Test Reactor Options Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petti, David Andrew; Hill, R.; Gehin, J.

Global efforts to address climate change will require large-scale decarbonization of energy production in the United States and elsewhere. Nuclear power already provides 20% of electricity production in the United States (U.S.) and is increasing in countries undergoing rapid growth around the world. Because reliable, grid-stabilizing, low emission electricity generation, energy security, and energy resource diversity will be increasingly valued, nuclear power’s share of electricity production has a potential to grow. In addition, there are non electricity applications (e.g., process heat, desalination, hydrogen production) that could be better served by advanced nuclear systems. Thus, the timely development, demonstration, and commercializationmore » of advanced nuclear reactors could diversify the nuclear technologies available and offer attractive technology options to expand the impact of nuclear energy for electricity generation and non-electricity missions. The purpose of this planning study is to provide transparent and defensible technology options for a test and/or demonstration reactor(s) to be built to support public policy, innovation and long term commercialization within the context of the Department of Energy’s (DOE’s) broader commitment to pursuing an “all of the above” clean energy strategy and associated time lines. This planning study includes identification of the key features and timing needed for advanced test or demonstration reactors to support research, development, and technology demonstration leading to the commercialization of power plants built upon these advanced reactor platforms. This planning study is consistent with the Congressional language contained within the fiscal year 2015 appropriation that directed the DOE to conduct a planning study to evaluate “advanced reactor technology options, capabilities, and requirements within the context of national needs and public policy to support innovation in nuclear energy�

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hahn, S; Jaffray, D; Chetty, I

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 technologiesmore » 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

AACR-FDA-NCI Cancer Biomarkers Collaborative consensus report: advancing the use of biomarkers in cancer drug development.

PubMed

Khleif, Samir N; Doroshow, James H; Hait, William N

2010-07-01

Recent discoveries in cancer biology have greatly increased our understanding of cancer at the molecular and cellular level, but translating this knowledge into safe and effective therapies for cancer patients has proved to be challenging. There is a growing imperative to modernize the drug development process by incorporating new techniques that can predict the safety and effectiveness of new drugs faster, with more certainty, and at lower cost. Biomarkers are central to accelerating the identification and adoption of new therapies, but currently, many barriers impede their use in drug development and clinical practice. In 2007, the AACR-FDA-NCI Cancer Biomarkers Collaborative stepped into the national effort to bring together disparate stakeholders to clearly delineate these barriers, to develop recommendations for integrating biomarkers into the cancer drug development enterprise, and to set in motion the necessary action plans and collaborations to see the promise of biomarkers come to fruition, efficiently delivering quality cancer care to patients.

Antitumor effect of the integrin α4 signaling inhibitor JK273 in non-small cell lung cancer NCI-H460 cells.

PubMed

Lu, Thien Nhan; Ganganna, Bogonda; Pham, Thuy Trang; Vo, Anh Van; Lu, Thien Phuc; Nguyen, Huong-Giang Thi; Nguyen, My-Nuong Thi; Huynh, Phuong Nguyen; Truong, Ngoc Tuyen; Lee, Jongkook

2017-09-16

Lung cancer accounts for the highest death rate among cancers worldwide, with most patients being diagnosed with non-small cell lung cancer (NSCLC), urging more effective therapies. We report that JK273, a pyrrolo[2,3-d]pyrimidine analog, which inhibits α4 integrin signaling, showed a selective cytotoxic effect against HCI-H460 NSCLC cells, with an IC 50 of 0.98 ± 0.15 μM, but showed less sensitivity to fibroblasts with a selectivity index (SI) greater than 30. This effect was attributed to cell cycle arrest at S phase by JK273 treatment, resulting in the apoptosis of NCI-H460 cells, further confirmed by exposing phosphatidylserine and morphological changes. Taken together with the previous study of JK273 inhibiting cell migration, we propose that JK273 could serve as an antitumor compound to specifically target cancer cells but not non-cancerous cells by triggering programmed cell death, in addition to anti-metastatic effects in cancer therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

The Influence of Neurocognitive Impairment, Depression, and Alcohol Use Disorders on Health-Related Quality of Life among Incarcerated, HIV-Infected, Opioid Dependent Malaysian Men: A Moderated Mediation Analysis

PubMed Central

Shrestha, Roman; Weikum, Damian; Copenhaver, Michael; Altice, Frederick L.

2017-01-01

Prior research has widely recognized neurocognitive impairment (NCI), depression, and alcohol use disorders (AUDs) as important negative predictors of health-related quality of life (HRQoL) among people living with HIV (PLWH). No studies to date, however, have explored how these neuropsychological factors operate together and affect HRQoL. Incarcerated male PLWH (N=301) meeting criteria for opioid dependence were recruited from Malaysia’s largest prison. Standardized scales for NCI, depression, alcohol use disorders (AUDs) and HRQoL were used to conduct a moderated mediation model to explore the extent to which depression mediated the relationship between NCI, HRQoL, and AUDs using an ordinary least squares regression-based path analytic framework. Results showed that increasing levels of NCI (B = −.1773, p<0.001) and depression (B = −.6147, p<0.001) were negatively associated with HRQoL. The effect of NCI on HRQoL was significantly (Sobel z = −3.5600, p < 0.001) mediated via depression (B = −.1230, p < 0.001). Furthermore, the conditional indirect effect of NCI on HRQoL via depression for individuals with AUDs was significant (B = −.9099, p = .0087), suggesting a moderated mediation effect. The findings disentangle the complex relationship using a moderated mediation model, demonstrating that increasing levels of NCI, which can be reduced with HIV treatment, negatively influenced HRQoL via depression for individuals with AUDs. This highlights the need for future interventions to target these complex interplay between neuropsychological factors in order to improve HRQoL among PLWH, particularly incarcerated PLWH with AUDs. PMID:27544515

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

Detroit Research on Cancer Survivors Study

Cancer.gov

An NCI press release about the launch of the Detroit Research on Cancer Survivors (ROCS) study, which will look at factors affecting cancer progression, recurrence, mortality, and quality of life among African-American cancer survivors.

Studying the Greenhouse Effect: A Simple Demonstration.

ERIC Educational Resources Information Center

Papageorgiou, G.; Ouzounis, K.

2000-01-01

Studies the parameters involved in a presentation of the greenhouse effect and describes a simple demonstration of this effect. Required equipment includes a 100-120 watt lamp, a 250mL beaker, and a thermometer capable of recording 0-750 degrees Celsius together with a small amount of chloroform. (Author/SAH)

Chromatin Pioneers | Center for Cancer Research

Cancer.gov

Taking advantage of their ability to explore provocative ideas, NCI investigators pioneered the study of chromatin to demonstrate its functional importance and lay the groundwork for understanding its role in cancer and other diseases.

Case studies for GSHP demonstration projects in the US

DOE PAGES

Liu, Xiaobing; Malhotra, Mini; Im, Piljae

2015-07-01

Under the American Recovery and Reinvestment Act , twenty-six ground source heat pump (GSHP) projects were competitively selected and carried out to demonstrate the benefits of GSHP systems and innovative technologies for cost reduction and/or performance improvement. This article gives an overview of the case studies for six of the systems. These case studies evaluated efficiencies, energy savings, and costs of the demonstrated systems. In addition, it was found that more energy savings could be achieved if controls of GSHP system are improved.

Discovery of Novel HIV-1 Integrase Inhibitors Using QSAR-Based Virtual Screening of the NCI Open Database.

PubMed

Ko, Gene M; Garg, Rajni; Bailey, Barbara A; Kumar, Sunil

2016-01-01

Quantitative structure-activity relationship (QSAR) models can be used as a predictive tool for virtual screening of chemical libraries to identify novel drug candidates. The aims of this paper were to report the results of a study performed for descriptor selection, QSAR model development, and virtual screening for identifying novel HIV-1 integrase inhibitor drug candidates. First, three evolutionary algorithms were compared for descriptor selection: differential evolution-binary particle swarm optimization (DE-BPSO), binary particle swarm optimization, and genetic algorithms. Next, three QSAR models were developed from an ensemble of multiple linear regression, partial least squares, and extremely randomized trees models. A comparison of the performances of three evolutionary algorithms showed that DE-BPSO has a significant improvement over the other two algorithms. QSAR models developed in this study were used in consensus as a predictive tool for virtual screening of the NCI Open Database containing 265,242 compounds to identify potential novel HIV-1 integrase inhibitors. Six compounds were predicted to be highly active (plC50 > 6) by each of the three models. The use of a hybrid evolutionary algorithm (DE-BPSO) for descriptor selection and QSAR model development in drug design is a novel approach. Consensus modeling may provide better predictivity by taking into account a broader range of chemical properties within the data set conducive for inhibition that may be missed by an individual model. The six compounds identified provide novel drug candidate leads in the design of next generation HIV- 1 integrase inhibitors targeting drug resistant mutant viruses.

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

Nanotechnology-based cancer therapeutics--promise and challenge--lessons learned through the NCI Alliance for Nanotechnology in Cancer.

PubMed

Farrell, Dorothy; Ptak, Krzysztof; Panaro, Nicholas J; Grodzinski, Piotr

2011-02-01

The new generation of nanotechnology-based drug formulations is challenging the accepted ways of cancer treatment. Multi-functional nanomaterial constructs have the capability to be delivered directly to the tumor site and eradicate cancer cells selectively, while sparing healthy cells. Tailoring of the nano-construct design can result in enhanced drug efficacy at lower doses as compared to free drug treatment, wider therapeutic window, and lower side effects. Nanoparticle carriers can also address several drug delivery problems which could not be effectively solved in the past and include reduction of multi-drug resistance effects, delivery of siRNA, and penetration of the blood-brain-barrier. Although challenges in understanding toxicity, biodistribution, and paving an effective regulatory path must be met, nanoscale devices carry a formidable promise to change ways cancer is diagnosed and treated. This article summarizes current developments in nanotechnology-based drug delivery and discusses path forward in this field. The discussion is done in context of research and development occurring within the NCI Alliance for Nanotechnology in Cancer program.

The Influence of Neurocognitive Impairment, Depression, and Alcohol Use Disorders on Health-Related Quality of Life among Incarcerated, HIV-Infected, Opioid Dependent Malaysian Men: A Moderated Mediation Analysis.

PubMed

Shrestha, Roman; Weikum, Damian; Copenhaver, Michael; Altice, Frederick L

2017-04-01

Prior research has widely recognized neurocognitive impairment (NCI), depression, and alcohol use disorders (AUDs) as important negative predictors of health-related quality of life (HRQoL) among people living with HIV (PLWH). No studies to date, however, have explored how these neuropsychological factors operate together and affect HRQoL. Incarcerated male PLWH (N = 301) meeting criteria for opioid dependence were recruited from Malaysia's largest prison. Standardized scales for NCI, depression, alcohol use disorders (AUDs) and HRQoL were used to conduct a moderated mediation model to explore the extent to which depression mediated the relationship between NCI, HRQoL, and AUDs using an ordinary least squares regression-based path analytic framework. Results showed that increasing levels of NCI (B = -0.1773, p < 0.001) and depression (B = -0.6147, p < 0.001) were negatively associated with HRQoL. The effect of NCI on HRQoL was significantly (Sobel z = -3.5600, p < 0.001) mediated via depression (B = -0.1230, p < 0.001). Furthermore, the conditional indirect effect of NCI on HRQoL via depression for individuals with AUDs was significant (B = -0.9099, p = 0.0087), suggesting a moderated mediation effect. The findings disentangle the complex relationship using a moderated mediation model, demonstrating that increasing levels of NCI, which can be reduced with HIV treatment, negatively influenced HRQoL via depression for individuals with AUDs. This highlights the need for future interventions to target these complex interplay between neuropsychological factors in order to improve HRQoL among PLWH, particularly incarcerated PLWH with AUDs.

Portraying emotions at their unfolding: a multilayered approach for probing dynamics of neural networks.

PubMed

Raz, Gal; Winetraub, Yonatan; Jacob, Yael; Kinreich, Sivan; Maron-Katz, Adi; Shaham, Galit; Podlipsky, Ilana; Gilam, Gadi; Soreq, Eyal; Hendler, Talma

2012-04-02

Dynamic functional integration of distinct neural systems plays a pivotal role in emotional experience. We introduce a novel approach for studying emotion-related changes in the interactions within and between networks using fMRI. It is based on continuous computation of a network cohesion index (NCI), which is sensitive to both strength and variability of signal correlations between pre-defined regions. The regions encompass three clusters (namely limbic, medial prefrontal cortex (mPFC) and cognitive), each previously was shown to be involved in emotional processing. Two sadness-inducing film excerpts were viewed passively, and comparisons between viewer's rated sadness, parasympathetic, and inter-NCI and intra-NCI were obtained. Limbic intra-NCI was associated with reported sadness in both movies. However, the correlation between the parasympathetic-index, the rated sadness and the limbic-NCI occurred in only one movie, possibly related to a "deactivated" pattern of sadness. In this film, rated sadness intensity also correlated with the mPFC intra-NCI, possibly reflecting temporal correspondence between sadness and sympathy. Further, only for this movie, we found an association between sadness rating and the mPFC-limbic inter-NCI time courses. To the contrary, in the other film in which sadness was reported to commingle with horror and anger, dramatic events coincided with disintegration of these networks. Together, this may point to a difference between the cinematic experiences with regard to inter-network dynamics related to emotional regulation. These findings demonstrate the advantage of a multi-layered dynamic analysis for elucidating the uniqueness of emotional experiences with regard to an unguided processing of continuous and complex stimulation. Copyright © 2012 Elsevier Inc. All rights reserved.

U.S. EPA's Ultraviolet Disinfection Technologies Demonstration Study

EPA Science Inventory

This presentation will give a background on USEPA's Disinfection Technologies Demonstration Study. This will include regulatory background, science background, goals of the project, and ultimate expected outcome of the project. This presentation will preceed a panel discussion ...

Proteinuria is associated with neurocognitive impairment in antiretroviral therapy treated HIV-infected individuals.

PubMed

Kalayjian, Robert C; Wu, Kunling; Evans, Scott; Clifford, David B; Pallaki, Muraldihar; Currier, Judith S; Smryzynski, Marlene

2014-09-01

Proteinuria is a marker of vascular dysfunction that predicted increased cardiovascular mortality and is associated with neurocognitive impairment (NCI) in population-based studies. We examined associations between proteinuria and HIV-associated NCI. Multivariable logistic regression was used to examine associations between NCI at the first neurocognitive assessment (baseline) and simultaneous, clinically significant proteinuria [as random spot urine protein-to-creatinine ratios (UP/Cr) ≥200 mg/g] in a prospective multicenter observational cohort study. Generalized estimating equations were used to examine associations between baseline proteinuria and subsequent NCI among subjects without NCI at baseline. NCI was defined as a Z-score, derived from the combination of normalized scores from the Trailmaking A and B and the Wechsler Adult Intelligence Scale-Revised Digit Symbol tests. A total of 1972 subjects were included in this analysis. Baseline proteinuria was associated with increased odds of NCI [odds ratio (OR): 1.41, 95% confidence interval (CI): 1.08 to 1.85; P = 0.01] and with subsequent NCI among subjects without NCI at baseline (OR: 1.39, 95% CI: 1.01 to 1.93; P = 0.046) in multivariable models adjusted for risk factors and potential confounders. Similar associations were evident when these analyses were limited to visits at which time study subjects maintained plasma HIV RNA levels <200 copies per milliliter. The association between proteinuria and NCI observed in this study adds to a growing body of evidence implicating contributions by vascular disease to NCI in antiretroviral treated individuals. Studies examining interventions that improve vascular function are warranted.

Study on Inhibitory Effect of MaiMenDong Decoction and WeiJing Decoction Combination with Cisplatin on NCI-A549 Xenograft in Nude Mice and Its Mechanism.

PubMed

Xiong, Fei; Jiang, Miao; Chen, Meijuan; Wang, Xiaoxia; Zhang, Shiping; Zhou, Jing; Li, Ke; Sheng, Yan; Yin, Lian; Tang, Yuping; Ye, Lihong; Wu, Mianhua; Fu, Haian; Zhang, Xu

2017-01-01

MaiMenDong Decoction and WeiJing Decoction (Jin formula) is a traditional Chinese medication that consists of 8 medicinal plants, which recorded in the classical TCM literature Jin Kui Yao Lue and has been utilized in the treatment of lung diseases for hundreds of years in China. The present study aimed to determine the anti-tumor activity and the underlying mechanisms of Jin formula combined with cisplatin in the treatment of non-small cell lung cancer (NSCLC). Xenograft model of NCI-A549 was established in Balb/c nude mice. Five groups, including normal, MOCK, Jin, cisplatin (DDP), and Jin+DDP were included in the study. We found that Jin formula ameliorated the body weight loss caused by DDP 15 days after drug administration. Moreover, the combination of Jin with DDP enhanced the anti-tumor function of DDP. Microarray analysis showed that Jin suppressed gene expression of certain pathways which regulating cell cycle and apoptosis. Furthermore, DDP mainly decreased the gene expression level of angiogenesis associated factors, such as VEGFA, TGF-β and MMP-1. Moreover, co-treatment with Jin and DDP not only down-regulated Bcl-2 and E2F1, but also decreased the expression of MYC, MET, and MCAM. In addition, co-formula decreased the levels of p-AKT (thr308) and p-PTEN, increased Bax/Bcl-2 value, and resulted in apoptosis of tumor cells. Taken together , Jin+DDP significantly inhibited the growth of A549 cell transplanted solid tumor with slight side effect compared to the treatment by DDP only, and had a better effect than the Jin group. The mechanisms may be mainly associated with inactivation of PI3K/AKT pathway and apoptosis induction.

Two novel sesquiterpene lactones, cytotoxic vernolide-A and -B, from Vernonia cinerea.

PubMed

Kuo, Yao-Haur; Kuo, Yu-Jen; Yu, Ang-Su; Wu, Ming-Der; Ong, Chi-Wi; Yang Kuo, Li-Ming; Huang, Jo-Ti; Chen, Chieh-Fu; Li, Shyh-Yuan

2003-04-01

Bioassay-directed fractionation of an ethanolic extract of stems of Vernonia cinerea has resulted in the isolation of two novel sesquiterpene lactones, vernolide-A and -B. Their structures were elucidated on the basis of spectroscopic analysis. Biological evaluation showed that vernolide-A demonstrated potent cytotoxicity against human KB, DLD-1, NCI-661, and Hela tumor cell lines (ED(50)=0.02, 0.05, 0.53, 0.04 microg/ml for KB, DLD-1, NCI-661, and Hela, respectively); vernolide-B had marginal cytoxicity (ED(50)=3.78, 5.88, 6.42 microg/ml for KB, NCI-661, and Hela, respectively).

Prostate, Lung, Colon, and Ovary Prospective Study

Cancer.gov

A large cohort study of etiologic determinants of cancer carried out within an NCI trial for the evaluation of screening procedures for the early detection of prostate, lung, colon, and ovarian cancer (the PLCO Trial) at 10 U.S. screening centers

A simple demonstration when studying the equivalence principle

NASA Astrophysics Data System (ADS)

Mayer, Valery; Varaksina, Ekaterina

2016-06-01

The paper proposes a lecture experiment that can be demonstrated when studying the equivalence principle formulated by Albert Einstein. The demonstration consists of creating stroboscopic photographs of a ball moving along a parabola in Earth's gravitational field. In the first experiment, a camera is stationary relative to Earth's surface. In the second, the camera falls freely downwards with the ball, allowing students to see that the ball moves uniformly and rectilinearly relative to the frame of reference of the freely falling camera. The equivalence principle explains this result, as it is always possible to propose an inertial frame of reference for a small region of a gravitational field, where space-time effects of curvature are negligible.

What is the Eating at America's Table Study (EATS)?

Cancer.gov

EATS is a study that was designed to validate the Diet History Questionnaire, a new and improved food frequency questionnaire developed by NCI staff. The study was novel in that it examined not only the DHQ, but also two other widely used FFQs.

Family history record and hereditary cancer risk perception according to National Cancer Institute criteria in a Spanish medical oncology service: a retrospective study.

PubMed

Márquez-Rodas, Iván; López-Trabada, Daniel; Rupérez Blanco, Ana Belén; Custodio Cabello, Sara; Peligros Gómez, María Isabel; Orera Clemente, María; Calvo, Felipe A; Martín, Miguel

2012-01-01

Identification of patients at risk of hereditary cancer is an essential component of oncology practice, since it enables clinicians to offer early detection and prevention programs. However, the large number of hereditary syndromes makes it difficult to take them all into account in daily practice. Consequently, the National Cancer Institute (NCI) has suggested a series of criteria to guide initial suspicion. It was the aim of this study to assess the perception of the risk of hereditary cancer according to the NCI criteria in our medical oncology service. We retrospectively analyzed the recordings of the family history in new cancer patients seen in our medical oncology service from January to November 2009, only 1 year before the implementation of our multidisciplinary hereditary cancer program. The family history was recorded in only 175/621 (28%) patients. A total of 119 (19%) patients met 1 or more NCI criteria (1 criterion, n = 91; 2 criteria, n = 23; 3 criteria, n = 4; and 4 criteria, n = 1), and only 14 (11.4%) patients were referred to genetic counseling. This study shows that few clinicians record the family history. The perception of the risk of hereditary cancer is low according to the NCI criteria in our medical oncology service. These findings can be explained by the lack of a multidisciplinary hereditary cancer program when the study was performed. Copyright © 2012 S. Karger AG, Basel.

Study Forecasts New Breast Cancer Cases by 2030

Cancer.gov

A new study from NCI researchers is forecasting important trends in the types and molecular makeup of breast cancer cases through 2030, including a reduction in the proportion of cases that are considered to be difficult to treat.

ASA24® Instructions for Study Staff & Respondents

Cancer.gov

The following documents have been created by the National Cancer Institute (NCI) as resources for study staff and Respondents. Each resource is available as a ready-to-use PDF to allow users to adapt the content as desired.

Studying the Genetic Basis of Kidney Cancer - TCGA

Cancer.gov

Dr. Marston Linehan, NCI's Chief of Urologic Surgery, has spent the last several decades studying kidney cancer genes and treating kidney cancer patients. Learn more about his experience as a kidney cancer physician scientist and TCGA contributor in this

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.

Regulation of voltage-gated potassium channels attenuates resistance of side-population cells to gefitinib in the human lung cancer cell line NCI-H460.

PubMed

Choi, Seon Young; Kim, Hang-Rae; Ryu, Pan Dong; Lee, So Yeong

2017-02-21

Side-population (SP) cells that exclude anti-cancer drugs have been found in various tumor cell lines. Moreover, SP cells have a higher proliferative potential and drug resistance than main population cells (Non-SP cells). Also, several ion channels are responsible for the drug resistance and proliferation of SP cells in cancer. To confirm the expression and function of voltage-gated potassium (Kv) channels of SP cells, these cells, as well as highly expressed ATP-binding cassette (ABC) transporters and stemness genes, were isolated from a gefitinib-resistant human lung adenocarcinoma cell line (NCI-H460), using Hoechst 33342 efflux. In the present study, we found that mRNA expression of Kv channels in SP cells was different compared to Non-SP cells, and the resistance of SP cells to gefitinib was weakened with a combination treatment of gefitinib and Kv channel blockers or a Kv7 opener, compared to single-treatment gefitinib, through inhibition of the Ras-Raf signaling pathway. The findings indicate that Kv channels in SP cells could be new targets for reducing the resistance to gefitinib.

