WorldWideScience

Sample records for underlying persistent cancer

  1. Molecular mechanisms underlying bacterial persisters

    DEFF Research Database (Denmark)

    Maisonneuve, Etienne; Gerdes, Kenn

    2014-01-01

    All bacteria form persisters, cells that are multidrug tolerant and therefore able to survive antibiotic treatment. Due to the low frequencies of persisters in growing bacterial cultures and the complex underlying molecular mechanisms, the phenomenon has been challenging to study. However, recent...

  2. Assessing persistence: Experiences documenting savings persistence under the California protocols

    Energy Technology Data Exchange (ETDEWEB)

    O' Drain, M.; Caulfield, T.O.

    1998-07-01

    As California enters the final stages of DSM evaluation and verification under regulation, documentation of energy savings persistence (persistence) takes center stage with respect to earnings claims. The California Protocols both simplify and complicate the process of measuring persistence. This paper discusses the California Protocols and the interaction between individual utility studies and cooperative statewide studies in fulfilling the requirements of the Protocols. It addresses measure effective useful life and measure technical degradation. The paper describes how California utilities are grappling with the practical issues of projecting effective useful life based on limited attrition data and speculative survival functions. Specifically, the paper discusses the difficulty of establishing meaningful survival functions for the breadth of measures represented in California DSM programs. Similarly, California utilities as a whole are attempting to establish exactly what measure technical degradation means, and whether it actually exists. The paper recounts the process, documents the approaches taken, and documents publicly available information on both retention based effective useful life and study based measure technical degradation. Finally, the authors propose improvements in the approach to persistence assessment.

  3. Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition* | Office of Cancer Genomics

    Science.gov (United States)

    Acquired drug resistance prevents cancer therapies from achieving stable and complete responses. Emerging evidence implicates a key role for non-mutational drug resistance mechanisms underlying the survival of residual cancer 'persister' cells. The persister cell pool constitutes a reservoir from which drug-resistant tumours may emerge. Targeting persister cells therefore presents a therapeutic opportunity to impede tumour relapse. We previously found that cancer cells in a high mesenchymal therapy-resistant cell state are dependent on the lipid hydroperoxidase GPX4 for survival.

  4. [Persistence of social representation regarding breast cancer].

    Science.gov (United States)

    Giraldo-Mora, Clara V

    2009-08-01

    Understanding the social representation of breast cancer and how it has influenced breast cancer prevention and self-care practice in a group of women from the city of Medellin. This was a qualitative study using 19 semi-structured interviews with adult females who had not had breast cancer, using maximum variation criterion as sampling technique. The analysis was orientated by grounded theory. Some women physiologically represented breast cancer while others represented it by its social and psychological effects. They identified its causes with personal and emotional problems and certain daily habits such as inadequate food ("a bodily payback for the abuses which we subject ourselves to"). The word "breast cancer" was associated with inevitable death, terror, suffering, incurability, devastation, powerlessness and pain. This cancer has strong social representation due to its severe implications for females, their attractiveness and self-image. The persistence of breast cancer's negative image is associated with "the life-style myth" (1) for which people tend to blame the patient. Our biological reductionism hides environmental, social and political factors. We are obsessed by the dangers and their control (2) and powerful images are added to these messages such as those in which "one out of nine women will develop breast cancer" to foster self-responsibility (2). However, the ghost of cancer in developing societies in which many people are still trapped is magnified and has also yet to be overcome.

  5. Stability under persistent perturbation by white noise

    International Nuclear Information System (INIS)

    Kalyakin, L

    2014-01-01

    Deterministic dynamical system which has an asymptotical stable equilibrium is considered under persistent perturbation by white noise. It is well known that if the perturbation does not vanish in the equilibrium position then there is not Lyapunov's stability. The trajectories of the perturbed system diverge from the equilibrium to arbitrarily large distances with probability 1 in finite time. New concept of stability on a large time interval is discussed. The length of interval agrees the reciprocal quantity of the perturbation parameter. The measure of stability is the expectation of the square distance from the trajectory till the equilibrium position. The method of parabolic equation is applied to both estimate the expectation and prove such stability. The main breakthrough is the barrier function derived for the parabolic equation. The barrier is constructed by using the Lyapunov function of the unperturbed system

  6. Forecasting autoregressive time series under changing persistence

    DEFF Research Database (Denmark)

    Kruse, Robinson

    Changing persistence in time series models means that a structural change from nonstationarity to stationarity or vice versa occurs over time. Such a change has important implications for forecasting, as negligence may lead to inaccurate model predictions. This paper derives generally applicable...... recommendations, no matter whether a change in persistence occurs or not. Seven different forecasting strategies based on a biasedcorrected estimator are compared by means of a large-scale Monte Carlo study. The results for decreasing and increasing persistence are highly asymmetric and new to the literature. Its...

  7. Persistent pain and sensory disturbances after treatment for breast cancer

    DEFF Research Database (Denmark)

    Mejdahl, Mathias Kvist; Andersen, Kenneth Geving; Gärtner, Rune

    2013-01-01

    To examine the development of persistent pain after treatment for breast cancer and to examine risk factors associated with continuing pain.......To examine the development of persistent pain after treatment for breast cancer and to examine risk factors associated with continuing pain....

  8. Establishment and early persistence of ten forage legumes under ...

    African Journals Online (AJOL)

    Establishment and early persistence of ten forage legumes under three grazing regimes in southern Mozambique. JP Muir. Abstract. Leucaena leucocephala, Clitoria ternatea, Macroptilium atropurpureum cv. Siratro, Cassia rotundifolia cv. Wynn, Macrotyloma axillare cv. Archer, Stylosanthes guianensis var. guianensis cv.

  9. Security Evaluation of the Cyber Networks under Advanced Persistent Threats

    NARCIS (Netherlands)

    Yang, L.; Li, Pengdeng; Yang, Xiaofan; Tang, Yuan Yan

    2017-01-01

    Advanced persistent threats (APTs) pose a grave threat to cyberspace, because they deactivate all the conventional cyber defense mechanisms. This paper addresses the issue of evaluating the security of the cyber networks under APTs. For this purpose, a dynamic model capturing the APT-based

  10. Persistent arm pain is distinct from persistent breast pain following breast cancer surgery.

    Science.gov (United States)

    Langford, Dale J; Paul, Steven M; West, Claudia; Abrams, Gary; Elboim, Charles; Levine, Jon D; Hamolsky, Deborah; Luce, Judith A; Kober, Kord M; Neuhaus, John M; Cooper, Bruce A; Aouizerat, Bradley E; Miaskowski, Christine

    2014-12-01

    Persistent pain following breast cancer surgery is well documented. However, it is not well characterized in terms of the anatomic site affected (ie, breast, arm). In 2 separate growth mixture modeling analyses, we identified subgroups of women (N = 398) with distinct breast pain and arm pain trajectories. The fact that these latent classes differed by anatomic site, types of tissue affected, and neural innervation patterns suggests the need for separate evaluations of these distinct persistent pain conditions. The purposes of this companion study were to identify demographic and clinical characteristics that differed between the 2 arm pain classes and determine if differences existed over time in sensitivity in the upper inner arm and axillary lymph node dissection sites, pain qualities, pain interference, and hand and arm function, as well as to compare findings with persistent breast pain. Higher occurrence rates for depression and lymphedema were found in the moderate arm pain class. Regardless of pain group membership, sensory loss was observed in the upper inner arm and axillary lymph node dissection site. Arm pain was described similarly to neuropathic pain and interfered with daily functioning. Persistent arm pain was associated with sustained impairments in shoulder mobility. For persistent breast and arm pain, changes in sensation following breast cancer surgery were notable. Persistent arm pain was associated with sustained interference with daily functioning and upper body mobility impairments. Long-term management of persistent pain following breast cancer surgery is warranted to improve the quality of survivorship for these women. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

  11. Neural Blockade for Persistent Pain After Breast Cancer Surgery

    DEFF Research Database (Denmark)

    Wijayasinghe, Nelun; Andersen, Kenneth Geving; Kehlet, Henrik

    2014-01-01

    involved in neuropathic pain syndromes or to be used as a treatment in its own right. The purpose of this review was to examine the evidence for neural blockade as a potential diagnostic tool or treatment for persistent pain after breast cancer surgery. In this systematic review, we found only 7 studies (n......Persistent pain after breast cancer surgery is predominantly a neuropathic pain syndrome affecting 25% to 60% of patients and related to injury of the intercostobrachial nerve, intercostal nerves, and other nerves in the region. Neural blockade can be useful for the identification of nerves...

  12. Neural processes underlying cultural differences in cognitive persistence.

    Science.gov (United States)

    Telzer, Eva H; Qu, Yang; Lin, Lynda C

    2017-08-01

    Self-improvement motivation, which occurs when individuals seek to improve upon their competence by gaining new knowledge and improving upon their skills, is critical for cognitive, social, and educational adjustment. While many studies have delineated the neural mechanisms supporting extrinsic motivation induced by monetary rewards, less work has examined the neural processes that support intrinsically motivated behaviors, such as self-improvement motivation. Because cultural groups traditionally vary in terms of their self-improvement motivation, we examined cultural differences in the behavioral and neural processes underlying motivated behaviors during cognitive persistence in the absence of extrinsic rewards. In Study 1, 71 American (47 females, M=19.68 years) and 68 Chinese (38 females, M=19.37 years) students completed a behavioral cognitive control task that required cognitive persistence across time. In Study 2, 14 American and 15 Chinese students completed the same cognitive persistence task during an fMRI scan. Across both studies, American students showed significant declines in cognitive performance across time, whereas Chinese participants demonstrated effective cognitive persistence. These behavioral effects were explained by cultural differences in self-improvement motivation and paralleled by increasing activation and functional coupling between the inferior frontal gyrus (IFG) and ventral striatum (VS) across the task among Chinese participants, neural activation and coupling that remained low in American participants. These findings suggest a potential neural mechanism by which the VS and IFG work in concert to promote cognitive persistence in the absence of extrinsic rewards. Thus, frontostriatal circuitry may be a neurobiological signal representing intrinsic motivation for self-improvement that serves an adaptive function, increasing Chinese students' motivation to engage in cognitive persistence. Copyright © 2017 Elsevier Inc. All rights

  13. Preoperative distress predicts persistent pain after breast cancer treatment

    DEFF Research Database (Denmark)

    Mejdahl, Mathias Kvist; Mertz, Birgitte Goldschmidt; Bidstrup, Pernille Envold Hansen

    2015-01-01

    , and evidence links signs of depression and anxiety with development of PPBCT. The purpose of this study was to assess preoperative distress as a predictive factor for development of PPBCT. METHODS: Between October 2008 and October 2009, 426 women diagnosed with primary breast cancer, undergoing surgery......PURPOSE: Persistent pain after breast cancer treatment (PPBCT) affects 25% to 60% of breast cancer survivors and is recognized as a clinical problem, with 10% to 15% reporting moderate to severe pain several years after treatment. Psychological comorbidity is known to influence pain perception...

  14. Cancer under graviditeten

    DEFF Research Database (Denmark)

    Pedersen, Berit Woetmann; Storgaard, Lone; Clausen, Mette Borg

    2015-01-01

    Cancer in pregnancy occurs in about one in 1,000 pregnancies. Recent reports have shown that most treatment regimes in second and third trimester are safe for the mother and the child. This has led to a paradigm shift in treating pregnant women with cancer. The management of the pregnant woman...

  15. Predicting, preventing and managing persistent pain after breast cancer surgery:

    DEFF Research Database (Denmark)

    Schreiber, Kristin L; Kehlet, Henrik; Belfer, Inna

    2014-01-01

    Persistent pain after breast cancer surgery (PPBCS) is increasingly recognized as a potential problem facing a sizeable subset of the millions of women who undergo surgery as part of their treatment of breast cancer. Importantly, an increasing number of studies suggest that individual variation...... in psychosocial factors such as catastrophizing, anxiety, depression, somatization and sleep quality play an important role in shaping an individual's risk of developing PPBCS. This review presents evidence for the importance of these factors and puts them within the context of other surgical, medical...

  16. Successive duopoly under moral hazard: Will incentive contracts persist?

    Directory of Open Access Journals (Sweden)

    Marta Fernández-Olmos

    2009-07-01

    Full Text Available The central purpose of this paper is to examine the incentive contract as an equilibrium phenomenon. We analyse a model of vertical differentiation in which we deal with the strategic role of the competitor’s decisions in a successive duopoly. Is it better for a processor to offer an incentive contract to an upstream producer or the spot market? We determine the equilibrium of a game in which the processors simultaneously decide whether to offer an incentive contract or to continue at the spot market to acquire their input. Our results show that under successive duopoly, offering an incentive contract constitutes the unique equilibrium solution, which highlights the incentive contract persistence.

  17. Persistence of Bacteroides ovatus under simulated sunlight irradiation

    KAUST Repository

    Dong, Shengkun

    2014-07-04

    Background: Bacteroides ovatus, a member of the genus Bacteroides, is considered for use in molecular-based methods as a general fecal indicator. However, knowledge on its fate and persistence after a fecal contamination event remains limited. In this study, the persistence of B. ovatus was evaluated under simulated sunlight exposure and in conditions similar to freshwater and seawater. By combining propidium monoazide (PMA) treatment and quantitative polymerase chain reaction (qPCR) detection, the decay rates of B. ovatus were determined in the presence and absence of exogenous photosensitizers and in salinity up to 39.5 parts per thousand at 27°C. Results: UVB was found to be important for B. ovatus decay, averaging a 4 log10 of decay over 6 h of exposure without the presence of extracellular photosensitizers. The addition of NaNO2, an exogenous sensitizer producing hydroxyl radicals, did not significantly change the decay rate of B. ovatus in both low and high salinity water, while the exogenous sensitizer algae organic matter (AOM) slowed down the decay of B. ovatus in low salinity water. At seawater salinity, the decay rate of B. ovatus was slower than that in low salinity water, except when both NaNO2 and AOM were present. Conclusion: The results of laboratory experiments suggest that if B. ovatus is released into either freshwater or seawater environment in the evening, 50% of it may be intact by the next morning; if it is released at noon, only 50% may be intact after a mere 5 min of full spectrum irradiation on a clear day. This study provides a mechanistic understanding to some of the important environmental relevant factors that influenced the inactivation kinetics of B. ovatus in the presence of sunlight irradiation, and would facilitate the use of B. ovatus to indicate the occurrence of fecal contamination.

  18. Blogging through cancer: young women's persistent problems shared online.

    Science.gov (United States)

    Keim-Malpass, Jessica; Baernholdt, Marianne; Erickson, Jeanne M; Ropka, Mary E; Schroen, Anneke T; Steeves, Richard H

    2013-01-01

    Many young women have turned to illness blogs to describe their lived experience with cancer. Blogs represent an untapped source of knowledge for researchers and clinicians. The purpose of this qualitative, exploratory study was to describe the life disruptions caused by cancer among young women, as well as to understand the facilitators and barriers in accessing healthcare services during and after active treatment. Sixteen Internet illness blogs were analyzed among women, aged between 20 and 39 years, diagnosed with cancer. These blogs were analyzed based on phenomenological qualitative methods and thematic analysis. There were 4 dimensions of persistent problems that were articulated in the narratives of the young women without any relief. They included pain and fatigue, insurance and financial barriers, concerns related to fertility, and symptoms of posttraumatic stress and anxiety. The young women's narratives capture fear, uncertainty, anger, and the debilitating nature of these persistent issues. Many of the women expressed their lingering physical, psychosocial, and emotional problems. Online illness narratives are a naturalistic form of inquiry that allows nurses to understand the experience of the patient through their own words and accounts. This study provides a foundation for nursing-based interventions that transcend traditional clinic experiences.

  19. Persistent fluctuations in stride intervals under fractal auditory stimulation.

    Science.gov (United States)

    Marmelat, Vivien; Torre, Kjerstin; Beek, Peter J; Daffertshofer, Andreas

    2014-01-01

    Stride sequences of healthy gait are characterized by persistent long-range correlations, which become anti-persistent in the presence of an isochronous metronome. The latter phenomenon is of particular interest because auditory cueing is generally considered to reduce stride variability and may hence be beneficial for stabilizing gait. Complex systems tend to match their correlation structure when synchronizing. In gait training, can one capitalize on this tendency by using a fractal metronome rather than an isochronous one? We examined whether auditory cues with fractal variations in inter-beat intervals yield similar fractal inter-stride interval variability as isochronous auditory cueing in two complementary experiments. In Experiment 1, participants walked on a treadmill while being paced by either an isochronous or a fractal metronome with different variation strengths between beats in order to test whether participants managed to synchronize with a fractal metronome and to determine the necessary amount of variability for participants to switch from anti-persistent to persistent inter-stride intervals. Participants did synchronize with the metronome despite its fractal randomness. The corresponding coefficient of variation of inter-beat intervals was fixed in Experiment 2, in which participants walked on a treadmill while being paced by non-isochronous metronomes with different scaling exponents. As expected, inter-stride intervals showed persistent correlations similar to self-paced walking only when cueing contained persistent correlations. Our results open up a new window to optimize rhythmic auditory cueing for gait stabilization by integrating fractal fluctuations in the inter-beat intervals.

  20. Forecasting long memory time series under a break in persistence

    DEFF Research Database (Denmark)

    Heinen, Florian; Sibbertsen, Philipp; Kruse, Robinson

    of this effect depends on whether the memory parameter is increasing or decreasing over time. A comparison of six forecasting strategies allows us to conclude that pre-testing for a change in persistence is highly recommendable in our setting. In addition we provide an empirical example which underlines......We consider the problem of forecasting time series with long memory when the memory parameter is subject to a structural break. By means of a large-scale Monte Carlo study we show that ignoring such a change in persistence leads to substantially reduced forecasting precision. The strength...

  1. Patients with persistent pain after breast cancer surgery show both delayed and enhanced cortical stimulus processing

    Directory of Open Access Journals (Sweden)

    Van den Broeke EN

    2012-06-01

    Full Text Available Emanuel N van den Broeke,1 Marjan de Vries,1 Harry van Goor,3 Kris CP Vissers,1 Clementina M van Rijn,2 Oliver HG Wilder-Smith11Department of Anesthesiology, Pain and Palliative Medicine, Pain and Nociception Neuroscience Research Group, 2Donders Institute for Brain, Cognition and Behavior, 3Department of Surgery, Radboud University Nijmegen Medical Centre, HB Nijmegen, The NetherlandsBackground: Women who undergo breast cancer surgery have a high risk of developing persistent pain. We investigated brain processing of painful stimuli using electroencephalograms (EEG to identify event-related potentials (ERPs in patients with persistent pain after breast cancer treatment.Methods: Nineteen patients (eight women with persistent pain, eleven without persistent pain, who were surgically treated more than 1 year previously for breast cancer (mastectomy, lumpectomy, and axillary lymph node dissection and/or had chemoradiotherapy, were recruited and compared with eleven healthy female volunteers. A block of 20 painful electrical stimuli was applied to the calf, somatopically remote from the initially injured or painful area. Simultaneously an EEG was recorded, and a visual analog scale (VAS pain rating obtained.Results: In comparison with healthy volunteers, breast cancer treatment without persistent pain is associated with accelerated stimulus processing (reduced P260 latency and shows a tendency to be less intense (lower P260 amplitude. In comparison to patients without persistent pain, persistent pain after breast cancer treatment is associated with stimulus processing that is both delayed (ie, increased latency of the ERP positivity between 250–310 ms [P260], and enhanced (ie, enhanced P260 amplitude.Conclusion: These results show that treatment and persistent pain have opposite effects on cortical responsiveness.Keywords: breast cancer surgery, persistent pain, nerve injury, event-related potentials, pain processing

  2. Cancer quackery: the persistent popularity of useless, irrational 'alternative' treatments.

    Science.gov (United States)

    Cassileth, Barrie R; Yarett, Ian R

    2012-08-01

    At a time when many readily believe that vaccines cause autism, or that government scientists created AIDS as a weapon of black genocide, it is not surprising that medical quackery, especially cancer quackery, remains a flourishing and lucrative business throughout the developed world. This review provides a brief recap of its history and an overview of the various types of unproven or disproved cancer therapies popular now in the United States and elsewhere.

  3. Persistence of docetaxel-induced neuropathy and impact on quality of life among breast cancer survivors

    DEFF Research Database (Denmark)

    Eckhoff, L.; Knoop, A.; Jensen, M. B.

    2015-01-01

    BACKGROUND: This study evaluates persistence and severity of docetaxel-induced neuropathy (peripheral neuropathy (PN)) and impact on health related quality of life in survivors from early-stage breast cancer. METHODS: One thousand and thirty-one patients with early-stage breast cancer, who received...... of Life Questionnaire (QLQ)-C30) after 1-3years. FINDINGS: Upon completion of docetaxel treatment, 241 patients (23%) reported PN, grades 2-4. PN persisted for 1-3years among 81 (34%) while PN regressed to grades 0-1 among 160 (66%). Among 790 patients (77%) without PN, 76 (10%) developed PN 1-3years...

  4. PKMζ is essential for spinal plasticity underlying the maintenance of persistent pain

    Directory of Open Access Journals (Sweden)

    Laferrière Andre

    2011-12-01

    Full Text Available Abstract Background Chronic pain occurs when normally protective acute pain becomes pathologically persistent. We examined here whether an isoform of protein kinase C (PKC, PKMζ, that underlies long-term memory storage in various brain regions, also sustains nociceptive plasticity in spinal cord dorsal horn (SCDH mediating persistent pain. Results Cutaneous injury or spinal stimulation produced persistent increases of PKMζ, but not other atypical PKCs in SCDH. Inhibiting spinal PKMζ, but not full-length PKCs, reversed plasticity-dependent persistent painful responses to hind paw formalin and secondary mechanical hypersensitivity and SCDH neuron sensitization after hind paw capsaicin, without affecting peripheral sensitization-dependent primary heat hypersensitivity after hind paw capsaicin. Inhibiting spinal PKMζ, but not full-length PKCs, also reversed mechanical hypersensitivity in the rat hind paw induced by spinal stimulation with intrathecal dihydroxyphenylglycine. Spinal PKMζ inhibition also alleviated allodynia 3 weeks after ischemic injury in rats with chronic post-ischemia pain (CPIP, at a point when allodynia depends on spinal changes. In contrast, spinal PKMζ inhibition did not affect allodynia in rats with chronic contriction injury (CCI of the sciatic nerve, or CPIP rats early after ischemic injury, when allodynia depends on ongoing peripheral inputs. Conclusions These results suggest spinal PKMζ is essential for the maintenance of persistent pain by sustaining spinal nociceptive plasticity.

  5. Receptor activities of persistent pollutant serum mixtures and breast cancer risk

    DEFF Research Database (Denmark)

    Wielsøe, Maria; Bjerregaard-Olesen, Christian; Kern, Peder

    2017-01-01

    Studies on associations between persistent organic pollutants (POPs) and breast cancer risk are inconclusive. The majority of studies have evaluated the effect of single compounds, without considering multiple exposures to and interactions between different POPs. The present study aimed at evalua...

  6. Tumor Tension Induces Persistent Inflammation and Promotes Breast Cancer Aggression

    Science.gov (United States)

    2016-10-01

    HLNL and DHLNL (Suppl. Figure 2). These data not only demonstrated a direct positive relationship between changes in stromal Lox expression, collagen...Force Microscopy (AFM). (Months 11-15 for Task 1B and 15-19 for Task 1C) Task 1G. Immunofluorescence analyses will be done using marker for...role for STAT3 activity in tumor-initiating cells (TICs) is well-known in mouse models of breast cancer; and 3) we have evidence that there is a direct

  7. Inhibition of HAS2 induction enhances the radiosensitivity of cancer cells via persistent DNA damage

    International Nuclear Information System (INIS)

    Shen, Yan Nan; Shin, Hyun-Jin; Joo, Hyun-Yoo; Park, Eun-Ran; Kim, Su-Hyeon; Hwang, Sang-Gu; Park, Sang Jun; Kim, Chun-Ho; Lee, Kee-Ho

    2014-01-01

    Highlights: •HAS2 may be a promising target for the radiosensitization of human cancer. •HAS2 is elevated (up to ∼10-fold) in irradiated radioresistant and -sensitive cancer cells. •HAS2 knockdown sensitizes cancer cells to radiation. •HAS2 knockdown potentiates irradiation-induced DNA damage and apoptotic death. •Thus, the irradiation-induced up-regulation of HAS2 contributes to the radioresistance of cancer cells. -- Abstract: Hyaluronan synthase 2 (HAS2), a synthetic enzyme for hyaluronan, regulates various aspects of cancer progression, including migration, invasion and angiogenesis. However, the possible association of HAS2 with the response of cancer cells to anticancer radiotherapy, has not yet been elucidated. Here, we show that HAS2 knockdown potentiates irradiation-induced DNA damage and apoptosis in cancer cells. Upon exposure to radiation, all of the tested human cancer cell lines exhibited marked (up to 10-fold) up-regulation of HAS2 within 24 h. Inhibition of HAS2 induction significantly reduced the survival of irradiated radioresistant and -sensitive cells. Interestingly, HAS2 depletion rendered the cells to sustain irradiation-induced DNA damage, thereby leading to an increase of apoptotic death. These findings indicate that HAS2 knockdown sensitizes cancer cells to radiation via persistent DNA damage, further suggesting that the irradiation-induced up-regulation of HAS2 contributes to the radioresistance of cancer cells. Thus, HAS2 could potentially be targeted for therapeutic interventions aimed at radiosensitizing cancer cells

  8. Associations of persistent organic pollutants in serum and adipose tissue with breast cancer prognostic markers

    Energy Technology Data Exchange (ETDEWEB)

    Arrebola, J.P., E-mail: jparrebola@ugr.es [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Virgen de las Nieves University Hospital, Radiation Oncology Department, Oncology Unit, Granada (Spain); CIBER en Epidemiología y Salud Pública (CIBERESP) (Spain); Fernández-Rodríguez, M.; Artacho-Cordón, F. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); University of Granada, Radiology and Physical Medicine Department (Spain); Garde, C. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Perez-Carrascosa, F.; Linares, I.; Tovar, I. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Virgen de las Nieves University Hospital, Radiation Oncology Department, Oncology Unit, Granada (Spain); González-Alzaga, B. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Escuela Andaluza de Salud Pública, Granada (Spain); Expósito, J. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); Virgen de las Nieves University Hospital, Radiation Oncology Department, Oncology Unit, Granada (Spain); Torne, P. [Instituto de Investigación Biosanitaria (ibs. GRANADA), Hospitales Universitarios de Granada (Spain); and others

    2016-10-01

    This study aimed to evaluate associations between exposure to a group of persistent organic pollutants, measured in both adipose tissue and serum samples from breast cancer patients, and a set of tumor prognostic markers. The study population comprised 103 breast cancer patients recruited in Granada, Southern Spain. Data for tumor prognostic markers were retrieved from hospital clinical records and socio-demographic information was gathered by questionnaire. Persistent organic pollutants were quantified by gas chromatography with electron capture detection. Exposure levels were categorized in quartiles, and associations were evaluated using unconditional logistic regression. Adipose tissue HCB concentrations were associated positively with ER and PR expression (p-trends = 0.044 and 0.005, respectively) and negatively with E-Cadherin and p53 expression (p-trends = 0.012 and 0.027, respectively). PCB-180 adipose tissue concentrations were positively associated with HER2 expression (p-trend = 0.036). Serum PCB-138 concentrations were positively associated with ER and PR expression (p-trends = 0.052 and 0.042, respectively). The risk of p53 expression was higher among women in the lowest quartile of serum PCB-138 concentrations, but no significant trend was observed (p-trend = 0.161). These findings indicate that human exposure to certain persistent organic pollutants might be related to breast cancer aggressiveness. We also highlight the influence on exposure assessment of the biological matrix selected, given that both serum and adipose tissue might yield relevant information on breast cancer prognosis. - Highlights: • The role of POP exposure on the pathogenesis breast cancer is still controversial. • POPs were analyzed in serum and adipose tissue from breast cancer patients. • POP concentrations were associated with breast cancer prognostic markers. • POPs in serum and adipose tissue of breast cancer patients may provide different clues.

  9. Persistent demographic differences in colorectal cancer screening utilization despite Medicare reimbursement

    Directory of Open Access Journals (Sweden)

    Kreuter William

    2005-03-01

    Full Text Available Abstract Background Colorectal cancer screening is widely recommended, but often under-utilized. In addition, significant demographic differences in screening utilization exist. Insurance coverage may be one factor influencing utilization of colorectal cancer screening tests. Methods We conducted a retrospective analysis of claims for outpatient services for Washington state Medicare beneficiaries in calendar year 2000. We determined the proportion of beneficiaries utilizing screening fecal occult blood tests, flexible sigmoidoscopy, colonoscopy, or double contrast barium enema in the overall population and various demographic subgroups. Multiple logistic regression analysis was used to determine the relative odds of screening in different demographic groups. Results Approximately 9.2% of beneficiaries had fecal occult blood tests, 7.2% had any colonoscopy, flexible sigmoidoscopy, or barium enema (invasive colon tests, and 3.5% had invasive tests for screening indications. Colonoscopy accounted for 41% of all invasive tests for screening indications. Women were more likely to receive fecal occult blood test screening (OR 1.18; 95%CI 1.15, 1.21 and less likely to receive invasive tests for screening indications than men (OR 0.80, 95%CI 0.77, 0.83. Whites were more likely than other racial groups to receive any type of screening. Rural residents were more likely than urban residents to have fecal occult blood tests (OR 1.20, 95%CI 1.17, 1.23 but less likely to receive invasive tests for screening indications (OR 0.89; 95%CI 0.85, 0.93. Conclusion Reported use of fecal occult blood testing remains modest. Overall use of the more invasive tests for screening indications remains essentially unchanged, but there has been a shift toward increased use of screening colonoscopy. Significant demographic differences in screening utilization persist despite consistent insurance coverage.

  10. TENACITY AND PERSISTENCE OF COPPER FUNGICIDES IN CITRUS SEEDLINGS UNDER SIMULATED RAINFALL

    Directory of Open Access Journals (Sweden)

    ANTONIO EDUARDO FONSECA

    2016-01-01

    Full Text Available The amount of fungicide that adheres to the leaf during spraying and the amount that remain on the leaf after weathering are the main factors that defines the amount of active residue on the leaf surface to effectively control plant pathogens. Thus, the objective of this work was to evaluate the tenacity and persistence of copper in citrus seedling leaves under simulated rainfall in Jaboticabal, State of São Paulo, Brazil. The evaluated variables were copper content, solution retention, surface tension and drop spectrum. A significant and inversely proportional linear relationship to drops <100 μm was found. The percentage of copper retained in leaves of citrus seedlings with copper fungicides of suspension concentrate (SC formulations after simulated rainfall was greater than 80%. Copper fungicides of SC formulations presented the lowest surface tension, allowing greater tenacity and persistence of copper on seedlings of citrus leaves after simulated rainfall and increased contact between the drops and leaf surface.

  11. Quality of Life and Care Needs of Patients With Persistent or Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Peritoneal Cancer

    Science.gov (United States)

    2017-05-03

    Anxiety; Fatigue; Nausea and Vomiting; Neurotoxicity Syndrome; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IB Fallopian Tube Cancer; Stage IC Fallopian Tube Cancer; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIB Fallopian Tube Cancer; Stage IIC Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIC Fallopian Tube Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  12. Pre-Ablation Thyroglobulin Levels and Persistence / Recurrence Associated to Early Differentiated Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Arturo Mejía López

    2014-01-01

    Full Text Available Introduction: Differentiated thyroid cancer is the most frequent endocrine neoplasm in the world and its incidence is growing rapidly. The relationship between levels of pre-ablation thyroglobulin (Tg and early persistence/recurrence of differentiated thyroid cancer was studied. Materials and Methods: 91 patients with papillary thyroid cancer who underwent post-surgical ablation with radioactive iodine registered in the Fundacion Cardioinfantil between January 2006 and January 2010 were evaluated. The analysis of the results was performed using the SPSS statistical package and the research hypothesis was evaluated using nonparametric methods. Results: The disease progressed in 20 patients during the first year post-ablation, at the end of this period (p=0.000 a significant relationship between pre-ablation Tg and disease status was found. In the group of individuals by whom the disease progressed there was no significant change in Tg between the first and the second semester post-ablation (p = 0.554; there were no cases of recurrence/persistence in those with levels less than or equal to 2.7 ng/mL; 80 % of these cases involved individuals with initial levels higher than 24 ng/mL. Conclusion: In patients with papillary thyroid cáncer the serum pre-ablation Tg is related to the disease status at the end of the first year post-ablation. The persistence/recurrence is less frequent in low levels and more frequent in higher levels.

  13. Single nucleotide polymorphisms in the PRDX3 and RPS19 and risk of HPV persistence and cervical precancer/cancer.

    Directory of Open Access Journals (Sweden)

    Mahboobeh Safaeian

    Full Text Available Host genetic factors might affect the risk of progression from infection with carcinogenic human papillomavirus (HPV, the etiologic agent for cervical cancer, to persistent HPV infection, and hence to cervical precancer and cancer.We assessed 18,310 tag single nucleotide polymorphisms (SNPs from 1113 genes in 416 cervical intraepithelial neoplasia 3 (CIN3/cancer cases, 356 women with persistent carcinogenic HPV infection (median persistence of 25 months and 425 randomly selected women (non-cases and non-HPV persistent from the 10,049 women from the Guanacaste, Costa Rica HPV natural history cohort. For gene and SNP associations, we computed age-adjusted odds ratio and p-trend. Three comparisons were made: 1 association with CIN3/cancer (compared CIN3/cancer cases to random controls, 2 association with persistence (compared HPV persistence to random controls, and 3 progression (compared CIN3/cancers with HPV-persistent group. Regions statistically significantly associated with CIN3/cancer included genes for peroxiredoxin 3 PRDX3, and ribosomal protein S19 RPS19. The single most significant SNPs from each gene associated with CIN3/cancer were PRDX3 rs7082598 (P(trend<0.0001, and RPS19 rs2305809 (P(trend=0.0007, respectively. Both SNPs were also associated with progression.These data suggest involvement of two genes, RSP19 and PRDX3, or other SNPs in linkage disequilibrium, with cervical cancer risk. Further investigation showed that they may be involved in both the persistence and progression transition stages. Our results require replication but, if true, suggest a role for ribosomal dysfunction, mitochondrial processes, and/or oxidative stress, or other unknown function of these genes in cervical carcinogenesis.

  14. Ultrasound guided intercostobrachial nerve blockade in patients with persistent pain after breast cancer surgery

    DEFF Research Database (Denmark)

    Wijayasinghe, Nelun; Duriaud, Helle M; Kehlet, Henrik

    2016-01-01

    BACKGROUND: Persistent pain after breast cancer surgery (PPBCS) affects 25 - 60% of breast cancer survivors and damage to the intercostobrachial nerve (ICBN) has been implicated as the cause of this predominantly neuropathic pain. Local anesthetic blockade of the ICBN could provide clues...... determined the sonoanatomy of the ICBN and part 2 examined effects of the ultrasound-guided ICBN blockade in patients with PPBCS. SETTING: Section for Surgical Pathophysiology at Rigshospitalet, Copenhagen, Denmark. METHODS: Part 1: Sixteen unoperated, pain free breast cancer patients underwent systematic...... to pathophysiological mechanisms as well as aiding diagnosis and treatment of PPBCS but has never been attempted. OBJECTIVES: To assess the feasibility of ICBN blockade and assess its effects on pain and sensory function in patients with PPBCS. STUDY DESIGN: This prospective pilot study was performed in 2 parts: Part 1...

  15. Ultrasound Guided Intercostobrachial Nerve Blockade in Patients with Persistent Pain after Breast Cancer Surgery

    DEFF Research Database (Denmark)

    Wijayasinghe, Nelun; Duriaud, Helle M; Kehlet, Henrik

    2016-01-01

    to pathophysiological mechanisms as well as aiding diagnosis and treatment of PPBCS but has never been attempted. OBJECTIVES: To assess the feasibility of ICBN blockade and assess its effects on pain and sensory function in patients with PPBCS. STUDY DESIGN: This prospective pilot study was performed in 2 parts: Part 1......BACKGROUND: Persistent pain after breast cancer surgery (PPBCS) affects 25 - 60% of breast cancer survivors and damage to the intercostobrachial nerve (ICBN) has been implicated as the cause of this predominantly neuropathic pain. Local anesthetic blockade of the ICBN could provide clues...... determined the sonoanatomy of the ICBN and part 2 examined effects of the ultrasound-guided ICBN blockade in patients with PPBCS. SETTING: Section for Surgical Pathophysiology at Rigshospitalet, Copenhagen, Denmark. METHODS: Part 1: Sixteen unoperated, pain free breast cancer patients underwent systematic...

  16. Preoperative Breast Pain Predicts Persistent Breast Pain and Disability After Breast Cancer Surgery.

    Science.gov (United States)

    Langford, Dale J; Schmidt, Brian; Levine, Jon D; Abrams, Gary; Elboim, Charles; Esserman, Laura; Hamolsky, Deborah; Mastick, Judy; Paul, Steven M; Cooper, Bruce; Kober, Kord; Dodd, Marylin; Dunn, Laura; Aouizerat, Bradley; Miaskowski, Christine

    2015-06-01

    Approximately 30% of the women report pain in the affected breast before breast cancer surgery. The purpose of this secondary analysis of our prospective study was to determine how women who experienced both preoperative and persistent postsurgical breast pain (n=107) differed from women who did not report preoperative breast pain and did (n=158) or did not (n=122) experience persistent postsurgical breast pain. Differences in demographic and clinical characteristics were evaluated. Linear mixed effects (LME) modeling was used to evaluate for group differences in symptom severity, function, sensation, and quality of life (QOL) over time. Between-group differences in demographic and clinical characteristics as well as trajectories of shoulder function and QOL were identified. Women with both preoperative and persistent postsurgical breast pain were younger; were more likely to report swelling, strange sensations, hardness, and numbness in the affected breast before surgery; and were more likely to have reconstruction at the time of surgery. Women with both preoperative and persistent postsurgical breast pain had more biopsies in the prior year, more lymph nodes removed, and reported more severe acute postsurgical pain than women without preoperative breast pain. The LME modeling revealed significant group effects for most outcomes evaluated. Over the six months of the study, women with both preoperative and persistent postsurgical pain had persistently poorer shoulder flexion and physical well-being than women without preoperative breast pain. Investigations of the etiology and molecular mechanisms of preoperative breast pain, as well as interventions for this high-risk group, are needed. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  17. Preoperative Breast Pain Predicts Persistent Breast Pain and Disability Following Breast Cancer Surgery

    Science.gov (United States)

    Langford, Dale J.; Schmidt, Brian; Levine, Jon D.; Abrams, Gary; Elboim, Charles; Esserman, Laura; Hamolsky, Deborah; Mastick, Judy; Paul, Steven M.; Cooper, Bruce; Kober, Kord; Dodd, Marylin; Dunn, Laura; Aouizerat, Bradley; Miaskowski, Christine

    2015-01-01

    Context Approximately 30% of women report pain in the affected breast prior to breast cancer surgery. Objectives The purpose of this secondary analysis of our prospective study was to determine how women who experienced both preoperative and persistent postsurgical breast pain (n=107) differed from women who did not report preoperative breast pain and did (n=158) or did not (n=122) experience persistent postsurgical breast pain. Methods Differences in demographic and clinical characteristics were evaluated. Linear mixed effects (LME) modeling was used to evaluate for group differences in symptom severity, function, sensation, and quality of life (QOL) over time. Results Between-group differences in demographic and clinical characteristics as well as trajectories of shoulder function and QOL were identified. Women with both preoperative and persistent postsurgical breast pain were younger; were more likely to report swelling, strange sensations, hardness, and numbness in the affected breast prior to surgery; and were more likely to have reconstruction at the time of surgery. Women with both preoperative and persistent postsurgical breast pain had more biopsies in the prior year, more lymph nodes removed, and reported more severe acute postsurgical pain than women without preoperative breast pain. LME modeling revealed significant group effects for the majority of outcomes evaluated. Over the six months of the study, women with both preoperative and persistent postsurgical pain had persistently poorer shoulder flexion and physical well-being than women without preoperative breast pain. Conclusion Investigations of the etiology and molecular mechanisms of preoperative breast pain, as well as interventions for this high risk group, are needed. PMID:25527442

  18. ER Stress Signaling Promotes the Survival of Cancer "Persister Cells" Tolerant to EGFR Tyrosine Kinase Inhibitors.

    Science.gov (United States)

    Terai, Hideki; Kitajima, Shunsuke; Potter, Danielle S; Matsui, Yusuke; Quiceno, Laura Gutierrez; Chen, Ting; Kim, Tae-Jung; Rusan, Maria; Thai, Tran C; Piccioni, Federica; Donovan, Katherine A; Kwiatkowski, Nicholas; Hinohara, Kunihiko; Wei, Guo; Gray, Nathanael S; Fischer, Eric S; Wong, Kwok-Kin; Shimamura, Teppei; Letai, Anthony; Hammerman, Peter S; Barbie, David A

    2018-02-15

    An increasingly recognized component of resistance to tyrosine kinase inhibitors (TKI) involves persistence of a drug-tolerant subpopulation of cancer cells that survive despite effective eradication of the majority of the cell population. Multiple groups have demonstrated that these drug-tolerant persister cells undergo transcriptional adaptation via an epigenetic state change that promotes cell survival. Because this mode of TKI drug tolerance appears to involve transcriptional addiction to specific genes and pathways, we hypothesized that systematic functional screening of EGFR TKI/transcriptional inhibitor combination therapy would yield important mechanistic insights and alternative drug escape pathways. We therefore performed a genome-wide CRISPR/Cas9 enhancer/suppressor screen in EGFR-dependent lung cancer PC9 cells treated with erlotinib + THZ1 (CDK7/12 inhibitor) combination therapy, a combination previously shown to suppress drug-tolerant cells in this setting. As expected, suppression of multiple genes associated with transcriptional complexes (EP300, CREBBP, and MED1) enhanced erlotinib/THZ1 synergy. Unexpectedly, we uncovered nearly every component of the recently described ufmylation pathway in the synergy suppressor group. Loss of ufmylation did not affect canonical downstream EGFR signaling. Instead, absence of this pathway triggered a protective unfolded protein response associated with STING upregulation, promoting protumorigenic inflammatory signaling but also unique dependence on Bcl-xL. These data reveal that dysregulation of ufmylation and ER stress comprise a previously unrecognized TKI drug tolerance pathway that engages survival signaling, with potentially important therapeutic implications. Significance: These findings reveal a novel function of the recently described ufmylation pathway, an ER stress survival signaling in drug-tolerant persister cells, which has important biological and therapeutic implications. Cancer Res; 78(4); 1044

  19. Enhanced desorption of persistent organic pollutants from microplastics under simulated physiological conditions

    International Nuclear Information System (INIS)

    Bakir, Adil; Rowland, Steven J.; Thompson, Richard C.

    2014-01-01

    Microplastics have the potential to uptake and release persistent organic pollutants (POPs); however, subsequent transfer to marine organisms is poorly understood. Some models estimating transfer of sorbed contaminants to organisms neglect the role of gut surfactants under differing physiological conditions in the gut (varying pH and temperature), examined here. We investigated the potential for polyvinylchloride (PVC) and polyethylene (PE) to sorb and desorb 14 C-DDT, 14 C-phenanthrene (Phe), 14 C-perfluorooctanoic acid (PFOA) and 14 C-di-2-ethylhexyl phthalate (DEHP). Desorption rates of POPs were quantified in seawater and under simulated gut conditions. Influence of pH and temperature was examined in order to represent cold and warm blooded organisms. Desorption rates were faster with gut surfactant, with a further substantial increase under conditions simulating warm blooded organisms. Desorption under gut conditions could be up to 30 times greater than in seawater alone. Of the POP/plastic combinations examined Phe with PE gave the highest potential for transport to organisms. Highlights: • PVC and PE (200–250 μm) were able to sorb phenanthrene, DDT, PFOA and DEHP. • Desorption rates were faster using a gut surfactant compared to seawater alone. • Desorption rates were further enhanced at lower pH and higher temperature. • Plastic-POPs were ranked according to their potential to cause “harm”. -- Desorption rates of sorbed POPs from plastics were substantially enhanced under gut conditions specific of warm blooded organisms, suggesting potential transfer following ingestion

  20. Receptor activities of persistent pollutant serum mixtures and breast cancer risk.

    Science.gov (United States)

    Wielsøe, Maria; Bjerregaard-Olesen, Christian; Kern, Peder; Bonefeld-Jørgensen, Eva Cecilie

    2018-03-01

    Studies on associations between persistent organic pollutants (POPs) and breast cancer risk are inconclusive. The majority of studies have evaluated the effect of single compounds, without considering multiple exposures to and interactions between different POPs. The present study aimed at evaluating breast cancer risk related to combined effects of serum POP mixtures on cellular receptor functions. Data on breast cancer cases ( n  = 77) and controls ( n  = 84) were collected among Greenlandic Inuit women. Serum mixtures of lipophilic POPs (lipPOPs), perfluoroalkyl acids (PFAAs) and dioxin-like POPs were extracted. The effect of the mixture extracts on the estrogen receptor (ER), androgen receptor (AR) and aryl hydrocarbon receptor (AhR) was determined using cell culture reporter gene assays. The serum mixtures were analyzed alone and upon co-exposure with natural receptor ligands to determine agonistic and antagonistic/competitive activity. We found that the frequency of lipPOP mixtures eliciting no, decreasing, or agonizing xenoandrogenic effect differed by breast cancer status. Using lipPOP mixtures with no effect on AR as reference, the mixtures with decreasing effects reduced breast cancer risk (OR: 0.30 (0.12; 0.76)). The AhR-toxic equivalent of serum mixtures was significantly lower in cases than in controls, and a reduced breast cancer risk was found when comparing the third tertile to the first (OR: 0.34 (0.14; 0.83)). We found no association between the xenoestrogenic activities of lipPOPs or PFAAs and breast cancer risk. Serum lipPOP mixtures are hormone disruptive and may influence breast cancer risk, whereas PFAAs seem to influence breast cancer risk through other pathways. © 2018 Society for Endocrinology.

  1. Optimal univariate expectations under high and persistent inflation: new evidence from Turkey

    Science.gov (United States)

    Us, Vuslat; Ozcan, Kıvılcım Metin

    2005-02-01

    The poor performance of sticky-price models with rational expectations in explaining the inflationary inertia in the US economy constitutes the basis for sticky-price models of near-rational expectations in the recent literature. However, previous studies on inflationary inertia in Turkey not only lack a model of nominal stickiness but also do not try to explain inflation persistence by expectations. Even though, there exists evidence for persistent inflation in Turkey as confirmed by earlier studies, and other studies provide evidence that expectations are neither perfectly rational nor purely adaptive, there is no attempt to link this near-rational behavior to inflationary inertia. Given this gap, this paper, therefore, tests empirically a sticky-price model under the assumption of near-rational expectations on two different inflation episodes in the Turkish economy. The near-rational expectations as described by optimal univariate expectations where agents use information on past inflation optimally while data on other variables are ignored, not only fit the data for both periods but also are not subject to Lucas critique. Alternatively, near-rational expectations are assumed to be backward looking. This alternative scenario shows that optimal univariate expectations perform even better during relatively higher inflation periods.

  2. The frontal aslant tract underlies speech fluency in persistent developmental stuttering.

    Science.gov (United States)

    Kronfeld-Duenias, Vered; Amir, Ofer; Ezrati-Vinacour, Ruth; Civier, Oren; Ben-Shachar, Michal

    2016-01-01

    The frontal aslant tract (FAT) is a pathway that connects the inferior frontal gyrus with the supplementary motor area (SMA) and pre-SMA. The FAT was recently identified and introduced as part of a "motor stream" that plays an important role in speech production. In this study, we use diffusion imaging to examine the hypothesis that the FAT underlies speech fluency, by studying its properties in individuals with persistent developmental stuttering, a speech disorder that disrupts the production of fluent speech. We use tractography to quantify the volume and diffusion properties of the FAT in a group of adults who stutter (AWS) and fluent controls. Additionally, we use tractography to extract these measures from the corticospinal tract (CST), a well-known component of the motor system. We compute diffusion measures in multiple points along the tracts, and examine the correlation between these diffusion measures and behavioral measures of speech fluency. Our data show increased mean diffusivity in bilateral FAT of AWS compared with controls. In addition, the results show regions within the left FAT and the left CST where diffusivity values are increased in AWS compared with controls. Last, we report that in AWS, diffusivity values measured within sub-regions of the left FAT negatively correlate with speech fluency. Our findings are the first to relate the FAT with fluent speech production in stuttering, thus adding to the current knowledge of the functional role that this tract plays in speech production and to the literature of the etiology of persistent developmental stuttering.

  3. Prevalence of and factors associated with persistent pain following breast cancer surgery

    DEFF Research Database (Denmark)

    Gärtner, Rune; Jensen, Maj-Britt; Nielsen, Jeanette

    2009-01-01

    January 1, 2005, and December 31, 2006. A study questionnaire was sent to the women between January and April 2008. MAIN OUTCOME MEASURES: Prevalence, location, and severity of persistent pain and sensory disturbances in 12 well-defined treatment groups assessed an average of 26 months after surgery......, and adjusted odds ratio (OR) of reported pain and sensory disturbances with respect to age, surgical technique, chemotherapy, and radiotherapy. RESULTS: By June 2008, 3253 of 3754 eligible women (87%) returned the questionnaire. A total of 1543 patients (47%) reported pain, of whom 201 (13%) had severe pain......CONTEXT: Persistent pain and sensory disturbances following surgical treatment for breast cancer is a significant clinical problem. The pathogenic mechanisms are complex and may be related to patient characteristics, surgical technique, and adjuvant therapy. OBJECTIVE: To examine prevalence...

  4. Challenges Persist Under Americans With Disabilities Act Amendments Act: How Can Oncology Providers Help?

    Science.gov (United States)

    Feuerstein, Michael; Gehrke, Amanda K; McMahon, Brian T; McMahon, Megan C

    2017-06-01

    To determine whether the Amendments to the hallmark Americans with Disabilities Act (ADA; effective January 2009), which provide increased access to the antidiscrimination laws for many with chronic illness, are related to changes in workplace discrimination allegations in individuals with a history of cancer. Information collected by the Equal Employment Opportunities Commission was used to compare allegations of discrimination and their merit before (2001 to 2008) and after (2009 to 2011) implementation of the Amendments Act. Allegations related to terms of employment (eg, promotions, wages) were more likely to be filed (odds ratio [OR], 1.34; 95% CI, 1.11 to 1.61) and determined to have merit (OR, 1.35; 95% CI, 1.03 to 1.77) after implementation of the Amendments Act. Allegations related to workplace relations (eg, harassment, discipline, discharge) were also more likely to be filed post Amendments Act (OR, 1.48; 95% CI, 1.23 to 1.78), although the merit of this complaint remained stable. Filing of all other allegations of discrimination (ie, hiring, reasonable accommodation, and termination) and their merit remained unchanged post Amendments Act. Despite the implementation of the Amendments Act, discrimination allegations in those with a history of cancer persisted or in certain areas increased. Although prevention of workplace discrimination rests primarily with employers, the oncology care team is uniquely qualified to provide information related to residual symptoms and function that can facilitate more personalized solutions to workplace discrimination, such as successful workplace accommodations. Information is provided that can assist the oncology team in their efforts to improve work outcomes.

  5. A new near-infrared persistent luminescence nanoparticle as a multifunctional nanoplatform for multimodal imaging and cancer therapy.

    Science.gov (United States)

    Shi, Junpeng; Sun, Xia; Zheng, Shenghui; Li, Jinlei; Fu, Xiaoyan; Zhang, Hongwu

    2018-01-01

    Multifunctional nanoplatforms with multimodal imaging and cancer therapy capabilities have attracted attention in biomedical applications. Near-infrared persistent luminescence nanoparticles (NPLNPs) were considered one of the most promising candidates for constructing multifunctional nanoplatforms due to the absence of in situ excitation and high signal-to-noise ratios (SNRs). Here, we report a novel NPLNP mSiO 2 @Gd 3 Ga 5 O 12 :Cr 3+ , Nd 3+ (mSiO 2 @GGO) as multifunctional nanoplatforms for multimodal imaging and cancer therapy. These NPs exhibited a persistent luminescence (745 nm) of more than 3 h in the first near-infrared window (NIR-I) after UV excitation, which can realize high SNRs and long-term in vivo imaging. Moreover, these NPs showed excellent NIR luminescence (1067 nm) in the second near-infrared window (NIR-II) under 808 nm excitation, which is more suitable for deep tissue imaging due to the lower photon scattering and deeper tissue penetration of NIR-II luminescence. Furthermore, the host Gd 3 Ga 5 O 12 with high Gd 3+ concentration showed a high r 1 value (10.70 mM -1  s -1 ) and was suitable for T 1 MR imaging. The mesoporous silica nanoparticles (mSiO 2 ) served as a framework to control the mSiO 2 @GGO particle morphology and provide low toxicity and drug loading capacity for cancer therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Persistent pain after breast cancer treatment: a critical review of risk factors and strategies for prevention

    DEFF Research Database (Denmark)

    Andersen, Kenneth Geving; Kehlet, Henrik

    2011-01-01

    . This review is a systematic analysis on methodology and evidence in research into persistent pain after breast cancer treatment during the period 1995 to 2010, in order to clarify the significance and relative role of potential risk factors. Literature was identified by a search in PubMed and OVID, as well...... principles of surgical and adjuvant therapy. In summary, the data show inconsistencies in definition of chronic pain and treatment groups, as well as in the collection of pre- intra- and post-operative data, precluding conclusions with regard to pathophysiologic mechanisms as well as rational strategies...... for prevention and treatment. However, nerve damage and radiotherapy appear to be significant risk factors for chronic pain. A proposal for the design of future prospective studies is presented. PERSPECTIVE: A comprehensive and systematic approach to research in chronic pain after breast cancer treatment...

  7. Ozone Therapy in the Management of Persistent Radiation-Induced Rectal Bleeding in Prostate Cancer Patients

    Directory of Open Access Journals (Sweden)

    Bernardino Clavo

    2015-01-01

    Full Text Available Introduction. Persistent radiation-induced proctitis and rectal bleeding are debilitating complications with limited therapeutic options. We present our experience with ozone therapy in the management of such refractory rectal bleeding. Methods. Patients (n=12 previously irradiated for prostate cancer with persistent or severe rectal bleeding without response to conventional treatment were enrolled to receive ozone therapy via rectal insufflations and/or topical application of ozonized-oil. Ten (83% patients had Grade 3 or Grade 4 toxicity. Median follow-up after ozone therapy was 104 months (range: 52–119. Results. Following ozone therapy, the median grade of toxicity improved from 3 to 1 (p<0.001 and the number of endoscopy treatments from 37 to 4 (p=0.032. Hemoglobin levels changed from 11.1 (7–14 g/dL to 13 (10–15 g/dL, before and after ozone therapy, respectively (p=0.008. Ozone therapy was well tolerated and no adverse effects were noted, except soft and temporary flatulence for some hours after each session. Conclusions. Ozone therapy was effective in radiation-induced rectal bleeding in prostate cancer patients without serious adverse events. It proved useful in the management of rectal bleeding and merits further evaluation.

  8. Hyper-Methylated Loci Persisting from Sessile Serrated Polyps to Serrated Cancers.

    Science.gov (United States)

    Andrew, Angeline S; Baron, John A; Butterly, Lynn F; Suriawinata, Arief A; Tsongalis, Gregory J; Robinson, Christina M; Amos, Christopher I

    2017-03-02

    Although serrated polyps were historically considered to pose little risk, it is now understood that progression down the serrated pathway could account for as many as 15%-35% of colorectal cancers. The sessile serrated adenoma/polyp (SSA/P) is the most prevalent pre-invasive serrated lesion. Our objective was to identify the CpG loci that are persistently hyper-methylated during serrated carcinogenesis, from the early SSA/P lesion through the later cancer phases of neoplasia development. We queried the loci hyper-methylated in serrated cancers within our rightsided SSA/Ps from the New Hampshire Colonoscopy Registry, using the Illumina Infinium Human Methylation 450 k panel to comprehensively assess the DNA methylation status. We identified CpG loci and regions consistently hyper-methylated throughout the serrated carcinogenesis spectrum, in both our SSA/P specimens and in serrated cancers. Hyper-methylated CpG loci included the known the tumor suppressor gene RET (p = 5.72 x 10-10), as well as loci in differentially methylated regions for GSG1L, MIR4493, NTNG1, MCIDAS, ZNF568, and RERG. The hyper-methylated loci that we identified help characterize the biology of SSA/P development, and could be useful as therapeutic targets, or for future identification of patients who may benefit from shorter surveillance intervals.

  9. Persistence of senescent prostate cancer cells following prolonged neoadjuvant androgen deprivation therapy.

    Directory of Open Access Journals (Sweden)

    Michael L Blute

    Full Text Available Androgen deprivation therapy (ADT commonly leads to incomplete cell death and the fate of persistent cells involves, in part, a senescent phenotype. Senescence is terminal growth arrest in response to cell stress that is characterized by increased lysosomal-β-galactosidase (GLB1 the origin of senescence associated-β-gal activity (SA-β-gal. In the current study senescence is examined in vivo after ADT use in a neoadjuvant trial.Tissue microarrays were generated from prostate cancer specimens (n = 126 from a multicenter neoadjuvant ADT trial. Arrays were subjected to multiplexed immunofluorescent staining for GLB1, Ki67, cleaved caspase 3 (CC3 and E-cadherin. Automated quantitative imaging was performed using Vectra™ and expression correlated with clinicopathologic features.Tissue was analyzed from 59 patients treated with neoadjuvant ADT and 67 receiving no therapy preoperatively. Median follow-up was 85.3 mo and median ADT treatment was 5 mo. In PC treated with neoadjuvant ADT, GLB1 expression increased in intermediate Gleason score (GS 6-7; p = 0.001, but not high grade (GS 8-10 cancer. Significantly higher levels of GLB1 were seen in tissues undergoing neoadjuvant ADT longer than 5 months compared to untreated tissues (p = 0.002. In contrast, apoptosis significantly increased earlier (1-4 mo after ADT treatment (p<0.5.Increased GLB1 after neoadjuvant ADT occurs primarily among more clinically favorable intermediate grade cancers and enrichment of the phenotype occurs in a temporally prolonged fashion. Senescence may explain the persistence of PCa cells after ADT. Given concerns for the detrimental longer term presence of senescent cells, targeting these cells for removal may improve outcomes.

  10. Significance of total hysterectomy for uterine cervical cancer persistent in the uterine cervix after radiotherapy

    International Nuclear Information System (INIS)

    Nakayama, Kazutake; Hamada, Tetsurou; Yamauchi, Kazuhiro; Fujimoto, Ikuno; Hasumi, Katsuhiko; Masubuchi, Kazumasa

    1988-01-01

    Radiation therapy is an important means for treating advanced cases of cervical cancer. There are cases, however, in which cancer cells persist even after treatment has been completed. We in the Department of Gynecology at the Cancer Institute Hospital actively performed total hysterectomies in such patients with no distant metastases and no extension of the parametrial induration to the pelvic wall, and obtained favorable results. In the present study, the clinical stage, histological type, degree of removal of involved tissue, and relationship between the prognosis and the maximum diameter of the tumor in the extirpated uterus were examined in 28 patients with advanced cervical cancer treated during the thirty-year period from 1957 to 1986. The following results were obtained: 1. The clinical stage and histological type of the cancer prior to radiation therapy did not significantly affect the prognosis after total hysterectomy. 2. The 3-year survival rate for the patients in whom all involved tissue could be removed was 81.0 percent. In contrast, all those in whom complete removal was impossible survived less than 3 years, despite additional therapy. 3. Prognosis was better in the patients who had tumors with a maximum diameter of less than 2 cm than in those who had tumors with a maximum diameter of 2 cm or more (p < 0.05). 4. Patients in whom all involved tissue could be removed and in whom the maximum diameter of the tumor was less than 2 cm had a good prognoses, with 88.9 percent surviving at least 3 years after surgery. (author)

  11. Randomized controlled pilot study of mindfulness-based stress reduction for persistently fatigued cancer survivors.

    Science.gov (United States)

    Johns, Shelley A; Brown, Linda F; Beck-Coon, Kathleen; Monahan, Patrick O; Tong, Yan; Kroenke, Kurt

    2015-08-01

    Cancer-related fatigue (CRF) is one of the most common, persistent, and disabling symptoms associated with cancer and its treatment. Evidence-based treatments that are acceptable to patients are critically needed. This study examined the efficacy of mindfulness-based stress reduction (MBSR) for CRF and related symptoms. A sample of 35 cancer survivors with clinically significant CRF was randomly assigned to a 7-week MBSR-based intervention or wait-list control group. The intervention group received training in mindfulness meditation, yoga, and self-regulatory responses to stress. Fatigue interference (primary outcome) and a variety of secondary outcomes (e.g., fatigue severity, vitality, disability, depression, anxiety, and sleep disturbance) were assessed at baseline, post-intervention, and 1-month follow-up. Bonferroni correction was employed to account for multiple comparisons. Controls received the intervention after the 1-month follow-up. Participants in both groups were followed for 6 months after completing their respective MBSR courses to assess maintenance of effects. Compared to controls, the MBSR group reported large post-intervention reductions as assessed by effect sizes (d) in the primary outcome, fatigue interference (d = -1.43, p mindfulness. Mindfulness-based stress reduction is a promising treatment for CRF and associated symptoms. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Colony Lysate Arrays for Proteomic Profiling of Drug-Tolerant Persisters of Cancer Cell.

    Science.gov (United States)

    Kume, Kohei; Nishizuka, Satoshi S

    2017-09-05

    Functional heterogeneity of cancer cells is one of the key properties to understanding relapse after drug treatment. Hence, clarification is needed with regard to which types of subgroups of cancer cells dominantly contribute to the initiation of relapse. Recently, we established the colony lysate array (CoLA), which is a method that allows comparison of individual colonies at the protein level to assess the initiation of anticancer drug-tolerant persisters (DTPs) based on the reverse-phase protein array (RPPA) system. DTPs grow in various drug concentrations and types showing 2-dimensional growth (∼1 mm) on a flat surface. The size of DTPs are larger than spheroids (∼0.3 mm) in agarose gel, which makes them easy to handle for a number of assays. DTPs provide functional information during the process of their formation, initiating from the origin of a drug-tolerant single cell. Using >2000 DTPs generated from various drugs and doses profiled on the basis of 44 proteins, we demonstrate that the DTPs are clustered on the basis of their proteomic profiles changing in response to drugs and doses. Of interest, nine transcription factors in the DTPs, such as STAT3 and OCT4A, were identified as having decreased or increased levels of proteins in response to gefitinib. Importantly, these results can be obtained only by individual proteomic colony profiling, which may identify alternative therapeutic targets and biomarkers for DTPs that may harbor critical mechanisms for cancer relapse.

  13. Consequences of the Allee effect and intraspecific competition on population persistence under adverse environmental conditions.

    Science.gov (United States)

    Petrovskii, Sergei; Blackshaw, Rod; Li, Bai-Lian

    2008-02-01

    The impact of intraspecific interactions on ecological stability and population persistence in terms of steady state(s) existence is considered theoretically based on a general competition model. We compare persistence of a structured population consisting of a few interacting (competitive) subpopulations, or groups, to persistence of the corresponding unstructured population. For a general case, we show that if the intra-group competition is stronger than the inter-group competition, then the structured population is less prone to extinction, i.e. it can persist in a parameter range where the unstructured population goes extinct. For a more specific case of a population with hierarchical competition, we show that relative viability of structured and unstructured populations depend on the type of density dependence in the population growth. Namely, while in the case of logistic growth, structured and unstructured populations exhibit equivalent persistence; in the case of Allee dynamics, the persistence of a hierarchically structured population is shown to be higher. We then apply these results to the case of behaviourally structured populations and demonstrate that an extreme form of individual aggression can be beneficial at the population level and enhance population persistence.

  14. Predictive factors for the development of persistent pain after breast cancer surgery

    DEFF Research Database (Denmark)

    Andersen, Kenneth Geving; Duriaud, Helle Molter; Jensen, Helle Elisabeth

    2015-01-01

    Previous studies have reported that 15% to 25% of patients treated for breast cancer experience long-term moderate-to-severe pain in the area of surgery, potentially lasting for several years. Few prospective studies have included all potential risk factors for the development of persistent pain...... were included, and 475 (88%) were available for analysis at 1 year. At 1-year follow-up, the prevalence of moderate-to-severe pain at rest was 14% and during movement was 7%. Factors associated with pain at rest were age ... = 0.006), axillary lymph node dissection with preservation of the intercostobrachial nerve (OR: 3.1, P = 0.0005), moderate-to-severe preoperative pain (OR: 5.7, P = 0.0002), acute postoperative pain (OR: 2.8, P = 0.0018), and signs of neuropathic pain at 1 week (OR: 2.1, P = 0.01). Higher preoperative...

  15. The Relationship Between Sensory Loss and Persistent Pain 1 Year After Breast Cancer Surgery

    DEFF Research Database (Denmark)

    Andersen, Kenneth Geving; Duriaud, Helle Molter; Kehlet, Henrik

    2017-01-01

    Moderate to severe persistent pain after breast cancer surgery (PPBCS) affects 10 to 20% of the patients. Sensory dysfunction is often concomitantly present suggesting a neuropathic pain state. The relationship between various postoperative pain states and sensory dysfunction has been examined......, mechanical pain threshold, and thermal thresholds. Two hundred ninety patients were enrolled and results showed that 38 (13%) had moderate to severe pain and 246 (85%) had hypoesthesia in the surgical area 1 year after surgery. Increased hypoesthesia areas were associated with pain at rest as well as during...... movement (P = .0001). Pain during movement was associated with a side-to-side difference of 140% (P = .001) for tactile detection threshold and 40% (P = .01) for mechanical pain threshold as well as increased thermal thresholds in the axilla (P > .001). Logistic regression models controlling...

  16. Proteoglycans remodeling in cancer: Underlying molecular mechanisms.

    Science.gov (United States)

    Theocharis, Achilleas D; Karamanos, Nikos K

    2017-11-08

    Extracellular matrix is a highly dynamic macromolecular network. Proteoglycans are major components of extracellular matrix playing key roles in its structural organization and cell signaling contributing to the control of numerous normal and pathological processes. As multifunctional molecules, proteoglycans participate in various cell functions during morphogenesis, wound healing, inflammation and tumorigenesis. Their interactions with matrix effectors, cell surface receptors and enzymes enable them with unique properties. In malignancy, extensive remodeling of tumor stroma is associated with marked alterations in proteoglycans' expression and structural variability. Proteoglycans exert diverse functions in tumor stroma in a cell-specific and context-specific manner and they mainly contribute to the formation of a permissive provisional matrix for tumor growth affecting tissue organization, cell-cell and cell-matrix interactions and tumor cell signaling. Proteoglycans also modulate cancer cell phenotype and properties, the development of drug resistance and tumor stroma angiogenesis. This review summarizes the proteoglycans remodeling and their novel biological roles in malignancies with particular emphasis to the underlying molecular mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Persistence of Gamma-H2AX Foci in Irradiated Bronchial Cells Correlates with Susceptibility to Radiation Associated Lung Cancer in Mice

    Science.gov (United States)

    Ochola, Donasian O.; Sharif, Rabab; Bedford, Joel S.; Keefe, Thomas J.; Kato, Takamitsu A.; Fallgren, Christina M.; Demant, Peter; Costes, Sylvain V.; Weil, Michael M.

    2018-01-01

    The risk of developing radiation-induced lung cancer differs between different strains of mice, but the underlying cause of the strain differences is unknown. Strains of mice also differ in their ability to efficiently repair DNA double strand breaks resulting from radiation exposure. We phenotyped mouse strains from the CcS/Dem recombinant congenic strain set for their efficacy in repairing DNA double strand breaks during protracted radiation exposures. We monitored persistent gamma-H2AX radiation induced foci (RIF) 24 hours after exposure to chronic gamma-rays as a surrogate marker for repair deficiency in bronchial epithelial cells for 17 of the CcS/Dem strains and the BALB/cHeN founder strain. We observed a very strong correlation R2 = 79.18%, P cancer percent incidence measured in the same strains. Interestingly, spontaneous levels of foci in non-irradiated strains also showed good correlation with lung cancer incidence (R2=32.74%, P =0.013). These results suggest that genetic differences in DNA repair capacity largely account for differing susceptibilities to radiation-induced lung cancer among CcS/Dem mouse strains and that high levels of spontaneous DNA damage is also a relatively good marker of cancer predisposition. In a smaller pilot study, we found that the repair capacity measured in peripheral blood leucocytes also correlated well with radiogenic lung cancer susceptibility, raising the possibility that such phenotyping assay could be used to detect radiogenic lung cancer susceptibility in humans.

