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Sample records for cancer absolutely normal

  1. Absolute cross-section normalization of magnetic neutron scattering data

    OpenAIRE

    Xu, Guangyong; Xu, Zhijun; Tranquada, J. M.

    2013-01-01

    We discuss various methods to obtain the resolution volume for neutron scattering experiments, in order to perform absolute normalization on inelastic magnetic neutron scattering data. Examples from previous experiments are given. We also try to provide clear definitions of a number of physical quantities which are commonly used to describe neutron magnetic scattering results, including the dynamic spin correlation function and the imaginary part of the dynamic susceptibility. Formulas that c...

  2. Cosmic backgrounds of relic gravitons and their absolute normalization

    CERN Document Server

    Giovannini, Massimo

    2014-01-01

    Provided the consistency relations are not violated, the recent Bicep2 observations pin down the absolute normalization, the spectral slope and the maximal frequency of the cosmic graviton background produced during inflation. The properly normalized spectra are hereby computed from the lowest frequencies (of the order of the present Hubble rate) up to the highest frequency range in the GHz region. Deviations from the conventional paradigm cannot be excluded and are examined by allowing for different physical possibilities including, in particular, a running of the tensor spectral index, an explicit breaking of the consistency relations and a spike in the high-frequency tail of the spectrum coming either from a post-inflationary phase dominated by a stiff fluid of from the contribution of waterfall fields in a hybrid inflationary context. The direct determinations of the tensor to scalar ratio at low frequencies, if confirmed by the forthcoming observations, will also affect and constrain the high-frequencies...

  3. Cosmic backgrounds of relic gravitons and their absolute normalization

    Science.gov (United States)

    Giovannini, Massimo

    2014-11-01

    Provided the consistency relations are not violated, the recent BICEP2 observations pin down the absolute normalization, the spectral slope and the maximal frequency of the cosmic graviton background produced during inflation. The properly normalized spectra are hereby computed from the lowest frequencies (of the order of the present Hubble rate) up to the highest frequency range in the GHz region. Deviations from the conventional paradigm cannot be excluded and are examined by allowing for different physical possibilities including, in particular, a running of the tensor spectral index, an explicit breaking of the consistency relations and a spike in the high-frequency tail of the spectrum coming either from a post-inflationary phase dominated by a stiff fluid or from the contribution of waterfall fields in a hybrid inflationary context. The direct determinations of the tensor to scalar ratio at low frequencies, if confirmed by the forthcoming observations, will also affect and constrain the high-frequency uncertainties. The limits on the cosmic graviton backgrounds coming from wide-band interferometers (such as LIGO/Virgo, LISA and BBO/DECIGO) together with a more accurate scrutiny of the tensor B-mode polarization at low frequencies will set direct bounds on the post-inflationary evolution and on other unconventional completions of the standard lore.

  4. Evaluation of Two Absolute Radiometric Normalization Algorithms for Pre-processing of Landsat Imagery

    Institute of Scientific and Technical Information of China (English)

    Xu Hanqiu

    2006-01-01

    In order to evaluate radiometric normalization techniques, two image normalization algorithms for absolute radiometric correction of Landsat imagery were quantitatively compared in this paper, which are the Illumination Correction Model proposed by Markham and Irish and the Illumination and Atmospheric Correction Model developed by the Remote Sensing and GIS Laboratory of the Utah State University. Relative noise, correlation coefficient and slope value were used as the criteria for the evaluation and comparison, which were derived from pseudo-invariant features identified from multitemtween the normalized multitemporal images were significantly reduced when the seasons of multitemporal images were different. However, there was no significant difference between the normalized and unnormalized images with a similar seasonal condition. Furthermore, the correction results of two algorithms are similar when the images are relatively clear with a uniform atmospheric condition. Therefore, the radiometric normalization procedures should be carried out if the multitemporal images have a significant seasonal difference.

  5. Is Absolute Lymphocyte Count Just Another Prognostic Factor in Cancer?

    OpenAIRE

    Porrata, Luis F.; Markovic, Svetomir N.

    2010-01-01

    The role of host immunity in cancer clinical outcomes has been wellestablished in animal models. In humans, the impact of the immune system as a therapeutic maneuver to treat malignancies has been proven by the development of graft-versus-tumor effect observed in the allogeneic stem cell transplantation. However, with few notable exceptions, no definitive conclusions have been reached as to the role of host immunity in humans and its impact on cancer outcomes. This article reviews the clinica...

  6. Greater absolute risk for all subtypes of breast cancer in the US than Malaysia.

    Science.gov (United States)

    Horne, Hisani N; Beena Devi, C R; Sung, Hyuna; Tang, Tieng Swee; Rosenberg, Philip S; Hewitt, Stephen M; Sherman, Mark E; Anderson, William F; Yang, Xiaohong R

    2015-01-01

    Hormone receptor (HR) negative breast cancers are relatively more common in low-risk than high-risk countries and/or populations. However, the absolute variations between these different populations are not well established given the limited number of cancer registries with incidence rate data by breast cancer subtype. We, therefore, used two unique population-based resources with molecular data to compare incidence rates for the 'intrinsic' breast cancer subtypes between a low-risk Asian population in Malaysia and high-risk non-Hispanic white population in the National Cancer Institute's surveillance, epidemiology, and end results 18 registries database (SEER 18). The intrinsic breast cancer subtypes were recapitulated with the joint expression of the HRs (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor-2 (HER2). Invasive breast cancer incidence rates overall were fivefold greater in SEER 18 than in Malaysia. The majority of breast cancers were HR-positive in SEER 18 and HR-negative in Malaysia. Notwithstanding the greater relative distribution for HR-negative cancers in Malaysia, there was a greater absolute risk for all subtypes in SEER 18; incidence rates were nearly 7-fold higher for HR-positive and 2-fold higher for HR-negative cancers in SEER 18. Despite the well-established relative breast cancer differences between low-risk and high-risk countries and/or populations, there was a greater absolute risk for HR-positive and HR-negative subtypes in the US than Malaysia. Additional analytical studies are sorely needed to determine the factors responsible for the elevated risk of all subtypes of breast cancer in high-risk countries like the United States.

  7. Absolute Quantitation of DNA Methylation of 28 Candidate Genes in Prostate Cancer Using Pyrosequencing

    Directory of Open Access Journals (Sweden)

    Nataڑa Vasiljeviš

    2011-01-01

    Full Text Available Aberrant DNA methylation plays a pivotal role in carcinogenesis and its mapping is likely to provide biomarkers for improved diagnostic and risk assessment in prostate cancer (PCa. We quantified and compared absolute methylation levels among 28 candidate genes in 48 PCa and 29 benign prostate hyperplasia (BPH samples using the pyrosequencing (PSQ method to identify genes with diagnostic and prognostic potential.

  8. (99m)Tc-DMSA absolute and relative renal uptake in cats: procedure and normal values.

    Science.gov (United States)

    Vandermeulen, Eva; Ham, Hamphrey R; Dobbeleir, André A; De Sadeleer, Carlos; Piepsz, Amy; Waelbers, Tim; Vermeire, Simon T; Slegers, Guido; Peremans, Kathelijne Y

    2011-06-01

    In this study we investigated the influence of technical factors (positioning, background (BG) correction and attenuation correction) on qualitative and quantitative (absolute (AU) and relative (RU) uptake) assessment of feline kidneys with (99m)technetium labelled dimercaptosuccinic acid ((99m)Tc-DMSA). Eleven healthy adult cats were included. Influence of BG and depth correction on quantitative assessment was evaluated. Depth correction was based on the geometric mean method (using dorsal and ventral images) and the use of two standards placed over each individual kidney. Visual evaluation showed superiority of dorsal and ventral over lateral positioning due to increased separation of the kidneys permitting region of interest (ROI) placement without overlap. No apparent influence of BG correction was found for RU. However, AU was systematically overestimated without BG correction. Depth correction did not seem to affect RU in most cases, however, in some cats the differences were not negligible. The values for AU without depth correction were lower compared to depth corrected values.

  9. Model linear absolute and relative risk estimates for cancer induced by ionizing radiation in Mexican cohort of occupationally exposed

    International Nuclear Information System (INIS)

    From the rate of natural mortality ms cancer (t) for every 100 thousand habitants, modeled by a fourth-degree polynomial function of the age data of the Mexican population (2008), and assuming: a) a relationship 1: 5 of cancer induced radiation respect to presented spontaneously, b) a size of initial cohort No = 100 k SOPs, c) a speed of HE = (2 ± 1) mSv / received by the SOPs from 18 to 65 years, d) a latency of 8 years for cancer induction after irradiation, e) a time tracking cohort to 75 years, f) and taking the coefficients absolute and relative risk BEIRs induction of cancer models II and VII (excluding leukemia); It determined: BEIR II for a total of 125 and 400 deaths from cancer for absolute and relative linear models respectively. For BEIR VII has a number of fatal cases of 345 and 927 deaths respectively for absolute and relative linear model cancer.

  10. Interval breast cancers: Absolute and proportional incidence and blinded review in a community mammographic screening program

    Energy Technology Data Exchange (ETDEWEB)

    Carbonaro, Luca A., E-mail: luca.carbonaro@gmail.com [Unità di Radiologia, IRCCS Policlinico San Donato, Piazza E. Malan 2, San Donato Milanese (Mi) 20097 (Italy); Azzarone, Antonio [Servizio di Radiologia, Azienda Ospedaliera Circolo di Melegnano, Via Pandina 1, Vizzolo Predabissi (Mi) 20070 (Italy); Paskeh, Bijan Babaei [Unità di Radiologia, IRCCS Policlinico San Donato, Piazza E. Malan 2, San Donato Milanese (Mi) 20097 (Italy); Brambilla, Giorgio [Dipartimento di Radiologia, IRCCS Istituto Clinico Humanitas, Via Manzoni 56, Rozzano (Mi) 20089 (Italy); Brunelli, Silvia [Centro di Prevenzione Senologica, ULSS 20, Piazza Lambranzi, Verona 37034 (Italy); Calori, Anna [Servizio di Radiologia, Azienda Ospedaliera Circolo di Melegnano, Via Pandina 1, Vizzolo Predabissi (Mi) 20070 (Italy); Caumo, Francesca [Centro di Prevenzione Senologica, ULSS 20, Piazza Lambranzi, Verona 37034 (Italy); Malerba, Paolo [Dipartimento di Radiologia, IRCCS Istituto Clinico Humanitas, Via Manzoni 56, Rozzano (Mi) 20089 (Italy); Menicagli, Laura [Unità di Radiologia, IRCCS Policlinico San Donato, Piazza E. Malan 2, San Donato Milanese (Mi) 20097 (Italy); Sconfienza, Luca M. [Unità di Radiologia, IRCCS Policlinico San Donato, Piazza E. Malan 2, San Donato Milanese (Mi) 20097 (Italy); Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milano (Italy); Vadalà, Giuseppe [Servizio di Radiologia, Azienda Ospedaliera Circolo di Melegnano, Via Pandina 1, Vizzolo Predabissi (Mi) 20070 (Italy); Brambilla, Gelma; Fantini, Luigi [Servizio di Medicina Preventiva delle Comunità, ASL Milano 2, Via Friuli 2, Lacchiarella (Mi) 20084 (Italy); Ciatto, Stefano [Screening Program, ULSS 16, Padova (Italy); and others

    2014-02-15

    Purpose: To evaluate the performance of the first years since the beginning of a mammographic population-based screening program. Materials and methods: Women aged 49–69 were invited biennially for two-view film-screen mammography and double reading without arbitration was performed. Interval cancers (ICs) from 2001 to 2006 were identified using screening archives, local pathology archives, and hospital discharge records. The proportional incidence of IC was determined considering breast cancers expected without screening. Three offsite radiologists experienced in breast cancer screening blindly evaluated mammograms prior to diagnosis, randomly mixed with negative mammograms (1:2 ratio). Cases unrecalled at review were considered as true ICs, those recalled by only one reviewer as minimal signs, and those recalled by two or three reviewers as missed cancers. T and N stage of the reviewed ICs were evaluated and compared. Results: A total of 86,276 first level mammograms were performed. Mean recall rate was 6.8% at first and 4.6% at repeat screening. We had 476 screen-detected cancers and 145 ICs (10 of them ductal carcinomas in situ). Absolute incidence was 17 per 10,000 screening examinations. Invasive proportional incidence was 19% (44/234) in the first year, 39% (91/234) in the second year, and 29% (135/468) in the two-year interval. Of 145 ICs, 130 (90%) were reviewed mixed with 287 negative controls: 55% (71/130) resulted to be true ICs, 24% (31/130) minimal signs, and 22% (28/130) missed cancers. The rate of ICs diagnosed in the first year interval was 21% (15/71) for true ICs, 46% (13/28) for missed cancers, and 39% (12/31) for minimal signs, with a significant difference of true ICs rate compared to missed cancers rate (p = 0.012). A higher rate of T3 and T4 stages was found for missed cancers (18%, 5/28) compared to minimal signs (6%, 2/31) or true ICs (8%, 6/71), while the rate of N2 and N3 stage for both minimal signs (19%, 6/31) or missed cancers (25

  11. Interval breast cancers: Absolute and proportional incidence and blinded review in a community mammographic screening program

    International Nuclear Information System (INIS)

    Purpose: To evaluate the performance of the first years since the beginning of a mammographic population-based screening program. Materials and methods: Women aged 49–69 were invited biennially for two-view film-screen mammography and double reading without arbitration was performed. Interval cancers (ICs) from 2001 to 2006 were identified using screening archives, local pathology archives, and hospital discharge records. The proportional incidence of IC was determined considering breast cancers expected without screening. Three offsite radiologists experienced in breast cancer screening blindly evaluated mammograms prior to diagnosis, randomly mixed with negative mammograms (1:2 ratio). Cases unrecalled at review were considered as true ICs, those recalled by only one reviewer as minimal signs, and those recalled by two or three reviewers as missed cancers. T and N stage of the reviewed ICs were evaluated and compared. Results: A total of 86,276 first level mammograms were performed. Mean recall rate was 6.8% at first and 4.6% at repeat screening. We had 476 screen-detected cancers and 145 ICs (10 of them ductal carcinomas in situ). Absolute incidence was 17 per 10,000 screening examinations. Invasive proportional incidence was 19% (44/234) in the first year, 39% (91/234) in the second year, and 29% (135/468) in the two-year interval. Of 145 ICs, 130 (90%) were reviewed mixed with 287 negative controls: 55% (71/130) resulted to be true ICs, 24% (31/130) minimal signs, and 22% (28/130) missed cancers. The rate of ICs diagnosed in the first year interval was 21% (15/71) for true ICs, 46% (13/28) for missed cancers, and 39% (12/31) for minimal signs, with a significant difference of true ICs rate compared to missed cancers rate (p = 0.012). A higher rate of T3 and T4 stages was found for missed cancers (18%, 5/28) compared to minimal signs (6%, 2/31) or true ICs (8%, 6/71), while the rate of N2 and N3 stage for both minimal signs (19%, 6/31) or missed cancers (25

  12. Adequacy of relative and absolute risk models for lifetime risk estimate of radiation-induced cancer

    International Nuclear Information System (INIS)

    This report examines the applicability of the relative (multiplicative) and absolute (additive) models in predicting lifetime risk of radiation-induced cancer. A review of the epidemiologic literature, and a discussion of the mathematical models of carcinogenesis and their relationship to these models of lifetime risk, are included. Based on the available data, the relative risk model for the estimation of lifetime risk is preferred for non-sex-specific epithelial tumours. However, because of lack of knowledge concerning other determinants of radiation risk and of background incidence rates, considerable uncertainty in modelling lifetime risk still exists. Therefore, it is essential that follow-up of exposed cohorts be continued so that population-based estimates of lifetime risk are available

  13. Metabolic Imaging of Breast Cancer and the Normal Brain

    DEFF Research Database (Denmark)

    Asghar Butt, Sadia

    biological systems - breast cancer and normal brain. Breast cancer metabolism was longitudinally monitored in a mouse model using MRS of hyperpolirized pyruvate. The results demonstrated that we could monitor the changes in metabolism with increasing disease severity. The normal cerebral metabolism of α......-ketoisocaproate (KIC) was studied in the rat brain. The findings showed that hyperpolarized KIC is a promising substrate for in vivo evaluation of specific enzymatic activity....

  14. Methionine enkephalin: immunomodulator in normal volunteers, cancer and AIDS patients

    Directory of Open Access Journals (Sweden)

    Nicholas P. Plotnikoff

    1987-01-01

    Full Text Available Clinical studies of the immunological effects of methionine enkephalin in normal volunteers, cancer, and AIDS patients are summarized. The major immunology changes seen were increases in T cell subsets, natural killer activity, as well as mitogen blastogenesis. Clinically, the cancer and ARC patients did not develop infections.

  15. Thyroid stem cells: lessons from normal development and thyroid cancer

    OpenAIRE

    Thomas, Dolly; Friedman, Susan; Lin, Reigh-Yi

    2008-01-01

    Ongoing advances in stem cell research have opened new avenues for therapy for many human disorders. Until recently, however, thyroid stem cells have been relatively understudied. Here, we review what is known about thyroid stem cells and explore their utility as models of normal and malignant biological development. We also discuss the cellular origin of thyroid cancer stem cells and explore the clinical implications of cancer stem cells in the thyroid gland. Since thyroid cancer is the most...

  16. Shared signaling pathways in normal and breast cancer stem cells

    Directory of Open Access Journals (Sweden)

    Gautam K Malhotra

    2011-01-01

    Full Text Available Recent advances in our understanding of breast cancer biology have led to the identification of a subpopulation of cells within tumors that appear to be responsible for initiating and propagating the cancer. These tumor initiating cells are not only unique in their ability to generate tumors, but also share many similarities with elements of normal adult tissue stem cells, and have therefore been termed cancer stem cells (CSCs. These CSCs often inappropriately use many of the same signaling pathways utilized by their normal stem cell counterparts which may present a challenge to the development of CSC specific therapies. Here, we discuss three major stem cell signaling pathways (Notch, Wnt, and Hedgehog; with a focus on their function in normal mammary gland development and their misuse in breast cancer stem cell fate determination.

  17. High-Risk and Low-Risk Human Papillomavirus and the Absolute Risk of Cervical Intraepithelial Neoplasia or Cancer

    DEFF Research Database (Denmark)

    Thomsen, Louise T; Frederiksen, Kirsten; Munk, Christian;

    2014-01-01

    OBJECTIVE: To determine the absolute risk of cervical intraepithelial neoplasia (CIN) grade 3 or cervical cancer (CIN 3 or worse) after detection of low-risk human papillomavirus (HPV) and after a negative high-risk HPV test. METHODS: In this prospective cohort study, consecutive liquid-based cer...

  18. Eosinophil count - absolute

    Science.gov (United States)

    Eosinophils; Absolute eosinophil count ... the white blood cell count to give the absolute eosinophil count. ... than 500 cells per microliter (cells/mcL). Normal value ranges may vary slightly among different laboratories. Talk ...

  19. Gene expression profiles in liver cancer and normal liver tissues

    Institute of Scientific and Technical Information of China (English)

    Lian Xin Liu; Hong Chi Jiang; An Long Zhu; Jin Zhou; Xiu Qin Wang; Min Wu

    2000-01-01

    AIM To describe a liver cancer = specific gene expression profile and to identify genes that showed alteredexpression between liver cancer tissues and their adjacent nearly normal tissues.METHODS The cDNA probes which were labeled with a-32P dATP were synthesized from total RNA ofliver cancer and adjacent normal tissues and hybridized separately to two identical Atlas human cancer eDNAexpression array membranes containing 588 known genes.RESULTS Autoradiographic results were analyzed by specific Atlas ImageTM (version 1. 0) software.Among the 588 genes analyzed, 18 genes were found up-regulated in cancer, including TFDP2, Aktl, E2F-3etc, and 25 genes were down-regulated in cancer, including TDGF1, BAK, LAR, etc. Expression levels ofgenes that associated with the regulation of cell proliferation, apoptosis, differentiation, cell-cellinteraction, invasion regulators and eytokines altered mostly.CONCLUSION The result obtained from Atlas microarray provides a comprehensive liver cancer-specificexpression profile. The results can lead to the identification of liver cancer-specific biomarkers and may behelpful in early diagnosis and dentifiction of target genes for designing rational therapeutic strategies.

  20. Carbon Nanotubes Preserve Normal Phenotypes Under Cancer-Promoting Conditions

    Science.gov (United States)

    Wailes, Elizabeth; Levi-Polyachenko, Nicole

    2015-03-01

    Tumor-associated fibroblasts and cancer cells have long been known to create a feedback loop that further stimulates the cancer. While this has been explored from a molecular biology standpoint, little is known about the physical relationship of the cell types even though both sets of cells are known to be mechanosensitive. Indeed, for both fibroblasts and cancer, mechanical signals can make the difference between a normal or pathological cell. To evaluate this relationship and test if it can be manipulated to favor normal cells, atomic force microscopy (AFM) and confocal microscopy was performed on fibroblast and breast cancer cell co-cultures with a collagen gel matrix to simulate the extracellular matrix. Pathological behavior was encouraged through the addition of transforming growth factor beta (TGF- β) . In a separate group, this behavior was discouraged through the doping of the collagen gel with multi-walled carbon nanotubes (MWNT). Significant differences were observed both in the elastic moduli of each cell type and the cancer cells' propensity to migrate through the gel as a model for metastasis. These results shed new light on how cancer progresses and promote the further investigation of nano-mechanical solutions to cancer.

  1. Cavitary lung cancer lined with normal bronchial epithelium and cancer cells.

    Science.gov (United States)

    Goto, Taichiro; Maeshima, Arafumi; Oyamada, Yoshitaka; Kato, Ryoichi

    2011-01-01

    Reports of cavitary lung cancer are not uncommon, and the cavity generally contains either dilated bronchi or cancer cells. Recently, we encountered a surgical case of cavitary lung cancer whose cavity tended to enlarge during long-term follow-up, and was found to be lined with normal bronchial epithelium and adenocarcinoma cells. PMID:21980325

  2. Cavitary Lung Cancer Lined with Normal Bronchial Epithelium and Cancer Cells

    OpenAIRE

    Goto, Taichiro; Maeshima, Arafumi; Oyamada, Yoshitaka; Kato, Ryoichi

    2011-01-01

    Reports of cavitary lung cancer are not uncommon, and the cavity generally contains either dilated bronchi or cancer cells. Recently, we encountered a surgical case of cavitary lung cancer whose cavity tended to enlarge during long-term follow-up, and was found to be lined with normal bronchial epithelium and adenocarcinoma cells.

  3. Cavitary Lung Cancer Lined with Normal Bronchial Epithelium and Cancer Cells

    Directory of Open Access Journals (Sweden)

    Taichiro Goto, Arafumi Maeshima, Yoshitaka Oyamada, Ryoichi Kato

    2011-01-01

    Full Text Available Reports of cavitary lung cancer are not uncommon, and the cavity generally contains either dilated bronchi or cancer cells. Recently, we encountered a surgical case of cavitary lung cancer whose cavity tended to enlarge during long-term follow-up, and was found to be lined with normal bronchial epithelium and adenocarcinoma cells.

  4. Association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury after intensity-modulated radiotherapy in lung cancer: a retrospective analysis

    OpenAIRE

    Chen, Jinmei; Hong, Jinsheng; Zou, Xi; Lv, Wenlong; Guo, Feibao; Hong, Hualan; Zhang, Weijian

    2015-01-01

    The aim of this study was to investigate the association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury (RILI) after intensity-modulated radiotherapy (IMRT) for lung cancer. The normal lung relative volumes receiving greater than 5, 10, 20 and 30 Gy (V5–30) mean lung dose (MLD), and absolute volumes spared from greater than 5, 10, 20 and 30 Gy (AVS5–30) for the bilateral and ipsilateral lungs of 83 patients were recorded. Any association of...

  5. Easy Absolute Values? Absolutely

    Science.gov (United States)

    Taylor, Sharon E.; Mittag, Kathleen Cage

    2015-01-01

    The authors teach a problem-solving course for preservice middle-grades education majors that includes concepts dealing with absolute-value computations, equations, and inequalities. Many of these students like mathematics and plan to teach it, so they are adept at symbolic manipulations. Getting them to think differently about a concept that they…

  6. Colorectal cancers mimic structural organization of normal colonic crypts.

    Directory of Open Access Journals (Sweden)

    Laura Cernat

    Full Text Available Colonic crypts are stereotypical structures with distinct stem cell, proliferating, and differentiating compartments. Colorectal cancers derive from colonic crypt epithelia but, in contrast, form morphologically disarrayed glands. In this study, we investigated to which extent colorectal cancers phenocopy colonic crypt architecture and thus preserve structural organization of the normal intestinal epithelium. A subset of colon cancers showed crypt-like compartments with high WNT activity and nuclear β-Catenin at the leading tumor edge, adjacent proliferation, and enhanced Cytokeratin 20 expression in most differentiated tumor epithelia of the tumor center. This architecture strongly depended on growth conditions, and was fully reproducible in mouse xenografts of cultured and primary colon cancer cells. Full crypt-like organization was associated with low tumor grade and was an independent prognostic marker of better survival in a collection of 221 colorectal cancers. Our findings suggest that full activation of preserved intestinal morphogenetic programs in colon cancer requires in vivo growth environments. Furthermore, crypt-like architecture was linked with less aggressive tumor biology, and may be useful to improve current colon cancer grading schemes.

  7. Mechanical properties of normal versus cancerous breast cells.

    Science.gov (United States)

    Smelser, Amanda M; Macosko, Jed C; O'Dell, Adam P; Smyre, Scott; Bonin, Keith; Holzwarth, George

    2015-11-01

    A cell's mechanical properties are important in determining its adhesion, migration, and response to the mechanical properties of its microenvironment and may help explain behavioral differences between normal and cancerous cells. Using fluorescently labeled peroxisomes as microrheological probes, the interior mechanical properties of normal breast cells were compared to a metastatic breast cell line, MDA-MB-231. To estimate the mechanical properties of cell cytoplasms from the motions of their peroxisomes, it was necessary to reduce the contribution of active cytoskeletal motions to peroxisome motion. This was done by treating the cells with blebbistatin, to inhibit myosin II, or with sodium azide and 2-deoxy-D-glucose, to reduce intracellular ATP. Using either treatment, the peroxisomes exhibited normal diffusion or subdiffusion, and their mean squared displacements (MSDs) showed that the MDA-MB-231 cells were significantly softer than normal cells. For these two cell types, peroxisome MSDs in treated and untreated cells converged at high frequencies, indicating that cytoskeletal structure was not altered by the drug treatment. The MSDs from ATP-depleted cells were analyzed by the generalized Stokes-Einstein relation to estimate the interior viscoelastic modulus G* and its components, the elastic shear modulus G' and viscous shear modulus G", at angular frequencies between 0.126 and 628 rad/s. These moduli are the material coefficients that enter into stress-strain relations and relaxation times in quantitative mechanical models such as the poroelastic model of the interior regions of cancerous and non-cancerous cells. PMID:25929519

  8. Blood Vessel Normalization in the Hamster Oral Cancer Model for Experimental Cancer Therapy Studies

    Energy Technology Data Exchange (ETDEWEB)

    Ana J. Molinari; Romina F. Aromando; Maria E. Itoiz; Marcela A. Garabalino; Andrea Monti Hughes; Elisa M. Heber; Emiliano C. C. Pozzi; David W. Nigg; Veronica A. Trivillin; Amanda E. Schwint

    2012-07-01

    Normalization of tumor blood vessels improves drug and oxygen delivery to cancer cells. The aim of this study was to develop a technique to normalize blood vessels in the hamster cheek pouch model of oral cancer. Materials and Methods: Tumor-bearing hamsters were treated with thalidomide and were compared with controls. Results: Twenty eight hours after treatment with thalidomide, the blood vessels of premalignant tissue observable in vivo became narrower and less tortuous than those of controls; Evans Blue Dye extravasation in tumor was significantly reduced (indicating a reduction in aberrant tumor vascular hyperpermeability that compromises blood flow), and tumor blood vessel morphology in histological sections, labeled for Factor VIII, revealed a significant reduction in compressive forces. These findings indicated blood vessel normalization with a window of 48 h. Conclusion: The technique developed herein has rendered the hamster oral cancer model amenable to research, with the potential benefit of vascular normalization in head and neck cancer therapy.

  9. An absolute risk model to identify individuals at elevated risk for pancreatic cancer in the general population.

    Directory of Open Access Journals (Sweden)

    Alison P Klein

    Full Text Available PURPOSE: We developed an absolute risk model to identify individuals in the general population at elevated risk of pancreatic cancer. PATIENTS AND METHODS: Using data on 3,349 cases and 3,654 controls from the PanScan Consortium, we developed a relative risk model for men and women of European ancestry based on non-genetic and genetic risk factors for pancreatic cancer. We estimated absolute risks based on these relative risks and population incidence rates. RESULTS: Our risk model included current smoking (multivariable adjusted odds ratio (OR and 95% confidence interval: 2.20 [1.84-2.62], heavy alcohol use (>3 drinks/day (OR: 1.45 [1.19-1.76], obesity (body mass index >30 kg/m(2 (OR: 1.26 [1.09-1.45], diabetes >3 years (nested case-control OR: 1.57 [1.13-2.18], case-control OR: 1.80 [1.40-2.32], family history of pancreatic cancer (OR: 1.60 [1.20-2.12], non-O ABO genotype (AO vs. OO genotype (OR: 1.23 [1.10-1.37] to (BB vs. OO genotype (OR 1.58 [0.97-2.59], rs3790844(chr1q32.1 (OR: 1.29 [1.19-1.40], rs401681(5p15.33 (OR: 1.18 [1.10-1.26] and rs9543325(13q22.1 (OR: 1.27 [1.18-1.36]. The areas under the ROC curve for risk models including only non-genetic factors, only genetic factors, and both non-genetic and genetic factors were 58%, 57% and 61%, respectively. We estimate that fewer than 3/1,000 U.S. non-Hispanic whites have more than a 5% predicted lifetime absolute risk. CONCLUSION: Although absolute risk modeling using established risk factors may help to identify a group of individuals at higher than average risk of pancreatic cancer, the immediate clinical utility of our model is limited. However, a risk model can increase awareness of the various risk factors for pancreatic cancer, including modifiable behaviors.

  10. Measuring, and identifying predictors of, women's perceptions of three types of breast cancer risk: population risk, absolute risk and comparative risk

    OpenAIRE

    Apicella, C.; Peacock, S.J.; Andrews, L.; Tucker, K.; Daly, M B; Hopper, J L

    2009-01-01

    Although a key function of cancer genetics services is to provide risk information, to date there has been little consistency in the way in which breast cancer risk perception has been measured. The aims of the study were to measure estimates of (i) population risk, (ii) absolute risk and (iii) comparative risk of developing breast cancer for Ashkenazi Jewish women, and to determine predictors of breast cancer risk perception. Of 152 women, 107 (70%) completed all questions. The mean (s.d.) e...

  11. Validation of methylation biomarkers that distinguish normal colon mucosa of cancer patients from normal colon mucosa of patients without cancer.

    Science.gov (United States)

    Cesaroni, Matteo; Powell, Jasmine; Sapienza, Carmen

    2014-07-01

    We have validated differences in DNA methylation levels of candidate genes previously reported to discriminate between normal colon mucosa of patients with colon cancer and normal colon mucosa of individuals without cancer. Here, we report that CpG sites in 16 of the 30 candidate genes selected show significant differences in mean methylation level in normal colon mucosa of 24 patients with cancer and 24 controls. A support vector machine trained on these data and data for an additional 66 CpGs yielded an 18-gene signature, composed of ten of the validated candidate genes plus eight additional candidates. This model exhibited 96% sensitivity and 100% specificity in a 40-sample training set and classified all eight samples in the test set correctly. Moreover, we found a moderate-strong correlation (Pearson coefficients r = 0.253-0.722) between methylation levels in colon mucosa and methylation levels in peripheral blood for seven of the 18 genes in the support vector model. These seven genes, alone, classified 44 of the 48 patients in the validation set correctly and five CpGs selected from only two of the seven genes classified 41 of the 48 patients in the discovery set correctly. These results suggest that methylation biomarkers may be developed that will, at minimum, serve as useful objective and quantitative diagnostic complements to colonoscopy as a cancer-screening tool. These data also suggest that it may be possible to monitor biomarker methylation levels in tissues collected much less invasively than by colonoscopy. PMID:24806665

  12. A simple algebraic cancer equation: calculating how cancers may arise with normal mutation rates

    Directory of Open Access Journals (Sweden)

    Shibata Darryl

    2010-01-01

    Full Text Available Abstract Background The purpose of this article is to present a relatively easy to understand cancer model where transformation occurs when the first cell, among many at risk within a colon, accumulates a set of driver mutations. The analysis of this model yields a simple algebraic equation, which takes as inputs the number of stem cells, mutation and division rates, and the number of driver mutations, and makes predictions about cancer epidemiology. Methods The equation [p = 1 - (1 - (1 - (1 - udkNm ] calculates the probability of cancer (p and contains five parameters: the number of divisions (d, the number of stem cells (N × m, the number of critical rate-limiting pathway driver mutations (k, and the mutation rate (u. In this model progression to cancer "starts" at conception and mutations accumulate with cell division. Transformation occurs when a critical number of rate-limiting pathway mutations first accumulates within a single stem cell. Results When applied to several colorectal cancer data sets, parameter values consistent with crypt stem cell biology and normal mutation rates were able to match the increase in cancer with aging, and the mutation frequencies found in cancer genomes. The equation can help explain how cancer risks may vary with age, height, germline mutations, and aspirin use. APC mutations may shorten pathways to cancer by effectively increasing the numbers of stem cells at risk. Conclusions The equation illustrates that age-related increases in cancer frequencies may result from relatively normal division and mutation rates. Although this equation does not encompass all of the known complexity of cancer, it may be useful, especially in a teaching setting, to help illustrate relationships between small and large cancer features.

  13. Wielandt-type absolute perturbation upper bound for eigenvalues of normal matrices%正规矩阵特征值的Wielandt型绝对扰动上界

    Institute of Scientific and Technical Information of China (English)

    孔祥强

    2011-01-01

    研究了一类特殊矩阵特征值的绝对扰动上界问题,利用矩阵的奇异值分解和矩阵计算方面的技巧,探讨了正规矩阵特征值的扰动问题,得到了正规矩阵特征值的Wielandt型绝对扰动上界。本文得到的结论还进一步推广了Wielandt-Hoffman定理.是比Wielandt-Hoffman定理更一般的形式。%This paper studies the absolute perturbation upper bounds for a class of special matrix eigenvalues. By using the techniques of singular value decomposition and matrix calculation, it discusses the perturbation for eigenvalues of normal matrices and obtai

  14. Mammographic breast density and breast cancer risk: interactions of percent density, absolute dense, and non-dense areas with breast cancer risk factors.

    Science.gov (United States)

    Yaghjyan, Lusine; Colditz, Graham A; Rosner, Bernard; Tamimi, Rulla M

    2015-02-01

    We investigated if associations of breast density and breast cancer differ according to the level of other known breast cancer risk factors, including body mass index (BMI), age at menarche, parity, age at first child's birth, age at menopause, alcohol consumption, a family history of breast cancer, a history of benign breast disease, and physical activity. This study included 1,044 postmenopausal incident breast cancer cases diagnosed within the Nurses' Health Study cohort and 1,794 matched controls. Percent breast density, absolute dense, and non-dense areas were measured from digitized film images with computerized techniques. Information on breast cancer risk factors was obtained prospectively from biennial questionnaires. Percent breast density was more strongly associated with breast cancer risk in current postmenopausal hormone users (≥50 vs. 10 %: OR 5.34, 95 % CI 3.36-8.49) as compared to women with past (OR 2.69, 95 % CI 1.32-5.49) or no hormone history (OR 2.57, 95 % CI 1.18-5.60, p-interaction = 0.03). Non-dense area was inversely associated with breast cancer risk in parous women, but not in women without children (p-interaction = 0.03). Associations of density with breast cancer risk did not differ by the levels of BMI, age at menarche, parity, age at first child's birth, age at menopause, alcohol consumption, a family history of breast cancer, a history of benign breast disease, and physical activity. Women with dense breasts, who currently use menopausal hormone therapy are at a particularly high risk of breast cancer. Most breast cancer risk factors do not modify the association between mammographic breast density and breast cancer risk.

  15. Electrical impedance characterization of normal and cancerous human hepatic tissue.

    Science.gov (United States)

    Laufer, Shlomi; Ivorra, Antoni; Reuter, Victor E; Rubinsky, Boris; Solomon, Stephen B

    2010-07-01

    The four-electrode method was used to measure the ex vivo complex electrical impedance of tissues from 14 hepatic tumors and the surrounding normal liver from six patients. Measurements were done in the frequency range 1-400 kHz. It was found that the conductivity of the tumor tissue was much higher than that of the normal liver tissue in this frequency range (from 0.14 +/- 0.06 S m(-1) versus 0.03 +/- 0.01 S m(-1) at 1 kHz to 0.25 +/- 0.06 S m(-1) versus 0.15 +/- 0.03 S m(-1) at 400 kHz). The Cole-Cole models were estimated from the experimental data and the four parameters (rho(0), rho(infinity), alpha, f(c)) were obtained using a least-squares fit algorithm. The Cole-Cole parameters for the cancerous and normal liver are 9 +/- 4 Omega m(-1), 2.2 +/- 0.7 Omega m(-1), 0.5 +/- 0.2, 140 +/- 103 kHz and 50 +/- 28 Omega m(-1), 3.2 +/- 0.6 Omega m(-1), 0.64 +/- 0.04, 10 +/- 7 kHz, respectively. These data can contribute to developing bioelectric applications for tissue diagnostics and in tissue treatment planning with electrical fields such as radiofrequency tissue ablation, electrochemotherapy and gene therapy with reversible electroporation, nanoscale pulsing and irreversible electroporation.

  16. Absolute polarimetry at RHIC

    OpenAIRE

    Okada, H.; Alekseev, I.; Bravar, A; Bunce, G.; Dhawan, S.; Eyser, K. O.; Gill, R; Haeberli, W.; Huang, H.; Jinnouchi, O.; Makdisi, Y.; Nakagawa, I.; Nass, A.; Saito, N; Stephenson, E.

    2007-01-01

    Precise and absolute beam polarization measurements are critical for the RHIC spin physics program. Because all experimental spin-dependent results are normalized by beam polarization, the normalization uncertainty contributes directly to final physics uncertainties. We aimed to perform the beam polarization measurement to an accuracy of $\\Delta P_{beam}/P_{beam} < 5%$. The absolute polarimeter consists of Polarized Atomic Hydrogen Gas Jet Target and left-right pairs of silicon strip detector...

  17. Can a Cancer Cell Turn into a Normal Cell?

    Directory of Open Access Journals (Sweden)

    Ranan Gülhan Aktas

    2014-09-01

    Full Text Available HepG2 cells, a human liver cancer cell line (hepatocellular carcinoma, are being considered as a future model for bioartificial liver studies. They have the ability to differentiate and demonstrate some features of normal liver cells. Our previous studies focused on examination of the morphological and functional properties of these cells under different extracellular environmental conditions. We have created a culture model that these cells demonstrate remarkable changes after 30 days. These changes include an increase in the cytoplasmic organelles, formation of bile canaliculi, occurrence of junctional complexes between the adjacent cells, existence of microvilli on the apical surfaces, accumulation of glycogen particles in the cytoplasm, an increase at the density of albumin labeled areas and a rise at the Na-K ATPase level on cellular membranes.

  18. A study of structural differences between liver cancer cells and normal liver cells using FTIR spectroscopy

    Science.gov (United States)

    Sheng, Daping; Xu, Fangcheng; Yu, Qiang; Fang, Tingting; Xia, Junjun; Li, Seruo; Wang, Xin

    2015-11-01

    Since liver cancer seriously threatens human health, it is very urgent to explore an effective method for diagnosing liver cancer early. In this study, we investigated the structure differences of IR spectra between neoplastic liver cells and normal liver cells. The major differences of absorption bands were observed between liver cancer cells and normal liver cells, the values of A2955/A2921, A1744/A1082, A1640/A1535, H1121/H1020 might be potentially useful factors for distinguishing liver cancer cells from normal liver cells. Curve fitting also provided some important information on structural differences between malignant and normal liver cancer cells. Furthermore, IR spectra combined with hierarchical cluster analysis could make a distinction between liver cancer cells and normal liver cells. The present results provided enough cell basis for diagnosis of liver cancer by FTIR spectroscopy, suggesting FTIR spectroscopy may be a potentially useful tool for liver cancer diagnosis.

  19. Electrical impedance characterization of normal and cancerous human hepatic tissue

    International Nuclear Information System (INIS)

    The four-electrode method was used to measure the ex vivo complex electrical impedance of tissues from 14 hepatic tumors and the surrounding normal liver from six patients. Measurements were done in the frequency range 1–400 kHz. It was found that the conductivity of the tumor tissue was much higher than that of the normal liver tissue in this frequency range (from 0.14 ± 0.06 S m−1 versus 0.03 ± 0.01 S m−1 at 1 kHz to 0.25 ± 0.06 S m−1 versus 0.15 ± 0.03 S m−1 at 400 kHz). The Cole–Cole models were estimated from the experimental data and the four parameters (ρ0, ρ∞, α, fc) were obtained using a least-squares fit algorithm. The Cole–Cole parameters for the cancerous and normal liver are 9 ± 4 Ω m−1, 2.2 ± 0.7 Ω m−1, 0.5 ± 0.2, 140 ± 103 kHz and 50 ± 28 Ω m−1, 3.2 ± 0.6 Ω m−1, 0.64 ± 0.04, 10 ± 7 kHz, respectively. These data can contribute to developing bioelectric applications for tissue diagnostics and in tissue treatment planning with electrical fields such as radiofrequency tissue ablation, electrochemotherapy and gene therapy with reversible electroporation, nanoscale pulsing and irreversible electroporation

  20. Absolute advantage

    NARCIS (Netherlands)

    J.G.M. van Marrewijk (Charles)

    2008-01-01

    textabstractA country is said to have an absolute advantage over another country in the production of a good or service if it can produce that good or service using fewer real resources. Equivalently, using the same inputs, the country can produce more output. The concept of absolute advantage can a

  1. Comparison of effective atomic numbers of the cancerous and normal kidney tissue

    International Nuclear Information System (INIS)

    The effective atomic number (Zeff) and electron density (Ne) of normal kidney and cancerous kidney have been computed for total and partial photon interactions by computing the molecular, atomic, and electronic cross section in the wide energy range of 1 keV-100 GeV using WinXCOM. The mean Zeff and Ne of normal kidney and cancerous kidney in the various energy ranges and for total and partial photon interactions are tabulated. The variation of effective Ne with energy is shown graphically for all photon interactions. In addition to this computer tomography (CT), numbers of normal kidney and cancerous kidney for photon interaction and energy absorption is also computed. The role of Zeff in the dual-energy dividing radiography is also discussed. The values of Zeff and Ne for cancerous kidney are higher than normal kidney. This is due to the levels of elements K, Ca, Fe, Ni, and Se are lower and those of the elements Ti, Co, Zn, As, and Cd are higher in the cancer tissue of kidney than those observed in the normal tissue. The soft tissue and cancerous tissue are very similar, but their atomic number differs. The cancerous tissue exhibits a higher Zeff than the normal tissue. This fact helps in the dual-energy dividing radiography which enables to improve the diagnosis of the kidney cancer. Hence, the computed values may be useful in the diagnosis of the kidney cancer. CT numbers for normal kidney are higher than cancerous kidney. (author)

  2. Characterization of normal and cancer stem cells: One experimental paradigm for two kinds of stem cells

    OpenAIRE

    Mayol, Jean-François; Loeuillet, Corinne; Hérodin, Francis; Wion, Didier

    2009-01-01

    The characterization of normal stem cells and cancer stem cells uses the same paradigm. These cells are isolated by a Fluorescent-Activated Cell Sorting step and their stemness is assayed following implantation into animals. However, differences exist between these two kinds of stem cells. Therefore, the translation of the experimental procedures used for normal stem cell isolation into the cancer stem cell research field is a potential source of artefacts. In addition, normal stem cell thera...

  3. Epithelial cell cultures from normal and cancerous human tissues.

    Science.gov (United States)

    Owens, R B; Smith, H S; Nelson-Rees, W A; Springer, E L

    1976-04-01

    Thirty epithelial cell strains were isolated from human carcinomas and normal epithelial tissues by collagenase digestion and selective removal of fibroblasts with trypsin-Versene. Most strains were obtained from metastatic carcinomas or epithelia of the urinary and intestinal tracts. The success rate for growth of both neoplastic and normal tissues (excluding skin) was 38%. Six of these strains showed gross morphologic and chromosome changes typical of malignant cells. Nine resembled normal epithelium. The other 15 exhibited some degree of morphologic change from normal. PMID:176412

  4. Absolute beginners

    OpenAIRE

    Costa, Carlos Casimiro da; Costa, Jacinta Casimiro da

    2012-01-01

    Tomorrow, I m recovering my Thursday child as an absolute beginner , Transporting you to the essential touch of surface skin and space, Only for you, i do not regret, looking for education in a materia set. My love is your love , my materiality is you making things, The legacy of our ethnography, craftsmen s old and disappear, make me strong hard feelings, Recovering experiences and knowledge sprinkled in powder of stone, wood and metal ( ) reflecting in your dirty face the ...

  5. A Study of Cancer Patients' Personality Profile and it's Comparison with that of Normal Persons

    Directory of Open Access Journals (Sweden)

    M. Imani

    2010-01-01

    Full Text Available Introduction & Objective: This study compared the personality profile of cancer patients with that of normal persons. The aim was identifying personality traits related to people who suffered from cancer, and helping them to cope with the situation and adjust with life.Materials & Methods: This research was a casual comparative study. For this purpose 100 persons were selected from hematology and oncology center and asked to complete (NEO personality inventory. Then 94 persons were selected as matched group. Results: The result showed that neuroticism was high in cancer patients (p<0.00. Also there were significant differences between normal people and cancer patients in adaptibility and extroversion with high scores in normal people (p<0.05. But there were no significant difference between the two groups in agreeableness and conscientious.Conclusion: In general the result of this research demonstrated that the cancer patients were more neurotic and less adaptable and extrovert therefore they need psychotherapy.

  6. Comparison of nuclear matrix proteins between gastric cancer and normal gastric tissue

    Institute of Scientific and Technical Information of China (English)

    Qin-Xian Zhang; Yi Ding; Zhuo Li; Xiao-Ping Le; Wei Zhang; Ling Sun; Hui-Rong Shi

    2004-01-01

    AIM: To study the alteration of nuclear matrix proteins (NMPs) in gastric cancer.METHODS: The NMPs extracted from 22 cases of gastric cancer and normal gastric tissues were investigated by SDS-PAGE technique and the data were analyzed using Genetools analysis software.RESULTS: Compared with normal gastric tissue, the expression of 30 ku and 28 ku NMPs in gastric cancer decreased significantly (P=0.002, P=0.001, P<0.05). No significant difference was found in the expression of the two NMPs between the various differentiated grades (P=0.947, P=0.356) and clinical stages of gastric cancer (P=0.920, P=0.243, P>0.05).CONCLUSION: The results suggested that the alteration of NMPs in gastric cancer occurred at the early stage of gastric cancer development.

  7. Art Therapy with Pediatric Cancer Patients: Helping Normal Children Cope with Abnormal Circumstances.

    Science.gov (United States)

    Councill, Tracy

    1993-01-01

    Notes that art therapy with pediatric cancer patients addresses emotional and developmental needs of normal population under extreme stress. Reviews literature on the problems likely to be encountered by pediatric cancer patient and presents case examples to illustrate the emergence of these issues and their management in art therapy. (Author/NB)

  8. Paraneoplastic Erythrocytosis of Colon Cancer, with Serum Erythropoietin within the Normal Reference Range

    OpenAIRE

    Kitayama, Hiromitsu; Kondo, Tomohiro; SUGIYAMA, Junko; Hirayama, Michiaki; Oyamada, Yumiko; Tsuji, Yasushi

    2016-01-01

    Patient: Female, 75 Final Diagnosis: Erythropoietin-secreting colon cancer Symptoms: None Medication: — Clinical Procedure: Immunohistochemistry Specialty: Hematology Objective: Rare disease Background: Paraneoplastic erythrocytosis can be brought on by ectopic erythropoietin production usually in kidney, brain, and liver tumor with increase of serum erythropoietin level. We report here a paraneoplastic erythrocytosis of colon cancer with serum erythropoietin within the normal reference, whic...

  9. Heme Oxygenase-1 Determines the Differential Response of Breast Cancer and Normal Cells to Piperlongumine

    OpenAIRE

    Lee, Ha-Na; Jin, Hyeon-Ok; Park, Jin-Ah; Kim, Jin-Hee; Kim, Ji-Young; Kim, Bora; Kim, Wonki; Hong, Sung-Eun; Lee, Yun-Han; CHANG, YOON HWAN; Hong, Seok-Il; HONG, YOUNG JUN; Park, In-Chul; Surh, Young-Joon; Lee, Jin Kyung

    2015-01-01

    Piperlongumine, a natural alkaloid isolated from the long pepper, selectively increases reactive oxygen species production and apoptotic cell death in cancer cells but not in normal cells. However, the molecular mechanism underlying piperlongumine-induced selective killing of cancer cells remains unclear. In the present study, we observed that human breast cancer MCF-7 cells are sensitive to piperlongumine-induced apoptosis relative to human MCF-10A breast epithelial cells. Interestingly, thi...

  10. Using multivariate regression model with least absolute shrinkage and selection operator (LASSO to predict the incidence of Xerostomia after intensity-modulated radiotherapy for head and neck cancer.

    Directory of Open Access Journals (Sweden)

    Tsair-Fwu Lee

    Full Text Available PURPOSE: The aim of this study was to develop a multivariate logistic regression model with least absolute shrinkage and selection operator (LASSO to make valid predictions about the incidence of moderate-to-severe patient-rated xerostomia among head and neck cancer (HNC patients treated with IMRT. METHODS AND MATERIALS: Quality of life questionnaire datasets from 206 patients with HNC were analyzed. The European Organization for Research and Treatment of Cancer QLQ-H&N35 and QLQ-C30 questionnaires were used as the endpoint evaluation. The primary endpoint (grade 3(+ xerostomia was defined as moderate-to-severe xerostomia at 3 (XER3m and 12 months (XER12m after the completion of IMRT. Normal tissue complication probability (NTCP models were developed. The optimal and suboptimal numbers of prognostic factors for a multivariate logistic regression model were determined using the LASSO with bootstrapping technique. Statistical analysis was performed using the scaled Brier score, Nagelkerke R(2, chi-squared test, Omnibus, Hosmer-Lemeshow test, and the AUC. RESULTS: Eight prognostic factors were selected by LASSO for the 3-month time point: Dmean-c, Dmean-i, age, financial status, T stage, AJCC stage, smoking, and education. Nine prognostic factors were selected for the 12-month time point: Dmean-i, education, Dmean-c, smoking, T stage, baseline xerostomia, alcohol abuse, family history, and node classification. In the selection of the suboptimal number of prognostic factors by LASSO, three suboptimal prognostic factors were fine-tuned by Hosmer-Lemeshow test and AUC, i.e., Dmean-c, Dmean-i, and age for the 3-month time point. Five suboptimal prognostic factors were also selected for the 12-month time point, i.e., Dmean-i, education, Dmean-c, smoking, and T stage. The overall performance for both time points of the NTCP model in terms of scaled Brier score, Omnibus, and Nagelkerke R(2 was satisfactory and corresponded well with the expected values

  11. Absolute Summ

    Science.gov (United States)

    Phillips, Alfred, Jr.

    Summ means the entirety of the multiverse. It seems clear, from the inflation theories of A. Guth and others, that the creation of many universes is plausible. We argue that Absolute cosmological ideas, not unlike those of I. Newton, may be consistent with dynamic multiverse creations. As suggested in W. Heisenberg's uncertainty principle, and with the Anthropic Principle defended by S. Hawking, et al., human consciousness, buttressed by findings of neuroscience, may have to be considered in our models. Predictability, as A. Einstein realized with Invariants and General Relativity, may be required for new ideas to be part of physics. We present here a two postulate model geared to an Absolute Summ. The seedbed of this work is part of Akhnaton's philosophy (see S. Freud, Moses and Monotheism). Most important, however, is that the structure of human consciousness, manifest in Kenya's Rift Valley 200,000 years ago as Homo sapiens, who were the culmination of the six million year co-creation process of Hominins and Nature in Africa, allows us to do the physics that we do. .

  12. Developing Multivariable Normal Tissue Complication Probability Model to Predict the Incidence of Symptomatic Radiation Pneumonitis among Breast Cancer Patients.

    Directory of Open Access Journals (Sweden)

    Tsair-Fwu Lee

    Full Text Available Symptomatic radiation pneumonitis (SRP, which decreases quality of life (QoL, is the most common pulmonary complication in patients receiving breast irradiation. If it occurs, acute SRP usually develops 4-12 weeks after completion of radiotherapy and presents as a dry cough, dyspnea and low-grade fever. If the incidence of SRP is reduced, not only the QoL but also the compliance of breast cancer patients may be improved. Therefore, we investigated the incidence SRP in breast cancer patients after hybrid intensity modulated radiotherapy (IMRT to find the risk factors, which may have important effects on the risk of radiation-induced complications.In total, 93 patients with breast cancer were evaluated. The final endpoint for acute SRP was defined as those who had density changes together with symptoms, as measured using computed tomography. The risk factors for a multivariate normal tissue complication probability model of SRP were determined using the least absolute shrinkage and selection operator (LASSO technique.Five risk factors were selected using LASSO: the percentage of the ipsilateral lung volume that received more than 20-Gy (IV20, energy, age, body mass index (BMI and T stage. Positive associations were demonstrated among the incidence of SRP, IV20, and patient age. Energy, BMI and T stage showed a negative association with the incidence of SRP. Our analyses indicate that the risk of SPR following hybrid IMRT in elderly or low-BMI breast cancer patients is increased once the percentage of the ipsilateral lung volume receiving more than 20-Gy is controlled below a limitation.We suggest to define a dose-volume percentage constraint of IV20< 37% (or AIV20< 310cc for the irradiated ipsilateral lung in radiation therapy treatment planning to maintain the incidence of SPR below 20%, and pay attention to the sequelae especially in elderly or low-BMI breast cancer patients. (AIV20: the absolute ipsilateral lung volume that received more than

  13. Alteration of proliferation and apoptotic markers in normal and premalignant tissue associated with prostate cancer

    International Nuclear Information System (INIS)

    Molecular markers identifying alterations in proliferation and apoptotic pathways could be particularly important in characterizing high-risk normal or pre-neoplastic tissue. We evaluated the following markers: Ki67, Minichromosome Maintenance Protein-2 (Mcm-2), activated caspase-3 (a-casp3) and Bcl-2 to determine if they showed differential expression across progressive degrees of intraepithelial neoplasia and cancer in the prostate. To identify field effects, we also evaluated whether high-risk expression patterns in normal tissue were more common in prostates containing cancer compared to those without cancer (supernormal), and in histologically normal glands adjacent to a cancer focus as opposed to equivalent glands that were more distant. The aforementioned markers were studied in 13 radical prostatectomy (RP) and 6 cystoprostatectomy (CP) specimens. Tissue compartments representing normal, low grade prostatic intraepithelial neoplasia (LGPIN), high grade prostatic intraepithelial neoplasia (HGPIN), as well as different grades of cancer were mapped on H&E slides and adjacent sections were analyzed using immunohistochemistry. Normal glands within 1 mm distance of a tumor focus and glands beyond 5 mm were considered 'near' and 'far', respectively. Randomly selected nuclei and 40 × fields were scored by a single observer; basal and luminal epithelial layers were scored separately. Both Ki-67 and Mcm-2 showed an upward trend from normal tissue through HGPIN and cancer with a shift in proliferation from basal to luminal compartment. Activated caspase-3 showed a significant decrease in HGPIN and cancer compartments. Supernormal glands had significantly lower proliferation indices and higher a-casp3 expression compared to normal glands. 'Near' normal glands had higher Mcm-2 indices compared to 'far' glands; however, they also had higher a-casp3 expression. Bcl-2, which varied minimally in normal tissue, did not show any trend

  14. Classification of normal and cancerous lung tissues by electrical impendence tomography.

    Science.gov (United States)

    Gao, Jianling; Yue, Shihong; Chen, Jun; Wang, Huaxiang

    2014-01-01

    Biological tissue impedance spectroscopy can provide rich physiological and pathological information by measuring the variation of the complex impedance of biological tissues under various frequencies of driven current. Electrical Impedance Tomography (EIT) technique can measure the impedance spectroscopy of biological tissue in medical field. Before application, a key problem must be solved on how to generally distinguish normal tissues from the cancerous in terms of measurable EIT data. In this paper, the impedance spectroscopy characteristics of human lung tissue are studied. On the basis of the measured data of 109 lung cancer patients, Cole-Cole Circle radius (CCCR) and the complex modulus are extracted. In terms of the two characteristics, 71.6% and 66.4% samples of cancerous and normal tissues can be correctly classified, respectively. Furthermore, two characteristics of the measured EIT data of each patient consist of a two-dimensional vector and all such vectors comprise a set of vectors. When classifying the vector set, the rate of correctly partitioning normal and cancerous tissues can be raised to 78.2%. The main factors to affect the classification results on normal and cancerous tissues are generally analyzed. The proposed method will play an important role in further working out an efficient and feasible diagnostic method for potential lung cancer patients, and provide theoretical basis and reference data for electrical impedance tomography technology in monitoring pulmonary function.

  15. A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

    Directory of Open Access Journals (Sweden)

    Thorsten Schlomm

    2013-03-01

    Full Text Available We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA levels (14 and 17 individuals, respectively were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs. Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b, which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ.

  16. [Profiles of DNA methylation in normal and cancer cells].

    Science.gov (United States)

    Weber, Michaël

    2008-01-01

    In eukaryotes, the epigenetic mark DNA methylation is found exclusively at cytosine residues in the CpG islands of genes, transposons and intergenic DNA. Among functional roles, DNA methylation is essential for mammalian embryonic development, and is classically thought to function by stably silencing promoter activity. However, until recently, understanding of the distribution of cytosine methylation in the whole genome - and hence, identification of its targets - was very limited. High-throughput methodologies, including methylated DNA immunoprecipitation, have recently revealed genome-wide mapping of DNA methylation, and provided new and unexpected data. Clearly DNA methylation is selectively associated with some key promoters- and is not a prerequisite for promoter inactivation, since strong CpG island promoters are mostly unmethylated, even when inactive. Most germline-specific genes are methylated and permanently silenced in somatic cells, suggesting a role of this mark in maintaining somatic cellular identity. These large scale studies will also help understanding the deregulation of DNA methylation associated with cancer, among which unmethylation of germinal cells genes, and recent observtion of large hypomethylated regions in tumoral specimens. The next challenge will be to understand if these methylation changes occur randomly, or more likely are specified by oncogenes or linked to environmental pressure. PMID:18789220

  17. A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth.

    Science.gov (United States)

    Bonnet, Sébastien; Archer, Stephen L; Allalunis-Turner, Joan; Haromy, Alois; Beaulieu, Christian; Thompson, Richard; Lee, Christopher T; Lopaschuk, Gary D; Puttagunta, Lakshmi; Bonnet, Sandra; Harry, Gwyneth; Hashimoto, Kyoko; Porter, Christopher J; Andrade, Miguel A; Thebaud, Bernard; Michelakis, Evangelos D

    2007-01-01

    The unique metabolic profile of cancer (aerobic glycolysis) might confer apoptosis resistance and be therapeutically targeted. Compared to normal cells, several human cancers have high mitochondrial membrane potential (DeltaPsim) and low expression of the K+ channel Kv1.5, both contributing to apoptosis resistance. Dichloroacetate (DCA) inhibits mitochondrial pyruvate dehydrogenase kinase (PDK), shifts metabolism from glycolysis to glucose oxidation, decreases DeltaPsim, increases mitochondrial H2O2, and activates Kv channels in all cancer, but not normal, cells; DCA upregulates Kv1.5 by an NFAT1-dependent mechanism. DCA induces apoptosis, decreases proliferation, and inhibits tumor growth, without apparent toxicity. Molecular inhibition of PDK2 by siRNA mimics DCA. The mitochondria-NFAT-Kv axis and PDK are important therapeutic targets in cancer; the orally available DCA is a promising selective anticancer agent. PMID:17222789

  18. Difference in Membrane Repair Capacity Between Cancer Cell Lines and a Normal Cell Line.

    Science.gov (United States)

    Frandsen, Stine Krog; McNeil, Anna K; Novak, Ivana; McNeil, Paul L; Gehl, Julie

    2016-08-01

    Electroporation-based treatments and other therapies that permeabilize the plasma membrane have been shown to be more devastating to malignant cells than to normal cells. In this study, we asked if a difference in repair capacity could explain this observed difference in sensitivity. Membrane repair was investigated by disrupting the plasma membrane using laser followed by monitoring fluorescent dye entry over time in seven cancer cell lines, an immortalized cell line, and a normal primary cell line. The kinetics of repair in living cells can be directly recorded using this technique, providing a sensitive index of repair capacity. The normal primary cell line of all tested cell lines exhibited the slowest rate of dye entry after laser disruption and lowest level of dye uptake. Significantly, more rapid dye uptake and a higher total level of dye uptake occurred in six of the seven tested cancer cell lines (p electroporation. Viability in the primary normal cell line (98 % viable cells) was higher than in the three tested cancer cell lines (81-88 % viable cells). These data suggest more effective membrane repair in normal, primary cells and supplement previous explanations why electroporation-based therapies and other therapies permeabilizing the plasma membrane are more effective on malignant cells compared to normal cells in cancer treatment. PMID:27312328

  19. Absolute quantification of cerebral blood flow in neurologically normal volunteers: dynamic-susceptibility contrast MRI-perfusion compared with computed tomography (CT)-perfusion.

    Science.gov (United States)

    Ziegelitz, Doerthe; Starck, Göran; Mikkelsen, Irene K; Tullberg, Mats; Edsbagge, Mikael; Wikkelsö, Carsten; Forssell-Aronson, Eva; Holtås, Stig; Knutsson, Linda

    2009-07-01

    To improve the reproducibility of arterial input function (AIF) registration and absolute cerebral blood flow (CBF) quantification in dynamic-susceptibility MRI-perfusion (MRP) at 1.5T, we rescaled the AIF by use of a venous output function (VOF). We compared CBF estimates of 20 healthy, elderly volunteers, obtained by computed tomography (CT)-perfusion (CTP) and MRP on two consecutive days. MRP, calculated without the AIF correction, did not result in any significant correlation with CTP. The rescaled MRP showed fair to moderate correlation with CTP for the central gray matter (GM) and the whole brain. Our results indicate that the method used for correction of partial volume effects (PVEs) improves MRP experiments by reducing AIF-introduced variance at 1.5T. PMID:19253361

  20. Synchronous luminescence spectroscopic characterization of blood elements of normal and patients with cervical cancer

    Science.gov (United States)

    Muthuvelu, K.; Shanmugam, Sivabalan; Koteeswaran, Dornadula; Srinivasan, S.; Venkatesan, P.; Aruna, Prakasarao; Ganesan, Singaravelu

    2011-03-01

    In this study the diagnostic potential of synchronous luminescence spectroscopy (SLS) technique for the characterization of normal and different pathological condition of cervix viz., moderately differentiated squamous cell carcinoma (MDSCC), poorly differentiated squamous cell carcinoma (PDSCC) and well differentiated squamous cell carcinoma (WDSSC). Synchronous fluorescence spectra were measured for 70 abnormal cases and 30 normal subjects. Characteristic, highly resolved peaks and significant spectral differences between normal and MDSCC, PDSCC and WDSCC cervical blood formed elements were obtained. The synchronous luminescence spectra of formed elements of normal and abnormal cervical cancer patients were subjected to statistical analysis. Synchronous luminescence spectroscopy provides 90% sensitivity and 92.6% specificity.

  1. Differences in gene expression in prostate cancer, normal appearing prostate tissue adjacent to cancer and prostate tissue from cancer free organ donors

    International Nuclear Information System (INIS)

    Typical high throughput microarrays experiments compare gene expression across two specimen classes – an experimental class and baseline (or comparison) class. The choice of specimen classes is a major factor in the differential gene expression patterns revealed by these experiments. In most studies of prostate cancer, histologically malignant tissue is chosen as the experimental class while normal appearing prostate tissue adjacent to the tumor (adjacent normal) is chosen as the baseline against which comparison is made. However, normal appearing prostate tissue from tumor free organ donors represents an alterative source of baseline tissue for differential expression studies. To examine the effect of using donor normal tissue as opposed to adjacent normal tissue as a baseline for prostate cancer expression studies, we compared, using oligonucleotide microarrays, the expression profiles of primary prostate cancer (tumor), adjacent normal tissue and normal tissue from tumor free donors. Statistical analysis using Significance Analysis of Microarrays (SAM) demonstrates the presence of unique gene expression profiles for each of these specimen classes. The tumor v donor expression profile was more extensive that the tumor v adjacent normal profile. The differentially expressed gene lists from tumor v donor, tumor v adjacent normal and adjacent normal v donor comparisons were examined to identify regulated genes. When donors were used as the baseline, similar genes are highly regulated in both tumor and adjacent normal tissue. Significantly, both tumor and adjacent normal tissue exhibit significant up regulation of proliferation related genes including transcription factors, signal transducers and growth regulators compared to donor tissue. These genes were not picked up in a direct comparison of tumor and adjacent normal tissues. The up-regulation of these gene types in both tissue types is an unexpected finding and suggests that normal appearing prostate tissue

  2. Identification of normal and cancerous human colorectal muscularis propria by multiphoton microscopy in different sections

    Science.gov (United States)

    Zhou, Yi; Chen, Zhifen; Kang, Deyong; li, Lianhuang; Zhuo, Shuangmu; Zhu, Xiaoqin; Guan, Guoxian; Chen, Jianxin

    2016-01-01

    Multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) as a potential diagnostic tool is attractive. MPM can effectively provide information about morphological and biochemical changes in biological tissues at the molecular level. In this paper, we attempt to identify normal and cancerous human colorectal muscularis propria by multiphoton microscopy in different sections (both in transverse and longitudinal sections). The results show that MPM can display different microstructure changes in the transverse and longitudinal sections of colorectal muscularis propria. MPM also can quantitatively describe the alteration of collagen content between normal and cancerous muscle layers. These are important pathological findings that MPM images can bring more detailed complementary information about tissue architecture and cell morphology through observing the transverse and longitudinal sections of colorectal muscularis propria. This work demonstrates that MPM can be better for identifying the microstructural characteristics of normal and cancerous human colorectal muscularis propria in different sections.

  3. Gene expression profile differences in gastric cancer, pericancerous epithelium and normal gastric mucosa by gene chip

    Institute of Scientific and Technical Information of China (English)

    Chuan-Ding Yu; Shen-Hua Xu; Hang-Zhou Mou; Zhi-Ming Jiang; Chi-Hong Zhu; Xiang-Lin Liu

    2005-01-01

    AIM: To study the difference of gene expression in gastric cancer (T), pericancerous epithelium (P) and normal tissue of gastric mucosa (C), and to screen an associated novel gene in early gastric carcinogenesis by oligonudeotide microarray.METHODS: U133A (Affymetrix, Santa Clara, CA) gene chip was used to detect the gene expression profile difference in T, P and C, respectively. Bioinformatics was used to analyze the detected results.RESULTS: When gastric cancer was compared with normal gastric mucosa, 766 genes were found, with a difference of more than four times in expression levels. Of the 766 genes,530 were up-regulated (Signal Log Ratio [SLR]>2), and 236 were down-regulated (SLR<-2). When pericancerous epithelium was compared with normal gastric mucosa, 64genes were found, with a difference of more than four times in expression levels. Of the 64 genes, 50 were up-regulated (SLR>2), and 14 were down-regulated (SLR<-2). Compared with normal gastric mucosa, a total of 143 genes with a difference in expression levels (more than four times, either in cancer or in pericancerous epithelium) were found in gastric cancer (T) and pericancerous epithelium (P). Of the 143 genes, 108 were up-regulated (SLR>2), and 35were down-regulated (SLR<-2).CONCLUSION: To apply a gene chip could find 143 genes associated with the genes of gastric cancer in pericancerous epithelium, although there were no pathological changes in the tissue slices. More interesting, six genes of pericancerous epithelium were up-regulated in comparison with genes of gastric cancer and three genes were down-regulated in comparison with genes of gastric cancer. It is suggested that these genes may be related to the carcinogenesis and development of early gastric cancer.

  4. Amino acid uptake in arterio-venous serum of normal and cancerous colon tissues

    Institute of Scientific and Technical Information of China (English)

    Lin-Bo Wang; Jian-Guo Shen; Su-Zhan Zhang; Ke-Feng Ding; Shu Zheng

    2004-01-01

    AIM: To investigate the difference of amino acid uptake between normal and cancerous colon tissues.METHODS: Sixteen patients with colon cancer were enrolled in our study. Blood samples were taken during operations, serum amino acid concentrations of blood from cancerous or normal colon were analyzed. Amino acid uptake rate was calculated by the A-V difference and evaluated statistically.RESULTS: Except for methionine, the uptake rate of amino acids in cancer was higher than that in normal colon (25.01% vs-2.29%, P<0.01). The amino acid uptake rate did not correlate to the size of tumor mass (P>0.05). There was no statistical significance in the amino acid uptake rate according to the Dukes stage, though it was higher in patients with Dukes stage C or D than that with Dukes stage B (P>0.05).CONCLUSION: Abnormal synthetic metabolism of colon cancer may contribute to its higher amino acid uptake rate than that of normal colon.

  5. Apparent diffusion coefficient in cervical cancer of the uterus: comparison with the normal uterine cervix

    Energy Technology Data Exchange (ETDEWEB)

    Naganawa, Shinji; Sato, Chiho; Ishigaki, Takeo [Nagoya University School of Medicine, Department of Radiology, Nagoya (Japan); Kumada, Hisashi; Miura, Shunichi [Toyohashi Municipal hospital, Department of Radiology, Toyohashi, Aich (Japan); Takizawa, Osamu [Siemens-Asahi Medical Technologies Ltd, Tokyo (Japan)

    2005-01-01

    A relation between apparent diffusion coefficient (ADC) values and tumor cellular density has been reported. The purpose of this study was to measure the ADC values of cervical cancers in the uterus and compare them with those of normal cervical tissues, and to test whether ADC could differentiate between normal and malignant cervical tissues in the uterus. Twelve consecutive female patients with cervical cancer of the uterus and ten female patients with other pelvic abnormalities were included in this study. ADC was measured at 1.5 T with b-factors of 0, 300 and 600 s/mm{sup 2} using single-shot echo-planar diffusion-weighted imaging and a parallel imaging technique. The mean ADC value of cervical cancer lesions was 1.09{+-}0.20 x 10{sup -3} mm{sup 2}/s, and that of normal cervix tissue was 1.79{+-}0.24 x 10{sup -3} mm{sup 2}/s (P<0.0001). In nine patients treated by chemotherapy and/or radiation therapy, the mean ADC value of the cervical cancer lesion increased significantly after therapy (P<0.001). The present study showed, with a small number of patients, that ADC measurement has a potential ability to differentiate between normal and cancerous tissue in the uterine cervix. Further study is necessary to determine the accuracy of ADC measurement in monitoring the treatment response. (orig.)

  6. Cancer stem cells - normal stem cells "Jedi" that went over to the "dark side"

    Directory of Open Access Journals (Sweden)

    Mariusz Z. Ratajczak

    2005-12-01

    Full Text Available Evidence has accumulated that cancer develops from a population of quiescent tissue committed/pluripotent stem cells (TCSC/PSC or cells developmentally closely related to them that are distributed in various organs. To support this notion, stem cells (SC are long lived cells and thus may become the subject of accumulating mutations that are crucial for initiation/progression of cancer. More important, they may maintain these mutations and pass them to the daughter stem cells. Therefore, mutations that occur in normal SC, accumulate during the life of an organism at the clonal level in the stem cell compartment committed to a given tissue/organ. As a consequence, this may lead to the malignant transformation of SC and tumor initiation. Furthermore, many biological features of normal and cancer SC such as the physiological trafficking of normal and metastasis of cancer stem cells involve similar molecular mechanisms, and we discuss these similarities here. Therefore, looking both at the origin and behavioral aspects we can envision cancer SC being normal SC "Jedi" that went over to the "dark side".

  7. Cytotoxicity and genotoxicity of capecitabine in head and neck cancer and normal cells

    OpenAIRE

    Wisniewska-Jarosinska, Maria; Sliwinski, Tomasz; Kasznicki, Jacek; Kaczmarczyk, Dariusz; Krupa, Renata; Bloch, Karolina; Drzewoski, Jozef; Chojnacki, Jan; Blasiak, Janusz; Morawiec-Sztandera, Alina

    2010-01-01

    The interaction between a chemical and a cell may strongly depend on whether this cell is normal or pathological. Side effects of anticancer drugs may sometimes overcome their benefit action, so it is important to investigate their effect in both the target and normal cells. Capecitabine (Xeloda, CAP), a prodrug of 5-fluorouracil, is mainly used in colon cancer, but little is known about its action in head and neck cancer. We compared the cyto- and genotoxicity of CAP in head and neck HTB-43 ...

  8. ALERT. Adverse late effects of cancer treatment. Vol. 2. Normal tissue specific sites and systems

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, Philip; Constine, Louis S. [Univ. Rochester Medical Center, NY (United States). Dept. of Radiation Oncology; Marks, Lawrence B. (ed.) [Univ. North Carolina and Lineberger, Comprehensive Cancer Center, Chapel Hill, NC (United States). Dept. of Radiation Oncology

    2014-09-01

    Comprehensively documents potential late effects in all the normal tissue sites in the human body. Considers in detail the detection, diagnosis, management and prevention of effects and discusses prognostic outcomes. Clearly presents radiation risk factors and interactions with chemotherapy effects. Provides the most current evidence-based medicine for cancer care survivorship guidelines. The literature on the late effects of cancer treatment is widely scattered in different journals since all major organ systems are affected and management is based on a variety of medical and surgical treatments. The aim of ALERT - Adverse Late Effects of Cancer Treatment is to offer a coherent multidisciplinary approach to the care of cancer survivors. The central paradigm is that cytotoxic multimodal therapy results in a perpetual cascade of events that affects each major organ system differently and is expressed continually over time. Essentially, radiation and chemotherapy are intense biologic modifiers that allow for cancer cure and cancer survivorship but accelerate senescence of normal tissues and increase the incidence of age-related diseases and second malignant tumors. Volume 2 of this two-volume work comprehensively documents potential late effects in all the normal tissue anatomic sites in the human body. The detection, diagnosis, management and prevention of effects are all considered in detail, and prognostic outcomes are discussed. Radiation risk factors and interactions with chemotherapy effects are clearly presented. The text is accompanied by numerous supportive illustrations and tables.

  9. Expression of BCRP Gene in the Normal Lung Tissue and Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the expression of novel multidrugresistance transporter (BCRP gene) from human MCF-7/AdrVp breast cancer cells in normal lung tissue and non-small lung cancer tissue. Methods: RNA was extracted immediately from fresh normal lung tissue and viable tumor tissue harvested from surgically resected specimens of non-small cell lung cancer patients. cDNA of BCRP gene was prepared by RT-PCR and was then amplified by PCR. cDNA products from those specimens were transferred to blotting membrane through electrophoresis and transferring technique and southern blot hybridization was eventually performed to detect the expression of BCRP gene. Results: RNA were extracted from 8 tumor tissue alone and 12 pairs of tumor tissue and normal lung tissue harvested from the same lung. Four patients' RNA samples with poor quality due to degrading were discarded. cDNA products of BCRP gene were obtained by RT-PCR and were then amplified by PCR in the remain 16 patients' RNA samples. Through southern blot hybridization, BCRP gene was found to be slightly expressed in various amounts in all normal lung tissue (10/10) and only in a half of tumor tissue samples (8/16). Conclusion: BCRP gene is slightly expressed in different amount in all normal lung tissue and only in a half of tumor tissue of non-small cell lung cancer patients. It is possible to induce it's overexpression and to develop multidrug resistance during chemotherapy if using anthracycline anticancer drugs.