The angular structure of ONC201, a TRAIL pathway-inducing compound, determines its potent anti-cancer activity

PubMed Central

Wagner, Jessica; Kline, Christina Leah; Pottorf, Richard S.; Nallaganchu, Bhaskara Rao; Olson, Gary L.; Dicker, David T.; Allen, Joshua E.; El-Deiry, Wafik S.

2014-01-01

We previously identified TRAIL-inducing compound 10 (TIC10), also known as NSC350625 or ONC201, from a NCI chemical library screen as a small molecule that has potent anti-tumor efficacy and a benign safety profile in preclinical cancer models. The chemical structure that was originally published by Stahle, et. al. in the patent literature was described as an imidazo[1,2-a]pyrido[4,3-d]pyrimidine derivative. The NCI and others generally accepted this as the correct structure, which was consistent with the mass spectrometry analysis outlined in the publication by Allen et. al. that first reported the molecule's anticancer properties. A recent publication demonstrated that the chemical structure of ONC201 material from the NCI is an angular [3,4-e] isomer of the originally disclosed, linear [4,3-d] structure. Here we confirm by NMR and X-ray structural analysis of the dihydrochloride salt form that the ONC201 material produced by Oncoceutics is the angular [3,4-e] structure and not the linear structure originally depicted in the patent literature and by the NCI. Similarly, in accordance with our biological evaluation, the previously disclosed anti-cancer activity is associated with the angular structure and not the linear isomer. Together these studies confirm that ONC201, produced by Oncoceutics or obtained from the NCI, possesses an angular [3,4-e] structure that represents the highly active anti-cancer compound utilized in prior preclinical studies and now entering clinical trials in advanced cancers. PMID:25587031

The angular structure of ONC201, a TRAIL pathway-inducing compound, determines its potent anti-cancer activity.

PubMed

Wagner, Jessica; Kline, Christina Leah; Pottorf, Richard S; Nallaganchu, Bhaskara Rao; Olson, Gary L; Dicker, David T; Allen, Joshua E; El-Deiry, Wafik S

2014-12-30

We previously identified TRAIL-inducing compound 10 (TIC10), also known as NSC350625 or ONC201, from a NCI chemical library screen as a small molecule that has potent anti-tumor efficacy and a benign safety profile in preclinical cancer models. The chemical structure that was originally published by Stahle, et. al. in the patent literature was described as an imidazo[1,2-a]pyrido[4,3-d]pyrimidine derivative. The NCI and others generally accepted this as the correct structure, which was consistent with the mass spectrometry analysis outlined in the publication by Allen et. al. that first reported the molecule's anticancer properties. A recent publication demonstrated that the chemical structure of ONC201 material from the NCI is an angular [3,4-e] isomer of the originally disclosed, linear [4,3-d] structure. Here we confirm by NMR and X-ray structural analysis of the dihydrochloride salt form that the ONC201 material produced by Oncoceutics is the angular [3,4-e] structure and not the linear structure originally depicted in the patent literature and by the NCI. Similarly, in accordance with our biological evaluation, the previously disclosed anti-cancer activity is associated with the angular structure and not the linear isomer. Together these studies confirm that ONC201, produced by Oncoceutics or obtained from the NCI, possesses an angular [3,4-e] structure that represents the highly active anti-cancer compound utilized in prior preclinical studies and now entering clinical trials in advanced cancers.

Quantitative Proteomics Analysis Identifies Mitochondria as Therapeutic Targets of Multidrug-Resistance in Ovarian Cancer

PubMed Central

Chen, Xiulan; Wei, Shasha; Ma, Ying; Lu, Jie; Niu, Gang; Xue, Yanhong; Chen, Xiaoyuan; Yang, Fuquan

2014-01-01

Doxorubicin is a widely used chemotherapeutic agent for the treatment of a variety of solid tumors. However, resistance to this anticancer drug is a major obstacle to the effective treatment of tumors. As mitochondria play important roles in cell life and death, we anticipate that mitochondria may be related to drug resistance. Here, stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomic strategy was applied to compare mitochondrial protein expression in doxorubicin sensitive OVCAR8 cells and its doxorubicin-resistant variant NCI_ADR/RES cells. A total of 2085 proteins were quantified, of which 122 proteins displayed significant changes in the NCI_ADR/RES cells. These proteins participated in a variety of cell processes including cell apoptosis, substance metabolism, transport, detoxification and drug metabolism. Then qRT-PCR and western blot were applied to validate the differentially expressed proteins quantified by SILAC. Further functional studies with RNAi demonstrated TOP1MT, a mitochondrial protein participated in DNA repair, was involved in doxorubicin resistance in NCI_ADR/RES cells. Besides the proteomic study, electron microscopy and fluorescence analysis also observed that mitochondrial morphology and localization were greatly altered in NCI_ADR/RES cells. Mitochondrial membrane potential was also decreased in NCI_ADR/RES cells. All these results indicate that mitochondrial function is impaired in doxorubicin-resistant cells and mitochondria play an important role in doxorubicin resistance. This research provides some new information about doxorubicin resistance, indicating that mitochondria could be therapeutic targets of doxorubicin resistance in ovarian cancer cells. PMID:25285166

RADON MITIGATION STUDIES: NASHVILLE DEMONSTRATION

EPA Science Inventory

The report gives results of an EPA radon mitigation demonstration project involving 14 houses in the Nashville, TN, area with indoor radon levels of 5.6-47.6 pCi/L, using a variety of techniques, designed to be the most cost effective methods possible to implement, and yet adequa...

THE LONG ISLAND BREAST CANCER STUDY (LIBCSP)

EPA Science Inventory

The NIEHS and the NCI are collaborating on the Long Island Breast Cancer Study Project (LIBCSP), which is designed to conduct epidemiologic research on the role of environmental factors in the etiology of breast cancer in women who live in Nassau and Suffolk counties, New York. T...

Demonstrator study for micro-ranging-laser device

NASA Astrophysics Data System (ADS)

Henkel, Hartmut; Bernhardt, Bodo; Pereira do Carmo, J.

2017-11-01

Within ESA's Innovation Triangle Initiative (ITI) a demonstrator breadboard for a micro-ranging-laser device "MYLRAD" has been developed. Its working principle is the measurement of the round-trip delay time of a laser beam as a phase shift. The demonstrator consists of the laser diode (30 mW, square wave AM), optics, APD detector, narrowband preamplifier, limiter, and a phase digitiser based on a novel noise-shaping synchroniser (NSS) circuit; this works without ADCs and can be built from rad-hard components for space. The system timing and the digitiser algorithm are performed by an FPGA. The demonstrator has been tested at ranges from 1 m to 30 m. With a static non-cooperative target an RMS noise of 1 mm at a result rate of 60 Hz was reached. The demonstrator needs less than 2.5 W power.

New Drug Formulary Will Help Expedite Use of Agents in Clinical Trials

Cancer.gov

NCI launched the “NCI Formulary” that will enable investigators at NCI-designated Cancer Centers to have quicker access to approved and investigational agents for use in preclinical studies and cancer clinical trials.

NIH mouse study finds gut microorganisms may determine cancer treatment outcome

Cancer.gov

An intact gut commensal microbiota, which is a population of microorganisms living in the intestine, is required for optimal response to cancer therapy, according to a mouse study by scientists at the National Cancer Institute (NCI)

Esters of Quinoxaline 1`4-Di-N-oxide with Cytotoxic Activity on Tumor Cell Lines Based on NCI-60 Panel.

PubMed

Rivera, Gildardo; Ahmad Shah, Syed Shoaib; Arrieta-Baez, Daniel; Palos, Isidro; Mongue, Antonio; Sánchez-Torres, Luvia Enid

2017-01-01

Quinoxalines display diverse and interesting pharmacological activities as antibacterial, antiviral, antiparasitic and anticancer agents. Particularly, their 1`4-di- N -oxide derivatives have proved to be cytotoxic agents that are active under hypoxic conditions as that of solid tumours. A new series of quinoxaline 1`4-di- N -oxide substitutes at 7-position with esters group were synthetized and characterized by infrared (IR), proton nuclear magnetic resonance ( 1 H-NMR), spectroscopy, and elemental analysis. Seventeen derivatives (M1-M3, E1-E8, P1-P3 and DR1-DR3) were selected and evaluated for antitumor activities using the NCI-60 human tumor cell lines screen. Results showed that E7, P3 and E6 were the most active compounds against the cell lines tested. Substitutions at 7-position with esters group not necessarily affect the biological activity, but the nature of the esters group could exert an influence on the selectivity. Additionally, substitutions at 2-position influenced the cytotoxic activity of the compounds.

Inhibition of crystallin ascorbylation by nucleophilic compounds in the hSVCT2 mouse model of lenticular aging.

PubMed

Fan, Xingjun; Monnier, Vincent M

2008-11-01

Senile cataracts are associated with oxidation, fragmentation, cross-linking, insolubilization, and yellow pigmentation of lens crystallins. This process is partially explained by advanced glycation end products (AGEs) from ascorbic acid (ASA), as the authors unequivocally demonstrated in an hSVCT2 transgenic mouse. The authors present the first pharmacologic intervention study against ascorbylation in these mice. Five groups of mice from 2 to 9 months of age (10 mice/group) were fed a diet containing 0.1% (wt/wt) aminoguanidine, pyridoxamine, penicillamine, and nucleophilic compounds NC-I and NC-II. AGEs were determined in crystallin digests using high-performance liquid chromatography, liquid chromatography-mass spectrometry, or gas chromatography-mass spectrometry. Lens protein extract was incubated in vitro with ASA or dehydroascorbic acid. The ASA level increased approximately 10-fold in all groups and was unaffected by treatment. AGEs were increased several-fold in transgenic compared with control lenses. Body weight, food intake, lenticular glutathione, and glycated lysine level were unaltered. In vitro, all compounds inhibited AGE formation. In vivo, NC-I and NC-II significantly decreased protein fluorescence at lambda(ex)335/(em)385 (P = 0.045, P = 0.017, respectively) and lambda(ex)370/(em)440 (P = 0.029, P = 0.007, respectively). Other inhibitors had no effect. After 7 months, only NC-I and NC-II induced a 50% reduction in pentosidine (P = NS for NC-I; P = 0.035 for NC-II). NC-I also decreased carboxymethyllysine (P = 0.032) and carboxyethyllysine (P = NS). Fluorescent cross-link K2P was decreased by NC-I, NC-II, aminoguanidine, and pyridoxamine (P = NS). Pharmacologically blocking protein ascorbylation with absorbable guanidino compounds is feasible and may represent a new strategy for the delay of age-related nuclear sclerosis of the lens.

Gene expression patterns associated with neurological disease in human HIV infection

PubMed Central

Repunte-Canonigo, Vez; Masliah, Eliezer; Lefebvre, Celine

2017-01-01

The pathogenesis and nosology of HIV-associated neurological disease (HAND) remain incompletely understood. Here, to provide new insight into the molecular events leading to neurocognitive impairments (NCI) in HIV infection, we analyzed pathway dysregulations in gene expression profiles of HIV-infected patients with or without NCI and HIV encephalitis (HIVE) and control subjects. The Gene Set Enrichment Analysis (GSEA) algorithm was used for pathway analyses in conjunction with the Molecular Signatures Database collection of canonical pathways (MSigDb). We analyzed pathway dysregulations in gene expression profiles of patients from the National NeuroAIDS Tissue Consortium (NNTC), which consists of samples from 3 different brain regions, including white matter, basal ganglia and frontal cortex of HIV-infected and control patients. While HIVE is characterized by widespread, uncontrolled inflammation and tissue damage, substantial gene expression evidence of induction of interferon (IFN), cytokines and tissue injury is apparent in all brain regions studied, even in the absence of NCI. Various degrees of white matter changes were present in all HIV-infected subjects and were the primary manifestation in patients with NCI in the absence of HIVE. In particular, NCI in patients without HIVE in the NNTC sample is associated with white matter expression of chemokines, cytokines and β-defensins, without significant activation of IFN. Altogether, the results identified distinct pathways differentially regulated over the course of neurological disease in HIV infection and provide a new perspective on the dynamics of pathogenic processes in the course of HIV neurological disease in humans. These results also demonstrate the power of the systems biology analyses and indicate that the establishment of larger human gene expression profile datasets will have the potential to provide novel mechanistic insight into the pathogenesis of neurological disease in HIV infection and

The potential of large studies for building genetic risk prediction models

Cancer.gov

NCI scientists have developed a new paradigm to assess hereditary risk prediction in common diseases, such as prostate cancer. This genetic risk prediction concept is based on polygenic analysis—the study of a group of common DNA sequences, known as singl

NIH study finds that coffee drinkers have lower risk of death

Cancer.gov

Older adults who drank coffee -- caffeinated or decaffeinated -- had a lower risk of death overall than others who did not drink coffee, according a study by researchers from the National Cancer Institute (NCI), part of the National Institutes of Health,

The neurovascular complexity index as a potential indicator of traumatic brain injury severity: A case-series study.

PubMed

Howard, Jeffrey T; Janak, Jud C; Bukhman, Vladislav; Robertson, Claudia; Frolov, Iurii; Nawn, Corinne D; Schiller, Alicia M; Convertino, Victor A

2017-07-01

Multimodal monitoring of brain physiology following a traumatic brain injury (TBI) shows promise as a strategy to improve management and outcomes of TBI patients within civilian and military trauma. Valid and reliable measures of different aspects of brain physiology following a TBI could prove critical to accurately capturing these changes. Using a case-series design with a control subject group comparison, we evaluated a new proprietary algorithm called the Neurovascular Complexity Index (NCI) using transcranial Doppler to noninvasively obtain measures of cerebral blood flow variability. Baseline NCI data from 169 control subjects were compared with 12 patients with moderate to severe TBI. Patients with TBI exhibited significantly greater mean and variability in NCI scores compared with control subjects (F = 195.48; p < 0.001). The mean absolute deviation (MAD) of NCI scores increased significantly and in a monotonic fashion with severity of injury, where control subjects exhibited a small MAD of 0.44, patients with moderate TBI had a higher MAD of 4.20, and patients with severe TBI had an MAD of 6.51 (p < 0.001). Advancement in multimodal monitoring of TBI patients is important in reducing the potential risk of secondary injury. This study reports results indicating that a new noninvasive quantifiable assessment of TBI based on a noninvasive measure of cerebral blood flow variability shows potential for continuous monitoring and early identification of brain-injured patients, deployable in far-forward military environments, to better inform individualized management. Case series, level IV.

Approaches for the Evaluation of the National Cancer Institute's Summer Curriculum in Cancer Prevention: lessons from the all-Ireland NCI cancer consortium.

PubMed

Otero, Isabel V; Williams, Makeda; Harford, Joe B

2012-06-01

The NCI Summer Curriculum in Cancer Prevention (SCCP) has provided interdisciplinary training in cancer prevention and control to cancer health-care professionals, including nurses, physicians, and scientists, since 1986. It has trained over 1,200 participants, 256 of them from Ireland and Northern Ireland through two summer courses: a 4-week course on Principles and Practice of Cancer Prevention and Control (PP) and 1-week on Molecular Prevention (MP). This report is our attempt to measure achievements and level of satisfaction among alumni from the island of Ireland upon return to their home institution. A questionnaire was developed to assess this. Our analysis found statistically significant differences in the types of accomplishments reported among respondents of the MP and PP courses as well as statistically significant differences in their level of satisfaction. More data are needed to better explain the differences observed as well as level of resources available to alumni upon their return home.

Whirl Flutter Studies for a SSTOL Transport Demonstrator

NASA Technical Reports Server (NTRS)

Acree, C. W., Jr.; Hoffman, Krishna

2004-01-01

A proposed new class of aircraft - the Advanced Theater Transport (ATT) will combine strategic range and high payload with 'Super-STOL' (short take-off and landing) capability. It is also proposed to modify a YC-15 into a technology demonstrator with a 20-deg tilt wing; four, eight-bladed propellers; cross-shafted gearboxes and V-22 engines. These constitute a unique combination of design features that potentially affect performance, loads and whirl-mode stability (whirl flutter). NASA Ames Research Center is working with Boeing and Hamilton Sundstrand on technology challenges presented by the concept; the purpose of NASA involvement is to establish requirements for the demonstrator and for early design guidance, with emphasis on whirl flutter. CAMRAD II is being used to study the effects of various design features on whirl flutter, with special attention to areas where such features differ from existing aircraft, notably tiltrotors. Although the stability margins appear to be more than adequate, the concept requires significantly different analytical methods, principally including far more blade modes, than typically used for tiltrotors.

NIH study finds regular aspirin use may reduce ovarian cancer risk

Cancer.gov

Women who take aspirin daily may reduce their risk of ovarian cancer by 20 percent, according to a study by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health. However, further research is needed before clinical r

Study finds stronger nicotine dependency associated with higher risk of lung cancer

Cancer.gov

NCI headed study finds people who are highly addicted to nicotine -- those who smoke their first cigarette within five minutes after awakening -- are at higher risk of developing lung cancer than those who wait for an hour or more to smoke.

Fruit & Vegetable Screeners in the Eating at America's Table Study (EATS): Instruments

Cancer.gov

These instruments are in the public domain and may be used by any investigator. However, because they were used in NCI's Eating at America's Table Study (EATS) project, investigators must remove the first page, which is the EATS identifier page.

Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress.

PubMed

Lu, Jun; Chen, Jian; Xu, Nianjun; Wu, Jun; Kang, Yani; Shen, Tingting; Kong, Hualei; Ma, Chao; Cheng, Ming; Shao, Zhifeng; Xu, Ling; Zhao, Xiaodong

2016-09-06

Application of cisplatin (DDP) for treating lung cancer is restricted due to its toxicity and lung cancer's drug resistance. In this study, we examined the effect of Jinfukang (JFK), an effective herbal medicine against lung cancer, on DDP-induced cytotoxicity in lung cancer cells. Morphologically, we observed that JFK increases DDP-induced pro-apoptosis in A549 cells in a synergistic manner. Transcriptome profiling analysis indicated that the combination of JFK and DDP regulates genes involved in apoptosis-related signaling pathways. Moreover, we found that the combination of JFK and DDP produces synergistic pro-apoptosis effect in other lung cancer cell lines, such as NCI-H1975, NCI-H1650, and NCI-H2228. Particularly, we demonstrated that AIFM2 is activated by the combined treatment of JFK and DDP and partially mediates the synergistic pro-apoptosis effect. Collectively, this study not only offered the first evidence that JFK promotes DDP-induced cytotoxicity, and activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress, but also provided a novel insight for improving cytotoxicity by combining JFK with DDP to treat lung cancer cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

THE AGRICULTURAL HEALTH STUDY: COLLABORATIVE HEALTH AND EXPOSURE RESEARCH FOR THE AGRICULTURAL COMMUNITY

EPA Science Inventory

The abstract describes the collaborative effort between the NCI, the NIEHS, the U.S. EPA, and NIOSH to conduct the Agricultural Health Study (AHS). The AHS is a prospective epidemiological study to identify factors that may affect the rate of cancer and other diseases among farme...

Nuclear-encoded mitochondrial complex I gene expression is restored to normal levels by inhibition of unedited ATP9 transgene expression in Arabidopsis thaliana.

PubMed

Busi, María V; Gómez-Casati, Diego F; Perales, Mariano; Araya, Alejandro; Zabaleta, Eduardo

2006-01-01

Mitochondria play an important role during sporogenesis in plants. The steady state levels of the nuclear-encoded mitochondrial complex I (nCI), PSST, TYKY and NADHBP transcripts increase in flowers of male-sterile plants with impairment of mitochondrial function generated by the expression of the unedited version of ATP9 (u-ATP9). This suggests a nuclear control of nCI genes in response to the mitochondrial flaw. To evaluate this hypothesis, transgenic plants carrying the GUS reporter gene, under the control of the PSST, TYKY and NADHBP promoters, were constructed. We present evidence that suppression by antisense strategy of the expression of u-ATP9 restores the normal levels of three nCI transcripts, indicating that the increase in PSST, TYKY and NADHBP in plants with a mitochondrial flaw occurs at the transcriptional level. The data presented here support the hypothesis that a mitochondrial dysfunction triggers a retrograde signaling which induce some nuclear-encoded mitochondrial genes. Moreover, these results demonstrate that this is a valuable experimental model for studying nucleus-mitochondria cross-talk events.

Wikipedia and osteosarcoma: a trustworthy patients' information?

PubMed

Leithner, Andreas; Maurer-Ertl, Werner; Glehr, Mathias; Friesenbichler, Joerg; Leithner, Katharina; Windhager, Reinhard

2010-01-01

The English version of the online encyclopedia, Wikipedia, has been recently reported to be the prominent source of online health information. However, there is little information concerning the quality of information found in Wikipedia. Therefore, we created a questionnaire asking for scope, completeness, and accuracy of information found on osteosarcoma. Three independent observers tested the English version of Wikipedia, as well as the patient version and the health professional version of the US National Cancer Institute (NCI) website. Answers were verified with authoritative resources and international guidelines. The results of our study demonstrate that the quality of osteosarcoma-related information found in the English Wikipedia is good but inferior to the patient information provided by the NCI. Therefore, non-peer-reviewed commonly used websites offering health information, such as Wikipedia, should include links to more definitive sources, such as those maintained by the NCI and professional international organizations on healthcare treatments. Furthermore, frequent checks should make sure such external links are to the highest quality and to the best-maintained aggregate sites on a given healthcare topic.

Wikipedia and osteosarcoma: a trustworthy patients' information?

PubMed Central

Maurer-Ertl, Werner; Glehr, Mathias; Friesenbichler, Joerg; Leithner, Katharina; Windhager, Reinhard

2010-01-01

The English version of the online encyclopedia, Wikipedia, has been recently reported to be the prominent source of online health information. However, there is little information concerning the quality of information found in Wikipedia. Therefore, we created a questionnaire asking for scope, completeness, and accuracy of information found on osteosarcoma. Three independent observers tested the English version of Wikipedia, as well as the patient version and the health professional version of the US National Cancer Institute (NCI) website. Answers were verified with authoritative resources and international guidelines. The results of our study demonstrate that the quality of osteosarcoma-related information found in the English Wikipedia is good but inferior to the patient information provided by the NCI. Therefore, non-peer-reviewed commonly used websites offering health information, such as Wikipedia, should include links to more definitive sources, such as those maintained by the NCI and professional international organizations on healthcare treatments. Furthermore, frequent checks should make sure such external links are to the highest quality and to the best-maintained aggregate sites on a given healthcare topic. PMID:20595302

Esters of Quinoxaline 1ˏ4-Di-N-oxide with Cytotoxic Activity on Tumor Cell Lines Based on NCI-60 Panel

PubMed Central

Rivera, Gildardo; Ahmad Shah, Syed Shoaib; Arrieta-Baez, Daniel; Palos, Isidro; Mongue, Antonio; Sánchez-Torres, Luvia Enid

2017-01-01

Quinoxalines display diverse and interesting pharmacological activities as antibacterial, antiviral, antiparasitic and anticancer agents. Particularly, their 1ˏ4-di-N-oxide derivatives have proved to be cytotoxic agents that are active under hypoxic conditions as that of solid tumours. A new series of quinoxaline 1ˏ4-di-N-oxide substitutes at 7-position with esters group were synthetized and characterized by infrared (IR), proton nuclear magnetic resonance (1H-NMR), spectroscopy, and elemental analysis. Seventeen derivatives (M1-M3, E1-E8, P1-P3 and DR1-DR3) were selected and evaluated for antitumor activities using the NCI-60 human tumor cell lines screen. Results showed that E7, P3 and E6 were the most active compounds against the cell lines tested. Substitutions at 7-position with esters group not necessarily affect the biological activity, but the nature of the esters group could exert an influence on the selectivity. Additionally, substitutions at 2-position influenced the cytotoxic activity of the compounds. PMID:29201086

Readability of Online Patient Educational Resources Found on NCI-Designated Cancer Center Web Sites.

