Sample records for cancer absolutely normal

  1. Absolute quantification of somatic DNA alterations in human cancer. (United States)

    Carter, Scott L; Cibulskis, Kristian; Helman, Elena; McKenna, Aaron; Shen, Hui; Zack, Travis; Laird, Peter W; Onofrio, Robert C; Winckler, Wendy; Weir, Barbara A; Beroukhim, Rameen; Pellman, David; Levine, Douglas A; Lander, Eric S; Meyerson, Matthew; Getz, Gad


    We describe a computational method that infers tumor purity and malignant cell ploidy directly from analysis of somatic DNA alterations. The method, named ABSOLUTE, can detect subclonal heterogeneity and somatic homozygosity, and it can calculate statistical sensitivity for detection of specific aberrations. We used ABSOLUTE to analyze exome sequencing data from 214 ovarian carcinoma tumor-normal pairs. This analysis identified both pervasive subclonal somatic point-mutations and a small subset of predominantly clonal and homozygous mutations, which were overrepresented in the tumor suppressor genes TP53 and NF1 and in a candidate tumor suppressor gene CDK12. We also used ABSOLUTE to infer absolute allelic copy-number profiles from 3,155 diverse cancer specimens, revealing that genome-doubling events are common in human cancer, likely occur in cells that are already aneuploid, and influence pathways of tumor progression (for example, with recessive inactivation of NF1 being less common after genome doubling). ABSOLUTE will facilitate the design of clinical sequencing studies and studies of cancer genome evolution and intra-tumor heterogeneity.

  2. Absolute cross-section normalization of magnetic neutron scattering data (United States)

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


    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 can be used for general purposes are provided and the advantages of the different normalization processes are discussed.

  3. Cosmic backgrounds of relic gravitons and their absolute normalization

    CERN Document Server

    Giovannini, Massimo


    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...

  4. Cosmic backgrounds of relic gravitons and their absolute normalization (United States)

    Giovannini, Massimo


    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.

  5. Absolute quantification of somatic DNA alterations in human cancer


    Carter, Scott L.; Cibulskis, Kristian; Helman, Elena; McKenna, Aaron; Shen, Hui; Zack, Travis; Laird, Peter W.; Onofrio, Robert C.; Winckler, Wendy; Weir, Barbara A; Beroukhim, Rameen; Pellman, David; Levine, Douglas A.; Lander, Eric S.; Meyerson, Matthew


    We developed a computational method (ABSOLUTE) that infers tumor purity and malignant cell ploidy directly from analysis of somatic DNA alterations. ABSOLUTE can detect subclonal heterogeneity, somatic homozygosity, and calculate statistical sensitivity to detect specific aberrations. We used ABSOLUTE to analyze ovarian cancer data and identified pervasive subclonal somatic point mutations. In contrast, mutations occurring in key tumor suppressor genes, TP53 and NF1 were predominantly clonal ...

  6. Absolute quantification of somatic DNA alterations in human cancer


    Carter, Scott L.; Cibulskis, Kristian; Helman, Elena; McKenna, Aaron; Shen, Hui; Zack, Travis; Laird, Peter W.; Onofrio, Robert C.; Winckler, Wendy; Weir, Barbara A; Beroukhim, Rameen; Pellman, David; Levine, Douglas A.; Lander, Eric S.; Meyerson, Matthew


    We developed a computational method (ABSOLUTE) that infers tumor purity and malignant cell ploidy directly from analysis of somatic DNA alterations. ABSOLUTE can detect subclonal heterogeneity, somatic homozygosity, and calculate statistical sensitivity to detect specific aberrations. We used ABSOLUTE to analyze ovarian cancer data and identified pervasive subclonal somatic point mutations. In contrast, mutations occurring in key tumor suppressor genes, TP53 and NF1 were predominantly clonal ...

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

    Institute of Scientific and Technical Information of China (English)

    Xu Hanqiu


    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.

  8. Quantifying cancer absolute risk and cancer mortality in the presence of competing events after a myotonic dystrophy diagnosis.

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    Shahinaz M Gadalla

    Full Text Available Recent studies show that patients with myotonic dystrophy (DM have an increased risk of specific malignancies, but estimates of absolute cancer risk accounting for competing events are lacking. Using the Swedish Patient Registry, we identified 1,081 patients with an inpatient and/or outpatient diagnosis of DM between 1987 and 2007. Date and cause of death and date of cancer diagnosis were extracted from the Swedish Cause of Death and Cancer Registries. We calculated non-parametric estimates of absolute cancer risk and cancer mortality accounting for the high non-cancer competing mortality associated with DM. Absolute cancer risk after DM diagnosis was 1.6% (95% CI=0.4-4%, 5% (95% CI=3-9% and 9% (95% CI=6-13% at ages 40, 50 and 60 years, respectively. Females had a higher absolute risk of all cancers combined than males: 9% (95% CI=4-14, and 13% (95% CI=9-20 vs. 2% (95%CI= 0.7-6 and 4% (95%CI=2-8 by ages 50 and 60 years, respectively and developed cancer at younger ages (median age =51 years, range=22-74 vs. 57, range=43-84, respectively, p=0.02. Cancer deaths accounted for 10% of all deaths, with an absolute cancer mortality risk of 2% (95%CI=1-4.5%, 4% (95%CI=2-6%, and 6% (95%CI=4-9% by ages 50, 60, and 70 years, respectively. No gender difference in cancer-specific mortality was observed (p=0.6. In conclusion, cancer significantly contributes to morbidity and mortality in DM patients, even after accounting for high competing DM mortality from non-neoplastic causes. It is important to apply population-appropriate, validated cancer screening strategies in DM patients.

  9. Derivation of the Limits for Control Chart Using the Median Absolute Deviation for Monitoring Non-Normal Process

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    P. I. Azubuike


    Full Text Available Problem statement: The Shewhart and S control charts, in the literature, were combined to evaluate the stability of a process. These charts were based on the fundamental assumption of normality of the quality characteristics under investigation. Approach: In practice, the normality assumption was often violated by real life data, therefore, use of the Shewhart and S control charts on real life data might leads to misplacement of control limits. There were many alternatives in the literature to handle non-normality of quality characteristics. The Median Absolute Deviation (MAD claimed in the literature to be the best estimate when the data under consideration is non-normal. Thus in this study, we derived the control limits for the-control chart using the median absolute deviation for monitoring process stability when the quality characteristic under investigation was non-normal. Results: The derived control limits were compared with the control limits when the sample standard deviation was used as a measure of controlling the process variability using manufacturing process (real life data. Furthermore, a simulation study was carried out to evaluate the performance of the proposed MAD based control charts on both normal and non-normal process. Conclusion: The obtained results show that the derived control limit is an improvement on the control limit of the Shewhart and that the MAD control charts performed better for non-normal process than for normal process.

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


    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.

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

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    Nataڑa Vasiljeviš


    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.

  12. (99m)Tc-DMSA absolute and relative renal uptake in cats: procedure and normal values. (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


    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.

  13. [Colorectal cancer screening: an absolute necessity and an imminent reality in the French community]. (United States)

    Polus, M; Stibbe, G; Van Laethem, J-L; Adler, M; Coche, E


    Colorectal cancer is a true problematic of public health. The screening is an absolute necessity. An ambitious program of screening is launched in French Community. Faecal occult blood test (FOBT) will be proposed to average risk patients in general population. A total colonoscopy will be performed if FOBT will be positive. First step colonoscopy will be proposed to high or very high risk patients. General practitioners are in the core of the multidisciplinary program.

  14. [Colorectal cancer screening: an absolute necessity and a concrete reality in the French community]. (United States)

    Polus, M; Montrieux, C; Giet, D; Louis, E; Belaiche, J; Coche, E


    Colorectal cancer is a real problem of public health. Screening is an absolute necessity. An ambitious program of screening is launched in the French Community. Faecal occult blood test will be proposed to average risk patients in the general population. A total colonoscopy will be performed if FOBT is positive. First step colonoscopy will be proposed to high or very high risk patients. General practitioners are in the core of the multi-disciplinary program.

  15. Methodology to predict long-term cancer survival from short-term data using Tobacco Cancer Risk and Absolute Cancer Cure models (United States)

    Mould, R. F.; Lederman, M.; Tai, P.; Wong, J. K. M.


    Three parametric statistical models have been fully validated for cancer of the larynx for the prediction of long-term 15, 20 and 25 year cancer-specific survival fractions when short-term follow-up data was available for just 1-2 years after the end of treatment of the last patient. In all groups of cases the treatment period was only 5 years. Three disease stage groups were studied, T1N0, T2N0 and T3N0. The models are the Standard Lognormal (SLN) first proposed by Boag (1949 J. R. Stat. Soc. Series B 11 15-53) but only ever fully validated for cancer of the cervix, Mould and Boag (1975 Br. J. Cancer 32 529-50), and two new models which have been termed Tobacco Cancer Risk (TCR) and Absolute Cancer Cure (ACC). In each, the frequency distribution of survival times of defined groups of cancer deaths is lognormally distributed: larynx only (SLN), larynx and lung (TCR) and all cancers (ACC). All models each have three unknown parameters but it was possible to estimate a value for the lognormal parameter S a priori. By reduction to two unknown parameters the model stability has been improved. The material used to validate the methodology consisted of case histories of 965 patients, all treated during the period 1944-1968 by Dr Manuel Lederman of the Royal Marsden Hospital, London, with follow-up to 1988. This provided a follow-up range of 20- 44 years and enabled predicted long-term survival fractions to be compared with the actual survival fractions, calculated by the Kaplan and Meier (1958 J. Am. Stat. Assoc. 53 457-82) method. The TCR and ACC models are better than the SLN model and for a maximum short-term follow-up of 6 years, the 20 and 25 year survival fractions could be predicted. Therefore the numbers of follow-up years saved are respectively 14 years and 19 years. Clinical trial results using the TCR and ACC models can thus be analysed much earlier than currently possible. Absolute cure from cancer was also studied, using not only the prediction models which

  16. 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: [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


    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

  17. Evolution of the excess absolute risk (EAR) in the Valencian breast cancer screening programme

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    Ferrer, S.; Ramos, M.; Villaescusa, J. I.; Verdu, G.; Salas, M. D.; Cuevas, M. D.


    Breast cancer is one of the most frequent diseases in women, with a high incidence rate. The best fight against the breast cancer is the early detection by menas of mammograms in a screening programme. The Valencian Breast Cancer Screening Programme (VBCSP) started at 1992, and it is composed of twenty-two mammography units. The programme is targeted towards asympotomatic women dfrom 45 to 69 years old, but this screening has a negative influence in the studied woman, whatever the diagnosis was. By means of MCNP-4c2 Monte Carlo code, some conversion factors from air kerma air kerma to glandular dose have been developed. Different breast woamn models, according to the Valencian brest anathomy (taking into account the relation breast radius / breast compression thickness obtained from real samples, have been simulated in order to obtain the glandular breast dose values. Quality control parameters as ESAK values were also employed for developing the methods. The conversion factors give a simple and fast wasy to obtain the mean glandular dose from mammography exposition parameters. The glandular dose has been also calculated following the European Protocol on Dosimetry in order to compare the results of the new methodology. Four sample populations of 100 omen from each uunit of the VBCSP have been taken innnn order to estimate the mean glandular dose and the associated excess absolute risk (EAR). Once the doses for each woman from the samples are obtained and according to the age of them, the EAR value for each sample has been determinated following the UNSCEAR 2000 projection risk model, which takes into account the characteristics of the Valencian population and gives the EAR for radio-induced breast cancer. The results have been calculated and compared by means of the ASQRAD software, but with an older risk projection model, the UNSCEAR 1994. Once the four sample average EAR have been calculated, the evolution of the induced risk in the Valencian Breast Cancer

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

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    Gautam K Malhotra


    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.

  19. Stem cells in normal mammary gland and breast cancer. (United States)

    Luo, Jie; Yin, Xin; Ma, Tao; Lu, Jun


    The mammary gland is a structurally dynamic organ that undergoes dramatic alterations with age, menstrual cycle, and reproductive status. Mammary gland stem cells, the minor cell population within the mature organ, are thought to have multiple functions in regulating mammary gland development, tissue maintenance, major growth, and structural remodeling. In addition, accumulative evidence suggests that breast cancers are initiated and maintained by a subpopulation of tumor cells with stem cell features (called cancer stem cells). A variety of methods have been developed to identify and characterize mammary stem cells, and several signal transduction pathways have been identified to be essential for the self-renewal and differentiation of mammary gland stem cells. Understanding the origin of breast cancer stem cells, their relationship to breast cancer development, and the differences between normal and cancer stem cells may lead to novel approaches to breast cancer diagnosis, prevention, and treatment.

  20. 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


    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.

  1. Effects of hyperbaric oxygen at 1.25 atmospheres absolute with normal air on macrophage number and infiltration during rat skeletal muscle regeneration. (United States)

    Fujita, Naoto; Ono, Miharu; Tomioka, Tomoka; Deie, Masataka


    Use of mild hyperbaric oxygen less than 2 atmospheres absolute (2026.54 hPa) with normal air is emerging as a common complementary treatment for severe muscle injury. Although hyperbaric oxygen at over 2 atmospheres absolute with 100% O2 promotes healing of skeletal muscle injury, it is not clear whether mild hyperbaric oxygen is equally effective. The purpose of the present study was to investigate the impact of hyperbaric oxygen at 1.25 atmospheres absolute (1266.59 hPa) with normal air on muscle regeneration. The tibialis anterior muscle of male Wistar rats was injured by injection of bupivacaine hydrochloride, and rats were randomly assigned to a hyperbaric oxygen experimental group or to a non-hyperbaric oxygen control group. Immediately after the injection, rats were exposed to hyperbaric oxygen, and the treatment was continued for 28 days. The cross-sectional area of centrally nucleated muscle fibers was significantly larger in rats exposed to hyperbaric oxygen than in controls 5 and 7 days after injury. The number of CD68- or CD68- and CD206-positive cells was significantly higher in rats exposed to hyperbaric oxygen than in controls 24 h after injury. Additionally, tumor necrosis factor-α and interleukin-10 mRNA expression levels were significantly higher in rats exposed to hyperbaric oxygen than in controls 24 h after injury. The number of Pax7- and MyoD- or MyoD- and myogenin-positive nuclei per mm2 and the expression levels of these proteins were significantly higher in rats exposed to hyperbaric oxygen than in controls 5 days after injury. These results suggest that mild hyperbaric oxygen promotes skeletal muscle regeneration in the early phase after injury, possibly due to reduced hypoxic conditions leading to accelerated macrophage infiltration and phenotype transition. In conclusion, mild hyperbaric oxygen less than 2 atmospheres absolute with normal air is an appropriate support therapy for severe muscle injuries.

  2. Easy Absolute Values? Absolutely (United States)

    Taylor, Sharon E.; Mittag, Kathleen Cage


    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…

  3. Carbon Nanotubes Preserve Normal Phenotypes Under Cancer-Promoting Conditions (United States)

    Wailes, Elizabeth; Levi-Polyachenko, Nicole


    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.

  4. Identification of transporters associated with Etoposide sensitivity of stomach cancer cell lines and methotrexate sensitivity of breast cancer cell lines by quantitative targeted absolute proteomics. (United States)

    Obuchi, Wataru; Ohtsuki, Sumio; Uchida, Yasuo; Ohmine, Ken; Yamori, Takao; Terasaki, Tetsuya


    Membrane transporter proteins may influence the sensitivity of cancer cells to anticancer drugs that can be recognized as substrates. The purpose of this study was to identify proteins that play a key role in the drug sensitivity of stomach and breast cancer cell lines by measuring the absolute protein expression levels of multiple transporters and other membrane proteins and examining their correlation to drug sensitivity. Absolute protein expression levels of 90 membrane proteins were examined by quantitative targeted absolute proteomics using liquid chromatography-linked tandem mass spectrometry. Among them, 11 and 14 membrane proteins, including transporters, were present in quantifiable amounts in membrane fraction of stomach cancer and breast cancer cell lines, respectively. In stomach cancer cell lines, the protein expression level of multidrug resistance-associated protein 1 (MRP1) was inversely correlated with etoposide sensitivity. MK571, an MRP inhibitor, increased both the cell-to-medium ratio of etoposide and the etoposide sensitivity of MRP1-expressing stomach cancer cell lines. In breast cancer cell lines, the protein expression level of reduced folate carrier 1 (RFC1) was directly correlated with methotrexate (MTX) sensitivity. Initial uptake rate and steady-state cell-to-medium ratio of [(3)H]MTX were correlated with both RFC1 expression level and MTX sensitivity. These results suggest that MRP1 modulates the etoposide sensitivity of stomach cancer cell lines and RFC1 modulates the MTX sensitivity of breast cancer cell lines. Our results indicate that absolute quantification of multiple membrane proteins could be a useful strategy for identification of candidate proteins involved in drug sensitivity.

  5. Microfluidic channel for characterizing normal and breast cancer cells (United States)

    TruongVo, T. N.; Kennedy, R. M.; Chen, H.; Chen, A.; Berndt, A.; Agarwal, M.; Zhu, L.; Nakshatri, H.; Wallace, J.; Na, S.; Yokota, H.; Ryu, J. E.


    A microfluidic channel was designed and fabricated for the investigation of behaviors of normal and cancer cells in a narrow channel. A specific question addressed in this study was whether it is possible to distinguish normal versus cancer cells by detecting their stationary and passing behaviors through a narrow channel. We hypothesized that due to higher deformability, softer cancer cells will pass through the channel further and quicker than normal cells. Two cell lines, employed herein, were non-tumor breast epithelial cells (MCF-10A; 11.2  ±  2.4 µm in diameter) and triple negative breast cancer cells (MDA-MB-231; 12.4  ±  2.1 µm in diameter). The microfluidic channel was 300 µm long and linearly tapered with a width of 30 µm at an inlet to 5 µm at an outlet. The result revealed that MDA-MB-231 cells entered and stuck further toward the outlet than MCF-10A cells in response to a slow flow (2 µl min‑1). Further, in response to a fast flow (5 µl min‑1), the passage time (mean  ±  s.d.) was 26.6  ±  43.9 s for normal cells (N  =  158), and 1.9  ±  1.4 s for cancer cells (N  =  128). The measurement of stiffness by atomic force microscopy as well as model-based predictions pointed out that MDA-MB-231 cells are significantly softer than MCF-10A cells. Collectively, the result in this study suggests that analysis of an individual cell’s behavior through a narrow channel can characterize deformable cancer cells from normal ones, supporting the possibility of enriching circulating tumor cells using novel microfluidics-based analysis.

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


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


    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.

  7. p53 orchestrates between normal differentiation and cancer. (United States)

    Rivlin, Noa; Koifman, Gabriela; Rotter, Varda


    During recent years, it is becoming more and more evident that there is a tight connection between abnormal differentiation processes and cancer. While cancer and stem cells are very different, especially in terms of maintaining genomic integrity, these cell types also share many similar properties. In this review, we aim to provide an over-view of the roles of the key tumor suppressor, p53, in regulating normal differentiation and function of both stem cells and adult cells. When these functions are disrupted, undifferentiated cells may become transformed. Understanding the function of p53 in stem cells and its role in maintaining the balance between differentiation and malignant transformation can help shed light on cancer initiation and propagation, and hopefully also on cancer prevention and therapy.

  8. High-risk and low-risk human papillomavirus and the absolute risk of cervical intraepithelial neoplasia or cancer

    DEFF Research Database (Denmark)

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


    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 cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark, during 2002-2005. Samples were tested with a clinical test for 13 high-risk and five low-risk HPV types. The cohort (N=35,539; aged 14-90 years) was monitored in a nationwide pathology register for up...... cytology. Detection of low-risk HPV does not predict CIN 3 or worse. Cervical cancer screening should not include testing for low-risk HPV types. LEVEL OF EVIDENCE: II....

  9. Validation of methylation biomarkers that distinguish normal colon mucosa of cancer patients from normal colon mucosa of patients without cancer. (United States)

    Cesaroni, Matteo; Powell, Jasmine; Sapienza, Carmen


    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.

  10. 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.

  11. 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


    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.

  12. Effects of Electrical Stimulation During Absolute Refractory Period on Contraction and Relaxation of Cardiomyocytes from Normal Guinea-pigs

    Institute of Scientific and Technical Information of China (English)

    赵晓静; 崔长琮; 张海柱


    Objectives To investi- gate the effect of electrical stimulation during absoluterefractory period on contraction and relaxation of ven-tricular myocytes from normal guinea-pigs. MethodsThe guinea -pig ventricular myocytes were obtainedby enzyme digesting, and the extent of its contractionand relaxation and Ca2+ transient were recordedthrough the motion edge detection system. Resultsmyocytes increased 15.45±6.48%, and the peakvelocity of shorting (contraction) and the peak velocity of relengthening (relaxation) increased 15.97±8.37% and 21.63 ± 8.06% respectively ( n = 10 );tio(360/380) (F360/F380) increased 22. 55 ± 9.08%,and the peak velocity of ventricular myocytes F360/F380 increased 36.75 ± 9.77% and 23.62 ± 4.47%during shorting and relengthening respectively (n =6) . Conclusions Appropriate electrical stimulationmay strengthen the contracting and relaxing function ofnormal guinea- pig ventricular myocytes.

  13. Cancer associated proteins in blood plasma: Determining normal variation. (United States)

    Stenemo, Markus; Teleman, Johan; Sjöström, Martin; Grubb, Gabriel; Malmström, Erik; Malmström, Johan; Niméus, Emma


    Protein biomarkers have the potential to improve diagnosis, stratification of patients into treatment cohorts, follow disease progression and treatment response. One distinct group of potential biomarkers comprises proteins which have been linked to cancer, known as cancer associated proteins (CAPs). We determined the normal variation of 86 CAPs in 72 individual plasma samples collected from ten individuals using SRM mass spectrometry. Samples were collected weekly during 5 weeks from ten volunteers and over one day at nine fixed time points from three volunteers. We determined the degree of the normal variation depending on interpersonal variation, variation due to time of day, and variation over weeks and observed that the variation dependent on the time of day appeared to be the most important. Subdivision of the proteins resulted in two predominant protein groups containing 21 proteins with relatively high variation in all three factors (day, week and individual), and 22 proteins with relatively low variation in all factors. We present a strategy for prioritizing biomarker candidates for future studies based on stratification over their normal variation and have made all data publicly available. Our findings can be used to improve selection of biomarker candidates in future studies and to determine which proteins are most suitable depending on study design.

  14. Discrimination of serum Raman spectroscopy between normal and colorectal cancer (United States)

    Li, Xiaozhou; Yang, Tianyue; Yu, Ting; Li, Siqi


    Raman spectroscopy of tissues has been widely studied for the diagnosis of various cancers, but biofluids were seldom used as the analyte because of the low concentration. Herein, serum of 30 normal people, 46 colon cancer, and 44 rectum cancer patients were measured Raman spectra and analyzed. The information of Raman peaks (intensity and width) and that of the fluorescence background (baseline function coefficients) were selected as parameters for statistical analysis. Principal component regression (PCR) and partial least square regression (PLSR) were used on the selected parameters separately to see the performance of the parameters. PCR performed better than PLSR in our spectral data. Then linear discriminant analysis (LDA) was used on the principal components (PCs) of the two regression method on the selected parameters, and a diagnostic accuracy of 88% and 83% were obtained. The conclusion is that the selected features can maintain the information of original spectra well and Raman spectroscopy of serum has the potential for the diagnosis of colorectal cancer.

  15. 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)



    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

  16. Mammographic breast density and breast cancer risk: interactions of percent density, absolute dense, and non-dense areas with breast cancer risk factors. (United States)

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


    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.

  17. Bridging the etiologic and prognostic outlooks in individualized assessment of absolute risk of an illness: application in lung cancer. (United States)

    Karp, Igor; Sylvestre, Marie-Pierre; Abrahamowicz, Michal; Leffondré, Karen; Siemiatycki, Jack


    Assessment of individual risk of illness is an important activity in preventive medicine. Development of risk-assessment models has heretofore relied predominantly on studies involving follow-up of cohort-type populations, while case-control studies have generally been considered unfit for this purpose. To present a method for individualized assessment of absolute risk of an illness (as illustrated by lung cancer) based on data from a 'non-nested' case-control study. We used data from a case-control study conducted in Montreal, Canada in 1996-2001. Individuals diagnosed with lung cancer (n = 920) and age- and sex-matched lung-cancer-free subjects (n = 1288) completed questionnaires documenting life-time cigarette-smoking history and occupational, medical, and family history. Unweighted and weighted logistic models were fitted. Model overfitting was assessed using bootstrap-based cross-validation and 'shrinkage.' The discriminating ability was assessed by the c-statistic, and the risk-stratifying performance was assessed by examination of the variability in risk estimates over hypothetical risk-profiles. In the logistic models, the logarithm of incidence-density of lung cancer was expressed as a function of age, sex, cigarette-smoking history, history of respiratory conditions and exposure to occupational carcinogens, and family history of lung cancer. The models entailed a minimal degree of overfitting ('shrinkage' factor: 0.97 for both unweighted and weighted models) and moderately high discriminating ability (c-statistic: 0.82 for the unweighted model and 0.66 for the weighted model). The method's risk-stratifying performance was quite high. The presented method allows for individualized assessment of risk of lung cancer and can be used for development of risk-assessment models for other illnesses.

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

    Directory of Open Access Journals (Sweden)

    Shibata Darryl


    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.

  19. Electrical impedance characterization of normal and cancerous human hepatic tissue. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Ranan Gülhan Aktas


    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.

  1. A study of structural differences between liver cancer cells and normal liver cells using FTIR spectroscopy (United States)

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


    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.

  2. Absolute advantage

    NARCIS (Netherlands)

    J.G.M. van Marrewijk (Charles)


    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

  3. Gene profile identifies zinc transporters differentially expressed in normal human organs and human pancreatic cancer. (United States)

    Yang, J; Zhang, Y; Cui, X; Yao, W; Yu, X; Cen, P; Hodges, S E; Fisher, W E; Brunicardi, F C; Chen, C; Yao, Q; Li, M


    Deregulated expression of zinc transporters was linked to several cancers. However, the detailed expression profile of all human zinc transporters in normal human organs and in human cancer, especially in pancreatic cancer is not available. The objectives of this study are to investigate the complete expression patterns of 14 ZIP and 10 ZnT transporters in a large number of normal human organs and in human pancreatic cancer tissues and cell lines. We examined the expression patterns of ZIP and ZnT transporters in 22 different human organs and tissues, 11 pairs of clinical human pancreatic cancer specimens and surrounding normal/benign tissues, as well as 10 established human pancreatic cancer cell lines plus normal human pancreatic ductal epithelium (HPDE) cells, using real time RT-PCR and immunohistochemistry. The results indicate that human zinc transporters have tissue specific expression patterns, and may play different roles in different organs or tissues. Almost all the ZIPs except for ZIP4, and most ZnTs were down-regulated in human pancreatic cancer tissues compared to the surrounding benign tissues. The expression patterns of individual ZIPs and ZnTs are similar among different pancreatic cancer lines. Those results and our previous studies suggest that ZIP4 is the only zinc transporter that is significantly up-regulated in human pancreatic cancer and might be the major zinc transporter that plays an important role in pancreatic cancer growth. ZIP4 might serve as a novel molecular target for pancreatic cancer diagnosis and therapy.

  4. [Study on FTIR spectra of finger nails of normal people and patients of esophagus cancer]. (United States)

    Wang, Hong-Yan; Lü, Yin; Wang, Fan; Ma, Xiao-Dong; Jiang, Shi-Ping; Wang, Wei; Li, Cheng-Xiang


    To investigate the application of human finger nails in the diagnosis of cancer, Fourier transform infrared (FTIR) spectroscopy was employed to study the finger nails from some normal people and some with esophagus cancer and others with an operation for curing esophagus cancer five months ago. The results showed that there are obvious differences between FTIR spectra in them in spectral parameters such as frequency, intensity and band shape etc. The changes in the phosphate symmetric stretching vibration v(s) (PO2-) and asymmetric stretching vibration v(a)s(PO2-) modes are uniform, the v(s) (PO2-) and v(a)s(PO2-) absorption peaks of cancerous ones shift to high wave number compared with those of normal people, while those with operation shift to low wave number compared with those of cancerous ones. The C-O stretching vibration mode of protein located at 1 164 cm(-1) is composed of three absorption peaks located at 1 173.3, 1 158.0 and 1 151.1 cm(-1) respectively, meanwhile, the intensities and the wave numbers of the three peaks of cancerous ones all increase compared with normal people. The wave numbers of amide I and amide II of cancerous ones are both lower than those of normal people, while those with operation are between the cancerous ones and normal people, which suggest that the contents of protein and alpha-helix in finger nails of normal people, cancerous ones and the ones with operation are discriminative. The peak of bending vibration delta(CH2) mode of CH2 groups of protein lipid of cancerous ones shifts to high wave number slightly and the intensity of the peak weakens compared with that of normal people, which indicate that the methylene chain in the finger nails membrane lipids of cancerous ones is more ordered than that of normal people. Nevertheless, the peak of stretching vibration v(s) (CH2) of cancerous ones is lower than that of normal people, while that of the ones with operation is between cancerous ones and normal ones. As a result, the

  5. Educating Normal Breast Mucosa to Prevent Breast Cancer (United States)


    Virus Control While Maintaining Efficacy in an Engineered Cancer Vaccine Kevin D Pavelko1, Michael P Bell1, Lavakumar Karyampudi1, Michael J Hansen1... Germany ). Congenic CD45.1 mice received 1 × 107 purified CD8+ T cells labeled with CFSE by intravenous transfer and were intraperitoneally infected...features. Clin Cancer Res 17: 888–895. 33. Chiu, CY, Greninger, AL, Kanada, K, Kwok, T, Fischer , KF, Runckel, C et al. (2008). Identification of

  6. 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

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

    Directory of Open Access Journals (Sweden)

    M. Imani


    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.

  8. Absolute Summ (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. .

  9. 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


    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.

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


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


    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...

  11. Art Therapy with Pediatric Cancer Patients: Helping Normal Children Cope with Abnormal Circumstances. (United States)

    Councill, Tracy


    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)

  12. Vascular normalization as an emerging strategy to enhance cancer immunotherapy


    Huang, Yuhui; Goel, Shom; Duda, Dan G.; Fukumura, Dai; Rakesh K Jain


    The recent approval of Provenge has brought new hope for anti-cancer vaccine therapies. However, the immunosuppressive tumor microenvironment seems to impair the efficacy of vaccine therapies. The abnormal tumor vasculature creates a hypoxic microenvironment that polarizes inflammatory cells toward immune suppression. Moreover, tumors systemically alter immune cells’ proliferation, differentiation and function via secretion of growth factors and cytokines. For example, vascular endothelial gr...

  13. 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

  14. Tissue specific DNA methylation in normal human breast epithelium and in breast cancer. (United States)

    Avraham, Ayelet; Cho, Sean Soonweng; Uhlmann, Ronit; Polak, Mia Leonov; Sandbank, Judith; Karni, Tami; Pappo, Itzhak; Halperin, Ruvit; Vaknin, Zvi; Sella, Avishay; Sukumar, Saraswati; Evron, Ella


    Cancer is a heterogeneous and tissue-specific disease. Thus, the tissue of origin reflects on the natural history of the disease and dictates the therapeutic approach. It is suggested that tissue differentiation, mediated mostly by epigenetic modifications, could guide tissue-specific susceptibility and protective mechanisms against cancer. Here we studied breast specific methylation in purified normal epithelium and its reflection in breast cancers. We established genome wide methylation profiles of various normal epithelial tissues and identified 110 genes that were differentially methylated in normal breast epithelium. A number of these genes also showed methylation alterations in breast cancers. We elaborated on one of them, TRIM29 (ATDC), and showed that its promoter was hypo-methylated in normal breast epithelium and heavily methylated in other normal epithelial tissues. Moreover, in breast carcinomas methylation increased and expression decreased whereas the reverse was noted for multiple other carcinomas. Interestingly, TRIM29 regulation in breast tumors clustered according to the PAM50 classification. Thus, it was repressed in the estrogen receptor positive tumors, particularly in the more proliferative luminal B subtype. This goes in line with previous reports indicating tumor suppressive activity of TRIM29 in estrogen receptor positive luminal breast cells in contrast to oncogenic function in pancreatic and lung cancers. Overall, these findings emphasize the linkage between breast specific epigenetic regulation and tissue specificity of cancer.

  15. Fingerprinting Breast Cancer vs. Normal Mammary Cells by Mass Spectrometric Analysis of Volatiles (United States)

    He, Jingjing; Sinues, Pablo Martinez-Lozano; Hollmén, Maija; Li, Xue; Detmar, Michael; Zenobi, Renato


    There is increasing interest in the development of noninvasive diagnostic methods for early cancer detection, to improve the survival rate and quality of life of cancer patients. Identification of volatile metabolic compounds may provide an approach for noninvasive early diagnosis of malignant diseases. Here we analyzed the volatile metabolic signature of human breast cancer cell lines versus normal human mammary cells. Volatile compounds in the headspace of conditioned culture medium were directly fingerprinted by secondary electrospray ionization-mass spectrometry. The mass spectra were subsequently treated statistically to identify discriminating features between normal vs. cancerous cell types. We were able to classify different samples by using feature selection followed by principal component analysis (PCA). Additionally, high-resolution mass spectrometry allowed us to propose their chemical structures for some of the most discriminating molecules. We conclude that cancerous cells can release a characteristic odor whose constituents may be used as disease markers.

  16. Label-free discrimination of normal and pulmonary cancer tissues using multiphoton fluorescence ratiometric microscopy (United States)

    Wang, Chun-Chin; Wu, Ruei-Jr; Lin, Sung-Jan; Chen, Yang-Fang; Dong, Chen-Yuan


    We performed multiphoton excited autofluorescence and second harmonic generation microscopy for the distinction of normal, lung adenocarcinoma (LAC), and squamous cell carcinoma (SCC) specimens. In addition to morphological distinction, we derived quantitative metrics of cellular redox ratios for cancer discrimination. Specifically, the redox ratios of paired normal/SCC and normal/LAC specimens were found to be 0.53±0.05/0.41±0.06 and 0.56±0.02/0.35±0.06, respectively. The lower redox ratios in cancer specimens, indicating an increase in metabolic activity. These results show that the combination of morphological multiphoton imaging along with redox ratio indices can be used for the discrimination of normal and pulmonary cancer tissues.


    Zhou, W-P; Liu, X; Yang, Y; Liu, Y-F


    This paper studies the effect and relationship of NOB1 in the development of gastric cancer, based on an analysis of NOB1expression in gastric cancer tissue and adjacent tissue. Thirty gastric cancer tissue samples taken during surgery with complete pathological data and their related adjacent normal tissue were examined in this study. NOB1 protein expression in gastric cancer tissue and adjacent normal tissue was detected by immunohistochemistry (IHC). Real-time PCR was used to detect NOB1 mRNA expression, which provided a basis on which to explore the clinical pathological characteristics for patients with gastric cancer. Results show that NOB1 protein in gastric cancer tissue and adjacent normal tissue were diffusely expressed both in the cytoplasm and nucleus. The positive expression rate in gastric cancer tissue was 73%, higher than that in adjacent normal tissue (47%). Both the reference NAPDH and NOB1 amplification are reflected in the amplification curve in standard S-shape and the unimodal solubility curve which was not altered by non-specific amplification and primer dimer. NOB1 mRNA relative expression in cancer tissue was 4.899∓1.412. NOB1 expression had no direct relationship with the patients’ age, gender, tumor differentiation or infiltration degree, lymphatic metastasis, distant metastasis nor pTNM periodization, but was directly related to the size of the tumor. All the findings in this paper suggest that NOB1 can be one of the focuses for diagnosing and treating gastric cancer and that its protein expression is likely to increase with the growth of tumor, thus playing a great role in the incidence and development of gastric cancer.

  18. Classification of normal and cancerous lung tissues by electrical impendence tomography. (United States)

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


    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.

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

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    Thorsten Schlomm


    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.