  18. Persistent STAT3 Activation in Colon Cancer Is Associated with Enhanced Cell Proliferation and Tumor Growth

    Directory of Open Access Journals (Sweden)

    Florian M. Corvinus

    2005-06-01

    Full Text Available Colorectal carcinoma (CRC is a major cause of morbidity and mortality in Western countries. It has so far been molecularly defined mainly by alterations of the Wnt pathway. We show here for the first time that aberrant activities of the signal transducer and activator of transcription STAT3 actively contribute to this malignancy and, thus, are a potential therapeutic target for CRC. Constitutive STAT3 activity was found to be abundant in dedifferentiated cancer cells and infiltrating lymphocytes of CRC samples, but not in non-neoplastic colon epithelium. Cell lines derived from malignant colorectal tumors lost persistent STAT3 activity in culture. However, implantation of colon carcinoma cells into nude mice resulted in restoration of STAT3 activity, suggesting a role of an extracellular stimulus within the tumor microenvironment as a trigger for STAT activation. STAT3 activity in CRC cells triggered through interleukin-6 or through a constitutively active STAT3 mutant promoted cancer cell multiplication, whereas STAT3 inhibition through a dominant-negative variant impaired IL-6-driven proliferation. Blockade of STAT3 activation in CRCderived xenograft tumors slowed down their development, arguing for a contribution of STAT3 to colorectal tumor growth.

  19. Adipose tissue concentrations of persistent organic pollutants and total cancer risk in an adult cohort from Southern Spain

    DEFF Research Database (Denmark)

    Arrebola, Juan P; Fernández, Mariana F; Martín-Olmedo, Piedad

    2014-01-01

    There is an increasing trend in the incidence of cancer worldwide, and it has been accepted that environmental factors account for an important proportion of the global burden. The present paper reports preliminary findings on the influence of the historical exposure to a group of persistent orga...

  20. Self-administered Acupressure for Persistent Cancer-related Fatigue: Fidelity Considerations.

    Science.gov (United States)

    Wyatt, Gwen Karilyn; Frambes, Dawn Annette; Harris, Richard E; Arnedt, John Todd; Murphy, Susan L; Zick, Suzanna M

    2015-01-01

    Complementary therapies are frequently used by breast cancer patients for symptom management; however, documentation of the components of intervention fidelity for studies is not widely available. This report examines the components of intervention fidelity, as put forth by the Treatment Fidelity Workgroup of the Behavior Change Consortium at the National Institutes for Health (NIH-BCC Workgroup), within an ongoing acupressure study of breast cancer survivors with persistent cancer-related fatigue (PCRF). For the acupressure study, the research team designed a randomized, controlled trial (RCT) with 3 parallel groups: (1) stimulating acupressure (intervention group); (2) relaxing acupressure (intervention group); and (3) standard care (control group). At baseline and at wk 3 and wk 6 of the study, women in the acupressure study attended sessions for training and data collection at clinics in the counties of Michigan where they lived. The self-administration of acupressure occurred in participants' homes. Targeted enrollment for the acupressure study is 300 breast cancer survivors who had experienced moderate-to-severe PCRF lasting longer than 1 y beyond treatment. The women are being recruited from 5 counties in Michigan, using the Michigan Tumor Registry to identify potential participants. The subsample report includes 183 participants who have completed all 10 wk of the acupressure study. Most participants in the acupressure study are Caucasian, are married, and have some college education. The acupressure study's educators teach participants in the intervention groups to self-administer either relaxing or stimulating acupressure for a 30-min period on a daily basis for 6 wk. All 3 groups receive the usual care for breast cancer survivors. For the acupressure study, the participants log the frequency of the self-administered acupressure sessions and their fatigue levels. Symptom assessments are made for all groups by telephone in the acupressure study at wk 2

  1. Persistent and automatic intraoperative 3D digitization of surfaces under dynamic magnifications of an operating microscope.

    Science.gov (United States)

    Kumar, Ankur N; Miga, Michael I; Pheiffer, Thomas S; Chambless, Lola B; Thompson, Reid C; Dawant, Benoit M

    2015-01-01

    One of the major challenges impeding advancement in image-guided surgical (IGS) systems is the soft-tissue deformation during surgical procedures. These deformations reduce the utility of the patient's preoperative images and may produce inaccuracies in the application of preoperative surgical plans. Solutions to compensate for the tissue deformations include the acquisition of intraoperative tomographic images of the whole organ for direct displacement measurement and techniques that combines intraoperative organ surface measurements with computational biomechanical models to predict subsurface displacements. The later solution has the advantage of being less expensive and amenable to surgical workflow. Several modalities such as textured laser scanners, conoscopic holography, and stereo-pair cameras have been proposed for the intraoperative 3D estimation of organ surfaces to drive patient-specific biomechanical models for the intraoperative update of preoperative images. Though each modality has its respective advantages and disadvantages, stereo-pair camera approaches used within a standard operating microscope is the focus of this article. A new method that permits the automatic and near real-time estimation of 3D surfaces (at 1 Hz) under varying magnifications of the operating microscope is proposed. This method has been evaluated on a CAD phantom object and on full-length neurosurgery video sequences (∼1 h) acquired intraoperatively by the proposed stereovision system. To the best of our knowledge, this type of validation study on full-length brain tumor surgery videos has not been done before. The method for estimating the unknown magnification factor of the operating microscope achieves accuracy within 0.02 of the theoretical value on a CAD phantom and within 0.06 on 4 clinical videos of the entire brain tumor surgery. When compared to a laser range scanner, the proposed method for reconstructing 3D surfaces intraoperatively achieves root mean square

  2. Technological leadership and persistence of monopoly under endogenous entry: static versus dynamic analysis

    Czech Academy of Sciences Publication Activity Database

    Kováč, E.; Vinogradov, V.; Žigić, Krešimir

    -, č. 401 (2009), s. 1-38 ISSN 1211-3298 R&D Projects: GA MŠk LC542 Institutional research plan: CEZ:MSM0021620846 Keywords : dynamic oligopoly * endogenous entry * persistence of monopoly Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp401.pdf

  3. Technological leadership and persistence of monopoly under endogenous entry: static versus dynamic analysis

    Czech Academy of Sciences Publication Activity Database

    Kováč, Eugen; Vinogradov, Viatcheslav; Žigić, K.

    2010-01-01

    Roč. 34, č. 8 (2010), s. 1421-1441 ISSN 0165-1889 Institutional research plan: CEZ:AV0Z70850503 Keywords : dynamic oligopoly * persistence of monopoly * strategic predation Subject RIV: AH - Economics Impact factor: 1.117, year: 2010

  4. Technological leadership and persistence of monopoly under endogenous entry: static versus dynamic analysis

    Czech Academy of Sciences Publication Activity Database

    Kováč, E.; Vinogradov, V.; Žigić, Krešimir

    2010-01-01

    Roč. 34, č. 8 (2010), s. 1421-1441 ISSN 0165-1889 R&D Projects: GA MŠk LC542 Institutional research plan: CEZ:MSM0021620846 Keywords : dynamic oligopoly * persistence of monopoly * strategic predation Subject RIV: AH - Economics Impact factor: 1.117, year: 2010

  5. California forests show early indications of both range shifts and local persistence under climate change

    Science.gov (United States)

    Josep M. Serra-Diaz; Janet Franklin; Whalen W. Dillon; Alexandra D. Syphard; Frank W. Davis; Ross K. Meentemeyer

    2015-01-01

    Aim Forest regeneration data provide an early signal of the persistence and migration of tree species, so we investigated whether species shifts due to climate change exhibit a common signal of response or whether changes vary by species. Location California Floristic Province, United...

  6. Technological leadership and persistence of monopoly under endogenous entry: static versus dynamic analysis

    Czech Academy of Sciences Publication Activity Database

    Kováč, Eugen; Vinogradov, Viatcheslav; Žigić, K.

    -, č. 401 (2009), s. 1-38 ISSN 1211-3298 R&D Projects: GA MŠk LC542 Institutional research plan: CEZ:AV0Z70850503 Keywords : dynamic oligopoly * endogenous entry * persistence of monopoly Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp401.pdf

  7. Radiation for persistent or recurrent epithelial ovarian cancer: a need for reassessment

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Noorie; Kim, Hak Jae [Dept. of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Chang, Ji Hyun; Kim, Suzy [Dept. of Radiation Oncology, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of)

    2017-06-15

    The role of radiotherapy (RT) was largely deserted after the introduction of platinum-based chemotherapy, but still survival rates are disappointingly low. This study focuses on assessing the clinical efficacy of RT in relation to chemotherapy resistance. From October 2002 to January 2015, 44 patients were diagnosed with epithelial ovarian cancer (EOC) and treated with palliative RT for persistent or recurrent EOC. All patients received initial treatment with optimal debulking surgery and adjuvant platinum-based chemotherapy. The biologically effective dose (BED) was calculated with α/β set at 10. Ninety-four sites were treated with RT with a median BED of 50.7 Gy (range 28.0 to 79.2 Gy). The primary end-point was the in-field local control (LC) interval, defined as the time interval from the date RT was completed to the date any progressive or newly recurring disease within the RT field was detected on radiographic imaging. The median follow-up duration was 52.3 months (range 7.7 to 179.0 months). The 1-year and 2-year in-field LC rates were 66.0% and 55.0%, respectively. Comparisons of percent change of in-field tumor response showed similar distribution of responses among chemoresistant and chemosensitive tumors. On multivariate analysis of predictive factors for in-field LC analyzed by sites treated, BED ≥ 50 Gy (hazard ratio, 0.4; confidence interval, 0.2–0.9; p = 0.025) showed better outcomes. Regardless of resistance to platinum-based chemotherapy, RT can be a feasible treatment modality for patients with persistent of recurrent EOC. The specific role of RT using updated approaches needs to be reassessed.

  8. Under what conditions do climate-driven sex ratios enhance versus diminish population persistence?

    Science.gov (United States)

    Boyle, Maria; Hone, Jim; Schwanz, Lisa E; Georges, Arthur

    2014-01-01

    For many species of reptile, crucial demographic parameters such as embryonic survival and individual sex (male or female) depend on ambient temperature during incubation. While much has been made of the role of climate on offspring sex ratios in species with temperature-dependent sex determination (TSD), the impact of variable sex ratio on populations is likely to depend on how limiting male numbers are to female fecundity in female-biased populations, and whether a climatic effect on embryonic survival overwhelms or interacts with sex ratio. To examine the sensitivity of populations to these interacting factors, we developed a generalized model to explore the effects of embryonic survival, hatchling sex ratio, and the interaction between these, on population size and persistence while varying the levels of male limitation. Populations with TSD reached a greater maximum number of females compared to populations with GSD, although this was often associated with a narrower range of persistence. When survival depended on temperature, TSD populations persisted over a greater range of temperatures than GSD populations. This benefit of TSD was greatly reduced by even modest male limitation, indicating very strong importance of this largely unmeasured biologic factor. Finally, when males were not limiting, a steep relationship between sex ratio and temperature favoured population persistence across a wider range of climates compared to the shallower relationships. The opposite was true when males were limiting – shallow relationships between sex ratio and temperature allowed greater persistence. The results highlight that, if we are to predict the response of populations with TSD to climate change, it is imperative to 1) accurately quantify the extent to which male abundance limits female fecundity, and 2) measure how sex ratios and peak survival coincide over climate. PMID:25512848

  9. Persistent activity in a recurrent circuit underlies courtship memory in Drosophila

    Science.gov (United States)

    Zhao, Xiaoliang; Lenek, Daniela; Dag, Ugur; Dickson, Barry J

    2018-01-01

    Recurrent connections are thought to be a common feature of the neural circuits that encode memories, but how memories are laid down in such circuits is not fully understood. Here we present evidence that courtship memory in Drosophila relies on the recurrent circuit between mushroom body gamma (MBγ), M6 output, and aSP13 dopaminergic neurons. We demonstrate persistent neuronal activity of aSP13 neurons and show that it transiently potentiates synaptic transmission from MBγ>M6 neurons. M6 neurons in turn provide input to aSP13 neurons, prolonging potentiation of MBγ>M6 synapses over time periods that match short-term memory. These data support a model in which persistent aSP13 activity within a recurrent circuit lays the foundation for a short-term memory. PMID:29322941

  10. Metapopulation modelling of riparian tree species persistence in river networks under climate change.

    Science.gov (United States)

    Van Looy, Kris; Piffady, Jérémy

    2017-11-01

    Floodplain landscapes are highly fragmented by river regulation resulting in habitat degradation and flood regime perturbation, posing risks to population persistence. Climate change is expected to pose supplementary risks in this context of fragmented landscapes, and especially for river systems adaptation management programs are developed. The association of habitat quality and quantity with the landscape dynamics and resilience to human-induced disturbances is still poorly understood in the context of species survival and colonization processes, but essential to prioritize conservation and restoration actions. We present a modelling approach that elucidates network connectivity and landscape dynamics in spatial and temporal context to identify vital corridors and conservation priorities in the Loire river and its tributaries. Alteration of flooding and flow regimes is believed to be critical to population dynamics in river ecosystems. Still, little is known of critical levels of alteration both spatially and temporally. We applied metapopulation modelling approaches for a dispersal-limited tree species, white elm; and a recruitment-limited tree species, black poplar. In different model steps the connectivity and natural dynamics of the river landscape are confronted with physical alterations (dams/dykes) to species survival and then future scenarios for climatic changes and potential adaptation measures are entered in the model and translated in population persistence over the river basin. For the two tree species we highlighted crucial network zones in relation to habitat quality and connectivity. Where the human impact model already shows currently restricted metapopulation development, climate change is projected to aggravate this persistence perspective substantially. For both species a significant drawback to the basin population is observed, with 1/3 for elm and ¼ for poplar after 25 years already. But proposed adaptation measures prove effective to even

  11. Neuroendocrine Associations Underlying the Persistent Therapeutic Effects of Classic Serotonergic Psychedelics

    OpenAIRE

    Emmanuelle A. D. Schindler; Emmanuelle A. D. Schindler; Ryan M. Wallace; Jordan A. Sloshower; Jordan A. Sloshower; Deepak C. D’Souza; Deepak C. D’Souza

    2018-01-01

    Recent reports on the effects of psychedelic-assisted therapies for mood disorders and addiction, as well as the effects of psychedelics in the treatment of cluster headache, have demonstrated promising therapeutic results. In addition, the beneficial effects appear to persist well after limited exposure to the drugs, making them particularly appealing as treatments for chronic neuropsychiatric and headache disorders. Understanding the basis of the long-lasting effects, however, will be criti...

  12. Temporal dynamics of 'HoBi'-like pestivirus quasispecies in persistently infected calves generated under experimental conditions.

    Science.gov (United States)

    Weber, Matheus N; Bauermann, Fernando V; Canal, Cláudio W; Bayles, Darrell O; Neill, John D; Ridpath, Julia F

    2017-01-02

    'HoBi'-like virus is an atypical group within the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections. Pestivirus strains exist as quasispecies (swarms of individual viruses) in infected animals and the viral populations making up the quasispecies differ widely in size and diversity in each animal. In the present study the viral quasispecies circulating in persistently infected (PI) calves, generated and maintained under experimental conditions using two different 'HoBi'-like strains, was observed over time. An increase in genetic variability and the development of certain mutations was observed over time. Mutations observed included the loss of a putative N-linked glycosylation site in the E2 region and the change of specific residues in E1/E2. It is hypothesized that these changes may be the results on continued adaption of the pestivirus to individual hosts. This is the first study characterizing variation in the viral swarms of animals persistently infected with HoBi-like viruses over time. Studies of the shifts in PI viral swarms will contribute to our understanding of the host and viral mechanisms that function in the maintenance of pestivirus persistent infections. Published by Elsevier B.V.

  13. Radioactive Iodine Administration Is Associated with Persistent Related Symptoms in Patients with Differentiated Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Pablo Florenzano

    2016-01-01

    Full Text Available Context. Radioiodine (RAI administration has adverse effects in patients treated for thyroid cancer (DTC, but there is scarce information regarding their intensity and duration. Objective. To evaluate frequency and intensity of early and late RAI-related symptoms in patients with DTC. Design. Observational prospective study. Patients. DTC patients who underwent thyroidectomy, with or without RAI. Measurements. Patients answered 2 surveys: (1 from 0 to 6 months and (2 between 6 and 18 months after initial treatment. Results. 110 patients answered the first survey and 61 both. Nearly 80 percent received RAI. Among early symptoms, periorbital edema, excessive tearing, salivary gland disturbances, dry mouth, taste disorders, and nausea were more frequent and intense among RAI patients. Regarding late symptoms, periorbital edema, salivary gland pain and swelling, and dry mouth were more frequent and intense in RAI patients. Frequency and intensity of adverse effects were not different between low and high RAI doses (50 versus ≥100 mCi. Conclusion. RAI-related symptoms are frequent and usually persist after 6 months of administration, even when low doses are given. This finding must be considered when deciding RAI administration, especially in low risk patients, among whom RAI benefit is controversial.

  14. Persistency of Prediction Accuracy and Genetic Gain in Synthetic Populations Under Recurrent Genomic Selection.

    Science.gov (United States)

    Müller, Dominik; Schopp, Pascal; Melchinger, Albrecht E

    2017-03-10

    Recurrent selection (RS) has been used in plant breeding to successively improve synthetic and other multiparental populations. Synthetics are generated from a limited number of parents [Formula: see text] but little is known about how [Formula: see text] affects genomic selection (GS) in RS, especially the persistency of prediction accuracy ([Formula: see text]) and genetic gain. Synthetics were simulated by intermating [Formula: see text]= 2-32 parent lines from an ancestral population with short- or long-range linkage disequilibrium ([Formula: see text]) and subjected to multiple cycles of GS. We determined [Formula: see text] and genetic gain across 30 cycles for different training set ( TS ) sizes, marker densities, and generations of recombination before model training. Contributions to [Formula: see text] and genetic gain from pedigree relationships, as well as from cosegregation and [Formula: see text] between QTL and markers, were analyzed via four scenarios differing in (i) the relatedness between TS and selection candidates and (ii) whether selection was based on markers or pedigree records. Persistency of [Formula: see text] was high for small [Formula: see text] where predominantly cosegregation contributed to [Formula: see text], but also for large [Formula: see text] where [Formula: see text] replaced cosegregation as the dominant information source. Together with increasing genetic variance, this compensation resulted in relatively constant long- and short-term genetic gain for increasing [Formula: see text] > 4, given long-range LD A in the ancestral population. Although our scenarios suggest that information from pedigree relationships contributed to [Formula: see text] for only very few generations in GS, we expect a longer contribution than in pedigree BLUP, because capturing Mendelian sampling by markers reduces selective pressure on pedigree relationships. Larger TS size ([Formula: see text]) and higher marker density improved persistency of

  15. Persistency of Prediction Accuracy and Genetic Gain in Synthetic Populations Under Recurrent Genomic Selection

    Directory of Open Access Journals (Sweden)

    Dominik Müller

    2017-03-01

    Full Text Available Recurrent selection (RS has been used in plant breeding to successively improve synthetic and other multiparental populations. Synthetics are generated from a limited number of parents ( Np , but little is known about how Np affects genomic selection (GS in RS, especially the persistency of prediction accuracy (rg , g ^ and genetic gain. Synthetics were simulated by intermating Np= 2–32 parent lines from an ancestral population with short- or long-range linkage disequilibrium (LDA and subjected to multiple cycles of GS. We determined rg , g ^ and genetic gain across 30 cycles for different training set (TS sizes, marker densities, and generations of recombination before model training. Contributions to rg , g ^ and genetic gain from pedigree relationships, as well as from cosegregation and LDA between QTL and markers, were analyzed via four scenarios differing in (i the relatedness between TS and selection candidates and (ii whether selection was based on markers or pedigree records. Persistency of rg , g ^ was high for small Np , where predominantly cosegregation contributed to rg , g ^ , but also for large Np , where LDA replaced cosegregation as the dominant information source. Together with increasing genetic variance, this compensation resulted in relatively constant long- and short-term genetic gain for increasing Np > 4, given long-range LDA in the ancestral population. Although our scenarios suggest that information from pedigree relationships contributed to rg , g ^ for only very few generations in GS, we expect a longer contribution than in pedigree BLUP, because capturing Mendelian sampling by markers reduces selective pressure on pedigree relationships. Larger TS size (NTS and higher marker density improved persistency of rg , g ^ and hence genetic gain, but additional recombinations could not increase genetic gain.

  16. Neuroendocrine Associations Underlying the Persistent Therapeutic Effects of Classic Serotonergic Psychedelics

    Directory of Open Access Journals (Sweden)

    Emmanuelle A. D. Schindler

    2018-03-01

    Full Text Available Recent reports on the effects of psychedelic-assisted therapies for mood disorders and addiction, as well as the effects of psychedelics in the treatment of cluster headache, have demonstrated promising therapeutic results. In addition, the beneficial effects appear to persist well after limited exposure to the drugs, making them particularly appealing as treatments for chronic neuropsychiatric and headache disorders. Understanding the basis of the long-lasting effects, however, will be critical for the continued use and development of this drug class. Several mechanisms, including biological and psychological ones, have been suggested to explain the long-lasting effects of psychedelics. Actions on the neuroendocrine system are some such mechanisms that warrant further investigation in the study of persisting psychedelic effects. In this report, we review certain structural and functional neuroendocrinological pathologies associated with neuropsychiatric disorders and cluster headache. We then review the effects that psychedelic drugs have on those systems and provide preliminary support for potential long-term effects. The circadian biology of cluster headache is of particular relevance in this area. We also discuss methodologic considerations for future investigations of neuroendocrine system involvement in the therapeutic benefits of psychedelic drugs.

  17. Neuroendocrine Associations Underlying the Persistent Therapeutic Effects of Classic Serotonergic Psychedelics.

    Science.gov (United States)

    Schindler, Emmanuelle A D; Wallace, Ryan M; Sloshower, Jordan A; D'Souza, Deepak C

    2018-01-01

    Recent reports on the effects of psychedelic-assisted therapies for mood disorders and addiction, as well as the effects of psychedelics in the treatment of cluster headache, have demonstrated promising therapeutic results. In addition, the beneficial effects appear to persist well after limited exposure to the drugs, making them particularly appealing as treatments for chronic neuropsychiatric and headache disorders. Understanding the basis of the long-lasting effects, however, will be critical for the continued use and development of this drug class. Several mechanisms, including biological and psychological ones, have been suggested to explain the long-lasting effects of psychedelics. Actions on the neuroendocrine system are some such mechanisms that warrant further investigation in the study of persisting psychedelic effects. In this report, we review certain structural and functional neuroendocrinological pathologies associated with neuropsychiatric disorders and cluster headache. We then review the effects that psychedelic drugs have on those systems and provide preliminary support for potential long-term effects. The circadian biology of cluster headache is of particular relevance in this area. We also discuss methodologic considerations for future investigations of neuroendocrine system involvement in the therapeutic benefits of psychedelic drugs.

  18. Persistent quality of life impairments in differentiated thyroid cancer patients: results from a monitoring programme

    Energy Technology Data Exchange (ETDEWEB)

    Gamper, Eva-Maria [Medical University Innsbruck, Department for Nuclear Medicine, Innsbruck (Austria); Medical University Innsbruck, Department for Psychiatry and Psychotherapy, Innsbruck (Austria); Wintner, Lisa M.; Holzner, Bernhard [Medical University Innsbruck, Department for Psychiatry and Psychotherapy, Innsbruck (Austria); Rodrigues, Margarida; Buxbaum, Sabine; Nilica, Bernhard; Virgolini, Irene [Medical University Innsbruck, Department for Nuclear Medicine, Innsbruck (Austria); Singer, Susanne [University of Mainz, Institute of Medical Biostatistics, Epidemiology, and Informatics, Mainz (Germany); Giesinger, Johannes M. [Netherlands Cancer Institute, Amsterdam (Netherlands)

    2015-07-15

    Health-related quality of life (HRQOL) in differentiated thyroid cancer (DTC) research has so far received little attention and available results are conflicting. We studied the HRQOL of radioiodine-naive DTC patients in comparison with the general population (GP), investigated the course of HRQOL up to 30 months after radioiodine remnant ablation (RAA) and sought to identify patient characteristics associated with HRQOL. We analysed data from routine HRQOL monitoring at a nuclear medicine department. Between 2005 and 2013, a total of 439 thyroid cancer patients (all histologies) completed the EORTC Quality of Life Questionnaire Core-30 (QLQ-C30) at least once during their treatment at the department. We compared patients' baseline HRQOL scores before RAA with scores from age-matched and sex-matched controls from the Austrian GP. We then determined the course of HRQOL over the 30 months after RAA and assessed the impact of the following clinical variables on HRQOL: method of thyroid-stimulating hormone (TSH) stimulation, histology (papillary vs. follicular) and disease stage. A total of 284 patients (mean age 48.3 years, SD 15.0 years; 71.6 % women; 80.7 % papillary type) with a baseline HRQOL assessment before RAA were available. We found clinically meaningful differences in the detriment in patients on almost all domains. These were largest for fatigue (23 points) and role functioning (25 points). Data from 241 patients (mean age 48.6 years, SD 15.9 years; 68.9 % women; 76.3 % papillary type) were included in the longitudinal analysis. Investigating the course of HRQOL, a significant improvement over time was found for role and emotional functioning, fatigue, pain, and dyspnoea. A range of HRQOL scores were improved in patients with exogenous TSH stimulation, but some scores both in patients with exogenous TSH stimulation and in those followed for 30 months, especially fatigue and role functioning, did not reach levels in the GP sample. Our results show that

  19. Persistence of Pasteurella multocida in Nebraska (USA) wetlands under epizootic conditions

    Science.gov (United States)

    Price, J.I.; Brand, C.J.

    1984-01-01

    Gleason Basin, a marsh located in the western part of the Rainwater Basin in Nebraska, was selected during the 1980 spring waterfowl migration as a study site to determine the presence and persistence of virulent Pasteurella multocida. Avian cholera mortality in migratory waterfowl using the Basin increased during a 2-wk period of a die-off beginning the first week of March when 2,409 carcasses were collected from the marsh. Study sites within the marsh were established for sampling water associated with and not associated with intact and scavenged carcasses. Isolations of virulent P. multocida were made from five of six study sites associated with either intact or scavenged carcasses for 3 days and from three of five non-carcass-associated study sites for 2 days. Recovery of these bacteria from this environment suggested a possible source of infection for susceptible waterfowl using the contaminated site.

  20. Discrete-time CMAC NN control of feedback linearizable nonlinear systems under a persistence of excitation.

    Science.gov (United States)

    Jagannathan, S

    1999-01-01

    The local structure of CMAC neural networks (NN) result in better and faster controllers for nonlinear dynamical systems. A CMAC neural network-based discrete-time controller which linearizes the unknown multiinput and multioutput (MIMO) nonlinear system through feedback is presented. Control action is defined in order to achieve tracking performance for this unknown nonlinear system. An efficient and localized weight addressing scheme for the CMAC NN's is described using an appropriate choice of the B-spline receptive field functions that form a basis. A uniform ultimate boundedness of the closed-loop system is given in the sense of Lyapunov using the persistency of excitation (PE) condition. Simulation results are shown to demonstrate the theoretical conclusions.

  1. Mechanisms underlying ectopic persistent tooth-pulp pain following pulpal inflammation.

    Science.gov (United States)

    Matsuura, Shingo; Shimizu, Kohei; Shinoda, Masamichi; Ohara, Kinuyo; Ogiso, Bunnai; Honda, Kuniya; Katagiri, Ayano; Sessle, Barry J; Urata, Kentaro; Iwata, Koichi

    2013-01-01

    In order to clarify the peripheral mechanisms of ectopic persistent pain in a tooth pulp following pulpal inflammation of an adjacent tooth, masseter muscle activity, phosphorylated extracellular signal-regulated protein kinase (pERK) and TRPV1 immunohistochemistries and satellite cell activation using glial fibrillary acidic protein (GFAP) immunohistochemistry in the trigeminal ganglion (TG) were studied in the rats with molar tooth-pulp inflammation. And, Fluorogold (FG) and DiI were also used in a neuronal tracing study to analyze if some TG neurons innervate more than one tooth pulp. Complete Freund's adjuvant (CFA) or saline was applied into the upper first molar tooth pulp (M1) in pentobarbital-anesthetized rats, and capsaicin was applied into the upper second molar tooth pulp (M2) on day 3 after the CFA or saline application. Mean EMG activity elicited in the masseter muscle by capsaicin application to M2 was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats. The mean number of pERK-immunoreactive (IR) TG cells was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats. Application of the satellite cell inhibitor fluorocitrate (FC) into TG caused a significant depression of capsaicin-induced masseter muscle activity and a significant reduction of satellite cell activation. The number of TRPV1-IR TG cells innervating M2 was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats, and that was decreased following FC injection into TG. Furthermore, 6% of TG neurons innervating M1 and/or M2 innervated both M1 and M2. These findings suggest that satellite cell activation following tooth pulp inflammation and innervation of multiple tooth pulps by single TG neurons may be involved in the enhancement of the activity of TG neurons innervating adjacent non-inflamed teeth that also show enhancement of TRPV1 expression in TG neurons, resulting in the ectopic persistent tooth-pulp pain

  2. Mechanisms underlying ectopic persistent tooth-pulp pain following pulpal inflammation.

    Directory of Open Access Journals (Sweden)

    Shingo Matsuura

    Full Text Available In order to clarify the peripheral mechanisms of ectopic persistent pain in a tooth pulp following pulpal inflammation of an adjacent tooth, masseter muscle activity, phosphorylated extracellular signal-regulated protein kinase (pERK and TRPV1 immunohistochemistries and satellite cell activation using glial fibrillary acidic protein (GFAP immunohistochemistry in the trigeminal ganglion (TG were studied in the rats with molar tooth-pulp inflammation. And, Fluorogold (FG and DiI were also used in a neuronal tracing study to analyze if some TG neurons innervate more than one tooth pulp. Complete Freund's adjuvant (CFA or saline was applied into the upper first molar tooth pulp (M1 in pentobarbital-anesthetized rats, and capsaicin was applied into the upper second molar tooth pulp (M2 on day 3 after the CFA or saline application. Mean EMG activity elicited in the masseter muscle by capsaicin application to M2 was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats. The mean number of pERK-immunoreactive (IR TG cells was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats. Application of the satellite cell inhibitor fluorocitrate (FC into TG caused a significant depression of capsaicin-induced masseter muscle activity and a significant reduction of satellite cell activation. The number of TRPV1-IR TG cells innervating M2 was significantly larger in M1 CFA-applied rats compared with M1 vehicle-applied rats, and that was decreased following FC injection into TG. Furthermore, 6% of TG neurons innervating M1 and/or M2 innervated both M1 and M2. These findings suggest that satellite cell activation following tooth pulp inflammation and innervation of multiple tooth pulps by single TG neurons may be involved in the enhancement of the activity of TG neurons innervating adjacent non-inflamed teeth that also show enhancement of TRPV1 expression in TG neurons, resulting in the ectopic persistent tooth

  3. Persistent cigarette smoking and other tobacco use after a tobacco-related cancer diagnosis

    Science.gov (United States)

    Townsend, Julie S.; Tai, Eric; White, Arica; Davis, Shane P.; Fairley, Temeika L.

    2015-01-01

    Introduction People who continue to smoke after a cancer diagnosis have an increased risk for recurrences or development of new malignancies. These risks may be even higher among tobacco-related cancer survivors (TRCS). We describe tobacco use behaviors among TRCS, other cancer survivors, and people without a history of cancer. Methods We used 2009 Behavioral Risk Factor Surveillance System data to describe demographic characteristics, smoking history, current smoking prevalence, and smokeless tobacco use among TRCS, other cancer survivors, and people without a history of cancer (cigarette smoking and smokeless tobacco use were calculated after adjusting for age, sex, race, and insurance status). Tobacco-related cancers were defined as lung/bronchial, pharyngeal, laryngeal, esophageal, stomach, pancreatic, kidney/renal, urinary bladder, cervical, and acute myeloid leukemia. Results A total of 20 % of all cancer survivors were TRCS. TRCS were primarily female (68 %) and white (78 %). Smoking prevalence was higher among TRCS (27 %) compared with other cancer survivors (16 %) and respondents without a history of cancer (18 %). Smokeless tobacco use was higher among respondents without a history of cancer (4 %) compared with TRCS (3 %) and other cancer survivors (3 %). Conclusions The self-reported smoking prevalence among TRCS is higher than among other cancer survivors and people without a history of cancer. Targeted smoking prevention and cessation interventions are needed for cancer survivors, especially those diagnosed with a tobacco-related cancer. Implications for cancer survivors We recommend all cancer survivors be made aware of the health risks associated with smoking after a cancer diagnosis, and smoking cessation services be offered to those who currently smoke. Condensed abstract We provide the first population-based report on demographic characteristics and tobacco use behaviors among self-reported tobacco-related cancer survivors. PMID:22706885

  4. Persistent cauda equina syndrome after caudal epidural injection under severe spinal stenosis: a case report

    Directory of Open Access Journals (Sweden)

    Seo YT

    2017-06-01

    Full Text Available Young Tak Seo,1 Hyun Ho Kong,1 Goo Joo Lee,1 Heui Je Bang1,2 1Department of Rehabilitation Medicine, Chungbuk National University Hospital, 2Department of Rehabilitation Medicine, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea Abstract: Caudal epidural injection (CEI is one of the most common treatments for low-back pain with sciatica. CEI rarely leads to neurologic complications. We report a case of persistent cauda equina syndrome after CEI. A 44-year-old male patient with severe L4 and L5 spinal stenosis underwent CEI for low-back pain and sciatica. The CEI solution consisted of bupivacaine, hyaluronidase, triamcinolone acetonide, and normal saline. He experienced motor weakness and sensory loss in both lower extremities and neurogenic bladder for more than 1 year after the procedure. His ankle dorsiflexors, big-toe extensors, and ankle plantar flexors on both sides were checked and categorized as motor-power Medical Research Council grade 0. His bilateral ankle-jerk reflection was absent. An electrophysiological study showed lumbosacral polyradiculopathy affecting both sides of the L5 and S1 nerve roots. A urodynamic study revealed hypoactive neurogenic bladder affecting both sacral roots. Keywords: epidural injection, cauda equina syndrome, complications

  5. Glomerular diseases and cancer: evaluation of underlying malignancy.

    Science.gov (United States)

    Pani, Antonello; Porta, Camillo; Cosmai, Laura; Melis, Patrizia; Floris, Matteo; Piras, Doloretta; Gallieni, Maurizio; Rosner, Mitchell; Ponticelli, Claudio

    2016-04-01

    Onconephrology is an emerging medical subspecialty focused on the numerous interconnections between cancer and kidney diseases. Patient with malignancies commonly experience kidney problems including acute kidney injury, tumor lysis syndrome, fluid and electrolyte disorders and chronic kidney disease, often as a consequence of the anti-cancer treatment. Conversely, a number of glomerulopathies, tubulopathies and vascular renal diseases can early signal the presence of an underlying cancer. Furthermore, the administration of immunosuppressive drugs, especially cytotoxic drugs and calcineurin inhibitors, may strongly impair the immune response increasing the risk of cancer. The objective of this review article is to: (i) discuss paraneoplastic glomerular disease, (ii) review cancer as an adverse effect of immunosuppressive agents used to treat glomerulopathies, and (iii) in the absence of international approved guidelines, propose a screening program based on expert opinion aimed at guiding nephrologists to early detect malignancies during their clinical practice.

  6. Virucides in apiculture: persistence of surrogate enterovirus under simulated field conditions.

    Science.gov (United States)

    Prodělalová, Jana; Malenovská, Hana; Moutelíková, Romana; Titěra, Dalibor

    2017-12-01

    Honeybee viruses have been recognized as being among the most important factors leading to colony losses worldwide. Colony food and faeces are regarded as possible sources of infectious viruses able to contaminate the environment and equipment of apiaries. Thus, methods for elimination of viruses are required. No cell culture assay for testing the effect of disinfectants on honeybee viruses is yet available. Therefore, surrogate virus was employed for testing of the efficacy of iodophor- and peracetic acid-based disinfectants in combination with six organic contaminants at +6 °C and +22 °C. Moreover, we evaluated the persistence of the surrogate in honey at +6 °C, +22 °C, and +50 °C. Iodophor-based disinfectant showed a maximum reduction of virus titre of 3.4 log 10 . Peracetic acid reduced the titre (≥4 log 10 ) only at 22 °C and without yeast extract/bovine serum albumin. After 25 days of incubation of the virus - honey mix, no decrease of virus titre was observed at +6 °C, whereas a significant reduction (3.5 log 10 ) was found at +50 °C already after 1 day. Both tested disinfectants can serve as appropriate virucides in apiaries. The effect of peracetic acid significantly depended on temperature and organic contaminants. The iodophor-based disinfectant showed a stable antiviral effect at different temperatures and with different contaminants. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  7. Homogeneous Catalysis Under Ultradilute Conditions: TAML/NaClO Oxidation of Persistent Metaldehyde.

    Science.gov (United States)

    Tang, Liang L; DeNardo, Matthew A; Schuler, Christopher J; Mills, Matthew R; Gayathri, Chakicherla; Gil, Roberto R; Kanda, Rakesh; Collins, Terrence J

    2017-01-18

    TAML activators enable homogeneous oxidation catalysis where the catalyst and substrate (S) are ultradilute (pM-low μM) and the oxidant is very dilute (high nM-low mM). Water contamination by exceptionally persistent micropollutants (MPs), including metaldehyde (Met), provides an ideal space for determining the characteristics and utilitarian limits of this ultradilute catalysis. The low MP concentrations decrease throughout catalysis with S oxidation (k II ) and catalyst inactivation (k i ) competing for the active catalyst. The percentage of substrate converted (%Cvn) can be increased by discovering methods to increase k II /k i . Here we show that NaClO extends catalyst lifetime to increase the Met turnover number (TON) 3-fold compared with H 2 O 2 , highlighting the importance of oxidant choice as a design tool in TAML systems. Met oxidation studies (pH 7, D 2 O, 0.01 M phosphate, 25 °C) monitored by 1 H NMR spectroscopy show benign acetic acid as the only significant product. Analysis of TAML/NaClO treated Met solutions employing successive identical catalyst doses revealed that the processes can be modeled by the recently published relationship between the initial and final [S] (S 0 and S ∞ , respectively), the initial [catalyst] (Fe Tot ) and k II /k i . Consequently, this study establishes that ΔS is proportional to S 0 and that the %Cvn is conserved across all catalyst doses in multicatalyst-dose processes because the rate of the k II process depends on [S] while that of the k i process does not. A general tool for determining the Fe Tot required to effect a desired %Cvn is presented. Examination of the dependence of TON on k II /k i and Fe Tot at a fixed S 0 indicates that for any TAML process employing Fe Tot < 1 × 10 -6 M, small catalyst doses are not more efficient than one large dose.

  8. The musician effect: Does it persist under degraded pitch conditions of cochlear implant simulations?

    Directory of Open Access Journals (Sweden)

    Christina eFuller

    2014-06-01

    Full Text Available Cochlear implants (CIs are auditory prostheses that restore hearing via electrical stimulation of the auditory nerve. Compared to normal acoustic hearing, sounds transmitted through the CI are spectro-temporally degraded, causing difficulties in challenging listening tasks such as speech intelligibility in noise and perception of music. In normal hearing (NH, musicians have been shown to better perform than non-musicians in auditory processing and perception, especially for challenging listening tasks. This ‘musician effect’ was attributed to better processing of pitch cues, as well as better overall auditory cognitive functioning in musicians. Does the musician effect persist when pitch cues are degraded, as it would be in signals transmitted through a CI? To answer this question, NH musicians and non-musicians were tested while listening to unprocessed signals or to signals processed by an acoustic CI simulation. The task increasingly depended on pitch perception: 1 speech intelligibility (words and sentences in quiet or in noise, 2 vocal emotion identification, and 3 melodic contour identification. For speech perception, there was no musician effect with the unprocessed stimuli, and a small musician effect only for word identification in one noise condition, in the CI simulation. For emotion identification, there was a small musician effect for both. For melodic contour identification, there was a large musician effect for both. Overall, the effect was stronger as the importance of pitch in the listening task increased. This suggests that the musician effect may be more rooted in pitch perception, rather than in a global advantage in cognitive processing (in which musicians would have performed better in all tasks. The results further suggest that musical training before (and possibly after implantation might offer some advantage in pitch processing that could partially benefit speech perception, and more strongly emotion and music

  9. Persistence of polycyclic aromatic hydrocarbon components of creosote under anaerobic enrichment conditions.

    Science.gov (United States)

    Sharak Genthner, B R; Townsend, G T; Lantz, S E; Mueller, J G

    1997-01-01

    Anaerobic biodegradation of an artificial mixture of polycyclic aromatic hydrocarbons (PAHs), which simulates the PAH component of creosote, was examined under methanogenic, sulfidogenic, and nitrate-reducing conditions using creosote-contaminated sediment as the source of inoculum. PAH degradation, CH4 formation and ion reduction were monitored for up to one year. Despite demonstrating active methanogenic and nitrate-reducing anaerobic bacterial communities, only limited degradation of a few PAHs was observed. Under methanogenic conditions limited degradation of all bicyclic (naphthalene, 1-and 2-methylnaphthalene, biphenyl, and 2,6-dimethylnaphthalene) and one tricyclic PAH, anthraquinone, was detected. 2-Methylanthracene was apparently degraded under nitrate-reducing conditions. Anthraquinone declined in sulfate enrichments, but this decline was not dependent upon sulfate reduction. None of the 4- or 5-ring PAHs were degraded under any of the enrichment conditions. These data indicate that under the anaerobic conditions tested there is only a limited potential to degrade PAHs which must be considered when proposing bioremediation technologies for PAH-contaminated sites, especially if high-molecular-weight PAHs are present.

  10. Photodynamic therapy in the therapy for recurrent/persistent nasopharyngeal cancer

    NARCIS (Netherlands)

    Wildeman, Maarten A. M.; Nyst, Heike J.; Karakullukcu, Baris; Tan, Bing I.

    2009-01-01

    To determine the efficacy of Photodynamic therapy of patients with recurrent Nasopharyngeal Carcinoma we reviewed all available literature. Since the treatment options for recurrent or persistent Nasopharyngeal Carcinoma are limited, the survival rates poor and the complications severe; there is

  11. Analgesic and Sensory Effects of the Pecs Local Anesthetic Block in Patients with Persistent Pain after Breast Cancer Surgery

    DEFF Research Database (Denmark)

    Wijayasinghe, Nelun; Andersen, Kenneth Geving; Kehlet, Henrik

    2017-01-01

    experienced analgesia (P = 0.008) and reduced hypoesthesia areas to cold (P = 0.004) and warmth (P = 0.01) after 30 minutes. The reported pain relief (P = 0.02) and reduced sleep interference (P = 0.01) persisted for 7 days after the block. CONCLUSIONS: This pilot study suggests that the pectoral nerves play......BACKGROUND: Persistent pain after breast cancer surgery (PPBCS) develops in 15% to 25% of patients, sometimes years after surgery. Approximately 50% of PPBCS patients have neuropathic pain in the breast, which may be due to dysfunction of the pectoral nerves. The Pecs local anesthetic block...... quantitative sensory testing [QST]) in eight patients with PPBCS. SPI and QST measurements were recorded before and 30 minutes after administration of the Pecs block (20 mL 0.25% bupivacaine). Pain intensity and sleep interference were measured daily before and after the block for 7 days. RESULTS: Patients...

  12. Persistence of dysphagia and odynophagia after mediastinal radiation and chemotherapy in patients with lung cancer or lymphoma.

    Science.gov (United States)

    Shields, Helen; Li, Justin; Pelletier, Stephen; Wang, Helen; Freedman, Rachel; Mamon, Harvey; Ng, Andrea; Freedman, Arnold; Come, Steven; Avigan, David; Huberman, Mark; Recht, Abram

    2017-02-01

    Esophageal symptoms are common during radiation and chemotherapy. It is unclear how often these symptoms persist after therapy. We retrospectively reviewed medical records of 320 adults treated for nonmetastatic breast cancer (84), lung cancer (109), or Hodgkin and non-Hodgkin lymphoma (127) who were disease-free at 10-14 months after therapy. Treatment included chemotherapy with or without nonmediastinal radiation therapy (150 patients), chemotherapy plus sequential mediastinal radiation therapy (MRT) (48 patients), chemotherapy plus concurrent MRT (61 patients), or non-MRT only (61 patients). Proton pump inhibitor use was documented. All treatment groups had similar prevalence of the esophageal symptom of heartburn before therapy. Rates were higher during treatment in those who received MRT with or without chemotherapy, but declined by 10-14 months after treatment. However, low baseline rates of dysphagia (4%) and odynophagia (2%) increased significantly after combined chemotherapy and MRT to 72% for dysphagia and 62% for odynophagia (P mediastinal radiation. Our data highlight the important challenge for clinicians of managing patients with lung cancer and lymphoma who have persistent esophageal problems, particularly dysphagia and odynophagia, at approximately 1 year after treatment. © 2016 International Society for Diseases of the Esophagus.

  13. A joint model of persistent human papillomavirus infection and cervical cancer risk: Implications for cervical cancer screening

    OpenAIRE

    Katki, Hormuzd A.; Cheung, Li C.; Fetterman, Barbara; Castle, Philip E.; Sundaram, Rajeshwari

    2015-01-01

    New cervical cancer screening guidelines in the US and many European countries recommend that women get tested for human papillomavirus (HPV). To inform decisions about screening intervals, we calculate the increase in precancer/cancer risk per year of continued HPV infection. However, both time to onset of precancer/cancer and time to HPV clearance are interval-censored, and onset of precancer/cancer strongly informatively censors HPV clearance. We analyze this bivariate informatively interv...

  14. Co-stimulatory signaling determines tumor antigen sensitivity and persistence of CAR T cells targeting PSCA+ metastatic prostate cancer.

    Science.gov (United States)

    Priceman, Saul J; Gerdts, Ethan A; Tilakawardane, Dileshni; Kennewick, Kelly T; Murad, John P; Park, Anthony K; Jeang, Brook; Yamaguchi, Yukiko; Yang, Xin; Urak, Ryan; Weng, Lihong; Chang, Wen-Chung; Wright, Sarah; Pal, Sumanta; Reiter, Robert E; Wu, Anna M; Brown, Christine E; Forman, Stephen J

    2018-01-01

    Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell antigen (PSCA), are widely over-expressed in metastatic disease. While antigen selectivity of CARs for solid cancers is crucial, it is problematic due to the absence of truly restricted tumor antigen expression and potential safety concerns with "on-target off-tumor" activity. Here, we show that the intracellular co-stimulatory signaling domain can determine a CAR's sensitivity for tumor antigen expression. A 4-1BB intracellular co-stimulatory signaling domain in PSCA-CARs confers improved selectivity for higher tumor antigen density, reduced T cell exhaustion phenotype, and equivalent tumor killing ability compared to PSCA-CARs containing the CD28 co-stimulatory signaling domain. PSCA-CARs exhibit robust in vivo anti-tumor activity in patient-derived bone-metastatic prostate cancer xenograft models, and 4-1BB-containing CARs show superior T cell persistence and control of disease compared with CD28-containing CARs. Our study demonstrates the importance of co-stimulation in defining an optimal CAR T cell, and also highlights the significance of clinically relevant models in developing solid cancer CAR T cell therapies.

  15. Co-stimulatory signaling determines tumor antigen sensitivity and persistence of CAR T cells targeting PSCA+ metastatic prostate cancer

    Science.gov (United States)

    Priceman, Saul J.; Gerdts, Ethan A.; Tilakawardane, Dileshni; Kennewick, Kelly T.; Murad, John P.; Park, Anthony K.; Jeang, Brook; Yamaguchi, Yukiko; Urak, Ryan; Weng, Lihong; Chang, Wen-Chung; Wright, Sarah; Pal, Sumanta; Reiter, Robert E.; Brown, Christine E.; Forman, Stephen J.

    2018-01-01

    ABSTRACT Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell antigen (PSCA), are widely over-expressed in metastatic disease. While antigen selectivity of CARs for solid cancers is crucial, it is problematic due to the absence of truly restricted tumor antigen expression and potential safety concerns with “on-target off-tumor” activity. Here, we show that the intracellular co-stimulatory signaling domain can determine a CAR's sensitivity for tumor antigen expression. A 4-1BB intracellular co-stimulatory signaling domain in PSCA-CARs confers improved selectivity for higher tumor antigen density, reduced T cell exhaustion phenotype, and equivalent tumor killing ability compared to PSCA-CARs containing the CD28 co-stimulatory signaling domain. PSCA-CARs exhibit robust in vivo anti-tumor activity in patient-derived bone-metastatic prostate cancer xenograft models, and 4-1BB-containing CARs show superior T cell persistence and control of disease compared with CD28-containing CARs. Our study demonstrates the importance of co-stimulation in defining an optimal CAR T cell, and also highlights the significance of clinically relevant models in developing solid cancer CAR T cell therapies. PMID:29308300

  16. Persistence of nosocomial bacteria on 2 biocidal fabrics based on silver under conditions of high relative humidity.

    Science.gov (United States)

    López-Gigosos, Rosa; Mariscal, Alberto; Gutierrez-Bedmar, Mario; Mariscal-Lopez, Eloisa; Fernández-Crehuet, Joaquín

    2014-08-01

    The survival of pathogenic microorganism on fabrics in the health care environment has a important role in nosocomial infections. The use of biocidal fabrics and surfaces could reduce the prevalence of the microorganisms in the hospital environment. In this study, the persistence of nosocomial bacteria on 2 fabrics containing biocidal fibers (BF) in the long term following desiccation and subsequent storage was examined at 40% and 90% relative humidity (RH). Very few strains survived more than 7 days at 40% RH on fabrics containing 67% BF, and only strains of Acinetobacter baumanii and Pseudomonas aeruginosa survived on fabric containing 100% BF. None of the strains tested survived 14 days on the 2 fabrics, 67% or 100% BF, under these environmental conditions. In contrast, at higher RH (∼90%), most of the strains tested showed prolonged survival on both fabrics, and all strains of Klebsiella pneumoniae, Enterobacter aerogenes, and A baumannii survived for more than 14 days; however, in a Petri dish, most of the microorganisms tested showed a higher survival even at 28 days. The gram-positive cocci and A baumannii were the most persistent bacteria on the Petri dish. This study emphasizes the effect of RH on the survival of nosocomial bacteria on 2 commercially available fabrics containing biocide. Evidence of the clinical efficacy of these BF-containing fabrics is lacking. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  17. Persistent luminescence upconversion for Er{sub 2}O{sub 3} under 975 nm excitation in vacuum

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiwei [Faculty of Physics, Liaoning University, Shenyang 110036 (China); Hao, Jian Hua [Department of Applied Physics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR (Hong Kong); Tanner, Peter A. [Department of Science and Environmental Studies, The Hong Kong Institute of Education, Tai Po, Hong Kong SAR (Hong Kong)

    2015-08-15

    The 975 nm excited emission of Er{sub 2}O{sub 3} in the infrared (IR) and visible spectral regions at powers below the threshold for broadband white light generation has been investigated. In this regime the log(emission intensity) vs log(power) plots for emission at 660 nm and 1540 nm exhibit slopes for the sample in air (vacuum) of ~1 (~5) and ~1 (~2), respectively and the excitation mechanisms are discussed. The build-up of the emission is on the timescale of seconds and the excitation and decay transients have been recorded and analyzed for various excitation powers. The decay of the IR and visible emission each follow biexponential processes on a second timescale. The duration and kinetics of the emission decay are characteristic of persistent luminescence. - Highlights: • Infrared and red emission of Er{sub 2}O{sub 3} under 975 nm excitation. • Power dependence of emission. • Fitting of decay and rise transients. • Features characteristic of persistent luminescence.

  18. Experimental study of dynamic diffusion tensor imaging in spinal cord of goats under persistent compression

    International Nuclear Information System (INIS)

    Liu Jicun; Liu Huaijun; He Dan; Huang Boyuan; Cui Caixia; Wang Zhihong; Xu Yingjin

    2009-01-01

    Objective: To explore the dynamic changes of diffusion tensor imaging (DTI) in spinal cord of goats with persistent compression injury. Methods: Eighteen goats weighted 20-25 kg were divided into three groups with completely random design: A, B and C. A balloon catheter was inserted into the epidural space at C3-4 level via intervertabral foramen for each goat. The balloon was inflated by injection of variable volumes of saline in group A and B 10 days following operation. The volume of saline was 0.3 ml in group A and 0.2 ml in group B, respectively. The compression sustained for 40 days. Group C served as uncompressed control without injection of saline. The locomotor rating score was applied to each group. Conventional MRI and DTI were performed. The apparent diffusion coefficient (ADC)and fractional anisotropy(FA) values were measured. Histopathological assessments of the compressed spinal cord were performed 50 days following operation with light microscope and transmission electron microscopy. Results: Before operation, the locomotor rating score was 5, the ADC value was (1.23 ± 0.05) x 10 -3 mm 2 /s and the FA value was (0.72 ± 0.05) each group. Of six goats in Group A, the locomotor rating score severely decreased and reached (1.5 ± 0.4)on the 40 th day after compression. The ADC value at compression site decreased soon and reached the minimum (0.75 ± 0.04) x 10 -3 mm 2 /s on the 5 th day after compression. Then the ADC value increased gradually, restored normal on the 10 th day or so, then became markedly higher than normal and reached (1.61±0.05) x 10 -3 mm 2 /s on the 40 th day. The FA value at compression site decreased soon, reached (0.54±0.04)on the 1st day, then decreased gradually and reached (0.43± 0.05) on the 40 th day. It appeared high signal intensity on T 2 WI on the 10 th day. In Group B, the locomotor rating score was moderately decreased and reached (3.4 ± 0.5) on the 40 th day. The ADC value at compression site decreased slightly

  19. Photocatalytic Activity and Optical Properties of Blue Persistent Phosphors under UV and Solar Irradiation

    Directory of Open Access Journals (Sweden)

    C. R. García

    2016-01-01

    Full Text Available Blue phosphorescent strontium aluminosilicate powders were prepared by combustion synthesis route and a postannealing treatments at different temperatures. X-ray diffraction analysis showed that phosphors are composed of two main hexagonal phases: SrAl2O4 and Sr3Al32O51. The morphology of the phosphors changed from micrograins (1000°C to a mixture of bars and hexagons (1200°C and finally to only hexagons (1300°C as the annealing temperature is increased. Photoluminescence spectra showed a strong blue-green phosphorescent emission centered at λem=455 nm, which is associated with 4f65d1→4f6  (8S7/2 transition of the Eu2+. The sample annealed at 1200°C presents the highest luminance value (40 Cd/m2 with CIE coordinates (0.1589, 0.1972. Also, the photocatalytic degradation of methylene blue (MB under UV light (at 365 nm was monitored. Samples annealed at 1000°C and 1300°C presented the highest percentage of degradation (32% and 38.5%, resp. after 360 min. In the case of photocatalytic activity under solar irradiation, the samples annealed at 1000°C, 1150°C, and 1200°C produced total degradation of MB after only 300 min. Hence, the results obtained with solar photocatalysis suggest that our powders could be useful for water cleaning in water treatment plants.

  20. [Persistent diarrhea

    Science.gov (United States)

    Andrade, J A; Moreira, C; Fagundes Neto, U

    2000-07-01

    INTRODUCTION: Persistent diarrhea has high impact on infantile morbidity and mortality rates in developing countries. Several studies have shown that 3 to 20% of acute diarrheal episodes in children under 5 years of age become persistent. DEFINITION: Persistent diarrhea is defined as an episode that lasts more than 14 days. ETIOLOGY: The most important agents isolated in persistent diarrhea are: Enteropathogenic E. coli (EPEC), Salmonella, Enteroaggregative E. coli (EAEC), Klebisiella and Cryptosporidium. CLINICAL ASPECTS: In general, the clinical characteristics of patients with persistent diarrhea do not change with the pathogenic agent. Persistent diarrhea seems to represent the final result of a several insults a infant suffers that predisposes to a more severe episode of diarrhea due to a combination of host factors and high rates of enviromental contamination. Therefore, efforts should be made to promptly treat all episodes of diarrhea with apropriate follow-up. THERAPY: The aim of the treatment is to restore hydroelectrolytic deficits and to replace losses until the diarrheal ceases. It is possible in the majority of the cases, using oral rehydration therapy and erly an appropriate type of diet. PREVENTION: It is imperative that management strategies also focus on preventive aspects. The most effective diarrheal prevention strategy in young infants worldwide is promotion of exclusive breast feeding.

  1. Weed control and persistence of two oxyfluorfen formulations in olive groves under non tillage conditions.

    Science.gov (United States)

    Martínez, M J; Farsaoui, K; de Prado, R

    2004-01-01

    To obtain profitable yields in olive groves, residual preemergence herbicides are applied in October or November before the winter rains, and before the winter annual weeds germinate. Simazine, one of the herbicides most used for weed control in olive groves, has recently been banned. Oxyfluorfen is presented as a good alternative to simazine in olive fields. Experiments were carried out in 2002 and 2003 to evaluate the behaviour of two oxyfluorfen formulations, 2XL and G4F, at 480 g a.i. ha(-1) for three different soil management systems with three replications (1. bare soil; 2. bare soil and grassed buffer strips, chemically controlled and 3. bare soil and grassed buffer strips with controlled mowing; under non tillage conditions in all three cases). The most important species that survived 2XL and G4F treatments was Sagina apetala ARD. Oxyfluorfen residues were evaluated throughout 158 days after the applications. Three soil samples from each plot were collected, mixed and air dried. The herbicide extractions were made with methanol and the residues were analyzed by HPLC. We found no differences between the two formulations, but results showed that recoveries of oxyfluorfen were higher in plots with chemically controlled buffer grassed strips than in the other soil management types.

  2. Long-term persistence of functional thymic epithelial progenitor cells in vivo under conditions of low FOXN1 expression

    DEFF Research Database (Denmark)

    Jin, Xin; Nowell, Craig S; Ulyanchenko, Svetlana

    2014-01-01

    does not require FOXN1. Here, we have used a revertible severely hypomorphic allele of Foxn1, Foxn1R, to test the stability of the common TEPC in vivo. By reactivating Foxn1 expression postnatally in Foxn1R/- mice we demonstrate that functional TEPCs can persist in the thymic rudiment until at least 6...... months of age, and retain the potential to give rise to both cortical and medullary thymic epithelial cells (cTECs and mTECs). These data demonstrate that the TEPC-state is remarkably stable in vivo under conditions of low Foxn1 expression, suggesting that manipulation of FOXN1 activity may prove...... a valuable method for long term maintenance of TEPC in vitro....

  3. Modeling the potential persistence of various ecological systems under CMIP5 future climate and land use scenarios throughout California, USA

    Science.gov (United States)

    Baker, B.; Ferschweiler, K.; Bachelet, D. M.; Sleeter, B. M.

    2016-12-01

    California's geographic location, topographic complexity and latitudinal climatic gradient give rise to great biological and ecological diversity. However, increased land use pressure, altered seasonal weather patterns, and changes in temperature and precipitation regimes are having pronounced effects on ecosystems and the multitude of services they provide for an increasing population. As a result, natural resource managers are faced with formidable challenges to maintain these critical services. The goals of this project were to better understand how projected 21st century climate and land-use change scenarios may alter ecosystem dynamics, the spatial distribution of various vegetation types and land-use patterns, and to provide a coarse scale "triage map" of where land managers may want to concentrate efforts to reduce ecological stress in order to mitigate the potential impacts of a changing climate. We used the MC2 dynamic global vegetation model and the LUCAS state-and-transition simulation model to simulate the potential effects of future climate and land-use change on ecological processes for the state of California. Historical climate data were obtained from the PRISM dataset and nine CMIP5 climate models were run for the RCP 8.5 scenario. Climate projections were combined with a business-as-usual land-use scenario based on local-scale land use histories. For ease of discussion, results from five simulation runs (historic, hot-dry, hot-wet, warm-dry, and warm-wet) are presented. Results showed large changes in the extent of urban and agricultural lands. In addition, several simulated potential vegetation types persisted in situ under all four future scenarios, although alterations in total area, total ecosystem carbon, and forest vigor (NPP/LAI) were noted. As might be expected, the majority of the forested types that persisted occurred on public lands. However, more than 78% of the simulated subtropical mixed forest and 26% of temperate evergreen

  4. Clinical Prediction Model and Tool for Assessing Risk of Persistent Pain After Breast Cancer Surgery

    DEFF Research Database (Denmark)

    Meretoja, Tuomo J; Andersen, Kenneth Geving; Bruce, Julie

    2017-01-01

    are missing. The aim was to develop a clinically applicable risk prediction tool. Methods The prediction models were developed and tested using three prospective data sets from Finland (n = 860), Denmark (n = 453), and Scotland (n = 231). Prediction models for persistent pain of moderate to severe intensity......), high body mass index ( P = .039), axillary lymph node dissection ( P = .008), and more severe acute postoperative pain intensity at the seventh postoperative day ( P = .003) predicted persistent pain in the final prediction model, which performed well in the Danish (ROC-AUC, 0.739) and Scottish (ROC......-AUC, 0.740) cohorts. At the 20% risk level, the model had 32.8% and 47.4% sensitivity and 94.4% and 82.4% specificity in the Danish and Scottish cohorts, respectively. Conclusion Our validated prediction models and an online risk calculator provide clinicians and researchers with a simple tool to screen...

  5. The roles of dispersal, fecundity, and predation in the population persistence of an oak (Quercus engelmannii) under global change.

    Science.gov (United States)

    Conlisk, Erin; Lawson, Dawn; Syphard, Alexandra D; Franklin, Janet; Flint, Lorraine; Flint, Alan; Regan, Helen M

    2012-01-01

    A species' response to climate change depends on the interaction of biotic and abiotic factors that define future habitat suitability and species' ability to migrate or adapt. The interactive effects of processes such as fire, dispersal, and predation have not been thoroughly addressed in the climate change literature. Our objective was to examine how life history traits, short-term global change perturbations, and long-term climate change interact to affect the likely persistence of an oak species--Quercus engelmannii (Engelmann oak). Specifically, we combined dynamic species distribution models, which predict suitable habitat, with stochastic, stage-based metapopulation models, which project population trajectories, to evaluate the effects of three global change factors--climate change, land use change, and altered fire frequency--emphasizing the roles of dispersal and seed predation. Our model predicted dramatic reduction in Q. engelmannii abundance, especially under drier climates and increased fire frequency. When masting lowers seed predation rates, decreased masting frequency leads to large abundance decreases. Current rates of dispersal are not likely to prevent these effects, although increased dispersal could mitigate population declines. The results suggest that habitat suitability predictions by themselves may under-estimate the impact of climate change for other species and locations.

  6. The roles of dispersal, fecundity, and predation in the population persistence of an oak (Quercus engelmannii under global change.

    Directory of Open Access Journals (Sweden)

    Erin Conlisk

    Full Text Available A species' response to climate change depends on the interaction of biotic and abiotic factors that define future habitat suitability and species' ability to migrate or adapt. The interactive effects of processes such as fire, dispersal, and predation have not been thoroughly addressed in the climate change literature. Our objective was to examine how life history traits, short-term global change perturbations, and long-term climate change interact to affect the likely persistence of an oak species--Quercus engelmannii (Engelmann oak. Specifically, we combined dynamic species distribution models, which predict suitable habitat, with stochastic, stage-based metapopulation models, which project population trajectories, to evaluate the effects of three global change factors--climate change, land use change, and altered fire frequency--emphasizing the roles of dispersal and seed predation. Our model predicted dramatic reduction in Q. engelmannii abundance, especially under drier climates and increased fire frequency. When masting lowers seed predation rates, decreased masting frequency leads to large abundance decreases. Current rates of dispersal are not likely to prevent these effects, although increased dispersal could mitigate population declines. The results suggest that habitat suitability predictions by themselves may under-estimate the impact of climate change for other species and locations.

  7. A joint model of persistent human papillomavirus infection and cervical cancer risk: Implications for cervical cancer screening.

    Science.gov (United States)

    Katki, Hormuzd A; Cheung, Li C; Fetterman, Barbara; Castle, Philip E; Sundaram, Rajeshwari

    2015-10-01

    New cervical cancer screening guidelines in the US and many European countries recommend that women get tested for human papillomavirus (HPV). To inform decisions about screening intervals, we calculate the increase in precancer/cancer risk per year of continued HPV infection. However, both time to onset of precancer/cancer and time to HPV clearance are interval-censored, and onset of precancer/cancer strongly informatively censors HPV clearance. We analyze this bivariate informatively interval-censored data by developing a novel joint model for time to clearance of HPV and time to precancer/cancer using shared random-effects, where the estimated mean duration of each woman's HPV infection is a covariate in the submodel for time to precancer/cancer. The model was fit to data on 9,553 HPV-positive/Pap-negative women undergoing cervical cancer screening at Kaiser Permanente Northern California, data that were pivotal to the development of US screening guidelines. We compare the implications for screening intervals of this joint model to those from population-average marginal models of precancer/cancer risk. In particular, after 2 years the marginal population-average precancer/cancer risk was 5%, suggesting a 2-year interval to control population-average risk at 5%. In contrast, the joint model reveals that almost all women exceeding 5% individual risk in 2 years also exceeded 5% in 1 year, suggesting that a 1-year interval is better to control individual risk at 5%. The example suggests that sophisticated risk models capable of predicting individual risk may have different implications than population-average risk models that are currently used for informing medical guideline development.

  8. Persistent pain after targeted intraoperative radiotherapy (TARGIT) or external breast radiotherapy for breast cancer: A randomized trial

    DEFF Research Database (Denmark)

    Andersen, Kenneth Geving; Gärtner, Rune; Kroman, Niels

    2012-01-01

    for participation, and a total of 244 patients were included and received a detailed questionnaire. The response rate was 98%, leaving 238 patients for the final analysis. Pain prevalence were 33.9% in the EBRT group and 24.6% in the IORT group (p = 0.11). Treatment with IORT may not alter the risk of PPBCT.......Persistent pain after breast cancer treatment (PPBCT) affects between 25 and 60% of patients depending on surgical and adjuvant treatment. External breast radiotherapy (EBRT) has been shown to be a riskfactor for PPBCT, raising the question whether intraoperative radiation therapy (IORT), with its...... smaller radiation field may reduce the development of PPBCT. Using data from the TARGIT-A trial, the aim of this study was to compare these two treatments with regard to development of PPBCT. A total of 281 patients enrolled in the TARGIT-A trial from the Copenhagen University Hospitals was screened...

  9. Autoradiographical in-vitro examination of the cell proliferation of persisting psoriatic plaques in preferred areas under therapy with ultraviolet light: Photochemotherapy (PUVA) and selective ultraviolet phototherapy (SUP)

    International Nuclear Information System (INIS)

    Middendorf, M.

    1982-01-01

    The application of ultraviolet rays (PUVA, SUP) brought significant progress in the treatment of psoriasis. The goal of UV-irradiation is to normalise the epidermal growth conditions. The cell cycle of persisting psoriatic plaque in preferred areas was examined under therapy with PUVA and SUP using an autoradiographic in-vitro method, double labelling with 14 C- and 3 H-thymididin. The results were compared to the known cell-kinetic parameters of psoriasis. The values thus obtained confirm the characteristic changes in the cell cycle of psoriasis. Furthermore, there is a block within the DNA-synthesis phase in the plaques persisting under UV-therapy. The resistence of persisting psoriatic plaques in preferred regions against UV-therapy is regarded as an indication of an extreme disturbance in the proliferation behaviour of the psoriatic skin. (orig./MG) [de

  10. Effect of persistent menopausal symptoms on the wellbeing of Japanese breast cancer survivors.

    Science.gov (United States)

    Yamamoto, Sena; Masutani, Eiko; Arao, Harue

    2016-09-01

    While more women with breast cancer survive because of advances in cancer treatment including hormonal therapy, they are at a risk of menopausal symptoms, which can threaten their psychological wellbeing. We examined the effect of menopausal symptoms on women's psychological wellbeing during three different phases of breast cancer: short-term (0-1 years since diagnosis), medium-term (2-5 years), and long-term (more than 5 years). In this cross-sectional study, 425 survivors treated with hormonal therapy were recruited from a convenience sample in Japan and completed an anonymous self-administered questionnaire. Multiple regression analysis revealed that menopausal symptoms significantly contributed to psychological wellbeing in all phases. In long-term survivors, menopausal symptoms were significantly milder; however, the negative effect was prolonged. One in three to four survivors was suspected to have poor psychological wellbeing, irrespective of time. Although the effect of menopausal symptoms on psychological wellbeing has been described in short-term survivors, little is known about the long-term effect. This study examines the effect of menopausal symptoms on psychological wellbeing, thereby providing useful information regarding long-term quality of life. © 2016 John Wiley & Sons Australia, Ltd.

  11. United Nations Environment Programme Capacity Building Pilot Project - Training on persistent organic pollutant analysis under the Stockholm Convention

    NARCIS (Netherlands)

    de Boer, J.; Leslie, H.A.; van Leeuwen, S.P.J.; Wegener, J.W.M.; van Bavel, B; Lindstrom, G.; Lahoutifard, N.; Fiedler, H.