PubMed

Rosenberg, Stephen A; Francis, David; Hullett, Craig R; Morris, Zachary S; Fisher, Michael M; Brower, Jeffrey V; Bradley, Kristin A; Anderson, Bethany M; Bassetti, Michael F; Kimple, Randall J

2016-06-01

The NIH and Department of Health & Human Services recommend online patient information (OPI) be written at a sixth grade level. We used a panel of readability analyses to assess OPI from NCI-Designated Cancer Center (NCIDCC) Web sites. Cancer.gov was used to identify 68 NCIDCC Web sites from which we collected both general OPI and OPI specific to breast, prostate, lung, and colon cancers. This text was analyzed by 10 commonly used readability tests: the New Dale-Chall Readability Formula, Flesch Reading Ease scale, Flesch-Kinaid Grade Level, FORCAST scale, Fry Readability Graph, Simple Measure of Gobbledygook test, Gunning Frequency of Gobbledygook index, New Fog Count, Raygor Readability Estimate Graph, and Coleman-Liau Index. We tested the hypothesis that the readability of NCIDCC OPI was written at the sixth grade level. Secondary analyses were performed to compare readability of OPI between comprehensive and noncomprehensive centers, by region, and to OPI produced by the American Cancer Society (ACS). A mean of 30,507 words from 40 comprehensive and 18 noncomprehensive NCIDCCs was analyzed (7 nonclinical and 3 without appropriate OPI were excluded). Using a composite grade level score, the mean readability score of 12.46 (ie, college level: 95% CI, 12.13-12.79) was significantly greater than the target grade level of 6 (middle-school: P<.001). No difference between comprehensive and noncomprehensive centers was identified. Regional differences were identified in 4 of the 10 readability metrics (P<.05). ACS OPI provides easier language, at the seventh to ninth grade level, across all tests (P<.01). OPI from NCIDCC Web sites is more complex than recommended for the average patient. Copyright © 2016 by the National Comprehensive Cancer Network.

Orbital construction demonstration study

NASA Technical Reports Server (NTRS)

1976-01-01

A conceptual design and program plan for an Orbital Construction Demonstration Article (OCDA) was developed that can be used for evaluating and establishing practical large structural assembly operations. A flight plan for initial placement and continued utility is presented as a basic for an entirely new shuttle payload line-item having great future potential benefit for space applications. The OCDA is a three-axis stabilized platform in low-earth orbit with many structural nodals for mounting large construction and fabrication equipments. This equipment would be used to explore methods for constructing the large structures for future missions. The OCDA would be supported at regular intervals by the shuttle. Construction experiments and consumables resupply are performed during shuttle visit periods. A 250 kw solar array provides sufficient power to support the shuttle while attached to the OCDA and to run construction experiments at the same time. Wide band communications with a Telemetry and Data Relay Satellite compatible high gain antenna can be used between shuttle revisits to perform remote controlled, TV assisted construction experiments.

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 Central

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

2017-01-01

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. PMID:28209610

Demonstration Report: ESTCP UXO Discrimination Study ESTCP PROJECT # MM-0838

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gasperikova, Erika

2010-02-15

In 2003, the Defense Science Board observed: 'The problem is that instruments that can detect the buried UXOs also detect numerous scrap metal objects and other artifacts, which leads to an enormous amount of expensive digging. Typically 100 holes may be dug before a real UXO is unearthed! The Task Force assessment is that much of this wasteful digging can be eliminated by the use of more advanced technology instruments that exploit modern digital processing and advanced multi-mode sensors to achieve an improved level of discrimination of scrap from UXOs.' Significant progress has been made in discrimination technology. To date,more » testing of these approaches has been primarily limited to test sites with only limited application at live sites. Acceptance of discrimination technologies requires demonstration of system capabilities at real UXO sites under real world conditions. Any attempt to declare detected anomalies to be harmless and requiring no further investigation will require demonstration to regulators of not only individual technologies, but of an entire decision making process. This characterization study was be the second phase in what is expected to be a continuing effort that will span several years. The FY06 Defense Appropriation contained funding for the 'Development of Advanced, Sophisticated, Discrimination Technologies for UXO Cleanup' in the Environmental Security Technology Certification Program (ESTCP). ESTCP responded by conducting a UXO Discrimination Study at the former Camp Sibert, AL. The results of this first demonstration were very encouraging. Although conditions were favorable at this site, a single target of interest (4.2-in mortar) and benign topography and geology, all of the classification approaches demonstrated were able to correctly identify a sizable fraction of the anomalies as arising from non-hazardous items that could be safely left in the ground. To build upon the success of the first phase of this study, ESTCP

Publishing Single-Case Research Design Studies That Do Not Demonstrate Experimental Control

ERIC Educational Resources Information Center

Tincani, Matt; Travers, Jason

2018-01-01

Demonstration of experimental control is considered a hallmark of high-quality single-case research design (SCRD). Studies that fail to demonstrate experimental control may not be published because researchers are unwilling to submit these papers for publication and journals are unlikely to publish negative results (i.e., the file drawer effect).…

Transit Pricing Demonstration in Bridgeport, Connecticut : A Case Study

DOT National Transportation Integrated Search

1986-03-01

Sponsored by the Urban Mass Transportation Administration, Office of Service and Management Demonstrations, the Bridgeport Pricing Demonstration began in September 1979 and ended in June 1985. It was one element of a broader brokerage demonstration a...

Oxytetracycline Inhibits Mucus Secretion and Inflammation in Human Airway Epithelial Cells.

PubMed

Shah, Said Ahmad; Ishinaga, Hajime; Takeuchi, Kazuhiko

2017-01-01

Oxytetracycline is a broad-spectrum antibiotic, but its nonantibacterial effects in the human respiratory tract are unknown. In this study, the effects of oxytetracycline on mucus secretion and inflammation were examined by PCR and ELISA in the human airway epithelial cell line NCI-H292. Oxytetracycline (10 μg/mL) significantly inhibited TNF-α-induced MUC5AC gene expression and MUC5AC protein levels in NCI-H292 cells. It also downregulated IL-8 and IL-1β gene expression and IL-1β protein levels. Our findings demonstrated that oxytetracycline suppressed mucus production and inflammation in human respiratory epithelial cells, providing further evidence for the usefulness of oxytetracycline for human airway inflammatory diseases. © 2017 S. Karger AG, Basel.

Poly(d,l-lactide-co-glycolide)–chitosan composite particles for the treatment of lung cancer

PubMed Central

Arya, Neha; Katti, Dhirendra S

2015-01-01

Tumor heterogeneity makes combination chemotherapy one of the preferred modes of treatment regimens. In this work, sequential exposure of two anticancer agents, paclitaxel (Tx) followed by topotecan (TPT), was shown to have a synergistic effect on non-small cell lung cancer (NSCLC) cell line, NCI-H460. In order to improve patient compliance, the aforementioned concept was translated into a drug delivery system comprising of poly(d,l-lactide-co-glycolide) (PLGA)–chitosan composite particles. TPT-containing chitosan micro-/nanoparticles were prepared by the facile technique of electrospraying and encapsulated within PLGA microparticles using emulsion-solvent evaporation technique for delayed release of TPT. The formulation containing Tx- and TPT-loaded composite particles demonstrated synergism when exposed to NCI-H460 cellular aggregates (tumoroids) generated in vitro. Overall, the results of this study demonstrated the potential of the formulation containing Tx and PLGA–chitosan (TPT-loaded) composite particles for the treatment of lung cancer. PMID:25945047

76 FR 21383 - Proposed Collection; Comment Request; Food Reporting Comparison Study (FORCS) and Food and Eating...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-15

... be submitted to the Office of Management and Budget (OMB) for review and approval. Proposed... Institute (NCI) Observational Feeding Studies.'' The objective of the two studies is to compare the performance of the newly developed computerized Automated Self- Administered 24-Hour Recall (ASA24) approach...

Health advertising: prevention for profit.

PubMed Central

Freimuth, V S; Hammond, S L; Stein, J A

1988-01-01

The National Cancer Institute (NCI) estimates on the basis of current knowledge alone that, at a minimum, 30,000 lives could be saved in the year 2000 if Americans would modify their dietary habits. A recent innovative way of responding to this challenge was the Kellogg Company/NCI All-Bran advertising campaign. This paper will describe the campaign, and its impact on consumers, cereal industry sales, food industry advertising practices, health regulatory policy, and the organizational credibility of both NCI and Kellogg. For the past three years, Kellogg has included NCI's cancer prevention messages in their advertisements for All-Bran cereal and on their bran cereal boxes. This collaborative effort has stimulated considerable controversy over whether the health claims made on the cereal label are in violation of federal food labeling regulations. Meanwhile, research has demonstrated the positive impact of the campaign on consumer's knowledge and behavior regarding fiber as well as on Kellogg's profits. Other manufacturers are anxious to jump on the "branwagon"; however, many unanswered questions remain about this new approach to health advertising. PMID:2833125

Environmental Technology Verification (ETV) Program Case Studies: Demonstrating Program Outcomes, Volume III

EPA Science Inventory

This booklet, ETV Program Case Studies: Demonstrating Program Outcomes, Volume III contains two case studies, addressing verified environmental technologies for decentalized wastewater treatment and converting animal waste to energy. Each case study contains a brief description ...

Orbital construction demonstration study. Volume 3: Requirements document

NASA Technical Reports Server (NTRS)

1977-01-01

A comprehensive set of requirements that defines the objective, scope and configuration of the orbital test facility needed to demonstrate the necessary automated fabrication, construction and assembly technology is provided. In addition to the requirements for the orbital demonstration facility, a detailed list of experiment requirements is included for various areas of technology.

Identifying and Creating the Next Generation of Community-Based Cancer Prevention Studies: Summary of a National Cancer Institute Think Tank

PubMed Central

McCaskill-Stevens, Worta; Pearson, Deborah C.; Kramer, Barnett S.; Ford, Leslie G.; Lippman, Scott M.

2016-01-01

In late 2015, The National Cancer Institute (NCI) Division of Cancer Prevention convened cancer prevention research experts and stakeholders to discuss the current state of cancer prevention research, identify key prevention research priorities for the NCI, and identify studies that could be conducted within the NCI Community Oncology Research Program (NCORP). Goals included identifying cancer prevention research opportunities offering the highest return on investment, exploring the concept of precision prevention and what is needed to advance this area of research, and identifying possible targets for prevention. Four study populations were considered for cancer prevention research: healthy people; those at increased risk for a specific cancer; people with preneoplastic lesions; and children, adolescents, and young adults. Priorities that emerged include screening (e.g., surveillance intervals, tomosynthesis vs. digital mammography), a pre-cancer genome atlas (PreTCGA), HPV vaccines, immunoprevention of non-infectious origins, and overdiagnosis. Challenges exist, as the priority list is ambitious and potentially expensive. Clinical trials need to be carefully designed to include and maximize prospective tissue collection. Exploring existing co-funding mechanisms will likely be necessary. Finally, relationships with a new generation of physician specialists will need to be cultivated in order to reach the target populations. PMID:27965286

Study of the Vermont Manpower Experimental and Demonstration Program. Final Report.

ERIC Educational Resources Information Center

Vermont State Employment Service, Montpelier. Dept. of Employment Security.

The purpose of this experimental and demonstration project was to provide work experience to unemployed, low-income clients to improve their employability so they can be moved into permanent, unsubsidized employment. Changes of attitudes and motivations as a result of project experience were studied. Study findings indicated that the post-project…

Case Study for the ARRA-funded GSHP Demonstration at University at Albany

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Xiaobing; Malhotra, Mini; Xiong, Zeyu

High initial costs and lack of public awareness of ground-source heat pump (GSHP) technology are the two major barriers preventing rapid deployment of this energy-saving technology in the United States. Under the American Recovery and Reinvestment Act (ARRA), 26 GSHP projects have been competitively selected and carried out to demonstrate the benefits of GSHP systems and innovative technologies for cost reduction and/or performance improvement. This report highlights the findings of a case study of one of the ARRA-funded GSHP demonstration projects—a distributed GSHP system at a new 500-bed apartment-style student residence hall at the University at Albany. This case studymore » is based on the analysis of detailed design documents, measured performance data, published catalog data of heat pump equipment, and actual construction costs. Simulations with a calibrated computer model are performed for both the demonstrated GSHP system and a baseline heating, ventilation, and airconditioning (HVAC) system to determine the energy savings and other related benefits achieved by the GSHP system. The evaluated performance metrics include the energy efficiency of the heat pump equipment and the overall GSHP system, as well as the pumping performance, energy savings, carbon emission reductions, and cost-effectiveness of the demonstrated GSHP system compared with the baseline HVAC system. This case study also identifies opportunities for improving the operational efficiency of the demonstrated GSHP system.« less

Improving maternity care using a personal health record: study protocol for a stepped-wedge, randomised, controlled trial.

PubMed

Groenen, Carola J M; Faber, Marjan J; Kremer, Jan A M; Vandenbussche, Frank P H A; van Duijnhoven, Noortje T L

2016-04-16

A personal health record (PHR) is an online application through which individuals can access, manage, and share their health information in a private, secure, and confidential environment. Personal health records empower patients, facilitate collaboration among healthcare professionals, and improve health outcomes. Given these anticipated positive effects, we want to implement a PHR, named MyPregn@ncy, in a Dutch maternity care setting and to evaluate its effects in routine care. This paper presents the study protocol. The effects of implementing a PHR in maternity care on patients and professionals will be identified in a stepped-wedge, cluster-randomised, controlled trial. The study will be performed in the region of Nijmegen, a Dutch area with an average of 4,500 births a year and more than 230 healthcare professionals involved in maternity care. Data analyses will describe the effects of MyPregn@ncy on health outcomes in maternity care, quality of care from the patients' perspectives, and collaboration among healthcare professionals. Additionally, a process evaluation of the implementation of MyPregn@ncy will be performed. Data will be collected using data from the Dutch perinatal registry, questionnaires, interviews, and log data. The study is expected to yield new information about the effects, strengths, possibilities, and challenges to the implementation and usage of a PHR in routine maternal care settings. Results may lead to new insights and improvements in the quality of maternal and perinatal care. Netherlands Trial Register: NTR4063.

In vitro growth inhibition and cytotoxicity of Euphorbia caducifolia against four human cancer cell lines and its phytochemical characterisation.

PubMed

Bano, Shaista; Siddiqui, Bina Shaheen; Farooq, Ahsana Dar; Begum, Sabira; Siddiqui, Faheema; Kashif, Muhammad; Azhar, Mudassar

2017-12-01

Several Euphorbia species have been used in folklore as cancer remedies, however, scientific studies on the cytotoxicity (in vitro studies) of Euphorbia caducifolia are lacking. In present study, anticancer potential of E. caducifolia aerial parts ethanol extract and its fractions were evaluated against human lung (NCI-H460), breast (MCF-7), prostate (PC-3) and cervical (HeLa) cancer cell lines, using sulphorhodamine-B in vitro cytotoxicity (in vitro studies) assay. The ethanol extract demonstrated growth inhibitory effect against all aforementioned cancer cell lines with IC 50 , 19-135 μg/mL and LC 50 , ~220 μg/mL, and its petroleum ether fraction obtained on bioactivity guided fraction showed highest activity with IC 50 , 28-70 μg/mL and LC 50 , 71 μg/mL against NCI-H460 and MCF-7 cell lines. Its phytochemicals were analysed by gas chromatography-mass spectrometry (GC-MS). The present study provides scientific justification for its traditional use against cancer.

77 FR 12598 - Notice Correction; A Multi-Center International Hospital-Based Case-Control Study of Lymphoma in...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Notice Correction; A Multi-Center International Hospital-Based Case-Control Study of Lymphoma in Asia (AsiaLymph) (NCI) The Federal... project titled, ``A multi-center international hospital-based case-control study of lymphoma in Asia (Asia...

77 FR 72871 - Proposed Collection; Comment Request (60-Day FRN): The Agricultural Health Study: A Prospective...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-06

... Disease Among Men and Women in Agriculture (NCI) Summary: In compliance with the requirement of Section... Prospective Cohort Study of Cancer and Other Disease Among Men and Women in Agriculture, 0925-0406, Expiration... Effects in Agriculture (BEEA). The primary objectives of the study are to determine the health effects...

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.

Clinicopathological characteristics of patients with amyotrophic lateral sclerosis resulting in a totally locked-in state (communication Stage V).

PubMed

Hayashi, Kentaro; Mochizuki, Yoko; Takeuchi, Ryoko; Shimizu, Toshio; Nagao, Masahiro; Watabe, Kazuhiko; Arai, Nobutaka; Oyanagi, Kiyomitsu; Onodera, Osamu; Hayashi, Masaharu; Takahashi, Hitoshi; Kakita, Akiyoshi; Isozaki, Eiji

2016-09-30

In the present study, we performed a comprehensive analysis to clarify the clinicopathological characteristics of patients with amyotrophic lateral sclerosis (ALS) that had progressed to result in a totally locked-in state (communication Stage V), in which all voluntary movements are lost and communication is impossible. In 11 patients, six had phosphorylated TAR DNA-binding protein 43 (pTDP-43)-immunoreactive (ir) neuronal cytoplasmic inclusions (NCI), two had fused in sarcoma (FUS)-ir NCI, and three had copper/zinc superoxide dismutase (SOD1)-ir NCI. The time from ALS onset to the need for tracheostomy invasive ventilation was less than 24 months in ten patients. Regardless of accumulated protein, all the patients showed common lesions in the pallido-nigro-luysian system, brainstem reticular formation, and cerebellar efferent system, in addition to motor neurons. In patients with pTDP-43-ir NCI, patients with NCI in the hippocampal dentate granule neurons (DG) showed a neuronal loss in the cerebral cortex, and patients without NCI in DG showed a preserved cerebral cortex. By contrast, in patients with FUS-ir NCI, patients with NCI in DG showed a preserved cerebral cortex and patients without NCI in DG showed marked cerebral degeneration. The cerebral cortex of patients with SOD1-ir NCI was preserved. Together, these findings suggest that lesions of the cerebrum are probably not necessary for progression to Stage V. In conclusion, patients with ALS that had progressed to result in communication Stage V showed rapidly-progressed symptoms, and their common lesions could cause the manifestations of communication Stage V.

The strategic case for establishing public-private partnerships in cancer care.

PubMed

Holden, Debra J; Reiter, Kristin; O'Brien, Donna; Dalton, Kathleen

2015-10-14

In 2007, the National Cancer Institute (NCI) launched the NCI Community Cancer Centers Program (NCCCP) as a public-private partnership with community hospitals with a goal of advancing cancer care and research. In order to leverage federal dollars in a time of limited resources, matching funds from each participating hospital were required. The purpose of this paper is to examine hospitals' level of and rationale for co-investment in this partnership, and whether there is an association between hospitals' co-investment and achievement of strategic goals. Analysis using a comparative case study and micro-cost data was conducted as part of a comprehensive evaluation of the NCCCP pilot to determine the level of co-investment made in support of NCI's goals. In-person or telephone interviews with key informants were conducted at 10 participating hospital and system sites during the first and final years of implementation. Micro-cost data were collected annually from each site from 2007 to 2010. Self-reported data from each awardee are presented on patient volume and physician counts, while secondary data are used to examine the local Medicare market share. The rationale expressed by interviewees for participation in a public-private partnership with NCI included expectations of increased market share, higher patient volumes, and enhanced opportunities for cancer physician recruitment as a result of affiliation with the NCI. On average, hospitals invested resources into the NCCCP at a level exceeding $3 for every $1 of federal funds. Six sites experienced a statistically significant change in their Medicare market share. Cancer patient volume increased by as much as one-third from Year 1 to Year 3 for eight of the sites. Nine sites reported an increase in key cancer physician recruitment. Demonstrated investments in cancer care and research were associated with increases in cancer patient volume and perhaps in recruitment of key cancer physicians, but not in increased

Patterns of care and outcomes in adolescent and young adult acute lymphoblastic leukemia: a population-based study.

PubMed

Muffly, Lori; Alvarez, Elysia; Lichtensztajn, Daphne; Abrahão, Renata; Gomez, Scarlett Lin; Keegan, Theresa

2018-04-24

Adolescents and young adults (AYAs, 15-39 years) with acute lymphoblastic leukemia (ALL) represent a heterogeneous population who receive care in pediatric or adult cancer settings. Using the California Cancer Registry, we describe AYA ALL patterns of care and outcomes over the past decade. Sociodemographics, treatment location, and front-line therapies administered to AYAs diagnosed with ALL between 2004 and 2014 were obtained. Cox regression models evaluated associations between ALL setting and regimen and overall survival (OS) and leukemia-specific survival (LSS) for the entire cohort, younger AYA (<25 years), and AYAs treated in the adult cancer setting only. Of 1473 cases, 67.7% were treated in an adult setting; of these, 24.8% received a pediatric ALL regimen and 40.7% were treated at a National Cancer Institute (NCI)-designated center. In multivariable analyses, front-line treatment in a pediatric (vs adult) setting (OS HR = 0.53, 95% confidence interval [CI], 0.37-0.76; LSS HR = 0.51, 95% CI, 0.35-0.74) and at an NCI/Children's Oncology Group (COG) center (OS HR = 0.80, 95% CI, 0.66-0.96; LSS HR = 0.80, 95% CI, 0.65-0.97) were associated with significantly superior survival. Results were similar when analyses were limited to younger AYAs. Outcomes for AYAs treated in an adult setting did not differ following front-line pediatric or adult ALL regimens. Our population-level findings demonstrate that two-thirds of AYAs with newly diagnosed ALL are treated in an adult cancer setting, with the majority receiving care in community settings. Given the potential survival benefits, front-line treatment of AYA ALL at pediatric and/or NCI/COG-designated cancer centers should be considered. © 2018 by The American Society of Hematology.

Differences in Neurocognitive Impairment among HIV-infected Latinos in the United States

PubMed Central

Marquine, María J.; Heaton, Anne; Johnson, Neco; Rivera-Mindt, Monica; Cherner, Mariana; Bloss, C.; Hulgan, T.; Umlauf, Anya; Moore, David J.; Fazeli, Pariya; Morgello, Susan; Franklin, Donald; Letendre, Scott; Ellis, Ron; Collier, Ann C.; Marra, Christina M.; Clifford, David. B.; Gelman, Benjamin B.; Sacktor, Ned; Simpson, David; McCutchan, J. Allen; Grant, Igor; Heaton, Robert K.