  20. Fluorescence-based co-culture of normal and cancerous cells as an indicator of therapeutic effects in cancer. (United States)

    Tamura, Masato; Matsui, Hirofumi; Hyodo, Ichinosuke; Tanaka, Junko; Miwa, Yoshihiro


    Comprehensive evaluation of the effects of cancer therapies in vitro is difficult because of the need to distinguish the main effects from the side effects within the data. This problem cannot be overcome by methods involving monoculture, because the effects of anti-cancer drugs in a monoculture can only be measured on either normal or cancerous cells in isolation. In order to promote therapeutic development, therefore, we need a novel drug evaluation method which can simultaneously determine both therapeutic activity and toxicity under a co-culture of normal and cancerous cells. Co-culture creates a more biomimetic condition in comparison to monoculture. The novel method proposed in this study uses an easy experiment for estimating the effects of treatments with various kinds of drugs as a solution to the abovementioned problems. We have previously established two cell lines: a rat gastric mucosal cell line (RGM) and its corresponding cancerous mutant cell line (RGK). In this study, we have developed a new evaluation procedure using a co-culture of green fluorescent protein-expressing RGM cells (RGM-GFP) and kusabira orange-expressing RGK cells (RGK-KO). These cell lines emit green and red fluorescence, respectively. We demonstrated the capability of the method in evaluations of the cancer-selective effects of anti-cancer drugs and X-ray treatment. These results clearly distinguished the cancer-selective toxicity of the applied therapies.

  1. Difference in Membrane Repair Capacity Between Cancer Cell Lines and a Normal Cell Line. (United States)

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


    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 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.

  2. Synchronous luminescence spectroscopic characterization of blood elements of normal and patients with cervical cancer (United States)

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


    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.

  3. Comparison of serum lipid profiles between normal controls and breast cancer patients

    Directory of Open Access Journals (Sweden)

    Pikul Laisupasin


    Full Text Available Background: Researchers have reported association of plasma/serum lipids and lipoproteins with different cancers. Increase levels of circulating lipids and lipoproteins have been associated with breast cancer risk. Aim: The aim of this study is to compare serum lipid profiles: total-cholesterol (T-CHOL, triglyceride (TG, high density lipoprotein-cholesterol (HDL-C, low density lipoprotein-cholesterol (LDL-C and very low density lipoprotein-cholesterol (VLDL-C between breast cancer patients and normal participants. Materials and Methods: A total of 403 women in this study were divided into two groups in the period during May 2006-April 2007. Blood samples were collected from 249 patients with early stage breast cancer and 154 normal controls for serum lipid profiles (T-CHOL, TG, HDL-C, LDL-C and VLDL-C analysis using Hitachi 717 Autoanalyzer (Roche Diagnostic GmbH, Germany. TG, LDL-C and VLDL-C levels in breast cancer group were significantly increased as compared with normal controls group (P < 0.001, whereas HDL-C and T-CHOL levels were not. Results: The results of this study suggest that increased serum lipid profiles may associate with breast cancer risk in Thai women. Further studies to group important factors including, cancer stages, types of cancer, parity, and menopausal status that may affect to lipid profiles in breast cancer patients along with an investigation of new lipid profiles to clarify most lipid factors that may involve in breast cancer development are needed.

  4. I-Xe systematics of the impact plume produced chondrules from the CB carbonaceous chondrites: Implications for the half-life value of 129I and absolute age normalization of 129I-129Xe chronometer (United States)

    Pravdivtseva, O.; Meshik, A.; Hohenberg, C. M.; Krot, A. N.


    It is inferred that magnesian non-porphyritic chondrules in the CB (Bencubbin-type) carbonaceous chondrites formed in an impact generated plume of gas and melt at 4562.49 ± 0.21 Ma (Bollard et al., 2015) and could be suitable for the absolute age normalization of relative chronometers. Here xenon isotopic compositions of neutron irradiated chondrules from the CB chondrites Gujba and Hammadah al Hamra (HH) 237 have been analyzed in an attempt to determine closure time of their I-Xe isotope systematics. One of the HH 237 chondrules, #1, yielded a well-defined I-Xe isochron that corresponds to a closure time of 0.29 ± 0.16 Ma after the Shallowater aubrite standard. Release profiles and diffusion properties of radiogenic 129*Xe and 128*Xe, extracted from this chondrule by step-wise pyrolysis, indicate presence of two iodine host phases with distinct activation energies of 73 and 120 kcal/mol. In spite of the activation energy differences, the I-Xe isotope systematics of these two phases closed simultaneously, suggesting rapid heating and cooling (possibly quenching) of the CB chondrules. The release profiles of U-fission Xe and I-derived Xe correlate in the high temperature host phase supporting simultaneous closure of 129I-129Xe and 207Pb-206Pb systematics. The absolute I-Xe age of Shallowater standard is derived from the observed correlation between I-Xe and Pb-Pb ages in a number of samples. It is re-evaluated here using Pb-Pb ages adjusted for an updated 238U/235U ratio of 137.794 and meteorite specific U-isotope ratios. With the addition of the new data for HH 237 chondrule #1, the re-evaluated absolute I-Xe age of Shallowater is 4562.4 ± 0.2 Ma. The absolute I-Xe age of the HH 237 chondrule #1 is 4562.1 ± 0.3 Ma, in good agreement with U-corrected Pb-Pb ages of the Gujba chondrules (Bollard et al., 2015) and HH 237 silicates (Krot et al., 2005). All I-Xe data used here, and in previous estimates of the absolute age of Shallowater, are calculated using 15.7

  5. Absolute Quantification of Choline-Related Biomarkers in Breast Cancer Biopsies by Liquid Chromatography Electrospray Ionization Mass Spectrometry

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    Maria Chiara Mimmi


    Full Text Available It has been repeatedly demonstrated that choline metabolism is altered in a wide variety of cancers. In breast tumours, the choline metabolite profile is characterized by an elevation of phosphocholine and total choline-compounds. This pattern is increasingly being exploited as biomarker in cancer diagnosis.

  6. 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


    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.

  7. 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


    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.

  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


    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)


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

    DEFF Research Database (Denmark)

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


    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......, 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...

  11. Distinguishing human normal or cancerous esophagus tissue ex vivo using multiphoton microscopy (United States)

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


    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.

  12. 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


    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.

  13. Passive microrheology of normal and cancer cells after ML7 treatment by atomic force microscopy (United States)

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


    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.

  14. 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


    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.

  15. Differentiation of cancerous and normal brain tissue using label free fluorescence and Stokes shift spectroscopy (United States)

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


    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.

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


    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.

  17. Comparison of Normal and Breast Cancer Cell lines using Proteome, Genome and Interactome data

    Energy Technology Data Exchange (ETDEWEB)

    Patwardhan, Anil J.; Strittmatter, Eric F.; Camp, David G.; Smith, Richard D.; Pallavicini, Maria


    Normal and cancer cell line proteomes were profiled using high throughput mass spectrometry techniques. Application of both protein-level and peptide-level sample fractionation combined with LC-MS/MS analysis enabled the confident identification of 2,235 unmodified proteins representing a broad range of functional and compartmental classes. An iterative multi-step search strategy was used to identify post-translational modifications and detected several proteins that are preferentially modified in cancer cells. Information regarding both unmodified and modified protein forms was combined with publicly available gene expression and protein-protein interaction data. The resulting integrated dataset revealed several functionally related proteins that are differentially regulated between normal and cancer cell lines.

  18. Scattering properties of normal and cancerous tissues from human stomach based on phase-contrast microscope (United States)

    Zhang, Hui; Li, Zhifang; Li, Hui


    In order to study scattering properties of normal and cancerous tissues from human stomach, we collect images for human gastric specimens by using phase-contrast microscope. The images were processed by the way of mathematics morphology. The equivalent particle size distribution of tissues can be obtained. Combining with Mie scattering theory, the scattering properties of tissues can be calculated. Assume scattering of light in biological tissue can be seen as separate scattering events by different particles, total scattering properties can be equivalent to as scattering sum of particles with different diameters. The results suggest that scattering coefficient of the cancerous tissue is significantly higher than that of normal tissue. The scattering phase function is different especially in the backscattering area. Those are significant clinical benefits to diagnosis cancerous tissue

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

    DEFF Research Database (Denmark)

    Gaedcke, Jochen; Grade, Marian; Camps, Jordi


    PURPOSE: miRNAs play a prominent role in a variety of physiologic and pathologic biologic processes, including cancer. For rectal cancers, only limited data are available on miRNA expression profiles, whereas the underlying genomic and transcriptomic aberrations have been firmly established. We...... therefore, aimed to comprehensively map the miRNA expression patterns of this disease. EXPERIMENTAL DESIGN: Tumor biopsies and corresponding matched mucosa samples were prospectively collected from 57 patients with locally advanced rectal cancers. Total RNA was extracted, and tumor and mucosa mi......RNA expression profiles were subsequently established for all patients. The expression of selected miRNAs was validated using semi-quantitative real-time PCR. RESULTS: Forty-nine miRNAs were significantly differentially expressed (log(2)-fold difference >0.5 and P cancer and normal rectal...

  20. 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


    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.

  1. Photoacoustic spectroscopy based investigatory approach to discriminate breast cancer from normal: a pilot study (United States)

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


    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.

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

    DEFF Research Database (Denmark)

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


    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...

  3. Significance of differential metal loads in normal versus cancerous cadaver tissues - biomed 2010. (United States)

    Farah, Ibrahim O; Trimble, Quannesha; Ndebele, Kenneth; Mawson, Anthony


    The bodys elemental/ metal loads are known to exert essential influence in maintaining normal and abnormal metabolism leading to eventual pathology of some forms of cancer phenotypes. Accumulation of potentially toxic or nonessential trace metals has been observed but not highly noted as an active factor in toxicogenesis and in the development of many diseases including cancers. The compositional balance and distribution of trace metals in various body tissues are essential key players in homeostasis in life. To this end the etiology of diseases including cancer has been linked with the accumulation of potentially toxic or nonessential trace metals. However, scarce literature / experimental evidence exist as a scientific proof that metal concentrations play important role in the etiology and development of cancer phenotypes. The aim of this study was to investigate the differential relationship of metal concentrations and profiles in cancer and normal tissues from cadavers of humans. The originated hypothesis was that elemental / metal concentrations and profiles seen in post mortem will show significant differences between normal and cancer-derived tissues as well as between various tissue types in humans. This study also establishes critical elemental /metal profiles that may be relevant in providing correlations with the development of three major cancers. Normal human and tumor tissues of cadaverous lung, breast and liver tissues used in this study were obtained from US Biomax Company. Tissue samples were prepared using standardized digestion procedures necessary for use with the Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). This equipment was utilized to determine the concentrations and profiles of 21 elements including Ag, Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Na, Ni, Pb, Sb, Se, Sr, Tl, V, and Zn. Twelve major elements of Al, Ba, Ca, Cr, Cu, Fe, Mg, Na, Pb, Se, Sr, and Zn were found to be significantly different in term of their

  4. 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


    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......) gene families, Vav1, monoglyceride lipase and NADP+-dependent malic enzyme, exhibited altered expression in MCB vs. ductal breast cancer, and the differences for some of these genes were confirmed on an extended panel of cell lines by quantitative PCR. Immunohistochemical analysis further established...

  5. 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;


    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......) gene families, Vav1, monoglyceride lipase and NADP+-dependent malic enzyme, exhibited altered expression in MCB vs. ductal breast cancer, and the differences for some of these genes were confirmed on an extended panel of cell lines by quantitative PCR. Immunohistochemical analysis further established...

  6. Teaching Absolute Value Meaningfully (United States)

    Wade, Angela


    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…

  7. Model-integrated estimation of normal tissue contamination for cancer SNP allelic copy number data. (United States)

    Stjernqvist, Susann; Rydén, Tobias; Greenman, Chris D


    SNP allelic copy number data provides intensity measurements for the two different alleles separately. We present a method that estimates the number of copies of each allele at each SNP position, using a continuous-index hidden Markov model. The method is especially suited for cancer data, since it includes the fraction of normal tissue contamination, often present when studying data from cancer tumors, into the model. The continuous-index structure takes into account the distances between the SNPs, and is thereby appropriate also when SNPs are unequally spaced. In a simulation study we show that the method performs favorably compared to previous methods even with as much as 70% normal contamination. We also provide results from applications to clinical data produced using the Affymetrix genome-wide SNP 6.0 platform.

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

    Institute of Scientific and Technical Information of China (English)



    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.

  9. 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.

  10. Stromal Androgen Receptor Roles in the Development of Normal Prostate, Benign Prostate Hyperplasia, and Prostate Cancer


    Wen, Simeng; Chang, Hong-Chiang; Tian, Jing; Shang, Zhiqun; Niu, Yuanjie; Chang, Chawnshang


    The prostate is an androgen-sensitive organ that needs proper androgen/androgen receptor (AR) signals for normal development. The progression of prostate diseases, including benign prostate hyperplasia (BPH) and prostate cancer (PCa), also needs proper androgen/AR signals. Tissue recombination studies report that stromal, but not epithelial, AR plays more critical roles via the mesenchymal-epithelial interactions to influence the early process of prostate development. However, in BPH and PCa,...

  11. 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: [Nonlinear Intelligent Structures Laboratory, Department of Mechanical Engineering, University of Alabama, Tuscaloosa, AL 35487-0276 (United States); Agah, M., E-mail: [VT MEMS Laboratory, The Bradley Department of Electrical and Computer Engineering, Blacksburg, VA 24061 (United States)


    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.

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

    DEFF Research Database (Denmark)

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


    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...

  13. Correlation between Fas and FasL proteins expression in normal gastric mucosa and gastric cancer

    Directory of Open Access Journals (Sweden)

    Jolanta Czyżewska


    Full Text Available The study’s objective was to assess the expressions of Fas and FasL proteins in gastric cancer in correlation with chosen clinicohistological parameters. Fas and FasL expression was analyzed in 68 patients with gastric cancer, using the immunohistochemical method. The expression of Fas was found to be lower in gastric cancer cells than in healthy mucosa, both in the lining epithelium and in glandular tubes (28% vs. 48% and 44%; p < 0.001. The expression of FasL was also markedly lower in cancer cells than in glandular tubes, yet higher than in the lining epithelium (51% vs. 73% and 14%; p < 0.01. Positive expressions of FasL and Fas were lower in less advanced gastric cancer cells (T1, T2, than in more advanced tumors (T3, T4, but only in the case of FasL was this difference statistically significant (p < 0.05. Our findings seem to confirm the theory of the impact of apoptotic disorders at the level of Fas receptor and FasL protein in the process of gastric cancer formation and growth, which is manifested in the varied expressions of these proteins in gastric cancer and in the normal lining and glandular epithelium of the stomach. However, the lack of significant differences in the expressions of Fas and FasL in correlation to other clinicohistological parameters indicates the existence of mechanisms that have a greater impact on the process of differentiation of gastric cancers. This in our opinion eliminates these proteins as prognostic factors. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 142–147

  14. Comparison of gene regulatory networks of benign and malignant breast cancer samples with normal samples. (United States)

    Chen, D B; Yang, H J


    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.

  15. Quantitative analysis of collagen change between normal and cancerous thyroid tissues based on SHG method (United States)

    Chen, Xiwen; Huang, Zufang; Xi, Gangqin; Chen, Yongjian; Lin, Duo; Wang, Jing; Li, Zuanfang; Sun, Liqing; Chen, Jianxin; Chen, Rong


    Second-harmonic generation (SHG) is proved to be a high spatial resolution, large penetration depth and non-photobleaching method. In our study, SHG method was used to investigate the normal and cancerous thyroid tissue. For SHG imaging performance, system parameters were adjusted for high-contrast images acquisition. Each x-y image was recorded in pseudo-color, which matches the wavelength range in the visible spectrum. The acquisition time for a 512×512-pixels image was 1.57 sec; each acquired image was averaged four frames to improve the signal-to-noise ratio. Our results indicated that collagen presence as determined by counting the ratio of the SHG pixels over the whole pixels for normal and cancerous thyroid tissues were 0.48+/-0.05, 0.33+/-0.06 respectively. In addition, to quantitatively assess collagen-related changes, we employed GLCM texture analysis to the SHG images. Corresponding results showed that the correlation both fell off with distance in normal and cancerous group. Calculated value of Corr50 (the distance where the correlation crossed 50% of the initial correlation) indicated significant difference. This study demonstrates that SHG method can be used as a complementary tool in thyroid histopathology.

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

    Directory of Open Access Journals (Sweden)

    Xing Xiaofang


    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.

  17. 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


    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.

  18. Absolute quantification of acetylation and phosphorylation of the histone variant H2AX upon ionizing radiation reveals distinct cellular responses in two cancer cell lines. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Davor Librenjak


    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.

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Kamlesh Awasthi


    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Utility of ADC measurement on diffusion-weighted MRI in differentiation of prostate cancer, normal prostate and prostatitis. (United States)

    Esen, Meltem; Onur, Mehmet Ruhi; Akpolat, Nusret; Orhan, Irfan; Kocakoc, Ercan


    To determine the utility of apparent diffusion coefficient (ADC) values in differentiation of prostate cancer from normal prostate parenchyma and prostatitis we obtained ADC values of 50 patients at b 100, 600 and 1,000 s/mm(2) diffusion gradients. The ADC values of prostate cancer group were significantly lower than normal prostate and prostatitis group at b 600 and 1,000 s/mm(2) gradients. The ADC values at high diffusion gradients may be used in differentiation prostate cancer from normal prostate and prostatitis.

  4. The effect of Stokes shift in the discrimination of urine of cervical cancer from normal subjects (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Magnusson Magnus K


    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.

  6. Iminolactones as tools for inversion of the absolute configuration of α-amino acids and as inhibitors of cancer cell proliferation. (United States)

    Jensen, Christina Mernøe; Chow, Hsiao-Qing; Chen, Ming; Zhai, Lin; Frydenvang, Karla; Liu, Huizhen; Franzyk, Henrik; Christensen, Søren Brøgger


    A library of iminolactones was prepared by esterification of several 2-hydroxyketones with a number of N-protected d- and l-α-amino acids. Some of the hydroxyketones were of terpenoid origin while others were obtained via synthesis. After N-deprotection of the intermediate esters, the free amines spontaneously underwent condensation with the ketone to form iminolactones. Esters of (1S,2S,5S)-2-hydroxypinan-3-one with both d- and l-α-amino acids were partially epimerized at the α-carbon atom to give a diastereomeric ester mixture. Only iminolactones of l-amino acids were formed after cyclization of (1S,2S,5S)-2-hydroxypinan-3-one, and correspondingly only d-amino acid iminolactones were formed after reaction with (1R,2R,5R)-2-hydroxypinan-3-one. The protocol thus enables inversion of the absolute configuration of amino acids. Some members of the prepared library of iminolactones displayed significant anti-proliferative effects toward three cancer cell lines (EL4, MCF7, PC3) with insignificant effect on non-malign cell lines (McCoy, MCF10A, NIH3T3). Thus, iminolactones appear to be potential lead structures for preparation of drugs selectively affecting proliferation of malign cell lines.

  7. Vitamin D receptor regulates autophagy in the normal mammary gland and in luminal breast cancer cells. (United States)

    Tavera-Mendoza, Luz E; Westerling, Thomas; Libby, Eric; Marusyk, Andriy; Cato, Laura; Cassani, Raymundo; Cameron, Lisa A; Ficarro, Scott B; Marto, Jarrod A; Klawitter, Jelena; Brown, Myles


    Women in North America have a one in eight lifetime risk of developing breast cancer (BC), and a significant proportion of these individuals will develop recurrent BC and will eventually succumb to the disease. Metastatic, therapy-resistant BC cells are refractory to cell death induced by multiple stresses. Here, we document that the vitamin D receptor (VDR) acts as a master transcriptional regulator of autophagy. Activation of the VDR by vitamin D induces autophagy and an autophagic transcriptional signature in BC cells that correlates with increased survival in patients; strikingly, this signature is present in the normal mammary gland and is progressively lost in patients with metastatic BC. A number of epidemiological studies have shown that sufficient vitamin D serum levels might be protective against BC. We observed that dietary vitamin D supplementation in mice increases basal levels of autophagy in the normal mammary gland, highlighting the potential of vitamin D as a cancer-preventive agent. These findings point to a role of vitamin D and the VDR in modulating autophagy and cell death in both the normal mammary gland and BC cells.

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

    Directory of Open Access Journals (Sweden)

    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

  9. Temsirolimus induced structural transition of cancerous renal cystatin to normal form in rats: In vitro mechanistic approach underlying renal cancer prevention. (United States)

    Shamsi, Anas; Ahmed, Azaj; Bano, Bilqees


    Globally, renal cell carcinomas (RCCs) represent a major portion of patients suffering from cancer. Temsirolimus is an anti-renal cancer drug that has already been approved in poor-risk metastatic RCC (mRCC) patients. In our present study, we have evaluated the in vitro effect of varying concentrations of temsirolimus on cancerous rat kidney cystatin; renal cancer was induced in rats making use of dimethylnitrosamine (DMN). It has already been reported that cancerous rat kidney cystatin performs its activity in an efficacious manner as compared to normal rat kidney cystatin, so here an attempt was made to see the effect of temsirolimus on this increased activity of cystatin in renal cancers. Anti-papain activity assay was utilized to see this effect and it was found that temsirolimus reduces the increased activity of cancerous rat kidney cystatin similar to that of normal rat kidney cystatin. Further, to have an insight into temsirolimus induced structural alterations in cancerous rat kidney cystatin; various spectroscopic assays viz. UV, Fluorescence, Circular dichroism (CD) and FTIR spectroscopy were employed. UV and Fluorescence spectroscopy shows cancerous rat kidney cystatin transformation to normal form in the presence of temsirolimus. FTIR and CD spectroscopy confirmed the complete structural reversion of cancerous rat kidney cystatin to normal form in the presence of 40μM temsirolimus. Thus, it can said that temsirolimus causes renal cystatin to revert to normal form; the increased activity of renal cystatin observed in incidences of renal cancer is restored back to normal thereby halting the progression of renal cancer.

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

    Directory of Open Access Journals (Sweden)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. A novel approach for determining cancer genomic breakpoints in the presence of normal DNA.

    Directory of Open Access Journals (Sweden)

    Yu-Tsueng Liu

    Full Text Available CDKN2A (encodes p16(INK4A and p14(ARF deletion, which results in both Rb and p53 inactivation, is the most common chromosomal anomaly in human cancers. To precisely map the deletion breakpoints is important to understanding the molecular mechanism of genomic rearrangement and may also be useful for clinical applications. However, current methods for determining the breakpoint are either of low resolution or require the isolation of relatively pure cancer cells, which can be difficult for clinical samples that are typically contaminated with various amounts of normal host cells. To overcome this hurdle, we have developed a novel approach, designated Primer Approximation Multiplex PCR (PAMP, for enriching breakpoint sequences followed by genomic tiling array hybridization to locate the breakpoints. In a series of proof-of-concept experiments, we were able to identify cancer-derived CDKN2A genomic breakpoints when more than 99.9% of wild type genome was present in a model system. This design can be scaled up with bioinformatics support and can be applied to validate other candidate cancer-associated loci that are revealed by other more systemic but lower throughput assays.

  13. Human BLCAP transcript: new editing events in normal and cancerous tissues. (United States)

    Galeano, Federica; Leroy, Anne; Rossetti, Claudia; Gromova, Irina; Gautier, Philippe; Keegan, Liam P; Massimi, Luca; Di Rocco, Concezio; O'Connell, Mary A; Gallo, Angela


    Bladder cancer-associated protein (BLCAP) is a highly conserved protein among species, and it is considered a novel candidate tumor suppressor gene originally identified from human bladder carcinoma. However, little is known about the regulation or the function of this protein. Here, we show that the human BLCAP transcript undergoes multiple A-to-I editing events. Some of the new editing events alter the highly conserved amino terminus of the protein creating alternative protein isoforms by changing the genetically coded amino acids. We found that both ADAR1 and ADAR2-editing enzymes cooperate to edit this transcript and that different tissues displayed distinctive ratios of edited and unedited BLCAP transcripts. Moreover, we observed a general decrease in BLCAP-editing level in astrocytomas, bladder cancer and colorectal cancer when compared with the related normal tissues. The newly identified editing events, found to be downregulated in cancers, could be useful for future studies as a diagnostic tool to distinguish malignancies or epigenetic changes in different tumors.

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

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    Kenneth C. Valkenburg


    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.

  15. 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.


    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.


    Institute of Scientific and Technical Information of China (English)

    李瑶琛; 孔令洪; 王一理; 司履生


    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.

  17. 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


    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.

  18. Automatic Classification of Normal and Cancer Lung CT Images Using Multiscale AM-FM Features. (United States)

    Magdy, Eman; Zayed, Nourhan; Fakhr, Mahmoud


    Computer-aided diagnostic (CAD) systems provide fast and reliable diagnosis for medical images. In this paper, CAD system is proposed to analyze and automatically segment the lungs and classify each lung into normal or cancer. Using 70 different patients' lung CT dataset, Wiener filtering on the original CT images is applied firstly as a preprocessing step. Secondly, we combine histogram analysis with thresholding and morphological operations to segment the lung regions and extract each lung separately. Amplitude-Modulation Frequency-Modulation (AM-FM) method thirdly, has been used to extract features for ROIs. Then, the significant AM-FM features have been selected using Partial Least Squares Regression (PLSR) for classification step. Finally, K-nearest neighbour (KNN), support vector machine (SVM), naïve Bayes, and linear classifiers have been used with the selected AM-FM features. The performance of each classifier in terms of accuracy, sensitivity, and specificity is evaluated. The results indicate that our proposed CAD system succeeded to differentiate between normal and cancer lungs and achieved 95% accuracy in case of the linear classifier.

  19. 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)


    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.

  20. DNA damage in oral cancer and normal cells induced by nitrogen atmospheric pressure plasma jets (United States)

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


    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.

  1. Attenuated total reflectance Fourier transform infrared spectroscopy method to differentiate between normal and cancerous breast cells. (United States)

    Lane, Randy; See, Seong S


    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.

  2. Evaluation of algorithm methods for fluorescence spectra of cancerous and normal human tissues (United States)

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


    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

  3. Ruta 6 selectively induces cell death in brain cancer cells but proliferation in normal peripheral blood lymphocytes: A novel treatment for human brain cancer. (United States)

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


    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.

  4. The normal breast epithelium of women with breast cancer displays an aberrant response to estradiol. (United States)

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


    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.

  5. The myoepithelial cell: its role in normal mammary glands and breast cancer. (United States)

    Sopel, M


    Mammary gland epithelium is composed of an inner layer of secretory cells (luminal) and an outer layer of myoepithelial cells (MEC) bordering the basal lamina which separates the epithelial layer from the extracellular matrix. Mature MECs morphologically resemble smooth muscle cells; however, they exhibit features typical for epithelial cells, such as the presence of specific cytokeratin filaments. During lactation, secretory cells synthesize milk components, which are collected in alveoli and duct lumen, and transported to the nipple as a result of MEC contraction. Although the induction of MEC contraction results from oxytocin action, also other, still unknown auto/paracrine mechanisms participate in the regulation of this process. As well as milk ejection, MECs are involved in mammary gland morphogenesis in all developmental stages, modulating proliferation and differentiation of luminal cells. They take part in the formation of extracellular matrix, synthesizing its components and secreting proteinases and their inhibitors. In addition, MECs are regarded as natural cancer suppressors, stabilizing the normal structure of the mammary gland, they secrete suppressor proteins (e.g. maspin) limiting cancer growth, invasiveness, and neoangiogenesis. The majority of malignant breast cancers are derived from luminal cells, whereas neoplasms of MEC origin are the most seldom and usually benign form of breast tumours. MECs are markedly resistant to malignant transformation and they are able to suppress the transformation of neighboring luminal cells. Therefore, a deeper insight into the role of MECs in the physiology and pathology of mammary glands would allow a better understanding of cancerogenesis mechanisms and possible application of specific MEC markers in the diagnosis and therapy of breast cancer.

  6. Cancer-secreted AGR2 induces programmed cell death in normal cells (United States)

    Vitello, Elizabeth A.; Quek, Sue-Ing; Kincaid, Heather; Fuchs, Thomas; Crichton, Daniel J.; Troisch, Pamela; Liu, Alvin Y.


    Anterior Gradient 2 (AGR2) is a protein expressed in many solid tumor types including prostate, pancreatic, breast and lung. AGR2 functions as a protein disulfide isomerase in the endoplasmic reticulum. However, AGR2 is secreted by cancer cells that overexpress this molecule. Secretion of AGR2 was also found in salamander limb regeneration. Due to its ubiquity, tumor secretion of AGR2 must serve an important role in cancer, yet its molecular function is largely unknown. This study examined the effect of cancer-secreted AGR2 on normal cells. Prostate stromal cells were cultured, and tissue digestion media containing AGR2 prepared from prostate primary cancer 10-076 CP and adenocarcinoma LuCaP 70CR xenograft were added. The control were tissue digestion media containing no AGR2 prepared from benign prostate 10-076 NP and small cell carcinoma LuCaP 145.1 xenograft. In the presence of tumor-secreted AGR2, the stromal cells were found to undergo programmed cell death (PCD) characterized by formation of cellular blebs, cell shrinkage, and DNA fragmentation as seen when the stromal cells were UV irradiated or treated by a pro-apoptotic drug. PCD could be prevented with the addition of the monoclonal AGR2-neutralizing antibody P3A5. DNA microarray analysis of LuCaP 70CR media-treated vs. LuCaP 145.1 media-treated cells showed downregulation of the gene SAT1 as a major change in cells exposed to AGR2. RT-PCR analysis confirmed the array result. SAT1 encodes spermidine/spermine N1-acetyltransferase, which maintains intracellular polyamine levels. Abnormal polyamine metabolism as a result of altered SAT1 activity has an adverse effect on cells through the induction of PCD. PMID:27283903

  7. Impact of the Choice of Normalization Method on Molecular Cancer Class Discovery Using Nonnegative Matrix Factorization (United States)

    Yang, Haixuan; Seoighe, Cathal


    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: PMID:27741311

  8. 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)


    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Satoshi Matsuzaki


    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

  10. Absolute nuclear material assay (United States)

    Prasad, Manoj K [Pleasanton, CA; Snyderman, Neal J [Berkeley, CA; Rowland, Mark S [Alamo, CA


    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.

  11. Variance computations for functional of absolute risk estimates. (United States)

    Pfeiffer, R M; Petracci, E


    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.

  12. 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


    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.

  13. 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


    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 iden......-karyotype AML, which allowed for the generation of a highly prognostic survival signature. Collectively, our CvN method holds great potential as a tool for the analysis of gene expression profiles of cancer patients.......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 identifying expression changes fundamental to disease etiology. Here we present a method that facilitates the comparison of any cancer sample to its nearest normal cellular counterpart, using acute myeloid leukemia (AML) as a model. We first generated a gene expression-based landscape of the normal...

  14. 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: [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)


    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.

  15. Absolute neutrino mass update

    CERN Document Server

    Päs, H; P\\"as, Heinrich; Weiler, Thomas J.


    The determination of absolute neutrino masses is crucial for the understanding of theories underlying the standard model, such as SUSY. We review the experimental prospects to determine absolute neutrino masses and the correlations among approaches, using the Delta m^2's inferred from neutrino oscillation experiments and assuming a three neutrino Universe.


    DEFF Research Database (Denmark)

    Schechter, J.; Shahid, M. N.


    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....

  17. The biology of progesterone receptor in the normal mammary gland and in breast cancer. (United States)

    Obr, Alison E; Edwards, Dean P


    This paper reviews work on progesterone and the progesterone receptor (PR) in the mouse mammary gland that has been used extensively as an experimental model. Studies have led to the concept that progesterone controls proliferation and morphogenesis of the luminal epithelium in a tightly orchestrated manner at distinct stages of development by paracrine signaling pathways, including receptor activator of nuclear factor κB ligand (RANKL) as a major paracrine factor. Progesterone also drives expansion of stem cells by paracrine signals to generate progenitors required for alveologenesis. During mid-to-late pregnancy, progesterone has another role to suppress secretory activation until parturition mediated in part by crosstalk between PR and prolactin/Stat5 signaling to inhibit induction of milk protein gene expression, and by inhibiting tight junction closure. In models of hormone-dependent mouse mammary tumors, the progesterone/PR signaling axis enhances pre-neoplastic progression by a switch from a paracrine to an autocrine mode of proliferation and dysregulation of the RANKL signaling pathway. Limited experiments with normal human breast show that progesterone/PR signaling also stimulates epithelial cell proliferation by a paracrine mechanism; however, the signaling pathways and whether RANKL is a major mediator remains unknown. Work with human breast cancer cell lines, patient tumor samples and clinical studies indicates that progesterone is a risk factor for breast cancer and that alteration in progesterone/PR signaling pathways contributes to early stage human breast cancer progression. However, loss of PR expression in primary tumors is associated with a less differentiated more invasive phenotype and worse prognosis, suggesting that PR may limit later stages of tumor progression.

  18. JS-K, a nitric oxide-releasing prodrug, induces breast cancer cell death while sparing normal mammary epithelial cells. (United States)

    McMurtry, Vanity; Saavedra, Joseph E; Nieves-Alicea, René; Simeone, Ann-Marie; Keefer, Larry K; Tari, Ana M


    Targeted therapy with reduced side effects is a major goal in cancer research. We investigated the effects of JS-K, a nitric oxide (NO) prodrug designed to release high levels of NO when suitably activated, on human breast cancer cell lines, on non-transformed human MCF-10A mammary cells, and on normal human mammary epithelial cells (HMECs). Cell viability assay, flow cytometry, electron microscopy, and Western blot analysis were used to study the effects of JS-K on breast cancer and on mammary epithelial cells. After a 3-day incubation, the IC50s of JS-K against the breast cancer cells ranged from 0.8 to 3 µM. However, JS-K decreased the viability of the MCF-10A cells by only 20% at 10-µM concentration, and HMECs were unaffected by 10 µM JS-K. Flow cytometry indicated that JS-K increased the percentages of breast cancer cells under-going apoptosis. Interestingly, flow cytometry indicated that JS-K increased acidic vesicle organelle formation in breast cancer cells, suggesting that JS-K induced autophagy in breast cancer cells. Electron microscopy confirmed that JS-K-treated breast cancer cells underwent autophagic cell death. Western blot analysis showed that JS-K induced the expression of microtubule light chain 3-II, another autophagy marker, in breast cancer cells. However, JS-K did not induce apoptosis or autophagy in normal human mammary epithelial cells. These data indicate that JS-K selectively induces programmed cell death in breast cancer cells while sparing normal mammary epithelial cells under the same conditions. The selective anti-tumor activity of JS-K warrants its further investigation in breast tumors.

  19. Cross-tissue Analysis of Gene and Protein Expression in Normal and Cancer Tissues. (United States)

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


    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.

  20. 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


    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.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Doyle Scott


    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

  3. 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


    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.

  4. Redox biology in normal cells and cancer: restoring function of the redox/Fyn/c-Cbl pathway in cancer cells offers new approaches to cancer treatment. (United States)

    Noble, Mark; Mayer-Pröschel, Margot; Li, Zaibo; Dong, Tiefei; Cui, Wanchang; Pröschel, Christoph; Ambeskovic, Ibro; Dietrich, Joerg; Han, Ruolan; Yang, Yin Miranda; Folts, Christopher; Stripay, Jennifer; Chen, Hsing-Yu; Stevens, Brett M


    This review discusses a unique discovery path starting with novel findings on redox regulation of precursor cell and signaling pathway function and identification of a new mechanism by which relatively small changes in redox status can control entire signaling networks that regulate self-renewal, differentiation, and survival. The pathway central to this work, the redox/Fyn/c-Cbl (RFC) pathway, converts small increases in oxidative status to pan-activation of the c-Cbl ubiquitin ligase, which controls multiple receptors and other proteins of central importance in precursor cell and cancer cell function. Integration of work on the RFC pathway with attempts to understand how treatment with systemic chemotherapy causes neurological problems led to the discovery that glioblastomas (GBMs) and basal-like breast cancers (BLBCs) inhibit c-Cbl function through altered utilization of the cytoskeletal regulators Cool-1/βpix and Cdc42, respectively. Inhibition of these proteins to restore normal c-Cbl function suppresses cancer cell division, increases sensitivity to chemotherapy, disrupts tumor-initiating cell (TIC) activity in GBMs and BLBCs, controls multiple critical TIC regulators, and also allows targeting of non-TICs. Moreover, these manipulations do not increase chemosensitivity or suppress division of nontransformed cells. Restoration of normal c-Cbl function also allows more effective harnessing of estrogen receptor-α (ERα)-independent activities of tamoxifen to activate the RFC pathway and target ERα-negative cancer cells. Our work thus provides a discovery strategy that reveals mechanisms and therapeutic targets that cannot be deduced by standard genetics analyses, which fail to reveal the metabolic information, isoform shifts, protein activation, protein complexes, and protein degradation critical to our discoveries.

  5. 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)


    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

  6. Unbiased Selection of Peptide-Peptoid Hybrids Specific for Lung Cancer Compared to Normal Lung Epithelial Cells. (United States)

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


    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.