    2008-01-01

    Within the framework of a United Nations Environment Programme (UNEP) Capacity Building Project for training of laboratory staff in developing countries on persistent organic pollutant (POP) analysis, an interlaboratory study was organised following an initial evaluation of the performance of

  12. Distribution of persistent, lipid-soluble chemicals in breast and abdominal adipose tissues: lessons learned from a breast cancer study.

    Science.gov (United States)

    Petreas, Myrto; Smith, Daniel; Hurley, Susan; Jeffrey, Stefanie S; Gilliss, Debra; Reynolds, Peggy

    2004-03-01

    We sought to determine differences between concentrations of persistent, lipid-soluble chemical contaminants in breast and abdominal adipose tissues and to explore whether concentrations measured in one tissue could predict concentrations in the other tissue. We analyzed surgical specimens and measured concentrations of prevalent dioxins, furans, polychlorinated biphenyls, organochlorine pesticides, and brominated diphenyl ethers to determine their partitioning between breast and abdominal adipose tissues of 21 women. The women constituted a subgroup, undergoing mastectomies with simultaneous breast reconstruction, of a case-control study evaluating links between breast cancer and body burdens of organohalogen contaminants. For every contaminant, differences between concentrations in breast and abdominal adipose tissues did not exceed the analytical error. Results indicated that, with some notable exceptions, measurements in breast and abdominal adipose tissues were correlated and that concentrations of target chemicals in one tissue could be derived from measurements in the other tissue. This information will allow comparison of results from body burden studies that used different tissues. It may also facilitate future breast cancer studies by allowing selection of controls among patients undergoing surgical procedures other than breast surgery, minimizing concerns about overmatching. We also observed large differences in the lipid content of surgical specimens. These differences underscore the need for lipid adjustment of concentrations to avoid misclassification.

  13. Glyphosate and AMPA, "pseudo-persistent" pollutants under real-world agricultural management practices in the Mesopotamic Pampas agroecosystem, Argentina.

    Science.gov (United States)

    Primost, Jezabel E; Marino, Damián J G; Aparicio, Virginia C; Costa, José Luis; Carriquiriborde, Pedro

    2017-10-01

    In the Pampas, public concern has strongly risen because of the intensive use of glyphosate for weed control and fallow associated with biotech crops. The present study was aimed to evaluate the occurrence and concentration of the herbicide and its main metabolite (AMPA) in soil and other environmental compartments of the mentioned agroecosystem, including groundwater, in relation to real-world agricultural management practices in the region. Occurrence was almost ubiquitous in solid matrices (83-100%) with maximum concentrations among the higher reported in the world (soil: 8105 and 38939; sediment: 3294 and 7219; suspended particulate matter (SPM): 584 and 475 μg/kg of glyphosate and AMPA). Lower detection frequency was observed in surface water (27-55%) with maximum concentrations in whole water of 1.80 and 1.90 μg/L of glyphosate and AMPA, indicating that SPM analysis would be more sensitive for detection in the aquatic ecosystem. No detectable concentrations of glyphosate or AMPA were observed in groundwater. Glyphosate soil concentrations were better correlated with the total cumulative dose and total number of applications than the last spraying event dose, and an increment of 1 mg glyphosate/kg soil every 5 spraying events was estimated. Findings allow to infer that, under current practices, application rates are higher than dissipation rates. Hence, glyphosate and AMPA should be considered "pseudo-persistent" pollutants and a revisions of management procedures, monitoring programs, and ecological risk for soil and sediments should be also recommended. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Polymorphisms in Phase I and Phase II genes and breast cancer risk and relations to persistent organic pollutant exposure: a case–control study in Inuit women

    DEFF Research Database (Denmark)

    Ghisari, Mandana; Eiberg, Hans; Long, Manhai

    2014-01-01

    Background: We have previously reported that chemicals belonging to the persistent organic pollutants (POPs) such as perfluorinated compounds (PFAS) and polychlorinated biphenyls (PCBs) are risk factors in Breast Cancer (BC) development in Greenlandic Inuit women. The present case–control study a...

  15. Impact of Transient and Persistent Acute Kidney Injury on Chronic Kidney Disease Progression and Mortality after Gastric Surgery for Gastric Cancer.

    Directory of Open Access Journals (Sweden)

    Chang Seong Kim

    Full Text Available Acute kidney injury (AKI is common after gastric surgery for gastric cancer and associated with adverse outcomes. However, the impact of transient or persistent AKI on clinical outcomes after gastric surgery for gastric cancer has not been described. We performed a retrospective study of 4,886 patients with normal renal function who underwent partial or total gastrectomy for gastric cancer between June 2002 and December 2012. AKI patients were classified as transient and persistent AKI based on the return of serum creatinine to the level indicating no AKI within 7 days. Our outcomes included occurrence of new-onset chronic kidney disease (CKD and mortality 1 year after gastric surgery. AKI occurred in 638 (13.1% after gastric surgery. Transient AKI was documented in 574 (90%. Use of diuretics and contrast agents was a common risk factor for persistent and transient AKI. Length of intensive care unit (ICU and hospital stay, and ICU admission rate were higher in patients with transient AKI than in those without AKI. Although patients with persistent AKI had a higher new-onset CKD 1 year after gastric surgery after adjusting for multiple covariates, transient AKI was not associated with new-onset CKD. The 1-year mortality rates were significantly higher in patients with transient and persistent AKI. Not only persistent AKI but transient AKI is associated with increased risk of hospital complications and a significantly higher risk of long-term mortality than patients without AKI after gastric surgery. Moreover, persistent AKI, but not transient AKI, is associated with CKD progression at 1 year.

  16. Stereotactic Body Radiation Therapy for Re-irradiation of Persistent or Recurrent Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Trovo, Marco, E-mail: marcotrovo33@hotmail.com [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Minatel, Emilio; Durofil, Elena [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Polesel, Jerry [Department of Epidemiology and Biostatistics, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Avanzo, Michele [Department of Medical Physics, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Baresic, Tania [Department of Nuclear Medicine, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Bearz, Alessandra [Department of Medical Oncology, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy); Del Conte, Alessandro [Department of Medical Oncology, Pordenone General Hospital, Aviano, Pordenone (Italy); Franchin, Giovanni; Gobitti, Carlo; Rumeileh, Imad Abu; Trovo, Mauro G. [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Pordenone (Italy)

    2014-04-01

    Purpose: To retrospectively assess toxicity and outcome of re-irradiation with stereotactic body radiation therapy (SBRT) in patients with recurrent or persistent non-small cell lung cancer (NSCLC), who were previously treated with radical radiation therapy (50-60 Gy). The secondary endpoint was to investigate whether there are dosimetric parameter predictors of severe radiation toxicity. Methods and Materials: The analysis was conducted in 17 patients with “in-field” recurrent/persistent centrally located NSCLC, who underwent re-irradiation with SBRT. SBRT consisted of 30 Gy in 5 to 6 fractions; these prescriptions would be equivalent for the tumor to 37.5 to 40 Gy, bringing the total 2-Gy-per-fraction cumulative dose to 87 to 100 Gy, considering the primary radiation therapy treatment. Actuarial analyses and survival were calculated by the Kaplan-Meier method, and P values were estimated by the log-rank test, starting from the date of completion of SBRT. Dosimetric parameters from the subgroups with and without grade ≥3 pulmonary toxicity were compared using a 2-tailed Student t test. Results: The median follow-up was 18 months (range, 4-57 months). Only 2 patients had local failure, corresponding to a local control rate of 86% at 1 year. The Kaplan-Meier estimates of overall survival (OS) rates at 1 and 2 years were 59% and 29%, respectively; the median OS was 19 months. Four patients (23%) experienced grade 3 radiation pneumonitis, and 1 patient developed fatal pneumonitis. One patient died of fatal hemoptysis 2 months after the completion of SBRT. Unexpectedly, heart maximum dose, D5 (minimum dose to at least 5% of the heart volume), and D10 were correlated with risk of radiation pneumonitis (P<.05). Conclusions: Re-irradiation with SBRT for recurrent/persistent centrally located NSCLC achieves excellent results in terms of local control. However, the high rate of severe toxicity reported in our study is of concern.

  17. Persistent/delayed toxic effects of low-dose sarin and pyridostigmine under physical stress (exercise) in mice.

    Science.gov (United States)

    Husain, Kazim; Somani, Satu M

    2004-04-01

    Pyridostigmine bromide, a reversible anticholinesterase drug, was used by military personnel during the Gulf War. They were under physical stress and might have been exposed to low-dose nerve gas, sarin. This study examined the interactions of low-dose sarin and pyridostigmine in exercised mice. Male NIH Swiss mice were treated as follows: 1) Control; 2) Sarin (0.01 mg/kg, sc); 3) exercise; 4) sarin plus exercise; 5) pyridostigmine; 6) pyridostigmine plus exercise; 7) pyridostigmine plus sarin; 8) pyridostigmine plus sarin plus exercise. Exercise was given daily for 10 weeks on treadmill and pyridostigmine and sarin were administered daily during the 5th and 6th weeks only. Respiratory exchange ratio decreased significantly during the dosing period of 5th and 6th weeks in groups 4, 6, and 8. Animals were sacrificed 24 hours after the ten-week exercise, tissues isolated and analyzed. Sarin significantly decreased butyrylcholine esterase (BChE) activity in plasma; AChE activity in platelet, triceps muscle, and striatum; neurotoxic esterase (NTE) activity in platelets, spinal cord, cortex and striatum and malondialdehyde (MDA) levels in sciatic nerve and cord. Sarin plus exercise significantly reduced BChE activity in plasma; acetylcholinesterase (AChE) activity in platelets, muscle, nerve and striatum; NTE activity in platelets, cord, cortex and striatum; and increased creatinine phosphokinase (CK) activity in plasma and MDA levels in cord. Pyridostigmine plus exercise significantly decrease BChE activity in plasma; AChE activity in muscle and enhanced malondialdehyde (MDA) levels in muscle. Pyridostigmine plus sarin significantly decreased NTE activity in platelets, cord, cortex and striatum. Pyridostigmine plus sarin plus exercise significantly altered AChE activity and MDA levels in muscle; and NTE activity in platelets, nerve, cord and cortex. Exercise significantly augmented the changes in plasma CK activity, muscle and nerve AChE activity, platelet NTE activity

  18. Temporal dynamics of ‘HoBi’-like pestivirus quasispecies in persistently infected calves generated under experimental conditions

    Science.gov (United States)

    ‘HoBi’-like virus is an atypical group within the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections. Pestivirus strains exist as quasispecies (swarms of individual viruses) in infected animals and the viral populations making up t...

  19. Cancer prostatae hos maend under 65 år. Forekomst og behov for udredning

    DEFF Research Database (Denmark)

    Brasso, K; Friis, S; Kjaer, S K

    1997-01-01

    Based on information from the nationwide Danish Cancer Registry, the development in prostate cancer incidence among Danish men under 65 years is reviewed. Changes in incidence rate, clinical stage and the number of possible candidates for radical treatment are discussed.......Based on information from the nationwide Danish Cancer Registry, the development in prostate cancer incidence among Danish men under 65 years is reviewed. Changes in incidence rate, clinical stage and the number of possible candidates for radical treatment are discussed....

  20. How do steppe plants follow their optimal environmental conditions or persist under suboptimal conditions? The differing strategies of annuals and perennials.

    Science.gov (United States)

    Ait Mouheb, Hocine; Kadik, Leila; Albert, Cécile Hélène; Berrached, Rachda; Prinzing, Andreas

    2018-01-01

    For a species to be able to respond to environmental change, it must either succeed in following its optimal environmental conditions or in persisting under suboptimal conditions, but we know very little about what controls these capacities. We parameterized species distribution models (SDMs) for 135 plant species from the Algerian steppes. We interpreted low false-positive rates as reflecting a high capacity to follow optimal environmental conditions and high false-negative rates as a high capacity to persist under suboptimal environmental conditions. We also measured functional traits in the field and built a unique plant trait database for the North-African steppe. For both perennial and annual species, we explored how these two capacities can be explained by species traits and whether relevant trait values reflect species strategies or biases in SDMs. We found low false-positive rates in species with small seeds, flowers attracting specialist pollinators, and specialized distributions (among annuals and perennials), low root:shoot ratios, wide root-systems, and large leaves (perennials only) ( R 2   = .52-58). We found high false-negative rates in species with marginal environmental distribution (among annuals and perennials), small seeds, relatively deep roots, and specialized distributions (annuals) or large leaves, wide root-systems, and monocarpic life cycle (perennials) ( R 2   = .38 for annuals and 0.65 for perennials). Overall, relevant traits are rarely indicative of the possible biases of SDMs, but rather reflect the species' reproductive strategy, dispersal ability, stress tolerance, and pollination strategies. Our results suggest that wide undirected dispersal in annual species and efficient resource acquisition in perennial species favor both capacities, whereas short life spans in perennial species favor persistence in suboptimal environmental conditions and flowers attracting specialist pollinators in perennial and annual species favor

  1. Breast cancer under age 40: a different approach.

    Science.gov (United States)

    Ribnikar, D; Ribeiro, J M; Pinto, D; Sousa, B; Pinto, A C; Gomes, E; Moser, E C; Cardoso, M J; Cardoso, F

    2015-04-01

    Breast cancer (BC) under age 40 is a complex disease to manage due to the additionally fertility-related factors to be taken in consideration. More than 90% of young patients with BC are symptomatic. Womenmanagement strategies for every individual patient with BC before the start of any therapy including surgery. This applies to both early (early breast cancer (EBC)) and advanced (advanced breast cancer (ABC)) disease, before the start of any therapy. Mastectomy even in young patients confers no overall survival advantage when compared to breast-conserving treatment (BCT), followed by radiotherapy. Regarding axillary approach, indications are identical to other age groups. Young age is one of the most important risk factors for local recurrence after both breast-conserving surgery (BCS) and mastectomy, associated with a higher risk of distant metastasis and death. Radiation after BCS reduces local recurrence from 19.5 to 10.2% in BC patients 40 years and younger. The indications for and the choice of systemic treatment for invasive BC (both early and advanced disease) should not be based on age alone but driven by the biological characteristics of the individual tumor (including hormone receptor status, human epidermal growth factor receptor 2 (HER-2) status, grade, and proliferative activity), disease stage, and patient's comorbidities. Recommendations regarding the use of genomic profiles such as MammaPrint, Oncotype Dx, and Genomic grade index in young women are similar to the general BC population. Especially in the metastatic setting, patient preferences should always be taken into account, as the disease is incurable. The best strategy for these patients is the inclusion into well-designed, independent, prospective randomized clinical trials. Metastatic disease should always be biopsied whenever feasible for histological confirmation and reassessment of biology. Endocrine therapy is the preferred option for hormone receptor-positive disease (HR+ve), even in

  2. Structural Characteristics of Gastric Cell Populations in Chronic Gastritis and Chronic Hepatitis under Conditions of Helicobacter pylori Persistence.

    Science.gov (United States)

    Lapii, G A; Bakarev, M A; Nepomnyashchikh, G I; Kapustina, V I; Nepomnyashchikh, D L; Vinogradova, E V; Postnikova, O A

    2016-02-01

    Helicobacter pylori persistence in patients with chronic gastritis is associated with a complex of nonspecific structural reactions, the type of these reactions correlates with the severity of infection: catarrhal fibrotic changes in the gastric mucosa predominate in cases with manifest colonization, while the absence of H. pylori is associated with predominance of fibrotic process. Analysis of the incidence of some pathomorphological phenomena (degeneration, atrophy, metaplasia, and dysplasia of the surface epithelium) shows no relationship between the presence of H. pylori and colonization intensity. In all patients with chronic hepatitis, the gastric mucosa is involved in the pathological process; fibrosis (gastropathy) was the most common process. No appreciable correlations between the structural changes and hepatitis activity and the presence of H. pylori were detected.

  3. Surgery on unfavourable persistent N2/N3 non-small-cell lung cancer after trimodal therapy: do the results justify the risk?

    Science.gov (United States)

    Steger, Volker; Walker, Tobias; Mustafi, Migdat; Lehrach, Karoline; Kyriss, Thomas; Veit, Stefanie; Friedel, Godehard; Walles, Thorsten

    2012-01-01

    OBJECTIVES Persistent mediastinal lymph node metastasis after neoadjuvant therapy is a significant negative indicator for survival. Even though there is still no consensus on the matter, some authors advocate a thorough restaging prior to surgery and deny surgery in cases of persistent N2 because of the poor outcome. We analysed our results after trimodal therapy in pN2/N3 stage III non-small-cell lung cancer (NSCLC) and persistent mediastinal lymph node metastasis after neoadjuvant chemoradiotherapy. METHODS We conducted a retrospective cohort analysis of 167 patients who received trimodal therapy for stage III NSCLC. Progression-free interval and survival were calculated. T-stage, N-stage, ypT-stage, ypN2/3-stage and surgical procedure were tested as risk factors. RESULTS Eighty-three patients with potentially resectable initial pN2/3 underwent 44 pneumonectomies and 76% extended resections. Thirty-five patients showed persistent mediastinal lymph node metastasis after trimodal therapy. Treatment-related comorbidity after an operative therapy was 58%. Hospital mortality was 2.4%. The ypT- and ypN2/N3 stages were significant risk factors and, in the case of persistent mediastinal lymph node metastasis, median progression-free period was 17 months and median survival time was 21 months. CONCLUSIONS Persistent but resectable N2/N3 after chemoradiotherapy in stage III NSCLC is the least favourable subgroup of patients in neoadjuvant approaches. If surgery can be carried out with curative intent and low morbidity, completing trimodal therapy is justified, with an acceptable outcome. PMID:22997251

  4. Antimicrobial drugs for persistent diarrhoea of unknown or non-specific cause in children under six in low and middle income countries: systematic review of randomized controlled trials.

    Science.gov (United States)

    Abba, Katharine; Sinfield, Rebecca; Hart, C Anthony; Garner, Paul

    2009-03-03

    A high proportion of children with persistent diarrhoea in middle and low income countries die. The best treatment is not clear. We conducted a systematic review to evaluate the effectiveness of antimicrobial drug treatment for persistent diarrhoea of unknown or non-specific cause. We included randomized comparisons of antimicrobial drugs for the treatment of persistent diarrhoea of unknown or non-specific cause in children under the age of six years in low and middle income countries. We searched the electronic databases MEDLINE, EMBASE, LILACS, WEB OF SCIENCE, and the Cochrane Central Register of Controlled Trials (CENTRAL) to May 2008 for relevant randomized or quasi randomized controlled trials. We summarised the characteristics of the eligible trials, assessed their quality using standard criteria, and extracted relevant outcomes data. Where appropriate, we combined the results of different trials. Three trials from South East Asia and one from Guatemala were included, all were small, and three had adequate allocation concealment. Two were in patients with diarrhoea of unknown cause, and two were in patients in whom known bacterial or parasitological causes of diarrhoea had been excluded. No difference was demonstrated for oral gentamicin compared with placebo (presence of diarrhoea at 6 or 7 days; 2 trials, n = 151); and for metronidazole compared with placebo (presence of diarrhoea at 3, 5 and 7 days; 1 trial, n = 99). In one small trial, sulphamethoxazole-trimethoprim appeared better than placebo in relation to diarrhoea at seven days and total stool volume (n = 55). There is little evidence as to whether or not antimicrobials help treat persistent diarrhoea in young children in low and middle income countries.

  5. Antimicrobial drugs for persistent diarrhoea of unknown or non-specific cause in children under six in low and middle income countries: systematic review of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Hart C Anthony

    2009-03-01

    Full Text Available Abstract Background A high proportion of children with persistent diarrhoea in middle and low income countries die. The best treatment is not clear. We conducted a systematic review to evaluate the effectiveness of antimicrobial drug treatment for persistent diarrhoea of unknown or non-specific cause. Methods We included randomized comparisons of antimicrobial drugs for the treatment of persistent diarrhoea of unknown or non-specific cause in children under the age of six years in low and middle income countries. We searched the electronic databases MEDLINE, EMBASE, LILACS, WEB OF SCIENCE, and the Cochrane Central Register of Controlled Trials (CENTRAL to May 2008 for relevant randomized or quasi randomized controlled trials. We summarised the characteristics of the eligible trials, assessed their quality using standard criteria, and extracted relevant outcomes data. Where appropriate, we combined the results of different trials. Results Three trials from South East Asia and one from Guatemala were included, all were small, and three had adequate allocation concealment. Two were in patients with diarrhoea of unknown cause, and two were in patients in whom known bacterial or parasitological causes of diarrhoea had been excluded. No difference was demonstrated for oral gentamicin compared with placebo (presence of diarrhoea at 6 or 7 days; 2 trials, n = 151; and for metronidazole compared with placebo (presence of diarrhoea at 3, 5 and 7 days; 1 trial, n = 99. In one small trial, sulphamethoxazole-trimethoprim appeared better than placebo in relation to diarrhoea at seven days and total stool volume (n = 55. Conclusion There is little evidence as to whether or not antimicrobials help treat persistent diarrhoea in young children in low and middle income countries.

  6. Upper-body morbidity following breast cancer treatment is common, may persist longer-term and adversely influences quality of life

    Directory of Open Access Journals (Sweden)

    Hayes Sandra C

    2010-08-01

    Full Text Available Abstract Background Impairments in upper-body function (UBF are common following breast cancer. However, the relationship between arm morbidity and quality of life (QoL remains unclear. This investigation uses longitudinal data to describe UBF in a population-based sample of women with breast cancer and examines its relationship with QoL. Methods Australian women (n = 287 with unilateral breast cancer were assessed at three-monthly intervals, from six- to 18-months post-surgery (PS. Strength, endurance and flexibility were used to assess objective UBF, while the Disability of the Arm, Shoulder and Hand questionnaire and the Functional Assessment of Cancer Therapy-Breast questionnaire were used to assess self-reported UBF and QoL, respectively. Results Although mean UBF improved over time, up to 41% of women revealed declines in UBF between six- and 18-months PS. Older age, lower socioeconomic position, treatment on the dominant side, mastectomy, more extensive lymph node removal and having lymphoedema each increased odds of declines in UBF by at least two-fold (p Conclusions Significant upper-body morbidity is experienced by many following breast cancer treatment, persisting longer term, and adversely influencing the QoL of breast cancer survivors.

  7. Determination of areas with the most significant shift in persistence of pests in Europe under climate change.

    Science.gov (United States)

    Svobodová, Eva; Trnka, Miroslav; Dubrovský, Martin; Semerádová, Daniela; Eitzinger, Josef; Stěpánek, Petr; Zalud, Zdeněk

    2014-05-01

    This study aimed to estimate the impact of climate change on the ranges of crop pest species in Europe. The organisms included in the study were species from the family Tortricidae (Cydia pomonella, Lobesia botrana) and the family Pyralidae (Ostrinia nubilalis), Chrysomelidae beetles (Leptinotarsa decemlineata, Oulema melanopus) and species from the family Aphididae (Ropalosiphum padi, Sitobion avenae). Climate conditions in the year 2055 were simulated using a subset of five representative global circulation models. Model simulations using these climate change scenarios showed significant shifts in the climatic niches of the species in this study. For Central Europe, the models predicted a shift in the ranges of pest species to higher altitudes and increases in the number of generations (NG) of the pests. In contrast, in the southern regions of Europe, the NG is likely to decrease owing to insufficient humidity. The ranges of species are likely to shift to the north. Based on the ensemble-scenario mean for 2055, a climate-driven northward shift of between 3° N (O. nubilalis) and 11° N (L. botrana) is expected. The areas that are most sensitive to experiencing a significant increase in climate suitability for future pest persistence were identified. These areas include Central Europe, the higher altitudes of the Alps and Carpathians and areas above 55° N. © 2013 Society of Chemical Industry.

  8. Persistence of biomarker ATP and ATP-generating capability in bacterial cells and spores contaminating spacecraft materials under earth conditions and in a simulated martian environment.

    Science.gov (United States)

    Fajardo-Cavazos, Patricia; Schuerger, Andrew C; Nicholson, Wayne L

    2008-08-01

    Most planetary protection research has concentrated on characterizing viable bioloads on spacecraft surfaces, developing techniques for bioload reduction prior to launch, and studying the effects of simulated martian environments on microbial survival. Little research has examined the persistence of biogenic signature molecules on spacecraft materials under simulated martian surface conditions. This study examined how endogenous adenosine-5'-triphosphate (ATP) would persist on aluminum coupons under simulated martian conditions of 7.1 mbar, full-spectrum simulated martian radiation calibrated to 4 W m(-2) of UV-C (200 to 280 nm), -10 degrees C, and a Mars gas mix of CO(2) (95.54%), N(2) (2.7%), Ar (1.6%), O(2) (0.13%), and H(2)O (0.03%). Cell or spore viabilities of Acinetobacter radioresistens, Bacillus pumilus, and B. subtilis were measured in minutes to hours, while high levels of endogenous ATP were recovered after exposures of up to 21 days. The dominant factor responsible for temporal reductions in viability and loss of ATP was the simulated Mars surface radiation; low pressure, low temperature, and the Mars gas composition exhibited only slight effects. The normal burst of endogenous ATP detected during spore germination in B. pumilus and B. subtilis was reduced by 1 or 2 orders of magnitude following, respectively, 8- or 30-min exposures to simulated martian conditions. The results support the conclusion that endogenous ATP will persist for time periods that are likely to extend beyond the nominal lengths of most surface missions on Mars, and planetary protection protocols prior to launch may require additional rigor to further reduce the presence and abundance of biosignature molecules on spacecraft surfaces.

  9. Combined Double Sleeve Lobectomy and Superior Vena Cava Resection for Non-small Cell Lung Cancer with Persistent Left Superior Vena Cava

    Directory of Open Access Journals (Sweden)

    Daxing ZHU

    2015-11-01

    Full Text Available A 65-year-old man with right central type of lung squamous carcinoma was admitted to our department. Bronchoscopy displayed complete obstruction of right upper lobe bronchus and infiltration of the bronchus intermedius with tumor. Chest contrast computed tomography revealed the tumor invaded right pulmonary artery, superior vena cava, and the persistant left superior vena cava flowed into the coronary sinus. The tumor was successfully removed by means of bronchial and pulmonary artery sleeve resection of the right upper and middle lobes combined with resection and reconstruction of superior vena cava (SVC utilizing ringed polytetrafluoroethylene graft. To the best of our knowledge, this was the first report of complete resection of locally advanced lung cancer involving superior vena cava, right pulmonary artery trunk and main bronchus with persistant left superior vena cava.

  10. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer

    DEFF Research Database (Denmark)

    Lu, Yi; Cuellar-Partida, Gabriel; Painter, Jodie N

    2015-01-01

    Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address...... this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested...... that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We...

  11. Formation of environmentally persistent free radicals as the mechanism for reduced catechol degradation on hematite-silica surface under UV irradiation.

    Science.gov (United States)

    Li, Hao; Pan, Bo; Liao, Shaohua; Zhang, Di; Xing, Baoshan

    2014-05-01

    Iron is rich in soils, and is recently reported to form stable complexes with organic free radicals, generating environmentally persistent free radicals (EPFRs). The observation may challenge the common viewpoint that iron is an effective catalyst to facilitate the degradation of various organic chemicals. But no study was specifically designed to investigate the possible inhibited degradation of organic chemicals because of the formation of EPFRs in dry environment. We observed that catechol degradation under UV irradiation was decreased over 20% in silica particles coated with 1% hematite in comparison to uncoated silica particles. Stabilized semiquinone or quinine and phenol radicals were involved in HMT-silica system. EPFR formation was thus the reason for the reduced catechol degradation on HMT-silica surface under UV irradiation at ambient temperature. EPFRs should be incorporated in the studies of organic contaminants geochemical behavior, and will be a new input in their environmental fate modeling. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Persistence of glyphosate and aminomethylphosphonic acid in loess soil under different combinations of temperature, soil moisture and light/darkness

    NARCIS (Netherlands)

    Martins Bento, Celia; Yang, Xiaomei; Gort, Gerrit; Xue, Sha; Dam, van Ruud; Zomer, Paul; Mol, Hans G.J.; Ritsema, Coen J.; Geissen, Violette

    2016-01-01

    The dissipation kinetics of glyphosate and its metabolite aminomethylphosphonic acid (AMPA) were studied in loess soil, under biotic and abiotic conditions, as affected by temperature, soil moisture (SM) and light/darkness. Nonsterile and sterile soil samples were spiked with 16 mg kg

  13. Usefulness of ultrasonography for detection of breast cancer in patients under 30 years of age

    International Nuclear Information System (INIS)

    Kim, Ji Hyung; Oh, Ki Keun; Yoon, Sang Wook

    1995-01-01

    The purpose of this study was to compare mammography and breast sonography in detection of breast cancer and to suggest reasonable guideline of breast imaging in breast cancer patients under 30 years of age in whom breast cancer shows different clinicopathologic characteristics compared with breast cancer in older women. Authors reviewed medical records of 27 patients under 30 years of age with pathologically-proven breast cancer. Age, family history, physical examination findings, indications for breast sonography were reviewed. Cases in whom breast cancer lesion is detectable and cases in whom not detectable using mammography or breast sonography were reviewed. And then, authors evaluated the usefulness of each method and reasons for nonvisualization of lesion on mammography. Among 27 patients, 25 patients had palpable breast mass as indication of mammography and breast sonography. Cancer lesions were detectable in 16 of 25 patients (64%) on mammography and 24 of 25 patients (96%) on breast ultrasonography. Reasons for nonvisualization of cancer lesions on mammography were dense breast with nodular parenchyma pattern and minimal breast change of ductal carcinoma in situ. In breast cancer patients under 30 years of age who have palpable breast mass as a initial, and main clinical problem, breast ultrasonography is superior to mammography in detecting and diagnosing breast cancer. We suggest that guidelines can avoid unnecessary mammography in these patients

  14. Oncogenic Effects of High MAPK Activity in Colorectal Cancer Mark Progenitor Cells and Persist Irrespective of RAS Mutations.

    Science.gov (United States)

    Blaj, Cristina; Schmidt, Eva Marina; Lamprecht, Sebastian; Hermeking, Heiko; Jung, Andreas; Kirchner, Thomas; Horst, David

    2017-04-01

    About 40% of colorectal cancers have mutations in KRAS accompanied by downstream activation of MAPK signaling, which promotes tumor invasion and progression. Here, we report that MAPK signaling shows strong intratumoral heterogeneity and unexpectedly remains regulated in colorectal cancer irrespective of KRAS mutation status. Using primary colorectal cancer tissues, xenograft models, and MAPK reporter constructs, we showed that tumor cells with high MAPK activity resided specifically at the leading tumor edge, ceased to proliferate, underwent epithelial-mesenchymal transition (EMT), and expressed markers related to colon cancer stem cells. In KRAS-mutant colon cancer, regulation of MAPK signaling was preserved through remaining wild-type RAS isoforms. Moreover, using a lineage tracing strategy, we provide evidence that high MAPK activity marked a progenitor cell compartment of growth-fueling colon cancer cells in vivo Our results imply that differential MAPK signaling balances EMT, cancer stem cell potential, and tumor growth in colorectal cancer. Cancer Res; 77(7); 1763-74. ©2017 AACR . ©2017 American Association for Cancer Research.

  15. Quality of life of elderly cancer patients under radiotherapy

    International Nuclear Information System (INIS)

    Peres de Oliveira, Patricia; Corte Pereira, Beltrina da Purificacao

    2004-01-01

    This research analyzed the effects of radiotherapy in the quality of life of elderly patients suffering from prostatic cancer. Our aim was to verify the psychometric properties of the Quality of Life Index (QLI), by Ferrans and Powers, describing the social-demographic characteristics that affect the quality of life; and patients concept of quality of life and their perception of how radiotherapy interferes with the quality of life. Interviews were carried out with a sample of seven elderly patients suffering from prostatic cancer. Two different approaches were utilized: descriptive and qualitative statistics. The results show that the QLI may have useful application in our field in the identification of those aspects of quality of life affected by cancer. (author)

  16. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwen Xiao

    2014-01-01

    Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

  17. Dermatomyositis presenting as a paraneoplastic syndrome due to underlying breast cancer.

    Science.gov (United States)

    Sandhu, Nicole P; Zakaria, Shaheen; Degnim, Amy C; Boughey, Judy C

    2011-02-02

    Breast cancer most often presents as a palpable mass or with an abnormal mammogram. Much less commonly, breast cancer may present as a paraneoplastic syndrome. Dermatomyositis (DM) is a rare disease most often considered a complement-mediated idiopathic inflammatory myopathy manifested by classic skin findings and proximal muscle weakness. However, DM may also be due to a paraneoplastic syndrome associated with an underlying malignancy. The authors present a case report of a woman with presumed contact dermatitis who was diagnosed with breast cancer in the setting of progressive fatigue and muscle weakness. DM was subsequently diagnosed. Treatment of DM simultaneous with treatment of the breast cancer led to regression of DM. The diagnosis of DM in an adult should raise suspicion of an underlying malignancy. Breast cancer is a common disease that may rarely present with uncommon features that may divert attention from the underlying malignancy.

  18. Persistence of circannual rhythms under constant periodic and aperiodic light conditions: sex differences and relationship with the external environment.

    Science.gov (United States)

    Budki, Puja; Rani, Sangeeta; Kumar, Vinod

    2012-11-01

    The timing and duration of gonadal phases in the year indicates that breeding cycles are regulated by endogenous mechanisms. The present study on tropical spotted munia (Lonchura punctulata) investigates whether such mechanisms are based on circannual rhythms, and whether circannual rhythms between sexes differ in their relationship with the light environment. Birds were subjected to 12 h light per day (12L:12D), alternate days of light and darkness (24L:24D, LL/DD) and continuous light (LL), with L=22 lx and D≤1 lx, for 28 months at constant temperature (18±1°C). Groups kept on natural day lengths (NDL) served as controls. Measurement of body mass, gonads and molts of the primary wing feathers and body plumage at regular intervals showed that birds underwent repeated cycles in gonads and molt, but not in body mass. Under NDL, gonadal phases in both sexes cycled with 12 month periods. Under other conditions, males cycled with similar periods of ~11 months, but females cycled with relatively large period variations, ~10-13 months. Gonadal recrudescence-regression phase was longer in males than in females and, in both sexes, longer in the second year compared with the first year. The molt of wing primaries was more closely coupled to gonadal maturation in groups on NDL and 12L:12D than in groups on LL and LL/DD, but this relationship drifted apart in the second year. Body plumage molts were relatively more highly variable in both frequency and pattern in females than in males. It is suggested that annual breeding cycle in spotted munia is regulated by the self-sustained circannual rhythms, which probably interact with the annual photoperiodic cycle to synchronize breeding cycles to calendar year. Both sexes seem to have independent timing strategies, but females appear to share a greater role in defining the reproductive season in relation with the environment.

  19. Mechanisms underlying social inequality in post-menopausal breast cancer.

    Science.gov (United States)

    Hvidtfeldt, Ulla Arthur

    2014-10-01

    This thesis is based on studies conducted in the period 2010-2014 at Department of Public Health, University of Copenhagen and at Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York. The results are presented in three scientific papers and a synopsis. The main objective of the thesis was to determine mechanisms underlying social inequality (defined by educational level) in postmenopausal breast cancer (BC) by addressing mediating effects through hormone therapy (HT) use, BMI, lifestyle and reproductive factors. The results of previous studies suggest that the higher risk of postmenopausal BC among women of high socioeconomic position (SEP) may be explained by reproductive factors and health behaviors. Women of higher SEP generally have fewer children and give birth at older ages than women of low SEP, and these factors have been found to affect the risk of BC - probably through altered hormone levels. Adverse effects on BC risk have also been documented for modifiable health behaviors that may affect hormone levels, such as alcohol consumption, high BMI, physical inactivity, and HT use. Alcohol consumption and HT use are likewise more common among women of higher SEP. The analyses were based on the Social Inequality in Cancer (SIC) cohort and a subsample of the Women's Health Initiative Observational Study (WHI-OS). The SIC cohort was derived by pooling 6 individual studies from the Copenhagen area including 33,562 women (1,733 BC cases) aged 50-70 years at baseline. The subsample of WHI-OS consisted of two case-cohort studies with measurements of endogenous estradiol (N = 1,601) and insulin (N = 791). Assessment of mediation often relies on comparing multiplicative models with and without the potential mediator. Such approaches provide potentially biased results, because they do not account for mediator-outcome confounding, exposure-dependent mediator-outcome confounding, exposure-mediator interaction and interactions

  20. Hypothyroidism in Cancer Patients on Immune Checkpoint Inhibitors with anti-PD1 Agents: Insights on Underlying Mechanisms.

    Science.gov (United States)

    Alhusseini, M; Samantray, J

    2017-04-01

    Background: Immune therapy using monoclonal antibodies against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 receptor (PD-1) for various cancers have been reported to cause thyroid dysfunction. Little is known, however, about the underlying pathogenic mechanisms and the course of hypothyroidism that subsequently develops. In this report, we use the change in thyroglobulin and thyroid antibody levels in patients on immune therapy who develop hypothyroidism to better understand its pathogenesis as well as examine the status of hypothyroidism in the long term. Methods: We report a case series of 10 patients who developed hypothyroidism after initiation of immune therapy (either anti-PD-1 alone or in combination with anti-CTLA-4). Available thyroid antibodies including anti-thyroglobulin (anti-Tg), anti-thyroid peroxidase (anti-TPO), and thyroid stimulating immunoglobulin (TSI) were noted during the initial thyroiditis phase as well as the hypothyroid phase. Persistence or remission of hypothyroidism was noted at 6 months. Summary: During the thyroiditis phase, 50% of the patients had elevated Tg titers, 40% had elevated anti-Tg, and 40% had elevated TSI. All of these titers decreased during the hypothyroid phase. Permanent hypothyroidism was noted in 80% of the cases. Conclusion: Hypothyroidism following initiation of immune therapy has immunologic and non-immunologic mediated mechanisms and is likely to be persistent. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Under Persistent Assault: Understanding the Factors that Deteriorate Human Skin and Clinical Efficacy of Topical Antioxidants in Treating Aging Skin

    Directory of Open Access Journals (Sweden)

    Patricia K. Farris

    2015-11-01

    Full Text Available Recent studies contend that the skin is subject to far more damage than just ultraviolet (UV light, with infrared radiation and pollution now clearly demonstrated to degrade cutaneous tissue. While consumers continue to strive for new ways to augment the aesthetic appeal and improve the health of their skin, awareness regarding environmental insults and effective ways to protect the skin remains low. New advances in dermatologic science have exponentially increased the available information on the underlying mechanism of cutaneous damage and potential of topical antioxidants to treat aging skin. Combining antioxidants that can work through multiple pathways holds great potential for a cumulative and synergistic way to treat aging skin. Our goal is to provide a comprehensive review on environmental factors that damage human skin, discuss scientifically proven benefits of topical antioxidants, understand challenges of formulating and administering topical antioxidants, evaluate novel mechanisms of antioxidant activity, and suggest practical ways of integrating topical antioxidants with aesthetic procedures to complement clinical outcomes.

  2. Evaluating Psychosocial Mechanisms Underlying STEM Persistence in Undergraduates: Evidence of Impact from a Six-Day Pre-College Engagement STEM Academy Program.

    Science.gov (United States)

    Findley-Van Nostrand, Danielle; Pollenz, Richard S

    2017-01-01

    The persistence of undergraduate students in science, technology, engineering, and mathematics (STEM) disciplines is a national issue based on STEM workforce projections. We implemented a weeklong pre-college engagement STEM Academy (SA) program aimed at addressing several areas related to STEM retention. We validated an instrument that was developed based on existing, validated measures and examined several psychosocial constructs related to STEM (science identity, self-efficacy, sense of belonging to the university and to STEM, career expectancies, and intention to leave STEM majors) before and after the program. We also compared students in the SA program with a matched comparison group of first-year students. Results show that SA students significantly increased in science identity and sense of belonging to STEM and to the university, all predictive of increased STEM retention and a primary aim of the program. Relative to the matched comparison group, SA students began their first semester with higher STEM self-efficacy, sense of belonging, and science identity, positive career expectancies, and lower intention to leave STEM. The SA cohort showed 98% first-year retention and 92% STEM major retention. The SA program serves as a model of a scalable, first-level, cocurricular engagement experience to enhance psychosocial factors that impact undergraduate persistence in STEM. © 2017 D. Findley-Van Nostrand and R. S. Pollenz. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  3. Trichostatin A enhances estrogen receptor-alpha repression in MCF-7 breast cancer cells under hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Hyunggyun; Park, Joonwoo; Shim, Myeongguk; Lee, YoungJoo, E-mail: yjlee@sejong.ac.kr

    2016-02-12

    Estrogen receptor (ER) is a crucial determinant of resistance to endocrine therapy, which may change during the progression of breast cancer. We previously showed that hypoxia induces ESR1 gene repression and ERα protein degradation via proteasome-mediated pathway in breast cancer cells. HDAC plays important roles in the regulation of histone and non-histone protein post-translational modification. HDAC inhibitors can induce epigenetic changes and have therapeutic potential for targeting various cancers. Trichostatin A exerts potent antitumor activities against breast cancer cells in vitro and in vivo. In this report, we show that TSA augments ESR1 gene repression at the transcriptional level and downregulates ERα protein expression under hypoxic conditions through a proteasome-mediated pathway. TSA-induced estrogen response element-driven reporter activity in the absence of estrogen was synergistically enhanced under hypoxia; however, TSA inhibited cell proliferation under both normoxia and hypoxia. Our data show that the hypoxia-induced repression of ESR1 and degradation of ERα are enhanced by concomitant treatment with TSA. These findings expand our understanding of hormone responsiveness in the tumor microenvironment; however, additional in-depth studies are required to elucidate the detailed mechanisms of TSA-induced ERα regulation under hypoxia. - Highlights: • TSA augments ESR1 gene repression at the transcriptional level under hypoxia. • TSA downregulates ERα protein expression under hypoxia. • TSA-induced ERα regulation under hypoxia is essential for understanding the behavior and progression of breast cancer.

  4. [The systems of molecular genetic markers under cancer of stomach].

    Science.gov (United States)

    Nemtsova, M V; Bykov, I I; Tchekinova, N V; Zaletaev, D V; Glikhov, A I; Khorobrykh, T V

    2013-11-01

    The study was organized to investigate the anomalous methylation of genes NA?1, RASSF1A, MLH1, N33, DAPK, the expression of genes hTERT. metalloproteinase MMP7, MMP9, survivin. COX-2, p53. The activity of telomerase in 106 samples of stomach tumors taken through intra-operation way and 53 samples of stomach tumors taken through endoscopic way and 50 samples of biopsy taken from patients with chronic calculous cholecystitis (comparison group) was analyzed too. These changes can be used as additional markers both in diagnostic of cancer of stomach and dynamic monitoring of operated patients.

  5. Reducing persistent postoperative pain and disability 1 year after breast cancer surgery: a randomized, controlled trial comparing thoracic paravertebral block to local anesthetic infiltration.

    Science.gov (United States)

    Chiu, Michelle; Bryson, Gregory L; Lui, Anne; Watters, James M; Taljaard, Monica; Nathan, Howard J

    2014-03-01

    The objective of this study was to compare the effect of thoracic paravertebral block (TPVB) and local anesthetic (LA) on persistent postoperative pain (PPP) 1 year following breast cancer surgery. Secondary objectives were to compare the effect on arm morbidity and quality of life. Women scheduled for elective breast cancer surgery were randomly assigned to either TPVB or LA followed by general anesthesia. An NRS value of >3 at rest or with movement 1 year following surgery defined PPP. Blinded interim analysis suggested rates of PPP much lower than anticipated, making detection of the specified 20 % absolute reduction in the primary outcome impossible. Recruitment was stopped, and all enrolled patients were followed to 1 year. A total of 145 participants were recruited; 65 were randomized to TPVB and 64 to LA. Groups were similar with respect to demographic and treatment characteristics. Only 9 patients (8 %; 95 % CI 4-14 %) met criteria for PPP 1 year following surgery; 5 were in the TPVB and 4 in the LA group. Brief Pain Inventory severity and interference scores were low in both groups. Arm morbidity and quality of life were similar in both groups. The 9 patients with PPP reported shoulder-arm morbidity and reduced quality of life. This study reports a low incidence of chronic pain 1 year following major breast cancer surgery. Although PPP was uncommon at 1 year, it had a large impact on the affected patients' arm morbidity and quality of life.

  6. Persistent Modelling

    DEFF Research Database (Denmark)

    2012-01-01

    on this subject, this book makes essential reading for anyone considering new ways of thinking about architecture. In drawing upon both historical and contemporary perspectives this book provides evidence of the ways in which relations between representation and the represented continue to be reconsidered......The relationship between representation and the represented is examined here through the notion of persistent modelling. This notion is not novel to the activity of architectural design if it is considered as describing a continued active and iterative engagement with design concerns – an evident...... characteristic of architectural practice. But the persistence in persistent modelling can also be understood to apply in other ways, reflecting and anticipating extended roles for representation. This book identifies three principle areas in which these extensions are becoming apparent within contemporary...

  7. Persistent Modelling

    DEFF Research Database (Denmark)

    on this subject, this book makes essential reading for anyone considering new ways of thinking about architecture. In drawing upon both historical and contemporary perspectives this book provides evidence of the ways in which relations between representation and the represented continue to be reconsidered......The relationship between representation and the represented is examined here through the notion of persistent modelling. This notion is not novel to the activity of architectural design if it is considered as describing a continued active and iterative engagement with design concerns – an evident...... characteristic of architectural practice. But the persistence in persistent modelling can also be understood to apply in other ways, reflecting and anticipating extended roles for representation. This book identifies three principle areas in which these extensions are becoming apparent within contemporary...

  8. [Rectal cancer - local staging and imaging under neoadjuvant therapy].

    Science.gov (United States)

    Karpitschka, M

    2012-06-01

    Rectal cancer restaging after neoadjuvant therapy is based on two principles: an anatomic definition of the tumor allowing surgical planning and prognostic stage grouping. Emerging data suggest that reassessment using a combination of different imaging modalities may help to provide valuable prognostic information before definitive surgery. Perfusion computed tomography (CT) may provide special information regarding tumor vascularity. Evaluation of therapy response, especially of the circumferential resection margin (CRM) is necessary for surgical planning. For local staging high-resolution and diffusion-weighted magnetic resonance imaging has proven to be of high diagnostic accuracy. The M status should be assessed using multidetector computed tomography (MDCT) according to response evaluation criteria in solid tumors (RECIST) while lymph node evaluation requires either magnetic resonance imaging or positron emission tomography/computed tomography scanning.

  9. Nursing workload for cancer patients under palliative care.

    Science.gov (United States)

    Fuly, Patrícia Dos Santos Claro; Pires, Livia Márcia Vidal; Souza, Claudia Quinto Santos de; Oliveira, Beatriz Guitton Renaud Baptista de; Padilha, Katia Grillo

    2016-01-01

    To verify the nursing workload required by cancer patients undergoing palliative care and possible associations between the demographic and clinical characteristics of the patients and the nursing workload. This is a quantitative, cross-sectional, prospective study developed in the Connective Bone Tissue (TOC) clinics of Unit II of the Brazilian National Cancer Institute José Alencar Gomes da Silva with patients undergoing palliative care. Analysis of 197 measures of the Nursing Activities Score (NAS) revealed a mean score of 43.09% and an association between the performance status of patients undergoing palliative care and the mean NAS scores. The results of the study point to the need to resize the team of the unit. The NAS has proven to be a useful tool in oncologic clinical units for patients undergoing palliative care. Verificar a carga de trabalho de enfermagem requerida por pacientes com câncer sob cuidados paliativos e possíveis associações entre as características demográficas e clínicas dos pacientes e a carga de trabalho de enfermagem. Trata-se de um estudo de abordagem quantitativa, transversal, prospectivo, desenvolvido na clínica de Tecido Ósseo Conectivo (TOC) da Unidade II do Instituto Nacional de Câncer José Alencar Gomes da Silva, com pacientes em cuidados paliativos. A análise de 197 medidas do Nursing Activities Score (NAS) revelou um escore médio de 43,09% e uma associação entre a performance status de pacientes em cuidados paliativos com os valores médios do NAS. Os resultados do estudo apontam para a necessidade de redimensionamento da equipe da Unidade. O NAS mostrou-se um instrumento passível de utilização em unidades clínicas oncológicas, com pacientes em cuidados paliativos.

  10. Beliefs Underlying Messages of Anti-Cancer-Screening Websites in Japan: A Qualitative Analysis

    Science.gov (United States)

    Okuhara, Tsuyoshi; Ishikawa, Hirono; Okada, Masahumi; Kato, Mio; Kiuchi, Takahiro

    2018-02-26

    Background: Cancer screening rates are lower in Japan than in Western countries. Meanwhile, anti-cancer-screening activists take to the internet to spread their messages that cancer screening has little or no efficacy, poses substantial health risks such as side effects from radiation exposure, and that people should forgo cancer screening. We applied a qualitative approach to explore the beliefs underlying the messages of anti-cancer-screening websites, by focusing on perceived value the beliefs provided to those who held them. Methods: We conducted online searches using Google Japan and Yahoo! Japan, targeting websites we classified as “pro,” “anti,” or “neutral” depending on their claims. We applied a dual analytic approach- inductive thematic analysis and deductive interpretative analysis- to the textual data of the anti websites. Results: Of the 88 websites analyzed, five themes that correspond to beliefs were identified: destruction of common knowledge, denial of standard cancer control, education about right cancer control, education about hidden truths, and sense of superiority that only I know the truth. Authors of anti websites ascribed two values (“safety of people” and “self-esteem”) to their beliefs. Conclusion: The beliefs of authors of anti-cancer-screening websites were supposed to be strong. It would be better to target in cancer screening promotion not outright screening refusers but screening hesitant people who are more amenable to changing their attitudes toward screening. The possible means to persuade them were discussed. Creative Commons Attribution License

  11. Modulation of MicroRNAs by Phytochemicals in Cancer: Underlying Mechanisms and Translational Significance

    Science.gov (United States)

    Srivastava, Sanjeev K.; Arora, Sumit; Averett, Courey; Singh, Ajay P.

    2015-01-01

    MicroRNAs (miRNAs) are small, endogenous noncoding RNAs that regulate a variety of biological processes such as differentiation, development, and survival. Recent studies suggest that miRNAs are dysregulated in cancer and play critical roles in cancer initiation, progression, and chemoresistance. Therefore, exploitation of miRNAs as targets for cancer prevention and therapy could be a promising approach. Extensive evidence suggests that many naturally occurring phytochemicals regulate the expression of numerous miRNAs involved in the pathobiology of cancer. Therefore, an understanding of the regulation of miRNAs by phytochemicals in cancer, their underlying molecular mechanisms, and functional consequences on tumor pathophysiology may be useful in formulating novel strategies to combat this devastating disease. These aspects are discussed in this review paper with an objective of highlighting the significance of these observations from the translational standpoint. PMID:25853141

  12. A Potential Role of Chronic Exposure to Extremely Low-Frequency Electromagnetic Fields in Triggering Persistent Pain Post Breast Cancer Surgery: A Review

    Directory of Open Access Journals (Sweden)

    Azadeh Stark

    2017-10-01

    Full Text Available Persistent Pain after Breast Cancer Surgery (PPBCS ranks second to amputation of extremities for neuropathic chronic pain. PPBCS is associated with the formation of intercostobrachial neuroma bulbs along the lateral chest. These neuroma bulbs are either un-/thinly myelinated and express hypersensitivity to environmental stimuli. Hypersensitivity is manifested as spontaneous pain in response to innocuous stimuli and exaggerating pain in response to noxious stimuli. Excision of neuromas, a common intervention to alleviate pain, has been reported as ineffective. Experience of individuals with amputation of extremities and experimental models of human nerve injuries confirm anthropogenic EMF evoke excruciating pain. Findings from invitro and animal studies clearly support that EMF exposure depolarizes cell membranes, interrupts voltage gated calcium channels which then activates peripheral sensory neurons and initiates propagation of a train of action potentials along the axons of primary afferent nerve fibers. The World Health Organization guidelines, established based on approximation of the human anatomy are limited and assumes no potential compounding effects of nerve injuries or alterations of physiological milieu of tissues. The objective of this review is to direct the attention of the medical community to the potential role of anthropogenic EMF as a risk factor for persistent pain after breast surgery. Patients rely heavily on the recommendations of their providers to manage their pain. The current epidemic of opioid abuse in the US has been partially attributed to the high prescription rate of opioid-based pain killers. Understanding the potential triggers of chronic pain can reduce dependency on pharmaceutical agents.

  13. Secretive and proliferative tumor profile helps to select the best imaging technique to identify postoperative persistent or relapsing medullary thyroid cancer.

    Science.gov (United States)

    Faggiano, A; Grimaldi, F; Pezzullo, L; Chiofalo, M G; Caracò, C; Mozzillo, N; Angeletti, G; Santeusanio, F; Lombardi, G; Colao, A; Avenia, N; Ferolla, P

    2009-03-01

    In patients with postoperative persistent medullary thyroid cancer (MTC), the tumor detection rate is generally low for most of the imaging techniques now available. The aim of this study was to investigate if the clinico-biological profile of the tumor may indicate which imaging technique to perform in order to identify postoperative persistent or relapsing MTC foci. Thirty-five consecutive MTC patients with detectable and progressively increasing postoperative serum concentrations of calcitonin were enrolled in the study. The detection rates of 18F-deoxy-d-glucose (FDG)-positron emission tomography (PET), somatostatin receptor scintigraphy (SRS), and 131I-metaiodobenzylguanidine scintigraphy (MIBG) were compared in relation with calcitonin and carcinoembryonic antigen serum concentrations, Ki-67 score and results of conventional imaging techniques (CIT). FDG-PET positivity was significantly associated with calcitonin serum concentrations >400 pg/ml and Ki-67 score >2.0% (P800 pg/ml (Ptechnique to use in the follow-up of patients with MTC. A Ki-67 score >2.0% suggests to perform a FDG-PET in addition to conventional imaging. Calcitonin secretion predicts both FDG-PET and SRS uptake but SRS positivity is generally found only in patients with well defined MTC lesions that are also detectable at the conventional imaging examination. MIBG outcome is not predicted by any clinico-biological factors here investigated.

  14. Semibiotic Persistence

    Science.gov (United States)

    Prothmann, C.; Zauner, K.-P.

    From observation, we find four different strategies to successfully enable structures to persist over extended periods of time. If functionally relevant features are very large compared to the changes that can be effectuated by entropy, the functional structure itself has a high enough probability to erode only slowly over time. If the functionally relevant features are protected from environmental influence by sacrificial layers that absorb the impinging of the environment, deterioration can be avoided or slowed. Loss of functionality can be delayed, even for complex systems, by keeping alternate options for all required components available. Biological systems also apply information processing to actively counter the impact of entropy by mechanisms such as self-repair. The latter strategy increases the overall persistence of living systems and enables them to maintain a highly complex functional organisation during their lifetime and over generations. In contrast to the other strategies, information processing has only low material overhead. While at present engineered technology is far from achieving the self-repair of evolved systems, the semibiotic combination of biological components with conventionally engineered systems may open a path to long-term persistence of functional devices in harsh environments. We review nature's strategies for persistence, and consider early steps taken in the laboratory to import such capabilities into engineered architectures.

  15. Comparison of ‘HoBi’-like viral populations among persistent infected calves generated under experimental conditions and to inoculum virus

    Science.gov (United States)

    Like other members from the Pestivirus genus, ‘HoBi’-like pestiviruses cause economic losses for cattle producers due to both acute and persistent infections. Pestivirus exist as quasispecies (swarms of individual viruses) in persistently infected (PI) animals leading to viral populations that are m...

  16. Radiotracer studies on the degradation and dissipation of lindane under Malaysian environment. Part of a coordinated programme on the fate of persistent pesticides in the tropics, using radioisotopes

    International Nuclear Information System (INIS)

    Jamaluddin, M.D.

    1983-11-01

    A protocol was designed to provide information on rates of dissipation and degradation of lindane (γ-isomer of 1,2,3,4,5,6-hexachlorocyclohexane), a chemical used in Malaysia for pest control in rice paddies. The parameters studied included adsorption to three Malaysian soils, volatilization, degradation, dissipation through leaching and terminal residues in the grain. 14 C-labelled lindane was used after mixing with appropriate concentrations of the cold chemical. Standard nuclear techniques such as liquid scintillation counting and radiochromatography were applied. Adsorption of lindane to soil decreased in the order clay>sandy clay>loam>sandy loam. Volatilization of lindane was proportional to the chemical concentration and was more rapid in non-flooded and sterilized flooded soils. Under flooding conditions, microorganismal activities seem to play a dominant role in the disappearance, possibly degradation, of lindane. The half-life of lindane in non-sterilized flooded soil ranged from 10.5 to 34.5 days depending on the type of soil. The chemical residue in the grain was well below the maximum residue level. This is part of a project designed to provide data on the degradation and dissipation of lindane in the Malaysian environment in an attempt to pass a realistic judgement as to its persistence

  17. Synergetic Action of Domain II and IV Underlies Persistent Current Generation in Nav1.3 as revealed by a tarantula toxin

    Science.gov (United States)

    Tang, Cheng; Zhou, Xi; Zhang, Yunxiao; xiao, Zhaohua; Hu, Zhaotun; Zhang, Changxin; Huang, Ying; Chen, Bo; Liu, Zhonghua; Liang, Songping

    2015-01-01

    The persistent current (INaP) through voltage-gated sodium channels enhances neuronal excitability by causing prolonged depolarization of membranes. Nav1.3 intrinsically generates a small INaP, although the mechanism underlying its generation remains unclear. In this study, the involvement of the four domains of Nav1.3 in INaP generation was investigated using the tarantula toxin α-hexatoxin-MrVII (RTX-VII). RTX-VII activated Nav1.3 and induced a large INaP. A pre-activated state binding model was proposed to explain the kinetics of toxin-channel interaction. Of the four domains of Nav1.3, both domain II and IV might play important roles in the toxin-induced INaP. Domain IV constructed the binding site for RTX-VII, while domain II might not participate in interacting with RTX-VII but could determine the efficacy of RTX-VII. Our results based on the use of RTX-VII as a probe suggest that domain II and IV cooperatively contribute to the generation of INaP in Nav1.3. PMID:25784299

  18. How do persistent organic pollutants be coupled with biogeochemical cycles of carbon and nutrients in terrestrial ecosystems under global climate change?

    Energy Technology Data Exchange (ETDEWEB)

    Teng, Ying [Chinese Academy of Sciences, Nanjing (China). Key Lab. of Soil Environment and Pollution Remediation; Griffith Univ., Nathan, QLD (Australia). Environmetnal Futures Centre and School of Biomolecular and Physical Sciences; Xu, Zhihong; Reverchon, Frederique [Griffith Univ., Nathan, QLD (Australia). Environmetnal Futures Centre and School of Biomolecular and Physical Sciences; Luo, Yongming [Chinese Academy of Sciences, Nanjing (China). Key Lab. of Soil Environment and Pollution Remediation

    2012-03-15

    Global climate change (GCC), especially global warming, has affected the material cycling (e.g., carbon, nutrients, and organic chemicals) and the energy flows of terrestrial ecosystems. Persistent organic pollutants (POPs) were regarded as anthropogenic organic carbon (OC) source, and be coupled with the natural carbon (C) and nutrient biogeochemical cycling in ecosystems. The objective of this work was to review the current literature and explore potential coupling processes and mechanisms between POPs and biogeochemical cycles of C and nutrients in terrestrial ecosystems induced by global warming. Global warming has caused many physical, chemical, and biological changes in terrestrial ecosystems. POPs environmental fate in these ecosystems is controlled mainly by temperature and biogeochemical processes. Global warming may accelerate the re-emissions and redistribution of POPs among environmental compartments via soil-air exchange. Soil-air exchange is a key process controlling the fate and transportation of POPs and terrestrial ecosystem C at regional and global scales. Soil respiration is one of the largest terrestrial C flux induced by microbe and plant metabolism, which can affect POPs biotransformation in terrestrial ecosystems. Carbon flow through food web structure also may have important consequences for the biomagnification of POPs in the ecosystems and further lead to biodiversity loss induced by climate change and POPs pollution stress. Moreover, the integrated techniques and biological adaptation strategy help to fully explore the coupling mechanisms, functioning and trends of POPs and C and nutrient biogeochemical cycling processes in terrestrial ecosystems. There is increasing evidence that the environmental fate of POPs has been linked with biogeochemical cycles of C and nutrients in terrestrial ecosystems under GCC. However, the relationships between POPs and the biogeochemical cycles of C and nutrients are still not well understood. Further

  19. High Flow Oxygen and Bilevel Positive Airway Pressure for Persistent Dyspnea in Patients With Advanced Cancer: A Phase II Randomized Trial

    Science.gov (United States)

    Hui, David; Morgado, Margarita; Chisholm, Gary; Withers, Laura; Nguyen, Quan; Finch, Clarence; Frisbee-Hume, Susan; Bruera, Eduardo

    2013-01-01

    Context Dyspnea is one of the most distressing symptoms for cancer patients. The role of high flow oxygen (HFO) and bilevel positive airway pressure (BiPAP) in the palliation of dyspnea has not been well characterized. Objectives To determine the feasibility of conducting a randomized trial of HFO and BiPAP in cancer patients, and to examine the changes in dyspnea, physiologic parameters and adverse effects with these modalities. Methods In this randomized study (ClinicalTrials.gov Identifier: NCT01518140), we assigned hospitalized patients with advanced cancer and persistent dyspnea to either HFO or BiPAP for two hours. We assessed dyspnea with a numeric rating scale (NRS) and modified Borg scale (MBS) before and after the intervention. We also documented vital signs, transcutaneous carbon dioxide and adverse effects. Results Thirty patients were enrolled (1:1 ratio) and 23 (77%) completed the assigned intervention. HFO was associated with improvements in both NRS (mean 1.9, 95% confidence interval [CI] 0.4, 3.4; P=0.02) and MBS (mean 2.1, 95% CI 0.6, 3.5; P=0.007). BiPAP also was associated with improvements in NRS (mean 3.2; 95% CI 1.3, 5.1; P=0.004) and MBS (mean 1.5, 95% CI −0.3, 3.2; P=0.13). There were no significant differences between HFO and BiPAP in dyspnea NRS (P=0.14) and MBS (P=0.47). Oxygen saturation improved with HFO (93% vs. 99%, P=0.003), and respiratory rate had a non-statistically significant decrease with both interventions (HFO -3; P=0.11; BiPAP -2, P=0.11 ). No significant adverse effects were observed. Conclusion HFO and BiPAP alleviated dyspnea, improved physiologic parameters and were safe. Our results justify larger randomized controlled trials to confirm these findings. PMID:23739633

  20. Predicting future major depression and persistent depressive symptoms: Development of a prognostic screener and PHQ-4 cutoffs in breast cancer patients.

    Science.gov (United States)

    Weihs, Karen L; Wiley, Joshua F; Crespi, Catherine M; Krull, Jennifer L; Stanton, Annette L

    2018-02-01

    Create a brief, self-report screener for recently diagnosed breast cancer patients to identify patients at risk of future depression. Breast cancer patients (N = 410) within 2 ± 1 months after diagnosis provided data on depression vulnerability. Depression outcomes were defined as a high depressive symptom trajectory or a major depressive episode during 16 months after diagnosis. Stochastic gradient boosting of regression trees identified 7 items highly predictive for the depression outcomes from a pool of 219 candidate depression vulnerability items. Three of the 7 items were from the Patient Health Questionnaire 4 (PHQ-4), a validated screener for current anxiety/depressive disorder that has not been tested to identify risk for future depression. Thresholds classifying patients as high or low risk on the new Depression Risk Questionnaire 7 (DRQ-7) and the PHQ-4 were obtained. Predictive performance of the DRQ-7 and PHQ-4 was assessed on a holdout validation subsample. DRQ-7 items assess loneliness, irritability, persistent sadness, and low acceptance of emotion as well as 3 items from the PHQ-4 (anhedonia, depressed mood, and worry). A DRQ-7 score of ≥6/23 identified depression outcomes with 0.73 specificity, 0.83 sensitivity, 0.68 positive predictive value, and 0.86 negative predictive value. A PHQ-4 score of ≥3/12 performed moderately well but less accurately than the DRQ-7 (net reclassification improvement = 10%; 95% CI [0.5-16]). The DRQ-7 and the PHQ-4 with a new cutoff score are clinically accessible screeners for risk of depression in newly diagnosed breast cancer patients. Use of the screener to select patients for preventive interventions awaits validation of the screener in other samples. Copyright © 2017 John Wiley & Sons, Ltd.

  1. Clinicopathological and imaging features of breast cancer in Korean Women under 40 years of age

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jun Woo; Jang, Mi Jung; Kim, Sun Mi; Yun, Bo La; Lee, Jong Yoon; Kim, Eun Kyu; Kang, Eun Young; Park, So Yeon [Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2017-06-15

    To evaluate the clinicopathological and imaging features of mammography, ultrasonography, and magnetic resonance imaging (MRI) for breast cancer in Korean women under 40 years of age according to molecular subtypes. We included 183 breast cancers in 176 consecutive women under 40 years old who had been diagnosed with breast cancer between January 2012 and November 2014. The patients' clinical and pathologic records were available as electronic medical records. A retrospective review of the pre-operative imaging studies was performed with 177 mammographies, 183 ultrasonographies, and 178 MRIs. Eighty-six percent (158/183) of lesions were symptomatic, with masses (147/183) as the most common presentation. Eighty percent (22/25) of the asymptomatic lesions were diagnosed via screening ultrasonography. The luminal A subtype was the most common (n = 79, 43%), human epidermal growth factor receptor 2-enriched subtype showed indistinct margins on mammography (p = 0.006), the triple negative subtype depicted a posterior enhancement on ultrasonography (p < 0.001) and rim enhancement on MRI (p < 0.001). Breast cancers in Korean women under 40 years of age are commonly presented with a palpable mass, and luminal A is the most common molecular subtype. In our study, the imaging and pathologic characteristics of breast cancer in younger women were similar to those previously reported for older patients.

  2. Glutamate production from ammonia via glutamate dehydrogenase 2 activity supports cancer cell proliferation under glutamine depletion.

    Science.gov (United States)

    Takeuchi, Yukiko; Nakayama, Yasumune; Fukusaki, Eiichiro; Irino, Yasuhiro

    2018-01-01

    Cancer cells rapidly consume glutamine as a carbon and nitrogen source to support proliferation, but the cell number continues to increase exponentially after glutamine is nearly depleted from the medium. In contrast, cell proliferation rates are strongly depressed when cells are cultured in glutamine-free medium. How cancer cells survive in response to nutrient limitation and cellular stress remains poorly understood. In addition, rapid glutamine catabolism yields ammonia, which is a potentially toxic metabolite that is secreted into the extracellular space. Here, we show that ammonia can be utilized for glutamate production, leading to cell proliferation under glutamine-depleted conditions. This proliferation requires glutamate dehydrogenase 2, which synthesizes glutamate from ammonia and α-ketoglutarate and is expressed in MCF7 and T47D cells. Our findings provide insight into how cancer cells survive under glutamine deprivation conditions and thus contribute to elucidating the mechanisms of tumor growth. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Long-term persistence of acquired resistance to 5-fluorouracil in the colon cancer cell line SW620

    Energy Technology Data Exchange (ETDEWEB)

    Tentes, I.K., E-mail: itentes@med.duth.gr [Department of Biochemistry, Medical School, Democritus University of Thrace, 6th km Alexandroupolis-Komotini (Dragana), 68100 Alexandroupolis (Greece); Schmidt, W.M. [Center for Anatomy and Cell Biology, Waehringer Strasse 13, 1090 Vienna (Austria); Krupitza, G. [Institute of Clinical Pathology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Steger, G.G.; Mikulits, W. [Department of Medicine I, Medical University of Vienna, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Kortsaris, A. [Department of Biochemistry, Medical School, Democritus University of Thrace, 6th km Alexandroupolis-Komotini (Dragana), 68100 Alexandroupolis (Greece); Mader, R.M. [Department of Medicine I, Medical University of Vienna, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)

    2010-11-15

    Treatment resistance to antineoplastic drugs represents a major clinical problem. Here, we investigated the long-term stability of acquired resistance to 5-fluorouracil (FU) in an in vitro colon cancer model, using four sub-clones characterised by increasing FU-resistance derived from the cell line SW620. The resistance phenotype was preserved after FU withdrawal for 15 weeks ({approx} 100 cell divisions) independent of the established level of drug resistance and of epigenetic silencing. Remarkably, resistant clones tolerated serum deprivation, adopted a CD133{sup +} CD44{sup -} phenotype, and further exhibited loss of membrane-bound E-cadherin together with predominant nuclear {beta}-catenin localisation. Thus, we provide evidence for a long-term memory of acquired drug resistance, driven by multiple cellular strategies (epithelial-mesenchymal transition and selective propagation of CD133{sup +} cells). These resistance phenomena, in turn, accentuate the malignant phenotype.