  10. Personalized identification of altered pathways in cancer using accumulated normal tissue data

    OpenAIRE

    Ahn, TaeJin; Lee, Eunjin; Huh, Nam; Park, Taesung

    2014-01-01

    Motivation: Identifying altered pathways in an individual is important for understanding disease mechanisms and for the future application of custom therapeutic decisions. Existing pathway analysis techniques are mainly focused on discovering altered pathways between normal and cancer groups and are not suitable for identifying the pathway aberrance that may occur in an individual sample. A simple way to identify individual’s pathway aberrance is to compare normal and tumor data from the same...

  11. Distinguishing human normal or cancerous esophagus tissue ex vivo using multiphoton microscopy

    International Nuclear Information System (INIS)

    Application of multiphoton microscopy (MPM) to clinical cancer research has greatly developed over the last few years. In this paper, we mainly focus on two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG) for investigating esophageal cancer. We chiefly discuss the SHG/TPEF image and spectral characteristics of normal and cancerous esophagus submucosa with the combined multi-channel imaging mode and Lambda mode of a multiphoton microscope (LSM 510 META). Great differences can be detected, such as collagen content and morphology, glandular-shaped cancer cells, TPEF/SHG intensity ratio, and so on, which demonstrate that the multiphoton imaging technique has the potential ability for minimally-invasive early cancer diagnosis. (paper)

  12. Distinguishing human normal or cancerous esophagus tissue ex vivo using multiphoton microscopy

    Science.gov (United States)

    Liu, N. R.; Chen, G. N.; Wu, S. S.; Chen, R.

    2014-02-01

    Application of multiphoton microscopy (MPM) to clinical cancer research has greatly developed over the last few years. In this paper, we mainly focus on two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG) for investigating esophageal cancer. We chiefly discuss the SHG/TPEF image and spectral characteristics of normal and cancerous esophagus submucosa with the combined multi-channel imaging mode and Lambda mode of a multiphoton microscope (LSM 510 META). Great differences can be detected, such as collagen content and morphology, glandular-shaped cancer cells, TPEF/SHG intensity ratio, and so on, which demonstrate that the multiphoton imaging technique has the potential ability for minimally-invasive early cancer diagnosis.

  13. Effective Alu repeat based RT-Qpcr normalization in cancer cell perturbation experiments.

    Directory of Open Access Journals (Sweden)

    Ali Rihani

    Full Text Available BACKGROUND: Measuring messenger RNA (mRNA levels using the reverse transcription quantitative polymerase chain reaction (RT-qPCR is common practice in many laboratories. A specific set of mRNAs as internal control reference genes is considered as the preferred strategy to normalize RT-qPCR data. Proper selection of reference genes is a critical issue, especially in cancer cells that are subjected to different in vitro manipulations. These manipulations may result in dramatic alterations in gene expression levels, even of assumed reference genes. In this study, we evaluated the expression levels of 11 commonly used reference genes as internal controls for normalization of 19 experiments that include neuroblastoma, T-ALL, melanoma, breast cancer, non small cell lung cancer (NSCL, acute myeloid leukemia (AML, prostate cancer, colorectal cancer, and cervical cancer cell lines subjected to various perturbations. RESULTS: The geNorm algorithm in the software package qbase+ was used to rank the candidate reference genes according to their expression stability. We observed that the stability of most of the candidate reference genes varies greatly in perturbation experiments. Expressed Alu repeats show relatively stable expression regardless of experimental condition. These Alu repeats are ranked among the best reference assays in all perturbation experiments and display acceptable average expression stability values (M<0.5. CONCLUSIONS: We propose the use of Alu repeats as a reference assay when performing cancer cell perturbation experiments.

  14. Association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury after intensity-modulated radiotherapy in lung cancer: a retrospective analysis.

    Science.gov (United States)

    Chen, Jinmei; Hong, Jinsheng; Zou, Xi; Lv, Wenlong; Guo, Feibao; Hong, Hualan; Zhang, Weijian

    2015-11-01

    The aim of this study was to investigate the association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury (RILI) after intensity-modulated radiotherapy (IMRT) for lung cancer. The normal lung relative volumes receiving greater than 5, 10, 20 and 30 Gy (V5-30) mean lung dose (MLD), and absolute volumes spared from greater than 5, 10, 20 and 30 Gy (AVS5-30) for the bilateral and ipsilateral lungs of 83 patients were recorded. Any association of clinical factors and dose-volume parameters with Grade ≥2 RILI was analyzed. The median follow-up was 12.3 months; 18 (21.7%) cases of Grade 2 RILI, seven (8.4%) of Grade 3 and two (2.4%) of Grade 4 were observed. Univariate analysis revealed the located lobe of the primary tumor. V5, V10, V20, MLD of the ipsilateral lung, V5, V10, V20, V30 and MLD of the bilateral lung, and AVS5 and AVS10 of the ipsilateral lung were associated with Grade ≥2 RILI (P lung was prognostic for Grade ≥2 RILI (P = 0.010, OR = 0.272, 95% CI: 0.102-0.729). Receiver operating characteristic curves indicated Grade ≥2 RILI could be predicted using AVS5 of the ipsilateral lung (area under curve, 0.668; cutoff value, 564.9 cm(3); sensitivity, 60.7%; specificity, 70.4%). The incidence of Grade ≥2 RILI was significantly lower with AVS5 of the ipsilateral lung ≥564.9 cm(3) than with AVS5 lung were associated with Grade ≥2 RILI, and AVS5 of the ipsilateral lung was prognostic for Grade ≥2 RILI for lung cancer after IMRT. PMID:26454068

  15. A single-molecule force spectroscopy study of the interactions between lectins and carbohydrates on cancer and normal cells

    Science.gov (United States)

    Zhao, Weidong; Cai, Mingjun; Xu, Haijiao; Jiang, Junguang; Wang, Hongda

    2013-03-01

    The interaction forces between carbohydrates and lectins were investigated by single-molecule force spectroscopy on both cancer and normal cells. The binding kinetics was also studied, which shows that the carbohydrate-lectin complex on cancer cells is less stable than that on normal cells.The interaction forces between carbohydrates and lectins were investigated by single-molecule force spectroscopy on both cancer and normal cells. The binding kinetics was also studied, which shows that the carbohydrate-lectin complex on cancer cells is less stable than that on normal cells. Electronic supplementary information (ESI) available: Experimental details. See DOI: 10.1039/c3nr00553d

  16. Analysis of differentially expressed proteins in cancerous and normal colonic tissues

    Institute of Scientific and Technical Information of China (English)

    Lay-Harn Gam; Chiuan-Herng Leow; Che Nin Man; Boon-Hui Gooi; Manjit Singh

    2006-01-01

    AIM: To identify and analyze the differentially expressed proteins in normal and cancerous tissues of four patients suffering from colon cancer.METHODS: Colon tissues (normal and cancerous)were homogenized and the proteins were extracted using three protein extraction buffers. The extraction buffers were used in an orderly sequence of increasing extraction strength for proteins with hydrophobic properties. The protein extracts were separated using the SDS-PAGE method and the images were captured and analyzed using Quantity One software. The target protein bands were subjected to in-gel digestion with trypsin and finally analyzed using an ESI-ion trap mass spectrometer.RESULTS: A total of 50 differentially expressed proteins in colonic cancerous and normal tissues were identified.CONCLUSION: Many of the identified proteins have been reported to be involved in the progression of similar or other types of cancers. However, some of the identified proteins have not been reported before. In addition, a number of hypothetical proteins were also identified.

  17. Diffusion optical spectroscopy of cancerous and normal prostate tissues in time-resolved and frequency domain

    Science.gov (United States)

    Zhou, Kenneth J.; Pu, Yang; Chen, Jun

    2014-03-01

    It is well-known that light transport can be well described using Maxwell's electromagnetic theory. In biological tissue, the scattering particles cause the interaction of scattered waves from neighboring particles. Since such interaction cannot be ignored, multiple scattering occurs. The theoretical solution of multiple scattering is complicated. A suitable description is that the wavelike behavior of light is ignored and the transport of an individual photon is considered to be absorbed or scattered. This is known as the Radiative Transfer Equation (RTE) theory. Analytical solutions to the RTE that explicitly describes photon migration can be obtained by introducing some proper approximations. One of the most popular models used in the field of tissue optics is the Diffusion Approximation (DA). In this study, we report on the results of our initial study of optical properties of ex vivo normal and cancerous prostate tissues and how tissue parameters affect the near infrared light transporting in the two types of tissues. The time-resolved transport of light is simulated as an impulse isotropic point source of energy within a homogeneous unbounded medium with different absorption and scattering properties of cancerous and normal prostate tissues. Light source is also modulated sinusoidally to yield a varied fluence rate in frequency domain at a distant observation point within the cancerous and normal prostate tissues. Due to difference of the absorption and scattering coefficients between cancerous and normal tissues, the expansion of light pulse, intensity, phase are found to be different.

  18. Passive microrheology of normal and cancer cells after ML7 treatment by atomic force microscopy

    Science.gov (United States)

    Lyapunova, Elena; Nikituk, Alexander; Bayandin, Yuriy; Naimark, Oleg; Rianna, Carmela; Radmacher, Manfred

    2016-08-01

    Mechanical properties of living cancer and normal thyroidal cells were investigated by atomic force microscopy (AFM). Cell mechanics was compared before and after treatment with ML7, which is known to reduce myosin activity and induce softening of cell structures. We recorded force curves with extended dwell time of 6 seconds in contact at maximum forces from 500 pN to 1 nN. Data were analyzed within different frameworks: Hertz fit was applied in order to evaluate differences in Young's moduli among cell types and conditions, while the fluctuations of the cantilever in contact with cells were analyzed with both conventional algorithms (probability density function and power spectral density) and multifractal detrended fluctuation analysis (MF-DFA). We found that cancer cells were softer than normal cells and ML7 had a substantial softening effect on normal cells, but only a marginal one on cancer cells. Moreover, we observed that all recorded signals for normal and cancer cells were monofractal with small differences between their scaling parameters. Finally, the applicability of wavelet-based methods of data analysis for the discrimination of different cell types is discussed.

  19. Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues

    International Nuclear Information System (INIS)

    During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS) are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC). Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue. We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue. Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells

  20. Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues

    Directory of Open Access Journals (Sweden)

    Nardulli Ann M

    2010-01-01

    Full Text Available Abstract Background During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH, ductal carcinoma in situ (DCIS and invasive breast cancer (IBC. Methods Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue. Results We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue. Conclusions Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells.

  1. Normal stroma suppresses cancer cell proliferation via mechanosensitive regulation of JMJD1a-mediated transcription.

    Science.gov (United States)

    Kaukonen, Riina; Mai, Anja; Georgiadou, Maria; Saari, Markku; De Franceschi, Nicola; Betz, Timo; Sihto, Harri; Ventelä, Sami; Elo, Laura; Jokitalo, Eija; Westermarck, Jukka; Kellokumpu-Lehtinen, Pirkko-Liisa; Joensuu, Heikki; Grenman, Reidar; Ivaska, Johanna

    2016-01-01

    Tissue homeostasis is dependent on the controlled localization of specific cell types and the correct composition of the extracellular stroma. While the role of the cancer stroma in tumour progression has been well characterized, the specific contribution of the matrix itself is unknown. Furthermore, the mechanisms enabling normal-not cancer-stroma to provide tumour-suppressive signals and act as an antitumorigenic barrier are poorly understood. Here we show that extracellular matrix (ECM) generated by normal fibroblasts (NFs) is softer than the CAF matrix, and its physical and structural features regulate cancer cell proliferation. We find that normal ECM triggers downregulation and nuclear exit of the histone demethylase JMJD1a resulting in the epigenetic growth restriction of carcinoma cells. Interestingly, JMJD1a positively regulates transcription of many target genes, including YAP/TAZ (WWTR1), and therefore gene expression in a stiffness-dependent manner. Thus, normal stromal restricts cancer cell proliferation through JMJD1a-dependent modulation of gene expression. PMID:27488962

  2. Differentiation of cancerous and normal brain tissue using label free fluorescence and Stokes shift spectroscopy

    Science.gov (United States)

    Zhou, Yan; Wang, Leana; Liu, Cheng-hui; He, Yong; Yu, Xinguang; Cheng, Gangge; Wang, Peng; Shu, Cheng; Alfano, Robert R.

    2016-03-01

    In this report, optical biopsy was applied to diagnose human brain cancer in vitro for the identification of brain cancer from normal tissues by native fluorescence and Stokes shift spectra (SSS). 77 brain specimens including three types of human brain tissues (normal, glioma and brain metastasis of lung cancers) were studied. In order to observe spectral changes of fluorophores via fluorescence, the selected excitation wavelength of UV at 300 and 340 nm for emission spectra and a different Stokes Shift spectra with intervals Δλ = 40 nm were measured. The fluorescence spectra and SSS from multiple key native molecular markers, such as tryptophan, collagen, NADH, alanine, ceroid and lipofuscin were observed in normal and diseased brain tissues. Two diagnostic criteria were established based on the ratios of the peak intensities and peak position in both fluorescence and SSS spectra. It was observed that the ratio of the spectral peak intensity of tryptophan (340 nm) to NADH (440 nm) increased in glioma, meningioma (benign), malignant meninges tumor, and brain metastasis of lung cancer tissues in comparison with normal tissues. The ratio of the SS spectral peak (Δλ = 40 nm) intensities from 292 nm to 366 nm had risen similarly in all grades of tumors.

  3. Raman spectra of normal and cancerous mouse mammary gland tissue using near infrared excitation energy

    Science.gov (United States)

    Naik, Vaman; Serhatkulu, G. K.; Dai, H.; Shukla, N.; Weber, R.; Thakur, J. S.; Freeman, D. C.; Pandya, A. K.; Auner, G. W.; Naik, R.; Miller, R. F.; Cao, A.; Klein, M. D.; Rabah, R.

    2006-03-01

    Raman spectra of normal mammary gland tissues, malignant mammary gland tumors, and lymph nodes have been recorded using fresh tissue from mice. Tumors were induced in mice by subcutaneously injecting 4T1 BALB/c mammary tumor (a highly malignant) cell line. The Raman spectra were collected using the same tissues that were examined by histopathology for determining the cancerous/normal state of the tissue. Differences in various peak intensities, peak shifts and peak ratios were analyzed to determine the Raman spectral features that differentiate mammary gland tumors from non-tumorous tissue. Tissues that were confirmed by pathology as cancerous (tumors) show several distinctive features in the Raman spectra compared to the spectra of the normal tissues. For example, the cancerous tissues show Raman peaks at 621, 642, 1004, 1032, 1175 and 1208 cm-1 that are assignable to amino acids containing aromatic side-chains such as phenylalanine, tryptophan and tyrosine. Further, the cancerous tissues show a greatly reduced level of phospholipids compared to the normal tissues. The Raman spectral regions that are sensitive to pathologic alteration in the tissue will be discussed.

  4. Comparison of cerebral metabolism of glucose in normal human and cancer patients

    International Nuclear Information System (INIS)

    Full text: Objective: To determine whether the cerebral metabolism in various regions of the normal human brain differs from those of cancer patients in aging by using 18F-FDG PET instrument and SPM software. Materials and Methods We reviewed clinical information of 295 healthy normal samples so called 'normal group' (ranging 21 to 88; mean age+/-SD: 50+/-14) and 290 cancer patients called 'cancer group' (ranging 21 to 85; mean age+/-SD: 54+/-14) who were examined by a whole body GE Discovery LS PET-CT instrument in our center from Aug. 2004 to Dec. 2005.They were selected with: (i) absence of clear focal brain lesions (epilepsy, cerebrovascular diseases etc.); (ii) absence of metabolic diseases, such as hyperthyroidism, hypothyroidism and diabetes; (iii) absence of psychiatric disorders and abuse of drugs and alcohol;( iiii) cancer patients were diagnosed definitely of variable cancers except brain cancer or brain metastasis. Both groups were sub grouped into six with the interval of 10 years old starting from 21, and the gender, educational background and serum glucose are matched. All 12 subgroups were compared to the subgroup of normal 31-40 years old called 'control subgroup' (84 samples; mean age+/-SD: 37.15+/- 2.63). All samples were injected with 18F-FDG (5.55MBq/kg), 45-60 minutes later; their brains were scanned for 10 minutes. Pixel-by-pixel t-statistic analysis was applied to all brain images using the Statistical parametric mapping (SPM2). The hypometabolic areas (p < 0. 01 or p<0.001, uncorrected) were identified in the Stereotaxic coordinate human brain atlas and three dimensional localized by MNI Space utility (MSU) software. Results:1.With increasing of age interval, similar hypometabolic brain areas are detected in both 'normal group' and 'cancer group', they are mainly in the cortical structures such as bilateral prefrontal cortex (BA9), superior temporal gyrus (BA22), parietal cortex (inferior parietal lobule and precuneus(BA40), insula (BA13

  5. Heme oxygenase-1 determines the differential response of breast cancer and normal cells to piperlongumine.

    Science.gov (United States)

    Lee, Ha-Na; Jin, Hyeon-Ok; Park, Jin-Ah; Kim, Jin-Hee; Kim, Ji-Young; Kim, BoRa; Kim, Wonki; Hong, Sung-Eun; Lee, Yun-Han; Chang, Yoon Hwan; Hong, Seok-Il; Hong, Young Jun; Park, In-Chul; Surh, Young-Joon; Lee, Jin Kyung

    2015-04-01

    Piperlongumine, a natural alkaloid isolated from the long pepper, selectively increases reactive oxygen species production and apoptotic cell death in cancer cells but not in normal cells. However, the molecular mechanism underlying piperlongumine-induced selective killing of cancer cells remains unclear. In the present study, we observed that human breast cancer MCF-7 cells are sensitive to piperlongumine-induced apoptosis relative to human MCF-10A breast epithelial cells. Interestingly, this opposing effect of piperlongumine appears to be mediated by heme oxygenase-1 (HO-1). Piperlongumine upregulated HO-1 expression through the activation of nuclear factor-erythroid-2-related factor-2 (Nrf2) signaling in both MCF-7 and MCF-10A cells. However, knockdown of HO-1 expression and pharmacological inhibition of its activity abolished the ability of piperlongumine to induce apoptosis in MCF-7 cells, whereas those promoted apoptosis in MCF-10A cells, indicating that HO-1 has anti-tumor functions in cancer cells but cytoprotective functions in normal cells. Moreover, it was found that piperlongumine-induced Nrf2 activation, HO-1 expression and cancer cell apoptosis are not dependent on the generation of reactive oxygen species. Instead, piperlongumine, which bears electrophilic α,β-unsaturated carbonyl groups, appears to inactivate Kelch-like ECH-associated protein-1 (Keap1) through thiol modification, thereby activating the Nrf2/HO-1 pathway and subsequently upregulating HO-1 expression, which accounts for piperlongumine-induced apoptosis in cancer cells. Taken together, these findings suggest that direct interaction of piperlongumine with Keap1 leads to the upregulation of Nrf2-mediated HO-1 expression, and HO-1 determines the differential response of breast normal cells and cancer cells to piperlongumine. PMID:25813625

  6. SU-E-T-168: Evaluation of Normal Tissue Damage in Head and Neck Cancer Treatments

    Energy Technology Data Exchange (ETDEWEB)

    Ai, H [IU School of Medicine, Indianapolis, IN (United States); Zhang, H [Northwestern Memorial Hospital, Chicago, IL (United States)

    2014-06-01

    Purpose: To evaluate normal tissue toxicity in patients with head and neck cancer by calculating average survival fraction (SF) and equivalent uniform dose (EUD) for normal tissue cells. Methods: 20 patients with head and neck cancer were included in this study. IMRT plans were generated using EclipseTM treatment planning system by dosimetrist following clinical radiotherapy treatment guidelines. The average SF for three different normal tissue cells of each concerned structure can be calculated from dose spectrum acquired from differential dose volume histogram (DVH) using linear quadratic model. The three types of normal tissues include radiosensitive, moderately radiosensitive and radio-resistant that represents 70%, 50% and 30% survival fractions, respectively, for a 2-Gy open field. Finally, EUDs for three types of normal tissue of each structure were calculated from average SF. Results: The EUDs of the brainstem, spinal cord, parotid glands, brachial plexus and etc were calculated. Our analysis indicated that the brainstem can absorb as much as 14.3% of prescription dose to the tumor if the cell line is radiosensitive. In addition, as much as 16.1% and 18.3% of prescription dose were absorbed by the brainstem for moderately radiosensitive and radio-resistant cells, respectively. For the spinal cord, the EUDs reached up to 27.6%, 35.0% and 42.9% of prescribed dose for the three types of radiosensitivities respectively. Three types of normal cells for parotid glands can get up to 65.6%, 71.2% and 78.4% of prescription dose, respectively. The maximum EUDs of brachial plexsus were calculated as 75.4%, 76.4% and 76.7% of prescription for three types of normal cell lines. Conclusion: The results indicated that EUD can be used to quantify and evaluate the radiation damage to surrounding normal tissues. Large variation of normal tissue EUDs may come from variation of target volumes and radiation beam orientations among the patients.

  7. Photoacoustic spectroscopy based investigatory approach to discriminate breast cancer from normal: a pilot study

    Science.gov (United States)

    Priya, Mallika; Rao, Bola Sadashiva Satish; Chandra, Subhash; Ray, Satadru; Mathew, Stanley; Datta, Anirbit; Nayak, Subramanya G.; Mahato, Krishna Kishore

    2016-02-01

    In spite of many efforts for early detection of breast cancer, there is still lack of technology for immediate implementation. In the present study, the potential photoacoustic spectroscopy was evaluated in discriminating breast cancer from normal, involving blood serum samples seeking early detection. Three photoacoustic spectra in time domain were recorded from each of 20 normal and 20 malignant samples at 281nm pulsed laser excitations and a total of 120 spectra were generated. The time domain spectra were then Fast Fourier Transformed into frequency domain and 116.5625 - 206.875 kHz region was selected for further analysis using a combinational approach of wavelet, PCA and logistic regression. Initially, wavelet analysis was performed on the FFT data and seven features (mean, median, area under the curve, variance, standard deviation, skewness and kurtosis) from each were extracted. PCA was then performed on the feature matrix (7x120) for discriminating malignant samples from the normal by plotting a decision boundary using logistic regression analysis. The unsupervised mode of classification used in the present study yielded specificity and sensitivity values of 100% in each respectively with a ROC - AUC value of 1. The results obtained have clearly demonstrated the capability of photoacoustic spectroscopy in discriminating cancer from the normal, suggesting its possible clinical implications.

  8. Comparative Proteome Analysis of Breast Cancer and Adjacent Normal Breast Tissues in Human

    Institute of Scientific and Technical Information of China (English)

    Shi-Shan Deng; Tian-Yong Xing; Hong-Ying Zhou; Ruo-Hong Xiong; You-Guang Lu; Bin Wen; Shang-Qing Liu; Hui-Jun Yang

    2006-01-01

    Two-dimensional polyacryiamide gel electrophoresis (2D-PAGE) and matrixassisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS), incorporated with online database searching, were performed to investigate differential proteins of breast cancer and adjacent normal breast tissues. Considering that serum albumin is abundantly presented in normal control samples, 15 differential spots detected in 11 out of 12 (91.7%) breast cancer samples were identified by online SIENA-2DPAGE database searching and MALDI-TOF/TOF-MS analysis. The results indicate that pathological changes of breast cancer are concerned with augmentation of substance metabolism, promotion of proteolytic activity, decline of activity of some inhibitors of enzymes, and so on. Some important proteins involved in the pathological process of breast cancer with changed expression may be useful biomarkers, such as alpha-1-antitrypsin, EF1-beta, cathepsin D, TCTP, SMT3A, RPS12, and PSMA1, among which SMT3A,RPS12, and PSMA1 were first reported for breast cancer in this study.

  9. FREE ENERGY MEASUREMENT DISTINGUISHES NORMAL FROM CANCER CELL, OFFERING A NEW PERSPECTIVE FOR CURING CANCER

    Directory of Open Access Journals (Sweden)

    Kambiz Afrasiabi

    2013-01-01

    Full Text Available The interplay of the second law of thermodynamics with the normal state and the methodology needed for the measurement of free energy of normal and malignant cells and its practical implications has not been clearly addressed in current literature. The second law of thermodynamics is one of the most fundamental laws governing the known universe at all levels. A normal cell has an exceptional ability to minimize the speed of rise in entropy to saturation of the limits of the second law. By virtue of this law, any normal resting cell is at a maximum allowable free energy. In this regard mitosis could be viewed as an attempt to maximize the lowered cellular free energy. Here we present the result of our first series of measurements, which show a significant measurable difference between the free energy of normal and malignant cells using an Olympus 510 Argon laser to calculate a diffusion correlation as well as direct visualization of motion of malignant and normal cells cultured overnight in collagen mesh. We found a significantly higher vibratory motion of the normal cells after correction for confounding factors. We also propose a new way to increase the free energy of the malignant cell to match that of its normal counterpart. This could offer hope for cure by conversion of distorted energetics of the malignant cell.

  10. Epidermal stem cells - role in normal, wounded and pathological psoriatic and cancer skin

    DEFF Research Database (Denmark)

    Kamstrup, M.; Faurschou, A.; Gniadecki, R.;

    2008-01-01

    In this review we focus on epidermal stem cells in the normal regeneration of the skin as well as in wounded and psoriatic skin. Furthermore, we discuss current data supporting the idea of cancer stem cells in the pathogenesis of skin carcinoma and malignant melanoma. Epidermal stem cells present...... or transit amplifying cells constitute a primary pathogenetic factor in the epidermal hyperproliferation seen in psoriasis. In cutaneous malignancies mounting evidence supports a stem cell origin in skin carcinoma and malignant melanoma and a possible existence of cancer stem cells Udgivelsesdato: 2008/5...

  11. Clinical Outcomes of the Endoscopic Submucosal Dissection of Early Gastric Cancer Are Comparable between Absolute and New Expanded Criteria

    OpenAIRE

    Shin, Keun Young; Jeon, Seong Woo; Cho, Kwang Bum; Park, Kyung Sik; Kim, Eun Soo; Park, Chang Keun; Chung, Yun Jin; Kwon, Joong Goo; Jung, Jin Tae; Kim, Eun Young; Kim, Kyeong Ok; Jang, Byung Ik; Lee, Si Hyung; Park, Jeong Bae; Yang, Chang Hun

    2014-01-01

    Background/Aims Advances in endoscopic submucosal dissection (ESD) techniques have led to the development of expanded criteria for endoscopic resection of early gastric cancer (EGC). The aim of this study was to evaluate the short- and long-term outcomes for ESD using indication criteria. Methods A total of 1,105 patients underwent ESD for EGC at six medical centers. The patients were classified into the following two groups based on the lesion size, presence of ulceration and pathological re...

  12. Comparing cancer vs normal gene expression profiles identifies new disease entities and common transcriptional programs in AML patients

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Bagger, Frederik Otzen; Jendholm, Johan;

    2014-01-01

    Gene expression profiling has been used extensively to characterize cancer, identify novel subtypes, and improve patient stratification. However, it has largely failed to identify transcriptional programs that differ between cancer and corresponding normal cells and has not been efficient in...... hematopoietic hierarchy, using expression profiles from normal stem/progenitor cells, and next mapped the AML patient samples to this landscape. This allowed us to identify the closest normal counterpart of individual AML samples and determine gene expression changes between cancer and normal. We find the...... cancer vs normal method (CvN method) to be superior to conventional methods in stratifying AML patients with aberrant karyotype and in identifying common aberrant transcriptional programs with potential importance for AML etiology. Moreover, the CvN method uncovered a novel poor-outcome subtype of normal...

  13. Mortalin imaging in normal and cancer cells with quantum dot immunoconjugates

    Institute of Scientific and Technical Information of China (English)

    ZEENIA KAUL; TOMOKO YAGUCHI; SUNIL C KAUL; TAKASHI HIRANO; RENU WADHWA; KAZUNARI TAIRA

    2003-01-01

    Quantum dots are the nanoparticles that are recently emerging as an alternative to organic fluorescence probes in cell biology and biomedicine,and have several predictive advantages.These include their i)broad absorption spectra allowing visualization with single light source,ii)exceptional photo-stability allowing long term studies and iii)narrow and symmetrical emission spectrum that is controlled by their size and material composition.These unique properties allow simultaneous excitation of different size of quantum dots with a single excitation light source,their simultaneous resolution and visualization as different colors.At present there are only a few studies that have tested quantum dots in cellular imaging.We describe here the use of quantum dots in mortalin imaging of normal and cancer cells.Mortalin staining pattern with quantum dots in both normal and cancer cells mimicked those obtained with organic florescence probes and were considerably stable.

  14. Ethanolic Extracts of California Mugwort (Artemisia douglasiana Besser) Are Cytotoxic against Normal and Cancerous Human Cells

    Science.gov (United States)

    Somaweera, Himali; Lai, Gary C.; Blackeye, Rachel; Littlejohn, Beverly; Kirksey, Justine; Aguirre, Richard M.; LaPena, Vince; Pasqua, Anna; Hintz, Mary McCarthy

    2013-01-01

    California mugwort (Artemisia douglasiana Besser) is used by many tribes throughout California to treat a variety of conditions, including colds, allergies, and pain. California mugwort is also utilized as women’s medicine. Its use is on the rise outside of Native communities, often without the guidance of a traditional healer or experienced herbalist. Because it has been shown to have antiproliferative activity against plant and animal cells, we investigated whether California mugwort extracts have an effect on normal human cells as well as estrogen receptor positive (ER+) and estrogen receptor negative (ER−) human breast cancer cells. Ethanolic and aqueous extracts of A. douglasiana leaves were tested for cytotoxicity against unstimulated normal human peripheral blood mononuclear cells (hPBMC), as well as against an ER+ human breast cancer cell line (BT-474) and an ER− human breast cancer cell line (MDA-MB-231). An ethanolic leaf extract killed hPBMC, BT-474, and MDA-MB-231 cells with IC50 values of 23.6 ± 0.3, 27 ± 5, and 37 ± 4 μg/ml, respectively. An aqueous extract killed hPBMC with an IC50 value of 60 ± 10 μg/ml, but had no effect on the two cancer cell lines at concentrations up to 100 μg/ml. The results of this study indicate that the cytotoxicity of California mugwort extends to normal human cells, as well as cancerous cells. Therefore, until further is known about the safety of this medicine, caution should be taken when consuming extracts of California mugwort, whether as a tincture or as a tea. PMID:24073389

  15. New castanospermine glycoside analogues inhibit breast cancer cell proliferation and induce apoptosis without affecting normal cells.

    Directory of Open Access Journals (Sweden)

    Ghada Allan

    Full Text Available sp²-Iminosugar-type castanospermine analogues have been shown to exhibit anti-tumor activity. However, their effects on cell proliferation and apoptosis and the molecular mechanism at play are not fully understood. Here, we investigated the effect of two representatives, namely the pseudo-S- and C-octyl glycoside 2-oxa-3-oxocastanospermine derivatives SO-OCS and CO-OCS, on MCF-7 and MDA-MB-231 breast cancer and MCF-10A mammary normal cell lines. We found that SO-OCS and CO-OCS inhibited breast cancer cell viability in a concentration- and time-dependent manner. This effect is specific to breast cancer cells as both molecules had no impact on normal MCF-10A cell proliferation. Both drugs induced a cell cycle arrest. CO-OCS arrested cell cycle at G1 and G2/M in MCF-7 and MDA-MB-231 cells respectively. In MCF-7 cells, the G1 arrest is associated with a reduction of CDK4 (cyclin-dependent kinase 4, cyclin D1 and cyclin E expression, pRb phosphorylation, and an overexpression of p21(Waf1/Cip1. In MDA-MB-231 cells, CO-OCS reduced CDK1 but not cyclin B1 expression. SO-OCS accumulated cells in G2/M in both cell lines and this blockade was accompanied by a decrease of CDK1, but not cyclin B1 expression. Furthermore, both drugs induced apoptosis as demonstrated by the increased percentage of annexin V positive cells and Bax/Bcl-2 ratio. Interestingly, in normal MCF-10A cells the two drugs failed to modify cell proliferation, cell cycle progression, cyclins, or CDKs expression. These results demonstrate that the effect of CO-OCS and SO-OCS is triggered by both cell cycle arrest and apoptosis, suggesting that these castanospermine analogues may constitute potential anti-cancer agents against breast cancer.

  16. Three-dimensional imaging of normal skin and nonmelanoma skin cancer with cellular resolution using Gabor domain optical coherence microscopy

    OpenAIRE

    Lee, Kye-Sung; Zhao, Huimin; Ibrahim, Sherrif F; Meemon, Natthani; Khoudeir, Laura; Rolland, Jannick P.

    2012-01-01

    Abstract. We investigate morphological differences in three-dimensional (3-D) images with cellular resolution between nonmelanoma skin cancer and normal skin using Gabor domain optical coherence microscopy. As a result, we show for the first time cellular optical coherence images of 3-D features differentiating cancerous skin from normal skin. In addition, in vivo volumetric images of normal skin from different anatomic locations are shown and compared.

  17. Sub-cellular force microscopy in single normal and cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Babahosseini, H. [VT MEMS Laboratory, The Bradley Department of Electrical and Computer Engineering, Blacksburg, VA 24061 (United States); Carmichael, B. [Nonlinear Intelligent Structures Laboratory, Department of Mechanical Engineering, University of Alabama, Tuscaloosa, AL 35487-0276 (United States); Strobl, J.S. [VT MEMS Laboratory, The Bradley Department of Electrical and Computer Engineering, Blacksburg, VA 24061 (United States); Mahmoodi, S.N., E-mail: nmahmoodi@eng.ua.edu [Nonlinear Intelligent Structures Laboratory, Department of Mechanical Engineering, University of Alabama, Tuscaloosa, AL 35487-0276 (United States); Agah, M., E-mail: agah@vt.edu [VT MEMS Laboratory, The Bradley Department of Electrical and Computer Engineering, Blacksburg, VA 24061 (United States)

    2015-08-07

    This work investigates the biomechanical properties of sub-cellular structures of breast cells using atomic force microscopy (AFM). The cells are modeled as a triple-layered structure where the Generalized Maxwell model is applied to experimental data from AFM stress-relaxation tests to extract the elastic modulus, the apparent viscosity, and the relaxation time of sub-cellular structures. The triple-layered modeling results allow for determination and comparison of the biomechanical properties of the three major sub-cellular structures between normal and cancerous cells: the up plasma membrane/actin cortex, the mid cytoplasm/nucleus, and the low nuclear/integrin sub-domains. The results reveal that the sub-domains become stiffer and significantly more viscous with depth, regardless of cell type. In addition, there is a decreasing trend in the average elastic modulus and apparent viscosity of the all corresponding sub-cellular structures from normal to cancerous cells, which becomes most remarkable in the deeper sub-domain. The presented modeling in this work constitutes a unique AFM-based experimental framework to study the biomechanics of sub-cellular structures. - Highlights: • The cells are modeled as a triple-layered structure using Generalized Maxwell model. • The sub-domains include membrane/cortex, cytoplasm/nucleus, and nuclear/integrin. • Biomechanics of corresponding sub-domains are compared among normal and cancer cells. • Viscoelasticity of sub-domains show a decreasing trend from normal to cancer cells. • The decreasing trend becomes most significant in the deeper sub-domain.

  18. Impact of different IMRT techniques to improve conformity and normal tissue sparing in upper esophageal cancer

    OpenAIRE

    Amin E Amin; Mohamed Kelaney; Samah K Elshamndy; Osiris W. Guirguis

    2015-01-01

    Purpose: Intensity modulated radiotherapy (IMRT) for cervical esophageal cancer is challenging. Although IMRT techniques using inverse planning algorithms are facilitating the treatment planning process, the irradiation dose to the normal tissues can be a critical issue. This study was performed to investigate the effect of beam numbers and their directions and local optimization on: (1) dose conformity and homogeneity to the planning target volume (PTV) and (2) dose to the organ at risks (OA...

  19. Effective Alu Repeat Based RT-Qpcr Normalization in Cancer Cell Perturbation Experiments

    OpenAIRE

    Ali Rihani; Tom Van Maerken; Filip Pattyn; Gert Van Peer; Anneleen Beckers; Sara De Brouwer; Candy Kumps; Evelien Mets; Joni Van der Meulen; Pieter Rondou; Carina Leonelli; Pieter Mestdagh; Frank Speleman; Jo Vandesompele

    2013-01-01

    BACKGROUND: Measuring messenger RNA (mRNA) levels using the reverse transcription quantitative polymerase chain reaction (RT-qPCR) is common practice in many laboratories. A specific set of mRNAs as internal control reference genes is considered as the preferred strategy to normalize RT-qPCR data. Proper selection of reference genes is a critical issue, especially in cancer cells that are subjected to different in vitro manipulations. These manipulations may result in dramatic alterations in ...

  20. Endogenous Voltage Potentials and the Microenvironment: Bioelectric Signals that Reveal, Induce and Normalize Cancer

    OpenAIRE

    Chernet, Brook; Levin, Michael

    2013-01-01

    Cancer may be a disease of geometry: a misregulation of the field of information that orchestrates individual cells’ activities towards normal anatomy. Recent work identified molecular mechanisms underlying a novel system of developmental control: bioelectric gradients. Endogenous spatio-temporal differences in resting potential of non-neural cells provide instructive cues for cell regulation and complex patterning during embryogenesis and regeneration. It is now appreciated that these cues a...

  1. Bombesin family receptor and ligand gene expression in human colorectal cancer and normal mucosa

    OpenAIRE

    Chave, H S; Gough, A C; Palmer, K.; Preston, S. R.; Primrose, J N

    1999-01-01

    Bombesin-like peptides and their receptors are widely distributed throughout the gut and are potential mitogens for a number of gastrointestinal (GI) cancers. We have analysed the expression of bombesin-like peptides and their receptor subtypes in normal and neoplastic colorectal tissue. Expression was analysed by reverse transcription polymerase chain reaction (RT-PCR) using receptor and ligand subtype-specific primers and then expression localized by in situ hybridization (ISH) with ribopro...

  2. ABSOLUTE POLARIMETRY AT RHIC.

    Energy Technology Data Exchange (ETDEWEB)

    OKADA; BRAVAR, A.; BUNCE, G.; GILL, R.; HUANG, H.; MAKDISI, Y.; NASS, A.; WOOD, J.; ZELENSKI, Z.; ET AL.

    2007-09-10

    Precise and absolute beam polarization measurements are critical for the RHIC spin physics program. Because all experimental spin-dependent results are normalized by beam polarization, the normalization uncertainty contributes directly to final physics uncertainties. We aimed to perform the beam polarization measurement to an accuracy Of {Delta}P{sub beam}/P{sub beam} < 5%. The absolute polarimeter consists of Polarized Atomic Hydrogen Gas Jet Target and left-right pairs of silicon strip detectors and was installed in the RHIC-ring in 2004. This system features proton-proton elastic scattering in the Coulomb nuclear interference (CNI) region. Precise measurements of the analyzing power A{sub N} of this process has allowed us to achieve {Delta}P{sub beam}/P{sub beam} = 4.2% in 2005 for the first long spin-physics run. In this report, we describe the entire set up and performance of the system. The procedure of beam polarization measurement and analysis results from 2004-2005 are described. Physics topics of AN in the CNI region (four-momentum transfer squared 0.001 < -t < 0.032 (GeV/c){sup 2}) are also discussed. We point out the current issues and expected optimum accuracy in 2006 and the future.

  3. Absolute polarimetry at RHIC

    CERN Document Server

    Okada, H; Bravar, A; Bunce, G; Dhawan, S; Eyser, K O; Gill, R; Haeberli, W; Huang, H; Jinnouchi, O; Makdisi, Y; Nakagawa, I; Nass, A; Saitô, N; Stephenson, E; Sviridia, D; Wise, T; Wood, J; Zelenski, A

    2007-01-01

    Precise and absolute beam polarization measurements are critical for the RHIC spin physics program. Because all experimental spin-dependent results are normalized by beam polarization, the normalization uncertainty contributes directly to final physics uncertainties. We aimed to perform the beam polarization measurement to an accuracy of $\\Delta P_{beam}/P_{beam} < 5%$. The absolute polarimeter consists of Polarized Atomic Hydrogen Gas Jet Target and left-right pairs of silicon strip detectors and was installed in the RHIC-ring in 2004. This system features \\textit{proton-proton} elastic scattering in the Coulomb nuclear interference (CNI) region. Precise measurements of the analyzing power $A_N$ of this process has allowed us to achieve $\\Delta P_{beam}/P_{beam} =4.2%$ in 2005 for the first long spin-physics run. In this report, we describe the entire set up and performance of the system. The procedure of beam polarization measurement and analysis results from 2004-2005 are described. Physics topics of $A...

  4. Comparison of gene regulatory networks of benign and malignant breast cancer samples with normal samples.

    Science.gov (United States)

    Chen, D B; Yang, H J

    2014-11-11

    The aim of this study was to explain the pathogenesis and deterioration process of breast cancer. Breast cancer expression profile data GSE27567 was downloaded from the Gene Expression Omnibus (GEO) database, and breast cancer-related genes were extracted from databases, including Cancer-Resource and Online Mendelian Inheritance In Man (OMIM). Next, h17 transcription factor data were obtained from the University of California, Santa Cruz. Database for Annotation, Visualization, and Integrated Discovery (DAVID)-enrichment analysis was applied and gene-regulatory networks were constructed by double-two-way t-tests in 3 states, including normal, benign, and malignant. Furthermore, network topological properties were compared between 2 states, and breast cancer-related bub genes were ranked according to their different degrees between each of the two states. A total of 2380 breast cancer-related genes and 215 transcription factors were screened by exploring databases; the genes were mainly enriched in their functions, such as cell apoptosis and proliferation, and pathways, such as p53 signaling and apoptosis, which were related with carcinogenesis. In addition, gene-regulatory networks in the 3 conditions were constructed. By comparing their network topological properties, we found that there is a larger transition of differences between malignant and benign breast cancer. Moreover, 8 hub genes (YBX1, ZFP36, YY1, XRCC5, XRCC4, ZFHX3, ZMAT3, and XPC) were identified in the top 10 genes ranked by different degrees. Through comparative analysis of gene-regulation networks, we identified the link between related genes and the pathogenesis of breast cancer. However, further experiments are needed to confirm our results.

  5. Biomechanical analysis of cancerous and normal cells based on bulge generation in a microfluidic device.

    Science.gov (United States)

    Kim, Yu Chang; Park, Sang-Jin; Park, Je-Kyun

    2008-10-01

    This paper presents a new biomechanical analysis method for discrimination between cancerous and normal cells through compression by poly(dimethylsiloxane) (PDMS) membrane deflection in a microfluidic device. When a cell is compressed, cellular membrane will expand and then small bulges will appear on the peripheral cell membrane beyond the allowable strain. It is well known that the amount of F-actin in cancer cells is less than that of normal cells and bulges occur at the sites where cytoskeleton becomes detached from the membrane bilayer. Accordingly, we have demonstrated the difference of the bulge generation between breast cancer cells (MCF7) and normal cells (MCF10A). After excessive deformation, the bulges generated in MCF7 cells were not evenly distributed on the cell periphery. Contrary to this, the bulges of MCF10A cells showed an even distribution. In addition, the morphologies of bulges of MCF7 and MCF10A cells looked swollen protrusion and tubular protrusion, respectively. Peripheral strains at the moment of the bulge generation were also 72% in MCF7 and 46% in MCF10A. The results show that the bulge generation can be correlated with the cytoskeleton quantity inside the cell, providing the first step of a new biomechanical approach. PMID:18810292

  6. Synuclein gamma predicts poor clinical outcome in colon cancer with normal levels of carcinoembryonic antigen

    Directory of Open Access Journals (Sweden)

    Xing Xiaofang

    2010-07-01

    Full Text Available Abstract Background Synuclein gamma (SNCG, initially identified as a breast cancer specific gene, is aberrantly expressed in many different malignant tumors but rarely expressed in matched nonneoplastic adjacent tissues. In this study, we investigated the prognostic potential of SNCG in colon cancer particularly in the patients with normal carcinoembryonic antigen (CEA levels. Methods SNCG levels were assessed immunohistochemically in cancer tissues from 229 colon adenocarcinoma patients with a mean follow-up of 44 months. Correlations between SNCG levels and clinicopathologic features, preoperative serum CEA level, and clinical outcome were analyzed statistically using SPSS. Results SNCG levels in colon adenocarcinoma were closely associated with intravascular embolus and tumor recurrence but independent of preoperative serum CEA levels. SNCG expression was an independent prognostic factor of a shorter disease-free survival (DFS and overall survival (OS (P P = 0.001, P = 0.001, 0.002 for 97 patients with normal preoperative serum CEA level. Conclusions Our results suggest for the first time that SNCG is a new independent predicator for poor prognosis in patients with colon adenocarcinoma, including those with normal CEA levels. Combination of CEA with SNCG improves prognostic evaluation for patients with colon adenocarcinoma.

  7. Gene Expression Profile Differences in Gastric Cancer and Normal Gastric Mucosa by Oligonucleotide Microarrays

    Institute of Scientific and Technical Information of China (English)

    Chuanding Yu; Shenhua Xu; HangZhou Mou; Zhiming Jiang; Chihong Zhu; Xianglin Liu

    2006-01-01

    OBJECTIVE To study the difference of gene expression in gastric cancer (T) and normal tissue of gastric mucosa (C), and to screen for associated novel genes in gastric cancers by oligonucleotide microarrays.METHODS U133A (Affymetrix, Santa Clara, CA) gene chip was used to detect the gene expression profile difference in T and C. Bioinformatics was used to analyze the detected results.RESULTS When gastric cancers were compared with normal gastric mucosa, a total of 270 genes were found with a difference of more than 9times in expression levels. Of the 270 genes, 157 were up-regulated (Signal Log Ratio [SLR] ≥3), and 113 were down-regulated (SLR ≤-3).Using a classification of function, the highest number of gene expression differences related to enzymes and their regulatory genes (67, 24.8%),followed by signal-transduction genes (43,15.9%). The third were nucleic acid binding genes (17, 6.3%), fourth were transporter genes (15, 5.5%)and fifth were protein binding genes (12, 4.4%). In addition there were 50genes of unknown function, accounting for 18.5%. The five above mentioned groups made up 56.9% of the total gene number.CONCLUSION The 5 gene groups (enzymes and their regulatory proteins, signal transduction proteins, nucleic acid binding proteins, transporter and protein binding) were abnormally expressed and are important genes for further study in gastric cancers.

  8. Biopsies of the normal-appearing urothelium in primary bladder cancer

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    Davor Librenjak

    2010-01-01

    Full Text Available Aim: The aim of the study was to determine the incidence of "positive" findings in biopsies of the normal-appearing urothelium near primary cancer and their influence on therapeutic decisions. Materials and Methods: Between January 2001 and October 2008, in 230 patients with primary bladder cancer during initial resection of tumor, we also performed random biopsy of surrounding normal-appearing urothelium. We analyzed retrospectively the number and type of positive biopsy findings and their impact on further treatment. Results: There were 40% of patients (92/230 whose normal-appearing urothelium biopsy revealed pathological findings such as tumor tissue, Tis, and dysplasia. In 24.4% of patients, the stage of the primary tumor was Ta (32/131, in 50% it was T1 stage (30/61, and in 79% T2 stage (30/38. When we assessed the grade of malignancy, we found 18% of biopsies with G1 tumors (16/88, 33% with G2 tumors (19/59, and 69% with G3 tumors (57/83. Tumor tissue that was found in the normal-appearing urothelium in biopsy specimens in 13% of patients was in stage Ta (17/131, in 16% it was T1 stage (10/61, and in 39% of patients, the tumor was in T2 stage (15/38. Pathological findings of random biopsies were crucial in changing therapeutical decisions in 4.6% (9/192 of patients. Conclusion: Biopsy of the normal-appearing urothelial tissue is easy to perform and may help in identifying patients with high risk of disease progression and recurrence. Based on our results and results from the literature we recommend this simple tool as part of the routine management during transurethral resection of primary bladder cancer.

  9. Monoallelic chromatin conformation flanking long-range silenced domains in cancer-derived and normal cells.

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    Domenic Di Paola

    Full Text Available Epigenetic inactivation of chromatin plays an important role in determining cell phenotype in both normal and cancer cells, but our knowledge is still incomplete with respect to any potential monoallelic nature of the phenomenon. We have genotyped DNA isolated from chromatin of two colorectal cancer-derived lines and a culture of normal human intestinal epithelial cells (HIEC, which was immunoprecipitated with antibodies to acetylated vs. methylated histone H3K9, and presented the data as B allele frequency differences over multiple single-nucleotide polymorphism (SNP moving window averages. [B allele is an arbitrary term defined as one of the two alleles at any given SNP, named A and B]. Three different validation tests confirmed that peaks exhibiting differences represented monoallelic domains. These complementary tests confirmed the following: 1 genes in the regions of high B allele frequency difference were expressed monoallelically; 2 in normal cells all five imprinting control regions which carried heterozygous SNPs were characterized by B allele difference peaks; and 3 the haplotypes in the B allele difference peaks were faithfully maintained in the chromatin immunoprecipitated with the respective antibodies. In both samples most of the monoallelic domains were found at the boundaries between regions of open and closed chromatin. With respect to the cancer line, this supports the established concept of conformation spreading, but the results from the normal cells were unexpected. Since these cells were polyclonal, the monoallelic structures were probably not determined by random choice as occurs in X-inactivation, so we propose that epigenetic inactivation in some domains may be heritable and polymorphic in normal human cells.

  10. Comparative evaluation of cancer stem cell markers in normal pancreas and pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Vizio, Barbara; Mauri, Francesco A; Prati, Adriana; Trivedi, Pritesh; Giacobino, Alice; Novarino, Anna; Satolli, Maria Antonietta; Ciuffreda, Libero; Camandona, Michele; Gasparri, Guido; Bellone, Graziella

    2012-01-01

    Chemoresistance and self-renewal of cancer stem cells (CSC), found in many tumors including pancreatic ductal adenocarcinoma (PDAC), are believed to underlie tumor mass regrowth. The distribution of cells carrying the putative stem-cell markers CD133, Nestin, Notch1-4, Jagged1 and 2, ABCG2 and aldehyde dehydrogenase (ALDH1) was assessed immunohistochemically using PDAC and normal pancreas tissue microarrays. The immunoreactivity was semi-quantitatively graded against the normal pancreas and was correlated with the differentiation grade and disease stage. No statistical significant differences were found between normal pancreas and PDAC in the expression of Nestin, Notch1, 3 and 4, ABCG2 or ALDH1. Notch2 and Jagged1 and 2 expression were increased in PDAC. CD133-positive cells were above-normal in PDAC, but the difference was not statistically significant. Nestin, Notch1-4, Jagged1, ABCG2 and ALDH1 immunostaining scores were not correlated with tumor grade or disease stage. CD133 and Notch2 expression was significantly inversely correlated with tumor grade, but not disease stage. Notch3 immunostaining positively correlated with tumor stage, but not with differentiation grade. Jagged2 protein expression correlated inversely with disease stage, but not with tumor grade. From the clinical standpoint, improved delineation of the tumor CSC signature, putatively responsible for tumor initiation and recurrence after initial response to chemotherapy, may offer novel therapeutic targets for this highly lethal cancer.

  11. Fluorescence Characteristics and Lifetime Images of Photosensitizers of Talaporfin Sodium and Sodium Pheophorbide a in Normal and Cancer Cells

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    Kamlesh Awasthi

    2015-05-01

    Full Text Available Fluorescence spectra and fluorescence lifetime images of talaporfin sodium and sodium-pheophorbide a, which can be regarded as photosensitizers for photodynamic therapy, were measured in normal and cancer cells. The reduction of the fluorescence intensity by photoirradiation was observed for both photosensitizers in both cells, but the quenching rate was much faster in cancer cells than in normal cells. These results are explained in terms of the excessive generation of reactive oxygen species via photoexcitation of these photosensitizers in cancer cells. The fluorescence lifetimes of both photosensitizers in cancer cells are different from those in normal cells, which originates from the different intracellular environments around the photosensitizers between normal and cancer cells.

  12. Intraoperative near-infrared imaging can distinguish cancer from normal tissue but not inflammation.

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    David Holt

    Full Text Available Defining tumor from non-tumor tissue is one of the major challenges of cancer surgery. Surgeons depend on visual and tactile clues to select which tissues should be removed from a patient. Recently, we and others have hypothesized near-infrared (NIR imaging can be used during surgery to differentiate tumors from normal tissue.We enrolled 8 canines and 5 humans undergoing cancer surgery for NIR imaging. The patients were injected with indocyanine green (ICG, an FDA approved non-receptor specific NIR dye that accumulates in hyperpermeable tissues, 16-24 hours prior to surgery. During surgery, NIR imaging was used to discriminate the tumor from non-tumor tissue.NIR imaging identified all tumors with a mean signal-to-background ratio of 6.7. Optical images were useful during surgery in discriminating normal tissue from cancer. In 3 canine cases and 1 human case, the tissue surrounding the tumor was inflamed due to obstruction of the vascular supply due to mass effect. In these instances, NIR imaging could not distinguish tumor tissue from tissue that was congested, edematous and did not contain cancer.This study shows that NIR imaging can identify tumors from normal tissues, provides excellent tissue contrast, and it facilitates the resection of tumors. However, in situations where there is significant peritumoral inflammation, NIR imaging with ICG is not helpful. This suggests that non-targeted NIR dyes that accumulate in hyperpermeable tissues will have significant limitations in the future, and receptor-specific NIR dyes may be necessary to overcome this problem.

  13. Absolute quantification of acetylation and phosphorylation of the histone variant H2AX upon ionizing radiation reveals distinct cellular responses in two cancer cell lines.

    Science.gov (United States)

    Matsuda, Shun; Furuya, Kanji; Ikura, Masae; Matsuda, Tomonari; Ikura, Tsuyoshi

    2015-11-01

    Histone modifications change upon the cellular response to ionizing radiation, and their cellular amounts could reflect the DNA damage response activity. We previously reported a sensitive and reliable method for the absolute quantification of γH2AX within cells, using liquid chromatography-tandem mass spectrometry (LC/MS/MS). The technique has broad adaptability to a variety of biological systems and can quantitate different modifications of histones. In this study, we applied it to quantitate the levels of γH2AX and K5-acetylated H2AX, and to compare the radiation responses between two cancer cell lines: HeLa and U-2 OS. The two cell lines have distinct properties in terms of their H2AX modifications. HeLa cells have relatively high γH2AX (3.1 %) against the total H2AX even in un-irradiated cells, while U-2 OS cells have an essentially undetectable level (nearly 0 %) of γH2AX. In contrast, the amounts of acetylated histones are lower in HeLa cells (9.3 %) and higher in U-2 OS cells (24.2 %) under un-irradiated conditions. Furthermore, after ionizing radiation exposure, the time-dependent increases and decreases in the amounts of histone modifications differed between the two cell lines, especially at the early time points. These results suggest that each biological system has distinct kinase/phosphatase and/or acetylase/deacetylase activities. In conclusion, for the first time, we have succeeded in simultaneously monitoring the absolute amounts of phosphorylated and acetylated cellular H2AX after ionizing radiation exposure. This multi-criteria assessment enables precise comparisons of the effects of radiation between any biological systems.

  14. Teaching Absolute Value Meaningfully

    Science.gov (United States)

    Wade, Angela

    2012-01-01

    What is the meaning of absolute value? And why do teachers teach students how to solve absolute value equations? Absolute value is a concept introduced in first-year algebra and then reinforced in later courses. Various authors have suggested instructional methods for teaching absolute value to high school students (Wei 2005; Stallings-Roberts…

  15. The effect of Stokes shift in the discrimination of urine of cervical cancer from normal subjects

    Science.gov (United States)

    Rajasekaran, Ramu; Brindha, Elumalai; Aruna, Prakasa Rao; Koteeswaran, Dornadula; Ganesan, Singaravelu

    2016-03-01

    Stokes shift spectroscopy has been considered as a potential tool in characterization of multiple components present in tissues and biofluids. Since, the intensity and resolution of the fluorophores depends on the Stokes shift, different opinion has been reflected by the researchers in fixing the Stokes shift. Also, not many studies have been reported on the characterization of biofluids and especially on the diagnosis of cancer. Urine is considered as an important diagnostic biofluid as it is rich in many metabolites where many of them are native fluorophores. In this study, we aimed at characterizing the urine of normal subjects and patients with cervical cancer as function of different Stokes shift. It is observed that Neopterin and Riboflavin are the main fluorophores contribute to the variation between normal and cervical cancer subjects. Ratio variables based linear discriminant analysis shows that the Stokes shift of 40 nm and 60 nm may be considered for better characterization with better signal to noise ratio when compared to others.

  16. Identification of genes with altered expression in medullary breast cancer vs. ductal breast cancer and normal breast epithelia

    DEFF Research Database (Denmark)

    Gjerstorff, Morten; Benoit, Vivian; Laenkholm, Anne-Vibeke;

    2006-01-01

    Medullary breast cancer (MCB) is a morphologically and biologically distinct subtype that, despite cytologically highly malignant characteristics, has a favorable prognosis compared to the more common infiltrating ductal breast carcinoma. MCB metastasizes less frequently, which has been attributed...... to both immunological and endogenous cellular factors, although little is known about the distinct biology of MCB that may contribute to the improved outcome of MCB patients. To identify candidate genes, we performed gene array expression analysis of cell lines of MCB, ductal breast cancer and normal...... breast epithelia, and the differential expression of a panel of candidate genes was further validated by quantitative PCR and immunohistochemical analysis of cell lines and tumor biopsies. A limited number of genes, including several members of the GAGE and insulin growth factor binding protein (IGFBP...

  17. Identification of genes with altered expression in medullary breast cancer vs. ductal breast cancer and normal breast epithelia

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Benoit, Vivian M; Laenkholm, Anne-Vibeke;

    2006-01-01

    to both immunological and endogenous cellular factors, although little is known about the distinct biology of MCB that may contribute to the improved outcome of MCB patients. To identify candidate genes, we performed gene array expression analysis of cell lines of MCB, ductal breast cancer and normal......Medullary breast cancer (MCB) is a morphologically and biologically distinct subtype that, despite cytologically highly malignant characteristics, has a favorable prognosis compared to the more common infiltrating ductal breast carcinoma. MCB metastasizes less frequently, which has been attributed...... breast epithelia, and the differential expression of a panel of candidate genes was further validated by quantitative PCR and immunohistochemical analysis of cell lines and tumor biopsies. A limited number of genes, including several members of the GAGE and insulin growth factor binding protein (IGFBP...

  18. Endothelial cells stimulate growth of normal and cancerous breast epithelial cells in 3D culture

    Directory of Open Access Journals (Sweden)

    Magnusson Magnus K

    2010-07-01

    Full Text Available Abstract Background Epithelial-stromal interaction provides regulatory signals that maintain correct histoarchitecture and homeostasis in the normal breast and facilitates tumor progression in breast cancer. However, research on the regulatory role of the endothelial component in the normal and malignant breast gland has largely been neglected. The aim of the study was to investigate the effects of endothelial cells on growth and differentiation of human breast epithelial cells in a three-dimensional (3D co-culture assay. Methods Breast luminal and myoepithelial cells and endothelial cells were isolated from reduction mammoplasties. Primary cells and established normal and malignant breast cell lines were embedded in reconstituted basement membrane in direct co-culture with endothelial cells and by separation of Transwell filters. Morphogenic and phenotypic profiles of co-cultures was evaluated by phase contrast microscopy, immunostaining and confocal microscopy. Results In co-culture, endothelial cells stimulate proliferation of both luminal- and myoepithelial cells. Furthermore, endothelial cells induce a subpopulation of luminal epithelial cells to form large acini/ducts with a large and clear lumen. Endothelial cells also stimulate growth and cloning efficiency of normal and malignant breast epithelial cell lines. Transwell and gradient co-culture studies show that endothelial derived effects are mediated - at least partially - by soluble factors. Conclusion Breast endothelial cells - beside their role in transporting nutrients and oxygen to tissues - are vital component of the epithelial microenvironment in the breast and provide proliferative signals to the normal and malignant breast epithelium. These growth promoting effects of endothelial cells should be taken into consideration in breast cancer biology.

  19. Labeling and biodistribution of therapeutic radiopharmaceutical for brain cancer 125I-Nimotuzumab in normal mice

    International Nuclear Information System (INIS)

    Nimotuzumab is a monoclonal antibody which known giving contribution in anti proliferation, pro apoptosis and antiangionik effect on the therapy of brain cancer (glioma). The labeling of monoclonal antibody nimotuzumab with 125I which radiate auger electrons has been done with idogen method. The best result of radiochemical purity (97%) was shown in fraction 6 with the mol ratio of nimotuzumab towards potassium iodide and iodogen was 1 : 2 : 1200. Radiochemical purity was examined by paper chromatography with whatman paper no. 1 as the stationary phase and ethano!-butanol-ammonium hydroxide with a ratio of 3 : 2 : 1 as the mobile phase. Rf Values for 125I-nimotuzumab is 0.0, while Rf value of 125I .is 0.9. The biodistribution result on normal mice for 72 hours showed that 125I-nimotuzumab not only has a long half-life time but also has high accumulation in liver (1.97 + 1.18%), kidney (0.82 + 0.28%) and muscle (0.61+ 0.98%). The highest accumulation in brain on normal mice (0.128 + 0.06 %) occurred 24 hours after injection. Based on the therapeutic effects and organ accumulation on normal mice, 125I-nimotuzumab could be potentially used for brain cancer therapy. (author)

  20. Nonlinear optical microscopy for histology of fresh normal and cancerous pancreatic tissues.

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    Wenyan Hu

    Full Text Available BACKGROUND: Pancreatic cancer is a lethal disease with a 5-year survival rate of only 1-5%. The acceleration of intraoperative histological examination would be beneficial for better management of pancreatic cancer, suggesting an improved survival. Nonlinear optical methods based on two-photon excited fluorescence (TPEF and second harmonic generation (SHG of intrinsic optical biomarkers show the ability to visualize the morphology of fresh tissues associated with histology, which is promising for real-time intraoperative evaluation of pancreatic cancer. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate whether the nonlinear optical imaging methods have the ability to characterize pancreatic histology at cellular resolution, we studied different types of pancreatic tissues by using label-free TPEF and SHG. Compared with other routine methods for the preparation of specimens, fresh tissues without processing were found to be most suitable for nonlinear optical imaging of pancreatic tissues. The detailed morphology of the normal rat pancreas was observed and related with the standard histological images. Comparatively speaking, the preliminary images of a small number of chemical-induced pancreatic cancer tissues showed visible neoplastic differences in the morphology of cells and extracellular matrix. The subcutaneous pancreatic tumor xenografts were further observed using the nonlinear optical microscopy, showing that most cells are leucocytes at 5 days after implantation, the tumor cells begin to proliferate at 10 days after implantation, and the extracellular collagen fibers become disordered as the xenografts grow. CONCLUSIONS/SIGNIFICANCE: In this study, nonlinear optical imaging was used to characterize the morphological details of fresh pancreatic tissues for the first time. We demonstrate that it is possible to provide real-time histological evaluation of pancreatic cancer by the nonlinear optical methods, which present an

  1. Quantitative Analysis of Differential Proteome Expression in Bladder Cancer vs. Normal Bladder Cells Using SILAC Method.

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    Ganglong Yang

    Full Text Available The best way to increase patient survival rate is to identify patients who are likely to progress to muscle-invasive or metastatic disease upfront and treat them more aggressively. The human cell lines HCV29 (normal bladder epithelia, KK47 (low grade nonmuscle invasive bladder cancer, NMIBC, and YTS1 (metastatic bladder cancer have been widely used in studies of molecular mechanisms and cell signaling during bladder cancer (BC progression. However, little attention has been paid to global quantitative proteome analysis of these three cell lines. We labeled HCV29, KK47, and YTS1 cells by the SILAC method using three stable isotopes each of arginine and lysine. Labeled proteins were analyzed by 2D ultrahigh-resolution liquid chromatography LTQ Orbitrap mass spectrometry. Among 3721 unique identified and annotated proteins in KK47 and YTS1 cells, 36 were significantly upregulated and 74 were significantly downregulated with >95% confidence. Differential expression of these proteins was confirmed by western blotting, quantitative RT-PCR, and cell staining with specific antibodies. Gene ontology (GO term and pathway analysis indicated that the differentially regulated proteins were involved in DNA replication and molecular transport, cell growth and proliferation, cellular movement, immune cell trafficking, and cell death and survival. These proteins and the advanced proteome techniques described here will be useful for further elucidation of molecular mechanisms in BC and other types of cancer.

  2. The Function of Steroid Receptor Coactivator-1 in Normal Tissues and Cancer

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    Claire A. Walsh, Li Qin, Jean Ching-Yi Tien, Leonie S. Young, Jianming Xu

    2012-01-01

    Full Text Available In 1995, the steroid receptor coactivator-1 (SRC-1 was identified as the first authentic steroid receptor coactivator. Since then, the SRC proteins have remained at the epicenter of coregulator biology, molecular endocrinology and endocrine-related cancer. Cumulative works on SRC-1 have shown that it is primarily a nuclear receptor coregulator and functions to construct highly specific enzymatic protein complexes which can execute efficient and successful transcriptional activation of designated target genes. The versatile nature of SRC-1 enables it to respond to steroid dependent and steroid independent stimulation, allowing it to bind across many families of transcription factors to orchestrate and regulate complex physiological reactions. This review highlights the multiple functions of SRC-1 in the development and maintenance of normal tissue functions as well as its major role in mediating hormone receptor responsiveness. Insights from genetically manipulated mouse models and clinical data suggest SRC-1 is significantly overexpressed in many cancers, in particular, cancers of the reproductive tissues. SRC-1 has been associated with cellular proliferation and tumor growth but its major tumorigenic contributions are promotion and execution of breast cancer metastasis and mediation of resistance to endocrine therapies. The ability of SRC-1 to coordinate multiple signaling pathways makes it an important player in tumor cells' escape of targeted therapy.

  3. Imaging normal and cancerous human gastric muscular layer in transverse and longitudinal sections by multiphoton microscopy.

    Science.gov (United States)

    Zhou, Yi; Kang, Deyong; Yang, Zhenrong; Li, Lianhuang; Zhuo, Shuangmu; Zhu, Xiaoqin; Zhou, Yongjian; Chen, Jianxin

    2016-07-01

    Multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) has been widely used for imaging microstructure of biological tissues. In this article, we used MPM to investigate the microstructure changes of normal and cancerous human gastric muscular layer in transverse and longitudinal sections. The results displayed different patterns of microstructure changes of smooth muscular tissue, cell morphology and interstitial fibers in transverse and longitudinal sections, being similar to standard histopathological images but without the need for tissue processing. Our study demonstrated that MPM can bring more detailed complementary information on tissue architecture through observing transverse and longitudinal sections of tissues, which are the important pathological information when the pathologists diagnose the gastrointestinal lesions. These observations indicate that MPM could be an important potential tool to provide real-time pathological diagnosis for gastric cancer in the future. SCANNING 38:357-364, 2016. © 2015 Wiley Periodicals, Inc. PMID:26435529

  4. Wnt/β-catenin Signaling in Normal and Cancer Stem Cells

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    Kenneth C. Valkenburg

    2011-04-01

    Full Text Available The ability of Wnt ligands to initiate a signaling cascade that results in cytoplasmic stabilization of, and nuclear localization of, β-catenin underlies their ability to regulate progenitor cell differentiation. In this review, we will summarize the current knowledge of the mechanisms underlying Wnt/β-catenin signaling and how the pathway regulates normal differentiation of stem cells in the intestine, mammary gland, and prostate. We will also discuss how dysregulation of the pathway is associated with putative cancer stem cells and the potential therapeutic implications of regulating Wnt signaling.

  5. Cancer antigen 125 after delivery in women with a normal pregnancy

    DEFF Research Database (Denmark)

    Szecsi, Pal B; Andersen, Malene R; Bjørngaard, Brian;

    2014-01-01

    , Denmark. POPULATION: Eight hundred and one women with expected normal pregnancies were investigated. Of these, 640 delivered vaginally, 82 by emergency cesarean section, and 79 by elective cesarean section; 720 women had uncomplicated pregnancies. METHODS: Samples were collected at gestational weeks 13...... gestational period and around delivery. RESULTS: CA-125 was fairly stable below 35 U/mL during pregnancy but increased markedly during vaginal delivery, to a minor degree during emergency cesarean section, and only slightly during elective cesarean section. In the early postpartum period, CA-125 decreased......OBJECTIVE: To establish reference intervals for cancer antigen 125 (CA-125) in women with expected normal pregnancy, delivery, and early postpartum period. DESIGN: Prospective observational study. SETTING: Department of Clinical Biochemistry and Obstetrics, Copenhagen University Hospital, Gentofte...

  6. Variance computations for functional of absolute risk estimates

    OpenAIRE

    Pfeiffer, R. M.; E. Petracci

    2011-01-01

    We present a simple influence function based approach to compute the variances of estimates of absolute risk and functions of absolute risk. We apply this approach to criteria that assess the impact of changes in the risk factor distribution on absolute risk for an individual and at the population level. As an illustration we use an absolute risk prediction model for breast cancer that includes modifiable risk factors in addition to standard breast cancer risk factors. Influence function base...

  7. Unraveling the microenvironmental influences on the normal mammary gland and induction and progression of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Weigelt, Britta; Bissell, Mina J.

    2008-06-26

    The normal mammary gland and invasive breast cancer are both complex 'organs' composed of multiple cell types as well as extracellular matrix (ECM) in three-dimensional (3D) space. Conventionally, both normal and malignant breast cells are studied in vitro as two-dimensional (2D) monolayers of epithelial cells, which results in the loss of structure and tissue function. Many laboratories are now investigating regulation of signaling function in normal mammary gland using 3D cultures. However, it is important also to assay malignant breast cells ex vivo in a physiologically relevant environment to more closely mimic tumor architecture, signal transduction regulation and tumor behavior in vivo. Here we present the potential of these 3D models for drug testing, target validation and guidance of patient selection for clinical trials. We argue also that in order to get full insight into the biology of the normal and malignant breast, and to create in vivo-like models for therapeutic approaches in humans, we need to continue to create more complex heterotypic models to approach the full context the cells encounter in the human body.

  8. STUDY OF ECK GENE EXON-3 FROM HUMAN NORMAL TISSUE AND BREAST CANCER CELL LINE

    Institute of Scientific and Technical Information of China (English)

    李瑶琛; 孔令洪; 王一理; 司履生

    2003-01-01

    Objective To establish a method cloning the exon 3 of eck gene from normal tissue and ZR-75-1 cell line (a human breast cancer cell line)and study whether these genes exist mutant. Methods Designed a pair of specific primers and amplified the exon 3 of eck gene fragment from the extracted genomic DNA derived from normal epithelial cells from skin tissue and ZR-75-1 cell line respectively by PCR technique. Transformed the E.coil. JM109 with recombinant plamids constructed by inserting the amplified fragments into medium vector pUCm-T and sequenced these amplified fragments after primary screening of endonuclease restriction digestion and PCR amplification. Results ① Obtained the genomic DNA of human normal epithelial cells and ZR-75-1 cell line respectively. ② Obtained the amplified fragments of human exon 3 of eck gene through PCR technique. ③ Obtained the cloning vectors of exon 3 of eck gene of human normal epithelial cells and ZR-75-1 cell line respectively. ④ ZR-75-1 cell line exists mutation of nucleotides. Conclusion Successfully established the method of cloning the human exon 3 of eck gene and found some mutations in the detected samples. This study lays a foundation for further studying the function of eck gene in tumorgenesis.

  9. Log-normal censored regression model detecting prognostic factors in gastric cancer: A study of 3018 cases

    Institute of Scientific and Technical Information of China (English)

    Bin-Bin Wang; Cai-Gang Liu; Ping Lu; A Latengbaolide; Yang Lu

    2011-01-01

    AIM: To investigate the efficiency of Cox proportional hazard model in detecting prognostic factors for gastric cancer.METHODS: We used the log-normal regression model to evaluate prognostic factors in gastric cancer and compared it with the Cox model. Three thousand and eighteen gastric cancer patients who received a gastrectomy between 1980 and 2004 were retrospectively evaluated. Clinic-pathological factors were included in a log-normal model as well as Cox model. The akaike information criterion (AIC) was employed to compare the efficiency of both models. Univariate analysis indicated that age at diagnosis, past history, cancer location, distant metastasis status, surgical curative degree, combined other organ resection, Borrmann type, Lauren's classification, pT stage, total dissected nodes and pN stage were prognostic factors in both log-normal and Cox models.RESULTS: In the final multivariate model, age at diagnosis,past history, surgical curative degree, Borrmann type, Lauren's classification, pT stage, and pN stage were significant prognostic factors in both log-normal and Cox models. However, cancer location, distant metastasis status, and histology types were found to be significant prognostic factors in log-normal results alone.According to AIC, the log-normal model performed better than the Cox proportional hazard model (AIC value:2534.72 vs 1693.56).CONCLUSION: It is suggested that the log-normal regression model can be a useful statistical model to evaluate prognostic factors instead of the Cox proportional hazard model.

  10. Diagnostic Classification of Normal Persons and Cancer Patients by Using Neural Network Based on Trace Metal Contents in Serum Samples

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Artificial neural network with the back-propagation(BP-ANN) approach was applied to the classification of normal persons and various cancer patients based on the elemental contents in serum samples. This method was verified by the cross-validation method. The effects of the net work parameters were investigated and the related problems were discussed. The samples of 72, 42, and 52 for lung, liver, and stomach cancer patients and normal persons, respectively, were used for the classification study. About 95% of the samples can be classified correctly. There fore, the method can be used as an auxiliary means of the diagnosis of cancer.

  11. Attenuated total reflectance Fourier transform infrared spectroscopy method to differentiate between normal and cancerous breast cells.

    Science.gov (United States)

    Lane, Randy; See, Seong S

    2012-09-01

    Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) is used to find the structural differences between cancerous breast cells (MCF-7 line) and normal breast cells (MCF-12F line). Gold nanoparticles were prepared and the hydrodynamic diameter of the gold nanoparticles found to be 38.45 nm. The Gold nanoparticles were exposed to both MCF-7 and MCF-12F cells from lower to higher concentrations. Spectroscopic studies founds nanoparticles were within the cells, and increasing the nanoparticles concentration inside the cells also resulted in sharper IR peaks as a result of localized surface Plasmon resonance. Asymmetric and symmetric stretching and bending vibrations between phosphate, COO-, CH2 groups were found to give negative shifts in wavenumbers and a decrease in peak intensities when going from noncancerous to cancerous cells. Cellular proteins produced peak assignments at the 1542 and 1644 cm(-1) wavenumbers which were attributed to the amide I and amide II bands of the polypeptide bond of proteins. Significant changes were found in the peak intensities between the cell lines in the spectrum range from 2854-2956 cm(-1). Results show that the concentration range of gold nanoparticles used in this research showed no significant changes in cell viability in either cell line. Therefore, we believe ATR-FTIR and gold nanotechnology can be at the forefront of cancer diagnosis for some time to come.