  7. Analysis of the Genetic Phylogeny of Multifocal Prostate Cancer Identifies Multiple Independent Clonal Expansions in Neoplastic and Morphologically Normal Prostate Tissue


    Cooper, Colin S.; Eeles, Rosalind; Wedge, David C.; Van Loo, Peter; Gundem, Gunes; Alexandrov, Ludmil B; Kremeyer, Barbara; Butler, Adam; Lynch, Andrew G.; Camacho, Niedzica; Massie, Charlie E.; Kay, Jonathan; Luxton, Hayley J.; Edwards, Sandra; Kote-Jarai, Zsofia


    Whole genome DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of on-going abnormal mutational pr...

  8. NGS Absolute Gravity Data (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...

  9. Decoherence at absolute zero


    Sinha, Supurna


    We present an analytical study of the loss of quantum coherence at absolute zero. Our model consists of a harmonic oscillator coupled to an environment of harmonic oscillators at absolute zero. We find that for an Ohmic bath, the offdiagonal elements of the density matrix in the position representation decay as a power law in time at late times. This slow loss of coherence in the quantum domain is qualitatively different from the exponential decay observed in studies of high temperature envir...

  10. 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


    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

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


    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.

  12. Absolute biological needs. (United States)

    McLeod, Stephen


    Absolute needs (as against instrumental needs) are independent of the ends, goals and purposes of personal agents. Against the view that the only needs are instrumental needs, David Wiggins and Garrett Thomson have defended absolute needs on the grounds that the verb 'need' has instrumental and absolute senses. While remaining neutral about it, this article does not adopt that approach. Instead, it suggests that there are absolute biological needs. The absolute nature of these needs is defended by appeal to: their objectivity (as against mind-dependence); the universality of the phenomenon of needing across the plant and animal kingdoms; the impossibility that biological needs depend wholly upon the exercise of the abilities characteristic of personal agency; the contention that the possession of biological needs is prior to the possession of the abilities characteristic of personal agency. Finally, three philosophical usages of 'normative' are distinguished. On two of these, to describe a phenomenon or claim as 'normative' is to describe it as value-dependent. A description of a phenomenon or claim as 'normative' in the third sense does not entail such value-dependency, though it leaves open the possibility that value depends upon the phenomenon or upon the truth of the claim. It is argued that while survival needs (or claims about them) may well be normative in this third sense, they are normative in neither of the first two. Thus, the idea of absolute need is not inherently normative in either of the first two senses.

  13. 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


    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.

  14. PATE, a gene expressed in prostate cancer, normal prostate, and testis, identified by a functional genomic approach (United States)

    Bera, Tapan K.; Maitra, Rangan; Iavarone, Carlo; Salvatore, Giuliana; Kumar, Vasantha; Vincent, James J.; Sathyanarayana, B. K.; Duray, Paul; Lee, B. K.; Pastan, Ira


    To identify target antigens for prostate cancer therapy, we have combined computer-based screening of the human expressed sequence tag database and experimental expression analysis to identify genes that are expressed in normal prostate and prostate cancer but not in essential human tissues. Using this approach, we identified a gene that is expressed specifically in prostate cancer, normal prostate, and testis. The gene has a 1.5-kb transcript that encodes a protein of 14 kDa. We named this gene PATE (expressed in prostate and testis). In situ hybridization shows that PATE mRNA is expressed in the epithelial cells of prostate cancers and in normal prostate. Transfection of the PATE cDNA with a Myc epitope tag into NIH 3T3 cells and subsequent cell fractionation analysis shows that the PATE protein is localized in the membrane fraction of the cell. Analysis of the amino acid sequence of PATE shows that it has structural similarities to a group of proteins known as three-finger toxins, which includes the extracellular domain of the type transforming growth factor receptor. Restricted expression of PATE makes it a potential candidate for the immunotherapy of prostate cancer.

  15. Cancer (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 ...

  16. Normal breast physiology: the reasons hormonal contraceptives and induced abortion increase breast-cancer risk. (United States)

    Lanfranchi, Angela


    A woman gains protection from breast cancer by completing a full-term pregnancy. In utero, her offspring produce hormones that mature 85 percent of the mother's breast tissue into cancer-resistant breast tissue. If the pregnancy ends through an induced abortion or a premature birth before thirty-two weeks, the mother's breasts will have only partially matured, retaining even more cancer-susceptible breast tissue than when the pregnancy began. This increased amount of immature breast tissue will leave the mother with more sites for cancer initiation, thereby increasing her risk of breast cancer. Hormonal contraceptives increase breast-cancer risk by their proliferative effect on breast tissue and their direct carcinogenic effects on DNA. Hormonal contraceptives include estrogen-progestin combination drugs prescribed in any manner of delivery: orally, transdermally, vaginally, or intrauterine. This article provides the detailed physiology and data that elucidate the mechanisms through which induced abortion and hormonal contraceptives increase breast-cancer risk.

  17. A multi-classifier system for the characterization of normal, infectious, and cancerous prostate tissues employing transrectal ultrasound images. (United States)

    Glotsos, Dimitris; Kalatzis, Ioannis; Theocharakis, Pantelis; Georgiadis, Pantelis; Daskalakis, Antonis; Ninos, Kostas; Zoumboulis, Pavlos; Filippidou, Anna; Cavouras, Dionisis


    A computer-aided diagnostic system has been developed for the discrimination of normal, infectious and cancer prostate tissues based on texture analysis of transrectal ultrasound images. The proposed system has been designed using a panel of three classifiers, which have been evaluated individually or as a mutli-classifier scheme, using the external cross-validation procedure. Clinical data consisted of 165 transrectal ultrasound images, characterized by an experienced physician as normal (55/165), cancerous (55/165), and infectious (55/165) prostate cases. From each image, the physician delineated the most representative regions of interest, from which, 23 textural features were extracted. Classification was seen as a two level hierarchical decision tree. Normal from infectious and infectious from cancer cases were discriminated at the 1st and 2nd level of the decision tree, respectively. The best classification results for the 1st level were 89.5%, whereas for the 2nd level 90.1%. The utilization of multi-classifier system improved the discrimination of prostate pathologies as compared to individual classifiers; for infectious prostate cases improvement was from 87.3% to 88.7% and for cancer prostate cases improvement was from 84.1% to 91.4%. In terms of overall system performance (the decision tree's node propagating error taken into account), best classification accuracies were 89.5%, 79.6% and 82.7% for the recognition of normal, infectious and cancer cases, respectively. The proposed system might be used as a second opinion tool for assisting diagnosis of different prostate pathologies.

  18. [The effect of alloxan on the multiplication of different types of normal or cancerous cells, and on the transformation of chick embryo fibroblasts by Rous virus in vitro]. (United States)

    Grobon, P; Latarjet, R


    The action of alloxan was studied in vitro, on different categories of normal or cancerous cells. At concentrations of 250 and 350 gamma/ml, alloxan does not significantly inhibit the growth of normal cells, whereas it does inhibit the growth of cancerous cells. Furthermore, alloxan inhibits infection and transformation of chicken-embryo fibroblasts infected by the Rous virus.

  19. Discrimination Between Cervical Cancer Cells and Normal Cervical Cells Based on Longitudinal Elasticity Using Atomic Force Microscopy (United States)

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


    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.

  20. Early detection of colorectal cancer relapse by infrared spectroscopy in ``normal'' anastomosis tissue (United States)

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


    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.

  1. Cyclooxygenases expression and distribution in the normal ovary and their role in ovarian cancer in the domestic hen (Gallus domesticus). (United States)

    Hales, Dale Buchanan; Zhuge, Yan; Lagman, Jo Ann Jaen; Ansenberger, Kristine; Mahon, Cassandra; Barua, Animesh; Luborsky, Judith L; Bahr, Janice M


    Cyclooxygenase (COX) (PTGS) is the rate-limiting enzyme in the biosynthesis of prostaglandins. Two COX isoforms have been identified, COX-1 and COX-2, which show distinct cell-specific expression and regulation. Ovarian cancer is the most lethal gynecological malignancy and the disease is poorly understood due to the lack of suitable animal models. The laying hen spontaneously develops epithelial ovarian cancer with few or no symptoms until the cancer has progresses to a late stage, similar to the human disease. The purpose of this study was to examine the relative expression and distribution of COX-1 and COX-2 in the ovaries of normal hens and in hens with ovarian cancer. The results demonstrate that COX-1 was localized to the granulosa cell layer and cortical interstitium, ovarian surface epithelium (OSE) and postovulatory follicle (POF) of the normal ovary. In ovarian cancer, COX-1 mRNA was significantly increased and COX-1 protein was broadly distributed throughout the tumor stroma. COX-2 protein was localized to the granulosa cell layer in the follicle and the ovarian stroma. COX-2 mRNA expression did not change as a function of age or in ovarian cancer. There was significantly higher expression of COX-1 mRNA in the first POF (POF-1) compared to POF-2 and POF-3. COX-2 mRNA expression was not significantly different among POFs. There was no difference in COX-1 or COX-2 mRNA in the OSE isolated from individual follicles in the follicular hierarchy. The results confirm previous findings of the high expression of COX-1 in ovarian tumors further supporting the laying hen as a model for ovarian cancer, and demonstrate for the first time the high expression of COX-1 in POF-1 which is the source of prostaglandins needed for oviposition.

  2. PARK2, a Large Common Fragile Site Gene, is Part of a Stress Response Network in Normal Cells that is Disrupted During the Development of Ovarian Cancer (United States)


    primary prostate tumor tissues. Top row RORA; Bottom row Actin. C. Ovary cancer cell lines, Lane 1 normal ovarian epithelium control (OSE); Lane 2...Liu D, Tang X, El-Naggar A, Hong WK, Mao L. Loss of Fhit expression is a predictor of poor outcome in tongue cancer. Cancer Res 2001: 61: 837-841. 7

  3. Passage from normal mucosa to adenoma and colon cancer: alteration of normal sCD30 mechanisms regulating TH1/TH2 cell functions. (United States)

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


    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.

  4. Transcriptome profiling of the cancer, adjacent non-tumor and distant normal tissues from a colorectal cancer patient by deep sequencing.

    Directory of Open Access Journals (Sweden)

    Yan'an Wu

    Full Text Available Colorectal cancer (CRC is one of the most commonly diagnosed cancers in the world. A genome-wide screening of transcriptome dysregulation between cancer and normal tissue would provide insight into the molecular basis of CRC initiation and progression. Compared with microarray technology, which is commonly used to identify transcriptional changes, the recently developed RNA-seq technique has the ability to detect other abnormal regulations in the cancer transcriptome, such as alternative splicing, novel transcripts or gene fusion. In this study, we performed high-throughput transcriptome sequencing at ~50× coverage on CRC, adjacent non-tumor and distant normal tissue. The results revealed cancer-specific, differentially expressed genes and differential alternative splicing, suggesting that the extracellular matrix and metabolic pathways are activated and the genes related to cell homeostasis are suppressed in CRC. In addition, one tumor-restricted gene fusion, PRTEN-NOTCH2, was also detected and experimentally confirmed. This study reveals some common features in tumor invasion and provides a comprehensive survey of the CRC transcriptome, which provides better insight into the complexity of regulatory changes during tumorigenesis.

  5. Precision of pyrosequencing assay to measure LINE-1 methylation in colon cancer, normal colonic mucosa, and peripheral blood cells. (United States)

    Irahara, Natsumi; Nosho, Katsuhiko; Baba, Yoshifumi; Shima, Kaori; Lindeman, Neal I; Hazra, Aditi; Schernhammer, Eva S; Hunter, David J; Fuchs, Charles S; Ogino, Shuji


    Genome-wide DNA hypomethylation plays an important role in epigenomic and genomic instability and colorectal carcinogenesis. DNA methylation in the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of global DNA methylation level. In addition, LINE-1 hypomethylation in blood cells has been associated with colorectal adenoma risk, and LINE-1 hypomethylation in colorectal cancer is related with prognosis and linearly predicts shorter patient survival. However, no study has comprehensively evaluated the precision of sodium bisulfite conversion and PCR-pyrosequencing to measure LINE-1 methylation. Using 10 paraffin-embedded colon cancers, 5 matched normal colon mucosa, and 5 unrelated peripheral blood buffy coat leukocyte specimens, we enriched tumor DNA by macrodissection and laser capture microdissection. LINE-1 methylation was calculated as an average of 100 * C/(C + T) at 4 CpG sites after bisulfite-PCR-pyrosequencing. The LINE-1 methylation value in colon cancers varied, ranging approximately from 30 to 80. To measure assay precision, we performed bisulfite conversion on seven different DNA specimen aliquots and repeated PCR-pyrosequencing seven times. Run-to-run (between-run) SD ranged from 1.3 to 4.4 (median, 3.0) in macrodissected colon cancers; 1.1 to 10.5 (median, 3.8) in laser capture microdissection specimens; 1.3 to 2.5 (median, 1.9) in normal colon; and 1.5 to 3.4 (median, 1.9) in leukocyte DNA. In conclusion, bisulfite conversion and PCR-pyrosequencing assay can measure LINE-1 methylation in macrodissected colon cancer, normal colon, and blood DNA, and may be useful in clinical and research settings.

  6. Role of vascular density and normalization in response to neoadjuvant bevacizumab and chemotherapy in breast cancer patients


    Tolaney, Sara M.; Boucher, Yves; Duda, Dan G.; Martin, John D.; Seano, Giorgio; Ancukiewicz, Marek; Barry, William T.; Goel, Shom; Lahdenrata, Johanna; Isakoff, Steven J.; Yeh, Eren D.; Jain, Saloni R.; Golshan, Mehra; Brock, Jane; Snuderl, Matija


    Emerging evidence indicates patients who benefit from antiangiogenic therapies have improved vessel function. To determine how bevacizumab modulates vessel morphology to improve vessel function we conducted a phase II trial of preoperative bevacizumab followed by bevacizumab combined with chemotherapy in HER2-negative breast cancer patients. Our results suggest that the clinical response to bevacizumab may occur through an increase in the extent of vascular normalization primarily in patients...

  7. Effect of capping agents on the cytotoxicity of silver nanoparticles in human normal and cancer skin cell lines (United States)

    Netchareonsirisuk, Ponsawan; Puthong, Songchan; Dubas, Stephan; Palaga, Tanapat; Komolpis, Kittinan


    Silver nanoparticles (AgNPs) are among the most widely used nanomaterials in medical and consumer products. However, safety in the uses of AgNPs is still controversial. The toxicity of AgNPs toward various cell types has been reported to depend on the surface properties of the nanoparticles. In this study, the effect of AgNPs with the average size of 5-15 nm on the viability of the CCD-986SK human normal skin fibroblast cell line and A375 human malignant melanoma cell line was evaluated. Comparative toxicity studies, based on MTT assay, were performed by using either sodium alginate or poly (4-styrenesulfonic acid-co-maleic acid) sodium salt (PSSMA) as capping agent in the nanoparticle preparation. The cytotoxicity tests revealed that AgNO3 alone was highly toxic to both cell types while both alginate and PSSMA alone were not toxic. AgNPs capped with alginate were selectively toxic to the cancer cell line but not to the normal cell line while AgNPs capped with PSSMA were toxic to both cancer and normal cell lines. Judging from the 50 % inhibition concentration (IC50), it was found that the cancer cell line was more sensitive to AgNPs than the normal cell line. Study on the mode of cell death by annexin V and propidium iodide staining revealed that AgNPs induced more apoptotic cell death (84-90 %) than necrosis (8-12 %) in the skin cancer cell line. These results suggest that the toxicity of AgNPs depended on the type of capping agent and the type of cell line.

  8. Investigation of scattering coefficients and anisotropy factors of human cancerous and normal prostate tissues using Mie theory (United States)

    Pu, Yang; Chen, Jun; Wang, Wubao


    The scattering coefficient, μs, the anisotropy factor, g, the scattering phase function, p(θ), and the angular dependence of scattering intensity distributions of human cancerous and normal prostate tissues were systematically investigated as a function of wavelength, scattering angle and scattering particle size using Mie theory and experimental parameters. The Matlab-based codes using Mie theory for both spherical and cylindrical models were developed and applied for studying the light propagation and the key scattering properties of the prostate tissues. The optical and structural parameters of tissue such as the index of refraction of cytoplasm, size of nuclei, and the diameter of the nucleoli for cancerous and normal human prostate tissues obtained from the previous biological, biomedical and bio-optic studies were used for Mie theory simulation and calculation. The wavelength dependence of scattering coefficient and anisotropy factor were investigated in the wide spectral range from 300 nm to 1200 nm. The scattering particle size dependence of μs, g, and scattering angular distributions were studied for cancerous and normal prostate tissues. The results show that cancerous prostate tissue containing larger size scattering particles has more contribution to the forward scattering in comparison with the normal prostate tissue. In addition to the conventional simulation model that approximately considers the scattering particle as sphere, the cylinder model which is more suitable for fiber-like tissue frame components such as collagen and elastin was used for developing a computation code to study angular dependence of scattering in prostate tissues. To the best of our knowledge, this is the first study to deal with both spherical and cylindrical scattering particles in prostate tissues.

  9. Finding Your New Normal: Outcomes of a Wellness-Oriented Psychoeducational Support Group for Cancer Survivors (United States)

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


    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…

  10. Pigment epithelium-derived factor enhances tumor response to radiation through vasculature normalization in allografted lung cancer in mice. (United States)

    Xu, Z; Dong, Y; Peng, F; Yu, Z; Zuo, Y; Dai, Z; Chen, Y; Wang, J; Hu, X; Zhou, Q; Ma, H; Bao, Y; Gao, G; Chen, M


    This study aimed to explore the potential therapeutic effects of the combination of pigment epithelium-derived factor (PEDF) and radiation on lung cancer. The Lewis lung cancer (LLC) allografts in nude mice were treated with radiation, PEDF and PEDF combined with radiation. The morphologic changes of tumor vasculature and the hypoxic fraction of tumor tissues were evaluated. Significant inhibition of tumor growth was observed when radiation was applied between the 3rd and 7th day (the vasculature normalization window) after the initiation of PEDF treatment. During the vasculature normalization window, the tumor blood vessels in PEDF-treated mice were less tortuous and more uniform than those in the LLC allograft tumor treated with phosphate-buffered saline. Meanwhile, the thickness of the basement membrane was remarkably reduced and pericyte coverage was significantly increased with the PEDF treatment. We also found that tumor hypoxic fraction decreased during the 3rd to the 7th day after PEDF treatment, suggesting improved intratumoral oxygenation. Taken together, our results show that PEDF improved the effects of radiation therapy on LLC allografts by inducing a vascular normalization window from the 3rd to the 7th day after PEDF treatment. Our findings provide a basis for treating lung cancer with the combination of PEDF and radiation.

  11. Distinguishing normal cells from cancer cells via lysosome-targetable pH biomarkers with benzo[a]phenoxazine skeleton

    Energy Technology Data Exchange (ETDEWEB)

    Zhan, Yan-Hua [College of Chemistry, Chemical Engineering and Material Science, State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, Soochow University, 199 Ren’Ai Road, Suzhou, 215123 (China); Li, Xiao-Jun [School of Radiation Medicine and Protection, Medicine College of Soochow University, Suzhou, 215123 (China); Sun, Ru, E-mail: [College of Chemistry, Chemical Engineering and Material Science, State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, Soochow University, 199 Ren’Ai Road, Suzhou, 215123 (China); Xu, Yu-Jie [School of Radiation Medicine and Protection, Medicine College of Soochow University, Suzhou, 215123 (China); Ge, Jian-Feng, E-mail: [College of Chemistry, Chemical Engineering and Material Science, State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, Soochow University, 199 Ren’Ai Road, Suzhou, 215123 (China); Jiangsu Key Laboratory of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163 (China)


    In this paper, the design of a lysosome-targetable pH probe that has a fluorescent OFF (pH = 4) to ON (pH = 5–6) response is described to identify lysosomes in normal cells. The mechanism of photoinduced electron transfer with a fluorophore-based reaction (FBR-PET) was proposed. Benzo[a]phenoxazines with electro-donating aryl groups were selected, its (2,5-dimethoxyphenyl)imino-, (2-hydroxyphenyl)imino- and (2-hydroxy-5-methoxyphenyl)- imino-derivatives (probes 1a−c) were prepared and their optical responses towards pH were evaluated; their fluorescence pH titration experiments gave regularly changes with the increasing electro-donating abilities at the linked aryl groups, the (2-hydroxy-5-methoxyphenyl)iminobenzo[a]phenoxazine (probe 1c) exhibited a nearly OFF−ON response at 580–800 nm. All probes were reversible, and they showed excellent selectivity toward the proton over other competitive species. Fluorescence confocal images were performed with HeLa, KB cancer cells and V79 normal cells, probes 1a−c are all lysosome-targetable pH probes, and benzo[a]phenoxazine with (2-hydroxy-5-methoxyphenyl)imino-group (probe 1c) has potential applications in selective differentiation of normal cells from cancer cells. - Highlights: • pH probes for lysosome detection in normal cells. • Differentiation of normal cells from cancer cells by lysosome-biomarker. • The PET mechanism promoted by fluorophore based reactions (FBR-PET).

  12. Absolute Neutrino Mass Determination

    CERN Document Server

    Päs, H


    We discuss four approaches to the determination of absolute neutrino mass. These are the measurement of the zero-neutrino double beta decay rate, of the tritium decay end-point spectrum, of the cosmic ray spectrum above the GZK cutoff, and the cosmological measurement of the power spectrum governing the CMB and large scale structure. The first two approaches are sensitive to the mass eigenstates coupling to the electron neutrino, whereas the latter two are sensitive to the heavy component of the cosmic neutrino background. All mass eigenstates are related by the $\\Delta m^2$'s inferred from neutrino oscillation data. Consequently, the potential for absolute mass determination of each of the four approaches is correlated with the other three, in ways that we point out.

  13. 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)


    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.

  14. Serum protein profile study of normal and cervical cancer subjects by high performance liquid chromatography with laser-induced fluorescence. (United States)

    Sujatha; Rai, Lavanya; Kumar, Pratap; Mahato, Krishna K; Kartha, Vasudevan B; Santhosh, Chidangil


    High performance liquid chromatography with high sensitivity laser-induced fluorescence detection is used to study the protein profiles of serum samples from healthy volunteers and cervical cancer subjects. The protein profiles are subjected to principal component analysis (PCA). PCA shows that the large number of chromatograms of a given class of serum samples--say normal/malignant--can be expressed in terms of a small number of factors (principal components). Three parameters--scores of the factors, squared residuals, and Mahalanobis distance--are derived from PCA. The parameters are observed to have a narrow range for protein profiles of standard calibration sets formed from groups of clinically confirmed normal/malignant classes. Limit tests using match/no match of the parameters of any test sample with parameters derived for the standard calibration sets give very good discrimination between malignant and normal samples with high sensitivity (approximately 100%) aand specificity (approximately 94%).

  15. High-resolution copy number arrays in cancer and the problem of normal genome copy number variation. (United States)

    Gorringe, Kylie L; Campbell, Ian G


    High-resolution techniques for analysis of genome copy number (CN) enable the analysis of complex cancer somatic genetics. However, the analysis of these data is difficult, and failure to consider a number of issues in depth may result in false leads or unnecessary rejection of true positives. First, segmental duplications may falsely generate CN breakpoints in aneuploid samples. Second, even when tumor data were each normalized to matching lymphocyte DNA, we still observed copy number polymorphisms masquerading as somatic alterations due to allelic imbalance. We investigated a number of different solutions and determined that evaluating matching normal DNA, or at least using locally derived normal baseline data, were preferable to relying on current online databases because of poor cross-platform compatibility and the likelihood of excluding genuine small somatic alterations.

  16. Vitamin D and the mammary gland: a review on its role in normal development and breast cancer. (United States)

    Lopes, Nair; Paredes, Joana; Costa, José Luis; Ylstra, Bauke; Schmitt, Fernando


    Breast cancer is a heterogeneous disease associated with diverse biological behaviours and clinical outcome. Although some molecular subgroups of breast cancer have a targeted therapy, the most aggressive tumours still lack a molecular target. Despite vitamin D being classically associated with the physiological role of calcium regulation and phosphate transport in bone metabolism, several studies have demonstrated a wide range of functions for this hormone, which are particularly important in the field of cancer. The mechanisms underlying the protective actions of vitamin D in cancer development are only sparsely understood, but evidence shows that vitamin D participates in cell growth regulation, apoptosis and cell differentiation. In addition, it has been implicated in the suppression of cancer cell invasion, angiogenesis and metastasis. Most of vitamin D biological actions are mediated by the vitamin D receptor and the synthesis and catabolism of this hormone are regulated by the enzymes CYP27B1 and CYP24A1. In the present review we highlight research data concerning the function of this hormone in the mammary gland, with a special focus on breast carcinogenesis. Hence, and although the available data are controversial, we consider not only updated information on the epidemiology of vitamin D in breast cancer and its potential value as a therapeutic agent or prophylactic (with an emphasis on molecular mechanisms and effectors of vitamin D action), but include data on its role in other stages of breast cancer progression as well. Accordingly, we review data on the influence of vitamin D in the development of normal breast and the expression of vitamin D-related proteins (VDR, CYP27B1 and CYP24A21) in benign mammary lesions and ductal carcinomas in situ.

  17. 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


    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.

  18. Normal physiologic and Benign foci with F-18 FDG avidity on PET/CT in patients with breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Park, Soon Ah; Lee, Kwang Man; Choi, Un Jong; Kim, Hun Soo; Kim, Hye Won; Song, Jeong Hoon [College of Medicine, Wonkwnag University, Iksan (Korea, Republic of)


    The aim of this study was to evaluate the physiologic and benign F-18 fluorodeoxyglucose (FDG) avid foci in patients with breast cancer. On 309 F-18 FDG PET/CT scans of 241 women with breast cancer, the hypermetabolic lesions compared with the surrounding normal region were evaluated retrospectively. Available reports of other relevant radiological imaging medical records, and follow-up PET/CT were reviewed for explanations of the abnormal uptake. Among the 70 physiologic foci, muscular uptake of the lower neck following the surgical and/or radiation therapy of ipsilateral breast (29%), hypermetabolic ovaries (16%) and uterine (10%) uptake during the ovulatory and menstrual phases during the normal menstrual cycle were identified, and also hypermetabolic brown fat in cold-induced thermogenesis (7%), non-specific bowel uptake (35%) were observed. Among the 147 benign lesions, sequelae of the chest wall and breasts following surgical and/or radiation therapy, were often observed (27%). Hypermetabolic thyroid glands were noted as adenomas and chronic thyroiditis (18%). Reactive hyperplasia of cervical or mediastinal lymph nodes (32%), degenerative osteoarthritis and healed fractures (15%), hypermetabolic benign lung lesions (6%) were observed. Altered physiologic and benign F-18 FDG uptake in the cervical muscle and chest wall following ipsilateral breast surgery or radiotherapy were common, and also normal physiologic uptake in ovary and uterus, brown fat, thyroid were considered as predominant findings in women patients with breast cancer. Knowledge of these findings might aid in the interpretation of FDG PET/CT in patients with breast cancer

  19. 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))


    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

  20. Absolute-Magnitude Distributions of Supernovae

    CERN Document Server

    Richardson, Dean; Wright, John; Maddox, Larry


    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.

  1. cis-Expression QTL analysis of established colorectal cancer risk variants in colon tumors and adjacent normal tissue.

    Directory of Open Access Journals (Sweden)

    Lenora W M Loo

    Full Text Available Genome-wide association studies (GWAS have identified 19 risk variants associated with colorectal cancer. As most of these risk variants reside outside the coding regions of genes, we conducted cis-expression quantitative trait loci (cis-eQTL analyses to investigate possible regulatory functions on the expression of neighboring genes. Forty microsatellite stable and CpG island methylator phenotype-negative colorectal tumors and paired adjacent normal colon tissues were used for genome-wide SNP and gene expression profiling. We found that three risk variants (rs10795668, rs4444235 and rs9929218, using near perfect proxies rs706771, rs11623717 and rs2059252, respectively were significantly associated (FDR q-value ≤0.05 with expression levels of nearby genes (<2 Mb up- or down-stream. We observed an association between the low colorectal cancer risk allele (A for rs10795668 at 10p14 and increased expression of ATP5C1 (q = 0.024 and between the colorectal cancer high risk allele (C for rs4444235 at 14q22.2 and increased expression of DLGAP5 (q = 0.041, both in tumor samples. The colorectal cancer low risk allele (A for rs9929218 at 16q22.1 was associated with a significant decrease in expression of both NOL3 (q = 0.017 and DDX28 (q = 0.046 in the adjacent normal colon tissue samples. Of the four genes, DLGAP5 and NOL3 have been previously reported to play a role in colon carcinogenesis and ATP5C1 and DDX28 are mitochondrial proteins involved in cellular metabolism and division, respectively. The combination of GWAS findings, prior functional studies, and the cis-eQTL analyses described here suggest putative functional activities for three of the colorectal cancer GWAS identified risk loci as regulating the expression of neighboring genes.

  2. Changes of collagen and nicotinamide adenine dinucleotide in human cancerous and normal prostate tissues studied using native fluorescence spectroscopy with selective excitation wavelength (United States)

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


    The fluorescence spectra of human cancerous and normal prostate tissues obtained by the selective excitation wavelength of 340 nm were measured. The contributions of principle biochemical components to tissue fluorescence spectra were investigated using the method of multivariate curve resolution with alternating least squares. The results show that there is a reduced contribution from the emission of collagen and increased contribution from nicotinamide adenine dinucleotide (NADH) in cancerous tissues as compared with normal tissue. This difference is attributed to the changes of relative contents of NADH and collagen during cancer development. This research may present a potential native biomarker for prostate cancer detection.

  3. Characterization of prostate cancer, benign prostatic hyperplasia and normal prostates using transrectal 31phosphorus magnetic resonance spectroscopy: a preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Narayan, P.; Jajodia, P.; Kurhanewicz, J.; Thomas, A.; MacDonald, J.; Hubesch, B.; Hedgcock, M.; Anderson, C.M.; James, T.L.; Tanagho, E.A. (Univ. of California School of Medicine, San Francisco (USA))


    We assessed the ability of 31phosphorus (31P) transrectal magnetic resonance spectroscopy to characterize normal human prostates as well as prostates with benign and malignant neoplasms. With a transrectal probe that we devised for surface coil spectroscopy we studied 15 individuals with normal (5), benign hyperplastic (4) and malignant (6) prostates. Digital rectal examination, transrectal ultrasonography and magnetic resonance imaging were used to aid in accurate positioning of the transrectal probe against the region of interest within the prostate. The major findings of the in vivo studies were that normal prostates had phosphocreatine-to-adenosine triphosphate (ATP) ratios of 1.2 +/- 0.2, phosphomonoester-to-beta-ATP ratios of 1.1 +/- 0.1 and phosphomonoester-to-phosphocreatine ratios of 0.9 +/- 0.1. Malignant prostates had phosphocreatine-to-beta-ATP ratios that were lower (0.7 +/- 0.1) than those of normal prostates (p less than 0.02) or prostates with benign hyperplasia. Malignant prostates had phosphomonoester-to-beta-ATP ratios (1.8 +/- 0.2) that were higher than that of normal prostates (p less than 0.02). Using the phosphomonoester-to-phosphocreatine ratio, it was possible to differentiate metabolically malignant (2.7 +/- 0.3) from normal prostates (p less than 0.001), with no overlap of individual ratios. The mean phosphomonoester-to-phosphocreatine ratio (1.5 +/- 0.5) of prostates with benign hyperplasia was midway between the normal and malignant ratios, and there was overlap between individual phosphomonoester-to-phosphocreatine ratios of benign prostatic hyperplasia glands with that of normal and malignant glands. To verify the in vivo results, we performed high resolution magnetic resonance spectroscopy on perchloric acid extracts of benign prostatic hyperplasia tissue obtained at operation and on a human prostatic cancer cell line DU145.

  4. Absolute airborne gravimetry (United States)

    Baumann, Henri

    This work consists of a feasibility study of a first stage prototype airborne absolute gravimeter system. In contrast to relative systems, which are using spring gravimeters, the measurements acquired by absolute systems are uncorrelated and the instrument is not suffering from problems like instrumental drift, frequency response of the spring and possible variation of the calibration factor. The major problem we had to resolve were to reduce the influence of the non-gravitational accelerations included in the measurements. We studied two different approaches to resolve it: direct mechanical filtering, and post-processing digital compensation. The first part of the work describes in detail the different mechanical passive filters of vibrations, which were studied and tested in the laboratory and later in a small truck in movement. For these tests as well as for the airborne measurements an absolute gravimeter FG5-L from Micro-G Ltd was used together with an Inertial navigation system Litton-200, a vertical accelerometer EpiSensor, and GPS receivers for positioning. These tests showed that only the use of an optical table gives acceptable results. However, it is unable to compensate for the effects of the accelerations of the drag free chamber. The second part describes the strategy of the data processing. It is based on modeling the perturbing accelerations by means of GPS, EpiSensor and INS data. In the third part the airborne experiment is described in detail, from the mounting in the aircraft and data processing to the different problems encountered during the evaluation of the quality and accuracy of the results. In the part of data processing the different steps conducted from the raw apparent gravity data and the trajectories to the estimation of the true gravity are explained. A comparison between the estimated airborne data and those obtained by ground upward continuation at flight altitude allows to state that airborne absolute gravimetry is feasible and

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


    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

  6. Differentiation between human normal colon mucosa and colon cancer tissue using ToF-SIMS imaging technique and principal component analysis (United States)

    Park, Ji-Won; Shon, Hyun Kyong; Yoo, Byong Chul; Kim, In Hoo; Moon, Dae Won; Lee, Tae Geol


    Human normal colon mucosa and colon cancer tissue were studied using the time-of-flight secondary ion mass spectroscopy (ToF-SIMS) and principal component analysis (PCA) techniques. The surfaces of the tissues were successfully cleaned by C 602+ cluster-ion beams before the ToF-SIMS images were obtained. A PCA on the spectra and images were performed to compare differences in the peaks and images of normal and cancer tissues. Significant differences in principal component 1 (PC 1) score values for normal and cancer tissues were observed, and each PC 1 loadings had a specific peak profile of proteins. In addition, the PC images obtained from the ToF-SIMS images for normal and cancer tissues were clearly distinguishable, and the amino acid fragments associated with normal and cancer tissues were found to have originated from the lamina propria region and the epithelium cells, respectively. Based on the PCA results, structural distortion of the crypts in the cancer colon tissue could be attributed to the proliferation of the cancerous epithelium cells. This work shows that the application of the ToF-SIMS imaging technique with PCA could be a useful method of obtaining valuable information for cancer analysis.

  7. Base excision repair activities differ in human lung cancer cells and corresponding normal controls

    DEFF Research Database (Denmark)

    Karahalil, Bensu; Bohr, Vilhelm A; De Souza-Pinto, Nadja C


    Oxidative damage to DNA is thought to play a role in carcinogenesis by causing mutations, and indeed accumulation of oxidized DNA bases has been observed in samples obtained from tumors but not from surrounding tissue within the same patient. Base excision repair (BER) is the main pathway...... for the repair of oxidized modifications both in nuclear and mitochondrial DNA. In order to ascertain whether diminished BER capacity might account for increased levels of oxidative DNA damage in cancer cells, the activities of BER enzymes in three different lung cancer cell lines and their non......-cancerous counterparts were measured using oligonucleotide substrates with single DNA lesions to assess specific BER enzymes. The activities of four BER enzymes, OGG1, NTH1, UDG and APE1, were compared in mitochondrial and nuclear extracts. For each specific lesion, the repair activities were similar among the three...

  8. Absolutely Indecomposable Modules

    CERN Document Server

    Göbel, Rüdiger


    A module is called absolutely indecomposable if it is directly indecomposable in every generic extension of the universe. We want to show the existence of large abelian groups that are absolutely indecomposable. This will follow from a more general result about R-modules over a large class of commutative rings R with endomorphism ring R which remains the same when passing to a generic extension of the universe. It turns out that `large' in this context has the precise meaning, namely being smaller then the first omega-Erdos cardinal defined below. We will first apply result on large rigid trees with a similar property established by Shelah in 1982, and will prove the existence of related ` R_omega-modules' (R-modules with countably many distinguished submodules) and finally pass to R-modules. The passage through R_omega-modules has the great advantage that the proofs become very transparent essentially using a few `linear algebra' arguments accessible also for graduate students. The result gives a new constru...

  9. On the Mean Absolute Error in Inverse Binomial Sampling


    Mendo, Luis


    A closed-form expression and an upper bound are obtained for the mean absolute error of the unbiased estimator of a probability in inverse binomial sampling. The results given permit the estimation of an arbitrary probability with a prescribed level of the normalized mean absolute error.