  4. The social experiences of cancer patients under treatment: a comparative study

    NARCIS (Netherlands)

    Tempelaar, R.; de Haes, J. C.; de Ruiter, J. H.; Bakker, D.; van den Heuvel, W. J.; van Nieuwenhuijzen, M. G.

    1989-01-01

    As part of a larger study on the quality of life of cancer patients under treatment, the positive and negative experiences in social interaction have been examined as compared to those of a control group (nonpatients, n = 201). Two patient groups were included: 109 patients who had recently

  5. Cancer drug pan-resistance: pumps, cancer stem cells, quiescence, epithelial to mesenchymal transition, blocked cell death pathways, persisters or what?

    NARCIS (Netherlands)

    Borst, Piet

    2012-01-01

    Although chemotherapy of tumours has scored successes, drug resistance remains the major cause of death of cancer patients. Initial treatment often leaves residual disease, from which the tumour regrows. Eventually, most tumours become resistant to all available chemotherapy. I call this

  6. Habit persistence

    DEFF Research Database (Denmark)

    Vinther Møller, Stig

    2009-01-01

    This paper uses an iterated GMM approach to estimate and test the consumption based habit persistence model of Campbell and Cochrane (1999) on the US stock market. The empirical evidence shows that the model is able to explain the size premium, but fails to explain the value premium. Further......, the state variable of the model - the surplus consumption ratio - explains counter-cyclical time-varying expected returns on stocks. The model also produces plausible low real risk-free rates despite high relative risk aversion....

  7. Stem cell Transplantation for Eradication of Minimal PAncreatic Cancer persisting after surgical Excision (STEM PACE Trial, ISRCTN47877138): study protocol for a phase II study

    International Nuclear Information System (INIS)

    Schmitz-Winnenthal, Friedrich H; Schmidt, Thomas; Lehmann, Monika; Beckhove, Philipp; Kieser, Meinhard; Ho, Anthony D; Dreger, Peter; Büchler, Markus W

    2014-01-01

    Pancreatic cancer is the third most common cancer related cause of death. Even in the 15% of patients who are eligible for surgical resection the outlook is dismal with less than 10% of patients surviving after 5 years. Allogeneic hematopoietic (allo-HSCT) stem cell transplantation is an established treatment capable of to providing cure in a variety of hematopoietic malignancies. Best results are achieved when the underlying neoplasm has been turned into a stage of minimal disease by chemotherapy. Allo-HSCT in advanced solid tumors including pancreatic cancer have been of limited success, however studies of allo-HSCT in solid tumors in minimal disease situations have never been performed. The aim of this trial is to provide evidence for the clinical value of allo-HSCT in pancreatic cancer put into a minimal disease status by effective surgical resection and standard adjuvant chemotherapy. The STEM PACE trial is a single center, phase II study to evaluate adjuvant allogeneic hematopoietic stem cell transplantation in pancreatic cancer after surgical resection. The study will evaluate as primary endpoint 2 year progression free survival and will generate first time state-of-the-art scientific clinical evidence if allo-HSCT is feasible and if it can provide long term disease control in patients with effectively resected pancreatic cancer. Screened eligible patients after surgical resection and standard adjuvant chemotherapy with HLA matched related stem cell donor can participate. Patients without a matched donor will be used as a historical control. Study patients will undergo standard conditioning for allo-HSCT followed by transplantation of allogeneic unmanipulated peripheral blood stem cells. The follow up of the patients will continue for 2 years. Secondary endpoints will be evaluated on 7 postintervention visits. The principal question addressed in this trial is whether allo-HSCT can change the unfavourable natural course of this disease. The underlying

  8. Prolonged local persistence of cisplatin-loaded gelatin microspheres and their chemoembolic anti-cancer effect in rabbits.

    Science.gov (United States)

    Ohta, Shinichi; Nitta, Norihisa; Sonoda, Akinaga; Seko, Ayumi; Tanaka, Toyohiko; Takahashi, Masashi; Takemura, Shizuki; Tabata, Yasuhiko; Murata, Kiyoshi

    2009-12-01

    To confirm prolonged cisplatin release from drug-loaded gelatin microspheres (GMSs) and their improved chemoembolic anti-cancer effect against VX2 liver tumors in rabbits. Two groups of twelve rabbits each were treated intraarterially either with 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) or 0.04 mg/kg cisplatin solution by administering them into the right renal artery. Platinum concentrations within the renal parenchyma were analyzed immediately following infusion (day 0) and on days 1, 3, and 7 using the atomic absorption method. In a second experiment four groups of five rabbits each with implanted VX2 liver tumors were treated intraarterially through the hepatic artery with the following drugs: 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) (group I), 2 mg/kg GMSs without any drug (group II), 1.5 mg/kg cisplatin solution (group III) and saline (group IV). Tumor volumes were analyzed pre-injection and 7 days after with MRI allowing calculating the relative tumor growth rate (%). Degree of liver cell necrosis was assessed on the histopathological specimens. The renal parenchymal platinum concentrations (microg/ml) with 4.51+/-2.25 (day 0), 1.59+/-0.70 (day 1), 0.72+/-0.10 (day 3) and 0.20+/-0.06 (day 7) were significantly more pronounced after cisplatin-loaded GMS on days one and three compared to cisplatin with 1.99+/-0.55, 0.08+/-0.03, 0.18+/-0.01 and 0.10+/-0.07, respectively. Relative tumor growth rates resulted in 84.5%+/-26.4 (group I); 241.4%+/-145.1 (II); 331.9%+/-72.2 (III), and 413.6%+/-103.6 (IV) with statistical significant differences between groups I and III, and groups I and IV. Similar degrees of necrosis were observed in both GMSs treated groups, while ballooning of hepatocytes was highest in cisplatin-loaded GMSs. With cisplatin-loaded GMSs more pronounced and prolonged local parenchymal cisplatin concentrations may be achieved offering the advantage of an increased and prolonged anti-cancer effect compared to cisplatin alone

  9. Prolonged local persistence of cisplatin-loaded gelatin microspheres and their chemoembolic anti-cancer effect in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Ohta, Shinichi [Department of Radiology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu City, Shiga 520-2192 (Japan)], E-mail: junryuhei@yahoo.co.jp; Nitta, Norihisa; Sonoda, Akinaga; Seko, Ayumi; Tanaka, Toyohiko; Takahashi, Masashi [Department of Radiology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu City, Shiga 520-2192 (Japan); Takemura, Shizuki [Department of Pathology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu City, Shiga (Japan); Tabata, Yasuhiko [Institute for Frontier Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto (Japan); Murata, Kiyoshi [Department of Radiology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu City, Shiga 520-2192 (Japan)

    2009-12-15

    Purpose: To confirm prolonged cisplatin release from drug-loaded gelatin microspheres (GMSs) and their improved chemoembolic anti-cancer effect against VX2 liver tumors in rabbits. Materials and methods: Two groups of twelve rabbits each were treated intraarterially either with 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) or 0.04 mg/kg cisplatin solution by administering them into the right renal artery. Platinum concentrations within the renal parenchyma were analyzed immediately following infusion (day 0) and on days 1, 3, and 7 using the atomic absorption method. In a second experiment four groups of five rabbits each with implanted VX2 liver tumors were treated intraarterially through the hepatic artery with the following drugs: 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) (group I), 2 mg/kg GMSs without any drug (group II), 1.5 mg/kg cisplatin solution (group III) and saline (group IV). Tumor volumes were analyzed pre-injection and 7 days after with MRI allowing calculating the relative tumor growth rate (%). Degree of liver cell necrosis was assessed on the histopathological specimens. Results: The renal parenchymal platinum concentrations ({mu}g/ml) with 4.51 {+-} 2.25 (day 0), 1.59 {+-} 0.70 (day 1), 0.72 {+-} 0.10 (day 3) and 0.20 {+-} 0.06 (day 7) were significantly more pronounced after cisplatin-loaded GMS on days one and three compared to cisplatin with 1.99 {+-} 0.55, 0.08 {+-} 0.03, 0.18 {+-} 0.01 and 0.10 {+-} 0.07, respectively. Relative tumor growth rates resulted in 84.5% {+-} 26.4 (group I); 241.4% {+-} 145.1 (II); 331.9% {+-} 72.2 (III), and 413.6% {+-} 103.6 (IV) with statistical significant differences between groups I and III, and groups I and IV. Similar degrees of necrosis were observed in both GMSs treated groups, while ballooning of hepatocytes was highest in cisplatin-loaded GMSs. Conclusions: With cisplatin-loaded GMSs more pronounced and prolonged local parenchymal cisplatin concentrations may be achieved offering

  10. Prolonged local persistence of cisplatin-loaded gelatin microspheres and their chemoembolic anti-cancer effect in rabbits

    International Nuclear Information System (INIS)

    Ohta, Shinichi; Nitta, Norihisa; Sonoda, Akinaga; Seko, Ayumi; Tanaka, Toyohiko; Takahashi, Masashi; Takemura, Shizuki; Tabata, Yasuhiko; Murata, Kiyoshi

    2009-01-01

    Purpose: To confirm prolonged cisplatin release from drug-loaded gelatin microspheres (GMSs) and their improved chemoembolic anti-cancer effect against VX2 liver tumors in rabbits. Materials and methods: Two groups of twelve rabbits each were treated intraarterially either with 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) or 0.04 mg/kg cisplatin solution by administering them into the right renal artery. Platinum concentrations within the renal parenchyma were analyzed immediately following infusion (day 0) and on days 1, 3, and 7 using the atomic absorption method. In a second experiment four groups of five rabbits each with implanted VX2 liver tumors were treated intraarterially through the hepatic artery with the following drugs: 2 mg/kg cisplatin-loaded GMSs (=0.04 mg/kg cisplatin) (group I), 2 mg/kg GMSs without any drug (group II), 1.5 mg/kg cisplatin solution (group III) and saline (group IV). Tumor volumes were analyzed pre-injection and 7 days after with MRI allowing calculating the relative tumor growth rate (%). Degree of liver cell necrosis was assessed on the histopathological specimens. Results: The renal parenchymal platinum concentrations (μg/ml) with 4.51 ± 2.25 (day 0), 1.59 ± 0.70 (day 1), 0.72 ± 0.10 (day 3) and 0.20 ± 0.06 (day 7) were significantly more pronounced after cisplatin-loaded GMS on days one and three compared to cisplatin with 1.99 ± 0.55, 0.08 ± 0.03, 0.18 ± 0.01 and 0.10 ± 0.07, respectively. Relative tumor growth rates resulted in 84.5% ± 26.4 (group I); 241.4% ± 145.1 (II); 331.9% ± 72.2 (III), and 413.6% ± 103.6 (IV) with statistical significant differences between groups I and III, and groups I and IV. Similar degrees of necrosis were observed in both GMSs treated groups, while ballooning of hepatocytes was highest in cisplatin-loaded GMSs. Conclusions: With cisplatin-loaded GMSs more pronounced and prolonged local parenchymal cisplatin concentrations may be achieved offering the advantage of an

  11. Paclitaxel and Carboplatin or Ifosfamide in Treating Patients With Newly Diagnosed, Persistent or Recurrent Uterine, Ovarian, Fallopian Tube, or Peritoneal Cavity Cancer

    Science.gov (United States)

    2018-01-09

    Mixed Mesodermal (Mullerian) Tumor; Ovarian Carcinosarcoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Uterine Sarcoma AJCC v7; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Uterine Sarcoma AJCC v7; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Uterine Sarcoma AJCC v7; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Uterine Sarcoma AJCC v7; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Uterine Sarcoma AJCC v7; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIA Uterine Sarcoma AJCC v7; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIB Uterine Sarcoma AJCC v7; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IIIC Uterine Sarcoma AJCC v7; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Stage IVA Uterine Sarcoma AJCC v7; Stage IVB Uterine Sarcoma AJCC v7; Uterine Carcinosarcoma

  12. Routine TP53 testing for breast cancer under age 30: ready for prime time?

    Science.gov (United States)

    McCuaig, Jeanna M; Armel, Susan R; Novokmet, Ana; Ginsburg, Ophira M; Demsky, Rochelle; Narod, Steven A; Malkin, David

    2012-12-01

    It is well known that early-onset breast cancer may be due to an inherited predisposition. When evaluating women diagnosed with breast cancer under age 30, two important syndromes are typically considered: Hereditary Breast and Ovarian Cancer Syndrome and Li-Fraumeni syndrome. Many women are offered genetic testing for mutations in the BRCA1 and BRCA2 genes; however, few are offered genetic testing for mutations in the TP53 gene. There is a concern that overly restrictive testing of TP53 may fail to recognize families with Li-Fraumeni syndrome. We reviewed the genetic test results and family histories of all women with early-onset breast cancer who had genetic testing of the TP53 gene at the Toronto Hospital for Sick Children. Of the 28 women tested, six (33.3 %) had a mutation in the TP53 gene; a mutation was found in 7.7 % of women who did not meet current criteria for Li-Fraumeni syndrome. By reviewing similar data published between 2000 and 2011, we estimate that 5-8 % of women diagnosed with early-onset breast cancer, and who have a negative family history, may have a mutation in the TP53 gene. Given the potential benefits versus harms of this testing, we discuss the option of simultaneous testing of all three genes (BRCA1, BRCA2, and TP53) for women diagnosed with breast cancer before age 30.

  13. Oxidative Stress and Mitochondrial Activation as the Main Mechanisms Underlying Graphene Toxicity against Human Cancer Cells

    Directory of Open Access Journals (Sweden)

    Anna Jarosz

    2016-01-01

    Full Text Available Due to the development of nanotechnology graphene and graphene-based nanomaterials have attracted the most attention owing to their unique physical, chemical, and mechanical properties. Graphene can be applied in many fields among which biomedical applications especially diagnostics, cancer therapy, and drug delivery have been arousing a lot of interest. Therefore it is essential to understand better the graphene-cell interactions, especially toxicity and underlying mechanisms for proper use and development. This review presents the recent knowledge concerning graphene cytotoxicity and influence on different cancer cell lines.

  14. Adaptação, produtividade e persistência de Arachis pintoi submetido a diferentes níveis de sombreamento Adaptation, productivity and persistence of Arachis pintoi under different levels of shading

    Directory of Open Access Journals (Sweden)

    Carlos Maurício Soares de Andrade

    1999-01-01

    Full Text Available Este experimento foi realizado com o objetivo de determinar o potencial forrageiro da leguminosa Arachis pintoi, submetida a 0, 30, 50 e 70% de sombreamento, em sistemas silvipastoris e como cobertura do solo em sistemas agroflorestais. O delineamento experimental usado foi o inteiramente casualizado, com quatro repetições. Realizou-se uma avaliação no final do período chuvoso e outra no final do período seco, usando as características altura e vigor de plantas, cobertura do solo e biomassa aérea, subterrânea e total. Os resultados mostraram que A. pintoi apresentou boa adaptação e persistência nos níveis de sombreamento estudados. A produtividade, apesar de ter diminuído com o aumento dos níveis de sombreamento, foi considerada adequada mesmo nos níveis mais altos. Concluiu-se que é possível usar esta leguminosa como cobertura do solo em sistemas agroflorestais e como forrageira em sistemas silvipastoris.The experiment was conducted to determine the forage potential of the Arachis pintoi submitted to 0, 30, 50 and 70% of shading, in silvopastoral systems and as ground cover in agroforestry systems. The experimental design was a completely randomized design with four replications. An evaluation was carried at the end of the rainy season and another at the end of the dry season, using the caracteristics height and plant vigor, ground cover, and total, above and below ground biomass. The results showed that A. pintoi presented good adaptation and persistence in the studied levels of shading. Although its productivity decreased with the increase of the levels of shading, it was considered adequate, even in the highest levels of shading. This indicates that it is possible to use this legume as ground cover in agroforestry systems and as forage in silvopastoral systems.

  15. The effect of under-treatment of breast cancer in women 80 years of age and older

    NARCIS (Netherlands)

    Van Leeuwen, Barbara L.; Rosenkranz, K. M.; Feng, L. Lei; Bedrosian, I.; Hartmann, K.; Hunt, K. K.; Kuerer, H. M.; Ross, M.; Singletary, S. E.; Babiera, Gildy V.

    Background: Several authors have demonstrated a trend toward the under-treatment of elderly and very elderly women with breast cancer. This study was undertaken to determine the impact of under-treatment of breast cancer in women age 80 and older. Methods: A retrospective chart review of all

  16. In Situ Persistence and Migration of Biochar Carbon and Its Impact on Native Carbon Emission in Contrasting Soils under Managed Temperate Pastures.

    Directory of Open Access Journals (Sweden)

    Bhupinder Pal Singh

    Full Text Available Pyrogenic carbon (PyC is an important component of the global soil carbon (C pool, but its fate, persistence, and loss dynamics in contrasting soils and environments under planted field conditions are poorly understood. To fill this knowledge gap, a 13C-labelled biochar, as a surrogate material for PyC, produced from Eucalyptus saligna by slow pyrolysis (450°C; δ13C -36.7‰ was surface (0-10 cm applied in C3 dominated temperate pasture systems across Arenosol, Cambisol and Ferralsol. The results show a low proportion of the applied biochar-C mineralised over 12 months in a relatively clay- and C-poor Arenosol (i.e., 2.0% loss via mineralisation, followed by a clay- and C-rich Cambisol (4.6%, and clay-, C- and earthworm-rich Ferralsol (7.0%. The biochar-C mean residence time (MRT, estimated by different models, varied between 44-1079 (Arenosol, 18-172 (Cambisol, and 11-29 (Ferralsol years, with the shorter MRT estimated by a one-pool exponential and the longer MRT by an infinite-pool power or a two-pool exponential model. The two-pool model was best fitted to biochar-C mineralisation. The biochar-C recovery in the 12-30 cm soil layer varied from between 1.2% (Arenosol, 2.5-2.7% (Cambisol and 13.8-15.7% (Ferralsol of the applied biochar-C after 8-12 months. There was a further migration of biochar-C below the 50-cm depth in the Arenosol, as the combined biochar-C recovery in the mineralised pool and soil profile (up to 30 or 50 cm was 82%, in contrast to 101% in the Cambisol and 104% in the Ferralsol after 12 months. These results indicate that the downward migration of biochar-C was greatest in the Arenosol (cf. Cambisol and Ferralsol. Cumulative CO2-C emission from native soil-plant sources was lower (p <0.10 in the biochar-amended vs. non-amended Ferralsol. This field-based study shows that the downward migration of biochar-C exceeded its loss via mineralisation in the Arenosol and Ferralsol, but not in the Cambisol. It is thus important to

  17. Non-target effect of continuous application of chlorpyrifos on soil microbes, nematodes and its persistence under sub-humid tropical rice-rice cropping system.

    Science.gov (United States)

    Kumar, Upendra; Berliner, J; Adak, Totan; Rath, Prakash C; Dey, Avro; Pokhare, Somnath S; Jambhulkar, Nitiprasad N; Panneerselvam, P; Kumar, Anjani; Mohapatra, Shyamranjan D

    2017-01-01

    Application of pesticide in agricultural fields is "unnecessary evil" for non-target microflora and fauna. Hence, to identify the safer pesticide molecules against non-target microbes, a long-term pesticide experiment was initiated at National Rice Research Institute, Cuttack, India. In the present study, the effect of continuous application of chlorpyrifos (0.5kgha -1 ) in rice fields on non-target groups of soil microbes and nematodes was studied for seven seasons (four wet and three dry seasons) during 2009-2013. Treatments were arranged in a randomized complete block design with four replications of chlorpyrifos-treated (0.5kg a.i. ha -1 ) (CT) and untreated control (UT) plots. During seven seasons of experimentation, regular application of chlorpyrifos had no significant effect on population of heterotrophic aerobic, anaerobic, oligotrophic and copiotrophic bacteria in CT compared to UT, whereas, population of asymbiotic aerobic nitrogen fixer, nitrifiers, denitrifiers, gram positive and spore-forming bacteria were significantly reduced by nearly 0.25-2 fold in CT than UT. However, comparatively less deviation in population of actinomycetes, fungi, phosphate solubilizing and sulfur oxidizing bacteria were observed in CT than UT. Significant interactions were found between effects of chlorpyrifos with time in population dynamics of microbes. In plant parasitic nematode species, Meloidogyne graminicola (RRKN) and Hirschmanniella spp. (RRN), were significantly lower (p<0.01) in CT compared to UT after first year onwards. The overall observation of five years data indicated that the RRKN population showed a decreasing trend (R 2 =0.644) whereas RRN showed increasing trend (R 2 =0.932) in CT. The drastic chlorpyrifos dissipation was noticed after 15 days of application from the initial residue of 0.25mgkg -1 soil, which indicated that chlorpyrifos residue in rice field soil was not persistent and its half-life was found to be 4.02 days. Overall, the present

  18. Acridine orange exhibits photodamage in human bladder cancer cells under blue light exposure.

    Science.gov (United States)

    Lin, Yi-Chia; Lin, Ji-Fan; Tsai, Te-Fu; Chen, Hung-En; Chou, Kuang-Yu; Yang, Shan-Che; Tang, Ya-Ming; Hwang, Thomas I-Sheng

    2017-10-26

    Human bladder cancer (BC) cells exhibit a high basal level of autophagic activity with accumulation of acridine-orange(AO)-stained acidic vesicular organelles. The rapid AO relocalization was observed in treated BC cells under blue-light emission. To investigate the cytotoxic effects of AO on human BC cell lines under blue-light exposure, human immortalized uroepithelial (SV-Huc-1) and BC cell lines (5637 and T24) were treated with indicated concentrations of AO or blue-light exposure alone and in combination. The cell viability was then determined using WST-1, time-lapse imaging with a Cytosmart System and continuous quantification with a multi-mode image-based reader. Treatment of AO or blue-light exposure alone did not cause a significant loss of viability in BC cells. However, AO exhibited a dose-dependent increment of cytotoxicity toward BC cells under blue-light exposure. Furthermore, the tumor formation of BC cells with treatment was significantly reduced when evaluated in a mouse xenograft model. The photodamage caused by AO was nearly neglected in SV-Huc-1 cells, suggesting a differential effect of this treatment between cancer and normal cells. In summary, AO, as a photosensitizer, disrupts acidic organelles and induces cancer cell death in BC cells under blue-light irradiation. Our findings may serve as a novel therapeutic strategy against human BC.

  19. Evaluating Psychosocial Mechanisms Underlying STEM Persistence in Undergraduates: Evidence of Impact from a Six-Day Pre-College Engagement STEM Academy Program

    Science.gov (United States)

    Findley-Van Nostrand, Danielle; Pollenz, Richard S.

    2017-01-01

    The persistence of undergraduate students in science, technology, engineering, and mathematics (STEM) disciplines is a national issue based on STEM workforce projections. We implemented a weeklong pre-college engagement STEM Academy (SA) program aimed at addressing several areas related to STEM retention. We validated an instrument that was…

  20. Influence of taste disorders on dietary behaviors in cancer patients under chemotherapy

    Directory of Open Access Journals (Sweden)

    Laviano Alessandro

    2010-03-01

    Full Text Available Abstract Objectives To determine the relationship between energy and nutrient consumption with chemosensory changes in cancer patients under chemotherapy. Methods We carried out a cross-sectional study, enrolling 60 subjects. Cases were defined as patients with cancer diagnosis after their second chemotherapy cycle (n = 30, and controls were subjects without cancer (n = 30. Subjective changes of taste during treatment were assessed. Food consumption habits were obtained with a food frequency questionnaire validated for Mexican population. Five different concentrations of three basic flavors --sweet (sucrose, bitter (urea, and a novel basic taste, umami (sodium glutamate-- were used to measure detection thresholds and recognition thresholds (RT. We determine differences between energy and nutrient consumption in cases and controls and their association with taste DT and RT. Results No demographic differences were found between groups. Cases showed higher sweet DT (6.4 vs. 4.4 μmol/ml; p = 0.03 and a higher bitter RT (100 vs. 95 μmol/ml; p = 0.04 than controls. Cases with sweet DT above the median showed significant lower daily energy (2,043 vs.1,586 kcal; p = 0.02, proteins (81.4 vs. 54 g/day; p = 0.01, carbohydrates (246 vs.192 g/day; p = 0.05, and zinc consumption (19 vs.11 mg/day; p = 0.01 compared to cases without sweet DT alteration. Cases with sweet DT and RT above median were associated with lower completion of energy requirements and consequent weight loss. There was no association between flavors DT or RT and nutrient ingestion in the control group. Conclusion Changes of sweet DT and bitter RT in cancer patients under chemotherapy treatment were associated with lower energy and nutrient ingestion. Taste detection and recognition thresholds disorders could be important factors in malnutrition development on patients with cancer under chemotherapy treatment.

  1. Endoplasmic Reticulum–Mitochondrial Ca2+ Fluxes Underlying Cancer Cell Survival

    Directory of Open Access Journals (Sweden)

    Hristina Ivanova

    2017-05-01

    Full Text Available Calcium ions (Ca2+ are crucial, ubiquitous, intracellular second messengers required for functional mitochondrial metabolism during uncontrolled proliferation of cancer cells. The mitochondria and the endoplasmic reticulum (ER are connected via “mitochondria-associated ER membranes” (MAMs where ER–mitochondria Ca2+ transfer occurs, impacting the mitochondrial biology related to several aspects of cellular survival, autophagy, metabolism, cell death sensitivity, and metastasis, all cancer hallmarks. Cancer cells appear addicted to these constitutive ER–mitochondrial Ca2+ fluxes for their survival, since they drive the tricarboxylic acid cycle and the production of mitochondrial substrates needed for nucleoside synthesis and proper cell cycle progression. In addition to this, the mitochondrial Ca2+ uniporter and mitochondrial Ca2+ have been linked to hypoxia-inducible factor 1α signaling, enabling metastasis and invasion processes, but they can also contribute to cellular senescence induced by oncogenes and replication. Finally, proper ER–mitochondrial Ca2+ transfer seems to be a key event in the cell death response of cancer cells exposed to chemotherapeutics. In this review, we discuss the emerging role of ER–mitochondrial Ca2+ fluxes underlying these cancer-related features.

  2. Clinical trial insurance coverage for cancer patients under the Affordable Care Act

    Directory of Open Access Journals (Sweden)

    Christine B. Mackay

    2016-04-01

    Conclusion: Three main factors limit the effectiveness of the ACA provisions in expanding clinical trial coverage: 1 ‘grandfathered’ self-funded employer plans not subject to state Employee Retirement Income Security Act (ERISA regulations, 2 Medicaid coverage limits not addressed under the ACA, 3 populations that remain uninsured. Kansas saw a negligible increase in insurance coverage as a result of the ACA thus lack of insurance coverage is likely to remain a concern for cancer patients.

  3. Clusterin and chemotherapy sensitivity under normoxic and graded hypoxic conditions in colorectal cancer.

    LENUS (Irish Health Repository)

    Kevans, David

    2012-06-01

    In vitro studies have shown that clusterin modulates treatment sensitivity in a number of human cancers; however, the interaction between clusterin expression and hypoxia in controlling treatment response in CRC has not previously been examined. The aim of this study was to assess the effect of clusterin overexpression in CRC cells on sensitivity to 5-fluorouracil (5-FU), oxaliplatin and FOLFOX treatment under normoxic and graded hypoxic conditions.

  4. Lumpectomy and sentinel lymph node navigation surgery for breast cancer under local anesthesia

    International Nuclear Information System (INIS)

    Nakajima, Hiroo; Fujiwara, Ikuya; Mizuta, Naruhiko; Sakaguchi, Koichi; Hachimine, Yasushi; Nakatsukasa, Katsuhiro; Kobayashi, Aya

    2007-01-01

    We studied and analyzed therapeutic outcomes of a radical surgery under local anesthesia for breast cancer in our department. Subjects were 53 patients with breast cancer whose diagnoses were definitely made before surgery. Indications were: localized ductal carcinoma in situ (DCIS) diagnosed preoperatively; invasive carcinoma less than 3 cm in tumor diameter on ultrasound and magnetic resonance imaging scan; and clinically tumors with negative axillary lymph nodes. Operative procedures included microdochectomy or lumpectomy associated with sentinel lymph node navigation biopsy (SLNB). We could perform the operation under local anesthesia in all the 53 patients, and were not demanded to shift from local to general anesthesia. Surgical stumps were positive in 10 patients (18.9%). Of the ten patients, additional resection was performed in one, and irradiation was added to the remaining nine patients. SLNB was performed in a total of 39 patients, six (15.4%) patients of them had metastasis and two out of the six patients underwent additional axillary lymph node dissection. None of serious complications were encountered. Local recurrence and hepatic metastasis occurred in each one patient in an averaged observation period of 15.1 months. This day's radical operation under local anesthesia for breast cancer is a useful procedure as minimally invasive surgery as for the indications employed in this study. (author)

  5. "Hard" and "soft" lesions underlying the HLA class I alterations in cancer cells: implications for immunotherapy.

    Science.gov (United States)

    Garrido, Federico; Cabrera, Teresa; Aptsiauri, Natalia

    2010-07-15

    The ability of cancer cells to escape from the natural or immunotherapy-induced antitumor immune response is often associated with alterations in the tumor cell surface expression of Major Histocompatibility Complex (MHC) Class I antigens. Considerable knowledge has been gained on the prevalence of various patterns of MHC Class I defects and the underlying molecular mechanisms in different types of cancer. In contrast, few data are available on the changes in MHC Class I expression happening during the course of cancer immunotherapy. We have recently proposed that the progression or regression of a tumor lesion in cancer patients undergoing immunotherapy could be predetermined by the molecular mechanism responsible for the MHC Class I alteration and not by the type of immunotherapy used, i.e., interleukin-2 (IL-2), Bacillus Calmette-Guèrin (BCG), interferon-alpha (IFN-alpha), peptides alone, dendritic cells loaded with peptides, protein-bound polysaccharide etc. If the molecular alteration responsible for the changes in MHC Class I expression is reversible by cytokines ("soft" lesion), the MHC Class I expression will be upregulated, the specific T cell-mediated response will increase and the lesion will regress. However, if the molecular defect is structural ("hard" lesion), the MHC Class I expression will remain low, the escape mechanism will prevail and the primary tumor or the metastatic lesion will progress. According to this idea, the nature of the preexisting MHC Class I lesion in the cancer cell has a crucial impact determining the final outcome of cancer immunotherapy. In this article, we discuss the importance of these two types of molecular mechanisms of MHC Class I-altered expression.

  6. Dietary exposure to persistent organochlorine compounds and health effects in women and their infants. Epidemiological studies on birth-weight, cancer incidence, and mortality

    Energy Technology Data Exchange (ETDEWEB)

    Rylander, L.

    1997-05-01

    In Sweden the main exposure route for both polychlorinated biphenyls (PCB) and other persistent organochlorine compounds is through consumption of fatty fish species from the Baltic Sea (the eastern coast of Sweden). Cohorts of fishermen`s wives from the Swedish east and west coasts were established. Interviewed east and west coast cohort women ate locally caught fish at least twice as often as women from the general population. The east coast cohort women displayed during the period 1968-1989 an increased breast cancer incidence and mortality in ischemic heart disease as compared with the west coast cohort. Due to lack of individual data on exposure and confounding factors, it is not possible to conclude that the differences were caused by fish intake. Infants from the east coast cohort had during the period 1973-1991 an increased risk for low birth weight, as compared with infants from the west coast cohort. A nested case-referent study within the east coast cohort indicated an increased risk of low birth weight among infants born to mothers who reported a relatively high current intake of fish from the Baltic Sea, as well as among mothers who had grown up in a fishing village. Moreover, maternal 2,2`,4,4`,5,5`-hexachlorobiphenyl (CB-153, which was showed to be a feasible biomarker for exposure to PCB) concentrations in plasma drawn in 1995 and the estimated concentrations during the year of childbirth showed effects on the risk for having an infant with low birth weight. Employing alternative plausible kinetic models, an increased risk for low birth weight was observed at a CB-153 concentration in plasma during year of childbirth around 300-400 ng/g lipid. 117 refs, 5 figs, 4 tabs

  7. Hypoxia inducible factor-1α-dependent epithelial to mesenchymal transition under hypoxic conditions in prostate cancer cells.

    Science.gov (United States)

    Li, Mingchuan; Wang, Yong Xing; Luo, Yong; Zhao, Jiahui; Li, Qing; Zhang, Jiao; Jiang, Yongguang

    2016-07-01

    Prostate cancer is the most commonly diagnosed cancer in men and the second leading cause of cancer death. Hypoxia is an environmental stimulus that plays an important role in the development and cancer progression especially for solid tumors. The key regulator under hypoxic conditions is stabilized hypoxia-inducible factor (HIF)-1α. In the present study, immune-fluorescent staining, siRNAs, qRT-PC, immunoblotting, cell migration and invasion assays were carried out to test typical epithelial to mesenchymal transition under hypoxia and the key regulators of this process in PC3, a human prostate cancer cell line. Our data demonstrated that hypoxia induces diverse molecular, phenotypic and functional changes in prostate cancer cells that are consistent with EMT. We also showed that a cell signal factor such as HIF-1α, which might be stabilized under hypoxic environment, is involved in EMT and cancer cell invasive potency. The induced hypoxia could be blocked by HIF-1α gene silencing and reoxygenation of EMT in prostate cancer cells, hypoxia partially reversed accompanied by a process of mesenchymal-epithelial reverting transition (MErT). EMT might be induced by activation of HIF-1α-dependent cell signaling in hypoxic prostate cancer cells.

  8. Pro-oxidant activity of dietary chemopreventive agents: an under-appreciated anti-cancer property

    Science.gov (United States)

    Azmi, Asfar S

    2013-01-01

    “ Let food be thy medicine and medicine be thy food” was quoted by Hippocrates more than two thousand years ago and since ancient times the health benefits of different natural agents have been exploited. In modern research, the disease preventive benefits of many such natural agents, particularly dietary compounds and their derivatives, has been attributed to their well recognized activity as the regulators of redox state of the cell. Nevertheless, most of these studies have focused on their antioxidant activity. A large body of evidence indicates that a major fraction of these agents can elicit pro-oxidant (radical generating) behavior which has been linked to their anti-cancer effects. This editorial provides an overview of the under-appreciated pro-oxidant activity of natural products, with a special focus on their ability to generate reactive oxygen species in the presence of transition metal ions, and discusses their possible use as cancer chemotherapeutic agents. PMID:24358870

  9. mTORC1-Dependent Metabolic Reprogramming Underlies Escape from Glycolysis Addiction in Cancer Cells.

    Science.gov (United States)

    Pusapati, Raju V; Daemen, Anneleen; Wilson, Catherine; Sandoval, Wendy; Gao, Min; Haley, Benjamin; Baudy, Andreas R; Hatzivassiliou, Georgia; Evangelista, Marie; Settleman, Jeff

    2016-04-11

    Although glycolysis is substantially elevated in many tumors, therapeutic targeting of glycolysis in cancer patients has not yet been successful, potentially reflecting the metabolic plasticity of tumor cells. In various cancer cells exposed to a continuous glycolytic block, we identified a recurrent reprogramming mechanism involving sustained mTORC1 signaling that underlies escape from glycolytic addiction. Active mTORC1 directs increased glucose flux via the pentose phosphate pathway back into glycolysis, thereby circumventing a glycolysis block and ensuring adequate ATP and biomass production. Combined inhibition of glycolysis and mTORC1 signaling disrupted metabolic reprogramming in tumor cells and inhibited their growth in vitro and in vivo. These findings reveal novel combinatorial therapeutic strategies to realize the potential benefit from targeting the Warburg effect. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. A TORC2-Akt feedforward topology underlies HER3 resiliency in HER2-amplified cancers

    Science.gov (United States)

    Amin, Dhara N.; Ahuja, Deepika; Yaswen, Paul; Moasser, Mark M.

    2015-01-01

    The requisite role of HER3 in HER2-amplified cancers is beyond what would be expected as a dimerization partner or effector substrate and it exhibits a substantial degree of resiliency that mitigates the effects of HER2-inhibitor therapies. To better understand the roots of this resiliency, we conducted an in-depth chemical-genetic interrogation of the signaling network downstream of HER3. A unique attribute of these tumors is the deregulation of TORC2. The upstream signals that ordinarily maintain TORC2 signaling are lost in these tumors, and instead TORC2 is driven by Akt. We find that in these cancers HER3 functions as a buffering arm of an Akt-TORC2 feed-forward loop that functions as a self-perpetuating module. This network topology alters the role of HER3 from a conditionally engaged ligand-driven upstream physiologic signaling input to an essential component of a concentric signaling throughput highly competent at preservation of homeostasis. The competence of this signaling topology is evident in its response to perturbation at any of its nodes. Thus a critical pathophysiological event in the evolution of HER2-amplified cancers is the loss of the input signals that normally drive TORC2 signaling, repositioning it under Akt dependency and fundamentally altering the role of HER3. This reprogramming of the downstream network topology is a key aspect in the pathogenesis of HER2-amplified cancers and constitutes a formidable barrier in the targeted therapy of these cancers. PMID:26438156

  11. Breast cancer features in women under the age of 40 years

    Directory of Open Access Journals (Sweden)

    Deise Santiago Girão Eugênio

    Full Text Available Summary Objective: To describe the clinical features, imaging findings and pathological aspects of breast cancer diagnosed in women under the age of 40 years. Method: A retrospective, descriptive study was performed through analysis of medical records between November 2008 and August 2012. One hundred and twenty (120 patients were included, of whom 112 underwent mammography, 113 underwent ultrasonography, and 105 underwent magnetic resonance imaging (MRI. The histopathological data was obtained in most cases from post-surgical analysis, which was available for 113 patients. Results: The mean age at diagnosis of primary breast cancer was 34 years. Only 11 patients (9.0% had a family history of breast or ovarian cancer in first-degree relative. Ninety-two (92 patients sought medical attention after showing breast symptoms, and the presence of a palpable nodule was the main complaint. One hundred and twenty-two (122 primary tumors were diagnosed, of which 112 were invasive (95%. The most common histological type was invasive ductal carcinoma (73.8%. Luminal B was the predominant molecular subtype (42.6%. Ultrasonography was positive in 94.5% of the cases and the most common finding were nodules (94.8%. At mammography, the malignancy was observed in 92.8% and the presence of suggestive calcifications was the dominant feature. The MRI was positive in 98% of patients, and mass lesions were the most common. Conclusion: Most cases of breast cancer diagnosed in patients under the age of 40 years, in our population, had symptoms at diagnosis and tumor with more aggressive biological behavior. Despite the ultrasound has been the most widely used method, we found improved characterization of breast lesions when also used mammography and MRI.

  12. [Clinical Benefits of Transurethral Resection Under Narrow Band Imaging for Non-Muscle Invasive Bladder Cancer].

    Science.gov (United States)

    Mita, Koji; Kobatake, Kohei; Ohara, Shinya; Kato, Masao

    2018-01-01

    The aim of this study was to reveal the clinical benefits of transurethral resection (TUR) under narrow band imaging (NBI-TUR) for non-muscle-invasive bladder cancer (NMIBC) compared with conventional white light imaging TUR (WLI-TUR). The subjects were 172 patients with NMIBC who were followed for more than 1 year after undergoing TUR with no additional postoperative treatment. In the WLI-TUR group (n=101), lesions that were detected as positive after systematic intravesical observation under WLI were resected completely under WLI. In the NBI-TUR group (n=71), similar observations under WLI were followed by systematic intravesical observation under NBI. After multiple site biopsy under NBI, TUR was performed for all lesions that were detected as positive under NBI. The sensitivity was calculated based on the results of cystoscopy and pathology of multiple site biopsy samples under WLI and NBI in the NBITUR group. The tumor recurrence rate was analyzed in both groups. Background factors did not differ significantly between the two groups, except for the observation period (63.3 months in the WLI-TUR group vs 42.0 months in the NBI-TUR group, p<0.01). The procedure under NBI had significantly higher sensitivity (94.6% vs 75.0%, p<0.01) compared with that under WLI. The recurrence-free rate in the NBITUR group was significantly higher than that in the WLI-TUR group (p=0.013). The tumor recurrencefree rate of NBI-TUR is higher than that of conventional WLI-TUR for patients with NMIBC.

  13. LDL-cholesterol goal attainment under persistent lipid-lowering therapy in northeast China: Subgroup analysis of the dyslipidemia international study of China (DYSIS-China).

    Science.gov (United States)

    Zheng, Wen; Zhang, Yu-Jiao; Bu, Xiang-Ting; Guo, Xin-Zhu; Hu, Da-Yi; Li, Zhan-Quan; Sun, Jian

    2017-11-01

    Lipid-lowering therapy with statins reduces the risk of cardiovascular events, but the efficacy of persistent treatment in a real-world setting may vary from regions. Routine lipid-lowering therapy in the region with a high prevalence of cardiovascular disease may lead to more failures of goal attainment. We therefore performed a study to observe different lipid-lowering strategies in northeast (NE) China with respect to low-density lipoprotein-cholesterol (LDL-C) reduction and goal attainments.A cross-sectional study (DYSIS-China) was conducted in 2012, involving 25,317 patients from 122 centers across China who were diagnosed with hyperlipidemia and treated with lipid-lowering therapy for at least 3 months. Of these patients, 4559 (18.0%) were assigned to the NE group according to their residential zones.Patients in the NE group tended to be younger, female, overweight, and had more comorbidities and higher blood lipid levels than those in the non-NE group (P 24 kg/m, drinking alcohol, smoking, and being residence in NE China as independent predictors of LDL-C attainment.Despite having received persistent lipid-lowering treatments, the current situation of dyslipidemia patients in NE China is unsatisfactory. The main treatment gap might be related to the choice of statin and effective combination therapy and the control of comorbidities and obesity, especially for high-risk patients.

  14. Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress

    OpenAIRE

    Schug, Zachary T.; Peck, Barrie; Jones, Dylan T.; Zhang, Qifeng; Grosskurth, Shaun; Alam, Israt S.; Goodwin, Louise M.; Smethurst, Elizabeth; Mason, Susan; Blyth, Karen; McGarry, Lynn; James, Daniel; Shanks, Emma; Kalna, Gabriela; Saunders, Rebecca E.

    2015-01-01

    Summary A functional genomics study revealed that the activity of acetyl-CoA synthetase 2 (ACSS2) contributes to cancer cell growth under low-oxygen and lipid-depleted conditions. Comparative metabolomics and lipidomics demonstrated that acetate is used as a nutritional source by cancer cells in an ACSS2-dependent manner, and supplied a significant fraction of the carbon within the fatty acid and phospholipid pools. ACSS2 expression is upregulated under metabolically stressed conditions and A...

  15. Anti-cancer effect and the underlying mechanisms of gypenosides on human colorectal cancer SW-480 cells.

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    Han Yan

    Full Text Available BACKGROUND: Gypenosides (Gyp, the main components from Gynostemma pentaphyllum Makino, are widely used in traditional Chinese medicine. The present study aimed to investigate the anti-cancer effect and the underlying mechanisms of Gyp on human colorectal cancer cells SW-480. MATERIALS AND METHODS: The inhibitory effect of Gyp on SW-480 cells was evaluated by MTT assay. Apoptotic cell death was detected by nuclear Hoechst 33342 staining and DNA fragmentation analysis. Apoptosis was analyzed using Annexin V-PE/7-amino-actinomycin D staining. Cell membrane integrity was evaluated with flow cytometry following PI staining. Changes of mitochondrial membrane potential (Δψm were detected through flow cytometry analysis of rhodamine 123 (Rh123. The role of reactive oxygen species (ROS in Gyp induced cell death was investigated by intracellular ROS generation and general ROS scavenger. Wound-healing assay was carried out to investigate Gyp-inhibited migration of SW-480 cells in vitro. Additionally, the alterations in F-actin microfilaments were analyzed by FITC-labeled phalloidin toxin staining and the morphological changes were evaluated under scanning electron microscope (SEM. RESULTS: After the Gyp treatment, the plasma membrane permeability of SW-480 cell was increased, Δψm was decreased significantly, the level of intracellular ROS level was increased, DNA fragmentation and apoptotic morphology were observed. Cells treated with Gyp exert serious microfilament network collapse as well as the significant decrease in the number of microvilli. Gyp induced the changes of cell viability, cell migration, intracellular ROS generation and nuclear morphology were alleviated obviously by NAC. CONCLUSION: The results in this study implied that ROS play an important role in Gyp induced cell toxicity and apoptosis, and the mitochondria damage may be upstream of ROS generation post Gyp treatment. The findings of the present study provide new evidences for anti

  16. Quantitative gene expression underlying 18f-fluorodeoxyglucose uptake in colon cancer

    DEFF Research Database (Denmark)

    Engelmann, Bodil E.; Binderup, Tina; Kjær, Andreas

    2015-01-01

    Background: Positron emission tomography (PET) with the glucose analogue 18F-fluorodeoxyglucose (FDG) is widely used in oncologic imaging. This study examines the molecular mechanism underlying the detection of colon cancer (CC) by FDG-PET. Methods: Pre-operative PET/CT scans and tissue samples....... Mean gene expression levels of GLUT1, HK2, ki67, HIF1α, VEGF and CaIX, but not HK1, were significantly higher in primary tumours than in surrounding normal colonic mucosa. Linear regressions pairing tumour SUVmax with gene expression levels showed significant correlations between SUVmax and HK2, ki67...

  17. Fates of Rare Species under Siege from Invasion: Persistence of Coccinella novemnotata Herbst in Western North America alongside an Invasive Congener

    Directory of Open Access Journals (Sweden)

    Edward W. Evans

    2017-12-01

    Full Text Available Species invading new geographic regions may threaten continued existence of similar, indigenous relatives, particularly those species whose rarity may reflect an already tenuous existence. The spectacular colonization of North America in recent decades by Coccinella septempunctata L. has generated widespread concern over potentially adverse effects on population viability of native species of ladybird beetles (Coccinellidae. Coccinella novemnotata Herbst in particular has been hypothesized to be at great risk, as this species apparently dwindled in numbers across much of North America during the twentieth century. Here results of sampling diverse habitats over three decades are examined to address the fate of C. novemnotata in the intermountain region of western North America following the establishment of C. septempunctata during the 1990s. Alfalfa fields have served as a major habitat for C. novemnotata in the intermountain west. Sweep sampling in the late 1980s and early 1990s demonstated that C. novemnotata and C. septempunctata were both rare members of the alfalfa lady beetle community. Subsequent sampling in alfalfa over the next two decades revealed that populations of C. septempunctata increased greatly, while populations of C. novemnotata remained low but persistent. Similarly, modest numbers of C. novemnotata were found continuing to persist, often alongside large numbers of C. septempunctata, in a variety of other habitats, including sagebrush steppe and weed-infested rangeland and riparian sites. Morphological comparison of these individuals of C. novemnotata with museum specimens collected throughout the twentieth century revealed no significant difference in mean body size between these recently and previously collected individuals, nor any significant long-term decrease in body size following the arrival of C. septempunctata, as might reflect increasing food limitation for larval C. novemnotata. Collectively these results

  18. Esophageal-gastric anastomosis in radical resection of esophageal cancer under thoracoscopy combined with laparoscopy.

    Science.gov (United States)

    Hao, Zhang; Zhenya, Shen; Lei, Wang

    2014-10-01

    To determine the feasibility of esophagogastric anastomosis in esophageal cancer radical resection under thoracoscopy combined with laparoscopy in terms of complications and operation time. Experimental study. Department of Thoracic Surgery, Affiliated with The First Hospital, Suzhou University, from June 2008 to June 2012. Clinical data of 136 patients operated for esophageal cancer by radical resection under thoracoscopy combined with laparoscopy was analyzed. Eighty one superior and middle segment esophageal carcinoma patients were operated through right thoracoscope, abdominoscope, and neck incision. The esophagogastric anastomosis was completed in the left side of neck by handiwork. Fifty five inferior segment esophageal carcinoma were operated through right thoracoscope, abdominoscope and the esophagogastric anastomosis was completed with stapler in right thoracic cavity through superior belly incision and diaphragmatic hiatus. The operation time and the intra-operative blood loss in patients with intrathoracic mechanical anastomosis was significantly lower than that of cervical anastomosis. Other variables were not significantly different. The practicability of this method of anastomosis that completed with stapler in right thoracic cavity through superior belly incision and diaphragmatic hiatus had been well confirmed.

  19. Esophageal - Gastric Anastomosis in Radical Resection of Esophageal Cancer under Thoracoscopy Combined with Laparoscopy

    International Nuclear Information System (INIS)

    Hao, Z.; Lei, W.; Zhenya, S.

    2014-01-01

    Objective: To determine the feasibility of esophagogastric anastomosis in esophageal cancer radical resection under thoracoscopy combined with laparoscopy in terms of complications and operation time. Study Design: Experimental study. Place and Duration of Study: Department of Thoracic Surgery, Affiliated with The First Hospital, Suzhou University, from June 2008 to June 2012. Methodology: Clinical data of 136 patients operated for esophageal cancer by radical resection under thoracoscopy combined with laparoscopy was analyzed. Eighty one superior and middle segment esophageal carcinoma patients were operated through right thoracoscope, abdominoscope, and neck incision. The esophagogastric anastomosis was completed in the left side of neck by handiwork. Fifty five inferior segment esophageal carcinoma were operated through right thoracoscope, abdominoscope and the esophagogastric anastomosis was completed with stapler in right thoracic cavity through superior belly incision and diaphragmatic hiatus. Results: The operation time and the intra-operative blood loss in patients with intrathoracic mechanical anastomosis was significantly lower than that of cervical anastomosis. Other variables were not significantly different. Conclusion: The practicability of this method of anastomosis that completed with stapler in right thoracic cavity through superior belly incision and diaphragmatic hiatus had been well confirmed. (author)

  20. Energy landscapes and persistent minima

    Energy Technology Data Exchange (ETDEWEB)

    Carr, Joanne M.; Wales, David J., E-mail: dw34@cam.ac.uk [University Chemical Laboratories, University of Cambridge, Lensfield Road, Cambridge CB2 1EW (United Kingdom); Mazauric, Dorian; Cazals, Frédéric, E-mail: frederic.cazals@inria.fr [Inria Sophia Antipolis Méditerranée, 2004 route des Lucioles, F-06902 Sophia Antipolis (France)

    2016-02-07

    We consider a coarse-graining of high-dimensional potential energy landscapes based upon persistences, which correspond to lowest barrier heights to lower-energy minima. Persistences can be calculated efficiently for local minima in kinetic transition networks that are based on stationary points of the prevailing energy landscape. The networks studied here represent peptides, proteins, nucleic acids, an atomic cluster, and a glassy system. Minima with high persistence values are likely to represent some form of alternative structural morphology, which, if appreciably populated at the prevailing temperature, could compete with the global minimum (defined as infinitely persistent). Threshold values on persistences (and in some cases equilibrium occupation probabilities) have therefore been used in this work to select subsets of minima, which were then analysed to see how well they can represent features of the full network. Simplified disconnectivity graphs showing only the selected minima can convey the funnelling (including any multiple-funnel) characteristics of the corresponding full graphs. The effect of the choice of persistence threshold on the reduced disconnectivity graphs was considered for a system with a hierarchical, glassy landscape. Sets of persistent minima were also found to be useful in comparing networks for the same system sampled under different conditions, using minimum oriented spanning forests.

  1. Development of a soil fugacity sampler for determination of air-soil partitioning of persistent organic pollutants under field controlled conditions.

    Science.gov (United States)

    Cabrerizo, Ana; Dachs, Jordi; Barceló, Damià

    2009-11-01

    Soils are the main reservoir of persistent organic pollutants (POPs) and thus air-soil exchange and partitioning are key processes controlling the fate and transport of POPs at regional and global scales. To date, soil fugacity has been estimated from models of the soil-air partition coefficients, with the associated unavoidable uncertainties; or by experimental procedures in the laboratory with uncertain application in field conditions. The development of an operational soil fugacity sampler is presented here; one which ensures optimal field data of the POP fugacity in soil and environmentally relevant surface (soil+grass, etc.) and therefore ensuring accurate soil-air partition coefficients and surface-air fugacity gradients. The sampler flow rate is optimized, sampler reproducibility is assessed, and equilibrium between the gas and soil concentrations of polychlorinated biphenyls and polycyclic aromatic hydrocarbons is demonstrated. The development and comprehensive validation of a soil fugacity sampler opens the door for the first time to field studies that accurately determine the variables driving the soil-air partitioning and fluxes of POPs.

  2. The ability to generate senescent progeny as a mechanism underlying breast cancer cell heterogeneity.

    Directory of Open Access Journals (Sweden)

    Mine Mumcuoglu

    Full Text Available BACKGROUND: Breast cancer is a remarkably heterogeneous disease. Luminal, basal-like, "normal-like", and ERBB2+ subgroups were identified and were shown to have different prognoses. The mechanisms underlying this heterogeneity are poorly understood. In our study, we explored the role of cellular differentiation and senescence as a potential cause of heterogeneity. METHODOLOGY/PRINCIPAL FINDINGS: A panel of breast cancer cell lines, isogenic clones, and breast tumors were used. Based on their ability to generate senescent progeny under low-density clonogenic conditions, we classified breast cancer cell lines as senescent cell progenitor (SCP and immortal cell progenitor (ICP subtypes. All SCP cell lines expressed estrogen receptor (ER. Loss of ER expression combined with the accumulation of p21(Cip1 correlated with senescence in these cell lines. p21(Cip1 knockdown, estrogen-mediated ER activation or ectopic ER overexpression protected cells against senescence. In contrast, tamoxifen triggered a robust senescence response. As ER expression has been linked to luminal differentiation, we compared the differentiation status of SCP and ICP cell lines using stem/progenitor, luminal, and myoepithelial markers. The SCP cells produced CD24+ or ER+ luminal-like and ASMA+ myoepithelial-like progeny, in addition to CD44+ stem/progenitor-like cells. In contrast, ICP cell lines acted as differentiation-defective stem/progenitor cells. Some ICP cell lines generated only CD44+/CD24-/ER-/ASMA- progenitor/stem-like cells, and others also produced CD24+/ER- luminal-like, but not ASMA+ myoepithelial-like cells. Furthermore, gene expression profiles clustered SCP cell lines with luminal A and "normal-like" tumors, and ICP cell lines with luminal B and basal-like tumors. The ICP cells displayed higher tumorigenicity in immunodeficient mice. CONCLUSIONS/SIGNIFICANCE: Luminal A and "normal-like" breast cancer cell lines were able to generate luminal-like and

  3. Clinical and psychological moderators of the effect of mindfulness-based cognitive therapy on persistent pain in women treated for primary breast cancer - explorative analyses from a randomized controlled trial.

    Science.gov (United States)

    Johannsen, M; O'Toole, M S; O'Connor, M; Jensen, A B; Zachariae, R

    2017-02-01

    Mindfulness-based intervention has been found efficacious in reducing persistent pain in women treated for breast cancer. Little, however, is known about possible moderators of the effect. We explored clinical and psychological moderators of the effect on pain intensity previously found in a randomized controlled trial of mindfulness-based cognitive therapy (MBCT) with women treated for breast cancer with persistent pain. A total of 129 women treated for breast cancer reporting persistent pain were randomized to MBCT or a wait-list control. The primary outcome of pain intensity (11-point numeric rating scale) was measured at baseline, post-intervention, three, and six months follow-up. Proposed clinical moderators included age, axillary lymph node dissection (ALND), radiotherapy, and endocrine treatment. Psychological moderators included psychological distress [the Hospital Anxiety and Depression Scale (HADS)], the adult attachment dimensions anxiety and avoidance [the Experiences in Close Relationships Short Form (the ECR-SF)], and alexithymia [the Toronto Alexithymia Scale (TAS-20)]. Multi-level models were used to test moderation effects over time, i.e. time × group × moderator. Only attachment avoidance (p = 0.03, d = 0.36) emerged as a statistically significant moderator. Higher levels of attachment avoidance predicted a larger effect of MBCT in reducing pain intensity compared with lower levels attachment avoidance. None of the remaining psychological or clinical moderators reached statistical significance. However, based on the effect size, radiotherapy (p = 0.075, d = 0.49) was indicated as a possible clinical moderator of the effect, with radiotherapy being associated with a smaller effect of MBCT on pain intensity over time compared with no radiotherapy. Attachment avoidance, and potentially radiotherapy, may be clinically relevant factors for identifying the patients who may benefit most from MBCT as a pain intervention. Due to

  4. Combination effects of sorafenib with PI3K inhibitors under hypoxia in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Bhatia DR

    2016-12-01

    Full Text Available Dimple R Bhatia, Padma Thiagarajan School of Biosciences and Technology, Vellore Institute of Technology University, Vellore, Tamil Nadu, India Aim: This study reports the influence of hypoxia on response of colorectal cancer cells to anticancer effects of sorafenib in combination with PI3K inhibitors GDC-0941 and BEZ-235.Materials and methods: All hypoxic exposures were carried out at 1% O2/5% CO2. Antiproliferation activity was evaluated by 48 hours propidium iodide and 14 days clonogenic assay. Protein levels were evaluated by fluorescence ELISA. Metabolites lactate and glucose were evaluated biochemically.Results: In the 48-hour proliferation assay, sorafenib acted synergistically with GDC-0941 but not with BEZ-235. In long-term colony-forming assays, both GDC-0941 and BEZ-235 were shown to potentiate the antiproliferative activity of sorafenib. At the molecular level, the synergism is mediated through inhibition of pAKT, pS6, p4EBP1, pERK, cyclin D1, and Bcl-2. No change in hypoxia-inducible factor-1α (HIF-1α levels was observed in cells treated with the combination of compounds under hypoxia. A significant reduction in glucose uptake and lactate release was observed in cells treated with the combination of compounds under normoxia and hypoxia.Conclusion: Combinations of sorafenib with PI3K inhibitors BEZ-235 and GDC-0941 are efficacious under hypoxia. Thus, these anticancer combinations have a potential to overcome the hypoxia-mediated resistance mechanisms to antiproliferative agents in cancer therapy. Keywords: GDC-0941, BEZ-235, anticancer, antiproliferation

  5. Optimal healthcare decision making under multiple mathematical models: application in prostate cancer screening.

    Science.gov (United States)

    Bertsimas, Dimitris; Silberholz, John; Trikalinos, Thomas

    2018-03-01

    Important decisions related to human health, such as screening strategies for cancer, need to be made without a satisfactory understanding of the underlying biological and other processes. Rather, they are often informed by mathematical models that approximate reality. Often multiple models have been made to study the same phenomenon, which may lead to conflicting decisions. It is natural to seek a decision making process that identifies decisions that all models find to be effective, and we propose such a framework in this work. We apply the framework in prostate cancer screening to identify prostate-specific antigen (PSA)-based strategies that perform well under all considered models. We use heuristic search to identify strategies that trade off between optimizing the average across all models' assessments and being "conservative" by optimizing the most pessimistic model assessment. We identified three recently published mathematical models that can estimate quality-adjusted life expectancy (QALE) of PSA-based screening strategies and identified 64 strategies that trade off between maximizing the average and the most pessimistic model assessments. All prescribe PSA thresholds that increase with age, and 57 involve biennial screening. Strategies with higher assessments with the pessimistic model start screening later, stop screening earlier, and use higher PSA thresholds at earlier ages. The 64 strategies outperform 22 previously published expert-generated strategies. The 41 most "conservative" ones remained better than no screening with all models in extensive sensitivity analyses. We augment current comparative modeling approaches by identifying strategies that perform well under all models, for various degrees of decision makers' conservativeness.

  6. Effects of curcumin on growth of human cervical cancer xenograft in nude mice and underlying mechanism

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    Aixue LIU

    Full Text Available Abstract The present study investigated the effects of curcumin (Cur on growth of human cervical cancer xenograft in nude mice and underlying mechanism. The nude mice modeled with human cervical cancer HeLa cell xenograft were treated with normal saline (control, 3 mg/kg Cisplatin, 50, 100 and 200 mg/kg Cur, respectively. The animal body weight and growth of tumor were measured. The expressions of Bax, Bcl-2, p53, p21, HIF-1α, VEGF and MIF protein in tumor tissue were determined. Results showed that, after treatment for 20 days, the tumor mass and tumor volume in 100 and 200 mg/kg Cur group were significantly lower than control group (P < 0.05. The expressions of Bax, p53 and p21 protein in tumor tissue in 200 mg/kg Cur group were significantly higher than control group (P < 0.05, and the expressions of Bcl-2, HIF-1α, VEGF and MIF protein in tumor tissue in 200 mg/kg Cur group were significantly lower than control group (P < 0.05. Cur can inhibit the growth of HeLa cell xenograft in nude mice. The possible mechanism may be related to its up-regulation of Bax, p53 and p21 protein expression in tumor tissue, and down-regulation of Bcl-2, HIF-1α, VEGF and MIF protein expression.

  7. Mathematical modelling of the destruction degree of cancer under the influence of a RF hyperthermia

    Science.gov (United States)

    Paruch, Marek; Turchan, Łukasz

    2018-01-01

    The article presents the mathematical modeling of the phenomenon of artificial hyperthermia which is caused by the interaction of an electric field. The electric field is induced by the applicator positioned within the biological tissue with cancer. In addition, in order to estimate the degree of tumor destruction under the influence of high temperature an Arrhenius integral has been used. The distribution of electric potential in the domain considered is described by the Laplace system of equations, while the temperature field is described by the Pennes system of equations. These problems are coupled by source function being the additional component in the Pennes equation and resulting from the electric field action. The boundary element method is applied to solve the coupled problem connected with the heating of biological tissues.

  8. Predictive value of serum CA-125 levels in patients with persistent or recurrent epithelial ovarian cancer or peritoneal cancer treated with bevacizumab on a Gynecologic Oncology Group phase II trial

    Science.gov (United States)

    Randall, Leslie M.; Sill, Michael W.; Burger, Robert A.; Monk, Bradley J.; Buening, Barbara; Sorosky, Joel I.

    2011-01-01

    Purpose To compare two methods of determining therapeutic response and disease progression - modified Gynecologic Cancer Intergroup (GCIG) criteria based on CA-125 and Radiographic Evaluation Criteria in Solid Tumors (RECIST), in a phase II trial of bevacizumab for patients with recurrent or persistent epithelial ovarian and peritoneal carcinoma.) Patients and Methods Patients were treated with bevacizumab 15 mg/kg every 21 days. Modified GCIG definitions of progression and response were retrospectively applied and compared to RECIST-defined progression and response. The prognostic significance of CA-125- and RECIST-defined responses and progressions were explored. Results Sixty-two patients were evaluable by RECIST, 59 for progression by CA-125, and 45 for response by CA-125. Median progression-free survival (PFS) by RECIST and progression-free interval (PFI) by CA-125 were 4.7 and 5.2 months respectively. However, 12.9% of those with CA-125 defined progression remained progression-free according to RECIST for at least 8 months. Thirteen of 62 patients (21%) had response by RECIST and 14/45 (31%) by CA-125. Time dependent analyses indicated that progression by CA-125 was associated with a 5.2 fold increased risk of progression by RECIST, and response by CA-125 had a 5 fold decrease in risk of progression by RECIST. Landmark and time dependent analyses showed prognostic value of responses by CA-125 and RECIST. Conclusions In this study, disease assessment by RECIST and CA-125 appear to correlate in general. However, approximately 10% of patients might demonstrate progression earlier by CA-125. PMID:22138229

  9. Child Abuse Potential: How Persistent?

    Science.gov (United States)

    Haapasalo, Jaana; Aaltonen, Terhi

    1999-01-01

    Compares mothers whose children had been under supervision of Child Protective Services (CPS) with comparison mothers for child abuse potential using Millner's Child Abuse Potential Inventory. CPS mothers scored significantly higher than the comparison mothers, indicating their persistent elevated child abuse potential; there was no significant…

  10. Persistent negative temperature response of mesophyll conductance in red raspberry (Rubus idaeus L.) leaves under both high and low vapour pressure deficits: a role for abscisic acid?

    Science.gov (United States)

    Qiu, Changpeng; Ethier, Gilbert; Pepin, Steeve; Dubé, Pascal; Desjardins, Yves; Gosselin, André

    2017-09-01

    The temperature dependence of mesophyll conductance (g m ) was measured in well-watered red raspberry (Rubus idaeus L.) plants acclimated to leaf-to-air vapour pressure deficit (VPDL) daytime differentials of contrasting amplitude, keeping a fixed diurnal leaf temperature (T leaf ) rise from 20 to 35 °C. Contrary to the great majority of g m temperature responses published to date, we found a pronounced reduction of g m with increasing T leaf irrespective of leaf chamber O 2 level and diurnal VPDL regime. Leaf hydraulic conductance was greatly enhanced during the warmer afternoon periods under both low (0.75 to 1.5 kPa) and high (0.75 to 3.5 kPa) diurnal VPDL regimes, unlike stomatal conductance (g s ), which decreased in the afternoon. Consequently, the leaf water status remained largely isohydric throughout the day, and therefore cannot be evoked to explain the diurnal decrease of g m . However, the concerted diurnal reductions of g m and g s were well correlated with increases in leaf abscisic acid (ABA) content, thus suggesting that ABA can induce a significant depression of g m under favourable leaf water status. Our results challenge the view that the temperature dependence of g m can be explained solely from dynamic leaf anatomical adjustments and/or from the known thermodynamic properties of aqueous solutions and lipid membranes.​. © 2017 John Wiley & Sons Ltd.

  11. High risk of under-grading and -staging in prostate cancer patients eligible for active surveillance.

    Science.gov (United States)

    Heidegger, Isabel; Skradski, Viktor; Steiner, Eberhard; Klocker, Helmut; Pichler, Renate; Pircher, Andreas; Horninger, Wolfgang; Bektic, Jasmin

    2015-01-01

    Active surveillance (AS) is increasingly offered to patients with low risk prostate cancer. The present study was conducted to evaluate the risk of tumor under-grading and -staging for AS eligibility. Moreover, we analyzed possible biomarkers for predicting more unfavorable final tumor histology. 197 patients who underwent radical prostatectomy (RPE) but would have met the EAU (European Association of Urology) criteria for AS (PSA4-10 ng/ml), PSA density (6, extraprostatic extension and positive resection margin (R1) or correlated significantly with up-grading and/or extraprostatic extension in a multivariate model. Only R1 resections were predictable by combining intermediate PSA levels with two positive biopsy cores (p = 0.004). Sub-analyses showed that the number of biopsy cores (10 vs. 15 biopsy cores) had no influence on above mentioned results on predicting biopsy undergrading. Clinical courses of patients showed that 19.9% of patients had a biochemical relapse after RPE, among all of them were undergraded in the initial biopsy. In summary, this study shows that a multitude of patients fulfilling the criteria for AS are under-diagnosed. The use of preoperative PSA levels, PSA density and the number of positive cores were not predictable for undergrading in the present patient collective.

  12. Cellular deformation characterization of human breast cancer cells under hydrodynamic forces

    Directory of Open Access Journals (Sweden)

    Ahmad Sohrabi Kashani

    2017-06-01

    Full Text Available Understanding how cells sense mechanical forces, and how respond biologically to themis an interesting and quickly-progressing area. Cells within their microenvironment are subjected tovarious physical forces such as mechanical loads and shear stress. Cells respond and adjust to theseforces by mechanotransduction mechanism in which deformation and mechanical forces are convertedinto biomechanical signals. To quantify mechanotransduction responses and to correctly interpretthe behavior of cell under in vitro stimulation, magnitude and distribution of the stresses on the cellmembrane should be characterized. In this study, a 2D Finite Element Model is introduced to simulatethe deformation of individual benign (MCF10A and malignant (MCF7 human breast cancer cellsunder hydrodynamic forces. A fluid-structure interaction method is implemented to model fluid flowand the adherent single cells inside a microchannel to study the nature of mechanical forces (viscousand pressure and to determine their contribution to the deformation of cells. Due to the differentmechanical properties, cells respond differently to the forces exerted by the fluid flow. It was foundthat the maximum stress and strain take place at the interface of the adherent cell and channel wall. Also, under the same boundary conditions, nucleolus and cytoplasm of an individual malignant cellundergo more deformation comparing a single benign cell. Furthermore, it was observed that both two cell lines experience much more stress when their attached area to the substrate is reduced.

  13. Systems biology analysis of drivers underlying hallmarks of cancer cell metabolism

    Science.gov (United States)

    Zielinski, Daniel C.; Jamshidi, Neema; Corbett, Austin J.; Bordbar, Aarash; Thomas, Alex; Palsson, Bernhard O.

    2017-01-01

    Malignant transformation is often accompanied by significant metabolic changes. To identify drivers underlying these changes, we calculated metabolic flux states for the NCI60 cell line collection and correlated the variance between metabolic states of these lines with their other properties. The analysis revealed a remarkably consistent structure underlying high flux metabolism. The three primary uptake pathways, glucose, glutamine and serine, are each characterized by three features: (1) metabolite uptake sufficient for the stoichiometric requirement to sustain observed growth, (2) overflow metabolism, which scales with excess nutrient uptake over the basal growth requirement, and (3) redox production, which also scales with nutrient uptake but greatly exceeds the requirement for growth. We discovered that resistance to chemotherapeutic drugs in these lines broadly correlates with the amount of glucose uptake. These results support an interpretation of the Warburg effect and glutamine addiction as features of a growth state that provides resistance to metabolic stress through excess redox and energy production. Furthermore, overflow metabolism observed may indicate that mitochondrial catabolic capacity is a key constraint setting an upper limit on the rate of cofactor production possible. These results provide a greater context within which the metabolic alterations in cancer can be understood.