  12. DNA damage in oral cancer and normal cells induced by nitrogen atmospheric pressure plasma jets

    Science.gov (United States)

    Han, Xu; Kapaldo, James; Liu, Yueying; Stack, M. Sharon; Ptasinska, Sylwia

    2015-09-01

    Nitrogen atmospheric pressure plasma jets (APPJs) have been shown to effectively induce DNA double strand breaks in SCC25 oral cancer cells. The APPJ source constructed in our laboratory operates based on dielectric barrier discharge. It consists of two copper electrodes alternatively wrapping around a fused silica tube with nitrogen as a feed gas. It is generally more challenging to ignite plasma in N2 atmosphere than in noble gases. However, N2 provides additional advantages such as lower costs compared to noble gases, thus this design can be beneficial for the future long-term clinical use. To compare the effects of plasma on cancer cells (SCC25) and normal cells (OKF), the cells from both types were treated at the same experimental condition for various treatment times. The effective area with different damage levels after the treatment was visualized as 3D maps. The delayed damage effects were also explored by varying the incubation times after the treatment. All of these studies are critical for a better understanding of the damage responses of cellular systems exposed to the plasma radiation, thus are useful for the development of the advanced plasma cancer therapy. The research described herein was supported by the Division of Chemical Sciences, Geosciences and Biosciences, Basic Energy Sciences, Office of Science, United States Department of Energy through Grant No. DE-FC02-04ER15533.

  13. Evaluation of algorithm methods for fluorescence spectra of cancerous and normal human tissues

    Science.gov (United States)

    Pu, Yang; Wang, Wubao; Alfano, Robert R.

    2016-03-01

    The paper focus on the various algorithms on to unravel the fluorescence spectra by unmixing methods to identify cancerous and normal human tissues from the measured fluorescence spectroscopy. The biochemical or morphologic changes that cause fluorescence spectra variations would appear earlier than the histological approach; therefore, fluorescence spectroscopy holds a great promise as clinical tool for diagnosing early stage of carcinomas and other deceases for in vivo use. The method can further identify tissue biomarkers by decomposing the spectral contributions of different fluorescent molecules of interest. In this work, we investigate the performance of blind source un-mixing methods (backward model) and spectral fitting approaches (forward model) in decomposing the contributions of key fluorescent molecules from the tissue mixture background when certain selected excitation wavelength is applied. Pairs of adenocarcinoma as well as normal tissues confirmed by pathologist were excited by selective wavelength of 340 nm. The emission spectra of resected fresh tissue were used to evaluate the relative changes of collagen, reduced nicotinamide adenine dinucleotide (NADH), and Flavin by various spectral un-mixing methods. Two categories of algorithms: forward methods and Blind Source Separation [such as Principal Component Analysis (PCA) and Independent Component Analysis (ICA), and Nonnegative Matrix Factorization (NMF)] will be introduced and evaluated. The purpose of the spectral analysis is to discard the redundant information which conceals the difference between these two types of tissues, but keep their diagnostically significance. The facts predicted by different methods were compared to the gold standard of histopathology. The results indicate that these key fluorophores within tissue, e.g. tryptophan, collagen, and NADH, and flavin, show differences of relative contents of fluorophores among different types of human cancer and normal tissues. The

  14. Ruta 6 selectively induces cell death in brain cancer cells but proliferation in normal peripheral blood lymphocytes: A novel treatment for human brain cancer.

    Science.gov (United States)

    Pathak, Sen; Multani, Asha S; Banerji, Pratip; Banerji, Prasanta

    2003-10-01

    Although conventional chemotherapies are used to treat patients with malignancies, damage to normal cells is problematic. Blood-forming bone marrow cells are the most adversely affected. It is therefore necessary to find alternative agents that can kill cancer cells but have minimal effects on normal cells. We investigated the brain cancer cell-killing activity of a homeopathic medicine, Ruta, isolated from a plant, Ruta graveolens. We treated human brain cancer and HL-60 leukemia cells, normal B-lymphoid cells, and murine melanoma cells in vitro with different concentrations of Ruta in combination with Ca3(PO4)2. Fifteen patients diagnosed with intracranial tumors were treated with Ruta 6 and Ca3(PO4)2. Of these 15 patients, 6 of the 7 glioma patients showed complete regression of tumors. Normal human blood lymphocytes, B-lymphoid cells, and brain cancer cells treated with Ruta in vitro were examined for telomere dynamics, mitotic catastrophe, and apoptosis to understand the possible mechanism of cell-killing, using conventional and molecular cytogenetic techniques. Both in vivo and in vitro results showed induction of survival-signaling pathways in normal lymphocytes and induction of death-signaling pathways in brain cancer cells. Cancer cell death was initiated by telomere erosion and completed through mitotic catastrophe events. We propose that Ruta in combination with Ca3(PO4)2 could be used for effective treatment of brain cancers, particularly glioma.

  15. Monitoring of permeability of different analytes in human normal and cancerous bladder tissues in vitro using optical coherence tomography

    Energy Technology Data Exchange (ETDEWEB)

    Bingsong Lei; Xiaoyuan Deng; Huajiang Wei; Zhouyi Guo [MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, Guangdong Province (China); Guoyong Wu [Department of Surgery, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, Guangdong Province (China); Hongqin Yang; Shusen Xie [Key Laboratory of Optoelectronic Science and Technology for Medicine of Ministry of Education of China, Fujian Normal University, Fuzhou 350007, Fujian (China); Yonghong He [Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, Guangdong (China)

    2014-12-31

    We report our preliminary results on quantification of glucose and dimethyl sulfoxide (DMSO) diffusion in normal and cancerous human bladder tissues in vitro by using a spectral domain optical coherence tomography (SD-OCT). The permeability coefficients (PCs) of a 30% aqueous solution of glucose are found to be (7.92 ± 0.81) × 10{sup -6} cm s{sup -1} and (1.19 ± 0.13) × 10{sup -5} cm s{sup -1} in normal and cancerous bladder tissues, respectively. The PCs of 50% DMSO are calculated to be (8.99 ± 0.93) × 10{sup -6} cm s{sup -1} and (1.43 ± 0.17) × 10{sup -5} cm s{sup -1} in normal and cancerous bladder tissues, respectively. The obtained results show a statistically significant difference in permeability of normal and cancerous tissue and indicate that the PC of 50% DMSO is about 1.13-and 1.21-fold higher than that of 30% glucose in normal bladder and cancerous bladder tissues, respectively. Thus, the quantitative measurements with the help of PCs from OCT images can be a potentially powerful method for bladder cancer detection. (optical coherence tomography)

  16. Monitoring of permeability of different analytes in human normal and cancerous bladder tissues in vitro using optical coherence tomography

    International Nuclear Information System (INIS)

    We report our preliminary results on quantification of glucose and dimethyl sulfoxide (DMSO) diffusion in normal and cancerous human bladder tissues in vitro by using a spectral domain optical coherence tomography (SD-OCT). The permeability coefficients (PCs) of a 30% aqueous solution of glucose are found to be (7.92 ± 0.81) × 10-6 cm s-1 and (1.19 ± 0.13) × 10-5 cm s-1 in normal and cancerous bladder tissues, respectively. The PCs of 50% DMSO are calculated to be (8.99 ± 0.93) × 10-6 cm s-1 and (1.43 ± 0.17) × 10-5 cm s-1 in normal and cancerous bladder tissues, respectively. The obtained results show a statistically significant difference in permeability of normal and cancerous tissue and indicate that the PC of 50% DMSO is about 1.13-and 1.21-fold higher than that of 30% glucose in normal bladder and cancerous bladder tissues, respectively. Thus, the quantitative measurements with the help of PCs from OCT images can be a potentially powerful method for bladder cancer detection. (optical coherence tomography)

  17. The normal breast epithelium of women with breast cancer displays an aberrant response to estradiol.

    Science.gov (United States)

    Khan, S A; Sachdeva, A; Naim, S; Meguid, M M; Marx, W; Simon, H; Halverson, J D; Numann, P J

    1999-10-01

    Breast epithelial response to estradiol may play an important role in breast cancer etiology. We have examined the relationship between serum estradiol and progesterone levels and normal breast epithelial expression of estrogen receptor (ER) alpha, progesterone receptor (PgR), and epithelial proliferation (as reflected by the Ki-67 labeling index) in 121 women (50 newly diagnosed breast cancer cases and 71 benign breast disease controls). Simultaneous samples of grossly normal breast tissue and venous blood were obtained from women undergoing breast surgery. Serum estradiol and progesterone levels were measured by radioimmunoassay; breast epithelial ER, PgR, and Ki-67 expression was measured by immunohistochemistry. Linear regression, controlled for patient age and ductal and lobular composition of the tissue, showed that the breast epithelium of control women displayed an inverse correlation between serum estradiol and ER-alpha, which was not seen in case women (P for the difference in regression slopes = 0.001). PgR expression displayed a significant positive correlation with serum estradiol in cases, but not in controls. Epithelial proliferation had no relationship to either estradiol or progesterone in both cases and controls but showed an inverse relationship with ER in controls and a direct relationship in cases (P for the difference in regression slopes = 0.066). These results suggest a dysregulation of hormonal response in the normal breast epithelium of high-risk women, with lack of regulation of ER by estradiol, increased estrogen responsiveness as reflected by PgR expression, and a dissociation of ER expression and proliferative response.

  18. Impact of the Choice of Normalization Method on Molecular Cancer Class Discovery Using Nonnegative Matrix Factorization

    Science.gov (United States)

    Yang, Haixuan; Seoighe, Cathal

    2016-01-01

    Nonnegative Matrix Factorization (NMF) has proved to be an effective method for unsupervised clustering analysis of gene expression data. By the nonnegativity constraint, NMF provides a decomposition of the data matrix into two matrices that have been used for clustering analysis. However, the decomposition is not unique. This allows different clustering results to be obtained, resulting in different interpretations of the decomposition. To alleviate this problem, some existing methods directly enforce uniqueness to some extent by adding regularization terms in the NMF objective function. Alternatively, various normalization methods have been applied to the factor matrices; however, the effects of the choice of normalization have not been carefully investigated. Here we investigate the performance of NMF for the task of cancer class discovery, under a wide range of normalization choices. After extensive evaluations, we observe that the maximum norm showed the best performance, although the maximum norm has not previously been used for NMF. Matlab codes are freely available from: http://maths.nuigalway.ie/~haixuanyang/pNMF/pNMF.htm. PMID:27741311

  19. Hole Burning Imaging Studies of Cancerous and Analogous Normal Ovarian Tissues Utilizing Organelle Specific Dyes

    Energy Technology Data Exchange (ETDEWEB)

    Matsuzaki, Satoshi [Iowa State Univ., Ames, IA (United States)

    2004-01-01

    Presented in this dissertation is the successful demonstration that nonphotochemical hole burning (NPWB) imaging can be used to study in vitro tissue cellular systems for discerning differences in cellular ultrastructures due to cancer development. This has been accomplished with the surgically removed cancerous ovarian and analogous normal peritoneal tissues from the same patient and the application of a fluorescent mitochondrion specific dye, Molecular Probe MitoFluor Far Red 680 (MF680), commonly known as rhodamine 800, that has been proven to exhibit efficient NPHB. From the results presented in Chapters 4 and 5 , and Appendix B, the following conclusions were made: (1) fluorescence excitation spectra of MF680 and confocal microscopy images of thin sliced tissues incubated with MF680 confirm the site-specificity of the probe molecules in the cellular systems. (2) Tunneling parameters, {lambda}{sub 0} and σΛ, as well as the standard hole burning parameters (namely, γ and S), have been determined for the tissue samples by hole growth kinetics (HGK) analyses. Unlike the preliminary cultured cell studies, these parameters have not shown the ability to distinguish tissue cellular matrices surrounding the chromophores. (3) Effects of an external electric (Stark) field on the nonphotochemical holes have been used to determine the changes in permanent dipole moment (fΔμ) for MF680 in tissue samples when burn laser polarization is parallel to the Stark field. Differences are detected between fΔμs in the two tissue samples, with the cancerous tissue exhibiting a more pronounced change (1.35-fold increase) in permanent dipole moment change relative to the normal analogs. It is speculated that the difference may be related to differences in mitochondrial membrane potentials in these tissue samples. (4) In the HGK mode, hole burning imaging (HBI) of cells adhered to coverslips and cooled to liquid helium temperatures in the complete absence of

  20. Hole Burning Imaging Studies of Cancerous and Analogous Normal Ovarian Tissues Utilizing Organelle Specific Dyes

    Energy Technology Data Exchange (ETDEWEB)

    Satoshi Matsuzaki

    2004-12-19

    Presented in this dissertation is the successful demonstration that nonphotochemical hole burning (NPWB) imaging can be used to study in vitro tissue cellular systems for discerning differences in cellular ultrastructures due to cancer development. This has been accomplished with the surgically removed cancerous ovarian and analogous normal peritoneal tissues from the same patient and the application of a fluorescent mitochondrion specific dye, Molecular Probe MitoFluor Far Red 680 (MF680), commonly known as rhodamine 800, that has been proven to exhibit efficient NPHB. From the results presented in Chapters 4 and 5 , and Appendix B, the following conclusions were made: (1) fluorescence excitation spectra of MF680 and confocal microscopy images of thin sliced tissues incubated with MF680 confirm the site-specificity of the probe molecules in the cellular systems. (2) Tunneling parameters, {lambda}{sub 0} and {sigma}{sub {lambda}}, as well as the standard hole burning parameters (namely, {gamma} and S), have been determined for the tissue samples by hole growth kinetics (HGK) analyses. Unlike the preliminary cultured cell studies, these parameters have not shown the ability to distinguish tissue cellular matrices surrounding the chromophores. (3) Effects of an external electric (Stark) field on the nonphotochemical holes have been used to determine the changes in permanent dipole moment (f{Delta}{mu}) for MF680 in tissue samples when burn laser polarization is parallel to the Stark field. Differences are detected between f{Delta}{mu}s in the two tissue samples, with the cancerous tissue exhibiting a more pronounced change (1.35-fold increase) in permanent dipole moment change relative to the normal analogs. It is speculated that the difference may be related to differences in mitochondrial membrane potentials in these tissue samples. (4) In the HGK mode, hole burning imaging (HBI) of cells adhered to coverslips and cooled to liquid helium temperatures in the

  1. Mast Cells in Adjacent Normal Colon Mucosa rather than Those in Invasive Margin are Related to Progression of Colon Cancer

    Institute of Scientific and Technical Information of China (English)

    Qing Xia; Xiao-shi Zhang; Ying-bo Chen; Ya Ding; Xiao-jun Wu; Rui-qing Peng; Qiang Zhou; Jing Zeng; Jing-hui Hou; Xing Zhang; Yi-xin Zeng

    2011-01-01

    Objective:Mast cells (MC) reside in the mucosa of the digestive tract as the first line against bacteria and toxins.Clinical evidence has implied that the infiltration of mast cells in colorectal cancers is related to malignant phenotypes and a poor prognosis.This study compared the role of mast cells in adjacent normal colon mucosa and in the invasive margin during the progression of colon cancer.Methods:Specimens were obtained from 39 patients with colon adenomas and 155 patients with colon cancers treated at the Sun Yat-sen University Cancer Center between January 1999 and July 2004.The density of mast cells was scored by an immunohistochemical assay.The pattern of mast cell distribution and its relationship with dinicopathologic parameters and 5-year survival were analyzed.Results:The majority of mast cells were located in the adjacent normal colon mucosa,followed by the invasive margin and least in the cancer stroma.Mast cell count in adjacent normal colon mucosa (MCCadjacent) was associated with pathologic classification,distant metastases and hepatic metastases,although it was not a prognostic factor.In contrast,mast cell count in the invasive margin (MCCinvasive) was associated with neither the clinicopathlogic parameters nor overall survival.Conclusion:Mast cells in the adjacent normal colon mucosa were related to the progression of colon cancer,suggesting that mast cells might modulate tumor progression via a long-distance mechanism.

  2. EDAC: Epithelial defence against cancer-cell competition between normal and transformed epithelial cells in mammals.

    Science.gov (United States)

    Kajita, Mihoko; Fujita, Yasuyuki

    2015-07-01

    During embryonic development or under certain pathological conditions, viable but suboptimal cells are often eliminated from the cellular society through a process termed cell competition. Cell competition was originally identified in Drosophila where cells with different properties compete for survival; 'loser' cells are eliminated from tissues and consequently 'winner' cells become dominant. Recent studies have shown that cell competition also occurs in mammals. While apoptotic cell death is the major fate for losers in Drosophila, outcompeted cells show more variable phenotypes in mammals, such as cell death-independent apical extrusion and cellular senescence. Molecular mechanisms underlying these processes have been recently revealed. Especially, in epithelial tissues, normal cells sense and actively eliminate the neighbouring transformed cells via cytoskeletal proteins by the process named epithelial defence against cancer (EDAC). Here, we introduce this newly emerging research field: cell competition in mammals. PMID:25991731

  3. Radiobiological Determination of Dose Escalation and Normal Tissue Toxicity in Definitive Chemoradiation Therapy for Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Warren, Samantha, E-mail: Samantha.warren@oncology.ox.ac.uk [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Partridge, Mike [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Carrington, Rhys [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hurt, Chris [Wales Cancer Trials Unit, School of Medicine, Heath Park, Cardiff (United Kingdom); Crosby, Thomas [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hawkins, Maria A. [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom)

    2014-10-01

    Purpose: This study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity. Methods and Materials: Twenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm{sup 3}. A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA{sub 62.5}) was compared to a standard dose plan of 50 Gy/25 fractions (RA{sub 50}). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared. Results: Clinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA{sub 50}) to 56.3% (RA{sub 62.5}), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA{sub 50}) versus 5.6% (RA{sub 62.5}) P<.001 and median lung NTCP 6.5% (RA{sub 50}) versus 7.5% (RA{sub 62.5}) P<.001. Conclusions: Dose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.

  4. Widespread expression of BORIS/CTCFL in normal and cancer cells.

    Directory of Open Access Journals (Sweden)

    Tania A Jones

    Full Text Available BORIS (CTCFL is the paralog of CTCF (CCCTC-binding factor; NM_006565, a ubiquitously expressed DNA-binding protein with diverse roles in gene expression and chromatin organisation. BORIS and CTCF have virtually identical zinc finger domains, yet display major differences in their respective C- and N-terminal regions. Unlike CTCF, BORIS expression has been reported only in the testis and certain malignancies, leading to its classification as a "cancer-testis" antigen. However, the expression pattern of BORIS is both a significant and unresolved question in the field of DNA binding proteins. Here, we identify BORIS in the cytoplasm and nucleus of a wide range of normal and cancer cells. We compare the localization of CTCF and BORIS in the nucleus and demonstrate enrichment of BORIS within the nucleolus, inside the nucleolin core structure and adjacent to fibrillarin in the dense fibrillar component. In contrast, CTCF is not enriched in the nucleolus. Live imaging of cells transiently transfected with GFP tagged BORIS confirmed the nucleolar accumulation of BORIS. While BORIS transcript levels are low compared to CTCF, its protein levels are readily detectable. These findings show that BORIS expression is more widespread than previously believed, and suggest a role for BORIS in nucleolar function.

  5. Plasma levels of OLFM4 in normals and patients with gastrointestinal cancer

    DEFF Research Database (Denmark)

    Clemmensen, Stine N; Glenthøj, Anders J; Heebøll, Sara;

    2015-01-01

    epithelial cells and in some carcinoma cells. We developed an Enzyme Linked Immunosorbent Assay for OLFM4 and investigated whether plasma levels of OLFM4 reflect colorectal malignancies, but were unable to see any such association. Instead, we observed two populations of individuals with respect to OLFM4...... levels in plasma, the majority with OLFM4 in plasma between 0 and 0.1 μg/ml, mean 0.028 μg/ml while 10% of both normals and patients with cancers had OLFM4 between 4 and 60 μg/ml, mean 15 μg/ml. The levels were constant over time. The background for this high plasma level is not known, but must be taken......Olfactomedin 4 (OLFM4) is a secreted glycoprotein predominantly expressed in bone marrow and gastrointestinal tissues. Aberrant expression of OLFM4 has been shown in several cancers. However, the clinical significance hereof is currently controversial. OLFM4 has been proposed as a candidate...

  6. Cross-tissue Analysis of Gene and Protein Expression in Normal and Cancer Tissues.

    Science.gov (United States)

    Kosti, Idit; Jain, Nishant; Aran, Dvir; Butte, Atul J; Sirota, Marina

    2016-01-01

    The central dogma of molecular biology describes the translation of genetic information from mRNA to protein, but does not specify the quantitation or timing of this process across the genome. We have analyzed protein and gene expression in a diverse set of human tissues. To study concordance and discordance of gene and protein expression, we integrated mass spectrometry data from the Human Proteome Map project and RNA-Seq measurements from the Genotype-Tissue Expression project. We analyzed 16,561 genes and the corresponding proteins in 14 tissue types across nearly 200 samples. A comprehensive tissue- and gene-specific analysis revealed that across the 14 tissues, correlation between mRNA and protein expression was positive and ranged from 0.36 to 0.5. We also identified 1,012 genes whose RNA and protein expression was correlated across all the tissues and examined genes and proteins that were concordantly and discordantly expressed for each tissue of interest. We extended our analysis to look for genes and proteins that were differentially correlated in cancer compared to normal tissues, showing higher levels of correlation in normal tissues. Finally, we explored the implications of these findings in the context of biomarker and drug target discovery. PMID:27142790

  7. Measurement of serum ferritin by radioimmunoassay: results in normal individuals and patients with breast cancer

    International Nuclear Information System (INIS)

    Ferritins are iron-containing proteins found in normal tissues; they increase in concentration in many tumors and the blood of tumor-bearing individuals. We utilized a double-antibody radioimmunoassay for measurement of serum ferritin and defined the upper limit of normal as 146 ng/ml for women (mean 34 ng/ml) and 193 ng/ml for men (mean 93 ng/ml). Serum ferritin levels exceeded these limits in preoperative sera of 41 percent of women with mammary carcinoma (mean 199 ng/ml) and in 67 percent of women with locally recurrent or metastatic mammary carcinoma (mean 671 ng/ml). Individuals with hepatic inflammatory states are known to have high serum ferritin, and ferritin was increased in 43 percent of patients with hepatitis or cirrhosis (mean 364 ng/ml) and in 13 percent of patients with ulcerative colitis or gastroduodenal ulcers (mean 106 ng/ml). Measurement of serum ferritin may be useful in evaluation of patients with breast cancer and in monitoring their response to therapy. (auth)

  8. Cross-tissue Analysis of Gene and Protein Expression in Normal and Cancer Tissues.

    Science.gov (United States)

    Kosti, Idit; Jain, Nishant; Aran, Dvir; Butte, Atul J; Sirota, Marina

    2016-05-04

    The central dogma of molecular biology describes the translation of genetic information from mRNA to protein, but does not specify the quantitation or timing of this process across the genome. We have analyzed protein and gene expression in a diverse set of human tissues. To study concordance and discordance of gene and protein expression, we integrated mass spectrometry data from the Human Proteome Map project and RNA-Seq measurements from the Genotype-Tissue Expression project. We analyzed 16,561 genes and the corresponding proteins in 14 tissue types across nearly 200 samples. A comprehensive tissue- and gene-specific analysis revealed that across the 14 tissues, correlation between mRNA and protein expression was positive and ranged from 0.36 to 0.5. We also identified 1,012 genes whose RNA and protein expression was correlated across all the tissues and examined genes and proteins that were concordantly and discordantly expressed for each tissue of interest. We extended our analysis to look for genes and proteins that were differentially correlated in cancer compared to normal tissues, showing higher levels of correlation in normal tissues. Finally, we explored the implications of these findings in the context of biomarker and drug target discovery.

  9. Absolute nuclear material assay

    Science.gov (United States)

    Prasad, Manoj K.; Snyderman, Neal J.; Rowland, Mark S.

    2010-07-13

    A method of absolute nuclear material assay of an unknown source comprising counting neutrons from the unknown source and providing an absolute nuclear material assay utilizing a model to optimally compare to the measured count distributions. In one embodiment, the step of providing an absolute nuclear material assay comprises utilizing a random sampling of analytically computed fission chain distributions to generate a continuous time-evolving sequence of event-counts by spreading the fission chain distribution in time.

  10. Influence of nanoparticles accumulation on optical properties of human normal and cancerous liver tissue in vitro estimated by OCT

    Science.gov (United States)

    Zhou, Fang; Wei, Huajiang; Ye, Xiangping; Hu, Kun; Wu, Guoyong; Yang, Hongqin; He, Yonghong; Xie, Shusen; Guo, Zhouyi

    2015-02-01

    In this work, the potential use of nanoparticles as contrast agents by using spectral domain optical coherence tomography (SD-OCT) in liver tissue was demonstrated. Gold nanoparticles (average size of 25 and 70 nm), were studied in human normal and cancerous liver tissues in vitro, respectively. Each sample was monitored with SD-OCT functional imaging for 240 min. Continuous OCT monitoring showed that, after application of gold nanoparticles, the OCT signal intensities of normal liver and cancerous liver tissue both increase with time, and the larger nanoparticles tend to produce a greater signal enhancement in the same type of tissue. The results show that the values of attenuation coefficients have significant differences between normal liver tissue and cancerous liver tissue. In addition, 25 nm gold nanoparticles allow higher penetration depth than 70 nm gold nanoparticles in liver tissues.

  11. Expression of a plant-associated human cancer antigen in normal,premalignant and malignant esophageal tissues

    Institute of Scientific and Technical Information of China (English)

    Jun Fu; Ping Qu; Mo Li; Hai-Mei Tian; Zhen-Hai Zheng; Xin-Wen Zheng; Wei Zhang

    2003-01-01

    AIM: To study the relationship between the expression profiles of a plant-associated human cancer antigen and carcinogenesis of esophagus and its significance. METHODS: We analyzed expression of a plant-associated human cancer antigen in biopsy specimens of normal (n=29),mildly hyperplastic (n=29), mildly (n=30), moderately (n=27)and severely dysplastic (n=29) and malignant esophageal (n=30) tissues by immunohistochemistry. RESULTS: The plant-associated human cancer antigen was mainly confined to the cytoplasm and showed diffuse type of staining. Positive staining was absent or weak in normal (0/30) and mildly hyperplastic tissue samples (2/29), while strong staining was observed in severe dysplasia (23/29) and carcinoma in situ (24/30). There was significant difference of its expression between normal mucosa and severely dysplastic tissues (P<0.001) or carcinoma in situ (P<0.001). Significant difference was also observed between mild dysplasia and severe dysplasia (P<0.001) or carcinomain situ (P<0.001). An overall trend toward increased staining intensity with increasing grade of dysplasia was found. There was a linear correlation between grade of lesions and staining intensity (r=0.794,P<0.001). Samples from esophageal cancer showed no higher levels of expression than those in severely dysplastic lesions (P>0.05). CONCLUSION: The abnormal expression of this plantassociated human cancer antigen in esophageal lesions is a frequent and early finding in the normal-dysplasiacarcinoma sequence in esophageal carcinogenesis. It might contribute to the carcinogenesis of esophageal cancer. The abnormal expression of this plant-associated human cancer antigen in esophageal lesion tissues may serve as a potential new biomarker for early identification of esophageal cancer.

  12. Nuclear nano-morphology markers of histologically normal cells detect the “field effect” of breast cancer

    OpenAIRE

    Bista, Rajan K.; Wang, Pin; Bhargava, Rohit; Uttam, Shikhar; Douglas J Hartman; Randall E Brand; Liu, Yang

    2012-01-01

    Accurate detection of breast malignancy from histologically normal cells (“field effect”) has significant clinical implications in a broad base of breast cancer management, such as high-risk lesion management, personalized risk assessment, breast tumor recurrence, and tumor margin management. More accurate and clinically applicable tools to detect markers characteristic of breast cancer “field effect” that are able to guide the clinical management are urgently needed. We have recently develop...

  13. Cascaded discrimination of normal, abnormal, and confounder classes in histopathology: Gleason grading of prostate cancer

    Directory of Open Access Journals (Sweden)

    Doyle Scott

    2012-10-01

    Full Text Available Abstract Background Automated classification of histopathology involves identification of multiple classes, including benign, cancerous, and confounder categories. The confounder tissue classes can often mimic and share attributes with both the diseased and normal tissue classes, and can be particularly difficult to identify, both manually and by automated classifiers. In the case of prostate cancer, they may be several confounding tissue types present in a biopsy sample, posing as major sources of diagnostic error for pathologists. Two common multi-class approaches are one-shot classification (OSC, where all classes are identified simultaneously, and one-versus-all (OVA, where a “target” class is distinguished from all “non-target” classes. OSC is typically unable to handle discrimination of classes of varying similarity (e.g. with images of prostate atrophy and high grade cancer, while OVA forces several heterogeneous classes into a single “non-target” class. In this work, we present a cascaded (CAS approach to classifying prostate biopsy tissue samples, where images from different classes are grouped to maximize intra-group homogeneity while maximizing inter-group heterogeneity. Results We apply the CAS approach to categorize 2000 tissue samples taken from 214 patient studies into seven classes: epithelium, stroma, atrophy, prostatic intraepithelial neoplasia (PIN, and prostate cancer Gleason grades 3, 4, and 5. A series of increasingly granular binary classifiers are used to split the different tissue classes until the images have been categorized into a single unique class. Our automatically-extracted image feature set includes architectural features based on location of the nuclei within the tissue sample as well as texture features extracted on a per-pixel level. The CAS strategy yields a positive predictive value (PPV of 0.86 in classifying the 2000 tissue images into one of 7 classes, compared with the OVA (0.77 PPV and OSC

  14. Variance computations for functional of absolute risk estimates.

    Science.gov (United States)

    Pfeiffer, R M; Petracci, E

    2011-07-01

    We present a simple influence function based approach to compute the variances of estimates of absolute risk and functions of absolute risk. We apply this approach to criteria that assess the impact of changes in the risk factor distribution on absolute risk for an individual and at the population level. As an illustration we use an absolute risk prediction model for breast cancer that includes modifiable risk factors in addition to standard breast cancer risk factors. Influence function based variance estimates for absolute risk and the criteria are compared to bootstrap variance estimates.

  15. Analysis of normal-tumour tissue interaction in tumours: prediction of prostate cancer features from the molecular profile of adjacent normal cells.

    Directory of Open Access Journals (Sweden)

    Victor Trevino

    Full Text Available Statistical modelling, in combination with genome-wide expression profiling techniques, has demonstrated that the molecular state of the tumour is sufficient to infer its pathological state. These studies have been extremely important in diagnostics and have contributed to improving our understanding of tumour biology. However, their importance in in-depth understanding of cancer patho-physiology may be limited since they do not explicitly take into consideration the fundamental role of the tissue microenvironment in specifying tumour physiology. Because of the importance of normal cells in shaping the tissue microenvironment we formulate the hypothesis that molecular components of the profile of normal epithelial cells adjacent the tumour are predictive of tumour physiology. We addressed this hypothesis by developing statistical models that link gene expression profiles representing the molecular state of adjacent normal epithelial cells to tumour features in prostate cancer. Furthermore, network analysis showed that predictive genes are linked to the activity of important secreted factors, which have the potential to influence tumor biology, such as IL1, IGF1, PDGF BB, AGT, and TGFβ.

  16. Utilizing a reference material for assessing absolute tumor mechanical properties in modality independent elastography

    Science.gov (United States)

    Kim, Dong Kyu; Weis, Jared A.; Yankeelov, Thomas E.; Miga, Michael I.

    2014-03-01

    There is currently no reliable method for early characterization of breast cancer response to neoadjuvant chemotherapy (NAC) [1,2]. Given that disruption of normal structural architecture occurs in cancer-bearing tissue, we hypothesize that further structural changes occur in response to NAC. Consequently, we are investigating the use of modalityindependent elastography (MIE) [3-8] as a method for monitoring mechanical integrity to predict long term outcomes in NAC. Recently, we have utilized a Demons non-rigid image registration method that allows 3D elasticity reconstruction in abnormal tissue geometries, making it particularly amenable to the evaluation of breast cancer mechanical properties. While past work has reflected relative elasticity contrast ratios [3], this study improves upon that work by utilizing a known stiffness reference material within the reconstruction framework such that a stiffness map becomes an absolute measure. To test, a polyvinyl alcohol (PVA) cryogel phantom and a silicone rubber mock mouse tumor phantom were constructed with varying mechanical stiffness. Results showed that an absolute measure of stiffness could be obtained based on a reference value. This reference technique demonstrates the ability to generate accurate measurements of absolute stiffness to characterize response to NAC. These results support that `referenced MIE' has the potential to reliably differentiate absolute tumor stiffness with significant contrast from that of surrounding tissue. The use of referenced MIE to obtain absolute quantification of biomarkers is also translatable across length scales such that the characterization method is mechanics-consistent at the small animal and human application.

  17. Trace elements of normal, benign hypertrophic and cancerous tissues of the Human prostate gland investigated by neutron activation analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zaichick, Sofia, E-mail: s-zaichick@northwestern.edu [Radionuclide Diagnostics Department, Medical Radiological Research Centre, Russian Academy of Medical Sciences, Koroleva Street- 4, Obninsk 249020, Kaluga Region (Russian Federation); Zaichick, Vladimir, E-mail: vezai@obninsk.com [Radionuclide Diagnostics Department, Medical Radiological Research Centre, Russian Academy of Medical Sciences, Koroleva Street- 4, Obninsk 249020, Kaluga Region (Russian Federation)

    2012-01-15

    The Ag, Co, Cr, Fe, Hg, Rb, Sb, Sc, Se, and Zn contents in normal (n=37), benign hypertrophic (n=43), and cancerous tissues (n=60) of the human prostate gland were investigated by neutron activation analysis. Mean values (M{+-}S{Epsilon}{Mu}) for content (mg/kg, dry weight basis) of trace elements in the normal tissue were: Ag-0.048{+-}0.009, Co-0.045{+-}0.004, Cr-0.53{+-}0.08, Fe-111{+-}9, Hg-0.056{+-}0.011, Rb-12.7{+-}0.9, Sb-0.045{+-}0.007, Sc-0.029{+-}0.005, Se-0.70{+-}0.04, and Zn-1000{+-}110, respectively. It was observed that in benign hypertrophic tissues the contents of Co, Cr, Hg, Sb, and Se were higher than in normal tissues, with statistically significant differences. The contents of Co, Rb, Sc, and Zn were significantly lower and those of Ag, Cr, Fe, Hg, and Sb were significantly higher in cancerous tissues than in normal tissues. - Highlights: Black-Right-Pointing-Pointer INAA is an adequate tool for the determination of trace element contents in the samples of human prostate. Black-Right-Pointing-Pointer In benign hypertrophic tissues the Co, Cr, Hg, Sb, and Se contents were higher than in normal tissues. Black-Right-Pointing-Pointer In cancerous tissues contents of Co, Rb, Sc, and Zn were significantly lower than in normal tissues. Black-Right-Pointing-Pointer In cancerous tissues the Ag, Cr, Fe, Hg, and Sb contents were higher than in normal tissues. Black-Right-Pointing-Pointer The estimation of Zn content in a needle-biopsy core may be used as a tool to diagnose prostate cancer.

  18. Quantum Stem Cell in the Infinity Loop: A New Concept for Our Understanding of the Normal State and Cancer

    Directory of Open Access Journals (Sweden)

    Kambiz Afrasiabi

    2010-01-01

    Full Text Available Problem statement: The scientific community is in need of more rigorous understanding of the mechanism of initiation of mitosis. The complete understanding of the initiation sequence may allow knowledge of the normal and disease states, including cancer. This understanding and knowledge would open the way for developing curative treatment of cancer. This article proposes a mechanism of initiation of mitosis based on preservation of maternal DNA and presents evidence in its support. Conclusion: This will be compared to the governing biology of the stem cell compartment. The implications for understanding and treatment of cancer will be described.

  19. ABSOLUTE NEUTRINO MASSES

    DEFF Research Database (Denmark)

    Schechter, J.; Shahid, M. N.

    2012-01-01

    We discuss the possibility of using experiments timing the propagation of neutrino beams over large distances to help determine the absolute masses of the three neutrinos.......We discuss the possibility of using experiments timing the propagation of neutrino beams over large distances to help determine the absolute masses of the three neutrinos....

  20. Accumulation of [{sup 11}C]acetate in normal prostate and benign prostatic hyperplasia: comparison with prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Takashi; Tsukamoto, Eriko; Takei, Toshiki; Shiga, Tohru; Nakada, Kunihiro; Tamaki, Nagara [Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 6, Kita-ku, Sapporo 060-8638 (Japan); Kuge, Yuji; Katoh, Chietsugu [Department of Tracer Kinetics, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Shinohara, Nobuo [Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine, Sapporo (Japan)

    2002-11-01

    Carbon-11 acetate positron emission tomography (PET) has been reported to be of clinical value for the diagnosis of prostate cancer. However, no detailed analysis has yet been carried out on the physiological accumulation of [{sup 11}C]acetate in the prostate. The purpose of this study was to elucidate the physiological accumulation of [{sup 11}C]acetate in the prostate using dynamic PET. The study included 30 subjects without prostate cancer [21 with normal prostate and nine with benign prostatic hyperplasia (BPH)] and six patients with prostate cancer. A dynamic PET study was performed for 20 min after intravenous administration of 555 MBq of [{sup 11}C]acetate. The standardised uptake value (SUV) at 16-20 min post tracer administration and the early-to-late-activity ratio of the SUV (E/L ratio), which was determined by dividing the SUV{sub 6-10} {sub min} by the SUV {sub 16-20min}, were calculated to evaluate the accumulation of [ {sup 11}C]acetate. The prostate was clearly visualised and distinguished from adjacent organs in PET images in most of the cases. The SUV of the prostate (2.6 {+-}0.8) was significantly higher than that of the rectum (1.7 {+-}0.4) or bone marrow (1.3 {+-}0.3) (P <0.0001 in each case). The SUV of the normal prostate of subjects aged <50 years (3.4 {+-}0.7) was significantly higher than both the SUV for the normal prostate of subjects aged {>=}50 years (2.3 {+-}0.7) and that of subjects with BPH (2.1 {+-}0.6) (P <0.01 in each case). The primary prostate cancer in six cases was visualised by [ {sup 11}C]acetate PET. However, the difference in the SUV between subjects aged {>=}50 with normal prostate or with BPH and the patients with prostate cancer (1.9 {+-}0.6) was not statistically significant. There was also no significant difference in the E/L ratio between subjects aged {>=}50 with normal prostate (0.98 {+-}0.04) or BPH (0.96 {+-}0.08) and patients with prostate cancer (1.02 {+-}0.12). In conclusion, a normal prostate exhibits age

  1. Unbiased Selection of Peptide-Peptoid Hybrids Specific for Lung Cancer Compared to Normal Lung Epithelial Cells.

    Science.gov (United States)

    Matharage, Jaya M; Minna, John D; Brekken, Rolf A; Udugamasooriya, D Gomika

    2015-12-18

    To develop widely applicable diagnostic and potentially therapeutic approaches overcoming protein heterogeneity in human cancer, we have developed a technology to unbiasedly select high specificity compound(s) that bind any biomolecule (e.g., proteins, lipids, carbohydrates) presented on the cancer cell surface but not on normal cells. We utilized a peptidomimetic based on-bead two-color (OBTC) combinatorial cell screen that can detect differences between two cell surfaces at high accuracy by looking for beads (where each bead in the library had one peptide-peptoid hybrid on the surface) that only bound cancer but not normal cells. We screened a library of 393 216 compounds targeting HCC4017 lung adenocarcinoma cells (labeled in red) in the presence of HBEC30KT normal bronchial epithelial cells (labeled in green) derived from the same tissue of the same patient. This screen identified a peptide-peptoid hybrid called PPS1 which displayed high specific binding for HCC4017 cancer cells over HBEC30KT cells. Specificity was validated through on-bead, ELISA-like and magnetic bead pulldown studies, while a scrambled version of PPS1 did not show any binding. Of interest, the simple dimeric version (PPS1D1) displayed cytotoxic activity on HCC4017 cells, but not on normal HBEC30KT cells. PPS1D1 also strongly accumulated in HCC4017 lung cancer xenografts in mice over control constructs. We conclude that such combinatorial screens using tumor and normal cells from the same patient have significant potential to develop new reagents for cancer biology, diagnosis, and potentially therapy.

  2. Impact of different IMRT techniques to improve conformity and normal tissue sparing in upper esophageal cancer

    Directory of Open Access Journals (Sweden)

    Amin E Amin

    2015-03-01

    Full Text Available Purpose: Intensity modulated radiotherapy (IMRT for cervical esophageal cancer is challenging. Although IMRT techniques using inverse planning algorithms are facilitating the treatment planning process, the irradiation dose to the normal tissues can be a critical issue. This study was performed to investigate the effect of beam numbers and their directions and local optimization on: (1 dose conformity and homogeneity to the planning target volume (PTV and (2 dose to the organ at risks (OARs.Methods: Four upper esophageal cancer cases were randomly selected for this treatment planning study. Eight IMRT plans were generated for each case with the same dose-volume constraints but with different beam numbers and arrangements. Local optimization using regular structures drawn automatically around the PTV with margins from 0.5-1.5 cm was performed. IMRT plans were evaluated with respect to isodose distributions, dose-volume histograms (DVHs parameters, homogeneity index (HI, and conformity index (CI. The statistical comparison between the types of plans was done using the One Way ANOVA test.Results: The results showed that IMRT using three or five beams was not sufficient to obtain good dose optimization. The seven field plans showed the best coverage for the PTV with tolerable doses for the OARs, and the beam orientation was very critical. Increasing beams (Bs number from 7 to 13 did not show significant differences in the PTV coverage, while the mean lung dose was increased. The PTV coverage were 95.1, 95.1, 98.1, 97.3, 97.3, 97.3, 97.0, and 97.0% for 3Bs, 5Bs, 7Bs, 9Bs, 13Bs, 7Bs(30, 7Bs(60 (beam angles were changed from 0o to 30o and 60o, and 7Bs(R (seven IMRT plans with ring, respectively. The mean heart dose did not exceed 0.36 Gy with p < 0.05. For lung doses, the best plan was the one with 9Bs which reduced lung volume doses V20Gy (% and V30Gy (%, and reduced mean lung dose from 5.4 to 4.5 Gy with p < 0.05 for 7Bs(R plans. IMRT improved the

  3. The Proliferative Activity of Mammary Epithelial Cells in Normal Tissue Predicts Breast Cancer Risk in Premenopausal Women.

    Science.gov (United States)

    Huh, Sung Jin; Oh, Hannah; Peterson, Michael A; Almendro, Vanessa; Hu, Rong; Bowden, Michaela; Lis, Rosina L; Cotter, Maura B; Loda, Massimo; Barry, William T; Polyak, Kornelia; Tamimi, Rulla M

    2016-04-01

    The frequency and proliferative activity of tissue-specific stem and progenitor cells are suggested to correlate with cancer risk. In this study, we investigated the association between breast cancer risk and the frequency of mammary epithelial cells expressing p27, estrogen receptor (ER), and Ki67 in normal breast tissue. We performed a nested case-control study of 302 women (69 breast cancer cases, 233 controls) who had been initially diagnosed with benign breast disease according to the Nurses' Health Studies. Immunofluorescence for p27, ER, and Ki67 was performed on tissue microarrays constructed from benign biopsies containing normal mammary epithelium and scored by computational image analysis. We found that the frequency of Ki67(+) cells was positively associated with breast cancer risk among premenopausal women [OR = 10.1, 95% confidence interval (CI) = 2.12-48.0]. Conversely, the frequency of ER(+) or p27(+) cells was inversely, but not significantly, associated with subsequent breast cancer risk (ER(+): OR = 0.70, 95% CI, 0.33-1.50; p27(+): OR = 0.89, 95% CI, 0.45-1.75). Notably, high Ki67(+)/low p27(+) and high Ki67(+)/low ER(+) cell frequencies were significantly associated with a 5-fold higher risk of breast cancer compared with low Ki67(+)/low p27(+) and low Ki67(+)/low ER(+) cell frequencies, respectively, among premenopausal women (Ki67(hi)/p27(lo): OR = 5.08, 95% CI, 1.43-18.1; Ki67(hi)/ER(lo): OR = 4.68, 95% CI, 1.63-13.5). Taken together, our data suggest that the fraction of actively cycling cells in normal breast tissue may represent a marker for breast cancer risk assessment, which may therefore impact the frequency of screening procedures in at-risk women. Cancer Res; 76(7); 1926-34. ©2016 AACR.

  4. Evaluation of Cellular Toxicity for Cisplatin, Arsenic And Acetaminophen in the Cancer and Normal Cell Line

    Directory of Open Access Journals (Sweden)

    S Saeedi Saravi

    2007-12-01

    Full Text Available Introduction: Cell culture is a process in which the cells ware isolated from original tissue, dispersed in liquid media and then placed in culture plate where the cells adhere together and propagate. Today, this method is used for assessment of cell toxicity, its mechanisms and effect of different compounds on intracellular components. Methods: Clonogenic assay was used for assessment of cell toxicity and amount of cell death after a specific time during which cells were exposed to different compounds. Thus, IC50 in caner cell lines (HePG2, SKOV3 and A549 and normal cell (LLCPK1, CHO and HGF1 was assessed after exposure to cisplatin, acetaminophen and arsenic. Results: Results showed that acetaminophen has maximum resistance and minimum sensitivity in CHO line with IC50=16.7±1.06 HePG2 with IC50=18.6±1.29. On the other hand, cisplatin showed minimum resistance and maximum sensitivity in HePG2 with IC50 = 0.87±0.07 and HGF1 with IC50 = 1.6±0.21 and lastly, arsenic showed minimum resistance and maximum sensitivity in A549 with IC50 = 4.59±0.29 and LLCPK1 with IC50= 1±0.37. Discussion: According to the evaluated IC50, there were differences between results of sensitivity of cell lines exposed to the three drugs (P<0.05. Entirely, resistance in cancer cell lines was lower than normal cells. The results showed the importance of cell defensive mechanisms encountering different substances like glutathione.

  5. Apples to origins: Identifying brain tumor stem cell genes by comparing transcriptomes of normal and cancer stem cells

    OpenAIRE

    Wortham, Matthew; Yan, Hai

    2012-01-01

    The mechanisms whereby medulloblastoma stem cells coordinate tumor propagation are poorly understood. Utilizing microarray analysis, Corno and colleagues draw parallels and distinctions between medulloblastoma stem cells from the Ptch+/− mouse and normal neural stem cells, identifying Ebf3 as a cancer stem cell-specific transcript critical for tumor growth.

  6. Reliability of Quantitative Ultrasonic Assessment of Normal-Tissue Toxicity in Breast Cancer Radiotherapy

    International Nuclear Information System (INIS)

    Purpose: We have recently reported that ultrasound imaging, together with ultrasound tissue characterization (UTC), can provide quantitative assessment of radiation-induced normal-tissue toxicity. This study’s purpose is to evaluate the reliability of our quantitative ultrasound technology in assessing acute and late normal-tissue toxicity in breast cancer radiotherapy. Method and Materials: Our ultrasound technique analyzes radiofrequency echo signals and provides quantitative measures of dermal, hypodermal, and glandular tissue toxicities. To facilitate easy clinical implementation, we further refined this technique by developing a semiautomatic ultrasound-based toxicity assessment tool (UBTAT). Seventy-two ultrasound studies of 26 patients (720 images) were analyzed. Images of 8 patients were evaluated for acute toxicity (<6 months postradiotherapy) and those of 18 patients were evaluated for late toxicity (≥6 months postradiotherapy). All patients were treated according to a standard radiotherapy protocol. To assess intraobserver reliability, one observer analyzed 720 images in UBTAT and then repeated the analysis 3 months later. To assess interobserver reliability, three observers (two radiation oncologists and one ultrasound expert) each analyzed 720 images in UBTAT. An intraclass correlation coefficient (ICC) was used to evaluate intra- and interobserver reliability. Ultrasound assessment and clinical evaluation were also compared. Results: Intraobserver ICC was 0.89 for dermal toxicity, 0.74 for hypodermal toxicity, and 0.96 for glandular tissue toxicity. Interobserver ICC was 0.78 for dermal toxicity, 0.74 for hypodermal toxicity, and 0.94 for glandular tissue toxicity. Statistical analysis found significant changes in dermal (p < 0.0001), hypodermal (p = 0.0027), and glandular tissue (p < 0.0001) assessments in the acute toxicity group. Ultrasound measurements correlated with clinical Radiation Therapy Oncology Group (RTOG) toxicity scores of patients

  7. Quantifying glucose permeability and enhanced light penetration in ex vivo human normal and cancerous esophagus tissues with optical coherence tomography

    International Nuclear Information System (INIS)

    We report our pilot results on quantification of glucose (G) diffusion permeability in human normal esophagus and ESCC tissues in vitro by using OCT technique. The permeability coefficient of 40% aqueous solution of G was found to be (1.74±0.04)×10-5 cm/s in normal esophagus and (2.45±0.06)×10-5 cm/s in ESCC tissues. The results from this study indicate that ESCC tissues had a higher permeability coefficient compared to normal esophageal tissues, and the light penetration depths gradually increase with the increase of applied topically with G time for the normal esophageal and ESCC tissues. The results indicate that the permeability coefficient of G in cancer tissues was 1.41-fold than that in normal tissues, and the light penetration depth for the ESCC tissues is significantly smaller than that of normal esophagus tissues in the same time range. These results demonstrate that the optical clearing of normal and cancer esophagus tissues are improved after application of G

  8. Two New Faces of Amifostine: Protector from DNA Damage in Normal Cells and Inhibitor of DNA Repair in Cancer Cells.

    Science.gov (United States)

    Hofer, Michal; Falk, Martin; Komůrková, Denisa; Falková, Iva; Bačíková, Alena; Klejdus, Bořivoj; Pagáčová, Eva; Štefančíková, Lenka; Weiterová, Lenka; Angelis, Karel J; Kozubek, Stanislav; Dušek, Ladislav; Galbavý, Štefan

    2016-04-14

    Amifostine protects normal cells from DNA damage induction by ionizing radiation or chemotherapeutics, whereas cancer cells typically remain uninfluenced. While confirming this phenomenon, we have revealed by comet assay and currently the most sensitive method of DNA double strand break (DSB) quantification (based on γH2AX/53BP1 high-resolution immunofluorescence microscopy) that amifostine treatment supports DSB repair in γ-irradiated normal NHDF fibroblasts but alters it in MCF7 carcinoma cells. These effects follow from the significantly lower activity of alkaline phosphatase measured in MCF7 cells and their supernatants as compared with NHDF fibroblasts. Liquid chromatography-mass spectrometry confirmed that the amifostine conversion to WR-1065 was significantly more intensive in normal NHDF cells than in tumor MCF cells. In conclusion, due to common differences between normal and cancer cells in their abilities to convert amifostine to its active metabolite WR-1065, amifostine may not only protect in multiple ways normal cells from radiation-induced DNA damage but also make cancer cells suffer from DSB repair alteration. PMID:26978566

  9. Expression profiles of inhibitor of growth protein 2 in normal and cancer tissues: An immunohistochemical screening analysis.

    Science.gov (United States)

    Zhao, Shuang; Yang, Xue-Feng; Gou, Wen-Feng; Lu, Hang; Li, Hua; Zhu, Zhi-Tu; Sun, Hong-Zhi; Zheng, Hua-Chuan

    2016-02-01

    Inhibitor of growth protein 2 (ING2) has an important role in the regulation of chromatin remodeling, cell proliferation, cell‑cycle arrest, senescence and apoptosis. The present study performed an immunohistochemical analysis for expression profiling of ING2 protein in an array of tissues comprising normal mouse and human tissues, as well as human hepatocellular (n=62), renal clear cell (n=62), pancreatic (n=62), esophageal squamous cell (n=45), cervical squamous cell (n=31), breast (n=144), gastric (n=196), colorectal (n=96), ovarian (n=208), endometrial (n=96) and lung (n=192) carcinoma tissues. In mouse tissues, ING2 was detected in the nuclei and cytoplasm of the glandular epithelium of breast, hepatocytes, intestine, bronchium and alveoli, as well as the squamous epithelium of skin and glomeruli, and in myocardial cells, while it was located in the cytoplasm of renal tubules and striated muscle cells. ING2 protein was scattered in the brain and spleen. In human tissues, ING2 protein was principally distributed in the cytoplasm, while in it was present in the cytoplasm and nuclei in the stomach, intestine, cervix, endometrium trachea, breast and pancreas. The nuclear location of ING2 in the stomach was more prominent than that in the cytoplasm. High ING2 immunoreactivity was detected in the tongue, stomach, skin, pancreas, cervix and breast, whereas weakly in the brain stem, thymus, thyroid, lung, striated muscle, testis, bladder and ovary. In total, 617 out of 1,194 of the tested cancer tissues (51.7%) were ING2-positive. In most cases, ING2 expression was found to be restricted to the cytoplasm of all cancer tissues, while in certain cancer types, including renal clear cell, ovarian and colorectal carcinoma, it was occasionally present in the nuclei. Among the cancer tissues examined, ING2 was most frequently expressed in breast cancer (67.4%) and gynecological cancer types, including ovarian cancer (61.5%) and endometrial cancer (57.3%). Compared with

  10. NGS Absolute Gravity Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The NGS Absolute Gravity data (78 stations) was received in July 1993. Principal gravity parameters include Gravity Value, Uncertainty, and Vertical Gradient. The...

  11. Absolute Pitch on Music

    OpenAIRE

    Çuhadar, C.Hakan

    2008-01-01

    Musicians are debated people in the academic circles with the claim of they have both various characteristics and different cognitive personalities on the analogy those other people. One of these different characteristics is absolute pitch ability. Absolute pitch (AP) is a cognitive ability which can be characterized as to identify any tones (labeling) at a given pitch without using any external references. According to the different studies which were held in different times, the prevalence ...

  12. Cancer

    Science.gov (United States)

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  13. Cancer associated epigenetic transitions identified by genome-wide histone methylation binding profiles in human colorectal cancer samples and paired normal mucosa

    International Nuclear Information System (INIS)

    Despite their well-established functional roles, histone modifications have received less attention than DNA methylation in the cancer field. In order to evaluate their importance in colorectal cancer (CRC), we generated the first genome-wide histone modification profiles in paired normal colon mucosa and tumor samples. Chromatin immunoprecipitation and microarray hybridization (ChIP-chip) was used to identify promoters enriched for histone H3 trimethylated on lysine 4 (H3K4me3) and lysine 27 (H3K27me3) in paired normal colon mucosa and tumor samples from two CRC patients and for the CRC cell line HT29. By comparing histone modification patterns in normal mucosa and tumors, we found that alterations predicted to have major functional consequences were quite rare. Furthermore, when normal or tumor tissue samples were compared to HT29, high similarities were observed for H3K4me3. However, the differences found for H3K27me3, which is important in determining cellular identity, indicates that cell lines do not represent optimal tissue models. Finally, using public expression data, we uncovered previously unknown changes in CRC expression patterns. Genes positive for H3K4me3 in normal and/or tumor samples, which are typically already active in normal mucosa, became hyperactivated in tumors, while genes with H3K27me3 in normal and/or tumor samples and which are expressed at low levels in normal mucosa, became hypersilenced in tumors. Genome wide histone modification profiles can be used to find epigenetic aberrations in genes associated with cancer. This strategy gives further insights into the epigenetic contribution to the oncogenic process and may identify new biomarkers

  14. Remodeling of central metabolism in invasive breast cancer compared to normal breast tissue – a GC-TOFMS based metabolomics study

    Directory of Open Access Journals (Sweden)

    Budczies Jan

    2012-07-01

    Full Text Available Abstract Background Changes in energy metabolism of the cells are common to many kinds of tumors and are considered a hallmark of cancer. Gas chromatography followed by time-of-flight mass spectrometry (GC-TOFMS is a well-suited technique to investigate the small molecules in the central metabolic pathways. However, the metabolic changes between invasive carcinoma and normal breast tissues were not investigated in a large cohort of breast cancer samples so far. Results A cohort of 271 breast cancer and 98 normal tissue samples was investigated using GC-TOFMS-based metabolomics. A total number of 468 metabolite peaks could be detected; out of these 368 (79% were significantly changed between cancer and normal tissues (p80%. Two-metabolite classifiers, constructed as ratios of the tumor and normal tissues markers, separated cancer from normal tissues with high sensitivity and specificity. Specifically, the cytidine-5-monophosphate / pentadecanoic acid metabolic ratio was the most significant discriminator between cancer and normal tissues and allowed detection of cancer with a sensitivity of 94.8% and a specificity of 93.9%. Conclusions For the first time, a comprehensive metabolic map of breast cancer was constructed by GC-TOF analysis of a large cohort of breast cancer and normal tissues. Furthermore, our results demonstrate that spectrometry-based approaches have the potential to contribute to the analysis of biopsies or clinical tissue samples complementary to histopathology.

  15. Discrimination Between Cervical Cancer Cells and Normal Cervical Cells Based on Longitudinal Elasticity Using Atomic Force Microscopy.

    Science.gov (United States)

    Zhao, Xueqin; Zhong, Yunxin; Ye, Ting; Wang, Dajing; Mao, Bingwei

    2015-12-01

    The mechanical properties of cells are considered promising biomarkers for the early diagnosis of cancer. Recently, atomic force microscopy (AFM)-based nanoindentation technology has been utilized for the examination of cell cortex mechanics in order to distinguish malignant cells from normal cells. However, few attempts to evaluate the biomechanical properties of cells have focused on the quantification of the non-homogeneous longitudinal elasticity of cellular structures. In the present study, we applied a variation of the method of Carl and Schillers to investigate the differences between longitudinal elasticity of human cervical squamous carcinoma cells (CaSki) and normal cervical epithelial cells (CRL2614) using AFM. The results reveal a three-layer heterogeneous structure in the probing volume of both cell types studied. CaSki cells exhibited a lower whole-cell stiffness and a softer nuclei zone compared to the normal counterpart cells. Moreover, a better differentiated cytoskeleton was found in the inner cytoplasm/nuclei zone of the normal CRL2614 cells, whereas a deeper cytoskeletal distribution was observed in the probing volume of the cancerous counterparts. The sensitive cortical panel of CaSki cells, with a modulus of 0.35~0.47 kPa, was located at 237~225 nm; in normal cells, the elasticity was 1.20~1.32 kPa at 113~128 nm. The present improved method may be validated using the conventional Hertz-Sneddon method, which is widely reported in the literature. In conclusion, our results enable the quantification of the heterogeneous longitudinal elasticity of cancer cells, in particular the correlation with the corresponding depth. Preliminary results indicate that our method may potentially be applied to improve the detection of cancerous cells and provide insights into the pathophysiology of the disease. PMID:26666911

  16. Discrimination Between Cervical Cancer Cells and Normal Cervical Cells Based on Longitudinal Elasticity Using Atomic Force Microscopy

    Science.gov (United States)

    Zhao, Xueqin; Zhong, Yunxin; Ye, Ting; Wang, Dajing; Mao, Bingwei

    2015-12-01

    The mechanical properties of cells are considered promising biomarkers for the early diagnosis of cancer. Recently, atomic force microscopy (AFM)-based nanoindentation technology has been utilized for the examination of cell cortex mechanics in order to distinguish malignant cells from normal cells. However, few attempts to evaluate the biomechanical properties of cells have focused on the quantification of the non-homogeneous longitudinal elasticity of cellular structures. In the present study, we applied a variation of the method of Carl and Schillers to investigate the differences between longitudinal elasticity of human cervical squamous carcinoma cells (CaSki) and normal cervical epithelial cells (CRL2614) using AFM. The results reveal a three-layer heterogeneous structure in the probing volume of both cell types studied. CaSki cells exhibited a lower whole-cell stiffness and a softer nuclei zone compared to the normal counterpart cells. Moreover, a better differentiated cytoskeleton was found in the inner cytoplasm/nuclei zone of the normal CRL2614 cells, whereas a deeper cytoskeletal distribution was observed in the probing volume of the cancerous counterparts. The sensitive cortical panel of CaSki cells, with a modulus of 0.35~0.47 kPa, was located at 237~225 nm; in normal cells, the elasticity was 1.20~1.32 kPa at 113~128 nm. The present improved method may be validated using the conventional Hertz-Sneddon method, which is widely reported in the literature. In conclusion, our results enable the quantification of the heterogeneous longitudinal elasticity of cancer cells, in particular the correlation with the corresponding depth. Preliminary results indicate that our method may potentially be applied to improve the detection of cancerous cells and provide insights into the pathophysiology of the disease.

  17. Early detection of colorectal cancer relapse by infrared spectroscopy in ``normal'' anastomosis tissue

    Science.gov (United States)

    Salman, Ahmad; Sebbag, Gilbert; Argov, Shmuel; Mordechai, Shaul; Sahu, Ranjit K.

    2015-07-01

    Colorectal cancer is one of the most aggressive cancers usually occurring in people above the age of 50 years. In the United States, colorectal cancer is the third most diagnosed cancer. The American Cancer Society has estimated 96,830 new cases of colon cancer and 40,000 new cases of rectal cancer in 2014 in the United States. According to the literature, up to 55% of colorectal cancer patients experience a recurrence within five years from the time of surgery. Relapse of colorectal cancer has a deep influence on the quality of patient life. Infrared (IR) spectroscopy has been widely used in medicine. It is a noninvasive, nondestructive technique that can detect changes in cells and tissues that are caused by different disorders, such as cancer. Abnormalities in the colonic crypts, which are not detectable using standard histopathological methods, could be determined using IR spectroscopic methods. The IR measurements were performed on formalin-fixed, paraffin-embedded colorectal tissues from eight patients (one control, four local recurrences, three distant recurrences). A total of 128 crypts were measured. Our results showed the possibility of differentiating among control, local, and distant recurrence crypts with more than a 92% success rate using spectra measured from the crypts' middle sites.

  18. Effect of different BNCT protocols on DNA synthesis in precancerous and normal tissues in an experimental model of oral cancer

    International Nuclear Information System (INIS)

    We previously reported the therapeutic success of different BNCT protocols in the treatment of oral cancer, employing the hamster cheek pouch model. The aim of the present study was to evaluate the effect of these BNCT protocols on DNA synthesis in precancerous and normal tissue in this model and assess the potential lag in the development of second primary tumors in precancerous tissue. The data are relevant to potential control of field cancerized tissue and tolerance of normal tissue. We evaluated DNA synthesis in precancerous and normal pouch tissue 1-30 days post-BNCT mediated by BPA, GB-10 or BPA + GB-10 employing incorporation of bromo-deoxyuridine as an end-point. The BNCT-induced potential lag in the development of second primary tumors in precancerous tissue was monitored. A drastic, statistically significant reduction in DNA synthesis occurred in pacancerous tissue as early as 1 day post-BNCT and was sustained at virtually all time points until 30 days post-BNCT for all protocols. The histological categories evaluated individually within precancerous tissue (dysplasia, hyperplasia and NUMF [no unusual microscopic features]) responded similarly. DNA synthesis in normal tissue treated with BNCT oscillated around the very low pre-treatment values. A BNCT-induced lag in the development of second primary tumors was observed. BNCT induced a drastic fall in DNA synthesis in precancerous tissue that would be associated to the observed lag in the development of second primary tumors. The minimum variations in DNA synthesis in BNCT-treated normal tissue would correlate with the absence of normal tissue radiotoxicity. The present data would contribute to optimize therapeutic efficacy in the treatment of field-cancerized areas. (author)

  19. Passage from normal mucosa to adenoma and colon cancer: alteration of normal sCD30 mechanisms regulating TH1/TH2 cell functions.

    Science.gov (United States)

    Contasta, Ida; Berghella, Anna Maria; Pellegrini, Patrizia; Adorno, Domenico

    2003-08-01

    The pathogenesis of cancer is currently under intensive investigation to identify reliable prognostic indices for the early detection of disease. Adenomas have been identified as precursors of colorectal cancer and tumor establishment, and disease progression has been found to reflect a malfunction of the immune system. On the basis of the role of the CD30 molecule in the regulation of TH1/TH2 functions and our previous results, strongly suggesting the validity of serum TH1/TH2 cytokines in the study of tumor progression, we studied network interaction between the production of soluble (s) CD30/sBCl2 in whole blood culture [in basic conditions and after PHA, LPS, and anti-CD3 monoclonal antibody (mAb) stimulation] and levels of TH1/TH2 cytokines (IL2, IFN gamma, IL12, IL4, IL5, IL10). Peripheral blood from a group of healthy subjects, as well as from patients with adenoma and colorectal cancer was used. Our objective was to gain a better insight into the role of the CD30 molecule in the passage from normal mucosa to adenoma and tumor and identify specific disease markers. Our results suggest that the decrease in CD30 expression and the abnormal increase in Bcl2 expression, observed in the peripheral cells of both adenoma and tumor groups determine an imbalance between TH1/TH2 functions. Consequently, changes in sCD30/sBcl2 culture production and TH1/TH2 cytokine serum levels may be reliable markers for tumor progression. In fact, our overall data show that a decrease of sCD30 levels in basic and PHA conditions and an increase of IFN gamma, IL4, IL5, and IL12 serum levels and sBcl2 in all activation condition are indicative of the passage from normal mucosa to adenoma; whilst a decrease of sBcl2 level in basic, LPS and anti-CD3 conditions and of IL2, IFN gamma serum levels, together with an increase of IL5 are indicative of the passage from adenoma to tumor.

  20. High-fidelity target sequencing of individual molecules identified using barcode sequences: de novo detection and absolute quantitation of mutations in plasma cell-free DNA from cancer patients

    Science.gov (United States)

    Kukita, Yoji; Matoba, Ryo; Uchida, Junji; Hamakawa, Takuya; Doki, Yuichiro; Imamura, Fumio; Kato, Kikuya

    2015-01-01

    Circulating tumour DNA (ctDNA) is an emerging field of cancer research. However, current ctDNA analysis is usually restricted to one or a few mutation sites due to technical limitations. In the case of massively parallel DNA sequencers, the number of false positives caused by a high read error rate is a major problem. In addition, the final sequence reads do not represent the original DNA population due to the global amplification step during the template preparation. We established a high-fidelity target sequencing system of individual molecules identified in plasma cell-free DNA using barcode sequences; this system consists of the following two steps. (i) A novel target sequencing method that adds barcode sequences by adaptor ligation. This method uses linear amplification to eliminate the errors introduced during the early cycles of polymerase chain reaction. (ii) The monitoring and removal of erroneous barcode tags. This process involves the identification of individual molecules that have been sequenced and for which the number of mutations have been absolute quantitated. Using plasma cell-free DNA from patients with gastric or lung cancer, we demonstrated that the system achieved near complete elimination of false positives and enabled de novo detection and absolute quantitation of mutations in plasma cell-free DNA. PMID:26126624

  1. High-fidelity target sequencing of individual molecules identified using barcode sequences: de novo detection and absolute quantitation of mutations in plasma cell-free DNA from cancer patients.

    Science.gov (United States)

    Kukita, Yoji; Matoba, Ryo; Uchida, Junji; Hamakawa, Takuya; Doki, Yuichiro; Imamura, Fumio; Kato, Kikuya

    2015-08-01

    Circulating tumour DNA (ctDNA) is an emerging field of cancer research. However, current ctDNA analysis is usually restricted to one or a few mutation sites due to technical limitations. In the case of massively parallel DNA sequencers, the number of false positives caused by a high read error rate is a major problem. In addition, the final sequence reads do not represent the original DNA population due to the global amplification step during the template preparation. We established a high-fidelity target sequencing system of individual molecules identified in plasma cell-free DNA using barcode sequences; this system consists of the following two steps. (i) A novel target sequencing method that adds barcode sequences by adaptor ligation. This method uses linear amplification to eliminate the errors introduced during the early cycles of polymerase chain reaction. (ii) The monitoring and removal of erroneous barcode tags. This process involves the identification of individual molecules that have been sequenced and for which the number of mutations have been absolute quantitated. Using plasma cell-free DNA from patients with gastric or lung cancer, we demonstrated that the system achieved near complete elimination of false positives and enabled de novo detection and absolute quantitation of mutations in plasma cell-free DNA. PMID:26126624

  2. CDK2 differentially controls normal cell senescence and cancer cell proliferation upon exposure to reactive oxygen species

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Chae Young; Lee, Seung-Min; Park, Sung Sup [Laboratory of Cell Signaling, Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahangno, Yusong, Daejeon 305-806 (Korea, Republic of); Kwon, Ki-Sun, E-mail: kwonks@kribb.re.kr [Laboratory of Cell Signaling, Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahangno, Yusong, Daejeon 305-806 (Korea, Republic of)

    2012-08-17

    Highlights: Black-Right-Pointing-Pointer H{sub 2}O{sub 2} differently adjusted senescence and proliferation in normal and cancer cells. Black-Right-Pointing-Pointer H{sub 2}O{sub 2} exposure transiently decreased PCNA levels in normal cells. Black-Right-Pointing-Pointer H{sub 2}O{sub 2} exposure transiently increased CDK2 activity in cancer cells. Black-Right-Pointing-Pointer p21{sup Cip1} is likely dispensable when H{sub 2}O{sub 2} induces senescence in normal cells. Black-Right-Pointing-Pointer Suggestively, CDK2 and PCNA play critical roles in H{sub 2}O{sub 2}-induced cell fate decision. -- Abstract: Reactive oxygen species modulate cell fate in a context-dependent manner. Sublethal doses of H{sub 2}O{sub 2} decreased the level of proliferating cell nuclear antigen (PCNA) in normal cells (including primary human dermal fibroblasts and IMR-90 cells) without affecting cyclin-dependent kinase 2 (CDK2) activity, leading to cell cycle arrest and subsequent senescence. In contrast, exposure of cancer cells (such as HeLa and MCF7 cells) to H{sub 2}O{sub 2} increased CDK2 activity with no accompanying change in the PCNA level, leading to cell proliferation. A CDK2 inhibitor, CVT-313, prevented H{sub 2}O{sub 2}-induced cancer cell proliferation. These results support the notion that the cyclin/CDK2/p21{sup Cip1}/PCNA complex plays an important role as a regulator of cell fate decisions.

  3. Damaging and protective bystander cross-talk between human lung cancer and normal cells after proton microbeam irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Desai, Sejal [Radiation Signalling and Cancer Biology Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Kobayashi, Alisa; Konishi, Teruaki; Oikawa, Masakazu [Radiation System and Engineering Section, Department of Technical Support and Development, Research, Development and Support Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Pandey, Badri N., E-mail: badrinarain@yahoo.co.in [Radiation Signalling and Cancer Biology Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)

    2014-05-15

    Graphical abstract: - Highlights: • Proton-microbeam irradiated A549 cells send damaging signals to bystander A549 cells. • Irradiated A549–A549 bystander response is through gap junctional communication. • Bystander WI38 cells exert protective signalling in irradiated A549 cells. • Rescue of irradiated A549 cells by WI38 cells is independent of gap junctions. - Abstract: Most of the studies of radiation-induced bystander effects (RIBE) have been focused on understanding the radiobiological changes observed in bystander cells in response to the signals from irradiated cells in a normal cell population with implications to radiation risk assessment. However, reports on RIBE with relevance to cancer radiotherapy especially investigating the bidirectional and criss-cross bystander communications between cancer and normal cells are limited. Hence, in present study employing co-culture approach, we have investigated the bystander cross-talk between lung cancer (A549) and normal (WI38) cells after proton-microbeam irradiation using γ-H2AX foci fluorescence as a measure of DNA double-strand breaks (DSBs). We observed that in A549–A549 co-cultures, irradiated A549 cells exert damaging effects in bystander A549 cells, which were found to be mediated through gap junctional intercellular communication (GJIC). However, in A549–WI38 co-cultures, irradiated A549 did not affect bystander WI38 cells. Rather, bystander WI38 cells induced inverse protective signalling (rescue effect) in irradiated A549 cells, which was independent of GJIC. On the other hand, in response to irradiated WI38 cells neither of the bystander cells (A549 or WI38) showed significant increase in γ-H2AX foci. The observed bystander signalling between tumour and normal cells may have potential implications in therapeutic outcome of cancer radiotherapy.

  4. The Clinical Relevance of Rising CA-125 Levels Within the Normal Range in Patients With Uterine Papillary Serous Cancer

    OpenAIRE

    Frimer, Marina; Hou, June Y.; McAndrew, Thomas C.; Gary L. Goldberg; Shahabi, Shohreh

    2013-01-01

    The utility of cancer antigen 125 (CA-125) levels as an adjunct method of monitoring patients with uterine papillary serous carcinoma (UPSC) or endometrial serous carcinoma after surgery and adjuvant treatment has been reported. Our goal was to determine the significance of rising CA-125 levels within the normal range in these patients in the posttreatment surveillance setting. All patients with UPSC who underwent surgical staging and had preoperative CA-125 measurement from...

  5. Finding Your New Normal: Outcomes of a Wellness-Oriented Psychoeducational Support Group for Cancer Survivors

    Science.gov (United States)

    Shannonhouse, Laura; Myers, Jane; Barden, Sejal; Clarke, Philip; Weimann, Rochelle; Forti, Allison; Moore-Painter, Terry; Knutson, Tami; Porter, Michael

    2014-01-01

    Group interventions have been useful for survivors to overcome the challenges of cancer. This study employed a pre/post, mixed-methods design to explore the influence of an 8-week support group on the holistic wellness of 14 breast cancer survivors. Pairing experiential activities with wellness-centered psychoeducation was viewed positively by…

  6. Inhibition of mTOR enhances radiosensitivity of lung cancer cells and protects normal lung cells against radiation.

    Science.gov (United States)

    Zheng, Hang; Wang, Miao; Wu, Jing; Wang, Zhi-Ming; Nan, Hai-Jun; Sun, He

    2016-06-01

    Radiotherapy has been used for a long time as a standard therapy for cancer; however, there have been no recent research breakthroughs. Radioresistance and various side-effects lead to the unexpected outcomes of radiation therapy. Specific and accurate targeting as well as reduction of radioresistance have been major challenges for irradiation therapy. Recent studies have shown that rapamycin shows promise for inhibiting tumorigenesis by suppressing mammalian target of rapamycin (mTOR). We found that the combination of rapamycin with irradiation significantly diminished cell viability and colony formation, and increased cell apoptosis, as compared with irradiation alone in lung cancer cell line A549, suggesting that rapamycin can enhance the effectiveness of radiation therapy by sensitizing cancer cells to irradiation. Importantly, we observed that the adverse effects of irradiation on a healthy lung cell line (WI-38) were also offset. No enhanced protein expression of mTOR signaling was observed in WI-38 cells, which is normally elevated in lung cancer cells. Moreover, DNA damage was significantly less with the combination therapy than with irradiation therapy alone. Our data suggest that the incorporation of rapamycin during radiation therapy could be a potent way to improve the sensitivity and effectiveness of radiation therapy as well as to protect normal cells from being damaged by irradiation. PMID:26999331

  7. Calibration with Absolute Shrinkage

    DEFF Research Database (Denmark)

    Øjelund, Henrik; Madsen, Henrik; Thyregod, Poul

    2001-01-01

    In this paper, penalized regression using the L-1 norm on the estimated parameters is proposed for chemometric je calibration. The algorithm is of the lasso type, introduced by Tibshirani in 1996 as a linear regression method with bound on the absolute length of the parameters, but a modification...

  8. Expression Levels of RFP in Normal and Cancer Human Tissues via Real-time RT-PCR Detection

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Ret finger protein(RFP) is a member of the tripartite motif family, which is characterized by a conserved RING finger of motif, a B-box, and a coiled-coil domain(they are called RBCC generally). Although RFP was known to be an oncogene when its RBCC moiety was connected with a tyrosine kinase domain by DNA rearrangement, its biological function was not well defined. In this study, by using real-time RT-PCR, the RFP expressions in human and mouse normal tissues, and in the cervical squamous cell carcinoma, endometrial adenocarcinoma, gastric adenocarcinoma, esophageal squamous cell carcinoma, and brain cancer tissues were analyzed. The result of the study proved that the highest level of mRNA reverse transcription appeared in the normal testical tissue, whereas that in other normal tissues of human and mice were low. The mRNA reverse transcription level of RFP was higher in the endometrial adenocarcinoma tissue than in the cervical squamous cell carcinoma tissue; the mRNA reverse transcription level of RFP in the gastric adenocarcinoma tissue was significantly higher than that in the esophageal squamous cell carcinoma tissue. It was also found that the mRNA reverse transcription level of RFP in the brain cancer tissue was higher than that in the normal brain tissue. These results suggested that RFP could possibly be a useful molecular target for the development of new therapeutics for malignant tumors.