  10. L-lactate metabolism can occur in normal and cancer prostate cells via the novel mitochondrial L-lactate dehydrogenase. (United States)

    De Bari, Lidia; Chieppa, Gabriella; Marra, Ersilia; Passarella, Salvatore


    Both normal (PTN1A) and cancer (PC3) prostate cells produce high levels of L-lactate because of a low energy supply via the citric cycle and oxidative phosphorylation. Since some mammalian mitochondria possess a mitochondrial L-lactate dehydrogenase (mLDH), we investigated whether prostate cells can take up L-lactate and metabolize it in the mitochondria. We report here that externally added L-lactate can enter both normal and cancer cells and mitochondria, as shown by both the oxygen consumption and by the increase in fluorescence of NAD(P)H which occur as a result of L-lactate addition. In both cell types L-lactate enters mitochondria in a carrier-mediated manner, as shown by the inhibition of swelling measurements due to the non-penetrant thiol reagent mersalyl. An L-lactate dehydrogenase exists in mitochondria of both cell types located in the inner compartment, as shown by kinetic investigation and by immunological analysis. The mLDHs proved to differ from the cytosolic enzymes (which themselves differ from one another) as functionally investigated with respect to kinetic features and pH profile. Normal and cancer cells were found to differ from one another with respect to mLDH protein level and activity, being the enzyme more highly expressed and of higher activity in PC3 cells. Moreover, the kinetic features and pH profiles of the PC3 mLDH also differ from those of the PNT1A enzyme, this suggesting the occurrence of separate isoenzymes.

  11. 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


    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.

  12. Flow cytometric determination of stem/progenitor content in epithelial tissues: an example from nonsmall lung cancer and normal lung. (United States)

    Donnenberg, Vera S; Landreneau, Rodney J; Pfeifer, Melanie E; Donnenberg, Albert D


    Single cell analysis and cell sorting has enabled the study of development, growth, differentiation, repair and maintenance of "liquid" tissues and their cancers. The application of these methods to solid tissues is equally promising, but several unique technical challenges must be addressed. This report illustrates the application of multidimensional flow cytometry to the identification of candidate stem/progenitor populations in non-small cell lung cancer and paired normal lung tissue. Seventeen paired tumor/normal lung samples were collected at the time of surgical excision and processed immediately. Tissues were mechanically and enzymatically dissociated into single cell suspension and stained with a panel of antibodies used for negative gating (CD45, CD14, CD33, glycophorin A), identification of epithelial cells (intracellular cytokeratin), and detection of stem/progenitor markers (CD44, CD90, CD117, CD133). DAPI was added to measure DNA content. Formalin fixed paraffin embedded tissue samples were stained with key markers (cytokeratin, CD117, DAPI) for immunofluorescent tissue localization of populations detected by flow cytometry. Disaggregated tumor and lung preparations contained a high proportion of events that would interfere with analysis, were they not eliminated by logical gating. We demonstrate how inclusion of doublets, events with hypodiploid DNA, and cytokeratin+ events also staining for hematopoietic markers reduces the ability to quantify epithelial cells and their precursors. Using the lung cancer/normal lung data set, we present an approach to multidimensional data analysis that consists of artifact removal, identification of classes of cells to be studied further (classifiers) and the measurement of outcome variables on these cell classes. The results of bivariate analysis show a striking similarity between the expression of stem/progenitor markers on lung tumor and adjacent tumor-free lung.

  13. Characterization of cell lines derived from breast cancers and normal mammary tissues for the study of the intrinsic molecular subtypes. (United States)

    Prat, Aleix; Karginova, Olga; Parker, Joel S; Fan, Cheng; He, Xiaping; Bixby, Lisa; Harrell, J Chuck; Roman, Erick; Adamo, Barbara; Troester, Melissa; Perou, Charles M


    Five molecular subtypes (luminal A, luminal B, HER2-enriched, basal-like, and claudin-low) with clinical implications exist in breast cancer. Here, we evaluated the molecular and phenotypic relationships of (1) a large in vitro panel of human breast cancer cell lines (BCCLs), human mammary fibroblasts (HMFs), and human mammary epithelial cells (HMECs); (2) in vivo breast tumors; (3) normal breast cell subpopulations; (4) human embryonic stem cells (hESCs); and (5) bone marrow-derived mesenchymal stem cells (hMSC). First, by integrating genomic data of 337 breast tumor samples with 93 cell lines we were able to identify all the intrinsic tumor subtypes in the cell lines, except for luminal A. Secondly, we observed that the cell lines recapitulate the differentiation hierarchy detected in the normal mammary gland, with claudin-low BCCLs and HMFs cells showing a stromal phenotype, HMECs showing a mammary stem cell/bipotent progenitor phenotype, basal-like cells showing a luminal progenitor phenotype, and luminal B cell lines showing a mature luminal phenotype. Thirdly, we identified basal-like and highly migratory claudin-low subpopulations of cells within a subset of triple-negative BCCLs (SUM149PT, HCC1143, and HCC38). Interestingly, both subpopulations within SUM149PT were enriched for tumor-initiating cells, but the basal-like subpopulation grew tumors faster than the claudin-low subpopulation. Finally, claudin-low BCCLs resembled the phenotype of hMSCs, whereas hESCs cells showed an epithelial phenotype without basal or luminal differentiation. The results presented here help to improve our understanding of the wide range of breast cancer cell line models through the appropriate pairing of cell lines with relevant in vivo tumor and normal cell counterparts.

  14. Role of ART-27, a Novel Androgen Receptor Coactivator, in Normal Prostate and Prostate Cancer (United States)


    07$15.00/0 Printed m U 8 .A. Molecular Endocrino logy 21 (12):2864- 2876 Copyright C’l 2007 by The Endocrine Society d ol: 10.121G/ me.2007-0094...mutations identified in prostate cancer and androgen insensitivity syndrome display aberrant ART -27 coacti- vator function. Mol Endocrino l 19

  15. 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)


    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

  16. Heterogeneous patterns of DNA methylation-based field effects in histologically normal prostate tissue from cancer patients. (United States)

    Møller, Mia; Strand, Siri Hundtofte; Mundbjerg, Kamilla; Liang, Gangning; Gill, Inderbir; Haldrup, Christa; Borre, Michael; Høyer, Søren; Ørntoft, Torben Falck; Sørensen, Karina Dalsgaard


    Prostate cancer (PC) diagnosis is based on histological evaluation of prostate needle biopsies, which have high false negative rates. Here, we investigated if cancer-associated epigenetic field effects in histologically normal prostate tissue may be used to increase sensitivity for PC. We focused on nine genes (AOX1, CCDC181 (C1orf114), GABRE, GAS6, HAPLN3, KLF8, MOB3B, SLC18A2, and GSTP1) known to be hypermethylated in PC. Using quantitative methylation-specific PCR, we analysed 66 malignant and 134 non-malignant tissue samples from 107 patients, who underwent ultrasound-guided prostate biopsy (67 patients had at least one cancer-positive biopsy, 40 had exclusively cancer-negative biopsies). Hypermethylation was detectable for all genes in malignant needle biopsy samples (AUC: 0.80 to 0.98), confirming previous findings in prostatectomy specimens. Furthermore, we identified a four-gene methylation signature (AOX1xGSTP1xHAPLN3xSLC18A2) that distinguished histologically non-malignant biopsies from patients with vs. without PC in other biopsies (AUC = 0.65; sensitivity = 30.8%; specificity = 100%). This signature was validated in an independent patient set (59 PC, 36 adjacent non-malignant, and 9 normal prostate tissue samples) analysed on Illumina 450 K methylation arrays (AUC = 0.70; sensitivity = 40.6%; specificity = 100%). Our results suggest that a novel four-gene signature may be used to increase sensitivity for PC diagnosis through detection of epigenetic field effects in histologically non-malignant prostate tissue samples.

  17. 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


    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...

  18. Effects of continuous wave and fractionated diode laser on human fibroblast cancer and dermal normal cells by zinc phthalocyanine in photodynamic therapy: A comparative study. (United States)

    Navaeipour, Farzaneh; Afsharan, Hadi; Tajalli, Habib; Mollabashi, Mahmood; Ranjbari, Farideh; Montaseri, Azadeh; Rashidi, Mohammad-Reza


    In this experimental study, cancer and normal cells behavior during an in vitro photodynamic therapy (PDT) under exposure of continuous wave (CW) and fractionated mode of laser with different irradiation power and time intervals was compared and investigated. At the first, human fibroblast cancer cell line (SW 872) and human dermal normal (HFFF2) cell line were incubated with different concentrations of zinc phthalocyanine (ZnPc), as a PDT drug. The cells, then, were irradiated with a 675nm diode laser and the cell viability was evaluated using MTT assay. Under optimized conditions, the viability of the cancer cells was eventually reduced to 3.23% and 13.17%, and that of normal cells was decreased to 20.83% and 36.23% using CW and fractionated diode lasers, respectively. In general, the ratio of ZnPc LD50 values for the normal cells to the cancer cells with CW laser was much higher than that of the fractionated laser. Subsequently, cancer cells in comparison with normal ones were found to be more sensitive toward the photodynamic damage induced by ZnPc. In addition, treatment with CW laser was found to be more effective against the cancer cells with a lower toxicity to the normal cells compared with the fractionated diode laser.

  19. Absolute Gravimetry in Fennoscandia

    DEFF Research Database (Denmark)

    Pettersen, B. R; TImmen, L.; Gitlein, O.

    The Fennoscandian postglacial uplift has been mapped geometrically using precise levelling, tide gauges, and networks of permanent GPS stations. The results identify major uplift rates at sites located around the northern part of the Gulf of Bothnia. The vertical motions decay in all directions...... motions) has its major axis in the direction of southwest to northeast and covers a distance of about 2000 km. Absolute gravimetry was made in Finland and Norway in 1976 with a rise-and fall instrument. A decade later the number of gravity stations was expanded by JILAg-5, in Finland from 1988, in Norway...... from 1991, and in Sweden from 1992. FG5 was introduced in these three countries in 1993 (7 stations) and continued with an extended campaign in 1995 (12 stations). In 2003 a project was initiated by IfE, Hannover to collect observations simultaneously with GRACE on an annual cycle. New instruments were...

  20. Optical tweezers absolute calibration

    CERN Document Server

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


    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...

  1. Computerized whole slide quantification shows increased microvascular density in pT2 prostate cancer as compared to normal prostate tissue.

    NARCIS (Netherlands)

    Niekerk, G.C. van; Laak, J.A.W.M. van der; Borger, E.; Huisman, H.J.; Witjes, J.A.; Barentsz, J.O.; Hulsbergen- van de Kaa, C.A.


    BACKGROUND: Contrast enhanced imaging enables powerful, non-invasive diagnostics, important for detection and staging of early prostate cancer. The uptake of contrast agent is increased in prostate cancer as compared to normal prostate tissue. To reveal the underlying physiological mechanisms, quant

  2. Absolute multilateration between spheres (United States)

    Muelaner, Jody; Wadsworth, William; Azini, Maria; Mullineux, Glen; Hughes, Ben; Reichold, Armin


    Environmental effects typically limit the accuracy of large scale coordinate measurements in applications such as aircraft production and particle accelerator alignment. This paper presents an initial design for a novel measurement technique with analysis and simulation showing that that it could overcome the environmental limitations to provide a step change in large scale coordinate measurement accuracy. Referred to as absolute multilateration between spheres (AMS), it involves using absolute distance interferometry to directly measure the distances between pairs of plain steel spheres. A large portion of each sphere remains accessible as a reference datum, while the laser path can be shielded from environmental disturbances. As a single scale bar this can provide accurate scale information to be used for instrument verification or network measurement scaling. Since spheres can be simultaneously measured from multiple directions, it also allows highly accurate multilateration-based coordinate measurements to act as a large scale datum structure for localized measurements, or to be integrated within assembly tooling, coordinate measurement machines or robotic machinery. Analysis and simulation show that AMS can be self-aligned to achieve a theoretical combined standard uncertainty for the independent uncertainties of an individual 1 m scale bar of approximately 0.49 µm. It is also shown that combined with a 1 µm m‑1 standard uncertainty in the central reference system this could result in coordinate standard uncertainty magnitudes of 42 µm over a slender 1 m by 20 m network. This would be a sufficient step change in accuracy to enable next generation aerospace structures with natural laminar flow and part-to-part interchangeability.

  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


    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. The expression and function of organic anion transporting polypeptides in normal tissues and in cancer. (United States)

    Obaidat, Amanda; Roth, Megan; Hagenbuch, Bruno


    Organic anion transporting polypeptides (OATPs) are members of the SLCO gene superfamily of proteins. The 11 human OATPs are classified into 6 families and subfamilies on the basis of their amino acid sequence similarities. OATPs are expressed in several epithelial tissues throughout the body and transport mainly amphipathic molecules with molecular weights of more than 300 kDa. Members of the OATP1 and OATP2 families are functionally the best-characterized OATPs. Among these are the multispecific OATP1A2, OATP1B1, OATP1B3, and OATP2B1. They transport various endo- and xenobiotics, including hormones and their conjugates as well as numerous drugs such as several anticancer agents. Recent reports demonstrate that some OATPs are up- or downregulated in several cancers and that OATP expression might affect cancer development. On the basis of the findings summarized in this review, we propose that OATPs could be valuable targets for anticancer therapy.

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

    Institute of Scientific and Technical Information of China (English)

    Lu-Yuan Li


    @@ "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(,an international conference held at Nankai University in Tianjin,China,on July 2-4,2010.About 300 cancer researchers and students attended the conference.

  6. Immune-Signatures for Lung Cancer Diagnostics: Evaluation of Protein Microarray Data Normalization Strategies



    New minimal invasive diagnostic methods for early detection of lung cancer are urgently needed. It is known that the immune system responds to tumors with production of tumor-autoantibodies. Protein microarrays are a suitable highly multiplexed platform for identification of autoantibody signatures against tumor-associated antigens (TAA). These microarrays can be probed using 0.1 mg immunoglobulin G (IgG), purified from 10 µL of plasma. We used a microarray comprising recombinant proteins der...

  7. Penicillium verruculosum SG: a source of polyketide and bioactive compounds with varying cytotoxic activities against normal and cancer lines. (United States)

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


    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.

  8. 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


    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.

  9. Cytotoxic, genotoxic and apoptotic effects of naringenin-oxime relative to naringenin on normal and cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Abdurrahim Kocyigit; Ismail Koyuncu; Murat Dikilitas; Fatemeh Bahadori; Baki Turkkan


    Objective: To assess and compare the cytotoxic, genotoxic, apoptotic and reactive oxygen species (ROS) generating effects of naringenin (NG) and its new derived compound naringenin-oxime (NG-Ox) on MCF-7, HT-29, PC-12 cancer and L-929 normal cell lines. Methods: The cells were incubated with different doses of NG-Ox and NG (50–1 000 mmol/L) for 24 h. The cell viability was assessed based on ATP cell viability assay. Intracellular accumulation of ROS was determined using the fluorescent probes 2070-dichlorodihydrofluorescin diacetate. Genotoxic effects were evaluated by alkaline single cell gel electrophoresis assay (comet assay) and, the apoptotic effect was evaluated by acridine orange staining at below the IC50 levels. Results: Both NG-Ox and NG exhibited cytotoxic, genotoxic and apoptotic effects and resulted in increased ROS values in a dose-dependent manner. The effects were more pronounced on cancer cell lines. The cytotoxic, genotoxic and apoptotic effects of NG-Ox were higher than that of NG in all cell lines. Significant correlations were observed be-tween cell viability, DNA damage, apoptosis and ROS, in all cell lines exposed to either NG-Ox or NG. Conclusions: This study showed that both NG-Ox and NG possess cytotoxic, genotoxic and apoptotic activities through the production of ROS on cells, NG-Ox being the more effective one. Therefore, derived compound of NG might be used as antiproliferative agents for the treatment of cancer.

  10. Cytogenetic, cytotoxic and GC-MS studies on concrete and absolute oils from Taif rose, Saudi Arabia. (United States)

    Hagag, Heba A; Bazaid, Salih A; Abdel-Hameed, El-Sayed S; Salman, Mahmood


    Taif rose (Rosa damascena trigintipetala Dieck) is a sort of damask rose, which is considered as one of the most important economic products of Taif. In this study, the authors investigated the possible cytotoxic, genotoxic, antimutagenic and anticancer effect of concrete and absolute rose oils. The results showed that both concrete and absolute rose oils were cytotoxically and genotoxically safe at a dose of 10 μg/ml when tested on cultures of normal human blood lymphocytes. Also, the results showed significant antimutagenic activity at p concrete and absolute oils exerted a cytotoxic activity against two kinds of human cancer cell lines: HepG2 and MCF7. Concrete oil showed cytotoxic activity against HepG2 and MCF7 with a half maximal inhibitory concentration (IC50) of 16.28 and 18.09 μg/ml, respectively, whereas absolute rose oil showed its cytotoxic activity against HepG2 and MCF7 with an IC50 of 24.94 and 19.69, respectively. From this study, it is concluded that concrete and absolute rose oils are cytotoxically and genotoxically safe at a dose of 10 μg/ml when tested on cultures of normal human blood lymphocytes. In addition, absolute oil has an antimutagenic activity at the same dose. Further investigations are needed to study the activity of higher doses of both oils in vitro and in vivo in experimental animals in order to evaluate the capability of using these oils as therapeutic for treatment of some kinds of cancers.

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

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Mary, E-mail: [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Demiroz, Candan; Vineberg, Karen A.; Eisbruch, Avraham; Balter, James M. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)


    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 cm{sup 3} ({sigma} 0.5 cm{sup 3}). Mean fractional overlap was 0.7 ({sigma} 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, {sigma} 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.

  12. Identification of metabolites in the normal ovary and their transformation in primary and metastatic ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Miranda Y Fong

    Full Text Available In this study, we characterized the metabolome of the human ovary and identified metabolic alternations that coincide with primary epithelial ovarian cancer (EOC and metastatic tumors resulting from primary ovarian cancer (MOC using three analytical platforms: gas chromatography mass spectrometry (GC/MS and liquid chromatography tandem mass spectrometry (LC/MS/MS using buffer systems and instrument settings to catalog positive or negative ions. The human ovarian metabolome was found to contain 364 biochemicals and upon transformation of the ovary caused changes in energy utilization, altering metabolites associated with glycolysis and β-oxidation of fatty acids--such as carnitine (1.79 fold in EOC, p<0.001; 1.88 fold in MOC, p<0.001, acetylcarnitine (1.75 fold in EOC, p<0.001; 2.39 fold in MOC, p<0.001, and butyrylcarnitine (3.62 fold, p<0.0094 in EOC; 7.88 fold, p<0.001 in MOC. There were also significant changes in phenylalanine catabolism marked by increases in phenylpyruvate (4.21 fold; p = 0.0098 and phenyllactate (195.45 fold; p<0.0023 in EOC. Ovarian cancer also displayed an enhanced oxidative stress response as indicated by increases in 2-aminobutyrate in EOC (1.46 fold, p = 0.0316 and in MOC (2.25 fold, p<0.001 and several isoforms of tocopherols. We have also identified novel metabolites in the ovary, specifically N-acetylasparate and N-acetyl-aspartyl-glutamate, whose role in ovarian physiology has yet to be determined. These data enhance our understanding of the diverse biochemistry of the human ovary and demonstrate metabolic alterations upon transformation. Furthermore, metabolites with significant changes between groups provide insight into biochemical consequences of transformation and are candidate biomarkers of ovarian oncogenesis. Validation studies are warranted to determine whether these compounds have clinical utility in the diagnosis or clinical management of ovarian cancer patients.

  13. Phytosynthesized gold nanoparticles from C. roxburghii DC. leaf and their toxic effects on normal and cancer cell lines. (United States)

    Balashanmugam, Pannerselvam; Durai, Prabhu; Balakumaran, Manickam Dakshinamoorthi; Kalaichelvan, Pudupalayam Thangavelu


    Gold nanoparticles are considered of great importance compared to other noble metal nanoparticles and its wide range of applications like pharmaceutics, therapeutics and diagnostics etc. During the past decade, phytosynthesized gold nanoparticles (AuNPs) are more focused in in vitro and in vivo study. The present study was focused on the gold chloride and phytosynthesized gold nanoparticles from aqueous leaf extract of Cassia roxburghii and their toxic effects on African green monkey normal kidney Vero cell line and three different cancer cell lines such as HepG2, MCF7 and HeLa. Phytosynthesized AuNPs were characterized by HRTEM, EDX, XRD and FTIR analysis. The particles size range of 25-35nm was confirmed by HRTEM. The elemental gold and the crystalline nature of AuNPs were confirmed by EDX and XRD, respectively. The reduction of functional groups was confirmed by FTIR. In in vitro study, the IC50 of HepG2 cells was found to be 30μg/ml compared to other cell lines, HeLa and MCF7 cell line showing IC50 of 50μg/ml and normal Vero cell line also nontoxic up to 75μg/ml confirmed by MTT assay. Further, apoptosis in HepG2 was analyzed by fluorescence microscope and DNA fragmentation was observed in HepG2 treated cells. These results suggested that phytosynthesized AuNPs of C. roxburghii extract clearly limited toxic on normal cells but toxic in cancer cells.

  14. Vitamin D3 modulated gene expression patterns in human primary normal and cancer prostate cells. (United States)

    Guzey, Meral; Luo, Jianhua; Getzenberg, Robert H


    The vitamin D receptor (VDR) is a member of the steroid/retinoid receptor superfamily of nuclear receptors and has potential tumor-suppressive functions in prostate and other cancer types. Vitamin D3 (VD3) exerts its biological actions by binding within cells to VDR. The VDR then interacts with specific regions of the DNA in cells, and triggers changes in the activity of genes involved in cell division, cell survival, and cellular function. Using human primary cultures and the prostate cancer (PCa) cell line, ALVA-31, we examined the effects of VD3 under different culture conditions. Complete G0/G1 arrest of ALVA-31 cells and approximately 50% inhibition of tumor stromal cell growth was observed. To determine changes in gene expression patterns related to VD3 activity, microarray analysis was performed. More than approximately 20,000 genes were evaluated for twofold relative increases and decreases in expression levels. A number of the gene targets that were up- and down-regulated are related to potential mechanisms of prostatic growth regulation. These include estrogen receptor (ER), heat shock proteins: 70 and 90, Apaf1, Her-2/neu, and paxillin. Utilizing antibodies generated against these targets, we were able to confirm the changes at the protein level. These newly reported gene expression patterns provide novel information not only potential markers, but also on the genes involved in VD3 induced apoptosis in PCa.

  15. Reprogramming of Normal Fibroblasts into Cancer-Associated Fibroblasts by miRNAs-Mediated CCL2/VEGFA Signaling (United States)

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


    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

  16. Liver X receptor ligand cytotoxicity in colon cancer cells and not in normal colon epithelial cells depends on LXRβ subcellular localization. (United States)

    Courtaut, Flavie; Derangère, Valentin; Chevriaux, Angélique; Ladoire, Sylvain; Cotte, Alexia K; Arnould, Laurent; Boidot, Romain; Rialland, Mickaël; Ghiringhelli, François; Rébé, Cédric


    Increasing evidence indicates that Liver X Receptors (LXRs) have some anticancer properties. We recently demonstrated that LXR ligands induce colon cancer cell pyroptosis through an LXRβ-dependent pathway. In the present study, we showed that human colon cancer cell lines presented differential cytoplasmic localizations of LXRβ. This localization correlated with caspase-1 activation and cell death induction under treatment with LXR ligand. The association of LXRβ with the truncated form of RXRα (t-RXRα) was responsible for the sequestration of LXRβ in the cytoplasm in colon cancer cells. Moreover t-RXRα was not expressed in normal colon epithelial cells. These cells presented a predominantly nuclear localization of LXRβ and were resistant to LXR ligand cytotoxicity. Our results showed that predominant cytoplasmic localization of LXRβ, which occurs in colon cancer cells but not in normal colon epithelial cells, allowed LXR ligand-induced pyroptosis. This study strengthens the hypothesis that LXRβ could be a promising target in cancer therapy.

  17. Estimating Absolute Site Effects

    Energy Technology Data Exchange (ETDEWEB)

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


    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

  18. DNA methylation combinations in adjacent normal colon tissue predict cancer recurrence: evidence from a clinical cohort study.

    Directory of Open Access Journals (Sweden)

    Jen Chun Kuan

    Full Text Available Accumulating evidence has suggested the requirement for further stratification of patients in the same tumor stage according to molecular factors. We evaluate the combination of cancer stage and DNA methylation status as an indicator of the risk of recurrence and mortality among patients with colorectal cancer (CRC. A cohort study of 215 patients with CRC (mean age 64.32 years; 50.5% of men from Tri-Service General Hospital in Taiwan examined the association between cancer stage and risk of CRC recurrence and mortality. A Cox proportional hazard model was used to analyze patient methylation status and clinical information at study entry, and their associations with CRC recurrence and mortality during follow-up. The advanced stage patients with p16, hMLH1, and MGMT methylation were associated with higher risk of CRC recurrence compared with the local stage patients with unmethylation status in tumor tissues, with adjusted hazard ratios (HRs (95% confidence interval [CI] of 9.64 (2.92-31.81, 8.29 (3.40-20.22, and 11.83 (3.49-40.12, respectively. When analyzing normal tissues, we observed similar risk of CRC recurrence with adjusted HRs (95% CI of 10.85 (4.06-28.96, 9.04 (3.79-21.54, and 12.61 (4.90-32.44, respectively. For combined analyses, the risk of recurrence in the patients in advanced stage with DNA methylation in both normal and tumor tissues, compared with local stage with unmethylation, was increased with adjusted HR (95% CI of 9.37 (3.36-26.09. In the advanced stage patients, methylation status and tissue subtype were associated with increased risk of 5-year cumulative CRC recurrence (p < 0.001. This study demonstrates that clustering DNA methylation status according to cancer stage and tissue subtype is critical for the assessment of risk of recurrence in CRC patients and also indicated an underlying mechanism.

  19. Markers of fibrosis and epithelial to mesenchymal transition demonstrate field cancerization in histologically normal tissue adjacent to breast tumors (United States)

    Trujillo, Kristina A.; Heaphy, Christopher M.; Mai, Minh; Vargas, Keith M.; Jones, Anna C.; Vo, Phung; Butler, Kimberly S.; Joste, Nancy E.; Bisoffi, Marco; Griffith, Jeffrey K


    Previous studies have shown that a field of genetically altered but histologically normal tissue extends 1 cm or more from the margins of human breast tumors. The extent, composition and biological significance of this field are only partially understood, but the molecular alterations in affected cells could provide mechanisms for limitless replicative capacity, genomic instability and a microenvironment that supports tumor initiation and progression. We demonstrate by microarray, qRT-PCR and immunohistochemistry a signature of differential gene expression that discriminates between patient-matched, tumor-adjacent histologically normal breast tissues located 1 cm and 5 cm from the margins of breast adenocarcinomas (TAHN-1 and TAHN-5, respectively). The signature includes genes involved in extracellular matrix remodeling, wound healing, fibrosis and epithelial to mesenchymal transition (EMT). Myofibroblasts, which are mediators of wound healing and fibrosis, and intra-lobular fibroblasts expressing MMP2, SPARC, TGF-β3, which are inducers of EMT, were both prevalent in TAHN-1 tissues, sparse in TAHN-5 tissues, and absent in normal tissues from reduction mammoplasty. Accordingly, EMT markers S100A4 and vimentin were elevated in both luminal and myoepithelial cells, and EMT markers α-smooth muscle actin and SNAIL were elevated in luminal epithelial cells of TAHN-1 tissues. These results identify cellular processes that are differentially activated between TAHN-1 and TAHN-5 breast tissues, implicate myofibroblasts as likely mediators of these processes, provide evidence that EMT is occurring in histologically normal tissues within the affected field and identify candidate biomarkers to investigate whether or how field cancerization contributes to the development of primary or recurrent breast tumors. PMID:21105047

  20. 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: [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States)


    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

  1. Effects of warm ischemic time on gene expression profiling in colorectal cancer tissues and normal mucosa.

    Directory of Open Access Journals (Sweden)

    Valeria Musella

    Full Text Available BACKGROUND: Genome-wide gene expression analyses of tumors are a powerful tool to identify gene signatures associated with biologically and clinically relevant characteristics and for several tumor types are under clinical validation by prospective trials. However, handling and processing of clinical specimens may significantly affect the molecular data obtained from their analysis. We studied the effects of tissue handling time on gene expression in human normal and tumor colon tissues undergoing routine surgical procedures. METHODS: RNA extracted from specimens of 15 patients at four time points (for a total of 180 samples after surgery was analyzed for gene expression on high-density oligonucleotide microarrays. A mixed-effects model was used to identify probes with different expression means across the four different time points. The p-values of the model were adjusted with the Bonferroni method. RESULTS: Thirty-two probe sets associated with tissue handling time in the tumor specimens, and thirty-one in the normal tissues, were identified. Most genes exhibited moderate changes in expression over the time points analyzed; however four of them were oncogenes, and two confirmed the effect of tissue handling by independent validation. CONCLUSIONS: Our results suggest that a critical time point for tissue handling in colon seems to be 60 minutes at room temperature. Although the number of time-dependent genes we identified was low, the three genes that already showed changes at this time point in tumor samples were all oncogenes, hence recommending standardization of tissue-handling protocols and effort to reduce the time from specimen removal to snap freezing accounting for warm ischemia in this tumor type.

  2. Automated selection of regions of interest for intensity-based FRET analysis of transferrin endocytic trafficking in normal vs. cancer cells. (United States)

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


    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

  3. The potential for dose dumping in normal tissues with IMRT for pelvic and H&N cancers. (United States)

    Reddy, Nandanuri M S; Mazur, Andrzej K; Sampath, Seshadri; Osian, Adrian; Sood, Brij M; Ravi, Akkamma; Nori, Dattatreyudu


    The purpose of this study is to understand the potential for dose dumping in normal tissues (>85% of prescription dose) and to analyze effectiveness of techniques used in reducing dose dumping during IMRT. Two hundred sixty-five intensity modulated radiation therapy (IMRT) plans for 55 patients with prostate, head-and-neck (H&N), and cervix cancers with 6-MV photon beams and >5 fields were reviewed to analyze why dose dumping occurred, and the techniques used to reduce dose dumping. Various factors including gantry angles, depth of beams (100-SSD), duration of optimization, severity of dose-volume constraints (DVC) on normal structures, and spatial location of planning treatment volumes (PTV) were reviewed in relation to dose dumping. In addition, the effect of partial contouring of rectum in beam's path on dose dumping in rectum was studied. Dose dumping occurred at d(max) in 17 pelvic cases (85% to 129%). This was related to (1) depth of beams (100 SSD [source-to-skin distance]), (2) PTV located between normal structures with DVC, and (3) relative lack of rectum and bladder in beam's path. Dose dumping could be reduced to 85% by changing beam angles and/or DVC for normal structures in 5 cases and by creating "phantom structures" in 12 cases. Decreasing the iterations (duration of optimization) also reduced dose dumping and monitor units (MUs). Part of uncontoured rectum, if present in the field, received a higher dose than the contoured rectum with DVC, indicating that complete delineation of normal structures and DVC is necessary to prevent dose dumping. In H&N, when PTV extends inadvertently into air beyond the body even by a few millimeters, dose dumping occurred in beam's path (220% for 5-field and 170%, 7-field plans). Keeping PTV margins within body contour reduced this type of dose dumping. Beamlet optimization, duration of optimization, spatial location of PTV, and DVC on PTV and normal structures has the potential to cause dose dumping. However, these

  4. Notes on absolute Hodge classes

    CERN Document Server

    Charles, François


    We survey the theory of absolute Hodge classes. The notes include a full proof of Deligne's theorem on absolute Hodge classes on abelian varieties as well as a discussion of other topics, such as the field of definition of Hodge loci and the Kuga-Satake construction.

  5. Cancer (United States)

    ... cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer Symptoms Symptoms of cancer ... tumor Obesity Pancreatic cancer Prostate cancer Stomach cancer Testicular cancer Throat or larynx cancer Thyroid cancer Patient Instructions ...

  6. 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


    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.

  7. Suppression of gastric cancer growth by baculovirus vector-mediated transfer of normal epithelial cell specific-1 gene

    Institute of Scientific and Technical Information of China (English)

    Wei Huang; Xiang-Long Tian; Yun-Lin Wu; Jie Zhong; Li-Fen Yu; Sheng-Ping Hu; Biao Li


    AIM: To study the inhibitory effect of baculovirus-mediated normal epithelial celt specific-1 (NES1) gene therapy on gastric cancer (GC) in vitro and in vivo.METHODS: We first constructed recombinant baculovirus vectors and then transfected them into gastric cancer cells (SGC-7901). Efficiency of the baculovirus for gene transfer into SGC-7901 cells and cell growth curves were detected by fluorescence microscopy, Western blot and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in vitro, respectively. The therapeutic effect of this gene therapy on GC was confirmed in xenografted nude mice. Tumor growth was determined by tumor volume, and expression of NES1 in tumor was analyzed by immunohistochemistry.RESULTS: Baculovirus vectors were successfully transfected into SGC-7901 cells. SGC-7901 cells transfected with the NES1 gene inhibited cell growth. In the Bac-NES1 treated group, tumor growth was significantly reduced with a high level of NES1 expression CONCLUSION: Baculovirus-mediated NES1 gene can be used in gene therapy for GC.

  8. Identification of candidate genes for prostate cancer-risk SNPs utilizing a normal prostate tissue eQTL data set (United States)

    Thibodeau, S. N.; French, A. J.; McDonnell, S. K.; Cheville, J.; Middha, S.; Tillmans, L.; Riska, S.; Baheti, S.; Larson, M. C.; Fogarty, Z.; Zhang, Y.; Larson, N.; Nair, A.; O'Brien, D.; Wang, L.; Schaid, D J.


    Multiple studies have identified loci associated with the risk of developing prostate cancer but the associated genes are not well studied. Here we create a normal prostate tissue-specific eQTL data set and apply this data set to previously identified prostate cancer (PrCa)-risk SNPs in an effort to identify candidate target genes. The eQTL data set is constructed by the genotyping and RNA sequencing of 471 samples. We focus on 146 PrCa-risk SNPs, including all SNPs in linkage disequilibrium with each risk SNP, resulting in 100 unique risk intervals. We analyse cis-acting associations where the transcript is located within 2 Mb (±1 Mb) of the risk SNP interval. Of all SNP–gene combinations tested, 41.7% of SNPs demonstrate a significant eQTL signal after adjustment for sample histology and 14 expression principal component covariates. Of the 100 PrCa-risk intervals, 51 have a significant eQTL signal and these are associated with 88 genes. This study provides a rich resource to study biological mechanisms underlying genetic risk to PrCa. PMID:26611117

  9. Evaluation of Glucose Uptake in Normal and Cancer Cell Lines by Positron Emission Tomography. (United States)

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


    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.

  10. Alterations in vitamin D signaling pathway in gastric cancer progression: a study of vitamin D receptor expression in human normal, premalignant, and malignant gastric tissue. (United States)

    Wen, Yanghui; Da, Mingxu; Zhang, Yongbin; Peng, Lingzhi; Yao, Jibin; Duan, Yaoxing


    Amount of studies in cells and animal models have proved vitamin D has multifarious antitumor effects. However, epidemiological studies showed inconsistent result on gastric cancer. The antitumor role is mainly mediated by the vitamin D receptor (VDR). Our hypothesis is that VDR may be abnormally (poorly) expressed in gastric cancer tissue. Present study is aimed at discovering and analyzing VDR expression in a series of human gastric tissues, including normal, premalignant, and malignant gastric tissue, and correlated VDR to the clinicopathological parameters of gastric cancer patients. VDR expression was detected by immunohistochemistry. The χ(2) test was used to analyze the VDR expression as well as the relationship between VDR and the clinicopathological factors of gastric cancer patients. Compared with normal (82.61%) and premalignant tissues (73.64%), VDR was lower expressed in cancer tissues (57.61%), with a statistically significant difference (P = 0.001). Among cancer tissues, VDR was higher expressed in well and moderate differentiated tissues contrasted with tissues with poor differentiation, and higher expressed in small tumors (gastric tissues. VDR expression has been on the decline from the premalignant stage, finally low expressed in gastric cancer tissues, especial in poorly differentiated tissues. VDR could be a potential prognostic factor for patients with gastric cancer.

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

    Directory of Open Access Journals (Sweden)


    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.