  14. Confirmatory bias and the persistent influence of discredited data in interpreting the stress-cancer link: commentary on Michael et al. (2009).

    Science.gov (United States)

    Coyne, James C; Johansen, Christoffer

    2011-05-01

    Comments on the original article, "Influence of stressors on breast cancer incidence in the Women's Health Initiative" by Y. L. Michael et al (see record 2009-03297-001). The current authors assert that Michael et al (2009) missed an opportunity for a straightforward reporting of null findings concerning the association between stress and incidence of cancer. They urge greater skepticism toward the claims about a stress-cancer link more generally. Using data from the Women's Health Initiative, Michael and colleagues suggested an association between stress and the incidence of breast cancer. However, the current authors believe their results and those from other studies failed to confirm that stress is a risk factor of breast cancer. Starting with their abstract and continuing in their discussion, Michael et al selectively and inaccurately reported findings with a strong confirmatory bias, and with further selective and uncritical reference to the existing literature. Moreover, they inadvertently perpetuated the direct and indirect influence of discredited data in the literature purporting to show a stress-cancer link. (c) 2011 APA, all rights reserved.

  15. Geospatial Disparities and the Underlying Causes of Major Cancers for Women in Taiwan

    Directory of Open Access Journals (Sweden)

    Chi-Ting Chiang

    2014-05-01

    Full Text Available Some specific types of cancer still pose a severe threat to the health of Taiwanese women. This study focuses on determining the geographical locations of hot spots and causal factors related to the major categories of cancers in Taiwanese women. Cancer mortality data from 1972 to 2001 of 346 townships in Taiwan were obtained from the Atlas of Cancer Mortality. Principal component analysis was conducted to determine the primary categories of female cancers. The spatial patterns of hot spots and cold spots for each major cancer category were identified using the local indicator of spatial association. Finally, the regional differences between the hot spots and cold spots were compared to confirm the possible factors causing cancer throughout Taiwan. A total of 21 cancer types in women were divided into seven major categories, which accounted for 68.0% of the total variance. The results from the spatial autocorrelation analysis showed significant spatial clusters of the cancer categories. Based on the overall consistency of results between this study and those of previous research, this study further identified the high-risk locations and some specific risk factors for major cancer types among Taiwanese women.

  16. Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa.

    Science.gov (United States)

    Verma, Meghna; Erwin, Samantha; Abedi, Vida; Hontecillas, Raquel; Hoops, Stefan; Leber, Andrew; Bassaganya-Riera, Josep; Ciupe, Stanca M

    2017-01-01

    Human immunodeficiency virus (HIV)-infected patients are at an increased risk of co-infection with human papilloma virus (HPV), and subsequent malignancies such as oral cancer. To determine the role of HIV-associated immune suppression on HPV persistence and pathogenesis, and to investigate the mechanisms underlying the modulation of HPV infection and oral cancer by HIV, we developed a mathematical model of HIV/HPV co-infection. Our model captures known immunological and molecular features such as impaired HPV-specific effector T helper 1 (Th1) cell responses, and enhanced HPV infection due to HIV. We used the model to determine HPV prognosis in the presence of HIV infection, and identified conditions under which HIV infection alters HPV persistence in the oral mucosa system. The model predicts that conditions leading to HPV persistence during HIV/HPV co-infection are the permissive immune environment created by HIV and molecular interactions between the two viruses. The model also determines when HPV infection continues to persist in the short run in a co-infected patient undergoing antiretroviral therapy. Lastly, the model predicts that, under efficacious antiretroviral treatment, HPV infections will decrease in the long run due to the restoration of CD4+ T cell numbers and protective immune responses.

  17. Atypical presentation of Legionella pneumonia among patients with underlying cancer: A fifteen-year review.

    Science.gov (United States)

    del Castillo, Maria; Lucca, Anabella; Plodkowski, Andrew; Huang, Yao-Ting; Kaplan, Janice; Gilhuley, Kathleen; Babady, N Esther; Seo, Susan K; Kamboj, Mini

    2016-01-01

    Immunocompromised patients, especially those receiving treatment with corticosteroids and cytotoxic chemotherapy are at increased risk for developing Legionella pneumonia. The aim of this study was to determine clinical and radiographic characteristics of pulmonary infection due to Legionella in persons undergoing treatment for cancer and stem cell transplant (SCT) recipients. Retrospective review of Legionella cases at MSKCC over a fifteen-year study period from January 1999 and December 2013. Cases were identified by review of microbiology records. During the study period, 40 cases of Legionella infection were identified; nine among these were due to non-pneumophila species. Most cases occurred during the summer. The majority [8/9, (89%)] of patients with non-pneumophila infection had underlying hematologic malignancy, compared to 18/31 (58%) with Legionella pneumophila infections. Radiographic findings were varied-nodular infiltrates mimicking invasive fungal infection were seen only among patients with hematologic malignancy and hematopoietic stem cell transplant (SCT) recipients and were frequently associated with non-pneumophila infections (50% vs 16%; P = 0.0594). All cases of nodular Legionella pneumonia were found incidentally or had an indolent clinical course. Legionella should be considered in the differential diagnosis of nodular lung lesions in immunocompromised patients, especially those with hematologic malignancy and SCT recipients. Most cases of nodular disease due to Legionella are associated with non-pneumophila infections. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  18. The effect of marital status on breast cancer-related outcomes in women under 65: A SEER database analysis.

    Science.gov (United States)

    Hinyard, Leslie; Wirth, Lorinette Saphire; Clancy, Jennifer M; Schwartz, Theresa

    2017-04-01

    Marital status is strongly associated with improved health and longevity. Being married has been shown to be positively associated with survival in patients with multiple different types of malignancy; however, little is known about the relationship between marital status and breast cancer in younger women. The purpose of this study is to investigate the effect of marital status on diagnosis, and survival of women under the age of 65 with breast cancer. The SEER 18 regions database was used to identify women between the ages of 25-64 diagnosed with invasive breast cancer in the years 2004-2009. Logistic regression was used to predict later stage diagnosis by marital status and Cox proportional hazards models were used to compare breast cancer-related and all-cause survival by marital status classification. Models were stratified by AJCC stage. After adjusting for age, race, and ER status, unmarried women were 1.18 times more likely to be diagnosed at a later stage than married women (95% CI 1.15, 1.20). In adjusted analysis unmarried women were more likely to die of breast cancer and more likely to die of all causes than married women across all AJCC stages. Younger unmarried women with breast cancer may benefit from additional counseling, psychosocial support and case management at the time of diagnosis to ensure their overall outcomes are optimized. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Quality of life of elderly cancer patients under radiotherapy; Qualidade de vida de idosos com cancer de prostata em radioterapia

    Energy Technology Data Exchange (ETDEWEB)

    Peres de Oliveira, Patricia; Corte Pereira, Beltrina da Purificacao [Pontificia Univ. Catolica de Sao Paulo, SP (Brazil). Programa de Pos-graduacao em Gerontologia]. E-mail: patiperes@uol.com.br

    2004-07-01

    This research analyzed the effects of radiotherapy in the quality of life of elderly patients suffering from prostatic cancer. Our aim was to verify the psychometric properties of the Quality of Life Index (QLI), by Ferrans and Powers, describing the social-demographic characteristics that affect the quality of life; and patients concept of quality of life and their perception of how radiotherapy interferes with the quality of life. Interviews were carried out with a sample of seven elderly patients suffering from prostatic cancer. Two different approaches were utilized: descriptive and qualitative statistics. The results show that the QLI may have useful application in our field in the identification of those aspects of quality of life affected by cancer. (author)

  20. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic ... grade, which refers to how abnormal the cancer cells look under a microscope. Grade provides clues about ...

  1. Dietary counselling and nutritional support in oropharyngeal cancer patients treated with radiotherapy: persistent weight loss during 1-year follow-ups.

    Science.gov (United States)

    Vlooswijk, C P; van Rooij, P H E; Kruize, J C; Schuring, H A; Al-Mamgani, A; de Roos, N M

    2016-01-01

    The need for dietary counselling and nutritional support in oropharyngeal cancer patients is generally accepted. However, evidence for the effectiveness is sparse. The aim of this study was to describe dietary counselling, nutritional support, body weight and toxicity during and after treatment, and investigate the effect of pre-treatment body mass index (BMI) on survival in oropharyngeal cancer patients. A retrospective chart review was made in 276 oropharyngeal cancer patients treated with radiotherapy (RT). End points were dietary consultations, weight loss, toxicity, overall survival and disease-free survival. Almost all oropharyngeal cancer patients received dietary counselling (94%) and nutritional support (99%). Dietary counselling decreased sharply shortly after treatment to 38% at 1 year after treatment. Overall weight loss increased during the first year of follow-up and ranged from 3% at start of RT, until 11% at 1 year after RT. Overall survival was significantly longer for patients with a BMI above average (P=0.01). Acute dysphagia (P=0.001), mucositis (P=0.000) and toxicity grade 3 (P=0.002) were significantly more prevalent in patients who had lost 10% or more of their body weight. This study showed that patients continue to lose body weight during and until 1 year after treatment, despite nutrition support and frequent dietetic consultation. A BMI above average appears to increase survival time. Future studies, preferably randomized trials, are needed to compare standard dietary counselling with more intensive dietary counselling that consists of earlier and/or prolonged treatment.

  2. Alzheimer's Disease as Subcellular `Cancer' --- The Scale-Invariant Principles Underlying the Mechanisms of Aging ---

    Science.gov (United States)

    Murase, M.

    1996-01-01

    with self-organization, has been thought to underlie `creative' aspects of biological phenomena such as the origin of life, adaptive evolution of viruses, immune recognition and brain function. It therefore must be surprising to find that the same principles will also underlie `non-creative' aspects, for example, the development of cancer and the aging of complex organisms. Although self-organization has extensively been studied in nonliving things such as chemical reactions and laser physics, it is undoubtedly true that the similar sources of the order are available to living things at different levels and scales. Several paradigm shifts are, however, required to realize how the general principles of natural selection can be extensible to non-DNA molecules which do not possess the intrinsic nature of self-reproduction. One of them is, from the traditional, genetic inheritance view that DNA (or RNA) molecules are the ultimate unit of heritable variations and natural selection at any organization level, to the epigenetic (nongenetic) inheritance view that any non-DNA molecule can be the target of heritable variations and molecular selection to accumulate in certain biochemical environment. Because they are all enriched with a β-sheet content, ready to mostly interact with one another, different denatured proteins like β-amyloid, PHF and prions can individually undergo self-templating or self-aggregating processes out of gene control. Other paradigm shifts requisite for a break-through in the etiology of neurodegenerative disorders will be discussed. As it is based on the scale-invariant principles, the present theory also predicts plausible mechanisms underlying quite different classes of disorders such as amyotrophic lateral sclerosis (ALS), atherosclerosis, senile cataract and many other symptoms of aging. The present theory, thus, provides the consistent and comprehensive account to the origin of aging by means of natural selection and self-organization.

  3. Demographics of antibiotic persistence

    DEFF Research Database (Denmark)

    Kollerova, Silvia; Jouvet, Lionel; Steiner, Ulrich

    Persister cells, cells that can survive antibiotic exposure but lack heritable antibiotic resistance, are assumed to play a crucial role for the evolution of antibiotic resistance. Persistence is a stage associated with reduced metabolic activity. Most previous studies have been done on batch...... cultures, rather than the individual level. Here, we used individual level bacteria data to confirm previous studies in how fast cells switch into a persistence stage, but our results challenge the fundamental idea that persistence comes with major costs of reduced growth (cell elongation) and division due...... even play a more prominent role for the evolution of resistance and failures of medical treatment by antibiotics as currently assumed....

  4. Fourier transform infrared spectroscopy imaging of live epithelial cancer cells under non-aqueous media.

    Science.gov (United States)

    Soh, JunYi; Chueng, Adeline; Adio, Aminat; Cooper, Alan J; Birch, Brian R; Lwaleed, Bashir A

    2013-04-01

    Fourier transform infrared (FT-IR) imaging is increasingly being applied to biomedical specimens, but strong IR absorption by water complicates live cell imaging. This study investigates the viability of adherent epithelial cells maintained for short periods under mineral oils in order to facilitate live cell spectroscopy using FT-IR with subsequent imaging. The MGH-U1 urothelial or CaCo2 colorectal cancer cell lines were grown on plastic surfaces or mid-range infrared transparent windows. Medium in established cultures was replaced with paraffin mineral oil, or Fluorolube, for up to 2 h, and viability assessed by supravital staining. Drug handling characteristics were also assessed. Imaging of preparations was attempted by reflectance and transmission using a Varian FT-IR microscope. Cells covered by mineral oil remained viable for 2 h, with recovery into normal medium possible. MTT ((3-(4,5-dimethylthlazol-2-yl)-2,5-diphenyl tetrazolium) conversion to crystalline formazan and differential patterns of drug uptake were maintained. The combination of a calcium fluoride substrate, Fluorolube oil, and transmission optics proved best for spectroscopy. Spectral features were used to obtain images of live cells. The viability of cells overlaid with IR transparent oils was assessed as part of a technique to optimise conditions for FT-IR imaging. Images of untreated cells were obtained using both reflectance and transmission. This represents an effective means of imaging live cells by IR spectroscopy, and also means that imaging is not necessarily a terminal event. It also increases options for producing images based on real-time biochemistry in a range of in vitro experimental and 'optical biopsy' contexts.

  5. Mindfulness-based cognitive therapy (MBCT) is cost-effective compared to a wait-list control for persistent pain in women treated for primary breast cancer

    DEFF Research Database (Denmark)

    Johannsen, M.; Sørensen, J.; O'Connor, M.

    2017-01-01

    Objective: To investigate the cost-effectiveness of mindfulness-based cognitive therapy (MBCT) compared to a wait-list control group for pain in women treated for breast cancer. Methods: A total of 129 women were randomly allocated to MBCT or a wait-list control group. The primary outcome...... assumed. Conclusions: Our results suggest that MBCT is a cost-effective pain intervention for women treated for breast cancer. Future studies could include utility measures, indirect costs, and active control groups to increase the generalizability and pragmatic value of the results....... group (N:14/48; 29.2%) achieved an MCID in pain intensity (OR=2.71, P =.03). The MBCT was cost-effective with a probability of 85% with a value of an additional women achieving MCID set to zero remained cost-effective with a probability of 70% to 82% when smaller effect and higher MBCT costs were...

  6. Phase II trial of nab-paclitaxel in the treatment of recurrent or persistent advanced cervix cancer: A gynecologic oncology group study

    Science.gov (United States)

    Alberts, David S.; Blessing, John A.; Landrum, Lisa M.; Warshal, David P.; Martin, Lainie P.; Rose, Stephen L.; Bonebrake, Albert J.; Ramondetta, Lois M.

    2013-01-01

    Background Metastatic and recurrent, platinum resistant cervix cancer has an extremely poor prognosis. The Gynecologic Oncology Group has studied >20 cytotoxic drugs or drug combinations in the second-line, phase II setting of advanced, drug resistant cervix cancer. Methods Nanoparticle, albumin-bound paclitaxel (nab-paclitaxel) was administered at 125 mg/m2 IV over 30 minutes on days 1, 8 and 15 of each 28 day cycle to 37 women with metastatic or recurrent cervix cancer that had progressed or relapsed following first-line cytotoxic drug treatment. A flexible, 2-stage accrual design that allowed stopping early for lack of treatment activity was utilized. Because of slow patient accrual, the second stage was not completed. Results Of 37 patients enrolled, 2 were ineligible due to no prior cytotoxic chemotherapy, which left 35 eligible patients evaluable for response and tolerability. All of the eligible patients had 1 prior chemotherapy regimen and 27 of them had prior radiation therapy with concomitant cisplatin. The median number of nab-paclitaxel cycles were 4 (range 1–15). Ten (28.6%; CI 14.6%–46.3%) of the 35 patients had a partial response and another 15 patients (42.9%) had stable disease. The median progression-free and overall survival were 5.0 and 9.4 months, respectively. The only NCI CTCAE grade 4 event was neutropenia in 2 patients (5.7%) which resolved following dose reduction. Grade 3 neurotoxicity was reported in 1 (2.9%) patient and resolved to grade 2 following dose discontinuation. Conclusions Nab-paclitaxel has considerable activity and moderate toxicity in the treatment of drug resistant, metastatic and recurrent cervix cancer. PMID:22986144

  7. Second primary cancers after adjuvant radiotherapy in early breast cancer patients: A national population based study under the Danish Breast Cancer Cooperative Group (DBCG)

    International Nuclear Information System (INIS)

    Grantzau, Trine; Mellemkjær, Lene; Overgaard, Jens

    2013-01-01

    Background and purpose: To analyze the long-term risk of second primary solid non-breast cancer in a national population-based cohort of 46,176 patients treated for early breast cancer between 1982 and 2007. Patients and methods: All patients studied were treated according to the national guidelines of the Danish Breast Cancer Cooperative Group. The risk of second primary cancers was estimated by Standardised incidence ratios (SIRs) and multivariate Cox regression models were used to estimate adjusted hazard ratios (HR) among irradiated women compared to non-irradiated. All irradiated patients were treated on linear accelerators. Second cancers were a priori categorized into two groups; radiotherapy-associated- (oesophagus, lung, heart/mediastinum, pleura, bones, and connective tissue) and non-radiotherapy-associated sites (all other cancers). Results: 2358 second cancers had occurred during the follow-up. For the radiotherapy-associated sites the HR among irradiated women was 1.34 (95% CI 1.11–1.61) with significantly increased HRs for the time periods of 10–14 years (HR 1.55; 95% CI 1.08–2.24) and ⩾15 years after treatment (HR 1.79; 95% CI 1.14–2.81). There was no increased risk for the non-radiotherapy-associated sites (HR 1.04; 95% CI 0.94–1.1). The estimated attributable risk related to radiotherapy for the radiotherapy-associated sites translates into one radiation-induced second cancer in every 200 women treated with radiotherapy. Conclusions: Radiotherapy treated breast cancer patients have a small but significantly excess risk of second cancers

  8. Effective and persistent antitumor activity of HER2-directed CAR-T cells against gastric cancer cells in vitro and xenotransplanted tumors in vivo.

    Science.gov (United States)

    Song, Yanjing; Tong, Chuan; Wang, Yao; Gao, Yunhe; Dai, Hanren; Guo, Yelei; Zhao, Xudong; Wang, Yi; Wang, Zizheng; Han, Weidong; Chen, Lin

    2017-03-10

    Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a high proportion of gastric cancer (GC) cases and affect the maintenance of cancer stem cell (CSC) subpopulations, which are used as targets for the clinical treatment of patients with HER2-positive GC. Despite improvements in survival, numerous HER2-positive patients fail treatment with trastuzumab, highlighting the need for more effective therapies. In this study, we generated a novel type of genetically modified human T cells, expressing a chimeric antigen receptor (CAR), and targeting the GC cell antigen HER2, which harbors the CD137 and CD3ζ moieties. Our findings show that the expanded CAR-T cells, expressing an increased central memory phenotype, were activated by the specific recognition of HER2 antigens in an MHC-independent manner, and effectively killed patient-derived HER2-positive GC cells. In HER2-positive xenograft tumors, CAR-T cells exhibited considerably enhanced tumor inhibition ability, long-term survival, and homing to targets, compared with those of non-transduced T cells. The sphere-forming ability and in vivo tumorigenicity of patient-derived gastric cancer stem-like cells, expressing HER2 and the CD44 protein, were also inhibited. Our results support the future development and clinical application of this adoptive immunotherapy in patients with HER2-positive advanced GC.

  9. Incidence of childhood cancer among Mexican children registered under a public medical insurance program.

    Science.gov (United States)

    Rivera-Luna, Roberto; Correa-González, Cecilia; Altamirano-Alvarez, Eduardo; Sánchez-Zubieta, Fernando; Cárdenas-Cardós, Rocio; Escamilla-Asian, Gabriela; Olaya-Vargas, Alberto; Bautista-Marquez, Aurora; Aguilar-Romo, Manuel

    2013-04-01

    Prior to 2005, 51% of children in Mexico diagnosed with cancer received no standardized optimal multidisciplinary medical care. A government-subsidized national cancer treatment program was therefore created for these patients and a National Cooperative Childhood Cancer Treatment Group was consequently formed for these patients. Pediatric patients with a proven diagnosis of leukemia, lymphoma or solid tumor and who were registered in the Popular Medical Insurance (PMI) program from January 2007 to December 2010, are described in this report. These patients had been enrolled and registered in one of the 49 nationwide certified medical institutions in Mexico. The national incidence and frequency data for childhood cancers were analyzed for the whole program. At the end of a 4-year study, the analysis revealed that 8,936 children from across Mexico had been diagnosed with cancer. The incidence rate for the PMI patients was 150.3/million/year (2010) for children of 0-18 years. The highest age incidence rate was 51.9 between 0 and 4 years and boys were the predominant group for all types of cancer. The leukemia incidence was 75.3/million/year (2010), and an average frequency of 50.75% throughout the 4 years. The overall mortality rate was measured at 5.4/100,000/year (2010). This study demonstrates a high frequency and incidence of childhood cancer and a beneficial impact of the PMI program over the quality of life in these children. Copyright © 2012 UICC.

  10. PBX1 Genomic Pioneer Function Drives ERα Signaling Underlying Progression in Breast Cancer

    Science.gov (United States)

    Magnani, Luca; Ballantyne, Elizabeth B.; Zhang, Xiaoyang; Lupien, Mathieu

    2011-01-01

    Altered transcriptional programs are a hallmark of diseases, yet how these are established is still ill-defined. PBX1 is a TALE homeodomain protein involved in the development of different types of cancers. The estrogen receptor alpha (ERα) is central to the development of two-thirds of all breast cancers. Here we demonstrate that PBX1 acts as a pioneer factor and is essential for the ERα-mediated transcriptional response driving aggressive tumors in breast cancer. Indeed, PBX1 expression correlates with ERα in primary breast tumors, and breast cancer cells depleted of PBX1 no longer proliferate following estrogen stimulation. Profiling PBX1 recruitment and chromatin accessibility across the genome of breast cancer cells through ChIP-seq and FAIRE-seq reveals that PBX1 is loaded and promotes chromatin openness at specific genomic locations through its capacity to read specific epigenetic signatures. Accordingly, PBX1 guides ERα recruitment to a specific subset of sites. Expression profiling studies demonstrate that PBX1 controls over 70% of the estrogen response. More importantly, the PBX1-dependent transcriptional program is associated with poor-outcome in breast cancer patients. Correspondingly, PBX1 expression alone can discriminate a priori the outcome in ERα-positive breast cancer patients. These features are markedly different from the previously characterized ERα-associated pioneer factor FoxA1. Indeed, PBX1 is the only pioneer factor identified to date that discriminates outcome such as metastasis in ERα-positive breast cancer patients. Together our results reveal that PBX1 is a novel pioneer factor defining aggressive ERα-positive breast tumors, as it guides ERα genomic activity to unique genomic regions promoting a transcriptional program favorable to breast cancer progression. PMID:22125492

  11. Depression and under-treatment of depression: potential risks and outcomes in black lung cancer patients

    Science.gov (United States)

    Traeger, Lara; Cannon, Sheila; Pirl, William F.; Park, Elyse R.

    2015-01-01

    In the U.S., black men are at higher risk than white men for lung cancer mortality whereas rates are comparable between black and white women. This paper draws from empirical work in lung cancer, mental health and health disparities to highlight that race and depression may overlap in predicting lower treatment access and utilization and poorer quality of life among patients. Racial barriers to depression identification and treatment in the general population may compound these risks. Prospective data are needed to examine whether depression plays a role in racial disparities in lung cancer outcomes. PMID:23514250

  12. Yoga for the Treatment of Insomnia among Cancer Patients: Evidence, Mechanisms of Action, and Clinical Recommendations

    OpenAIRE

    Mustian, Karen M.; Janelsins, Michelle; Peppone, Luke J.; Kamen, Charles

    2014-01-01

    Up to 90% of cancer patients report symptoms of insomnia during and after treatment. Symptoms of insomnia include excessive daytime sleepiness, difficulty falling asleep, difficulty staying asleep, and waking up too early. Insomnia symptoms are among the most prevalent, distressing and persistent cancer- and cancer treatment-related toxicities reported by patients, and can be severe enough to increase cancer morbidity and mortality. Despite the ubiquity of insomnia symptoms, they are under-sc...

  13. Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress.

    Science.gov (United States)

    Schug, Zachary T; Peck, Barrie; Jones, Dylan T; Zhang, Qifeng; Grosskurth, Shaun; Alam, Israt S; Goodwin, Louise M; Smethurst, Elizabeth; Mason, Susan; Blyth, Karen; McGarry, Lynn; James, Daniel; Shanks, Emma; Kalna, Gabriela; Saunders, Rebecca E; Jiang, Ming; Howell, Michael; Lassailly, Francois; Thin, May Zaw; Spencer-Dene, Bradley; Stamp, Gordon; van den Broek, Niels J F; Mackay, Gillian; Bulusu, Vinay; Kamphorst, Jurre J; Tardito, Saverio; Strachan, David; Harris, Adrian L; Aboagye, Eric O; Critchlow, Susan E; Wakelam, Michael J O; Schulze, Almut; Gottlieb, Eyal

    2015-01-12

    A functional genomics study revealed that the activity of acetyl-CoA synthetase 2 (ACSS2) contributes to cancer cell growth under low-oxygen and lipid-depleted conditions. Comparative metabolomics and lipidomics demonstrated that acetate is used as a nutritional source by cancer cells in an ACSS2-dependent manner, and supplied a significant fraction of the carbon within the fatty acid and phospholipid pools. ACSS2 expression is upregulated under metabolically stressed conditions and ACSS2 silencing reduced the growth of tumor xenografts. ACSS2 exhibits copy-number gain in human breast tumors, and ACSS2 expression correlates with disease progression. These results signify a critical role for acetate consumption in the production of lipid biomass within the harsh tumor microenvironment. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Gastric cancer in young people under 30 years of age: worse prognosis, or delay in diagnosis?

    International Nuclear Information System (INIS)

    López-Basave, Horacio Noé; Morales-Vásquez, Flavia; Ruiz-Molina, Juan Manuel; Ñamendys-Silva, Silvio A; Vela-Sarmiento, Itzel; Ruan, Javier Melchor; Rosciano, Alejandro E Padilla; Calderillo-Ruiz, German; Díaz-Romero, Consuelo; Herrera-Gómez, Angel; Meneses-García, Abelardo A

    2013-01-01

    Gastric cancer is an aggressive disease with nonspecific early symptoms. Its incidence and prognosis in young patients has shown considerable variability. Our objective was to retrospectively study patients from our institution aged <30 years with gastric carcinoma. The study was undertaken to describe the experience of gastric cancer in this population, and to demonstrate its specific clinical and pathological characteristics. We reviewed the cases of histologically confirmed gastric cancer between 1985 and 2006 at the Instituto Nacional de Cancerología of Mexico (INCan); emphasis in our review was placed on clinical presentation, diagnostic and therapeutic intervention, pathology, and the results. Thirty cases of gastric carcinoma were reviewed. The patients’ median age was 27 years (range, 18–30 years) and the male:female ratio was 1:1. Gastric cancer exhibits different behavior in patients aged, 30 years, but delay in diagnosis and the tumor’s behavior appear to be the most important factors in prognosis of the disease

  15. Elucidation of the Molecular Mechanisms Underlying Lymph Node Metastasis in Prostate Cancer

    National Research Council Canada - National Science Library

    Datta, Kaustubh

    2005-01-01

    .... This finding leads one to think that understanding the role of angiogenic molecules like VEGF-C and VEGF-D in molecular detail for lymphatic formation in prostate cancer will provide information...

  16. A comprehensive sensitivity analysis of microarray breast cancer classification under feature variability

    NARCIS (Netherlands)

    Sontrop, H.M.J.; Moerland, P.D.; Van den Ham, R.; Reinders, M.J.T.; Verhaegh, W.F.J.

    2009-01-01

    Background: Large discrepancies in signature composition and outcome concordance have been observed between different microarray breast cancer expression profiling studies. This is often ascribed to differences in array platform as well as biological variability. We conjecture that other reasons for

  17. The dietary flavonoid kaempferol effectively inhibits HIF-1 activity and hepatoma cancer cell viability under hypoxic conditions

    International Nuclear Information System (INIS)

    Mylonis, Ilias; Lakka, Achillia; Tsakalof, Andreas; Simos, George

    2010-01-01

    Research highlights: → Kaempferol inhibits HIF-1 activity in hepatocarcinoma cells; → Kaempferol causes cytoplasmic mislocalization of HIF-1α by impairing the MAPK pathway. → Viability of hepatocarcinoma cells under hypoxia is reduced by kaempferol. -- Abstract: Hepatocellular carcinoma (HCC) is characterized by high mortality rates and resistance to conventional treatment. HCC tumors usually develop local hypoxia, which stimulates proliferation of cancer cells and renders them resilient to chemotherapy. Adaptation of tumor cells to the hypoxic conditions depends on the hypoxia-inducible factor 1 (HIF-1). Over-expression of its regulated HIF-1α subunit, an important target of anti-cancer therapy, is observed in many cancers including HCC and is associated with severity of tumor growth and poor patient prognosis. In this report we investigate the effect of the dietary flavonoid kaempferol on activity, expression levels and localization of HIF-1α as well as viability of human hepatoma (Huh7) cancer cells. Treatment of Huh7 cells with kaempferol under hypoxic conditions (1% oxygen) effectively inhibited HIF-1 activity in a dose-dependent manner (IC 50 = 5.16 μM). The mechanism of this inhibition did not involve suppression of HIF-1α protein levels but rather its mislocalization into the cytoplasm due to inactivation of p44/42 MAPK by kaempferol (IC 50 = 4.75 μM). Exposure of Huh7 cells to 10 μΜ kaempferol caused significant reduction of their viability, which was remarkably more evident under hypoxic conditions. In conclusion, kaempferol, a non-toxic natural food component, inhibits both MAPK and HIF-1 activity at physiologically relevant concentrations (5-10 μM) and suppresses hepatocarcinoma cell survival more efficiently under hypoxia. It has, therefore, potential as a therapeutic or chemopreventive anti-HCC agent.

  18. The dietary flavonoid kaempferol effectively inhibits HIF-1 activity and hepatoma cancer cell viability under hypoxic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Mylonis, Ilias; Lakka, Achillia; Tsakalof, Andreas [Laboratory of Biochemistry, School of Medicine, University of Thessaly, BIOPOLIS, 41110 Larissa (Greece); Institute of Biomedical Research and Technology (BIOMED), 51 Papanastasiou str., 41222 Larissa (Greece); Simos, George, E-mail: simos@med.uth.gr [Laboratory of Biochemistry, School of Medicine, University of Thessaly, BIOPOLIS, 41110 Larissa (Greece); Institute of Biomedical Research and Technology (BIOMED), 51 Papanastasiou str., 41222 Larissa (Greece)

    2010-07-16

    Research highlights: {yields} Kaempferol inhibits HIF-1 activity in hepatocarcinoma cells; {yields} Kaempferol causes cytoplasmic mislocalization of HIF-1{alpha} by impairing the MAPK pathway. {yields} Viability of hepatocarcinoma cells under hypoxia is reduced by kaempferol. -- Abstract: Hepatocellular carcinoma (HCC) is characterized by high mortality rates and resistance to conventional treatment. HCC tumors usually develop local hypoxia, which stimulates proliferation of cancer cells and renders them resilient to chemotherapy. Adaptation of tumor cells to the hypoxic conditions depends on the hypoxia-inducible factor 1 (HIF-1). Over-expression of its regulated HIF-1{alpha} subunit, an important target of anti-cancer therapy, is observed in many cancers including HCC and is associated with severity of tumor growth and poor patient prognosis. In this report we investigate the effect of the dietary flavonoid kaempferol on activity, expression levels and localization of HIF-1{alpha} as well as viability of human hepatoma (Huh7) cancer cells. Treatment of Huh7 cells with kaempferol under hypoxic conditions (1% oxygen) effectively inhibited HIF-1 activity in a dose-dependent manner (IC{sub 50} = 5.16 {mu}M). The mechanism of this inhibition did not involve suppression of HIF-1{alpha} protein levels but rather its mislocalization into the cytoplasm due to inactivation of p44/42 MAPK by kaempferol (IC{sub 50} = 4.75 {mu}M). Exposure of Huh7 cells to 10 {mu}{Mu} kaempferol caused significant reduction of their viability, which was remarkably more evident under hypoxic conditions. In conclusion, kaempferol, a non-toxic natural food component, inhibits both MAPK and HIF-1 activity at physiologically relevant concentrations (5-10 {mu}M) and suppresses hepatocarcinoma cell survival more efficiently under hypoxia. It has, therefore, potential as a therapeutic or chemopreventive anti-HCC agent.

  19. Persistent idiopathic facial pain.

    Science.gov (United States)

    Benoliel, Rafael; Gaul, Charly

    2017-06-01

    Background Persistent idiopathic facial pain (PIFP) is a chronic disorder recurring daily for more than two hours per day over more than three months, in the absence of clinical neurological deficit. PIFP is the current terminology for Atypical Facial Pain and is characterized by daily or near daily pain that is initially confined but may subsequently spread. Pain cannot be attributed to any pathological process, although traumatic neuropathic mechanisms are suspected. When present intraorally, PIFP has been termed 'Atypical Odontalgia', and this entity is discussed in a separate article in this special issue. PIFP is often a difficult but important differential diagnosis among chronic facial pain syndromes. Aim To summarize current knowledge on diagnostic criteria, differential diagnosis, pathophysiology and management of PIFP. Methods We present a narrative review reporting current literature and personal experience. Additionally, we discuss and differentiate the common differential diagnoses associated with PIFP including traumatic trigeminal neuropathies, regional myofascial pain, atypical neurovascular pains and atypical trigeminal neuropathic pains. Results and conclusion The underlying pathophysiology in PIFP is still enigmatic, however neuropathic mechanisms may be relevant. PIFP needs interdisciplinary collaboration to rule out and manage secondary causes, psychiatric comorbidities and other facial pain syndromes, particularly trigeminal neuralgia. Burden of disease and psychiatric comorbidity screening is recommended at an early stage of disease, and should be addressed in the management plan. Future research is needed to establish clear diagnostic criteria and treatment strategies based on clinical findings and individual pathophysiology.

  20. Comparison of standard and delayed imaging to improve the detection rate of [{sup 68}Ga]PSMA I and T PET/CT in patients with biochemical recurrence or prostate-specific antigen persistence after primary therapy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schmuck, Sebastian; Nordlohne, Stefan; Sohns, Jan M.; Ross, Tobias L.; Bengel, Frank M.; Derlin, Thorsten [Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany); Klot, Christoph A. von [Hannover Medical School, Department of Urology and Urologic Oncology, Hannover (Germany); Henkenberens, Christoph; Christiansen, Hans [Hannover Medical School, Department of Radiation Oncology, Hannover (Germany); Wester, Hans-Juergen [Technische Universitaet Muenchen, Pharmaceutical Radiochemistry, Garching (Germany)

    2017-06-15

    The aim of this study was to assess the value of dual-time point imaging in PET/CT for detection of biochemically recurrent or persistent prostate cancer, using the prostate-specific membrane antigen (PSMA) ligand [{sup 68}Ga]PSMA I and T. 240 patients who underwent a [{sup 68}Ga]PSMA I and T PET/CT in the context of biochemical relapse of prostate cancer were included in this retrospective analysis. Imaging consisted of a standard whole-body PET/CT (1 h p.i.), followed by delayed (3 h p.i.) imaging of the abdomen. PSA-stratified proportions of positive PET/CT results, standardized uptake values and target-to-background ratios were analyzed, and compared between standard and delayed imaging. The overall detection rates of [{sup 68}Ga]PSMA I and T PET/CT were 94.2, 71.8, 58.6, 55.9 and 38.9% for PSA levels of ≥2, 1 to <2, 0.5 to <1, >0.2 to <0.5, and 0.01 to 0.2 ng/mL, respectively. Although the target-to-background ratio improved significantly over time (P < 0.0001), the majority (96.6%) of all lesions suggestive of recurrent disease could already be detected in standard imaging. Delayed imaging at 3 h p.i. exclusively identified pathologic findings in 5.4% (10/184) of abnormal [{sup 68}Ga]PSMA I and T PET/CT scans, and exclusively detected 3.4% (38/1134) of all lesions suggestive of recurrent disease. [{sup 68}Ga]PSMA I and T PET/CT shows high detection rates in patients with prostate-specific antigen persistence or biochemical recurrence of prostate cancer. Delayed imaging can detect lesions with improved contrast compared to standard imaging. However, the impact on detection rates was limited in this study. (orig.)

  1. Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells

    International Nuclear Information System (INIS)

    Spink, Barbara C.; Bennett, James A.; Pentecost, Brian T.; Lostritto, Nicole; Englert, Neal A.; Benn, Geoffrey K.; Goodenough, Angela K.; Turesky, Robert J.; Spink, David C.

    2009-01-01

    The cumulative exposure to estrogens is an important determinant in the risk of breast cancer, yet the full range of mechanisms involving estrogens in the genesis and progression of breast cancer remains a subject of debate. Interactions of estrogens and environmental toxicants have received attention as putative factors contributing to carcinogenesis. Mechanistic studies have demonstrated interactions between estrogen receptor α (ERα) and the aryl hydrocarbon receptor (AhR), with consequences on the genes that they regulate. Many studies of ERα and AhR-mediated effects and crosstalk between them have focused on the initial molecular events. In this study, we investigated ERα- and AhR-mediated effects in long-term estrogen exposed (LTEE) MCF-7 human breast cancer cells, which were obtained by continuous culturing for at least 12 weeks in medium supplemented with 1 nM of 17β-estradiol (E 2 ). With these LTEE cells and with parallel control cells cultured without E 2 supplementation, we performed an extensive study of cytochrome P450 (CYP) induction, carcinogen bioactivation, global gene expression, and tumorigenicity in immunocompromised mice. We found that LTEE cells, in comparison with control cells, had higher levels of AhR mRNA and protein, greater responsiveness for AhR-regulated CYP1A1 and CYP1B1 induction, a 6-fold higher initial level of benzo(a)pyrene-DNA adducts as determined by liquid chromatography tandem mass spectrometry, marked differences in the expression of numerous genes, and a higher rate of E 2 -dependent tumor growth as xenografts. These studies indicate that LTEE causes adaptive responses in MCF-7 cells, which may reflect processes that contribute to the overall carcinogenic effect of E 2 .

  2. Light-grown plants of transgenic tobacco expressing an introduced oat phytochrome A gene under the control of a constitutive viral promoter exhibit persistent growth inhibition by far-red light

    International Nuclear Information System (INIS)

    McCormac, A.; Whitelam, G.; Smith, H.

    1992-01-01

    A comparison of the photoregulation of development has been made for etiolated and light-grown plants of wild-type (WT) tobacco (Nicotiana tabacun L.) and an isogenic transgenic line which expresses an introduced oat phytochrome gene (phyA) under the control of a constitutive viral promoter. Etiolated seedlings of both the WT and transgenic line showed irradiance-dependent inhibition of hypocotyl growth under continuous far-red (FR) light; transgenic seedlings showed a greater level of inhibition under a given fluence rate and this is considered to be the result of the heterologous phytochrome protein (PhyA) functioning in a compatible manner with the native etiolated phytochrome. Deetiolation of WT seedlings resulted in a loss of responsiveness to prolonged FR. Light-grown transgenic seedlings, however, continued to respond in an irradiance-dependent manner to prolonged FR and it is proposed that this is a specific function of the constitutive PhyA. Mature green plants of the WT and transgenic lines showed a qualitatively similar growth promotion to a brief end-of-day FR-treatment but this response was abolished in the transgenic plants under prolonged irradiation by this same FR source. Growth inhibition (McCormac et al. 1991, Planta 185, 162-170) and enhanced levels of nitrate-reductase activity under irradiance of low red:far-red ratio, as achieved by the FR-supplementation of white light, emphasised that the introduced PhyA was eliciting an aberrant mode of photoresponse compared with the normal phytochrome population of light-grown plants. Total levels of the oat-encoded phytochrome in the etiolated transgenic tobacco were shown to be influenced by the wavelength of continuous irradiation in a manner which was qualitatively similar to that seen for the native, etiolated tobacco phytochrome, and distinct from that seen in etiolated oat tissues. These results are discussed in terms of the proposal that the constitutive oat-PhyA pool in the transgenic plants

  3. A TORC2-Akt Feed-Forward Topology Underlies HER3 Resiliency in HER2-Amplified Cancers.

    Science.gov (United States)

    Amin, Dhara N; Ahuja, Deepika; Yaswen, Paul; Moasser, Mark M

    2015-12-01

    The requisite role of HER3 in HER2-amplified cancers is beyond what would be expected as a dimerization partner or effector substrate and it exhibits a substantial degree of resiliency that mitigates the effects of HER2-inhibitor therapies. To better understand the roots of this resiliency, we conducted an in-depth chemical-genetic interrogation of the signaling network downstream of HER3. A unique attribute of these tumors is the deregulation of TORC2. The upstream signals that ordinarily maintain TORC2 signaling are lost in these tumors, and instead TORC2 is driven by Akt. We find that in these cancers HER3 functions as a buffering arm of an Akt-TORC2 feed-forward loop that functions as a self-perpetuating module. This network topology alters the role of HER3 from a conditionally engaged ligand-driven upstream physiologic signaling input to an essential component of a concentric signaling throughput highly competent at preservation of homeostasis. The competence of this signaling topology is evident in its response to perturbation at any of its nodes. Thus, a critical pathophysiologic event in the evolution of HER2-amplified cancers is the loss of the input signals that normally drive TORC2 signaling, repositioning it under Akt dependency, and fundamentally altering the role of HER3. This reprogramming of the downstream network topology is a key aspect in the pathogenesis of HER2-amplified cancers and constitutes a formidable barrier in the targeted therapy of these cancers. ©2015 American Association for Cancer Research.

  4. Sequential occurrence of dyspnea at the end of life in palliative care, according to the underlying cancer

    Science.gov (United States)

    Guirimand, Frédéric; Sahut d'izarn, Marine; Laporte, Lucy; Francillard, Marie; Richard, Jean-François; Aegerter, Philippe

    2015-01-01

    Dyspnea is a symptom that severely affects the quality of life of terminally ill patients. Its frequency differs considerably between studies. We aimed to characterize the frequency of dyspnea in a palliative care hospital (PCH) and to identify factors predisposing to dyspnea, particularly during the very last days of life, as a function of the underlying disease. Episodes of dyspnea were identified by the computerized extraction of prospectively collected data from the reports of care assistants or from medical observations recorded in the medical files for all stays at our PCH during the last 6 years. There were 6455 hospital stays, 88% ending in the death of the patient; 13,282 episodes of dyspnea were recorded during 2608 hospital stays (40%). Dyspnea was more frequently observed in cases of cancer than in other conditions (RR = 1.30; 95% CI: 1.14–1.48). Pulmonary metastasis increased the risk of dyspnea from 37% to 51% (RR = 1.37; 95% CI: 1.29–1.46). Dyspnea frequency varied with the primary cancer site, from 24% (brain cancer) to 60% (esophageal cancer). The data for cancer patients staying for more than 6 days who subsequently died indicated that 8% of patients experienced dyspnea exclusively during the last 4 days of the life, independently of the site of the primary cancer. Dyspnea during the last few days of life requires systematic assessment. Exclusively terminal dyspnea should be distinguished from more precocious dyspnea, as the pathophysiological mechanisms and treatments of these two forms are probably different. PMID:25644607

  5. Pancreatic Fibroblasts Stimulate the Motility of Pancreatic Cancer Cells through IGF1/IGF1R Signaling under Hypoxia.

    Directory of Open Access Journals (Sweden)

    Toshiki Hirakawa

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is characterized by its hypovascularity, with an extremely poor prognosis because of its highly invasive nature. PDAC proliferates with abundant stromal cells, suggesting that its invasive activity might be controlled by intercellular interactions between cancer cells and fibroblasts. Using four PDAC cell lines and two pancreas cancer-associated fibroblasts (CAFs, the expression of insulin-like growth factor-1 (IGF1 and IGF1 receptor (IGF1R was evaluated by RT-PCR, FACScan, western blot, or ELISA. Correlation between IGF1R and the hypoxia marker carbonic anhydrase 9 (CA9 was examined by immunohistochemical staining of 120 pancreatic specimens. The effects of CAFs, IGF1, and IGF1R inhibitors on the motility of cancer cells were examined by wound-healing assay or invasion assay under normoxia (20% O2 and hypoxia (1% O2. IGF1R expression was significantly higher in RWP-1, MiaPaCa-2, and OCUP-AT cells than in Panc-1 cells. Hypoxia increased the expression level of IGF1R in RWP-1, MiaPaCa-2, and OCUP-AT cells. CA9 expression was correlated with IGF1R expression in pancreatic specimens. CAFs produced IGF1 under hypoxia, but PDAC cells did not. A conditioned medium from CAFs, which expressed αSMA, stimulated the migration and invasion ability of MiaPaCa-2, RWP-1, and OCUP-AT cells. The motility of all PDAC cells was greater under hypoxia than under normoxia. The motility-stimulating ability of CAFs was decreased by IGF1R inhibitors. These findings might suggest that pancreas CAFs stimulate the invasion activity of PDAC cells through paracrine IGF1/IGF1R signaling, especially under hypoxia. Therefore the targeting of IGF1R signaling might represent a promising therapeutic approach in IGF1R-dependent PDAC.

  6. The dietary flavonoid kaempferol effectively inhibits HIF-1 activity and hepatoma cancer cell viability under hypoxic conditions.

    Science.gov (United States)

    Mylonis, Ilias; Lakka, Achillia; Tsakalof, Andreas; Simos, George

    2010-07-16

    Hepatocellular carcinoma (HCC) is characterized by high mortality rates and resistance to conventional treatment. HCC tumors usually develop local hypoxia, which stimulates proliferation of cancer cells and renders them resilient to chemotherapy. Adaptation of tumor cells to the hypoxic conditions depends on the hypoxia-inducible factor 1 (HIF-1). Over-expression of its regulated HIF-1alpha subunit, an important target of anti-cancer therapy, is observed in many cancers including HCC and is associated with severity of tumor growth and poor patient prognosis. In this report we investigate the effect of the dietary flavonoid kaempferol on activity, expression levels and localization of HIF-1alpha as well as viability of human hepatoma (Huh7) cancer cells. Treatment of Huh7 cells with kaempferol under hypoxic conditions (1% oxygen) effectively inhibited HIF-1 activity in a dose-dependent manner (IC(50)=5.16microM). The mechanism of this inhibition did not involve suppression of HIF-1alpha protein levels but rather its mislocalization into the cytoplasm due to inactivation of p44/42 MAPK by kaempferol (IC(50)=4.75microM). Exposure of Huh7 cells to 10microM kaempferol caused significant reduction of their viability, which was remarkably more evident under hypoxic conditions. In conclusion, kaempferol, a non-toxic natural food component, inhibits both MAPK and HIF-1 activity at physiologically relevant concentrations (5-10microM) and suppresses hepatocarcinoma cell survival more efficiently under hypoxia. It has, therefore, potential as a therapeutic or chemopreventive anti-HCC agent. Copyright 2010 Elsevier Inc. All rights reserved.

  7. Search along persistent random walks

    Science.gov (United States)

    Friedrich, Benjamin M.

    2008-06-01

    Optimal search strategies and their implementations in biological systems are a subject of active research. Here we study a search problem which is motivated by the hunt of sperm cells for the egg. We ask for the probability for an active swimmer to find a target under the condition that the swimmer starts at a certain distance from the target. We find that success probability is maximal for a certain level of fluctuations characterized by the persistence length of the swimming path of the swimmer. We derive a scaling law for the optimal persistence length as a function of the initial target distance and search time by mapping the search on a polymer physics problem.

  8. Mathematical Models of Androgen Resistance in Prostate Cancer Patients under Intermittent Androgen Suppression Therapy

    Directory of Open Access Journals (Sweden)

    Javier Baez

    2016-11-01

    Full Text Available Predicting the timing of a castrate resistant prostate cancer is critical to lowering medical costs and improving the quality of life of advanced prostate cancer patients. We formulate, compare and analyze two mathematical models that aim to forecast future levels of prostate-specific antigen (PSA. We accomplish these tasks by employing clinical data of locally advanced prostate cancer patients undergoing androgen deprivation therapy (ADT. While these models are simplifications of a previously published model, they fit data with similar accuracy and improve forecasting results. Both models describe the progression of androgen resistance. Although Model 1 is simpler than the more realistic Model 2, it can fit clinical data to a greater precision. However, we found that Model 2 can forecast future PSA levels more accurately. These findings suggest that including more realistic mechanisms of androgen dynamics in a two population model may help androgen resistance timing prediction.

  9. [Explore the influence factors on primary lung cancer in Fujian province Han population under the use of generalized linear model].

    Science.gov (United States)

    He, Fei; Xiao, Rendong; Yu, Tingting; Zhang, Xin; Liu, Zhiqiang; Cai, Lin

    2015-08-01

    The purpose of this study was to use the data on lung cancer in Han Chinese in Fujian province to explore the value of a generalized, linear model and to investigate the impact related to environment factors on lung cancer as well as the independent and interaction effects on the development of lung cancer. SAS 9.2 was used to build a generalized linear model to evaluate the influence factors and interaction of lung cancer on both smokers and non-smokers. Results showed that the relationship of the factors was multiplied. Under the logistic regression analysis, seven risk factors and nine risk factors were noticed in smokers or in non-smokers, respectively. Heavy smokers and lung diseases appeared a positive multiplying effect on smokers while passive smoking and fresh fruits showed positive multiplying effects on non-smokers. The generalized linear models could filter suitable models thus facilitating further research on the interaction between the two. It seemed easy to carry on the comprehensive and rational analysis on related epidemiological data.

  10. Hit by waves-living with local advanced or localized prostate cancer treated with endocrine therapy or under active surveillance.

    Science.gov (United States)

    Ervik, Bente; Nordøy, Tone; Asplund, Kenneth

    2010-01-01

    Previous studies of living with prostate cancer have shown that the illness and the treatment cause physical as well as psychosocial problems. The aim of this study was to illuminate men's experiences living with localized or local advanced prostate cancer when curative treatment such as surgery or radiation therapy is not an option at the time of diagnosis. The study was conducted via qualitative interviews, using a phenomenological hermeneutic approach. Ten men treated with endocrine therapy or under active surveillance were interviewed. Being diagnosed with prostate cancer was described as a shock, with different aspects of the illness revealed gradually. The limited amount of time available for meeting with health care providers contributed to patients' feelings of being left alone with difficulty getting information and help. Sexual and urinary problems were perceived as a threat to their manhood. The spouses provided the closest everyday support. The life situation of these patients can be understood as living in a "state of readiness," expecting something to happen regarding their illness, and not always knowing where to get help. The results confirm existing knowledge of patient's experiences in living with prostate cancer regarding the initial shock perceived by the patients, the bodily alterations, and the important role of their spouses. Nurses, as well as general practitioners, must play a more active role in follow-up to ensure that the men and their spouses receive better help and support.

  11. Effectiveness of a Brief Health Education Intervention for Breast Cancer Prevention in Greece Under Economic Crisis

    Directory of Open Access Journals (Sweden)

    Kyriakoula Merakou

    2013-01-01

    Full Text Available Background: Prevalence rates in breast cancer have now reached epidemic levels. One of the main reasons behind onset of breast cancer is poor preventive beliefs and behavior of women towards cancer prevention. We examined the effectiveness of health education intervention in two communities of South Greece.Objective: The study investigates the effectiveness of a brief health education intervention on women’s beliefs and behaviour changes concerning breast cancer prevention.Methodology: A 90-minute, one-off encounter, health education study was designed for 300 women from Peloponissos, South Greece. A Health Belief Model questionnaire, was used before the intervention, immediately after and 6-months after the intervention.Results: Despite certain perception-related barriers (embarrassment, anxiety, ect women’s overall beliefs towards breast cancer prevention (perceived susceptibility, perceived benefits and perceived barriers changed positively after the health education intervention and this change was sustained at 6-month follow up. However, specific barriers (embarrassment, fear of pain, anxiety when anticipating tests’ results were not maintained at the same level of post-intervention during the same follow up. During the follow up period, women performed breast self-examination every month (73% and 55.10% had breast examination by a clinician and underwent a mammography.Conclusions: Short, low cost, health education interventions for breast cancer prevention to women can be effective in changing beliefs and behaviour. Tailored interventions are necessary to overcome relapsing of specific barriers. Emphasis should be given on the importance of doctor/nurse role in breast screening.

  12. Persistence in youth unemployment

    OpenAIRE

    Caporale, Guglielmo Maria; Gil-Alana, Luis A.

    2012-01-01

    This paper examines the degree of persistence of youth unemployment (total, male and female) in twenty-four countries by using two alternative measures: the AR coefficient and the fractional differencing parameter, based on short- and long-memory processes respectively. The evidence suggests that persistence is particularly high in Japan and some EU countries such as Spain, Portugal, Ireland and Finland, where appropriate policy actions are of the essence. Specifically, active labour market p...

  13. Economic burden of gastrointestinal cancer under the protection of the New Rural Cooperative Medical Scheme in a region of rural China with high incidence of oesophageal cancer: cross-sectional survey.

    Science.gov (United States)

    Li, Xiang; Cai, Hong; Wang, Chaoyi; Guo, Chuanhai; He, Zhonghu; Ke, Yang

    2016-07-01

    To evaluate the financial burden of oesophageal cancer under the protection of the new Rural Cooperative Medical Scheme (NCMS) and to provide evidence and suggestions to policymakers in a high-incidence region in China. We analysed inpatient claim data for oesophageal cancer, gastric cancer and colorectal cancer from 1 January to 31 December 2013. The data were extracted from the NCMS management system of Hua County, Henan Province, a typical high-risk region for oesophageal cancer in China. Cancer-specific health economic indicators were calculated to evaluate the financial burden under the protection of the local NCMS. The total cost of oesophageal cancer was 2.7-3.6 times higher than that of gastric cancer and colorectal cancer, respectively, due to high incidence of oesophageal cancer. For each hospitalisation to treat oesophageal cancer, the average total cost and out-of-pocket expenses after reimbursement equalled an entire year's gross domestic product per capita and per capita disposable income, respectively, for the local area. The average total cost per hospitalisation for oesophageal cancer increased monotonically with hospital level for surgical hospitalisations, and it increased more rapidly for non-surgical hospitalisations (from $301 to $2589, 860%) than for gastric cancer (from $289 to $1453, 503%) and colorectal cancer (from $359 to $1610, 448%). Vulnerable groups with less access to high-level hospitals were found in different gender and age groups. Oesophageal cancer imposes serious financial burdens on communities and patients' households in this high-incidence region, and no preferential policy from the local NCMS has been designed to address this issue. A special supportive policy should be developed on the basis of local disease profiles and population characteristics to alleviate the financial burden of populations at high risk for certain high-cost diseases. © 2016 John Wiley & Sons Ltd.

  14. Treatment of persistent pain from torture

    DEFF Research Database (Denmark)

    Williams, Amanda C de C; Amris, Kirstine

    2017-01-01

    Torture and the conditions under which it is inflicted often leave persistent painful disorders. Because there may be no lasting signs, persistent pain is often misconceived as a somatic representation of psychological distress, also common after torture. This serious failure to understand...... the nature of persistent pain means that pain is largely overlooked and untreated in torture survivors. We carried out a systematic review on treatments for pain from torture, but found few studies and little use of current understanding and evidence. We discuss this in the context of treating pain...

  15. Descriptive Epidemiology in Mexican children with cancer under an open national public health insurance program.

    Science.gov (United States)

    Rivera-Luna, Roberto; Shalkow-Klincovstein, Jaime; Velasco-Hidalgo, Liliana; Cárdenas-Cardós, Rocio; Zapata-Tarrés, Marta; Olaya-Vargas, Alberto; Aguilar-Ortiz, Marco R; Altamirano-Alvarez, Eduardo; Correa-Gonzalez, Cecilia; Sánchez-Zubieta, Fernando; Pantoja-Guillen, Francisco

    2014-10-29

    All the children registered at the National Council for the Prevention and Treatment of Childhood Cancer were analyzed. The rationale for this Federal Government Council is to financially support the treatment of all children registered into this system. All patients are within a network of 55 public certified hospitals nationwide. In the current study, data from 2007 to 2012 are presented for all patients (0-18 years) with a pathological diagnosis of leukemia, lymphoma and solid tumors. The parameters analyzed were prevalence, incidence, mortality, and abandonment rate. A diagnosis of cancer was documented in 14,178 children. The incidence was of 156.9/million/year (2012). The median age was 4.9. The most common childhood cancer is leukemia, which occurs in 49.8% of patients (2007-2012); and has an incidence rate of 78.1/million/year (2012). The national mortality rate was 5.3/100,000 in 2012, however in the group between 15 to 18 years it reaches a level of 8.6. The study demonstrates that there is a high incidence of childhood cancer in Mexico. In particular, the results reveal an elevated incidence and prevalence of leukemia especially from 0 to 4 years. Only 4.7% of these patients abandoned treatment. The clinical outcome for all of the children studied improved since the establishment of this national program.

  16. Cisplatin and gemcitabine in patients with advanced biliary tract cancer (ABC) and persistent jaundice despite optimal stenting: Effective intervention in patients with luminal disease.

    Science.gov (United States)

    Lamarca, Angela; Benafif, Sarah; Ross, Paul; Bridgewater, John; Valle, Juan W

    2015-09-01

    The advanced biliary tract cancer (ABC)-02 study established cisplatin and gemcitabine (CisGem) as a reference 1(st)-line regimen for patients with advanced/metastatic biliary tract cancer; patients with bilirubin ⩾ 1.5 × upper limit of normal (ULN) were excluded and there are few extant data for systemic treatment in the context of elevated bilirubin. Patients with ABC, receiving CisGem with a baseline bilirubin of ⩾ 1.5 × ULN were eligible for this retrospective analysis; response, toxicity and survival data were collected. Thirty-three patients of 545 screened; median age 59 years, range 23-79; 58% male, 58% with metastases (79% in the liver) of performance status (PS) 0 (33%), 1 (64%) or 2 (3%) were eligible. The median baseline bilirubin was 55 μmol/L (range 32-286); due to biliary tract obstruction (BTO, 76%) or liver metastases (LM, 24%). Toxicity was comparable to the ABC-02 study; bilirubin normalised in 64% during chemotherapy/follow-up. The median progression-free survival (PFS) was 6.9 months (95% confidence interval (CI): 4.4-9.0) and median overall survival (OS) 9.5 months (95% CI: 5.7-12.8). Patients with BTO had a longer PFS and OS than those with LM (7.0 versus 2.6 months; p = 0.1633 and 9.8 versus 4.4 months, hazard ratio (HR) 0.74; p = 0.465, respectively); not statistically significant (due to small sample size). Normalisation of bilirubin and completion of eight CisGem cycles were associated with longer OS (11.4 versus 2.9 months, HR 0.49; p = 0.08 and 15.2 versus 5.4 months, HR 0.12 p < 0.001, respectively). No difference in OS was shown between the bilirubin percentiles (for either PFS or OS). For PS 0-1 patients with ABC and high bilirubin due to luminal disease despite optimal stenting CisGem can be used safely with results similar to those in patients with normal bilirubin. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Randomized controlled pilot trial of mindfulness-based stress reduction compared to psychoeducational support for persistently fatigued breast and colorectal cancer survivors.

    Science.gov (United States)

    Johns, Shelley A; Brown, Linda F; Beck-Coon, Kathleen; Talib, Tasneem L; Monahan, Patrick O; Giesler, R Brian; Tong, Yan; Wilhelm, Laura; Carpenter, Janet S; Von Ah, Diane; Wagner, Christina D; de Groot, Mary; Schmidt, Karen; Monceski, Diane; Danh, Marie; Alyea, Jennifer M; Miller, Kathy D; Kroenke, Kurt

    2016-10-01

    Cancer-related fatigue (CRF) is a disruptive symptom for many survivors. Despite promising evidence for efficacy of mindfulness-based stress reduction (MBSR) in reducing CRF, no trials comparing it to an active comparator for fatigued survivors have been published. The purpose of this trial was to compare MBSR to psychoeducation for CRF and associated symptoms. Breast (n = 60) and colorectal (n = 11) cancer survivors (stage 0-III) with clinically significant CRF after completing chemotherapy and/or radiation therapy an average of 28 months prior to enrollment were randomized to MBSR or psychoeducation/support groups (PES). MBSR focused on mindfulness training; PES focused on CRF self-management. Outcomes included CRF interference (primary), CRF severity and global improvement, vitality, depression, anxiety, sleep disturbance, and pain. Outcomes were assessed at baseline (T1), post-intervention (T2), and 6-month follow-up (T3) using intent-to-treat analysis. Between-group differences in CRF interference were not significant at any time point; however, there was a trend favoring MBSR (d = -0.46, p = 0.073) at T2. MBSR participants reported significantly greater improvement in vitality (d = 0.53, p = 0.003) and were more likely to report CRF as moderately to completely improved compared to the PES group (χ2 (1) = 4.1765, p = 0.041) at T2. MBSR participants also reported significantly greater reductions in pain at T2 (d = 0.53, p = 0.014). In addition, both MBSR and PES produced moderate-to-large and significant within-group improvements in all fatigue outcomes, depression, anxiety, and sleep at T2 and T3 compared to T1. MBSR and PES appear efficacious for CRF and related symptoms. Larger trials including a usual care arm are warranted. ClinicalTrials.gov Identifier: NCT01724333.

  18. Demethylation by 5-aza-2'-deoxycytidine in colorectal cancer cells targets genomic DNA whilst promoter CpG island methylation persists

    Directory of Open Access Journals (Sweden)

    Kim Kyu-Tae

    2010-07-01

    Full Text Available Abstract Background DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. Aberrant epigenetic gene silencing in tumours is a frequent event, yet the factors which dictate which genes are targeted for inactivation are unknown. DNA methylation and histone acetylation can be modified with the chemical agents 5-aza-2'-deoxycytidine (5-aza-dC and Trichostatin A (TSA respectively. The aim of this study was to analyse de-methylation and re-methylation and its affect on gene expression in colorectal cancer cell lines treated with 5-aza-dC alone and in combination with TSA. We also sought to identify methylation patterns associated with long term reactivation of previously silenced genes. Method Colorectal cancer cell lines were treated with 5-aza-dC, with and without TSA, to analyse global methylation decreases by High Performance Liquid Chromatography (HPLC. Re-methylation was observed with removal of drug treatments. Expression arrays identified silenced genes with differing patterns of expression after treatment, such as short term reactivation or long term reactivation. Sodium bisulfite sequencing was performed on the CpG island associated with these genes and expression was verified with real time PCR. Results Treatment with 5-aza-dC was found to affect genomic methylation and to a lesser extent gene specific methylation. Reactivated genes which remained expressed 10 days post 5-aza-dC treatment featured hypomethylated CpG sites adjacent to the transcription start site (TSS. In contrast, genes with uniformly hypermethylated CpG islands were only temporarily reactivated. Conclusion These results imply that 5-aza-dC induces strong de-methylation of the genome and initiates reactivation of transcriptionally inactive genes, but this does not require gene associated CpG island de-methylation to occur. In addition, for three of our selected genes, hypomethylation at the TSS of an epigenetically

  19. Demethylation by 5-aza-2'-deoxycytidine in colorectal cancer cells targets genomic DNA whilst promoter CpG island methylation persists

    International Nuclear Information System (INIS)

    Mossman, David; Kim, Kyu-Tae; Scott, Rodney J

    2010-01-01

    DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. Aberrant epigenetic gene silencing in tumours is a frequent event, yet the factors which dictate which genes are targeted for inactivation are unknown. DNA methylation and histone acetylation can be modified with the chemical agents 5-aza-2'-deoxycytidine (5-aza-dC) and Trichostatin A (TSA) respectively. The aim of this study was to analyse de-methylation and re-methylation and its affect on gene expression in colorectal cancer cell lines treated with 5-aza-dC alone and in combination with TSA. We also sought to identify methylation patterns associated with long term reactivation of previously silenced genes. Colorectal cancer cell lines were treated with 5-aza-dC, with and without TSA, to analyse global methylation decreases by High Performance Liquid Chromatography (HPLC). Re-methylation was observed with removal of drug treatments. Expression arrays identified silenced genes with differing patterns of expression after treatment, such as short term reactivation or long term reactivation. Sodium bisulfite sequencing was performed on the CpG island associated with these genes and expression was verified with real time PCR. Treatment with 5-aza-dC was found to affect genomic methylation and to a lesser extent gene specific methylation. Reactivated genes which remained expressed 10 days post 5-aza-dC treatment featured hypomethylated CpG sites adjacent to the transcription start site (TSS). In contrast, genes with uniformly hypermethylated CpG islands were only temporarily reactivated. These results imply that 5-aza-dC induces strong de-methylation of the genome and initiates reactivation of transcriptionally inactive genes, but this does not require gene associated CpG island de-methylation to occur. In addition, for three of our selected genes, hypomethylation at the TSS of an epigenetically silenced gene is associated with the long term reversion of

  20. Chemosensitizing effects of carbon-based nanomaterials in cancer cells: enhanced apoptosis and inhibition of proliferation as underlying mechanisms

    International Nuclear Information System (INIS)

    Erdmann, Kati; Ringel, Jessica; Rieger, Christiane; Huebner, Doreen; Wirth, Manfred P; Fuessel, Susanne; Hampel, Silke

    2014-01-01

    Recent studies have shown that carbon nanomaterials such as carbon nanofibres (CNFs) and multi-walled carbon nanotubes (CNTs) can exert antitumor activities themselves and sensitize cancer cells to conventional chemotherapeutics such as carboplatin and cisplatin. In the present study, the chemosensitizing effect of CNFs and CNTs on cancer cells of urological origin was investigated regarding the underlying mechanisms. Prostate cancer (DU-145, PC-3) and bladder cancer (EJ28) cells were treated with carbon nanomaterials (CNFs, CNTs) and chemotherapeutics (carboplatin, cisplatin) alone as well as in combination for 24 h. Forty-eight (EJ28) or 72 h (DU-145, PC-3) after the end of treatment the effects on cellular proliferation, clonogenic survival, cell death rate and cell cycle distribution were evaluated. Depending on the cell line, simultaneous administration of chemotherapeutics and carbon nanomaterials produced an additional inhibition of cellular proliferation and clonogenic survival of up to 77% and 98%, respectively, compared to the inhibitory effects of the chemotherapeutics alone. These strongly enhanced antiproliferative effects were accompanied by an elevated cell death rate, which was predominantly mediated via apoptosis and not by necrosis. The antitumor effects of combinations with CNTs were less pronounced than those with CNFs. The enhanced effects of the combinatory treatments on cellular function were mostly of additive to partly synergistic nature. Furthermore, cell cycle analysis demonstrated an arrest at the G2/M phase mediated by a monotreatment with chemotherapeutics. Following combinatory treatments, mostly less than or nearly additive increases of cell fractions in the G2/M phase could be observed. In conclusion, the pronounced chemosensitizing effects of CNFs and CNTs were mediated by an enhanced apoptosis and inhibition of proliferation. The combination of carbon-based nanomaterials and conventional chemotherapeutics represents a novel

  1. Oxidative Stress Promotes Doxorubicin-Induced Pgp and BCRP Expression in Colon Cancer Cells Under Hypoxic Conditions.

    Science.gov (United States)

    Pinzón-Daza, Martha L; Cuellar-Saenz, Yenith; Nualart, Francisco; Ondo-Mendez, Alejandro; Del Riesgo, Lilia; Castillo-Rivera, Fabio; Garzón, Ruth

    2017-07-01

    P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) are ATP binding cassette (ABC) transporters that are overexpressed in different drug-resistant cancer cell lines. In this study, we investigated whether doxorubicin promotes Pgp and/or BCRP expression to induce drug resistance in colon cancer cells under hypoxic conditions. We analyzed HIF-1α activity via ELISA, Pgp, and BCRP expression by qRT-PCR and the relationship between doxorubicin uptake and ABC transporter expression via confocal microscopy in HT-29WT and HT-29 doxorubicin-resistant colon cancer cells (HT-29DxR). These cells were treated with doxorubicin and/or CoCl 2 (chemical hypoxia), and reactive oxygen species inductors. We found that the combination of chemically induced hypoxia and doxorubicin promoted Pgp mRNA expression within 24 h in HT-29WT and HT-29DxR cells. Both doxorubicin and CoCl 2 alone or in combination induced Pgp and BCRP expression, as demonstrated via confocal microscopy in each of the above two cell lines. Thus, we surmised that Pgp and BCRP expression may result from synergistic effects exerted by the combination of doxorubicin-induced ROS production and HIF-1α activity under hypoxic conditions. However, HIF-1α activity disruption via the administration of E3330, an APE-1 inhibitor, downregulated Pgp expression and increased doxorubicin delivery to HT-29 cells, where it served as a substrate for Pgp, indicating the existence of an indirect relationship between Pgp expression and doxorubicin accumulation. Thus, we concluded that Pgp and BCRP expression can be regulated via cross-talk between doxorubicin and hypoxia, promoting drug resistance in HT-29 WT, and HT-29DxR cells and that this process may be ROS dependent. J. Cell. Biochem. 118: 1868-1878, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  2. A Phase II Evaluation of Nintedanib (BIBF-1120) in the Treatment of Recurrent or Persistent Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study

    Science.gov (United States)

    Dizon, Don S.; Sill, Michael W.; Schilder, Jeanne M.; McGonigle, Kathryn F.; Rahman, Zia; Miller, David S.; Mutch, David G.; Leslie, Kimberly K.