2017-01-01

Objective HIV disproportionately affects Hispanics/Latinos in the U.S., yet little is known about neurocognitive impairment (NCI) in this group. We compared the rates of NCI in large well-characterized samples of HIV-infected (HIV+) Latinos and (non-Latino) Whites, and examined HIV-associated NCI among subgroups of Latinos. Method Participants included English-speaking HIV+ adults assessed at six U.S. medical centers (194 Latinos, 600 Whites). For overall group, Age: M=42.65, SD=8.93; 86% Male; Education: M=13.17, SD=2.73; 54% had AIDS. NCI was assessed with a comprehensive test battery with normative corrections for age, education and gender. Covariates examined included HIV-disease characteristics, comorbidities, and genetic ancestry. Results Compared to Whites, Latinos had higher rates of global NCI (42% vs. 54%), and domain NCI in executive function, learning, recall, working memory, and processing speed. Latinos also fared worse than Whites on current and historical HIV-disease characteristics, and nadir CD4 partially mediated ethnic differences in NCI. Yet, Latinos continued to have more global NCI (OR=1.59, 95%CI=1.13–2.23, p<.01) after adjusting for significant covariates. Higher rates of global NCI were observed with Puerto Rican (n=60; 71%) vs. Mexican (n=79, 44%) origin/descent; this disparity persisted in models adjusting for significant covariates (OR=2.40, CI=1.11–5.29, p=.03). Conclusions HIV+ Latinos, especially of Puerto Rican (vs. Mexican) origin/descent had increased rates of NCI compared to Whites. Differences in rates of NCI were not completely explained by worse HIV-disease characteristics, neurocognitive comorbidities, or genetic ancestry. Future studies should explore culturally-relevant psychosocial, biomedical and genetic factors that might explain these disparities and inform the development of targeted interventions. PMID:28874213

78 FR 23942 - Proposed Collection; 60-Day Comment Request: The Agricultural Health Study: A Prospective Cohort...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-23

... Among Men and Women in Agriculture (NCI) SUMMARY: In compliance with the requirement of Section 3506(c... Health Study: A Prospective Cohort Study of Cancer and Other Disease Among Men and Women in Agriculture... of Biomarkers of Exposures and Effects in Agriculture (BEEA) as well as continue and complete phase...

Cigar Smoking and Cancer

MedlinePlus

... About NCI NCI Overview History Contributing to Cancer Research Leadership Director's Page Deputy Director's Page Previous NCI Directors ... Overview & Mission History of NCI Contributing to Cancer Research Senior Leadership Director Deputy Director Previous Directors NCI Organization Divisions, ...

Demonstration of load rating capabilities through physical load testing : Sioux County bridge case study.

DOT National Transportation Integrated Search

2013-08-01

The objective of this work, Pilot Project - Demonstration of Capabilities and Benefits of Bridge Load Rating through Physical Testing, was to demonstrate the capabilities for load testing and rating bridges in Iowa, study the economic benefit of perf...

Demonstration of load rating capabilities through physical load testing : Ida County bridge case study.

DOT National Transportation Integrated Search

2013-08-01

The objective of this work, Pilot Project - Demonstration of Capabilities and Benefits of Bridge Load Rating through Physical Testing, was to demonstrate the capabilities for load testing and rating bridges in Iowa, study the economic benefit of perf...

Demonstration of load rating capabilities through physical load testing : Johnson County bridge case study.

DOT National Transportation Integrated Search

2013-08-01

The objective of this work, Pilot Project - Demonstration of Capabilities and Benefits of Bridge Load Rating through Physical Testing, was to demonstrate the capabilities for load testing and rating bridges in Iowa, study the economic benefit of perf...

Pre-implementation studies of a workforce planning tool for nurse staffing and human resource management in university hospitals.

PubMed

van Oostveen, Catharina J; Ubbink, Dirk T; Mens, Marian A; Pompe, Edwin A; Vermeulen, Hester

2016-03-01

To investigate the reliability, validity and feasibility of the RAFAELA workforce planning system (including the Oulu patient classification system - OPCq), before deciding on implementation in Dutch hospitals. The complexity of care, budgetary restraints and demand for high-quality patient care have ignited the need for transparent hospital workforce planning. Nurses from 12 wards of two university hospitals were trained to test the reliability of the OPCq by investigating the absolute agreement of nursing care intensity (NCI) measurements among nurses. Validity was tested by assessing whether optimal NCI/nurse ratio, as calculated by a regression analysis in RAFAELA, was realistic. System feasibility was investigated through a questionnaire among all nurses involved. Almost 67 000 NCI measurements were performed between December 2013 and June 2014. Agreement using the OPCq varied between 38% and 91%. For only 1 in 12 wards was the optimal NCI area calculated judged as valid. Although the majority of respondents was positive about the applicability and user-friendliness, RAFAELA was not accepted as useful workforce planning system. Nurses' performance using the RAFAELA system did not warrant its implementation. Hospital managers should first focus on enlarging the readiness of nurses regarding the implementation of a workforce planning system. © 2015 John Wiley & Sons Ltd.

Hexamethoxylated Monocarbonyl Analogues of Curcumin Cause G2/M Cell Cycle Arrest in NCI-H460 Cells via Michael Acceptor-Dependent Redox Intervention.

PubMed

Li, Yan; Zhang, Li-Ping; Dai, Fang; Yan, Wen-Jing; Wang, Hai-Bo; Tu, Zhi-Shan; Zhou, Bo

2015-09-09

Curcumin, derived from the dietary spice turmeric, holds promise for cancer prevention. This prompts much interest in investigating the action mechanisms of curcumin and its analogues. Two symmetrical hexamethoxy-diarylpentadienones (1 and 2) as cucumin analogues were reported to possess significantly enhanced cytotoxicity compared with the parent molecule. However, the detailed mechanisms remain unclear. In this study, compounds 1 and 2 were identified as the G2/M cell cycle arrest agents to mediate the cytotoxicity toward NCI-H460 cells via Michael acceptor-dependent redox intervention. Compared with curcumin, they could more easily induce a burst of reactive oxygen species (ROS) and collapse of the redox buffering system. One possible reason is that they could more effectively target intracellular TrxR to convert this antioxidant enzyme into a ROS promoter. Additionally, they caused up-regulation of p53 and p21 and down-regulation of redox-sensitive Cdc25C along with cyclin B1/Cdk1 in a Michael acceptor- and ROS-dependent fashion. Interestingly, in comparison with compound 2, compound 1 displayed a relatively weak ability to generate ROS but increased cell cycle arrest activity and cytotoxicity probably due to its Michael acceptor-dependent microtubule-destabilizing effect and greater GST-inhibitory activity, as well as its enhanced cellular uptake. This work provides useful information for understanding Michael acceptor-dependent and redox-mediated cytotoxic mechanisms of curcumin and its active analogues.

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

BCI induces apoptosis via generation of reactive oxygen species and activation of intrinsic mitochondrial pathway in H1299 lung cancer cells.

PubMed

Shin, Jong-Woon; Kwon, Sae-Bom; Bak, Yesol; Lee, Sang-Ku; Yoon, Do-Young

2018-03-28

The compound (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI) is known as an inhibitor of dual specific phosphatase 1/6 and mitogen-activated protein kinase. However, its precise anti-lung cancer mechanism remains unknown. In this study, the effects of BCI on the viability of non-small cell lung cancer cell lines NCI-H1299, A549, and NCI-H460 were evaluated. We confirmed that BCI significantly inhibited the viability of p53(-) NCI-H1299 cells as compared to NCI-H460 and A549 cells, which express wild-type p53. Furthermore, BCI treatment increased the level of cellular reactive oxygen species and pre-treatment of cells with N-acetylcysteine markedly attenuated BCI-mediated apoptosis of NCI-H1299 cells. BCI induced cellular morphological changes, inhibited viability, and produced reactive oxygen species in NCI-H1299 cells in a dose-dependent manner. BCI induced processing of caspase-9, caspase-3, and poly ADP-ribose polymerase as well as the release of cytochrome c from the mitochondria into the cytosol. In addition, BCI downregulated Bcl-2 expression and enhanced Bax expression in a dose-dependent manner in NCI-H1299 cells. However, BCI failed to modulate the expression of the death receptor and extrinsic factor caspase-8 and Bid, a linker between the intrinsic and extrinsic apoptotic pathways in NCI-H1299 cells. Thus, BCI induces apoptosis via generation of reactive oxygen species and activation of the intrinsic pathway in NCI-H1299 cells.

Sex-Related Differences in Self-Reported Neurocognitive Impairment among High-Risk Cocaine Users in Methadone Maintenance Treatment Program.

PubMed

Shrestha, Roman; Huedo-Medina, Tania B; Copenhaver, Michael M

2015-01-01

Previous research has suggested possible sex-related differences in executive functioning among cocaine users; however, no studies specifically explain sex-related differences in neurocognitive impairment (NCI) among cocaine users receiving clinical care. Knowledge about this association can aid in the development of targeted prevention strategies to reduce adverse health outcomes. This study was designed to examine the sex-related differences in NCI among high-risk cocaine users receiving substance-abuse treatment. The Neuropsychological Impairment Scale (NIS) was administered to 199 cocaine users (98 men; 101 women), receiving methadone maintainance treatment, to assess self-reported NCI by identifying the patients' awareness of neuropsychological symptoms. We used T-test comparison to find differences in NCI between men and women and multiple regression analysis to explore the relative contribution of sex to NCI. Consistent with prior work, high NCI was evident within this sample, as indicated by high scores on most of the NIS subscales. Women reported greater impairment than men, as evidenced by significantly higher scores on several NIS subscales, after controlling for demographic and other confounding variables. Interestingly, cocaine craving significantly predicted NCI among men but not among women, as suggested by the significant association between cocaine craving and all except one of the NIS subscales. These findings suggest that cocaine users enter into treatment with a range of NCI - with women having significantly more neurocognitive deficits than men - that may contribute to differential treatment outcomes. This highlights the need to include additional services such as neuropsychological screening and sex-specific treatment programs to optimally reduce adverse health outcomes in these high-risk, cognitively impaired patients.

Increased Intrathecal Immune Activation in Virally Suppressed HIV-1 Infected Patients with Neurocognitive Impairment

PubMed Central

Edén, Arvid; Marcotte, Thomas D.; Heaton, Robert K.; Nilsson, Staffan; Zetterberg, Henrik; Fuchs, Dietmar; Franklin, Donald; Price, Richard W.; Grant, Igor; Letendre, Scott L.; Gisslén, Magnus

2016-01-01

Objective Although milder forms of HIV-associated neurocognitive disorder (HAND) remain prevalent, a correlation to neuronal injury has not been established in patients on antiretroviral therapy (ART). We examined the relationship between mild HAND and CSF neurofilament light protein (NFL), a biomarker of neuronal injury; and CSF neopterin, a biomarker of CNS immunoactivation, in virally suppressed patients on antiretroviral therapy (ART). Design and Methods We selected 99 subjects on suppressive ART followed longitudinally from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Based on standardized comprehensive neurocognitive performance (NP) testing, subjects were classified as neurocognitively normal (NCN; n = 29) or impaired (NCI; n = 70). The NCI group included subjects with asymptomatic (ANI; n = 37) or mild (MND; n = 33) HAND. CSF biomarkers were analyzed on two occasions. Results Geometric mean CSF neopterin was 25% higher in the NCI group (p = 0.04) and NFL and neopterin were significantly correlated within the NCI group (r = 0.30; p<0.001) but not in the NCN group (r = -0.13; p = 0.3). Additionally, a trend towards higher NFL was seen in the NCI group (p = 0.06). Conclusions Mild HAND was associated with increased intrathecal immune activation, and the correlation between neopterin and NFL found in NCI subjects indicates an association between neurocognitive impairment, CNS inflammation and neuronal damage. Together these findings suggest that NCI despite ART may represent an active pathological process within the CNS that needs further characterization in prospective studies. PMID:27295036

Increased Intrathecal Immune Activation in Virally Suppressed HIV-1 Infected Patients with Neurocognitive Impairment.

PubMed

Edén, Arvid; Marcotte, Thomas D; Heaton, Robert K; Nilsson, Staffan; Zetterberg, Henrik; Fuchs, Dietmar; Franklin, Donald; Price, Richard W; Grant, Igor; Letendre, Scott L; Gisslén, Magnus

2016-01-01

Although milder forms of HIV-associated neurocognitive disorder (HAND) remain prevalent, a correlation to neuronal injury has not been established in patients on antiretroviral therapy (ART). We examined the relationship between mild HAND and CSF neurofilament light protein (NFL), a biomarker of neuronal injury; and CSF neopterin, a biomarker of CNS immunoactivation, in virally suppressed patients on antiretroviral therapy (ART). We selected 99 subjects on suppressive ART followed longitudinally from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Based on standardized comprehensive neurocognitive performance (NP) testing, subjects were classified as neurocognitively normal (NCN; n = 29) or impaired (NCI; n = 70). The NCI group included subjects with asymptomatic (ANI; n = 37) or mild (MND; n = 33) HAND. CSF biomarkers were analyzed on two occasions. Geometric mean CSF neopterin was 25% higher in the NCI group (p = 0.04) and NFL and neopterin were significantly correlated within the NCI group (r = 0.30; p<0.001) but not in the NCN group (r = -0.13; p = 0.3). Additionally, a trend towards higher NFL was seen in the NCI group (p = 0.06). Mild HAND was associated with increased intrathecal immune activation, and the correlation between neopterin and NFL found in NCI subjects indicates an association between neurocognitive impairment, CNS inflammation and neuronal damage. Together these findings suggest that NCI despite ART may represent an active pathological process within the CNS that needs further characterization in prospective studies.

The Microgravity Demonstrator

NASA Technical Reports Server (NTRS)

Rogers, Melissa J. B.; Wargo, Michael J.

1999-01-01

The Demonstrator is a tool to create microgravity conditions in your classroom. A series of demonstrations is used to provide a dramatically visual, physical connection between free-fall and microgravity conditions and to understand why various types of experiments are performed under microgravity conditions. A wealth of back-round material on free-fall, microgravity, and micro-gravity sciences is available in two educational documents available through the NASA Teacher Resource Centers: Microgravity-Activity Guide for Science, Mathematics, and Technology Education, and The Mathematics of Microgravity. The remainder of this manual is divided into five sections. The first explains how to put the Microgravity Demonstrator together. The next section introduces the individual demonstrations and discusses the underlying physical science concepts. Following that are detailed steps for conducting each demonstration to make your use of the Demonstrator most effective. Next are some ideas on how to make your own Microgravity Demonstrator. The last section is a tips and troubleshooting guide for video connections and operations. If you have one of the NASA Microgravity Demonstrators, this entire manual should be useful. If you have a copy of the Microgravity Demonstrator Videotape and would like to use that as a teaching tool, the Demonstrations and Scientific Background section of this manual will give you insight into the science areas studied in microgravity.

Mortality risk from comorbidities independent of triple-negative breast cancer status: NCI-SEER-based cohort analysis.

PubMed

Swede, Helen; Sarwar, Amna; Magge, Anil; Braithwaite, Dejana; Cook, Linda S; Gregorio, David I; Jones, Beth A; R Hoag, Jessica; Gonsalves, Lou; L Salner, Andrew; Zarfos, Kristen; Andemariam, Biree; Stevens, Richard G; G Dugan, Alicia; Pensa, Mellisa; A Brockmeyer, Jessica

2016-05-01

A comparatively high prevalence of comorbidities among African-American/Blacks (AA/B) has been implicated in disparate survival in breast cancer. There is a scarcity of data, however, if this effect persists when accounting for the adverse triple-negative breast cancer (TNBC) subtype which occurs at threefold the rate in AA/B compared to white breast cancer patients. We reviewed charts of 214 white and 202 AA/B breast cancer patients in the NCI-SEER Connecticut Tumor Registry who were diagnosed in 2000-2007. We employed the Charlson Co-Morbidity Index (CCI), a weighted 17-item tool to predict risk of death in cancer populations. Cox survival analyses estimated hazard ratios (HRs) for all-cause mortality in relation to TNBC and CCI adjusting for clinicopathological factors. Among patients with SEER local stage, TNBC increased the risk of death (HR 2.18, 95 % CI 1.14-4.16), which was attenuated when the CCI score was added to the model (Adj. HR 1.50, 95 % CI 0.74-3.01). Conversely, the adverse impact of the CCI score persisted when controlling for TNBC (Adj. HR 1.49, 95 % CI 1.29-1.71; per one point increase). Similar patterns were observed in SEER regional stage, but estimated HRs were lower. AA/B patients with a CCI score of ≥3 had a significantly higher risk of death compared to AA/B patients without comorbidities (Adj. HR 5.65, 95 % CI 2.90-11.02). A lower and nonsignificant effect was observed for whites with a CCI of ≥3 (Adj. HR 1.90, 95 % CI 0.68-5.29). comorbidities at diagnosis increase risk of death independent of TNBC, and AA/B patients may be disproportionately at risk.

CPTAC Releases Cancer Proteome Confirmatory Colon Study Data | Office of Cancer Clinical Proteomics Research

Cancer.gov

The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) announces the release of the cancer proteome confirmatory colon study data. The goal of the study is to analyze the proteomes of approximately 100 confirmatory colon tumor patients, which includes tumor and adjacent normal samples, with liquid chromatography-tandem mass spectrometry (LC-MS/MS) global proteomic and phosphoproteomic profiling.

A Chinaman's Chance in Civil Rights Demonstration: A Case Study.

ERIC Educational Resources Information Center

Sim, Yawsoon

A traffic incident in April of 1975 developed into an unprecedented civil rights demonstration by Chinese residents in New York City's Chinatown in May of that year. This paper attempts to trace the factors which led to this large scale demonstration and analyze the development of decision making in this case. The demonstration was the result of…

Cohesiveness in Financial News and its Relation to Market Volatility

PubMed Central

Piškorec, Matija; Antulov-Fantulin, Nino; Novak, Petra Kralj; Mozetič, Igor; Grčar, Miha; Vodenska, Irena; Šmuc, Tomislav

2014-01-01

Motivated by recent financial crises, significant research efforts have been put into studying contagion effects and herding behaviour in financial markets. Much less has been said regarding the influence of financial news on financial markets. We propose a novel measure of collective behaviour based on financial news on the Web, the News Cohesiveness Index (NCI), and we demonstrate that the index can be used as a financial market volatility indicator. We evaluate the NCI using financial documents from large Web news sources on a daily basis from October 2011 to July 2013 and analyse the interplay between financial markets and finance-related news. We hypothesise that strong cohesion in financial news reflects movements in the financial markets. Our results indicate that cohesiveness in financial news is highly correlated with and driven by volatility in financial markets. PMID:24849598

Cytotoxic effects of pyrrolidine dithiocarbamate in small-cell lung cancer cells, alone and in combination with cisplatin.

PubMed

Tahata, Shinichi; Yuan, Bo; Kikuchi, Hidetomo; Takagi, Norio; Hirano, Toshihiko; Toyoda, Hiroo

2014-10-01

The cytocidal effect of pyrrolidine dithiocarbamate (PDTC) was investigated by focusing on cell viability, cell cycle arrest and apoptosis induction in small-cell lung cancer (SCLC) cell lines (NCI-H196 and NCI-H889). PDTC exhibited a much stronger dose-dependent cytotoxic activity against NCI-H196 compared to NCI-H889, while no such activity was observed in normal human embryonal lung fibroblast MRC-5 cells. Cell cycle arrest in S phase paralleled with suppression of c-myc expression without accompanying DNA fragmentation was observed in NCI-H196 cells. A transient increase in the intracellular ROS accompanied with an alteration of expression of oxidative stress-related genes was also confirmed in NCI-H196 cells. Furthermore, the addition of N-acetyl-l-cysteine (NAC), a free radical scavenger, not only abolished PDTC-trigger alterations of expression of these oxidative-related genes, but also almost completely abrogated PDTC-induced reduction in cell viability and morphological changes associated with cell damage. These results thus suggest that PDTC-induced cytotoxicity is attributed to its pro-oxidant activity. PDTC-induced cytotoxicity was further enhanced by CuCl2, however, abolished by bathocuproine disulfonate (BCPS), a non-permeable copper-specific chelator, supporting the plausibility that accumulation of intracellular Cu plays an important role in the cytotoxicity. Importantly, we demonstrated for the first time that PDTC downregulated the expression of ATP7A, known to be responsible for Cu efflux, but did not affect the expression of CTR1, known as a copper uptake transporter. Intriguingly, combination of much lower dose of cisplatin (5 µM) and non-toxic dose of PDTC (0.1 µM) synergistically induced a significant cytotoxicity in NCI-H196 cells. Given that ATP7A plays a critical role in the resistance of platinum-drug (such as cisplatin) representing a first-line treatment for SCLC, PDTC could be a promising candidate of adjunct therapeutic reagent

Breast cancer in women aging 35 years old and younger: The Egyptian National Cancer Institute (NCI) experience.

PubMed

Darwish, A D; Helal, A M; Aly El-Din, N H; Solaiman, L L; Amin, A

2017-02-01

The aim is to identify the epidemiological and clinicopathological features associated with young breast cancer (BC) patients and to discuss factors affecting tumor recurrence and DFS. A retrospective analysis was conducted based on medical records from young females patients aged ≤35 years with pathologically confirmed primary breast cancer treated during 2008-2010 at NCI. Cases with non invasive cancer and non carcinoma histology are excluded. Of the 5408 cases diagnosed with breast cancer, 554 were young. Four hundred & fifty eight patients representing 9.2% were within our inclusion criteria. Almost half of the patients (45.9%) presented with stage III. Axillary nodes involvement was in 63.9%, 83.3% were grade 2. More than one quarter of tumors was hormone receptors negative (28.8%) & Her2 was over-expressed in 30%. Mastectomy was offered in 72% while conservative breast surgery in 26%, 69.2% received chemotherapy either adjuvant, neoadjuvant or both, 82.5% received adjuvant radiotherapy, 68.6% received hormonal therapy. Metastatic disease developed in 51.3%, with 31% having more than one site of metastases. After a median follow up period of 66 months, the median DFS of patients was 60 months. The median DFS was significantly shorter among patients with positive lymph nodes (P < 0.0001), ER negative disease (P = 0.045) and stage III disease (P < 0.0001). Breast cancer in young women is aggressive from the time of diagnosis. Our results provide baseline data of young BC in the Middle East & North Africa region; thus, contributing to future epidemiological and hospital-based researches. Copyright © 2016 Elsevier Ltd. All rights reserved.

Orbital construction demonstration study. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

1977-01-01

A conceptual design and program plan for an Orbital Construction Demonstration Article (OCDA), that can be used for technology growth and verification, and as the construction facility for a variety of large structures is presented. The OCDA design includes a large work platform, a rotating manipulator boom, a 250 kw solar array, and a core module of subsystems with a total mass of 37,093 kg, that can be assembled in three shuttle flights. An analysis of OCDA continued utility potential indicates that a shuttle tended platform with 250 kW of power can effectively be used to construct highly beneficial antenna systems and large demonstration articles that advance solar power satellite technologies. The construction of 100 m parabolic reflectors for use as a radiometer for measuring soil moisture and water salinity was found to be within the capabilities of OCDA concept. With 252 fixed beams for high population centers, and 16 scanning beams for rural areas, the antenna has the potential to significantly improve U.S. space based communications systems. The OCDA, that is slightly increased in size, was found adequate to build a large 2 MW solar array which, when coupled to a transmit antenna, demonstrate power transfer from space to ground.

[Study on secondary metabolites of marine fungus Penicillium sp. FS60 from the South China Sea].

PubMed

Zhang, Ling; Li, Dong-Li; Chen, Yu-Chan; Tao, Mei-Hua; Zhang, Wei-Min

2012-07-01

To study the secondary metabolites of the marine fungus Penicillium sp. FS60 from the South China Sea and their cytotoxicities. The compounds were isolated from the culture of strain FS60 by various chromatographic methods (silica gel, reverse silica gel, Sephadex-LH20, preparative TLC, HPLC and PTLC) and recrystallization. Their structures were identified by extensive analysis of their spectroscopic data. Compounds were tested for their cytotoxicities against SF-268, MCF-7, and NCI-H460 cell lines by SRB method. While, Compounds were tested for their antibacterial activities against S. aureus, E. coli and P. aeruginosa. Seven compounds were isolated from the culture and identified as methyl 2,4-dihydroxy-3,5,6-trimethylbenzoate (1), 4-hydroxyacetophenone (2), 5-hydroxymethyl-furoic acid (3), isochromophilones VIII (4), ergosterol (5), ergosterol peroxide (6), and cerevisterol (7). Compound 1 is isolated from the genus Penicillium for the first time. Compound 3 is demonstrated to have significant inhibition against S. aureus and P. aeruginosa. Compound 4 is demonstrated to have significant inhibition against the three cell lines.