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


    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

  13. Analysis of the expression of SDF-1 splicing variants in human colorectal cancer and normal mucosa tissues. (United States)

    Allami, Risala Hussain; Graf, Claudine; Martchenko, Ksenia; Voss, Beatrice; Becker, Marc; Berger, Martin R; Galle, Peter R; Theobald, Matthias; Wehler, Thomas C; Schimanski, Carl C


    C-X-C motif chemokine ligand 12 (CXCL12), also termed stromal cell-derived factor-1 (SDF-1) is a small protein 8-14 kDa in length that is expressed as six isoforms, consisting of SDF-1α, SDF-1β, SDF-1γ, SDF-1δ, SDF-1ε and SDF-1θ. All six isoforms are encoded by the single CXCL12 gene on chromosome 10. This gene regulates leukocyte trafficking and is variably expressed in a number of normal and cancer tissues. The potential role of the novel CXCL12 splice variants as components of the CXCR4 axis in cancer development is not fully understood. The present study aimed to analyze the expression profile of the various SDF-1 isoforms and SDF-1 polymorphisms, and the association with the clinicopathological features and overall survival of patients with colorectal cancer (CRC). SDF-1 polymorphism analysis was performed using restriction fragment length polymorphism (RFLP) analysis in 73 histologically confirmed human CRC tissue samples at various stages of disease. The expression pattern of the SDF-1 isoforms was analyzed by reverse transcription-polymerase chain reaction in 40 histologically confirmed human CRC tissue samples obtained at various stages of disease, as well as in matched adjacent normal mucosa samples. The presence of the CXCL12 gene polymorphism rs1801157 demonstrated an association with local progression of the primary tumor, as indicated by the T stage. The frequency of the GG genotype was slightly increased in patients with stage 3 and 4 tumors (78.0%) compared with the incidence of the GA/AA genotype (69.5%; P=0.067). The expression of SDF-1β was associated with the presence of metastases (P=0.0656) and the expression of SDF-1γ was significantly associated with tumor size (P=0.0423). The present study is the first to analyze the association between the expression profile of the chemokine CXCL12 splice variants in human CRC tissues and their clinical relevance. The present results reveal that the CXCL12 G801A polymorphism is a low

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

  15. 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


    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.

  16. 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: [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)


    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.

  17. 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


    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

  18. Evaluation of human epidermal growth factor receptor 2 (HER2) single nucleotide polymorphisms (SNPs) in normal and breast tumor tissues and their link with breast cancer prognostic factors. (United States)

    Furrer, Daniela; Lemieux, Julie; Côté, Marc-André; Provencher, Louise; Laflamme, Christian; Barabé, Frédéric; Jacob, Simon; Michaud, Annick; Diorio, Caroline


    Amplification of the human epidermal growth factor receptor 2 (HER2) gene is associated with worse prognosis and decreased overall survival in breast cancer patients. The HER2 gene contains several polymorphisms; two of the best-characterized HER2 polymorphisms are Ile655Val and Ala1170Pro. The aim of this study was to evaluate the association between these two HER2 polymorphisms in normal breast and breast cancer tissues and known breast cancer prognostic factors in a retrospective cohort study of 73 women with non-metastatic HER2-positive breast cancer. HER2 polymorphisms were assessed in breast cancer tissue and normal breast tissue using TaqMan assay. Ala1170Pro polymorphism in normal breast tissue was associated with age at diagnosis (p = 0.007), tumor size (p = 0.004) and lymphovascular invasion (p = 0.06). Similar significant associations in cancer tissues were observed. No association between the Ile655Val polymorphism and prognostic factors were observed. However, we found significant differences in the distribution of Ile655Val (p = 0.03) and Ala1170Pro (p = 0.01) genotypes between normal breast and breast tumor tissues. This study demonstrates that only the Ala1170Pro polymorphism is associated with prognostic factors in HER2-positive breast cancer patients. Moreover, our results suggest that both HER2 polymorphisms could play a significant role in carcinogenesis in non-metastatic HER2-positive breast cancer women.

  19. Discrimination of bladder cancer cells from normal urothelial cells with high specificity and sensitivity: combined application of atomic force microscopy and modulated Raman spectroscopy. (United States)

    Canetta, Elisabetta; Riches, Andrew; Borger, Eva; Herrington, Simon; Dholakia, Kishan; Adya, Ashok K


    Atomic force microscopy (AFM) and modulated Raman spectroscopy (MRS) were used to discriminate between living normal human urothelial cells (SV-HUC-1) and bladder tumour cells (MGH-U1) with high specificity and sensitivity. MGH-U1 cells were 1.5-fold smaller, 1.7-fold thicker and 1.4-fold rougher than normal SV-HUC-1 cells. The adhesion energy was 2.6-fold higher in the MGH-U1 cells compared to normal SV-HUC-1 cells, which possibly indicates that bladder tumour cells are more deformable than normal cells. The elastic modulus of MGH-U1 cells was 12-fold lower than SV-HUC-1 cells, suggesting a higher elasticity of the bladder cancer cell membranes. The biochemical fingerprints of cancer cells displayed a higher DNA and lipid content, probably due to an increase in the nuclear to cytoplasm ratio. Normal cells were characterized by higher protein contents. AFM studies revealed a decrease in the lateral dimensions and an increase in thickness of cancer cells compared to normal cells; these studies authenticate the observations from MRS. Nanostructural, nanomechanical and biochemical profiles of bladder cells provide qualitative and quantitative markers to differentiate between normal and cancerous cells at the single cellular level. AFM and MRS allow discrimination between adhesion energy, elasticity and Raman spectra of SV-HUC-1 and MGH-U1 cells with high specificity (83, 98 and 95%) and sensitivity (97, 93 and 98%). Such single-cell-level studies could have a pivotal impact on the development of AFM-Raman combined methodologies for cancer profiling and screening with translational significance.

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


    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

  1. Sclerotium rolfsii lectin induces stronger inhibition of proliferation in human breast cancer cells than normal human mammary epithelial cells by induction of cell apoptosis. (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


    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.

  2. MicroRNA-17 promotes normal ovarian cancer cells to cancer stem cells development via suppression of the LKB1-p53-p21/WAF1 pathway. (United States)

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


    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.

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

    Gomberawalla, Ameer; Love, Susan


    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.

  4. 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;


    and the proteins extracted. The tissue and serum concentrations of HER1-4 were determined quantitatively using a commercially available enzyme linked immunosorbent assay (ELISA) method. Results: HER1 was down regulated in cancer tissue when compared to autologous reference tissue (p=8x10(-6)), while HER2 (p...-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...

  5. 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;


    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...... 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...... of gastrointestinal cancer within the first year after upper endoscopy. Consequently, unexplained chest/epigastric pain might be an early gastrointestinal cancer symptom....

  6. 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: [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)


    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.

  7. 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.

  8. Quantitative comparison of cancer and normal cell adhesion using organosilane monolayer templates: an experimental study on the anti-adhesion effect of green-tea catechins. (United States)

    Sakamoto, Rumi; Kakinuma, Eisuke; Masuda, Kentaro; Takeuchi, Yuko; Ito, Kosaku; Iketaki, Kentaro; Matsuzaki, Takahisa; Nakabayashi, Seiichiro; Yoshikawa, Hiroshi Y; Yamamoto, Hideaki; Sato, Yuko; Tanii, Takashi


    The main constituent of green tea, (-)-Epigallocatechin-3-O-gallate (EGCG), is known to have cancer-specific chemopreventive effects. In the present work, we investigated how EGCG suppresses cell adhesion by comparing the adhesion of human pancreatic cancer cells (AsPC-1 and BxPC-3) and their counterpart, normal human embryonic pancreas-derived cells (1C3D3), in catechin-containing media using organosilane monolayer templates (OMTs). The purpose of this work is (1) to evaluate the quantitativeness in the measurement of cell adhesion with the OMT and (2) to show how green-tea catechins suppress cell adhesion in a cancer-specific manner. For the first purpose, the adhesion of cancer and normal cells was compared using the OMT. The cell adhesion in different type of catechins such as EGCG, (-)-Epicatechin-3-O-gallate (ECG) and (-)-Epicatechin (EC) was also evaluated. The measurements revealed that the anti-adhesion effect of green-tea catechins is cancer-specific, and the order is EGCG≫ECG>EC. The results agree well with the data reported to date, showing the quantitativeness of the new method. For the second purpose, the contact area of cells on the OMT was measured by reflection interference contrast microscopy. The cell-OMT contact area of cancer cells decreases with increasing EGCG concentration, whereas that of normal cells remains constant. The results reveal a twofold action of EGCG on cancer cell adhesion-suppressing cell attachment to a candidate adhesion site and decreasing the contact area of the cells-and validates the use of OMT as a tool for screening cancer cell adhesion.

  9. Expression of adiponectin receptors, AdipoR1 and AdipoR2, in normal colon epithelium and colon cancer tissue. (United States)

    Yoneda, Kyoko; Tomimoto, Ayako; Endo, Hiroki; Iida, Hiroshi; Sugiyama, Michiko; Takahashi, Hirokazu; Mawatari, Hironori; Nozaki, Yuichi; Fujita, Koji; Yoneda, Masato; Inamori, Masahiko; Nakajima, Noriko; Wada, Koichiro; Nagashima, Yoji; Nakagama, Hitoshi; Uozaki, Hitoshi; Fukayama, Masashi; Nakajima, Atsushi


    Adiponectin is secreted by adipocytes and is a key hormone responsible for insulin sensitization. Recent studies have shown that plasma adiponectin is decreased in patients with breast, endometrial and gastric cancer. However, the effect of adiponectin on colorectal carcinogenesis is controversial. It is now well known that the adiponectin receptor exists in two isoforms, adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2). We examined the expression of the adiponectin receptors on normal colon mucosa and colon cancer tissues in a human study using real-time RT-PCR, Western blotting and immunohistochemical staining. Adiponectin receptors, AdipoR1/AdipoR2, were expressed in normal colon epithelial and colon cancer cells. Furthermore, laser microdissection was performed to confirm our results. These results suggest that adiponectin may exert some effects on normal colon epithelium or colon cancer cells directly through adiponectin receptors. Further studies are required to elucidate the function of the AdipoRs activated by adiponectin and the downstream mechanisms of AdipoRs in colon cancer cells.

  10. 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


    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.

  11. Assessment of normal tissue complications following prostate cancer irradiation: Comparison of radiation treatment modalities using NTCP models

    Energy Technology Data Exchange (ETDEWEB)

    Takam, Rungdham; Bezak, Eva; Yeoh, Eric E.; Marcu, Loredana [School of Chemistry and Physics, University of Adelaide, Adelaide SA 5000 (Australia) and Department of Medical Physics, Royal Adelaide Hospital, Adelaide SA 5000 (Australia); School of Medicine, University of Adelaide, Adelaide SA 5000 (Australia) and Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide SA 5000 (Australia); School of Chemistry and Physics, University of Adelaide, Adelaide SA 5000 (Australia) and Faculty of Science, University of Oradea, Oradea 410086 (Romania)


    Purpose: Normal tissue complication probability (NTCP) of the rectum, bladder, urethra, and femoral heads following several techniques for radiation treatment of prostate cancer were evaluated applying the relative seriality and Lyman models. Methods: Model parameters from literature were used in this evaluation. The treatment techniques included external (standard fractionated, hypofractionated, and dose-escalated) three-dimensional conformal radiotherapy (3D-CRT), low-dose-rate (LDR) brachytherapy (I-125 seeds), and high-dose-rate (HDR) brachytherapy (Ir-192 source). Dose-volume histograms (DVHs) of the rectum, bladder, and urethra retrieved from corresponding treatment planning systems were converted to biological effective dose-based and equivalent dose-based DVHs, respectively, in order to account for differences in radiation treatment modality and fractionation schedule. Results: Results indicated that with hypofractionated 3D-CRT (20 fractions of 2.75 Gy/fraction delivered five times/week to total dose of 55 Gy), NTCP of the rectum, bladder, and urethra were less than those for standard fractionated 3D-CRT using a four-field technique (32 fractions of 2 Gy/fraction delivered five times/week to total dose of 64 Gy) and dose-escalated 3D-CRT. Rectal and bladder NTCPs (5.2% and 6.6%, respectively) following the dose-escalated four-field 3D-CRT (2 Gy/fraction to total dose of 74 Gy) were the highest among analyzed treatment techniques. The average NTCP for the rectum and urethra were 0.6% and 24.7% for LDR-BT and 0.5% and 11.2% for HDR-BT. Conclusions: Although brachytherapy techniques resulted in delivering larger equivalent doses to normal tissues, the corresponding NTCPs were lower than those of external beam techniques other than the urethra because of much smaller volumes irradiated to higher doses. Among analyzed normal tissues, the femoral heads were found to have the lowest probability of complications as most of their volume was irradiated to lower

  12. Hypoxia primes human normal prostate epithelial cells and cancer cell lines for the NLRP3 and AIM2 inflammasome activation. (United States)

    Panchanathan, Ravichandran; Liu, Hongzhu; Choubey, Divaker


    The molecular mechanisms by which hypoxia contributes to prostatic chronic inflammation (PCI) remain largely unknown. Because hypoxia stimulates the transcriptional activity of NF-κB, which "primes" cells for inflammasome activation by inducing the expression of NLRP3 or AIM2 receptor and pro-IL-1β, we investigated whether hypoxia could activate the NLRP3 and AIM2 inflammasome in human normal prostate epithelial cells (PrECs) and cancer cell lines. Here we report that hypoxia (1% O2) treatment of PrECs, prostate cell lines, and a macrophage cell line (THP-1) increased the levels of NLRP3, AIM2, and pro-IL-1β. Further, hypoxia in cells potentiated activation of the NLRP3 and AIM2 inflammasome activity. Notably, hypoxia "primed" cells for NLRP3 and AIM2 inflammasome activation through stimulation of the NF-κB activity. Our observations support the idea that hypoxia in human prostatic tumors contributes to PCI, in part, by priming cells for the activation of NLRP3 and AIM2 inflammasome.

  13. Plantaricin A, a peptide pheromone produced by Lactobacillus plantarum, permeabilizes the cell membrane of both normal and cancerous lymphocytes and neuronal cells. (United States)

    Sand, Sverre L; Oppegård, Camilla; Ohara, Shinya; Iijima, Toshio; Naderi, Soheil; Blomhoff, Heidi K; Nissen-Meyer, Jon; Sand, Olav


    Antimicrobial peptides produced by multicellular organisms protect against pathogenic microorganisms, whereas such peptides produced by bacteria provide an ecological advantage over competitors. Certain antimicrobial peptides of metazoan origin are also toxic to eukaryotic cells, with preference for a variety of cancerous cells. Plantaricin A (PlnA) is a peptide pheromone with membrane permeabilizing strain-specific antibacterial activity, produced by Lactobacillus plantarum C11. Recently, we have reported that PlnA also permeabilizes cancerous rat pituitary cells (GH(4) cells), whereas normal rat anterior pituitary cells are resistant. To investigate if preferential effect on cancerous cells is a general feature of PlnA, we have studied effects of the peptide on normal and cancerous lymphocytes and neuronal cells. Normal human B and T cells, Reh cells (from human B cell leukemia), and Jurkat cells (from human T cell leukemia) were studied by flow cytometry to detect morphological changes (scatter) and viability (propidium iodide uptake), and by patch clamp recordings to monitor membrane conductance. Ca(2+) imaging based on a combination of fluo-4 and fura-red was used to monitor PlnA-induced membrane permeabilization in normal rat cortical neurons and glial cells, PC12 cells (from a rat adrenal chromaffin tumor), and murine N2A cells (from a spinal cord tumor). All the tested cell types were affected by 10-100 microM PlnA, whereas concentrations below 10 microM had no significant effect. We conclude that normal and cancerous lymphocytes and neuronal cells show similar sensitivity to PlnA.

  14. Meta-analysis of type-specific human papillomavirus prevalence in Iranian women with normal cytology, precancerous cervical lesions and invasive cervical cancer: Implications for screening and vaccination. (United States)

    Jalilvand, Somayeh; Shoja, Zabihollah; Nourijelyani, Keramat; Tohidi, Hamid Reza; Hamkar, Rasool


    To predict the impact of current vaccines on cervical cancer and for the improvement of screening programs, regional data on distribution of human papillomavirus (HPV) types in women with or without cervical cancer is crucial. The present meta-analysis intend to comprehensively evaluate the HPV burden in women with invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal cytology, as these data will help decision making in regards with screening programs and HPV vaccination in Iran. To determine the HPV prevalence and type distribution in Iranian women with or without cervical cancer, 20 published studies were included in this meta-analysis. In total, 713, 124, 104, 60, and 2577 women invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal were reviewed, respectively. Overall HPV prevalence in women with invasive cervical cancer, high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 2 and 3), low-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia 1), atypical squamous cells of undetermined significance and normal cytology were 77.4%, 71.8%, 65.3%, 61.7%, and 8.4%, respectively. The six most common types were HPV 16, 18, 6/11, 31, and 33; among them HPV 16 was the most frequent type in all five different groups. According to this study, it was estimated that HPV vaccines could have a great impact on prevention of cervical cancer in Iran. In conclusion, this meta-analysis highlights the necessity of introducing vaccination program in Iran.

  15. Database applicaton for absolute spectrophotometry (United States)

    Bochkov, Valery V.; Shumko, Sergiy


    32-bit database application with multidocument interface for Windows has been developed to calculate absolute energy distributions of observed spectra. The original database contains wavelength calibrated observed spectra which had been already passed through apparatus reductions such as flatfielding, background and apparatus noise subtracting. Absolute energy distributions of observed spectra are defined in unique scale by means of registering them simultaneously with artificial intensity standard. Observations of sequence of spectrophotometric standards are used to define absolute energy of the artificial standard. Observations of spectrophotometric standards are used to define optical extinction in selected moments. FFT algorithm implemented in the application allows performing convolution (deconvolution) spectra with user-defined PSF. The object-oriented interface has been created using facilities of C++ libraries. Client/server model with Windows Socket functionality based on TCP/IP protocol is used to develop the application. It supports Dynamic Data Exchange conversation in server mode and uses Microsoft Exchange communication facilities.

  16. 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.


    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

  17. 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


    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

  18. Long range epigenetic silencing is a trans-species mechanism that results in cancer specific deregulation by overriding the chromatin domains of normal cells. (United States)

    Forn, Marta; Muñoz, Mar; Tauriello, Daniele V F; Merlos-Suárez, Anna; Rodilla, Verónica; Bigas, Anna; Batlle, Eduard; Jordà, Mireia; Peinado, Miguel A


    DNA methylation and chromatin remodeling are frequently implicated in the silencing of genes involved in carcinogenesis. Long Range Epigenetic Silencing (LRES) is a mechanism of gene inactivation that affects multiple contiguous CpG islands and has been described in different human cancer types. However, it is unknown whether there is a coordinated regulation of the genes embedded in these regions in normal cells and in early stages of tumor progression. To better characterize the molecular events associated with the regulation and remodeling of these regions we analyzed two regions undergoing LRES in human colon cancer in the mouse model. We demonstrate that LRES also occurs in murine cancer in vivo and mimics the molecular features of the human phenomenon, namely, downregulation of gene expression, acquisition of inactive histone marks, and DNA hypermethylation of specific CpG islands. The genes embedded in these regions showed a dynamic and autonomous regulation during mouse intestinal cell differentiation, indicating that, in the framework considered here, the coordinated regulation in LRES is restricted to cancer. Unexpectedly, benign adenomas in Apc(Min/+) mice showed overexpression of most of the genes affected by LRES in cancer, which suggests that the repressive remodeling of the region is a late event. Chromatin immunoprecipitation analysis of the transcriptional insulator CTCF in mouse colon cancer cells revealed disrupted chromatin domain boundaries as compared with normal cells. Malignant regression of cancer cells by in vitro differentiation resulted in partial reversion of LRES and gain of CTCF binding. We conclude that genes in LRES regions are plastically regulated in cell differentiation and hyperproliferation, but are constrained to a coordinated repression by abolishing boundaries and the autonomous regulation of chromatin domains in cancer cells.

  19. PLZF Expression during Colorectal Cancer Development and in Normal Colorectal Mucosa according to Body Size, as Marker of Colorectal Cancer Risk

    Directory of Open Access Journals (Sweden)

    Francesco Mariani


    Full Text Available Promyelocytic leukemia zinc finger protein (PLZF is a protein involved in various signaling, growth regulatory, and differentiation pathways, including development/function of some T cells. Here, we aimed at the detection of PLZF during colorectal carcinogenesis, using immunofluorescence, and at the evaluation of the colocalization of PLZF with CD2 and CD56 positive cells (T, γδ, NK, and NKT cells, using confocal-microscopy, along colorectal carcinogenesis, since its earliest stages, that is, dysplastic aberrant crypt foci (ACF. Furthermore, we analyzed PLZF in the normal colonic mucosa (NM according to anthropometric parameters of the subject. NM exhibited strong CD56 fluorescent staining. This infiltration was lost in both ACF and colorectal carcinoma (CRC, while PLZF presence increased from NM to ACF and CRC. Strong association was found between CD56+ colonic mucosa cell infiltration and body mass index. Interestingly, an increased stromal PLZF-reactivity was present in NM of obese subjects. This study shows that overexpression of PLZF and exclusion of NK cells in dysplastic microenvironment are very early events in the stepwise sequence leading to CRC and that lower levels of CD56+ cells in NM, together with increased levels of PLZF+ cells, can be a reflection of colon cancer risk due to obesity.

  20. Toponome imaging system: in situ protein network mapping in normal and cancerous colon from the same patient reveals more than five-thousand cancer specific protein clusters and their subcellular annotation by using a three symbol code. (United States)

    Bhattacharya, Sayantan; Mathew, George; Ruban, Ernie; Epstein, David B A; Krusche, Andreas; Hillert, Reyk; Schubert, Walter; Khan, Michael


    In a proof of principle study, we have applied an automated fluorescence toponome imaging system (TIS) to examine whether TIS can find protein network structures, distinguishing cancerous from normal colon tissue present in a surgical sample from the same patient. By using a three symbol code and a power of combinatorial molecular discrimination (PCMD) of 2(21) per subcellular data point in one single tissue section, we demonstrate an in situ protein network structure, visualized as a mosaic of 6813 protein clusters (combinatorial molecular phenotype or CMPs), in the cancerous part of the colon. By contrast, in the histologically normal colon, TIS identifies nearly 5 times the number of protein clusters as compared to the cancerous part (32 009). By subcellular visualization procedures, we found that many cell surface membrane molecules were closely associated with the cell cytoskeleton as unique CMPs in the normal part of the colon, while the same molecules were disassembled in the cancerous part, suggesting the presence of dysfunctional cytoskeleton-membrane complexes. As expected, glandular and stromal cell signatures were found, but interestingly also found were potentially TIS signatures identifying a very restricted subset of cells expressing several putative stem cell markers, all restricted to the cancerous tissue. The detection of these signatures is based on the extreme searching depth, high degree of dimensionality, and subcellular resolution capacity of TIS. These findings provide the technological rationale for the feasibility of a complete colon cancer toponome to be established by massive parallel high throughput/high content TIS mapping.

  1. 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


    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

  2. Relativistic Absolutism in Moral Education. (United States)

    Vogt, W. Paul


    Discusses Emile Durkheim's "Moral Education: A Study in the Theory and Application of the Sociology of Education," which holds that morally healthy societies may vary in culture and organization but must possess absolute rules of moral behavior. Compares this moral theory with current theory and practice of American educators. (MJL)

  3. Absolute luminosity measurements at LHCb

    CERN Document Server

    Hopchev, Plamen


    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 ...

  4. Absolute Standards for Climate Measurements (United States)

    Leckey, J.


    In a world of changing climate, political uncertainty, and ever-changing budgets, the benefit of measurements traceable to SI standards increases by the day. To truly resolve climate change trends on a decadal time scale, on-orbit measurements need to be referenced to something that is both absolute and unchanging. One such mission is the Climate Absolute Radiance and Refractivity Observatory (CLARREO) that will measure a variety of climate variables with an unprecedented accuracy to definitively quantify climate change. In the CLARREO mission, we will utilize phase change cells in which a material is melted to calibrate the temperature of a blackbody that can then be observed by a spectrometer. A material's melting point is an unchanging physical constant that, through a series of transfers, can ultimately calibrate a spectrometer on an absolute scale. CLARREO consists of two primary instruments: an infrared (IR) spectrometer and a reflected solar (RS) spectrometer. The mission will contain orbiting radiometers with sufficient accuracy to calibrate other space-based instrumentation and thus transferring the absolute traceability. The status of various mission options will be presented.

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

    LENUS (Irish Health Repository)

    Sheridan, Juliette


    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.

  6. Tissue-specific gene expression templates for accurate molecular characterization of the normal physiological states of multiple human tissues with implication in development and cancer studies

    Directory of Open Access Journals (Sweden)

    Yuan Shinsheng


    Full Text Available Abstract Background To elucidate the molecular complications in many complex diseases, we argue for the priority to construct a model representing the normal physiological state of a cell/tissue. Results By analyzing three independent microarray datasets on normal human tissues, we established a quantitative molecular model GET, which consists of 24 tissue-specific Gene Expression Templates constructed from a set of 56 genes, for predicting 24 distinct tissue types under disease-free condition. 99.2% correctness was reached when a large-scale validation was performed on 61 new datasets to test the tissue-prediction power of GET. Network analysis based on molecular interactions suggests a potential role of these 56 genes in tissue differentiation and carcinogenesis. Applying GET to transcriptomic datasets produced from tissue development studies the results correlated well with developmental stages. Cancerous tissues and cell lines yielded significantly lower correlation with GET than the normal tissues. GET distinguished melanoma from normal skin tissue or benign skin tumor with 96% sensitivity and 89% specificity. Conclusions These results strongly suggest that a normal tissue or cell may uphold its normal functioning and morphology by maintaining specific chemical stoichiometry among genes. The state of stoichiometry can be depicted by a compact set of representative genes such as the 56 genes obtained here. A significant deviation from normal stoichiometry may result in malfunction or abnormal growth of the cells.

  7. Absolute measurements of chlorine Cl+ cation single photoionization cross section

    NARCIS (Netherlands)

    Hernandez, E. M.; Juarez, A. M.; Kilcoyne, A. L. D.; Aguilar, A.; Hernandez, L.; Antillon, A.; Macaluso, D.; Morales-Mori, A.; Gonzalez-Magana, O.; Hanstorp, D.; Covington, A. M.; Davis, V.; Calabrese, D.; Hinojosa, G.


    The photoionization of Cl+ leading to Cl2+ was measured in the photon energy range of 19.5-28.0 eV. A spectrum with a photon energy resolution of 15 meV normalized to absolute cross-section measurements is presented. The measurements were carried out by merging a Cl+ ion beam with a photon beam of h

  8. 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.

  9. Optomechanics for absolute rotation detection (United States)

    Davuluri, Sankar


    In this article, we present an application of optomechanical cavity for the absolute rotation detection. The optomechanical cavity is arranged in a Michelson interferometer in such a way that the classical centrifugal force due to rotation changes the length of the optomechanical cavity. The change in the cavity length induces a shift in the frequency of the cavity mode. The phase shift corresponding to the frequency shift in the cavity mode is measured at the interferometer output to estimate the angular velocity of absolute rotation. We derived an analytic expression to estimate the minimum detectable rotation rate in our scheme for a given optomechanical cavity. Temperature dependence of the rotation detection sensitivity is studied.

  10. Physics of negative absolute temperatures (United States)

    Abraham, Eitan; Penrose, Oliver


    Negative absolute temperatures were introduced into experimental physics by Purcell and Pound, who successfully applied this concept to nuclear spins; nevertheless, the concept has proved controversial: a recent article aroused considerable interest by its claim, based on a classical entropy formula (the "volume entropy") due to Gibbs, that negative temperatures violated basic principles of statistical thermodynamics. Here we give a thermodynamic analysis that confirms the negative-temperature interpretation of the Purcell-Pound experiments. We also examine the principal arguments that have been advanced against the negative temperature concept; we find that these arguments are not logically compelling, and moreover that the underlying "volume" entropy formula leads to predictions inconsistent with existing experimental results on nuclear spins. We conclude that, despite the counterarguments, negative absolute temperatures make good theoretical sense and did occur in the experiments designed to produce them.

  11. Immunological and Functional Characterization of RhoGDI3 and Its Molecular Targets RhoG and RhoB in Human Pancreatic Cancerous and Normal Cells (United States)

    de León-Bautista, Mercedes Piedad; Cardenas-Aguayo, Maria del Carmen; Casique-Aguirre, Diana; Almaraz-Salinas, Manuel; Parraguirre-Martinez, Sara; Olivo-Diaz, Angelica; Thompson-Bonilla, María del Rocío


    RhoGDI proteins have been implicated in several human cancers; changes in their expression levels have shown pro- or anti-tumorigenic effects. Pancreatic Ductal Adenocarcinoma (PDAC) is a complex pathology, with poor prognosis, and most patients die shortly after diagnosis. Efforts have been focused on understanding the role of RhoGDI's in PDAC, specially, RhoGDI1 and RhoGDI2. However, the role of RhoGDI3 has not been studied in relation to cancer or to PDAC. Here, we characterized the expression and functionality of RhoGDI3 and its target GTPases, RhoG and RhoB in pancreatic cell lines from both normal pancreatic tissue and tissue in late stages of PDAC, and compared them to human biopsies. Through immunofluorescences, pulldown assays and subcellular fractionation, we found a reduction in RhoGDI3 expression in the late stages of PDAC, and this reduction correlates with tumor progression and aggressiveness. Despite the reduction in the expression of RhoGDI3 in PDAC, we found that RhoB was underexpressed while RhoG was overexpressed, suggesting that cancerous cells preserve their capacity to activate this pathway, thus these cells may be more eager to response to the stimuli needed to proliferate and become invasive unlike normal cells. Surprisingly, we found nuclear localization of RhoGDI3 in non-cancerous pancreatic cell line and normal pancreatic tissue biopsies, which could open the possibility of novel nuclear functions for this protein, impacting gene expression regulation and cellular homeostasis. PMID:27832197

  12. MnTnBuOE-2-PyP protects normal colorectal fibroblasts from radiation damage and simultaneously enhances radio/chemotherapeutic killing of colorectal cancer cells (United States)

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


    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

  13. Stathmin/oncoprotein 18, a microtubule regulatory protein, is required for survival of both normal and cancer cell lines lacking the tumor suppressor, p53. (United States)

    Carney, Bruce K; Cassimeris, Lynne


    Stathmin, a microtubule regulatory protein, is overexpressed in many cancers and required for survival of several cancer lines. In a study of breast cancer cell lines(1) proposed that stathmin is required for survival of cells lacking p53, but this hypothesis was not tested directly. Here we tested their hypothesis by examining cell survival in cells depleted of stathmin, p53 or both proteins. Comparing HCT116 colon cancer cell lines differing in TP53 genotype, stathmin depletion resulted in significant death only in cells lacking p53. As a second experimental system, we compared the effects of stathmin depletion from HeLa cells, which normally lack detectable levels of p53 due to expression of the HPV E6 protein. Stathmin depletion caused a large percentage of HeLa cells to die. Restoring p53, by depletion of HPV E6, rescued HeLa cells from stathmin-depletion induced death. Cleaved PARP was detected in HCT116(p53-/-) cells depleted of stathmin and cell death in stathmin-depleted HeLa cells was blocked by the caspase inhibitor Z-VAD-FMK, consistent with apoptotic death. The stathmin-dependent survival of cells lacking p53 was not confined to cancerous cells because both proteins were required for survival of normal human fibroblasts. In HCT116 and HeLa cells, depletion of both stathmin and p53 leads to a cell cycle delay through G(2). Our results demonstrate that stathmin is required for cell survival in cells lacking p53, suggesting that stathmin depletion could be used therapeutically to induce apoptosis in tumors without functional p53.

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

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    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.

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

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    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: [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 2, CH-8093 Zurich (Switzerland)


    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

  16. Android Apps for Absolute Beginners

    CERN Document Server

    Jackson, Wallace


    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

  17. 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. (United States)

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


    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

  18. Absolute neutrophil values in malignant patients on cytotoxic chemotherapy. (United States)

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


    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.

  19. 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.

  20. Correlating two-photon excited fluorescence imaging of breast cancer cellular redox state with seahorse flux analysis of normalized cellular oxygen consumption (United States)

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


    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.

  1. 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


    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.

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

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


    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%.

  3. TRPM8 ion channels differentially modulate proliferation and cell cycle distribution of normal and cancer prostate cells. (United States)

    Valero, María Ll; Mello de Queiroz, Fernanda; Stühmer, Walter; Viana, Félix; Pardo, Luis A


    Overexpression of the cation-permeable channel TRPM8 in prostate cancers might represent a novel opportunity for their treatment. Inhibitors of TRPM8 reduce the growth of prostate cancer cells. We have used two recently described and highly specific blockers, AMTB and JNJ41876666, and RNAi to determine the relevance of TRPM8 expression in the proliferation of non-tumor and tumor cells. Inhibition of the expression or function of the channel reduces proliferation rates and proliferative fraction in all tumor cells tested, but not of non-tumor prostate cells. We observed no consistent acceleration of growth after stimulation of the channel with menthol or icilin, indicating that basal TRPM8 expression is enough to sustain growth of prostate cancer cells.

  4. TRPM8 ion channels differentially modulate proliferation and cell cycle distribution of normal and cancer prostate cells.

    Directory of Open Access Journals (Sweden)

    María Ll Valero

    Full Text Available Overexpression of the cation-permeable channel TRPM8 in prostate cancers might represent a novel opportunity for their treatment. Inhibitors of TRPM8 reduce the growth of prostate cancer cells. We have used two recently described and highly specific blockers, AMTB and JNJ41876666, and RNAi to determine the relevance of TRPM8 expression in the proliferation of non-tumor and tumor cells. Inhibition of the expression or function of the channel reduces proliferation rates and proliferative fraction in all tumor cells tested, but not of non-tumor prostate cells. We observed no consistent acceleration of growth after stimulation of the channel with menthol or icilin, indicating that basal TRPM8 expression is enough to sustain growth of prostate cancer cells.

  5. The effect of nanoparticle size and NLS density on nuclear targeting in cancer and normal cells; impaired nuclear import and aberrant nanoparticle intracellular trafficking in glioma. (United States)

    Tammam, Salma N; Azzazy, Hassan M E; Lamprecht, Alf


    The cell nucleus is an interesting target in many diseases with particular interest in cancer. Previously, nuclear targeted small and large chitosan nanoparticles (S-NPs≈25nm, and L-NPs≈150nm respectively), modified with low, intermediate and high densities of NLS (L-NLS, I-NLS and H-NLS) were developed and assessed in L929 fibroblasts. However, to evade apoptosis and stimulate tumor growth cancer cells are capable of manipulating the nuclear-cytoplasmic transport on many levels, making NPs that are capable of nuclear targeting in normal cells incapable of doing so in cancer. For such reason, here, the nuclear delivery efficiency of S-NPs and L-NPs was assessed as a function of their NLS density in cancer and non-cancer cells. For S-NPs, in all cells tested, NLS was unnecessary for nuclear delivery; unmodified S-NPs showed higher nuclear delivery than NLS-S-NPs due to their ability to gain nuclear entry in a passive manner. For L-NPs, L-NLS-L-NPs showed ≈ 8.5, 33, 1.8 and 7.2 fold higher nuclear deliveries than H-NLS-L-NPs in L929 fibroblasts, primary human fibroblasts, HEK 293 and lung cancer cells, respectively. In glioma however, unmodified L-NPs showed highest nuclear delivery, whereas NLS-L-NPs were retained in the cytoplasm. Experiments conducted in the presence of inhibitors of the classical nuclear import pathway indicated that due to overexpression of importin α, classical nuclear import in glioma is impaired leading to aberrant NP intracellular trafficking and nuclear import.

  6. Absolute configuration of novel bioactive flavonoids from Tephrosia purpurea. (United States)

    Chang, L C; Chávez, D; Song, L L; Farnsworth, N R; Pezzuto, J M; Kinghorn, A D


    [structure: see text] Three novel flavonoids, (+)-tephrorins A (1) and B (2) and (+)-tephrosone (3), were isolated from Tephrosia purpurea. Their structures were elucidated by NMR spectral analysis, and their absolute configurations were determined by Mosher ester methodology. Compounds 1 and 2 are flavanones containing an unusual tetrahydrofuran moiety. Compounds 1-3 were evaluated for their potential cancer chemopreventive properties using a cell-based quinone reductase induction assay.

  7. Study on discrimination of oral cancer from normal using blood plasma based on fluorescence steady and excited state at excitation wavelength 280 nm (United States)

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


    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.