  9. Comparison of additive (absolute) risk projection models and multiplicative (relative) risk projection models in estimating radiation-induced lifetime cancer risk

    International Nuclear Information System (INIS)

    Lifetime cancer risk estimates depend on risk projection models. While the increasing lengths of follow-up observation periods of atomic bomb survivors in Hiroshima and Nagasaki bring about changes in cancer risk estimates, the validity of the two risk projection models, the additive risk projection model (AR) and multiplicative risk projection model (MR), comes into question. This paper compares the lifetime risk or loss of life-expectancy between the two projection models on the basis of BEIR-III report or recently published RERF report. With Japanese cancer statistics the estimates of MR were greater than those of AR, but a reversal of these results was seen when the cancer hazard function for India was used. When we investigated the validity of the two projection models using epidemiological human data and animal data, the results suggested that MR was superior to AR with respect to temporal change, but there was little evidence to support its validity. (author)

  10. Physiological antioxidant system and oxidative stress in stomach cancer patients with normal renal and hepatic function

    Directory of Open Access Journals (Sweden)

    E Prabhakar Reddy

    2010-04-01

    Full Text Available Role of free radicals has been proposed in the pathogenesis of many diseases. Gastric cancer is a common disease worldwide, and leading cause of cancer death in India. Severe oxidative stress produces reactive oxygen species (ROS and induces uncontrolled lipid peroxidation. Albumin, uric acid (UA and Bilirubin are important physiological antioxidants. We aimed to evaluate and assess the role of oxidative stress (OS and physiological antioxidant system in stomach cancer patients. Lipid peroxidation measured as plasma Thio Barbituric Acid Reactive substances (TBARS, was found to be elevated significantly (p=0.001 in stomach cancer compared to controls along with a decrease in plasma physiological antioxidant system. The documented results were due to increased lipid peroxidation and involvement of physiological antioxidants in scavenging free radicals but not because of impaired hepatic and renal functions.

  11. The rectal cancer microRNAome - microRNA expression in rectal cancer and matched normal mucosa

    DEFF Research Database (Denmark)

    Gaedcke, Jochen; Grade, Marian; Camps, Jordi;

    2012-01-01

    mucosa. The predicted targets for these miRNAs were enriched for the following pathways: Wnt, TGF-beta, mTOR, insulin, mitogen-activated protein kinase, and ErbB signaling. Thirteen of these 49 miRNAs seem to be rectal cancer-specific, and have not been previously reported for colon cancers: miR-492, miR......-542-5p, miR-584, miR-483-5p, miR-144, miR-2110, miR-652, miR-375, miR-147b, miR-148a, miR-190, miR-26a/b, and miR-338-3p. Of clinical impact, miR-135b expression correlated significantly with disease-free and cancer-specific survival in an independent multicenter cohort of 116 patients. CONCLUSION......: This comprehensive analysis of the rectal cancer miRNAome uncovered novel miRNAs and pathways associated with rectal cancer. This information contributes to a detailed view of this disease. Moreover, the identification and validation of miR-135b may help to identify novel molecular targets and pathways...

  12. Comparison of dose contribution to normal pelvic tissues among conventional, conformal and intensity-modulated radiotherapy techniques in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yungan Tao; Lefkopoulos, Dimitri; Ibrahima, Diallo; Bridier, Andre; Polizzi, Maria del Pilar; Wibault, Pierre; Crevoisier, Renaud de; Arriagada, Rodrigo; Bourhis, Jean (Dept. of Radiotherapy, Institut Gustave-Roussy, Villejuif (France))

    2008-03-15

    High-energy external radiotherapy has become one of the most common treatment in localized prostate cancer. We compared the difference of dose distribution, mainly at the 5-30 Gy dose level, in the irradiated pelvic volume among three modalities of radiotherapy for patients with prostate cancer: conventional, conformal and intensity-modulated radiotherapy (IMRT). We selected six patients with prostate cancer treated by conformal radiotherapy at the doses of 46 Gy to PTVN (prostate and seminal vesicles), and 70 Gy to PTV-T (prostate). The conventional technique: an 8-field arrangement was used; the conformal technique 4 fields with a boost through 6 fields. For IMRT, a five-beam arrangement was used. Dose-volume histograms (DVH) were analyzed and compared among the three techniques. The IMRT technique significantly increased the pelvic volume covered by the isodose surfaces below 15 Gy as compared with the conventional and conformal techniques. The mean absolute increase for the pelvic volume included between 5-30 Gy for the IMRT technique, was about 2 900 ml as compared with the conventional technique. However, IMRT significantly reduced the irradiated volume of the rectum in the dose range of 5 to 40 Gy, also significantly reduced the irradiated volume of bladder and femoral heads, and obtained a similar or improved isodose distribution in the PTVs. In addition, the use of IMRT slightly increased the relative dose delivered to the body volume outside the pelvis, as estimated by the use of specific software. A long-term follow-up will be needed to evaluate potential late treatment complications related to the use of IMRT and the low or moderate irradiation dose level obtained in the pelvis and in the whole body

  13. Epidermal differentiation complex (locus 1q21) gene expression in head and neck cancer and normal mucosa.

    Science.gov (United States)

    Tyszkiewicz, Tomasz; Jarzab, Michal; Szymczyk, Cezary; Kowal, Monika; Krajewska, Jolanta; Jaworska, Magdalena; Fraczek, Marcin; Krajewska, Anna; Hadas, Ewa; Swierniak, Michal; Markowski, Jaroslaw; Lange, Dariusz; Poltorak, Stanislaw; Wiench, Malgorzata; Krecicki, Tomasz; Jarzab, Jerzy; Maciejewski, Adam

    2014-01-01

    Epidermal differentiation complex (EDC) comprises a number of genes associated with human skin diseases including psoriasis, atopic dermatitis and hyperkeratosis. These genes have also been linked to numerous cancers, among them skin, gastric, colorectal, lung, ovarian and renal carcinomas. The involvement of EDC components encoding S100 proteins, small proline-rich proteins (SPRRs) and other genes in the tumorigenesis of head and neck squamous cell cancer (HNSCC) has been previously suggested. The aim of the study was to systematically analyze the expression of EDC components on the transcript level in HNSCC. Tissue specimens from 93 patients with HNC of oral cavity and 87 samples from adjacent or distant grossly normal oral mucosawere analyzed. 48 samples (24 tumor and 24 corresponding surrounding tissue) were hybridized to Affymetrix GeneChip Human 1.0 ST Arrays. For validation by quantitative real-time PCR (QPCR) the total RNA from all180 samples collected in the study was analyzed with Real-Time PCR system and fluorescent amplicon specific-probes. Additional set of samples from 14 patients with laryngeal carcinoma previously obtained by HG-U133 Plus 2.0 microarray was also included in the analyses. The expression of analyzed EDC genes was heterogeneous. Two transcripts (S100A1 and S100A4) were significantly down-regulated in oral cancer when compared to normal mucosa (0.69 and 0.36-fold change, respectively), showing an opposite pattern of expression to the remaining S100 genes. Significant up-regulation in tumors was found for S100A11, S100A7, LCE3D, S100A3 and S100A2 genes. The increased expression of S100A7 was subsequently validated by QPCR, confirming significant differences. The remaining EDC genes, including all encoding SPRR molecules, did not show any differences between oral cancer and normal mucosa. The observed differences were also assessed in the independent set of laryngeal cancer samples, confirming the role of S100A3 and LCE3D transcripts in

  14. The expression of Dicer and Drosha in matched normal tissues, tumours and lymph node metastases in triple negative breast cancer

    International Nuclear Information System (INIS)

    Breast cancer is the most common malignancy in women world-wide. Triple negative breast cancer (TNBC) is a highly aggressive subtype that lacks expression of hormone receptors for estrogen, progesterone and human epidermal growth factor 2; and is associated with a high propensity for metastatic spread. Several studies have identified critical roles for microRNAs in breast cancer, but the role of two critical enzymes involved in microRNA biogenesis, Dicer and Drosha, is not well understood, particularly with respect to metastatic progression in this subtype. We examined the expression of Dicer and Drosha in a series of invasive 35 TNBCs with matched normal adjacent tissues (n = 18) and lymph node metastases (n = 15) using semi-quantitative real time RT-PCR. The relationship of their expression with clinical features including age at diagnosis, lymph node positivity and tumour size was analysed. We report that Dicer was significantly decreased while Drosha was significantly increased in tumours when compared to normal adjacent tissues. While there was no difference in Drosha expression in lymph node metastases when compared to the primary tumour, Dicer was significantly increased. There was no correlation between the expression of either Dicer or Drosha to age at diagnosis, lymph node positivity and tumour size. In conclusion, Dicer and Drosha are dysregulated in TNBC and matched lymph node metastases however, the clinical relevance of this is still not known. The altered expression of Dicer and Drosha may serve as markers for disrupted miRNA biogenesis in TNBC

  15. Effects of radiation on T regulatory cells in normal states and cancer: mechanisms and clinical implications.

    Science.gov (United States)

    Liu, Shu; Sun, Xiangdong; Luo, Jinhua; Zhu, Hongcheng; Yang, Xi; Guo, Qing; Song, Yaqi; Sun, Xinchen

    2015-01-01

    Radiation remains an important component of cancer treatment. In addition to inducing tumor cell death through direct cytotoxic effects, radiation can also promote the regression of tumor via augment of immune response. Regulatory T cells (Tregs) are a unique subpopulation of CD4 positive cells, which are characterized by expression of the forkhead box P3 (Foxp3) transcription factor and high levels of CD25. Mounting evidence has shown that Tregs are implicated in the development and progression of various types of cancer, which makes Tregs an important target in cancer therapeutics. Generally, lymphocytes are regarded as radiosensitive. However, Tregs have been demonstrated to be relatively resistant to radiotherapy, which is partly mediated by downregulation of pro-apoptotic proteins and upregulation of anti-apoptotic proteins. Moreover, radiotherapy can increase the production of Tregs and the recruitment of Tregs to local tumor microenvironment. Tregs can attenuate radiation-induced tumor death, which cause the resistance of tumor to radiotherapy. Recent experimental studies and clinical trails have demonstrated that the combination of radiation with medications that target Tregs is promising in the treatment of several types of neoplasms. In this review, we discussed the effect of radiation on Tregs in physiological states and cancer. Further, we presented an overview of therapies that target Tregs to enhance the efficacy of radiation in cancer therapeutics. PMID:26807310

  16. Is the planning dosimetry accurate to estimate the Normal Tissue Complication Probability (NTCP) in case of prostate cancer radiotherapy (RT)?

    International Nuclear Information System (INIS)

    The prediction of toxicity is crucial to manage prostate cancer radiotherapy. This prediction is classically based on the dose volume histogram (DVH) calculated at the planning time and using the mathematical Lyman NTCP (Normal Tissue Complication Probability) model. However, anatomical deformations occur during the 8 weeks of radiotherapy and consequently the planned dose does not correspond to the actual delivered dose, leading to uncertainties in NTCP calculation. The objective of this study was to compare the planned DVH-based rectal NTCP with a cumulative DVH-based rectal NTCP, in one case of prostate cancer radiotherapy. The average difference between planning DVH-based NTCP and cumulative-based DVH NTCP was 14% and the standard deviation 10.7%. We showed the impact of organ deformation on NTCP calculation, which leads to significant uncertainties in toxicity prediction. Cumulative DVH, being more representative of the actual received dose, should lead to a more reliable NTCP model

  17. Excess mortality from breast cancer 20 years after diagnosis when life expectancy is normal

    NARCIS (Netherlands)

    M.W.J. Louwman (Marieke); W.J. Klokman (Willem); J.W.W. Coebergh (Jan Willem)

    2001-01-01

    textabstractIn a population-based study, causes of death were traced of 418 deceased breast cancer patients diagnosed in 1960-1979 who survived at least 10 years after diagnosis. The pattern of causes of death in these patients was compared with the general female population using standardized morta

  18. Local Tumor Control and Normal Tissue Toxicity of Pulsed Low-Dose Rate Radiotherapy for Recurrent Lung Cancer

    Directory of Open Access Journals (Sweden)

    Peng Zhang

    2015-05-01

    Full Text Available Objectives: This study investigates (1 local tumor control and (2 normal tissue toxicity of pulsed low-dose rate radiotherapy (PLDR for recurrent lung cancer. Methods: For study 1, nude mice were implanted with A549 tumors and divided into the following 3 groups: (1 control (n = 10, (2 conventional radiotherapy (RT; n = 10, and (3 PLDR (n = 10. Tumor-bearing mice received 2 Gy daily dose for 2 consecutive days. Weekly magnetic resonance imaging was used for tumor growth monitoring. For study 2, 20 mice received 8 Gy total body irradiation either continuously (n = 10 or 40 × 0.2 Gy pulses with 3-minute intervals (n = 10. Results: For study 1, both conventional RT and PLDR significantly inhibited the growth of A549 xenografts compared with the control group (>35% difference in the mean tumor volume; P .05. For study 2, the average weight was 20.94 ± 1.68 g and 25.69 ± 1.27 g and the survival time was 8 days and 12 days for mice treated with conventional RT and PLDR (P < .05, respectively. Conclusion: This study showed that PLDR could control A549 tumors as effectively as conventional RT, and PLDR induced much less normal tissue toxicity than conventional RT. Thus, PLDR would be a good modality for recurrent lung cancers. Advances in Knowledge: This article reports our results of an in vivo animal investigation of PLDR for the treatment of recurrent cancers, which may not be eligible for treatment because of the dose limitations on nearby healthy organs that have been irradiated in previous treatments. This was the first in vivo study to quantify the tumor control and normal tissue toxicities of PLDR using mice with implanted tumors, and our findings provided evidence to support the clinical trials that employ PLDR treatment techniques.

  19. Absolute-Magnitude Distributions of Supernovae

    CERN Document Server

    Richardson, Dean; Wright, John; Maddox, Larry

    2014-01-01

    The absolute-magnitude distributions of seven supernova types are presented. The data used here were primarily taken from the Asiago Supernova Catalogue, but were supplemented with additional data. We accounted for both foreground and host-galaxy extinction. A bootstrap method is used to correct the samples for Malmquist bias. Separately, we generate volume-limited samples, restricted to events within 100 Mpc. We find that the superluminous events (M_B -15) make up about 3%. The normal Ia distribution was the brightest with a mean absolute blue magnitude of -19.25. The IIP distribution was the dimmest at -16.75.

  20. Artichoke compound cynarin differentially affects the survival, growth and stress response of normal, immortalized and cancerous human cells

    DEFF Research Database (Denmark)

    Gezer, Ceren; Yücecan, Sevinç; Rattan, Suresh Inder Singh

    2015-01-01

    Cynarin (CYN) is the main derivative of caffeoylquinic acid, found in leaves and heads of artichoke. Potential health-beneficial effects of CYN include as being choloretic-cholesterol lowering, hepatoprotective, anti-atherosclerotic, and antioxidative. We have tested the effects of various doses...... of CYN on the proliferative potential, survival, morphology, and stress response (SR) markers haemoxygenase-1 (HO-1) and heat shock protein-70 (HSP70) in normal human skin fibroblasts (FSF-1), telomerase-immortalized mesenchymal stem cells (hTERT-MSC) and cervical cancer cells, HeLa. Effects of CYN...

  1. Fluorine-18-labeled boronophenylalanine positron emission tomography for oral cancers: Qualitative and quantitative analyses of malignant tumors and normal structures in oral and maxillofacial regions

    OpenAIRE

    Ariyoshi, Yasunori; Shimahara, Masashi; Kimura,Yoshihiro; Ito, Yuichi; SHIMAHARA, TAKESHI; MIYATAKE, SHIN-ICHI; Kawabata, Shinji

    2011-01-01

    The present study aimed to demonstrate the features of fluorine-18-labeled boronophenylalanine positron emission tomography (18F-BPA-PET) to reveal oral cancer, as well as normal structures in the oral and maxillofacial regions. We analyzed 18F-BPA-PET findings from 8 patients with histologically confirmed recurrent and/or advanced oral cancer scheduled for boron neutron capture therapy. The capacity of 18F-BPA-PET to delineate tumor and normal structures was assessed qualitatively and quanti...

  2. Mesenteric ischemia after capecitabine treatment in rectal cancer and resultant short bowel syndrome is not an absolute contraindication for radical oncological treatment

    OpenAIRE

    Perpar Ana; Brecelj Erik; Kozjek Nada Rotovnik; Anderluh Franc; Oblak Irena; Vidmar Marija Skoblar; Velenik Vaneja

    2015-01-01

    Background. Thrombotic events, arterial or venous in origin, still remain a source of substantial morbidity and mortality in cancer patients. The propensity for their development in oncology patients is partially a consequence of the disease itself and partially a result of our attempts to treat it. One of the rarest and deadliest thromboembolic complications is arterial mesenteric ischemia. The high mortality rate is caused by its rarity and by its non-specific clinical presentation, both of...

  3. Protein Profiling of Isolated Leukocytes, Myofibroblasts, Epithelial, Basal, and Endothelial Cells from Normal, Hyperplastic, Cancerous, and Inflammatory Human Prostate Tissues

    Directory of Open Access Journals (Sweden)

    Zahraa I. Khamis, Kenneth A. Iczkowski, Ziad J. Sahab, Qing-Xiang Amy Sang

    2010-01-01

    Full Text Available In situ neoplastic prostate cells are not lethal unless they become invasive and metastatic. For cells to become invasive, the prostate gland must undergo degradation of the basement membrane and disruption of the basal cell layer underneath the luminal epithelia. Although the roles of proteinases in breaking down the basement membrane have been well-studied, little is known about the factors that induce basal cell layer disruption, degeneration, and its eventual disappearance in invasive cancer. It is hypothesized that microenvironmental factors may affect the degradation of the basal cell layer, which if protected may prevent tumor progression and invasion. In this study, we have revealed differential protein expression patterns between epithelial and stromal cells isolated from different prostate pathologies and identified several important epithelial and stromal proteins that may contribute to inflammation and malignant transformation of human benign prostate tissues to cancerous tissues using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and proteomics methods. Cellular retinoic acid-binding protein 2 was downregulated in basal cells of benign prsotate. Caspase-1 and interleukin-18 receptor 1 were highly expressed in leukocytes of prostate cancer. Proto-oncogene Wnt-3 was downregulated in endothelial cells of prostatitis tissue and tyrosine phosphatase non receptor type 1 was only found in normal and benign endothelial cells. Poly ADP-ribose polymerase 14 was downregulated in myofibroblasts of prostatitis tissue. Interestingly, integrin alpha-6 was upregulated in epithelial cells but not detected in myofibroblasts of prostate cancer. Further validation of these proteins may generate new strategies for the prevention of basal cell layer disruption and subsequent cancer invasion.

  4. Tumor microenvironment:bidirectional interactions between cancer cells and normal cells

    Institute of Scientific and Technical Information of China (English)

    Lu-Yuan Li

    2010-01-01

    @@ "The road to metastasis is paved with tumor-microenvironment interactions",claimed Dr.Isaac Witz from Tel Aviv University,Israel,in his keynote speech at the first Tianjin Forum on Tumor Microenvironment(http://TFTM.nankai.edu.cn),an international conference held at Nankai University in Tianjin,China,on July 2-4,2010.About 300 cancer researchers and students attended the conference.

  5. Penicillium verruculosum SG: a source of polyketide and bioactive compounds with varying cytotoxic activities against normal and cancer lines.

    Science.gov (United States)

    Shah, Salma Gul; Shier, W Thomas; Jamaluddin; Tahir, Nawaz; Hameed, Abdul; Ahmad, Safia; Ali, Naeem

    2014-04-01

    A newly isolated fungus Penicillium verruculosum SG was evaluated for the production and characterization of bioactive colored secondary metabolites using solid-state fermentation along with their cytotoxic activities against normal and cancer cell lines. Logical fragmentation pattern following column chromatography, thin layer chromatography and liquid chromatography and mass spectrometry of crude culture filtrate of fungus revealed the presence of different polyketide pigments and other bioactive compounds. Cytotoxicity of the selected colored fractions of fungal filtrate containing different compounds revealed IC50 (μg/ml) values ranging from 5 to 100. It was significantly higher in case of orevactaene (5 + 0.44) and monascorubrine followed by pyripyropene (8 + 0.63) against cancer cell line KA3IT. Overall, these compounds considerably showed less toxicity toward normal cell lines NIH3T3, HSCT6, HEK293 and MDCK. XRD of a yellow crystalline compound (224.21 m/z) confirmed its 3-dimensional structure as phenazine 1 carboxylic acid (C13H8N2O2) (broad spectrum antibiotic), and it is first time reported in fungi.

  6. In vivo study for the discrimination of cancerous and normal skin using fibre probe-based Raman spectroscopy.

    Science.gov (United States)

    Schleusener, Johannes; Gluszczynska, Patrycja; Reble, Carina; Gersonde, Ingo; Helfmann, Jürgen; Fluhr, Joachim W; Lademann, Jürgen; Röwert-Huber, Joachim; Patzelt, Alexa; Meinke, Martina C

    2015-10-01

    Raman spectroscopy has proved its capability as an objective, non-invasive tool for the detection of various melanoma and non-melanoma skin cancers (NMSC) in a number of studies. Most publications are based on a Raman microspectroscopic ex vivo approach. In this in vivo clinical evaluation, we apply Raman spectroscopy using a fibre-coupled probe that allows access to a multitude of affected body sites. The probe design is optimized for epithelial sensitivity, whereby a large part of the detected signal originates from within the epidermal layer's depth down to the basal membrane where early stages of skin cancer develop. Data analysis was performed on measurements of 104 subjects scheduled for excision of lesions suspected of being malignant melanoma (MM) (n = 36), basal cell carcinoma (BCC) (n = 39) and squamous cell carcinoma (SCC) (n = 29). NMSC were discriminated from normal skin with a balanced accuracy of 73% (BCC) and 85% (SCC) using partial least squares discriminant analysis (PLS-DA). Discriminating MM and pigmented nevi (PN) resulted in a balanced accuracy of 91%. These results lie within the range of comparable in vivo studies and the accuracies achieved by trained dermatologists using dermoscopy. Discrimination proved to be unsuccessful between cancerous lesions and suspicious lesions that had been histopathologically verified as benign by dermoscopy. PMID:26010742

  7. Cost-effectiveness of CT thorax and bronchoscopy in haemoptysis with normal CXR for exclusion of lung cancer

    International Nuclear Information System (INIS)

    As fibre-optic bronchoscopy and CT thorax become more widely used, patients with haemoptysis who had normal chest x-ray radiography (CXR) and sputum results are more commonly offered both CT and bronchoscopy to exclude lung cancer. Doctors who are under possible litigation pressure arising from missed diagnoses of lung cancer are often exhaustive in their investigations, even when the haemoptysis has been transient. The present study aims to investigate the number of cancer patients who can be detected with the two investigations, and compare recent similar study results with archive results. We found that despite the use of more efficient investigation tools, the yield is paradoxically much lower and, hence, less cost-effective than that of previous studies. The likely reason is that doctors tend to over-investigate, even for short-term, minimal blood-streaked sputum, which is common among simple bronchitis. In order to be more cost-effective, these investigations should be used more selectively and for high risk patients such as those with prolonged haemoptysis and those who are heavy smokers. Copyright (2002) Blackwell Science Pty Ltd

  8. Normal Tissue Anatomy for Oropharyngeal Cancer: Contouring Variability and Its Impact on Optimization

    International Nuclear Information System (INIS)

    Purpose: To evaluate the variability of organ at risk (OAR) delineation and the resulting impact on intensity modulated radiation therapy (IMRT) treatment plan optimization in head-and-neck cancer. Methods and Materials: An expert panel of 3 radiation oncologists jointly delineated OARs, including the parotid and submandibular glands (SM), pharyngeal constrictors (PC), larynx, and glottis (GL), in 10 patients with advanced oropharynx cancer in 3 contouring sessions, spaced at least 1 week apart. Contour variability and uncertainty, as well as their dosimetric impact on IMRT planning for each case, were assessed. Results: The mean difference in total volume for each OAR was 1 cm3 (σ 0.5 cm3). Mean fractional overlap was 0.7 (σ 0.1) and was highest (0.8) for the larynx and bilateral SMs and parotids and lowest (0.5) for PC. There were considerable spatial differences in contours, with the ipsilateral parotid and PC displaying the most variability (0.9 cm), which was most prominent in cases in which tumors obliterated fat planes. Both SMs and GL had the smallest differences (0.5 cm). The mean difference in OAR dose was 0.9 Gy (range 0.6-1.1 Gy, σ 0.1 Gy), with the smallest difference for GL and largest for both SMs and the larynx. Conclusions: Despite substantial difference in OAR contours, optimization was barely affected, with a 0.9-Gy mean difference between optimizations, suggesting relative insensitivity of dose distributions for IMRT of oropharynx cancer to the extent of OARs.

  9. Discrimination between normal and cancer cells by using spectral analysis of delayed luminescence.

    Science.gov (United States)

    Musumeci, Francesco; Privitera, Giuseppe; Scordino, Agata; Tudisco, Salvatore; Lo Presti, Carmine; Applegate, Lee Ann; Niggli, Hugo J.

    2005-04-01

    In our present studies, the time-resolved emission spectrum of delayed luminescence of cell cultures of human fibroblast and human melanoma have been measured using a sophisticated single photon device. Noticeable differences have been found both in the emission spectra, which are time dependent, and in the timing aspects of the different spectral components. This powerful and noninvasive technique can be applied in all fields of skin research, such as the investigation of skin abnormalities and to test the effect of products involved in regeneration, antiaging, and UV-light protection in order to prevent skin cancer.

  10. Comparison of end normal inspiration and expiration for gated intensity modulated radiation therapy (IMRT) of lung cancer

    International Nuclear Information System (INIS)

    Background and purpose: Gated delivery of radiation during part of the respiration cycle may improve the treatment of lung cancer with intensity modulated radiation therapy (IMRT). In terms of the respiration phase for gated treatment, normal end-expiration (EE) is more stable but normal end-inspiration (EI) increases lung volume. We compare the relative merit of using EI and EE in gated IMRT for sparing normal lung tissue. Patients and methods: Ten patients received EI and EE respiration-triggered CT scans in the treatment position. An IMRT plan for a prescription dose of 70 Gy was generated for each patient and at each respiration phase. The optimization constraints included target dose uniformity, less than 35% of the total lung receiving 20 Gy or more and maximum cord dose ≤45 Gy. We compared planning target volume (PTV) coverage, mean lung dose, percentage of total lung receiving 20 Gy or more (V 20) and lung normal tissue complication probability (NTCP). Results: For 9 of the 10 patients, cord and lung doses were acceptable and PTV coverage was similar for EE and EI, with lung sparing was equal to or slightly better at EI than at EE. For the 10th patient, lung sparing at EI was significantly better. Patient averaged mean lung dose was 15.4 Gy (range: 7.1-20.4) at EI and 16.3 Gy (range: 6.9-21.9) at EE. The average V 20 was 23.8% (range: 13-36.4) at EI and 25.3% (range: 13-37.3) at EE. The average NTCP at EI was 8 versus 12% at EE. Conclusions: Dosimetric indices of lung protection for IMRT plans at EI are better than at EE. For 9 out of the 10 patients in our study, this difference is small. Thus other factors such as reproducibility, reliability and duty cycle at normal end expiration may be more critical for selecting treatment breathing phase

  11. Individualized Radical Radiotherapy of Non-Small-Cell Lung Cancer Based on Normal Tissue Dose Constraints: A Feasibility Study

    International Nuclear Information System (INIS)

    Purpose: Local recurrence is a major problem after (chemo-)radiation for non-small-cell lung cancer. We hypothesized that for each individual patient, the highest therapeutic ratio could be achieved by increasing total tumor dose (TTD) to the limits of normal tissues, delivered within 5 weeks. We report first results of a prospective feasibility trial. Methods and Materials: Twenty-eight patients with medically inoperable or locally advanced non-small-cell lung cancer, World Health Organization performance score of 0-1, and reasonable lung function (forced expiratory volume in 1 second > 50%) were analyzed. All patients underwent irradiation using an individualized prescribed TTD based on normal tissue dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8-Gy fractions twice daily. No concurrent chemoradiation was administered. Toxicity was scored using the Common Terminology Criteria for Adverse Events criteria. An 18F-fluoro-2-deoxy-glucose-positron emission tomography-computed tomography scan was performed to evaluate (metabolic) response 3 months after treatment. Results: Mean delivered dose was 63.0 ± 9.8 Gy. The TTD was most often limited by the mean lung dose (32.1%) or spinal cord (28.6%). Acute toxicity generally was mild; only 1 patient experienced Grade 3 cough and 1 patient experienced Grade 3 dysphagia. One patient (3.6%) died of pneumonitis. For late toxicity, 2 patients (7.7%) had Grade 3 cough or dyspnea; none had severe dysphagia. Complete metabolic response was obtained in 44% (11 of 26 patients). With a median follow-up of 13 months, median overall survival was 19.6 months, with a 1-year survival rate of 57.1%. Conclusions: Individualized maximal tolerable dose irradiation based on normal tissue dose constraints is feasible, and initial results are promising

  12. HER1-4 protein concentrations in normal breast tissue from breast cancer patients are expressed by the same profile as in the malignant tissue

    DEFF Research Database (Denmark)

    Olsen, Dorte Aa; Ostergaard, Birthe; Bokmand, Susanne;

    2009-01-01

    Abstract Background: The epidermal growth factor receptor HER2 is overexpressed or amplified in 25%-30% of patients with breast cancer. The mechanism behind HER2 amplification is unknown, but may be a patho-physiological phenomenon caused by continuous stimulation and activation of the HER1......-4 system. We have mapped the protein concentrations of HER1-4 in breast cancer tissue, autologous reference tissue, normal breast tissue and serum samples, to see whether non-cancer cells from these patients express a protein profile indicating general activation. Methods: Tissue samples from malignant...... and adjacent normal breast tissue (autologous reference tissue) were collected from 118 women consecutively admitted for surgical treatment of breast cancer. In addition, 26 samples of normal breast tissue were collected from healthy women having breast reduction surgery. The tissue samples were homogenized...

  13. Optical tweezers absolute calibration

    CERN Document Server

    Dutra, R S; Neto, P A Maia; Nussenzveig, H M

    2014-01-01

    Optical tweezers are highly versatile laser traps for neutral microparticles, with fundamental applications in physics and in single molecule cell biology. Force measurements are performed by converting the stiffness response to displacement of trapped transparent microspheres, employed as force transducers. Usually, calibration is indirect, by comparison with fluid drag forces. This can lead to discrepancies by sizable factors. Progress achieved in a program aiming at absolute calibration, conducted over the past fifteen years, is briefly reviewed. Here we overcome its last major obstacle, a theoretical overestimation of the peak stiffness, within the most employed range for applications, and we perform experimental validation. The discrepancy is traced to the effect of primary aberrations of the optical system, which are now included in the theory. All required experimental parameters are readily accessible. Astigmatism, the dominant effect, is measured by analyzing reflected images of the focused laser spo...

  14. Reprogramming of Normal Fibroblasts into Cancer-Associated Fibroblasts by miRNAs-Mediated CCL2/VEGFA Signaling

    Science.gov (United States)

    Shen, Hua; Yu, Xiaobo; Yang, Fengming; Zhang, Zhihua; Shen, Jianxin; Sun, Jin; Choksi, Swati; Jitkaew, Siriporn; Shu, Yongqian

    2016-01-01

    Cancer-associated fibroblasts (CAFs), the most common constituent of the tumor stoma, are known to promote tumor initiation, progression and metastasis. However, the mechanism of how cancer cells transform normal fibroblasts (NFs) into CAFs is largely unknown. In this study, we determined the contribution of miRNAs in the transformation of NFs into CAFs. We found that miR-1 and miR-206 were down-regulated, whereas miR-31 was up-regulated in lung CAFs when compared with matched NFs. Importantly, modifying the expression of these three deregulated miRNAs induced a functional conversion of NFs into CAFs and vice versa. When the miRNA-reprogrammed NFs and CAFs were co-cultured with lung cancer cells (LCCs), a similar pattern of cytokine expression profiling were observed between two groups. Using a combination of cytokine expression profiling and miRNAs algorithms, we identified VEGFA/CCL2 and FOXO3a as direct targets of miR-1, miR-206 and miR-31, respectively. Importantly, systemic delivery of anti-VEGFA/CCL2 or pre-miR-1, pre-miR-206 and anti-miR-31 significantly inhibited tumor angiogenesis, TAMs accumulation, tumor growth and lung metastasis. Our results show that miRNAs-mediated FOXO3a/VEGF/CCL2 signaling plays a prominent role in LCCs-mediated NFs into CAFs, which may have clinical implications for providing novel biomarker(s) and potential therapeutic target(s) of lung cancer in the future. PMID:27541266

  15. Gene expression relationship between prostate cancer cells of Gleason 3, 4 and normal epithelial cells as revealed by cell type-specific transcriptomes

    International Nuclear Information System (INIS)

    Prostate cancer cells in primary tumors have been typed CD10-/CD13-/CD24hi/CD26+/CD38lo/CD44-/CD104-. This CD phenotype suggests a lineage relationship between cancer cells and luminal cells. The Gleason grade of tumors is a descriptive of tumor glandular differentiation. Higher Gleason scores are associated with treatment failure. CD26+ cancer cells were isolated from Gleason 3+3 (G3) and Gleason 4+4 (G4) tumors by cell sorting, and their gene expression or transcriptome was determined by Affymetrix DNA array analysis. Dataset analysis was used to determine gene expression similarities and differences between G3 and G4 as well as to prostate cancer cell lines and histologically normal prostate luminal cells. The G3 and G4 transcriptomes were compared to those of prostatic cell types of non-cancer, which included luminal, basal, stromal fibromuscular, and endothelial. A principal components analysis of the various transcriptome datasets indicated a closer relationship between luminal and G3 than luminal and G4. Dataset comparison also showed that the cancer transcriptomes differed substantially from those of prostate cancer cell lines. Genes differentially expressed in cancer are potential biomarkers for cancer detection, and those differentially expressed between G3 and G4 are potential biomarkers for disease stratification given that G4 cancer is associated with poor outcomes. Differentially expressed genes likely contribute to the prostate cancer phenotype and constitute the signatures of these particular cancer cell types

  16. Mesenteric ischemia after capecitabine treatment in rectal cancer and resultant short bowel syndrome is not an absolute contraindication for radical oncological treatment

    Directory of Open Access Journals (Sweden)

    Perpar Ana

    2015-06-01

    Full Text Available Background. Thrombotic events, arterial or venous in origin, still remain a source of substantial morbidity and mortality in cancer patients. The propensity for their development in oncology patients is partially a consequence of the disease itself and partially a result of our attempts to treat it. One of the rarest and deadliest thromboembolic complications is arterial mesenteric ischemia. The high mortality rate is caused by its rarity and by its non-specific clinical presentation, both of which make early diagnosis and treatment difficult. Hence, most diagnoses and treatments occur late in the course of the disease. The issue survivors of arterial mesenteric ischemia may face is short bowel syndrome, which has become a chronic condition after the introduction of parenteral nutrition at home.

  17. Variability of Target and Normal Structure Delineation Using Multimodality Imaging for Radiation Therapy of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dalah, Entesar; Moraru, Ion [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Paulson, Eric [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Erickson, Beth [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Li, X. Allen, E-mail: ali@mcw.edu [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States)

    2014-07-01

    Purpose: To explore the potential of multimodality imaging (dynamic contrast–enhanced magnetic resonance imaging [DCE-MRI], apparent diffusion-coefficient diffusion-weighted imaging [ADC-DWI], fluorodeoxyglucose positron emission tomography [FDG-PET], and computed tomography) to define the gross tumor volume (GTV) and organs at risk in radiation therapy planning for pancreatic cancer. Delineated volumetric changes of DCE-MRI, ADC-DWI, and FDG-PET were assessed in comparison with the finding on 3-dimensional/4-dimensional CT with and without intravenous contrast, and with pathology specimens for resectable and borderline resectable cases of pancreatic cancer. Methods and Materials: We studied a total of 19 representative patients, whose DCE-MRI, ADC-DWI, and FDG-PET data were reviewed. Gross tumor volume and tumor burden/active region inside pancreatic head/neck or body were delineated on MRI (denoted GTV{sub DCE}, and GTV{sub ADC}), a standardized uptake value (SUV) of 2.5, 40%SUVmax, and 50%SUVmax on FDG-PET (GTV2.5, GTV{sub 40%}, and GTV{sub 50%}). Volumes of the pancreas, duodenum, stomach, liver, and kidneys were contoured according to CT (V{sub CT}), T1-weighted MRI (V{sub T1}), and T2-weighted MRI (V{sub T2}) for 7 patients. Results: Significant statistical differences were found between the GTVs from DCE-MRI, ADC-DW, and FDG-PET, with a mean and range of 4.73 (1.00-9.79), 14.52 (3.21-25.49), 22.04 (1.00-45.69), 19.10 (4.84-45.59), and 9.80 (0.32-35.21) cm{sup 3} for GTV{sub DCE}, GTV{sub ADC}, GTV2.5, GTV{sub 40%}, and GTV{sub 50%}, respectively. The mean difference and range in the measurements of maximum dimension of tumor on DCE-MRI, ADC-DW, SUV2.5, 40%SUVmax, and 50%SUVmax compared with pathologic specimens were −0.84 (−2.24 to 0.9), 0.41 (−0.15 to 2.3), 0.58 (−1.41 to 3.69), 0.66 (−0.67 to 1.32), and 0.15 (−1.53 to 2.38) cm, respectively. The T1- and T2-based volumes for pancreas, duodenum, stomach, and liver were generally smaller

  18. Wavelet-based multiscale analysis of bioimpedance data measured by electric cell-substrate impedance sensing for classification of cancerous and normal cells

    Science.gov (United States)

    Das, Debanjan; Shiladitya, Kumar; Biswas, Karabi; Dutta, Pranab Kumar; Parekh, Aditya; Mandal, Mahitosh; Das, Soumen

    2015-12-01

    The paper presents a study to differentiate normal and cancerous cells using label-free bioimpedance signal measured by electric cell-substrate impedance sensing. The real-time-measured bioimpedance data of human breast cancer cells and human epithelial normal cells employs fluctuations of impedance value due to cellular micromotions resulting from dynamic structural rearrangement of membrane protrusions under nonagitated condition. Here, a wavelet-based multiscale quantitative analysis technique has been applied to analyze the fluctuations in bioimpedance. The study demonstrates a method to classify cancerous and normal cells from the signature of their impedance fluctuations. The fluctuations associated with cellular micromotion are quantified in terms of cellular energy, cellular power dissipation, and cellular moments. The cellular energy and power dissipation are found higher for cancerous cells associated with higher micromotions in cancer cells. The initial study suggests that proposed wavelet-based quantitative technique promises to be an effective method to analyze real-time bioimpedance signal for distinguishing cancer and normal cells.

  19. Automated selection of regions of interest for intensity-based FRET analysis of transferrin endocytic trafficking in normal vs. cancer cells.

    Science.gov (United States)

    Talati, Ronak; Vanderpoel, Andrew; Eladdadi, Amina; Anderson, Kate; Abe, Ken; Barroso, Margarida

    2014-03-15

    The overexpression of certain membrane-bound receptors is a hallmark of cancer progression and it has been suggested to affect the organization, activation, recycling and down-regulation of receptor-ligand complexes in human cancer cells. Thus, comparing receptor trafficking pathways in normal vs. cancer cells requires the ability to image cells expressing dramatically different receptor expression levels. Here, we have presented a significant technical advance to the analysis and processing of images collected using intensity based Förster resonance energy transfer (FRET) confocal microscopy. An automated Image J macro was developed to select region of interests (ROI) based on intensity and statistical-based thresholds within cellular images with reduced FRET signal. Furthermore, SSMD (strictly standardized mean differences), a statistical signal-to-noise ratio (SNR) evaluation parameter, was used to validate the quality of FRET analysis, in particular of ROI database selection. The Image J ROI selection macro together with SSMD as an evaluation parameter of SNR levels, were used to investigate the endocytic recycling of Tfn-TFR complexes at nanometer range resolution in human normal vs. breast cancer cells expressing significantly different levels of endogenous TFR. Here, the FRET-based assay demonstrates that Tfn-TFR complexes in normal epithelial vs. breast cancer cells show a significantly different E% behavior during their endocytic recycling pathway. Since E% is a relative measure of distance, we propose that these changes in E% levels represent conformational changes in Tfn-TFR complexes during endocytic pathway. Thus, our results indicate that Tfn-TFR complexes undergo different conformational changes in normal vs. cancer cells, indicating that the organization of Tfn-TFR complexes at the nanometer range is significantly altered during the endocytic recycling pathway in cancer cells. In summary, improvements in the automated selection of FRET ROI datasets

  20. Prevalence of H pylori associated 'high risk gastritis' for development of gastric cancer in patients with normal endoscopic findings

    Institute of Scientific and Technical Information of China (English)

    Andreas Leodolter; Matthias P Ebert; Ulrich Peitz; Kathlen Wolle; Stefan Kahl; Michael Vieth; Peter Malfertheiner

    2006-01-01

    AIM: To investigate the prevalence of H pylori associated corpus-predominant gastritis (CPG) or pangastritis, severe atrophy, and intestinal metaplasia (IM) in patients without any significant abnormal findings during upper GI endoscopy.METHODS: Gastric biopsies from 3548 patients were obtained during upper GI-endoscopy in a 4-year period. Two biopsies from antrum and corpus were histologically assessed according to the updated Sydney-System.Eight hundred and forty-five patients (mean age 54.8 ±2.8 years) with H pylori infection and no peptic ulcer or abnormal gross findings in the stomach were identified and analyzed according to gastritis phenotypes using different scoring systems.RESULTS: The prevalence of severe H pylori associated changes like pangastritis, CPG, IM, and severe atrophy increased with age, reaching a level of 20% in patients of the age group over 45 years. No differences in frequencies between genders were observed. The prevalence of IM had the highest increase, being 4-fold higher at the age of 65 years versus in individuals less than 45 years.CONCLUSION: The prevalence of gastritis featuring at risk for cancer development increases with age. These findings reinforce the necessity for the histological assessment, even in subjects with normal endoscopic appearance. The age-dependent increase in prevalence of severe histopathological changes in gastric mucosa, however, does not allow estimating the individual risk for gastric cancer development-only a proper follow-up can provide this information.

  1. Evaluation of Glucose Uptake in Normal and Cancer Cell Lines by Positron Emission Tomography.

    Science.gov (United States)

    Maddalena, Francesca; Lettini, Giacomo; Gallicchio, Rosj; Sisinni, Lorenza; Simeon, Vittorio; Nardelli, Anna; Venetucci, Angela Assunta; Storto, Giovanni; Landriscina, Matteo

    2015-01-01

    To date, there is no definitive demonstration of the utility of positron emission tomography (PET) in studying glucose metabolism in cultured cell lines. Thus, this study was designed to compare PET to more standardized methods for the quantitative assessment of glucose uptake in nontransformed and transformed living cells and to validate PET for metabolic studies in vitro. Human colon and breast carcinoma cell lines and mouse embryo fibroblasts were evaluated for [(18)F]fluorodeoxyglucose ([(18)F]FDG) uptake by PET and autoradiography and 2-deoxyglucose (2-DG) incorporation by colorimetric assay and analyzed for the radiotoxic effects of [(18)F]FDG and the expression levels of glucose transporters. Indeed, [(18)F]FDG incorporation on PET was comparable to [(18)F]FDG uptake by autoradiography and 2-DG incorporation by colorimetric assay, although radiotracer-based methods exhibited more pronounced differences between individual cell lines. As expected, these data correlated with glucose transporters 1 to 4 and hexokinase II expression in tumor cell lines and mouse fibroblasts. Notably, [(18)F]FDG incorporation resulted in low apoptotic rates, with fibroblasts being slightly more sensitive to radiotracer-induced cell death. The quantitative analysis of [(18)F]FDG uptake in living cells by PET represents a valuable and reproducible method to study tumor cell metabolism in vitro, being representative of the differences in the molecular profile of normal and tumor cell lines.

  2. Application of Small Angle X-ray Scattering (SAXS for Differentiation between Normal and Cancerous Breast Tissue

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available Introduction: Small angle, between 3° and 10°, X ray scattering is predominantly coherent giving rise to diffraction effects that can be observed as constructive and destructive interferences. These interferences carry information about the molecular structure of the tissue and hence can be used to identify changes that occur due to cancer. Method: In this study an energy dispersive X-ray diffraction method was used. The optimum scattering angle, determined from a series of measurements on adipose breast tissue at several angles from 4 to 7.3 degrees, was found to be 6.5°. Once optimized the system was used to measure the diffraction profiles (corrected scattered intensity versus momentum transfer of a total of 99 breast tissue samples. The samples were both normal and tumour samples. Results: Adipose tissue showed a sharp, high intensity peak at low momentum transfer values of approximately 1.1nm-1. Adipose tissue, mixed tissue (adipose & fibroglandular and tumor have peaks at different values of momentum transfer that can be used to identify the tissue. Benign and malignant breast tissues can also be differentiated by both peak positions and peak heights. It was also observed that the results were reproducible even after the tissue had been preserved at liquid nitrogen temperatures. Conclusion: We were able to differentiate between normal, benign and malignant breast tissues by using energy dispersive small angle x-ray scattering.

  3. Gold Nanoparticle–Mediated Targeted Delivery of Recombinant Human Endostatin Normalizes Tumour Vasculature and Improves Cancer Therapy

    Science.gov (United States)

    Li, Wei; Zhao, Xiaoxu; Du, Bin; Li, Xin; Liu, Shuhao; Yang, Xiao-Yan; Ding, Hui; Yang, Wende; Pan, Fan; Wu, Xiaobo; Qin, Li; Pan, Yunlong

    2016-01-01

    Tumour vasculature is generally disordered because of the production of excessive angiogenic factors by tumour cells, which results in tumour progression and reduces the effectiveness of radiotherapy or chemotherapy. Transient anti-angiogenic therapies that regulate tumour vascular morphology and function and improve the efficiency of antitumour therapy are under investigation. Recombinant human endostatin (Endostar/rhES) is a vascular angiogenesis–disrupting agent that has been used to treat non-small cell lung cancer (NSCLC) in the clinical setting. In this study, we used gold nanoparticles (AuNPs) as a drug-delivery system (DDS) for targeted tumour delivery of rhES for short therapy, which resulted in transient tumour vascular normalization, reduced permeability and hypoxia, strengthened blood vessel integrity, and increased blood-flow perfusion. Moreover, combination therapy with 5-FU over this timeframe was substantially more effective than 5-FU monotherapy. In conclusion, our research demonstrates the potential use of AuNPs as a drug-delivery platform for transporting rhES into a tumour to induce transient tumour vascular normalization and enhance the antitumour efficacy of cytotoxic drugs. PMID:27470938

  4. The clinical relevance of rising CA-125 levels within the normal range in patients with uterine papillary serous cancer.

    Science.gov (United States)

    Frimer, Marina; Hou, June Y; McAndrew, Thomas C; Goldberg, Gary L; Shahabi, Shohreh

    2013-04-01

    The utility of cancer antigen 125 (CA-125) levels as an adjunct method of monitoring patients with uterine papillary serous carcinoma (UPSC) or endometrial serous carcinoma after surgery and adjuvant treatment has been reported. Our goal was to determine the significance of rising CA-125 levels within the normal range in these patients in the posttreatment surveillance setting. All patients with UPSC who underwent surgical staging and had preoperative CA-125 measurement from 1999 to 2008 were included in this analysis. Information was extracted from records to assess the changes in CA-125 values with clinical and/or radiographic detection of recurrence. Of the 56 evaluable patients, 23 (41%) recurred. Of the 23 patients that recurred, 11 had serial CA-125 levels measured in remission. Elevated CA-125 levels at diagnosis were significantly associated with disease recurrence and advanced stage (P = .01, P = .001, respectively). The rise in CA-125 by 10 U/mL in the normal range and ≥ 15 U/mL were associated with disease recurrence (P UPSC after remission, surveillance of CA-125 levels may have a role in disease surveillance and management. PMID:22995987

  5. Influence of nanoparticles accumulation on optical properties of human normal and cancerous liver tissue in vitro estimated by OCT

    International Nuclear Information System (INIS)

    In this work, the potential use of nanoparticles as contrast agents by using spectral domain optical coherence tomography (SD-OCT) in liver tissue was demonstrated. Gold nanoparticles (average size of 25 and 70 nm), were studied in human normal and cancerous liver tissues in vitro, respectively. Each sample was monitored with SD-OCT functional imaging for 240 min. Continuous OCT monitoring showed that, after application of gold nanoparticles, the OCT signal intensities of normal liver and cancerous liver tissue both increase with time, and the larger nanoparticles tend to produce a greater signal enhancement in the same type of tissue. The results show that the values of attenuation coefficients have significant differences between normal liver tissue and cancerous liver tissue. In addition, 25 nm gold nanoparticles allow higher penetration depth than 70 nm gold nanoparticles in liver tissues. (paper)

  6. Volume effects of late term normal tissue toxicity in prostate cancer radiotherapy

    Science.gov (United States)

    Bonta, Dacian Viorel

    Modeling of volume effects for treatment toxicity is paramount for optimization of radiation therapy. This thesis proposes a new model for calculating volume effects in gastro-intestinal and genito-urinary normal tissue complication probability (NTCP) following radiation therapy for prostate carcinoma. The radiobiological and the pathological basis for this model and its relationship to other models are detailed. A review of the radiobiological experiments and published clinical data identified salient features and specific properties a biologically adequate model has to conform to. The new model was fit to a set of actual clinical data. In order to verify the goodness of fit, two established NTCP models and a non-NTCP measure for complication risk were fitted to the same clinical data. The method of fit for the model parameters was maximum likelihood estimation. Within the framework of the maximum likelihood approach I estimated the parameter uncertainties for each complication prediction model. The quality-of-fit was determined using the Aikaike Information Criterion. Based on the model that provided the best fit, I identified the volume effects for both types of toxicities. Computer-based bootstrap resampling of the original dataset was used to estimate the bias and variance for the fitted parameter values. Computer simulation was also used to estimate the population size that generates a specific uncertainty level (3%) in the value of predicted complication probability. The same method was used to estimate the size of the patient population needed for accurate choice of the model underlying the NTCP. The results indicate that, depending on the number of parameters of a specific NTCP model, 100 (for two parameter models) and 500 patients (for three parameter models) are needed for accurate parameter fit. Correlation of complication occurrence in patients was also investigated. The results suggest that complication outcomes are correlated in a patient, although

  7. Estimating Absolute Site Effects

    Energy Technology Data Exchange (ETDEWEB)

    Malagnini, L; Mayeda, K M; Akinci, A; Bragato, P L

    2004-07-15

    The authors use previously determined direct-wave attenuation functions as well as stable, coda-derived source excitation spectra to isolate the absolute S-wave site effect for the horizontal and vertical components of weak ground motion. They used selected stations in the seismic network of the eastern Alps, and find the following: (1) all ''hard rock'' sites exhibited deamplification phenomena due to absorption at frequencies ranging between 0.5 and 12 Hz (the available bandwidth), on both the horizontal and vertical components; (2) ''hard rock'' site transfer functions showed large variability at high-frequency; (3) vertical-motion site transfer functions show strong frequency-dependence, and (4) H/V spectral ratios do not reproduce the characteristics of the true horizontal site transfer functions; (5) traditional, relative site terms obtained by using reference ''rock sites'' can be misleading in inferring the behaviors of true site transfer functions, since most rock sites have non-flat responses due to shallow heterogeneities resulting from varying degrees of weathering. They also use their stable source spectra to estimate total radiated seismic energy and compare against previous results. they find that the earthquakes in this region exhibit non-constant dynamic stress drop scaling which gives further support for a fundamental difference in rupture dynamics between small and large earthquakes. To correct the vertical and horizontal S-wave spectra for attenuation, they used detailed regional attenuation functions derived by Malagnini et al. (2002) who determined frequency-dependent geometrical spreading and Q for the region. These corrections account for the gross path effects (i.e., all distance-dependent effects), although the source and site effects are still present in the distance-corrected spectra. The main goal of this study is to isolate the absolute site effect (as a function of frequency

  8. 血管正常化与肿瘤免疫治疗%Vascular Normalization and Cancer Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    曾俊莉; 袁冬梅; 刘红兵; 宋勇

    2014-01-01

    免疫治疗是一种颇有前景的抗肿瘤策略。然而,肿瘤中的免疫抑制微环境阻碍了免疫治疗的发展。异常肿瘤血管造成的缺氧,使免疫细胞趋向免疫抑制。并且异常血管通过分泌生长因子及细胞因子,改变免疫细胞的增殖、分化及功能,最终形成免疫抑制的微环境。因此,有效的利用血管生成及肿瘤免疫之间的相互作用,适当的抑制血管形成,促进肿瘤血管正常化,可以改变肿瘤的免疫抑制微环境,成为改善免疫治疗的新策略。现就血管正常化与肿瘤免疫的关系,及二者的联合治疗进行综述。。%Immunotherapies, as a promising anticancer therapy stratrgy, has been paid more and more attentions. However, the abnormal tumor vasculature creates a hypoxic microenvironment that make immune cells toward immune sup-pression. hTe immunosuppressive microenvironment seems to impede the development of immunotherapies. Hence, normal-ization tumor vascular by anti-angiogenesis properly could improve the immunosuppressive miroenvironment. Consequently, the effcacy of the immunotherapies was enhanced. Here, we discuss the effects of vascular normalizing on tumor immunity and propose a potentially strategy to re-engineer the tumor-immune microenvironment and improve cancer immunotherapy.

  9. Protons Offer Reduced Normal-Tissue Exposure for Patients Receiving Postoperative Radiotherapy for Resected Pancreatic Head Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nichols, Romaine C., E-mail: rnichols@floridaproton.org [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Huh, Soon N. [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Prado, Karl L.; Yi, Byong Y.; Sharma, Navesh K. [Department of Radiation Oncology, University of Maryland, Baltimore, MD (United States); Ho, Meng W.; Hoppe, Bradford S.; Mendenhall, Nancy P.; Li, Zuofeng [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland, Baltimore, MD (United States)

    2012-05-01

    Purpose: To determine the potential role for adjuvant proton-based radiotherapy (PT) for resected pancreatic head cancer. Methods and Materials: Between June 2008 and November 2008, 8 consecutive patients with resected pancreatic head cancers underwent optimized intensity-modulated radiotherapy (IMRT) treatment planning. IMRT plans used between 10 and 18 fields and delivered 45 Gy to the initial planning target volume (PTV) and a 5.4 Gy boost to a reduced PTV. PTVs were defined according to the Radiation Therapy Oncology Group 9704 radiotherapy guidelines. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Normal tissue constraints were as follows: right kidney V18 Gy to <70%; left kidney V18 Gy to <30%; small bowel/stomach V20 Gy to <50%, V45 Gy to <15%, V50 Gy to <10%, and V54 Gy to <5%; liver V30 Gy to <60%; and spinal cord maximum to 46 Gy. Optimized two- to three-field three-dimensional conformal proton plans were retrospectively generated on the same patients. The team generating the proton plans was blinded to the dose distributions achieved by the IMRT plans. The IMRT and proton plans were then compared. A Wilcoxon paired t-test was performed to compare various dosimetric points between the two plans for each patient. Results: All proton plans met all normal tissue constraints and were isoeffective with the corresponding IMRT plans in terms of PTV coverage. The proton plans offered significantly reduced normal-tissue exposure over the IMRT plans with respect to the following: median small bowel V20 Gy, 15.4% with protons versus 47.0% with IMRT (p = 0.0156); median gastric V20 Gy, 2.3% with protons versus 20.0% with IMRT (p = 0.0313); and median right kidney V18 Gy, 27.3% with protons versus 50.5% with IMRT (p = 0.0156). Conclusions: By reducing small bowel and stomach exposure, protons have the potential to reduce the acute and late toxicities of postoperative chemoradiation in this setting.

  10. The Balance of Cell Surface and Soluble Type III TGF-β Receptor Regulates BMP Signaling in Normal and Cancerous Mammary Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Catherine E. Gatza

    2014-06-01

    Full Text Available Bone morphogenetic proteins (BMPs are members of the TGF-β superfamily that are over-expressed in breast cancer, with context dependent effects on breast cancer pathogenesis. The type III TGF-β receptor (TβRIII mediates BMP signaling. While TβRIII expression is lost during breast cancer progression, the role of TβRIII in regulating BMP signaling in normal mammary epithelium and breast cancer cells has not been examined. Restoring TβRIII expression in a 4T1 murine syngeneic model of breast cancer suppressed Smad1/5/8 phosphorylation and inhibited the expression of the BMP transcriptional targets, Id1 and Smad6, in vivo. Similarly, restoring TβRIII expression in human breast cancer cell lines or treatment with sTβRIII inhibited BMP-induced Smad1/5/8 phosphorylation and BMP-stimulated migration and invasion. In normal mammary epithelial cells, shRNA-mediated silencing of TβRIII, TβRIII over-expression, or treatment with sTβRIII inhibited BMP-mediated phosphorylation of Smad1/5/8 and BMP induced migration. Inhibition of TβRIII shedding through treatment with TAPI-2 or expression of a non-shedding TβRIII mutant rescued TβRIII mediated inhibition of BMP induced Smad1/5/8 phosphorylation and BMP induced migration and/or invasion in both in normal mammary epithelial cells and breast cancer cells. Conversely, expression of a TβRIII mutant, which exhibited increased shedding, significantly reduced BMP-mediated Smad1/5/8 phosphorylation, migration, and invasion. These data demonstrate that TβRIII regulates BMP-mediated signaling and biological effects, primarily through the ligand sequestration effects of sTβRIII in normal and cancerous mammary epithelial cells and suggest that the ratio of membrane bound versus sTβRIII plays an important role in mediating these effects.

  11. Comparison of molecular signatures in large scale protein interaction networks in normal and cancer conditions of brain, cervix, lung, ovary and prostate

    Directory of Open Access Journals (Sweden)

    Rajat Suvra Banik

    2016-04-01

    Full Text Available Background Cancer, the disease of intricateness, has remained beyond our complete perception so far. Network systems biology (termed NSB is one of the most recent approaches to understand the unsolved problems of cancer development. From this perspective, differential protein networks (PINs have been developed based on the expression and interaction data of brain, cervix, lung, ovary and prostate for normal and cancer conditions. Methods Differential expression database GeneHub-GEPIS and interaction database STRING were applied for primary data retrieval. Cytoscape platform and related plugins named network analyzer; MCODE and ModuLand were used for visualization of complex networks and subsequent analysis. Results Significant differences were observedamong different common network parameters between normal and cancer states. Moreover, molecular complex numbers and overlapping modularization found to be varying significantly between normal and cancerous tissues. The number of the ranked molecular complex and the nodes involved in the overlapping modules were meaningfully higher in cancer condition.We identified79 commonly up regulated and 6 down regulated proteins in all five tissues. Number of nodes, edges; multi edge node pair, and average number of neighbor are found with significant fluctuations in case of cervix and ovarian tissues.Cluster analysis showed that the association of Myc and Cdk4 proteins is very close with other proteins within the network.Cervix and ovarian tissue showed higher increment of the molecular complex number and overlapping module network during cancer in comparison to normal state. Conclusions The differential molecular signatures identified from the work can be studied further to understand the cancer signaling process, and potential therapeutic and detection approach. [Biomed Res Ther 2016; 3(4.000: 605-615

  12. A pilot study to determine the timing and effect of bevacizumab on vascular normalization of metastatic brain tumors in breast cancer

    OpenAIRE

    Chen, Bang-Bin; Lu, Yen-Shen; Lin, Ching-Hung; Chen, Wei-Wu; Wu, Pei-Fang; Hsu, Chao-Yu; Yu, Chih-Wei; Wei, Shwu-Yuan; Cheng, Ann-Lii; Shih, Tiffany Ting-Fang

    2016-01-01

    Background To determine the appropriate time of concomitant chemotherapy administration after antiangiogenic treatment, we investigated the timing and effect of bevacizumab administration on vascular normalization of metastatic brain tumors in breast cancer patients. Methods Eight patients who participated in a phase II trial for breast cancer-induced refractory brain metastases were enrolled and subjected to 4 dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examinations that e...

  13. Sclerotium rolfsii Lectin Induces Stronger Inhibition of Proliferation in Human Breast Cancer Cells than Normal Human Mammary Epithelial Cells by Induction of Cell Apoptosis

    Science.gov (United States)

    Savanur, Mohammed Azharuddin; Eligar, Sachin M.; Pujari, Radha; Chen, Chen; Mahajan, Pravin; Borges, Anita; Shastry, Padma; Ingle, Arvind.; Kalraiya, Rajiv D.; Swamy, Bale M.; Rhodes, Jonathan M.; Yu, Lu-Gang; Inamdar, Shashikala R.

    2014-01-01

    Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast epithelial cells (MCF-10A) and normal mammary epithelial cells (HMECs). SRL caused marked, dose-dependent, inhibition of proliferation of MCF-7 and ZR-75 cells but only weak inhibition of proliferation of non-tumorigenic MCF-10A and HMEC cells. The inhibitory effect of SRL on cancer cell proliferation was shown to be a consequence of SRL cell surface binding and subsequent induction of cellular apoptosis, an effect that was largely prevented by the presence of inhibitors against caspases -3, -8, or -9. Lectin histochemistry using biotin-labelled SRL showed little binding of SRL to normal human breast tissue but intense binding to cancerous tissues. In conclusion, SRL inhibits the growth of human breast cancer cells via induction of cell apoptosis but has substantially less effect on normal epithelial cells. As a lectin that binds specifically to a cancer-associated glycan, has potential to be developed as an anti-cancer agent. PMID:25364905

  14. The Expression of Toll-like Receptors in Normal Human and Murine Gastrointestinal Organs and the Effect of Microbiome and Cancer.

    Science.gov (United States)

    Huhta, Heikki; Helminen, Olli; Kauppila, Joonas H; Salo, Tuula; Porvari, Katja; Saarnio, Juha; Lehenkari, Petri P; Karttunen, Tuomo J

    2016-08-01

    Toll-like receptors (TLRs) are innate immune receptors expressed in all parts of the alimentary tract. However, analyses comparing expression in different segments and data on germ-free animals are lacking. Alimentary tract cancers show increased TLR expression. According to the field effect concept, carcinogenetic factors induce subtle cancer predisposing alterations in the whole organ. We studied TLR1 to TLR9 expression in all segments of the alimentary tract from cancer patients' tumor-adjacent normal mucosa, healthy organ donors, and conventional and germ-free mice by using immunohistochemistry and quantitative PCR. All TLRs were expressed in all segments of the alimentary tract. Expression was most intensive in the small intestine in humans and conventional mice, but germ-free mice showed less expression in the small intestine. TLR expression levels were similar in cancer patients and organ donors. We provide systematic baseline data on the TLR expression in the alimentary tract. Normal epithelium adjacent to tumor seems to have similar TLR expression compared with healthy tissues suggesting absence of any field effect in TLR expression. Accordingly, specimens from cancer patients' normal tumor-adjacent tissue can be used as control tissues in immunohistochemical TLR studies in gastrointestinal cancer. PMID:27370795

  15. MicroRNA-17 promotes normal ovarian cancer cells to cancer stem cells development via suppression of the LKB1-p53-p21/WAF1 pathway.

    Science.gov (United States)

    Liu, Te; Qin, Wenxing; Hou, Lengchen; Huang, Yongyi

    2015-03-01

    The mechanism underlying the development of human ovarian cancer is poorly understood. The liver kinase protein, LKB1, is hypothesized to play a pivotal role in tumor cell proliferation and invasion capacity through regulation of p53 and p21/WAF1 expression. Previous studies suggest LKB1 may, in turn, be regulated by microRNA-17. Here, we examined the role of miR-17 in the expression of LKB1 and the downstream effects on proliferation and invasion capacity of normal ovarian cancer cells (OCCs) and ovarian stem cells. In this study, both the mRNA and protein expression levels of LKB1, p53, and p21 decreased in OCCs following transfection with a miR-17 expression plasmid. MiR-17 expression affected cell cycle regulation and stimulated the proliferation and invasion capacity of OCCs in vitro. ChIP assays indicated that the binding efficiency of p53 to the p21/WAF1 gene promoter was much lower in miR-17 transfected OCCs than in OCCs transfected with a mutated miR-17. Co-immunoprecipitation and western blotting showed significantly lower levels of p53 and p53 Ser15-pho in the miR-17 transfected OCCs as compared to the mutant miR-17 transfected OCCs. Xenograft experiments confirmed that suppression of tumor growth in vivo occurred in the absence of functional miR-17. These findings suggest that mature miR-17 expression may have an important role in the pathogenesis of human ovarian tumors through its interference with the LKB1-p53-p21/WAF1 pathway expression by epigenetic modification. These findings are of potential importance in the identification of novel therapeutic targets in human ovarian cancer.

  16. Be Resolute about Absolute Value

    Science.gov (United States)

    Kidd, Margaret L.

    2007-01-01

    This article explores how conceptualization of absolute value can start long before it is introduced. The manner in which absolute value is introduced to students in middle school has far-reaching consequences for their future mathematical understanding. It begins to lay the foundation for students' understanding of algebra, which can change…

  17. The 8th international symposium on the breast: Using next-generation science to understand the normal breast and the development of breast cancer- conference report.

    Science.gov (United States)

    Gomberawalla, Ameer; Love, Susan

    2015-12-01

    Dr. Susan Love Research Foundation is committed to performing and advancing research that will lead to the discovery of what causes cancer to develop in the human breast. As part of this effort, the Foundation hosted the 8th International Symposium on the Breast in Santa Monica, Calif., Feb. 19 to Feb. 21, 2015. More than 120 forward-thinking clinical researchers, epidemiologists, pathologists, basic scientists, translational investigators, and breast cancer advocates from six countries attended this year's conference, "Using Next Generation Science to Understand the Normal Breast and the Development of Cancer." The highlights from this year's symposium are summarized in this report.

  18. Risk of gastrointestinal cancer in patients with unexplained chest/epigastric pain and normal upper endoscopy: a Danish 10-year follow-up study

    DEFF Research Database (Denmark)

    Munk, Estrid Muff; Drewes, Asbjørn Mohr; Gorst-Rasmussen, Anders;

    2007-01-01

    patients with chest/epigastric pain, normal upper endoscopy, and no prior discharge diagnosis of ischemic heart disease (N = 386), compared with population controls (N = 3860). The overall 10-year risk of gastrointestinal cancer (stomach, colorectal, liver, and pancreas) was 2.9% for patients......Unexplained chest/epigastric pain is a common symptom in the general population. However, it has not previously been studied whether such pain could be a marker of subsequent gastrointestinal cancer. We aimed to estimate the risk of gastrointestinal cancers in a Danish 10-year follow-up study among...... of gastrointestinal cancer within the first year after upper endoscopy. Consequently, unexplained chest/epigastric pain might be an early gastrointestinal cancer symptom....

  19. Iodine-131 dose dependent gene expression in thyroid cancers and corresponding normal tissues following the Chernobyl accident.

    Directory of Open Access Journals (Sweden)

    Michael Abend

    Full Text Available The strong and consistent relationship between irradiation at a young age and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis in humans. We thus evaluated differential gene expression in thyroid tissue in relation to iodine-131 (I-131 doses received from the Chernobyl accident. Sixty three of 104 papillary thyroid cancers diagnosed between 1998 and 2008 in the Ukrainian-American cohort with individual I-131 thyroid dose estimates had paired RNA specimens from fresh frozen tumor (T and normal (N tissue provided by the Chernobyl Tissue Bank and satisfied quality control criteria. We first hybridized 32 randomly allocated RNA specimen pairs (T/N on 64 whole genome microarrays (Agilent, 4×44 K. Associations of differential gene expression (log(2(T/N with dose were assessed using Kruskall-Wallis and trend tests in linear mixed regression models. While none of the genes withstood correction for the false discovery rate, we selected 75 genes with a priori evidence or P kruskall/P trend <0.0005 for validation by qRT-PCR on the remaining 31 RNA specimen pairs (T/N. The qRT-PCR data were analyzed using linear mixed regression models that included radiation dose as a categorical or ordinal variable. Eleven of 75 qRT-PCR assayed genes (ACVR2A, AJAP1, CA12, CDK12, FAM38A, GALNT7, LMO3, MTA1, SLC19A1, SLC43A3, ZNF493 were confirmed to have a statistically significant differential dose-expression relationship. Our study is among the first to provide direct human data on long term differential gene expression in relation to individual I-131 doses and to identify a set of genes potentially important in radiation carcinogenesis.

  20. Reduced Activity of Double-Strand Break Repair Genes in Prostate Cancer Patients With Late Normal Tissue Radiation Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Oorschot, Bregje van, E-mail: b.vanoorschot@amc.uva.nl [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Hovingh, Suzanne E. [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Moerland, Perry D. [Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Medema, Jan Paul; Stalpers, Lukas J.A. [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Vrieling, Harry [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Franken, Nicolaas A.P. [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands)

    2014-03-01

    Purpose: To investigate clinical parameters and DNA damage response as possible risk factors for radiation toxicity in the setting of prostate cancer. Methods and Materials: Clinical parameters of 61 prostate cancer patients, 34 with (overresponding, OR) and 27 without (non-responding, NR) severe late radiation toxicity were assembled. In addition, for a matched subset the DNA damage repair kinetics (γ-H2AX assay) and expression profiles of DNA repair genes were determined in ex vivo irradiated lymphocytes. Results: Examination of clinical data indicated none of the considered clinical parameters to be correlated with the susceptibility of patients to develop late radiation toxicity. Although frequencies of γ-H2AX foci induced immediately after irradiation were similar (P=.32), significantly higher numbers of γ-H2AX foci were found 24 hours after irradiation in OR compared with NR patients (P=.03). Patient-specific γ-H2AX foci decay ratios were significantly higher in NR patients than in OR patients (P<.0001). Consequently, NR patients seem to repair DNA double-strand breaks (DSBs) more efficiently than OR patients. Moreover, gene expression analysis indicated several genes of the homologous recombination pathway to be stronger induced in NR compared with OR patients (P<.05). A similar trend was observed in genes of the nonhomologous end-joining repair pathway (P=.09). This is congruent with more proficient repair of DNA DSBs in patients without late radiation toxicity. Conclusions: Both gene expression profiling and DNA DSB repair kinetics data imply that less-efficient repair of radiation-induced DSBs may contribute to the development of late normal tissue damage. Induction levels of DSB repair genes (eg, RAD51) may potentially be used to assess the risk for late radiation toxicity.

  1. Analysis of Normal-Tumour Tissue Interaction in Tumours: Prediction of Prostate Cancer Features from the Molecular Profile of Adjacent Normal Cells

    OpenAIRE

    Trevino, Victor; Tadesse, Mahlet G.; Vannucci, Marina; Al-Shahrour, Fatima; Antczak, Philipp; Durant, Sarah; Bikfalvi, Andreas; Dopazo, Joaquin; Campbell, Moray J.; Falciani, Francesco

    2011-01-01

    Statistical modelling, in combination with genome-wide expression profiling techniques, has demonstrated that the molecular state of the tumour is sufficient to infer its pathological state. These studies have been extremely important in diagnostics and have contributed to improving our understanding of tumour biology. However, their importance in in-depth understanding of cancer patho-physiology may be limited since they do not explicitly take into consideration the fundamental role of the t...

  2. Breast Cancer Heterogeneity Examined by High-Sensitivity Quantification of PIK3CA, KRAS, HRAS, and BRAF Mutations in Normal Breast and Ductal Carcinomas.

    Science.gov (United States)

    Myers, Meagan B; Banda, Malathi; McKim, Karen L; Wang, Yiying; Powell, Michael J; Parsons, Barbara L

    2016-04-01

    Mutant cancer subpopulations have the potential to derail durable patient responses to molecularly targeted cancer therapeutics, yet the prevalence and size of such subpopulations are largely unexplored. We employed the sensitive and quantitative Allele-specific Competitive Blocker PCR approach to characterize mutant cancer subpopulations in ductal carcinomas (DCs), examining five specific hotspot point mutations (PIK3CA H1047R, KRAS G12D, KRAS G12V, HRAS G12D, and BRAF V600E). As an approach to aid interpretation of the DC results, the mutations were also quantified in normal breast tissue. Overall, the mutations were prevalent in normal breast and DCs, with 9/9 DCs having measureable levels of at least three of the five mutations. HRAS G12D was significantly increased in DCs as compared to normal breast. The most frequent point mutation reported in DC by DNA sequencing, PIK3CA H1047R, was detected in all normal breast tissue and DC samples and was present at remarkably high levels (mutant fractions of 1.1 × 10(-3) to 4.6 × 10(-2)) in 4/10 normal breast samples. In normal breast tissue samples, PIK3CA mutation levels were positively correlated with age. However, the PIK3CA H1047R mutant fraction distributions for normal breast tissues and DCs were similar. The results suggest PIK3CA H1047R mutant cells have a selective advantage in breast, contribute to breast cancer susceptibility, and drive tumor progression during breast carcinogenesis, even when present as only a subpopulation of tumor cells. PMID:27108388

  3. Multivariable normal-tissue complication modeling of acute esophageal toxicity in advanced stage non-small cell lung cancer patients treated with intensity-modulated (chemo-)radiotherapy

    NARCIS (Netherlands)

    Wijsman, R.; Dankers, F.; Troost, E.G.; Hoffman, A.L.; Heijden, E. van der; Geus-Oei, L.F. de; Bussink, J.

    2015-01-01

    BACKGROUND AND PURPOSE: The majority of normal-tissue complication probability (NTCP) models for acute esophageal toxicity (AET) in advanced stage non-small cell lung cancer (AS-NSCLC) patients treated with (chemo-)radiotherapy are based on three-dimensional conformal radiotherapy (3D-CRT). Due to d

  4. Evaluation of prostatic cancer prevalence in patients with prostatic-specific antigen between 4 and 10 and normal digital rectal examination

    Directory of Open Access Journals (Sweden)

    Farhad Tadayon

    2016-01-01

    Conclusion: In males with PSA between 4 and 10 and normal DRE, PSA density smaller than 0.12-0.15, and percent of free PSA greater than 18%, the prevalence of prostate cancer is very few and we can safely ignore the TRUS and prostate biopsy in these males and eliminate its costs and side effects.