Study Identifies New Lymphoma Treatment Target

Cancer.gov

NCI researchers have identified new therapeutic targets for diffuse large B-cell lymphoma. Drugs that hit these targets are under clinical development and the researchers hope to begin testing them in clinical trials of patients with DLBCL.

78 FR 56901 - Submission for OMB Review; 30-day Comment Request: Family Life, Activity, Sun, Health, and Eating...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-16

...; 30-day Comment Request: Family Life, Activity, Sun, Health, and Eating (FLASHE) Study (NCI) SUMMARY... expense and topic of the study. An email response was sent on July 8, 2013 stating ``Your comments will be taken into consideration. The Division of Cancer Prevention at the NCI supports research that studies...

Interaction Effects between HIV and Aging on Selective Neurocognitive Impairment.

PubMed

Ding, Yingying; Lin, Haijiang; Shen, Weiwei; Wu, Qionghai; Gao, Meiyang; He, Na

2017-12-01

HIV infection and aging are each associated with neurocognitive impairment (NCI). This study examined the combined effects of HIV infection and aging on NCI. We performed a cross-sectional survey among 345 HIV-infected and 345 HIV-uninfected participants aged at least 40 years. The International HIV Dementia Scale (IHDS) and Chinese version of Mini-mental State Examination (MMSE) were administered to screen for NCI. HIV-infected individuals had higher prevalence of NCI than uninfected individuals (46.7% vs 15.1% for IHDS using cut-off of ≤ 10; 17.1% vs 2.6% for MMSE). Significant main effects of HIV and age were observed on IHDS and MMSE composite scores and all domains except for HIV on attention and calculation. Significant interaction effects between HIV and age were observed on motor speed, orientation, registration and recall, and mainly attributed to the inferior performance of HIV-infected patients aged over 60 years. Among HIV-infected individuals, in multivariable logistic models, older age, depressive symptoms and history of nevirapine treatment were associated with NCI using both IHDS and MMSE, whereas lower education current smoker and current CD4 ≥ 800 cells/μL were associated only with NCI using IHDS, and hypertension was associated only with NCI using MMSE. Findings suggest that HIV and older age may confer interactive effects on cognitive function in several domains with older HIV-infected adults experiencing greater NCI, which requires further longitudinal investigation. Furthermore, HIV early diagnosis and treatment may prevent or reverse NCI, but extra attention should be given to adverse effects including metabolic changes associated with long-term treatment.

USFWS demonstration fees

USGS Publications Warehouse

Taylor, Jonathan; Vaske, Jerry; Donnelly, Maureen; Shelby, Lori

2002-01-01

This study examined National Wildlife Refuge (NWR) visitors' reactions to changes in fees implemented as part of the fee demonstration program. Visitors' evaluations of the fees paid were examined in addition to their beliefs about fees and the fee demonstration program, and the impact of fees paid on their intention to return. All results were analyzed relative to socio-demographic characteristics.

Separation and Analysis of Adherent and Non-Adherent Cancer Cells Using a Single-Cell Microarray Chip.

PubMed

Yamamura, Shohei; Yamada, Eriko; Kimura, Fukiko; Miyajima, Kumiko; Shigeto, Hajime

2017-10-21

A new single-cell microarray chip was designed and developed to separate and analyze single adherent and non-adherent cancer cells. The single-cell microarray chip is made of polystyrene with over 60,000 microchambers of 10 different size patterns (31-40 µm upper diameter, 11-20 µm lower diameter). A drop of suspension of adherent carcinoma (NCI-H1650) and non-adherent leukocyte (CCRF-CEM) cells was placed onto the chip, and single-cell occupancy of NCI-H1650 and CCRF-CEM was determined to be 79% and 84%, respectively. This was achieved by controlling the chip design and surface treatment. Analysis of protein expression in single NCI-H1650 and CCRF-CEM cells was performed on the single-cell microarray chip by multi-antibody staining. Additionally, with this system, we retrieved positive single cells from the microchambers by a micromanipulator. Thus, this system demonstrates the potential for easy and accurate separation and analysis of various types of single cells.

Fire vs. Metal: A Laboratory Study Demonstrating Microbial Responses to Soil Disturbances

ERIC Educational Resources Information Center

Stromberger, Mary E.

2005-01-01

Incubation studies are traditionally used in soil microbiology laboratory classes to demonstrate microbial respiration and N mineralization-immobilization processes. Sometimes these exercises are done to calculate a N balance in N fertilizer-amended soils. However, examining microbial responses to environmental perturbations would appeal to soil…

Assessing alcohol intake & its dose-dependent effects on liver enzymes by 24-h recall and questionnaire using NHANES 2001-2010 data

DOE PAGES

Agarwal, Sanjiv; Fulgoni, III, Victor L.; Lieberman, Harris R.

2016-06-22

Alcohol is a significant component of the diet with dose-dependent risks and benefits. High doses of alcohol damage the liver and early symptoms of liver disease include changes in routinely assessed liver enzymes. Less is known regarding the mechanisms responsible for the benefits of moderate alcohol consumption, including their effects on the liver. The objectives of this study were to examine alcohol’s dose-dependent effects on markers of liver function (alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), and bilirubin), as well as to compare the different methods of assessing alcohol intake using NHANES 2001–2010 adultmore » data (N =24,807). Three methods were used to estimate alcohol intake from all volunteers: 24-h recall; the National Cancer Institute (NCI) method of usual intake; and a specific alcohol intake questionnaire. Mean alcohol intake by 24-h recall, NCI method and questionnaire was 41.0 ± 0.8 g/d, 10.9 ± 0.2 g/d and 11.0 ± 0.2 g/d, respectively. Alcohol consumers had significantly lower levels of ALP and higher levels of AST, GGT and bilirubin compared to non-consumers (P < 0.01) and activities of ALT, AST, and GGT increased and of ALP decreased as alcohol intake increased, regardless of intake assessment method used. The most sensitive measure of alcohol consumption was GGT. Since alcohol had a graded linear effect on several liver enzymes, including at low and moderate doses, benefits as well as risks of alcohol intake may be related to liver function. In conclusion, since the NCI method and alcohol questionnaire yielded very similar alcohol intake estimates, this study cross-validated these methods and demonstrated the robustness of the NCI method for estimating intake of irregularly consumed foods.« less

Assessing alcohol intake & its dose-dependent effects on liver enzymes by 24-h recall and questionnaire using NHANES 2001-2010 data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agarwal, Sanjiv; Fulgoni, III, Victor L.; Lieberman, Harris R.

Alcohol is a significant component of the diet with dose-dependent risks and benefits. High doses of alcohol damage the liver and early symptoms of liver disease include changes in routinely assessed liver enzymes. Less is known regarding the mechanisms responsible for the benefits of moderate alcohol consumption, including their effects on the liver. The objectives of this study were to examine alcohol’s dose-dependent effects on markers of liver function (alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), and bilirubin), as well as to compare the different methods of assessing alcohol intake using NHANES 2001–2010 adultmore » data (N =24,807). Three methods were used to estimate alcohol intake from all volunteers: 24-h recall; the National Cancer Institute (NCI) method of usual intake; and a specific alcohol intake questionnaire. Mean alcohol intake by 24-h recall, NCI method and questionnaire was 41.0 ± 0.8 g/d, 10.9 ± 0.2 g/d and 11.0 ± 0.2 g/d, respectively. Alcohol consumers had significantly lower levels of ALP and higher levels of AST, GGT and bilirubin compared to non-consumers (P < 0.01) and activities of ALT, AST, and GGT increased and of ALP decreased as alcohol intake increased, regardless of intake assessment method used. The most sensitive measure of alcohol consumption was GGT. Since alcohol had a graded linear effect on several liver enzymes, including at low and moderate doses, benefits as well as risks of alcohol intake may be related to liver function. In conclusion, since the NCI method and alcohol questionnaire yielded very similar alcohol intake estimates, this study cross-validated these methods and demonstrated the robustness of the NCI method for estimating intake of irregularly consumed foods.« less

National Cancer Institute News

MedlinePlus

... Workshop NCI Annual Fact Book NCI Visuals Online Social Media @NCIMedia NCI YouTube Subscribe to NCI News Releases ... posts Subscribe Events Scientific Meetings and Lectures Conferences Social Media Events News Archive 2018 2017 2016 2015 2014 ...

A Correlational Study Examining Demonstrated Emotional Intelligence and Perceptions of School Climate

ERIC Educational Resources Information Center

Anderson, Chris James

2016-01-01

A quantitative study with a correlational design, this research investigated whether certified teachers' ratings of their school leader's demonstrated emotional intelligence behaviors correlated with the teacher's perceptions of school climate. A sample of 42 graduate and post baccalaureate students from a Mid-Atlantic region college accessed a…

78 FR 43215 - Submission for OMB review; 30-day Comment Request: The Agricultural Health Study: A Prospective...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-19

... Disease Among Men and Women in Agriculture (NCI) SUMMARY: Under the provisions of Section 3507(a)(1)(D) of... Among Men and Women in Agriculture, 0925-0406--REVISION--National Institute of Environmental Health... the ongoing Study of Biomarkers of Exposures and Effects in Agriculture (BEEA) as well as continue and...

CPTAC Releases Cancer Proteome Confirmatory Ovarian Study Data | Office of Cancer Clinical Proteomics Research

Cancer.gov

A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying diagnostics and therapies that will improve patients’ lives. Because a comprehensive molecular view of cancer is important for ultimately guiding treatment, the National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) has released the cancer proteome confirmatory ovarian study data sets.

NCORP Gets Underway

Cancer.gov

NCI has awarded 53 new 5-year grants to researchers across the country to conduct multi-site cancer clinical trials and cancer care delivery research studies in their communities. The grants are being awarded under the NCI Community Oncology Research Prog

Grants Process Overview

Cancer.gov

This infographic shows the steps in the National Institutes of Health and National Cancer Institute Grants Process. The graphic shows which steps are done by the Principle Investigator, Grantee Institution, and by NIH. The process is represented by a circular flow of steps. Starting from the top and reading clockwise: The Principle Investigator “Initiates Research Idea and Prepares Application” The Grantee Institution “Submits Application” NIH “NIH Center For Scientific Review, Assigns To NCI And To Study Section” NIH “Scientific Review Group (NCI OR CSR) Evaluates for Scientific Merit” NIH “National Cancer Advisory Board Recommends Action” NIH “NCI Evaluates Program Relevance And Need” NIH “NCI Makes Funding Selections And Issues Grant Awards” (NIH) NIH “NCI Monitors Programmatic and Business Management Performance of the Grant” The Grantee Institution “Manages Funds” The Principle Investigator “Conducts Research” Source: www.cancer.gov Icons made by Freepik from http://www.flaticon.com is licensed by CC BY3.0”

Cytomegalovirus-Specific CD4+ T-cell Responses and CMV-IgG Levels are associated with Neurocognitive Impairment in People Living with HIV.

PubMed

Ballegaard, Vibe; Pedersen, Karin Kaereby; Pedersen, Maria; Brændstrup, Peter; Kirkby, Nikolai; Buus, Anette Stryhn; Ryder, Lars P; Gerstoft, Jan; Nielsen, Susanne Dam

2018-05-30

Mechanisms leading to neurocognitive impairment (NCI) in people living with HIV (PLWHIV) on stable antiretroviral therapy (cART) remain unknown. We investigated the association between CMV immunity, HIV-specific variables and NCI in PLWHIV on stable cART and with low comorbidity. 52 PLWHIV on stable cART and 31 HIV-uninfected controls matched on age, gender, education and comorbidity were tested with a neurocognitive test-battery and CMV-immunoglobulin G (CMV-IgG) levels were measured. In PLWHIV, CMV-specific (CMV-pp65 and CMV-gB) CD4+ and CD8+ T-cell responses were measured using intracellular-cytokine-staining and flowcytometry. NCI was defined as a global-deficit-scale score (GDS-score) ≥ 0.5. GDS-scores and domain-specific-scores defined severity of NCI. Logistic and linear multivariate regression analyses were used. NCI was detected in 30.8% of PLWHIV, and HIV was associated with an adjusted odds ratio (aOR) of 5.18 (95%CI: 1.15; 23.41, p=0.033) for NCI. In PLWHIV, higher CMV-specific CD4+ T-cell responses increased the probability of NCI with an aOR of 1.68 (95%CI: 1.10; 2.57) for CMV-pp65 or an aOR of 3.73 (95%CI: 1.61; 16.98) for CMV-gB, respectively. Similar associations were not found with CMV-IgG or CMV-specific CD8+ T-cells, but when assessing severity of NCI, higher CMV-IgG (per 100 U/ml) was associated with worse GDS-scores (β=0.08 (0.01-0.16), p=0.044), specifically in the domain of speed of information processing (β=0.20 (0.04-0.36, p=0.019). PLWHIV had increased risk of NCI. Excess risk may be associated with CMV-specific CD4+ T-cell responses and CMV-IgG. Larger longitudinal studies investigating the impact of CMV immunity on risk of NCI are warranted.

Mortality Risk from Co-Morbidities independent of Triple-Negative Breast Cancer Status: NCI SEER-based Cohort Analysis

PubMed Central

Swede, Helen; Sarwar, Amna; Magge, Anil; Braithwaite, Dejana; Cook, Linda S.; Gregorio, David I.; Jones, Beth A; Hoag, Jessica; Gonsalves, Lou; Salner, Andrew; Zarfos, Kristen; Andemariam, Biree; Stevens, Richard G; Dugan, Alicia; Pensa, Mellisa; Brockmeyer, Jessica

2017-01-01

Purpose A comparatively high prevalence of co-morbidities among African-American/Blacks (AA/B) has been implicated in disparate survival in breast cancer. There is a scarcity of data, however, if this effect persists when accounting for the adverse triple-negative breast cancer (TNBC) subtype which occurs at three-fold the rate in AA/B compared to white breast cancer patients. Methods We reviewed charts of 214 white and 202 AA/B breast cancer patients in the NCI-SEER Connecticut Tumor Registry who were diagnosed in 2000-07. We employed the Charlson Co-Morbidity Index (CCI), a weighted 17-item tool to predict risk of death in cancer populations. Cox Survival Analyses estimated hazard ratios (HR) for all-cause mortality in relation to TNBC and CCI adjusting for clinicopathological factors. Results Among patients with SEER-Local Stage, TNBC increased the risk of death (HR=2.18, 95% CI 1.14-4.16), which was attenuated when the CCI score was added to the model (Adj. HR=1.50, 95% CI 0.74-3.01). Conversely, the adverse impact of the CCI score persisted when controlling for TNBC (Adj. HR=1.49, 95% CI 1.29-1.71; per one point increase). Similar patterns were observed in SEER-Regional Stage but estimated HRs were lower. AA/B patients with a CCI score of ≥3 had a significantly higher risk of death compared to AA/B patients without comorbidities (Adj. HR=5.65, 95% CI 2.90-11.02). A lower and non-significant effect was observed for whites with a CCI of ≥3 (Adj. HR=1.90, 95% CI 0.68-5.29). Conclusions Co-morbidities at diagnosis increase risk of death independent of TNBC, and AA/B patients may be disproportionately at risk. PMID:27000206

Strategies to improve success of pediatric cancer cooperative group quality of life studies: a report from the Children's Oncology Group.

PubMed

Whitlow, Puja G; Caparas, Mae; Cullen, Patricia; Trask, Christine; Schulte, Fiona; Embry, Leanne; Nagarajan, Rajaram; Johnston, Donna L; Sung, Lillian

2015-06-01

Quality of life (QoL) has been increasingly emphasized in National Cancer Institute (NCI)-sponsored multisite clinical trials. Little is known about the outcomes of these trials in pediatric cancer. Objectives were to describe the proportion of Children's Oncology Group (COG) QoL studies that successfully accrued subjects and were analyzed, presented or published. We conducted a survey to describe outcomes of COG QoL studies. We included studies that contained at least one QoL assessment and were closed to patient accrual at the time of survey dissemination. Respondents were the investigators most responsible for the QoL aim. Sixteen studies were included; response rate was 100%. Nine (56%) studies were embedded into a cancer treatment trial. Only 3 (19%) studies accrued their intended sample size. Seven (44%) studies were analyzed, 9 (56%) were presented, and 6 (38%) were published. NCI-sponsored pediatric QoL studies have high rates of failure to accrue. Many were not analyzed or disseminated. Using these data, strategies have been implemented to improve conduct in future trials. Monitoring of QoL studies is important to maximize the chances of study success.

A model for making project funding decisions at the National Cancer Institute.

PubMed

Hall, N G; Hershey, J C; Kessler, L G; Stotts, R C

1992-01-01

This paper describes the development of a model for making project funding decisions at The National Cancer Institute (NCI). The American Stop Smoking Intervention Study (ASSIST) is a multiple-year, multiple-site demonstration project, aimed at reducing smoking prevalence. The initial request for ASSIST proposals was answered by about twice as many states as could be funded. Scientific peer review of the proposals was the primary criterion used for funding decisions. However, a modified Delphi process made explicit several criteria of secondary importance. A structured questionnaire identified the relative importance of these secondary criteria, some of which we incorporated into a composite preference function. We modeled the proposal funding decision as a zero-one program, and adjusted the preference function and available budget parametrically to generate many suitable outcomes. The actual funding decision, identified by our model, offers significant advantages over manually generated solutions found by experts at NCI.

Realising the Benefits of Adopting and Adapting Existing CF Metadata Conventions to a Broader Range of Geoscience Data

NASA Astrophysics Data System (ADS)

Druken, K. A.; Trenham, C. E.; Wang, J.; Bastrakova, I.; Evans, B. J. K.; Wyborn, L. A.; Ip, A. I.; Poudjom Djomani, Y.

2016-12-01

The National Computational Infrastructure (NCI) hosts one of Australia's largest repositories (10+ PBytes) of research data, colocated with a petascale High Performance Computer and a highly integrated research cloud. Key to maximizing benefit of NCI's collections and computational capabilities is ensuring seamless interoperable access to these datasets. This presents considerable data management challenges across the diverse range of geoscience data; spanning disciplines where netCDF-CF is commonly utilized (e.g., climate, weather, remote-sensing), through to the geophysics and seismology fields that employ more traditional domain- and study-specific data formats. These data are stored in a variety of gridded, irregularly spaced (i.e., trajectories, point clouds, profiles), and raster image structures. They often have diverse coordinate projections and resolutions, thus complicating the task of comparison and inter-discipline analysis. Nevertheless, much can be learned from the netCDF-CF model that has long served the climate community, providing a common data structure for the atmospheric, ocean and cryospheric sciences. We are extending the application of the existing Climate and Forecast (CF) metadata conventions to NCI's broader geoscience data collections. We present simple implementations that can significantly improve interoperability of the research collections, particularly in the case of line survey data. NCI has developed a compliance checker to assist with the data quality across all hosted netCDF-CF collections. The tool is an extension to one of the main existing CF Convention checkers, that we have modified to incorporate the Attribute Convention for Data Discovery (ACDD) and ISO19115 standards, and to perform parallelised checks over collections of files, ensuring compliance and consistency across the NCI data collections as a whole. It is complemented by a checker that also verifies functionality against a range of scientific analysis, programming

Non-physics peer demonstrators in undergraduate laboratories: a study of students’ perceptions

NASA Astrophysics Data System (ADS)

Braun, Michael; Kirkup, Les

2016-01-01

Laboratory demonstrators play a crucial role in facilitating students’ learning in physics subjects. Inspired by the success of peer-led activities, we introduced peer demonstrators to support student learning in first-year physics subjects that enrol students not intending to major in physics. Surveys were administered to 1700 students over 4 years in four subjects to examine student perceptions of how demonstrators assisted them in the laboratory. Scores awarded to peer demonstrators by students were no lower than those awarded to demonstrators traditionally employed in the first year physics laboratory. These latter demonstrators were drawn mainly from the ranks of physics research students. The findings validate the recruitment of peer demonstrators and will be used to inform the recruitment and support programmes for laboratory demonstrators.

Sorafenib improved progression-free survival in desmoid tumor study

Cancer.gov

In an NCI-funded trial for patients with desmoid tumors or aggressive fibromatosis (DT/DF), rare sarcomas with limited treatment options, the drug sorafenib tosylate (Nexavar) extended progression-free survival compared with a placebo.

List of gene variants developed for cancer cells from nine tissue types

Cancer.gov

NCI scientists have developed a comprehensive list of genetic variants for each of the types of cells that comprise what is known as the NCI-60 cell line collection. This new list adds depth to the most frequently studied human tumor cell lines in cancer

A Case Study of Technical Assistance to Demonstration Programs for Young Handicapped Children. Part III.

ERIC Educational Resources Information Center

Behr, Shirley K.; And Others

The report describes the third and final year of a 3-year case study of the technical assistance process as implemented by the Technical Assistance Development System (TADS) for the staffs of two demonstration programs for preschool handicapped children and their families. Following a review of TADS and the two demonstration programs, the…

Helping Young Children Understand Graphs: A Demonstration Study.

ERIC Educational Resources Information Center

Freeland, Kent; Madden, Wendy

1990-01-01

Outlines a demonstration lesson showing third graders how to make and interpret graphs. Includes descriptions of purpose, vocabulary, and learning activities in which students graph numbers of students with dogs at home and analyze the contents of M&M candy packages by color. Argues process helps students understand large amounts of abstract…

Strategies to Improve Success of Pediatric Cancer Co-operative Group Quality of Life Studies: A Report from the Children’s Oncology Group

PubMed Central

Whitlow, Puja G.; Caparas, Mae; Cullen, Patricia; Trask, Christine; Schulte, Fiona; Embry, Leanne; Nagarajan, Rajaram; Johnston, Donna L.; Sung, Lillian

2015-01-01

Purpose Quality of life (QoL) has been increasingly emphasized in National Cancer Institute (NCI) sponsored multi-site clinical trials. Little is known about the outcomes of these trials in pediatric cancer. Objectives were to describe the proportion of Children’s Oncology Group (COG) QoL studies that successfully accrued subjects and were analyzed, presented or published. Methods We conducted a survey to describe outcomes of COG QoL studies. We included studies that contained at least one QoL assessment and were closed to patient accrual at the time of survey dissemination. Respondents were the investigators most responsible for the QoL aim. Results Sixteen studies were included; response rate was 100%. Nine (56%) studies were embedded into a cancer treatment trial. Only 3 (19%) studies accrued their intended sample size. Seven (44%) studies were analyzed, 9 (56%) were presented and 6 (38%) were published. Conclusions NCI-sponsored pediatric QoL studies have high rates of failure to accrue. Many were not analyzed or disseminated. Using this data, strategies have been implemented to improve conduct in future trials. Monitoring of QoL studies is important to maximize the chances of study success. PMID:25429821

Structural and reliability analysis of a patient satisfaction with cancer-related care measure: a multisite patient navigation research program study.