  8. DeltaNp63alpha repression of the Notch1 gene supports the proliferative capacity of normal human keratinocytes and cervical cancer cells. (United States)

    Yugawa, Takashi; Narisawa-Saito, Mako; Yoshimatsu, Yuki; Haga, Kei; Ohno, Shin-ichi; Egawa, Nagayasu; Fujita, Masatoshi; Kiyono, Tohru


    The p53 family member p63 is a master regulator of epithelial development. One of its isoforms, DeltaNp63alpha, is predominantly expressed in the basal cells of stratified epithelia and plays a fundamental role in control of regenerative potential and epithelial integrity. In contrast to p53, p63 is rarely mutated in human cancers, but it is frequently overexpressed in squamous cell carcinomas (SCC). However, its functional relevance to tumorigenesis remains largely unclear. We previously identified the Notch1 gene as a novel transcriptional target of p53. Here, we show that DeltaNp63alpha functions as a transcriptional repressor of the Notch1 gene through the p53-responsive element. Knockdown of p63 caused upregulation of Notch1 expression and marked reduction in proliferation and clonogenicity of both normal human keratinocytes and cervical cancer cell lines overexpressing DeltaNp63alpha. Concomitant silencing of Notch1 significantly rescued this phenotype, indicating the growth defect induced by p63 deficiency to be, at least in part, attributable to Notch1 function. Conversely, overexpression of DeltaNp63alpha decreased basal levels of Notch1, increased proliferative potential of normal human keratinocytes, and inhibited both p53-dependent and p53-independent induction of Notch1 and differentiation markers upon genotoxic stress and serum exposure, respectively. These results suggest that DeltaNp63alpha maintains the self-renewing capacity of normal human keratinocytes and cervical cancer cells partly through transcriptional repression of the Notch1 gene and imply a novel pathogenetical significance of frequently observed overexpression of DeltaNp63alpha together with p53 inactivation in SCCs.

  9. The Use of Normal Colon Cell Culture to Assess Toxicities and Cancer Molecular Pathway Alterations Induced by Disinfection Byproducts. (United States)

    Recent Epidemiological studies have linked the consumption of disinfected surface waters to an increased risk of colorectal cancer (Bove, GE, Jr et al., Int. J. Health Geogr., 6:18, 2007). Approximately 600 disinfection byproducts (DBP) have been identified. Because it would be...

  10. Increased zinc finger protein zFOC1 transcripts in gastric cancer compared with normal gastric tissue


    Stephen, R L; Crabtree, J E; Yoshimura, T; Clayton, C L; Dixon, M F; Robinson, P A


    Background: Screening of cDNA arrays of the IMAGE library identified human zFOC1 as a differentially expressed cDNA that was upregulated in KATO III gastric cancer cells following stimulation with the gastric pathogen Helicobacter pylori.

  11. Cytotoxic, genotoxic and apoptotic effects of naringenin-oxime relative to naringenin on normal and cancer cell lines

    Directory of Open Access Journals (Sweden)

    Abdurrahim Kocyigit


    Conclusions: This study showed that both NG-Ox and NG possess cytotoxic, genotoxic and apoptotic activities through the production of ROS on cells, NG-Ox being the more effective one. Therefore, derived compound of NG might be used as antiproliferative agents for the treatment of cancer.

  12. Combined cytotoxic effect of UV-irradiation and TiO2 microbeads in normal urothelial cells, low-grade and high-grade urothelial cancer cells. (United States)

    Imani, Roghayeh; Veranič, Peter; Iglič, Aleš; Kreft, Mateja Erdani; Pazoki, Meysam; Hudoklin, Samo


    The differentiation of urothelial cells results in normal terminally differentiated cells or by alternative pathways in low-grade or high-grade urothelial carcinomas. Treatments with traditional surgical and chemotherapeutical approaches are still inadequate and expensive, as bladder tumours are generally highly recurrent. In such situations, alternative approaches, using irradiation of the cells and nanoparticles, are promising. The ways in which urothelial cells, at different differentiation levels, respond to UV-irradiation (photolytic treatment) or to the combination of UV-irradiation and nanoparticles (photocatalytic treatment), are unknown. Here we tested cytotoxicity of UV-irradiation on (i) normal porcine urothelial cells (NPU), (ii) human low-grade urothelial cancer cells (RT4), and (iii) human high-grade urothelial cancer cells (T24). The results have shown that 1 minute of UV-irradiation is enough to kill 90% of the cells in NPU and RT4 cultures, as determined by the live/dead viability assay. On the other hand, the majority of T24 cells survived 1 minute of UV-irradiation. Moreover, even a prolonged UV-irradiation for 30 minutes killed TiO2 microbeads and then UV-irradiated, the viability of these high-grade urothelial cancer cells was reduced to TiO2 photocatalysis. Using electron microscopy, we confirmed that the mesoporous TiO2 microbeads were internalized into T24 cells, and that the cell's ultrastructure was heavily compromised after UV-irradiation. In conclusion, our results show major differences in the sensitivity to UV-irradiation among the urothelial cells with respect to cell differentiation. To achieve an increased cytotoxicity of urothelial cancer cells, the photocatalytic approach is recommended.

  13. Normalization of hypothalamic serotonin (5-HT 1B) receptor and NPY in cancer anorexia after tumor resection: an immunocytochemical study. (United States)

    Makarenko, Irina G; Meguid, Michael M; Gatto, Louis; Chen, Chung; Ramos, Eduardo J B; Goncalves, Carolina G; Ugrumov, Michael V


    Tumor growth leads to anorexia and decreased food intake, the regulation of which is via the integrated hypothalamic peptidergic and monoaminergic system. Serotonin (5-HT), an anorectic monoamine acts primarily via 5-HT 1B-receptors in hypothalamic nuclei while neuropeptide Y (NPY) acts an orexigenic peptide. We previously reported that 5-HT 1B-receptors are up regulated while NPY is down regulated in tumor-bearing (TB)-related anorexia, contributing to food intake reduction. In anorectic TB rats we hypothesize that after tumor resection when food intake has reverted to normal, normalization of 5-HT 1B-receptor and NPY will occur. The aim of this study was to demonstrate normalization of these hypothalamic changes compared to Controls. In anorectic tumor-bearing rats after tumor resection (TB-R) and in sham-operated (Control) rats, distribution of 5-HT 1B-receptors and NPY in hypothalamic nuclei was analyzed using peroxidase antiperoxidase immunocytochemical methods. Image analysis of immunostaining was performed and the data were statistically analyzed. Immunostaining specificity was controlled by omission of primary or secondary antibodies and pre-absorption test. Our results show that after TB-R versus Controls a normalization of food intake, 5-H-1B-receptor and NPY expression in the hypothalamus occurs. These data, discussed in context with our previous studies, support the hypothesis that tumor resection results not only in normalization of food intake but also in reversible changes of anorectic and orexigenic hypothalamic modulators.

  14. Cosmology with Negative Absolute Temperatures

    CERN Document Server

    Vieira, J P P; Lewis, Antony


    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.

  15. Cosmology with negative absolute temperatures (United States)

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


    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.

  16. 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


    [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

  17. Effect of ginger root on cyclooxygenase-1 and 15-hydroxyprostaglandin dehydrogenase expression in colonic mucosa of humans at normal and increased risk for colorectal cancer. (United States)

    Jiang, Yan; Turgeon, Danielle K; Wright, Benjamin D; Sidahmed, Elkhansa; Ruffin, Mack T; Brenner, Dean E; Sen, Ananda; Zick, Suzanna M


    Elevated tissue levels of prostaglandin E2, produced by cyclooxygenase (COX), are an early event in colorectal cancer (CRC). Data suggest the efficacy of nonsteroidal anti-inflammatory drugs, such as cancer preventives, in the inhibition of COX activity; however, side effects of nonsteroidal anti-inflammatory pose unacceptable limitations. Ginger has been reported to have anti-inflammatory activities with significant CRC preventive potential. We investigated whether consumption of 2.0 g ginger daily regulated the level of two key enzymes that control prostaglandin E2 production, COX-1 and NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Thirty participants at normal and 20 participants at increased risk for CRC were randomized and given 2.0 g/day ginger or placebo for 28 days. Flexible sigmoidoscopy was used to obtain colon biopsies at baseline and the end of the study. Tissue levels of COX-1 and 15-PGDH were assessed using western blotting. After ginger consumption, participants at increased risk for CRC had a significantly reduced colonic COX-1 protein level (23.8±41%) compared with the placebo group (18.9±52%; P=0.03). Protein levels of 15-PGDH in the colon were unchanged. In participants who were at normal risk for CRC, neither protein levels of COX-1 nor 15-PGDH in the colon were altered by ginger consumption. Ginger significantly lowered COX-1 protein expression in participants at increased risk for CRC but not in those at normal risk for CRC. Ginger did not alter 15-PGDH protein expression in either increased or normal-risk participants. Further investigation, in larger studies with a longer ginger intervention, is needed to examine the ability of ginger to impact tissue levels of prostaglandin.

  18. 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)


    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.

  19. Allele Imbalance or Loss of Heterozygosity, in Normal Appearing Breast Epithelium as a Novel Biomarker to Predict Future Breast Cancer (United States)


    were either in cassettes too large to fit a standard microtome [7/22] or were in large wax blocks [15/22]. We requested that the tissue be Initially unuseable Not Poor Poor TDLUs TDLUs ɛ Stroma Too Histo Large Cassettes enough quality quality too lost TDLUs only many logically wax ...biopsies lacked atypia, and who had no fa mily history of breast cancer. 10-μ sections were cut from paraffin blocks and TDLUs were removed by laser

  20. Myc post-transcriptionally induces HIF1 protein and target gene expression in normal and cancer cells (United States)

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


    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

  1. Discrimination of prostate cancer from normal peripheral zone and central gland tissue by using dynamic contrast-enhanced MR imaging.

    NARCIS (Netherlands)

    Engelbrecht, M.R.W.; Huisman, H.J.; Laheij, R.J.F.; Jager, G.J.; Leenders, G.J.L.H. van; Hulsbergen-van de Kaa, C.A.; Rosette, J.J.M.H.C. de la; Blickman, J.G.; Barentsz, J.O.


    PURPOSE: To evaluate which parameters of dynamic magnetic resonance (MR) imaging and T2 relaxation rate would result in optimal discrimination of prostatic carcinoma from normal peripheral zone (PZ) and central gland (CG) tissues and to correlate these parameters with tumor stage, Gleason score, pat

  2. Current smoking-specific gene expression signature in normal bronchial epithelium is enhanced in squamous cell lung cancer

    NARCIS (Netherlands)

    Boelens, Mirjam C.; van den Berg, Anke; Fehrmann, Rudolf S. N.; Geerlings, Marie; de Jong, Wouter K.; te Meerman, Gerard J; Sietsma, Hannie; Timens, Winn; Postma, Dirkje S.; Groen, Harry J. M.


    Cigarette smoking is the main risk factor for the development of squamous cell lung carcinoma (SCC). However, the smoking-related molecular changes in SCC have not been studied. Gene expression studies in both histologically normal bronchial epithelium and SCC epithelial samples identified genes dif

  3. Cytotoxicity Induced by Extracts of Pisolithus tinctorius Spores on Human Cancer and Normal Cell Lines-Evaluation of the Anticancer Potential. (United States)

    Alves, Ricardo; Preto, Marco; Vasconcelos, Vitor; Oliveira, Rui S; Martins, Rosário


    Fungi have been considered a potential source of natural anticancer drugs. However, studies on these organisms have mainly focused on compounds present in the sporocarp and mycelium. The aim of this study was to assess the anticancer potential of fungal spores using a bioassay-guided fractionation with cancer and normal cell lines. Crude extracts from spores of the basidiomycetous fungus Pisolithus tinctorius were prepared using five solvents/solvent mixtures in order to select the most effective crude extraction procedure. A dichloromethane/methanol (DCM/MeOH) mixture was found to produce the highest extraction yield, and this extract was fractionated into 11 fractions. Crude extracts and fractions were assayed for cytotoxicity in the human osteocarcinoma cell line MG63, the human breast carcinoma cell line T47D, the human colon adenocarcinoma cell line RKO, and the normal human brain capillary endothelial cell line hCMEC/D3. Cytotoxicity was assessed by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) reduction assay. The results showed a reduction in cancer cell viability of approximately 95% with 4 of 11 fractions without a significant reduction in viability of hCMEC/D3 cells. Data demonstrated that spores of P. tinctorius might serve as an interesting source of compounds with potential anticancer properties.

  4. 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. (United States)

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


    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.

  5. Antagonistic effects of black tea against gamma radiation-induced oxidative damage to normal lymphocytes in comparison with cancerous K562 cells. (United States)

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


    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.

  6. N-ω-chloroacetyl-l-ornithine, a new competitive inhibitor of ornithine decarboxylase, induces selective growth inhibition and cytotoxicity on human cancer cells versus normal cells. (United States)

    Medina-Enríquez, Miriam Marlene; Alcántara-Farfán, Verónica; Aguilar-Faisal, Leopoldo; Trujillo-Ferrara, José Guadalupe; Rodríguez-Páez, Lorena; Vargas-Ramírez, Alba Laura


    Many cancer cells have high expression of ornithine decarboxylase (ODC) and there is a concerted effort to seek new inhibitors of this enzyme. The aim of the study was to initially characterize the inhibition properties, then to evaluate the cytotoxicity/antiproliferative cell based activity of N-ω-chloroacetyl-l-ornithine (NCAO) on three human cancer cell lines. Results showed NCAO to be a reversible competitive ODC inhibitor (Ki = 59 µM) with cytotoxic and antiproliferative effects, which were concentration- and time-dependent. The EC50,72h of NCAO was 15.8, 17.5 and 10.1 µM for HeLa, MCF-7 and HepG2 cells, respectively. NCAO at 500 µM completely inhibited growth of all cancer cells at 48 h treatment, with almost no effect on normal cells. Putrescine reversed NCAO effects on MCF-7 and HeLa cells, indicating that this antiproliferative activity is due to ODC inhibition.

  7. 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: [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)


    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.

  8. 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


    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.

  9. Evaluating the Normal Distribution

    Directory of Open Access Journals (Sweden)

    George Marsaglia


    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.

  10. 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


    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.

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


    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

  12. 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.

  13. Diatom-derived polyunsaturated aldehydes activate cell death in human cancer cell lines but not normal cells. (United States)

    Sansone, Clementina; Braca, Alessandra; Ercolesi, Elena; Romano, Giovanna; Palumbo, Anna; Casotti, Raffaella; Francone, Maria; Ianora, Adrianna


    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.

  14. 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


    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

  15. 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)


    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.

  16. Heterogenous induction of carcinoma-associated fibroblast-like differentiation in normal human prostatic fibroblasts by co-culturing with prostate cancer cells. (United States)

    Ishii, Kenichiro; Mizokami, Atsushi; Tsunoda, Toshiyuki; Iguchi, Kazuhiro; Kato, Manabu; Hori, Yasuhide; Arima, Kiminobu; Namiki, Mikio; Sugimura, Yoshiki


    In the tumor microenvironment, carcinoma-associated fibroblasts (CAFs) are considered to play a critical role in the promotion of tumorigenesis. However, the mechanisms that generate CAFs are not well elucidated. To understand how CAFs are generated during primary cancer progression, we investigated the biochemical characteristics of normal human prostate stromal cells (PrSC) co-cultured with human prostate cancer (PCa) cells in vitro. In primary cultures of human PCa-derived stromal cells (PCaSC-8 and PCaSC-9), expression of TNC, ACTA2, EGF, FGF7, and IGF1 mRNA was generally higher than PrSC but gene expression patterns were not uniform between PCaSC-8 and PCaSC-9 cells. Transforming growth factor β (TGFβ) and vascular endothelial growth factor (VEGF) protein levels in both PCaSC-8 and PCaSC-9 cells were generally higher than PrSC but levels of both secreted proteins were not same. When PrSCs were co-cultured with androgen-sensitive LNCaP cells or its sublines, androgen-low-sensitive E9 cells and androgen-insensitive AIDL cells, mRNA expression of IGF1 was significantly increased in all combinations. In contrast, expression of COL1A1, TNC, and ACTA2 mRNA was significantly increased only in LNCaP + PrSC and E9 + PrSC co-cultures. Protein production of VEGF was significantly increased only in LNCaP + PrSC and E9 + PrSC co-cultures. Increase of TGFβ protein was observed only in E9 + PrSC co-cultures. These biochemical characteristics of PrSC were partially recapitulated in TGFβ-treated PrSC. We have demonstrated that normal fibroblasts co-cultured with cancer cells become activated and exhibit biochemical characteristics of CAFs in a heterogenous manner. Our results suggest that heterogenous induction of CAF-like differentiation might be strongly dependent on biochemical characteristics of adjacent cancer cells.

  17. 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:


    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

  18. Selections, Extensions and Collectionwise Normality

    CERN Document Server

    Gutev, Valentin


    We demonstrate that the classical Michael's selection theorem for l.s.c. mappings with a collectionwise normal domain can be reduced only to compact-valued mappings modulo the Dowker's extension theorem for such spaces. The technique developed to achieve this result is applied to construct selections for set-valued mappings whose point images are in completely metrizable absolute retracts.

  19. 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.

  20. Breast Field Cancerization: Isolation and Comparison of Telomerase-Expressing Cells in Tumor and Tumor Adjacent, Histologically Normal Breast Tissue (United States)

    Trujillo, Kristina A.; Hines, William C.; Vargas, Keith M.; Jones, Anna C.; Joste, Nancy E.; Bisoffi, Marco; Griffith, Jeffrey K.


    Telomerase stabilizes chromosomes by maintaining telomere length, immortalizes mammalian cells, and is expressed in more than 90% of human tumors. However, the expression of human telomerase reverse transcriptase (hTERT) is not restricted to tumor cells. We have previously shown that a subpopulation of human mammary epithelial cells (HMEC) in tumor-adjacent, histologically normal (TAHN) breast tissues expresses hTERT mRNA at levels comparable with levels in breast tumors. In the current study, we first validated a reporter for measuring levels of hTERT promoter activity in early-passage HMECs and then used this reporter to compare hTERT promoter activity in HMECs derived from tumor and paired TAHN tissues 1, 3, and 5 cm from the tumor (TAHN-1, TAHN-3, and TAHN-5, respectively). Cell sorting, quantitative real-time PCR, and microarray analyses showed that the 10% of HMECs with the highest hTERT promoter activity in both tumor and TAHN-1 tissues contain more than 95% of hTERT mRNA and overexpress many genes involved in cell cycle and mitosis. The percentage of HMECs within this subpopulation showing high hTERT promoter activity was significantly reduced or absent in TAHN-3 and TAHN-5 tissues. We conclude that the field of normal tissue proximal to the breast tumors contains a population of HMECs similar in hTERT expression levels and in gene expression to the HMECs within the tumor mass and that this population is significantly reduced in tissues more distal to the tumor. PMID:21775421

  1. 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.

  2. Newton On Absolute Space A Commentary

    CERN Document Server

    Adewole, A I A


    Newton seems to have stated a quantitative relationship between the position of a body in relative space and the position of the body in absolute space in the first scholium of his Principia. We show that if this suspected relationship is assumed to hold, it will dispel many errors and misrepresentations that have befallen Newton's ideas on absolute space.

  3. Monolithically integrated absolute frequency comb laser system

    Energy Technology Data Exchange (ETDEWEB)

    Wanke, Michael C.


    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.

  4. Absolute Income, Relative Income, and Happiness (United States)

    Ball, Richard; Chernova, Kateryna


    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…

  5. The DNA damage response: a common pathway in the regulation of NKG2D and DNAM-1 ligand expression in normal, infected and cancer cells.

    Directory of Open Access Journals (Sweden)

    Cristina eCerboni


    Full Text Available NKG2D and DNAM-1 are two activating receptors, present on the surface of NK cells and other cells of the immune system. Their ligands – MICA, MICB, ULBP1-6 for NKG2D, PVR/CD155 and Nectin-2/CD112 for DNAM-1 - can be constitutively expressed at low levels in some normal cells, but they are more often defined as stress-induced, since different stimuli can positively regulate their expression. In this review, we describe the molecular mechanisms involved in the up-regulation of NKG2D and DNAM-1 ligands under different physiological and pathological stress conditions, including mitosis, viral infections, and cancer. We will focus on the DNA damage response, as recent advances in the field have uncovered its important role as a common signaling pathway in the regulation of both NKG2D and DNAM-1 ligand expression in response to very diverse conditions and stimuli.

  6. Phenotypic changes of p53, HER2, and FAS system in multiple normal tissues surrounding breast cancer. (United States)

    Mottolese, Marcella; Nádasi, Edit A; Botti, Claudio; Cianciulli, Anna M; Merola, Roberta; Buglioni, Simonetta; Benevolo, Maria; Giannarelli, Diana; Marandino, Ferdinando; Donnorso, Raffaele Perrone; Venturo, Irene; Natali, Pier Giorgio


    To determine whether phenotypic field changes occur in tissues adjacent to carcinoma, we assayed, by immunohistochemistry, the expression of HER-2, p53, Fas, and FasL in 72 breast cancers (BC) and multiple autologous peritumoral tissues (PTTs) sampled up to 5 cm distance and in 44 benign breast tumors (BBTs). About 5% and 3% of the PTTs and 4.5% and 6.8% of BBTs showed alterations in HER2 and p53 expression, respectively. Of interest, gene amplification was observed in 50% of HER2 positive PTTs, but not in any HER2 positive BBTs. Fas, highly expressed in BBTs and downregulated in BC, maintained its expression in PTTs, whereas FasL, usually negative in BBTs, was upregulated in BC as well as in the PTTs closest (1 cm) to the invasive lesion. Our data suggest that FasL could be a potential novel biomarker of transformation, which may identify, along with HER2 and p53, precursor lesions in a genetically altered breast tissue.

  7. Heart Risks May Boost Women's Colon Cancer Risk, Too (United States)

    ... wasn't involved in the research. Excluding skin cancers, colon cancer is the third most common cancer diagnosed in ... Cancer Society says. The "absolute" risk of developing colon cancer over a specified period of time varies by ...

  8. 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;


    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 diagn......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......-defined layering in OCT and PS-OCT images and dark lobules in BCC. Discrimination of AK from BCC had an error rate of 50% to 52%. CONCLUSION OCT features in NMSC are identified, but AK and BCC cannot be differentiated. OCT diagnosis is less accurate than clinical diagnosis, but high accuracy in distinguishing...

  9. iSERS microscopy guided by wide field immunofluorescence: analysis of HER2 expression on normal and breast cancer FFPE tissue sections. (United States)

    Wang, Xin-Ping; Zhang, Yuying; König, Matthias; Papadopoulou, Evanthia; Walkenfort, Bernd; Kasimir-Bauer, Sabine; Bankfalvi, Agnes; Schlücker, Sebastian


    Surface-enhanced Raman scattering (SERS) microscopy is an emerging imaging technique for tissue-based cancer diagnostics. Specifically, immuno-SERS (iSERS) microscopy employs antibodies labelled by molecularly functionalized noble metal colloids for antigen localization on tissue specimen. Spectrally resolved iSERS acquisition schemes are typically rather time-consuming when large tissue areas must be scanned. Here, we demonstrate the application of iSERS imaging guided by wide field immunofluorescence (IF) for localization of the human epidermal growth factor receptor 2 (HER2) on breast tissue sections. The addition of unlabelled anti-HER2 primary antibodies to the tissue is followed by the incubation with secondary antibodies labelled with both Alexa-647 (for IF) and hydrophilically stabilized gold nanostars coated with aromatic thiols (for iSERS). False-color iSERS images clearly reveal the different HER2 expression levels on normal and breast cancer tissue, respectively. A series of negative controls confirms that the binding specificity of the secondary antibody is maintained after conjugation to the SERS nanoparticles.

  10. Effect of different cytokines on mammaglobin and maspin gene expression in normal leukocytes: possible relevance to the assays for the detection of micrometastatic breast cancer. (United States)

    Ballestrero, A; Garuti, A; Bertolotto, M; Rocco, I; Boy, D; Nencioni, A; Ottonello, L; Patrone, F


    In cancer patients, the ability to detect disseminated tumour cells in peripheral blood or bone marrow could improve prognosis and consent both early detection of metastatic disease and monitoring of the efficacy of systemic therapy. These objectives remain elusive mainly due to the lack of specific genetic markers for solid tumours. The use of surrogate tissue-specific markers can reduce the specificity of the assays and give rise to a clinically unacceptable false-positive rate. Mammaglobin (MAM) and maspin are two putative breast tissue-specific markers frequently used for detection of occult tumour cells in the peripheral blood, bone marrow and lymph nodes of breast cancer patients. In this study, it was evaluated whether MAM and maspin gene expression may be induced in the normal blood and bone marrow cells exposed to a panel of cytokines, including chemotactic factors (C5a, interleukin (IL)-8), LPS, proinflammatory cytokines (TNF-alpha, IL-1beta) and growth factors (IL-3, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor). The experimental data show that all cytokines included in the panel, except for IL-8, were able to induce maspin expression; on the contrary, MAM gene was never induced. These results suggest that MAM is more specific than maspin and that the possible interference of cytokines should be taken into account in interpreting molecular assays for detection of isolated tumour cells.

  11. 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)


    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.

  12. Electroporation-assisted penetration of zinc oxide nanoparticles in ex vivo normal and cancerous human colon tissue (United States)

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


    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.

  13. Absolute V-R colors of trans-Neptunian objects (United States)

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


    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.

  14. Absolute quantitation of protein posttranslational modification isoform. (United States)

    Yang, Zhu; Li, Ning


    Mass spectrometry has been widely applied in characterization and quantification of proteins from complex biological samples. Because the numbers of absolute amounts of proteins are needed in construction of mathematical models for molecular systems of various biological phenotypes and phenomena, a number of quantitative proteomic methods have been adopted to measure absolute quantities of proteins using mass spectrometry. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) coupled with internal peptide standards, i.e., the stable isotope-coded peptide dilution series, which was originated from the field of analytical chemistry, becomes a widely applied method in absolute quantitative proteomics research. This approach provides more and more absolute protein quantitation results of high confidence. As quantitative study of posttranslational modification (PTM) that modulates the biological activity of proteins is crucial for biological science and each isoform may contribute a unique biological function, degradation, and/or subcellular location, the absolute quantitation of protein PTM isoforms has become more relevant to its biological significance. In order to obtain the absolute cellular amount of a PTM isoform of a protein accurately, impacts of protein fractionation, protein enrichment, and proteolytic digestion yield should be taken into consideration and those effects before differentially stable isotope-coded PTM peptide standards are spiked into sample peptides have to be corrected. Assisted with stable isotope-labeled peptide standards, the absolute quantitation of isoforms of posttranslationally modified protein (AQUIP) method takes all these factors into account and determines the absolute amount of a protein PTM isoform from the absolute amount of the protein of interest and the PTM occupancy at the site of the protein. The absolute amount of the protein of interest is inferred by quantifying both the absolute amounts of a few PTM

  15. 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)


    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.

  16. 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


    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.

  17. Clarifying Normalization (United States)

    Carpenter, Donald A.


    Confusion exists among database textbooks as to the goal of normalization as well as to which normal form a designer should aspire. This article discusses such discrepancies with the intention of simplifying normalization for both teacher and student. This author's industry and classroom experiences indicate such simplification yields quicker…

  18. TU-F-12A-09: GLCM Texture Analysis for Normal-Tissue Toxicity: A Prospective Ultrasound Study of Acute Toxicity in Breast-Cancer Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Liu, T; Yang, X; Curran, W; Torres, M [Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA (United States)


    Purpose: To evaluate the morphologic and structural integrity of the breast glands using sonographic textural analysis, and identify potential early imaging signatures for radiation toxicity following breast-cancer radiotherapy (RT). Methods: Thirty-eight patients receiving breast RT participated in a prospective ultrasound imaging study. Each participant received 3 ultrasound scans: 1 week before RT (baseline), and at 6-week and 3-month follow-ups. Patients were imaged with a 10-MHz ultrasound on the four quadrant of the breast. A second order statistical method of texture analysis, called gray level co-occurrence matrix (GLCM), was employed to assess RT-induced breast-tissue toxicity. The region of interest (ROI) was 28 mm × 10 mm in size at a 10 mm depth under the skin. Twenty GLCM sonographic features, ratios of the irradiated breast and the contralateral breast, were used to quantify breast-tissue toxicity. Clinical assessment of acute toxicity was conducted using the RTOG toxicity scheme. Results: Ninety-seven ultrasound studies (776 images) were analyzed; and 5 out of 20 sonographic features showed significant differences (p < 0.05) among the baseline scans, the acute toxicity grade 1 and 2 groups. These sonographic features quantified the degree of tissue damage through homogeneity, heterogeneity, randomness, and symmetry. Energy ratio value decreased from 108±0.05 (normal) to 0.99±0.05 (Grade 1) and 0.84±0.04 (Grade 2); Entropy ratio value increased from 1.01±0.01 to 1.02±0.01 and 1.04±0.01; Contrast ratio value increased from 1.03±0.03 to 1.07±0.06 and 1.21±0.09; Variance ratio value increased from 1.06±0.03 to 1.20±0.04 and 1.42±0.10; Cluster Prominence ratio value increased from 0.98±0.02 to 1.01±0.04 and 1.25±0.07. Conclusion: This work has demonstrated that the sonographic features may serve as imaging signatures to assess radiation-induced normal tissue damage. While these findings need to be validated in a larger cohort, they suggest

  19. 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


    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.

  20. Thyroid Cancer (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 ...

  1. 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


    -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.

  2. The Benefits of Including Clinical Factors in Rectal Normal Tissue Complication Probability Modeling After Radiotherapy for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Defraene, Gilles, E-mail: [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Van den Bergh, Laura [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Al-Mamgani, Abrahim [Department of Radiation Oncology, Erasmus Medical Center - Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Haustermans, Karin [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Heemsbergen, Wilma [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Van den Heuvel, Frank [Radiation Oncology Department, University Hospitals Leuven, Leuven (Belgium); Lebesque, Joos V. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)


    Purpose: To study the impact of clinical predisposing factors on rectal normal tissue complication probability modeling using the updated results of the Dutch prostate dose-escalation trial. Methods and Materials: Toxicity data of 512 patients (conformally treated to 68 Gy [n = 284] and 78 Gy [n = 228]) with complete follow-up at 3 years after radiotherapy were studied. Scored end points were rectal bleeding, high stool frequency, and fecal incontinence. Two traditional dose-based models (Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) and a logistic model were fitted using a maximum likelihood approach. Furthermore, these model fits were improved by including the most significant clinical factors. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminating ability of all fits. Results: Including clinical factors significantly increased the predictive power of the models for all end points. In the optimal LKB, RS, and logistic models for rectal bleeding and fecal incontinence, the first significant (p = 0.011-0.013) clinical factor was 'previous abdominal surgery.' As second significant (p = 0.012-0.016) factor, 'cardiac history' was included in all three rectal bleeding fits, whereas including 'diabetes' was significant (p = 0.039-0.048) in fecal incontinence modeling but only in the LKB and logistic models. High stool frequency fits only benefitted significantly (p = 0.003-0.006) from the inclusion of the baseline toxicity score. For all models rectal bleeding fits had the highest AUC (0.77) where it was 0.63 and 0.68 for high stool frequency and fecal incontinence, respectively. LKB and logistic model fits resulted in similar values for the volume parameter. The steepness parameter was somewhat higher in the logistic model, also resulting in a slightly lower D{sub 50}. Anal wall DVHs were used for fecal incontinence, whereas anorectal wall dose best described the other two endpoints

  3. Absolute instability in viscoelastic mixing layers (United States)

    Ray, Prasun K.; Zaki, Tamer A.


    The spatiotemporal linear stability of viscoelastic planar mixing layers is investigated. A one-parameter family of velocity profiles is used as the base state with the parameter, S, controlling the amount of shear and backflow. The influence of viscoelasticity in dilute polymer solutions is modeled with the Oldroyd-B and FENE-P constitutive equations. Both models require the specification of the ratio of the polymer-relaxation and convective time scales (the Weissenberg number, We) and the ratio of solvent and solution viscosities (β). The maximum polymer extensibility, L, must also be specified for the FENE-P model. We examine how the variation of these parameters along with the Reynolds number, Re, affects the minimum value of S at which the flow becomes locally absolutely unstable. With the Oldroyd-B model, the influence of viscoelasticity is shown to be almost fully captured by the elasticity, E^* equiv (1-β ) We/Re, and Scrit decreases as elasticity is increased, i.e., elasticity is destabilizing. A simple approximate dispersion relation obtained via long-wave asymptotic analysis is shown to accurately capture this destabilizing influence. Results obtained with the FENE-P model exhibit a rich variety of behavior. At large values of the extensibility, L, results are similar to those for the Oldroyd-B fluid as expected. However, when the extensibility is reduced to more realistic values (L ≈ 100), one must consider the scaled shear rate, η _c equiv We S/2L, in addition to the elasticity. When ηc is large, the base-state polymer stress obtained by the FENE-P model is reduced, and there is a corresponding reduction in the overall influence of viscoelasticity on stability. Additionally, elasticity exhibits a stabilizing effect which is driven by the streamwise-normal perturbation polymer stress. As ηc is reduced, the base-state and perturbation normal polymer stresses predicted by the FENE-P model move towards the Oldroyd-B values, and the destabilizing

  4. Magnifying absolute instruments for optically homogeneous regions

    CERN Document Server

    Tyc, Tomas


    We propose a class of magnifying absolute optical instruments with a positive isotropic refractive index. They create magnified stigmatic images, either virtual or real, of optically homogeneous three-dimensional spatial regions within geometrical optics.

  5. The Simplicity Argument and Absolute Morality (United States)

    Mijuskovic, Ben


    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)

  6. Vibrational Circular Dichroism Absolute Configuration of 9,12-Cyclomulin-13-ol, a Diterpene from Azorella and Laretia Species. (United States)

    Muñoz, Marcelo A; San-Martín, Aurelio; Joseph-Nathan, Pedro


    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.

  7. 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)


    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.

  8. 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: [Center for Advanced Radiotherapy Technologies, Department of Radiation Oncology, University of California San Diego, La Jolla, CA (United States)


    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.

  9. 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


    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 ...

  10. The absolute infrared magnitudes of type Ia supernovae

    CERN Document Server

    Meikle, W P S


    The absolute luminosities and homogeneity of early-time infrared (IR) light curves of type Ia supernovae are examined. Eight supernovae are considered. These are selected to have accurately known epochs of maximum blue light as well as having reliable distance estimates and/or good light curve coverage. Two approaches to extinction correction are considered. Owing to the low extinction in the IR, the differences in the corrections via the two methods are small. Absolute magnitude light curves in the J, H and K-bands are derived. Six of the events, including five established ``Branch-normal'' supernovae show similar coeval magnitudes. Two of these, SNe 1989B and 1998bu, were observed near maximum infrared light. This occurs about 5 days {\\it before} maximum blue light. Absolute peak magnitudes of about -19.0, -18.7 and -18.8 in J, H & K respectively were obtained. The two spectroscopically peculiar supernovae in the sample, SNe 1986G and 1991T, also show atypical IR behaviour. The light curves of the six s...

  11. Phase II study of the effects of ginger root extract on eicosanoids in colon mucosa in people at normal risk for colorectal cancer. (United States)

    Zick, Suzanna M; Turgeon, D Kim; Vareed, Shaiju K; Ruffin, Mack T; Litzinger, Amie J; Wright, Benjamin D; Alrawi, Sara; Normolle, Daniel P; Djuric, Zora; Brenner, Dean E


    Inhibitors of COX indicate that upregulation of inflammatory eicosanoids produced by COX, and in particular prostaglandin E(2) (PGE(2)), are early events in the development of colorectal cancer (CRC). Ginger has shown downregulation of COX in vitro and decreased incidence/multiplicity of adenomas in rats. This study was conducted to determine if 2.0 g/d of ginger could decrease the levels of PGE(2), 13-hydroxy-octadecadienoic acids, and 5-, 12-, and 15-hydroxyeicosatetraenoic acid (5-, 12-, and 15-HETE), in the colon mucosa of healthy volunteers. To investigate this aim, we randomized 30 subjects to 2.0 g/d ginger or placebo for 28 days. Flexible sigmoidoscopy at baseline and day 28 was used to obtain colon biopsies. A liquid chromatography mass spectrometry method was used to determine eicosanoid levels in the biopsies, and levels were expressed per protein or per free arachidonic acid. There were no significant differences in mean percent change between baseline and day 28 for any of the eicosanoids, when normalized to protein. There was a significant decrease in mean percent change in PGE(2) (P = 0.05) and 5-HETE (P = 0.04), and a trend toward significant decreases in 12-HETE (P = 0.09) and 15-HETE (P = 0.06) normalized to free arachidonic acid. There was no difference between the groups in terms of total adverse events P = 0.55). On the basis of these results, it seems that ginger has the potential to decrease eicosanoid levels, perhaps by inhibiting their synthesis from arachidonic acid. Ginger also seemed to be tolerable and safe. Further investigation in people at high risk for CRC seems warranted.