  5. A large-scale study of the ultrawideband microwave dielectric properties of normal, benign and malignant breast tissues obtained from cancer surgeries

    Energy Technology Data Exchange (ETDEWEB)

    Lazebnik, Mariya [Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI (United States); Popovic, Dijana [Department of Electrical and Computer Engineering, University of Calgary, Calgary, AB (Canada); McCartney, Leah [Department of Electrical and Computer Engineering, University of Calgary, Calgary, AB (Canada); Watkins, Cynthia B [Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI (United States); Lindstrom, Mary J [Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI (United States); Harter, Josephine [Department of Pathology, University of Wisconsin, Madison, WI (United States); Sewall, Sarah [Department of Pathology, University of Wisconsin, Madison, WI (United States); Ogilvie, Travis [Department of Pathology, University of Calgary, Calgary, AB (Canada); Magliocco, Anthony [Department of Pathology, University of Calgary, Calgary, AB (Canada); Breslin, Tara M [Department of Surgery, University of Wisconsin, Madison, WI (United States); Temple, Walley [Department of Surgery and Oncology, University of Calgary, Calgary, AB (Canada); Mew, Daphne [Department of Surgery and Oncology, University of Calgary, Calgary, AB (Canada); Booske, John H [Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI (United States); Okoniewski, Michal [Department of Electrical and Computer Engineering, University of Calgary, Calgary, AB (Canada); Hagness, Susan C [Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI (United States)

    2007-10-21

    The development of microwave breast cancer detection and treatment techniques has been driven by reports of substantial contrast in the dielectric properties of malignant and normal breast tissues. However, definitive knowledge of the dielectric properties of normal and diseased breast tissues at microwave frequencies has been limited by gaps and discrepancies across previously published studies. To address these issues, we conducted a large-scale study to experimentally determine the ultrawideband microwave dielectric properties of a variety of normal, malignant and benign breast tissues, measured from 0.5 to 20 GHz using a precision open-ended coaxial probe. Previously, we reported the dielectric properties of normal breast tissue samples obtained from reduction surgeries. Here, we report the dielectric properties of normal (adipose, glandular and fibroconnective), malignant (invasive and non-invasive ductal and lobular carcinomas) and benign (fibroadenomas and cysts) breast tissue samples obtained from cancer surgeries. We fit a one-pole Cole-Cole model to the complex permittivity data set of each characterized sample. Our analyses show that the contrast in the microwave-frequency dielectric properties between malignant and normal adipose-dominated tissues in the breast is considerable, as large as 10:1, while the contrast in the microwave-frequency dielectric properties between malignant and normal glandular/fibroconnective tissues in the breast is no more than about 10%.

  6. Downregulation of p63 upon exposure to bile salts and acid in normal and cancer esophageal cells in culture.

    Science.gov (United States)

    Roman, Sabine; Pétré, Aurélia; Thépot, Amélie; Hautefeuille, Agnès; Scoazec, Jean-Yves; Mion, François; Hainaut, Pierre

    2007-07-01

    p63 is a member of the p53 protein family that regulates differentiation and morphogenesis in epithelial tissues and is required for the formation of squamous epithelia. Barrett's mucosa is a glandular metaplasia of the squamous epithelium that develops in the lower esophagus in the context of chronic, gastroesophageal reflux and is considered as a precursor for adenocarcinoma. Normal or squamous cancer esophageal cells were exposed to deoxycholic acid (DCA, 50, 100, or 200 microM) and chenodeoxycholic and taurochenodeoxycholic acid at pH 5. p63 and cyclooxygenase-2 (COX-2) expressions were studied by Western blot and RT-PCR. DCA exposure at pH 5 led to a spectacular decrease in the levels of all isoforms of the p63 proteins. This decrease was observed within minutes of exposure, with a synergistic effect between DCA and acid. Within the same time frame, levels of p63 mRNA were relatively unaffected, whereas levels of COX-2, a marker of stress responses often induced in Barrett's mucosa, were increased. Similar results were obtained with chenodeoxycholic acid but not its taurine conjugate at pH 5. Proteasome inhibition by lactacystin or MG-132 partially blocked the decrease in p63, suggesting a posttranslational degradation mechanism. These results show that combined exposure to bile salt and acid downregulates a critical regulator of squamous differentiation, providing a mechanism to explain the replacement of squamous epithelium by a glandular metaplasia upon exposure of the lower esophagus to gastric reflux. PMID:17615180

  7. ROE Absolute Sea Level Changes

    Data.gov (United States)

    U.S. Environmental Protection Agency — This raster dataset represents changes in absolute sea level along U.S. coasts from 1993 to 2014. Data were provided by the University of Colorado at Boulder (2015)...

  8. Cigarette smoke induces C/EBP-β-mediated activation of miR-31 in normal human respiratory epithelia and lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Sichuan Xi

    Full Text Available BACKGROUND: Limited information is available regarding mechanisms by which miRNAs contribute to pulmonary carcinogenesis. The present study was undertaken to examine expression and function of miRNAs induced by cigarette smoke condensate (CSC in normal human respiratory epithelia and lung cancer cells. METHODOLOGY: Micro-array and quantitative RT-PCR (qRT-PCR techniques were used to assess miRNA and host gene expression in cultured cells, and surgical specimens. Software-guided analysis, RNA cross-link immunoprecipitation (CLIP, 3' UTR luciferase reporter assays, qRT-PCR, focused super-arrays and western blot techniques were used to identify and confirm targets of miR-31. Chromatin immunoprecipitation (ChIP techniques were used to evaluate histone marks and transcription factors within the LOC554202 promoter. Cell count and xenograft experiments were used to assess effects of miR-31 on proliferation and tumorigenicity of lung cancer cells. RESULTS: CSC significantly increased miR-31 expression and activated LOC554202 in normal respiratory epithelia and lung cancer cells; miR-31 and LOC554202 expression persisted following discontinuation of CSC exposure. miR-31 and LOC554202 expression levels were significantly elevated in lung cancer specimens relative to adjacent normal lung tissues. CLIP and reporter assays demonstrated direct interaction of miR-31 with Dickkopf-1 (Dkk-1 and DACT-3. Over-expression of miR-31 markedly diminished Dkk-1 and DACT3 expression levels in normal respiratory epithelia and lung cancer cells. Knock-down of miR-31 increased Dkk-1 and DACT3 levels, and abrogated CSC-mediated decreases in Dkk-1 and DACT-3 expression. Furthermore, over-expression of miR-31 diminished SFRP1, SFRP4, and WIF-1, and increased Wnt-5a expression. CSC increased H3K4Me3, H3K9/14Ac and C/EBP-β levels within the LOC554202 promoter. Knock-down of C/EBP-β abrogated CSC-mediated activation of LOC554202. Over-expression of miR-31 significantly enhanced

  9. The activity of a new 2-amino-1,3,4-thiadiazole derivative 4ClABT in cancer and normal cells

    Directory of Open Access Journals (Sweden)

    Andrzej Niewiadomy

    2011-10-01

    Full Text Available The 2-amino-5-(2,4-dihydroxyphenyl-1,3,4-thiadiazole set are well known compounds with interesting in vitro and in vivo anti-cancer profiles. The aim of this study was an in vitro evaluation of the anti-cancer activity of a new synthesized aminothiadiazole derivative 2-(3-chlorophenyloamino-5-(2,4-dihydroxyphenyl- -1,3,4-thiadiazole 4ClABT. The effect on tumor cell proliferation, motility and morphology, DNA synthesis as well as the influence on normal cells was assessed. The antiproliferative activity of 4ClABT in tumor cells derived from peripheral cancers including breast carcinoma (T47D, colon carcinoma (HT-29, thyroid carcinoma (FTC-238, teratoma (P19, and T-cell leukemia (Jurkat E6.1, as well as cancers of the nervous system including rhabdomyosarcoma/medulloblastoma (TE671, brain astrocytoma (MOGGCCM and glioma (C6 was studied by means of MTT assay. DNA synthesis level was determined in BrdU ELISA test. Wound assay model was applied for tumor cell motility assessment. Morphological changes induced by 4ClABT in cancer and normal cells were analyzed in HE staining specimens. Moreover, the influence of 4ClABT on normal cells including skin fibroblasts (HSF, hepatocytes (Fao, astroglia and neurons was studied by means of LDH assay. The tested compound inhibited the proliferation of tumor cells in dose-dependent fashion. The anti-cancer effect was attributed to decreased DNA synthesis, prominent changes in tumor cell morphology as well as reduced cell motility. In antiproliferative concentrations, 4ClABT was not toxic to normal cells. Our study showed prominent anti-cancer effects of the tested aminothiadiazole derivative in the absence of toxicity in normal cells. The obtained results confirmed the promising anti-cancer profile of previously tested 2-(monohalogenphenylamino- -5-(2,4-dihydroxyphenyl-1,3,4-thiadiazole derivatives (ClABT — chlorophenyl derivative, FABT and 3FABT — fluorophenyl derivatives and 4BrABT

  10. Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Vrba, Lukas; Jensen, Taylor J.; Garbe, James C.; Heimark, Ronald L.; Cress, Anne E.; Dickinson, Sally; Stampfer, Martha R.; Futscher, Bernard W.

    2009-12-23

    BACKGROUND: The microRNA-200 family participates in the maintenance of an epithelial phenotype and loss of its expression can result in epithelial to mesenchymal transition (EMT). Furthermore, the loss of expression of miR-200 family members is linked to an aggressive cancer phenotype. Regulation of the miR-200 family expression in normal and cancer cells is not fully understood. METHODOLOGY/ PRINCIPAL FINDINGS: Epigenetic mechanisms participate in the control of miR-200c and miR-141 expression in both normal and cancer cells. A CpG island near the predicted mir-200c/mir-141 transcription start site shows a striking correlation between miR-200c and miR-141 expression and DNA methylation in both normal and cancer cells, as determined by MassARRAY technology. The CpG island is unmethylated in human miR-200/miR-141 expressing epithelial cells and in miR-200c/miR-141 positive tumor cells. The CpG island is heavily methylated in human miR-200c/miR-141 negative fibroblasts and miR-200c/miR-141 negative tumor cells. Mouse cells show a similar inverse correlation between DNA methylation and miR-200c expression. Enrichment of permissive histone modifications, H3 acetylation and H3K4 trimethylation, is seen in normal miR-200c/miR-141-positive epithelial cells, as determined by chromatin immunoprecipitation coupled to real-time PCR. In contrast, repressive H3K9 dimethylation marks are present in normal miR-200c/miR-141-negative fibroblasts and miR-200c/miR-141 negative cancer cells and the permissive histone modifications are absent. The epigenetic modifier drug, 5-aza-2'-deoxycytidine, reactivates miR-200c/miR-141 expression showing that epigenetic mechanisms play a functional role in their transcriptional control. CONCLUSIONS/ SIGNIFICANCE: We report that DNA methylation plays a role in the normal cell type-specific expression of miR-200c and miR-141 and this role appears evolutionarily conserved, since similar results were obtained in mouse. Aberrant DNA methylation

  11. Characteristic gene expression profiles in the progression from normal gastric epithelial cells to moderate gastric epithelial dysplasia and to gastric cancer

    Institute of Scientific and Technical Information of China (English)

    LI Mao-lan; DING Qi-chen; WU Xiang-song; MU Jia-sheng; YANG Jia-hua; ZHANG Wen-jie; CHEN Lei; LIU Ying-bin; ZHANG Jing-cheng; LI Song-gang; WU Wen-guang; RAO Long-hua; DONG Ping; GU Jun; LU Jian-hua; ZHANG Lin

    2012-01-01

    Background Gastric cancer ranks high among the most common causes of cancer-related death worldwide.This study was designed to explore key genes involved in the progression of normal gastric epithelial cells to moderate gastric epithelial dysplasia (mGED) and to gastric cancer.Methods Twelve pairs of mGED tissues,gastric cancer tissues,and normal gastric tissues were collected by gastroscopy.Total RNA was then extracted and purified.After the addition of fluorescent tags,hybridization was carried out on a Gene chip microarray slide.Significance analysis of microarrays was performed to determine significant differences in gene expression between the different tissue types.Results Microarray data analysis revealed totally 34 genes that were expressed differently:18 highly expressed (fold change>2; P<0.01) and 16 down-regulated (fold change >2; P <0.01).Of the 34 genes,24 belonged to several different functional categories such as structural molecule activity,extracellular regions,structural formation,cell death,biological adhesion,developmental processes,locomotion,and biological regulation that were associated with cancer.The remaining 10 genes were not involved in cancer research.Of these genes,the expression levels of Matrix metalloproteinase-12 (MMP12),Caspase-associated recruitment domain 14 (CARD14),and Chitinase 3-like 1 (CHI3L1)were confirmed by semi-quantitative RT-PCR.A two-way clustering algorithm divided the 36 samples into three categories and the overall correct classification efficiency was 80.6% (29/36).Almost all of these genes (31/34) showed constant changes in the process of normal gastric epithelial cells to mGED to gastric cancer.Conclusions The results of this study provided global gene expression profiles during the development and progression from normal gastric epithelial cells to mGED to gastric cancer.These data may provide new insights into the molecular pathology of gastric cancer which may be useful for the detection

  12. A fuzzy logic controller based approach to model the switching mechanism of the mammalian central carbon metabolic pathway in normal and cancer cells.

    Science.gov (United States)

    Dasgupta, Abhijit; Paul, Debjyoti; De, Rajat K

    2016-07-19

    Dynamics of large nonlinear complex systems, like metabolic networks, depend on several parameters. A metabolic pathway may switch to another pathway in accordance with the current state of parameters in both normal and cancer cells. Here, most of the parameter values are unknown to us. A fuzzy logic controller (FLC) has been developed here for the purpose of modeling metabolic networks by approximating the reasons for the behaviour of a system and applying expert knowledge to track switching between metabolic pathways. The simulation results can track the switching between glycolysis and gluconeogenesis, as well as glycolysis and pentose phosphate pathways (PPP) in normal cells. Unlike normal cells, pyruvate kinase (M2 isoform) (PKM2) switches alternatively between its two oligomeric forms, i.e. an active tetramer and a relatively low activity dimer, in cancer cells. Besides, there is a coordination among PKM2 switching and enzymes catalyzing PPP. These phenomena help cancer cells to maintain their high energy demand and macromolecular synthesis. However, the reduction of initial adenosine triphosphate (ATP) to a very low concentration, decreasing initial glucose uptake, destroying coordination between glycolysis and PPP, and replacement of PKM2 by its relatively inactive oligomeric form (dimer) or inhibition of the translation of PKM2 may destabilize the mutated control mechanism of the mammalian central carbon metabolic (CCM) pathway in cancer cells. The performance of the model is compared appropriately with some existing ones. PMID:27225801

  13. (18)F Sodium Fluoride PET/CT in Patients with Prostate Cancer: Quantification of Normal Tissues, Benign Degenerative Lesions, and Malignant Lesions.

    Science.gov (United States)

    Oldan, Jorge D; Hawkins, A Stewart; Chin, Bennett B

    2016-01-01

    Understanding the range and variability of normal, benign degenerative, and malignant (18)F sodium fluoride ((18)F NaF) positron emission tomography/computed tomography (PET/CT) uptake is important in influencing clinical interpretation. Further, it is essential for the development of realistic semiautomated quantification techniques and simulation models. The purpose of this study is to determine the range of these values in a clinically relevant patient population with prostate cancer. (18)F NaF PET/CT scans were analyzed in patients with prostate cancer (n = 47) referred for evaluation of bone metastases. Mean and maximum standardized uptake values [SUVs (SUVmean and SUVmax)] were made in normal background regions (n = 470) including soft tissues (liver, aorta, bladder, adipose, brain, and paraspinal muscle) and osseous structures (T12 vertebral body, femoral diaphyseal cortex, femoral head medullary space, and ribs). Degenerative joint disease (DJD; n = 281) and bone metastases (n = 159) were identified and quantified by an experienced reader using all scan information including coregistered CT. For normal bone regions, the highest (18)F NaF PET SUVmean occurred in T12 (6.8 ± 1.4) and it also showed the lowest coefficient of variation (cv = 21%). For normal soft tissues, paraspinal muscles showed very low SUVmean (0.70 ± 0.11) and also showed the lowest variability (cv = 16%). Average SUVmean in metastatic lesions is higher than uptake in benign degenerative lesions but values showed a wide variance and overlapping values (16.3 ± 13 vs 11.1 ± 3.8; P disease, and osseous metastases are comparable to those reported for a general population with a wide variety of diagnoses. These normal ranges, specifically for prostate cancer patients, will aid in clinical interpretation and also help to establish the basis of normal limits in a semiautomated data analysis algorithm. PMID:27134560

  14. Effects of radiation on levels of DNA damage in normal non-adjacent mucosa from colorectal cancer cases.

    LENUS (Irish Health Repository)

    Sheridan, Juliette

    2013-03-01

    Defects in DNA repair pathways have been linked with colorectal cancer (CRC). Adjuvant radiotherapy has become commonplace in the treatment of rectal cancer however it is associated with a higher rate of second cancer formation. It is known that radiation results in DNA damage directly or indirectly by radiation-induced bystander effect (RIBE) by causing double-strand breaks (DSBs). The majority of work in RIBE has been performed in cell lines and limited studies have been in or ex vivo.

  15. DNA double strand break repair pathway plays a significant role in determining the radiotherapy induced normal tissue toxicity among head-and-neck and breast cancer

    International Nuclear Information System (INIS)

    The ability to predict individual risk of radiotherapy induced normal tissue complications prior to the therapy may give an opportunity to personalize the treatment aiming improved therapeutic effect and quality of life. Therefore, predicting the risk of developing acute reactions before the initiation of radiation therapy may serve as a potential biomarker. DNA double-strand break (DSB) induction and its repair kinetics in lymphocytes of Head-and-Neck (n = 183) and Breast cancer (n = 132) patients undergoing chemoradiation or radiation therapy alone were analyzed by performing γ-H2AX foci, neutral comet and a modified neutral filter elution assay. Candidate radioresponsive genes like DNA repair, antioxidant pathway, profibrotic cytokine genes were screened for the common variants for their association with normal tissue toxicity outcome. Patients were stratified as non-over responders (NOR) and over responders (OR) based on their Radiation Therapy Oncology Group grading for normal tissue adverse reactions. Our results suggest that DSB repair plays a major role in the development of normal tissue adverse reactions in H and N and Breast cancer patients. The cellular (γ-H2AX analysis) and SNP analysis may have the potential to be developed into a clinically useful predictive assay for identifying the normal tissue over reactors

  16. Paciente oncológico con incapacidad laboral absoluta: características epidemiológicas, supervivencia y seguimiento de su incapacidad laboral Cancer patients with absolut permanent incapacity: epidemiology, survival and monitoring work disability

    Directory of Open Access Journals (Sweden)

    Raúl Jesús Regal Ramos

    2011-06-01

    formación oncológica y aumentando las revisiones. Estas revisiones podrán establecerse en el momento de la calificación de la invalidez o a posteriori, tras seleccionar aquellos casos que, con una supervivencia y edad razonables, no presenten otras limitaciones constitutivas de IPA.Each year the incidence of cancer in Spain increases, as well as the survival, and at the same time the economic cost due to Absolute Permanent Disability (APD caused by these diseases. Objective: Know the epidemiological characteristics of cancer patients with APD and what variables are associated to survival beyond 5 years, in order to establish criteria for the review of the working capacity of these patients. Method: We analyzed all patients evaluated in the Medical Unit of The National Institute of Social Security in Madrid in 2005, under 55 years of age, with the diagnosis of neoplasic disease and whose final evaluation was APD. We analyzed the following variables: age, sex, marital status, occupation, type of Social Security affiliation, type of cancer (distinguishing whether it was widespread and / or had had relapses, the presence of other associated diseases, the presence of other conditions which in themselves were constitutive of APD and finally the survival beyond 5 years. Among the patients who were alive in November 2010 we studied the relationship of variables with the survival and evolution of the degree of disability. Results: The total number of patients studied was 212. The most frequent type of tumors in women were breast and lung cancer and in men lung and colon-rectum. The 5-year survival was 30 %.This survival decreases with age, depending on the type of tumor, the presence of metastasis and / or relapses and the presence of comorbidity. Tumors that cause most number of deaths are lung cancer in men and breast cancer in women. Regarding the followup of disability, 54 % (35 of 64 of the survivors had not been reviewed and had no sequels or other conditions

  17. Metabolites of ginger component [6]-shogaol remain bioactive in cancer cells and have low toxicity in normal cells: chemical synthesis and biological evaluation.

    Directory of Open Access Journals (Sweden)

    Yingdong Zhu

    Full Text Available Our previous study found that [6]-shogaol, a major bioactive component in ginger, is extensively metabolized in cancer cells and in mice. It is unclear whether these metabolites retain bioactivity. The aim of the current study is to synthesize the major metabolites of [6]-shogaol and evaluate their inhibition of growth and induction of apoptosis in human cancer cells. Twelve metabolites of [6]-shogaol (M1, M2, and M4-M13 were successfully synthesized using simple and easily accessible chemical methods. Growth inhibition assays showed that most metabolites of [6]-shogaol had measurable activities against human cancer cells HCT-116 and H-1299. In particular, metabolite M2 greatly retained the biological activities of [6]-shogaol, with an IC(50 of 24.43 µM in HCT-116 human colon cancer cells and an IC(50 of 25.82 µM in H-1299 human lung cancer cells. Also exhibiting a relatively high potency was thiol-conjugate M13, with IC(50 values of 45.47 and 47.77 µM toward HCT-116 and H-1299 cells, respectively. The toxicity evaluation of the synthetic metabolites (M1, M2, and M4-M13 against human normal fibroblast colon cells CCD-18Co and human normal lung cells IMR-90 demonstrated a detoxifying metabolic biotransformation of [6]-shogaol. The most active metabolite M2 had almost no toxicity to CCD-18Co and IMR-90 normal cells with IC(50s of 99.18 and 98.30 µM, respectively. TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling assay indicated that apoptosis was triggered by metabolites M2, M13, and its two diastereomers M13-1 and M13-2. There was no significant difference between the apoptotic effect of [6]-shogaol and the effect of M2 and M13 after 6 hour treatment.

  18. Metabolites of ginger component [6]-shogaol remain bioactive in cancer cells and have low toxicity in normal cells: chemical synthesis and biological evaluation.

    Science.gov (United States)

    Zhu, Yingdong; Warin, Renaud F; Soroka, Dominique N; Chen, Huadong; Sang, Shengmin

    2013-01-01

    Our previous study found that [6]-shogaol, a major bioactive component in ginger, is extensively metabolized in cancer cells and in mice. It is unclear whether these metabolites retain bioactivity. The aim of the current study is to synthesize the major metabolites of [6]-shogaol and evaluate their inhibition of growth and induction of apoptosis in human cancer cells. Twelve metabolites of [6]-shogaol (M1, M2, and M4-M13) were successfully synthesized using simple and easily accessible chemical methods. Growth inhibition assays showed that most metabolites of [6]-shogaol had measurable activities against human cancer cells HCT-116 and H-1299. In particular, metabolite M2 greatly retained the biological activities of [6]-shogaol, with an IC(50) of 24.43 µM in HCT-116 human colon cancer cells and an IC(50) of 25.82 µM in H-1299 human lung cancer cells. Also exhibiting a relatively high potency was thiol-conjugate M13, with IC(50) values of 45.47 and 47.77 µM toward HCT-116 and H-1299 cells, respectively. The toxicity evaluation of the synthetic metabolites (M1, M2, and M4-M13) against human normal fibroblast colon cells CCD-18Co and human normal lung cells IMR-90 demonstrated a detoxifying metabolic biotransformation of [6]-shogaol. The most active metabolite M2 had almost no toxicity to CCD-18Co and IMR-90 normal cells with IC(50)s of 99.18 and 98.30 µM, respectively. TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) assay indicated that apoptosis was triggered by metabolites M2, M13, and its two diastereomers M13-1 and M13-2. There was no significant difference between the apoptotic effect of [6]-shogaol and the effect of M2 and M13 after 6 hour treatment. PMID:23382939

  19. Identification of valid reference genes for the normalization of RT-qPCR expression studies in human breast cancer cell lines treated with and without transient transfection.

    Directory of Open Access Journals (Sweden)

    Lin-Lin Liu

    Full Text Available Reverse transcription-quantitative polymerase chain reaction (RT-qPCR is a powerful technique for examining gene expression changes during tumorigenesis. Target gene expression is generally normalized by a stably expressed endogenous reference gene; however, reference gene expression may differ among tissues under various circumstances. Because no valid reference genes have been documented for human breast cancer cell lines containing different cancer subtypes treated with transient transfection, we identified appropriate and reliable reference genes from thirteen candidates in a panel of 10 normal and cancerous human breast cell lines under experimental conditions with/without transfection treatments with two transfection reagents. Reference gene expression stability was calculated using four algorithms (geNorm, NormFinder, BestKeeper and comparative delta Ct, and the recommended comprehensive ranking was provided using geometric means of the ranking values using the RefFinder tool. GeNorm analysis revealed that two reference genes should be sufficient for all cases in this study. A stability analysis suggests that 18S rRNA-ACTB is the best reference gene combination across all cell lines; ACTB-GAPDH is best for basal breast cancer cell lines; and HSPCB-ACTB is best for ER+ breast cancer cells. After transfection, the stability ranking of the reference gene fluctuated, especially with Lipofectamine 2000 transfection reagent in two subtypes of basal and ER+ breast cell lines. Comparisons of relative target gene (HER2 expression revealed different expressional patterns depending on the reference genes used for normalization. We suggest that identifying the most stable and suitable reference genes is critical for studying specific cell lines under certain circumstances.

  20. A comparison of mantle versus involved-field radiotherapy for Hodgkin's lymphoma: reduction in normal tissue dose and second cancer risk

    OpenAIRE

    Xu Tony; Pintilie Melania; Brenner David J; Tsang Richard W; Sachs Rainer K; Heydarian Mostafa; Tran Tu; Koh Eng-Siew; Chung June; Paul Narinder; Hodgson David C

    2007-01-01

    Abstract Background Hodgkin's lymphoma (HL) survivors who undergo radiotherapy experience increased risks of second cancers (SC) and cardiac sequelae. To reduce such risks, extended-field radiotherapy (RT) for HL has largely been replaced by involved field radiotherapy (IFRT). While it has generally been assumed that IFRT will reduce SC risks, there are few data that quantify the reduction in dose to normal tissues associated with modern RT practice for patients with mediastinal HL, and no es...

  1. Factors determining acute normal tissue reactions during postoperative radiotherapy in endometrial cancer: analysis of 317 consecutive cases

    International Nuclear Information System (INIS)

    Background and purpose: Acute radiotherapy reactions are commonly underestimated and under-reported in the literature. Our aim was to evaluate the incidence and risk factors for acute reactions during postoperative radiotherapy in endometrial cancer patients. Material and methods: Performed was detailed retrospective analysis of 317 endometrial cancer patients given postoperative radiotherapy. Two hundred forty seven patients (78%) received both intracavitary (BRT) and external beam irradiation (EBRT), 49 patients (15%) received only BRT and 21 patients (7%) - only EBRT. BRT included radium (Ra) or cesium (Cs). The mean total dose at 0.5 cm for Ra and Cs was 50.5±10.3 Gy and 48.4±15.0 Gy, respectively, and the mean dose rate - 0.47±0.06 Gy/h and 1.42±0.41 Gy/h, respectively. Mean EBRT dose in the ICRU reference point was 49.0±3.7 Gy given in fractions of 1.54-2.49 Gy (mean 2.0±0.17 Gy). Radiotherapy and Oncology Group classification system was employed to score acute reactions. The impact of patient- and treatment-related factors on the risk of acute bowel and urinary bladder reactions was assessed with uni- and multivariate tests. Results: Acute radiotherapy reactions of any grade occurred in 265 patients (84%) including bowel complications in 66% and urinary bladder complications in 36%. There were 21 severe (grade 3 or 4) reactions, all but one seen in the patients treated with combined EBRT and BRT. Higher total dose (P=0.024), higher EBRT dose (P=0.022) and higher age (P=0.026) were correlated with increased acute bowel toxicity in univariate analysis. Multivariate analysis showed that higher EBRT dose (P=0.015) and older age (P=0.016) were independently correlated with the risk of acute bowel events. Higher total dose (P=0.009), BRT dose (P=0.029), BRT dose rate (P=0.004), EBRT fraction size (P=0.007), the use of Cs BRT (P=0.001) and lower parity (P=0.041) were correlated with increased risk of acute bladder toxicity in univariate test. Multivariate

  2. Multivariate normal tissue complication probability modeling of gastrointestinal toxicity after external beam radiotherapy for localized prostate cancer

    International Nuclear Information System (INIS)

    The risk of radio-induced gastrointestinal (GI) complications is affected by several factors other than the dose to the rectum such as patient characteristics, hormonal or antihypertensive therapy, and acute rectal toxicity. Purpose of this work is to study clinical and dosimetric parameters impacting on late GI toxicity after prostate external beam radiotherapy (RT) and to establish multivariate normal tissue complication probability (NTCP) model for radiation-induced GI complications. A total of 57 men who had undergone definitive RT for prostate cancer were evaluated for GI events classified using the RTOG/EORTC scoring system. Their median age was 73 years (range 53–85). The patients were assessed for GI toxicity before, during, and periodically after RT completion. Several clinical variables along with rectum dose-volume parameters (Vx) were collected and their correlation to GI toxicity was analyzed by Spearman’s rank correlation coefficient (Rs). Multivariate logistic regression method using resampling techniques was applied to select model order and parameters for NTCP modeling. Model performance was evaluated through the area under the receiver operating characteristic curve (AUC). At a median follow-up of 30 months, 37% (21/57) patients developed G1-2 acute GI events while 33% (19/57) were diagnosed with G1-2 late GI events. An NTCP model for late mild/moderate GI toxicity based on three variables including V65 (OR = 1.03), antihypertensive and/or anticoagulant (AH/AC) drugs (OR = 0.24), and acute GI toxicity (OR = 4.3) was selected as the most predictive model (Rs = 0.47, p < 0.001; AUC = 0.79). This three-variable model outperforms the logistic model based on V65 only (Rs = 0.28, p < 0.001; AUC = 0.69). We propose a logistic NTCP model for late GI toxicity considering not only rectal irradiation dose but also clinical patient-specific factors. Accordingly, the risk of G1-2 late GI increases as V65 increases, it is higher for patients experiencing

  3. Differential detection of alternatively spliced variants of Ciz1 in normal and cancer cells using a custom exon-junction microarray

    International Nuclear Information System (INIS)

    Ciz1 promotes initiation of mammalian DNA replication and is present within nuclear matrix associated DNA replication factories. Depletion of Ciz1 from normal and cancer cells restrains entry to S phase and inhibits cell proliferation. Several alternative splicing events with putative functional consequences have been identified and reported, but many more variants are predicted to exist based on publicly available mRNAs and expressed sequence tags. Here we report the development and validation of a custom exon and exon-junction microarray focused on the human CIZ1 gene, capable of reproducible detection of differential splice-variant expression. Using a pair of paediatric cancer cell lines and a pool of eight normal lines as reference, the array identified expected and novel CIZ1 splicing events. One novel variant (delta 8-12) that encodes a predicted protein lacking key functional sites, was validated by quantitative RT-PCR and found to be over-represented in a range of other cancer cell lines, and over half of a panel of primary lung tumours. Expression of CIZ1 delta 8-12 appears to be restricted to cancer cells, and may therefore be a useful novel biomarker

  4. Absolute transition probabilities of phosphorus.

    Science.gov (United States)

    Miller, M. H.; Roig, R. A.; Bengtson, R. D.

    1971-01-01

    Use of a gas-driven shock tube to measure the absolute strengths of 21 P I lines and 126 P II lines (from 3300 to 6900 A). Accuracy for prominent, isolated neutral and ionic lines is estimated to be 28 to 40% and 18 to 30%, respectively. The data and the corresponding theoretical predictions are examined for conformity with the sum rules.-

  5. Absolute luminosity measurements at LHCb

    CERN Document Server

    Hopchev, Plamen

    2011-01-01

    Absolute luminosity measurements are of general interest for colliding-beam experiments at storage rings. These measurements are necessary to determine the absolute cross-sections of reaction processes and are valuable to quantify the performance of the accelerator. LHCb has applied two methods to determine the absolute scale of its luminosity measurements for proton-proton collisions at the LHC running at a centre-of-mass energy of 7 TeV. In addition to the classic ``van der Meer'' scan method a novel technique has been developed which makes use of direct imaging of the individual beams using both proton-gas and proton-proton interactions. The beam imaging method is made possible by the high resolution of the LHCb vertex detector and the close proximity of the detector to the beams, and allows beam parameters such as positions, angles and widths to be determined. We describe both methods and compare the two results. In addition, we present the techniques used to transport the absolute luminosity measurement ...

  6. Assessment of Optical Coherence Tomography Imaging in the Diagnosis of Non-Melanoma Skin Cancer and Benign Lesions Versus Normal Skin:

    DEFF Research Database (Denmark)

    Mogensen, Mette; Jørgensen, Thomas Martini; Nürnberg, Birgit Meincke;

    2009-01-01

    BACKGROUND Optical coherence tomography (OCT) is an optical imaging technique that may be useful in diagnosis of non-melanoma skin cancer (NMSC). OBJECTIVES To describe OCT features in NMSC such as actinic keratosis (AK) and basal cell carcinoma (BCC) and in benign lesions and to assess...... the diagnostic accuracy of OCT in differentiating NMSC from benign lesions and normal skin. METHODS AND MATERIALS OCT and polarization-sensitive (PS) OCT from 104 patients were studied. Observer-blinded evaluation of OCT images from 64 BCCs, 1 baso-squamous carcinoma, 39 AKs, two malignant melanomas, nine benign...... lesions, and 105 OCT images from perilesional skin was performed; 50 OCT images of NMSC and 50 PS-OCT images of normal skin were evaluated twice. RESULTS Sensitivity was 79% to 94% and specificity 85% to 96% in differentiating normal skin from lesions. Important features were absence of well...

  7. Careful selection of reference genes is required for reliable performance of RT-qPCR in human normal and cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Francis Jacob

    Full Text Available Reverse Transcription - quantitative Polymerase Chain Reaction (RT-qPCR is a standard technique in most laboratories. The selection of reference genes is essential for data normalization and the selection of suitable reference genes remains critical. Our aim was to 1 review the literature since implementation of the MIQE guidelines in order to identify the degree of acceptance; 2 compare various algorithms in their expression stability; 3 identify a set of suitable and most reliable reference genes for a variety of human cancer cell lines. A PubMed database review was performed and publications since 2009 were selected. Twelve putative reference genes were profiled in normal and various cancer cell lines (n = 25 using 2-step RT-qPCR. Investigated reference genes were ranked according to their expression stability by five algorithms (geNorm, Normfinder, BestKeeper, comparative ΔCt, and RefFinder. Our review revealed 37 publications, with two thirds patient samples and one third cell lines. qPCR efficiency was given in 68.4% of all publications, but only 28.9% of all studies provided RNA/cDNA amount and standard curves. GeNorm and Normfinder algorithms were used in 60.5% in combination. In our selection of 25 cancer cell lines, we identified HSPCB, RRN18S, and RPS13 as the most stable expressed reference genes. In the subset of ovarian cancer cell lines, the reference genes were PPIA, RPS13 and SDHA, clearly demonstrating the necessity to select genes depending on the research focus. Moreover, a cohort of at least three suitable reference genes needs to be established in advance to the experiments, according to the guidelines. For establishing a set of reference genes for gene normalization we recommend the use of ideally three reference genes selected by at least three stability algorithms. The unfortunate lack of compliance to the MIQE guidelines reflects that these need to be further established in the research community.

  8. Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal differential expression patterns in cancer and low antigen expression in normal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Bujak, Emil [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 2, CH-8093 Zurich (Switzerland); Pretto, Francesca; Ritz, Danilo; Gualandi, Laura; Wulhfard, Sarah [Philochem AG, Libernstrasse 3, CH-8112 Otelfingen (Switzerland); Neri, Dario, E-mail: neri@pharma.ethz.ch [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 2, CH-8093 Zurich (Switzerland)

    2014-09-10

    There is a considerable interest for the discovery and characterization of tumor-associated antigens, which may facilitate antibody-based pharmacodelivery strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted proteins, which have previously been reported to be overexpressed during remodeling typical for wound healing and tumor progression and to possibly play a functional role in cell proliferation, migration and apoptosis. To our knowledge, a complete immunohistochemical characterization of thrombospondins levels in normal rodent tissues has not been reported so far. Using antibody phage technology, we have generated and characterized monoclonal antibodies specific to murine thrombospondin-1 and thrombospondin-2, two antigens which share 62% aminoacid identity. An immunofluorescence analysis revealed that both antigens are virtually undetectable in normal mouse tissues, except for a weak staining of heart tissue by antibodies specific to thrombospondin-1. The analysis also showed that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in nude mice, while it was only barely detectable in 3/8 murine tumors grafted in immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2 revealed a much lower level of expression of this antigen in cancer specimens. Our analysis resolves ambiguities related to conflicting reports on thrombosponding expression in health and disease. Based on our findings, thrombospondin-1 (and not thrombospondin-2) may be considered as a target for antibody-based pharmacodelivery strategies, in consideration of its low expression in normal tissues and its upregulation in cancer. - Highlights: • High affinity monoclonal antibodies to murine and human TSP1 and 2 were raised. • Both antigens are virtually undetectable in normal mouse tissues. • Strong positivity of human tumor xenografts for TSP1 was detected. • Study revealed much lower level of TSP2 expression in cancer specimens

  9. MnTnBuOE-2-PyP protects normal colorectal fibroblasts from radiation damage and simultaneously enhances radio/chemotherapeutic killing of colorectal cancer cells

    Science.gov (United States)

    Kosmacek, Elizabeth A.; Chatterjee, Arpita; Tong, Qiang; Lin, Chi; Oberley, Rebecca E.

    2016-01-01

    Manganese porphyrins have been shown to be potent radioprotectors in a variety of cancer models. However, the mechanism as to how these porphyrins protect normal tissues from radiation damage still remains largely unknown. In the current study, we determine the effects of the manganese porphyrin, MnTnBuOE-2-PyP, on primary colorectal fibroblasts exposed to irradiation. We found that 2 Gy of radiation enhances the fibroblasts' ability to contract a collagen matrix, increases cell size and promotes cellular senesence. Treating fibroblasts with MnTnBuOE-2-PyP significantly inhibited radiation-induced collagen contraction, preserved cell morphology and also inhibited cellular senescence. We further showed that MnTnBuOE-2-PyP enhanced the overall viability of the fibroblasts following exposure to radiation but did not protect colorectal cancer cell viability. Specifically, MnTnBuOE-2-PyP in combination with irradiation, caused a significant decrease in tumor clonogenicity. Since locally advanced rectal cancers are treated with chemoradiation therapy followed by surgery and non-metastatic anal cancers are treated with chemoradiation therapy, we also investigated the effects of MnTnBuOE-2-PyP in combination with radiation, 5-fluorouracil with and without Mitomycin C. We found that MnTnBuOE-2-PyP in combination with Mitomycin C or 5-fluorouracil further enhances those compounds' ability to suppress tumor cell growth. When MnTnBuOE-2-PyP was combined with the two chemotherapeutics and radiation, we observed the greatest reduction in tumor cell growth. Therefore, these studies indicate that MnTnBuOE-2-PyP could be used as a potent radioprotector for normal tissue, while at the same time enhancing radiation and chemotherapy treatment for rectal and anal cancers. PMID:27119354

  10. Molecular decoy to the Y-box binding protein-1 suppresses the growth of breast and prostate cancer cells whilst sparing normal cell viability.

    Directory of Open Access Journals (Sweden)

    Jennifer H Law

    Full Text Available The Y-box binding protein-1 (YB-1 is an oncogenic transcription/translation factor that is activated by phosphorylation at S102 whereby it induces the expression of growth promoting genes such as EGFR and HER-2. We recently illustrated by an in vitro kinase assay that a novel peptide to YB-1 was highly phosphorylated by the serine/threonine p90 S6 kinases RSK-1 and RSK-2, and to a lesser degree PKCα and AKT. Herein, we sought to develop this decoy cell permeable peptide (CPP as a cancer therapeutic. This 9-mer was designed as an interference peptide that would prevent endogenous YB-1(S102 phosphorylation based on molecular docking. In cancer cells, the CPP blocked P-YB-1(S102 and down-regulated both HER-2 and EGFR transcript level and protein expression. Further, the CPP prevented YB-1 from binding to the EGFR promoter in a gel shift assay. Notably, the growth of breast (SUM149, MDA-MB-453, AU565 and prostate (PC3, LNCap cancer cells was inhibited by ∼90% with the CPP. Further, treatment with this peptide enhanced sensitivity and overcame resistance to trastuzumab in cells expressing amplified HER-2. By contrast, the CPP had no inhibitory effect on the growth of normal immortalized breast epithelial (184htert cells, primary breast epithelial cells, nor did it inhibit differentiation of hematopoietic progenitors. These data collectively suggest that the CPP is a novel approach to suppressing the growth of cancer cells while sparing normal cells and thereby establishes a proof-of-concept that blocking YB-1 activation is a new course of cancer therapeutics.

  11. Conjugation of a Ru(II) arene complex to neomycin or to guanidinoneomycin leads to compounds with differential cytotoxicities and accumulation between cancer and normal cells.

    Science.gov (United States)

    Grau-Campistany, Ariadna; Massaguer, Anna; Carrion-Salip, Dolors; Barragán, Flavia; Artigas, Gerard; López-Senín, Paula; Moreno, Virtudes; Marchán, Vicente

    2013-05-01

    A straightforward methodology for the synthesis of conjugates between a cytotoxic organometallic ruthenium(II) complex and amino- and guanidinoglycosides, as potential RNA-targeted anticancer compounds, is described. Under microwave irradiation, the imidazole ligand incorporated on the aminoglycoside moiety (neamine or neomycin) was found to replace one triphenylphosphine ligand from the ruthenium precursor [(η(6)-p-cym)RuCl(PPh3)2](+), allowing the assembly of the target conjugates. The guanidinylated analogue was easily prepared from the neomycin-ruthenium conjugate by reaction with N,N'-di-Boc-N″-triflylguanidine, a powerful guanidinylating reagent that was compatible with the integrity of the metal complex. All conjugates were purified by semipreparative high-performance liquid chromatography (HPLC) and characterized by electrospray ionization (ESI) and matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) and NMR spectroscopy. The cytotoxicity of the compounds was tested in MCF-7 (breast) and DU-145 (prostate) human cancer cells, as well as in the normal HEK293 (Human Embryonic Kidney) cell line, revealing a dependence on the nature of the glycoside moiety and the type of cell (cancer or healthy). Indeed, the neomycin-ruthenium conjugate (2) displayed moderate antiproliferative activity in both cancer cell lines (IC50 ≈ 80 μM), whereas the neamine conjugate (4) was inactive (IC50 ≈ 200 μM). However, the guanidinylated analogue of the neomycin-ruthenium conjugate (3) required much lower concentrations than the parent conjugate for equal effect (IC50 = 7.17 μM in DU-145 and IC50 = 11.33 μM in MCF-7). Although the same ranking in antiproliferative activity was found in the nontumorigenic cell line (3 ≫ 2 > 4), IC50 values indicate that aminoglycoside-containing conjugates are about 2-fold more cytotoxic in normal cells (e.g., IC50 = 49.4 μM for 2) than in cancer cells, whereas an opposite tendency was found

  12. Methylation of MGMT and ADAMTS14 in normal colon mucosa: biomarkers of a field defect for cancerization preferentially targeting elder African-Americans.

    Science.gov (United States)

    Alonso, Sergio; Dai, Yuichi; Yamashita, Kentaro; Horiuchi, Shina; Dai, Tomoko; Matsunaga, Akihiro; Sánchez-Muñoz, Rosa; Bilbao-Sieyro, Cristina; Díaz-Chico, Juan Carlos; Chernov, Andrei V; Strongin, Alex Y; Perucho, Manuel

    2015-02-20

    Somatic hypermethylation of the O6-methylguanine-DNA methyltransferase gene (MGMT) was previously associated with G > A transition mutations in KRAS and TP53 in colorectal cancer (CRC). We tested the association of MGMT methylation with G > A mutations in KRAS and TP53 in 261 CRCs. Sixteen cases, with and without MGMT hypermethylation, were further analyzed by exome sequencing. No significant association of MGMT methylation with G > A mutations in KRAS, TP53 or in the whole exome was found (p > 0.5 in all comparisons). The result was validated by in silico comparison with 302 CRCs from The Cancer Genome Atlas (TCGA) consortium dataset. Transcriptional silencing associated with hypermethylation and stratified into monoallelic and biallelic. We also found a significant clustering (p = 0.001) of aberrant hypermethylation of MGMT and the matrix metalloproteinase gene ADAMTS14 in normal colonic mucosa of CRC patients. This suggested the existence of an epigenetic field defect for cancerization disrupting the methylation patterns of several loci, including MGMT or ADAMTS14, that may lead to predictive biomarkers for CRC. Methylation of these loci in normal mucosa was more frequent in elder (p = 0.001) patients, and particularly in African Americans (p = 1 × 10-5), thus providing a possible mechanistic link between somatic epigenetic alterations and CRC racial disparities in North America. PMID:25638164

  13. Differential control of Notch1 gene transcription by Klf4 and Sp3 transcription factors in normal versus cancer-derived keratinocytes.

    Directory of Open Access Journals (Sweden)

    Chiara Lambertini

    Full Text Available In specific cell types like keratinocytes, Notch signaling plays an important pro-differentiation and tumor suppressing function, with down-modulation of the Notch1 gene being associated with cancer development. Besides being controlled by p53, little else is known on regulation of Notch1 gene expression in this context. We report here that transcription of this gene is driven by a TATA-less "sharp peak" promoter and that the minimal functional region of this promoter, which extends from the -342 bp position to the initiation codon, is differentially active in normal versus cancer cells. This GC rich region lacks p53 binding sites, but binds Klf4 and Sp3. This finding is likely to be of biological significance, as Klf4 and, to a lesser extent, Sp3 are up-regulated in a number of cancer cells where Notch1 expression is down-modulated, and Klf4 over-expression in normal cells is sufficient to down-modulate Notch1 gene transcription. The combined knock-down of Klf4 and Sp3 was necessary for the reverse effect of increasing Notch1 transcription, consistent with the two factors exerting an overlapping repressor function through their binding to the Notch1 promoter.

  14. Correlating two-photon excited fluorescence imaging of breast cancer cellular redox state with seahorse flux analysis of normalized cellular oxygen consumption

    Science.gov (United States)

    Hou, Jue; Wright, Heather J.; Chan, Nicole; Tran, Richard; Razorenova, Olga V.; Potma, Eric O.; Tromberg, Bruce J.

    2016-06-01

    Two-photon excited fluorescence (TPEF) imaging of the cellular cofactors nicotinamide adenine dinucleotide and oxidized flavin adenine dinucleotide is widely used to measure cellular metabolism, both in normal and pathological cells and tissues. When dual-wavelength excitation is used, ratiometric TPEF imaging of the intrinsic cofactor fluorescence provides a metabolic index of cells-the "optical redox ratio" (ORR). With increased interest in understanding and controlling cellular metabolism in cancer, there is a need to evaluate the performance of ORR in malignant cells. We compare TPEF metabolic imaging with seahorse flux analysis of cellular oxygen consumption in two different breast cancer cell lines (MCF-7 and MDA-MB-231). We monitor metabolic index in living cells under both normal culture conditions and, for MCF-7, in response to cell respiration inhibitors and uncouplers. We observe a significant correlation between the TPEF-derived ORR and the flux analyzer measurements (R=0.7901, p<0.001). Our results confirm that the ORR is a valid dynamic index of cell metabolism under a range of oxygen consumption conditions relevant for cancer imaging.

  15. Expression of IL-18, IL-18 Binding Protein, and IL-18 Receptor by Normal and Cancerous Human Ovarian Tissues: Possible Implication of IL-18 in the Pathogenesis of Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Liat Medina

    2014-01-01

    Full Text Available Proinflammatory cytokine IL-18 has been shown to be elevated in the sera of ovarian carcinoma patients. The aim of the study was to examine the levels and cellular origin of IL-18, IL-18 binding protein, and IL-18 receptor in normal and cancerous ovarian tissues. Ovarian tissue samples were examined by immunohistochemical staining for IL-18, IL-18BP, and IL-18R and mRNA of these cytokines was analyzed with semiquantitative PT-PCR. IL-18 levels were significantly higher in cancerous ovarian tissues (P=0.0007, IL-18BP levels were significantly higher in normal ovarian tissues (P=0.04, and the ratio of IL-18/IL-18BP was significantly higher in cancerous ovarian tissues (P=0.036. Cancerous ovarian tissues expressed significantly higher IL-18 mRNA levels (P=0.025, while there was no difference in the expression of IL-18BP mRNA and IL-18R mRNA between cancerous and normal ovarian tissues. IL-18 and IL-18BP were expressed dominantly in the epithelial cells of both cancerous and normal ovarian tissues, while IL-18R was expressed dominantly in the epithelial cells of cancerous ovarian tissues but expressed similarly in the epithelial and stromal cells of normal cancerous tissues. This study indicates a possible role of IL-18, IL-18BP, and IL-18R in the pathogenesis of epithelial ovarian carcinoma.

  16. The effect of uterine motion and uterine margins on target and normal tissue doses in intensity modulated radiation therapy of cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, J J; Weiss, E; Abayomi, O K; Siebers, J V; Dogan, N, E-mail: jjgordon@vcu.edu [Department of Radiation Oncology, Virginia Commonwealth University, PO Box 980058, Richmond, VA 23298 (United States)

    2011-05-21

    In intensity modulated radiation therapy (IMRT) of cervical cancer, uterine motion can be larger than cervix motion, requiring a larger clinical target volume to planning target volume (CTV-to-PTV) margin around the uterine fundus. This work simulates different motion models and margins to estimate the dosimetric consequences. A virtual study used image sets from ten patients. Plans were created with uniform margins of 1 cm (PTV{sub A}) and 2.4 cm (PTV{sub C}), and a margin tapering from 2.4 cm at the fundus to 1 cm at the cervix (PTV{sub B}). Three inter-fraction motion models (MM) were simulated. In MM1, all structures moved with normally distributed rigid body translations. In MM2, CTV motion was progressively magnified as one moved superiorly from the cervix to the fundus. In MM3, both CTV and normal tissue motion were magnified as in MM2, modeling the scenario where normal tissues move into the void left by the mobile uterus. Plans were evaluated using static and percentile DVHs. For a conventional margin (PTV{sub A}), quasi-realistic uterine motion (MM3) reduces fundus dose by about 5 Gy and increases normal tissue volumes receiving 30-50 Gy by {approx}5%. A tapered CTV-to-PTV margin can restore fundus and CTV doses, but will increase normal tissue volumes receiving 30-50 Gy by a further {approx}5%.

  17. Differential expression of autocrine motility factor receptor (AMFR) mRNA in normal and cancer cells detected by in situ hybridization

    Institute of Scientific and Technical Information of China (English)

    HUANGBAIQU; AVRAHAMRAZ

    1995-01-01

    The receptor for autocrine motility factor(AMFR) is known to be involved in the process of MF-mediated cell migration and metastasis.This paper describes the procedures of non-radioactive in situ hybridization(ISH) detection of AMFR mRNA in both paraffin-embedded surgical sections and cultured cells using either biotinylated oligonucleotide probes of digoxigenin-labeled RNA probes.The results showed that the AMFR mRNA was expressed at an enhanced level in hyperplastic and malignant tissues of breast and prostate cancer patient surgical specimens,indicating that the elevated AMFR expression was associated with the tissue malignancy.Moreover,AMFR mRNA was detected in both normal and carcinoma cells when cultured at a subconfluent density.However,AMFR expression was inhibited in confluent normal(3T3-A31 murine fibroblast and FHs 738 BL huamn bladder)cells while it continued to express in carcinoma(J82 human bladder) and metastatic(3T3-M murine fibroblast) cells irrespective of cell density.This suggested a cell-cell contact down-regulation of AMFR mRNA expression in normal but not in cancer cells.The ISH data obtained in this study are closely consistent with the AMFR protein expression pattern previously reported,implying that the differential expression of AMFR gene may be rgeualted and controlled at the transcriptional level.

  18. In vitro effects of a new fused azaisocytosine-like congener on relative cell proliferation, necrosis and cell cycle in cancer and normal cell cultures.

    Science.gov (United States)

    Sztanke, Małgorzata; Rzymowska, Jolanta; Sztanke, Krzysztof

    2016-07-01

    The study was aimed at describing the mode of action of an innovative drug-like congener of fused azaisocytosine-EIMTC (ethyl 8-(4-methoxyphenyl)-4-oxo-6,7-dihydroimidazo[2,1-c][1,2,4]triazine-3-carboxylate)-on cancer cells in early in vitro oncology-related bioassays. Micromolar concentrations of EIMTC were effective at inhibiting the growth of two types of malignant multiple myeloma cells (including cells resistant to thalidomide) while having less cytotoxic effect on normal HSF cells. Furthermore, EIMTC was disclosed as capable of producing the statistically significant decrease in the number of cells in the S phase (in HeLa, TOV112D, T47D and Vero cells) and in the G2/M phase (in TOV112D cells) as well as evoking the distinctly higher necrosis rates in malignant than normal cells of the same epithelial origin. These results are promising in the sense that the bicyclic nucleobase-like structure related to azaisocytosine may target epithelial cancer cells and inhibit their growth while having less effect on normal cells. This may be due to induction of necrosis. PMID:27334755

  19. How reassuring is a normal breast ultrasound in assessment of a screen-detected mammographic abnormality? A review of interval cancers after assessment that included ultrasound evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, M.L. [Breastscreen WA, Perth (Australia); Department of Diagnostic and Interventional Radiology, Royal Perth Hospital, Perth (Australia); Welman, C.J. [Breastscreen WA, Perth (Australia); Department of Diagnostic and Interventional Radiology, Royal Perth Hospital, Perth (Australia); Department of Radiology, Fremantle Hospital and Health Service, Fremantle (Australia); Celliers, L.M., E-mail: liesl.celliers@health.wa.gov.au [Department of Diagnostic and Interventional Radiology, Royal Perth Hospital, Perth (Australia); Department of Radiology, Fremantle Hospital and Health Service, Fremantle (Australia)

    2011-10-15

    Aim: To review factors resulting in a false-negative outcome or delayed cancer diagnosis in women recalled for further evaluation, including ultrasound, after an abnormal screening mammogram. Materials and methods: Of 646,692 screening mammograms performed between 1 January 1995 and 31 December 2004, 34,533 women were recalled for further assessment. Nine hundred and sixty-four interval cancers were reported in this period. Forty-six of these women had been recalled for further assessment, which specifically included ultrasound evaluation in the preceding 24 months, and therefore, met the inclusion criteria for this study. Screening mammograms, further mammographic views, ultrasound scans, clinical findings, and histopathology results were retrospectively reviewed by two consultant breast radiologists. Results: The interval cancer developed in the contralateral breast (n = 9), ipsilateral breast, but different site (n = 6), and ipsilateral breast at the same site (n = 31) as the abnormality for which they had recently been recalled. In the latter group, 10 were retrospectively classified as a false-negative outcome, nine had a delay in obtaining a biopsy, and 12 had a delay due to a non-diagnostic initial biopsy. Various factors relating to these outcomes are discussed. Conclusion: Out of 34,533 women who attended for an assessment visit and the 46 women who subsequently developed an interval breast cancer, 15 were true interval cancers, 10 had a false-negative assessment outcome, and 21 had a delay to cancer diagnosis on the basis of a number of factors. When there is discrepancy between the imaging and histopathology results, a repeat biopsy rather than early follow-up would have avoided a delay in some cases. A normal ultrasound examination should not deter the radiologist from proceeding to stereotactic biopsy, if the index mammographic lesion is suspicious of malignancy.

  20. How reassuring is a normal breast ultrasound in assessment of a screen-detected mammographic abnormality? A review of interval cancers after assessment that included ultrasound evaluation

    International Nuclear Information System (INIS)

    Aim: To review factors resulting in a false-negative outcome or delayed cancer diagnosis in women recalled for further evaluation, including ultrasound, after an abnormal screening mammogram. Materials and methods: Of 646,692 screening mammograms performed between 1 January 1995 and 31 December 2004, 34,533 women were recalled for further assessment. Nine hundred and sixty-four interval cancers were reported in this period. Forty-six of these women had been recalled for further assessment, which specifically included ultrasound evaluation in the preceding 24 months, and therefore, met the inclusion criteria for this study. Screening mammograms, further mammographic views, ultrasound scans, clinical findings, and histopathology results were retrospectively reviewed by two consultant breast radiologists. Results: The interval cancer developed in the contralateral breast (n = 9), ipsilateral breast, but different site (n = 6), and ipsilateral breast at the same site (n = 31) as the abnormality for which they had recently been recalled. In the latter group, 10 were retrospectively classified as a false-negative outcome, nine had a delay in obtaining a biopsy, and 12 had a delay due to a non-diagnostic initial biopsy. Various factors relating to these outcomes are discussed. Conclusion: Out of 34,533 women who attended for an assessment visit and the 46 women who subsequently developed an interval breast cancer, 15 were true interval cancers, 10 had a false-negative assessment outcome, and 21 had a delay to cancer diagnosis on the basis of a number of factors. When there is discrepancy between the imaging and histopathology results, a repeat biopsy rather than early follow-up would have avoided a delay in some cases. A normal ultrasound examination should not deter the radiologist from proceeding to stereotactic biopsy, if the index mammographic lesion is suspicious of malignancy.

  1. A new index combining the absolute and relative aspects of income poverty: Theory and application

    OpenAIRE

    DECERF, Benoit

    2015-01-01

    I derive a new index combining the absolute and relative aspects of income poverty. Earning a larger income decreases one’s absolute poverty but experiencing a larger income inequality increases one’s relative poverty. Provided that the individual poverty is not computed based on the normalized income, the two aspects can be weighed such that absolutely poor individuals are always considered poorer than relatively poor individuals. Only the value of poverty aversion associated with the Povert...

  2. Study on discrimination of oral cancer from normal using blood plasma based on fluorescence steady and excited state at excitation wavelength 280 nm

    Science.gov (United States)

    Rekha, Pachaiappan; Aruna, Prakasa Rao; Ganesan, Singaravelu

    2016-03-01

    Many research works based on fluorescence spectroscopy have proven its potential in the diagnosis of various diseases using the spectral signatures of the native key fluorophores such as tryptophan, tyrosine, collagen, NADH, FAD and porphyrin. These fluorophores distribution, concentration and their conformation may be changed depending upon the pathological and metabolic conditions of cells and tissues. In this study, we have made an attempt to characterize the blood plasma of normal subject and oral cancer patients by native fluorescence spectroscopy at 280 nm excitation. Further, the fluorescence data were analyzed by employing the multivariate statistical method - linear discriminant analyses (LDA) using leaves one out cross validation method. The results illustrate the potential of fluorescence spectroscopy technique in the diagnosis of oral cancer using blood plasma.

  3. DNA damage enhanced by the attenuation of SLD5 delays cell cycle restoration in normal cells but not in cancer cells.

    Directory of Open Access Journals (Sweden)

    Zhi-Yuan Gong

    Full Text Available SLD5 is a member of the GINS complex composed of PSF1, PSF2, PSF3 and SLD5, playing a critical role in the formation of the DNA replication fork with CDC45 in yeast. Previously, we had isolated a PSF1 orthologue from a murine hematopoietic stem cell DNA library and were then able to identify orthologues of all the other GINS members by the yeast two hybrid approach using PSF1 as the bait. These GINS orthologues may also function in DNA replication in mammalian cells because they form tetrameric complexes as observed in yeast, and gene deletion mutants of both PSF1 and SLD5 result in a lack of epiblast proliferation and early embryonic lethality. However, we found that PSF1 is also involved in chromosomal segregation in M phase, consistent with recent suggestions that homologues of genes associated with DNA replication in lower organisms also regulate cellular events other than DNA replication in mammalian cells. Here we analyzed the function of SLD5 other than DNA replication and found that it is active in DNA damage and repair. Attenuation of SLD5 expression results in marked DNA damage in both normal cells and cancer cells, suggesting that it protects against DNA damage. Attenuation of SLD5 delays the DNA repair response and cell cycle restoration in normal cells but not in cancer cells. These findings suggest that SLD5 might represent a therapeutic target molecule acting at the level of tumor stromal cells rather than the cancerous cells themselves, because development of the tumor microenvironment could be delayed or disrupted by the suppression of its expression in the normal cell types within the tumor.

  4. Android Apps for Absolute Beginners

    CERN Document Server

    Jackson, Wallace

    2011-01-01

    Anybody can start building simple apps for the Android platform, and this book will show you how! Android Apps for Absolute Beginners takes you through the process of getting your first Android applications up and running using plain English and practical examples. It cuts through the fog of jargon and mystery that surrounds Android application development, and gives you simple, step-by-step instructions to get you started.* Teaches Android application development in language anyone can understand, giving you the best possible start in Android development * Provides simple, step-by-step exampl

  5. Diagnostic Classification of Normal Persons and Cancer Patients by Using Neural Network Based on Trace Metal Contents in Serum Samples

    Institute of Scientific and Technical Information of China (English)

    ZHANG; Zhuo-yong

    2001-01-01

    [1]Miatto, O. , Casaril, M. , Gabriell, G. B. , et al. , Cancer, 55, 774(1985)[2]Margalioth, E. J., Udassin, R., Maor, J. , et al. , Cancer, 56, 856(1986)[3]Xu, B., Chinese Journal of Tumor, 12, 512(1990)[4]Jayadeep, A. , Raveendran, P. K. , Kannan, S. , et al. , J. Exp. Clin. Cancer Res. , 16, 295 (1997)[5]Sattar, N. , Scott, H. R. , McMillan, D. C. , et al. , Nutr. Cancer, 28, 308(1997)[6]Koksoy, C. , Kavas, G. O. , Akcil, E. , et al. , Breast Cancer Res. Treat. , 45, 1(1997)[7]Leung,P. L. , Huang, H. M. , Biol. Trace Elem. Res. , 57, 19(1997)[8]Antila, E. , Mussalo-Rauhamaa, H. , Kantola, M. , et al. , Sci. Total Environ. , 186, 251(1996)[9]Tariq, M. A. , Qama-un-Nisa, Fatima, A. , Sci. Total Environ. , 175, 43(1995)[10]Martin-Lagos, F. , Navarro-Alarcon, M. , Terres-Martos, C. , et al. , Sci. Total Environ. , 204, 27(1997)[11]Poo, J. L. , Romero, R. R. , Robles, J. A. , et al. , Arch. Med. Res. , 28, 259(1997)[12]Magalova, T., Bella, V. , Brtkova, A. , et al. , Neoplasma, 46, 100(1999)[13]Ferrigno, D. , Buccheri, G. , Camilla, T. , et al. , Archives for Chest Disease, 54, 204(1999)[14]Huang, Y. L. , Sheu, J. Y. , Lin, T. H. , Clinical Biochem. , 32, 131(1999)[15]Songchitsomboon, S. , Komindr, S. , Komindr, A. , et al. , J. Med. Assoc. Thai, 82, 701(1999)[16]Mason, R. P. , Cancer, 85, 2 093(1999)[17]Wargovith, M. J. , Ed. Moon T. E. , Micozz M. S. , Calcium, Vitamin D and the Prevention of Gastrointestinal Cancer, in Nutrition and Cancer Prevention, Marcel Dekker Inc. , New York, 1989:291[18]Leung, P. L. , Li, X. L. , Li, Z. X. , et al. , Biol. Trace Elem. Res. , 42, 1(1994)[19]Jing, X. ,Han, C., Cancer Research on Prevention and Treatment, 25, 186(1998)[20]Huang, Y. , Li, J. , Carcinogenesis, Teratogenesis and Mutagenesis, 10, 123(1998)[21]Wang, X. , Zhu, E. ,Yan, X. , et al. , Acta Chimica Sinica, 51, 1 094(1993)[22]Wan, T. , Qin, S. , Zhuang, S. , et al. , Rock and Mineral

  6. Absolute neutrophil values in malignant patients on cytotoxic chemotherapy.

    Science.gov (United States)

    Madu, A J; Ibegbulam, O G; Ocheni, S; Madu, K A; Aguwa, E N

    2011-01-01

    A total of eighty patients with various malignancies seen between September 2008 and April 2009 at the University of Nigeria Teaching Hospital (UNTH) Ituku Ozalla, Enugu, Nigeria, had their absolute neutrophil counts, done at Days 0 and 12 of the first cycle of their various chemotherapeutic regimens. They were adult patients who had been diagnosed of various malignancies, consisting of Breast cancer 36 (45%), Non-Hodgkin's lymphoma 8 (10%), Hodgkin's lymphoma 13 (16.25%), Colorectal carcinoma 6 (7.5%), Multiple myeloma 7 (8.75%), Cervical carcinoma 1 (1.25%) and other malignancies 9 (11.25%), Manual counting of absolute neutrophil count was done using Turks solution and improved Neubauer counting chamber and Galen 2000 Olympus microscope. The socio demographic data of the patients were assessed from a questionnaire. There were 27 males (33.75%) and 53 females (66.25%). Their ages ranged from 18 - 80 years with a median of 45 years. The mean absolute neutrophil count of the respondents pre-and post chemotherapy was 3.7 +/- 2.1 x 10(9)/L and 2.5 +/- 1.6 x 10(9)/L respectively. There were significant differences in both the absolute neutrophil count (p=0.00) compared to the pre-chemotherapy values. Chemotherapeutic combinations containing cyclophosphamide and Adriamycin were observed to cause significant reduction in absolute neutrophil.

  7. Relative and absolute risk in epidemiology and health physics

    International Nuclear Information System (INIS)

    The health risk from ionizing radiation commonly is expressed in two forms: (1) the relative risk, which is the percentage increase in natural disease rate and (2) the absolute or attributable risk which represents the difference between the natural rate and the rate associated with the agent in question. Relative risk estimates for ionizing radiation generally are higher than those expressed as the absolute risk. This raises the question of which risk estimator is the most appropriate under different conditions. The absolute risk has generally been used for radiation risk assessment, although mathematical combinations such as the arithmetic or geometric mean of both the absolute and relative risks, have also been used. Combinations of the two risk estimators are not valid because the absolute and relative risk are not independent variables. Both human epidemiologic studies and animal experimental data can be found to illustrate the functional relationship between the natural cancer risk and the risk associated with radiation. This implies that the radiation risk estimate derived from one population may not be appropriate for predictions in another population, unless it is adjusted for the difference in the natural disease incidence between the two populations

  8. SU-E-J-190: Characterization of Radiation Induced CT Number Changes in Tumor and Normal Lung During Radiation Therapy for Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, C; Liu, F; Tai, A; Gore, E; Johnstone, C; Li, X [Medical College of Wisconsin Milwaukee WI (United States)

    2014-06-01

    Purpose: To measure CT number (CTN) changes in tumor and normal lung as a function of radiation therapy (RT) dose during the course of RT delivery for lung cancer using daily IGRT CT images and single respiration phase CT images. Methods: 4D CT acquired during planning simulation and daily 3D CT acquired during daily IGRT for 10 lung cancer cases randomly selected in terms of age, caner type and stage, were analyzed using an in-house developed software tool. All patients were treated in 2 Gy fractions to primary tumors and involved nodal regions. Regions enclosed by a series of isodose surfaces in normal lung were delineated. The obtained contours along with target contours (GTVs) were populated to each singlephase planning CT and daily CT. CTN in term of Hounsfield Unit (HU) of each voxel in these delineated regions were collectively analyzed using histogram, mean, mode and linear correlation. Results: Respiration induced normal lung CTN change, as analyzed from single-phase planning CTs, ranged from 9 to 23 (±2) HU for the patients studied. Normal lung CTN change was as large as 50 (±12) HU over the entire treatment course, was dose and patient dependent and was measurable with dose changes as low as 1.5 Gy. For patients with obvious tumor volume regression, CTN within the GTV drops monotonically as much as 10 (±1) HU during the early fractions with a total dose of 20 Gy delivered. The GTV and CTN reductions are significantly correlated with correlation coefficient >0.95. Conclusion: Significant RT dose induced CTN changes in lung tissue and tumor region can be observed during even the early phase of RT delivery, and may potentially be used for early prediction of radiation response. Single respiration phase CT images have dramatically reduced statistical noise in ROIs, making daily dose response evaluation possible.

  9. Could Intermittent Energy Restriction and Intermittent Fasting Reduce Rates of Cancer in Obese, Overweight, and Normal-Weight Subjects? A Summary of Evidence.

    Science.gov (United States)

    Harvie, Michelle N; Howell, Tony

    2016-07-01

    Animal studies and human observational data link energy restriction (ER) to reduced rates of carcinogenesis. Most of these studies have involved continuous energy restriction (CER), but there is increasing public and scientific interest in the potential health and anticancer effects of intermittent energy restriction (IER) or intermittent fasting (IF), which comprise periods of marked ER or total fasting interspersed with periods of normal eating. This review summarizes animal studies that assessed tumor rates with IER and IF compared with CER or ad libitum feed consumption. The relevance of these animal data to human cancer is also considered by summarizing available human studies of the effects of IER or IF compared with CER on cancer biomarkers in obese, overweight, and normal-weight subjects. IER regimens that include periods of ER alternating with ad libitum feed consumption for 1, 2, or 3 wk have been reported to be superior to CER in reducing tumor rates in most spontaneous mice tumor models. Limited human data from short-term studies (≤6 mo) in overweight and obese subjects have shown that IER can lead to greater improvements in insulin sensitivity (homeostasis model assessment) than can CER, with comparable reductions in adipokines and inflammatory markers and minor changes in the insulin-like growth factor axis. There are currently no data comparing IER or IF with CER in normal-weight subjects. The benefits of IER in these short-term trials are of interest, but not sufficient evidence to recommend the use of IER above CER. Longer-term human studies of adherence to and efficacy and safety of IER are required in obese and overweight subjects, as well as normal-weight subjects. PMID:27422504

  10. Detection of metabolic differences between normal and cancerous prostate tissues with in-vitro hydrogen MR spectroscopy

    International Nuclear Information System (INIS)

    High-resolution in vitro hydrogen spectroscopy of perchloric acid extracts of human prostate cell lines prepared from radical prostatectomy specimens was performed at 360 MHz. Epithelial cell strains representing normal peripheral zone, normal central zone, carcinoma of varying Gleason grades, and benign prostatic hypertrophy were evaluated. The spectral peak assignments for metabolities, including lactate, citrate, and various amino acids, were determined from the literature, reference standards, gas chromatography-mass spectroscopy. Inferences as to the possibility of differentiating various types of prostatic tissues based on hydrogen spectral signatures are discussed

  11. DNA damage and repair in lymphocytes of normal individuals and cancer patients: studies by the comet assay and micronucleus tests

    International Nuclear Information System (INIS)

    A population study is reported in which the DNA damage induced by γ-radiation (2 Gy) and the kinetics of the subsequent repair were estimated by the comet and micronucleus assays in isolated lymphocytes of 82 healthy donors and patients with head and neck cancer before radiotherapy. The parameters of background and radiation-induced DNA damage, rate of repair, and residual non-repaired damage were measured by comet assay, and the repair kinetics for every donor were computer-fitted to an exponential curve. The level of background DNA damage before irradiation measured by comet assay as well as the level of micronuclei were significantly higher in the head and neck cancer patient group than in the healthy donors, while the parameters of repair were widely scattered in both groups. Cancer patient group contained significantly more individuals, whose irradiated lymphocytes showed high DNA damage, low repair rate and high non-repaired DNA damage level. Lymphocytes of donors belonging to this subgroup showed significantly lower inhibition of cell cycle after irradiation. (author)

  12. Myc post-transcriptionally induces HIF1 protein and target gene expression in normal and cancer cells

    Science.gov (United States)

    Doe, Megan R.; Ascano, Janice; Kaur, Mandeep; Cole, Michael D.

    2012-01-01

    c-Myc is frequently overexpressed in tumors and plays an important role in the regulation of cancer metabolism. Hypoxia-inducible factor-1 (HIF1), the master regulator of the hypoxic response, enhances tumorigenesis and influences metabolism via upregulation of the glycolytic pathway and suppression of mitochondrial respiration. Together, deregulated Myc and HIF1 cooperate to lend metabolic advantages to proliferating cancer cells and contribute to the Warburg Effect. Here we show that overexpression of Myc significantly stabilizes the alpha subunit of HIF1 (HIF1alpha) under normoxic conditions and enhances HIF1alpha accumulation under hypoxic conditions in cells. Post-transcriptional regulation of HIF1α by Myc led to the induction of HIF1α gene targets. Normoxic HIF1α protein expression was also dependent on Myc. Functionally; HIF1α expression was required for Myc-induced anchorage-independent growth and cell proliferation. Myc-dependent stabilization of HIF1α involved either disruption of binding to the VHL complex or post-translational protein modifications. Taken together, our findings uncover a previously uncharacterized regulatory relationship between Myc and HIF1 that has important implications for cancer metabolism and development. PMID:22186139

  13. TFF3 is a normal breast epithelial protein and is associated with differentiated phenotype in early breast cancer but predisposes to invasion and metastasis in advanced disease.

    Science.gov (United States)

    Ahmed, Ahmed R H; Griffiths, Andrew B; Tilby, Michael T; Westley, Bruce R; May, Felicity E B

    2012-03-01

    The trefoil protein TFF3 stimulates invasion and angiogenesis in vitro. To determine whether it has a role in breast tumor metastasis and angiogenesis, its levels were measured by immunohistochemistry in breast tissue with a specific monoclonal antibody raised against human TFF3. TFF3 is expressed in normal breast lobules and ducts, at higher levels in areas of fibrocystic change and papillomas, in all benign breast disease lesions, and in 89% of in situ and in 83% of invasive carcinomas. In well-differentiated tumor cells, TFF3 is concentrated at the luminal edge, whereas in poorly differentiated cells polarity is inverted and expression is directed toward the stroma. Expression was high in well-differentiated tumors and was associated significantly with low histological grade and with estrogen and progesterone receptor expression, accordant with induction of TFF3 mRNA by estrogen in breast cancer cells. Paradoxically, TFF3 expression was associated with muscle, neural, and lymphovascular invasion and the presence and number of involved lymph nodes, and it was an independent predictive marker of lymphovascular invasion and lymph node involvement. Consistent with an angiogenic function, TFF3 expression correlated strongly with microvessel density evaluated with CD31 and CD34. In conclusion, TFF3 is expressed in both the normal and diseased breast. Although associated with features of good prognosis, its profile of expression in invasive cancer is consistent with a role in breast tumor progression and tumor cell dissemination.

  14. Antagonistic effects of black tea against gamma radiation-induced oxidative damage to normal lymphocytes in comparison with cancerous K562 cells.

    Science.gov (United States)

    Ghosh, Debjani; Dey, Subrata Kumar; Saha, Chabita

    2014-11-01

    The potential of naturally occurring antioxidants to reduce the cellular oxidative damage induced by ionizing radiation has been studied for more than a decade for their pharmacological application during cancer treatment. It is already known that radioprotective efficacy of phytochemicals might influence various end points of radiation damage. Flavonoids are well-known natural radioprotectors, and their biological effects depend upon their chemical structure. In the present study, radioprotective effect of black tea rich in flavonoids was evaluated against gamma radiation-induced oxidative damage on normal lymphocytes and compared with erythroleukemic K562 cells. Pre-treatment with black tea extract (BTE) significantly reduced radiation-induced loss of cell viability, generation of reactive oxygen species, mitochondrial dysfunction, activation of caspase-3 and apoptosis in normal lymphocytes compared to K562 cells. BTE also regulates the activity of endogenous antioxidant enzymes. The changes in the mRNA expression of bax, bcl2, p53 and Nrf2 were also followed to evaluate regulation of radiation-induced apoptosis by BTE. These findings suggest that black tea may have the potential of a natural radioprotective agent which can be used as adjunct with radiation during cancer treatment.

  15. Evaluations of thyme extract effects in human normal bronchial and tracheal epithelial cell lines and in human lung cancer cell line.