PubMed

Jean-Pierre, Pascal; Fiscella, Kevin; Freund, Karen M; Clark, Jack; Darnell, Julie; Holden, Alan; Post, Douglas; Patierno, Steven R; Winters, Paul C

2011-02-15

Patient satisfaction is an important outcome measure of quality of cancer care and 1 of the 4 core study outcomes of the National Cancer Institute (NCI)-sponsored Patient Navigation Research Program to reduce race/ethnicity-based disparities in cancer care. There is no existing patient satisfaction measure that spans the spectrum of cancer-related care. The objective of this study was to develop a Patient Satisfaction With Cancer Care measure that is relevant to patients receiving diagnostic/therapeutic cancer-related care. The authors developed a conceptual framework, an operational definition of Patient Satisfaction With Cancer Care, and an item pool based on literature review, expert feedback, group discussion, and consensus. The 35-item Patient Satisfaction With Cancer Care measure was administered to 891 participants from the multisite NCI-sponsored Patient Navigation Research Program. Principal components analysis (PCA) was conducted for latent structure analysis. Internal consistency was assessed using Cronbach coefficient alpha (α). Divergent analysis was performed using correlation analyses between the Patient Satisfaction With Cancer Care, the Communication and Attitudinal Self-Efficacy-Cancer, and demographic variables. The PCA revealed a 1-dimensional measure with items forming a coherent set explaining 62% of the variance in patient satisfaction. Reliability assessment revealed high internal consistency (α ranging from 0.95 to 0.96). The Patient Satisfaction With Cancer Care demonstrated good face validity, convergent validity, and divergent validity, as indicated by moderate correlations with subscales of the Communication and Attitudinal Self-Efficacy-Cancer (all P < .01) and nonsignificant correlations with age, primary language, marital status, and scores on the Rapid Estimate of Adult Literacy in Medicine Long Form (all P > .05). The Patient Satisfaction With Cancer Care is a valid tool for assessing satisfaction with cancer-related care for

A design study for a medium-scale field demonstration of the viscous barrier technology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moridis, G.; Yen, P.; Persoff, P.

1996-09-01

This report is the design study for a medium-scale field demonstration of Lawrence Berkeley National Laboratory`s new subsurface containment technology for waste isolation using a new generation of barrier liquids. The test site is located in central California in a quarry owned by the Los Banos Gravel Company in Los Banos, California, in heterogeneous unsaturated deposits of sand, silt, and -ravel typical of many of the and DOE cleanup sites and particularly analogous to the Hanford site. The coals of the field demonstration are (a) to demonstrate the ability to create a continuous subsurface barrier isolating a medium-scale volume (30more » ft long by 30 ft wide by 20 ft deep, i.e. 1/10th to 1/8th the size of a buried tank at the Hanford Reservation) in the subsurface, and (b) to demonstrate the continuity, performance, and integrity of the barrier.« less

New Round of Studies Begin in Phase 0/I/II Cancer Prevention Clinical Trials Program | Division of Cancer Prevention

Cancer.gov

The NCI Division of Cancer Prevention’s Phase 0/I/II Cancer Prevention Clinical Trials Program, also known as the Consortia for Early Phase Prevention Trials, is beginning a new round of studies in the effort toward systematic early clinical development of promising preventive agents for people at increased risk of developing cancer. |

75 FR 63833 - Proposed Collection; Comment Request; the NIH-American Association for Retired Persons (AARP...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-18

... information technology. FOR FURTHER INFORMATION CONTACT: To request more information on the proposed project... Interview by Computer Study (iCLIC) (NCI) SUMMARY: In compliance with the requirement of Section 3506(c)(2... collection projects, the National Cancer Institute (NCI), the National Institutes of Health (NIH) will...

CPTAC Releases Cancer Proteome Confirmatory Breast Study Data | Office of Cancer Clinical Proteomics Research

Cancer.gov

An estimated 252,710 new cases of female breast cancer, accounting for 15% of all new cancer cases, occurred in 2017. To better understand proteogenomic abnormalities in breast cancer, the National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) announces the release of the cancer proteome confirmatory breast study data. The goal of the study was to comprehensively characterize the proteome and phosphoproteome on approximately 100 prospectively collected breast tumor and adjacent normal tissues.

NCI study shows feasibility of cancer screening protocol for high-risk population

Cancer.gov

In a new study from the National Cancer Institute, researchers found a high prevalence of cancer at baseline screening in individuals with Li-Fraumeni syndrome, a rare inherited disorder that leads to a higher risk of developing certain cancers.

Cancer pharmacogenomics and pharmacoepidemiology: setting a research agenda to accelerate translation.

PubMed

Freedman, Andrew N; Sansbury, Leah B; Figg, William D; Potosky, Arnold L; Weiss Smith, Sheila R; Khoury, Muin J; Nelson, Stefanie A; Weinshilboum, Richard M; Ratain, Mark J; McLeod, Howard L; Epstein, Robert S; Ginsburg, Geoffrey S; Schilsky, Richard L; Liu, Geoffrey; Flockhart, David A; Ulrich, Cornelia M; Davis, Robert L; Lesko, Lawrence J; Zineh, Issam; Randhawa, Gurvaneet; Ambrosone, Christine B; Relling, Mary V; Rothman, Nat; Xie, Heng; Spitz, Margaret R; Ballard-Barbash, Rachel; Doroshow, James H; Minasian, Lori M

2010-11-17

Recent advances in genomic research have demonstrated a substantial role for genomic factors in predicting response to cancer therapies. Researchers in the fields of cancer pharmacogenomics and pharmacoepidemiology seek to understand why individuals respond differently to drug therapy, in terms of both adverse effects and treatment efficacy. To identify research priorities as well as the resources and infrastructure needed to advance these fields, the National Cancer Institute (NCI) sponsored a workshop titled "Cancer Pharmacogenomics: Setting a Research Agenda to Accelerate Translation" on July 21, 2009, in Bethesda, MD. In this commentary, we summarize and discuss five science-based recommendations and four infrastructure-based recommendations that were identified as a result of discussions held during this workshop. Key recommendations include 1) supporting the routine collection of germline and tumor biospecimens in NCI-sponsored clinical trials and in some observational and population-based studies; 2) incorporating pharmacogenomic markers into clinical trials; 3) addressing the ethical, legal, social, and biospecimen- and data-sharing implications of pharmacogenomic and pharmacoepidemiologic research; and 4) establishing partnerships across NCI, with other federal agencies, and with industry. Together, these recommendations will facilitate the discovery and validation of clinical, sociodemographic, lifestyle, and genomic markers related to cancer treatment response and adverse events, and they will improve both the speed and efficiency by which new pharmacogenomic and pharmacoepidemiologic information is translated into clinical practice.

Icotinib antagonizes ABCG2-mediated multidrug resistance, but not the pemetrexed resistance mediated by thymidylate synthase and ABCG2

PubMed Central

Shukla, Suneet; Zhang, Yun-Kai; Wang, Yi-Jun; Kathawala, Rishil J.; Robey, Robert W.; Zhang, Li; Yang, Dong-Hua; Talele, Tanaji T.; Bates, Susan E.; Ambudkar, Suresh V.; Chen, Zhe-Sheng

2014-01-01

ABCG2 is a potential biomarker causing multidrug resistance (MDR) in Non-Small Cell Lung Cancer (NSCLC). We conducted this study to investigate whether Icotinib, a small-molecule inhibitor of EGFR tyrosine kinase, could interact with ABCG2 transporter in NSCLC. Our results showed that Icotinib reversed ABCG2-mediated MDR by antagonizing the drug efflux function of ABCG2. Icotinib stimulated the ATPase activity in a concentration-dependent manner and inhibited the photolabeling of ABCG2 with [125I]-Iodoarylazidoprazosin, demonstrating that it interacts at the drug-binding pocket. Homology modeling predicted the binding conformation of Icotinib at Asn629 centroid-based grid of ABCG2. However, Icotinib at reversal concentration did not affect the expression levels of AKT and ABCG2. Furthermore, a combination of Icotinib and topotecan exhibited significant synergistic anticancer activity against NCI-H460/MX20 tumor xenografts. However, the inhibition of transport activity of ABCG2 was insufficient to overcome pemetrexed resistance in NCI-H460/MX20 cells, which was due to the co-upregulated thymidylate synthase (TS) and ABCG2 expression. This is the first report to show that the up-regulation of TS in ABCG2-overexpressing cell line NCI-H460/MX20 may play a role of resistance to pemetrexate. Our findings suggested different possible strategies of overcoming the resistance of topotecan and pemetrexed in the NSCLC patients. PMID:24980828

Icotinib antagonizes ABCG2-mediated multidrug resistance, but not the pemetrexed resistance mediated by thymidylate synthase and ABCG2.

PubMed

Wang, De-Shen; Patel, Atish; Shukla, Suneet; Zhang, Yun-Kai; Wang, Yi-Jun; Kathawala, Rishil J; Robey, Robert W; Zhang, Li; Yang, Dong-Hua; Talele, Tanaji T; Bates, Susan E; Ambudkar, Suresh V; Xu, Rui-Hua; Chen, Zhe-Sheng

2014-06-30

ABCG2 is a potential biomarker causing multidrug resistance (MDR) in Non-Small Cell Lung Cancer (NSCLC). We conducted this study to investigate whether Icotinib, a small-molecule inhibitor of EGFR tyrosine kinase, could interact with ABCG2 transporter in NSCLC. Our results showed that Icotinib reversed ABCG2-mediated MDR by antagonizing the drug efflux function of ABCG2. Icotinib stimulated the ATPase activity in a concentration-dependent manner and inhibited the photolabeling of ABCG2 with [125I]-Iodoarylazidoprazosin, demonstrating that it interacts at the drug-binding pocket. Homology modeling predicted the binding conformation of Icotinib at Asn629 centroid-based grid of ABCG2. However, Icotinib at reversal concentration did not affect the expression levels of AKT and ABCG2. Furthermore, a combination of Icotinib and topotecan exhibited significant synergistic anticancer activity against NCI-H460/MX20 tumor xenografts. However, the inhibition of transport activity of ABCG2 was insufficient to overcome pemetrexed resistance in NCI-H460/MX20 cells, which was due to the co-upregulated thymidylate synthase (TS) and ABCG2 expression. This is the first report to show that the up-regulation of TS in ABCG2-overexpressing cell line NCI-H460/MX20 may play a role of resistance to pemetrexate. Our findings suggested different possible strategies of overcoming the resistance of topotecan and pemetrexed in the NSCLC patients.

Tested Demonstrations.

ERIC Educational Resources Information Center

Gilbert, George L., Ed.

1988-01-01

Details three demonstrations for use in chemistry classrooms. Includes: "A Demonstration of Corrosion by Differential Aeration"; "A Simple Demonstration of the Activation Energy Concept"; and "A Boiling Demonstration at Room Temperature." Each description includes equipment, materials, and methods. (CW)

Design of Phase I Combination Trials: Recommendations of the Clinical Trial Design Task Force of the NCI Investigational Drug Steering Committee

PubMed Central

Paller, Channing J.; Bradbury, Penelope A.; Ivy, S. Percy; Seymour, Lesley; LoRusso, Patricia M.; Baker, Laurence; Rubinstein, Larry; Huang, Erich; Collyar, Deborah; Groshen, Susan; Reeves, Steven; Ellis, Lee M.; Sargent, Daniel J.; Rosner, Gary L.; LeBlanc, Michael L.; Ratain, Mark J.

2014-01-01

Anticancer drugs are combined in an effort to treat a heterogeneous tumor or to maximize the pharmacodynamic effect. The development of combination regimens, while desirable, poses unique challenges. These include the selection of agents for combination therapy that may lead to improved efficacy while maintaining acceptable toxicity, the design of clinical trials that provide informative results for individual agents and combinations, and logistical and regulatory challenges. The phase 1 trial is often the initial step in the clinical evaluation of a combination regimen. In view of the importance of combination regimens and the challenges associated with developing them, the Clinical Trial Design (CTD) Task Force of the National Cancer Institute (NCI) Investigational Drug Steering Committee developed a set of recommendations for the phase 1 development of a combination regimen. The first two recommendations focus on the scientific rationale and development plans for the combination regimen; subsequent recommendations encompass clinical design aspects. The CTD Task Force recommends that selection of the proposed regimens be based on a biological or pharmacological rationale supported by clinical and/or robust and validated preclinical evidence, and accompanied by a plan for subsequent development of the combination. The design of the phase 1 clinical trial should take into consideration the potential pharmacokinetic and pharmacodynamic interactions as well as overlapping toxicity. Depending on the specific hypothesized interaction, the primary endpoint may be dose optimization, pharmacokinetics, and/or pharmacodynamic (i.e., biomarker). PMID:25125258

Cancer communication science funding trends, 2000-2012.

PubMed

Ramírez, A Susana; Galica, Kasia; Blake, Kelly D; Chou, Wen-Ying Sylvia; Hesse, Bradford W

2013-12-01

Since 2000, the field of health communication has grown tremendously, owing largely to research funding by the National Cancer Institute (NCI). This study provides an overview of cancer communication science funding trends in the past decade. We conducted an analysis of communication-related grant applications submitted to the NCI in fiscal years 2000-2012. Using 103 keywords related to health communication, data were extracted from the Portfolio Management Application, a grants management application used at NCI. Automated coding described key grant characteristics such as mechanism and review study section. Manual coding determined funding across the cancer control continuum, by cancer site, and by cancer risk factors. A total of 3307 unique grant applications met initial inclusion criteria; 1013 of these were funded over the 12-year period. The top funded grant mechanisms were the R01, R21, and R03. Applications were largely investigator-initiated proposals as opposed to responses to particular funding opportunity announcements. Among funded communication research, the top risk factor being studied was tobacco, and across the cancer control continuum, cancer prevention was the most common stage investigated. NCI support of cancer communication research has been an important source of growth for health communication science over the last 12 years. The analysis' findings describe NCI's priorities in cancer communication science and suggest areas for future investments.

Evaluation of the anti-adhesive effect of milk fat globule membrane glycoproteins on Helicobacter pylori in the human NCI-N87 cell line and C57BL/6 mouse model.

PubMed

Horemans, Tessa; Kerstens, Monique; Clais, Sofie; Struijs, Karin; van den Abbeele, Pieter; Van Assche, Tim; Maes, Louis; Cos, Paul

2012-08-01

 The interest in non-antibiotic therapies for Helicobacter pylori infections in man has considerably grown because increasing numbers of antibiotic-resistant strains are being reported. Intervention at the stage of bacterial attachment to the gastric mucosa could be an approach to improve the control/eradication rate of this infection.  Fractions of purified milk fat globule membrane glycoproteins were tested in vitro for their cytotoxic and direct antibacterial effect. The anti-adhesive effect on H. pylori was determined first in a cell model using the mucus-producing gastric epithelial cell line NCI-N87 and next in the C57BL/6 mouse model after dosing at 400 mg/kg protein once or twice daily from day -2 to day 4 post-infection. Bacterial loads were determined by using quantitative real-time PCR and the standard plate count method.  The milk fat globule membrane fractions did not show in vitro cytotoxicity, and a marginal antibacterial effect was demonstrated for defatted milk fat globule membrane at 256 μg/mL. In the anti-adhesion assay, the results varied from 56.0 ± 5.3% inhibition for 0.3% crude milk fat globule membrane to 79.3 ± 3.5% for defatted milk fat globule membrane. Quite surprisingly, in vivo administration of the same milk fat globule membrane fractions did not confirm the anti-adhesive effects and even caused an increase in bacterial load in the stomach.  The promising anti-adhesion in vitro results could not be confirmed in the mouse model, even after the highest attainable exposure. It is concluded that raw or defatted milk fat globule membrane fractions do not have any prophylactic or therapeutic potential against Helicobacter infection. © 2012 Blackwell Publishing Ltd.

Tested Demonstrations

ERIC Educational Resources Information Center

Gilbert, George L., Ed.

1977-01-01

Three demonstrations are described: paramagnetic properties of Fe(11) and Fe(111), the preparation of polyurethane foam: a lecture demonstration and the electrolysis of water-fuel cell reactions. A small discussion of the concepts demonstrated is included in each demonstration's description. (MR)

Diarachidonoylphosphoethanolamine induces apoptosis of malignant pleural mesothelioma cells through a Trx/ASK1/p38 MAPK pathway.

PubMed

Tsuchiya, Ayako; Kaku, Yoshiko; Nakano, Takashi; Nishizaki, Tomoyuki

2015-11-01

1,2-Diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE) induces both necrosis/necroptosis and apoptosis of NCI-H28 malignant pleural mesothelioma (MPM) cells. The present study was conducted to understand the mechanism for DAPE-induced apoptosis of NCI-H28 cells. DAPE induced caspase-independent apoptosis of NCI-H28 malignant pleural mesothelioma (MPM) cells, and the effect of DAPE was prevented by antioxidants or an inhibitor of NADPH oxidase (NOX). DAPE generated reactive oxygen species (ROS) and inhibited activity of thioredoxin (Trx) reductase (TrxR). DAPE decreased an association of apoptosis signal-regulating kinase 1 (ASK1) with thioredoxin (Trx), thereby releasing ASK1. DAPE activated p38 mitogen-activated protein kinase (MAPK), which was inhibited by an antioxidant or knocking-down ASK1. In addition, DAPE-induced NCI-H28 cell death was also prevented by knocking-down ASK1. Taken together, the results of the present study indicate that DAPE stimulates NOX-mediated ROS production and suppresses TrxR activity, resulting in the decrease of reduced Trx and the dissociation of ASK1 from a complex with Trx, allowing sequential activation of ASK1 and p38 MAPK, to induce apoptosis of NCI-H28 MPM cells. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Modulators of sensitivity and resistance to inhibition of PI3K identified in a pharmacogenomic screen of the NCI-60 human tumor cell line collection.

PubMed

Kwei, Kevin A; Baker, Joffre B; Pelham, Robert J

2012-01-01

The phosphoinositide 3-kinase (PI3K) signaling pathway is significantly altered in a wide variety of human cancers, driving cancer cell growth and survival. Consequently, a large number of PI3K inhibitors are now in clinical development. To begin to improve the selection of patients for treatment with PI3K inhibitors and to identify de novo determinants of patient response, we sought to identify and characterize candidate genomic and phosphoproteomic biomarkers predictive of response to the selective PI3K inhibitor, GDC-0941, using the NCI-60 human tumor cell line collection. In this study, sixty diverse tumor cell lines were exposed to GDC-0941 and classified by GI(50) value as sensitive or resistant. The most sensitive and resistant cell lines were analyzed for their baseline levels of gene expression and phosphorylation of key signaling nodes. Phosphorylation or activation status of both the PI3K-Akt signaling axis and PARP were correlated with in vitro response to GDC-0941. A gene expression signature associated with in vitro sensitivity to GDC-0941 was also identified. Furthermore, in vitro siRNA-mediated silencing of two genes in this signature, OGT and DDN, validated their role in modulating sensitivity to GDC-0941 in numerous cell lines and begins to provide biological insights into their role as chemosensitizers. These candidate biomarkers will offer useful tools to begin a more thorough understanding of determinants of patient response to PI3K inhibitors and merit exploration in human cancer patients treated with PI3K inhibitors.

Modulators of Sensitivity and Resistance to Inhibition of PI3K Identified in a Pharmacogenomic Screen of the NCI-60 Human Tumor Cell Line Collection

PubMed Central

Kwei, Kevin A.; Baker, Joffre B.; Pelham, Robert J.

2012-01-01

The phosphoinositide 3-kinase (PI3K) signaling pathway is significantly altered in a wide variety of human cancers, driving cancer cell growth and survival. Consequently, a large number of PI3K inhibitors are now in clinical development. To begin to improve the selection of patients for treatment with PI3K inhibitors and to identify de novo determinants of patient response, we sought to identify and characterize candidate genomic and phosphoproteomic biomarkers predictive of response to the selective PI3K inhibitor, GDC-0941, using the NCI-60 human tumor cell line collection. In this study, sixty diverse tumor cell lines were exposed to GDC-0941 and classified by GI50 value as sensitive or resistant. The most sensitive and resistant cell lines were analyzed for their baseline levels of gene expression and phosphorylation of key signaling nodes. Phosphorylation or activation status of both the PI3K-Akt signaling axis and PARP were correlated with in vitro response to GDC-0941. A gene expression signature associated with in vitro sensitivity to GDC-0941 was also identified. Furthermore, in vitro siRNA-mediated silencing of two genes in this signature, OGT and DDN, validated their role in modulating sensitivity to GDC-0941 in numerous cell lines and begins to provide biological insights into their role as chemosensitizers. These candidate biomarkers will offer useful tools to begin a more thorough understanding of determinants of patient response to PI3K inhibitors and merit exploration in human cancer patients treated with PI3K inhibitors. PMID:23029544

A Phase 2 Study of Flavopiridol (Alvocidib) in Combination with Docetaxel in Refractory, Metastatic Pancreatic Cancer (NCI#6366)

PubMed Central

Carvajal, Richard D.; Tse, Archie; Shah, Manish A.; Lefkowitz, Robert A.; Gonen, Mithat; Gilman-Rosen, Lisa; Kortmansky, Jeremy; Kelsen, David P.; Schwartz, Gary K.; O'Reilly, Eileen M.

2014-01-01

Background/Aims Pancreatic adenocarcinoma (PC) harbors frequent alterations of p16, resulting in cell cycle dysregulation. A phase I study of docetaxel and flavopiridol, a pan-cyclin dependent kinase inhibitor, demonstrated encouraging clinical activity in PC. This phase II study was designed to further define the efficacy and toxicity of this regimen in patients with previously treated PC. Methods Patients with gemcitabine-refractory, metastatic PC were treated with docetaxel 35 mg/m2 followed by flavopiridol 80 mg/m2 on days 1, 8, and 15 of a 28 day cycle. Tumor measurements were performed every two cycles. A Simon two-stage design was used to evaluate the primary endpoint of response. Results Ten patients were enrolled; nine were evaluable for response. No objective responses were observed; however, three patients (33%) achieved transient stable disease, with one of these patients achieving a 20% reduction in tumor size. Median survival was 4.2 months, with no patients alive at the time of analysis. Adverse events were significant, with seven patients (78%) requiring ≥1 dose reduction for transaminitis (11%), grade 4 neutropenia (33%), grade 3 fatigue (44%), and grade 3 diarrhea (22%) Conclusions The combination of flavopiridol and docetaxel has minimal activity and significant toxicity in this patient population. These results reflect the challenges of treating patients with PC in a second-line setting where the risk/benefit equation is tightly balanced. PMID:19451750

Decreased early mortality associated with the treatment of acute myeloid leukemia at National Cancer Institute-designated cancer centers in California.

PubMed

Ho, Gwendolyn; Wun, Ted; Muffly, Lori; Li, Qian; Brunson, Ann; Rosenberg, Aaron S; Jonas, Brian A; Keegan, Theresa H M

2018-05-01

To the authors' knowledge, few population-based studies to date have evaluated the association between location of care, complications with induction therapy, and early mortality in patients with acute myeloid leukemia (AML). Using linked data from the California Cancer Registry and Patient Discharge Dataset (1999-2014), the authors identified adult (aged ≥18 years) patients with AML who received inpatient treatment within 30 days of diagnosis. A propensity score was created for treatment at a National Cancer Institute-designated cancer center (NCI-CC). Inverse probability-weighted, multivariable logistic regression models were used to determine associations between location of care, complications, and early mortality (death ≤60 days from diagnosis). Of the 7007 patients with AML, 1762 (25%) were treated at an NCI-CC. Patients with AML who were treated at NCI-CCs were more likely to be aged ≤65 years, live in higher socioeconomic status neighborhoods, have fewer comorbidities, and have public health insurance. Patients treated at NCI-CCs had higher rates of renal failure (23% vs 20%; P = .010) and lower rates of respiratory failure (11% vs 14%; P = .003) and cardiac arrest (1% vs 2%; P = .014). After adjustment for baseline characteristics, treatment at an NCI-CC was associated with lower early mortality (odds ratio, 0.46; 95% confidence interval, 0.38-0.57). The impact of complications on early mortality did not differ by location of care except for higher early mortality noted among patients with respiratory failure treated at non-NCI-CCs. The initial treatment of adult patients with AML at NCI-CCs is associated with a 53% reduction in the odds of early mortality compared with treatment at non-NCI-CCs. Lower early mortality may result from differences in hospital or provider experience and supportive care. Cancer 2018;124:1938-45. © 2018 American Cancer Society. © 2018 American Cancer Society.