  12. Birkhoff normalization

    NARCIS (Netherlands)

    Broer, H.; Hoveijn, I.; Lunter, G.; Vegter, G.


    The Birkhoff normal form procedure is a widely used tool for approximating a Hamiltonian systems by a simpler one. This chapter starts out with an introduction to Hamiltonian mechanics, followed by an explanation of the Birkhoff normal form procedure. Finally we discuss several algorithms for comput

  13. A global algorithm for estimating Absolute Salinity

    Directory of Open Access Journals (Sweden)

    T. J. McDougall


    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.

  14. 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


    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.

  15. Absolute photoacoustic thermometry in deep tissue. (United States)

    Yao, Junjie; Ke, Haixin; Tai, Stephen; Zhou, Yong; Wang, Lihong V


    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.

  16. Quantum theory allows for absolute maximal contextuality (United States)

    Amaral, Barbara; Cunha, Marcelo Terra; Cabello, Adán


    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.

  17. Total synthesis and absolute stereochemistry of the proteasome inhibitors cystargolides A and B. (United States)

    Tello-Aburto, Rodolfo; Hallada, Liam P; Niroula, Doleshwar; Rogelj, Snezna


    The absolute stereochemistry of the cystargolides was determined by total synthesis. Evaluation of synthetic cystargolides and derivatives showed that the natural (2S,3R) stereochemistry is essential for activity. Moreover, benzyl esters (-)-10 and (-)-15 were found to be about 100 times more potent, and to selectively kill MCF-7 cancerous cells.

  18. Absolute Stability Limit for Relativistic Charged Spheres

    CERN Document Server

    Giuliani, Alessandro


    We find an exact solution for the stability limit of relativistic charged spheres for the case of constant gravitational mass density and constant charge density. We argue that this provides an absolute stability limit for any relativistic charged sphere in which the gravitational mass density decreases with radius and the charge density increases with radius. We then provide a cruder absolute stability limit that applies to any charged sphere with a spherically symmetric mass and charge distribution. We give numerical results for all cases. In addition, we discuss the example of a neutral sphere surrounded by a thin, charged shell.

  19. Absolute Asymmetric Synthesis Using A Cocrystal Approach

    Institute of Scientific and Technical Information of China (English)



    1 Results Absolute asymmetric synthesis by means of solid-state reaction of chiral crystals self-assembled from achiral molecules is an attractive and promising methodology for asymmetric synthesis because it is not necessary to employ any external chiral source like a chiral catalyst.In order to design reliably absolute asymmetric syntheses in the solid state,it is inevitable to prepare and predict the formation of chiral crystals from achiral compounds.We have prepared a number of chiral cocrystals co...

  20. Normal Coagulation (United States)


    clotting or inflam - mation. These include thrombin, histamine, acetylcholine, bradykinin, epinephrine, interleukins, shear stress, and vaso...humans include the liver, spleen, adipose tissue, and cells of the vasculature, including endothelial cells, smooth muscle cells, macrophages , and...1999. 225. Quax PH, et al: Protein and messenger RNA levels of plasminogen activators and inhibitors analyzed in 22 human tumor cell lines. Cancer

  1. The Aging Prostate Is Never "Normal"

    DEFF Research Database (Denmark)

    Schlomm, Thorsten; Weischenfeldt, Joachim; Korbel, Jan


    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.......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....

  2. Statistical Validation of Normal Tissue Complication Probability Models

    Energy Technology Data Exchange (ETDEWEB)

    Xu Chengjian, E-mail: [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)


    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.

  3. Thin-film magnetoresistive absolute position detector

    NARCIS (Netherlands)

    Groenland, Johannes Petrus Jacobus


    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. Det demokratiske argument for absolut ytringsfrihed

    DEFF Research Database (Denmark)

    Lægaard, Sune


    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 hvorfor...

  5. New Techniques for Absolute Gravity Measurements. (United States)


    Hammond, J.A. (1978) Bollettino Di Geofisica Teorica ed Applicata Vol. XX. 8. Hammond, J. A., and Iliff, R. L. (1979) The AFGL absolute gravity system...International Gravimetric Bureau, No. L:I-43. 7. Hammond. J.A. (1978) Bollettino Di Geofisica Teorica ed Applicata Vol. XX. 8. Hammond, J.A., and

  6. Teaching Absolute Value Inequalities to Mature Students (United States)

    Sierpinska, Anna; Bobos, Georgeana; Pruncut, Andreea


    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…

  7. Time Function and Absolute Black Hole

    DEFF Research Database (Denmark)

    Javadi, Hossein; Forouzbakhsh, Farshid


    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....

  8. Magnetoresistive sensor for absolute position detection

    NARCIS (Netherlands)

    Groenland, J.P.J.


    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.

  9. Generalized Norms Inequalities for Absolute Value Operators

    Directory of Open Access Journals (Sweden)

    Ilyas Ali


    Full Text Available In this article, we generalize some norms inequalities for sums, differences, and products of absolute value operators. Our results based on Minkowski type inequalities and generalized forms of the Cauchy-Schwarz inequality. Some other related inequalities are also discussed.

  10. Stimulus Probability Effects in Absolute Identification (United States)

    Kent, Christopher; Lamberts, Koen


    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…

  11. Absolute Radiation Thermometry in the NIR (United States)

    Bünger, L.; Taubert, R. D.; Gutschwager, B.; Anhalt, K.; Briaudeau, S.; Sadli, M.


    A near infrared (NIR) radiation thermometer (RT) for temperature measurements in the range from 773 K up to 1235 K was characterized and calibrated in terms of the "Mise en Pratique for the definition of the Kelvin" (MeP-K) by measuring its absolute spectral radiance responsivity. Using Planck's law of thermal radiation allows the direct measurement of the thermodynamic temperature independently of any ITS-90 fixed-point. To determine the absolute spectral radiance responsivity of the radiation thermometer in the NIR spectral region, an existing PTB monochromator-based calibration setup was upgraded with a supercontinuum laser system (0.45 μm to 2.4 μm) resulting in a significantly improved signal-to-noise ratio. The RT was characterized with respect to its nonlinearity, size-of-source effect, distance effect, and the consistency of its individual temperature measuring ranges. To further improve the calibration setup, a new tool for the aperture alignment and distance measurement was developed. Furthermore, the diffraction correction as well as the impedance correction of the current-to-voltage converter is considered. The calibration scheme and the corresponding uncertainty budget of the absolute spectral responsivity are presented. A relative standard uncertainty of 0.1 % (k=1) for the absolute spectral radiance responsivity was achieved. The absolute radiometric calibration was validated at four temperature values with respect to the ITS-90 via a variable temperature heatpipe blackbody (773 K ...1235 K) and at a gold fixed-point blackbody radiator (1337.33 K).

  12. Immunohistochemical study of the Nrf2 pathway in colorectal cancer: Nrf2 expression is closely correlated to Keap1 in the tumor and Bach1 in the normal tissue. (United States)

    Chang, Liang-Che; Fan, Chung-Wei; Tseng, Wen-Ko; Chen, Jim-Ray; Chein, Hui-Ping; Hwang, Cheng-Cheng; Hua, Chung-Ching


    Oxidative stress is a contributing factor in the carcinogenesis of colorectal cancer. The Nrf2 [nuclear factor (erythroid-derived 2)-like 2; NFE2L2] pathway is one of the major cellular defense mechanisms against oxidative stress. This study investigated the expression of the Nrf2 pathway in colorectal cancer. Formalin-fixed paraffin-embedded tissue arrays consisting of the tumor, adjacent normal, and distant normal tissues from the resected specimens of 83 colorectal cancer patients were subjected to immunohistochemical (IHC) staining with antibodies against Nrf2, kelch-like ECH-associated protein 1 (Keap1), p21, P62, Parkinson protein 7 (Park7), prohibitin, BTB and CNC homology 1 (Bach1), CD34 and 8-hydroxy-2'-deoxyguanosine (8-OHdG). The mean IHC density of each IHC staining was digitally analyzed. The results showed that molecules of the Nrf2 pathway were actively expressed, with different expression profiles among the tumor and normal tissues. The oxidative stress, represented by the mean IHC staining density of 8-OHdG, did not differ but was correlated with the expressions of different Nrf2 pathway molecules to a varied extent in tumor and normal tissues of colorectal cancer. Keap1 [estimate, 0.49; 95% confidence interval (CI), 0.19-0.79] and Bach1 (estimate, 0.24; 95% CI, 0.11-0.38) were significant predictors for the expression of 8-OHdG and had the closest proximity to Nrf2 in the cluster dendrogram of the tumor and distant normal tissues, respectively. Advanced stage (estimate, 14.9; 95% CI, 2.99-26.8) and current smoker (estimate, 15.6; 95% CI, 1.92-29.3) were significant predictors with high estimates for Bach1 in the adjacent and distant normal tissues, respectively. In colorectal cancer, the molecules of the Nrf2 pathway have different expression profiles and a difference in their importance, especially Keap1 and Bach1, related to Nrf2 and oxidative stress among tumor and normal tissues.

  13. Experimental study of absolute instability over a rotating disk (United States)

    Othman Bekhit, Hesham Abdel Ghafar


    A series of experiments were performed to study the absolute instability of Type I traveling cross-flow modes in the boundary layer on a smooth disk rotating at constant speed. The basic flow agreed with analytic theory, and the growth of natural disturbances matched linear theory predictions. Controlled temporal disturbances were introduced by a short-duration air pulse from a hypodermic tube located above the disk and outside the boundary layer. The air pulse was positioned just outboard of the critical radius for Type I cross-flow modes. A hot-wire sensor primarily sensitive to the azirnuthal velocity component, was positioned at different spatial locations on the disk to document the growth of disturbances produced by the air pulses. Ensemble averages conditioned on the air pulses revealed wave packets that evolved in time and space. Two amplitudes of air pulses were used. The lower amplitude produced wave packets with linear amplitude characteristics that agreed with linear-theory wall-normal eigenfunction distributions and spatial growth rates. The higher amplitude pulse produced wave packets that had nonlinear amplitude characteristics. The space-time evolution of the leading and trailing edges of the wave packets were followed well past the critical radius for the absolute instability based on Lingwood (1995). With the linear amplitudes, the absolute instability was dominated by the convective modes, agreeing with the linear DNS simulations of Davies and Carpenter (2003). With the nonlinear amplitudes, larger temporal growth of the wave packets existed which supports the finite amplitude analysis of Pier (2003), and more closely resembles the wave packet evolution in the experimental study of Lingwood (1996). This suggests that the disturbance levels in the experiment that was intended to demonstrate the linear analysis, were likely fuite.

  14. 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)


    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

  15. Maintaining a Normal Life: Proceedings of the National Conference for Parents of Children with Cancer (1st, Arlington, Virginia, June 23-25, 1978). (United States)

    National Cancer Inst. (NIH), Bethesda, MD.

    Twenty presentations from a 1978 conference for parents of children with cancer focus on the teenager and cancer, long term survival of children, the parents and treatment, and practical problems involved. The following papers and authors are represented: "The Role of the Patient Family" (Clark, Fox-Kolenda); "How the Child Perceives Illness and…

  16. An absolute measure for a key currency (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.

  17. From Hubble's NGSL to Absolute Fluxes (United States)

    Heap, Sara R.; Lindler, Don


    Hubble's Next Generation Spectral Library (NGSL) consists of R-l000 spectra of 374 stars of assorted temperature, gravity, and metallicity. Each spectrum covers the wavelength range, 0.18-1.00 microns. The library can be viewed and/or downloaded from the website, Stars in the NGSL are now being used as absolute flux standards at ground-based observatories. However, the uncertainty in the absolute flux is about 2%, which does not meet the requirements of dark-energy surveys. We are therefore developing an observing procedure that should yield fluxes with uncertainties less than 1 % and will take part in an HST proposal to observe up to 15 stars using this new procedure.

  18. Asteroid absolute magnitudes and slope parameters (United States)

    Tedesco, Edward F.


    A new listing of absolute magnitudes (H) and slope parameters (G) has been created and published in the Minor Planet Circulars; this same listing will appear in the 1992 Ephemerides of Minor Planets. Unlike previous listings, the values of the current list were derived from fits of data at the V band. All observations were reduced in the same fashion using, where appropriate, a single basis default value of 0.15 for the slope parameter. Distances and phase angles were computed for each observation. The data for 113 asteroids was of sufficiently high quality to permit derivation of their H and G. These improved absolute magnitudes and slope parameters will be used to deduce the most reliable bias-corrected asteroid size-frequency distribution yet made.

  19. Learning in a unidimensional absolute identification task. (United States)

    Rouder, Jeffrey N; Morey, Richard D; Cowan, Nelson; Pfaltz, Monique


    We tested whether there is long-term learning in the absolute identification of line lengths. Line lengths are unidimensional stimuli, and there is a common belief that learning of these stimuli quickly reaches a low-level asymptote of about seven items and progresses no more. We show that this is not the case. Our participants served in a 1.5-h session each day for over a week. Although they did not achieve perfect performance, they continued to improve day by day throughout the week and eventually learned to distinguish between 12 and 20 line lengths. These results are in contrast to common characterizations of learning in absolute identification tasks with unidimensional stimuli. We suggest that this learning reflects improvement in short-term processing.

  20. Absolute and relative dosimetry for ELIMED

    Energy Technology Data Exchange (ETDEWEB)

    Cirrone, G. A. P.; Schillaci, F.; Scuderi, V. [INFN, Laboratori Nazionali del Sud, Via Santa Sofia 62, Catania, Italy and Institute of Physics Czech Academy of Science, ELI-Beamlines project, Na Slovance 2, Prague (Czech Republic); Cuttone, G.; Candiano, G.; Musumarra, A.; Pisciotta, P.; Romano, F. [INFN, Laboratori Nazionali del Sud, Via Santa Sofia 62, Catania (Italy); Carpinelli, M. [INFN Sezione di Cagliari, c/o Dipartimento di Fisica, Università di Cagliari, Cagliari (Italy); Leonora, E.; Randazzo, N. [INFN-Sezione di Catania, Via Santa Sofia 64, Catania (Italy); Presti, D. Lo [INFN-Sezione di Catania, Via Santa Sofia 64, Catania, Italy and Università di Catania, Dipartimento di Fisica e Astronomia, Via S. Sofia 64, Catania (Italy); Raffaele, L. [INFN, Laboratori Nazionali del Sud, Via Santa Sofia 62, Catania, Italy and INFN-Sezione di Catania, Via Santa Sofia 64, Catania (Italy); Tramontana, A. [INFN, Laboratori Nazionali del Sud, Via Santa Sofia 62, Catania, Italy and Università di Catania, Dipartimento di Fisica e Astronomia, Via S. Sofia 64, Catania (Italy); Cirio, R.; Sacchi, R.; Monaco, V. [INFN, Sezione di Torino, Via P.Giuria, 1 10125 Torino, Italy and Università di Torino, Dipartimento di Fisica, Via P.Giuria, 1 10125 Torino (Italy); Marchetto, F.; Giordanengo, S. [INFN, Sezione di Torino, Via P.Giuria, 1 10125 Torino (Italy)


    The definition of detectors, methods and procedures for the absolute and relative dosimetry of laser-driven proton beams is a crucial step toward the clinical use of this new kind of beams. Hence, one of the ELIMED task, will be the definition of procedures aiming to obtain an absolute dose measure at the end of the transport beamline with an accuracy as close as possible to the one required for clinical applications (i.e. of the order of 5% or less). Relative dosimetry procedures must be established, as well: they are necessary in order to determine and verify the beam dose distributions and to monitor the beam fluence and the energetic spectra during irradiations. Radiochromic films, CR39, Faraday Cup, Secondary Emission Monitor (SEM) and transmission ionization chamber will be considered, designed and studied in order to perform a fully dosimetric characterization of the ELIMED proton beam.

  1. Absolute and relative dosimetry for ELIMED (United States)

    Cirrone, G. A. P.; Cuttone, G.; Candiano, G.; Carpinelli, M.; Leonora, E.; Lo Presti, D.; Musumarra, A.; Pisciotta, P.; Raffaele, L.; Randazzo, N.; Romano, F.; Schillaci, F.; Scuderi, V.; Tramontana, A.; Cirio, R.; Marchetto, F.; Sacchi, R.; Giordanengo, S.; Monaco, V.


    The definition of detectors, methods and procedures for the absolute and relative dosimetry of laser-driven proton beams is a crucial step toward the clinical use of this new kind of beams. Hence, one of the ELIMED task, will be the definition of procedures aiming to obtain an absolute dose measure at the end of the transport beamline with an accuracy as close as possible to the one required for clinical applications (i.e. of the order of 5% or less). Relative dosimetry procedures must be established, as well: they are necessary in order to determine and verify the beam dose distributions and to monitor the beam fluence and the energetic spectra during irradiations. Radiochromic films, CR39, Faraday Cup, Secondary Emission Monitor (SEM) and transmission ionization chamber will be considered, designed and studied in order to perform a fully dosimetric characterization of the ELIMED proton beam.

  2. Absolute calibration of TFTR helium proportional counters

    Energy Technology Data Exchange (ETDEWEB)

    Strachan, J.D.; Diesso, M.; Jassby, D.; Johnson, L.; McCauley, S.; Munsat, T.; Roquemore, A.L. [Princeton Univ., NJ (United States). Plasma Physics Lab.; Barnes, C.W. [Princeton Univ., NJ (United States). Plasma Physics Lab.]|[Los Alamos National Lab., NM (United States); Loughlin, M. [Princeton Univ., NJ (United States). Plasma Physics Lab.]|[JET Joint Undertaking, Abingdon (United Kingdom)


    The TFTR helium proportional counters are located in the central five (5) channels of the TFTR multichannel neutron collimator. These detectors were absolutely calibrated using a 14 MeV neutron generator positioned at the horizontal midplane of the TFTR vacuum vessel. The neutron generator position was scanned in centimeter steps to determine the collimator aperture width to 14 MeV neutrons and the absolute sensitivity of each channel. Neutron profiles were measured for TFTR plasmas with time resolution between 5 msec and 50 msec depending upon count rates. The He detectors were used to measure the burnup of 1 MeV tritons in deuterium plasmas, the transport of tritium in trace tritium experiments, and the residual tritium levels in plasmas following 50:50 DT experiments.

  3. Absolute vs. Relative Notion of Wealth Changes



    This paper discusses solutions derived from lottery experiments using two alternative assumptions: that people perceive wealth changes as absolute amounts of money; and that people consider wealth changes as a proportion of some reference value dependant on the context of the problem under consideration. The former assumption leads to the design of Prospect Theory, the latter - to a solution closely resembling the utility function hypothesized by Markowitz (1952B). This paper presents several...

  4. The absolute differential calculus (calculus of tensors)

    CERN Document Server

    Levi-Civita, Tullio


    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

  5. 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: [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)


    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

  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. (United States)

    Algan, Ozer; Jamgade, Ambarish; Ali, Imad; Christie, Alana; Thompson, J Spencer; Thompson, David; Ahmad, Salahuddin; Herman, Terence


    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 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 parameter for the surrounding normal tissue except for the dose received by the penile bulb and the right hip. Our dosimetric evaluation suggests significant underdosing with inaccurate target localization and emphasizes the importance of accurate patient setup and target localization. Further studies are needed to evaluate the impact of intrafraction organ motion, rotation

  7. Thrombopoietin mobilizes CD34+ cell subsets into peripheral blood and expands multilineage progenitors in bone marrow of cancer patients with normal hematopoiesis. (United States)

    Murray, L J; Luens, K M; Estrada, M F; Bruno, E; Hoffman, R; Cohen, R L; Ashby, M A; Vadhan-Raj, S


    Thrombopoietin (TPO), the primary regulator of megakaryocytopoiesis, also mediates biologic effects in vitro on hematopoietic cells more primitive than those committed to the megakaryocyte (MK) lineage. To assess the spectrum of hematopoietic effects of recombinant human (rh)TPO in vivo, we evaluated its proliferative effect on bone marrow (BM) progenitor cells, its maturation effect on BM MKs, and its mobilizing effect on peripheral blood (PB) progenitor cells during a phase I clinical laboratory investigation in which rhTPO was administered to cancer patients with normal hematopoiesis. Twelve patients received a single dose of rhTPO (0.3, 0.6, 1.2, or 2.4 microg/kg of body weight) prior to chemotherapy. BM and PB samples from these patients were analyzed 1 to 2 days before (baseline) and 7 days after rhTPO administration. At higher doses (1.2-2.4 microg/kg), rhTPO produced increased concentrations of primitive CD34+Thy-1+Lin-cells (mean 2.1-fold), CD34+mpl+ cells (mean 5.2-fold), CD34+CD41+CD14- promegakaryoblasts (mean 2.9-fold), and myeloerythroid colony-forming cells (mean threefold) in BM. No significant increases in the frequency of BM colony-forming unit (CFU)-MK were observed. Elevated numbers of both immature (2N-8N) and more mature (64N and 128N) CD41+ MKs were detected in BM, with modal ploidy remaining at 16N. Higher doses of rhTPO (1.2-2.4 microg/kg) also induced increased concentrations of CD34+ cell subsets in PB, including both primitive CD34+Thy-1+Lin- (mean 8.8-fold) and MK lineage-committed CD34+CD41+CD14- cells (mean 14.6-fold) as well as various myeloerythroid colony-forming cells (mean 3.6- to 5.5-fold). These results demonstrate that rhTPO given as a single dose not only promotes proliferation and maturation of cells of the MK lineage, but also expands the pool of BM primitive hematopoietic cells. In addition, rhTPO induces mobilization of hematopoietic progenitors into peripheral circulation. The extent to which such multilineage effects on

  8. Measurement of absolute gravity acceleration in Firenze (United States)

    de Angelis, M.; Greco, F.; Pistorio, A.; Poli, N.; Prevedelli, M.; Saccorotti, G.; Sorrentino, F.; Tino, G. M.


    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.

  9. Measurement of absolute gravity acceleration in Firenze

    Directory of Open Access Journals (Sweden)

    M. de Angelis


    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.

  10. The accumulation of DNA demethylation in Sat α in normal gastric tissues with Helicobacter pylori infection renders susceptibility to gastric cancer in some individuals. (United States)

    Saito, Masaaki; Suzuki, Koichi; Maeda, Takafumi; Kato, Takaharu; Kamiyama, Hidenori; Koizumi, Kei; Miyaki, Yuichiro; Okada, Shinichiro; Kiyozaki, Hirokazu; Konishi, Fumio


    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 (PSat 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 (PSat 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 (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.

  11. 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


    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

  12. Sulindac inhibits beta-catenin expression in normal-appearing colon of hereditary nonpolyposis colorectal cancer and familial adenomatous polyposis patients

    NARCIS (Netherlands)

    Koornstra, JJ; Rijcken, FEM; Oldenhuis, CNAM; Zwart, N; van der Sluis, T; Hollema, H; deVries, EGE; Keller, JJ; Offerhaus, JA; Giardiello, FM; Kleibeuker, JH


    Sulindac reduces colorectal cancer risk in genetically susceptible humans and animals. The molecular mechanisms underlying these effects are incompletely understood. Many studies suggest an important role for induction of apoptosis involving the mitochondrial pathway and the death receptor pathway.

  13. 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


    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.

  14. Achieving Climate Change Absolute Accuracy in Orbit (United States)

    Wielicki, Bruce A.; Young, D. F.; Mlynczak, M. G.; Thome, K. J; Leroy, S.; Corliss, J.; Anderson, J. G.; Ao, C. O.; Bantges, R.; Best, F.; Bowman, K.; Brindley, H.; Butler, J. J.; Collins, W.; Dykema, J. A.; Doelling, D. R.; Feldman, D. R.; Fox, N.; Huang, X.; Holz, R.; Huang, Y.; Jennings, D.; Jin, Z.; Johnson, D. G.; Jucks, K.; Kato, S.; Kratz, D. P.; Liu, X.; Lukashin, C.; Mannucci, A. J.; Phojanamongkolkij, N.; Roithmayr, C. M.; Sandford, S.; Taylor, P. C.; Xiong, X.


    The Climate Absolute Radiance and Refractivity Observatory (CLARREO) mission will provide a calibration laboratory in orbit for the purpose of accurately measuring and attributing climate change. CLARREO measurements establish new climate change benchmarks with high absolute radiometric accuracy and high statistical confidence across a wide range of essential climate variables. CLARREO's inherently high absolute accuracy will be verified and traceable on orbit to Système Internationale (SI) units. The benchmarks established by CLARREO will be critical for assessing changes in the Earth system and climate model predictive capabilities for decades into the future as society works to meet the challenge of optimizing strategies for mitigating and adapting to climate change. The CLARREO benchmarks are derived from measurements of the Earth's thermal infrared spectrum (5-50 micron), the spectrum of solar radiation reflected by the Earth and its atmosphere (320-2300 nm), and radio occultation refractivity from which accurate temperature profiles are derived. The mission has the ability to provide new spectral fingerprints of climate change, as well as to provide the first orbiting radiometer with accuracy sufficient to serve as the reference transfer standard for other space sensors, in essence serving as a "NIST [National Institute of Standards and Technology] in orbit." CLARREO will greatly improve the accuracy and relevance of a wide range of space-borne instruments for decadal climate change. Finally, CLARREO has developed new metrics and methods for determining the accuracy requirements of climate observations for a wide range of climate variables and uncertainty sources. These methods should be useful for improving our understanding of observing requirements for most climate change observations.

  15. ABSOLUT LOMO绝对创意

    Institute of Scientific and Technical Information of China (English)



    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。

  16. Absolute quantification of myocardial blood flow. (United States)

    Yoshinaga, Keiichiro; Manabe, Osamu; Tamaki, Nagara


    With the increasing availability of positron emission tomography (PET) myocardial perfusion imaging, the absolute quantification of myocardial blood flow (MBF) has become popular in clinical settings. Quantitative MBF provides an important additional diagnostic or prognostic information over conventional visual assessment. The success of MBF quantification using PET/computed tomography (CT) has increased the demand for this quantitative diagnostic approach to be more accessible. In this regard, MBF quantification approaches have been developed using several other diagnostic imaging modalities including single-photon emission computed tomography, CT, and cardiac magnetic resonance. This review will address the clinical aspects of PET MBF quantification and the new approaches to MBF quantification.

  17. 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.


    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.

  18. 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:


    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.

  19. Musical Activity Tunes Up Absolute Pitch Ability

    DEFF Research Database (Denmark)

    Dohn, Anders; Garza-Villarreal, Eduardo A.; Ribe, Lars Riisgaard


    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...

  20. Antiausterity activity of arctigenin enantiomers: importance of (2R,3R)-absolute configuration. (United States)

    Awale, Suresh; Kato, Mamoru; Dibwe, Dya Fita; Li, Feng; Miyoshi, Chika; Esumi, Hiroyasu; Kadota, Shigetoshi; Tezuka, Yasuhiro


    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.


    Institute of Scientific and Technical Information of China (English)

    甘作新; 葛渭高; 赵素霞; 仵永先


    In this paper, by introducing a new concept of absolute stability for a certain argument, necessary and sufficient conditions for absolute stability of general Lurie indirect control systems are obtained, and some practical sufficient conditions are also given.

  2. Bioefficacy of tea catechins encapsulated in casein micelles tested on a normal mouse cell line (4D/WT) and its cancerous counterpart (D/v-src) before and after in vitro digestion. (United States)

    Haratifar, Sanaz; Meckling, Kelly A; Corredig, Milena


    Numerous studies have demonstrated that tea catechins form complexes with milk proteins, especially caseins. Much less work has been conducted to understand the metabolic conversions of tea-milk complexes during gastro-duodenal digestion. The objective of this study was to determine the significance of this association on the digestibility of the milk proteins and on the bioaccessibility of the tea polyphenol epigallocatechin gallate (EGCG). An in vitro digestion model mimicking the gastric and duodenal phases of the human gastrointestinal tract was employed to follow the fate of the milk proteins during digestion and determine the bioefficacy of EGCG isolated or encapsulated with the caseins. The samples, before and after digestion, were tested using two parallel colonic epithelial cell lines, a normal line (4D/WT) and its cancerous transformed counterpart (D/v-src). EGCG caused a decrease in proliferation of cancer cells, while in normal cells, neither isolated nor encapsulated EGCG affected cell proliferation, at concentrations <0.15 mg ml(-1). At higher concentrations, both isolated and encapsulated produced similar decreases in proliferation. On the other hand, the bioefficacy on the cancer cell line showed some differences at lower concentrations. The results demonstrated that regardless of the extent of digestion of the nanoencapsulated EGCG, the bioefficacy of EGCG was not diminished, confirming that casein micelles are an appropriate delivery system for polyphenols.

  3. Absolute stereochemistry of altersolanol A and alterporriols. (United States)

    Kanamaru, Saki; Honma, Miho; Murakami, Takanori; Tsushima, Taro; Kudo, Shinji; Tanaka, Kazuaki; Nihei, Ken-Ichi; Nehira, Tatsuo; Hashimoto, Masaru


    The absolute stereochemistry of altersolanol A (1) was established by observing a positive exciton couplet in the circular dichroism (CD) spectrum of the C3,C4-O-bis(2-naphthoyl) derivative 10 and by chemical correlations with known compound 8. Before the discussion, the relative stereochemistry of 1 was confirmed by X-ray crystallographic analysis. The shielding effect at C7'-OMe group by C1-O-benzoylation established the relative stereochemical relationship between the C8-C8' axial bonding and the C1-C4/C1'-C4' polyol moieties of alterporriols E (3), an atropisomer of the C8-C8' dimer of 1. As 3 could be obtained by dimerization of 1 in vitro, the absolute configuration of its central chirality elements (C1-C4) must be identical to those of 1. Spectral comparison between the experimental and theoretical CD spectra supported the above conclusion. Axial stereochemistry of novel C4-O-deoxy dimeric derivatives, alterporriols F (4) and G (5), were also revealed by comparison of their CD spectra to those of 2 and 3.

  4. Absolute Electron Extraction Efficiency of Liquid Xenon (United States)

    Kamdin, Katayun; Mizrachi, Eli; Morad, James; Sorensen, Peter


    Dual phase liquid/gas xenon time projection chambers (TPCs) currently set the world's most sensitive limits on weakly interacting massive particles (WIMPs), a favored dark matter candidate. These detectors rely on extracting electrons from liquid xenon into gaseous xenon, where they produce proportional scintillation. The proportional scintillation from the extracted electrons serves to internally amplify the WIMP signal; even a single extracted electron is detectable. Credible dark matter searches can proceed with electron extraction efficiency (EEE) lower than 100%. However, electrons systematically left at the liquid/gas boundary are a concern. Possible effects include spontaneous single or multi-electron proportional scintillation signals in the gas, or charging of the liquid/gas interface or detector materials. Understanding EEE is consequently a serious concern for this class of rare event search detectors. Previous EEE measurements have mostly been relative, not absolute, assuming efficiency plateaus at 100%. I will present an absolute EEE measurement with a small liquid/gas xenon TPC test bed located at Lawrence Berkeley National Laboratory.

  5. Absolute Orientation Based on Distance Kernel Functions

    Directory of Open Access Journals (Sweden)

    Yanbiao Sun


    Full Text Available The classical absolute orientation method is capable of transforming tie points (TPs from a local coordinate system to a global (geodetic coordinate system. The method is based only on a unique set of similarity transformation parameters estimated by minimizing the total difference between all ground control points (GCPs and the fitted points. Nevertheless, it often yields a transformation with poor accuracy, especially in large-scale study cases. To address this problem, this study proposes a novel absolute orientation method based on distance kernel functions, in which various sets of similarity transformation parameters instead of only one set are calculated. When estimating the similarity transformation parameters for TPs using the iterative solution of a non-linear least squares problem, we assigned larger weighting matrices for the GCPs for which the distances from the point are short. The weighting matrices can be evaluated using the distance kernel function as a function of the distances between the GCPs and the TPs. Furthermore, we used the exponential function and the Gaussian function to describe distance kernel functions in this study. To validate and verify the proposed method, six synthetic and two real datasets were tested. The accuracy was significantly improved by the proposed method when compared to the classical method, although a higher computational complexity is experienced.

  6. Expression of matrix metalloproteinases 2 and 9 in human gastric cancer and superficial gastritis (United States)

    Sampieri, Clara Luz; de la Peña, Sol; Ochoa-Lara, Mariana; Zenteno-Cuevas, Roberto; León-Córdoba, Kenneth


    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

  7. 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


    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...... and pathology and was the best general LC marker examined here. SMA was weakly expressed in peritubular cells in the fetal and infantile testis, but strongly expressed in the adult testis. In pathological testes, the numbers of DLK1-positive interstitial cells were increased. The proportion of DLK1-positive LCs...... 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 interest....

  8. A Conceptual Approach to Absolute Value Equations and Inequalities (United States)

    Ellis, Mark W.; Bryson, Janet L.


    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…

  9. Invariant and Absolute Invariant Means of Double Sequences

    Directory of Open Access Journals (Sweden)

    Abdullah Alotaibi


    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.

  10. Monoclonal antibody mapping of keratins 8 and 17 and of vimentin in normal human mammary gland, benign tumors, dysplasias and breast cancer. (United States)

    Guelstein, V I; Tchypysheva, T A; Ermilova, V D; Litvinova, L V; Troyanovsky, S M; Bannikov, G A


    The distribution of keratins 8 and 17 and of vimentin in 28 normal human mammary tissue samples, 16 benign tumors, 26 fibrocytic diseases and 52 malignant breast tumors have been studied using monoclonal antibodies HI, E3 and NT30, respectively. Three cell populations in normal mammary epithelium have been identified: luminal epithelium containing keratin 8, myoepithelium of the lobular structures positive for vimentin, and myoepithelium of extralobular ducts positive for keratin 17. In different kinds of benign tumor and dysplastic proliferation a mosaic of cells with all normal phenotypes has been observed. The majority of cells co-expressed keratins 8 and 17 or vimentin. In the overwhelming majority of carcinomas, cells did not contain myoepithelial markers (keratin 17 and vimentin) but expressed only keratin 8 specific to normal luminal epithelium.

  11. c-Jun N-terminal kinase 2 prevents luminal cell commitment in normal mammary glands and tumors by inhibiting p53/Notch1 and breast cancer gene 1 expression. (United States)

    Cantrell, Michael A; Ebelt, Nancy D; Pfefferle, Adam D; Perou, Charles M; Van Den Berg, Carla Lynn


    Breast cancer is a heterogeneous disease with several subtypes carrying unique prognoses. Patients with differentiated luminal tumors experience better outcomes, while effective treatments are unavailable for poorly differentiated tumors, including the basal-like subtype. Mechanisms governing mammary tumor subtype generation could prove critical to developing better treatments. C-Jun N-terminal kinase 2 (JNK2) is important in mammary tumorigenesis and tumor progression. Using a variety of mouse models, human breast cancer cell lines and tumor expression data, studies herein support that JNK2 inhibits cell differentiation in normal and cancer-derived mammary cells. JNK2 prevents precocious pubertal mammary development and inhibits Notch-dependent expansion of luminal cell populations. Likewise, JNK2 suppresses luminal populations in a p53-competent Polyoma Middle T-antigen tumor model where jnk2 knockout causes p53-dependent upregulation of Notch1 transcription. In a p53 knockout model, JNK2 restricts luminal populations independently of Notch1, by suppressing Brca1 expression and promoting epithelial to mesenchymal transition. JNK2 also inhibits estrogen receptor (ER) expression and confers resistance to fulvestrant, an ER inhibitor, while stimulating tumor progression. These data suggest that therapies inhibiting JNK2 in breast cancer may promote tumor differentiation, improve endocrine therapy response, and inhibit metastasis.

  12. 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


    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.

  13. Normal tissue complication probability (NTCP) models for late rectal bleeding, stool frequency and fecal incontinence after radiotherapy in prostate cancer patients

    NARCIS (Netherlands)

    Schaake, Wouter; van der Schaaf, Arjen; van Dijk, Lisanne V.; Bongaerts, Alfons H. H.; van den Bergh, Alfons C. M.; Langendijk, Johannes A.


    Background and purpose: Curative radiotherapy for prostate cancer may lead to anorectal side effects, including rectal bleeding, fecal incontinence, increased stool frequency and rectal pain. The main objective of this study was to develop multivariable NTCP models for these side effects. Material a

  14. 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


    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.

  15. 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


    the 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....

  16. Use of Absolute and Comparative Performance Feedback in Absolute and Comparative Judgments and Decisions (United States)

    Moore, Don A.; Klein, William M. P.