    Science.gov (United States)

    Oliviero, Marinelli; Romilde, Iannarelli; Beatrice, Morelli Maria; Matteo, Valisi; Giovanna, Nicotra; Consuelo, Amantini; Claudio, Cardinali; Giorgio, Santoni; Filippo, Maggi; Massimo, Nabissi

    2016-08-25

    Thyme (Thymus vulgaris) is used traditionally to prepare herbal remedies possessing expectorant, mucolytic, antitussive and antispasmodic properties. The aim of the present study was to investigate the effects of a standardized hydroalcoholic extract of thyme on primary human airway (bronchial/tracheal) epithelial cell lines in a model of lung inflammation induced by LPS. In addition, the effects of thyme extract on human lung cancer cell line (H460) were analysed. Thyme extract showed significant anti-inflammatory properties by reducing the NF-κB p65 and NF-κB p52 transcription factors protein levels followed by the decrease of pro-inflammatory cytokines (IL-1 beta and IL-8), and Muc5ac secretion in human normal bronchial and tracheal epithelial cells. Moreover, the extract showed cytotoxic effects on H460 cancer cells, modulated the release of IL-1 beta, IL-8 and down-regulated NF-κB p65 and NF-κB p52 proteins. Taken together, these results substantiated the traditional uses of thyme in the treatment of respiratory diseases. Thyme extract might be an effective treatment of chronic diseases based on inflammatory processes when hypersecretion of mucus overwhelms the ciliary clearance and obstructs airways, causing morbidity and mortality. Moreover thyme extract, evaluated in H460 lung cancer cell line, demonstrated to induce cell cytotoxicity in addition to reduce inflammatory cell signals. PMID:27369807

  16. Cosmology with Negative Absolute Temperatures

    CERN Document Server

    Vieira, J P P; Lewis, Antony

    2016-01-01

    Negative absolute temperatures (NAT) are an exotic thermodynamical consequence of quantum physics which has been known since the 1950's (having been achieved in the lab on a number of occasions). Recently, the work of Braun et al (2013) has rekindled interest in negative temperatures and hinted at a possibility of using NAT systems in the lab as dark energy analogues. This paper goes one step further, looking into the cosmological consequences of the existence of a NAT component in the Universe. NAT-dominated expanding Universes experience a borderline phantom expansion ($w<-1$) with no Big Rip, and their contracting counterparts are forced to bounce after the energy density becomes sufficiently large. Both scenarios might be used to solve horizon and flatness problems analogously to standard inflation and bouncing cosmologies. We discuss the difficulties in obtaining and ending a NAT-dominated epoch, and possible ways of obtaining density perturbations with an acceptable spectrum.

  17. Cosmology with negative absolute temperatures

    Science.gov (United States)

    Vieira, J. P. P.; Byrnes, Christian T.; Lewis, Antony

    2016-08-01

    Negative absolute temperatures (NAT) are an exotic thermodynamical consequence of quantum physics which has been known since the 1950's (having been achieved in the lab on a number of occasions). Recently, the work of Braun et al. [1] has rekindled interest in negative temperatures and hinted at a possibility of using NAT systems in the lab as dark energy analogues. This paper goes one step further, looking into the cosmological consequences of the existence of a NAT component in the Universe. NAT-dominated expanding Universes experience a borderline phantom expansion (w inflation and bouncing cosmologies. We discuss the difficulties in obtaining and ending a NAT-dominated epoch, and possible ways of obtaining density perturbations with an acceptable spectrum.

  18. An association between low-dose hyper-radiosensitivity and the early G2-phase checkpoint in normal fibroblasts of cancer patients.

    Science.gov (United States)

    Słonina, Dorota; Gasińska, Anna; Biesaga, Beata; Janecka, Anna; Kabat, Damian

    2016-03-01

    In our previous study, low-dose hyper-radiosensitivity (HRS) effect was demonstrated for normal fibroblasts (asynchronous and G2-phase enriched) of 4 of the 25 cancer patients investigated. For the rest of patients, HRS was not defined in either of the 2 fibroblast populations. Thus, the study indicated that G2-phase enrichment had no influence on HRS identification. The conclusion contradicts that reported for human tumor cells, and suggests different mechanism of HRS in normal human cells. In the present paper we report, for the first time, the activity of early G2-phase checkpoint after low-dose irradiation in normal fibroblasts of these 4 HRS-positive patients and 4 HRS-negative patients and answer the question regarding the role of this checkpoint in normal human cells. The response of the early G2-phase checkpoint was determined by assessment of the progression of irradiated cells into mitosis using the mitotic marker, phosphorylated histone H3. We found evident differences in the activity of the early G2-phase checkpoint between HRS-positive and HRS-negative fibroblasts. In HRS-positive fibroblasts the checkpoint was not triggered and DNA damage was not recognized after doses lower than 0.2Gy resulting in HRS response. On the contrary, in HRS-negative fibroblasts the early G2-phase checkpoint was activated regardless of the dose in the range 0.1-2Gy. In conclusion, although cell cycle phase has no effect on the presence of HRS effect in normal human fibroblasts, the data reported here indicate that HRS response in these cells is associated with the functioning of early G2-phase checkpoint in a threshold-dose dependent manner, similarly as it takes place in most of human tumor and other cells. PMID:26725161

  19. Keratin 8/18 regulation of glucose metabolism in normal versus cancerous hepatic cells through differential modulation of hexokinase status and insulin signaling

    Energy Technology Data Exchange (ETDEWEB)

    Mathew, Jasmin; Loranger, Anne; Gilbert, Stéphane [Centre de recherche en cancérologie de l' Université Laval and Centre de recherche du CHUQ (L' Hôtel-Dieu de Québec), 9 McMahon, Québec, Qc, Canada G1R 2J6 (Canada); Faure, Robert [Département de Pédiatrie, Université Laval and Centre de recherche du CHUQ (Centre Mère-Enfant), Québec, Qc, Canada G1V 4G2 (Canada); Marceau, Normand, E-mail: normand.marceau@crhdq.ulaval.ca [Centre de recherche en cancérologie de l' Université Laval and Centre de recherche du CHUQ (L' Hôtel-Dieu de Québec), 9 McMahon, Québec, Qc, Canada G1R 2J6 (Canada)

    2013-02-15

    As differentiated cells, hepatocytes primarily metabolize glucose for ATP production through oxidative phosphorylation of glycolytic pyruvate, whereas proliferative hepatocellular carcinoma (HCC) cells undergo a metabolic shift to aerobic glycolysis despite oxygen availability. Keratins, the intermediate filament (IF) proteins of epithelial cells, are expressed as pairs in a lineage/differentiation manner. Hepatocyte and HCC (hepatoma) cell IFs are made solely of keratins 8/18 (K8/K18), thus providing models of choice to address K8/K18 IF functions in normal and cancerous epithelial cells. Here, we demonstrate distinctive increases in glucose uptake, glucose-6-phosphate formation, lactate release, and glycogen formation in K8/K18 IF-lacking hepatocytes and/or hepatoma cells versus their respective IF-containing counterparts. We also show that the K8/K18-dependent glucose uptake/G6P formation is linked to alterations in hexokinase I/II/IV content and localization at mitochondria, with little effect on GLUT1 status. In addition, we find that the insulin-stimulated glycogen formation in normal hepatocytes involves the main PI-3 kinase-dependent signaling pathway and that the K8/K18 IF loss makes them more efficient glycogen producers. In comparison, the higher insulin-dependent glycogen formation in K8/K18 IF-lacking hepatoma cells is associated with a signaling occurring through a mTOR-dependent pathway, along with an augmentation in cell proliferative activity. Together, the results uncover a key K8/K18 regulation of glucose metabolism in normal and cancerous hepatic cells through differential modulations of mitochondrial HK status and insulin-mediated signaling.

  20. A comparison of mantle versus involved-field radiotherapy for Hodgkin's lymphoma: reduction in normal tissue dose and second cancer risk

    Directory of Open Access Journals (Sweden)

    Xu Tony

    2007-03-01

    Full Text Available Abstract Background Hodgkin's lymphoma (HL survivors who undergo radiotherapy experience increased risks of second cancers (SC and cardiac sequelae. To reduce such risks, extended-field radiotherapy (RT for HL has largely been replaced by involved field radiotherapy (IFRT. While it has generally been assumed that IFRT will reduce SC risks, there are few data that quantify the reduction in dose to normal tissues associated with modern RT practice for patients with mediastinal HL, and no estimates of the expected reduction in SC risk. Methods Organ-specific dose-volume histograms (DVH were generated for 41 patients receiving 35 Gy mantle RT, 35 Gy IFRT, or 20 Gy IFRT, and integrated organ mean doses were compared for the three protocols. Organ-specific SC risk estimates were estimated using a dosimetric risk-modeling approach, analyzing DVH data with quantitative, mechanistic models of radiation-induced cancer. Results Dose reductions resulted in corresponding reductions in predicted excess relative risks (ERR for SC induction. Moving from 35 Gy mantle RT to 35 Gy IFRT reduces predicted ERR for female breast and lung cancer by approximately 65%, and for male lung cancer by approximately 35%; moving from 35 Gy IFRT to 20 Gy IFRT reduces predicted ERRs approximately 40% more. The median reduction in integral dose to the whole heart with the transition to 35 Gy IFRT was 35%, with a smaller (2% reduction in dose to proximal coronary arteries. There was no significant reduction in thyroid dose. Conclusion The significant decreases estimated for radiation-induced SC risks associated with modern IFRT provide strong support for the use of IFRT to reduce the late effects of treatment. The approach employed here can provide new insight into the risks associated with contemporary IFRT for HL, and may facilitate the counseling of patients regarding the risks associated with this treatment.

  1. Laser Capture Microdissection of Cervical Human Papillomavirus Infections: Copy Number of the Virus in Cancerous and Normal Tissue and Heterogeneous DNA Methylation

    Science.gov (United States)

    Kalantari, Mina; Garcia-Carranca, Alejandro; Morales-Vazquez, Claudia Dalia; Zuna, Rosemary; Montiel, Delia Perez; Calleja-Macias, Itzel E.; Johansson, Bo; Andersson, Sonia; Bernard, Hans-Ulrich

    2009-01-01

    Research on the pathogenicity of human papillomaviruses (HPVs) during cervical carcinogenesis often relies on the study of homogenized tissue or cultured cells. This approach does not detect molecular heterogeneities within the infected tissue. It is desirable to understand molecular properties in specific histological contexts. We asked whether Laser Capture Microdissection (LCM) of archival cervical tumors in combination with real-time polymerase chain reaction and bisulfite sequencing permits (i) sensitive DNA diagnosis of small clusters of formalin fixed cells, (ii) quantification of HPV DNA in neoplastic and normal cells, and (iii) analysis of HPV DNA methylation, a marker of tumor progression. We analyzed 26 tumors containing HPV-16 or 18. We prepared DNA from LCM dissected thin sections of 100 to 2000 cells, and analyzed aliquots corresponding to between nine and 70 cells. We detected nine to 630 HPV-16 genome copies and one to 111 HPV-18 genome copies per tumor cell, respectively. In 17 of the 26 samples, HPV DNA existed in histologically normal cells distant from the margins of the tumors, but at much lower concentrations than in the tumor, suggesting that HPVs can infect at low levels without pathogenic changes. Methylation of HPV DNA, a biomarker of integration of the virus into cellular DNA, could be measured only in few samples due to limited sensitivity, and indicated heterogeneous methylation patterns in small clusters of cancerous and normal cells. LCM is powerful to study molecular parameters of cervical HPV infections like copy number, latency and epigenetics. PMID:19497607

  2. Diatom-derived polyunsaturated aldehydes activate cell death in human cancer cell lines but not normal cells.

    Directory of Open Access Journals (Sweden)

    Clementina Sansone

    Full Text Available Diatoms are an important class of unicellular algae that produce bioactive polyunsaturated aldehydes (PUAs that induce abortions or malformations in the offspring of invertebrates exposed to them during gestation. Here we compare the effects of the PUAs 2-trans,4-trans-decadienal (DD, 2-trans,4-trans-octadienal (OD and 2-trans,4-trans-heptadienal (HD on the adenocarcinoma cell lines lung A549 and colon COLO 205, and the normal lung/brunch epithelial BEAS-2B cell line. Using the viability MTT/Trypan blue assays, we show that PUAs have a toxic effect on both A549 and COLO 205 tumor cells but not BEAS-2B normal cells. DD was the strongest of the three PUAs tested, at all time-intervals considered, but HD was as strong as DD after 48 h. OD was the least active of the three PUAs. The effect of the three PUAs was somewhat stronger for A549 cells. We therefore studied the death signaling pathway activated in A549 showing that cells treated with DD activated Tumor Necrosis Factor Receptor 1 (TNFR1 and Fas Associated Death Domain (FADD leading to necroptosis via caspase-3 without activating the survival pathway Receptor-Interacting Protein (RIP. The TNFR1/FADD/caspase pathway was also observed with OD, but only after 48 h. This was the only PUA that activated RIP, consistent with the finding that OD causes less damage to the cell compared to DD and HD. In contrast, cells treated with HD activated the Fas/FADD/caspase pathway. This is the first report that PUAs activate an extrinsic apoptotic machinery in contrast to other anticancer drugs that promote an intrinsic death pathway, without affecting the viability of normal cells from the same tissue type. These findings have interesting implications also from the ecological viewpoint considering that HD is one of the most common PUAs produced by diatoms.

  3. 3D-conformal-intensity modulated radiotherapy with compensators for head and neck cancer: clinical results of normal tissue sparing

    Directory of Open Access Journals (Sweden)

    Koscielny Sven

    2006-06-01

    Full Text Available Abstract Background To investigate the potential of parotic gland sparing of intensity modulated radiotherapy (3D-c-IMRT performed with metallic compensators for head and neck cancer in a clinical series by analysis of dose distributions and clinical measures. Materials and methods 39 patients with squamous cell cancer of the head and neck irradiated using 3D-c-IMRT were evaluable for dose distribution within PTVs and at one parotid gland and 38 patients for toxicity analysis. 10 patients were treated primarily, 29 postoperatively, 19 received concomittant cis-platin based chemotherapy, 20 3D-c-IMRT alone. Initially the dose distribution was calculated with Helax ® and photon fluence was modulated using metallic compensators made of tin-granulate (n = 22. Later the dose distribution was calculated with KonRad ® and fluence was modified by MCP 96 alloy compensators (n = 17. Gross tumor/tumor bed (PTV 1 was irradiated up to 60–70 Gy, [5 fractions/week, single fraction dose: 2.0–2.2 (simultaneously integrated boost], adjuvantly irradiated bilateral cervical lymph nodes (PTV 2 with 48–54 Gy [single dose: 1.5–1.8]. Toxicity was scored according the RTOG scale and patient-reported xerostomia questionnaire (XQ. Results Mean of the median doses at the parotid glands to be spared was 25.9 (16.3–46.8 Gy, for tin graulate 26 Gy, for MCP alloy 24.2 Gy. Tin-granulate compensators resulted in a median parotid dose above 26 Gy in 10/22, MCP 96 alloy in 0/17 patients. Following acute toxicities were seen (°0–2/3: xerostomia: 87%/13%, dysphagia: 84%/16%, mucositis: 89%/11%, dermatitis: 100%/0%. No grade 4 reaction was encountered. During therapy the XQ forms showed °0–2/3: 88%/12%. 6 months postRT chronic xerostomia °0–2/3 was observed in 85%/15% of patients, none with °4 xerostomia. Conclusion 3D-c-IMRT using metallic compensators along with inverse calculation algorithm achieves sufficient parotid gland sparing in virtually all advanced

  4. Sci—Thur AM: YIS - 02: Radiogenomic Modeling of Normal Tissue Toxicities in Prostate Cancer Patients Receiving Hypofractionated Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Coates, J [Department of Oncology, Medical Physics Unit, McGill University Health Center, Montreal, QC (Canada); Jeyaseelan, K; Ybarra, N; David, M; Faria, S; Souhami, L; Cury, F; Duclos, M; El Naqa, I [Department of Oncology, Medical Physics Unit, McGill University Health Center, Montreal, QC (Canada); Department of Oncology, Radiation Oncology Division, McGill University Health Centre, Montreal, QC Canada (Canada)

    2014-08-15

    Inter-patient radiation sensitivity variability has recently been shown to have a genetic component. This genetic component may play a key role in explaining the fluctuating rates of radiation-induced toxicities (RITs). Single nucleotide polymorphisms (SNPs) have thus far yielded inconsistent results in delineating RITs while copy number variations (CNVs) have not yet been investigated for such purposes. We explore a radiogenomic modeling approach to investigate the association of CNVs and SNPs, along with clinical and dosimetric variables, in radiation induced rectal bleeding (RB) and erectile dysfunction (ED) in prostate cancer patients treated with curative hypofractionated irradiation. A cohort of 62 prostate cancer patients who underwent hypofractionated radiotherapy (66 Gy in 22 fractions) between 2002 to 2010 were retrospectively genotyped for CNV and SNP rs5489 in the xrcc1 DNA repair gene. Late toxicity rates for RB grade 2 and 3 and grade 3 alone were 29.0% and 12.9%, respectively. ED toxicity was found to be 62.9%. Radiogenomic model performance was evaluated using receiver operating characteristic area under the curve (AUC) and resampling by cross-validation. Binary variables were evaluated using Chi-squared contingency table analysis and multivariate models by Spearman's rank correlation coefficient (rs). Ten patients were found to have three copies of xrcc1 CNV (RB: χ{sup 2}=14.6, p<0.001 and ED: χ{sup 2}=4.88, p=0.0272) and twelve had heterozygous rs25489 SNP (RB: χ{sup 2}=0.278, p=0.599 and ED: χ{sup 2}=0.112, p=0.732). Radiogenomic modeling yielded significant, cross-validated NTCP models for RB (AUC=0.665) and ED (AUC=0.754). These results indicate that CNVs may be potential predictive biomarkers of both late ED and RB.

  5. Evaluating the Normal Distribution

    Directory of Open Access Journals (Sweden)

    George Marsaglia

    2004-07-01

    Full Text Available This article provides a little table-free C function that evaluates the normal distribution with absolute error less than 8 x 10 -16 . A small extension provides relative error near the limit available in double precision: 14 to 16 digits, the limits determined mainly by the computer's ability to evaluate exp(-t for large t. Results are compared with those provided by calls to erf or erfc functions, the best of which compare favorably, others do not, and all appear to be much more complicated than need be to get either absolute accuracy less than 10-15 or relative accuracy to the exp(-limited 14 to 16 digits. Also provided: A short history of the error function erf and its intended use, as well as, in the "browse files" attachment, various erf or erfc versions used for comparison.

  6. Adeno-associated virus type 2 infection activates caspase dependent and independent apoptosis in multiple breast cancer lines but not in normal mammary epithelial cells

    Directory of Open Access Journals (Sweden)

    Tandon Apurva

    2011-08-01

    Full Text Available Abstract Background In normal cells proliferation and apoptosis are tightly regulated, whereas in tumor cells the balance is shifted in favor of increased proliferation and reduced apoptosis. Anticancer agents mediate tumor cell death via targeting multiple pathways of programmed cell death. We have reported that the non-pathogenic, tumor suppressive Adeno-Associated Virus Type 2 (AAV2 induces apoptosis in Human Papillomavirus (HPV positive cervical cancer cells, but not in normal keratinocytes. In the current study, we examined the potential of AAV2 to inhibit proliferation of MCF-7 and MDA-MB-468 (both weakly invasive, as well as MDA-MB-231 (highly invasive human breast cancer derived cell lines. As controls, we used normal human mammary epithelial cells (nHMECs isolated from tissue biopsies of patients undergoing breast reduction surgery. Results AAV2 infected MCF-7 line underwent caspase-independent, and MDA-MB-468 and MDA-MB-231 cell lines underwent caspase-dependent apoptosis. Death of MDA-MB-468 cells was marked by caspase-9 activation, whereas death of MDA-MB-231 cells was marked by activation of both caspase-8 and caspase-9, and resembled a mixture of apoptotic and necrotic cell death. Cellular demise was correlated with the ability of AAV2 to productively infect and differentially express AAV2 non-structural proteins: Rep78, Rep68 and Rep40, dependent on the cell line. Cell death in the MCF-7 and MDA-MB-231 lines coincided with increased S phase entry, whereas the MDA-MB-468 cells increasingly entered into G2. AAV2 infection led to decreased cell viability which correlated with increased expression of proliferation markers c-Myc and Ki-67. In contrast, nHMECs that were infected with AAV2 failed to establish productive infection or undergo apoptosis. Conclusion AAV2 regulated enrichment of cell cycle check-point functions in G1/S, S and G2 phases could create a favorable environment for Rep protein expression. Inherent Rep associated

  7. Normal Tissue Complication Probability (NTCP) modeling of late rectal bleeding following external beam radiotherapy for prostate cancer: A Test of the QUANTEC-recommended NTCP model

    International Nuclear Information System (INIS)

    Purpose/background. Validating a predictive model for late rectal bleeding following external beam treatment for prostate cancer would enable safer treatments or dose escalation. We tested the normal tissue complication probability (NTCP) model recommended in the recent QUANTEC review (quantitative analysis of normal tissue effects in the clinic). Material and methods. One hundred and sixty one prostate cancer patients were treated with 3D conformal radiotherapy for prostate cancer at the British Columbia Cancer Agency in a prospective protocol. The total prescription dose for all patients was 74 Gy, delivered in 2 Gy/fraction. 159 3D treatment planning datasets were available for analysis. Rectal dose volume histograms were extracted and fitted to a Lyman-Kutcher-Burman NTCP model. Results. Late rectal bleeding (>grade 2) was observed in 12/159 patients (7.5%). Multivariate logistic regression with dose-volume parameters (V50, V60, V70, etc.) was non-significant. Among clinical variables, only age was significant on a Kaplan-Meier log-rank test (p=0.007, with an optimal cut point of 77 years). Best-fit Lyman-Kutcher-Burman model parameters (with 95% confidence intervals) were: n = 0.068 (0.01, +infinity); m =0.14 (0.0, 0.86); and TD50 81 (27, 136) Gy. The peak values fall within the 95% QUANTEC confidence intervals. On this dataset, both models had only modest ability to predict complications: the best-fit model had a Spearman's rank correlation coefficient of rs = 0.099 (p = 0.11) and area under the receiver operating characteristic curve (AUC) of 0.62; the QUANTEC model had rs=0.096 (p= 0.11) and a corresponding AUC of 0.61. Although the QUANTEC model consistently predicted higher NTCP values, it could not be rejected according to the χ2 test (p = 0.44). Conclusions. Observed complications, and best-fit parameter estimates, were consistent with the QUANTEC-preferred NTCP model. However, predictive power was low, at least partly because the rectal dose

  8. Normal Tissue Complication Probability (NTCP) modeling of late rectal bleeding following external beam radiotherapy for prostate cancer: A Test of the QUANTEC-recommended NTCP model

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Mitchell; Agranovich, Alexander; Karvat, Anand; Kwan, Winkle (Fraser Valley Centre, British Columbia Cancer Centre, Surrey, BC (Canada)); Moiseenko, Vitali (Vancouver Centre, British Columbia Cancer Agency, Vancouver, BC (Canada)); Saleh, Ziad H.; Apte, Aditya A.; Deasy, Joseph O. (Dept. of Radiation Oncology and the Mallinckrodt Inst. of Radiology, Washington Univ., St. Louis, MO (United States)), e-mail: deasyj@mskcc.org

    2010-10-15

    Purpose/background. Validating a predictive model for late rectal bleeding following external beam treatment for prostate cancer would enable safer treatments or dose escalation. We tested the normal tissue complication probability (NTCP) model recommended in the recent QUANTEC review (quantitative analysis of normal tissue effects in the clinic). Material and methods. One hundred and sixty one prostate cancer patients were treated with 3D conformal radiotherapy for prostate cancer at the British Columbia Cancer Agency in a prospective protocol. The total prescription dose for all patients was 74 Gy, delivered in 2 Gy/fraction. 159 3D treatment planning datasets were available for analysis. Rectal dose volume histograms were extracted and fitted to a Lyman-Kutcher-Burman NTCP model. Results. Late rectal bleeding (>grade 2) was observed in 12/159 patients (7.5%). Multivariate logistic regression with dose-volume parameters (V50, V60, V70, etc.) was non-significant. Among clinical variables, only age was significant on a Kaplan-Meier log-rank test (p=0.007, with an optimal cut point of 77 years). Best-fit Lyman-Kutcher-Burman model parameters (with 95% confidence intervals) were: n = 0.068 (0.01, +infinity); m =0.14 (0.0, 0.86); and TD50 81 (27, 136) Gy. The peak values fall within the 95% QUANTEC confidence intervals. On this dataset, both models had only modest ability to predict complications: the best-fit model had a Spearman's rank correlation coefficient of rs = 0.099 (p = 0.11) and area under the receiver operating characteristic curve (AUC) of 0.62; the QUANTEC model had rs=0.096 (p= 0.11) and a corresponding AUC of 0.61. Although the QUANTEC model consistently predicted higher NTCP values, it could not be rejected according to the chi2 test (p = 0.44). Conclusions. Observed complications, and best-fit parameter estimates, were consistent with the QUANTEC-preferred NTCP model. However, predictive power was low, at least partly because the rectal dose

  9. Standardization of Gene Expression Quantification by Absolute Real-Time qRT-PCR System Using a Single Standard for Marker and Reference Genes

    Directory of Open Access Journals (Sweden)

    Yi-Hong Zhou

    2010-08-01

    Full Text Available In the last decade, genome-wide gene expression data has been collected from a large number of cancer specimens. In many studies utilizing either microarray-based or knowledge-based gene expression profiling, both the validation of candidate genes and the identification and inclusion of biomarkers in prognosis-modeling has employed real-time quantitative PCR on reverse transcribed mRNA (qRT-PCR because of its inherent sensitivity and quantitative nature. In qRT-PCR data analysis, an internal reference gene is used to normalize the variation in input sample quantity. The relative quantification method used in current real-time qRT-PCR analysis fails to ensure data comparability pivotal in identification of prognostic biomarkers. By employing an absolute qRT-PCR system that uses a single standard for marker and reference genes (SSMR to achieve absolute quantification, we showed that the normalized gene expression data is comparable and independent of variations in the quantities of sample as well as the standard used for generating standard curves. We compared two sets of normalized gene expression data with same histological diagnosis of brain tumor from two labs using relative and absolute real-time qRT-PCR. Base-10 logarithms of the gene expression ratio relative to ACTB were evaluated for statistical equivalence between tumors processed by two different labs. The results showed an approximate comparability for normalized gene expression quantified using a SSMR-based qRT-PCR. Incomparable results were seen for the gene expression data using relative real-time qRT-PCR, due to inequality in molar concentration of two standards for marker and reference genes. Overall results show that SSMR-based real-time qRT-PCR ensures comparability of gene expression data much needed in establishment of prognostic/predictive models for cancer patients—a process that requires large sample sizes by combining independent sets of data.

  10. The differences in ultrasound and clinicopathological features between basal-like and normal-like subtypes of triple negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Ziyao Li

    Full Text Available The aim of this study was to identify the ultrasound features and clinicopathological characteristics of basal-like subtype of triple negative breast cancers (TNBCs.This study was approved by the ethical board of the Second Affiliated Hospital of Harbin Medical University. The patients' clinicopathological information was available. The ultrasound features of 62 tumors from 62 TNBC patients were interpreted. The immunohistochemical results of cytokertain5/6 (CK5/6 and Epidermal Growth Factor Receptor (EGFR were used to classify the tumor into basal-like and normal-like groups. The association of the ultrasound features interpreted by experienced ultrasound doctors with the immunohistochemical classification was studied.Of the 62 TNBC cases, 42 (67.7% exhibited the basal-like phenotype and 20 (32.3% exhibited the normal-like phenotype based on the immunohistochemical CK5/6 and EGFR markers. Of all the tumors, 90.3% were invasive carcinomas. The basal-like tumors were significantly associated with a maximum diameter on ultrasound of more than 20 mm (36, 85.7% (P = 0.0014. The normal-like tumors usually exhibited lateral shadows (15, 75% (P = 0.0115 as well as microlobulated margins (12, 60% (P = 0.0204 compared to the basal-like subtype. Other ultrasound features showed no significant differences between the two groups.Although ultrasound cannot yet be used to differentiate between the basal-like subtype and normal-like subtype of TNBC, ultrasound can be used to provide some useful information to the clinicians.

  11. Withaferin A Induces Cell Death Selectively in Androgen-Independent Prostate Cancer Cells but Not in Normal Fibroblast Cells.

    Directory of Open Access Journals (Sweden)

    Yukihiro Nishikawa

    Full Text Available Withaferin A (WA, a major bioactive component of the Indian herb Withania somnifera, induces cell death (apoptosis/necrosis in multiple types of tumor cells, but the molecular mechanism underlying this cytotoxicity remains elusive. We report here that 2 μM WA induced cell death selectively in androgen-insensitive PC-3 and DU-145 prostate adenocarcinoma cells, whereas its toxicity was less severe in androgen-sensitive LNCaP prostate adenocarcinoma cells and normal human fibroblasts (TIG-1 and KD. WA also killed PC-3 cells in spheroid-forming medium. DNA microarray analysis revealed that WA significantly increased mRNA levels of c-Fos and 11 heat-shock proteins (HSPs in PC-3 and DU-145, but not in LNCaP and TIG-1. Western analysis revealed increased expression of c-Fos and reduced expression of the anti-apoptotic protein c-FLIP(L. Expression of HSPs such as HSPA6 and Hsp70 was conspicuously elevated; however, because siRNA-mediated depletion of HSF-1, an HSP-inducing transcription factor, reduced PC-3 cell viability, it is likely that these heat-shock genes were involved in protecting against cell death. Moreover, WA induced generation of reactive oxygen species (ROS in PC-3 and DU-145, but not in normal fibroblasts. Immunocytochemistry and immuno-electron microscopy revealed that WA disrupted the vimentin cytoskeleton, possibly inducing the ROS generation, c-Fos expression and c-FLIP(L suppression. These observations suggest that multiple events followed by disruption of the vimentin cytoskeleton play pivotal roles in WA-mediated cell death.

  12. Measurement of the absolute speed is possible?

    OpenAIRE

    Sergey V. Shevchenko; Tokarevsky, Vladimir V.

    2016-01-01

    One of popular problems, which  are experimentally studied in physics in a long time, is the testing of the special relativity theory, first of all – measurements of isotropy and constancy of light speed; as well as attempts to determine so called “absolute speed”, i.e. the Earth speed in the absolute spacetime (absolute reference frame), if this spacetime (ARF) exists.  Corresponding experiments aimed at the measuring of proper speed of some reference frame in oth...

  13. SU-D-16A-01: A Novel Method to Estimate Normal Tissue Dose for Radiotherapy Patients to Support Epidemiologic Studies of Second Cancer Risk

    International Nuclear Information System (INIS)

    Purpose: Patient cohort of second cancer study often involves radiotherapy patients with no radiological images available: We developed methods to construct a realistic surrogate anatomy by using computational human phantoms. We tested this phantom images both in a commercial treatment planning system (Eclipse) and a custom Monte Carlo (MC) transport code. Methods: We used a reference adult male phantom defined by International Commission on Radiological Protection (ICRP). The hybrid phantom which was originally developed in Non-Uniform Rational B-Spline (NURBS) and polygon mesh format was converted into more common medical imaging format. Electron density was calculated from the material composition of the organs and tissues and then converted into DICOM format. The DICOM images were imported into the Eclipse system for treatment planning, and then the resulting DICOM-RT files were imported into the MC code for MC-based dose calculation. Normal tissue doses were calculation in Eclipse and MC code for an illustrative prostate treatment case and compared to each other. Results: DICOM images were generated from the adult male reference phantom. Densities and volumes of selected organs between the original phantom and ones represented within Eclipse showed good agreements, less than 0.6%. Mean dose from Eclipse and MC code match less than 7%, whereas maximum and minimum doses were different up to 45%. Conclusion: The methods established in this study will be useful for the reconstruction of organ dose to support epidemiological studies of second cancer in cancer survivors treated by radiotherapy. We also work on implementing body size-dependent computational phantoms to better represent patient's anatomy when the height and weight of patients are available

  14. SU-D-16A-01: A Novel Method to Estimate Normal Tissue Dose for Radiotherapy Patients to Support Epidemiologic Studies of Second Cancer Risk

    Energy Technology Data Exchange (ETDEWEB)

    Lee, C [University of Michigan, Ann Arbor, MI (United States); Jung, J; Pelletier, C [East Carolina University, Greenville, NC (United States); Kim, J [University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Lee, C [National Cancer Institute, Bethesda, MD (United States)

    2014-06-01

    Purpose: Patient cohort of second cancer study often involves radiotherapy patients with no radiological images available: We developed methods to construct a realistic surrogate anatomy by using computational human phantoms. We tested this phantom images both in a commercial treatment planning system (Eclipse) and a custom Monte Carlo (MC) transport code. Methods: We used a reference adult male phantom defined by International Commission on Radiological Protection (ICRP). The hybrid phantom which was originally developed in Non-Uniform Rational B-Spline (NURBS) and polygon mesh format was converted into more common medical imaging format. Electron density was calculated from the material composition of the organs and tissues and then converted into DICOM format. The DICOM images were imported into the Eclipse system for treatment planning, and then the resulting DICOM-RT files were imported into the MC code for MC-based dose calculation. Normal tissue doses were calculation in Eclipse and MC code for an illustrative prostate treatment case and compared to each other. Results: DICOM images were generated from the adult male reference phantom. Densities and volumes of selected organs between the original phantom and ones represented within Eclipse showed good agreements, less than 0.6%. Mean dose from Eclipse and MC code match less than 7%, whereas maximum and minimum doses were different up to 45%. Conclusion: The methods established in this study will be useful for the reconstruction of organ dose to support epidemiological studies of second cancer in cancer survivors treated by radiotherapy. We also work on implementing body size-dependent computational phantoms to better represent patient's anatomy when the height and weight of patients are available.

  15. Contrasting analytical and data-driven frameworks for radiogenomic modeling of normal tissue toxicities in prostate cancer

    International Nuclear Information System (INIS)

    Background and purpose: We explore analytical and data-driven approaches to investigate the integration of genetic variations (single nucleotide polymorphisms [SNPs] and copy number variations [CNVs]) with dosimetric and clinical variables in modeling radiation-induced rectal bleeding (RB) and erectile dysfunction (ED) in prostate cancer patients. Materials and methods: Sixty-two patients who underwent curative hypofractionated radiotherapy (66 Gy in 22 fractions) between 2002 and 2010 were retrospectively genotyped for CNV and SNP rs5489 in the xrcc1 DNA repair gene. Fifty-four patients had full dosimetric profiles. Two parallel modeling approaches were compared to assess the risk of severe RB (Grade ⩾3) and ED (Grade ⩾1); Maximum likelihood estimated generalized Lyman–Kutcher–Burman (LKB) and logistic regression. Statistical resampling based on cross-validation was used to evaluate model predictive power and generalizability to unseen data. Results: Integration of biological variables xrcc1 CNV and SNP improved the fit of the RB and ED analytical and data-driven models. Cross-validation of the generalized LKB models yielded increases in classification performance of 27.4% for RB and 14.6% for ED when xrcc1 CNV and SNP were included, respectively. Biological variables added to logistic regression modeling improved classification performance over standard dosimetric models by 33.5% for RB and 21.2% for ED models. Conclusion: As a proof-of-concept, we demonstrated that the combination of genetic and dosimetric variables can provide significant improvement in NTCP prediction using analytical and data-driven approaches. The improvement in prediction performance was more pronounced in the data driven approaches. Moreover, we have shown that CNVs, in addition to SNPs, may be useful structural genetic variants in predicting radiation toxicities

  16. Electroporation-assisted penetration of zinc oxide nanoparticles in ex vivo normal and cancerous human colon tissue

    Science.gov (United States)

    Zhou, L. P.; Wu, G. Y.; Wei, H. J.; Guo, Z. Y.; Yang, H. Q.; He, Y. H.; Xie, S. S.

    2015-11-01

    In this study, we presented the research of the penetration of zinc oxide nanoparticles (ZnO NPs) (30 and 90 nm), and electroporation (EP) assisted penetration of the ZnO NPs in the human normal colon (NC) and adenomatous colon (AC) tissues studied with optical coherence tomography (OCT) and diffuse reflectance (DR) measurement. The results have shown that the attenuation coefficient of colon tissue after the application of 30 or 90 nm ZnO NPs alone decreased approximately by 28% and 14% for NC tissue, 35% and 22% for AC tissue, respectively; while the attenuation coefficient of colon tissue after combined application of 30 or 90 nm ZnO NPs/EP decreased approximately by 46% and 30% for NC tissue, and 53% and 42% for AC tissue, respectively. The results illustrate EP can significantly increase the penetration of ZnO NPs in the colon tissue, especially in AC tissue. Through the analysis of attenuation coefficient and reflectance intensity of the colon tissue, we find that the accumulation of the ZnO NPs in the colon tissue greatly influenced the tissue optical properties.

  17. Low-Dose Hyper-Radiosensitivity Is Not a Common Effect in Normal Asynchronous and G2-Phase Fibroblasts of Cancer Patients

    International Nuclear Information System (INIS)

    Purpose: In our previous study, using the micronucleus assay, a low-dose hyper-radiosensitivity (HRS)-like phenomenon was observed for normal fibroblasts of 2 of the 40 cancer patients investigated. In this article we report, for the first time, the survival response of primary fibroblasts from 25 of these patients to low-dose irradiation and answer the question regarding the effect of G2-phase enrichment on HRS elicitation. Methods and Materials: The clonogenic survival of asynchronous as well as G2-phase enriched fibroblast populations was measured. Separation of G2-phase cells and precise cell counting was performed using a fluorescence-activated cell sorter. Sorted and plated cells were irradiated with single doses (0.1-4 Gy) of 6-MV x-rays. For each patient, at least 4 independent experiments were performed, and the induced-repair model was fitted over the whole data set to confirm the presence of HRS effect. Results: The HRS response was demonstrated for the asynchronous and G2-phase enriched cell populations of 4 patients. For the rest of patients, HRS was not defined in either of the 2 fibroblast populations. Thus, G2-phase enrichment had no effect on HRS elicitation. Conclusions: The fact that low-dose hyper-radiosensitivity is not a common effect in normal human fibroblasts implies that HRS may be of little consequence in late-responding connective tissues with regard to radiation fibrosis

  18. Low-Dose Hyper-Radiosensitivity Is Not a Common Effect in Normal Asynchronous and G2-Phase Fibroblasts of Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Słonina, Dorota, E-mail: z5slonin@cyfronet.pl [Department of Applied Radiobiology, Centre of Oncology, Maria-Skłodowska-Curie Memorial Institute Kraków, Kraków (Poland); Biesaga, Beata; Janecka, Anna [Department of Applied Radiobiology, Centre of Oncology, Maria-Skłodowska-Curie Memorial Institute Kraków, Kraków (Poland); Kabat, Damian [Department of Medical Physics, Centre of Oncology, Maria-Skłodowska-Curie Memorial Institute Kraków, Kraków (Poland); Bukowska-Strakova, Karolina [Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, Kraków (Poland); Gasińska, Anna [Department of Applied Radiobiology, Centre of Oncology, Maria-Skłodowska-Curie Memorial Institute Kraków, Kraków (Poland)

    2014-02-01

    Purpose: In our previous study, using the micronucleus assay, a low-dose hyper-radiosensitivity (HRS)-like phenomenon was observed for normal fibroblasts of 2 of the 40 cancer patients investigated. In this article we report, for the first time, the survival response of primary fibroblasts from 25 of these patients to low-dose irradiation and answer the question regarding the effect of G2-phase enrichment on HRS elicitation. Methods and Materials: The clonogenic survival of asynchronous as well as G2-phase enriched fibroblast populations was measured. Separation of G2-phase cells and precise cell counting was performed using a fluorescence-activated cell sorter. Sorted and plated cells were irradiated with single doses (0.1-4 Gy) of 6-MV x-rays. For each patient, at least 4 independent experiments were performed, and the induced-repair model was fitted over the whole data set to confirm the presence of HRS effect. Results: The HRS response was demonstrated for the asynchronous and G2-phase enriched cell populations of 4 patients. For the rest of patients, HRS was not defined in either of the 2 fibroblast populations. Thus, G2-phase enrichment had no effect on HRS elicitation. Conclusions: The fact that low-dose hyper-radiosensitivity is not a common effect in normal human fibroblasts implies that HRS may be of little consequence in late-responding connective tissues with regard to radiation fibrosis.

  19. Dynamic OCT monitoring and quantification of light penetration enhancement for normal, benign and cancerous human lung tissues at different concentrations of glycerol

    International Nuclear Information System (INIS)

    We have evaluated the dynamic effects of the analyte diffusion on the 1/e light penetration depths of normal, benign and cancerous human lung tissue in vitro, as well as have monitored and quantified the dynamic change in the light penetration depths of the mentioned human lung tissue after application of 25 % and 50 % glycerol solution, respectively. The light penetration depths of the analyte diffusion in the lung tissue are measured using the Fourierdomain optical coherence tomography (FD-OCT). Experimental results show that the application of glycerol as a chemical agent can significantly enhance light penetration depths into the human normal lung (NL), lung benign granulomatosis (LBG) and lung squamous cell carcinoma (LSCC) tissue. In-depth transport of the glycerol molecules in the NL, LBG and LSCC tissue at a lower glycerol concentration (25 %) are faster than those at a higher glycerol concentration (50 %), and the 1/e light penetration depths at a lower glycerol concentration (25 %) are smaller than those at a higher glycerol concentration (50 %), respectively. Their differences in the maximal 1/e light penetration depths of the NL, LBG and LSCC tissue at a higher and a lower glycerol concentrations were only 8.8 %, 6.8 % and 4.7 %, respectively. (biophotonics)

  20. Normal tissue complication probability model parameter estimation for xerostomia in head and neck cancer patients based on scintigraphy and quality of life assessments

    International Nuclear Information System (INIS)

    With advances in modern radiotherapy (RT), many patients with head and neck (HN) cancer can be effectively cured. However, xerostomia is a common complication in patients after RT for HN cancer. The purpose of this study was to use the Lyman–Kutcher–Burman (LKB) model to derive parameters for the normal tissue complication probability (NTCP) for xerostomia based on scintigraphy assessments and quality of life (QoL) questionnaires. We performed validation tests of the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) guidelines against prospectively collected QoL and salivary scintigraphic data. Thirty-one patients with HN cancer were enrolled. Salivary excretion factors (SEFs) measured by scintigraphy and QoL data from self-reported questionnaires were used for NTCP modeling to describe the incidence of grade 3+ xerostomia. The NTCP parameters estimated from the QoL and SEF datasets were compared. Model performance was assessed using Pearson’s chi-squared test, Nagelkerke’s R2, the area under the receiver operating characteristic curve, and the Hosmer–Lemeshow test. The negative predictive value (NPV) was checked for the rate of correctly predicting the lack of incidence. Pearson’s chi-squared test was used to test the goodness of fit and association. Using the LKB NTCP model and assuming n=1, the dose for uniform irradiation of the whole or partial volume of the parotid gland that results in 50% probability of a complication (TD50) and the slope of the dose–response curve (m) were determined from the QoL and SEF datasets, respectively. The NTCP-fitted parameters for local disease were TD50=43.6 Gy and m=0.18 with the SEF data, and TD50=44.1 Gy and m=0.11 with the QoL data. The rate of grade 3+ xerostomia for treatment plans meeting the QUANTEC guidelines was specifically predicted, with a NPV of 100%, using either the QoL or SEF dataset. Our study shows the agreement between the NTCP parameter modeling based on SEF and QoL data

  1. Human Renal Normal, Tumoral, and Cancer Stem Cells Express Membrane-Bound Interleukin-15 Isoforms Displaying Different Functions

    Directory of Open Access Journals (Sweden)

    Sandy Azzi

    2015-06-01

    Full Text Available Intrarenal interleukin-15 (IL-15 participates to renal pathophysiology, but the role of its different membrane-bound isoforms remains to be elucidated. In this study, we reassess the biology of membrane-bound IL-15 (mb-IL-15 isoforms by comparing primary cultures of human renal proximal tubular epithelial cells (RPTEC to peritumoral (ptumTEC, tumoral (RCC, and cancer stem cells (CSC/CD105+. RPTEC express a 14 to 16 kDa mb-IL-15, whose existence has been assumed but never formally demonstrated and likely represents the isoform anchored at the cell membrane through the IL-15 receptor α (IL-15Rα chain, because it is sensitive to acidic treatment and is not competent to deliver a reverse signal. By contrast, ptumTEC, RCC, and CSC express a novel N-hyperglycosylated, short-lived transmembrane mb-IL-15 (tmb-IL-15 isoform around 27 kDa, resistant to acidic shock, delivering a reverse signal in response to its soluble receptor (sIL-15Rα. This reverse signal triggers the down-regulation of the tumor suppressor gene E-cadherin in ptumTEC and RCC but not in CSC/CD105+, where it promotes survival. Indeed, through the AKT pathway, tmb-IL-15 protects CSC/CD105+ from non-programmed cell death induced by serum starvation. Finally, both mb-IL-15 and tmb-IL-15 are sensitive to metalloproteases, and the cleaved tmb-IL-15 (25 kDa displays a powerful anti-apoptotic effect on human hematopoietic cells. Overall, our data indicate that both mb-IL-15 and tmb-IL-15 isoforms play a complex role in renal pathophysiology downregulating E-cadherin and favoring cell survival. Moreover, “apparently normal” ptumTEC cells, sharing different properties with RCC, could contribute to organize an enlarged peritumoral “preneoplastic” environment committed to favor tumor progression.

  2. SU-E-T-572: Normal Lung Tissue Sparing in Radiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: To compare normal lung-sparing capabilities of three advanced radiation therapy techniques for locally advanced non-small cell lung cancer (LA-NSCLC). Methods: Four-dimensional computed tomography (4DCT) was performed in 10 patients with stage IIIb LA-NSCLC. The internal target volume (ITV); planning target volume (PTV); and organs at risks (OARs) such as spinal cord, total normal lung, heart, and esophagus were delineated for each CT data set. Intensity-modulated radiation therapy (IMRT), Tomohelical-IMRT (TH-IMRT), and TomoDirect-IMRT (TD-IMRT) plans were generated (total prescribed dose, 66 Gy in 33 fractions to the PTV) for each patient. To reduce the normal lung dose, complete and directional block function was applied outside the normal lung far from the target for both TH-IMRT and TD-IMRT, while pseudo- OAR was set in the same region for IMRT. Dosimetric characteristics of the three plans were compared in terms of target coverage, the sparing capability for the OAR, and the normal tissue complication probability (NTCP). Beam delivery efficiency was also compared. Results: TH-IMRT and TD-IMRT provided better target coverage than IMRT plans. Lung volume receiving ≥–30 Gy, mean dose, and NTCP were significant with TH-IMRT than with IMRT (p=0.006), and volume receiving ≥20–30 Gy was lower in TD-IMRT than in IMRT (p<0.05). Compared with IMRT, TH-IMRT had better sparing effect on the spinal cord (Dmax, NTCP) and heart (V45) (p<0.05). NTCP for the spinal cord, V45 and V60 for the heart, and Dmax for the esophagus were significantly lower in TD-IMRT than in IMRT. The monitor units per fraction were clearly smaller for IMRT than for TH-IMRT and TD-IMRT (p=0.006). Conclusion: In LA-NSCLC, TH-IMRT gave superior PTV coverage and OAR sparing compared to IMRT. TH-IMRT provided better control of the lung volume receiving ≥5–30 Gy. The delivery time and monitor units were lower in TD-IMRT than in TH-IMRT

  3. SU-E-T-572: Normal Lung Tissue Sparing in Radiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hong, C; Ju, S; Ahn, Y [Samsung Medical Center, Seoul (Korea, Republic of)

    2015-06-15

    Purpose: To compare normal lung-sparing capabilities of three advanced radiation therapy techniques for locally advanced non-small cell lung cancer (LA-NSCLC). Methods: Four-dimensional computed tomography (4DCT) was performed in 10 patients with stage IIIb LA-NSCLC. The internal target volume (ITV); planning target volume (PTV); and organs at risks (OARs) such as spinal cord, total normal lung, heart, and esophagus were delineated for each CT data set. Intensity-modulated radiation therapy (IMRT), Tomohelical-IMRT (TH-IMRT), and TomoDirect-IMRT (TD-IMRT) plans were generated (total prescribed dose, 66 Gy in 33 fractions to the PTV) for each patient. To reduce the normal lung dose, complete and directional block function was applied outside the normal lung far from the target for both TH-IMRT and TD-IMRT, while pseudo- OAR was set in the same region for IMRT. Dosimetric characteristics of the three plans were compared in terms of target coverage, the sparing capability for the OAR, and the normal tissue complication probability (NTCP). Beam delivery efficiency was also compared. Results: TH-IMRT and TD-IMRT provided better target coverage than IMRT plans. Lung volume receiving ≥–30 Gy, mean dose, and NTCP were significant with TH-IMRT than with IMRT (p=0.006), and volume receiving ≥20–30 Gy was lower in TD-IMRT than in IMRT (p<0.05). Compared with IMRT, TH-IMRT had better sparing effect on the spinal cord (Dmax, NTCP) and heart (V45) (p<0.05). NTCP for the spinal cord, V45 and V60 for the heart, and Dmax for the esophagus were significantly lower in TD-IMRT than in IMRT. The monitor units per fraction were clearly smaller for IMRT than for TH-IMRT and TD-IMRT (p=0.006). Conclusion: In LA-NSCLC, TH-IMRT gave superior PTV coverage and OAR sparing compared to IMRT. TH-IMRT provided better control of the lung volume receiving ≥5–30 Gy. The delivery time and monitor units were lower in TD-IMRT than in TH-IMRT.

  4. Role of IAPs in prostate cancer progression: immunohistochemical study in normal and pathological (benign hyperplastic, prostatic intraepithelial neoplasia and cancer human prostate

    Directory of Open Access Journals (Sweden)

    Olmedilla Gabriel

    2010-01-01

    Full Text Available Abstract Background In this study was investigate IAPs in normal human prostate (NP, benign prostatic hyperplasia (BPH, prostatic intraepithelial neoplasia (PIN and prostatic carcinoma (PC, and their involvement in apoptosis/proliferation via NF-kB (TNF-α, IL-1 stimulation. Methods Immunohistochemical and Western blot analyses were performed in 10 samples of normal prostates, 35 samples of BPH, 27 samples diagnosis of PIN (with low-grade PIN or high-grade PIN and 95 samples of PC (with low, medium or high Gleason grades. Results In NP, cytoplasm of epithelial cells were positive to c-IAP1/2 (80% of samples, c-IAP-2 (60%, ILP (20%, XIAP (20%; negative to NAIP and survivin. In BPH, epithelial cells were immunostained to c-IAP1/2 (57.57%, c-IAP-2 (57.57%, ILP (66.6%, NAIP (60.6%, XIAP (27.27%, survivin (9.1%. Whereas low-grade PIN showed intermediate results between NP and BPH; results in high-grade PIN were similar to those found in PC. In PC, epithelial cells were immunostained to c-IAP1/2, c-IAP-2, ILP, NAIP, XIAP (no Gleason variation and survivin (increasing with Gleason. Conclusions IAPs could be involved in prostate disorder (BPH, PIN and PC development since might be provoke inhibition of apoptosis and subsequently cell proliferation. At the same time, different transduction pathway such as IL-1/NIK/NF-kB or TNF/NF-kB (NIK or p38 also promotes proliferation. Inhibitions of IAPs, IL-1α and TNFα might be a possible target for PC treatment since IAPs are the proteins that inhibited apoptosis (favour proliferation and IL-1α and TNFα would affect all the transduction pathway involucrate in the activation of transcription factors related to survival or proliferation (NF-kB, Elk-1 or ATF-2.

  5. Role of IAPs in prostate cancer progression: immunohistochemical study in normal and pathological (benign hyperplastic, prostatic intraepithelial neoplasia and cancer) human prostate

    International Nuclear Information System (INIS)

    In this study was investigate IAPs in normal human prostate (NP), benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma (PC), and their involvement in apoptosis/proliferation via NF-kB (TNF-α, IL-1) stimulation. Immunohistochemical and Western blot analyses were performed in 10 samples of normal prostates, 35 samples of BPH, 27 samples diagnosis of PIN (with low-grade PIN or high-grade PIN) and 95 samples of PC (with low, medium or high Gleason grades). In NP, cytoplasm of epithelial cells were positive to c-IAP1/2 (80% of samples), c-IAP-2 (60%), ILP (20%), XIAP (20%); negative to NAIP and survivin. In BPH, epithelial cells were immunostained to c-IAP1/2 (57.57%), c-IAP-2 (57.57%), ILP (66.6%), NAIP (60.6%), XIAP (27.27%), survivin (9.1%). Whereas low-grade PIN showed intermediate results between NP and BPH; results in high-grade PIN were similar to those found in PC. In PC, epithelial cells were immunostained to c-IAP1/2, c-IAP-2, ILP, NAIP, XIAP (no Gleason variation) and survivin (increasing with Gleason). IAPs could be involved in prostate disorder (BPH, PIN and PC) development since might be provoke inhibition of apoptosis and subsequently cell proliferation. At the same time, different transduction pathway such as IL-1/NIK/NF-kB or TNF/NF-kB (NIK or p38) also promotes proliferation. Inhibitions of IAPs, IL-1α and TNFα might be a possible target for PC treatment since IAPs are the proteins that inhibited apoptosis (favour proliferation) and IL-1α and TNFα would affect all the transduction pathway involucrate in the activation of transcription factors related to survival or proliferation (NF-kB, Elk-1 or ATF-2)

  6. Thyroid Cancer

    Science.gov (United States)

    ... body work normally. There are several types of cancer of the thyroid gland. You are at greater ... imaging tests, and a biopsy to diagnose thyroid cancer. Treatment depends on the type of cancer you ...

  7. Natural dietary anti-cancer chemopreventive compounds: redox-mediated differential signaling mechanisms in cytoprotection of normal cellsversus cytotoxicity in tumor cells

    Institute of Scientific and Technical Information of China (English)

    Sujit NAIR; Wenge LI; Ah-Ng Tony KONG

    2007-01-01

    -sensitive transcription factors. We will also discuss the kelch-like erythroid Cap'n'Collar homologue-associated protein 1 (Keap1)-Nrf2axis in redox signaling of induction of phase Ⅱ detoxifying/antioxidant defense mechanisms, an important target and preventive strategy for normal cells against carcinogenesis, and the converse inhibition of cell growth/inflammatory signaling pathways that would confer therapeutic intervention in many types of cancers.Finally, we will summarize the Nrf2 paradigm in gene expression, the pharma-cotoxicogenomic relevance of redox-sensitive Nrf2, and the redox regulation of cell death mechanisms.

  8. Inequalities, Absolute Value, and Logical Connectives.

    Science.gov (United States)

    Parish, Charles R.

    1992-01-01

    Presents an approach to the concept of absolute value that alleviates students' problems with the traditional definition and the use of logical connectives in solving related problems. Uses a model that maps numbers from a horizontal number line to a vertical ray originating from the origin. Provides examples solving absolute value equations and…

  9. Absolute Income, Relative Income, and Happiness

    Science.gov (United States)

    Ball, Richard; Chernova, Kateryna

    2008-01-01

    This paper uses data from the World Values Survey to investigate how an individual's self-reported happiness is related to (i) the level of her income in absolute terms, and (ii) the level of her income relative to other people in her country. The main findings are that (i) both absolute and relative income are positively and significantly…

  10. Investigating Absolute Value: A Real World Application

    Science.gov (United States)

    Kidd, Margaret; Pagni, David

    2009-01-01

    Making connections between various representations is important in mathematics. In this article, the authors discuss the numeric, algebraic, and graphical representations of sums of absolute values of linear functions. The initial explanations are accessible to all students who have experience graphing and who understand that absolute value simply…

  11. Monolithically integrated absolute frequency comb laser system

    Energy Technology Data Exchange (ETDEWEB)

    Wanke, Michael C.

    2016-07-12

    Rather than down-convert optical frequencies, a QCL laser system directly generates a THz frequency comb in a compact monolithically integrated chip that can be locked to an absolute frequency without the need of a frequency-comb synthesizer. The monolithic, absolute frequency comb can provide a THz frequency reference and tool for high-resolution broad band spectroscopy.

  12. Absolute V-R colors of trans-Neptunian objects

    Science.gov (United States)

    Alvarez-Candal, Alvaro; Ayala-Loera, Carmen; Ortiz, Jose-Luis; Duffard, Rene; Estela, Fernandez-Valenzuela; Santos-Sanz, Pablo

    2016-10-01

    The absolute magnitude of a minor body is the apparent magnitude that the body would have if observed from the Sun at a distance of 1AU. Absolute magnitudes are measured using phase curves, showing the change of the magnitude, normalized to unit helio and geo-centric distance, vs. phase angle. The absolute magnitude is then the Y-intercept of the curve. Absolute magnitudes are related to the total reflecting surface of the body and thus bring information of its size, coupled with the reflecting properties.Since 2011 our team has been collecting data from several telescopes spread in Europe and South America. We complemented our data with those available in the literature in order to construct phase curves of trans-Neptunian objects with at least three points. In a first release (Alvarez-Candal et al. 2016, A&A, 586, A155) we showed results for 110 trans-Neptunian objects using V magnitudes only, assuming an overall linear trend and taking into consideration rotational effects, for objects with known light-curves.In this contribution we show results for more than 130 objects, about 100 of them with phase curves in two filters: V and R. We compute absolute magnitudes and phase coefficients in both filters, when available. The average values are HV = 6.39 ± 2.37, βV = (0.09 ± 0.32) mag per degree, HR = 5.38 ± 2.30, and βR = (0.08 ± 0.42) mag per degree.

  13. High-fidelity target sequencing of individual molecules identified using barcode sequences: de novo detection and absolute quantitation of mutations in plasma cell-free DNA from cancer patients

    OpenAIRE

    Kukita, Yoji; Matoba, Ryo; Uchida, Junji; Hamakawa, Takuya; Doki, Yuichiro; Imamura, Fumio; Kato, Kikuya

    2015-01-01

    Circulating tumour DNA (ctDNA) is an emerging field of cancer research. However, current ctDNA analysis is usually restricted to one or a few mutation sites due to technical limitations. In the case of massively parallel DNA sequencers, the number of false positives caused by a high read error rate is a major problem. In addition, the final sequence reads do not represent the original DNA population due to the global amplification step during the template preparation. We established a high-fi...

  14. Normal Tissue Complication Probability Analysis of Acute Gastrointestinal Toxicity in Cervical Cancer Patients Undergoing Intensity Modulated Radiation Therapy and Concurrent Cisplatin

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, Daniel R.; Song, William Y. [Center for Advanced Radiotherapy Technologies, Department of Radiation Oncology, University of California San Diego, La Jolla, CA (United States); Moiseenko, Vitali [Department of Medical Physics, Vancouver Cancer Centre, BC (Canada); Rose, Brent S.; Yashar, Catheryn M.; Mundt, Arno J. [Center for Advanced Radiotherapy Technologies, Department of Radiation Oncology, University of California San Diego, La Jolla, CA (United States); Mell, Loren K., E-mail: lmell@ucsd.edu [Center for Advanced Radiotherapy Technologies, Department of Radiation Oncology, University of California San Diego, La Jolla, CA (United States)

    2012-05-01

    Purpose: To test the hypothesis that increased bowel radiation dose is associated with acute gastrointestinal (GI) toxicity in cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated radiation therapy (IMRT), using a previously derived normal tissue complication probability (NTCP) model. Methods: Fifty patients with Stage I-III cervical cancer undergoing IMRT and concurrent weekly cisplatin were analyzed. Acute GI toxicity was graded using the Radiation Therapy Oncology Group scale, excluding upper GI events. A logistic model was used to test correlations between acute GI toxicity and bowel dosimetric parameters. The primary objective was to test the association between Grade {>=}2 GI toxicity and the volume of bowel receiving {>=}45 Gy (V{sub 45}) using the logistic model. Results: Twenty-three patients (46%) had Grade {>=}2 GI toxicity. The mean (SD) V{sub 45} was 143 mL (99). The mean V{sub 45} values for patients with and without Grade {>=}2 GI toxicity were 176 vs. 115 mL, respectively. Twenty patients (40%) had V{sub 45} >150 mL. The proportion of patients with Grade {>=}2 GI toxicity with and without V{sub 45} >150 mL was 65% vs. 33% (p = 0.03). Logistic model parameter estimates V50 and {gamma} were 161 mL (95% confidence interval [CI] 60-399) and 0.31 (95% CI 0.04-0.63), respectively. On multivariable logistic regression, increased V{sub 45} was associated with an increased odds of Grade {>=}2 GI toxicity (odds ratio 2.19 per 100 mL, 95% CI 1.04-4.63, p = 0.04). Conclusions: Our results support the hypothesis that increasing bowel V{sub 45} is correlated with increased GI toxicity in cervical cancer patients undergoing IMRT and concurrent cisplatin. Reducing bowel V{sub 45} could reduce the risk of Grade {>=}2 GI toxicity by approximately 50% per 100 mL of bowel spared.

  15. Transcatheter hepatic artery embolization of liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Tae; Yoo, Hyung Sik; Suh, Jung Ho [Yonsei University College of Medicine, Seoul (Korea, Republic of); Yun, Heun Yung [Indiana University Hospital, Bloomington (United States)

    1985-12-15

    From March 1985 to September 1985, transcatheter hepatic arterial embolization was performed in 17 primary hepatoma and 8 metastasis of liver in Department of Radiology, Yonsei University College of Medicine. Metastasis cancers of liver were one nasopharyngeal cancer, one small bowel leiomyosarcoma, one gall bladder cancer and 5 colon cancers. The used embolization materials were the followings: Gelfoam particles for one primary hepatoma, 95% absolute ethanol for 4 patients, lvalon (250-590 {mu} m) for 19 patients and autologous blood clots for one metastasis. The results were summarized as the follows: 1. The devascularization of tumor vessels in post-embolization hepatic angiogram was complete in 6 primary hepatoma and one metastasis and partial in 11 primary hepatoma and 7 metastasis. 2. In the follow-up CT evaluation 3 to 4 weeks after embolization, well necrotic density was revealed in 8 primary hepatoma and one metastasis. 3. The complications were fever with higher than 38 .deg. C (92%), abdominal pain (72%) and nausea or vomiting (40%). They were subsided within one to 7 days after embolization. 4. In liver function study, sGOT and sGPT were elevated in 96% of total cases and retuned to normal within 3 to 7 days. Alkaline phosphatase was elevated in 80% of total cases and retuned to normal within 15 to 30 days. LDH was variable. In 4 cases of absolute ethanol infusion, above liver enzymes were markedly elevated as 10 times or more as normal range.

  16. Microelectrical Impedance Spectroscopy for the Differentiation between Normal and Cancerous Human Urothelial Cell Lines: Real-Time Electrical Impedance Measurement at an Optimal Frequency

    Directory of Open Access Journals (Sweden)

    Yangkyu Park

    2016-01-01

    Full Text Available Purpose. To distinguish between normal (SV-HUC-1 and cancerous (TCCSUP human urothelial cell lines using microelectrical impedance spectroscopy (μEIS. Materials and Methods. Two types of μEIS devices were designed and used in combination to measure the impedance of SV-HUC-1 and TCCSUP cells flowing through the channels of the devices. The first device (μEIS-OF was designed to determine the optimal frequency at which the impedance of two cell lines is most distinguishable. The μEIS-OF trapped the flowing cells and measured their impedance at a frequency ranging from 5 kHz to 1 MHz. The second device (μEIS-RT was designed for real-time impedance measurement of the cells at the optimal frequency. The impedance was measured instantaneously as the cells passed the sensing electrodes of μEIS-RT. Results. The optimal frequency, which maximized the average difference of the amplitude and phase angle between the two cell lines (p<0.001, was determined to be 119 kHz. The real-time impedance of the cell lines was measured at 119 kHz; the two cell lines differed significantly in terms of amplitude and phase angle (p<0.001. Conclusion. The μEIS-RT can discriminate SV-HUC-1 and TCCSUP cells by measuring the impedance at the optimal frequency determined by the μEIS-OF.

  17. Microelectrical Impedance Spectroscopy for the Differentiation between Normal and Cancerous Human Urothelial Cell Lines: Real-Time Electrical Impedance Measurement at an Optimal Frequency

    Science.gov (United States)

    Park, Yangkyu; Kim, Hyeon Woo; Yun, Joho; Seo, Seungwan; Park, Chang-Ju; Lee, Jeong Zoo; Lee, Jong-Hyun

    2016-01-01

    Purpose. To distinguish between normal (SV-HUC-1) and cancerous (TCCSUP) human urothelial cell lines using microelectrical impedance spectroscopy (μEIS). Materials and Methods. Two types of μEIS devices were designed and used in combination to measure the impedance of SV-HUC-1 and TCCSUP cells flowing through the channels of the devices. The first device (μEIS-OF) was designed to determine the optimal frequency at which the impedance of two cell lines is most distinguishable. The μEIS-OF trapped the flowing cells and measured their impedance at a frequency ranging from 5 kHz to 1 MHz. The second device (μEIS-RT) was designed for real-time impedance measurement of the cells at the optimal frequency. The impedance was measured instantaneously as the cells passed the sensing electrodes of μEIS-RT. Results. The optimal frequency, which maximized the average difference of the amplitude and phase angle between the two cell lines (p < 0.001), was determined to be 119 kHz. The real-time impedance of the cell lines was measured at 119 kHz; the two cell lines differed significantly in terms of amplitude and phase angle (p < 0.001). Conclusion. The μEIS-RT can discriminate SV-HUC-1 and TCCSUP cells by measuring the impedance at the optimal frequency determined by the μEIS-OF. PMID:26998490

  18. The Simplicity Argument and Absolute Morality

    Science.gov (United States)

    Mijuskovic, Ben

    1975-01-01

    In this paper the author has maintained that there is a similarity of thought to be found in the writings of Cudworth, Emerson, and Husserl in his investigation of an absolute system of morality. (Author/RK)

  19. Absolute calibration technique for spontaneous fission sources

    International Nuclear Information System (INIS)

    An absolute calibration technique for a spontaneously fissioning nuclide (which involves no arbitrary parameters) allows unique determination of the detector efficiency for that nuclide, hence of the fission source strength

  20. Absolute distance metrology for space interferometers

    OpenAIRE

    Swinkels, B L; Wendrich, T.J.; Bhattacharya, N; Wielders, A.A.; Braat, J.J.M.

    2004-01-01

    Space interferometers consisting of several free flying telescopes, such as the planned Darwin mission, require a complex metrology system to make all the components operate as a single instrument. Our research focuses on one of its sub-systems that measures the absolute distance between two satellites with high accuracy. For Darwin the required accuracy would be in the order of 10 μm over 250 meter. To measure this absolute distance, we are currently exploring the frequency sweeping interfer...

  1. Vibrational Circular Dichroism Absolute Configuration of 9,12-Cyclomulin-13-ol, a Diterpene from Azorella and Laretia Species.

    Science.gov (United States)

    Muñoz, Marcelo A; San-Martín, Aurelio; Joseph-Nathan, Pedro

    2015-08-01

    The absolute configuration of the diterpenoid 9,12-cyclomulin-13-ol (1), a constituent of Azorella and Laretia species, has been established by vibrational circular dichroism spectroscopy in combination with density functional theory calculations. The obtained normal diterpene absolute configuration confirms that of azorellanol (2), which was determined by single crystal X-ray diffraction.

  2. Absolute orientations from EBSD measurements - as easy as it seems?

    Science.gov (United States)

    Kilian, Rüdiger; Bestmann, Michel; Heilbronner, Renée

    2016-04-01

    In structural geology, some problems can be addressed by inspecting the crystal orientation of grains in a rock. Deriving shear senses, kinematics of flow, information on deformation processes and recrystallization are some examples. Usually, oriented samples are taken in the field and, if inspected in an universal stage, the researcher has full control over the procedure and can make sure that the derived orientation is related to our geographic reference frame - that it is an absolute orientation. Nowadays, usage of electron backscatter diffraction (EBSD) has greatly improved the information in the derived data (fully crystal orientations, mappings, etc…), and the speed of data acquisition. However, this comes to the price of having to rely on the vendor supplied software and machine setup. Recent benchmarks and comparison of reference data revealed that for various EBSD setups around the world, the orientation data defaults to the wrong absolute orientation. The absolute orientation is not correctly derived - it commonly suffer a 180 degree rotation around the normal of the sample surface. In this contribution we will discuss the implications of such erroneous measurements and what kind of interpretations derived by orientation and texture data will be affected.

  3. The Absolute Magnitudes of Type Ia Supernovae in the Ultraviolet

    CERN Document Server

    Brown, Peter J; Milne, Peter; Bufano, Filomena; Ciardullo, Robin; Elias-Rosa, Nancy; Filippenko, Alexei V; Foley, Ryan J; Gehrels, Neil; Gronwall, Caryl; Hicken, Malcolm; Holland, Stephen T; Hoversten, Erik A; Immler, Stefan; Kirshner, Robert P; Li, Weidong; Mazzali, Paolo; Phillips, Mark M; Pritchard, Tyler; Still, Martin; Turatto, Massimo; Berk, Daniel Vanden

    2010-01-01

    We examine the absolute magnitudes and light-curve shapes of 14 nearby(redshift z = 0.004--0.027) Type Ia supernovae (SNe~Ia) observed in the ultraviolet (UV) with the Swift Ultraviolet/Optical Telescope. Colors and absolute magnitudes are calculated using both a standard Milky Way (MW) extinction law and one for the Large Magellanic Cloud that has been modified by circumstellar scattering. We find very different behavior in the near-UV filters (uvw1_rc covering ~2600-3300 A after removing optical light, and u ~3000--4000 A) compared to a mid-UV filter (uvm2 ~2000-2400 A). The uvw1_rc-b colors show a scatter of ~0.3 mag while uvm2-b scatters by nearly 0.9 mag. Similarly, while the scatter in colors between neighboring filters is small in the optical and somewhat larger in the near-UV, the large scatter in the uvm2-uvw1 colors implies significantly larger spectral variability below 2600 A. We find that in the near-UV the absolute magnitudes at peak brightness of normal SNe Ia in our sample are correlated with ...

  4. The Aging Prostate Is Never "Normal"

    DEFF Research Database (Denmark)

    Schlomm, Thorsten; Weischenfeldt, Joachim; Korbel, Jan;

    2015-01-01

    We argue against the recently published statement that tumor-specific molecular alterations found in "normal" prostate tissue from cancer patients challenge focal therapy approaches that only target a visible cancer lesion and not the adjacent molecular field....

  5. A global algorithm for estimating Absolute Salinity

    Directory of Open Access Journals (Sweden)

    T. J. McDougall

    2012-12-01

    Full Text Available The International Thermodynamic Equation of Seawater – 2010 has defined the thermodynamic properties of seawater in terms of a new salinity variable, Absolute Salinity, which takes into account the spatial variation of the composition of seawater. Absolute Salinity more accurately reflects the effects of the dissolved material in seawater on the thermodynamic properties (particularly density than does Practical Salinity.

    When a seawater sample has standard composition (i.e. the ratios of the constituents of sea salt are the same as those of surface water of the North Atlantic, Practical Salinity can be used to accurately evaluate the thermodynamic properties of seawater. When seawater is not of standard composition, Practical Salinity alone is not sufficient and the Absolute Salinity Anomaly needs to be estimated; this anomaly is as large as 0.025 g kg−1 in the northernmost North Pacific. Here we provide an algorithm for estimating Absolute Salinity Anomaly for any location (x, y, p in the world ocean.

    To develop this algorithm, we used the Absolute Salinity Anomaly that is found by comparing the density calculated from Practical Salinity to the density measured in the laboratory. These estimates of Absolute Salinity Anomaly however are limited to the number of available observations (namely 811. In order to provide a practical method that can be used at any location in the world ocean, we take advantage of approximate relationships between Absolute Salinity Anomaly and silicate concentrations (which are available globally.

  6. Universal Cosmic Absolute and Modern Science

    Science.gov (United States)

    Kostro, Ludwik

    The official Sciences, especially all natural sciences, respect in their researches the principle of methodic naturalism i.e. they consider all phenomena as entirely natural and therefore in their scientific explanations they do never adduce or cite supernatural entities and forces. The purpose of this paper is to show that Modern Science has its own self-existent, self-acting, and self-sufficient Natural All-in Being or Omni-Being i.e. the entire Nature as a Whole that justifies the scientific methodic naturalism. Since this Natural All-in Being is one and only It should be considered as the own scientifically justified Natural Absolute of Science and should be called, in my opinion, the Universal Cosmic Absolute of Modern Science. It will be also shown that the Universal Cosmic Absolute is ontologically enormously stratified and is in its ultimate i.e. in its most fundamental stratum trans-reistic and trans-personal. It means that in its basic stratum. It is neither a Thing or a Person although It contains in Itself all things and persons with all other sentient and conscious individuals as well, On the turn of the 20th century the Science has begun to look for a theory of everything, for a final theory, for a master theory. In my opinion the natural Universal Cosmic Absolute will constitute in such a theory the radical all penetrating Ultimate Basic Reality and will substitute step by step the traditional supernatural personal Absolute.

  7. Absolute calibration in vivo measurement systems

    International Nuclear Information System (INIS)

    Lawrence Livermore National Laboratory (LLNL) is currently investigating a new method for obtaining absolute calibration factors for radiation measurement systems used to measure internally deposited radionuclides in vivo. Absolute calibration of in vivo measurement systems will eliminate the need to generate a series of human surrogate structures (i.e., phantoms) for calibrating in vivo measurement systems. The absolute calibration of in vivo measurement systems utilizes magnetic resonance imaging (MRI) to define physiological structure, size, and composition. The MRI image provides a digitized representation of the physiological structure, which allows for any mathematical distribution of radionuclides within the body. Using Monte Carlo transport codes, the emission spectrum from the body is predicted. The in vivo measurement equipment is calibrated using the Monte Carlo code and adjusting for the intrinsic properties of the detection system. The calibration factors are verified using measurements of existing phantoms and previously obtained measurements of human volunteers. 8 refs

  8. Quantum theory allows for absolute maximal contextuality

    Science.gov (United States)

    Amaral, Barbara; Cunha, Marcelo Terra; Cabello, Adán

    2015-12-01

    Contextuality is a fundamental feature of quantum theory and a necessary resource for quantum computation and communication. It is therefore important to investigate how large contextuality can be in quantum theory. Linear contextuality witnesses can be expressed as a sum S of n probabilities, and the independence number α and the Tsirelson-like number ϑ of the corresponding exclusivity graph are, respectively, the maximum of S for noncontextual theories and for the theory under consideration. A theory allows for absolute maximal contextuality if it has scenarios in which ϑ /α approaches n . Here we show that quantum theory allows for absolute maximal contextuality despite what is suggested by the examination of the quantum violations of Bell and noncontextuality inequalities considered in the past. Our proof is not constructive and does not single out explicit scenarios. Nevertheless, we identify scenarios in which quantum theory allows for almost-absolute-maximal contextuality.

  9. Absolute photoacoustic thermometry in deep tissue.

    Science.gov (United States)

    Yao, Junjie; Ke, Haixin; Tai, Stephen; Zhou, Yong; Wang, Lihong V

    2013-12-15

    Photoacoustic thermography is a promising tool for temperature measurement in deep tissue. Here we propose an absolute temperature measurement method based on the dual temperature dependences of the Grüneisen parameter and the speed of sound in tissue. By taking ratiometric measurements at two adjacent temperatures, we can eliminate the factors that are temperature irrelevant but difficult to correct for in deep tissue. To validate our method, absolute temperatures of blood-filled tubes embedded ~9 mm deep in chicken tissue were measured in a biologically relevant range from 28°C to 46°C. The temperature measurement accuracy was ~0.6°C. The results suggest that our method can be potentially used for absolute temperature monitoring in deep tissue during thermotherapy.

  10. Statistical Validation of Normal Tissue Complication Probability Models

    Energy Technology Data Exchange (ETDEWEB)

    Xu Chengjian, E-mail: c.j.xu@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schaaf, Arjen van der; Veld, Aart A. van' t; Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schilstra, Cornelis [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Radiotherapy Institute Friesland, Leeuwarden (Netherlands)

    2012-09-01

    Purpose: To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. Methods and Materials: A penalized regression method, LASSO (least absolute shrinkage and selection operator), was used to build NTCP models for xerostomia after radiation therapy treatment of head-and-neck cancer. Model assessment was based on the likelihood function and the area under the receiver operating characteristic curve. Results: Repeated double cross-validation showed the uncertainty and instability of the NTCP models and indicated that the statistical significance of model performance can be obtained by permutation testing. Conclusion: Repeated double cross-validation and permutation tests are recommended to validate NTCP models before clinical use.