Controlling the numerical Cerenkov instability in PIC simulations using a customized finite difference Maxwell solver and a local FFT based current correction

DOE PAGES

Li, Fei; Yu, Peicheng; Xu, Xinlu; ...

2017-01-12

In this study we present a customized finite-difference-time-domain (FDTD) Maxwell solver for the particle-in-cell (PIC) algorithm. The solver is customized to effectively eliminate the numerical Cerenkov instability (NCI) which arises when a plasma (neutral or non-neutral) relativistically drifts on a grid when using the PIC algorithm. We control the EM dispersion curve in the direction of the plasma drift of a FDTD Maxwell solver by using a customized higher order finite difference operator for the spatial derivative along the direction of the drift (1ˆ direction). We show that this eliminates the main NCI modes with moderate |k 1|, while keepsmore » additional main NCI modes well outside the range of physical interest with higher |k 1|. These main NCI modes can be easily filtered out along with first spatial aliasing NCI modes which are also at the edge of the fundamental Brillouin zone. The customized solver has the possible advantage of improved parallel scalability because it can be easily partitioned along 1ˆ which typically has many more cells than other directions for the problems of interest. We show that FFTs can be performed locally to current on each partition to filter out the main and first spatial aliasing NCI modes, and to correct the current so that it satisfies the continuity equation for the customized spatial derivative. This ensures that Gauss’ Law is satisfied. Lastly, we present simulation examples of one relativistically drifting plasma, of two colliding relativistically drifting plasmas, and of nonlinear laser wakefield acceleration (LWFA) in a Lorentz boosted frame that show no evidence of the NCI can be observed when using this customized Maxwell solver together with its NCI elimination scheme.« less

Controlling the numerical Cerenkov instability in PIC simulations using a customized finite difference Maxwell solver and a local FFT based current correction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Fei; Yu, Peicheng; Xu, Xinlu

In this study we present a customized finite-difference-time-domain (FDTD) Maxwell solver for the particle-in-cell (PIC) algorithm. The solver is customized to effectively eliminate the numerical Cerenkov instability (NCI) which arises when a plasma (neutral or non-neutral) relativistically drifts on a grid when using the PIC algorithm. We control the EM dispersion curve in the direction of the plasma drift of a FDTD Maxwell solver by using a customized higher order finite difference operator for the spatial derivative along the direction of the drift (1ˆ direction). We show that this eliminates the main NCI modes with moderate |k 1|, while keepsmore » additional main NCI modes well outside the range of physical interest with higher |k 1|. These main NCI modes can be easily filtered out along with first spatial aliasing NCI modes which are also at the edge of the fundamental Brillouin zone. The customized solver has the possible advantage of improved parallel scalability because it can be easily partitioned along 1ˆ which typically has many more cells than other directions for the problems of interest. We show that FFTs can be performed locally to current on each partition to filter out the main and first spatial aliasing NCI modes, and to correct the current so that it satisfies the continuity equation for the customized spatial derivative. This ensures that Gauss’ Law is satisfied. Lastly, we present simulation examples of one relativistically drifting plasma, of two colliding relativistically drifting plasmas, and of nonlinear laser wakefield acceleration (LWFA) in a Lorentz boosted frame that show no evidence of the NCI can be observed when using this customized Maxwell solver together with its NCI elimination scheme.« less

Effects of guanyl nucleotides on CCKB receptor binding in brain tissue and continuous cell lines: a comparative study.

PubMed

Kaufmann, R; Schöneberg, T; Henklein, P; Meyer, R; Martin, H; Ott, T

1995-07-01

The effects of non-hydrolyzable guanyl nucleotide analogue GTP-gamma S on CCKB receptor binding in human and guinea-pig cortex, Jurkat T-cells, rat pituitary GH3 cells, rat glioma C6 cells and human small cell lung cancer NCI-H69 cells were investigated by using [3H]CCK-8S saturation and competition binding studies. GTP-gamma S caused inhibition of specific [3H]CCK-8S binding in a concentration dependent manner with a plateau at 10-25 microM. 25 microM GTP-gamma S resulted in a small but significant increase in Kd and IC50 values with amount very similar in all CCKB receptor models tested. However, the maximal number of specific [3H]CCK-8S binding sites (Bmax) was unaffected. Results suggest that CCKB receptors are G-protein coupled in a similar way to human and guinea-pig cortex, Jurkat cells, GH3 cells, C6 cells and NCI-H69 cells.

Evaluation of an exposure assessment used in epidemiological studies of diesel exhaust and lung cancer in underground mines

PubMed Central

Crump, Kenny; Van Landingham, Cynthia

2012-01-01

NIOSH/NCI (National Institute of Occupational Safety and Health and National Cancer Institute) developed exposure estimates for respirable elemental carbon (REC) as a surrogate for exposure to diesel exhaust (DE) for different jobs in eight underground mines by year beginning in the 1940s—1960s when diesel equipment was first introduced into these mines. These estimates played a key role in subsequent epidemiological analyses of the potential relationship between exposure to DE and lung cancer conducted in these mines. We report here on a reanalysis of some of the data from this exposure assessment. Because samples of REC were limited primarily to 1998–2001, NIOSH/NCI used carbon monoxide (CO) as a surrogate for REC. In addition, because CO samples were limited, particularly in the earlier years, they used the ratio of diesel horsepower (HP) to the mine air exhaust rate as a surrogate for CO. There are considerable uncertainties connected with each of these surrogate-based steps. The estimates of HP appear to involve considerable uncertainty, although we had no data upon which to evaluate the magnitude of this uncertainty. A sizable percentage (45%) of the CO samples used in the HP to CO model was below the detection limit which required NIOSH/NCI to assign CO values to these samples. In their preferred REC estimates, NIOSH/NCI assumed a linear relation between C0 and REC, although they provided no credible support for that assumption. Their assumption of a stable relationship between HP and CO also is questionable, and our reanalysis found a statistically significant relationship in only one-half of the mines. We re-estimated yearly REC exposures mainly using NIOSH/NCI methods but with some important differences: (i) rather than simply assuming a linear relationship, we used data from the mines to estimate the CO—REC relationship; (ii) we used a different method for assigning values to nondetect CO measurements; and (iii) we took account of statistical

IP and Data Access | Division of Cancer Prevention

Cancer.gov

The following outlines the different patent and licensing mechanisms applicable to studies of third-party agents in the PREVENT Program. Please note that the NCI has a variety of agreement mechanisms by which these terms may be applied and will work with the NCI Technology Transfer Center to determine the appropriate agreement for the studies approved by the PREVENT Program. |

Cryogenic Propellant Storage and Transfer Technology Demonstration: Prephase A Government Point-of-Departure Concept Study

NASA Technical Reports Server (NTRS)

Mulqueen, J. A.; Addona, B. M.; Gwaltney, D. A.; Holt, K. A.; Hopkins, R. C.; Matis, J. A.; McRight, P. S.; Popp, C. G.; Sutherlin, S. G.; Thomas, H. D.;

Minority Use of a National Cancer Institute-Designated Comprehensive Cancer Center and Non-specialty Hospitals in Two Florida Regions.

PubMed

Sultan, Dawood H; Gishe, Jemal; Hanciles, Angella; Comins, Meg M; Norris, Claire M

2015-09-01

To examine cancer treatment disparities at a National Cancer Institute-designated comprehensive cancer center (NCI-CCC) and non-specialty hospitals. Florida hospital discharge datasets were used. ICD9-CM codes were used to define patients with female reproductive organ cancers (FROC), male reproductive organ cancers (MROC), and OTHER cancer diagnoses. A total of 7462 NCI-CCC patients and 21,875 non-specialty hospital patients were included in the statistical analysis. Data analysis was conducted in SAS 9.2. Increases in age reduced the odds of receiving treatment at the NCI-CCC. Male patients were more likely than female patients to be treated at the NCI-CCC. Age-adjusted odds of African American and Hispanic out/inpatients being treated at the NCI-CCC were significantly lower than those of White out/inpatients. Only patients with workers' compensation, charity, or other insurance had higher odds of being treated at the NCI-CCC. The odds of minority patients receiving outpatient treatment at the NCI-CCC declined after 2005. The odds of receiving inpatient treatment at the NCI-CCC significantly increased after 2006. More targeted outreach by the NCI-CCC is required. However, we expect the creation of local Accountable Care Organizations (ACOs) to reduce the numbers of minority and older patients at the NCI-CCC. Coordinated quality care at ACOs implies a potential for retaining the patient market share held by non-specialty hospitals and a potential for increased demand for ACO care by minority and older patients.

Tobacco Use Behavior in Grades 5-12.

ERIC Educational Resources Information Center

Lynch, Daniel O.

This study examined the responses of 3,915 Oshkosh, Wisconsin students (in grades 5 through 12) to the National Cancer Institute's (NCI) standard form of common questions for school-based interventions. Also, a pilot questionnaire of knowledge, beliefs, and attitudes concerning and predicting tobacco use was administered. NCI findings indicated an…

Using discrepant events in science demonstrations to promote student engagement in scientific investigations: An action research study

NASA Astrophysics Data System (ADS)

Mancuso, Vincent J.

Students' scientific investigations have been identified in national standards and related reform documents as a critical component of students' learning experiences in school, yet it is not easy to implement them in science classrooms. Could science demonstrations help science teachers put this recommendation into practice? While demonstrations are a common practice in the science classroom and research has documented some positive effects in terms of student motivation and engagement from their use, the literature also shows that, as traditionally presented, science demonstrations do not always achieve their intended outcomes. This, in turn, suggested the value of investigating what design elements of demonstrations could be used to promote specific instructional goals. Employing action research as a methodology, the proposed study was developed to explore how science demonstrations can be designed so as to most effectively promote student engagement in scientific investigations. More specifically, I was interested in examining the effects of using a discrepant event as part of the demonstration, as a way to create cognitive conflict and, thus, increase interest and engagement. I also investigated the relative merit of the well-researched POE (Predict, Observe, Explain) design versus employing demonstrations that appear to the student to be unplanned (what I will refer to as NOE, or a Naturally Occurring Experience). This study was informed by Constructivism, Situated Cognition and Conceptual Change as theoretical frameworks. The project included the design, implementation and study of an intervention consisting of three instructional units designed to support students' learning of the concepts of density, molecular arrangement of gas particles, and cohesion, respectively. In each of these units, lasting a total of two 80-minute class periods, students were asked to design and conduct an investigation to gain a better understanding of the concept under study. In

Tested Demonstrations.

ERIC Educational Resources Information Center

Gilbert, George L., Ed.

1979-01-01

Presents two demonstrations which are intended for chemistry college students. These demonstrations are: (1) enhancement of concentration quenching by micelles; and (2) the thermite lecture demonstration. (HM)

Tested Demonstrations.

ERIC Educational Resources Information Center

Gilbert, George L., Ed.

1990-01-01

Three demonstrations (a mechanical model of chemical equilibrium, a demonstration of Raoult's Law, and a demonstration of permanganate reduction) are presented. Materials and procedures are detailed. (CW)

Tested Demonstrations.

ERIC Educational Resources Information Center

Gilbert, George L., Ed.

1984-01-01

Procedures for two demonstrations are presented. The first is a demonstration of chemiluminescence. The second is a demonstration using a secondary battery constructed from common household articles. (JN)

78 FR 105 - Proposed Collection; Comment Request (60-Day FRN); A Generic Submission for Formative Research...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-02

..., it is beneficial for NCI through its Office of Communications and Education (OCE), to pretest NCI... NCI's OCE also is responsible for the design, implementation, and evaluation of education programs...

Tested Demonstrations.

ERIC Educational Resources Information Center

Gilbert, George L., Ed.

1987-01-01

Presented are three demonstrations for chemical education. The activities include: (1) demonstration of vapor pressure; (2) a multicolored luminol-based chemiluminescence demonstration; and (3) a Charles's Law/Vapor pressure apparatus. (RH)

NCI CRCHD

Cancer.gov

The Center to Reduce Cancer Health Disparities (CRCHD) is central to NCI’s efforts to reduce the unequal burden of cancer in our society via basic and community research, as well as networks, and to train the next generation of competitive researchers from diverse populations in cancer and cancer health disparities research.

Fostering young children's interest in numeracy through demonstration of its value: the Footsteps Study

NASA Astrophysics Data System (ADS)

Colliver, Yeshe

2017-07-01

Children's early mathematical abilities are fundamental to their later academic achievement. An interest in mathematics in the early years is likely to establish a positive attitude to later mathematical learning, hopefully sustaining continued interest in mathematics and mathematical learning. Approaches to early mathematics teaching in the early years, however, are typically adult-initiated, which may fail to capture children's interest. Given the importance of children's motivation and sustained interest, the study described here strove to spark children's interests in mathematical problems in everyday life. The study sought to determine if children would incorporate more numeracy-related concepts into their free play if exposed to adult demonstrations of age-appropriate numeracy activities such as patterning. For at least 15 min three times weekly, participating children's parents and educators demonstrated numeracy problem-solving nearby, while children engaged in other activities. Demonstrations were thought to ascribe social value to the problem-solving activities. If children became interested in participating, adults told them to wait until the demonstrations finished, further indicating social value. Results show these children chose to play with numeracy-related activities in their free play time at preschool significantly more than children in a control group. These results suggest that seeking to foster children's interest in mathematics through child-initiated play, rather than prescribing adult-initiated mathematics activities, may be an important means of laying the foundation for lifelong mathematics learning. Ascribing social value to numeracy applications is proposed as a new approach to teaching mathematics in the early years.

Overhead Projector Demonstrations.

ERIC Educational Resources Information Center

Kolb, Doris, Ed.

1989-01-01

Described are three chemistry demonstrations: (1) a simple qualitative technique for taste pattern recognition in structure-activity relationships; (2) a microscale study of gaseous diffusion using bleach, HCl, ammonia, and phenolphthalein; and (3) the rotation of polarized light by stereoisomers of limonene. (MVL)

Tested Demonstrations.

ERIC Educational Resources Information Center

Gilbert, George L., Ed.

1981-01-01

Provides procedures for demonstrations: (1) the ferrioxalate actinometer, which demonstrates a photochemical reaction; and (2) the silver mirror, which demonstrates the reduction of a metal salt to the metal and/or the reducing power of sugars. (CS)

Study reveals potentially prognostic gene, metabolism changes in kidney cancers | Center for Cancer Research

Cancer.gov

The Cancer Genome Atlas Research Network investigators, including CCR scientists, identified genetic and metabolic pathway changes linked to reduced survival of patients within and across subtypes of renal cell carcinoma (RCC), a type of kidney cancer. The study, published April 5, 2018, in Cell Reports, is part of The Cancer Genome Atlas (TCGA) Program, a joint effort of the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI).

Fluorescent Probes of the Apoptolidins and their Utility in Cellular Localization Studies

PubMed Central

DeGuire, Sean M.; Earl, David C.; Du, Yu; Crews, Brenda A.; Jacobs, Aaron T.; Ustione, Alessandro; Daniel, Cristina; Chong, Katherine; Marnett, Lawrence J.; Piston, David W.; Bachmann, Brian O.; Sulikowski, Gary A.

2014-01-01

Apoptolidin A has been described as among the top 0.1% most cell selective cytotoxic agents to be evaluated in the NCI 60 cell line panel. The molecular structure of apoptolidin A consists of a 20-membered macrolide with mono- and disaccharide moieties located at C9 and C27, respectively. In contrast to apoptolidin A, the aglycone (apoptolidinone) shows no cytotoxicity (>10 μM) when evaluated against several tumor cell lines. Apoptolidin H, the C27 deglycosylated analog of apoptolidin A, was produced by targeted glycosyl transferase gene deletion and displayed sub-micromolar activity against H292 lung carcinoma cells. Selective esterification of the C2′ hydroxyl group of apoptolidins A and H with 5-azidopentanoic acid afforded azido functionalized derivatives of potency equal to their parent macrolide. Azido apoptolidins readily underwent strain-promoted alkyne azido cycloaddition (SPAAC) reactions to provide access to fluorescent and biotin functionalized probes. Microscopy studies demonstrate apoptolidins A and H localize in the mitochondria of H292 human lung carcinoma cells. PMID:25430909

Spacecraft servicing demonstration plan

NASA Technical Reports Server (NTRS)

Bergonz, F. H.; Bulboaca, M. A.; Derocher, W. L., Jr.

1984-01-01

A preliminary spacecraft servicing demonstration plan is prepared which leads to a fully verified operational on-orbit servicing system based on the module exchange, refueling, and resupply technologies. The resulting system can be applied at the space station, in low Earth orbit with an orbital maneuvering vehicle (OMV), or be carried with an OMV to geosynchronous orbit by an orbital transfer vehicle. The three phase plan includes ground demonstrations, cargo bay demonstrations, and free flight verifications. The plan emphasizes the exchange of multimission modular spacecraft (MMS) modules which involves space repairable satellites. Three servicer mechanism configurations are the engineering test unit, a protoflight quality unit, and two fully operational units that have been qualified and documented for use in free flight verification activity. The plan balances costs and risks by overlapping study phases, utilizing existing equipment for ground demonstrations, maximizing use of existing MMS equipment, and rental of a spacecraft bus.

Use of Interactive Lecture Demonstrations: A Ten Year Study

ERIC Educational Resources Information Center

Sharma, Manjula D.; Johnston, Ian D.; Johnston, Helen; Varvell, Kevin; Robertson, Gordon; Hopkins, Andrew; Stewart, Chris; Cooper, Ian; Thornton, Ronald

2010-01-01

The widely held constructivist view of learning advocates student engagement via interactivity. Within the physics education research community, several specific interactive strategies have been developed to enhance conceptual understanding. One such strategy, the Interactive Lecture Demonstration (ILD) is designed for large lecture classes and,…

Road surface erosion on the Jackson Demonstration State Forest: results of a pilot study

Treesearch

Brian Barrett; Rosemary Kosaka; David. Tomberlin

2012-01-01

This paper presents results of a 3 year pilot study of surface erosion on forest roads in the Jackson Demonstration State Forest in California’s coastal redwood region. Ten road segments representing a range of surface, grade, and ditch conditions were selected for the study. At each segment, settling basins with tipping buckets were installed to measure...

Tested Demonstrations.

ERIC Educational Resources Information Center

Gilbert, George L., Ed.

1985-01-01

List of materials needed, procedures used, and results obtained are provided for two demonstrations. The first is an inexpensive and quick method for demonstrating column chromatography of plant pigments of spinach extract. The second is a demonstration of cathodic protection by impressed current. (JN)

A Demonstration of Sample Segregation

ERIC Educational Resources Information Center

Fritz, Mark D.; Brumbach, Stephen B.; Hartman, JudithAnn R.

2005-01-01

The demonstration of sample segregation, which is simple, and visually compelling illustrates the importance of sample handling for students studying analytical chemistry and environmental chemistry. The mixture used in this demonstration has two components, which have big particle size, and different colors, which makes the segregation graphic.

Genome-wide identification of genetic determinants for the cytotoxicity of perifosine

PubMed Central

2008-01-01

Perifosine belongs to the class of alkylphospholipid analogues, which act primarily at the cell membrane, thereby targeting signal transduction pathways. In phase I/II clinical trials, perifosine has induced tumour regression and caused disease stabilisation in a variety of tumour types. The genetic determinants responsible for its cytotoxicity have not been comprehensively studied, however. We performed a genome-wide analysis to identify genes whose expression levels or genotypic variation were correlated with the cytotoxicity of perifosine, using public databases on the US National Cancer Institute (NCI)-60 human cancer cell lines. For demonstrating drug specificity, the NCI Standard Agent Database (including 171 drugs acting through a variety of mechanisms) was used as a control. We identified agents with similar cytotoxicity profiles to that of perifosine in compounds used in the NCI drug screen. Furthermore, Gene Ontology and pathway analyses were carried out on genes more likely to be perifosine specific. The results suggested that genes correlated with perifosine cytotoxicity are connected by certain known pathways that lead to the mitogen-activated protein kinase signalling pathway and apoptosis. Biological processes such as 'response to stress', 'inflammatory response' and 'ubiquitin cycle' were enriched among these genes. Three single nucleotide polymorphisms (SNPs) located in CACNA2DI and EXOC4 were found to be correlated with perifosine cytotoxicity. Our results provided a manageable list of genes whose expression levels or genotypic variation were strongly correlated with the cytotoxcity of perifosine. These genes could be targets for further studies using candidate-gene approaches. The results also provided insights into the pharmacodynamics of perifosine. PMID:19129090

Demonstrating Diffusion

ERIC Educational Resources Information Center

Foy, Barry G.

1977-01-01

Two demonstrations are described. Materials and instructions for demonstrating movement of molecules into cytoplasm using agar blocks, phenolphthalein, and sodium hydroxide are given. A simple method for demonstrating that the rate of diffusion of a gas is inversely proportional to its molecular weight is also presented. (AJ)

Tested Demonstrations.

ERIC Educational Resources Information Center

Gilbert, George L., Ed.

1987-01-01

Describes two classroom chemistry demonstrations which focus on the descriptive chemistry of bromine and iodine. Outlines the chemicals and equipment needed, experimental procedures, and discussion of one demonstration of the oxidation states of bromine and iodine, and another demonstration of the oxidation states of iodine. (TW)

Plasma dickkopf-related protein 1, an antagonist of the Wnt pathway, is associated with HIV-associated neurocognitive impairment.

PubMed

Yu, Chunjiang; Seaton, Melanie; Letendre, Scott; Heaton, Robert; Al-Harthi, Lena

2017-06-19

Dickkopf-related protein 1 (DKK1) is a soluble antagonist of the Wningless (Wnt) pathway. It binds to and sequesters low-density lipoprotein receptor-related proteins 5/6 away from Wnts. Because the Wnt pathway regulates synaptic transmission and plasticity, we hypothesized that increased DKK1 would increase the risk for neurocognitive impairment (NCI) in HIV-positive (HIV) individuals. We evaluated, here, the relationship between plasma DKK1 and global NCI. Plasma samples and data from 41 HIV to 42 HIV adults were obtained from the University of California, San Diego, California, USA. Concentrations of DKK1 and a comparator protein, monocyte chemoattractant protein-1 (MCP-1), were quantified in plasma by immunoassay. All study participants completed a standardized comprehensive neuropsychological test battery and their performance was summarized using the global deficit score method. A higher DKK1 level was associated with NCI among HIV participants (d = 0.63, P = 0.05), particularly among the 26 participants whose plasma HIV RNA level was suppressed (d = 0.74, P = 0.08). DKK1 level was not associated with NCI among HIV participants (P = 0.98). was not associated with NCI in either group. In HIV adults with suppressed plasma HIV RNA, a receiver operator characteristic curve identified that a DKK1 level of at least 735 pg/ml had a positive predictive value of 83.3% for a diagnosis of NCI. This association did not weaken after accounting for the effect of AIDS, nadir CD4 T-cell count, addictive drug use, or demographic characteristics. DKK1 is a specific biomarker for NCI in HIV adults, implicating the Wnt pathway in HIV neuropathogenesis.

News | Division of Cancer Prevention

Cancer.gov

News about scientific advances in cancer prevention, program activities, and new projects are included here in NCI press releases and fact sheets, articles from the NCI Cancer Bulletin, and Clinical Trial News from the NCI website.