    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…

  17. Human papillomavirus infections in Mexican women with normal cytology, precancerous lesions, and cervical cancer: type-specific prevalence and HPV coinfections. (United States)

    Aguilar-Lemarroy, Adriana; Vallejo-Ruiz, Verónica; Cortés-Gutiérrez, Elva I; Salgado-Bernabé, Manuel Eduardo; Ramos-González, Norma Patricia; Ortega-Cervantes, Laura; Arias-Flores, Rafael; Medina-Díaz, Irma M; Hernández-Garza, Fernando; Santos-López, Gerardo; Piña-Sánchez, Patricia


    The prevalence and genotype distribution of human papillomavirus (HPV) provides the basis for designing HPV prevention programs. The prevalence rates of type-specific HPV and coinfections in samples of Mexican women were investigated in 822 women aged 18-87 years. HPV detection was performed using a Linear Array™ genotyping test. HPV infection was found in 12.4% of controls, 46.3% of those with cervical intraepithelial neoplasia 1, and 100% of those with cervical intraepithelial neoplasia 3 or cervical cancer. HPV 16 was the most prevalent type in all diagnosis groups. The HPV types most frequently found in cervical cancers were 16, 18, 45, 52, 58, and 39; HPV types 16, 62, 51, 84, 18, 53, and CP6108 were the most prevalent in control women. Considering HPV-positive samples only, coinfections occurred most often in controls (63%) and were less frequent in those with cervical cancer (26%). The most frequent viral types in coinfections with HPV 16 in control women were HPV 62, 51, and 84; in women with cervical cancers, HPV 18, 39, and 70 were most common. In conclusion, in addition to HPV types 16 and 18, types 45, 39, 58, 52, and 71 were found in cervical cancers in Mexican women (78%); among them, only 65% were attributable to HPV types 16 and 18. Therefore, it is necessary to consider these viral types in the design of new vaccines, and to determine whether certain HPV types coinfecting with HPV 16 in precursor lesions determine tumor progression or regression.

  18. How is an absolute democracy possible?

    Directory of Open Access Journals (Sweden)

    Joanna Bednarek


    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.

  19. Absolute geostrophic currents in global tropical oceans (United States)

    Yang, Lina; Yuan, Dongliang


    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.


    Directory of Open Access Journals (Sweden)



    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.

  1. Colon Cancer Risk Assessment - Gauss Program (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.

  2. MSH6 Mutations are Frequent in Hereditary Nonpolyposis Colorectal Cancer Families With Normal pMSH6 Expression as Detected by Immunohistochemistry

    DEFF Research Database (Denmark)

    Okkels, Henrik; Larsen, K.L.; Thorlacius-Ussing, O.;


    INTRODUCTION:: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant condition accounting for 2% to 4% of all colorectal cancer cases worldwide. Families with germ line mutations in 1 of 6 mismatch repair genes are known as Lynch syndrome families. The largest number...... of mutations has been detected in the mismatch repair genes MLH1 and MSH2, but several mutations in MSH6 have also been demonstrated. AIM:: Whether HNPCC families are screened for mutations in mismatch repair genes often relies on their immunohistochemical profile. The aim of the present study was to evaluate...... this approach in Lynch families carrying mutations in MSH6. MATERIALS AND METHODS:: Results of the screening of the MSH6 gene in HNPCC families were compared with those obtained on immunohistochemical protein analysis. RESULTS:: In 56 (7%) of 815 families, at least 1 MSH6 mutation, 23 definitively pathogenic...

  3. Genetic polymorphisms of PAI-1 and PAR-1 are associated with acute normal tissue toxicity in Chinese rectal cancer patients treated with pelvic radiotherapy. (United States)

    Zhang, Hui; Wang, Mengyun; Shi, Tingyan; Shen, Lijun; Zhu, Ji; Sun, Menghong; Deng, Yun; Liang, Liping; Li, Guichao; Wu, Yongxin; Fan, Ming; Wei, Qingyi; Zhang, Zhen


    Plasminogen activator inhibitor type 1 (PAI-1) and protease-activated receptor-1 (PAR-1) are crucial mediators of the intestinal microenvironment and are involved in radiation-induced acute and chronic injury. To evaluate whether genetic polymorphisms of PAI-1 and PAR-1 were predictors of radiation-induced injury in patients with rectal cancer, we retrospectively evaluated 356 rectal cancer patients who had received pelvic radiotherapy and analyzed the association of genetic polymorphisms of PAI-1 and PAR-1 with acute toxicities after radiotherapy. Acute adverse events were scored, including dermatitis, fecal incontinence (anal toxicity), hematological toxicity, diarrhea, and vomiting. The patients were grouped into grade ≥2 and grade 0-1 toxicity groups to analyze the acute toxicities. Genotyping of six single nucleotide polymorphisms (SNPs) of PAI-1 and PAR-1 was performed using TaqMan assays. A logistic regression model was used to estimate the odds ratios and 95% confidence intervals. Of the 356 individuals, 264 (72.5%) had grade ≥2 total toxicities; within this group, there were 65 (18.3%) individuals who reached grade ≥3 toxicities. There were 19.5% (69/354) and 36.9% (130/352) patients that developed grade ≥2 toxicities for diarrhea and fecal incontinence, respectively. The variant genotype GG of rs1050955 in PAI-1 was found to be negatively associated with the risk of diarrhea and incontinence (PPAI-1 were associated with an increased risk of incontinence. The CT genotype of PAR-1 rs32934 was associated with an increased risk of total toxicity compared with the CC allele. Our results demonstrated that SNPs in the PAI-1 and PAR-1 genes were associated with acute injury in rectal cancer patients treated with pelvic irradiation. These SNPs may be useful biomarkers for predicting acute radiotoxicity in patients with rectal cancer if validated in future studies.

  4. Effect of different cytokines on mammaglobin and maspin gene expression in normal leukocytes: possible relevance to the assays for the detection of micrometastatic breast cancer


    Ballestrero, A.; Garuti, A.; Bertolotto, M.; Rocco, I; Boy, D.; Nencioni, A.; Ottonello, L; Patrone, F.


    In cancer patients, the ability to detect disseminated tumour cells in peripheral blood or bone marrow could improve prognosis and consent both early detection of metastatic disease and monitoring of the efficacy of systemic therapy. These objectives remain elusive mainly due to the lack of specific genetic markers for solid tumours. The use of surrogate tissue-specific markers can reduce the specificity of the assays and give rise to a clinically unacceptable false-positive rate. Mammaglobin...

  5. CHRNA5 as negative regulator of nicotine signaling in normal and cancer bronchial cells: effects on motility, migration and p63 expression. (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


    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.

  6. HDR monotherapy for prostate cancer: A simulation study to determine the effect of catheter displacement on target coverage and normal tissue irradiation

    NARCIS (Netherlands)

    I.-K.K. Kolkman-Deurloo (Inger-Karina); M.A. Roos (Martin); S. Aluwini (Shafak)


    textabstractPurpose: The aim of this study was to systematically analyse the effect of catheter displacements both on target coverage and normal tissue irradiation in fractionated high dose rate (HDR) prostate brachytherapy, using a simulation study, and to define tolerances for catheter displacemen

  7. Cancer (United States)

    ... uses a surgical tool to remove the tumor.Mohs' surgery. Layers of cancer cells are removed one ... usually have not been approved by the U.S. Food and Drug Administration (FDA). The medicine may have ...

  8. 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

    Directory of Open Access Journals (Sweden)

    Uram Ł


    Full Text Available Łukasz Uram,1 Magdalena Szuster,1 Aleksandra Filipowicz,2 Krzysztof Gargasz,3 Stanisław Wołowiec,3 Elżbieta Wałajtys-Rode4 1Bioorganic Chemistry Laboratory, Faculty of Chemistry, Rzeszow University of Technology, 2Cosmetology Department, University of Information Technology and Management in Rzeszow, 3Institute of Nursery and Health Sciences, Faculty of Medicine, University of Rzeszow, Rzeszow, 4Department of Drug Technology and Biotechnology, Faculty of Chemistry, Warsaw University of Technology, Warsaw, Poland Abstract: 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

  9. Discordant assessment of tumor biomarkers by histopathological and molecular assays in the EORTC randomized controlled 10041/BIG 03-04 MINDACT trial breast cancer : Intratumoral heterogeneity and DCIS or normal tissue components are unlikely to be the cause of discordance. (United States)

    Viale, Giuseppe; Slaets, Leen; de Snoo, Femke A; Bogaerts, Jan; Russo, Leila; van't Veer, Laura; Rutgers, Emiel J T; Piccart-Gebhart, Martine J; Stork-Sloots, Lisette; Dell'Orto, Patrizia; Glas, Annuska M; Cardoso, Fatima


    Accurate identification of breast cancer patients most likely to benefit from adjuvant systemic therapies is crucial. Better understanding of differences between methods can lead to an improved ER, PgR, and HER-2 assessment. The purpose of this preplanned translational research is to investigate the correlation of central IHC/FISH assessments with microarray mRNA readouts of ER, PgR, and HER-2 status in the MINDACT trial and to determine if any discordance could be attributed to intratumoral heterogeneity or the DCIS and normal tissue components in the specimens. MINDACT is an international, prospective, randomized, phase III trial investigating the clinical utility of MammaPrint in selecting patients with early breast cancer for adjuvant chemotherapy (n = 6694 patients). Gene-expression data were obtained by TargetPrint; IHC and/or FISH were assessed centrally (n = 5788; 86 %). Macroscopic and microscopic evaluation of centrally submitted FFPE blocks identified 1427 cases for which the very same sample was submitted for gene-expression analysis. TargetPrint ER had a positive agreement of 98 %, and a negative agreement of 95 % with central pathology. Corresponding figures for PgR were 85 and 94 % and for HER-2 72 and 99 %. Agreement of mRNA versus central protein was not different when the same or a different portion of the tumor tissue was analyzed or when DCIS and/or normal tissue was included in the sample subjected to mRNA assays. This is the first large analysis to assess the discordance rate between protein and mRNA analysis of breast cancer markers, and to look into intratumoral heterogeneity, DCIS, or normal tissue components as a potential cause of discordance. The observed difference between mRNA and protein assessment for PgR and HER-2 needs further research; the present analysis does not support intratumoral heterogeneity or the DCIS and normal tissue components being likely causes of the discordance.

  10. Proliferation and ovarian hormone signaling are impaired in normal breast tissues from women with BRCA1 mutations: benefit of a progesterone receptor modulator treatment as a breast cancer preventive strategy in women with inherited BRCA1 mutations (United States)

    Communal, Laudine; Courtin, Aurélie; Mourra, Najat; Lahlou, Najiba; Le Guillou, Morwenna; de Jotemps, Muriel Perrault; Chauvet, Marie-Pierre; Chaouat, Marc; Pujol, Pascal; Feunteun, Jean; Delaloge, Suzette; Forgez, Patricia; Gompel, Anne


    Women with inherited BRCA1 mutations have an elevated risk (40-80%) for developing breast and ovarian cancers. Reproductive history has been reported to alter this risk, suggesting a relationship between ovarian hormone signaling and BRCA1-related tumor development. BRCA1 interactions with estrogen receptor (ER) and progesterone receptor (PR) signaling were previously described in human breast cancer cell lines and mouse models. However, few studies have examined the effect of ovarian hormone regulation in normal human breast tissues bearing a heterozygous BRCA1 mutation. This study compares the proliferation level (Ki67) and the expression of ER, PR, and of the PR target gene, fatty acid synthase (FASN), in histologically normal breast tissues from women with BRCA1 mutations (BRCA1+/mut, n=23) or without BRCA1 mutations (BRCA1+/+, n=28). BRCA1+/mut tissues showed an increased proliferation and impaired hormone receptor expression with a marked loss of the PR isoform, PR-B. Responses to estradiol and progesterone treatments in BRCA1+/mut and BRCA1+/+ breast tissues were studied in a mouse xenograft model, and showed that PR and FASN expression were deregulated in BRCA1+/mut breast tissues. Progesterone added to estradiol treatment increased the proliferation in a subset of BRCA1+/mut breast tissues. The PR inhibitor, ulipristal acetate (UPA), was able to reverse this aberrant progesterone-induced proliferation. This study suggests that a subset of women with BRCA1 mutations could be candidates for a UPA treatment as a preventive breast cancer strategy. PMID:27246982

  11. Immunohistochemical expression of ornithine decarboxylase, diamine oxidase, putrescine, and spermine in normal canine enterocolic mucosa, in chronic colitis, and in colorectal cancer. (United States)

    Rossi, Giacomo; Cerquetella, Matteo; Pengo, Graziano; Mari, Subeide; Balint, Emilia; Bassotti, Gabrio; Manolescu, Nicolae


    We compared the immunohistochemical expression of putrescine (PUT), spermine (SPM), ornithine decarboxylase (ODC), and diamine oxidase (DAO) in bioptic samples of canine colonic mucosa with chronic inflammation (i.e., granulomatous colitis and lymphoplasmacytic colitis) or neoplasia. Single and total polyamines levels were significantly higher in neoplastic tissue than in normal samples. Samples with different degrees of inflammation showed a general decrease expression of ODC if compared to controls; SPM was practically not expressed in control samples and very low in samples with chronic-granulomatous inflammation. In carcinomatous samples, the ODC activity was higher with respect to controls and samples with inflammation. This is the first description of polyamines expression in dog colonic mucosa in normal and in different pathological conditions, suggesting that the balance between polyamine degradation and biosynthesis is evidently disengaged during neoplasia.

  12. Immunohistochemical Expression of Ornithine Decarboxylase, Diamine Oxidase, Putrescine, and Spermine in Normal Canine Enterocolic Mucosa, in Chronic Colitis, and in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Giacomo Rossi


    Full Text Available We compared the immunohistochemical expression of putrescine (PUT, spermine (SPM, ornithine decarboxylase (ODC, and diamine oxidase (DAO in bioptic samples of canine colonic mucosa with chronic inflammation (i.e., granulomatous colitis and lymphoplasmacytic colitis or neoplasia. Single and total polyamines levels were significantly higher in neoplastic tissue than in normal samples. Samples with different degrees of inflammation showed a general decrease expression of ODC if compared to controls; SPM was practically not expressed in control samples and very low in samples with chronic-granulomatous inflammation. In carcinomatous samples, the ODC activity was higher with respect to controls and samples with inflammation. This is the first description of polyamines expression in dog colonic mucosa in normal and in different pathological conditions, suggesting that the balance between polyamine degradation and biosynthesis is evidently disengaged during neoplasia.

  13. 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


    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.


    Directory of Open Access Journals (Sweden)

    Daniela SIMTION


    Full Text Available Profitability of an economic unit is expressed through a system of indicators, because "no index or economic category can reflect the total, perfect, complex reality of economic phenomena or processes. Each expresses a side of concrete, essential details (indexes, but a full one (economic category. This system of indexes for profitability is characterized by a higher degree of consolidation, of reflection of the economic-financial results. They must be correlated to the other indexes of economic efficiency from the various subsystems that constitute the factors which determine the actual amount of profit and the rate of return. Each indicator has a certain form of expression according to the phenomena to which it refers. Thus, they can be expressed in relative sizes as medium sizes or indexes. They can also be expressed in physical, conventional or value units. The ability to develop monetary results can not be judged independently to the employed means for achieving them. Therefore, the profitability analysis is not limited to investigating its absolute indexes but also the relative ones, obtained by comparing the results to the means employed or consumed for developing the specific activity

  15. Gyrokinetic Statistical Absolute Equilibrium and Turbulence

    Energy Technology Data Exchange (ETDEWEB)

    Jian-Zhou Zhu and Gregory W. Hammett


    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.

  16. FGFR4 Gly388Arg polymorphism may affect the clinical stage of patients with lung cancer by modulating the transcriptional profile of normal lung. (United States)

    Falvella, Felicia S; Frullanti, Elisa; Galvan, Antonella; Spinola, Monica; Noci, Sara; De Cecco, Loris; Nosotti, Mario; Santambrogio, Luigi; Incarbone, Matteo; Alloisio, Marco; Calabrò, Elisa; Pastorino, Ugo; Skaug, Vidar; Haugen, Aage; Taioli, Emanuela; Dragani, Tommaso A


    The association of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism with clinical stage and overall survival in a series of 541 Italian lung adenocarcinoma (ADCA) patients indicated a significantly decreased survival in patients carrying the rare Arg388 allele as compared to that in Gly/Gly homozygous patients [hazard ratio (HR) = 1.5; 95% confidence interval (CI) 1.1-1.9], with the decrease related to the association of the same polymorphism with clinical stage (HR = 1.8, 95% CI 1.3-2.6). By contrast, no significant association was detected in small series of either Norwegian lung ADCA patients or Italian lung squamous cell carcinoma (SQCC) patients. Single nucleotide polymorphisms of known FGFR4 ligands expressed in lung (FGF9, FGF18 and FGF19) were not associated with clinical stage or survival and showed no interaction with FGFR4. Analysis of gene expression profile in normal lungs according to FGFR4 genotype indicated a specific transcript pattern associated with the allele carrier status, suggesting a functional role for the FGFR4 polymorphism already detectable in normal lung. These findings confirm the significant association of the FGFR4 Gly388Arg polymorphism with clinical stage and overall survival in an Italian lung ADCA population and demonstrate a FGFR4 genotype-dependent transcriptional profile present in normal lung tissue.

  17. Positioning, alignment and absolute pointing of the ANTARES neutrino telescope

    Energy Technology Data Exchange (ETDEWEB)

    Fehr, F [Erlangen Centre for Astroparticle Physics, Erwin-Rommel-Str. 1 (Germany); Distefano, C, E-mail: fehr@physik.uni-erlangen.d [INFN Laboratori Nazional del Sud, Via S. Sofia 62, 95123 Catania (Italy)


    A precise detector alignment and absolute pointing is crucial for point-source searches. The ANTARES neutrino telescope utilises an array of hydrophones, tiltmeters and compasses for the relative positioning of the optical sensors. The absolute calibration is accomplished by long-baseline low-frequency triangulation of the acoustic reference devices in the deep-sea with a differential GPS system at the sea surface. The absolute pointing can be independently verified by detecting the shadow of the Moon in cosmic rays.

  18. 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


    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.

  19. The absolute disparity anomaly and the mechanism of relative disparities. (United States)

    Chopin, Adrien; Levi, Dennis; Knill, David; Bavelier, Daphne


    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).

  20. Comparison of available measurements of the absolute fluorescence yield

    CERN Document Server

    Rosado, J; Arqueros, F


    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...

  1. 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


    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.

  2. ZIP8 expression in human proximal tubule cells, human urothelial cells transformed by Cd+2 and As+3 and in specimens of normal human urothelium and urothelial cancer


    Ajjimaporn Amornpan; Botsford Tom; Garrett Scott H; Sens Mary; Zhou Xu; Dunlevy Jane R; Sens Donald A; Somji Seema


    Abstract Background ZIP8 functions endogenously as a Zn+2/HCO3- symporter that can also bring cadmium (Cd+2) into the cell. It has also been proposed that ZIP8 participates in Cd-induced testicular necrosis and renal disease. In this study real-time PCR, western analysis, immunostaining and fluorescent localization were used to define the expression of ZIP8 in human kidney, cultured human proximal tubule (HPT) cells, normal and malignant human urothelium and Cd+2 and arsenite (As+3) transform...

  3. Evaluation of the absolute regional temperature potential

    Directory of Open Access Journals (Sweden)

    D. T. Shindell


    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.

  4. Absolute Radiometric Calibration of KOMPSAT-3A (United States)

    Ahn, H. Y.; Shin, D. Y.; Kim, J. S.; Seo, D. C.; Choi, C. U.


    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.

  5. Normalizing the causality between time series

    CERN Document Server

    Liang, X San


    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 ...

  6. 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.


    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.

  7. 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. (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


    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.


    Institute of Scientific and Technical Information of China (English)

    GAN Zuoxin; HAN Jingqing; ZHAO Suxia; WU Yongxian


    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.

  9. A Global Forecast of Absolute Poverty and Employment. (United States)

    Hopkins, M. J. D.


    Estimates are made of absolute poverty and employment under the hypothesis that existing trends continue. Concludes that while the number of people in absolute poverty is not likely to decline by 2000, the proportion will fall. Jobs will have to grow 3.9% per year in developing countries to achieve full employment. (JOW)

  10. Absolute Humidity and the Seasonality of Influenza (Invited) (United States)

    Shaman, J. L.; Pitzer, V.; Viboud, C.; Grenfell, B.; Goldstein, E.; Lipsitch, M.


    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.

  11. Novalis' Poetic Uncertainty: A "Bildung" with the Absolute (United States)

    Mika, Carl


    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…

  12. Determination of Absolute Zero Using a Computer-Based Laboratory (United States)

    Amrani, D.


    We present a simple computer-based laboratory experiment for evaluating absolute zero in degrees Celsius, which can be performed in college and undergraduate physical sciences laboratory courses. With a computer, absolute zero apparatus can help demonstrators or students to observe the relationship between temperature and pressure and use…

  13. Absolute instruments and perfect imaging in geometrical optics

    CERN Document Server

    Tyc, Tomas; Sarbort, Martin; Bering, Klaus


    We investigate imaging by spherically symmetric absolute instruments that provide perfect imaging in the sense of geometrical optics. We derive a number of properties of such devices, present a general method for designing them and use this method to propose several new absolute instruments, in particular a lens providing a stigmatic image of an optically homogeneous region and having a moderate refractive index range.

  14. Normal Pressure Hydrocephalus (NPH) (United States)

    ... local chapter Join our online community Normal Pressure Hydrocephalus (NPH) Normal pressure hydrocephalus is a brain disorder ... Symptoms Diagnosis Causes & risks Treatments About Normal Pressure Hydrocephalus Normal pressure hydrocephalus occurs when excess cerebrospinal fluid ...

  15. 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)


    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

  16. Identification of biomarkers of radioresponse and subsequent progression towards lung cancer in normal human bronchial epithelial cells after HZE particle irradiation (United States)

    Story, Michael; Ding, Liang-Hao; Park, Seongmi; Minna, John

    mice. Tumors that develop will be examined for radiosensitivity and aggres-siveness and will be also be examined for genomic, epigenomic and proteomic changes. Com-parisons of unirradiated cells, transformed cells, and tumor cells will allow the development of biomarkers of radiation-induced lung cancer, in particular HZE-induced lung tumors, and help to generate risk factors for lung cancer as a result of travel through deep space environments.

  17. CANCER

    Directory of Open Access Journals (Sweden)

    N. Kavoussi


    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.

  18. Correlation of contrast-enhanced MR images with the histopathology of minimally invasive thermal and cryoablation cancer treatments in normal dog prostates (United States)

    Bouley, D. M.; Daniel, B.; Butts Pauly, K.; Liu, E.; Kinsey, A.; Nau, W.; Diederich, C. J.; Sommer, G.


    Magnetic Resonance Imaging (MRI) is a promising tool for visualizing the delivery of minimally invasive cancer treatments such as high intensity ultrasound (HUS) and cryoablation. We use an acute dog prostate model to correlate lesion histopathology with contrast-enhanced (CE) T1 weighted MR images, to aid the radiologists in real time interpretation of in vivo lesion boundaries and pre-existing lesions. Following thermal or cryo treatments, prostate glands are removed, sliced, stained with the vital dye triphenyl tetrazolium chloride, photographed, fixed and processed in oversized blocks for routine microscopy. Slides are scanned by Trestle Corporation at .32 microns/pixel resolution, the various lesions traced using annotation software, and digital images compared to CE MR images. Histologically, HUS results in discrete lesions characterized by a "heat-fixed" zone, in which glands subjected to the highest temperatures are minimally altered, surrounded by a rim or "transition zone" composed of severely fragmented, necrotic glands, interstitial edema and vascular congestion. The "heat-fixed" zone is non-enhancing on CE MRI while the "transition zone" appears as a bright, enhancing rim. Likewise, the CE MR images for cryo lesions appear similar to thermally induced lesions, yet the histopathology is significantly different. Glands subjected to prolonged freezing appear totally disrupted, coagulated and hemorrhagic, while less intensely frozen glands along the lesion edge are partially fragmented and contain apoptotic cells. In conclusion, thermal and cryo-induced lesions, as well as certain pre-existing lesions (cystic hyperplasia - non-enhancing, chronic prostatitis - enhancing) have particular MRI profiles, useful for treatment and diagnostic purposes.

  19. 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: [Institute of Biomedical Engineering, École Polytechnique de Montréal, Montreal, Quebec H3C 3A7 (Canada); Montreal Heart Institute, Montreal, Quebec H1T 1C8 (Canada)


    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.

  20. 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: [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


    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.

  1. Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development

    Directory of Open Access Journals (Sweden)

    Nick D.L. Owens


    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.

  2. 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


    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].

  3. 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.


    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.

  4. Application of the rank-based method to DNA methylation for cancer diagnosis. (United States)

    Li, Hongdong; Hong, Guini; Xu, Hui; Guo, Zheng


    Detecting aberrant DNA methylation as diagnostic or prognostic biomarkers for cancer has been a topic of considerable interest recently. However, current classifiers based on absolute methylation values detected from a cohort of samples are typically difficult to be transferable to other cohorts of samples. Here, focusing on relative methylation levels, we employed a modified rank-based method to extract reversal pairs of CpG sites whose relative methylation level orderings differ between disease samples and normal controls for cancer diagnosis. The reversal pairs identified for five cancer types respectively show excellent prediction performance with the accuracy above 95%. Furthermore, when evaluating the reversal pairs identified for one cancer type in an independent cohorts of samples, we found that they could distinguish different subtypes of this cancer or different malignant stages including early stage of this cancer from normal controls. The identified reversal pairs also appear to be specific to cancer type. In conclusion, the reversal pairs detected by the rank-based method could be used for accurate cancer diagnosis, which are transferable to independent cohorts of samples.

  5. 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


    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.

  6. Normalization: A Preprocessing Stage


    Patro, S. Gopal Krishna; Sahu, Kishore Kumar


    As we know that the normalization is a pre-processing stage of any type problem statement. Especially normalization takes important role in the field of soft computing, cloud computing etc. for manipulation of data like scale down or scale up the range of data before it becomes used for further stage. There are so many normalization techniques are there namely Min-Max normalization, Z-score normalization and Decimal scaling normalization. So by referring these normalization techniques we are ...

  7. Absolute homogeneity test of Kelantan catchment precipitation series (United States)

    Ros, Faizah Che; Tosaka, Hiroyuki; Sasaki, Kenji; Sidek, Lariyah Mohd; Basri, Hidayah


    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.

  8. An All Fiber White Light Interferometric Absolute Temperature Measurement System

    Directory of Open Access Journals (Sweden)

    Jeonggon Harrison Kim


    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.

  9. Lower liver cancer risk with antiviral therapy in chronic hepatitis B patients with normal to minimally elevated ALT and no cirrhosis (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.


    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

  10. Testicular Cancer (United States)

    ... or testicles that aren't shaped normally.Have Klinefelter's syndrome (a genetic condition where male infants are born ... contributed by: editorial staff Tags: cryptorehidism, Klinefelter's syndrome, malignancies, scrotal mass, scrotal masses, testicular cancer, testicular ...

  11. Breast Cancer Risk Assessment SAS Macro (Gail Model) (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.

  12. Changes in Absolute Sea Level Along U.S. Coasts (United States)

    U.S. Environmental Protection Agency — This map shows changes in absolute sea level from 1960 to 2016 based on satellite measurements. Data were adjusted by applying an inverted barometer (air pressure)...

  13. Monochromator-Based Absolute Calibration of Radiation Thermometers (United States)

    Keawprasert, T.; Anhalt, K.; Taubert, D. R.; Hartmann, J.


    A monochromator integrating-sphere-based spectral comparator facility has been developed to calibrate standard radiation thermometers in terms of the absolute spectral radiance responsivity, traceable to the PTB cryogenic radiometer. The absolute responsivity calibration has been improved using a 75 W xenon lamp with a reflective mirror and imaging optics to a relative standard uncertainty at the peak wavelength of approximately 0.17 % ( k = 1). Via a relative measurement of the out-of-band responsivity, the spectral responsivity of radiation thermometers can be fully characterized. To verify the calibration accuracy, the absolutely calibrated radiation thermometer is used to measure Au and Cu freezing-point temperatures and then to compare the obtained results with the values obtained by absolute methods, resulting in T - T 90 values of +52 mK and -50 mK for the gold and copper fixed points, respectively.

  14. Significance of absolute energy scale for physics at BESⅢ

    Institute of Scientific and Technical Information of China (English)

    FU Cheng-Dong; MO Xiao-Hu


    The effects of absolute energy calibration on BESⅢ physics are discussed in detail,which mainly involve the effects on τ mass measurement,cross section scan measurement,and generic error determination in other measurements.


    Directory of Open Access Journals (Sweden)

    Farhat Iqbal


    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.

  16. Absolute Free Energies for Biomolecules in Implicit or Explicit Solvent (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.

  17. Spectra of absolute instruments from the WKB approximation

    CERN Document Server

    Tyc, Tomas


    We calculate frequency spectra of absolute optical instruments using the WKB approximation. The resulting eigenfrequencies approximate the actual values very accurately, in some cases they even give the exact values. Our calculations confirm results obtained previously by a completely different method. In particular, the eigenfrequencies of absolute instruments form tight groups that are almost equidistantly spaced. We demonstrate our method and its results on several examples.

  18. Global trends in relative and absolute wealth concentrations



    This paper compares changes in relative and absolute wealth concentrations to establish if both processes have followed similar trajectories. The findings indicate that while the level of relative wealth concentration has increased recently, it is not extraordinarily high in an historical perspective. On the contrary, the level of absolute wealth concentration is most likely higher than that previously occurred because of the increase in the wealth holdings and population size of high net wor...

  19. Expression profile of saccharide epitope CaMBr1 in normal and neoplastic tissue from dogs, cats, and rats: implication for the development of human-derived cancer vaccines. (United States)

    Adobati, E; Zacchetti, A; Perico, M E; Cremonesi, F; Rasi, G; Vallebona, P S; Hagenaars, M; Kuppen, P J; Pastan, I; Panza, L; Russo, G; Colnaghi, M I; Canevari, S


    CaMBr1 is a blood group-related tumour-associated antigen, whose pattern of expression provides a therapeutic window for passive or active immunotherapy and points to the promise of a vaccine against carcinomas overexpressing this antigen. In this context, an animal model that closely mimics the human situation would be extremely useful. We, therefore, utilised the murine monoclonal antibody MBr1, which defines CaMBr1, as a useful probe to detect the molecule targeted for vaccine development on canine and feline spontaneous breast and uterus tumours and on their normal counterparts, and on rat normal tissues and carcinoma cell lines. Immunoperoxidase staining of cryostat sections revealed homogeneous CaMBr1 expression only in normal feline uterus and a uterus papilloma, whereas MBr1 reactivity was very weak and heterogeneous in normal (1/3 and 1/3) and tumour (1/10 and 1/6) breast tissues from dogs and cats, respectively. In contrast, the data obtained in rat tissues were reproducible in the strains tested and showed that CaMBr1 was expressed in all epithelial tissues of the digestive tract, although with variable intensities. Monoclonal antibody staining appeared to correspond to membrane-bound structures as well as mucinous secretions. Similarly, secretion products of lactating mammary glands expressed CaMBr1. The spectrum of expression on rat digestive tract was broader than that in humans but the specificity of MBr1 reactivity was confirmed by competition assay with a synthetic tetrasaccharide that mimics the CaMBr1 antigen. On FACS analysis, only one of two clonal derivatives of the rat breast carcinoma line RAMA 25 expressed CaMBr1, and a negative cell subset was evident in repeated experiments. By contrast, both colon carcinoma lines, DHD/K12 and CC531, showed staining with MBr1, albeit at different levels of intensity, and no evidence of a negative subset. The cell line CC531 maintained or even increased CaMBr1 expression levels following transplantation in

  20. Impact of statistical learning methods on the predictive power of multivariate normal tissue complication probability models

    NARCIS (Netherlands)

    Xu, Cheng-Jian; van der Schaaf, Arjen; Schilstra, Cornelis; Langendijk, Johannes A.; van t Veld, Aart A.


    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

  1. Cancer immunology: the search for specificity. (United States)

    Old, L J


    The major focus of cancer immunology has shifted away from arguments about the validity of the immunosurveillance theory of cancer to the more basic question of tumor-specific antigens. Despite vast effort aimed at demonstrations of such antigens, their existence in the generality of cancer remains unproved. Serological analysis of 3 tumor types, mouse leukemia and sarcoma and human malignant melanoma, has received the most attention, and a rudimentary classification of the surface antigens expressed by these tumors has begun to emerge. The prime candidates for antigens that can be considered tumor specific are the few instances of Class 1 antigens that have now been serologically defined on mouse and human tumors. These antigens show an absolute restriction to individual tumors and are not demonstrable on any other normal or malignant cell type. Biochemical and genetic characterizations of Class 1 antigens represent an essential next step in an evaluation of the significance of these antigens. The surprising features of the thymus leukemia (TL) antigens of the mouse provide insight into the genetic origin of another key class of tumor antigens, i.e., those with characteristic properties of both differentiation and tumor-specific antigens. In normal mice, TL antigens are restricted to cells in the thymus, and strains differ with regard to expression versus nonexpression of TL antigens. Genetic information for TL is universal in mice, however, as leukemias that develop in mice normally lacking TL are found to express TL. What is clear from the past two decades of research in cancer immunology is that a far more detailed knowledge of surface antigens of tumor cells will be necessary before we can begin to assess the possibility of immunological control of cancer.

  2. Facile synthesis of mercaptosuccinic acid-capped CdTe/CdS/ZnS core/double shell quantum dots with improved cell viability on different cancer cells and normal cells (United States)

    Parani, Sundararajan; Bupesh, Giridharan; Manikandan, Elayaperumal; Pandian, Kannaiyan; Oluwafemi, Oluwatobi Samuel


    Water-soluble, mercaptosuccinic acid (MSA)-capped CdTe/CdS/ZnS core/double shell quantum dots (QDs) were prepared by successive growth of CdS and ZnS shells on the as-synthesized CdTe/CdSthin core/shell quantum dots. The formation of core/double shell structured QDs was investigated by ultraviolet-visible (UV-Vis) absorption and photoluminescence (PL) spectroscopy, PL decay studies, X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The core/double shell QDs exhibited good photoluminescence quantum yield (PLQY) which is 70% higher than that of the parent core/shell QDs, and they are stable for months. The average particle size of the core/double shell QDs was ˜3 nm as calculated from the transmission electron microscope (TEM) images. The cytotoxicity of the QDs was evaluated on a variety of cancer cells such as HeLa, MCF-7, A549, and normal Vero cells by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cell viability assay. The results showed that core/double shell QDs were less toxic to the cells when compared to the parent core/shell QDs. MCF-7 cells showed proliferation on incubation with QDs, and this is attributed to the metalloestrogenic activity of cadmium ions released from QDs. The core/double shell CdTe/CdS/ZnS (CSS) QDs were conjugated with transferrin and successfully employed for the biolabeling and fluorescent imaging of HeLa cells. These core/double shell QDs are highly promising fluorescent probe for cancer cell labeling and imaging applications.

  3. 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


    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.

  4. Differential Inequalities, Normality and Quasi-Normality

    CERN Document Server

    Liu, Xiaojun; Pang, Xuecheng


    We prove that if D is a domain in C, alpha>1 and c>0, then the family F of functions meromorphic in D such that |f'(z)|/(1+|f(z)|^alpha)>c for every z in D is normalin D. For alpha=1, the same assumptions imply quasi-normality but not necessarily normality.

  5. Response of MiRNA-22-3p and MiRNA-149-5p to Folate Deficiency and the Differential Regulation of MTHFR Expression in Normal and Cancerous Human Hepatocytes (United States)

    Li, Chao; Ni, Juan; Liu, Yao-Xian; Wang, Han; Liang, Zi-Qing; Wang, Xu


    Background/Aims Folic acid (FA) is a core micronutrient involved in DNA synthesis/methylation, and the metabolism of FA is responsible for genomic stability. MicroRNAs may affect gene expression during folate metabolism when cellular homeostasis is changed. This study aimed to reveal the relationship between FA deficiency and the expression of miR-22-p/miR-149-5p and the targeted regulation of miR-22-3p/miR-149-5p on the key folate metabolic gene Methylenetetrahydrofolate reductase (MTHFR). Methods Normal (HL-7702 cells) and cancerous (QGY-7703 cells) human hepatocytes were intervened in modified RPMI 1640 with FA deficiency for 21 days. The interaction between MTHFR and the tested miRNAs was verified by Dual-Luciferase Reporter Assays.