  11. Absolute Stability And Hyperstability In Hilbert Space

    Science.gov (United States)

    Wen, John Ting-Yung

    1989-01-01

    Theorems on stabilities of feedback control systems proved. Paper presents recent developments regarding theorems of absolute stability and hyperstability of feedforward-and-feedback control system. Theorems applied in analysis of nonlinear, adaptive, and robust control. Extended to provide sufficient conditions for stability in system including nonlinear feedback subsystem and linear time-invariant (LTI) feedforward subsystem, state space of which is Hilbert space, and input and output spaces having finite numbers of dimensions. (In case of absolute stability, feedback subsystem memoryless and possibly time varying. For hyperstability, feedback system dynamical system.)

  12. Precise Measurement of the Absolute Fluorescence Yield

    Science.gov (United States)

    Ave, M.; Bohacova, M.; Daumiller, K.; Di Carlo, P.; di Giulio, C.; San Luis, P. Facal; Gonzales, D.; Hojvat, C.; Hörandel, J. R.; Hrabovsky, M.; Iarlori, M.; Keilhauer, B.; Klages, H.; Kleifges, M.; Kuehn, F.; Monasor, M.; Nozka, L.; Palatka, M.; Petrera, S.; Privitera, P.; Ridky, J.; Rizi, V.; D'Orfeuil, B. Rouille; Salamida, F.; Schovanek, P.; Smida, R.; Spinka, H.; Ulrich, A.; Verzi, V.; Williams, C.

    2011-09-01

    We present preliminary results of the absolute yield of fluorescence emission in atmospheric gases. Measurements were performed at the Fermilab Test Beam Facility with a variety of beam particles and gases. Absolute calibration of the fluorescence yield to 5% level was achieved by comparison with two known light sources--the Cherenkov light emitted by the beam particles, and a calibrated nitrogen laser. The uncertainty of the energy scale of current Ultra-High Energy Cosmic Rays experiments will be significantly improved by the AIRFLY measurement.

  13. What Is Cancer?

    Science.gov (United States)

    ... unneeded cells. Cancer cells may be able to influence the normal cells, molecules, and blood vessels that ... Cancers . We also have collections of information on childhood cancers and cancers in adolescents and young adults . ...

  14. Cancer

    Science.gov (United States)

    ... Blood tests (which look for chemicals such as tumor markers) Bone marrow biopsy (for lymphoma or leukemia) Chest ... the case with skin cancers , as well as cancers of the lung, breast, and colon. If the tumor has spread ...

  15. Det demokratiske argument for absolut ytringsfrihed

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2014-01-01

    Artiklen diskuterer den påstand, at absolut ytringsfrihed er en nødvendig forudsætning for demokratisk legitimitet med udgangspunkt i en rekonstruktion af et argument fremsat af Ronald Dworkin. Spørgsmålet er, hvorfor ytringsfrihed skulle være en forudsætning for demokratisk legitimitet, og hvorf...

  16. Time Function and Absolute Black Hole

    DEFF Research Database (Denmark)

    Javadi, Hossein; Forouzbakhsh, Farshid

    2006-01-01

    Einstein’s theory of gravity is not consistent with quantum mechanics, because general relativity cannot be quantized. [1] But without conversion of force and energy, it is impossible to find a grand unified theory. A very important result of CPH theory is time function that allows we give a new ...... description of absolute black hole and before the big bang....

  17. Teaching Absolute Value Inequalities to Mature Students

    Science.gov (United States)

    Sierpinska, Anna; Bobos, Georgeana; Pruncut, Andreea

    2011-01-01

    This paper gives an account of a teaching experiment on absolute value inequalities, whose aim was to identify characteristics of an approach that would realize the potential of the topic to develop theoretical thinking in students enrolled in prerequisite mathematics courses at a large, urban North American university. The potential is…

  18. ABSOLUTE MEASUREMENT OF THE GANIL BEAM ENERGY

    NARCIS (Netherlands)

    CASANDJIAN, JM; MITTIG, W; BEUNARD, R; GAUDARD, L; LEPINESZILY, A; VILLARI, ACC; AUGER, G; BIANCHI, L; CUNSOLO, A; FOTI, A; LICHTENTHALER, R; PLAGNOL, E; SCHUTZ, Y; SIEMSSEN, RH; WIELECZKO, JP

    1993-01-01

    The energy of the GANIL cyclotron beam was measured on-line during the Pb-208 + Pb-208 elastic scattering experiment ''Search for Color van der Waals Force in the Pb-208 + Pb-208 Mott scattering'' with an absolute precision of 7 x 10(-5) at approximately 1.0 GeV, which represents an improvement of o

  19. Stimulus Probability Effects in Absolute Identification

    Science.gov (United States)

    Kent, Christopher; Lamberts, Koen

    2016-01-01

    This study investigated the effect of stimulus presentation probability on accuracy and response times in an absolute identification task. Three schedules of presentation were used to investigate the interaction between presentation probability and stimulus position within the set. Data from individual participants indicated strong effects of…

  20. Solving Absolute Value Equations Algebraically and Geometrically

    Science.gov (United States)

    Shiyuan, Wei

    2005-01-01

    The way in which students can improve their comprehension by understanding the geometrical meaning of algebraic equations or solving algebraic equation geometrically is described. Students can experiment with the conditions of the absolute value equation presented, for an interesting way to form an overall understanding of the concept.

  1. Absolute-stability results in infinite dimensions

    NARCIS (Netherlands)

    Curtain, RF; Logemann, H; Staffans, O

    2004-01-01

    We derive absolute-stability results of Popov and circle-criterion type for infinite-dimensional systems in an input-output setting. Our results apply to feedback systems in which the linear part is the series interconnection of an input-output stable linear system and an integrator, and the nonline

  2. Magnetoresistive sensor for absolute position detection

    NARCIS (Netherlands)

    Groenland, J.P.J.

    1984-01-01

    A digital measurement principle for absolute position is decscribed. The position data is recorded serially into a single track of a hard-magnetic layer with the help of longitudinal saturation recording. Detection is possible by means of an array of sensor elements which can be made of a substrate.

  3. Thin-film magnetoresistive absolute position detector

    NARCIS (Netherlands)

    Groenland, Johannes Petrus Jacobus

    1990-01-01

    The subject of this thesis is the investigation of a digital absolute posi- tion-detection system, which is based on a position-information carrier (i.e. a magnetic tape) with one single code track on the one hand, and an array of magnetoresistive sensors for the detection of the informatio

  4. Magnetoresistive transducer for absolute position detection

    NARCIS (Netherlands)

    Groenland, J.P.J.

    1984-01-01

    In this paper a new method is presented for the measurement of absolute linear or angular position. The digital position information is recorded serially into one track of a suitable hard-magnetic medium. The stray field of this information layer determines the angular magnetisation distribution in

  5. Prevention of normal tissue complications in radiation therapy of head and neck cancer : the role of 3D conformal radiation therapy (3DCRT)

    NARCIS (Netherlands)

    O.B. Wijers (Oda)

    2002-01-01

    textabstractIn The Netherlands. head and neck cancer (3.9%) ranks the eighth most frequemly diagnoscd malignant tumor. Radiation therapy (IIT) plays an important role in the treatmem of patients with head and neck cancer, as they constitute approximately 6% of those treated in a routine radiation th

  6. The dosimetric impact of daily setup error on target volumes and surrounding normal tissue in the treatment of prostate cancer with intensity-modulated radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Algan, Ozer, E-mail: oalgan@ouhsc.edu [Department of Radiation Oncology, Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Jamgade, Ambarish; Ali, Imad; Christie, Alana; Thompson, J. Spencer; Thompson, David; Ahmad, Salahuddin; Herman, Terence [Department of Radiation Oncology, Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

    2012-01-01

    The purpose of this study was to evaluate the impact of daily setup error and interfraction organ motion on the overall dosimetric radiation treatment plans. Twelve patients undergoing definitive intensity-modulated radiation therapy (IMRT) treatments for prostate cancer were evaluated in this institutional review board-approved study. Each patient had fiducial markers placed into the prostate gland before treatment planning computed tomography scan. IMRT plans were generated using the Eclipse treatment planning system. Each patient was treated to a dose of 8100 cGy given in 45 fractions. In this study, we retrospectively created a plan for each treatment day that had a shift available. To calculate the dose, the patient would have received under this plan, we mathematically 'negated' the shift by moving the isocenter in the exact opposite direction of the shift. The individualized daily plans were combined to generate an overall plan sum. The dose distributions from these plans were compared with the treatment plans that were used to treat the patients. Three-hundred ninety daily shifts were negated and their corresponding plans evaluated. The mean isocenter shift based on the location of the fiducial markers was 3.3 {+-} 6.5 mm to the right, 1.6 {+-} 5.1 mm posteriorly, and 1.0 {+-} 5.0 mm along the caudal direction. The mean D95 doses for the prostate gland when setup error was corrected and uncorrected were 8228 and 7844 cGy (p < 0.002), respectively, and for the planning target volume (PTV8100) was 8089 and 7303 cGy (p < 0.001), respectively. The mean V95 values when patient setup was corrected and uncorrected were 99.9% and 87.3%, respectively, for the PTV8100 volume (p < 0.0001). At an individual patient level, the difference in the D95 value for the prostate volume could be >1200 cGy and for the PTV8100 could approach almost 2000 cGy when comparing corrected against uncorrected plans. There was no statistically significant difference in the D35

  7. The accumulation of DNA demethylation in Sat α in normal gastric tissues with Helicobacter pylori infection renders susceptibility to gastric cancer in some individuals.

    Science.gov (United States)

    Saito, Masaaki; Suzuki, Koichi; Maeda, Takafumi; Kato, Takaharu; Kamiyama, Hidenori; Koizumi, Kei; Miyaki, Yuichiro; Okada, Shinichiro; Kiyozaki, Hirokazu; Konishi, Fumio

    2012-06-01

    Helicobacter pylori (HP) infection is widely recognized as a risk factor for gastric cancer, but only a minority of infected individuals develop gastric cancer. The aim of this study was to determine whether DNA demethylation in non-cancerous gastric mucosa (NGM) significantly enhances susceptibility to gastric cancer. A total of 165 healthy volunteers, including 83 HP-positive and 82-negative individuals, as well as 83 patients with single and 18 with synchronous double gastric cancer (GC) were enrolled in this study. The relative demethylation levels (RDLs) of repetitive sequences, including Alu, LINE-1 and Sat α, were quantified by real-time methylation-specific polymerase chain reaction. The Alu RDL did not exhibit any differences within each respective group, whereas LINE-1 RDL was significantly elevated in cancer tissues compared with the NGM in the other groups (P<0.001). Our results indicated that a gradual increase in Sat α RDL correlated with HP infection and cancer development. Sat α RDL was significantly elevated in the NGM in HP-positive compared with HP-negative (P<0.001), and significantly elevated in cancer tissues (P<0.001). Although the Sat α RDL of the NGM in the total population increased in an age-dependent manner, it was significantly increased in a fraction of younger GC patients (<45 years) compared with all of the others (45 years or older, P=0.0391). In addition, double GC exhibited a significantly higher Sat α RDL in the NGM compared with single GC (P=0.0014). In these two fractions, Sat α RDL in the NGM exhibited an inverse correlation with age. In conclusion, the present study demonstrated that the accumulation of DNA demethylation in Sat α RDL in the NGM with HP infection potentially renders susceptibility to gastric cancer in a fraction of GC patients younger than 45 years or in patients with multiple cancers. PMID:22426602

  8. 癌和正常细胞熵产生的差异性及其治疗意义%Attempts to Introduce Thermodynamics in Anticancer Therapy Using Entropy Production Difference between Cancer and Normal Cells

    Institute of Scientific and Technical Information of China (English)

    罗辽复; Molnar J; 丁辉; 吕晓桂; Spengler G

    2006-01-01

    During the tumor growth there are many differences between the healthy tissue and growing tumor,including metabolic,structural and thermodynamic differences,etc.Both structural and thermodynamic differences can be used to follow the entropy differences in cancer and normal tissue.Entropy productions due to various dissipation mechanisms based on temperature-differences,chemical potential gradient,chemical affinity,viscous stress and exerted field as driving forces are promising tools to be calculated as a potential targets for tumor isolation and demarcation.The relative importance of five terms of entropy production was compared by numerical estimation.It was demonstrated by quantitative calculation that the entropy production rate of cancerous cell is always higher than healthy cell apart from the case of external field applied.Different entropy production rates between two kinds of cells determine the direction of entropy flow among cells.The entropy flow from cancers to healthy cells would take along the harmful information of cancerous cell,propagating its toxic action to healthy tissues.To change the direction of entropy flow two ways are proposed.One is to reduce entropy production rate of cancerous cells through designing certain biochemical pathways,for example,producing pH gradient between cancer and normal.Another is to apply an external field (including electric field and ultrasound) to cells and enhance the entropy production rate of normal cells.We prove that an applied electric field with enough intensity and frequency or a low frequency and low intensity ultrasound irradiation may induce increasing entropy production rate in normal tissue around the tumor,consequently reverse the direction of entropy current.%通过热力学计算证明通常条件下癌细胞的熵产生率高于正常细胞,熵流方向为从癌到正常组织.但在适当外场作用下, 正常细胞的熵产生率可提高更多,因而可以改变熵流方向,从而抑止癌的

  9. Lymphatic abnormalities in the normal contralateral arms of subjects with breast cancer-related lymphedema as assessed by near-infrared fluorescent imaging

    OpenAIRE

    Aldrich, Melissa B.; Guilliod, Renie; Fife, Caroline E.; Maus, Erik A.; Smith, Latisha; Rasmussen, John C.; Sevick-Muraca, Eva M.

    2012-01-01

    Current treatment of unilateral breast cancer-related lymphedema (BCRL) is only directed to the afflicted arm. Near-infrared fluorescent imaging (NIRF) of arm lymphatic vessel architecture and function in BCRL and control subjects revealed a trend of increased lymphatic abnormalities in both the afflicted and unafflicted arms with increasing time after lymphedema onset. These pilot results show that BCRL may progress to affect the clinically “normal” arm, and suggest that cancer-related lymph...

  10. Exploring the spatial dimension of estrogen and progesterone signaling: detection of nuclear labeling in lobular epithelial cells in normal mammary glands adjacent to breast cancer

    OpenAIRE

    Grote, Anne; Abbas, Mahmoud; Linder, Nina; Kreipe, Hans H.; Lundin, Johan; Feuerhake, Friedrich

    2014-01-01

    Abstract Background Comprehensive spatial assessment of hormone receptor immunohistochemistry staining in digital whole slide images of breast cancer requires accurate detection of positive nuclei within biologically relevant regions of interest. Herein, we propose a combination of automated region labeling at low resolution and subsequent detailed tissue evaluation of subcellular structures in lobular structures adjacent to breast cancer, as a proof of concept for the approach to analy...

  11. Metabolites of Ginger Component [6]-Shogaol Remain Bioactive in Cancer Cells and Have Low Toxicity in Normal Cells: Chemical Synthesis and Biological Evaluation

    OpenAIRE

    Yingdong Zhu; Warin, Renaud F.; Soroka, Dominique N.; Huadong Chen; Shengmin Sang

    2013-01-01

    Our previous study found that [6]-shogaol, a major bioactive component in ginger, is extensively metabolized in cancer cells and in mice. It is unclear whether these metabolites retain bioactivity. The aim of the current study is to synthesize the major metabolites of [6]-shogaol and evaluate their inhibition of growth and induction of apoptosis in human cancer cells. Twelve metabolites of [6]-shogaol (M1, M2, and M4-M13) were successfully synthesized using simple and easily accessible chemic...

  12. An absolute measure for a key currency

    Science.gov (United States)

    Oya, Shunsuke; Aihara, Kazuyuki; Hirata, Yoshito

    It is generally considered that the US dollar and the euro are the key currencies in the world and in Europe, respectively. However, there is no absolute general measure for a key currency. Here, we investigate the 24-hour periodicity of foreign exchange markets using a recurrence plot, and define an absolute measure for a key currency based on the strength of the periodicity. Moreover, we analyze the time evolution of this measure. The results show that the credibility of the US dollar has not decreased significantly since the Lehman shock, when the Lehman Brothers bankrupted and influenced the economic markets, and has increased even relatively better than that of the euro and that of the Japanese yen.

  13. Absolute Parallelism Geometry: Developments, Applications and Problems

    OpenAIRE

    Wanas, M. I.

    2002-01-01

    Absolute parallelism geometry is frequently used for physical applications. It has two main defects, from the point of view of applications. The first is the identical vanishing of its curvature tensor. The second is that its autoparallel paths do not represent physical trajectories. The present work shows how these defects were treated in the course of development of the geometry. The new version of this geometry contains simultaneous non-vanishing torsion and curvatures. Also, the new paths...

  14. Cosmological frames for theories with absolute parallelism

    OpenAIRE

    Ferraro, Rafael; Fiorini, Franco

    2011-01-01

    The vierbein (tetrad) fields for closed and open Friedmann-Robertson-Walker cosmologies are hard to work out in most of the theories featuring absolute parallelism. The difficulty is traced in the fact that these theories are not invariant under local Lorentz transformations of the vierbein. We illustrate this issue in the framework of f(T) theories and Born-Infeld determinantal gravity. In particular, we show that the early Universe as described by the Born-Infeld scheme is singularity free ...

  15. The absolute differential calculus (calculus of tensors)

    CERN Document Server

    Levi-Civita, Tullio

    2013-01-01

    Written by a towering figure of twentieth-century mathematics, this classic examines the mathematical background necessary for a grasp of relativity theory. Tullio Levi-Civita provides a thorough treatment of the introductory theories that form the basis for discussions of fundamental quadratic forms and absolute differential calculus, and he further explores physical applications.Part one opens with considerations of functional determinants and matrices, advancing to systems of total differential equations, linear partial differential equations, algebraic foundations, and a geometrical intro

  16. Absolute clock synchronisation and special relativity paradoxes

    OpenAIRE

    Ciborowski, Jacek; Wlodarczyk, Marta

    2012-01-01

    Solving special relativity paradoxes requires rigorous analysis of event timing, due to relative simultaneity in consequence of the Lorentz transformation. Since clock synchronisation is a convention in special theory of relativity, instead of the Einstein's procedure one may choose such that offers absolute simultaneity. We present in short the corresponding formalism in one spatial dimension. We show that paradoxes do not arise with this choice of synchronisation and descriptions of these i...

  17. Absolute distance metrology for space interferometers

    OpenAIRE

    Swinkels, B L; Bhattacharya, N; Wielders, A.A.; Braat, J.J.M.

    2005-01-01

    Future space missions, among which the Darwin Space Interferometer, will consist of several free flying satellites. A complex metrology system is required to have all the components fly accurately in formation and have it operate as a single instrument. Our work focuses on a possible implementation of the sub-system that measures the absolute distance between two satellites with high accuracy. For Darwin the required accuracy is on the order of 70 micrometer over a distance of 250 meter. We a...

  18. [Cancer].

    Science.gov (United States)

    de la Peña-López, Roberto; Remolina-Bonilla, Yuly Andrea

    2016-09-01

    Cancer is a group of diseases which represents a significant public health problem in Mexico and worldwide. In Mexico neoplasms are the second leading cause of death. An increased morbidity and mortality are expected in the next decades. Several preventable risk factors for cancer development have been identified, the most relevant including tobacco use, which accounts for 30% of the cancer cases; and obesity, associated to another 30%. These factors, in turn, are related to sedentarism, alcohol abuse and imbalanced diets. Some agents are well knokn to cause cancer such as ionizing radiation, viruses such as the papilloma virus (HPV) and hepatitis virus (B and C), and more recently environmental pollution exposure and red meat consumption have been pointed out as carcinogens by the International Agency for Research in Cancer (IARC). The scientific evidence currently available is insufficient to consider milk either as a risk factor or protective factor against different types of cancer. PMID:27603890

  19. Measurement of absolute gravity acceleration in Firenze

    Directory of Open Access Journals (Sweden)

    M. de Angelis

    2011-01-01

    Full Text Available This paper reports the results from the accurate measurement of the acceleration of gravity g taken at two separate premises in the Polo Scientifico of the University of Firenze (Italy. In these laboratories, two separate experiments aiming at measuring the Newtonian constant and testing the Newtonian law at short distances are in progress. Both experiments require an independent knowledge on the local value of g. The only available datum, pertaining to the italian zero-order gravity network, was taken more than 20 years ago at a distance of more than 60 km from the study site. Gravity measurements were conducted using an FG5 absolute gravimeter, and accompanied by seismic recordings for evaluating the noise condition at the site. The absolute accelerations of gravity at the two laboratories are (980 492 160.6 ± 4.0 μGal and (980 492 048.3 ± 3.0 μGal for the European Laboratory for Non-Linear Spectroscopy (LENS and Dipartimento di Fisica e Astronomia, respectively. Other than for the two referenced experiments, the data here presented will serve as a benchmark for any future study requiring an accurate knowledge of the absolute value of the acceleration of gravity in the study region.

  20. Measurement of absolute gravity acceleration in Firenze

    Science.gov (United States)

    de Angelis, M.; Greco, F.; Pistorio, A.; Poli, N.; Prevedelli, M.; Saccorotti, G.; Sorrentino, F.; Tino, G. M.

    2011-01-01

    This paper reports the results from the accurate measurement of the acceleration of gravity g taken at two separate premises in the Polo Scientifico of the University of Firenze (Italy). In these laboratories, two separate experiments aiming at measuring the Newtonian constant and testing the Newtonian law at short distances are in progress. Both experiments require an independent knowledge on the local value of g. The only available datum, pertaining to the italian zero-order gravity network, was taken more than 20 years ago at a distance of more than 60 km from the study site. Gravity measurements were conducted using an FG5 absolute gravimeter, and accompanied by seismic recordings for evaluating the noise condition at the site. The absolute accelerations of gravity at the two laboratories are (980 492 160.6 ± 4.0) μGal and (980 492 048.3 ± 3.0) μGal for the European Laboratory for Non-Linear Spectroscopy (LENS) and Dipartimento di Fisica e Astronomia, respectively. Other than for the two referenced experiments, the data here presented will serve as a benchmark for any future study requiring an accurate knowledge of the absolute value of the acceleration of gravity in the study region.

  1. Absolute Oxygenation Metabolism Measurements Using Magnetic Resonance Imaging

    OpenAIRE

    An, Hongyu; Liu, Qingwei; Eldeniz, Cihat; Lin, Weili

    2011-01-01

    Cerebral oxygen metabolism plays a critical role in maintaining normal function of the brain. It is the primary energy source to sustain neuronal functions. Abnormalities in oxygen metabolism occur in various neuro-pathologic conditions such as ischemic stroke, cerebral trauma, cancer, Alzheimer’s disease and shock. Therefore, the ability to quantitatively measure tissue oxygenation and oxygen metabolism is essential to the understanding of pathophysiology and treatment of various diseases. T...

  2. Screening for Prostate Cancer

    Science.gov (United States)

    ... absolute reduction in mortal- ity. Preliminary results from PIVOT (Prostate Cancer In- tervention Versus Observation Trial), in ... early PSA screening era, prelim- inary findings from PIVOT show that, after 12 years, in- tention to ...

  3. Expression patterns of DLK1 and INSL3 identify stages of Leydig cell differentiation during normal development and in testicular pathologies, including testicular cancer and Klinefelter syndrome

    DEFF Research Database (Denmark)

    Lottrup, G; Nielsen, J E; Maroun, L L;

    2014-01-01

    STUDY QUESTION: What is the differentiation stage of human testicular interstitial cells, in particular Leydig cells (LC), within micronodules found in patients with infertility, testicular cancer and Klinefelter syndrome? SUMMARY ANSWER: The Leydig- and peritubular-cell populations in testes with......, are impaired in adult men with testicular pathologies including testis cancer and Klinefelter syndrome. STUDY FUNDING/COMPETING INTERESTS: This work was funded by Rigshospitalet's research funds, the Danish Cancer Society and Kirsten and Freddy Johansen's foundation. The authors have no conflicts of...... specimens and in 58 adult testis samples from patients with testicular germ cell tumours, including precursor carcinoma in situ (CIS), infertility or Klinefelter syndrome. PARTICIPANTS/MATERIALS, SETTING, METHODS: The expression patterns of DLK1, INSL3, chicken ovalbumin upstream promoter transcription...

  4. Existing conditions of full bandgaps and absolute negative refraction in metallic-dielectric photonic crystal

    Institute of Scientific and Technical Information of China (English)

    Dong Jian-Wen; Hu Xin-Hua; Wang He-Zhou

    2007-01-01

    This paper has theoretically studied the characteristic frequencies of band structures in two-dimensional metallicdielectric photonic crystals. It is demonstrated that a large filling fraction benefits the existence of absolute photonic band gap, while a smaller filling fraction benefits an absolute negative refraction band. In addition, it also finds that the relation between the cut-off frequency of E-polarized wave and the filling fraction exceeding 10% is content with a linear increasing function, whose coefficients are exponential to the normalized lattice constant. These investigations have significant implications for tuning the operational frequencies to desired applications and manufacturing photonic crystals.

  5. Expression of matrix metalloproteinases 2 and 9 in human gastric cancer and superficial gastritis

    Science.gov (United States)

    Sampieri, Clara Luz; de la Peña, Sol; Ochoa-Lara, Mariana; Zenteno-Cuevas, Roberto; León-Córdoba, Kenneth

    2010-01-01

    AIM: To assess expression of matrix metalloproteinases 2 (MMP2) and MMP9 in gastric cancer, superficial gastritis and normal mucosa, and to measure metalloproteinase activity. METHODS: MMP2 and MMP9 mRNA expression was determined by quantitative real-time polymerase chain reaction. Normalization was carried out using three different factors. Proteins were analyzed by quantitative gelatin zymography (qGZ). RESULTS: 18S ribosomal RNA (18SRNA) was very highly expressed, while hypoxanthine ribosyltransferase-1 (HPRT-1) was moderately expressed. MMP2 was highly expressed, while MMP9 was not detected or lowly expressed in normal tissues, moderately or highly expressed in gastritis and highly expressed in cancer. Relative expression of 18SRNA and HPRT-1 showed no significant differences. Significant differences in MMP2 and MMP9 were found between cancer and normal tissue, but not between gastritis and normal tissue. Absolute quantification of MMP9 echoed this pattern, but differential expression of MMP2 proved conflictive. Analysis by qGZ indicated significant differences between cancer and normal tissue in MMP-2, total MMP-9, 250 and 110 kDa bands. CONCLUSION: MMP9 expression is enhanced in gastric cancer compared to normal mucosa; interpretation of differential expression of MMP2 is difficult to establish. PMID:20333791

  6. Classification of Laser Induced Fluorescence Spectra from Normal and Malignant bladder tissues using Learning Vector Quantization Neural Network in Bladder Cancer Diagnosis

    DEFF Research Database (Denmark)

    Karemore, Gopal Raghunath; Mascarenhas, Kim Komal; Patil, Choudhary;

    2008-01-01

    classification accuracy of LVQ with other classifiers (eg. SVM and Multi Layer Perceptron) for the same data set. Good agreement has been obtained between LVQ based classification of spectroscopy data and histopathology results which demonstrate the use of LVQ classifier in bladder cancer diagnosis....

  7. Circulating Vascular Endothelial Growth Factor (VEGF Levels in Advanced Stage Cancer Patients Compared to Normal Controls and Diabetes Mellitus Patients with Critical Ischemia

    Directory of Open Access Journals (Sweden)

    Yoka H. Kusumanto

    2007-01-01

    Full Text Available Anti-angiogenic therapy is emerging as a valuable tool in the treatment of patients with cancer. As VEGF is a central target in anti-angiogenic therapy, its levels in the circulation might be relevant in selecting tumor types or patients likely to respond to this treatment. Additional VEGF has been recognized as a key factor in the pathogenesis of diabetic retinopathy. Recently anti-angiogenic therapy has been advocated in this situation. We measured VEGF levels in whole blood in 42 patients with high grade (n = 26 and low grade (n = 16 end stage cancer, and in 28 healthy controls and 37 patients with diabetes related vascular disease. Only 2/26 patients in the group of high grade cancer had signifi cantly elevated VEGF levels, 1/16 in the low grade group and 1/28 in the healthy control group. In contrast, in 10/37 diabetic patients the mean VEGF levels were significantly elevated compared to the other groups. The mean level in these diabetic patients was significantly elevated compared to the other groups. These data indicate the limitation of the use of circulating VEGF levels as a potential selection criterion for anti-angiogenic therapy in cancer patients and suggest further studies into its application in the management of diabetic complications.

  8. Absolute calibration of the Auger fluorescence detectors

    Energy Technology Data Exchange (ETDEWEB)

    Bauleo, P.; Brack, J.; Garrard, L.; Harton, J.; Knapik, R.; Meyhandan, R.; Rovero, A.C.; /Buenos Aires, IAFE; Tamashiro, A.; Warner, D.

    2005-07-01

    Absolute calibration of the Pierre Auger Observatory fluorescence detectors uses a light source at the telescope aperture. The technique accounts for the combined effects of all detector components in a single measurement. The calibrated 2.5 m diameter light source fills the aperture, providing uniform illumination to each pixel. The known flux from the light source and the response of the acquisition system give the required calibration for each pixel. In the lab, light source uniformity is studied using CCD images and the intensity is measured relative to NIST-calibrated photodiodes. Overall uncertainties are presently 12%, and are dominated by systematics.

  9. Musical Activity Tunes Up Absolute Pitch Ability

    DEFF Research Database (Denmark)

    Dohn, Anders; Garza-Villarreal, Eduardo A.; Ribe, Lars Riisgaard;

    2014-01-01

    Absolute pitch (AP) is the ability to identify or produce pitches of musical tones without an external reference. Active AP (i.e., pitch production or pitch adjustment) and passive AP (i.e., pitch identification) are considered to not necessarily coincide, although no study has properly compared...... that APs generally undershoot when adjusting musical pitch, a tendency that decreases when musical activity increases. Finally, APs are less accurate when adjusting the pitch to black key targets than to white key targets. Hence, AP ability may be partly practice-dependent and we speculate that APs may...... benefit from frequent contact with fixed standard chroma to keep in tune....

  10. Absolute Priority for a Vehicle in VANET

    Science.gov (United States)

    Shirani, Rostam; Hendessi, Faramarz; Montazeri, Mohammad Ali; Sheikh Zefreh, Mohammad

    In today's world, traffic jams waste hundreds of hours of our life. This causes many researchers try to resolve the problem with the idea of Intelligent Transportation System. For some applications like a travelling ambulance, it is important to reduce delay even for a second. In this paper, we propose a completely infrastructure-less approach for finding shortest path and controlling traffic light to provide absolute priority for an emergency vehicle. We use the idea of vehicular ad-hoc networking to reduce the imposed travelling time. Then, we simulate our proposed protocol and compare it with a centrally controlled traffic light system.

  11. Development of an absolute neutron dosimeter

    Energy Technology Data Exchange (ETDEWEB)

    Acevedo, C; Birstein, L; Loyola, H [Section de Desarrollos Innovativos, Comision Chilena de EnergIa Nuclear (CCHEN), Casilla 188-D, Santiago (Chile)], E-mail: lbirstei@cchen.cl

    2008-11-01

    An Absolute Neutron Dosimeter was developed to be used as a calibration standard for the Radiation Metrology Laboratory at CCHEN. The main component of the Dosimeter consists of a Proportional Counter of cylindrical shape, with Polyethylene walls and Ethylene gas in its interior. It includes a cage shaped arrangement of graphite bars that operates like the Proportional Counter cathode and a tungsten wire of 25 {mu}m in diameter {mu}m as the anode. Results of a Montecarlo modeling for the Dosimeter operation and results of tests and measurements performed with a radioactive source are presented.

  12. ABSOLUT LOMO绝对创意

    Institute of Scientific and Technical Information of China (English)

    婷婷(整理)

    2007-01-01

    ABSOLUT与创意素来有着不解之缘。由Andy Warhal的ABSOLUT WARHOL至今,已有超过400位不同领域的创意大师为ABSOLUT的当代艺术宝库贡献了自己的得意之作。ABSOLUT的创意仿佛永远不会枯竭,而一系列的作品也让惊喜从未落空。

  13. In vitro and in silico evaluation of NF-κB targeted costunolide action on estrogen receptor-negative breast cancer cells--a comparison with normal breast cells.

    Science.gov (United States)

    Pitchai, Daisy; Roy, Anita; Banu, Sakhila

    2014-10-01

    Costunolide, a sesquiterpene lactone is a plant-derived secondary metabolite found to be present in most of the pharmacologically active herbs, being the cause for their medicinal values. The present study aims to evaluate the cytotoxic effect of costunolide isolated from Costus speciosus rhizome extract on MDA-MB-231 cells and explore its targeted action in comparison with its action on the normal breast cells (MCF 10A). The effect of costunolide on cell viability of the cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay. The targeted action of the compound was analyzed comparing the effectiveness of the compound to alter the protein expression levels of NF-κB subunits in the normal and the cancer cells using western blotting analysis. In silico studies were performed to predict the targeted interaction of costunolide with the NF-κB subunit proteins. Costunolide inhibited the cell viability of MDA-MB-231 cells in a dose-dependent manner leaving no significant change in the viability of the normal breast cells. The over expressed NF-κB subunits - p65, 52 and 100 in the cancer cells were found to be downregulated when treated with costunolide at an effective dose of 20 and 40 μM costunolide. In silico results provided stable interactions between costunolide and the target proteins, supporting the in vitro results in addition. Thus, costunolide derived from C. speciosus plant source elevates a fresh conviction for its use in breast cancer therapy for its cytotoxic efficacy and non-toxic nature. PMID:24733523

  14. Low doses of ethanolic extract of Boldo (Peumus boldus) can ameliorate toxicity generated by cisplatin in normal liver cells of mice in vivo and in WRL-68 cells in vitro, but not in cancer cells in vivo or in vitro

    Institute of Scientific and Technical Information of China (English)

    Jesmin Mondal; Kausik Bishayee; Ashis Kumar Panigrahi; Anisur Rahman Khuda-Bukhsh

    2014-01-01

    OBJECTIVE:Use of cisplatin, a conventional anticancer drug, is restricted because it generates strong hepatotoxicity by accumulating in liver. Therefore its anticancer potential can only be fully exploited if its own toxicity is considerably reduced. Towards this goal, ethanolic extract of the plant, Boldo (Peumus boldus), known for its antihepatotoxic effects, was used simultaneously with cisplatin, to test its ability to reduce cisplatin’s cytotoxicity without affecting its anticancer potential. METHODS: The cytotoxicity of Boldo extract (BE) and cisplatin, administered alone and in combination, was determined in three cancer cell lines (A549, HeLa, and HepG2) and in normal liver cells (WRL-68). Drug-DNA interaction, DNA damage, cell cycle, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP, ΔΨ) were also studied. Hepatotoxicity and antioxidant activity levels were determined by alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and glutathione assays in mice. The cytotoxicity of related proteins was tested by Western blotting. RESULTS:Co-administration of BE and cisplatin increased viability of normal cells, but had no effect on the viability of cancer cells. Boldo protected liver from damage and normalized different antioxidant enzyme levels in vivo and also reduced ROS and re-polarized MMP in vitro. Bax and cytochrome c translocation was reduced with caspase 3 down-regulation. Further, a drug-DNA interaction study revealed that BE reduced cisplatin’s DNA-binding capacity, resulting in a reduction in DNA damage. CONCLUSION: Results indicated that a low dose of BE could be used beneifcial y in combination with cisplatin to reduce its toxicity without hampering cisplatin’s anticancer effect. These ifndings signify a potential future use of BE in cancer therapy.

  15. Antiausterity activity of arctigenin enantiomers: importance of (2R,3R)-absolute configuration.

    Science.gov (United States)

    Awale, Suresh; Kato, Mamoru; Dibwe, Dya Fita; Li, Feng; Miyoshi, Chika; Esumi, Hiroyasu; Kadota, Shigetoshi; Tezuka, Yasuhiro

    2014-01-01

    From a MeOH extract of powdered roots of Wikstroemia indica, six dibenzyl-gamma-butyrolactone-type lignans with (2S,3S)-absolute configuration [(+)-arctigenin (1), (+)-matairesinol (2), (+)-trachelogenin (3), (+)-nortrachelogenin (4), (+)-hinokinin (5), and (+)-kusunokinin (6)] were isolated, whereas three dibenzyl-gamma-butyrolactone-type lignans with (2R,3R)-absolute configuration [(-)-arctigenin (1*), (-)-matairesinol (2*), (-)-trachelogenin (3*)] were isolated from Trachelospermum asiaticum. The in vitro preferential cytotoxic activity of the nine compounds was evaluated against human pancreatic PANC-1 cancer cells in nutrient-deprived medium (NDM), but none of the six lignans (1-6) with (2S,3S)-absolute configuration showed preferential cytotoxicity. On the other hand, three lignans (1*-3*) with (2R,3R)-absolute configuration exhibited preferential cytotoxicity in a concentration-dependent manner with PC50 values of 0.54, 6.82, and 5.85 microM, respectively. Furthermore, the effect of (-)- and (+)-arctigenin was evaluated against the activation of Akt, which is a key process in the tolerance to nutrition starvation. Interestingly, only (-)-arctigenin (1*) strongly suppressed the activation of Akt. These results indicate that the (2R,3R)-absolute configuration of (-)-enantiomers should be required for the preferential cytotoxicity through the inhibition of Akt activation. PMID:24660468

  16. Isotope dilution strategies for absolute quantitative proteomics

    International Nuclear Information System (INIS)

    The development of mass spectrometry (MS)-based methodologies for high-throughput protein identification has generated a concomitant need for protein quantification. Numerous MS-based relative quantification methodologies have been dedicated to the extensive comparison of multiple proteomes. On the other hand, absolute quantification methodologies, which allow the determination of protein concentrations in biological samples, are generally restricted to defined sets of proteins. Depending on the selected analytical procedure, absolute quantification approaches can provide accurate and precise estimations. These analytical performances are crucial for specific applications such as the evaluation of clinical bio-marker candidates. According to bioanalytical guidelines, accurate analytical processes require internal standards and quality controls. Regarding MS-based analysis of small molecules, isotope dilution has been recognized as the reference method for internal standardization. However, protein quantification methodologies which rely on the isotope dilution principle have been implemented in the proteomic field only recently. In these approaches, the sample is spiked with defined amounts of isotope-labeled analogue(s) of specific proteolytic peptide(s) (AQUA and QconCAT strategies) or protein(s) (PSAQ strategy). In this review, we present a critical overview of these isotope dilution methodologies. (authors)

  17. A Conceptual Approach to Absolute Value Equations and Inequalities

    Science.gov (United States)

    Ellis, Mark W.; Bryson, Janet L.

    2011-01-01

    The absolute value learning objective in high school mathematics requires students to solve far more complex absolute value equations and inequalities. When absolute value problems become more complex, students often do not have sufficient conceptual understanding to make any sense of what is happening mathematically. The authors suggest that the…

  18. Using, Seeing, Feeling, and Doing Absolute Value for Deeper Understanding

    Science.gov (United States)

    Ponce, Gregorio A.

    2008-01-01

    Using sticky notes and number lines, a hands-on activity is shared that anchors initial student thinking about absolute value. The initial point of reference should help students successfully evaluate numeric problems involving absolute value. They should also be able to solve absolute value equations and inequalities that are typically found in…

  19. Invariant and Absolute Invariant Means of Double Sequences

    Directory of Open Access Journals (Sweden)

    Abdullah Alotaibi

    2012-01-01

    Full Text Available We examine some properties of the invariant mean, define the concepts of strong σ-convergence and absolute σ-convergence for double sequences, and determine the associated sublinear functionals. We also define the absolute invariant mean through which the space of absolutely σ-convergent double sequences is characterized.

  20. Optimization of an Enrichment process for Circulating tumor cells from the blood of Head and Neck Cancer patients through depletion of normal cells

    OpenAIRE

    Yang, Liying; Lang, James C.; Balasubramanian, Priya; Jatana, Kris R.; Schuller, David; Agrawal, Amit; Zborowski, Maciej; Chalmers, Jeffrey J.

    2009-01-01

    The optimization of a purely negative depletion, enrichment process for circulating tumor cells, CTC's, in the peripheral blood of Head and Neck cancer patients is presented. The enrichment process uses a red cell lysis step followed by immunomagnetic labeling, and subsequent depletion, of CD45 positive cells. A number of relevant variables are quantified, or attempted to be quantified, which control the performance of the enrichment process. Six different immunomagnetic labeling combinations...

  1. CHRNA5 as negative regulator of nicotine signaling in normal and cancer bronchial cells: effects on motility, migration and p63 expression.

    Science.gov (United States)

    Krais, Annette M; Hautefeuille, Agnès H; Cros, Marie-Pierre; Krutovskikh, Vladimir; Tournier, Jean-Marie; Birembaut, Philippe; Thépot, Amélie; Paliwal, Anupam; Herceg, Zdenko; Boffetta, Paolo; Brennan, Paul; Hainaut, Pierre L

    2011-09-01

    Genome-wide association studies have linked lung cancer risk with a region of chromosome 15q25.1 containing CHRNA3, CHRNA5 and CHRNB4 encoding α3, α5 and β4 subunits of nicotinic acetylcholine receptors (nAChR), respectively. One of the strongest associations was observed for a non-silent single-nucleotide polymorphism at codon 398 in CHRNA5. Here, we have used pharmacological (antagonists) or genetic (RNA interference) interventions to modulate the activity of CHRNA5 in non-transformed bronchial cells and in lung cancer cell lines. In both cell types, silencing CHRNA5 or inhibiting receptors containing nAChR α5 with α-conotoxin MII exerted a nicotine-like effect, with increased motility and invasiveness in vitro and increasing calcium influx. The effects on motility were enhanced by addition of nicotine but blocked by inhibiting CHRNA7, which encodes the homopentameric receptor α7 subunit. Silencing CHRNA5 also decreased the expression of cell adhesion molecules P120 and ZO-1 in lung cancer cells as well as the expression of DeltaNp63α in squamous cell carcinoma cell lines. These results demonstrate a role for CHRNA5 in modulating adhesion and motility in bronchial cells, as well as in regulating p63, a potential oncogene in squamous cell carcinoma. PMID:21586512

  2. Colon Cancer Risk Assessment - Gauss Program

    Science.gov (United States)

    An executable file (in GAUSS) that projects absolute colon cancer risk (with confidence intervals) according to NCI’s Colorectal Cancer Risk Assessment Tool (CCRAT) algorithm. GAUSS is not needed to run the program.

  3. What Is Stomach Cancer?

    Science.gov (United States)

    ... the key statistics about stomach cancer? What is stomach cancer? Cancer starts when cells in the body ... normal structure and function of the stomach. The stomach After food is chewed and swallowed, it enters ...

  4. Use of Absolute and Comparative Performance Feedback in Absolute and Comparative Judgments and Decisions

    Science.gov (United States)

    Moore, Don A.; Klein, William M. P.

    2008-01-01

    Which matters more--beliefs about absolute ability or ability relative to others? This study set out to compare the effects of such beliefs on satisfaction with performance, self-evaluations, and bets on future performance. In Experiment 1, undergraduate participants were told they had answered 20% correct, 80% correct, or were not given their…

  5. Absolute geostrophic currents in global tropical oceans

    Science.gov (United States)

    Yang, Lina; Yuan, Dongliang

    2016-11-01

    A set of absolute geostrophic current (AGC) data for the period January 2004 to December 2012 are calculated using the P-vector method based on monthly gridded Argo profiles in the world tropical oceans. The AGCs agree well with altimeter geostrophic currents, Ocean Surface Current Analysis-Real time currents, and moored current-meter measurements at 10-m depth, based on which the classical Sverdrup circulation theory is evaluated. Calculations have shown that errors of wind stress calculation, AGC transport, and depth ranges of vertical integration cannot explain non-Sverdrup transport, which is mainly in the subtropical western ocean basins and equatorial currents near the Equator in each ocean basin (except the North Indian Ocean, where the circulation is dominated by monsoons). The identified non-Sverdrup transport is thereby robust and attributed to the joint effect of baroclinicity and relief of the bottom (JEBAR) and mesoscale eddy nonlinearity.

  6. Absolute measurements of fast neutrons using yttrium

    International Nuclear Information System (INIS)

    Yttrium is presented as an absolute neutron detector for pulsed neutron sources. It has high sensitivity for detecting fast neutrons. Yttrium has the property of generating a monoenergetic secondary radiation in the form of a 909 keV gamma-ray caused by inelastic neutron interaction. It was calibrated numerically using MCNPX and does not need periodic recalibration. The total yttrium efficiency for detecting 2.45 MeV neutrons was determined to be fn∼4.1x10-4 with an uncertainty of about 0.27%. The yttrium detector was employed in the NX2 plasma focus experiments and showed the neutron yield of the order of 108 neutrons per discharge.

  7. MAGSAT: Vector magnetometer absolute sensor alignment determination

    Science.gov (United States)

    Acuna, M. H.

    1981-01-01

    A procedure is described for accurately determining the absolute alignment of the magnetic axes of a triaxial magnetometer sensor with respect to an external, fixed, reference coordinate system. The method does not require that the magnetic field vector orientation, as generated by a triaxial calibration coil system, be known to better than a few degrees from its true position, and minimizes the number of positions through which a sensor assembly must be rotated to obtain a solution. Computer simulations show that accuracies of better than 0.4 seconds of arc can be achieved under typical test conditions associated with existing magnetic test facilities. The basic approach is similar in nature to that presented by McPherron and Snare (1978) except that only three sensor positions are required and the system of equations to be solved is considerably simplified. Applications of the method to the case of the MAGSAT Vector Magnetometer are presented and the problems encountered discussed.

  8. Absolute astrometry in the next 50 years

    CERN Document Server

    Høg, Erik

    2014-01-01

    With ESA's astrometry satellite Gaia in orbit since December 2013 it is time to look at the future of fundamental astrometry and a time frame of 50 years is needed in this matter. A dozen science issues for a Gaia successor mission in twenty years are presented and in this context the possibilities for absolute astrometry with mas or sub-mas accuracies are discussed. The three powerful techniques: VLBI, the MICADO camera on the E-ELT, and the LSST are described and documented by literature references and by an extensive correspondence with leading astronomers who readily responded with all the information I needed. In brief, the two Gaia-like missions would provide an astrometric foundation for all branches of astronomy from the solar system and stellar systems to compact galaxies, quasars and dark matter by data which cannot be surpassed in the next 50 years.

  9. How is an absolute democracy possible?

    Directory of Open Access Journals (Sweden)

    Joanna Bednarek

    2011-01-01

    Full Text Available In the last part of the Empire trilogy, Commonwealth, Negri and Hardt ask about the possibility of the self-governance of the multitude. When answering, they argue that absolute democracy, understood as the political articulation of the multitude that does not entail its unification (construction of the people is possible. As Negri states, this way of thinking about political articulation is rooted in the tradition of democratic materialism and constitutes the alternative to the dominant current of modern political philosophy that identifies political power with sovereignty. The multitude organizes itself politically by means of the constitutive power, identical with the ontological creativity or productivity of the multitude. To state the problem of political organization means to state the problem of class composition: political democracy is at the same time economic democracy.

  10. Absolute radiometric calibration of the CCRS SAR

    Science.gov (United States)

    Ulander, Lars M. H.; Hawkins, Robert K.; Livingstone, Charles E.; Lukowski, Tom I.

    1991-11-01

    Determining the radar scattering coefficients from SAR (synthetic aperture radar) image data requires absolute radiometric calibration of the SAR system. The authors describe an internal calibration methodology for the airborne Canada Centre for Remote Sensing (CCRS) SAR system, based on radar theory, a detailed model of the radar system, and measurements of system parameters. The methodology is verified by analyzing external calibration data acquired over a 6-month period in 1988 by the C-band radar using HH polarization. The results indicate that the overall error is +/- 0.8 dB (1-sigma) for incidence angles +/- 20 deg from antenna boresight. The dominant error contributions are due to the antenna radome and uncertainties in the elevation angle relative to the antenna boresight.

  11. WHY DOES LEIBNIZ NEED ABSOLUTE TIME?

    Directory of Open Access Journals (Sweden)

    NICOLÁS VAUGHAN C.

    2007-08-01

    Full Text Available Resumen: En este ensayo pongo en contraposición dos doctrinas conspicuamenteleibnicianas: la doctrina del tiempo relacional e ideal, y la doctrina de la armonía preestablecida. Argumentaré que si todas las substancias están necesariamentecoordinadas, entonces no tiene sentido negar el carácter absoluto y real del tiempo. En la primera sección describiré la concepción newtoniana y clarkeana del tiempo absoluto; en la segunda discutiré la crítica leibniciana a dicha concepción, crítica sobre la que se erige su doctrina relacional e ideal del tiempo; en la tercera sección daré un vistazo a la metafísica monádica madura de Leibniz, haciendo especial énfasis en la doctrina de la armonía preestablecida; finalmente, en la última sección sugeriré la existencia de una tensión irreconciliable entre estas dos doctrinas.Abstract: In this paper I bring together two characteristically Leibnizean doctrines:the doctrine of relational and ideal time, and the doctrine of preestablished harmony. I will argue that, if every substance is necessarily connected with another, then it makes no sense to deny absolute and real time. In the first section, I will describe Newton’s and Clarke’s conception of absolute time; then, in the second section, I will consider Leibniz’s critique of that conception, on which he bases his ideal and relational doctrine of time. In the third section I will look briefly at Leibniz’s mature monadic metaphysics, taking special account of his doctrine of preestablished harmony. In the last section, I will suggest that there is an irreconcilable tension between these two doctrines.

  12. The Effect of 217 Hz Magnetic Field of Cell Phone with Different Intensities on Apoptosis of Normal and Cancerous Cells Treated with Chemotherapy Drug

    Directory of Open Access Journals (Sweden)

    Mahsa Mansourian

    2012-03-01

    Full Text Available Background: According to the increasing development of home and business electronic equipment in today's world, the biological effects of ELF magnetic fields have been studied at two molecular-cellular and animal- human levels. Considering the therapeutic viewpoint of this study regarding the effects of low-frequency fields of mobile phone, the effect of acute exposure to this field on chemotherapy will be studied.Materials and Methods: In this experimental study, based on measurement of the intensity of the magnetic fields from mobile phones in another research, flux densities of magnetic field of 159.44, 93.25 and 120µ tesla with frequency of 217Hz was generated in magnetic field generator system, and the apoptosis level in K562 cancer cells and healthy cells of lymphocytes was assessed after exposure to field using flow cytometry method. This evaluation method was also performed for the cells treated with bleomycin after exposure to this field.Results: 217 Hz magnetic field exposure significantly increases the rate of apoptosis percentage (p > 0.05 in K562 cancer cells and in two intensities of 120 and 159.44µ tesla compared to the control group, but such effect is not observed in lymphocyte cells. Bleomycin-induced apoptosis percentage following exposure to the mentioned magnetic field shows no significant difference compared to the group of treatment with drug and without field exposure. This lack of significant difference is observed between the groups of drug after field exposure and field alone as well as between groups exposed to field and groups treated with bleomycin.Conclusion: Study results showed that 217 Hz magnetic field of mobile phone can induce apoptosis on cancer cells, but it has no effect on healthy cells. Thus, in order to use mobile phone as an effective factor in their treatment, some studies should be conducted at animal-human level.

  13. CHRNA5 as negative regulator of nicotine signaling in normal and cancer bronchial cells: effects on motility, migration and p63 expression

    OpenAIRE

    Krais, Annette M.; Hautefeuille, Agnès H.; Cros, Marie-Pierre; Krutovskikh, Vladimir; Tournier, Jean-Marie; Birembaut, Philippe; Thépot, Amélie; Paliwal, Anupam; Herceg, Zdenko; Boffetta, Paolo; Brennan, Paul; Hainaut, Pierre L.

    2011-01-01

    Genome-wide association studies have linked lung cancer risk with a region of chromosome 15q25.1 containing CHRNA3, CHRNA5 and CHRNB4 encoding α3, α5 and β4 subunits of nicotinic acetylcholine receptors (nAChR), respectively. One of the strongest associations was observed for a non-silent single-nucleotide polymorphism at codon 398 in CHRNA5. Here, we have used pharmacological (antagonists) or genetic (RNA interference) interventions to modulate the activity of CHRNA5 in non-transformed bronc...

  14. Quantification of telomerase activity in normal oral mucosal tissue and oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Arpita Rai

    2016-01-01

    Full Text Available Background and Objective: The role of telomeres and telomerase in oral cancer is an area of much recent interest. The understanding of the role of telomere biology, the end replication problem leading to genomic instability and the reactivation of telomerase, is absolutely critical to our understanding of oral cancer, and more so, to our ability of early diagnosis and developing novel therapies and cancer prevention approaches. The aim of the present study was to quantify telomerase activity (TA in oral squamous cell carcinoma (OSCC and normal oral mucosa and assess the role of telomerase as diagnostic and prognostic marker of oral malignancy. Materials and Methods: We quantified TA in 45 patients with OSCC and 20 normal oral mucosal specimens using polymerase chain reaction-based telomeric repeat amplification protocol assay and compared it with the clinical status and grade of malignancy. Results: TA was detected in 89% of malignant and 5% of normal oral mucosal tissue. The TA levels ranged from 0.28 to 6.91 (mean 2.05, standard deviation [SD] 1.33 in OSCC and 0.21 to 1.09 (mean 0.54, SD 0.27 in normal oral mucosa. There was no relationship between TA levels and clinical stages, site of the lesion, history of adverse habits, or sex of the patient. However, under the WHO classification, there were significant differences (P < 0.00 between Grades I, II, and III. Furthermore, increasing age of the patient significantly correlated with TA. Interpretation and Conclusion: The results of the present study indicate that activation of TA is frequent in OSCC. Statistically significant difference in quantified telomerase levels of OSCC and normal oral mucosa (P < 0.00 demonstrates the significant clinical usefulness of telomerase activation as a valuable marker for diagnosis while significant correlation of TA with grades of malignancy indicates its effectiveness as marker for prognosis of OSCC.

  15. Quantification of telomerase activity in normal oral mucosal tissue and oral squamous cell carcinoma

    Science.gov (United States)

    Rai, Arpita; Naikmasur, Venkatesh G.; Sattur, Atul

    2016-01-01

    Background and Objective: The role of telomeres and telomerase in oral cancer is an area of much recent interest. The understanding of the role of telomere biology, the end replication problem leading to genomic instability and the reactivation of telomerase, is absolutely critical to our understanding of oral cancer, and more so, to our ability of early diagnosis and developing novel therapies and cancer prevention approaches. The aim of the present study was to quantify telomerase activity (TA) in oral squamous cell carcinoma (OSCC) and normal oral mucosa and assess the role of telomerase as diagnostic and prognostic marker of oral malignancy. Materials and Methods: We quantified TA in 45 patients with OSCC and 20 normal oral mucosal specimens using polymerase chain reaction-based telomeric repeat amplification protocol assay and compared it with the clinical status and grade of malignancy. Results: TA was detected in 89% of malignant and 5% of normal oral mucosal tissue. The TA levels ranged from 0.28 to 6.91 (mean 2.05, standard deviation [SD] 1.33) in OSCC and 0.21 to 1.09 (mean 0.54, SD 0.27) in normal oral mucosa. There was no relationship between TA levels and clinical stages, site of the lesion, history of adverse habits, or sex of the patient. However, under the WHO classification, there were significant differences (P < 0.00) between Grades I, II, and III. Furthermore, increasing age of the patient significantly correlated with TA. Interpretation and Conclusion: The results of the present study indicate that activation of TA is frequent in OSCC. Statistically significant difference in quantified telomerase levels of OSCC and normal oral mucosa (P < 0.00) demonstrates the significant clinical usefulness of telomerase activation as a valuable marker for diagnosis while significant correlation of TA with grades of malignancy indicates its effectiveness as marker for prognosis of OSCC.

  16. Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin–pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro

    Science.gov (United States)

    Uram, Łukasz; Szuster, Magdalena; Filipowicz, Aleksandra; Gargasz, Krzysztof; Wołowiec, Stanisław; Wałajtys-Rode, Elżbieta

    2015-01-01

    The intracellular localization and colocalization of a fluorescently labeled G3 amine-terminated cationic polyamidoamine (PAMAM) dendrimer and its biotin–pyridoxal (BC-PAMAM) bioconjugate were investigated in a concentration-dependent manner in normal human fibroblast (BJ) and squamous epithelial carcinoma (SCC-15) cell lines. After 24 hours treatment, both cell lines revealed different patterns of intracellular dendrimer accumulation depending on their cytotoxic effects. Cancer cells exhibited much higher (20-fold) tolerance for native PAMAM treatment than fibroblasts, whereas BC-PAMAM was significantly toxic only for fibroblasts at 50 µM concentration. Fibroblasts accumulated the native and bioconjugated dendrimers in a concentration-dependent manner at nontoxic range of concentration, with significantly lower bioconjugate loading. After reaching the cytotoxicity level, fluorescein isothiocyanate-PAMAM accumulation remains at high, comparable level. In cancer cells, native PAMAM loading at higher, but not cytotoxic concentrations, was kept at constant level with a sharp increase at toxic concentration. Mander’s coefficient calculated for fibroblasts and cancer cells confirmed more efficient native PAMAM penetration as compared to BC-PAMAM. Significant differences in nuclear dendrimer penetration were observed for both cell lines. In cancer cells, PAMAM signals amounted to ~25%–35% of the total nuclei area at all investigated concentrations, with lower level (15%–25%) observed for BC-PAMAM. In fibroblasts, the dendrimer nuclear signal amounted to 15% at nontoxic and up to 70% at toxic concentrations, whereas BC-PAMAM remained at a lower concentration-dependent level (0.3%–20%). Mitochondrial localization of PAMAM and BC-PAMAM revealed similar patterns in both cell lines, depending on the extracellular dendrimer concentration, and presented significantly lower signals from BC-PAMAM, which correlated well with the cytotoxicity. PMID:26379435

  17. Microsatellite instability analysis in hereditary non-polyposis colon cancer using the Bethesda consensus panel of microsatellite markers in the absence of proband normal tissue

    Directory of Open Access Journals (Sweden)

    Dourisboure Ricardo J

    2006-01-01

    Full Text Available Abstract Background Hereditary non-polyposis colon cancer (HNPCC is an autosomal dominant syndrome predisposing to the early development of various cancers including those of colon, rectum, endometrium, ovarium, small bowel, stomach and urinary tract. HNPCC is caused by germline mutations in the DNA mismatch repair genes, mostly hMSH2 or hMLH1. In this study, we report the analysis for genetic counseling of three first-degree relatives (the mother and two sisters of a male who died of colorectal adenocarcinoma at the age of 23. The family fulfilled strict Amsterdam-I criteria (AC-I with the presence of extracolonic tumors in the extended pedigree. We overcame the difficulty of having a proband post-mortem non-tumor tissue sample for MSI testing by studying the alleles carried by his progenitors. Methods Tumor MSI testing is described as initial screening in both primary and metastasis tumor tissue blocks, using the reference panel of 5 microsatellite markers standardized by the National Cancer Institute (NCI for the screening of HNPCC (BAT-25, BAT-26, D2S123, D5S346 and D17S250. Subsequent mutation analysis of the hMLH1 and hMSH2 genes was performed. Results Three of five microsatellite markers (BAT-25, BAT-26 and D5S346 presented different alleles in the proband's tumor as compared to those inherited from his parents. The tumor was classified as high frequency microsatellite instability (MSI-H. We identified in the HNPCC family a novel germline missense (c.1864C>A mutation in exon 12 of hMSH2 gene, leading to a proline 622 to threonine (p.Pro622Thr amino acid substitution. Conclusion This approach allowed us to establish the tumor MSI status using the NCI recommended panel in the absence of proband's non-tumor tissue and before sequencing the obligate carrier. According to the Human Gene Mutation Database (HGMD and the International Society for Gastrointestinal Hereditary Tumors (InSiGHT Database this is the first report of this mutation.

  18. Carcinogenic HPV prevalence and age-specific type distribution in 40,382 women with normal cervical cytology, ASCUS/LSIL, HSIL, or cervical cancer

    DEFF Research Database (Denmark)

    Kjær, Susanne K; Munk, Christian; Junge, Jette;

    2014-01-01

    BACKGROUND: Assessment of the prevaccination type-specific prevalence of human papillomavirus (HPV) in the general population is important for the prediction of the impact of HPV vaccination. METHODS: We collected consecutively residual specimens from liquid-based cytology samples from 40,382 women...... % in cervical cancer and the corresponding prevalence of HPV16/18/31/33/45/52/58 was 89 %. CONCLUSION: This study forms a valuable starting point for monitoring the effect of HPV vaccination in Denmark. In addition, the particular carcinogenic role of HPV16 and 18 is confirmed and may support a role...... from the general population in Copenhagen, Denmark, during 2002-2005. All samples were tested for high-risk HPV using the Hybrid Capture 2 technique, and genotyping was done using LiPa (Innogenetics). Through linkage with the Pathology Data Bank, we obtained information on the cytology result...

  19. Effect of radiation on normal hematopoiesis and on viral induced cancers of the hematopoietic system. Technical progress report, August 1, 1974--May 1, 1975. [Mice, x radiation

    Energy Technology Data Exchange (ETDEWEB)

    Okunewick, J.P.

    1975-01-01

    Studies carried out during the above period on viral leukemia have conclusively shown that the pluripotent hematopoietic colony forming stem cell (CFU-S) is a target cell for the leukemia virus. Treatment of this cell population with antiserum prepared in syngeneic mice against the disease resulted in inactivation of up to 50 percent of the CFU-S obtained from the spleens of viral leukemic mice. At the same time, normal serum had no effect on these cells, nor did the antiserum have any effect on normal CFU-S. Data indicated that a considerable time delay, on the order of a week, preceded the expression of the viral antigen in the leukemic CFU-S, but that it could be seen at all times after that up to the terminal point of the disease. We examined the effect of the virus on DNA synthesis (S-phase cells) in the CFU-S immediately after virus injection. The results showed that a doubling of the number of cells in S could be seen as early as four hours after introduction of the virus into the animal. Studies with ethidium bromide, an inhibitor of viral reverse transcriptase, were found to be in agreement with this observation. When given to viral leukemic animals in combination with fractionated exposure to x-ray, the data suggested that ethidium bromide did act to extend survival somewhat, but not much over that seen through the use of x-ray alone.

  20. Quasi-Degenerate Neutrino Masses with Normal and Inverted Hierarchy

    CERN Document Server

    Francis, Ng K

    2012-01-01

    The effects of CP-phases on the three absolute quasi-degenerate Majorana neutrino (QDN) masses are stud-ied with neutrino mass matrices obeying {\\mu} - {\\tau} symmetry for normal as well as inverted hierarchical mass patterns. We have made further investigations on 1) the prediction of solar mixing angle which lies below tri-bimaximal mixing value in consistent with neutrino oscillation observational data, 2) the prediction on absolute neutrino mass parameter (mee) in 0{\

  1. Gyrokinetic Statistical Absolute Equilibrium and Turbulence

    Energy Technology Data Exchange (ETDEWEB)

    Jian-Zhou Zhu and Gregory W. Hammett

    2011-01-10

    A paradigm based on the absolute equilibrium of Galerkin-truncated inviscid systems to aid in understanding turbulence [T.-D. Lee, "On some statistical properties of hydrodynamical and magnetohydrodynamical fields," Q. Appl. Math. 10, 69 (1952)] is taken to study gyrokinetic plasma turbulence: A finite set of Fourier modes of the collisionless gyrokinetic equations are kept and the statistical equilibria are calculated; possible implications for plasma turbulence in various situations are discussed. For the case of two spatial and one velocity dimension, in the calculation with discretization also of velocity v with N grid points (where N + 1 quantities are conserved, corresponding to an energy invariant and N entropy-related invariants), the negative temperature states, corresponding to the condensation of the generalized energy into the lowest modes, are found. This indicates a generic feature of inverse energy cascade. Comparisons are made with some classical results, such as those of Charney-Hasegawa-Mima in the cold-ion limit. There is a universal shape for statistical equilibrium of gyrokinetics in three spatial and two velocity dimensions with just one conserved quantity. Possible physical relevance to turbulence, such as ITG zonal flows, and to a critical balance hypothesis are also discussed.

  2. Normalizing the causality between time series

    CERN Document Server

    Liang, X San

    2015-01-01

    Recently, a rigorous yet concise formula has been derived to evaluate the information flow, and hence the causality in a quantitative sense, between time series. To assess the importance of a resulting causality, it needs to be normalized. The normalization is achieved through distinguishing three types of fundamental mechanisms that govern the marginal entropy change of the flow recipient. A normalized or relative flow measures its importance relative to other mechanisms. In analyzing realistic series, both absolute and relative information flows need to be taken into account, since the normalizers for a pair of reverse flows belong to two different entropy balances; it is quite normal that two identical flows may differ a lot in relative importance in their respective balances. We have reproduced these results with several autoregressive models. We have also shown applications to a climate change problem and a financial analysis problem. For the former, reconfirmed is the role of the Indian Ocean Dipole as ...

  3. Quantitative patterns of Hsps in tubular adenoma compared with normal and tumor tissues reveal the value of Hsp10 and Hsp60 in early diagnosis of large bowel cancer.

    Science.gov (United States)

    Rappa, Francesca; Pitruzzella, Alessandro; Marino Gammazza, Antonella; Barone, Rosario; Mocciaro, Emanuele; Tomasello, Giovanni; Carini, Francesco; Farina, Felicia; Zummo, Giovanni; Conway de Macario, Everly; Macario, Alberto Jl; Cappello, Francesco

    2016-09-01

    Large bowel carcinogenesis involves accumulation of genetic alterations leading to transformation of normal mucosa into dysplasia and, lastly, adenocarcinoma. It is pertinent to elucidate the molecular changes occurring in the pre-neoplastic lesions to facilitate early diagnosis and treatment. Heat shock proteins (Hsps), many of which are molecular chaperones, are implicated in carcinogenesis, and their variations with tumor progression encourage their study as biomarkers. There are many reports on Hsps and cancer but none to our knowledge on their systematic quantification in pre-neoplastic lesions of the large bowel. We performed immunohistochemical determinations of Hsp10, Hsp60, Hsp70, and Hsp90 in biopsies of large bowel tubular adenomas with moderate grade of dysplasia and compared to normal mucosa and adenocarcinoma with a moderate grade of differentiation (G2). A significant elevation of Hsp10 and Hsp60 only, i.e., in the absence of elevation of Hsp70 or Hsp90, in both epithelium and lamina propria was found in tubular adenoma by comparison with normal mucosa. In contrast, adenocarcinoma was characterized by the highest levels of Hsp10 and Hsp60 in epithelium and lamina propria, accompanied by the highest levels of Hsp70 only in epithelium and of Hsp90 only in lamina propria, by comparison with normal and tubular adenoma counterparts. Hsp10 and Hsp60 are promising biomarkers for early diagnosis of tubular adenoma and for its differentiation from more advanced malignant lesions. Hsp10 and Hsp60 may be implicated in carcinogenesis from its very early steps and, thus, are potentially convenient targets for therapy.

  4. Nonlinear Absolute Nodal Coordinate Formulation of a Flexible Beam Considering Shear Effect

    Institute of Scientific and Technical Information of China (English)

    LIU Jin-yang; SHEN Ling-jie; HONG Jia-zhen

    2005-01-01

    Nonlinear modeling of a flexible beam with large deformation was investigated. Absolute nodal cooridnate formulation is employed to describe the motion, and Lagrange equations of motion of a flexible beam are derived based on the geometric nonlinear theory. Different from the previous nonlinear formulation with EulerBernoulli assumption, the shear strain and transverse normal strain are taken into account. Computational example of a flexible pendulum with a tip mass is given to show the effects of the shear strain and transverse normal strain. The constant total energy verifies the correctness of the present formulation.

  5. CANCER

    Directory of Open Access Journals (Sweden)

    N. Kavoussi

    1973-09-01

    Full Text Available There are many carcinogenetic elements in industry and it is for this reason that study and research concerning the effect of these materials is carried out on a national and international level. The establishment and growth of cancer are affected by different factors in two main areas:-1 The nature of the human or animal including sex, age, point and method of entry, fat metabolism, place of agglomeration of carcinogenetic material, amount of material absorbed by the body and the immunity of the body.2 The different nature of the carcinogenetic material e.g. physical, chemical quality, degree of solvency in fat and purity of impurity of the element. As the development of cancer is dependent upon so many factors, it is extremely difficult to determine whether a causative element is principle or contributory. Some materials are not carcinogenetic when they are pure but become so when they combine with other elements. All of this creates an industrial health problem in that it is almost impossible to plan an adequate prevention and safety program. The body through its system of immunity protects itself against small amounts of carcinogens but when this amount increases and reaches a certain level the body is not longer able to defend itself. ILO advises an effective protection campaign against cancer based on the Well –equipped laboratories, Well-educated personnel, the establishment of industrial hygiene within factories, the regular control of safety systems, and the implementation of industrial health principles and research programs.

  6. WE-D-BRE-02: BEST IN PHYSICS (THERAPY) - Radiogenomic Modeling of Normal Tissue Toxicities in Prostate Cancer Patients Receiving Hypofractionated Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Coates, J; Jeyaseelan, K; Ybarra, N; David, M; Faria, S; Souhami, L; Cury, F; Duclos, M; Naqa, I El [McGill University, Montreal, QC (Canada)

    2014-06-15

    Purpose: It has been realized that inter-patient radiation sensitivity variability is a multifactorial process involving dosimetric, clinical, and genetic factors. Therefore, we explore a new framework to integrate physical, clinical, and biological data denoted as radiogenomic modeling. In demonstrating the feasibility of this work, we investigate the association of genetic variants (copy number variations [CNVs] and single nucleotide polymorphisms [SNPs]) with radiation induced rectal bleeding (RB) and erectile dysfunction (ED) while taking into account dosimetric and clinical variables in prostate cancer patients treated with curative irradiation. Methods: A cohort of 62 prostate cancer patients who underwent hypofractionated radiotherapy (66 Gy in 22 fractions) was retrospectively genotyped for CNV and SNP rs25489 in the xrcc1 DNA repair gene. Dosevolume metrics were extracted from treatment plans of 54 patients who had complete dosimetric profiles. Treatment outcomes were considered to be a Result of functional mapping of radiogenomic input variables according to a logit transformation. Model orders were estimated using resampling by leave-one out cross-validation (LOO-CV). Radiogenomic model performance was evaluated using area under the ROC curve (AUC) and LOO-CV. For continuous univariate dosimetric and clinical variables, Spearmans rank coefficients were calculated and p-values reported accordingly. In the case of binary variables, Chi-squared statistics and contingency table calculations were used. Results: Ten patients were found to have three copies of xrcc1 CNV (RB: χ2=14.6 [p<0.001] and ED: χ2=4.88[p=0.0272]) and twelve had heterozygous rs25489 SNP (RB: χ2=0.278[p=0.599] and ED: χ2=0.112[p=0.732]). LOO-CV identified penile bulb D60 as the only significant QUANTEC predictor (rs=0.312 [p=0.0145]) for ED. Radiogenomic modeling yielded statistically significant, cross-validated NTCP models for RB (rs=0.243[p=0.0443], AUC=0.665) and ED (rs=0.276[p=0

  7. Absolute value preconditioning for symmetric indefinite linear systems

    OpenAIRE

    Vecharynski, Eugene; Knyazev, Andrew V.

    2011-01-01

    We introduce a novel strategy for constructing symmetric positive definite (SPD) preconditioners for linear systems with symmetric indefinite matrices. The strategy, called absolute value preconditioning, is motivated by the observation that the preconditioned minimal residual method with the inverse of the absolute value of the matrix as a preconditioner converges to the exact solution of the system in at most two steps. Neither the exact absolute value of the matrix nor its exact inverse ar...

  8. Absolute nuclear material assay using count distribution (LAMBDA) space

    Science.gov (United States)

    Prasad, Manoj K.; Snyderman, Neal J.; Rowland, Mark S.

    2012-06-05

    A method of absolute nuclear material assay of an unknown source comprising counting neutrons from the unknown source and providing an absolute nuclear material assay utilizing a model to optimally compare to the measured count distributions. In one embodiment, the step of providing an absolute nuclear material assay comprises utilizing a random sampling of analytically computed fission chain distributions to generate a continuous time-evolving sequence of event-counts by spreading the fission chain distribution in time.

  9. Absolute nuclear material assay using count distribution (LAMBDA) space

    Science.gov (United States)

    Prasad, Mano K.; Snyderman, Neal J.; Rowland, Mark S.

    2015-12-01

    A method of absolute nuclear material assay of an unknown source comprising counting neutrons from the unknown source and providing an absolute nuclear material assay utilizing a model to optimally compare to the measured count distributions. In one embodiment, the step of providing an absolute nuclear material assay comprises utilizing a random sampling of analytically computed fission chain distributions to generate a continuous time-evolving sequence of event-counts by spreading the fission chain distribution in time.

  10. Comparison of available measurements of the absolute fluorescence yield

    CERN Document Server

    Rosado, J; Arqueros, F

    2010-01-01

    The uncertainty in the absolute value of the fluorescence yield is still one of the main contributions to the total error in the reconstruction of the primary energy of ultra-energetic air showers using the fluorescence technique. A significant number of experimental values of the fluorescence yield have been published in the last years, however reported results are given very often in different units (photons/MeV or photons/m) and for different wavelength intervals. In this work we present a comparison of available results normalized to its value in photons/MeV for the 337 nm band at 800 hPa and 293 K. Possible sources of systematic errors on these measurements are discussed. In particular, the conversion of photons/m to photons/MeV requires an accurate determination of the energy deposited by the electrons in the field of view of the experimental setup. We have calculated the energy deposition for each experiment by means of a detailed Monte Carlo simulation including when possible the geometrical details o...

  11. Sonographic Measurement of Absolute and Relative Renal Length in Healthy Isfahani Adults

    Directory of Open Access Journals (Sweden)

    A Hekmatnia

    2004-04-01

    Full Text Available Background: There is no information on renal size and its relation to age, sex and height in the area of Isfahan. The aim of this study was to define sonographically measured absolute renal lengths and their relations to height in normal Isfahani adults. Methods: 400 healthy Isfahani subjects aged 20 to 69 years with normal blood pressure, no history of renal disease in them or their first degree relatives and with normal sonographic appearance were chosen in 2002-2003. The study was cross-sectional. With real-time sonography, absolute renal length was measured. Results: Four hundred healthy adults (230 men and 170 women aged 20 to 69 years (39.6 ± 13.6 year were evaluated. The length of left kidney was longer than the right one (111 ± 9.8 mm vs. 109 ± 8.4 mm in right kidney; P < 0.01. Renal length was significantly greater in males compared to females (P < 0.01. Renal length decreased with age and the rate of decrease was accelerated at the age of 60 years and older. There was a significant correlation between kidney length and the subject's height (P < 0.01. Conclusion: The result of this study shows the normal values for renal length in Iranian males and females, which may be helpful in assessing the size of patients’ kidneys in different clinical settings. Keywords: Kidney size, Renal length, Ultrasonography, Normal values.