    2014-01-01

    Introduction Patients presenting with advanced, recurrent, or metastatic endometrial cancer have limited treatment options. On behalf of the Gynecologic Oncology Group, we conducted this phase II trial of nintedanib (BIBF 1120), a potent small molecule triple receptor tyrosine kinase inhibitor of PDGFR α and β, FGFR 1/3, and VEGFR 1-3, in this population. Objectives The primary objectives were to estimate event-free survival (EFS) at six months and the proportion of patients who have an objective tumor response. In addition, we sought to determine the nature and degree of toxicity. Secondary objectives were to estimate progression-free and overall survival. Methods This was a two-stage, single-arm phase II study. Eligible patients were treated with single-agent nintedanib at a dose of 200 mg twice daily. Results Of 37 patients enrolled, 32 were eligible. There were zero complete and three partial responses for an overall response rate of 9.4% (90% 2-sided CI 2.6 ~ 22.5%). Seven patients (21.9%; 90% 2-sided CI 10.7 ~ 37.2%) were EFS at six months, with one patient continuing on study at the time of this writing. Serious toxicity included the following grade 3 events: gastrointestinal toxicity (5), neutropenia (1), edema (1), hypertension (1), and liver function abnormalities (5). Conclusions Nintedanib lacked sufficient activity as a single agent to warrant enrollment to second stage. However, preclinical data indicate it may be synergistic with paclitaxel in a population of patients enriched for specific p53 mutations that result in loss of function. Subsequent studies may evaluate this agent in combination with paclitaxel. PMID:25312396

  3. Coping, psychopathology, and quality of life in cancer patients under palliative care.

    Science.gov (United States)

    Sorato, Daniela B; Osório, Flávia L

    2015-06-01

    To assess hopelessness, anxiety, depression, and quality of life in cancer patients undergoing palliative treatment by comparing their scores at the onset of treatment and one month later and by assessing possible correlations with coping strategies. Participants included 85 patients of both genders (56.5% female) diagnosed with advanced cancer who did not have curative therapeutic options who were assessed with self-applied instruments (the Beck Hopelessness Scale, the European Organization for the Research and Treatment of Cancer Quality of Life Core Questionnaire-Cancer 30, the Hospital Anxiety and Depression Scale, and the Coping Strategies Inventory by Folkman and Lazarus) at two timepoints: first before their appointment with doctors and other professionals in their first visit to the palliative care outpatient clinic (PCOC) and then as soon as patients arrived at the PCOC for their first medical follow-up visit (approximately 30 days after the first appointment). The scores for hopelessness, anxiety, and depression remained stable (p = 0.24). The results were the same for the quality-of-life (QoL) variables, except for the fatigue and pain scores, which decreased (p = 0.01), and social impairment, which increased (p = 0.03). Analysis of the correlations between the coping mechanisms used after the onset of palliative treatment showed that confronting coping, seeking social support, and positive reappraisal were inversely correlated with hopelessness. Seeking social support, planful problem solving, and positive reappraisal were inversely correlated with indicators of depression. In contrast, use of the escape-avoidance strategy and reduced use of the planful problem-solving strategy were associated with increased anxiety. The employment of problem-focused coping strategies exerted a positive impact on the end-of-life process and, above all, protected patients from the negative experiences associated with psychiatric symptoms, thus enabling them to look for

  4. Vitamins in pancreatic cancer: a review of underlying mechanisms and future applications.

    Science.gov (United States)

    Davis-Yadley, Ashley H; Malafa, Mokenge P

    2015-11-01

    Although there is increasing evidence that vitamins influence pancreatic adenocarcinoma biology and carcinogenesis, a comprehensive review is lacking. In this study, we performed a PubMed literature search to review the anticancer mechanisms and the preclinical and clinical studies that support the development of the bioactive vitamins A, C, D, E, and K in pancreatic cancer intervention. Preclinical studies have shown promising results for vitamin A in pancreatic cancer prevention, with clinical trials showing intriguing responses in combination with immunotherapy. For vitamin C, preclinical studies have shown slower tumor growth rates and/or increased survival when used alone or in combination with gemcitabine, with clinical trials with this combination revealing decreased primary tumor sizes and improved performance status. Preclinical studies with vitamin D analogues have shown potent antiproliferative effects and repression of migration and invasion of pancreatic cancer cells, with a clinical trial showing increased time to progression when calciferol was added to docetaxel. For vitamin E, preclinical studies have shown that δ-tocotrienol and γ-tocotrienol inhibited tumor cell growth and survival and augmented gemcitabine activity. Early-phase clinical trials with δ-tocotrienol are ongoing. Vitamin K demonstrates activation of apoptosis and inhibition of cellular growth in pancreatic tumor cells; however, there are no clinical studies available for further evaluation. Although preclinical and clinical studies are encouraging, randomized controlled trials with endpoints based on insights gained from mechanistic and preclinical studies and early-phase clinical trials are required to determine the efficacy of bioactive vitamin interventions in pancreatic cancer. © 2015 American Society for Nutrition.

  5. Vitamins in Pancreatic Cancer: A Review of Underlying Mechanisms and Future Applications12

    Science.gov (United States)

    Davis-Yadley, Ashley H; Malafa, Mokenge P

    2015-01-01

    Although there is increasing evidence that vitamins influence pancreatic adenocarcinoma biology and carcinogenesis, a comprehensive review is lacking. In this study, we performed a PubMed literature search to review the anticancer mechanisms and the preclinical and clinical studies that support the development of the bioactive vitamins A, C, D, E, and K in pancreatic cancer intervention. Preclinical studies have shown promising results for vitamin A in pancreatic cancer prevention, with clinical trials showing intriguing responses in combination with immunotherapy. For vitamin C, preclinical studies have shown slower tumor growth rates and/or increased survival when used alone or in combination with gemcitabine, with clinical trials with this combination revealing decreased primary tumor sizes and improved performance status. Preclinical studies with vitamin D analogues have shown potent antiproliferative effects and repression of migration and invasion of pancreatic cancer cells, with a clinical trial showing increased time to progression when calciferol was added to docetaxel. For vitamin E, preclinical studies have shown that δ-tocotrienol and γ-tocotrienol inhibited tumor cell growth and survival and augmented gemcitabine activity. Early-phase clinical trials with δ-tocotrienol are ongoing. Vitamin K demonstrates activation of apoptosis and inhibition of cellular growth in pancreatic tumor cells; however, there are no clinical studies available for further evaluation. Although preclinical and clinical studies are encouraging, randomized controlled trials with endpoints based on insights gained from mechanistic and preclinical studies and early-phase clinical trials are required to determine the efficacy of bioactive vitamin interventions in pancreatic cancer. PMID:26567201

  6. Identification of key processes underlying cancer phenotypes using biologic pathway analysis.

    Directory of Open Access Journals (Sweden)

    Sol Efroni

    2007-05-01

    Full Text Available Cancer is recognized to be a family of gene-based diseases whose causes are to be found in disruptions of basic biologic processes. An increasingly deep catalogue of canonical networks details the specific molecular interaction of genes and their products. However, mapping of disease phenotypes to alterations of these networks of interactions is accomplished indirectly and non-systematically. Here we objectively identify pathways associated with malignancy, staging, and outcome in cancer through application of an analytic approach that systematically evaluates differences in the activity and consistency of interactions within canonical biologic processes. Using large collections of publicly accessible genome-wide gene expression, we identify small, common sets of pathways - Trka Receptor, Apoptosis response to DNA Damage, Ceramide, Telomerase, CD40L and Calcineurin - whose differences robustly distinguish diverse tumor types from corresponding normal samples, predict tumor grade, and distinguish phenotypes such as estrogen receptor status and p53 mutation state. Pathways identified through this analysis perform as well or better than phenotypes used in the original studies in predicting cancer outcome. This approach provides a means to use genome-wide characterizations to map key biological processes to important clinical features in disease.

  7. Molecular Mechanisms Underlying Curcumin-Mediated Therapeutic Effects in Type 2 Diabetes and Cancer

    Directory of Open Access Journals (Sweden)

    Marzena Wojcik

    2018-01-01

    Full Text Available The growing prevalence of age-related diseases, especially type 2 diabetes mellitus (T2DM and cancer, has become global health and economic problems. Due to multifactorial nature of both diseases, their pathophysiology is not completely understood so far. Compelling evidence indicates that increased oxidative stress, resulting from an imbalance between production of reactive oxygen species (ROS and their clearance by antioxidant defense mechanisms, as well as the proinflammatory state contributes to the development and progression of the diseases. Curcumin (CUR; diferuloylmethane, a well-known polyphenol derived from the rhizomes of turmeric Curcuma longa, has attracted a great deal of attention as a natural compound with beneficial antidiabetic and anticancer properties, partly due to its antioxidative and anti-inflammatory actions. Although this polyphenolic compound is increasingly being recognized for its growing number of protective health effects, the precise molecular mechanisms through which it reduces diabetes- and cancer-related pathological events have not been fully unraveled. Hence, CUR is the subject of intensive research in the fields Diabetology and Oncology as a potential candidate in the treatment of both T2DM and cancer, particularly since current therapeutic options for their treatment are not satisfactory in clinics. In this review, we summarize the recent progress made on the molecular targets and pathways involved in antidiabetic and anticancer activities of CUR that are responsible for its beneficial health effects.

  8. Persistent and recurrent hyperparathyroidism.

    Science.gov (United States)

    Guerin, Carole; Paladino, Nunzia Cinzia; Lowery, Aoife; Castinetti, Fréderic; Taieb, David; Sebag, Fréderic

    2017-06-01

    Despite remarkable progress in imaging modalities and surgical management, persistence or recurrence of primary hyperparathyroidism (PHPT) still occurs in 2.5-5% of cases of PHPT. The aim of this review is to expose the management of persistent and recurrent hyperparathyroidism. A literature search was performed on MEDLINE using the search terms "recurrent" or "persistent" and "hyperparathyroidism" within the past 10 years. We also searched the reference lists of articles identified by this search strategy and selected those we judged relevant. Before considering reoperation, the surgeon must confirm the diagnosis of PHPT. Then, the patient must be evaluated with new imaging modalities. A single adenoma is found in 68% of cases, multiglandular disease in 28%, and parathyroid carcinoma in 3%. Others causes (<1%) include parathyromatosis and graft recurrence. The surgeon must balance the benefits against the risks of a reoperation (permanent hypocalcemia and recurrent laryngeal nerve palsy). If surgery is necessary, a focused approach can be considered in cases of significant imaging foci, but in the case of multiglandular disease, a bilateral neck exploration could be necessary. Patients with multiple endocrine neoplasia syndromes are at high risk of recurrence and should be managed regarding their hereditary pathology. The cure rate of persistent-PHPT or recurrent-PHPT in expert centers is estimated from 93 to 97%. After confirming the diagnosis of PHPT, patients with persistent-PHPT and recurrent-PHPT should be managed in an expert center with all dedicated competencies.

  9. Persistent toxic substances: sources, fates and effects.

    Science.gov (United States)

    Wong, Ming H; Armour, Margaret-Ann; Naidu, Ravi; Man, Ming

    2012-01-01

    Persistent toxic substances (PTS) include the Stockholm persistent organic pollutants, like dichlorodiphenyltrichloroethane, polychlorinated biphenyls, dioxin/furan, etc., and organometallic compounds, like organomercury, organotin, and organolead, which all share the same characteristics of being persistent, toxic, bioaccumulative, and able to travel long distances through different media. The adverse health effects of some of the emerging chemicals like pentabromodiphenyl ether, bisphenol A, and di(2-ethylhexyl)phthalate, which are widely used in daily appliances (e.g., TVs, computers, mobile phones, plastic baby bottles), have become a public health concern due to more evidence now available showing their adverse effects like disturbance of the endocrine system and cancer. This article is an attempt to review the current status of PTS in our environment, citing case studies in China and North America, and whether our existing drinking water treatment and wastewater treatment processes are adequate in removing them from water. Some management issues of these emerging chemicals of concern are also discussed.

  10. The interplay between GRP78 expression and Akt activation in human colon cancer cells under celecoxib treatment.

    Science.gov (United States)

    Tian, Shaobo; Chang, Weilong; Du, Hansong; Bai, Jie; Sun, Zhenhai; Zhang, Qing; Wang, Hui; Zhu, Guangsheng; Tao, Kaixiong; Long, Yueping

    2015-10-01

    It has been reported previously that celecoxib shows antitumor effects in many types of cancers. Here, we detected its effects on DLD-1 and SW480 (two human colon cancer cell lines) and investigated the dynamic relationship between the 78-kDa glucose-regulatory protein (GRP78) and the phosphoinositide 3-kinase (PI3K)/Akt pathway. Gene expression was detected by real-time PCR and western blot analysis; the cytotoxicity was determined by the MTT assay and flow cytometry. First, the results showed that celecoxib induced cytotoxicity in a dose-dependent and time-dependent manner. Furthermore, we found the celecoxib-triggered unfolded protein response and the bidirectional regulation of Akt activation in both cell lines. Inhibiting the Akt activation by the PI3K inhibitor LY294002 markedly enhanced GRP78 expression. Besides, silencing the GRP78 expression regulated Akt activation in a time-dependent manner and increased the induction of the C/EBP homologous protein (CHOP) as well as considerably promoted celecoxib-induced apoptosis. In conclusion, these findings provide evidence that under the celecoxib treatment, GRP78 plays a protective role by modulating Akt activation and abrogating CHOP expression. However, Akt activation can provide a feedback loop to inhibit GRP78 expression. These studies can lead to novel therapeutic strategies for human colon cancer.

  11. Mechanisms underlying p53 regulation of PIK3CA transcription in ovarian surface epithelium and in ovarian cancer.

    Science.gov (United States)

    Astanehe, Arezoo; Arenillas, David; Wasserman, Wyeth W; Leung, Peter C K; Dunn, Sandra E; Davies, Barry R; Mills, Gordon B; Auersperg, Nelly

    2008-03-01

    Inactivation of the transcription factor and tumor suppressor p53, and overexpression or mutational activation of PIK3CA, which encodes the p110alpha catalytic subunit of phosphatidylinositol-3-kinase (PI3K), are two of the most common deleterious genomic changes in cancer, including in ovarian carcinomas. We investigated molecular mechanisms underlying interactions between these two mediators and their possible roles in ovarian tumorigenesis. We identified two alternate PIK3CA promoters and showed direct binding of and transcriptional inhibition by p53 to one of these promoters. Conditional suppression of functional p53 increased p110alpha transcripts, protein levels and PI3K activity in immortalized, non-tumorigenic ovarian surface epithelial (OSE) cells, the precursors of ovarian carcinoma. Conversely, overexpression of p53 by adenoviral infection and activation of p53 by gamma-irradiation both diminished p110alpha protein levels in normal OSE and ovarian cancer cells. The demonstration that p53 binds directly to the PIK3CA promoter and inhibits its activity identifies a novel mechanism whereby these two mediators regulate cellular functions, and whereby inactivation of p53 and subsequent upregulation of PIK3CA might contribute to the pathophysiology of ovarian cancer.

  12. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast–ovarian cancer susceptibility locus

    Science.gov (United States)

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J.; Li, Qiyuan; Delgado, Melissa K.; Lee, Janet M.; Aittomäki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K.; Arver, Brita; Bandera, Elisa V.; Barile, Monica; Barkardottir, Rosa B.; Barrowdale, Daniel; Beckmann, Matthias W.; Benitez, Javier; Berchuck, Andrew; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Blot, William; Bogdanova, Natalia; Bojesen, Anders; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Børresen-Dale, Anne-Lise; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Bruinsma, Fiona; Brunet, Joan; Buhari, Shaik Ahmad; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S.; Cai, Qiuyin; Caldes, Trinidad; Campbell, Ian; Canniotto, Rikki; Chang-Claude, Jenny; Chiquette, Jocelyne; Choi, Ji-Yeob; Claes, Kathleen B. M.; Collonge-Rame, Marie- Agnès; Damette, Alexandre; Barouk-Simonet, Emmanuelle; Bonnet, Françoise; Bubien, Virginie; Sevenet, Nicolas; Longy, Michel; Berthet, Pascaline; Vaur, Dominique; Castera, Laurent; Ferrer, Sandra Fert; Bignon, Yves-Jean; Uhrhammer, Nancy; Coron, Fanny; Faivre, Laurence; Baurand, Amandine; Jacquot, Caroline; Bertolone, Geoffrey; Lizard, Sarab; Leroux, Dominique; Dreyfus, Hélène; Rebischung, Christine; Peysselon, Magalie; Peyrat, Jean-Philippe; Fournier, Joëlle; Révillion, Françoise; Adenis, Claude; Vénat-Bouvet, Laurence; Léone, Mélanie; Boutry-Kryza, Nadia; Calender, Alain; Giraud, Sophie; Verny-Pierre, Carole; Lasset, Christine; Bonadona, Valérie; Barjhoux, Laure; Sobol, Hagay; Bourdon, Violaine; Noguchi, Tetsuro; Remenieras, Audrey; Coupier, Isabelle; Pujol, Pascal; Sokolowska, Johanna; Bronner, Myriam; Delnatte, Capucine; Bézieau, Stéphane; Mari, Véronique; Gauthier-Villars, Marion; Buecher, Bruno; Rouleau, Etienne; Golmard, Lisa; Moncoutier, Virginie; Belotti, Muriel; de Pauw, Antoine; Elan, Camille; Fourme, Emmanuelle; Birot, Anne-Marie; Saule, Claire; Laurent, Maïté; Houdayer, Claude; Lesueur, Fabienne; Mebirouk, Noura; Coulet, Florence; Colas, Chrystelle; Soubrier, Florent; Warcoin, Mathilde; Prieur, Fabienne; Lebrun, Marine; Kientz, Caroline; Muller, Danièle; Fricker, Jean-Pierre; Toulas, Christine; Guimbaud, Rosine; Gladieff, Laurence; Feillel, Viviane; Mortemousque, Isabelle; Bressac-de-Paillerets, Brigitte; Caron, Olivier; Guillaud-Bataille, Marine; Cook, Linda S.; Cox, Angela; Cramer, Daniel W.; Cross, Simon S.; Cybulski, Cezary; Czene, Kamila; Daly, Mary B.; Damiola, Francesca; Dansonka-Mieszkowska, Agnieszka; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Diez, Orland; Doherty, Jennifer A.; Domchek, Susan M.; Dorfling, Cecilia M.; Dörk, Thilo; Dumont, Martine; Ehrencrona, Hans; Ejlertsen, Bent; Ellis, Steve; Gregory, Helen; Miedzybrodzka, Zosia; Morrison, Patrick J.; Donaldson, Alan; Rogers, Mark T.; Kennedy, M. John; Porteous, Mary E.; Brady, Angela; Barwell, Julian; Foo, Claire; Lalloo, Fiona; Side, Lucy E.; Eason, Jacqueline; Henderson, Alex; Walker, Lisa; Cook, Jackie; Snape, Katie; Murray, Alex; McCann, Emma; Engel, Christoph; Lee, Eunjung; Evans, D. Gareth; Fasching, Peter A.; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Foretova, Lenka; Fostira, Florentia; Foulkes, William D.; Fridley, Brooke L.; Friedman, Eitan; Frost, Debra; Gambino, Gaetana; Ganz, Patricia A.; Garber, Judy; García-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Ghoussaini, Maya; Giles, Graham G.; Glasspool, Rosalind; Godwin, Andrew K.; Goldberg, Mark S.; Goldgar, David E.; González-Neira, Anna; Goode, Ellen L.; Goodman, Marc T.; Greene, Mark H.; Gronwald, Jacek; Guénel, Pascal; Haiman, Christopher A.; Hall, Per; Hallberg, Emily; Hamann, Ute; Hansen, Thomas V. O.; Harrington, Patricia A.; Hartman, Mikael; Hassan, Norhashimah; Healey, Sue; Rookus, M. A.; van Leeuwen, F. E.; van der Kolk, L. E.; Schmidt, M. K.; Russell, N. S.; de Lange, J. L.; Wijnands, R.; Collée, J. M.; Hooning, M. J.; Seynaeve, C.; van Deurzen, C. H. M.; Obdeijn, I. M.; van Asperen, C. J.; Tollenaar, R. A. E. M.; van Cronenburg, T. C. T. E. F.; Kets, C. M.; Ausems, M. G. E. M.; van der Pol, C. C.; van Os, T. A. M.; Waisfisz, Q.; Meijers-Heijboer, H. E. J.; Gómez-Garcia, E. B.; Oosterwijk, J. C.; Mourits, M. J.; de Bock, G. H.; Vasen, H. F.; Siesling, S.; Verloop, J.; Overbeek, L. I. H.; Heitz, Florian; Herzog, Josef; Høgdall, Estrid; Høgdall, Claus K.; Hogervorst, Frans B. L.; Hollestelle, Antoinette; Hopper, John L.; Hulick, Peter J.; Huzarski, Tomasz; Imyanitov, Evgeny N.; Fox, Stephen; Kirk, Judy; Lindeman, Geoff; Price, Melanie; Bowtell, David; deFazio, Anna; Webb, Penny; Isaacs, Claudine; Ito, Hidemi; Jakubowska, Anna; Janavicius, Ramunas; Jensen, Allan; John, Esther M.; Johnson, Nichola; Kabisch, Maria; Kang, Daehee; Kapuscinski, Miroslav; Karlan, Beth Y.; Khan, Sofia; Kiemeney, Lambertus A.; Kjaer, Susanne Kruger; Knight, Julia A.; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kupryjanczyk, Jolanta; Kwong, Ava; de la Hoya, Miguel; Laitman, Yael; Lambrechts, Diether; Le, Nhu; De Leeneer, Kim; Lester, Jenny; Levine, Douglas A.; Li, Jingmei; Lindblom, Annika; Long, Jirong; Lophatananon, Artitaya; Loud, Jennifer T.; Lu, Karen; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Le Marchand, Loic; Margolin, Sara; Marme, Frederik; Massuger, Leon F. A. G.; Matsuo, Keitaro; Mazoyer, Sylvie; McGuffog, Lesley; McLean, Catriona; McNeish, Iain; Meindl, Alfons; Menon, Usha; Mensenkamp, Arjen R.; Milne, Roger L.; Montagna, Marco; Moysich, Kirsten B.; Muir, Kenneth; Mulligan, Anna Marie; Nathanson, Katherine L.; Ness, Roberta B.; Neuhausen, Susan L.; Nevanlinna, Heli; Nord, Silje; Nussbaum, Robert L.; Odunsi, Kunle; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I.; Olson, Janet E.; Olswold, Curtis; O'Malley, David; Orlow, Irene; Orr, Nick; Osorio, Ana; Park, Sue Kyung; Pearce, Celeste L.; Pejovic, Tanja; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M.; Poole, Elizabeth M.; Pylkäs, Katri; Radice, Paolo; Rantala, Johanna; Rashid, Muhammad Usman; Rennert, Gad; Rhenius, Valerie; Rhiem, Kerstin; Risch, Harvey A.; Rodriguez, Gus; Rossing, Mary Anne; Rudolph, Anja; Salvesen, Helga B.; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schildkraut, Joellen M.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Sellers, Thomas A.; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Sieh, Weiva; Singer, Christian F.; Sinilnikova, Olga M.; Slager, Susan; Song, Honglin; Soucy, Penny; Southey, Melissa C.; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Sutter, Christian; Swerdlow, Anthony; Tchatchou, Sandrine; Teixeira, Manuel R.; Teo, Soo H.; Terry, Kathryn L.; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; Toland, Amanda Ewart; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Tseng, Chiu-chen; Tung, Nadine; Tworoger, Shelley S.; Vachon, Celine; van den Ouweland, Ans M. W.; van Doorn, Helena C.; van Rensburg, Elizabeth J.; Van't Veer, Laura J.; Vanderstichele, Adriaan; Vergote, Ignace; Vijai, Joseph; Wang, Qin; Wang-Gohrke, Shan; Weitzel, Jeffrey N.; Wentzensen, Nicolas; Whittemore, Alice S.; Wildiers, Hans; Winqvist, Robert; Wu, Anna H.; Yannoukakos, Drakoulis; Yoon, Sook-Yee; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Khanna, Kum Kum; Simard, Jacques; Monteiro, Alvaro N.; French, Juliet D.; Couch, Fergus J.; Freedman, Matthew L.; Easton, Douglas F.; Dunning, Alison M.; Pharoah, Paul D.; Edwards, Stacey L.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Gayther, Simon A.

    2016-01-01

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10−3) and ABHD8 (P<2 × 10−3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk. PMID:27601076

  13. Regulation of matrix stiffness on the epithelial-mesenchymal transition of breast cancer cells under hypoxia environment

    Science.gov (United States)

    Lv, Yonggang; Chen, Can; Zhao, Boyuan; Zhang, Xiaomei

    2017-06-01

    Substrate stiffness and hypoxia are associated with tumor development and progression, respectively. However, the synergy of them on the biological behavior of human breast cancer cell is still largely unknown. This study explored how substrate stiffness regulates the cell phenotype, viability, and epithelial-mesenchymal transition (EMT) of human breast cancer cells MCF-7 under hypoxia (1% O2). TRITC-phalloidin staining showed that MCF-7 cells transformed from round to irregular polygon with stiffness increase either in normoxia or hypoxia. While being accompanied with the upward tendency from a 0.5- to a 20-kPa substrate, the percentage of cell apoptosis was significantly higher in hypoxia than that in normoxia, especially on the 20-kPa substrate. Additionally, it was hypoxia, but not normoxia, that promoted the EMT of MCF-7 by upregulating hypoxia-inducible factor-1α (HIF-1α), vimentin, Snail 1, and matrix metalloproteinase 2 (MMP 2) and 9 (MMP 9), and downregulating E-cadherin simultaneously regardless of the change of substrate stiffness. In summary, this study discovered that hypoxia and stiffer substrate (20 kPa) could synergistically induce phenotype change, apoptosis, and EMT of MCF-7 cells. Results of this study have an important significance on further exploring the synergistic effect of stiffness and hypoxia on the EMT of breast cancer cells and its molecular mechanism.

  14. Optimizing Persistent Random Searches

    Science.gov (United States)

    Tejedor, Vincent; Voituriez, Raphael; Bénichou, Olivier

    2012-02-01

    We consider a minimal model of persistent random searcher with a short range memory. We calculate exactly for such a searcher the mean first-passage time to a target in a bounded domain and find that it admits a nontrivial minimum as function of the persistence length. This reveals an optimal search strategy which differs markedly from the simple ballistic motion obtained in the case of Poisson distributed targets. Our results show that the distribution of targets plays a crucial role in the random search problem. In particular, in the biologically relevant cases of either a single target or regular patterns of targets, we find that, in strong contrast to repeated statements in the literature, persistent random walks with exponential distribution of excursion lengths can minimize the search time, and in that sense perform better than any Levy walk.

  15. Defining persistent hotspots

    DEFF Research Database (Denmark)

    Kittur, Nupur; Binder, Sue; Campbell, Carl H.

    2017-01-01

    , investigators and neglected tropical disease (NTD) program managers need to define them based on changes in prevalence and/or intensity. But how should the data be analyzed to define a persistent hotspot? We have analyzed a dataset from an operational research study in western Tanzania after three annual MDAs...... and contrast the outcomes of these analyses. Our intent is to showhowthe samedataset yields different numbers of persistent hotspots depending on the approach used to define them. We suggest that investigators and NTD program managers use the approach most suited for their study or program, but whichever...... using four different approaches to define persistent hotspots. The four approaches are 1) absolute percent change in prevalence; 2) percent change in prevalence; 3) change in World Health Organization guideline categories; 4) change (absolute or percent) in both prevalence and intensity. We compare...

  16. Persistent luminescence nanothermometers

    Science.gov (United States)

    Martín Rodríguez, Emma; López-Peña, Gabriel; Montes, Eduardo; Lifante, Ginés; García Solé, José; Jaque, Daniel; Diaz-Torres, Luis Armando; Salas, Pedro

    2017-08-01

    Persistent phosphorescence nanoparticles emitting in the red and near-infrared spectral regions are strongly demanded as contrast nanoprobes for autofluorescence free bioimaging and biosensing. In this work, we have developed Sr4Al14O25:Eu2+, Cr3+, Nd3+ nanopowders that produce persistent red phosphorescence peaking at 694 nm generated by Cr3+ ions. This emission displays temperature sensitivity in the physiological temperature range (20-60 °C), which makes these nanoparticles potentially useful as fluorescence (contactless) nanothermometers operating without requiring optical excitation. Nd3+ ions, which act as shallow electron traps for the red Cr3+ persistent emission, also display infrared emission bands, extending the fluorescence imaging capability to the second biological window. This unique combination of properties makes these nanoparticles multifunctional luminescent probes with great potential applications in nanomedicine.

  17. Persistent physical symptoms as perceptual dysregulation

    DEFF Research Database (Denmark)

    Henningsen, Peter; Gündel, Harald; Kop, Willem J

    2018-01-01

    OBJECTIVE: The mechanisms underlying the perception and experience of persistent physical symptoms are not well understood, and in the models, the specific relevance of peripheral input versus central processing, or of neurobiological versus psychosocial factors in general, is not clear.In this a......OBJECTIVE: The mechanisms underlying the perception and experience of persistent physical symptoms are not well understood, and in the models, the specific relevance of peripheral input versus central processing, or of neurobiological versus psychosocial factors in general, is not clear...... of predictions and sensory input. Two possibilities exist: adaptation of the generative model underlying the predictions or alteration of the sensory input via autonomic nervous activation (in the case of interoception). Following this model, persistent physical symptoms can be described as "failures...

  18. Evaluation of radioactive seeds implantation under PET-CT guidance for the treatment of central lung cancer with obstructive atelectasis

    International Nuclear Information System (INIS)

    Zhou Yi; Jiang Zhongpu; Wang Haiting; Zhang Yanjun; Jiang Qiang; Wang Jun; Ren Lijun; Xie Bin

    2010-01-01

    Objective: To evaluate percutaneous puncturing 125 I seed implantation by using PET-CT guided target localization technique in treating central lung cancer complicated by obstructive pulmonary atelectasis. Methods: A total of 30 patients with suspected central lung cancer complicated by obstructive pulmonary atelectasis on preoperative chest films were enrolled in this study. As no clear distinction existed between the tumor and the atelectatic consolidation shadow on plain chest films, CT scanning was carried out in all patients. If CT scan was still not able to determine the margin of the tumor, an additional PET-CT scanning was adopted. After ascertaining the location of the lung cancer, percutaneous puncturing implantation of 125 I seeds under PET-CT guidance was performed. The clinical data and the therapeutic results were evaluated. Results: A sharp distinction between the tumor and the atelectatic consolidation shadow was demonstrated on PET-CT scans in 21 cases. The mean volume of the targeted lesion reckoned from PET-CT scans was 26 cm 3 , and the 125 I seeds were implanted. The mean volume of the targeted lesion calculated on CT scans was 37 cm 3 . Six months after the treatment, the follow-up CT exam showed that the effective rate was 93% (28/30). The one-year survival rate was 100% . The complications included pneumothorax (n = 8), small amount of hemoptysis (n = 12) and fever (n = 2). No displacement or immigration of the implanted seeds occurred. Conclusion: PET-CT scanning is far superior to conventional CT scanning in determining the target area of the tumor in patients with central lung cancer complicated by obstructive pulmonary atelectasis. (authors)

  19. Sexual well-being of cervical cancer survivors under 50 years old and the factors affecting their libido.

    Science.gov (United States)

    Tian, Jun

    2013-01-01

    This paper aims to study the relationship between the sexual well-being and quality of life (QOL) of cervical cancer patients and analyze the factors influencing their libidos. The subjects in this study were Chinese cervical cancer survivors under 50 years old. The information on their disease and treatments was obtained through their medical records. The subjects were surveyed in their homes regarding their sexual well-being, age, educational level, and QOL. 59% of the subjects did not want to have a sex life, and 65.09% were unsatisfied with their sex life. Among the women who did not want to have a sex life, the following reasons were given: 52.38% due to the side effects of treatments, 23.81% feared that sex would damage their surgical sites, 9.52% lacked libido, 9.52% feared that sex would make their conditions worse, and 4.76% feared that having sex would transmit the disease to their spouses. After adjusting the age and survival time, the women's sexual well-being was able to explain 61.80% of the variations in QOL. In addition, libido and sexual satisfaction affected the women's social/family well-being (both p < 0.01). The sexual well-being of Chinese women with cervical cancer is poor. The main reasons for not wanting to have a sex life are treatment-induced vaginal conditions and lack of disease- and treatment-related knowledge. Improvement of women's sexual well-being plays an important role in the improvement of their QOL. Healthcare nurses should be concerned about women's needs for sex-related knowledge after cervical cancer treatment and provide them with psychological help.

  20. Hormonal homeostasis in lung cancer patients under combined and radiation treatment

    International Nuclear Information System (INIS)

    Zotova, I.A.; Firsova, P.P.; Matveenko, E.G.

    1984-01-01

    Radioimmunoassay of hormonal homeostasis was performed in 200 lung cancer patients before and after combined and radiation treatment and in 25 healthy subjects (controls). The study showed an increase in the basal level of hormones of pituitary - adrenal system matched by a decline in thyroid function. Adequate combined and radiation treatment brought hormone levels to normal. Hormonal disorders accompanying recurrence were identical to those registered at disease onset. In some cases, changes in hormonal homeostasis developed as early as 3-6 months prior to clinically manifest recurrences or dissemination

  1. Vascular damage as an underlying mechanism of cardiac and cerebral toxicity in irradiated cancer patients.

    Science.gov (United States)

    Stewart, F A; Hoving, S; Russell, N S

    2010-12-01

    Radiation is an independent risk factor for cardiovascular and cerebrovascular disease in cancer patients. Modern radiotherapy techniques reduce the volume of the heart and major coronary vessels exposed to high doses, but some exposure is often unavoidable. Radiation damage to the myocardium is caused primarily by inflammatory changes in the microvasculature, leading to microthrombi and occlusion of vessels, reduced vascular density, perfusion defects and focal ischemia. This is followed by progressive myocardial cell death and fibrosis. Clinical studies also demonstrate regional perfusion defects in non-symptomatic breast cancer patients after radiotherapy. The incidence and extent of perfusion defects are related to the volume of left ventricle included in the radiation field. Irradiation of endothelial cells lining large vessels also increases expression of inflammatory molecules, leading to adhesion and transmigration of circulating monocytes. In the presence of elevated cholesterol, invading monocytes transform into activated macrophages and form fatty streaks in the intima, thereby initiating the process of atherosclerosis. Experimental studies have shown that radiation predisposes to the formation of inflammatory plaque, which is more likely to rupture and cause a fatal heart attack or stroke. This paper presents a brief overview of the current knowledge on mechanisms for development of radiation-induced cardiovascular and cerebrovascular damage. It does not represent a comprehensive review of the literature, but reference is made to several excellent recent reviews on the topic.

  2. Directed migration of cancer cells by the graded texture of the underlying matrix

    Science.gov (United States)

    Park, JinSeok; Kim, Deok-Ho; Kim, Hong-Nam; Wang, Chiaochun Joanne; Kwak, Moon Kyu; Hur, Eunmi; Suh, Kahp-Yang; An, Steven S.; Levchenko, Andre

    2016-01-01

    Living cells and the extracellular matrix (ECM) can display complex interactions that define key developmental, physiological and pathological processes. Here, we report a new type of directed migration — which we term ‘topotaxis’ — by which cell movement is guided by the gradient of the nanoscale topographic features in the cells’ ECM environment. We show that the direction of topotaxis is reflective of the effective cell stiffness, and that it depends on the balance of the ECM-triggered signalling pathways PI3K-Akt and ROCK-MLCK. In melanoma cancer cells, this balance can be altered by different ECM inputs, pharmacological perturbations or genetic alterations, particularly a loss of PTEN in aggressive melanoma cells. We conclude that topotaxis is a product of the material properties of cells and the surrounding ECM, and propose that the invasive capacity of many cancers may depend broadly on topotactic responses, providing a potentially attractive mechanism for controlling invasive and metastatic behaviour. PMID:26974411

  3. Contributions to Persistence Theory

    Directory of Open Access Journals (Sweden)

    Du Dong

    2014-12-01

    Full Text Available Persistence theory discussed in this paper is an application of algebraic topology (Morse Theory [29] to Data Analysis, precisely to qualitative understanding of point cloud data, or PCD for short. PCD can be geometrized as a filtration of simplicial complexes (Vietoris-Rips complex [25] [36] and the homology changes of these complexes provide qualitative information about the data. Bar codes describe the changes in homology with coefficients in a fixed field. When the coefficient field is ℤ2, the calculation of bar codes is done by ELZ algorithm (named after H. Edelsbrunner, D. Letscher, and A. Zomorodian [20]. When the coefficient field is ℝ, we propose an algorithm based on the Hodge decomposition [17]. With Dan Burghelea and Tamal K. Dey we developed a persistence theory which involves level sets discussed in Section 4. We introduce and discuss new computable invariants, the “relevant level persistence numbers” and the “positive and negative bar codes”, and explain how they are related to the bar codes for level persistence. We provide enhancements and modifications of ELZ algorithm to calculate such invariants and illustrate them by examples.

  4. Persistent organic pollutants

    NARCIS (Netherlands)

    Dungen, van den M.W.

    2016-01-01

    Wild caught fish, especially marine fish, can contain high levels of persistent organic pollutants (POPs). In the Netherlands, especially eel from the main rivers have high POP levels. This led to a ban in 2011 on eel fishing due to health concerns. Many of the marine POPs have been related to

  5. Persistent organic pollutants

    NARCIS (Netherlands)

    Dungen, van den M.W.

    2016-01-01

    Wild caught fish, especially marine fish, can contain high levels of persistent organic pollutants (POPs). In the Netherlands, especially eel from the main rivers have high POP levels. This led to a ban in 2011 on eel fishing due to health concerns. Many of the marine POPs have been related to

  6. Is corruption really persistent?

    NARCIS (Netherlands)

    Seldadyo, H.; de Haan, J.

    Theoretical and empirical research on corruption generally concludes that corruption is persistent. However, using International Country Risk Guide data for the period 1984-2008 for 101 countries, we find strong evidence that corruption changes over time. In the present study, corruption levels of

  7. Antiproliferative activity of 8-methoxypsoralen on DU145 prostate cancer cells under UVA and blue light.

    Science.gov (United States)

    Sturaro, Giulio; Cigolini, Giulia; Menilli, Luca; Cola, Fabio; Di Liddo, Rosa; Tasso, Alessia; Conconi, Maria Teresa; Miolo, Giorgia

    2017-07-01

    The use of photoactivatable 8-methoxypsoralen (8-MOP) as potential focal treatment towards prostate cancer cells is proposed here. Our results, obtained on isolated DNA and DU145 cells, indicate that blue light, besides UVA, is able to activate 8-MOP. When compared to UVA, blue light irradiation led to a modulation of the extent and the types of 8-MOP-DNA damage, specially cross-links, coupled to a still valuable antiproliferative effect. Our data suggest that the proapototic activity of 8-MOP is related not only to DNA damage and reactive oxygen species generation but also to the modulation of cell signalling pathways. In particular, a different activation of p38 and p44/42 mitogen-activated protein kinases was detected depending on the light wavelengths.

  8. Bone marrow-derived mesenchymal stromal cells promote colorectal cancer cell death under low-dose irradiation.

    Science.gov (United States)

    Feng, Hao; Zhao, Jing-Kun; Schiergens, Tobias S; Wang, Pu-Xiongzhi; Ou, Bao-Chi; Al-Sayegh, Rami; Li, Ming-Lun; Lu, Ai-Guo; Yin, Shuai; Thasler, Wolfgang E

    2018-02-06

    Radiotherapy remains one of the cornerstones to improve the outcome of colorectal cancer (CRC) patients. Radiotherapy of the CRC not only help to destroy cancer cells but also remodel the tumour microenvironment by enhancing tumour-specific tropism of bone marrow-derived mesenchymal stromal cell (BM-MSC) from the peripheral circulation. However, the role of local MSCs and recruited BM-MSC under radiation were not well defined. Indeed, the functions of BM-MSC without irradiation intervention remained controversial in tumour progression: BM-MSC was previously shown to modulate the immune function of major immune cells, resulting in an impaired immunological sensitivity and to induce an increased risk of tumour recurrence. In contrast, it could also secrete various cytokines and possess anticancer effect. Three co-cultivation modules, 3D culture modules, and cancer organoids were established. The induction of cytokines secretion in hBM-MSCs after irradiation was analysed by ELISA array and flow cytometry. AutoMac separator was used to separate hBM-MSC and CRC automatically. Cells from the co-cultured group and the control group were then irradiated by UV-C lamp and X-ray. Proliferation assay and viability assay were performed. In this study, we show that BM-MSCs can induce the EMT progression of CRC cells in vitro. When irradiated with low doses of ultraviolet radiation and X-rays, BM-MSCs show an anti-tumour effect by secreting certain cytokine (TNF-α, IFN-γ) that lead to the inhibition of proliferation and induction of apoptosis of CRC cells. This was further verified in a 3D culture model of a CRC cell in vitro. Furthermore, irradiation on the co-culture system induced the cleavage of caspase3, and attenuated the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT and extracellular signal-regulated kinase in cancer cells. The signal pathways above might contribute to the cancer cell death. Taken together, we show that BM-MSC can potentially promote the

  9. Blinded Anonymization: a method for evaluating cancer prevention programs under restrictive data protection regulations.

    Science.gov (United States)

    Bartholomäus, Sebastian; Hense, Hans Werner; Heidinger, Oliver

    2015-01-01

    Evaluating cancer prevention programs requires collecting and linking data on a case specific level from multiple sources of the healthcare system. Therefore, one has to comply with data protection regulations which are restrictive in Germany and will likely become stricter in Europe in general. To facilitate the mortality evaluation of the German mammography screening program, with more than 10 Million eligible women, we developed a method that does not require written individual consent and is compliant to existing privacy regulations. Our setup is composed of different data owners, a data collection center (DCC) and an evaluation center (EC). Each data owner uses a dedicated software that preprocesses plain-text personal identifiers (IDAT) and plaintext evaluation data (EDAT) in such a way that only irreversibly encrypted record assignment numbers (RAN) and pre-aggregated, reversibly encrypted EDAT are transmitted to the DCC. The DCC uses the RANs to perform a probabilistic record linkage which is based on an established and evaluated algorithm. For potentially identifying attributes within the EDAT ('quasi-identifiers'), we developed a novel process, named 'blinded anonymization'. It allows selecting a specific generalization from the pre-processed and encrypted attribute aggregations, to create a new data set with assured k-anonymity, without using any plain-text information. The anonymized data is transferred to the EC where the EDAT is decrypted and used for evaluation. Our concept was approved by German data protection authorities. We implemented a prototype and tested it with more than 1.5 Million simulated records, containing realistically distributed IDAT. The core processes worked well with regard to performance parameters. We created different generalizations and calculated the respective suppression rates. We discuss modalities, implications and limitations for large data sets in the cancer registry domain, as well as approaches for further

  10. Cancer

    Science.gov (United States)

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

  11. The Effects of Compliance with Nutritional Counselling on Body Composition Parameters in Head and Neck Cancer Patients under Radiotherapy

    Directory of Open Access Journals (Sweden)

    D. Hopanci Bicakli

    2017-01-01

    Full Text Available Background. Radiotherapy (RT has been associated with increased risk of malnutrition in cancer patients, particularly in those with head and neck cancer (HNC. The aim of this prospective study was to evaluate the effects of compliance of patients with individual dietary counselling on body composition parameters in HNC patients under RT. Material and Methods. Sixty-nine consecutive patients (mean age: 61.0±13.8 were prospectively followed. Bioelectrical impedance analysis (BIA was performed to determine body composition parameters before, in the middle of, and at the end of RT. All patients received nutritional counselling and majority of them (94.6% received oral nutritional supplement (ONS during RT or chemoradiotherapy. If a patient consumed ≥75% of the recommended energy and protein intake via ONS and regular food, he/she was considered to be “compliant” (n=18, while those who failed to meet this criteria were considered to be “noncompliant” (n=30. Results. Body mass index, weight, fat percentage, fat mass, fat free mass, and muscle mass did not decrease significantly over time in compliant patients, but in noncompliant patients, all of these indices decreased significantly from baseline compared to the end of treatment (p<0.001. Hand grip strength did not differ significantly between the two groups at baseline and over time in each group. When retrospectively evaluated, heavy mucositis was less commonly observed in compliant than noncompliant patients (11.1% versus 88.9%, resp. (p<0.009. Conclusion. We conclude that body composition parameters were better in head and neck cancer patients considered as compliant with nutritional counselling than noncompliant ones during RT period.

  12. Modulation of cellular redox state underlies antagonism between oxaliplatin and cetuximab in human colorectal cancer cell lines.

    Science.gov (United States)

    Dahan, Laetitia; Sadok, Amine; Formento, Jean-Louis; Seitz, Jean François; Kovacic, Hervé

    2009-09-01

    Oxaliplatin is the first platinum-based compound effective in the treatment of colorectal cancer. Oxaliplatin combined with cetuximab for metastatic colorectal cancer is under evaluation. The preliminary results seem controversial, particularly for the use of cetuximab in K-Ras mutated patients. K-Ras mutation is known to affect redox homeostasis. Here we evaluated how the efficacy of oxaliplatin alone or combined with cetuximab varied according to the Ras mutation and redox status in a panel of colorectal tumour cell lines. Viability was evaluated by methylthiazoletetrazolium assay, reactive oxygen species production by DCFDA and lucigenin on HT29-D4, Caco-2, SW480 and SW620 cell lines. Combination of oxaliplatin and cetuximab was less cytotoxic than oxaliplatin alone in colorectal cells harbouring wild-type Ras and membrane expression of receptors for epidermal growth factor receptor (EGFR), such as HT29-D4 and Caco-2 cells. In contrast, cetuximab did not affect oxaliplatin efficiency in cells harbouring K-Ras(V12) mutation, irrespective of membrane EGFR expression (SW620 and SW480 cells). Transfection of HT29-D4 with K-Ras(V12) decreased oxaliplatin IC(50) and impaired cetuximab sensitivity, without affecting expression of membrane EGFR compared with HT29-D4 control. Oxaliplatin efficacy relies on endogenous production of H(2)O(2). Cetuximab inhibits H(2)O(2) production inhibiting the EGFR/Nox1 NADPH oxidase pathway. Oxaliplatin efficacy was impaired by short hairpin RNA for Nox1 and by catalase (H(2)O(2) scavenger). Cetuximab limited oxaliplatin efficiency by affecting the redox status of cancer cells through Nox1. Such combined therapy might be improved by controlling H(2)O(2) elimination.

  13. Introduction: Persistent Modelling

    DEFF Research Database (Denmark)

    Ayres, Phil

    2012-01-01

    of this relationship is becoming increasingly variegated. This is apparent in three principle areas; the duration of active influence that representation can hold in relation to the represented; the means, methods and media through which representations are constructed and used; what it is that is being represented.......This introduction to 'Persistent Modelling – an extended role for architectural representation' identifies how the book probes the relationship between representation and the represented, in an architectural context. It discusses how the book presents an examination and discussion of historical......, familiar contemporary and, perhaps, not so familiar emerging manifestations of this relation. What persists from this probing, fully intact, is that representation and the represented remain inextricably related in our contemporary and emerging practices. What comes into focus is that the nature...

  14. Persistent facial pain conditions

    DEFF Research Database (Denmark)

    Forssell, Heli; Alstergren, Per; Bakke, Merete

    2016-01-01

    Persistent facial pains, especially temporomandibular disorders (TMD), are common conditions. As dentists are responsible for the treatment of most of these disorders, up-to date knowledge on the latest advances in the field is essential for successful diagnosis and management. The review covers...... TMD, and different neuropathic or putative neuropathic facial pains such as persistent idiopathic facial pain and atypical odontalgia, trigeminal neuralgia and painful posttraumatic trigeminal neuropathy. The article presents an overview of TMD pain as a biopsychosocial condition, its prevalence......, clinical features, consequences, central and peripheral mechanisms, diagnostic criteria (DC/TMD), and principles of management. For each of the neuropathic facial pain entities, the definitions, prevalence, clinical features, and diagnostics are described. The current understanding of the pathophysiology...

  15. Persistent Hiccups Following Stapedectomy

    Directory of Open Access Journals (Sweden)

    Aidonis I

    2010-10-01

    Full Text Available Objective: We report a case of a 37 year-old man who developed persistent hiccups after elective stapedectomy. Method and Results: The diagnostic approach is discussed as well as the non-pharmacologic and pharmacologic treatments and overall management. The aim is to stress that there is a variety of potential factors that can induce hiccups perioperatively and in cases like this a step by step approach must be taken. Conclusion: Persistent hiccups are very rare following stapedectomy, control of them is crucial for the successful outcome. The trigger may be more than one factors and the good response to treatment may be due to dealing successfully with more than one thing.

  16. Persistent misconceptions regarding SERS.

    Science.gov (United States)

    Moskovits, Martin

    2013-04-21

    SERS is some 35 years old, and the subject of over 11 000 articles. The field of Plasmonics, and large aspects of Metamaterials are clearly based on concepts that became current as a result of SERS. Despite this, a number of persistent, fuzzy ideas about the origin of the enhancement in SERS continue to be current even among SERS researchers, leading to the external impression that SERS is uniquely poorly understood. Six such ideas are discussed.

  17. MEK inhibitors under development for treatment of non-small-cell lung cancer.

    Science.gov (United States)

    Kim, Chul; Giaccone, Giuseppe

    2018-01-01

    The mitogen-activated protein kinase (MAPK) pathway is intimately implicated in the molecular pathogenesis of non-small-cell lung cancer (NSCLC). Aberrant MAPK signaling resulting from the upstream activating mutations converges on mitogen-activated protein kinase kinase 1/2 (MEK1/2), making MEK inhibition an attractive strategy for the treatment of NSCLC. Several MEK inhibitors have demonstrated anticancer activity in patients with NSCLC. Areas covered: In this article, we discuss the biological rationale for the use of MEK inhibitors and summarize the clinical experience with MEK1/2 inhibitors for the treatment of NSCLC, from initial phase I studies to phase II/III studies, both as monotherapy or in combination with other anticancer agents. Expert opinion: Trametinib in combination with the BRAF inhibitor dabrafenib represents the first MEK1/2 inhibitor containing regimen that is approved for advanced BRAF V600E -mutant NSCLC. Other MEK1/2 inhibitors that are also in advanced stages of clinical development include selumetinib, cobimetinib, and binimetinib. Several studies of MEK inhibitor combination therapies are underway, including trials using combined MEK inhibition and immune checkpoint blockade. Further research aimed at discovering biomarkers of response and resistance to MEK1/2 inhibitors will be needed to develop rational combination strategies for the treatment of NSCLC driven by aberrant MAPK signaling.

  18. Numeric invariants from multidimensional persistence

    Energy Technology Data Exchange (ETDEWEB)

    Skryzalin, Jacek [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Carlsson, Gunnar [Stanford Univ., Stanford, CA (United States)

    2017-05-19

    In this paper, we analyze the space of multidimensional persistence modules from the perspectives of algebraic geometry. We first build a moduli space of a certain subclass of easily analyzed multidimensional persistence modules, which we construct specifically to capture much of the information which can be gained by using multidimensional persistence over one-dimensional persistence. We argue that the global sections of this space provide interesting numeric invariants when evaluated against our subclass of multidimensional persistence modules. Lastly, we extend these global sections to the space of all multidimensional persistence modules and discuss how the resulting numeric invariants might be used to study data.

  19. Type I and Type II Interferon Coordinately Regulate Suppressive Dendritic Cell Fate and Function during Viral Persistence.

    Directory of Open Access Journals (Sweden)

    Cameron R Cunningham

    2016-01-01

    Full Text Available Persistent viral infections are simultaneously associated with chronic inflammation and highly potent immunosuppressive programs mediated by IL-10 and PDL1 that attenuate antiviral T cell responses. Inhibiting these suppressive signals enhances T cell function to control persistent infection; yet, the underlying signals and mechanisms that program immunosuppressive cell fates and functions are not well understood. Herein, we use lymphocytic choriomeningitis virus infection (LCMV to demonstrate that the induction and functional programming of immunosuppressive dendritic cells (DCs during viral persistence are separable mechanisms programmed by factors primarily considered pro-inflammatory. IFNγ first induces the de novo development of naive monocytes into DCs with immunosuppressive potential. Type I interferon (IFN-I then directly targets these newly generated DCs to program their potent T cell immunosuppressive functions while simultaneously inhibiting conventional DCs with T cell stimulating capacity. These mechanisms of monocyte conversion are constant throughout persistent infection, establishing a system to continuously interpret and shape the immunologic environment. MyD88 signaling was required for the differentiation of suppressive DCs, whereas inhibition of stimulatory DCs was dependent on MAVS signaling, demonstrating a bifurcation in the pathogen recognition pathways that promote distinct elements of IFN-I mediated immunosuppression. Further, a similar suppressive DC origin and differentiation was also observed in Mycobacterium tuberculosis infection, HIV infection and cancer. Ultimately, targeting the underlying mechanisms that induce immunosuppression could simultaneously prevent multiple suppressive signals to further restore T cell function and control persistent infections.

  20. Type I and Type II Interferon Coordinately Regulate Suppressive Dendritic Cell Fate and Function during Viral Persistence

    Science.gov (United States)

    Cunningham, Cameron R.; Champhekar, Ameya; Tullius, Michael V.; Dillon, Barbara Jane; Zhen, Anjie; de la Fuente, Justin Rafael; Herskovitz, Jonathan; Elsaesser, Heidi; Snell, Laura M.; Wilson, Elizabeth B.; de la Torre, Juan Carlos; Kitchen, Scott G.; Horwitz, Marcus A.; Bensinger, Steven J.; Smale, Stephen T.; Brooks, David G.

    2016-01-01

    Persistent viral infections are simultaneously associated with chronic inflammation and highly potent immunosuppressive programs mediated by IL-10 and PDL1 that attenuate antiviral T cell responses. Inhibiting these suppressive signals enhances T cell function to control persistent infection; yet, the underlying signals and mechanisms that program immunosuppressive cell fates and functions are not well understood. Herein, we use lymphocytic choriomeningitis virus infection (LCMV) to demonstrate that the induction and functional programming of immunosuppressive dendritic cells (DCs) during viral persistence are separable mechanisms programmed by factors primarily considered pro-inflammatory. IFNγ first induces the de novo development of naive monocytes into DCs with immunosuppressive potential. Type I interferon (IFN-I) then directly targets these newly generated DCs to program their potent T cell immunosuppressive functions while simultaneously inhibiting conventional DCs with T cell stimulating capacity. These mechanisms of monocyte conversion are constant throughout persistent infection, establishing a system to continuously interpret and shape the immunologic environment. MyD88 signaling was required for the differentiation of suppressive DCs, whereas inhibition of stimulatory DCs was dependent on MAVS signaling, demonstrating a bifurcation in the pathogen recognition pathways that promote distinct elements of IFN-I mediated immunosuppression. Further, a similar suppressive DC origin and differentiation was also observed in Mycobacterium tuberculosis infection, HIV infection and cancer. Ultimately, targeting the underlying mechanisms that induce immunosuppression could simultaneously prevent multiple suppressive signals to further restore T cell function and control persistent infections. PMID:26808628

  1. Oxaliplatin-Induced Leukocytoclastic Vasculitis under Adjuvant Chemotherapy for Colorectal Cancer: Two Cases of a Rare Adverse Event

    Directory of Open Access Journals (Sweden)

    Henriette Quack

    2013-12-01

    Full Text Available Leukocytoclastic vasculitis is a multicausal systemic inflammatory disease of the small vessels, histologically characterized by inflammation and deposition of both nuclear debris and fibrin in dermal postcapillary venules. The clinical picture typically involves palpable purpura of the lower legs and may be associated with general symptoms such as fatigue, arthralgia and fever. Involvement of the internal organs, most notably the kidneys, the central nervous system or the eyes, is possible and determines the prognosis. Oxaliplatin-induced leukocytoclastic vasculitis is a very rare event that limits treatment options in affected patients. We report 2 patients who developed the condition under chemotherapy for advanced rectal and metastatic colon carcinoma, respectively; a termination of the therapy was therefore necessary. While current therapies for colorectal cancer include the combination of multimodal treatment with new and targeted agents, rare and unusual side effects elicited by established agents also need to be taken into account for the clinical management.

  2. Survival of cancer stem cells under hypoxia and serum depletion via decrease in PP2A activity and activation of p38-MAPKAPK2-Hsp27.

    Directory of Open Access Journals (Sweden)

    Shih-Pei Lin

    Full Text Available Hypoxia and serum depletion are common features of solid tumors that occur upon antiangiogenesis, irradiation and chemotherapy across a wide variety of malignancies. Here we show that tumor cells expressing CD133, a marker for colorectal cancer initiating or stem cells, are enriched and survive under hypoxia and serum depletion conditions, whereas CD133- cells undergo apoptosis. CD133+ tumor cells increase cancer stem cell and epithelial-mesenchymal transition properties. Moreover, via screening a panel of tyrosine and serine/threonine kinase pathways, we identified Hsp27 is constitutively activated in CD133+ cells rather than CD133- cell under hypoxia and serum depletion conditions. However, there was no difference in Hsp27 activation between CD133+ and CD133- cells under normal growth condition. Hsp27 activation, which was mediated by the p38MAPK-MAPKAPK2-Hsp27 pathway, is required for CD133+ cells to inhibit caspase 9 and 3 cleavage. In addition, inhibition of Hsp27 signaling sensitizes CD133+ cells to hypoxia and serum depletion -induced apoptosis. Moreover, the antiapoptotic pathway is also activated in spheroid culture-enriched CD133+ cancer stem cells from a variety of solid tumor cells including lung, brain and oral cancer, suggesting it is a common pathway activated in cancer stem cells from multiple tumor types. Thus, activation of PP2A or inactivation of the p38MAPK-MAPKAPK2-Hsp27 pathway may develop new strategies for cancer therapy by suppression of their TIC population.

  3. Persistent Postmastectomy Pain in Breast Cancer Survivors

    DEFF Research Database (Denmark)

    Belfer, Inna; Schreiber, Kristin L; Shaffer, John R

    2013-01-01

    to PPMP. Postmastectomy patients (611) were queried about pain location, severity, and burden 38.3 ± 35.4 months postoperatively. Validated questionnaires for depressive symptoms, anxiety, sleep, perceived stress, emotional stability, somatization, and catastrophizing were administered. Detailed surgical...

  4. Poverty persistence and poverty dynamics

    OpenAIRE

    Martin Biewen

    2014-01-01

    A considerable part of the poverty that is measured in a single period is transitory rather than persistent. In most countries, only a portion of people who are currently poor are persistently poor. People who are persistently poor or who cycle into and out of poverty should be the main focus of anti-poverty policies. Understanding the characteristics of the persistently poor, and the circumstances and mechanisms associated with entry into and exit from poverty, can help to inform governments...

  5. Photoinduced Dynamics and Toxicity of a Cancer Drug in Proximity of Inorganic Nanoparticles under Visible Light.

    Science.gov (United States)

    Chaudhuri, Siddhi; Sardar, Samim; Bagchi, Damayanti; Dutta, Shreyasi; Debnath, Sushanta; Saha, Partha; Lemmens, Peter; Pal, Samir Kumar

    2016-01-18

    Drug sensitization with various inorganic nanoparticles (NPs) has proved to be a promising and an emergent concept in the field of nanomedicine. Rose bengal (RB), a notable photosensitizer, triggers the formation of reactive oxygen species under green-light irradiation, and consequently, it induces cytotoxicity and cell death. In the present study, the effect of photoinduced dynamics of RB upon complexation with semiconductor zinc oxide NPs is explored. To accomplish this, we successfully synthesized nanohybrids of RB with ZnO NPs with a particle size of 24 nm and optically characterized them. The uniform size and integrity of the particles were confirmed by high-resolution transmission electron microscopy. UV/Vis absorption and steady-state fluorescence studies reveal the formation of the nanohybrids. ultrafast picosecond-resolved fluorescence studies of RB-ZnO nanohybrids demonstrate an efficient electron transfer from the photoexcited drug to the semiconductor NPs. Picosecond-resolved Förster resonance energy transfer from ZnO NPs to RB unravel the proximity of the drug to the semiconductor at the molecular level. The photoinduced ROS formation was monitored using a dichlorofluorescin oxidation assay, which is a conventional oxidative stress indicator. It is observed that the ROS generation under green light illumination is greater at low concentrations of RB-ZnO nanohybrids compared with free RB. Substantial photodynamic activity of the nanohybrids in bacterial and fungal cell lines validated the in vitro toxicity results. Furthermore, the cytotoxic effect of the nanohybrids in HeLa cells, which was monitored by MTT assay, is also noteworthy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Term Structure Persistence

    OpenAIRE

    Abbritti, M. (Mirko); Gil-Alana, L.A. (Luis A.); Lovcha, Y. (Yuliya); Moreno, A. (Antonio)

    2012-01-01

    Stationary I(0) models employed in yield curve analysis typically imply an unrealistically low degree of volatility in long-run short-rate expectations due to fast mean reversion. In this paper we propose a novel multivariate affine term structure model with a two-fold source of persistence in the yield curve: Long-memory and short-memory. Our model, based on an I(d) specification, nests the I(0) and I(1) models as special cases and the I(0) model is decisively rejected by the data. Our model...

  7. Persistent marine debris

    International Nuclear Information System (INIS)

    Levy, E.M.

    1992-01-01

    In this paper the distribution of persistent marine debris, adrift on world oceans and stranded on beaches globally, is reviewed and related to the known inputs and transport by the major surface currents. Since naturally occurring processes eventually degrade petroleum in the environment, international measures to reduce the inputs have been largely successful in alleviating oil pollution on a global, if not on a local, scale. Many plastics, however, are so resistant to natural degradation that merely controlling inputs will be insufficient, and more drastic and costly measures will be needed to cope with the emerging global problem posed by these materials

  8. Inefficiencies of over-screening and under-screening for cervical cancer prevention in the U.S.

    Science.gov (United States)

    Castle, Philip E; Wheeler, Cosette M; Campos, Nicole G; Sy, Stephen; Burger, Emily A; Kim, Jane J

    2018-03-14

    There is limited information on the cost-inefficiencies of non-adherence to recommended cervical cancer screening or the potential value for improving non-adherence. We estimated the incremental value of adhering to recommended screening every three years with cytology, using a disease simulation model that integrated real-world screening practice data from New Mexico. The amount that can be spent to improve adherence was estimated by calculating the incremental net monetary benefit (INMB) under scenarios of Current Practice (assuming a population of mixed adherence) and Uniformly Non-Adherent populations with imperfect or perfect adherence to follow-up of screen-positive women. Getting unscreened women screened every three years by cytology was a better value than increasing screening in the under-screened or reducing screening in the over-screened. For example, INMBs were $3998 for screening previously unscreened women versus $136 for eliminating annual screening at a willingness-to-pay threshold of $100,000 per quality-adjusted life-year gained. Strategies to reach unscreened women are potentially high-value investments. Copyright © 2018. Published by Elsevier Inc.

  9. Knowledge Regarding Symptoms and Risk Factors and Screening of Breast Cancer in Women Under 30 Years and Their Practice Relative to Self-Examination

    Directory of Open Access Journals (Sweden)

    F. Jafari

    2013-08-01

    Full Text Available Background: Breast cancer is the most common malignancy among women worldwide. In Iran, breast cancer ranks first among cancers diagnosed in women. Nevertheless, many of women haven’t enough knowledge about breast cancer risk factors and symptoms. The main reason for this escalating mortality is lack of awareness and late diagnosis of disease. The aim of present study assessed the knowledge about risk factors and symptoms of breast cancer, also the screening method and practice (Breast self examination about it. Methods: This is a descriptive and cross-sectional study. In this study 340 red crescent volunteer women participated in a national congress were selected with convenience sampling method. The data collection instrument consisted of a three part questionnaire which included demographic factors, Knowledge level about risk factors, symptoms and screening methods of breast cancer and questions concerning practice about breast self examination (BSE.The study tool was a researcher-designed questionnaire which could evaluated a number of variables. After data collection, analysis was carried out with descriptive tests by SPSS.16 software. Results: The mean age of subjects was 23±2.1yrs. Knowledge about breast cancer risk factors was very poor, the most widely known risk factor and lowest among the participants was family history of breast cancer (30.6 % and early menarche (under 12 years (0.3% respectively. Only 47.9% respondents correctly recognized breast lump and 11.2% breast discharge as the most common symptoms of breast cancer.30% of subjects were aware of BSE. However, a lesser proportion (9.4% was done BSE regular monthly every few months. Conclusion: Regarding the low level of the women’s knowledge about breast cancer especially in young educated women, screening and interventional programs to improve awareness and practice is essential.

  10. Six persistent research misconceptions.

    Science.gov (United States)

    Rothman, Kenneth J

    2014-07-01

    Scientific knowledge changes rapidly, but the concepts and methods of the conduct of research change more slowly. To stimulate discussion of outmoded thinking regarding the conduct of research, I list six misconceptions about research that persist long after their flaws have become apparent. The misconceptions are: 1) There is a hierarchy of study designs; randomized trials provide the greatest validity, followed by cohort studies, with case-control studies being least reliable. 2) An essential element for valid generalization is that the study subjects constitute a representative sample of a target population. 3) If a term that denotes the product of two factors in a regression model is not statistically significant, then there is no biologic interaction between those factors. 4) When categorizing a continuous variable, a reasonable scheme for choosing category cut-points is to use percentile-defined boundaries, such as quartiles or quintiles of the distribution. 5) One should always report P values or confidence intervals that have been adjusted for multiple comparisons. 6) Significance testing is useful and important for the interpretation of data. These misconceptions have been perpetuated in journals, classrooms and textbooks. They persist because they represent intellectual shortcuts that avoid more thoughtful approaches to research problems. I hope that calling attention to these misconceptions will spark the debates needed to shelve these outmoded ideas for good.

  11. Persistence of airline accidents.

    Science.gov (United States)

    Barros, Carlos Pestana; Faria, Joao Ricardo; Gil-Alana, Luis Alberiko

    2010-10-01

    This paper expands on air travel accident research by examining the relationship between air travel accidents and airline traffic or volume in the period from 1927-2006. The theoretical model is based on a representative airline company that aims to maximise its profits, and it utilises a fractional integration approach in order to determine whether there is a persistent pattern over time with respect to air accidents and air traffic. Furthermore, the paper analyses how airline accidents are related to traffic using a fractional cointegration approach. It finds that airline accidents are persistent and that a (non-stationary) fractional cointegration relationship exists between total airline accidents and airline passengers, airline miles and airline revenues, with shocks that affect the long-run equilibrium disappearing in the very long term. Moreover, this relation is negative, which might be due to the fact that air travel is becoming safer and there is greater competition in the airline industry. Policy implications are derived for countering accident events, based on competition and regulation. © 2010 The Author(s). Journal compilation © Overseas Development Institute, 2010.

  12. Mechanisms underlying apoptosis-inducing effects of Kaempferol in HT-29 human colon cancer cells.

    Science.gov (United States)

    Lee, Hyun Sook; Cho, Han Jin; Yu, Rina; Lee, Ki Won; Chun, Hyang Sook; Park, Jung Han Yoon

    2014-02-17

    We previously noted that kaempferol, a flavonol present in vegetables and fruits, reduced cell cycle progression of HT-29 cells. To examine whether kaempferol induces apoptosis of HT-29 cells and to explore the underlying molecular mechanisms, cells were treated with various concentrations (0-60 μmol/L) of kaempferol and analyzed by Hoechst staining, Annexin V staining, JC-1 labeling of the mitochondria, immunoprecipitation, in vitro kinase assays, Western blot analyses, and caspase-8 assays. Kaempferol increased chromatin condensation, DNA fragmentation and the number of early apoptotic cells in HT-29 cells in a dose-dependent manner. In addition, kaempferol increased the levels of cleaved caspase-9, caspase-3 and caspase-7 as well as those of cleaved poly (ADP-ribose) polymerase. Moreover, it increased mitochondrial membrane permeability and cytosolic cytochrome c concentrations. Further, kaempferol decreased the levels of Bcl-xL proteins, but increased those of Bik. It also induced a reduction in Akt activation and Akt activity and an increase in mitochondrial Bad. Additionally, kaempferol increased the levels of membrane-bound FAS ligand, decreased those of uncleaved caspase-8 and intact Bid and increased caspase-8 activity. These results indicate that kaempferol induces the apoptosis of HT-29 cells via events associated with the activation of cell surface death receptors and the mitochondrial pathway.