Antitumor activity of the selective ALK inhibitor alectinib in models of intracranial metastases.

PubMed

Kodama, Tatsushi; Hasegawa, Masami; Takanashi, Kenji; Sakurai, Yuji; Kondoh, Osamu; Sakamoto, Hiroshi

2014-11-01

The clinical efficacy of the anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been demonstrated in ALK fusion-positive non-small cell lung cancer (NSCLC); however, brain metastases are frequent sites of initial failure in patients due to poor penetration of the central nervous system by crizotinib. Here, we examined the efficacy of a selective ALK inhibitor alectinib/CH5424802 in preclinical models of intracranial tumors. We established intracranial tumor implantation mouse models of EML4-ALK-positive NSCLC NCI-H2228 and examined the antitumor activity of alectinib in this model. Plasma distribution and brain distribution of alectinib were examined by quantitative whole-body autoradiography administrating a single oral dose of (14)C-labeled alectinib to rats. The drug permeability of alectinib was evaluated in Caco-2 cell. Alectinib resulted in regression of NCI-H2228 tumor in mouse brain and provided a survival benefit. In a pharmacokinetic study using rats, alectinib showed a high brain-to-plasma ratio, and in an in vitro drug permeability study using Caco-2 cells, alectinib was not transported by P-glycoprotein efflux transporter that is a key factor in blood-brain barrier penetration. We established intracranial tumor implantation models of EML4-ALK-positive NSCLC. Alectinib showed potent efficacy against intracranial EML4-ALK-positive tumor. These results demonstrated that alectinib might provide therapeutic opportunities for crizotinib-treated patients with brain metastases.

Favorite Demonstrations: Gaseous Diffusion: A Demonstration of Graham's Law.

ERIC Educational Resources Information Center

Kauffman, George B.; Ebner, Ronald D.

1985-01-01

Describes a demonstration in which gaseous ammonia and hydrochloric acid are used to illustrate rates of diffusion (Graham's Law). Simple equipment needed for the demonstration include a long tube, rubber stoppes, and cotton. Two related demonstrations are also explained. (DH)

Treatment Choices for Men with Early-Stage Prostate Cancer

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When Cancer Returns

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Thinking about Complementary and Alternative Medicine

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Children with Cancer: A Guide for Parents

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Coping with Advanced Cancer

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A Case Study of Technical Assistance to Demonstration Programs for Young Handicapped Children. Part I.

ERIC Educational Resources Information Center

Behr, Shirley K.; And Others

The interim report presents an evaluation of TADS (Technical Assistance Development System) through case studies of TADS technical assistance to the staffs of two demonstration programs for preschool handicapped children and their families. Purposes of the study included obtaining indepth descriptions of the technical assistance process to…

Postmastectomy radiation therapy for lymph node-negative, locally advanced breast cancer after modified radical mastectomy: analysis of the NCI Surveillance, Epidemiology, and End Results database.

PubMed

Yu, James B; Wilson, Lynn D; Dasgupta, Tina; Castrucci, William A; Weidhaas, Joanne B

2008-07-01

The role of postmastectomy radiotherapy (PMRT) for lymph node-negative locally advanced breast carcinoma (T3N0M0) after modified radical mastectomy (MRM) with regard to improvement in survival remains an area of controversy. The 1973-2004 National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) database was examined for patients with T3N0M0 ductal, lobular, or mixed ductal and lobular carcinoma of the breast who underwent MRM, treated from 1988-2003. Patients who were men, who had positive lymph nodes, who survived < or =6 months, for whom breast cancer was not the first malignancy, who had nonbeam radiation, intraoperative or preoperative radiation were excluded. The average treatment effect of PMRT on mortality was estimated with a propensity score case-matched analysis. In all, 1777 patients were identified; 568 (32%) patients received PMRT. Median tumor size was 6.3 cm. The median number of lymph nodes examined was 14 (range, 1-49). Propensity score matched case-control analysis showed no improvement in overall survival with the delivery of PMRT in this group. Older patients, patients with ER- disease (compared with ER+), and patients with high-grade tumors (compared with well differentiated) had increased mortality. The use of PMRT for T3N0M0 breast carcinoma after MRM is not associated with an increase in overall survival. It was not possible to analyze local control in this study given the limitations of the SEER database. The impact of potential improvement in local control as it relates to overall survival should be the subject of further investigation. (Copyright) 2008 American Cancer Society.

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.

Sponsoring Organization | Division of Cancer Prevention

Cancer.gov

The National Cancer Institute (NCI) project officers are responsible for the design and oversight of all aspects of the PLCO trial. These NCI components work directly with the Coordinating Center which provides support for development and implementation of the study protocol; and with the Principal Investigators from each of the Screening Centers to ensure that the technical

Tested Demonstrations.

ERIC Educational Resources Information Center

Sands, Robert; And Others

1982-01-01

Procedures for two demonstrations are provided. The solubility of ammonia gas in water is demonstrated by introducing water into a closed can filled with the gas, collapsing the can. The second demonstration relates scale of standard reduction potentials to observed behavior of metals in reactions with hydrogen to produce hydrogen gas. (Author/JN)

Health Marketing for the Massachusetts Childhood Obesity Research Demonstration Study: A Case Study.

PubMed

Criss, Shaniece; Blaine, Rachel E; Palamé, Megan; Perkins, Meghan; Davison, Kirsten; Kwass, Jo-Ann; Taveras, Elsie M

2018-03-01

This case study describes the Massachusetts Childhood Obesity Research Demonstration Study (MA-CORD) health marketing campaign, examines the strategies used in such campaigns, and offers lessons learned to improve health marketing for future interventions. MA-CORD Health Marketing Components and Implementation. The three main components were an outdoor printed advertisement and texting campaign, social media with a focus on Facebook, and the Summer Passport Program, an event-based initiative in parks for children. The advertisements consisted of billboards, bus advertisements, and handouts. The text messaging component, which required families to actively text a keyword to join, had a low opt-in rate. Facebook page "likes" increased from 1,024 to 1,453 in New Bedford and from 175 to 1,091 in Fitchburg. Fitchburg received technical assistance and paid for ads on Facebook. The Summer Passport participation in parks ranged from 120 to 875 children with participation in the free park lunch program doubling in Fitchburg. Key lessons learned are engage communication experts from each community at the beginning of the project, use text messaging components with in-person staff onsite to assist participants in the opt-in process, build momentum for a Facebook presence through purchasing Facebook advertisements, and partner with local park departments for programming.

Initial Development and Pilot Study Design of Interactive Lecture Demonstrations for ASTRO 101

NASA Astrophysics Data System (ADS)

Schwortz, Andria C.; French, D. A; Gutierrez, Joseph V; Sanchez, Richard L; Slater, Timothy F.; Tatge, Coty

2014-06-01

Interactive lecture demonstrations (ILDs) have repeatedly shown to be effective tools for improving student achievement in the context of learning physics. As a first step toward systematic development of interactive lecture demonstrations in ASTRO 101, the introductory astronomy survey course, a systematic review of education research, describing educational computer simulations (ECSs) reveals that initial development requires a targeted study of how ASTRO 101 students respond to ECSs in the non-science majoring undergraduate lecture setting. In this project we have adopted the process by which ILDs were designed, pilot-tested, and successfully implemented in the context of physics teaching (Sokoloff & Thornton, 1997; Sokoloff & Thornton, 2004). We have designed the initial pilot-test set of ASTRO 101 ILD instructional materials relying heavily on ECSs. Both an instructor’s manual and a preliminary classroom-ready student workbook have been developed, and we are implementing a pilot study to explore their effectiveness in communicating scientific content, and the extent to which they might enhance students’ knowledge of and perception about astronomy and science in general. The study design uses a pre-/post-test quasi-experimental study design measuring students’ normalized gain scores, calculated as per Hake (1998) and Prather (2009), using a slightly modified version of S. Slater’s (2011) Test Of Astronomy STandards TOAST combined with other instruments. The results of this initial study will guide the iterative development of ASTRO 101 ILDs that are intended to both be effective at enhancing student achievement and easy for instructors to successfully implement.

In vitro, in vivo and in silico analysis of the anticancer and estrogen-like activity of guava leaf extracts.

PubMed

Rizzo, L Y; Longato, G B; Ruiz, A Lt G; Tinti, S V; Possenti, A; Vendramini-Costa, D B; Sartoratto, A; Figueira, G M; Silva, F L N; Eberlin, M N; Souza, T A C B; Murakami, M T; Rizzo, E; Foglio, M A; Kiessling, F; Lammers, T; Carvalho, J E

2014-01-01

Anticancer drug research based on natural compounds enabled the discovery of many drugs currently used in cancer therapy. Here, we report the in vitro, in vivo and in silico anticancer and estrogen-like activity of Psidium guajava L. (guava) extracts and enriched mixture containing the meroterpenes guajadial, psidial A and psiguadial A and B. All samples were evaluated in vitro for anticancer activity against nine human cancer lines: K562 (leukemia), MCF7 (breast), NCI/ADR-RES (resistant ovarian cancer), NCI-H460 (lung), UACC-62 (melanoma), PC-3 (prostate), HT-29 (colon), OVCAR-3 (ovarian) and 786-0 (kidney). Psidium guajava's active compounds displayed similar physicochemical properties to estradiol and tamoxifen, as in silico molecular docking studies demonstrated that they fit into the estrogen receptors (ERs). The meroterpene-enriched fraction was also evaluated in vivo in a Solid Ehrlich murine breast adenocarcinoma model, and showed to be highly effective in inhibiting tumor growth, also demonstrating uterus increase in comparison to negative controls. The ability of guajadial, psidial A and psiguadials A and B to reduce tumor growth and stimulate uterus proliferation, as well as their in silico docking similarity to tamoxifen, suggest that these compounds may act as Selective Estrogen Receptors Modulators (SERMs), therefore holding significant potential for anticancer therapy.

The effects of desvenlafaxine on neurocognitive and work functioning in employed outpatients with major depressive disorder.

PubMed

Lam, Raymond W; Iverson, Grant L; Evans, Vanessa C; Yatham, Lakshmi N; Stewart, Kurtis; Tam, Edwin M; Axler, Auby; Woo, Cindy

2016-10-01

Major depressive disorder (MDD) is associated with staggering personal and economic costs, a major proportion of which stem from impaired psychosocial and occupational functioning. Few studies have examined the impact of depression-related cognitive dysfunction on work functioning. We examined the association between neurocognitive and work functioning in employed patients with MDD. Employed adult outpatients (n=36) with MDD of at least moderate severity (≥23 on the Montgomery Asberg Depression Rating Scale, MADRS) and subjective cognitive complaints completed neurocognitive tests (CNS Vital Signs computerized battery) and validated self-reports of their work functioning (LEAPS, HPQ) before and after 8 weeks of open-label treatment with flexibly-dosed desvenlafaxine 50-100mg/day. Relationships between neurocognitive tests and functional measures were examined using bivariate correlational and multiple regression analyses, as appropriate. An ANCOVA model examined whether significant change in neurocognitive performance, defined as improvement of ≥1SD in the Neurocognition Index (NCI) from baseline to post-treatment, was associated with improved outcomes. Patients showed significant improvements in depressive symptom, neurocognitive, and work functioning measures following treatment with desvenlafaxine (e.g., MADRS response=77% and MADRS remission=49%). There were no significant correlations between changes in NCI or cognitive domain subscales and changes in MADRS, LEAPS, or HPQ scores. However, patients demonstrating significant improvement in NCI scores (n=11, 29%) had significantly greater improvement in clinical and work functioning outcomes compared to those without NCI improvement. The limitations of this study include small sample size, lack of a placebo control group, and lack of a healthy comparison group. Our sample also had more years of education and higher premorbid intelligence than the general population. There were no significant correlations

Mutual influence between triel bond and cation-π interactions: an ab initio study

NASA Astrophysics Data System (ADS)

Esrafili, Mehdi D.; Mousavian, Parisasadat

2017-12-01

Using ab initio calculations, the cooperative and solvent effects on cation-π and B...N interactions are studied in some model ternary complexes, where these interactions coexist. The nature of the interactions and the mechanism of cooperativity are investigated by means of quantum theory of atoms in molecules (QTAIM), noncovalent interaction (NCI) index and natural bond orbital analysis. The results indicate that all cation-π and B...N binding distances in the ternary complexes are shorter than those of corresponding binary systems. The QTAIM analysis reveals that ternary complexes have higher electron density at their bond critical points relative to the corresponding binary complexes. In addition, according to the QTAIM analysis, the formation of cation-π interaction increases covalency of B...N bonds. The NCI analysis indicates that the cooperative effects in the ternary complexes make a shift in the location of the spike associated with each interaction, which can be regarded as an evidence for the reinforcement of both cation-π and B...N interactions in these systems. Solvent effects on the cooperativity of cation-π and B...N interactions are also investigated.

Demonstrating Empathy for Foreign-Born Employees through Openness and Acceptance: A Quasi-Experimental Field Study.

ERIC Educational Resources Information Center

Stull, James B.

1986-01-01

Reports on a study measuring foreign-born employees' perceptions of supervisors' acceptance of and openness to "open" messages from the employee. Suggests ways to improve supervisory demonstrations of empathy. (MS)

Indian Institute of Technology Bombay and Tata Memorial Centre Join the International Efforts in Clinical Proteogenomics Cancer Research | Office of Cancer Clinical Proteomics Research

Cancer.gov

The National Cancer Institute’s (NCI) Office of Cancer Clinical Proteomics Research, part of the National Institutes of Health, along with the Indian Institute of Technology Bombay (IITB) and Tata Memorial Centre (TMC) have signed a Memorandum of Understanding (MOU) on clinical proteogenomics cancer research. The MOU between NCI, IITB, and Tata Memorial Centre represents the thirtieth and thirty-first institutions and the twelfth country to join the International Cancer Proteogenome Consortium (ICPC). The purpose of the MOU is to facilitate scientific and programmatic collaborations between NCI, IITB, and TMC in basic and clinical proteogenomic studies leading to patient care and public dissemination and information sharing to the research community.

About OBF

Cancer.gov

The Office of Budget and Finance (OBF) advises the NCI Office of the Director and senior NCI staff on the effective management of financial and other resources to ensure that NCI operates in an efficient and fiscally responsible manner.

Cancer Information Summaries: Screening/Detection

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Pain Control: Support for People with Cancer

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Chemotherapy and You: Support for People with Cancer

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Caring for the Caregiver

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Facing Forward Series: Life After Cancer Treatment

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Radiation Therapy and You: Support for People with Cancer

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Eating Hints: Before, During, and After Cancer Treatment

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Taking Time: Support for People with Cancer

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Low prevalence of neurocognitive impairment in early diagnosed and managed HIV-infected persons

PubMed Central

Moore, David J.; Letendre, Scott; Poehlman Roediger, Mollie; Eberly, Lynn; Weintrob, Amy; Ganesan, Anuradha; Johnson, Erica; Del Rosario, Raechel; Agan, Brian K.; Hale, Braden R.

2013-01-01

Objective: To describe the prevalence of neurocognitive impairment (NCI) among early diagnosed and managed HIV-infected persons (HIV+) compared to HIV-negative controls. Methods: We performed a cross-sectional study among 200 HIV+ and 50 matched HIV-uninfected (HIV−) military beneficiaries. HIV+ patients were categorized as earlier (<6 years of HIV, no AIDS-defining conditions, and CD4 nadir >200 cells/mm3) or later stage patients (n = 100 in each group); both groups were diagnosed early and had access to care. NCI was diagnosed using a comprehensive battery of standardized neuropsychological tests. Results: HIV+ patients had a median age of 36 years, 91% were seroconverters (median window of 1.2 years), had a median duration of HIV of 5 years, had a CD4 nadir of 319, had current CD4 of 546 cells/mm3, and 64% were on highly active antiretroviral therapy (initiated 1.3 years after diagnosis at a median CD4 of 333 cells/mm3). NCI was diagnosed among 38 (19%, 95% confidence interval 14%–25%) HIV+ patients, with a similar prevalence of NCI among earlier and later stage patients (18% vs 20%, p = 0.72). The prevalence of NCI among HIV+ patients was similar to HIV− patients. Conclusions: HIV+ patients diagnosed and managed early during the course of HIV infection had a low prevalence of NCI, comparable to matched HIV-uninfected persons. Early recognition and management of HIV infection may be important in limiting neurocognitive impairment. PMID:23303852

The Altus Cumulus Electrification Study (ACES): A UAV-Based Science Demonstration

NASA Technical Reports Server (NTRS)

Blakeslee, R. J.; Croskey, C. L.; Desch, M. D.; Farrell, W. M.; Goldberg, R. A.; Houser, J. G.; Kim, H. S.; Mach, D. M.; Mitchell, J. D.; Stoneburner, J. C.

2003-01-01

The Altus Cumulus Electrification Study (ACES) is an unmanned aerial vehicle (UAV)- based project that investigated thunderstorms in the vicinity of the Florida Everglades in August 2002. ACES was conducted to investigate storm electrical activity and its relationship to storm morphology, and to validate satellite-based lightning measurements. In addition, as part of the NASA sponsored UAV-based science demonstration program, this project provided a scientifically useful demonstration of the utility and promise of UAV platforms for Earth science and applications observations. ACES employed the Altus II aircraft, built by General Atomics - Aeronautical Systems, Inc. Key science objectives simultaneously addressed by ACES are to: (1) investigate lightning-storm relationships, (2) study storm electrical budgets, and provide Lightning Imaging Sensor validation. The ACES payload included electrical, magnetic, and optical sensors to remotely characterize the lightning activity and the electrical environment within and around thunderstorms. ACES contributed important electrical and optical measurements not available from other sources. Also, the high altitude vantage point of the UAV observing platform (up to 55,000 feet) provided cloud-top perspective. By taking advantage of its slow flight speed (70 to 100 knots), long endurance, and high altitude flight, the Altus was flown near, and when possible, over (but never into) thunderstorms for long periods of time that allowed investigations to be conducted over entire storm life cycles. An innovative real time weather system was used to identify and vector the aircraft to selected thunderstorms and safely fly around these storms, while, at the same time monitor the weather near our base of operations. In addition, concurrent ground-based observations that included radar (Miami and Key West WSRBD, NASA NPOL), satellite imagery, and lightning (NALDN and Los Alamos EDOT) enable the UAV measurements to be more completely

Nicotine Suppressed Fetal Adrenal StAR Expression via YY1 Mediated-Histone Deacetylation Modification Mechanism.

PubMed

Liu, Lian; Wang, Jian-Fei; Fan, Jie; Rao, Yi-Song; Liu, Fang; Yan, You-E; Wang, Hui

2016-09-03

Steroidogenic acute regulatory (StAR) protein plays a pivotal role in steroidogenesis. Previously, we have demonstrated that prenatal nicotine exposure suppressed fetal adrenal steroidogenesis via steroidogenic factor 1 deacetylation. This study further explored the potential role of the transcriptional repressor Yin Yang 1 (YY1) in nicotine-mediated StAR inhibition. Nicotine was subcutaneously administered (1.0 mg/kg) to pregnant rats twice per day and NCI-H295A cells were treated with nicotine. StAR and YY1 expression were analyzed by real-time PCR, immunohistochemistry, and Western blotting. Histone modifications and the interactions between the YY1 and StAR promoter were assessed using chromatin immunoprecipitation (ChIP). Prenatal nicotine exposure increased YY1 expression and suppressed StAR expression. ChIP assay showed that there was a decreasing trend for histone acetylation at the StAR promoter in fetal adrenal glands, whereas H3 acetyl-K14 at the YY1 promoter presented an increasing trend following nicotine exposure. Furthermore, in nicotine-treated NCI-H295A cells, nicotine enhanced YY1 expression and inhibited StAR expression. ChIP assay showed that histone acetylation decreased at the StAR promoter in NCI-H295A cells and that the interaction between the YY1 and StAR promoter increased. These data indicated that YY1-medicated histone deacetylation modification in StAR promoters might play an important role in the inhibitory effect of nicotine on StAR expression.

Nicotine Suppressed Fetal Adrenal StAR Expression via YY1 Mediated-Histone Deacetylation Modification Mechanism

PubMed Central

Liu, Lian; Wang, Jian-Fei; Fan, Jie; Rao, Yi-Song; Liu, Fang; Yan, You-E; Wang, Hui

2016-01-01

Steroidogenic acute regulatory (StAR) protein plays a pivotal role in steroidogenesis. Previously, we have demonstrated that prenatal nicotine exposure suppressed fetal adrenal steroidogenesis via steroidogenic factor 1 deacetylation. This study further explored the potential role of the transcriptional repressor Yin Yang 1 (YY1) in nicotine-mediated StAR inhibition. Nicotine was subcutaneously administered (1.0 mg/kg) to pregnant rats twice per day and NCI-H295A cells were treated with nicotine. StAR and YY1 expression were analyzed by real-time PCR, immunohistochemistry, and Western blotting. Histone modifications and the interactions between the YY1 and StAR promoter were assessed using chromatin immunoprecipitation (ChIP). Prenatal nicotine exposure increased YY1 expression and suppressed StAR expression. ChIP assay showed that there was a decreasing trend for histone acetylation at the StAR promoter in fetal adrenal glands, whereas H3 acetyl-K14 at the YY1 promoter presented an increasing trend following nicotine exposure. Furthermore, in nicotine-treated NCI-H295A cells, nicotine enhanced YY1 expression and inhibited StAR expression. ChIP assay showed that histone acetylation decreased at the StAR promoter in NCI-H295A cells and that the interaction between the YY1 and StAR promoter increased. These data indicated that YY1-medicated histone deacetylation modification in StAR promoters might play an important role in the inhibitory effect of nicotine on StAR expression. PMID:27598153

Anti-cancer synergy of dichloroacetate and EGFR tyrosine kinase inhibitors in NSCLC cell lines.

PubMed

Yang, Zheng; Tam, Kin Y

2016-10-15

Glycolysis has been observed as a predominant process for most cancer cells to utilize glucose, which was referred to as "Warburg Effect". Targeting critical enzymes, such as pyruvate dehydrogenase kinase (PDK) that inversely regulating the process of glycolysis could be a promising approach to work alone or in combination with other treatments for cancer therapy. EGFR inhibitors for Non-Small-Cell Lung Cancer (NSCLC) treatment have been applied for decades in clinical practices with great success, but also their clinical benefits were somewhat hampered by the rising acquired-resistance. Combination drug therapy is an effective strategy to cope with the challenge. In this study, we utilized Dichloroacetate (DCA), a widely regarded PDK inhibitor, together with Erlotinib and Gefitinib, two well-known EGFR inhibitors, and demonstrated that the applications of DCA in combination with either Erlotinib or Gefitinib significantly attenuated the viability of EGFR mutant NSCLC cells (NCI-H1975 and NCI-H1650) in a synergistic manner. This synergistic outcome appears to be a combination effect in promoting apoptosis, rather than co-suppression of either EGFR or PDK signaling pathways. Moreover, we have shown that the combination treatment did not exhibit synergistic effect in other NSCLC cell lines without EGFR mutations (A549 or NCI-H460). Together, these observations suggested that combined targeting of EGFR and PDK in NSCLC cells exerted synergistic effects in an EGFR mutation-dependent fashion. Copyright © 2016 Elsevier B.V. All rights reserved.

The Cancer Moonshot Summit: Reaching New Heights

Cancer.gov

An NCI Cancer Currents blog from acting NCI Director Dr. Doug Lowy on the Cancer Moonshot national summit hosted by Vice President Joe Biden in Washington, D.C., including a summary of the NCI-related activities stimulated by the Cancer Moonshot.