  12. The absolute disparity anomaly and the mechanism of relative disparities.

    Science.gov (United States)

    Chopin, Adrien; Levi, Dennis; Knill, David; Bavelier, Daphne

    2016-06-01

    There has been a long-standing debate about the mechanisms underlying the perception of stereoscopic depth and the computation of the relative disparities that it relies on. Relative disparities between visual objects could be computed in two ways: (a) using the difference in the object's absolute disparities (Hypothesis 1) or (b) using relative disparities based on the differences in the monocular separations between objects (Hypothesis 2). To differentiate between these hypotheses, we measured stereoscopic discrimination thresholds for lines with different absolute and relative disparities. Participants were asked to judge the depth of two lines presented at the same distance from the fixation plane (absolute disparity) or the depth between two lines presented at different distances (relative disparity). We used a single stimulus method involving a unique memory component for both conditions, and no extraneous references were available. We also measured vergence noise using Nonius lines. Stereo thresholds were substantially worse for absolute disparities than for relative disparities, and the difference could not be explained by vergence noise. We attribute this difference to an absence of conscious readout of absolute disparities, termed the absolute disparity anomaly. We further show that the pattern of correlations between vergence noise and absolute and relative disparity acuities can be explained jointly by the existence of the absolute disparity anomaly and by the assumption that relative disparity information is computed from absolute disparities (Hypothesis 1).

  13. Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy.

    Science.gov (United States)

    Liu, Wai M; Scott, Katherine A; Dennis, Jayne L; Kaminska, Elwira; Levett, Alan J; Dalgleish, Angus G

    2016-08-01

    It has been reported that lower doses of the opioid antagonist naltrexone are able to reduce tumour growth by interfering with cell signalling as well as by modifying the immune system. We have evaluated the gene expression profile of a cancer cell line after treatment with low-dose naltrexone (LDN), and assessed the effect that adapting treatment schedules with LDN may have on enhancing efficacy. LDN had a selective impact on genes involved with cell cycle regulation and immune modulation. Similarly, the pro-apoptotic genes BAD and BIK1 were increased only after LDN. Continuous treatment with LDN had little effect on growth in different cell lines; however, altering the treatment schedule to include a phase of culture in the absence of drug following an initial round of LDN treatment, resulted in enhanced cell killing. Furthermore, cells pre-treated with LDN were more sensitive to the cytotoxic effects of a number of common chemotherapy agents. For example, priming HCT116 with LDN before treatment with oxaliplatin significantly increased cell killing to 49±7.0 vs. 14±2.4% in cultures where priming was not used. Interestingly, priming with NTX before oxaliplatin resulted in just 32±1.8% cell killing. Our data support further the idea that LDN possesses anticancer activity, which can be improved by modifying the treatment schedule. PMID:27279602

  14. Evaluation of the absolute regional temperature potential

    Directory of Open Access Journals (Sweden)

    D. T. Shindell

    2012-09-01

    Full Text Available The Absolute Regional Temperature Potential (ARTP is one of the few climate metrics that provides estimates of impacts at a sub-global scale. The ARTP presented here gives the time-dependent temperature response in four latitude bands (90–28° S, 28° S–28° N, 28–60° N and 60–90° N as a function of emissions based on the forcing in those bands caused by the emissions. It is based on a large set of simulations performed with a single atmosphere-ocean climate model to derive regional forcing/response relationships. Here I evaluate the robustness of those relationships using the forcing/response portion of the ARTP to estimate regional temperature responses to the historic aerosol forcing in three independent climate models. These ARTP results are in good accord with the actual responses in those models. Nearly all ARTP estimates fall within ±20% of the actual responses, though there are some exceptions for 90–28° S and the Arctic, and in the latter the ARTP may vary with forcing agent. However, for the tropics and the Northern Hemisphere mid-latitudes in particular, the ±20% range appears to be roughly consistent with the 95% confidence interval. Land areas within these two bands respond 39–45% and 9–39% more than the latitude band as a whole. The ARTP, presented here in a slightly revised form, thus appears to provide a relatively robust estimate for the responses of large-scale latitude bands and land areas within those bands to inhomogeneous radiative forcing and thus potentially to emissions as well. Hence this metric could allow rapid evaluation of the effects of emissions policies at a finer scale than global metrics without requiring use of a full climate model.

  15. Absolute Radiometric Calibration of KOMPSAT-3A

    Science.gov (United States)

    Ahn, H. Y.; Shin, D. Y.; Kim, J. S.; Seo, D. C.; Choi, C. U.

    2016-06-01

    This paper presents a vicarious radiometric calibration of the Korea Multi-Purpose Satellite-3A (KOMPSAT-3A) performed by the Korea Aerospace Research Institute (KARI) and the Pukyong National University Remote Sensing Group (PKNU RSG) in 2015.The primary stages of this study are summarized as follows: (1) A field campaign to determine radiometric calibrated target fields was undertaken in Mongolia and South Korea. Surface reflectance data obtained in the campaign were input to a radiative transfer code that predicted at-sensor radiance. Through this process, equations and parameters were derived for the KOMPSAT-3A sensor to enable the conversion of calibrated DN to physical units, such as at-sensor radiance or TOA reflectance. (2) To validate the absolute calibration coefficients for the KOMPSAT-3A sensor, we performed a radiometric validation with a comparison of KOMPSAT-3A and Landsat-8 TOA reflectance using one of the six PICS (Libya 4). Correlations between top-of-atmosphere (TOA) radiances and the spectral band responses of the KOMPSAT-3A sensors at the Zuunmod, Mongolia and Goheung, South Korea sites were significant for multispectral bands. The average difference in TOA reflectance between KOMPSAT-3A and Landsat-8 image over the Libya 4, Libya site in the red-green-blue (RGB) region was under 3%, whereas in the NIR band, the TOA reflectance of KOMPSAT-3A was lower than the that of Landsat-8 due to the difference in the band passes of two sensors. The KOMPSAT-3Aensor includes a band pass near 940 nm that can be strongly absorbed by water vapor and therefore displayed low reflectance. Toovercome this, we need to undertake a detailed analysis using rescale methods, such as the spectral bandwidth adjustment factor.

  16. Ultrasound guided fluorescence molecular tomography with improved quantification by an attenuation compensated born-normalization and in vivo preclinical study of cancer

    Energy Technology Data Exchange (ETDEWEB)

    Li, Baoqiang; Berti, Romain; Abran, Maxime; Lesage, Frédéric, E-mail: frederic.lesage@polymtl.ca [Institute of Biomedical Engineering, École Polytechnique de Montréal, Montreal, Quebec H3C 3A7 (Canada); Montreal Heart Institute, Montreal, Quebec H1T 1C8 (Canada)

    2014-05-15

    Ultrasound imaging, having the advantages of low-cost and non-invasiveness over MRI and X-ray CT, was reported by several studies as an adequate complement to fluorescence molecular tomography with the perspective of improving localization and quantification of fluorescent molecular targets in vivo. Based on the previous work, an improved dual-modality Fluorescence-Ultrasound imaging system was developed and then validated in imaging study with preclinical tumor model. Ultrasound imaging and a profilometer were used to obtain the anatomical prior information and 3D surface, separately, to precisely extract the tissue boundary on both sides of sample in order to achieve improved fluorescence reconstruction. Furthermore, a pattern-based fluorescence reconstruction on the detection side was incorporated to enable dimensional reduction of the dataset while keeping the useful information for reconstruction. Due to its putative role in the current imaging geometry and the chosen reconstruction technique, we developed an attenuation compensated Born-normalization method to reduce the attenuation effects and cancel off experimental factors when collecting quantitative fluorescence datasets over large area. Results of both simulation and phantom study demonstrated that fluorescent targets could be recovered accurately and quantitatively using this reconstruction mechanism. Finally, in vivo experiment confirms that the imaging system associated with the proposed image reconstruction approach was able to extract both functional and anatomical information, thereby improving quantification and localization of molecular targets.

  17. Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jakobi, Annika, E-mail: Annika.Jakobi@OncoRay.de [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Bandurska-Luque, Anna [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Stützer, Kristin; Haase, Robert; Löck, Steffen [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Wack, Linda-Jacqueline [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); Mönnich, David [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); German Cancer Research Center, Heidelberg (Germany); German Cancer Consortium, Tübingen (Germany); Thorwarth, Daniela [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); and others

    2015-08-01

    Purpose: The purpose of this study was to determine, by treatment plan comparison along with normal tissue complication probability (NTCP) modeling, whether a subpopulation of patients with head and neck squamous cell carcinoma (HNSCC) could be identified that would gain substantial benefit from proton therapy in terms of NTCP. Methods and Materials: For 45 HNSCC patients, intensity modulated radiation therapy (IMRT) was compared to intensity modulated proton therapy (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP values, using modern models for acute mucositis, xerostomia, aspiration, dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based on primary tumor location. Results: Generally, IMPT reduced the NTCP values while keeping similar target coverage for all patients. Subgroup analyses revealed a higher individual reduction of swallowing-related side effects by IMPT for patients with tumors in the upper head and neck area, whereas the risk reduction of acute mucositis was more pronounced in patients with tumors in the larynx region. More patients with tumors in the upper head and neck area had a reduction in NTCP of more than 10%. Conclusions: Subgrouping can help to identify patients who may benefit more than others from the use of IMPT and, thus, can be a useful tool for a preselection of patients in the clinic where there are limited PT resources. Because the individual benefit differs within a subgroup, the relative merits should additionally be evaluated by individual treatment plan comparisons.

  18. Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study was to determine, by treatment plan comparison along with normal tissue complication probability (NTCP) modeling, whether a subpopulation of patients with head and neck squamous cell carcinoma (HNSCC) could be identified that would gain substantial benefit from proton therapy in terms of NTCP. Methods and Materials: For 45 HNSCC patients, intensity modulated radiation therapy (IMRT) was compared to intensity modulated proton therapy (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP values, using modern models for acute mucositis, xerostomia, aspiration, dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based on primary tumor location. Results: Generally, IMPT reduced the NTCP values while keeping similar target coverage for all patients. Subgroup analyses revealed a higher individual reduction of swallowing-related side effects by IMPT for patients with tumors in the upper head and neck area, whereas the risk reduction of acute mucositis was more pronounced in patients with tumors in the larynx region. More patients with tumors in the upper head and neck area had a reduction in NTCP of more than 10%. Conclusions: Subgrouping can help to identify patients who may benefit more than others from the use of IMPT and, thus, can be a useful tool for a preselection of patients in the clinic where there are limited PT resources. Because the individual benefit differs within a subgroup, the relative merits should additionally be evaluated by individual treatment plan comparisons

  19. Impact of Statistical Learning Methods on the Predictive Power of Multivariate Normal Tissue Complication Probability Models

    International Nuclear Information System (INIS)

    Purpose: To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. Methods and Materials: In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator (LASSO), and Bayesian model averaging (BMA), were used to build NTCP models of xerostomia following radiotherapy treatment for head and neck cancer. Performance of each learning method was evaluated by a repeated cross-validation scheme in order to obtain a fair comparison among methods. Results: It was found that the LASSO and BMA methods produced models with significantly better predictive power than that of the stepwise selection method. Furthermore, the LASSO method yields an easily interpretable model as the stepwise method does, in contrast to the less intuitive BMA method. Conclusions: The commonly used stepwise selection method, which is simple to execute, may be insufficient for NTCP modeling. The LASSO method is recommended.

  20. Impact of Statistical Learning Methods on the Predictive Power of Multivariate Normal Tissue Complication Probability Models

    Energy Technology Data Exchange (ETDEWEB)

    Xu Chengjian, E-mail: c.j.xu@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schaaf, Arjen van der; Schilstra, Cornelis; Langendijk, Johannes A.; Veld, Aart A. van' t [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands)

    2012-03-15

    Purpose: To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. Methods and Materials: In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator (LASSO), and Bayesian model averaging (BMA), were used to build NTCP models of xerostomia following radiotherapy treatment for head and neck cancer. Performance of each learning method was evaluated by a repeated cross-validation scheme in order to obtain a fair comparison among methods. Results: It was found that the LASSO and BMA methods produced models with significantly better predictive power than that of the stepwise selection method. Furthermore, the LASSO method yields an easily interpretable model as the stepwise method does, in contrast to the less intuitive BMA method. Conclusions: The commonly used stepwise selection method, which is simple to execute, may be insufficient for NTCP modeling. The LASSO method is recommended.

  1. Influence of different sized nanoparticles combined with ultrasound on the optical properties of in vitro normal and cancerous human lung tissue studied with OCT and diffuse reflectance spectra

    International Nuclear Information System (INIS)

    The present study is concerned with the in vitro study of different sized titanium dioxide (TiO2) nanoparticles’ (NPs) penetration and accumulation in human normal lung (NL) tissue and lung adenocarcinoma tumor (LAT) tissue by the methods of continuous optical coherence tomography (OCT) monitoring and diffuse reflectance (DR) spectra measurement, and their evaluating the effects of TiO2 NPs in two sizes (60 nm and 100 nm) and their combination with ultrasound (US) on the optical properties of human NL and LAT tissue. Spectral measurements indicate that TiO2 NPs penetrate and accumulate into the tissues and thus induce enhancement of DR. The averaged and normalized OCT signal intensity suggests that light penetration depth is significantly enlarged by ultrasound. The average attenuation coefficient of NL tissue changes from 5.10  ±  0.26 mm−1 to 3.12  ±  0.43 mm−1 and 2.15  ±  0.54 mm−1 at 120 min for 60 nm TiO2 NPs and 60 nm TiO2NPs/US treatment, respectively, and from 5.54  ±  0.46 mm−1 to 3.24  ±  0.73 mm−1 and 2.69  ±  0.34 mm−1 at 150 min for 100 nm TiO2 NPs and 100 nm TiO2NPs/US, respectively. The average attenuation coefficient of LAT tissue changes from 9.12  ±  0.54 mm−1 to 4.54  ±  0.39 mm−1 and 3.61  ±  0.38 mm−1 at 120 min for 60 nm TiO2 NPs and 60 nm TiO2NPs/US treatment, respectively, and from 9.79  ±  0.32 mm−1 to 5.12  ±  0.47 mm−1 and 4.89  ±  0.59 mm−1 at 150 min for 100 nm TiO2 NPs and 100 nm TiO2NPs/US, respectively. The results suggest that the optical properties of NL and LAT tissues are greatly influenced by TiO2 NPs and their combination with ultrasound. (paper)

  2. Increase in tumor control and normal tissue complication probabilities in advanced head-and-neck cancer for dose-escalated intensity-modulated photon and proton therapy

    Directory of Open Access Journals (Sweden)

    Annika eJakobi

    2015-11-01

    Full Text Available Introduction:Presently used radio-chemotherapy regimens result in moderate local control rates for patients with advanced head and neck squamous cell carcinoma (HNSCC. Dose escalation (DE may be an option to improve patient outcome, but may also increase the risk of toxicities in healthy tissue. The presented treatment planning study evaluated the feasibility of two DE levels for advanced HNSCC patients, planned with either intensity-modulated photon therapy (IMXT or proton therapy (IMPT.Materials and Methods:For 45 HNSCC patients, IMXT and IMPT treatment plans were created including DE via a simultaneous integrated boost (SIB in the high-risk volume, while maintaining standard fractionation with 2 Gy per fraction in the remaining target volume. Two DE levels for the SIB were compared: 2.3 Gy and 2.6 Gy. Treatment plan evaluation included assessment of tumor control probabilities (TCP and normal tissue complication probabilities (NTCP.Results:An increase of approximately 10% in TCP was estimated between the DE levels. A pronounced high-dose rim surrounding the SIB volume was identified in IMXT treatment. Compared to IMPT, this extra dose slightly increased the TCP values and to a larger extent the NTCP values. For both modalities, the higher DE level led only to a small increase in NTCP values (mean differences < 2% in all models, except for the risk of aspiration, which increased on average by 8% and 6% with IMXT and IMPT, respectively, but showed a considerable patient dependence. Conclusions:Both DE levels appear applicable to patients with IMXT and IMPT since all calculated NTCP values, except for one, increased only little for the higher DE level. The estimated TCP increase is of relevant magnitude. The higher DE schedule needs to be investigated carefully in the setting of a prospective clinical trial, especially regarding toxicities caused by high local doses that lack a sound dose response description, e.g., ulcers.

  3. Next-generation sequencing of RNA and DNA isolated from paired fresh-frozen and formalin-fixed paraffin-embedded samples of human cancer and normal tissue.

    Directory of Open Access Journals (Sweden)

    Jakob Hedegaard

    Full Text Available Formalin-fixed, paraffin-embedded (FFPE tissues are an invaluable resource for clinical research. However, nucleic acids extracted from FFPE tissues are fragmented and chemically modified making them challenging to use in molecular studies. We analysed 23 fresh-frozen (FF, 35 FFPE and 38 paired FF/FFPE specimens, representing six different human tissue types (bladder, prostate and colon carcinoma; liver and colon normal tissue; reactive tonsil in order to examine the potential use of FFPE samples in next-generation sequencing (NGS based retrospective and prospective clinical studies. Two methods for DNA and three methods for RNA extraction from FFPE tissues were compared and were found to affect nucleic acid quantity and quality. DNA and RNA from selected FFPE and paired FF/FFPE specimens were used for exome and transcriptome analysis. Preparations of DNA Exome-Seq libraries was more challenging (29.5% success than that of RNA-Seq libraries, presumably because of modifications to FFPE tissue-derived DNA. Libraries could still be prepared from RNA isolated from two-decade old FFPE tissues. Data were analysed using the CLC Bio Genomics Workbench and revealed systematic differences between FF and FFPE tissue-derived nucleic acid libraries. In spite of this, pairwise analysis of DNA Exome-Seq data showed concordance for 70-80% of variants in FF and FFPE samples stored for fewer than three years. RNA-Seq data showed high correlation of expression profiles in FF/FFPE pairs (Pearson Correlations of 0.90 +/- 0.05, irrespective of storage time (up to 244 months and tissue type. A common set of 1,494 genes was identified with expression profiles that were significantly different between paired FF and FFPE samples irrespective of tissue type. Our results are promising and suggest that NGS can be used to study FFPE specimens in both prospective and retrospective archive-based studies in which FF specimens are not available.

  4. Absolute Humidity and the Seasonality of Influenza (Invited)

    Science.gov (United States)

    Shaman, J. L.; Pitzer, V.; Viboud, C.; Grenfell, B.; Goldstein, E.; Lipsitch, M.

    2010-12-01

    Much of the observed wintertime increase of mortality in temperate regions is attributed to seasonal influenza. A recent re-analysis of laboratory experiments indicates that absolute humidity strongly modulates the airborne survival and transmission of the influenza virus. Here we show that the onset of increased wintertime influenza-related mortality in the United States is associated with anomalously low absolute humidity levels during the prior weeks. We then use an epidemiological model, in which observed absolute humidity conditions temper influenza transmission rates, to successfully simulate the seasonal cycle of observed influenza-related mortality. The model results indicate that direct modulation of influenza transmissibility by absolute humidity alone is sufficient to produce this observed seasonality. These findings provide epidemiological support for the hypothesis that absolute humidity drives seasonal variations of influenza transmission in temperate regions. In addition, we show that variations of the basic and effective reproductive numbers for influenza, caused by seasonal changes in absolute humidity, are consistent with the general timing of pandemic influenza outbreaks observed for 2009 A/H1N1 in temperate regions. Indeed, absolute humidity conditions correctly identify the region of the United States vulnerable to a third, wintertime wave of pandemic influenza. These findings suggest that the timing of pandemic influenza outbreaks is controlled by a combination of absolute humidity conditions, levels of susceptibility and changes in population mixing and contact rates.

  5. Supplementary and Enrichment Series: Absolute Value. Teachers' Commentary. SP-25.

    Science.gov (United States)

    Bridgess, M. Philbrick, Ed.

    This is one in a series of manuals for teachers using SMSG high school supplementary materials. The pamphlet includes commentaries on the sections of the student's booklet, answers to the exercises, and sample test questions. Topics covered include addition and multiplication in terms of absolute value, graphs of absolute value in the Cartesian…

  6. Supplementary and Enrichment Series: Absolute Value. SP-24.

    Science.gov (United States)

    Bridgess, M. Philbrick, Ed.

    This is one in a series of SMSG supplementary and enrichment pamphlets for high school students. This series is designed to make material for the study of topics of special interest to students readily accessible in classroom quantity. Topics covered include absolute value, addition and multiplication in terms of absolute value, graphs of absolute…

  7. ABSOLUTE STABILITY OF GENERAL LURIE DISCRETE NONLINEAR CONTROL SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    GAN Zuoxin; HAN Jingqing; ZHAO Suxia; WU Yongxian

    2002-01-01

    In the present paper, the absolute stability of general Lurie discrete nonlinear control systems has been discussed by Lyapunov function approach. A sufficient condition of absolute stability for the general Lurie discrete nonlinear control systems is derived, and some necessary and sufficient conditions are obtained in special cases. Meanwhile, we give a simple example to illustrate the effectiveness of the results.

  8. Novalis' Poetic Uncertainty: A "Bildung" with the Absolute

    Science.gov (United States)

    Mika, Carl

    2016-01-01

    Novalis, the Early German Romantic poet and philosopher, had at the core of his work a mysterious depiction of the "absolute." The absolute is Novalis' name for a substance that defies precise knowledge yet calls for a tentative and sensitive speculation. How one asserts a truth, represents an object, and sets about encountering things…

  9. Absolute neutronic performance of SNS from gold foil application

    International Nuclear Information System (INIS)

    The determination of absolute neutron fluxes by white beam activation of thick gold foils in conjuction with spectral analysis by time-of-flight monitors is described. A numerical integration procedure is presented and the method applied to determining the absolute performance of SNS from data obtained during the initial commissioning run in December 1984. (author)

  10. High-precision absolute coordinate measurement using frequency scanned interferometry

    International Nuclear Information System (INIS)

    We reported previously on measurements of absolute distance with frequency scanned interferometry (FSI) method [1, 2]. In this paper, we extend the FSI method into 2-dimensional and 3-dimensional high-precision absolute coordinate measurements using a single laser. Absolute position is determined by several related absolute distances measured simultaneously. The achieved precision on X and Y in 2- and in 3-dimensional measurements is confirmed to be below 1 μm, while the precision in Z (in 3D case) is found to be about 2 μm. The last one is limited by the accuracy of the available translational stage used in the tests. A much more powerful laser and a better real-time data acquirement system will be required in case of measurements of larger absolute distances

  11. Lower liver cancer risk with antiviral therapy in chronic hepatitis B patients with normal to minimally elevated ALT and no cirrhosis

    Science.gov (United States)

    Hoang, Joseph K.; Yang, Hwai-I; Le, An; Nguyen, Nghia H.; Lin, Derek; Vu, Vinh D.; Chaung, Kevin; Nguyen, Vincent; Trinh, Huy N.; Li, Jiayi; Zhang, Jian Q.; Chen, Chien-Jen; Nguyen, Mindie H.

    2016-01-01

    Abstract For chronic hepatitis B (CHB), alanine aminotransferase (ALT) ≥2 × upper limit of normal (ULN) is often used as a major criteria to initiate treatment in absence of cirrhosis, though patients with lower ALT may not be free from future risk of hepatocellular carcinoma (HCC). We aimed to examine the effect of antiviral therapy on HCC incidence based on ALT levels. We performed a retrospective study on 3665 patients consisting of United States and Taiwanese REVEAL-HBV cohort who were consecutive, treatment-naïve, noncirrhotic CHB patients aged ≥40 years. Patients were categorized by ALT cutoffs (≥2 × ULN vs <2 × ULN) and subgrouped by treatment status. Kaplan–Meier and Cox proportional hazards models were used to calculate cumulative incidence and hazard ratio (HR) of HCC adjusting for REACH-B scores. A total of 202 patients developed HCC. Antiviral treatment significantly reduced HCC risk: HR 0.24, 95% confidence interval 0.10–0.58; P = 0.001. HCC incidence per 100,000 person-years was significantly higher in untreated versus treated patients, even for those with ALT < 2 × ULN: 314.46 versus 0 per 100,000 person-years, P = 0.0042. For patients with Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) ≥ 2000 IU/mL, the number-needed-to-treat (NNT) were 15 and 14 to prevent 1 incident HCC at year 10 for patients with ALT < 2 × ULN and ≥2 × ULN, respectively. After adjustment by REACH-B score, antiviral treatment significantly decreased HCC incidence even in patients with ALT < 2 × ULN. NNT to prevent 1 incident HCC after 10 years of therapy was low (14–15) in patients with mildly elevated HBV DNA ≥ 2000 IU/mL regardless of ALT levels. PMID:27495067

  12. Improvements in the absolute standardization of large-area reference sources.

    Science.gov (United States)

    Stanga, D; De Felice, P

    2009-09-01

    Using a simple gas-gain model, the efficiency sensitivity of gas-flow proportional counters to changes in the influence quantities (applied anode voltage, gas purity, gas-flow rate, ambient pressure and temperature) was analyzed and applied for the absolute standardization of large-area reference sources. Thus, the uncertainty of measurement was evaluated by taking into account the fluctuations of these quantities in normal conditions of counter operation. It was shown that the uncertainty is small in these conditions but accidental and large changes in the influence quantities may give rise to large errors of measurement. In addition, a cleaning procedure and a simple way of stabilizing the gain of gas-flow proportional counters were used to improve the absolute standardization of large-area reference sources. As a result, measurements were performed with uncertainties smaller than 0.55% and the reproducibility better than 0.42%. PMID:19376713

  13. Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development

    Directory of Open Access Journals (Sweden)

    Nick D.L. Owens

    2016-01-01

    Full Text Available Transcript regulation is essential for cell function, and misregulation can lead to disease. Despite technologies to survey the transcriptome, we lack a comprehensive understanding of transcript kinetics, which limits quantitative biology. This is an acute challenge in embryonic development, where rapid changes in gene expression dictate cell fate decisions. By ultra-high-frequency sampling of Xenopus embryos and absolute normalization of sequence reads, we present smooth gene expression trajectories in absolute transcript numbers. During a developmental period approximating the first 8 weeks of human gestation, transcript kinetics vary by eight orders of magnitude. Ordering genes by expression dynamics, we find that “temporal synexpression” predicts common gene function. Remarkably, a single parameter, the characteristic timescale, can classify transcript kinetics globally and distinguish genes regulating development from those involved in cellular metabolism. Overall, our analysis provides unprecedented insight into the reorganization of maternal and embryonic transcripts and redefines our ability to perform quantitative biology.

  14. Absolute measurement of the nitrogen fluorescence yield in air between 300 and 430 nm

    CERN Document Server

    Lefeuvre, G; Gorodetzky, P; Patzak, T; Salin, P

    2007-01-01

    The nitrogen fluorescence induced in air is used to detect ultra-high energy cosmic rays and to measure their energy. The precise knowledge of the absolute fluorescence yield is the key quantity to improve the accuracy on the cosmic ray energy. The total yield has been measured in dry air using a 90Sr source and a [300-430 nm] filter. The fluorescence yield in air is 4.23 $\\pm$ 0.20 photons per meter when normalized to 760 mmHg, 15 degrees C and with an electron energy of 0.85 MeV. This result is consistent with previous experiments made at various energies, but with an accuracy improved by a factor of about 3. For the first time, the absolute continuous spectrum of nitrogen excited by 90Sr electrons has also been measured with a spectrometer. Details of this experiment are given in one of the author's PhD thesis [32].

  15. The Absolute, Relative and Multi-Wavelength Calibration of the Pierre Auger Observatory Fluorescence Detectors

    Energy Technology Data Exchange (ETDEWEB)

    Knapik, R.; Bauleo, P.; Becker, B.R.; Brack, J.; Caruso, R.; Fratte, C.Delle; Dorofeev, A.; Harton, J.; Insolia, A.; Matthews, J.A.J.; Menshikov, A.

    2007-08-01

    Absolute calibration of the Pierre Auger Observatory fluorescence detectors uses a 375 nm light source at the telescope aperture. This end-to-end technique accounts for the combined effects of all detector components in a single measurement. The relative response has been measured at wavelengths of 320, 337, 355, 380 and 405 nm, defining a spectral response curve which has been normalized to the absolute calibration. Before and after each night of data taking a relative calibration of the phototubes is performed. This relative calibration is used to track both short and long term changes in the detector's response. A cross check of the calibration in some phototubes is performed using an independent laser technique. Overall uncertainties, current results and future plans are discussed.

  16. 毛细管电泳检测肺癌及癌旁正常组织蛋白质混合物差异%Capillary Electrophoresis Detection of Lung Cancer and Adjacent Normal Tissue Differences in Protein Mixture

    Institute of Scientific and Technical Information of China (English)

    刘勇; 王荣; 高岚; 贾正平; 谢华; 张军莉; 马骏; 张爱梅; 谢希晖

    2011-01-01

    以建立的毛细管电泳(CE)-激光诱导荧光(LIF)检测蛋白质的方法对提取肺癌及癌旁正常组织蛋白质混合物(变性/活性)差异进行检测.采用异硫氰酸荧光素(FITC)为衍生剂,电泳缓冲液为1×TBE(TBE为Tris-硼酸-EDTA,变性电泳pH 10.0,活性电泳为pH 8.3且含有2 mg/L考马斯亮蓝),分离电压15 kV,柱温15℃,电动进样(10 kV×10 s),激发波长/发射波长=488/520 nm检测时,肺癌及癌旁正常组织蛋白质混合物样品得到较好分离且有明显差异.与目前常用蛋白分析方法:变性SDS-聚丙烯酰胺凝胶电泳(SDS-PAGE)以及活性蓝绿温和胶电泳(BN-PAGE)进行比较.BN-PAGE结果显示肺癌组织相比正常组织有较明显蛋白种类差异;SDS-PAGE结果表明一些蛋白质表达量差异也是肺癌及癌旁正常组织的显著差别,且主要集中在20~116 kDa.CE-LIF检测结果与PAGE结果大致相同,且CE-LIF检测蛋白质的灵敏度高于PAGE,能更准确反映肺癌及癌旁正常组织的蛋白质差异.结论是CE-LIF可用于蛋白质差异检测,时间短,效果较好,对活性蛋白质进行分析体现了其优点:可提供较强的动力--电压,及强动力下良好的温度稳定性.%Protein mixture (denatured and native) differences of extracted from lung cancer and adjacent normal tissue by established method of capillary electrophoresis (CE)-laser-induced fluorescence (LIF) detection of protein was detected using the fluorescein isothiocyanate (FITC) as a derivative agent. When detected by the 1 × TBE electrophoresis buffer solution (pH 10.0 of denaturing gel electrophoresis and pH 8.3of native gel electrophoresis containing 2 mg/L Coomassie brilliant blue), separation voltage of 15 kV, column temperature of 15 ℃, electric injection (10 kV × 10 s), and excitation wavelength/emission wavelength of 488/520 nm, lung cancer and adjacent normal tissue protein mixture samples obtained a better separation and there was significant difference

  17. A review on thyroid cancer during pregnancy: Multitasking is required.

    Science.gov (United States)

    Khaled, Hussein; Al Lahloubi, Nasr; Rashad, Noha

    2016-07-01

    Thyroid cancer is the second most common cancer diagnosed during pregnancy after breast cancer. The goal of management is to control malignancy and prevent maternal and fetal complications as a result of maternal hypothyroidism. The role of female sex hormones as an etiologic factor was investigated, with no clear association. Pregnancy can cause an increase in size of a previously existed thyroid nodule through the structural similarity between TSH and BHCG, and the normally expressed estrogen receptors on thyroid gland cells. Effect of pregnancy on development and prognosis of differentiated thyroid malignancies (papillary and follicular) has also been studied. The prognosis of thyroid cancer is not worse in patients diagnosed during pregnancy or those who got pregnant after curative treatment. Termination of pregnancy is not indicated at all, surgery can be delayed till after delivery except in rapidly growing aggressive tumors. While radioactive iodine ablation is absolutely contra-indicated, the new systemic therapies are not well studied during pregnancy. However, almost all these new agents are classified as FDA category C or D and are better to be avoided. The effect of pregnancy on other types of thyroid cancer (medullary and anaplastic thyroid tumors) is not well studied because of very low incidence with pregnancy. The endocrinological management of thyroid cancer during pregnancy is of utmost importance. The hypothyroidism after total thyroidectomy can cause fetal hypothyroidism. Therefore, the management of thyroid cancer related to pregnancy needs a multidisciplinary team. PMID:27408758

  18. Absolute homogeneity test of Kelantan catchment precipitation series

    Science.gov (United States)

    Ros, Faizah Che; Tosaka, Hiroyuki; Sasaki, Kenji; Sidek, Lariyah Mohd; Basri, Hidayah

    2015-05-01

    Along the Kelantan River in north east of Malaysia Peninsular, there are several areas often damaged by flood during north-east monsoon season every year. It is vital to predict the expected behavior of precipitation and river runoff for reducing flood damages of the area under rapid urbanization and future planning. Nevertheless, the accuracy and reliability of any hydrological and climate studies vary based on the quality of the data used. The factors causing variations on these data are the method of gauging and data collection, stations environment, station relocation and the reliability of the measurement tool affect the homogenous precipitation records. Hence in this study, homogeneity of long precipitation data series is checked via the absolute homogeneity test consisting of four methods namely Pettitt test, standard normal homogeneity test (SNHT), Buishand range test and Von Neumann ratio test. For homogeneity test, the annual rainfall amount from the daily precipitation records at stations located in Kelantan operated by Department of Irrigation and Drainage Malaysia were considered in this study. The missing values were completed using the correlation and regression and inverse distance method. The data network consists of 103 precipitation gauging stations where 31 points are inactive, 6 gauging stations had missing precipitation values more than five years in a row and 16 stations have records less than twenty years. So total of 50 stations gauging stations were evaluated in this analysis. With the application of the mentioned methods and further graphical analysis, inhomogeneity was detected at 4 stations and 46 stations are found to be homogeneous.

  19. Breast Cancer Risk Assessment SAS Macro (Gail Model)

    Science.gov (United States)

    A SAS macro (commonly referred to as the Gail Model) that projects absolute risk of invasive breast cancer according to NCI’s Breast Cancer Risk Assessment Tool (BCRAT) algorithm for specified race/ethnic groups and age intervals.

  20. Absolute brightness temperature measurements at 2.1-mm wavelength

    Science.gov (United States)

    Ulich, B. L.

    1974-01-01

    Absolute measurements of the brightness temperatures of the Sun, new Moon, Venus, Mars, Jupiter, Saturn, and Uranus, and of the flux density of DR21 at 2.1-mm wavelength are reported. Relative measurements at 3.5-mm wavelength are also preented which resolve the absolute calibration discrepancy between The University of Texas 16-ft radio telescope and the Aerospace Corporation 15-ft antenna. The use of the bright planets and DR21 as absolute calibration sources at millimeter wavelengths is discussed in the light of recent observations.

  1. An All Fiber White Light Interferometric Absolute Temperature Measurement System

    Directory of Open Access Journals (Sweden)

    Jeonggon Harrison Kim

    2008-11-01

    Full Text Available Recently the author of this article proposed a new signal processing algorithm for an all fiber white light interferometer. In this article, an all fiber white light interferometric absolute temperature measurement system is presented using the previously proposed signal processing algorithm. Stability and absolute temperature measurement were demonstrated. These two tests demonstrated the feasibility of absolute temperature measurement with an accuracy of 0.015 fringe and 0.0005 fringe, respectively. A hysteresis test from 373K to 873K was also presented. Finally, robustness of the sensor system towards laser diode temperature drift, AFMZI temperature drift and PZT non-linearity was demonstrated.

  2. Absolute angular calibration of a submarine km3 neutrino telescope

    International Nuclear Information System (INIS)

    A requirement for neutrino telescope is the ability to resolve point sources of neutrinos. In order to understand its resolving power a way to perform absolute angular calibration with muons is required. Muons produced by cosmic rays in the atmosphere offer an abundant calibration source. By covering a surface vessel with 200 modules of 5 m2 plastic scintillator a surface air shower array can be set up. Running this array in coincidence with a deep-sea km3 size neutrino detector, where the coincidence is defined by the absolute clock timing stamp for each event, would allow absolute angular calibration to be performed. Monte Carlo results simulating the absolute angular calibration of the km3 size neutrino detector will be presented. Future work and direction will be discussed.

  3. A proposal to measure absolute environmental sustainability in lifecycle assessment

    DEFF Research Database (Denmark)

    Bjørn, Anders; Margni, Manuele; Roy, Pierre-Olivier;

    2016-01-01

    in supporting decisions aimed at simultaneously reducing environmental impacts efficiently and maintaining or achieving environmental sustainability. We have demonstrated that LCA indicators can be modified from being relative to being absolute indicators of environmental sustainability. Further research should...

  4. Absolute value preconditioning for symmetric indefinite linear systems

    CERN Document Server

    Vecharynski, Eugene

    2011-01-01

    We introduce a novel strategy for constructing symmetric positive definite (SPD) preconditioners for linear systems with symmetric indefinite coefficient matrices. The strategy is motivated by the observation that the preconditioned minimal residual method with the inverse of the absolute value of the coefficient matrix as a preconditioner converges to the exact solution of the system in at most two steps. Neither the exact absolute value of the coefficient matrix, nor its exact inverse are computationally feasible to construct in general. However, as the proof of concept, we provide two practical examples of SPD preconditioners, which are based on the suggested approach, called absolute value preconditioning. The first example is for strictly (block) diagonally dominant coefficient matrices, where we propose using the inverse to the absolute value of the (block) diagonal as the preconditioner. Our second example is less intuitive. We consider a model problem with a shifted discrete negative Laplacian, and su...

  5. Absolute Value Boundedness, Operator Decomposition, and Stochastic Media and Equations

    Science.gov (United States)

    Adomian, G.; Miao, C. C.

    1973-01-01

    The research accomplished during this period is reported. Published abstracts and technical reports are listed. Articles presented include: boundedness of absolute values of generalized Fourier coefficients, propagation in stochastic media, and stationary conditions for stochastic differential equations.

  6. Preparation of an oakmoss absolute with reduced allergenic potential.

    Science.gov (United States)

    Ehret, C; Maupetit, P; Petrzilka, M; Klecak, G

    1992-06-01

    Synopsis Oakmoss absolute, an extract of the lichen Evernia prunastri, is known to cause allergenic skin reactions due to the presence of certain aromatic aldehydes such as atranorin, chloratranorin, ethyl hematommate and ethyl chlorohematommate. In this paper it is shown that treatment of Oakmoss absolute with amino acids such as lysine and/or leucine, lowers considerably the content of these allergenic constituents including atranol and chloratranol. The resulting Oakmoss absolute, which exhibits an excellent olfactive quality, was tested extensively in comparative studies on guinea pigs and on man. The results of the Guinea Pig Maximization Test (GPMT) and Human Repeated Insult Patch Test (HRIPT) indicate that, in comparison with the commercial test sample, the allergenicity of this new quality of Oakmoss absolute was considerably reduced, and consequently better skin tolerance of this fragrance for man was achieved. PMID:19272096

  7. Self-normalized processes

    CERN Document Server

    Heyde, C C

    2008-01-01

    Self-normalized processes are of common occurrence in probabilistic and statistical studies. This volume covers developments in the area, including self-normalized large and moderate deviations, and laws of the iterated logarithms for self-normalized martingales. It treats the theory and applications of self-normalization.

  8. Absolute Free Energies for Biomolecules in Implicit or Explicit Solvent

    Science.gov (United States)

    Berryman, Joshua T.; Schilling, Tanja

    Methods for absolute free energy calculation by alchemical transformation of a quantitative model to an analytically tractable one are discussed. These absolute free energy methods are placed in the context of other methods, and an attempt is made to describe the best practice for such calculations given the current state of the art. Calculations of the equilibria between the four free energy basins of the dialanine molecule and the two right- and left-twisted basins of DNA are discussed as examples.

  9. Establishment of Absolute Gravity Datum in CMONOC and Its Application

    OpenAIRE

    XING Lelin; LI Hui; Li, Jianguo; Zhang, Weimin; HE Zhitang

    2016-01-01

    The high accuracy absolute gravity datum covered the Chinese mainland area is established by using absolute gravity measurement data of one hundred stations in CMONOC(Crustal Movement Observation Network of China), the accuracy of each station is better than 5.0 μGal/a. The high accuracy gravity datum can be used for relative gravity measurements in adjustment, and the real gravity value can be determined from relative gravity measurement data of adjustment by using the gravity datum to avoid...

  10. Absolute Baseline for Testing of Electronic Distance Meters

    OpenAIRE

    Jaroslav Braun; Filip Dvořáček; Martin Štroner

    2014-01-01

    The paper deals with the construction and determination of coordinates of the absoluteEDMs baseline in a laboratory with 16 pillars with forced centring. Leica Absolute TrackerAT401 (standard deviation of distance measurement: 5 μ m, standard deviation of anglemeasurement: 0.15 mgon), which is designed for very accurate industrial measurements,was used for our purpose. Lengths between the baseline points were determined with astandard deviation of 0.02 mm. The baseline is used for determining...

  11. Absolute Branching Fraction Measurements of Exclusive D^0 Semileptonic Decays

    CERN Document Server

    Coan, T E; Liu, F; Artuso, M; Boulahouache, C; Blusk, S; Butt, J; Dambasuren, E; Dorjkhaidav, O; Li, J; Menaa, N; Mountain, R; Nandakumar, R; Redjimi, R; Sia, R; Skwarnicki, T; Stone, S; Wang, J C; Zhang, K; Csorna, S E; Bonvicini, G; Cinabro, D; Dubrovin, M; Briere, R A; Chen, G P; Chen, J; Ferguson, T; Tatishvili, G T; Vogel, H; Watkins, M E; Rosner, J L; Adam, N E; Alexander, J P; Berkelman, K; Cassel, D G; Credé, V; Duboscq, J E; Ecklund, K M; Ehrlich, R; Fields, L; Gibbons, L; Gittelman, B; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Hsu, L; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Meyer, T O; Onyisi, P U E; Patterson, J R; Peterson, D; Pivarski, J; Phillips, E A; Riley, D; Ryd, A; Sadoff, A J; Schwarthoff, H; Shepherd, M R; Stroiney, S; Sun, W M; Urner, D; Wilksen, T; Weinberger, M; Athar, S B; Avery, P; Breva-Newell, L; Patel, R; Potlia, V; Stöck, H; Yelton, J; Rubin, P; Cawlfield, C; Eisenstein, B I; Gollin, G D; Karliner, I; Kim, D; Lowrey, N; Naik, P; Sedlack, C; Selen, M; Williams, J; Wiss, J; Edwards, K W; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Gong, D T; Kubota, Y; Klein, T; Lang, B W; Li, S Z; Poling, R; Scott, A W; Smith, A; Dobbs, S; Metreveli, Z V; Seth, K K; Tomaradze, A G; Zweber, P; Ernst, J; Mahmood, A H; Severini, H; Asner, D M; Dytman, S A; Love, W; Mehrabyan, S S; Müller, J A; Savinov, V; Li, Z; López, A; Méndez, H; Ramírez, J; Huang, G S; Miller, D H; Pavlunin, V; Sanghi, B; Shibata, E I; Shipsey, I P J; Adams, G S; Chasse, M; Cravey, M; Cummings, J P; Danko, I; Napolitano, J; He, Q; Muramatsu, H; Park, C S; Park, W; Thorndike, E H

    2005-01-01

    With the first data sample collected by the CLEO-c detector at the psi(3770) resonance we have studied four exclusive semileptonic decays of the D0 meson. Our results include the first observation and absolute branching fraction measurement for D0 --> rho- e+ nu_e and improved measurements of the absolute branching fractions for D0 decays to K- e+ nu_e, pi- e+ nu_e, and K*- e+ nu_e.

  12. DIAGNOSTIC TEST FOR GARCH MODELS BASED ON ABSOLUTE RESIDUAL AUTOCORRELATIONS

    Directory of Open Access Journals (Sweden)

    Farhat Iqbal

    2013-10-01

    Full Text Available In this paper the asymptotic distribution of the absolute residual autocorrelations from generalized autoregressive conditional heteroscedastic (GARCH models is derived. The correct asymptotic standard errors for the absolute residual autocorrelations are also obtained and based on these results, a diagnostic test for checking the adequacy of GARCH-type models are developed. Our results do not depend on the existence of higher moments and is therefore robust under heavy-tailed distributions.

  13. Tests for Liver Cancer

    Science.gov (United States)

    ... has come back after treatment Alpha-fetoprotein blood (AFP) test AFP is normally present at high levels in the ... liver disease, liver cancer, or other cancers. If AFP levels are very high in someone with a ...

  14. Stages of Skin Cancer

    Science.gov (United States)

    ... cells than in normal cells. For skin cancer, laser light is shined onto the skin and the drug becomes active and kills the cancer cells. Photodynamic therapy causes little damage to healthy tissue. Biologic therapy ...

  15. Skin Cancer Treatment

    Science.gov (United States)

    ... cells than in normal cells. For skin cancer, laser light is shined onto the skin and the drug becomes active and kills the cancer cells. Photodynamic therapy causes little damage to healthy tissue. Biologic therapy ...

  16. Cancer in Children

    Science.gov (United States)

    Cancer begins in the cells, which are the building blocks of your body. Normally, new cells form ... can form a tumor. Benign tumors aren't cancer while malignant ones are. Malignant tumor cells can ...

  17. The Pragmatics of "Unruly" Dative Absolutes in Early Slavic

    Directory of Open Access Journals (Sweden)

    Daniel E. Collins

    2011-08-01

    Full Text Available This chapter examines some uses of the dative absolute in Old Church Slavonic and in early recensional Slavonic texts that depart from notions of how Indo-European absolute constructions should behave, either because they have subjects coreferential with the (putative main-clause subjects or because they function as if they were main clauses in their own right. Such "noncanonical" absolutes have generally been written off as mechanistic translations or as mistakes by scribes who did not understand the proper uses of the construction. In reality, the problem is not with literalistic translators or incompetent scribes but with the definition of the construction itself; it is quite possible to redefine the Early Slavic dative absolute in a way that accounts for the supposedly deviant cases. While the absolute is generally dependent semantically on an adjacent unit of discourse, it should not always be regarded as subordinated syntactically. There are good grounds for viewing some absolutes not as dependent clauses but as independent sentences whose collateral character is an issue not of syntax but of the pragmatics of discourse.

  18. Cancer Basics

    Science.gov (United States)

    ... Cancer? Breast Cancer Colon/Rectum Cancer Lung Cancer Prostate Cancer Skin Cancer Show All Cancer Types News and Features Cancer Glossary ACS Bookstore Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects ...

  19. Absolute Measurement of Hadronic Branching Fractions of the D_s^+ Meson

    CERN Document Server

    Alexander, J; Cassel, D G; Duboscq, J E; Ehrlich, R; Fields, L; Gibbons, L; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Mohapatra, D; Onyisi, P U E; Patterson, J R; Peterson, D; Riley, D; Ryd, A; Sadoff, A J; Shi, X; Stroiney, S; Sun, W M; Wilksen, T; Athar, S B; Patel, R; Yelton, J; Rubin, P; Eisenstein, B I; Karliner, I; Mehrabyan, S; Lowrey, N; Selen, M; White, E J; Wiss, J; Mitchell, R E; Shepherd, M R; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Poling, R; Scott, A W; Zweber, P; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A G; Libby, J; Powell, A; Wilkinson, G; Ecklund, K M; Love, W; Savinov, V; López, A; Méndez, H; Ramírez, J; Ge, J Y; Miller, D H; Sanghi, B; Shipsey, I P J; Xin, B; Adams, G S; Anderson, M; Cummings, J P; Danko, I; Hu, D; Moziak, B; Napolitano, J; He, Q; Insler, J; Muramatsu, H; Park, C S; Thorndike, E H; Yang, F; Artuso, M; Blusk, S; Khalil, S; Li, J; Mountain, R; Nisar, S; Randrianarivony, K; Sultana, N; Skwarnicki, T; Stone, S; Wang, J C; Zhang, L M; Bonvicini, G; Cinabro, D; Dubrovin, M; Lincoln, A; Rademacker, J; Asner, D M; Edwards, K W; Naik, P; Briere, R A; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L

    2008-01-01

    The branching fractions of D_s meson decays serve to normalize many measurements of processes involving charm quarks. Using 298 /pb of e+ e- collisions recorded at a center of mass energy of 4.17 GeV, we determine absolute branching fractions for eight D_s decays with a double tag technique. In particular we determine the branching fraction B(D_s -> K- K+ pi+) = (5.50 +- 0.23 +- 0.16)%, where the uncertainties are statistical and systematic respectively. We also provide partial branching fractions for kinematic subsets of the K- K+ pi+ decay mode.

  20. Method to obtain absolute impurity density profiles combining charge exchange and beam emission spectroscopy without absolute intensity calibrationa)

    Science.gov (United States)

    Kappatou, A.; Jaspers, R. J. E.; Delabie, E.; Marchuk, O.; Biel, W.; Jakobs, M. A.

    2012-10-01

    Investigation of impurity transport properties in tokamak plasmas is essential and a diagnostic that can provide information on the impurity content is required. Combining charge exchange recombination spectroscopy (CXRS) and beam emission spectroscopy (BES), absolute radial profiles of impurity densities can be obtained from the CXRS and BES intensities, electron density and CXRS and BES emission rates, without requiring any absolute calibration of the spectra. The technique is demonstrated here with absolute impurity density radial profiles obtained in TEXTOR plasmas, using a high efficiency charge exchange spectrometer with high etendue, that measures the CXRS and BES spectra along the same lines-of-sight, offering an additional advantage for the determination of absolute impurity densities.

  1. Method to obtain absolute impurity density profiles combining charge exchange and beam emission spectroscopy without absolute intensity calibration

    Energy Technology Data Exchange (ETDEWEB)

    Kappatou, A.; Delabie, E. [FOM Institute DIFFER - Dutch Institute for Fundamental Energy Research, Association EURATOM-FOM, 3430 BE Nieuwegein (Netherlands); Jaspers, R. J. E.; Jakobs, M. A. [Science and Technology of Nuclear Fusion, Eindhoven University of Technology, 5600 MB Eindhoven (Netherlands); Marchuk, O.; Biel, W. [Institute for Energy and Climate Research, Forschungszentrum Julich GmbH, Trilateral Euregio Cluster, 52425 Julich (Germany)

    2012-10-15

    Investigation of impurity transport properties in tokamak plasmas is essential and a diagnostic that can provide information on the impurity content is required. Combining charge exchange recombination spectroscopy (CXRS) and beam emission spectroscopy (BES), absolute radial profiles of impurity densities can be obtained from the CXRS and BES intensities, electron density and CXRS and BES emission rates, without requiring any absolute calibration of the spectra. The technique is demonstrated here with absolute impurity density radial profiles obtained in TEXTOR plasmas, using a high efficiency charge exchange spectrometer with high etendue, that measures the CXRS and BES spectra along the same lines-of-sight, offering an additional advantage for the determination of absolute impurity densities.

  2. Commissioning of the Absolute Luminosity For ATLAS detector at the LHC

    CERN Document Server

    Jakobsen, Sune; Hansen, Peter; Hansen, Jørgen Beck

    The startup of the LHC (Large Hadron Collider) has initialized a new era in particle physics. The standard model of particle physics has for the last 40 years with tremendous success described all measurements with phenomenal precision. The experiments at the LHC are testing the standard model in a new energy regime. To normalize the measurements and understand the potential discoveries of the LHC experiments it is often crucial to know the interaction rate - the absolute luminosity. The ATLAS (A Toroidal LHC ApparatuS) detector will measure luminosity by numerous methods. But for most of the methods only the relative luminosity is measured with good precision. The absolute scale has to be provided from elsewhere. ATLAS is like the other LHC experiments mainly relying of absolute luminosity calibration from van der Meer scans (beam separation scans). To cross check and maybe even improve the precision; ATLAS has built a sub-detector to measure the flux of protons scattered under very small angles as this flux...

  3. Data-driven intensity normalization of PET group comparison studies is superior to global mean normalization

    DEFF Research Database (Denmark)

    Borghammer, Per; Aanerud, Joel; Gjedde, Albert

    2009-01-01

    BACKGROUND: Global mean (GM) normalization is one of the most commonly used methods of normalization in PET and SPECT group comparison studies of neurodegenerative disorders. It requires that no between-group GM difference is present, which may be strongly violated in neurodegenerative disorders....... Importantly, such GM differences often elude detection due to the large intrinsic variance in absolute values of cerebral blood flow or glucose consumption. Alternative methods of normalization are needed for this type of data. MATERIALS AND METHODS: Two types of simulation were performed using CBF images...... from 49 controls. Two homogeneous groups of 20 subjects were sampled repeatedly. In one group, cortical CBF was artificially decreased moderately (simulation I) or slightly (simulation II). The other group served as controls. Ratio normalization was performed using five reference regions: (1) Global...

  4. Pre-therapeutic dosimetry of normal organs and tissues of {sup 177}Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kabasakal, Levent; AbuQbeitah, Mohammad; Ayguen, Aslan; Yeyin, Nami [Istanbul University, Department of Nuclear Medicine, Cerrahpasa Medical Faculty, Istanbul (Turkey); Ocak, Meltem [Istanbul University, Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul (Turkey); Demirci, Emre [Sisli Etfal Training and Research Hospital, Department of Nuclear Medicine, Istanbul (Turkey); Toklu, Turkay [Yeditepe University Medical Faculty, Department of Nuclear Medicine, Istanbul (Turkey)

    2015-12-15

    {sup 177}Lu-617-prostate-specific membrane antigen (PSMA) ligand seems to be a promising tracer for radionuclide therapy of progressive prostate cancer. However, there are no published data regarding the radiation dose given to the normal tissues. The aim of the present study was to estimate the pretreatment radiation doses in patients who will undergo radiometabolic therapy using a tracer amount of {sup 177}Lu-labeled PSMA ligand. The study included seven patients with progressive prostate cancer with a mean age of 63.9 ± 3.9 years. All patients had prior PSMA positron emission tomography (PET) imaging and had intense tracer uptake at the lesions. The injected {sup 177}Lu-PSMA-617 activity ranged from 185 to 210 MBq with a mean of 192.6 ± 11.0 MBq. To evaluate bone marrow absorbed dose 2-cc blood samples were withdrawn in short variable times (3, 15, 30, 60, and 180 min and 24, 48, and 120 h) after injection. Whole-body images were obtained at 4, 24, 48, and 120 h post-injection (p.i.). The geometric mean of anterior and posterior counts was determined through region of interest (ROI) analysis. Attenuation correction was applied using PSMA PET/CT images. The OLINDA/EXM dosimetry program was used for curve fitting, residence time calculation, and absorbed dose calculations. The calculated radiation-absorbed doses for each organ showed substantial variation. The highest radiation estimated doses were calculated for parotid glands and kidneys. Calculated radiation-absorbed doses per megabecquerel were 1.17 ± 0.31 mGy for parotid glands and 0.88 ± 0.40 mGy for kidneys. The radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands (p < 0.05). The calculated radiation dose to bone marrow was 0.03 ± 0.01 mGy/MBq. Our first results suggested that {sup 177}Lu-PSMA-617 therapy seems to be a safe method. The dose-limiting organ seems to be the parotid glands rather than kidneys and bone marrow. The lesion radiation doses are

  5. Should Patient Setup in Lung Cancer Be Based on the Primary Tumor? An Analysis of Tumor Coverage and Normal Tissue Dose Using Repeated Positron Emission Tomography/Computed Tomography Imaging

    International Nuclear Information System (INIS)

    Purpose: Evaluation of the dose distribution for lung cancer patients using a patient setup procedure based on the bony anatomy or the primary tumor. Methods and materials: For 39 patients with non–small-cell lung cancer, the planning fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scan was registered to a repeated FDG-PET/CT scan made in the second week of treatment. Two patient setup methods were analyzed based on the bony anatomy or the primary tumor. The original treatment plan was copied to the repeated scan, and target and normal tissue structures were delineated. Dose distributions were analyzed using dose–volume histograms for the primary tumor, lymph nodes, lungs, and spinal cord. Results: One patient showed decreased dose coverage of the primary tumor caused by progressive disease and required replanning to achieve adequate coverage. For the other patients, the minimum dose to the primary tumor did not significantly deviate from the planned dose: −0.2 ± 1.7% (p = 0.71) and −0.1 ± 1.7% (p = 0.85) for the bony anatomy setup and the primary tumor setup, respectively. For patients (n = 31) with nodal involvement, 10% showed a decrease in minimum dose larger than 5% for the bony anatomy setup and 13% for the primary tumor setup. The mean lung dose exceeded the maximum allowed 20 Gy in 21% of the patients for the bony anatomy setup and in 13% for the primary tumor setup, whereas for the spinal cord this occurred in 10% and 13% of the patients, respectively. Conclusions: In 10% and 13% of patients with nodal involvement, setup based on bony anatomy or primary tumor, respectively, led to important dose deviations in nodal target volumes. Overdosage of critical structures occurred in 10–20% of the patients. In cases of progressive disease, repeated imaging revealed underdosage of the primary tumor. Development of practical ways for setup procedures based on repeated high-quality imaging of all tumor sites during

  6. Comparison of whole-body PET/CT and PET/MRI in breast cancer patients: Lesion detection and quantitation of 18F-deoxyglucose uptake in lesions and in normal organ tissues

    Energy Technology Data Exchange (ETDEWEB)

    Pace, Leonardo, E-mail: lpace@unisa.it [Dipartimento di Medicina e Chirurgia, Università degli Studi di Salerno (Italy); Nicolai, Emanuele, E-mail: enicolai@sdn-napoli.it [IRCCS–SDN, Napoli (Italy); Luongo, Angelo, E-mail: angelo_luongo@libero.it [Dipartimento di Scienze Biomediche Avanzate, Università degli Studi di Napoli Federico II (Italy); Aiello, Marco, E-mail: maiello@sdn-napoli.it [IRCCS–SDN, Napoli (Italy); Catalano, Onofrio A., E-mail: onofriocatalano@yahoo.it [IRCCS–SDN, Napoli (Italy); Soricelli, Andrea, E-mail: andrea.soricelli@uniparthenope.it [Dipartimento di Studi delle Istituzioni e dei Sistemi Territoriali, Università degli Studi Parthenope di Napoli (Italy); Salvatore, Marco, E-mail: marsalva@unina.it [Dipartimento di Scienze Biomediche Avanzate, Università degli Studi di Napoli Federico II (Italy)

    2014-02-15

    Purpose: To compare the performance of PET/MRI imaging using MR attenuation correction (MRAC) (DIXON-based 4-segment -map) in breast cancer patients with that of PET/CT using CT-based attenuation correction and to compare the quantification accuracy in lesions and in normal organ tissues. Methods: A total of 36 patients underwent a whole-body PET/CT scan 1 h after injection and an average of 62 min later a second scan using a hybrid PET/MRI system. PET/MRI and PET/CT were compared visually by rating anatomic allocation and image contrast. Regional tracer uptake in lesions was quantified using volumes of interest, and maximal and mean standardized uptake values (SUVmax and SUVmean, respectively) were calculated. Metabolic tumor volume (MTV) of each lesion was computed on PET/MRI and PET/CT. Tracer uptake in normal organ tissue was assessed as SUVmax and SUVmean in liver, spleen, left ventricular myocardium, lung, and muscle. Results: Overall 74 FDG positive lesions were visualized by both PET/CT and PET/MRI. No significant differences in anatomic allocation scores were found between PET/CT and PERT/MRI, while contrast score of lesions on PET/MRI was significantly higher. Both SUVmax and SUVmean of lesions were significantly higher on PET/MRI than on PET/CT, with strong correlations between PET/MRI and PET/CT data (ρ = 0.71–0.88). MTVs of all lesions were 4% lower on PET/MRI than on PET/CT, but no statistically significant difference was observed, and an excellent correlation between measurements of MTV with PET/MRI and PET/CT was found (ρ = 0.95–0.97; p < 0.0001). Both SUVmax and SUVmean were significantly lower by PET/MRI than by PET/CT for lung, liver and muscle, no significant difference was observed for spleen, while either SUVmax and SUVmean of myocardium were significantly higher by PET/MRI. High correlations were found between PET/MRI and PET/CT for both SUVmax and SUVmean of the left ventricular myocardium (ρ = 0.91; p < 0.0001), while moderate

  7. Comparison of whole-body PET/CT and PET/MRI in breast cancer patients: Lesion detection and quantitation of 18F-deoxyglucose uptake in lesions and in normal organ tissues

    International Nuclear Information System (INIS)

    Purpose: To compare the performance of PET/MRI imaging using MR attenuation correction (MRAC) (DIXON-based 4-segment -map) in breast cancer patients with that of PET/CT using CT-based attenuation correction and to compare the quantification accuracy in lesions and in normal organ tissues. Methods: A total of 36 patients underwent a whole-body PET/CT scan 1 h after injection and an average of 62 min later a second scan using a hybrid PET/MRI system. PET/MRI and PET/CT were compared visually by rating anatomic allocation and image contrast. Regional tracer uptake in lesions was quantified using volumes of interest, and maximal and mean standardized uptake values (SUVmax and SUVmean, respectively) were calculated. Metabolic tumor volume (MTV) of each lesion was computed on PET/MRI and PET/CT. Tracer uptake in normal organ tissue was assessed as SUVmax and SUVmean in liver, spleen, left ventricular myocardium, lung, and muscle. Results: Overall 74 FDG positive lesions were visualized by both PET/CT and PET/MRI. No significant differences in anatomic allocation scores were found between PET/CT and PERT/MRI, while contrast score of lesions on PET/MRI was significantly higher. Both SUVmax and SUVmean of lesions were significantly higher on PET/MRI than on PET/CT, with strong correlations between PET/MRI and PET/CT data (ρ = 0.71–0.88). MTVs of all lesions were 4% lower on PET/MRI than on PET/CT, but no statistically significant difference was observed, and an excellent correlation between measurements of MTV with PET/MRI and PET/CT was found (ρ = 0.95–0.97; p < 0.0001). Both SUVmax and SUVmean were significantly lower by PET/MRI than by PET/CT for lung, liver and muscle, no significant difference was observed for spleen, while either SUVmax and SUVmean of myocardium were significantly higher by PET/MRI. High correlations were found between PET/MRI and PET/CT for both SUVmax and SUVmean of the left ventricular myocardium (ρ = 0.91; p < 0.0001), while moderate

  8. Phase I/II study of preoperative chemo-radiotherapy (CT-RT) using twice daily radiation as concomitant boost during two cycles of taxol (T), cisplatin (C), 5-FU (F) in esophageal cancer: normal tissue tolerance and early results

    International Nuclear Information System (INIS)

    Purpose/Objective: Even though preoperative CT has failed to show survival benefit over surgery alone, preoperative CT-RT may provide such survival advantage. The goal of this study was to evaluate an intensified radiotherapy (RT) schedule in preoperative concurrent CT-RT for toxicities, resection rate, tumor downstaging, pathologic complete remission (CR) and treatment outcome. Materials and Methods: Eligibility included biopsy proven squamous or adenocarcinoma, T2-4N0-1M0 lesions, performance status ≤ 2 of ECOG scale, creatinine ≤ 2.0 mg/dl, WBC ≥ 2,500/μl, and platelets ≥ 75,000//μl. CT consisted of cisplatin (P) 20 mg/m2/day (d) x 5 d, 5-FU (F) 800 mg/m2/d continuous infusion x 5 d and Taxol (T) 75-125 mg/m2 (3 hour infusion) on d1 of each cycle. RT delivered 58.5 Gy/34 fractions (F) /5 weeks (wks) to the gross tumor volume by a combination of 45 Gy/25 F/5 wks to a large target volume (6 cm proximal and distal, and 3 cm radial margins beyond the gross tumor) and a boost dose of 13.5 Gy/9 F (1.5 Gy/F x 5 d with the first cycle [wk 1] and 1.5 Gy/F x 4 d with the second cycle [wk 5] of CT) with an interval of ≥ 5 hours between RT to the gross tumor (am) and large target volume (pm) as a means of concomitant boost. Staging work up included barium swallow, chest and head computed tomography, bone scan, esophagoscopy, and endoscopic ultrasound study (EUS). Results: Between April 1995 and February 1997, 38 patients (pts) with locoregional esophageal cancer have been entered into this study. Patient characteristics were as follows: Age 33-84 (median 63), male: female 30 : 8, adenocarcinoma: squamous cell carcinoma 31 : 7. Tumor stages by EUS included T2N0 11 (29%), T2N1 3 (8%), T3N0 14 (37%), T3N1 8 (21%) and T4N0 2 (5%). Taxol dose was escalated from 75 mg/m2 (7 pts) to 125 mg/m2 (5 pts) at which dose limiting toxicities were observed in (3(5)) pts (myocardial infarction, pneumonia, grade 4 neutropenia). The remaining 26 pts have been treated with T 100 mg

  9. Normal Pressure Hydrocephalus

    Science.gov (United States)

    ... involves surgical placement of a shunt in the brain to drain excess CSF into the abdomen where it can be absorbed as part of the normal circulatory process. This allows the brain ventricles to return to their normal size. Regular ...

  10. Is My Penis Normal?

    Science.gov (United States)

    ... I Help a Friend Who Cuts? Is My Penis Normal? KidsHealth > For Teens > Is My Penis Normal? Print A A A Text Size en ... any guy who's ever worried about whether his penis is a normal size. There's a fairly wide ...

  11. Absolute cerebral blood flow and blood volume measured by magnetic resonance imaging bolus tracking: comparison with positron emission tomography values

    DEFF Research Database (Denmark)

    Østergaard, Leif; Smith, D F; Vestergaard-Poulsen, Peter;

    1998-01-01

    The authors determined cerebral blood flow (CBF) with magnetic resonance imaging (MRI) of contrast agent bolus passage and compared the results with those obtained by O-15 labeled water (H215O) and positron emission tomography (PET). Six pigs were examined by MRI and PET under normo......- and hypercapnic conditions. After dose normalization and introduction of an empirical constant phi Gd, absolute regional CBF was calculated from MRI. The spatial resolution and the signal-to-noise ratio of CBF measurements by MRI were better than by the H215O-PET protocol. Magnetic resonance imaging cerebral...... blood volume (CBV) estimates obtained using this normalization constant correlated well with values obtained by O-15 labeled carbonmonooxide (C15O) PET. However, PET CBV values were approximately 2.5 times larger than absolute MRI CBV values, supporting the hypothesized sensitivity of MRI to small...

  12. Minimally Invasive Treatment for Lung Cancer

    Medline Plus

    Full Text Available ... cancer surgery was done. It’s really an elaborate video game, and I would like to show you ... a whole lobe, you know, by doing the video-assisted thorascopic surgery alone? Absolutely. And you know ...

  13. Word recognition in competing babble and the effects of age, temporal processing, and absolute sensitivity.

    Science.gov (United States)

    Snell, Karen B; Mapes, Frances M; Hickman, Elizabeth D; Frisina, D Robert

    2002-08-01

    This study was designed to clarify whether speech understanding in a fluctuating background is related to temporal processing as measured by the detection of gaps in noise bursts. Fifty adults with normal hearing or mild high-frequency hearing loss served as subjects. Gap detection thresholds were obtained using a three-interval, forced-choice paradigm. A 150-ms noise burst was used as the gap carrier with the gap placed close to carrier onset. A high-frequency masker without a temporal gap was gated on and off with the noise bursts. A continuous white-noise floor was present in the background. Word scores for the subjects were obtained at a presentation level of 55 dB HL in competing babble levels of 50, 55, and 60 dB HL. A repeated measures analysis of covariance of the word scores examined the effects of age, absolute sensitivity, and temporal sensitivity. The results of the analysis indicated that word scores in competing babble decreased significantly with increases in babble level, age, and gap detection thresholds. The effects of absolute sensitivity on word scores in competing babble were not significant. These results suggest that age and temporal processing influence speech understanding in fluctuating backgrounds in adults with normal hearing or mild high-frequency hearing loss.

  14. Simple unbiased estimation of absolute free energies for biomolecules

    CERN Document Server

    Ytreberg, F M

    2005-01-01

    One reason that free energy difference calculations are notoriously difficult in molecular systems is due to insufficient conformational overlap, or similarity, between the two states or systems of interest. The degree of overlap is irrelevant, however, if the absolute free energy of each state can be computed. We present a method for calculating the absolute free energy that employs a simple construction of an exactly computable reference system which possesses high overlap with the state of interest. The approach requires only a physical ensemble of conformations generated via simulation, and an auxiliary calculation of approximately equal CPU cost. Moreover, the calculations can converge to the correct free energy value even when the physical ensemble is incomplete or improperly distributed. We use the approach to correctly predict free energies for test systems where the absolute values can be calculated exactly, and also to predict the conformational equilibrium for leucine dipeptide in GBSA implicit sol...

  15. The mixed Littlewood conjecture for pseudo-absolute values

    CERN Document Server

    Harrap, Stephen

    2010-01-01

    In this paper we prove the mixed Littlewood conjecture for a p-adic absolute value and any pseudo-absolute value with bounded ratios. More precisely we show that if p is a prime and D is a pseudo-absolute value sequence with elements divisible by finitely many primes not equal to p, and if the terms of D grow more slowly than the exponential of a polynomial then the infimum over natural numbers n of the quantity n.|n|_p.|n|_D.||nx|| equals 0 for all real x. Our proof relies on two deep results, a measure rigidity theorem due to Lindenstrauss and lower bounds for linear forms in logarithms due to Baker and Wustholz. We also deduce the answer to the related metric question of how fast the infimum above tends to zero, for almost every x.

  16. System and method for calibrating a rotary absolute position sensor

    Science.gov (United States)

    Davis, Donald R. (Inventor); Permenter, Frank Noble (Inventor); Radford, Nicolaus A (Inventor)

    2012-01-01

    A system includes a rotary device, a rotary absolute position (RAP) sensor generating encoded pairs of voltage signals describing positional data of the rotary device, a host machine, and an algorithm. The algorithm calculates calibration parameters usable to determine an absolute position of the rotary device using the encoded pairs, and is adapted for linearly-mapping an ellipse defined by the encoded pairs to thereby calculate the calibration parameters. A method of calibrating the RAP sensor includes measuring the rotary position as encoded pairs of voltage signals, linearly-mapping an ellipse defined by the encoded pairs to thereby calculate the calibration parameters, and calculating an absolute position of the rotary device using the calibration parameters. The calibration parameters include a positive definite matrix (A) and a center point (q) of the ellipse. The voltage signals may include an encoded sine and cosine of a rotary angle of the rotary device.

  17. An algorithm for estimating Absolute Salinity in the global ocean

    Directory of Open Access Journals (Sweden)

    T. J. McDougall

    2009-02-01

    Full Text Available To date, density and other thermodynamic properties of seawater have been calculated from Practical Salinity, S P. It is more accurate however to use Absolute Salinity, S A (the mass fraction of dissolved material in seawater. Absolute Salinity S A can be expressed in terms of Practical Salinity S P as

    S A=(35.165 04 g kg-1/35S PS A(φ, λ, p

    where δ S A is the Absolute Salinity Anomaly as a function of longitude φ, latitude λ and pressure. When a seawater sample has standard composition (i.e. the ratios of the constituents of sea salt are the same as those of surface water of the North Atlantic, the Absolute Salinity Anomaly is zero. When seawater is not of standard composition, the Absolute Salinity Anomaly needs to be estimated; this anomaly is as large as 0.025 g kg−1 in the northernmost North Pacific. Here we provide an algorithm for estimating Absolute Salinity Anomaly for any location (φ, λ, p in the world ocean.

    To develop this algorithm we use the Absolute Salinity Anomaly that is found by comparing the density calculated from Practical Salinity to the density measured in the laboratory. These estimates of Absolute Salinity Anomaly however are limited to the number of available observations (namely 811. To expand our data set we take advantage of approximate relationships between Absolute Salinity Anomaly and silicate concentrations (which are available globally. We approximate the laboratory-determined values of δ S A of the 811 seawater samples as a series of simple functions of the silicate concentration of the seawater sample and latitude; one function for each ocean basin. We use these basin-specific correlations and a digital atlas of silicate in the world ocean to deduce the Absolute Salinity

  18. Risk of second non-breast cancer after radiotherapy for breast cancer: A systematic review and meta-analysis of 762,468 patients

    International Nuclear Information System (INIS)

    Background and purpose: Radiotherapy for breast cancer both decreases loco-regional recurrence rates and improves overall survival. However, radiotherapy has also been associated with increased second cancer risk at exposed sites. In this meta-analysis, we estimated the risk of second non-breast cancers after radiotherapy for breast cancer. Material and methods: The databases Medline/Pubmed, Cochrane, Embase and Cinahl were systematically searched, for cohort studies on second cancer after radiotherapy for breast cancer, from inception to August 1st 2013. Included studies were to report the relative risk (RR) of second cancers comparing irradiated female breast cancer patients to unirradiated patients. Primary endpoints were all second non-breast-cancers and second cancers of the lung, esophagus, thyroid and second sarcomas. RRs were pooled using random-effects meta-analysis. Results: Thirteen studies comprising 762,468 breast cancer patients were included in the meta-analysis. Five or more years after breast cancer diagnosis radiotherapy was significantly associated with an increased risk of second non-breast cancer RR 1.12 (95% confidence interval [CI] 1.06–1.19), second cancer of the lung RR 1.39 (95% CI 1.28–1.51), esophagus RR 1.53 (95% CI 1.01–2.31) and second sarcomas RR 2.53 (95% CI 1.74–3.70). The risk increased over time, and was highest 15 or more years after breast cancer diagnosis, for second lung RR 1.66 (95% CI 1.36–2.01) and second esophagus cancer RR 2.17 (95% CI 1.11–4.25). There was no significant association between radiotherapy and second thyroid cancer. Conclusions: Radiotherapy for breast cancer is significantly associated with increased risks of second non-breast cancer, overall and in organs adjacent to the previous treatment fields. Despite a relative small absolute risk, the growing number of long-time survivors after breast cancer warrants the need for normal tissue sparing radiotherapy techniques

  19. Do normal hips dislocate?

    Science.gov (United States)

    Alshameeri, Zeiad; Rehm, Andreas

    2014-11-01

    There have been a small number of case reports describing late normal-hip dislocations in children who were later diagnosed with developmental dysplasia of the hip. Here, we contest the assumption that normal hips can dislocate. We argue that (as in our case) the ultrasound scans in all published case reports on late dislocated normal hips did not show results that were entirely normal and therefore, so far, there has been no convincing evidence of a dislocation of a normal hip. We also want to highlight the importance of meticulous ultrasound and clinical assessments of high-risk children by an experienced orthopaedic surgeon. PMID:25144883

  20. Neural sensitivity to absolute and relative anticipated reward in adolescents.

    Science.gov (United States)

    Vaidya, Jatin G; Knutson, Brian; O'Leary, Daniel S; Block, Robert I; Magnotta, Vincent

    2013-01-01

    Adolescence is associated with a dramatic increase in risky and impulsive behaviors that have been attributed to developmental differences in neural processing of rewards. In the present study, we sought to identify age differences in anticipation of absolute and relative rewards. To do so, we modified a commonly used monetary incentive delay (MID) task in order to examine brain activity to relative anticipated reward value (neural sensitivity to the value of a reward as a function of other available rewards). This design also made it possible to examine developmental differences in brain activation to absolute anticipated reward magnitude (the degree to which neural activity increases with increasing reward magnitude). While undergoing fMRI, 18 adolescents and 18 adult participants were presented with cues associated with different reward magnitudes. After the cue, participants responded to a target to win money on that trial. Presentation of cues was blocked such that two reward cues associated with $.20, $1.00, or $5.00 were in play on a given block. Thus, the relative value of the $1.00 reward varied depending on whether it was paired with a smaller or larger reward. Reflecting age differences in neural responses to relative anticipated reward (i.e., reference dependent processing), adults, but not adolescents, demonstrated greater activity to a $1 reward when it was the larger of the two available rewards. Adults also demonstrated a more linear increase in ventral striatal activity as a function of increasing absolute reward magnitude compared to adolescents. Additionally, reduced ventral striatal sensitivity to absolute anticipated reward (i.e., the difference in activity to medium versus small rewards) correlated with higher levels of trait Impulsivity. Thus, ventral striatal activity in anticipation of absolute and relative rewards develops with age. Absolute reward processing is also linked to individual differences in Impulsivity. PMID:23544046