  13. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer ... cancer’s grade, which refers to how abnormal the cancer cells look under a microscope. Grade provides clues about ...

  14. Persistent agents in Axelrod's social dynamics model

    Science.gov (United States)

    Reia, Sandro M.; Neves, Ubiraci P. C.

    2016-01-01

    Axelrod's model of social dynamics has been studied under the effect of external media. Here we study the formation of cultural domains in the model by introducing persistent agents. These are agents whose cultural traits are not allowed to change but may be spread through local neighborhood. In the absence of persistent agents, the system is known to present a transition from a monocultural to a multicultural regime at some critical Q (number of traits). Our results reveal a dependence of critical Q on the occupation probability p of persistent agents and we obtain the phase diagram of the model in the (p,Q) -plane. The critical locus is explained by the competition of two opposite forces named here barrier and bonding effects. Such forces are verified to be caused by non-persistent agents which adhere (adherent agents) to the set of traits of persistent ones. The adherence (concentration of adherent agents) as a function of p is found to decay for constant Q. Furthermore, adherence as a function of Q is found to decay as a power law with constant p.

  15. Diabetes medication persistence, different medications have different persistence rates.

    Science.gov (United States)

    Shani, Michal; Lustman, Alex; Vinker, Shlomo

    2017-08-01

    To assess the persistence of diabetic patients to oral medications. The study included all type 2 diabetic patients over 40 years, members of one District of Clalit Health Services Israel, who were diagnosed with diabetes mellitus before 2008 and who filled at least one prescription per year during 2008-2010, for the following medications: metformin, glibenclamide, acarbose, statins, angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARBs). Purchase of at least 9 monthly prescriptions during 2009 was considered "good medication persistence". We compared HbA1c and LDL levels, according to medication persistence, for each medication; and cross persistence rates between medications. 21,357 patients were included. Average age was 67.0±11.0years, 48.9% were men, and 35.8% were from low SES. Good medication persistence rates for ARBs were 78.8%, ACEI 69.0%, statins 66.6%, acarbose 67.8%, metformin 58.6%, and glibenclamide 55.3%. Good persistence to any of the medications tested was associated with a higher rate of good persistence to other medications. Patients who took more medications had better persistence rates. Different oral medications used by diabetic patients have different persistence rates. Good persistence for any one medication is an indicator of good persistence to other medications. Investment in enhancing medication persistence in persons with diabetes may improve persistence to other medications, as well as improve glycemic control. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  16. Caliber-Persistent Artery

    Directory of Open Access Journals (Sweden)

    Sabrina Araújo Pinho Costa

    2015-01-01

    Full Text Available Caliber-persistent artery (CPLA of the lip is a common vascular anomaly in which a main arterial branch extends to the surface of the mucous tissue with no reduction in its diameter. It usually manifests as pulsatile papule, is easily misdiagnosed, and is observed more frequently among older people, suggesting that its development may involve a degenerative process associated with aging; CPLA is also characterized by the loss of tone of the adjacent supporting connective tissue. Although the diagnosis is clinical, high-resolution Doppler ultrasound is a useful noninvasive tool for evaluating the lesion. This report describes the case of a 58-year-old male patient who complained of a lesion of the lower lip with bleeding and recurrent ulceration. The patient was successfully treated in our hospital after a diagnosis of CPLA and is currently undergoing a clinical outpatient follow-up with no complaints.

  17. Persistent Aerial Tracking

    KAUST Repository

    Mueller, Matthias

    2016-04-13

    In this thesis, we propose a new aerial video dataset and benchmark for low altitude UAV target tracking, as well as, a photo-realistic UAV simulator that can be coupled with tracking methods. Our benchmark provides the rst evaluation of many state of-the-art and popular trackers on 123 new and fully annotated HD video sequences captured from a low-altitude aerial perspective. Among the compared trackers, we determine which ones are the most suitable for UAV tracking both in terms of tracking accuracy and run-time. We also present a simulator that can be used to evaluate tracking algorithms in real-time scenarios before they are deployed on a UAV "in the field", as well as, generate synthetic but photo-realistic tracking datasets with free ground truth annotations to easily extend existing real-world datasets. Both the benchmark and simulator will be made publicly available to the vision community to further research in the area of object tracking from UAVs. Additionally, we propose a persistent, robust and autonomous object tracking system for unmanned aerial vehicles (UAVs) called Persistent Aerial Tracking (PAT). A computer vision and control strategy is applied to a diverse set of moving objects (e.g. humans, animals, cars, boats, etc.) integrating multiple UAVs with a stabilized RGB camera. A novel strategy is employed to successfully track objects over a long period, by \\'handing over the camera\\' from one UAV to another. We integrate the complete system into an off-the-shelf UAV, and obtain promising results showing the robustness of our solution in real-world aerial scenarios.

  18. Fear conditioning, persistence of disruptive behavior and psychopathic traits: an fMRI study

    NARCIS (Netherlands)

    Cohn, M.D.; Popma, A.; van den Brink, W.; Pape, L.E.; Kindt, M.; van Domburgh, L.; Doreleijers, T.A.H.; Veltman, D.J.

    2013-01-01

    Children diagnosed with Disruptive Behavior Disorders (DBD), especially those with psychopathic traits, are at risk of developing persistent and severe antisocial behavior. Deficient fear conditioning may be a key mechanism underlying persistence, and has been associated with altered regional brain

  19. Predictability of persistent frequent attendance in primary care: a temporal and geographical validation study

    NARCIS (Netherlands)

    Smits, Frans T.; Brouwer, Henk J.; Zwinderman, Aeilko H.; van den Akker, Marjan; van Steenkiste, Ben; Mohrs, Jacob; Schene, Aart H.; van Weert, Henk C.; ter Riet, Gerben

    2013-01-01

    Frequent attenders are patients who visit their general practitioner exceptionally frequently. Frequent attendance is usually transitory, but some frequent attenders become persistent. Clinically, prediction of persistent frequent attendance is useful to target treatment at underlying diseases or

  20. Radiosensitization of prostate cancer cells by the dual PI3K/mTOR inhibitor BEZ235 under normoxic and hypoxic conditions

    International Nuclear Information System (INIS)

    Potiron, Vincent A.; Abderrhamani, Rym; Giang, Eric; Chiavassa, Sophie; Di Tomaso, Emmanuelle; Maira, Sauveur-Michel; Paris, François; Supiot, Stéphane

    2013-01-01

    Background and purpose: Despite appropriate radiotherapy, high-risk prostate cancer patients often experience local relapse and progression to metastatic disease. Radioresistance may be due to tumor-hypoxia but also due to the PTEN mutation/deletion present in 70% prostate cancers. We investigated whether the novel PI3K/mTOR inhibitor BEZ235 might sensitize prostate cancer cells to radiation and reduce hypoxia-induced radioresistance. Materials and methods: The potential radiosensitizing properties of BEZ235 were investigated in vitro and in vivo using two prostate cancer cell lines, PC3 (PTEN −/− ) and DU145 (PTEN +/+ ), under normoxic (21% O 2 ) and hypoxic (0.5% O 2 ) conditions. Results: BEZ235 rapidly inhibited PI3K and mTOR signaling in a dose dependent manner and limited tumor cell proliferation and clonogenic survival in both cell lines independently of PTEN status. In vivo, BEZ235 pretreatment enhanced the efficacy of radiation therapy on PC3 xenograft tumors in mice without inducing intestinal radiotoxicity. In culture, BEZ235 radiosensitized both cell lines in a comparable manner. Moreover, BEZ235 inhibited PI3K/mTOR activation and radiosensitized both cell lines under normoxia and hypoxia. BEZ235 radiosensitizing effects correlated with a decrease in γH2AX foci repair and increased G2/M cell cycle arrest. Conclusions: BEZ235 is a potent radiosensitizer of normoxic and hypoxic prostate cancer cells

  1. Persistence Testing of Brucella suis on Outdoor Materials ...

    Science.gov (United States)

    Report This report presents the results of an investigation to evaluate Brucella suis persistence on five materials (typically found in the outdoor environment) under various environmental conditions and exposure durations.

  2. Searching for new biomarkers in ovarian cancer patients: Rationale and design of a retrospective study under the Mermaid III project

    Directory of Open Access Journals (Sweden)

    Julie L. Hentze

    2017-12-01

    A thorough investigation of biomarkers in ovarian cancer, including large numbers of different markers, has never been done before. Besides from improving diagnosis and treatment, other outcomes could be markers for screening, knowledge of the molecular aspects of cancer and the discovery of new drugs. Moreover, biomarkers are a prerequisite for the development of precision medicine. This study will attack the ovarian cancer problem from several angles, thereby increasing the chance of successfully contributing to saving lives.

  3. Epigenetic regulation of persistent pain

    Science.gov (United States)

    Bai, Guang; Ren, Ke; Dubner, Ronald

    2014-01-01

    Persistent or chronic pain is tightly associated with various environmental changes and linked to abnormal gene expression within cells processing nociceptive signaling. Epigenetic regulation governs gene expression in response to environmental cues. Recent animal model and clinical studies indicate that epigenetic regulation plays an important role in the development/maintenance of persistent pain and, possibly the transition of acute pain to chronic pain, thus shedding light in a direction for development of new therapeutics for persistent pain. PMID:24948399

  4. The positioning of economic principles under the changing conditions of the novel drug developmental process in cancer.

    Science.gov (United States)

    Wilking, Nils; Wilking, Ulla; Jönsson, Bengt

    2014-06-01

    Cancer is a major burden to the health care system, presently mainly in developed countries, but is rapidly becoming a problem of similar magnitude in developing countries. Cancer ranks number two or three measured in loss of "good years of life" in Europe. The direct cost of cancer are estimated to be around 50% of total health care costs and of these costs a major part is linked to cancer drugs. With the ongoing revolution in the understanding of cancer and the development of an increasing number of new, but often very costly drugs, the health care systems in all parts of the world need to have a systematic way of evaluating new cancer drugs. Health technology assessment (HTA) now plays a major role in many parts of Europe. HTA has its focus on determining the value of new innovations in order to balance allocation of health care resources in a fair and equal way. This paper reviews the HTA process in general and for cancer drugs specifically. The key findings are that cancer drugs must be evaluated in a similar way as other health care technologies. One must however take into account that cancer drugs are often approved with a high level of uncertainty. Thus, it is of key importance that not only clinical efficacy, i.e., effect in pivotal clinical trials, is taken into account, but that there is a great need for follow-up studies so that post regulatory approval is able to properly measure population based effects [clinical effectiveness (CLE)].

  5. Persistent homology of complex networks

    International Nuclear Information System (INIS)

    Horak, Danijela; Maletić, Slobodan; Rajković, Milan

    2009-01-01

    Long-lived topological features are distinguished from short-lived ones (considered as topological noise) in simplicial complexes constructed from complex networks. A new topological invariant, persistent homology, is determined and presented as a parameterized version of a Betti number. Complex networks with distinct degree distributions exhibit distinct persistent topological features. Persistent topological attributes, shown to be related to the robust quality of networks, also reflect the deficiency in certain connectivity properties of networks. Random networks, networks with exponential connectivity distribution and scale-free networks were considered for homological persistency analysis

  6. Intrinsic and Inherited Inflation Persistence

    OpenAIRE

    Jeffrey C. Fuhrer

    2006-01-01

    In the now conventional view of the inflation process, the New Keynesian Phillips Curve (NKPC) captures most of the persistence in inflation. The sources of persistence are twofold. First, the “driving process” for inflation—the output gap or, more commonly, real marginal cost—is itself quite persistent, and a casual inspection of the NKPC reveals that inflation must “inherit” this persistence. Second, a modest amount of backward-looking or indexing behavior imparts some “intrinsic” persisten...

  7. Cancer

    Science.gov (United States)

    ... example, in Japan, there are many cases of stomach cancer . But in the United States, this type of ... Blood tests (which look for chemicals such as tumor markers) Bone marrow biopsy (for lymphoma or leukemia) Chest ...

  8. Aromatic Hydrocarbon Receptor Suppresses Prostate Cancer Bone Metastasis Cells-Induced Vasculogenesis of Endothelial Progenitor Cells under Hypoxia

    Directory of Open Access Journals (Sweden)

    Shuai Huang

    2016-07-01

    Full Text Available Background/Aims: Hypoxia leads to the development of neovascularization in solid tumor by regulating VEGF expression. Aromatic hydrocarbon receptor (AHR, a receptor for dioxin-like compounds, functions as a transcription factor through dimerization with hypoxia-inducible factors 1β (HIF-1β and inhibits the secretion of vascular endothelial growth factor (VEGF. The purpose of this study was to explore whether AHR can suppress hypoxia-induced VEGF production in prostate bone metastasis cells and repress neovascularization in endothelial progenitor cells (EPCs, and, if so, through what mechanisms. Methods: PC-3 or LNCaP cells induced angiogenesis was detected by Matrigel-based tube formation assay, mRNA expression levels was measured by qRT-PCR, VEGF secretion level was determined by ELISA assay, respectively. Results: AHR activation inhibits hypoxia-induced adhesiveness and vasculogenesis of EPCs induced by PC-3 or LNCaP cells under hypoxia. Moreover, AHR activation suppressed hypoxia-induced VEGF production in PC-3 and LNCaP cells (48 ± 14% in PC-3, p = 0.000; 41 ± 14% in LNCaP, p = 0.000 by attenuating HIF-1α and HIF-1β level that in turn diminished the angiogenic ability of EPCs in vitro. Furthermore, we found the mRNA level of hypoxia-inducible factors 1α (HIF-1α (1.54 ± 0.13 fold in PC-3, p = 0.002, 1.62 ± 0.12 fold in LNCaP, p = 0.001 and HIF-1β (1.67 ± 0.23 fold in PC-3, p = 0.007; 1.75 ± 0.26 fold in LNCaP, p=0.008 were upregulated in prostate cancer bone metastasis PC-3 and LNCaP cell lines in response to hypoxia, and revealed that the regulation of VEGF by HIF-1α and HIF-1β was possibly mediated by the activation of phosphatidylinositol 3-kinase pathway. Conclusion: By providing a mechanistic insight into the modulation of neovascularization by AHR ligand, we suggest that AHR ligand has a strong potential of being a new therapeutic agent with applications in the field of bone metastatic prostate cancer.

  9. Neglected Under Lip Cancer

    Directory of Open Access Journals (Sweden)

    Georgi Tchernev

    2018-01-01

    Full Text Available The lip represents an anatomical area of the interface between the skin and oral mucosa. It is, therefore, not entirely surprising that SCC of the lip exhibits mixed features between cutaneous and oral mucosal SCC, namely regarding risk factors and biological behaviour. The main risk factors for lip SCC include ultraviolet radiation exposure, low phototype, tobacco and alcohol use, and immunosuppression. Lip SCC usually presents clinically as a nodule or a tumour with a keratotic surface that commonly ulcerates. There is often a background of actinic cheilitis. The particularly exuberant presentation of our case can most probably be explained by the long evolution of a tumour before the patient reached medical attention. Patients with regional lymph node metastasis are usually offered regional lymph node dissection (usually of the neck. Radiotherapy and/or chemotherapy may be used in advanced cases, particularly in unresectable tumours, tumours with high-risk features and metastatic disease. The large size of a tumour in our case, most probably due to its long evolution, highlights the importance of timely diagnosis to avoid such extreme presentations and the consequent need for more aggressive treatment.

  10. Recent progress in biomedical applications of persistent luminescence nanoparticles.

    Science.gov (United States)

    Wang, Jie; Ma, Qinqin; Wang, Yingqian; Shen, Haijing; Yuan, Quan

    2017-05-18

    Persistent luminescence nanoparticles (PLNPs) are an emerging group of promising luminescent materials that can remain luminescent after the excitation ceases. In the past decade, PLNPs with intriguing optical properties have been developed and their applications in biomedicine have been widely studied. Due to the ultra-long decay time of persistent luminescence, autofluorescence interference in biosensing and bioimaging can be efficiently eliminated. Moreover, PLNPs can remain luminescent for hours, making them valuable in bio-tracing. Also, persistent luminescence imaging can guide cancer therapy with a high signal-to-noise ratio (SNR) and superior sensitivity. Briefly, PLNPs are demonstrated to be a newly-emerging class of functional materials with unprecedented advantages in biomedicine. In this review, we summarized recent advances in the preparation of PLNPs and the applications of PLNPs in biosensing, bioimaging and cancer therapy.

  11. Interval colon cancer in a Lynch syndrome patient under annual colonoscopic surveillance: a case for advanced imaging techniques?

    Directory of Open Access Journals (Sweden)

    Oxentenko Amy S

    2012-05-01

    Full Text Available Abstract Background Lynch syndrome confers increased risk for various malignancies, including colorectal cancer. Colonoscopic surveillance programs have led to reduced incidence of colorectal cancer and reduced mortality from colorectal cancer. Colonoscopy every 1–2 years beginning at age 20–25, or 10 years earlier than the first diagnosis of colorectal cancer in a family, with annual colonoscopy after age 40, is the recommended management for mutation carriers. Screening programs have reduced colon cancer mortality, but interval cancers may occur. Case presentation We describe a 48-year-old woman with Lynch syndrome who was found to have an adenoma with invasive colorectal cancer within one year after a normal colonoscopy. Conclusion Our patient illustrates two current concepts about Lynch syndrome: 1 adenomas are the cancer precursor and 2 such adenomas may be “aggressive,” in the sense that the adenoma progresses more readily and more rapidly to carcinoma in this setting compared to usual colorectal adenomas. Our patient’s resected tumor invaded only into submucosa and all lymph nodes were negative; in that sense, she represents a success for annual colonoscopic surveillance. Still, this case does raise the question of whether advanced imaging techniques are advisable for surveillance colonoscopy in these high-risk patients.

  12. Transcriptional profiling of human breast cancer cells cultured under microgravity conditions revealed the key role of genetic gravity sensors previously detected in Drosophila melanogaster

    Science.gov (United States)

    Valdivia-Silva, Julio E.; Lavan, David; Diego Orihuela-Tacuri, M.; Sanabria, Gabriela

    2016-07-01

    Currently, studies in Drosophila melanogaster has shown emerging evidence that microgravity stimuli can be detected at the genetic level. Analysis of the transcriptome in the pupal stage of the fruit flies under microgravity conditions versus ground controls has suggested the presence of a few candidate genes as "gravity sensors" which are experimentally validated. Additionally, several studies have shown that microgravity causes inhibitory effects in different types of cancer cells, although the genes involved and responsible for these effects are still unknown. Here, we demonstrate that the genes suggested as the sensors of gravitational waves in Drosophila melanogaster and their human counterpart (orthologous genes) are highly involved in carcinogenesis, proliferation, anti-apoptotic signals, invasiveness, and metastatic potential of breast cancer cell tumors. The transcriptome analyses suggested that the observed inhibitory effect in cancer cells could be due to changes in the genetic expression of these candidates. These results encourage the possibility of new therapeutic targets managed together and not in isolation.

  13. Imaging characters of the lung cancer phantoms under the simulative clinical condition performed with hard X-ray in-line holography

    International Nuclear Information System (INIS)

    Zhang, J; Chen, Y; Li, G; Jiang, X

    2013-01-01

    The simulative lung cancer tissues under the approximate clinical condition were imaged using in-line holography method with 35 keV synchrotron radiation hard X-ray. The millimeter scale simulative cancer phantoms showed adequate contrast to lung tissues in our experiment. It demonstrates that in-line holography method with synchrotron radiation hard X-ray promises to be a potential sensitive method for the early detection of lung cancer. The image contrast, standard deviation (SD) and normalized standard deviation (NSD) of different areas were calculated. It shows that the traditional method of contrast calculation does not always give a convincible result in image judgment; a standard deviation map of image taken with a proper distance of sample to detector (DSD) will correspond well to the projecting image and supply effective assistance in diagnostic judgment.

  14. Multidimensional persistence in biomolecular data.

    Science.gov (United States)

    Xia, Kelin; Wei, Guo-Wei

    2015-07-30

    Persistent homology has emerged as a popular technique for the topological simplification of big data, including biomolecular data. Multidimensional persistence bears considerable promise to bridge the gap between geometry and topology. However, its practical and robust construction has been a challenge. We introduce two families of multidimensional persistence, namely pseudomultidimensional persistence and multiscale multidimensional persistence. The former is generated via the repeated applications of persistent homology filtration to high-dimensional data, such as results from molecular dynamics or partial differential equations. The latter is constructed via isotropic and anisotropic scales that create new simiplicial complexes and associated topological spaces. The utility, robustness, and efficiency of the proposed topological methods are demonstrated via protein folding, protein flexibility analysis, the topological denoising of cryoelectron microscopy data, and the scale dependence of nanoparticles. Topological transition between partial folded and unfolded proteins has been observed in multidimensional persistence. The separation between noise topological signatures and molecular topological fingerprints is achieved by the Laplace-Beltrami flow. The multiscale multidimensional persistent homology reveals relative local features in Betti-0 invariants and the relatively global characteristics of Betti-1 and Betti-2 invariants. © 2015 Wiley Periodicals, Inc.

  15. Student Persistence in Community Colleges

    Science.gov (United States)

    Nakajima, Mikiko A.; Dembo, Myron H.; Mossler, Ron

    2012-01-01

    The current study extends the research on student persistence in community colleges by investigating factors likely to influence a student's decision to drop out or stay in school. Specifically, this study examined demographic, financial, academic, academic integration, and psychosocial variables and their relationship to student persistence. A…

  16. Translating Romans: some persistent headaches

    Directory of Open Access Journals (Sweden)

    A.B. du Toit

    2010-07-01

    Full Text Available Translating Romans: some persistent headaches Gone are the days when it was axiomatic that expertise in biblical languages automatically qualified one as a Bible translator. In 1949, Ronald Knox, who for nine years conscientiously struggled with translating the Bible for his generation, published a booklet under the title The trials of a translator. At that stage Bible translation as the subject of scientific study was still in its infancy. Since then, research into the intricacies of communicating the biblical message in an authentic but understandable manner, has made significant progress (cf. Roberts, 2009. However, the frustrations of Bible translators, first of all to really understand what the biblical authors wanted to convey to their original addressees, and then to commu-nicate that message to their own targeted readers in a meaningful way, have not disappeared. In fact, the challenge to meet the vary-ing requirements of the multiple kinds of translation that are present-ly in vogue, has only increased.

  17. Surveying the effect of a self-care education program on severity of nausea and emesis in colorectal cancer patients under chemotherapy.

    Science.gov (United States)

    Karimi, Saba; Makhsosi, Behnam Reza; Seyedi-Andi, Seyed Jalil; Behzadi, Maryam; Moghofeh, Yasaman; Mohammadinasrabadi, Kourosh; Abdi, Alireza; Ahmadi, Pegah

    2017-01-01

    Colorectal cancer is one of the main causes of mortality in both developed and developing countries, including Iran. One of the treatments available for colorectal cancer is chemotherapy, of which nausea and emesis are the side effects. Owing to problems in controlling the side effects, a combination of medicine and non-medicine interventions is usually used. Self-care is one of the non-medicine interventions in this regard. The present study was aimed at surveying the effect of a self-care education program on severity of nausea and emesis in colorectal cancer patients under chemotherapy. A semi-experimental study was carried out in Imam Reza Hospital of Kermanshah, Iran. The sample group comprised 52 patients with colorectal cancer under chemotherapy. Data gathering tools included a demographics questionnaire and Morrow Assessment of Nausea and Emesis. To control intensity of nausea and emesis, a package of self-care measures including muscular progressive relaxation, music, and education on nutrition was used. Afterward, the collected data were analyzed using statistical tests such as Shapiro-Wilk test (to check normal distribution of the data), Mann-Whitney U test, Wilcoxon test, and chi-square test with the help of SPSS 20. The results showed a considerable decrease in intensity and frequency of nausea and emesis after the intervention. The p -value of Mann-Whitney U test results with regard to intensity of nausea in the experiment and control groups after the intervention was 0.029; this figure for intensity of emesis was 0.009, which indicated effectiveness of the self-care program. As the results showed, using self-care program could be effective in attenuating intensity of emesis and nausea in colorectal cancer patients under chemotherapy. So, it can be concluded that the use of this program can increase the patient's self-care ability to control vomiting and nausea, which can be considered as a complementary approach to the antiemetic medications.

  18. Specific Colon Cancer Cell Cytotoxicity Induced by Bacteriophage E Gene Expression under Transcriptional Control of Carcinoembryonic Antigen Promoter.

    Science.gov (United States)

    Rama, Ana R; Hernandez, Rosa; Perazzoli, Gloria; Burgos, Miguel; Melguizo, Consolación; Vélez, Celia; Prados, Jose

    2015-06-04

    Colorectal cancer is one of the most prevalent cancers in the world. Patients in advanced stages often develop metastases that require chemotherapy and usually show a poor response, have a low survival rate and develop considerable toxicity with adverse symptoms. Gene therapy may act as an adjuvant therapy in attempts to destroy the tumor without affecting normal host tissue. The bacteriophage E gene has demonstrated significant antitumor activity in several cancers, but without any tumor-specific activity. The use of tumor-specific promoters may help to direct the expression of therapeutic genes so they act against specific cancer cells. We used the carcinoembryonic antigen promoter (CEA) to direct E gene expression (pCEA-E) towards colon cancer cells. pCEA-E induced a high cell growth inhibition of human HTC-116 colon adenocarcinoma and mouse MC-38 colon cancer cells in comparison to normal human CCD18co colon cells, which have practically undetectable levels of CEA. In addition, in vivo analyses of mice bearing tumors induced using MC-38 cells showed a significant decrease in tumor volume after pCEA-E treatment and a low level of Ki-67 in relation to untreated tumors. These results suggest that the CEA promoter is an excellent candidate for directing E gene expression specifically toward colon cancer cells.

  19. Specific Colon Cancer Cell Cytotoxicity Induced by Bacteriophage E Gene Expression under Transcriptional Control of Carcinoembryonic Antigen Promoter

    Directory of Open Access Journals (Sweden)

    Ana R. Rama

    2015-06-01

    Full Text Available Colorectal cancer is one of the most prevalent cancers in the world. Patients in advanced stages often develop metastases that require chemotherapy and usually show a poor response, have a low survival rate and develop considerable toxicity with adverse symptoms. Gene therapy may act as an adjuvant therapy in attempts to destroy the tumor without affecting normal host tissue. The bacteriophage E gene has demonstrated significant antitumor activity in several cancers, but without any tumor-specific activity. The use of tumor-specific promoters may help to direct the expression of therapeutic genes so they act against specific cancer cells. We used the carcinoembryonic antigen promoter (CEA to direct E gene expression (pCEA-E towards colon cancer cells. pCEA-E induced a high cell growth inhibition of human HTC-116 colon adenocarcinoma and mouse MC-38 colon cancer cells in comparison to normal human CCD18co colon cells, which have practically undetectable levels of CEA. In addition, in vivo analyses of mice bearing tumors induced using MC-38 cells showed a significant decrease in tumor volume after pCEA-E treatment and a low level of Ki-67 in relation to untreated tumors. These results suggest that the CEA promoter is an excellent candidate for directing E gene expression specifically toward colon cancer cells.

  20. Recent mortality statistics for distally exposed A-bomb survivors: The lifetime cancer risk for exposure under 50 cGy (rad)

    International Nuclear Information System (INIS)

    Nussbaum, R.H.; Belsey, R.E.; Koehnlein, W.

    1990-01-01

    An analysis of mortality statistics from the most recent Life Span Study reports of Hiroshima and Nagasaki survivors (covering both the 1950-1982 and the 1950-1985 follow-up periods) indicates a significant difference (p < 0.001) in cancer mortality rates between two distally exposed groups of survivors with organ-absorbed radiation doses under 40 cSv. This implies a mean incremental lifetime cancer risk (exclusive of leukemias) of about 25 excess fatal cancers per 10,000 persons exposed to one additional cSv (rem) of ionizing radiation for persons who had been exposed to doses in the range 1-40 cSv above background levels. This risk value is independent of whether the original (T65DR) dosimetry assignments (choosing a value of 10 for the relative biological effectiveness of neutrons) or the new dosimetry estimates (DS86) are used. The present estimate of A-bomb survivor radiogenic cancer risk associated with low dose exposure was obtained directly from the observed cancer deaths in the low-dose exposure groups without reliance on model-dependent extrapolation from high-dose data. This low-dose risk estimate is about ten times larger than the risk estimates adopted previously by national and international radiation commissions as a basis for current radiation safety guidelines for workers and the general public. (author)

  1. Mechanisms underlying differential response to estrogen-induced apoptosis in long-term estrogen-deprived breast cancer cells

    OpenAIRE

    SWEENEY, ELIZABETH E.; FAN, PING; JORDAN, V. CRAIG

    2014-01-01

    Models of long-term estrogen-deprived breast cancer cells are utilized in the laboratory to mimic clinical aromatase inhibitor-resistant breast cancer and serve as a tool to discover new therapeutic strategies. The MCF-7:5C and MCF-7:2A subclones were generated through long-term estrogen deprivation of estrogen receptor (ER)-positive MCF-7 cells, and represent anti-hormone-resistant breast cancer. MCF-7:5C cells paradoxically undergo estrogen-induced apoptosis within seven days of estrogen (e...

  2. GFP transgenic medaka (Oryzias latipes under the inducible cyp1a promoter provide a sensitive and convenient biological indicator for the presence of TCDD and other persistent organic chemicals.

    Directory of Open Access Journals (Sweden)

    Grace Hwee Boon Ng

    Full Text Available Persistent organic pollutants (POPs are resistant to environmental degradation and can cause multitude of health problems. Cytochrome P450 1A (Cyp1a is often up-regulated by POPs through the activation of aryl hydrocarbon receptor (AhR pathway and is thus usually used as a biomarker for xenobiotics exposure. To develop a convenient in vivo tool to monitor xenobiotic contamination in the water, we have established GFP transgenic medaka using the inducible cyp1a promoter, Tg(cyp1a:gfp. Here we tested Tg(cyp1a:gfp medaka at three different stages, prehatching embryos, newly hatched fry and adult with 2,3,7,8-tetrachlorodiebnzo-p-dioxin (TCDD, a dioxin. While GFP induction was observed in all three stages, newly hatched fry were the most sensitive with the lowest observed effective concentration of 0.005 nM or 16.1 ng/L. The highly sensitive organs included the kidney, liver and intestine. With high concentrations of TCDD, several other organs such as the olfactory pit, tail fin, gills, lateral line neuromast cells and blood vessels also showed GFP expression. In addition, Tg(cyp1a:gfp medaka fry also responded to two other AhR agonists, 3-methylcholanthrene and benzo[a]pyrene, for GFP induction, but no significant GFP induction was observed towards several other chemicals tested, indicating the specificity of this transgenic line. The GFP inducibility of Tg(cyp1a:gfp medaka at both fry and adult stages may be useful for development of high-throughput assays as well as online water monitoring system to detect xenobiotic toxicity.

  3. Persistence, resistance, resonance

    Science.gov (United States)

    Tsadka, Maayan

    form of musical consumption and experience. The three pieces draw lines connecting different aspects of persistence, resistance, and resonance.

  4. Using Persistent Homology to Describe Rayleigh-Bénard Convection

    Science.gov (United States)

    Tithof, Jeffrey; Suri, Balachandra; Xu, Mu; Kramar, Miroslav; Levanger, Rachel; Mischaikow, Konstantin; Paul, Mark; Schatz, Michael

    2015-11-01

    Complex spatial patterns that exhibit aperiodic dynamics commonly arise in a wide variety of systems in nature and technology. Describing, understanding, and predicting the behavior of such patterns is an open problem. We explore the use of persistent homology (a branch of algebraic topology) to characterize spatiotemporal dynamics in a canonical fluid mechanics problem, Rayleigh Bénard convection. Persistent homology provides a powerful mathematical formalism in which the topological characteristics of a pattern (e.g. the midplane temperature field) are encoded in a so-called persistence diagram. By applying a metric to measure the pairwise distances across multiple persistence diagrams, we can quantify the similarities between different states in a time series. Our results show that persistent homology yields new physical insights into the complex dynamics of large spatially extended systems that are driven far-from-equilibrium. This work is supported under NSF grant DMS-1125302.

  5. [The toy library as a possibility to unveil the daily life of children with cancer under outpatient treatment].

    Science.gov (United States)

    Melo, Luciana de Lione; do Valle, Elizabeth Ranier Martins

    2010-06-01

    The purpose of this study is to learn the meaning of being-a-child with cancer submitted to ambulatory treatment and using the toy library as a possibility to enable their expression about their world. Participants were seven children of ages 3 to 9 years, who had been diagnosed with some kind of childhood cancer. With the objective of learning about the meaning of these experiences to children with cancer, an analysis of these data was performed based on Martin Heidegger's existential phenomenology. The child-with-cancer showed a movement that was permeated sometimes by authenticity, when the child assumed the disease and their being-toward-death and also by the lack of authenticity, when they were influenced by the decadence attitude of their relatives and health team members. Playing provided a rich contact with the existence of these severely ill children.

  6. studies on hair growth, hair density, hair diameter, hair shape, trichodynia and skin-specific quality of life on women with breast cancer under antineoplastic treatment

    OpenAIRE

    Lindner, Julia

    2013-01-01

    The purpose of this study was to investigate changes of hair growth rates, hair density, hair diameter, hair shape, trichodynia and skin-specific quality of life under antineoplastic treatment. Participants in this prospective study were 34 women, suffering from breast cancer, receiving either chemotherapy (n = 17) or tamoxifen (n = 17). The following methods were used: TrichoScan for the evaluation of hair density, anagen and telogen hair rates, optical coherence tomography for the determina...

  7. Fish population persistence in hydrologically variable landscapes.

    Science.gov (United States)

    Bond, Nick R; Balcombe, Stephen R; Crook, David A; Marshall, Jonathan C; Menke, Norbert; Lobegeiger, Jaye S

    2015-06-01

    Forecasting population persistence in environments subjected to periodic disturbances represents a general challenge for ecologists. In arid and semiarid regions, climate change and human water use pose significant threats to the future persistence of aquatic biota whose populations typically depend on permanent refuge waterholes for their viability. As such, habitats are increasingly being lost as a result of decreasing runoff and increasing water extraction. We constructed a spatially explicit population model for golden perch Macquaria ambigua (Richardson), a native freshwater fish in the Murray-Darling Basin in eastern Australia. We then used the model to examine the effects of increased aridity, increased drought frequency, and localized human water extraction on population viability. Consistent with current observations, the model predicted golden perch population persistence under the current climate and levels of water use. Modeled increases in local water extraction greatly increased the risk of population decline, while scenarios of increasing aridity and drought frequency were associated with only minor increases in this risk. We conclude that natural variability in abundances and high turnover rates (extinction/recolonization) of local populations dictate the importance of spatial connectivity and periodic cycles of population growth. Our study also demonstrates an effective way to examine population persistence in intermittent and ephemeral river systems by integrating spatial and temporal dynamics of waterhole persistence with demographic processes (survival, recruitment, and dispersal) within a stochastic modeling framework. The approach can be used to help understand the impacts of natural and anthropogenic drivers, including water resource development, on the viability of biota inhabiting highly dynamic environments.

  8. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    NARCIS (Netherlands)

    K. Lawrenson (Kate); S. Kar (Siddhartha); K. McCue (Karen); Kuchenbaeker, K. (Karoline); K. Michailidou (Kyriaki); J.P. Tyrer (Jonathan); J. Beesley (Jonathan); S.J. Ramus (Susan); Li, Q. (Qiyuan); Delgado, M.K. (Melissa K.); J.M. Lee (Janet M.); K. Aittomäki (Kristiina); I.L. Andrulis (Irene); H. Anton-Culver (Hoda); Arndt, V. (Volker); B.K. Arun (Banu); B. Arver (Brita Wasteson); E.V. Bandera (Elisa); M. Barile (Monica); Barkardottir, R.B. (Rosa B.); D. Barrowdale (Daniel); M.W. Beckmann (Matthias); J. Benítez (Javier); A. Berchuck (Andrew); M. Bisogna (Maria); L. Bjorge (Line); C. Blomqvist (Carl); W.J. Blot (William); N.V. Bogdanova (Natalia); Bojesen, A. (Anders); S.E. Bojesen (Stig); M.K. Bolla (Manjeet K.); B. Bonnani (Bernardo); A.-L. Borresen-Dale (Anne-Lise); H. Brauch (Hiltrud); P. Brennan (Paul); H. Brenner (Hermann); F. Bruinsma (Fiona); J. Brunet (Joan); S.A.B.S. Buhari (Shaik Ahmad Bin Syed); B. Burwinkel (Barbara); R. Butzow (Ralf); S.S. Buys (Saundra); Q. Cai (Qiuyin); T. Caldes (Trinidad); I. Campbell (Ian); Canniotto, R. (Rikki); J. Chang-Claude (Jenny); Chiquette, J. (Jocelyne); Choi, J.-Y. (Ji-Yeob); K.B.M. Claes (Kathleen B.M.); L.S. Cook (Linda S.); A. Cox (Angela); D.W. Cramer (Daniel); S.S. Cross (Simon); C. Cybulski (Cezary); K. Czene (Kamila); M.B. Daly (Mary B.); F. Damiola (Francesca); A. Dansonka-Mieszkowska (Agnieszka); H. Darabi (Hatef); J. Dennis (Joe); P. Devilee (Peter); O. Díez (Orland); J.A. Doherty (Jennifer A.); S.M. Domchek (Susan); C.M. Dorfling (Cecilia); T. Dörk (Thilo); M. Dumont (Martine); H. Ehrencrona (Hans); B. Ejlertsen (Bent); S.D. Ellis (Steve); C.W. Engel (Christoph); E. Lee (Eunjung); Evans, D.G. (D. Gareth); P.A. Fasching (Peter); L. Feliubadaló (L.); J.D. Figueroa (Jonine); D. Flesch-Janys (Dieter); O. Fletcher (Olivia); H. Flyger (Henrik); L. Foretova (Lenka); F. Fostira (Florentia); W.D. Foulkes (William); B.L. Fridley (Brooke); E. Friedman (Eitan); D. Frost (Debra); Gambino, G. (Gaetana); P.A. Ganz (Patricia A.); J. Garber (Judy); M. García-Closas (Montserrat); A. Gentry-Maharaj (Aleksandra); M. Ghoussaini (Maya); G.G. Giles (Graham); R. Glasspool (Rosalind); A.K. Godwin (Andrew K.); M.S. Goldberg (Mark); D. Goldgar (David); A. González-Neira (Anna); E.L. Goode (Ellen); M.T. Goodman (Marc); M.H. Greene (Mark H.); J. Gronwald (Jacek); P. Guénel (Pascal); C.A. Haiman (Christopher A.); P. Hall (Per); Hallberg, E. (Emily); U. Hamann (Ute); T.V.O. Hansen (Thomas); P. harrington (Patricia); J.M. Hartman (Joost); N. Hassan (Norhashimah); S. Healey (Sue); P.U. Heitz; J. Herzog (Josef); E. Høgdall (Estrid); C.K. Høgdall (Claus); F.B.L. Hogervorst (Frans); A. Hollestelle (Antoinette); J.L. Hopper (John); P.J. Hulick (Peter); T. Huzarski (Tomasz); E.N. Imyanitov (Evgeny); C. Isaacs (Claudine); H. Ito (Hidemi); A. Jakubowska (Anna); R. Janavicius (Ramunas); A. Jensen (Allan); E.M. John (Esther); Johnson, N. (Nichola); M. Kabisch (Maria); D. Kang (Daehee); M.K. Kapuscinski (Miroslav K.); Karlan, B.Y. (Beth Y.); S. Khan (Sofia); L.A.L.M. Kiemeney (Bart); M. Kjaer (Michael); J.A. Knight (Julia); I. Konstantopoulou (I.); V-M. Kosma (Veli-Matti); V. Kristensen (Vessela); J. Kupryjanczyk (Jolanta); A. Kwong (Ava); M. de La Hoya (Miguel); Y. Laitman (Yael); Lambrechts, D. (Diether); N.D. Le (Nhu D.); K. De Leeneer (Kim); K.J. Lester (Kathryn); D.A. Levine (Douglas); J. Li (Jingmei); A. Lindblom (Annika); J. Long (Jirong); A. Lophatananon (Artitaya); J.T. Loud (Jennifer); K.H. Lu (Karen); J. Lubinski (Jan); A. Mannermaa (Arto); S. Manoukian (Siranoush); L. Le Marchand (Loic); S. Margolin (Sara); F. Marme (Frederick); L.F. Massuger (Leon); K. Matsuo (Keitaro); S. Mazoyer (Sylvie); L. McGuffog (Lesley); C.A. McLean (Catriona Ann); I. McNeish (Iain); A. Meindl (Alfons); U. Menon (Usha); Mensenkamp, A.R. (Arjen R.); R.L. Milne (Roger); M. Montagna (Marco); K.B. Moysich (Kirsten); K.R. Muir (K.); A.-M. Mulligan (Anna-Marie); K.L. Nathanson (Katherine); R.B. Ness (Roberta); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); S. Nord (Silje); R.L. Nussbaum (Robert L.); K. Odunsi (Kunle); K. Offit (Kenneth); E. Olah; O.I. Olopade (Olufunmilayo I.); J.E. Olson (Janet); C. Olswold (Curtis); D.M. O'Malley (David M.); I. Orlow (Irene); N. Orr (Nick); A. Osorio (Ana); Park, S.K. (Sue Kyung); C.L. Pearce (Celeste); T. Pejovic (Tanja); P. Peterlongo (Paolo); G. Pfeiler (Georg); C. Phelan (Catherine); E.M. Poole (Elizabeth); K. Pykäs (Katri); P. Radice (Paolo); J. Rantala (Johanna); M.U. Rashid (Muhammad); G. Rennert (Gad); V. Rhenius (Valerie); K. Rhiem (Kerstin); H. Risch (Harvey); G.C. Rodriguez (Gustavo); M.A. Rossing (Mary Anne); Rudolph, A. (Anja); H.B. Salvesen (Helga); Sangrajrang, S. (Suleeporn); Sawyer, E.J. (Elinor J.); J.M. Schildkraut (Joellen); M.K. Schmidt (Marjanka); R.K. Schmutzler (Rita); T.A. Sellers (Thomas A.); C.M. Seynaeve (Caroline); Shah, M. (Mitul); C.-Y. Shen (Chen-Yang); X.-O. Shu (Xiao-Ou); W. Sieh (Weiva); C.F. Singer (Christian); O. Sinilnikova (Olga); S. Slager (Susan); H. Song (Honglin); Soucy, P. (Penny); M.C. Southey (Melissa); M. Stenmark-Askmalm (Marie); D. Stoppa-Lyonnet (Dominique); C. Sutter (Christian); A.J. Swerdlow (Anthony ); Tchatchou, S. (Sandrine); P.J. Teixeira; S.-H. Teo (Soo-Hwang); K.L. Terry (Kathryn); M.B. Terry (Mary Beth); M. Thomassen (Mads); M.G. Tibiletti (Maria Grazia); L. Tihomirova (Laima); S. Tognazzo (Silvia); A.E. Toland (Amanda); I.P. Tomlinson (Ian); D. Torres (Diana); T. Truong (Thérèse); C.-C. Tseng (Chiu-Chen); N. Tung (Nadine); Tworoger, S.S. (Shelley S.); C. Vachon (Celine); Van Den Ouweland, A.M.W. (Ans M.W.); Van Doorn, H.C. (Helena C.); E.J. van Rensburg (Elizabeth); L.J. van 't Veer (Laura); A. Vanderstichele (Adriaan); I. Vergote (Ignace); J. Vijai (Joseph); Wang, Q. (Qin); S. Wang-Gohrke (Shan); J.N. Weitzel (Jeffrey); N. Wentzensen (N.); A.S. Whittemore (Alice); H. Wildiers (Hans); R. Winqvist (Robert); A.H. Wu (Anna); Yannoukakos, D. (Drakoulis); S.-Y. Yoon (Sook-Yee); J-C. Yu (Jyh-Cherng); W. Zheng (Wei); Y. Zheng (Ying); Khanna, K.K. (Kum Kum); J. Simard (Jacques); A.N.A. Monteiro (Alvaro N.); J.D. French (Juliet); F.J. Couch (Fergus); M. Freedman (Matthew); D.F. Easton (Douglas F.); A.M. Dunning (Alison); P.D.P. Pharoah (Paul); S.L. Edwards (Stacey); G. Chenevix-Trench (Georgia); A.C. Antoniou (Antonis C.); S.A. Gayther (Simon); D. Bowtell (David); A. DeFazio (Anna); P. Webb (Penny); M.-A. Collonge-Rame; Damette, A. (Alexandre); E. Barouk-Simonet (Emmanuelle); F. Bonnet (Françoise); V. Bubien (Virginie); N. Sevenet (Nicolas); M. Longy (Michel); P. Berthet (Pascaline); D. Vaur (Dominique); L. Castera (Laurent); S.F. Ferrer; Y.-J. Bignon (Yves-Jean); N. Uhrhammer (Nancy); F. Coron (Fanny); L. Faivre (Laurence); Baurand, A. (Amandine); Jacquot, C. (Caroline); Bertolone, G. (Geoffrey); Lizard, S. (Sarab); D. Leroux (Dominique); H. Dreyfus (Hélène); C. Rebischung (Christine); Peysselon, M. (Magalie); J.-P. Peyrat; J. Fournier (Joëlle); F. Révillion (Françoise); C. Adenis (Claude); L. Vénat-Bouvet (Laurence); M. Léone (Mélanie); N. Boutry-Kryza (N.); A. Calender (Alain); S. Giraud (Sophie); C. Verny-Pierre (Carole); C. Lasset (Christine); V. Bonadona (Valérie); Barjhoux, L. (Laure); H. Sobol (Hagay); V. Bourdon (Violaine); Noguchi, T. (Tetsuro); A. Remenieras (Audrey); I. Coupier (Isabelle); P. Pujol (Pascal); J. Sokolowska (Johanna); M. Bronner (Myriam); C.D. Delnatte (Capucine); Bézieau, S. (Stéphane); Mari, V. (Véronique); M. Gauthier-Villars (Marion); B. Buecher (Bruno); E. Rouleau (Etienne); L. Golmard (Lisa); V. Moncoutier (Virginie); M. Belotti (Muriel); A. de Pauw (Antoine); Elan, C. (Camille); Fourme, E. (Emmanuelle); Birot, A.-M. (Anne-Marie); Saule, C. (Claire); Laurent, M. (Maïté); C. Houdayer (Claude); F. Lesueur (Fabienne); N. Mebirouk (Noura); F. Coulet (Florence); C. Colas (Chrystelle); F. Soubrier; Warcoin, M. (Mathilde); F. Prieur (Fabienne); M. Lebrun (Marine); C. Kientz (Caroline); D.W. Muller (Danièle); J.P. Fricker (Jean Pierre); C. Toulas (Christine); R. Guimbaud (Rosine); L. Gladieff (Laurence); V. Feillel (Viviane); I. Mortemousque (Isabelle); B. Bressac-de Paillerets (Brigitte); O. Caron (Olivier); M. Guillaud-Bataille (Marine); H. Gregory (Helen); Z. Miedzybrodzka (Zosia); P.J. Morrison (Patrick); A. Donaldson (Alan); M.T. Rogers (Mark); M.J. Kennedy (John); M.E. Porteous (Mary); A. Brady (A.); J. Barwell (Julian); Foo, C. (Claire); F. Lalloo (Fiona); L. Side (Lucy); J. Eason (Jacqueline); Henderson, A. (Alex); L.J. Walker (Lisa); J. Cook (Jackie); Snape, K. (Katie); A. Murray (Alexandra); E. McCann (Emma); M.A. Rookus (Matti); F.E. van Leeuwen (F.); L. van der Kolk (Lizet); M.K. Schmidt (Marjanka); N.S. Russell (Nicola); J.L. de Lange (J.); Wijnands, R.; J.M. Collée (Margriet); M.J. Hooning (Maartje); Seynaeve, C.; C.H.M. van Deurzen (Carolien); A.I.M. Obdeijn (Inge-Marie); C.J. van Asperen (Christi); R.A.E.M. Tollenaar (Rob); T.C.T.E.F. van Cronenburg; C.M. Kets; M.G.E.M. Ausems (Margreet); C. van der Pol (Carmen); T.A.M. van Os (Theo); Q. Waisfisz (Quinten); E.J. Meijers-Heijboer (Hanne); E.B. Gómez García (Encarna); J.C. Oosterwijk (Jan); M.J. Mourits (Marjan); G.H. de Bock (Geertruida); H. Vasen (Hans); Siesling, S.; Verloop, J.; L.I.H. Overbeek (Lucy); S.B. Fox (Stephen); J. Kirk (Judy); G.J. Lindeman; M. Price (Melanie)

    2016-01-01

    textabstractA locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 ×

  9. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    DEFF Research Database (Denmark)

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen

    2016-01-01

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER-n...

  10. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

    DEFF Research Database (Denmark)

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen

    2016-01-01

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER...

  11. Multiple mechanisms underlying acquired resistance to taxanes in selected docetaxel-resistant MCF-7 breast cancer cells

    OpenAIRE

    Wang, Harris; Vo, The; Hajar, Ali; Li, Sarah; Chen, Xinmei; Parissenti, Amadeo M; Brindley, David N; Wang, Zhixiang

    2014-01-01

    Background Chemoresistance is a major factor involved in a poor response and reduced overall survival in patients with advanced breast cancer. Although extensive studies have been carried out to understand the mechanisms of chemoresistance, many questions remain unanswered. Methods In this research, we used two isogenic MCF-7 breast cancer cell lines selected for resistance to doxorubicin (MCF-7DOX) or docetaxel (MCF-7TXT) and the wild type parental cell line (MCF-7CC) to study mechanisms und...

  12. Experimental Evolution of Escherichia coli Persister Levels Using Cyclic Antibiotic Treatments.

    Science.gov (United States)

    Van den Bergh, Bram; Michiels, Joran E; Michiels, Jan

    2016-01-01

    Persister cells are difficult to study owing to their transient nature and their usually small number in bacterial populations. In the past, numerous attempts have been made to elucidate persistence mechanisms. However, because of the challenges involved in studying persisters and the clear redundancy in mechanisms underlying their generation, our knowledge of molecular pathways to persistence remains incomplete. Here, we describe how to use experimental evolution with cyclic antibiotic treatments to generate mutants with an increased persister level in stationary phase, ranging from the initial ancestral level up to 100 %. This method will help to unravel molecular pathways to persistence, and opens up a myriad of new possibilities in persister research, such as the convenient study of nearly pure persister cultures and the possibility to investigate the role of time and environmental aspects in the evolution of persistence.

  13. Persistent photoconductivity in strontium titanate.

    Science.gov (United States)

    Tarun, Marianne C; Selim, Farida A; McCluskey, Matthew D

    2013-11-01

    Persistent photoconductivity was observed in strontium titanate (SrTiO(3)) single crystals. When exposed to sub-bandgap light (2.9 eV or higher) at room temperature, the free-electron concentration increases by over 2 orders of magnitude. After the light is turned off, the enhanced conductivity persists for several days, with negligible decay. From positron lifetime measurements, the persistent photoconductivity is attributed to the excitation of an electron from a titanium vacancy defect into the conduction band, with a very low recapture rate.

  14. Hospitalizations in Pediatric and Adult Patients for All Cancer Type in Italy: The EPIKIT Study under the E.U. COHEIRS Project on Environment and Health

    Directory of Open Access Journals (Sweden)

    Prisco Piscitelli

    2017-05-01

    Full Text Available Background: Cancer Registries (CRs remain the gold standard for providing official epidemiological estimations. However, due to CRs’ partial population coverage, hospitalization records might represent a valuable tool to provide additional information on cancer occurrence and expenditures at national/regional level for research purposes. The Epidemiology of Cancer in Italy (EPIKIT study group has been built up, within the framework of the Civic Observers for Health and Environment: Initiative of Responsibility and Sustainability (COHEIRS project under the auspices of the Europe for Citizens Program, to assess population health indicators. Objective: To assess the burden of all cancers in Italian children and adults. Methods: We analyzed National Hospitalization Records from 2001 to 2011. Based on social security numbers (anonymously treated, we have excluded from our analyses all re-hospitalizations of the same patients (n = 1,878,109 over the entire 11-year period in order to minimize the overlap between prevalent and incident cancer cases. To be more conservative, only data concerning the last five years (2007–2011 have been taken into account for final analyses. The absolute number of hospitalizations and standardized hospitalization rates (SHR were computed for each Italian province by sex and age-groups (0–19 and 20–49. Results: The EPIKIT database included a total of 4,113,169 first hospital admissions due to main diagnoses of all tumors. The annual average number of hospital admissions due to cancer in Italy has been computed in 2362 and 43,141 hospitalizations in pediatric patients (0–19 years old and adults (20–49 years old, respectively. Women accounted for the majority of cancer cases in adults aged 20–49. As expected, the big city of Rome presented the highest average annual number of pediatric cancers (n = 392, SHR = 9.9, followed by Naples (n = 378; SHR = 9.9 and Milan (n = 212; SHR = 7.3. However, when we look at SHR

  15. Serum biomarkers of habitual coffee consumption may provide insight into the mechanism underlying the association between coffee consumption and colorectal cancer.

    Science.gov (United States)

    Guertin, Kristin A; Loftfield, Erikka; Boca, Simina M; Sampson, Joshua N; Moore, Steven C; Xiao, Qian; Huang, Wen-Yi; Xiong, Xiaoqin; Freedman, Neal D; Cross, Amanda J; Sinha, Rashmi

    2015-05-01

    Coffee intake may be inversely associated with colorectal cancer; however, previous studies have been inconsistent. Serum coffee metabolites are integrated exposure measures that may clarify associations with cancer and elucidate underlying mechanisms. Our aims were 2-fold as follows: 1) to identify serum metabolites associated with coffee intake and 2) to examine these metabolites in relation to colorectal cancer. In a nested case-control study of 251 colorectal cancer cases and 247 matched control subjects from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we conducted untargeted metabolomics analyses of baseline serum by using ultrahigh-performance liquid-phase chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. Usual coffee intake was self-reported in a food-frequency questionnaire. We used partial Pearson correlations and linear regression to identify serum metabolites associated with coffee intake and conditional logistic regression to evaluate associations between coffee metabolites and colorectal cancer. After Bonferroni correction for multiple comparisons (P = 0.05 ÷ 657 metabolites), 29 serum metabolites were positively correlated with coffee intake (partial correlation coefficients: 0.18-0.61; P 0.40) included trigonelline (N'-methylnicotinate), quinate, and 7 unknown metabolites. Of 29 serum metabolites, 8 metabolites were directly related to caffeine metabolism, and 3 of these metabolites, theophylline (OR for 90th compared with 10th percentiles: 0.44; 95% CI: 0.25, 0.79; P-linear trend = 0.006), caffeine (OR for 90th compared with 10th percentiles: 0.56; 95% CI: 0.35, 0.89; P-linear trend = 0.015), and paraxanthine (OR for 90th compared with 10th percentiles: 0.58; 95% CI: 0.36, 0.94; P-linear trend = 0.027), were inversely associated with colorectal cancer. Serum metabolites can distinguish coffee drinkers from nondrinkers; some caffeine-related metabolites were inversely associated with colorectal

  16. Serum biomarkers of habitual coffee consumption may provide insight into the mechanism underlying the association between coffee consumption and colorectal cancer12345

    Science.gov (United States)

    Guertin, Kristin A; Loftfield, Erikka; Boca, Simina M; Sampson, Joshua N; Moore, Steven C; Xiao, Qian; Huang, Wen-Yi; Xiong, Xiaoqin; Freedman, Neal D; Cross, Amanda J; Sinha, Rashmi

    2015-01-01

    Background: Coffee intake may be inversely associated with colorectal cancer; however, previous studies have been inconsistent. Serum coffee metabolites are integrated exposure measures that may clarify associations with cancer and elucidate underlying mechanisms. Objectives: Our aims were 2-fold as follows: 1) to identify serum metabolites associated with coffee intake and 2) to examine these metabolites in relation to colorectal cancer. Design: In a nested case-control study of 251 colorectal cancer cases and 247 matched control subjects from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we conducted untargeted metabolomics analyses of baseline serum by using ultrahigh-performance liquid-phase chromatography–tandem mass spectrometry and gas chromatography–mass spectrometry. Usual coffee intake was self-reported in a food-frequency questionnaire. We used partial Pearson correlations and linear regression to identify serum metabolites associated with coffee intake and conditional logistic regression to evaluate associations between coffee metabolites and colorectal cancer. Results: After Bonferroni correction for multiple comparisons (P = 0.05 ÷ 657 metabolites), 29 serum metabolites were positively correlated with coffee intake (partial correlation coefficients: 0.18–0.61; P coffee intake (partial correlation coefficients >0.40) included trigonelline (N′-methylnicotinate), quinate, and 7 unknown metabolites. Of 29 serum metabolites, 8 metabolites were directly related to caffeine metabolism, and 3 of these metabolites, theophylline (OR for 90th compared with 10th percentiles: 0.44; 95% CI: 0.25, 0.79; P-linear trend = 0.006), caffeine (OR for 90th compared with 10th percentiles: 0.56; 95% CI: 0.35, 0.89; P-linear trend = 0.015), and paraxanthine (OR for 90th compared with 10th percentiles: 0.58; 95% CI: 0.36, 0.94; P-linear trend = 0.027), were inversely associated with colorectal cancer. Conclusions: Serum metabolites can

  17. Hospitalizations in Pediatric and Adult Patients for All Cancer Type in Italy: The EPIKIT Study under the E.U. COHEIRS Project on Environment and Health.

    Science.gov (United States)

    Piscitelli, Prisco; Marino, Immacolata; Falco, Andrea; Rivezzi, Matteo; Romano, Roberto; Mazzella, Restituta; Neglia, Cosimo; Della Rosa, Giulia; Pellerano, Giuseppe; Militerno, Giuseppe; Bonifacino, Adriana; Rivezzi, Gaetano; Romizi, Roberto; Miserotti, Giuseppe; Montella, Maurizio; Bianchi, Fabrizio; Marinelli, Alessandra; De Donno, Antonella; De Filippis, Giovanni; Serravezza, Giuseppe; Di Tanna, Gianluca; Black, Dennis; Gennaro, Valerio; Ascolese, Mario; Distante, Alessandro; Burgio, Ernesto; Crespi, Massimo; Colao, Annamaria

    2017-05-09

    Background : Cancer Registries (CRs) remain the gold standard for providing official epidemiological estimations. However, due to CRs' partial population coverage, hospitalization records might represent a valuable tool to provide additional information on cancer occurrence and expenditures at national/regional level for research purposes. The Epidemiology of Cancer in Italy (EPIKIT) study group has been built up, within the framework of the Civic Observers for Health and Environment: Initiative of Responsibility and Sustainability (COHEIRS) project under the auspices of the Europe for Citizens Program, to assess population health indicators. Objective : To assess the burden of all cancers in Italian children and adults. Methods : We analyzed National Hospitalization Records from 2001 to 2011. Based on social security numbers (anonymously treated), we have excluded from our analyses all re-hospitalizations of the same patients ( n = 1,878,109) over the entire 11-year period in order to minimize the overlap between prevalent and incident cancer cases. To be more conservative, only data concerning the last five years (2007-2011) have been taken into account for final analyses. The absolute number of hospitalizations and standardized hospitalization rates (SHR) were computed for each Italian province by sex and age-groups (0-19 and 20-49). Results : The EPIKIT database included a total of 4,113,169 first hospital admissions due to main diagnoses of all tumors. The annual average number of hospital admissions due to cancer in Italy has been computed in 2362 and 43,141 hospitalizations in pediatric patients (0-19 years old) and adults (20-49 years old), respectively. Women accounted for the majority of cancer cases in adults aged 20-49. As expected, the big city of Rome presented the highest average annual number of pediatric cancers ( n = 392, SHR = 9.9), followed by Naples ( n = 378; SHR = 9.9) and Milan ( n = 212; SHR = 7.3). However, when we look at SHR, minor

  18. Cancer Screening

    Directory of Open Access Journals (Sweden)

    Krishna Prasad

    2004-10-01

    Full Text Available Cancer screening is a means to detect cancer early with the goal of decreasing morbidity and mortality. At present, there is a reasonable consensus regarding screening for breast, cervical and colorectal cances and the role of screening is under trial in case of cancers of the lung,  ovaries and prostate. On the other hand, good screening tests are not available for some of the commonest cancers in India like the oral, pharyngeal, esophageal and stomach cancers.

  19. Utility of PTEN protein dosage in predicting for underlying germline PTEN mutations among patients presenting with thyroid cancer and Cowden-like phenotypes.

    Science.gov (United States)

    Ngeow, Joanne; He, Xin; Mester, Jessica L; Lei, Junying; Romigh, Todd; Orloff, Mohammed S; Milas, Mira; Eng, Charis

    2012-12-01

    Thyroid cancer is a major component of Cowden syndrome (CS). CS patients with an underlying PTEN mutation (PTEN(mut+)) have a 70-fold increased risk of developing epithelial thyroid cancer. In contrast, less than 1% of sporadic epithelial thyroid cancer patients carry a germline PTEN mutation. Cost-efficient markers capable of shortlisting thyroid cancers for CS genetic testing would be clinically useful. Our objective was to analyze the utility of patient blood phosphate and tensin homolog deleted on chromosome 10 (PTEN) protein levels in predicting germline PTEN mutations. We conducted a 5-yr, multicenter prospective study of 2792 CS and CS-like patients, all of whom had comprehensive PTEN analysis. Analysis of PTEN and downstream proteins by immunoblotting was performed on total protein lysates from patient-derived lymphoblast lines. We compared blood PTEN protein levels between PTEN(mut+) patients and those with variants of unknown significance or wild-type PTEN (PTEN(wt/vus)). We assessed the utility of PTEN protein levels in predicting germline PTEN mutations. Of 2792 CS/CS-like patients, 721 patients had thyroid cancer; 582 of them (81%) had blood PTEN protein analyzed. PTEN germline pathogenic mutations were present in 27 of 582 patients (4.6%). Ninety-six percent (26 of 27) of PTEN(mut+) patients had blood PTEN protein levels in the lowest quartile as compared with 25% (139 of 555) of PTEN(wt/vus) patients (P PTEN levels predicted for PTEN(mut+) cases with a 99.76% negative predictive value (95% confidence interval = 98.67-99.96) and a positive test likelihood ratio of 3.84 (95% confidence interval = 3.27-4.52). Our study shows that low blood PTEN protein expression could serve as a screening molecular correlate to predict for germline PTEN mutation in CS and CS-like presentations of thyroid cancer.

  20. Object-oriented Persistent Homology.

    Science.gov (United States)

    Wang, Bao; Wei, Guo-Wei

    2016-01-15

    Persistent homology provides a new approach for the topological simplification of big data via measuring the life time of intrinsic topological features in a filtration process and has found its success in scientific and engineering applications. However, such a success is essentially limited to qualitative data classification and analysis. Indeed, persistent homology has rarely been employed for quantitative modeling and prediction. Additionally, the present persistent homology is a passive tool, rather than a proactive technique, for classification and analysis. In this work, we outline a general protocol to construct object-oriented persistent homology methods. By means of differential geometry theory of surfaces, we construct an objective functional, namely, a surface free energy defined on the data of interest. The minimization of the objective functional leads to a Laplace-Beltrami operator which generates a multiscale representation of the initial data and offers an objective oriented filtration process. The resulting differential geometry based object-oriented persistent homology is able to preserve desirable geometric features in the evolutionary filtration and enhances the corresponding topological persistence. The cubical complex based homology algorithm is employed in the present work to be compatible with the Cartesian representation of the Laplace-Beltrami flow. The proposed Laplace-Beltrami flow based persistent homology method is extensively validated. The consistence between Laplace-Beltrami flow based filtration and Euclidean distance based filtration is confirmed on the Vietoris-Rips complex for a large amount of numerical tests. The convergence and reliability of the present Laplace-Beltrami flow based cubical complex filtration approach are analyzed over various spatial and temporal mesh sizes. The Laplace-Beltrami flow based persistent homology approach is utilized to study the intrinsic topology of proteins and fullerene molecules. Based on a

  1. Differences in Meteorological Conditions between Days with Persistent and Non-Persistent Pollution in Beijing, China

    Science.gov (United States)

    You, Ting; Wu, Renguang; Huang, Gang

    2018-02-01

    We compared the regional synoptic patterns and local meteorological conditions during persistent and non-persistent pollution events in Beijing using US NCEP-Department of Energy reanalysis outputs and observations from meteorological stations. The analysis focused on the impacts of high-frequency (period pollution events (those lasting for at least 3 days). Persistent pollution events tended to occur in association with slow-moving weather systems producing stagnant weather conditions, whereas rapidly moving weather systems caused a dramatic change in the local weather conditions so that the pollution event was short-lived. Although Beijing was under the influence of anomalous southerly winds in all four seasons during pollution events, notable differences were identified in the regional patterns of sea-level pressure and local anomalies in relative humidity among persistent pollution events in different seasons. A region of lower pressure was present to the north of Beijing in spring, fall, and winter, whereas regions of lower and higher pressures were observed northwest and southeast of Beijing, respectively, in summer. The relative humidity near Beijing was higher in fall and winter, but lower in spring and summer. These differences may explain the seasonal dependence of the relationship between air pollution and the local meteorological variables. Our analysis showed that the temperature inversion in the lower troposphere played an important part in the occurrence of air pollution under stagnant weather conditions. Some results from this study are based on a limited number of events and thus require validation using more data.

  2. Strategies used by helicobacter pylori to establish persistent infection

    Science.gov (United States)

    Abadi, Amin Talebi Bezmin

    2017-01-01

    Helicobacter pylori (H. pylori) is a Gram-negative and motile bacterium that colonizes the hostile microniche of the human stomach, then persists for the host’s entire life, if not effectively treated. Clinically, H. pylori plays a causative role in the development of a wide spectrum of diseases including chronic active gastritis, peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Due to the global distribution of H. pylori, it is no exaggeration to conclude that smart strategies are contributing to adaptation of the bacterium to its permanent host. Thirty-four years after the discovery of this bacterium, there are still many unanswered questions. For example, which strategies help the bacterium to survive in this inhospitable microniche? This question is slightly easier to answer if we presume the same clinical concept for both persistent infection and disease. Understanding the mechanisms governing H. pylori persistence will improve identification of the increased risk of diseases such as gastric cancer in patients infected with this bacterium. A well-defined and long-term equilibrium between the human host and H. pylori allows bacterial persistence in the gastric microniche; although this coexistence leads to a high risk of severe diseases such as gastric cancer. To escape the bactericidal activity of stomach acid, H. pylori secretes large amounts of surface-associated and cytosolic urease. The potential to avoid acidic conditions and immune evasion are discussed in order to explain the persistence of H. pylori colonization in the gastric mucosa, and data on bacterial genetic diversity are included. Information on the mechanisms related to H. pylori persistence can also provide the direction for future research concerning effective therapy and management of gastroduodenal disorders. The topics presented in the current review are important for elucidating the strategies used by H. pylori to help the bacterium

  3. The convergence of lung cancer rates between blacks and whites under the age of 40, United States.

    Science.gov (United States)

    Jemal, Ahmedin; Center, Melissa M; Ward, Elizabeth

    2009-12-01

    Lung cancer rates in the United States have been consistently higher in blacks than in whites at all ages in men and at younger ages in women. However, since the 1970s, smoking initiation decreased more rapidly among blacks than whites. We examined trends in lung cancer rates for white and black young adults (ages 20-39) from 1992 to 2006 using joinpoint models and black-to-white rate ratios by sex. Lung cancer death rates in 20- to 39-year-olds significantly decreased in all groups but was much steeper for blacks than for whites. From 1992 to 1994 and 2004 to 2006, the black-to-white mortality rate ratio (95% confidence interval) decreased from 2.16 (1.90-2.44) to 1.28 (1.05-1.55) for men and from 1.47 (1.25-1.71) to 0.97 (0.78-1.19) for women. A similar convergence was observed in the lung cancer incidence rates. These findings suggest that if current smoking trends in the young continue, racial differences in overall lung cancer rates in men will be eliminated in the next 40 to 50 years.

  4. New Enlightenment of Skin Cancer Chemoprevention through Phytochemicals: In Vitro and In Vivo Studies and the Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Madhulika Singh

    2014-01-01

    Full Text Available Skin cancer is still a major cause of morbidity and mortality worldwide. Skin overexposure to ultraviolet irradiations, chemicals, and several viruses has a capability to cause severe skin-related disorders including immunosuppression and skin cancer. These factors act in sequence at various steps of skin carcinogenesis via initiation, promotion, and/or progression. These days cancer chemoprevention is recognized as the most hopeful and novel approach to prevent, inhibit, or reverse the processes of carcinogenesis by intervention with natural products. Phytochemicals have antioxidant, antimutagenic, anticarcinogenic, and carcinogen detoxification capabilities thereby considered as efficient chemopreventive agents. Considerable efforts have been done to identify the phytochemicals which may possibly act on one or several molecular targets that modulate cellular processes such as inflammation, immunity, cell cycle progression, and apoptosis. Till date several phytochemicals in the light of chemoprevention have been studied by using suitable skin carcinogenic in vitro and in vivo models and proven as beneficial for prevention of skin cancer. This revision presents a comprehensive knowledge and the main molecular mechanisms of actions of various phytochemicals in the chemoprevention of skin cancer.

  5. A Pilot Study of Self-Reported Physical Activity and Eating Habits in Turkish Cancer Patients Under Chemotherapy.

    Science.gov (United States)

    Gunes-Bayir, Ayse; Kiziltan, Huriye Senay; Sentürk, Nidanur; Mayadaglı, Alpaslan; Gumus, Mahmut

    2015-01-01

    As in all individuals, improving the quality of life, balanced nutrition and physical activity habits must be acquired in cancer patients. The purpose of this study was to determine eating habits and physical activity of cancer patients receiving chemotherapy. Sixty-six patients were completed the questionnaire included sociodemographic data, type of cancer, anthropometric measurements (size and body weight), dietary and physical activity habits. Body mass index for each patient was calculated. Data were analyzed using Statistical Package for Social Science software. Patients were ranged from underweight to obese according to their body mass index: 6.1% of patients were classified as underweight. Almost half (48.5%, n = 32) reported to be regularly physical active, and 46.9% (n = 15) thereof reported 30 min brisk walking. More vegetables consumption was the most popular answer with 62.1% (n = 41), whereas vegetables/fruit or vegetables/legume consumption was 22.7% (n = 15). Gender differences in food choice and preferring the taste of food were not seen as statistically significant. In this article, patients with different types of cancer reported their eating habits and physical activity. Disease-related and worse prognostic factors were found. An institutional program should be offered to cancer patients for consulting about nutrition and physical activity.

  6. The underlying cause of cervical cancer in oral contraceptive users may be related to cervical mucus changes.

    Science.gov (United States)

    Guven, Suleyman; Kart, Cavit; Guvendag Guven, Emine Seda; Gunalp, G Serdar

    2007-01-01

    Oral contraceptives (OCs) remain among the most effective reversible methods of birth control available today, providing almost 100% effectiveness with an impressively high margin of safety and other important health benefits. However, concerns have been raised about the role that the hormones in OCs might play in the pathogenesis of cervical cancer. Evidence shows that long-term use of OCs (five or more years) may be associated with an increased risk of cancer of the cervix. The mechanism of increased risk of cervical cancer in OCs users has long been debated, and remains uncertain. Our hypothesis is that scanty, thick, and highly viscous cervical mucus obtained in OCs users intimately involved in the pathogenesis of cervical cancer. Possibly, this architecture of cervical mucus may modulate and prolong the effect of carcinogenic agents, which have been carried by coitus and stored in posterior vaginal fornix, on squamocolumnar junction of cervix by not permitting them to be removed because of its highly viscous pattern. The role of cervical mucus changes by means of specific mucin protein changes on the pathophysiology of cervical cancer in OCs users should be investigated.

  7. New Enlightenment of Skin Cancer Chemoprevention through Phytochemicals: In Vitro and In Vivo Studies and the Underlying Mechanisms

    Science.gov (United States)

    Singh, Madhulika; Suman, Shankar; Shukla, Yogeshwer

    2014-01-01

    Skin cancer is still a major cause of morbidity and mortality worldwide. Skin overexposure to ultraviolet irradiations, chemicals, and several viruses has a capability to cause severe skin-related disorders including immunosuppression and skin cancer. These factors act in sequence at various steps of skin carcinogenesis via initiation, promotion, and/or progression. These days cancer chemoprevention is recognized as the most hopeful and novel approach to prevent, inhibit, or reverse the processes of carcinogenesis by intervention with natural products. Phytochemicals have antioxidant, antimutagenic, anticarcinogenic, and carcinogen detoxification capabilities thereby considered as efficient chemopreventive agents. Considerable efforts have been done to identify the phytochemicals which may possibly act on one or several molecular targets that modulate cellular processes such as inflammation, immunity, cell cycle progression, and apoptosis. Till date several phytochemicals in the light of chemoprevention have been studied by using suitable skin carcinogenic in vitro and in vivo models and proven as beneficial for prevention of skin cancer. This revision presents a comprehensive knowledge and the main molecular mechanisms of actions of various phytochemicals in the chemoprevention of skin cancer. PMID:24757666

  8. Teriparatide Induced Delayed Persistent Hypercalcemia

    OpenAIRE

    Thiruchelvam, Nirosshan; Randhawa, Jaskirat; Sadiek, Happy; Kistangari, Gaurav

    2014-01-01

    Teriparatide, a recombinant PTH, is an anabolic treatment for osteoporosis that increases bone density. Transient hypercalcemia is a reported side effect of teriparatide that is seen few hours following administration of teriparatide and resolves usually within 16 hours of drug administration. Persistent hypercalcemia, although not observed in clinical trials, is rarely reported. The current case describes a rare complication of teriparatide induced delayed persistent hypercalcemia.

  9. Teriparatide Induced Delayed Persistent Hypercalcemia

    Directory of Open Access Journals (Sweden)

    Nirosshan Thiruchelvam

    2014-01-01

    Full Text Available Teriparatide, a recombinant PTH, is an anabolic treatment for osteoporosis that increases bone density. Transient hypercalcemia is a reported side effect of teriparatide that is seen few hours following administration of teriparatide and resolves usually within 16 hours of drug administration. Persistent hypercalcemia, although not observed in clinical trials, is rarely reported. The current case describes a rare complication of teriparatide induced delayed persistent hypercalcemia.

  10. Posttraumatic Stress Disorder After High-Dose-Rate Brachytherapy for Cervical Cancer With 2 Fractions in 1 Application Under Spinal/Epidural Anesthesia: Incidence and Risk Factors

    Energy Technology Data Exchange (ETDEWEB)

    Kirchheiner, Kathrin, E-mail: kathrin.kirchheiner@meduniwien.ac.at [Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna/General Hospital of Vienna, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna (Austria); Czajka-Pepl, Agnieszka [Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna/General Hospital of Vienna, Vienna (Austria); Ponocny-Seliger, Elisabeth [Department of Psychology, Sigmund Freud Private University Vienna, Vienna (Austria); Scharbert, Gisela; Wetzel, Léonore [Department of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna/General Hospital of Vienna, Vienna (Austria); Nout, Remi A. [Department of Clinical Oncology, Leiden University Medical Center, Leiden (Netherlands); Sturdza, Alina [Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna/General Hospital of Vienna, Vienna (Austria); Dimopoulos, Johannes C. [Metropolitan Hospital, Athens (Greece); Dörr, Wolfgang; Pötter, Richard [Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna/General Hospital of Vienna, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna (Austria)

    2014-06-01

    Purpose: To investigate the psychological consequences of high-dose-rate brachytherapy with 2 fractions in 1 application under spinal/epidural anesthesia in the treatment of locally advanced cervical cancer. Methods and Materials: In 50 patients with locally advanced cervical cancer, validated questionnaires were used for prospective assessment of acute and posttraumatic stress disorder (ASD/PTSD) (Impact of Event Scale–Revision), anxiety/depression (Hospital Anxiety and Depression Scale), quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30/Cervical Cancer 24), physical functioning (World Health Organization performance status), and pain (visual analogue scale), before and during treatment and 1 week and 3 months after treatment. Qualitative interviews were recorded in open format for content analysis. Results: Symptoms of ASD occurred in 30% of patients 1 week after treatment; and of PTSD in 41% 3 months after treatment in association with this specific brachytherapy procedure. Pretreatment predictive variables explain 82% of the variance of PTSD symptoms. Helpful experiences were the support of the treatment team, psychological support, and a positive attitude. Stressful factors were pain, organizational problems during treatment, and immobility between brachytherapy fractions. Conclusions: The specific brachytherapy procedure, as performed in the investigated mono-institutional setting with 2 fractions in 1 application under spinal/epidural anesthesia, bears a considerable risk of traumatization. The source of stress seems to be not the brachytherapy application itself but the maintenance of the applicator under epidural anesthesia in the time between fractions. Patients at risk may be identified before treatment, to offer targeted psycho-social support. The patients' open reports regarding helpful experiences are an encouraging feedback for the treatment team; the reported stressful

  11. Posttraumatic Stress Disorder After High-Dose-Rate Brachytherapy for Cervical Cancer With 2 Fractions in 1 Application Under Spinal/Epidural Anesthesia: Incidence and Risk Factors

    International Nuclear Information System (INIS)

    Kirchheiner, Kathrin; Czajka-Pepl, Agnieszka; Ponocny-Seliger, Elisabeth; Scharbert, Gisela; Wetzel, Léonore; Nout, Remi A.; Sturdza, Alina; Dimopoulos, Johannes C.; Dörr, Wolfgang; Pötter, Richard

    2014-01-01

    Purpose: To investigate the psychological consequences of high-dose-rate brachytherapy with 2 fractions in 1 application under spinal/epidural anesthesia in the treatment of locally advanced cervical cancer. Methods and Materials: In 50 patients with locally advanced cervical cancer, validated questionnaires were used for prospective assessment of acute and posttraumatic stress disorder (ASD/PTSD) (Impact of Event Scale–Revision), anxiety/depression (Hospital Anxiety and Depression Scale), quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30/Cervical Cancer 24), physical functioning (World Health Organization performance status), and pain (visual analogue scale), before and during treatment and 1 week and 3 months after treatment. Qualitative interviews were recorded in open format for content analysis. Results: Symptoms of ASD occurred in 30% of patients 1 week after treatment; and of PTSD in 41% 3 months after treatment in association with this specific brachytherapy procedure. Pretreatment predictive variables explain 82% of the variance of PTSD symptoms. Helpful experiences were the support of the treatment team, psychological support, and a positive attitude. Stressful factors were pain, organizational problems during treatment, and immobility between brachytherapy fractions. Conclusions: The specific brachytherapy procedure, as performed in the investigated mono-institutional setting with 2 fractions in 1 application under spinal/epidural anesthesia, bears a considerable risk of traumatization. The source of stress seems to be not the brachytherapy application itself but the maintenance of the applicator under epidural anesthesia in the time between fractions. Patients at risk may be identified before treatment, to offer targeted psycho-social support. The patients' open reports regarding helpful experiences are an encouraging feedback for the treatment team; the reported stressful

  12. Resonant persistent currents for ultracold bosons on a lattice ring

    Science.gov (United States)

    Arwas, Geva; Cohen, Doron; Hekking, Frank; Minguzzi, Anna

    2017-12-01

    We consider a one-dimensional bosonic gas on a ring lattice, in the presence of a localized barrier, and under the effect of an artificial gauge field. By means of exact diagonalization we study the persistent currents at varying interactions and barrier strength, for various values of lattice filling. While generically the persistent currents are strongly suppressed in the Mott insulator phase, they show a resonant behavior when the barrier strength becomes of the order of the interaction energy. We explain this phenomenon using an effective single-particle model. We show that this effect is robust at finite temperature, up the temperature scale where persistent currents vanish.

  13. Surveying the effect of a self-care education program on severity of nausea and emesis in colorectal cancer patients under chemotherapy

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    Karimi S

    2017-08-01

    Full Text Available Saba Karimi,1 Behnam Reza Makhsosi,2 Seyed Jalil Seyedi-Andi,3 Maryam Behzadi,4 Yasaman Moghofeh,5 Kourosh Mohammadinasrabadi,1 Alireza Abdi,1 Pegah Ahmadi1 1School of Nursing and Midwifery, 2Surgical Department, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, 3Social Determinants of Health Research Center, Babol University of Medical Sciences, Babol, 4Taleghani Hospital, 5Imam Khomeini Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran Background and objective: Colorectal cancer is one of the main causes of mortality in both developed and developing countries, including Iran. One of the treatments available for colorectal cancer is chemotherapy, of which nausea and emesis are the side effects. Owing to problems in controlling the side effects, a combination of medicine and non-medicine interventions is usually used. Self-care is one of the non-medicine interventions in this regard. The present study was aimed at surveying the effect of a self-care education program on severity of nausea and emesis in colorectal cancer patients under chemotherapy.Methods: A semi-experimental study was carried out in Imam Reza Hospital of Kermanshah, Iran. The sample group comprised 52 patients with colorectal cancer under chemotherapy. Data gathering tools included a demographics questionnaire and Morrow Assessment of Nausea and Emesis. To control intensity of nausea and emesis, a package of self-care measures including muscular progressive relaxation, music, and education on nutrition was used. Afterward, the collected data were analyzed using statistical tests such as Shapiro–Wilk test (to check normal distribution of the data, Mann–Whitney U test, Wilcoxon test, and chi-square test with the help of SPSS 20.Results: The results showed a considerable decrease in intensity and frequency of nausea and emesis after the intervention. The p-value of Mann–Whitney U test results with regard to intensity of nausea in

  14. Nuclear factor-κB-dependent epithelial to mesenchymal transition induced by HIF-1α activation in pancreatic cancer cells under hypoxic conditions.

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    Zhuo-Xin Cheng

    Full Text Available Epithelial to mesenchymal transition (EMT induced by hypoxia is one of the critical causes of treatment failure in different types of human cancers. NF-κB is closely involved in the progression of EMT. Compared with HIF-1α, the correlation between NF-κB and EMT during hypoxia has been less studied, and although the phenomenon was observed in the past, the molecular mechanisms involved remained unclear.Here, we report that hypoxia or overexpression of hypoxia-inducible factor-1α (HIF-1α promotes EMT in pancreatic cancer cells. On molecular or pharmacologic inhibition of NF-κB, hypoxic cells regained expression of E-cadherin, lost expression of N-cadherin, and attenuated their highly invasive and drug-resistant phenotype. Introducing a pcDNA3.0/HIF-1α into pancreatic cancer cells under normoxic conditions heightened NF-κB activity, phenocopying EMT effects produced by hypoxia. Conversely, inhibiting the heightened NF-κB activity in this setting attenuated the EMT phenotype.These results suggest that hypoxia or overexpression of HIF-1α induces the EMT that is largely dependent on NF-κB in pancreatic cancer cells.

  15. Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences

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    Birman Tatiana

    2009-08-01

    Full Text Available Abstract Background Ovarian cancer ascites fluid (OCAF, contains malignant cells, is usually present in women with an advanced stage disease and currently has no effective therapy. Hence, we developed a new therapy strategy to target the expression of diphtheria toxin gene under the control of H19 regulatory sequences in ovarian tumor cells. H19 RNA is present at high levels in human cancer tissues (including ovarian cancer, while existing at a nearly undetectable level in the surrounding normal tissue. Methods H19 gene expression was tested in cells from OCAF by the in-situ hybridization technique (ISH using an H19 RNA probe. The therapeutic potential of the toxin vector DTA-H19 was tested in ovarian carcinoma cell lines and in a heterotopic animal model for ovarian cancer. Results H19 RNA was detected in 90% of patients with OCAF as determined by ISH. Intratumoral injection of DTA-H19 into ectopically developed tumors caused 40% inhibition of tumor growth. Conclusion These observations may be the first step towards a major breakthrough in the treatment of human OCAF, while the effect in solid tumors required further investigation. It should enable us to identify likely non-responders in advance, and to treat patients who are resistant to all known therapies, thereby avoiding treatment failure.

  16. Assessing Inflation Persistence: Micro Evidence on an Inflation Targeting Economy

    OpenAIRE

    Jan Babecký; Fabrizio Coricelli; Roman Horváth

    2009-01-01

    The paper provides an empirical analysis of inflation persistence in one of the inflation targeting countries, the Czech Republic, using 412 detailed product-level consumer price indexes underlying the consumer basket over the period from 1994:M1 to 2005:M12. Subject to various sensitivity tests, the authors´ results suggest that raw goods and non-durables, followed by services, display smaller inflation persistence than durables and processed goods. Inflation seems to be somewhat less persis...

  17. The Long Persistence of Regional Entrepreneurship Culture: Germany 1925 - 2005

    OpenAIRE

    Michael Fritsch; Michael Wyrwich

    2012-01-01

    We investigate the persistence of levels of self-employment and new business formation in different time periods and under different framework conditions. The analysis shows that high levels of regional self-employment and new business formation tend to be persistent for periods as long as 80 years and that such an entrepreneurial culture can even survive abrupt and drastic changes in the politic-economic environment. We thus conclude that regional entrepreneurship cultures do exist and that ...

  18. Insulin-like growth factor stimulation increases radiosensitivity of a pancreatic cancer cell line through endoplasmic reticulum stress under hypoxic conditions

    International Nuclear Information System (INIS)

    Isohashi, Fumiaki; Endo, Hiroko; Mukai, Mutsuko; Inoue, Masahiro; Inoue, Takehiro

    2008-01-01

    Tumor hypoxia is an obstacle to radiotherapy. Radiosensitivity under hypoxic conditions is determined by molecular oxygen levels, as well as by various biological cellular responses. The insulin-like growth factor (IGF) signaling pathway is a widely recognized survival signal that confers radioresistance. However, under hypoxic conditions the role of IGF signaling in radiosensitivity is still poorly understood. Here, we demonstrate that IGF-II stimulation decreases clonogenic survival under hypoxic conditions in the pancreatic cancer cell lines AsPC-1 and Panc-1, and in the human breast cancer cell line MCF-7. IGF treatment under hypoxic conditions suppressed increased radiation sensitivity in these cell lines by pharmacologically inhibiting the phosphoinositide 3-kinase-mammalian target of rapamycin pathway, a major IGF signal-transduction pathway. Meanwhile, IGF-II induced the endoplasmic reticulum stress response under hypoxia, including increased protein levels of CHOP and ATF4, mRNA levels of CHOP, GADD34, and BiP as well as splicing levels of XBP-1. The response was suppressed by inhibiting phosphoinositide 3-kinase and mammalian target of rapamycin activity. Overexpression of CHOP in AsPC-1 cells increased radiation sensitivity by IGF-II simulation under hypoxic conditions, whereas suppression of CHOP expression levels with small hairpin RNA or a dominant negative form of a proline-rich extensin-like receptor protein kinase in hypoxia decreased IGF-induced radiosensitivity. IGF-induced endoplasmic reticulum stress contributed to radiosensitization independent of cell cycle status. Taken together, IGF stimulation increased radiosensitivity through the endoplasmic reticulum stress response under hypoxic conditions. (author)

  19. RECURRENT/PERSISTENT PNEUMONIA AMONG CHILDREN IN UPPER EGYPT

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    Khaled Saad

    2013-04-01

    Full Text Available Abstract Objectives: Recurrent/persistent pneumonia in children continues to be a major challenge for the paediatricians. We aimed to determine the prevalence and underlying causes of recurrent/persistent pneumonia in children in Upper Egypt. Settings: Assiut University Children Hospital, Assiut, Egypt.   Methods: Patients with pneumonia admitted to the hospital during 2 years were investigated (microbiological, biochemical, immunological and radiological tests for recurrent/persistent pneumonia to determine its prevalence and to find out the underlying causes.   Results: 113 out of 1228 patients (9.2% met the diagnosis of recurrent/persistent pneumonia. Identified causes were;  aspiration syndromes (17.7%, pulmonary TB (14%, congenital heart disease (11.5%, bronchial asthma (9.7%, immune deficiency disorders (8.8% and vitamin D deficiency rickets (7%. Other causes included; congenital anomalies of the respiratory tract, interstitial lung diseases, bronchiectasis, and sickle cell anemia. No predisposing factors could be identified in 15% of cases. Conclusion: Approximately 1 in 10 children with pneumonia in our locality had recurrent/persistent pneumonia. The most frequent underlying cause for recurrent/persistent pneumonia in children in Upper Egypt is aspiration syndromes, followed by pulmonary TB.

  20. Radiosensitization by 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide under oxia and hypoxia in human colon cancer cells

    International Nuclear Information System (INIS)

    Itani, Wafica; Geara, Fady; Haykal, Joelle; Haddadin, Makhluf; Gali-Muhtasib, Hala

    2007-01-01

    The sensitizing effects of 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide (DCQ) and ionizing radiation (IR) were determined in four colon cancer cells and in FHs74Int normal intestinal cells. Cell cycle modulation, TUNEL assay, clonogenic survival and DNA damage were examined under oxia or hypoxia. Effects on apoptotic molecules and on p-Akt and Cox-2 protein expression were investigated. The four cell lines responded differently to DCQ+IR; HT-29 cells were most resistant. Combination treatment caused significant increases in preG 1 (apoptosis) in HCT-116, while G 2 /M arrest occurred in DLD-1. DCQ potentiated IR effects more so under hypoxia than oxia. Pre-exposure of DLD-1 to hypoxia induced 30% apoptosis, and G 2 /M arrest in oxia. The survival rate was 50% lower in DCQ+IR than DCQ alone and this rate further decreased under hypoxia. FHs74Int normal intestinal cells were more resistant to DCQ+IR than cancer cells.Greater ssDNA damage occurred in DLD-1 exposed to DCQ+IR under hypoxia than oxia. In oxia, p-Akt protein expression increased upon IR exposure and drug pre-treatment inhibited this increase. In contrast, in hypoxia, exposure to IR reduced p-Akt protein and DCQ restored its expression to the untreated control. Apoptosis induced in hypoxic DLD-1 cells was independent of p53-p21 modulation but was associated with an increase in Bax/Bcl-2 ratio and the inhibition of the Cox-2 protein. DCQ is a hypoxic cell radiosensitizer in DLD-1 human colon cancer cells

  1. A Case of Brainstem Cavernous Angioma Presenting with Persistent Hiccups

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Arami

    2010-07-01

    Full Text Available "nIntractable hiccup most be considered as a symptom of underlying serious pathologies. We report a case of medulla oblongata cavernous angima presented with persistant hiccup and without any improvement during routine nonpharmacologic and pharmacologic treatment regimns. The patient is under our follow up visits and surgery is very high risk for this young girl.

  2. "It's More Flexible": Persistence of Women Engineers in the Academy

    Science.gov (United States)

    Mlambo, Yeukai Angela; Mabokela, Reitumetse Obakeng

    2017-01-01

    The under-representation of women in engineering is an issue of concern for policy-makers. While much of the existing literature has focussed on understanding reasons for women's under-representation in engineering and related technical fields, there is a paucity of research that examines why women who are already in engineering persist. This…

  3. Metastatic carcinoma of the urinary bladder in a 67-year-old female with underlying triple primary cancers

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    Chia-Yen Hung

    2016-06-01

    A 67-year-old Taiwanese female presented to our institution in November 1997 with gastric signet ring cell carcinoma, pT2N0M0, status post subtotal gastrectomy. In February 2003 she was diagnosed with left breast invasive lobular carcinoma status post modified radical mastectomy, pT2N2M0. Further examination in January 2005 revealed proximal transverse colon cancer, Dukes' C2, with status post right hemicolectomy. She achieved disease-free status from all three malignancies after surgical resection and adjuvant chemotherapy for breast and colon cancers sequentially. In November 2011, she complained about sudden onset of gross hematuria for several days. Diagnostic cystoscopy showed a mass lesion over her urinary bladder. Cystoscope-assisted biopsy showed metastatic poorly differentiated adenocarcinoma with signet ring appearance. Herein we have discussed the pathologic role in the diagnosis of metastatic tumor involving a patient with multiple primary cancers. We also explored the epidemiologic risk and potential causal mechanism of patients with multiple primary cancers.

  4. Uptake of tamoxifen in consecutive premenopausal women under surveillance in a high-risk breast cancer clinic.

    Science.gov (United States)

    Donnelly, L S; Evans, D G; Wiseman, J; Fox, J; Greenhalgh, R; Affen, J; Juraskova, I; Stavrinos, P; Dawe, S; Cuzick, J; Howell, A

    2014-04-02

    Randomised trials of tamoxifen versus placebo indicate that tamoxifen reduces breast cancer risk by approximately 33%, yet uptake is low. Approximately 10% of women in our clinic entered the IBIS-I prevention trial. We assess the uptake of tamoxifen in a consecutive series of premenopausal women not in a trial and explore the reasons for uptake through interviews. All eligible women between 33 and 46 years at ≥17% lifetime risk of breast cancer and undergoing annual mammography in our service were invited to take a 5-year course of tamoxifen. Reasons for accepting (n=15) or declining (n=15) were explored using semi-structured interviews. Of 1279 eligible women, 136 (10.6%) decided to take tamoxifen. Women >40 years (74 out of 553 (13.4%)) and those at higher non-BRCA-associated risk were more likely to accept tamoxifen (129 out of 1109 (11.6%)). Interviews highlighted four themes surrounding decision making: perceived impact of side effects, the impact of others' experience on beliefs about tamoxifen, tamoxifen as a 'cancer drug', and daily reminder of cancer risk. Tamoxifen uptake was similar to previously ascertained uptake in a randomised controlled trial (IBIS-I). Concerns were similar in women who did or did not accept tamoxifen. Decision making appeared to be embedded in the experience of significant others.

  5. Mechanisms underlying the dualistic mode of action of major soy isoflavones in relation to cell proliferation and cancer risks

    NARCIS (Netherlands)

    Rietjens, I.M.C.M.; Sotoca, A.M.; Vervoort, J.; Louisse, J.

    2013-01-01

    Isoflavones are phytoestrogens that have been linked to both beneficial as well as adverse effects in relation to cell proliferation and cancer risks. The present article presents an overview of these seemingly contradicting health effects and of mechanisms that could be involved in this dualistic

  6. Mutational analysis of primary and metastatic colorectal cancer samples underlying the resistance to cetuximab-based therapy

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    Nemecek R

    2016-07-01

    Full Text Available Radim Nemecek,1 Jitka Berkovcova,2 Lenka Radova,3 Tomas Kazda,4 Jitka Mlcochova,3 Petra Vychytilova-Faltejskova,1,3 Ondrej Slaby,1,3 Marek Svoboda1 1Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Masaryk University, Brno, Czech Republic; 2Department of Oncological and Experimental Pathology, Masaryk Memorial Cancer Institute, Brno, Czech Republic; 3Central European Institute of Technology, Masaryk University, Brno, Czech Republic; 4Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Masaryk University, Brno, Czech Republic Purpose: Although several molecular markers predicting resistance to cetuximab- or panitumumab-based therapy of metastatic colorectal cancer were described, mutations in RAS proto-oncogenes remain the only predictors being used in daily clinical practice. However, 35%–45% of wild-type RAS patients still do not respond to this anti-epidermal growth factor receptor (anti-EGFR monoclonal antibody-based therapy, and therefore the definition of other predictors forms an important clinical need. The aim of the present retrospective single-institutional study was to evaluate potential genes responsible for resistance to anti-EGFR therapy in relation to mutational analysis of primary versus metastatic lesions. Patients and methods: Twenty-four paired primary and corresponding metastatic tissue samples from eight nonresponding and four responding metastatic colorectal cancer patients treated with cetuximab-based therapy were sequenced using a next-generation sequencing panel of 26 genes involved in EGFR signaling pathway and colorectal carcinogenesis. Results: Mutational status of primary tumors and metastatic lesions was highly concordant in TP53, APC, CTNNB1, KRAS, PIK3CA, PTEN, and FBXW7 genes. Metastatic samples harbor significantly more mutations than primary tumors. Potentially negative predictive value of FBXW7 mutations in relationship to anti-EGFR treatment outcomes was confirmed

  7. Microbial profile of canine persistent wound infections

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    A. Padhy

    2014-04-01

    Full Text Available Aim: To analyse the microbial profile of canine persistent wound infections. Materials and Methods: The total wound samples (n=172 taken from both traumatic (140 and post-surgical (32 persistent wounds in canines were processed for routine microbial isolation and identification during a period of 15 months. Results: Staphylococcus intermedius was found to be the predominant isolate from all types of wounds under study. It was followed by Staphylococcus aureus, Pseudomonas aeruginosa, E. coli, Pasteurella spp., Corynaebacterium spp. and Bacillus spp. From different traumatic wounds of dogs, S. intermedius (92/140=65.7% and from surgical wounds, P. aeruginosa (24/32=75% were found to be the predominant isolates recovered whereas the most commonly isolated bacterial genus in both traumatic and surgical wounds of dogs was Staphylococcus spp. Conclusion: Canine wounds are polymicrobial in nature. Hence proper microbial laboratory diagnosis and presence of multiple organisms in a wound are to be taken into consideration for effective treatment of persistent wound infections in dogs.

  8. Resonant activation: a strategy against bacterial persistence

    Science.gov (United States)

    Fu, Yan; Zhu, Meng; Xing, Jianhua

    2010-03-01

    A bacterial colony may develop a small number of cells genetically identical to, but phenotypically different from, other normally growing bacteria. These so-called persister cells keep themselves in a dormant state and thus are insensitive to antibiotic treatment, resulting in serious problems of drug resistance. In this paper, we proposed a novel strategy to 'kill' persister cells by triggering them to switch, in a fast and synchronized way, into normally growing cells that are susceptible to antibiotics. The strategy is based on resonant activation (RA), a well-studied phenomenon in physics where the internal noise of a system can constructively facilitate fast and synchronized barrier crossings. Through stochastic Gilliespie simulation with a generic toggle switch model, we demonstrated that RA exists in the phenotypic switching of a single bacterium. Further, by coupling single cell level and population level simulations, we showed that with RA, one can greatly reduce the time and total amount of antibiotics needed to sterilize a bacterial population. We suggest that resonant activation is a general phenomenon in phenotypic transition, and can find other applications such as cancer therapy.

  9. Self-esteem and spiritual health in cancer patients under chemotherapy in Semnan University of Medical Sciences in 2014

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    Farah Abbasian

    2016-12-01

    Full Text Available Background and Objectives: Cancer as a frightening disease may affect people's confidence in their abilities, sense of controlling over their lives, and in other words self-esteem. Spiritual health as the main aspect of health can be an important source for calmness, decrease in existential distress, improvement of self-esteem and coping with the disease. This study was conducted to investigate the correlation between spiritual health and self-esteem in Iranian cancer patients. Methods: This cross-sectional study was accomplished by obtaining Rosenberg Self-Esteem and Paloutzian & Ellison scales questionnaire from a  convenience sample of 170 cancer patients who were referred for chemotherapy to hospitals of SEMNAN University of Medical Sciences. Data were analyzed by SPSS using one-way analysis of variance and Pearson correlation, and level of significance (P was considered <0.05. Results: Study group has shown a mean self-esteem score of 18.5±3.5 and 98.1±13.2 for spiritual well- being. There was a direct correlation between spiritual health and self- esteem after adjustment for sex, age, education level and marital status (r=0.55. Conclusion: This study demonstrated that spiritual health was significantly associated with self-esteem in cancer patients. Considering critical conditions of cancer patients and their urgent need for maintaining and improving spiritual well-being, enhancement of spiritual health and self-esteem should be further emphasized in the treatment programs of these patients such that they and their families that represent a large population can be assisted to overcome the critical conditions.

  10. Persistence of Rift Valley fever virus in East Africa

    Science.gov (United States)

    Gachohi, J.; Hansen, F.; Bett, B.; Kitala, P.

    2012-04-01

    Rift Valley fever virus (RVFv) is a mosquito-borne pathogen of livestock, wildlife and humans that causes severe outbreaks in intervals of several years. One of the open questions is how the virus persists between outbreaks. We developed a spatially-explicit, individual-based simulation model of the RVFv transmission dynamics to investigate this question. The model, is based on livestock and mosquito population dynamics. Spatial aspects are explicitly represented by a set of grid cells that represent mosquito breeding sites. A grid cell measures 500 by 500m and the model considers a grid of 100 by 100 grid cells; the model thus operates on the regional scale of 2500km2. Livestock herds move between grid cells, and provide connectivity between the cells. The model is used to explore the spatio-temporal dynamics of RVFv persistence in absence of a wildlife reservoir in an east African semi-arid context. Specifically, the model assesses the importance of local virus persistence in mosquito breeding sites relative to global virus persistence mitigated by movement of hosts. Local persistence is determined by the length of time the virus remains in a mosquito breeding site once introduced. In the model, this is a function of the number of mosquitoes that emerge infected and their lifespan. Global persistence is determined by the level of connectivity between isolated grid cells. Our work gives insights into the ecological and epidemiological conditions under which RVFv persists. The implication for disease surveillance and management are discussed.

  11. Persistence Statements: Describing Digital Stickiness

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    John Kunze

    2017-08-01

    Full Text Available In this paper we present a draft vocabulary for making “persistence statements.” These are simple tools for pragmatically addressing the concern that anyone feels upon experiencing a broken web link. Scholars increasingly use scientific and cultural assets in digital form, but choosing which among many objects to cite for the long term can be difficult. There are few well-defined terms to describe the various kinds and qualities of persistence that object repositories and identifier resolvers do or don’t provide. Given an object’s identifier, one should be able to query a provider to retrieve human- and machine-readable information to help judge the level of service to expect and help gauge whether the identifier is durable enough, as a sort of long-term bet, to include in a citation. The vocabulary should enable providers to articulate persistence policies and set user expectations.

  12. Missed diagnosis-persistent delirium

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    Aseem Mehra

    2014-01-01

    Full Text Available Delirium is in general considered as an acute short lasting reversible neuropsychiatric syndrome. However, there is some evidence to suggest that in a small proportion of cases delirium may be a chronic or persistent condition. However, making this diagnosis requires clinical suspicion and ruling other differential diagnosis. In this report, we present a case of a 55-year-old man who had cognitive symptoms, psychotic symptoms and depressive symptoms along with persistent hypokalemia and glucose intolerance. He was seen by 3 psychiatrists with these symptoms and was initially diagnosed as having depressive disorder and later diagnosis of bipolar affective disorder (current episode mania, and psychosis were considered by the third psychiatrist. However, despite the presence of persistent neurocognitive deficits, evening worsening of symptoms, hypokalemia and glucose intolerance diagnosis of delirium was not suspected.

  13. Monitoring of Biodistribution and Persistence of Conditionally Replicative Adenovirus in a Murine Model of Ovarian Cancer Using Capsid-Incorporated mCherry and Expression of Human Somatostatin Receptor Subtype 2 Gene

    Directory of Open Access Journals (Sweden)

    Igor P. Dmitriev

    2014-10-01

    Full Text Available A significant limiting factor to the human clinical application of conditionally replicative adenovirus (CRAd-based virotherapy is the inability to noninvasively monitor these agents and their potential persistence. To address this issue, we proposed a novel imaging approach that combines transient expression of the human somatostatin receptor (SSTR subtype 2 reporter gene with genetic labeling of the viral capsid with mCherry fluorescent protein. To test this dual modality system, we constructed the Ad5/3Δ24pIXcherry/SSTR CRAd and validated its capacity to generate fluorescent and nuclear signals in vitro and following intratumoral injection. Analysis of 64Cu-CB-TE2A-Y3-TATE biodistribution in mice revealed reduced uptake in tumors injected with the imaging CRAd relative to the replication-incompetent, Ad-expressing SSTR2 but significantly greater uptake compared to the negative CRAd control. Optical imaging demonstrated relative correlation of fluorescent signal with virus replication as determined by viral genome quantification in tumors. Positron emission tomography/computed tomography studies demonstrated that we can visualize radioactive uptake in tumors injected with imaging CRAd and the trend for greater uptake by standardized uptake value analysis compared to control CRAd. In the aggregate, the plasticity of our dual imaging approach should provide the technical basis for monitoring CRAd biodistribution and persistence in preclinical studies while offering potential utility for a range of clinical applications.

  14. Persistence or Clearance of Human Papillomavirus Infections in Women in Ouro Preto, Brazil

    Science.gov (United States)

    Miranda, P. M.; Silva, N. N. T.; Pitol, B. C. V.; Silva, I. D. C. G.; Lima-Filho, J. L.; Carvalho, R. F.; Stocco, R. C.; Beçak, W.; Lima, A. A.

    2013-01-01

    Persistent high-risk (HR) human papillomavirus (HPV) infection is necessary for development of precursor lesions and cervical cancer. We investigate persistence and clearance of HPV infections and cofactors in unvaccinated women. Cervical samples of 569 women (18–75 years), received for routine evaluation in the Health Department of Ouro Preto, Brazil, were collected and subjected to PCR (MY09/11 or GP5+/6+ primers), followed by RFLP or sequencing. All women were interviewed to collect sociodemographic and behavioral information. Viral infection persistence or clearance was reevaluated after 24 months and was observed in 59.6% and 40.4% of women, respectively. HPVs 16, 33, 59, 66, 69, and 83 (HR) were the most persistent types whereas HPVs 31, 45, and 58 were less persistent. Clearance or persistence did not differ between groups infected by HPVs 18, 53, and 67. In low-risk (LR) types, HPV 6 infected samples were associated with clearance, while HPV 11, 61, 72, or 81 infected samples were persistent in the follow-up. No statistically significant association was detected between persistent HPV infections and sociodemographic and behavioral characteristics analyzed. To study persistence or clearance in HPV infection allows the identification of risk groups, cofactors, and strategies for prevention of cervical cancer. PMID:24298551

  15. Persistence or clearance of human papillomavirus infections in women in Ouro Preto, Brazil.

    Science.gov (United States)

    Miranda, P M; Silva, N N T; Pitol, B C V; Silva, I D C G; Lima-Filho, J L; Carvalho, R F; Stocco, R C; Beçak, W; Lima, A A

    2013-01-01

    Persistent high-risk (HR) human papillomavirus (HPV) infection is necessary for development of precursor lesions and cervical cancer. We investigate persistence and clearance of HPV infections and cofactors in unvaccinated women. Cervical samples of 569 women (18-75 years), received for routine evaluation in the Health Department of Ouro Preto, Brazil, were collected and subjected to PCR (MY09/11 or GP5+/6+ primers), followed by RFLP or sequencing. All women were interviewed to collect sociodemographic and behavioral information. Viral infection persistence or clearance was reevaluated after 24 months and was observed in 59.6% and 40.4% of women, respectively. HPVs 16, 33, 59, 66, 69, and 83 (HR) were the most persistent types whereas HPVs 31, 45, and 58 were less persistent. Clearance or persistence did not differ between groups infected by HPVs 18, 53, and 67. In low-risk (LR) types, HPV 6 infected samples were associated with clearance, while HPV 11, 61, 72, or 81 infected samples were persistent in the follow-up. No statistically significant association was detected between persistent HPV infections and sociodemographic and behavioral characteristics analyzed. To study persistence or clearance in HPV infection allows the identification of risk groups, cofactors, and strategies for prevention of cervical cancer.

  16. Perioperative intravenous lidocaine decreases the incidence of persistent pain after breast surgery.

    LENUS (Irish Health Repository)

    Grigoras, Anca

    2012-09-01

    Breast cancer surgery is associated with a high incidence of persistent postsurgical pain (PPSP). The aim of this study was to evaluate the impact of intravenous (IV) lidocaine on acute and PPSP, analgesic requirements, and sensation abnormalities in patients undergoing surgery for breast cancer.

  17. Levels of persisters influenced by aeration in Acinetobacter calcoaceticus-baumannii.

    Science.gov (United States)

    Donamore, Bruna Kern; Gallo, Stephanie Wagner; Abreu Ferreira, Pedro Maria; Sanchez Ferreira, Carlos Alexandre; de Oliveira, Sílvia Dias

    2018-02-01

    To evaluate the influence of aeration on persister levels from Acinetobacter calcoaceticus-baumannii isolates exposed to meropenem or tobramycin, as well as analyze morphological and structural changes in persisters. Levels of persisters were determined after a 48-h exposure to tobramycin or meropenem under aerated or static conditions, and persisters were analyzed by scanning and transmission electron microscopy. The fractions of persisters varied between isolates. Aeration reduced cell survival under each antibiotic treatment, and cell survival decreased as the tobramycin concentration was increased. Interestingly, division septa were observed in persisters by electron microscopy. Aeration may have stimulated bacterial growth, providing more targets for antibiotic action and leading to increased production of reactive oxygen species, which decreased levels of persisters.

  18. Energy Savings Lifetimes and Persistence

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, Ian M. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Schiller, Steven R. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Todd, Annika [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Billingsley, Megan A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Goldman, Charles A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Schwartz, Lisa C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2016-02-01

    This technical brief explains the concepts of energy savings lifetimes and savings persistence and discusses how program administrators use these factors to calculate savings for efficiency measures, programs and portfolios. Savings lifetime is the length of time that one or more energy efficiency measures or activities save energy, and savings persistence is the change in savings throughout the functional life of a given efficiency measure or activity. Savings lifetimes are essential for assessing the lifecycle benefits and cost effectiveness of efficiency activities and for forecasting loads in resource planning. The brief also provides estimates of savings lifetimes derived from a national collection of costs and savings for electric efficiency programs and portfolios.

  19. [Thunder-fire Moxibustion forQiDeficiency-induced Fatigue in Breast Cancer Patients Under-going Chemotherapy].

    Science.gov (United States)

    Lu, Lu; Li, Wei-Han; Guo, Xiao-Chuan; Fu, Wen-Bin

    2018-02-25

    To observe the clinical effect of thunder-fire moxibustion in the treatment of qi deficiency-induced fatigue in breast cancer patients undergoing chemotherapy. Sixty breast cancer patients undergoing chemotherapy were randomly divided into thunder-fire moxibustion (Moxi) and conventional nursing (nursing) groups ( n =30 in each group). Patients in the Moxi group were treated with thunder-fire moxibustion applied to the back part of body from Pishu (BL 20) to Qihaishu (BL 24) on the bilateral sides and to the abdominal part from Zhongwan (CV 12) to Guanyuan (CV 4) for 30 min, once a day for 14 days. Patients in the nursing group were treated with health education and conventional nursing care. The simple fatigue scale, traditional Chinese medicine (TCM) syndrome score, clinical curative effect were observed before and after the treatment, and white blood cell (WBC) count was observed 5 days ofter chemotherapy and after the treatment respectively. After the treatment, the simple fatigue scales and TCM syndrome scores were significantly decreased and WBC counts were significantly increased in both groups relevant to their individual pre-treatment ( P Thunder-fire moxibustion can effectively relieve the degree of fatigue and the symptoms of qi deficiency in breast cancer patients undergoing chemotherapy.

  20. Could dysregulation of UPS be a common underlying mechanism for cancer and neurodegeneration? Lessons from UCHL1.

    Science.gov (United States)

    Jara, Javier H; Frank, Dominic D; Özdinler, P Hande

    2013-09-01

    Ubiquitin proteasome system (UPS) determines the timing and extent of protein turnover in cells, and it is one of the most strictly controlled cellular mechanisms. Lack of proper control over UPS is attributed to both cancer and to neurodegenerative diseases, yet in different context and direction. Cancerous cells have altered cellular metabolisms, uncontrolled cellular division, and increased proteasome activity. The specialized function prevent neurons from undergoing cellular division but allow them to extend an axon over long distances, establish connections, and to form stable neuronal circuitries. Neurons heavily depend on the proper function of the proteasome and the UPS for their proper function. Reduction of UPS function in vulnerable neurons results in protein aggregation, increased ER stress, and cell death. Identification of compounds that selectively block proteasome function in distinct set of malignancies added momentum to drug discovery efforts, and deubiquitinases (DUBs) gained much attention. This review will focus on ubiquitin carboxy-terminal hydrolase L1 (UCHL1), a DUB that is attributed to both cancer and neurodegeneration. The potential of developing effective treatment strategies for two major health problems by controlling the function of UPS opens up new avenues for innovative approaches and therapeutic interventions.

  1. Graphene oxide nanoparticles for enhanced photothermal cancer cell therapy under the irradiation of a femtosecond laser beam.

    Science.gov (United States)

    Li, Jing-Liang; Hou, Xue-Liang; Bao, Hong-Chun; Sun, Lu; Tang, Bin; Wang, Jin-Feng; Wang, Xun-Gai; Gu, Min

    2014-07-01

    Nano-sized graphene and graphene oxide (GO) are promising for biomedical applications, such as drug delivery and photothermal therapy of cancer. It is observed in this work that the ultrafast reduction of GO nanoparticles (GONs) with a femtosecond laser beam creates extensive microbubbling. To understand the surface chemistry of GONs on the microbubble formation, the GONs were reduced to remove most of the oxygen-containing groups to get reduced GONs (rGONs). Microbubbling was not observed when the rGONs were irradiated by the laser. The instant collapse of the microbubbles may produce microcavitation effect that brings about localized mechanical damage. To understand the potential applications of this phenomenon, cancer cells labeled with GONs or rGONs were irradiated with the laser. Interestingly, the microbubbling effect greatly facilitated the destruction of cancer cells. When microbubbles were produced, the effective laser power was reduced to less than half of what is needed when microbubbling is absent. This finding will contribute to the safe application of femtosecond laser in the medical area by taking advantage of the ultrafast reduction of GONs. It may also find other important applications that need highly localized microcavitation effects. © 2013 Wiley Periodicals, Inc.

  2. Survival of Mexican Children with Acute Lymphoblastic Leukaemia under Treatment with the Protocol from the Dana-Farber Cancer Institute 00-01

    Science.gov (United States)

    Jiménez-Hernández, Elva; Jaimes-Reyes, Ethel Zulie; Arellano-Galindo, José; García-Jiménez, Xochiketzalli; Tiznado-García, Héctor Manuel; Sánchez-Jara, Berenice; Bekker-Méndez, Vilma Carolina; Ortíz-Torres, María Guadalupe; Ortíz-Fernández, Antonio; Marín-Palomares, Teresa; Mejía-Aranguré, Juan Manuel

    2015-01-01

    Our aim in this paper is to describe the results of treatment of acute lymphoblastic leukaemia (ALL) in Mexican children treated from 2006 to 2010 under the protocol from the Dana-Farber Cancer Institute (DFCI) 00-01. The children were younger than 16 years of age and had a diagnosis of ALL de novo. The patients were classified as standard risk if they were 1–9.9 years old and had a leucocyte count 100 × 109/L. The poor outcomes were associated with toxic death during induction, complete remission, and relapse. These factors remain the main obstacles to the success of this treatment in our population. PMID:25922837

  3. Sequence-Dependent Persistence Length of Long DNA

    Science.gov (United States)

    Chuang, Hui-Min; Reifenberger, Jeffrey G.; Cao, Han; Dorfman, Kevin D.

    2017-12-01

    Using a high-throughput genome-mapping approach, we obtained circa 50 million measurements of the extension of internal human DNA segments in a 41 nm ×41 nm nanochannel. The underlying DNA sequences, obtained by mapping to the reference human genome, are 2.5-393 kilobase pairs long and contain percent GC contents between 32.5% and 60%. Using Odijk's theory for a channel-confined wormlike chain, these data reveal that the DNA persistence length increases by almost 20% as the percent GC content increases. The increased persistence length is rationalized by a model, containing no adjustable parameters, that treats the DNA as a statistical terpolymer with a sequence-dependent intrinsic persistence length and a sequence-independent electrostatic persistence length.

  4. Environmental reservoirs and mechanisms of persistence of Vibrio cholerae

    Science.gov (United States)

    Lutz, Carla; Erken, Martina; Noorian, Parisa; Sun, Shuyang; McDougald, Diane

    2013-01-01

    It is now well accepted that Vibrio cholerae, the causative agent of the water-borne disease cholera, is acquired from environmental sources where it persists between outbreaks of the disease. Recent advances in molecular technology have demonstrated that this bacterium can be detected in areas where it has not previously been isolated, indicating a much broader, global distribution of this bacterium outside of endemic regions. The environmental persistence of V. cholerae in the aquatic environment can be attributed to multiple intra- and interspecific strategies such as responsive gene regulation and biofilm formation on biotic and abiotic surfaces, as well as interactions with a multitude of other organisms. This review will discuss some of the mechanisms that enable the persistence of this bacterium in the environment. In particular, we will discuss how V. cholerae can survive stressors such as starvation, temperature, and salinity fluctuations as well as how the organism persists under constant predation by heterotrophic protists. PMID:24379807

  5. Regional Persistent Organic Pollutants' Environmental Impact Assessment and Control Model

    Directory of Open Access Journals (Sweden)

    Jurgis Staniskis

    2008-10-01

    Full Text Available The sources of formation, environmental distribution and fate of persistent organic pollutants (POPs are increasingly seen as topics to be addressed and solved at the global scale. Therefore, there are already two international agreements concerning persistent organic pollutants: the Protocol of 1998 to the 1979 Convention on the Long-Range Transboundary Air Pollution on Persistent Organic Pollutants (Aarhus Protocol; and the Stockholm Convention on Persistent Organic Pollutants. For the assessment of environmental pollution of POPs, for the risk assessment, for the evaluation of new pollutants as potential candidates to be included in the POPs list of the Stokholmo or/and Aarhus Protocol, a set of different models are developed or under development. Multimedia models help describe and understand environmental processes leading to global contamination through POPs and actual risk to the environment and human health. However, there is a lack of the tools based on a systematic and integrated approach to POPs management difficulties in the region.

  6. Potential Roles of GLUT12 for Glucose Sensing and Cellular Migration in MCF-7 Human Breast Cancer Cells Under High Glucose Conditions.

    Science.gov (United States)

    Matsui, Chihiro; Takatani-Nakase, Tomoka; Maeda, Sachie; Nakase, Ikuhiko; Takahashi, Koichi

    2017-12-01

    Recent reports have indicated that hyperglycaemia is associated with breast cancer progression. High glucose conditions corresponding to hyperglycaemia significantly promote migration of MCF-7 human breast cancer cells, however, little is known about the mechanisms of glucose sensing for the acquisition of migratory properties by MCF-7 cells. This study investigated glucose sensing and mediation, which are responsible for the high motility of MCF-7 cells. We evaluated the migration of MCF-7 cells cultured in high glucose-containing medium and essential regulatory factors from the perspective of the glucose transport system. We demonstrated that glucose transporter 12 (GLUT12) protein level increased in MCF-7 cells and co-localized with actin organization under high glucose conditions. Moreover, GLUT12-knockdown completely abrogated high glucose-induced migration, indicating that GLUT12 functionally participates in sensing high glucose concentrations. GLUT12 plays a critical role in the model of breast cancer progression through high glucose concentrations. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  7. Modelling Withdrawal and Persistence for Initial Teacher Training: Revising Tinto's Longitudinal Model of Departure

    Science.gov (United States)

    Roberts, Deborah

    2012-01-01

    This paper proposes a theoretical model to explain trainee withdrawal and persistence within higher education (HE) based initial teacher training (ITT). Within ITT, attrition and persistence are under-researched and under-theorised, thus providing the rationale for this study. Within HE more broadly, a number of models have been proposed, most…

  8. Persistence of chironomids in metal polluted Andean high altitude streams: does melanin play a role?

    NARCIS (Netherlands)

    Loayza Muro, R.A.; Marticorena-Ruíz, J.K.; Palomino, E.J.; Merritt, C.; de Baat, M.L.; van Gemert, M.; Verweij, R.A.; Kraak, M.H.S.; Admiraal, W.

    2013-01-01

    In high altitude Andean streams an intense solar radiation and coinciding metal pollution allow the persistence of only a few specialized taxa, including chironomids. The aim of the present study was therefore to determine the mechanisms underlying the persistence of chironomids under these multiple

  9. Persistent postoperative hiccups: a review

    DEFF Research Database (Denmark)

    Hansen, B J; Rosenberg, J

    1993-01-01

    . Numerous treatment modalities have been tried but with questionable success. Valproate has proven effective in two trials investigating persistent non-surgical hiccups. The simple application of a nasogastric tube may successfully treat the hiccups, possibly because of an alteration of the activity...

  10. Rhinophototherapy in persistent allergic rhinitis.

    Science.gov (United States)

    Bella, Zsolt; Kiricsi, Ágnes; Viharosné, Éva Dósa-Rácz; Dallos, Attila; Perényi, Ádám; Kiss, Mária; Koreck, Andrea; Kemény, Lajos; Jóri, József; Rovó, László; Kadocsa, Edit

    2017-03-01

    Previous published results have revealed that Rhinolight ® intranasal phototherapy is safe and effective in intermittent allergic rhinitis. The present objective was to assess whether phototherapy is also safe and effective in persistent allergic rhinitis. Thirty-four patients with persistent allergic rhinitis were randomized into two groups; twenty-five subjects completed the study. The Rhinolight ® group was treated with a combination of UV-B, UV-A, and high-intensity visible light, while the placebo group received low-intensity visible white light intranasal phototherapy on a total of 13 occasions in 6 weeks. The assessment was based on the diary of symptoms, nasal inspiratory peak flow, quantitative smell threshold, mucociliary transport function, and ICAM-1 expression of the epithelial cells. All nasal symptom scores and nasal inspiratory peak flow measurements improved significantly in the Rhinolight ® group relative to the placebo group and this finding persisted after 4 weeks of follow-up. The smell and mucociliary functions did not change significantly in either group. The number of ICAM-1 positive cells decreased non-significantly in the Rhinolight ® group. No severe side-effects were reported during the treatment period. These results suggest that Rhinolight ® treatment is safe and effective in persistent allergic rhinitis.

  11. Do some Firms Persistently Outperform?

    NARCIS (Netherlands)

    Capasso, M.|info:eu-repo/dai/nl/314016627; Cefis, E.|info:eu-repo/dai/nl/274516233; Frenken, K.|info:eu-repo/dai/nl/207145253

    2009-01-01

    This study analyses persistence in growth rates of the entire population of Dutch manufacturing firms. Previous literature on firm growth rates shows that extreme growth events are likely to be negatively correlated over time. A rebound effect following an extreme growth event questions the

  12. Do some firms persistently outperform?

    NARCIS (Netherlands)

    Capasso, M.; Cefis, E.; Frenken, K.

    2009-01-01

    This study analyses persistence in growth rates of the entire population of Dutch manufacturing firms. Previous literature on firm growth rates shows that extreme growth events are likely to be negatively correlated over time. A rebound effect following an extreme growth event questions the

  13. Coping with persistent environmental problems

    DEFF Research Database (Denmark)

    Varjopuro, Riku; Andrulewicz, Eugeniusz; Brandt, Urs Steiner

    2014-01-01

    ABSTRACT In this paper we focus on systemic delays in the Baltic Sea that cause the problem of eutrophication to persist. These problems are demonstrated in our study by addressing three types of delays: (1) decision delay: the time it takes for an idea or perceived need to be launched as a polic...

  14. Profiles of persistent slip markings and internal structure of underlying persistent slip bands

    Czech Academy of Sciences Publication Activity Database

    Polák, Jaroslav; Mazánová, Veronika; Heczko, Milan; Kuběna, Ivo; Man, Jiří

    2017-01-01

    Roč. 40, č. 7 (2017), s. 1101-1116 ISSN 8756-758X R&D Projects: GA MŠk(CZ) ED1.1.00/02.0068; GA MŠk LM2015069; GA ČR(CZ) GA13-23652S Institutional support: RVO:68081723 Keywords : copper * dislocation structure * extrusions * fatigue crack initiation * intrusions * stainless steel Subject RIV: JL - Materials Fatigue, Friction Mechanics OBOR OECD: Audio engineering, reliability analysis Impact factor: 2.335, year: 2016

  15. Mechanisms underlying the growth inhibitory effects of the cyclo-oxygenase-2 inhibitor celecoxib in human breast cancer cells

    International Nuclear Information System (INIS)

    Basu, Gargi D; Pathangey, Latha B; Tinder, Teresa L; Gendler, Sandra J; Mukherjee, Pinku

    2005-01-01

    Inhibitors of cyclo-oxygenase (COX)-2 are being extensively studied as anticancer agents. In the present study we evaluated the mechanisms by which a highly selective COX-2 inhibitor, celecoxib, affects tumor growth of two differentially invasive human breast cancer cell lines. MDA-MB-231 (highly invasive) and MDA-MB-468 (moderately invasive) cell lines were treated with varying concentrations of celecoxib in vitro, and the effects of this agent on cell growth and angiogenesis were monitored by evaluating cell proliferation, apoptosis, cell cycle arrest, and vasculogenic mimicry. The in vitro results of MDA-MB-231 cell line were further confirmed in vivo in a mouse xenograft model. The highly invasive MDA-MB-231 cells express higher levels of COX-2 than do the less invasive MDA-MB-468 cells. Celecoxib treatment inhibited COX-2 activity, indicated by prostaglandin E 2 secretion, and caused significant growth arrest in both breast cancer cell lines. In the highly invasive MDA-MB-231 cells, the mechanism of celecoxib-induced growth arrest was by induction of apoptosis, associated with reduced activation of protein kinase B/Akt, and subsequent activation of caspases 3 and 7. In the less invasive MDA-MB-468 cells, growth arrest was a consequence of cell cycle arrest at the G 0 /G 1 checkpoint. Celecoxib-induced growth inhibition was reversed by addition of exogenous prostaglandin E 2 in MDA-MB-468 cells but not in MDA-MB-231 cells. Furthermore, MDA-MB-468 cells formed significantly fewer extracellular matrix associated microvascular channels in vitro than did the high COX-2 expressing MDA-MB-231 cells. Celecoxib treatment not only inhibited cell growth and vascular channel formation but also reduced vascular endothelial growth factor levels. The in vitro findings corroborated in vivo data from a mouse xenograft model in which daily administration of celecoxib significantly reduced tumor growth of MDA-MB-231 cells, which was associated with reduced vascularization and

  16. Mechanisms underlying the growth inhibitory effects of the cyclo-oxygenase-2 inhibitor celecoxib in human breast cancer cells.

    Science.gov (United States)

    Basu, Gargi D; Pathangey, Latha B; Tinder, Teresa L; Gendler, Sandra J; Mukherjee, Pinku

    2005-01-01

    Inhibitors of cyclo-oxygenase (COX)-2 are being extensively studied as anticancer agents. In the present study we evaluated the mechanisms by which a highly selective COX-2 inhibitor, celecoxib, affects tumor growth of two differentially invasive human breast cancer cell lines. MDA-MB-231 (highly invasive) and MDA-MB-468 (moderately invasive) cell lines were treated with varying concentrations of celecoxib in vitro, and the effects of this agent on cell growth and angiogenesis were monitored by evaluating cell proliferation, apoptosis, cell cycle arrest, and vasculogenic mimicry. The in vitro results of MDA-MB-231 cell line were further confirmed in vivo in a mouse xenograft model. The highly invasive MDA-MB-231 cells express higher levels of COX-2 than do the less invasive MDA-MB-468 cells. Celecoxib treatment inhibited COX-2 activity, indicated by prostaglandin E2 secretion, and caused significant growth arrest in both breast cancer cell lines. In the highly invasive MDA-MB-231 cells, the mechanism of celecoxib-induced growth arrest was by induction of apoptosis, associated with reduced activation of protein kinase B/Akt, and subsequent activation of caspases 3 and 7. In the less invasive MDA-MB-468 cells, growth arrest was a consequence of cell cycle arrest at the G0/G1 checkpoint. Celecoxib-induced growth inhibition was reversed by addition of exogenous prostaglandin E2 in MDA-MB-468 cells but not in MDA-MB-231 cells. Furthermore, MDA-MB-468 cells formed significantly fewer extracellular matrix associated microvascular channels in vitro than did the high COX-2 expressing MDA-MB-231 cells. Celecoxib treatment not only inhibited cell growth and vascular channel formation but also reduced vascular endothelial growth factor levels. The in vitro findings corroborated in vivo data from a mouse xenograft model in which daily administration of celecoxib significantly reduced tumor growth of MDA-MB-231 cells, which was associated with reduced vascularization and

  17. The management of tumor motions in the stereotactic irradiation to lung cancer under the use of Abches to control active breathing

    Energy Technology Data Exchange (ETDEWEB)

    Tarohda, Tohru I.; Ishiguro, Mitsuru; Hasegawa, Kouhei; Kohda, Yukihiko; Onishi, Hiroaki; Aoki, Tetsuya; Takanaka, Tsuyoshi [Department of Radiology, Asanogawa General Hospital, 83 Kosaka-naka, Kanazawa 920-8621 (Japan); Department of Neurosurgery, Asanogawa General Hospital, 83 Kosaka-naka, Kanazawa 920-8621 (Japan); Naruwa Clinic, 1-16-6 Naruwa, Kanazawa 920-0818 (Japan); Department of Radiation Therapy, Kanazawa University, 13-1 Takaramachi, Kanazawa 920-8641 (Japan)

    2011-07-15

    Purpose: Breathing control is crucial to ensuring the accuracy of stereotactic irradiation for lung cancer. This study monitored respiration in patients with inoperable nonsmall-cell lung cancer using a respiration-monitoring apparatus, Abches, and investigated the reproducibility of tumor position in these patients. Methods: Subjects comprised 32 patients with nonsmall-cell lung cancer who were administered stereotactic radiotherapy under breath-holding conditions monitored by Abches. Computed tomography (CT) was performed under breath-holding conditions using Abches (Abches scan) for treatment planning. A free-breathing scan was performed to determine the range of tumor motions in a given position. After the free-breathing scan, Abches scan was repeated and the tumor position thus defined was taken as the intrafraction tumor position. Abches scan was also performed just before treatment, and the tumor position thus defined was taken as the interfraction tumor position. To calculate the errors, tumor positions were compared based on Abches scan for the initial treatment plan. The error in tumor position was measured using the BrainSCAN treatment-planning device, then compared for each lung lobe. Results: Displacements in tumor position were calculated in three dimensions (i.e., superior-inferior (S-I), left-right (L-R), and anterior-posterior (A-P) dimensions) and recorded as absolute values. For the whole lung, average intrafraction tumor displacement was 1.1 mm (L-R), 1.9 mm (A-P), and 2.0 mm (S-I); the average interfraction tumor displacement was 1.1 mm (L-R), 2.1 mm (A-P), and 2.0 mm (S-I); and the average free-breathing tumor displacement was 2.3 mm (L-R), 3.5 mm (A-P), and 7.9 mm (S-I). The difference between using Abches and free breathing could be reduced from approximately 20 mm at the maximum to approximately 3 mm in the S-I direction for both intrafraction and interfraction positions in the lower lobe. In addition, maximum intrafraction tumor

  18. The management of tumor motions in the stereotactic irradiation to lung cancer under the use of Abches to control active breathing

    International Nuclear Information System (INIS)

    Tarohda, Tohru I.; Ishiguro, Mitsuru; Hasegawa, Kouhei; Kohda, Yukihiko; Onishi, Hiroaki; Aoki, Tetsuya; Takanaka, Tsuyoshi

    2011-01-01

    Purpose: Breathing control is crucial to ensuring the accuracy of stereotactic irradiation for lung cancer. This study monitored respiration in patients with inoperable nonsmall-cell lung cancer using a respiration-monitoring apparatus, Abches, and investigated the reproducibility of tumor position in these patients. Methods: Subjects comprised 32 patients with nonsmall-cell lung cancer who were administered stereotactic radiotherapy under breath-holding conditions monitored by Abches. Computed tomography (CT) was performed under breath-holding conditions using Abches (Abches scan) for treatment planning. A free-breathing scan was performed to determine the range of tumor motions in a given position. After the free-breathing scan, Abches scan was repeated and the tumor position thus defined was taken as the intrafraction tumor position. Abches scan was also performed just before treatment, and the tumor position thus defined was taken as the interfraction tumor position. To calculate the errors, tumor positions were compared based on Abches scan for the initial treatment plan. The error in tumor position was measured using the BrainSCAN treatment-planning device, then compared for each lung lobe. Results: Displacements in tumor position were calculated in three dimensions (i.e., superior-inferior (S-I), left-right (L-R), and anterior-posterior (A-P) dimensions) and recorded as absolute values. For the whole lung, average intrafraction tumor displacement was 1.1 mm (L-R), 1.9 mm (A-P), and 2.0 mm (S-I); the average interfraction tumor displacement was 1.1 mm (L-R), 2.1 mm (A-P), and 2.0 mm (S-I); and the average free-breathing tumor displacement was 2.3 mm (L-R), 3.5 mm (A-P), and 7.9 mm (S-I). The difference between using Abches and free breathing could be reduced from approximately 20 mm at the maximum to approximately 3 mm in the S-I direction for both intrafraction and interfraction positions in the lower lobe. In addition, maximum intrafraction tumor

  19. Persistence

    DEFF Research Database (Denmark)

    Hansen, Kis Boisen

    2012-01-01

    The note shows an example of an architure for buildin g stand-alone program, where the programming language is object oriented and the databas system is a relational database system. Together with the notes is an example program.......The note shows an example of an architure for buildin g stand-alone program, where the programming language is object oriented and the databas system is a relational database system. Together with the notes is an example program....

  20. EMERALD: Emergency visit audit of patients treated under medical oncology in a tertiary cancer center: Logical steps to decrease the burden.

    Science.gov (United States)

    Joshi, Amit; Patil, Vijay M; Noronha, Vanita; Ramaswamy, Anant; Gupta, Sudeep; Bhattacharjee, Atanu; Bonda, Avinash; Chandrakanth, M V; Ostwal, Vikas; Khattry, Navin; Banavali, Shripad; Prabhash, Kumar

    2017-01-01

    We are a tertiary care cancer center and have approximately 1000-1500 emergency visits by cancer patients undergoing treatment under the adult medical oncology unit each month. However, due to the lack of a systematic audit, we are unable to plan steps toward the improvement in quality of emergency services, and hence the audit was planned. All emergency visits under the adult medical oncology department in the month of July 2015 were audited. The cause of visit, the demographic details, cancer details, and chemotherapy status were obtained from the electronic medical records. The emergency visits were classified as avoidable or unavoidable. Descriptive statistics were performed. Reasons for avoidable emergency visits were sought. Out of 1199 visits, 1168 visits were classifiable. Six hundred and ninety-six visits were classified as unavoidable (59.6%, 95% CI: 56.7-62.4), 386 visits were classified as probably avoidable visit (33.0%, 95% CI: 30.4-35.8) whereas the remaining 86 (7.4%, 95% CI: 6.0-9.01) were classified as absolutely avoidable. Two hundred and ninety-seven visits happened on weekends (25.6%) and 138 visits converted into an inpatient admission (11.9%). The factors associated with avoidable visits were curative intention of treatment (odds ratio - 2.49), discontinued chemotherapy status (risk ratio [RR] - 8.28), and private category file status (RR - 1.89). A proportion of visits to emergency services can be curtailed. Approximately one-fourth of patients are seen on weekends, and only about one-tenth of patients get admitted.

  1. Monitoring trifluridine incorporation in the peripheral blood mononuclear cells of colorectal cancer patients under trifluridine/tipiracil medication.

    Science.gov (United States)

    Nakanishi, Ryota; Kitao, Hiroyuki; Kiniwa, Mamoru; Morodomi, Yosuke; Iimori, Makoto; Kurashige, Junji; Sugiyama, Masahiko; Nakashima, Yuichiro; Saeki, Hiroshi; Oki, Eiji; Maehara, Yoshihiko

    2017-12-05

    Trifluridine/tipiracil (TFTD, TAS-102) is an orally administrated anti-cancer drug with efficacy validated for patients with metastatic colorectal cancer (mCRC). Trifluridine (FTD) is an active cytotoxic component of TFTD and mediates the anticancer effect via its incorporation into DNA. However, it has not been examined whether FTD is incorporated into the tissues of patients who received TFTD medication. By detecting FTD incorporation into DNA by a specific antibody, we successfully detected FTD in the bone marrow and spleen cells isolated from FTD-challenged mice as well as human peripheral blood mononuclear cells (PBMCs) activated with phytohemagglutinin-P and exposed to FTD in vitro. FTD was also detected in PBMCs isolated from mCRC patients who had administrated TFTD medication. Intriguingly, weekly evaluation of PBMCs from mCRC patients revealed the percentage of FTD-positive PBMCs increased and decreased in parallel with the administration and cessation of TFTD medication, respectively. To our knowledge, this is the first report to detect an active cytotoxic component of a chemotherapeutic drug in clinical specimens using a specific antibody. This technique may enable us to predict the clinical benefits or the adverse effects of TFTD in mCRC patients.

  2. Is there an epigenetic component underlying the resistance of triple-negative breast cancers to parp inhibitors?

    Science.gov (United States)

    Lovato, Amanda; Panasci, Lawrence; Witcher, Michael

    2012-01-01

    Poly(ADP-ribose) polymerase (Parp) is an enzyme responsible for catalyzing post-translational modifications through the addition of poly(ADP-ribose) chains (known as PARylation). Modification by PARylation modulates numerous cellular processes including transcription, chromatin remodeling, apoptosis, and DNA damage repair. In particular, the role of Parp activation in response to DNA damage has been intensely studied. Tumors bearing mutations of the breast cancer susceptibility genes, Brca1/2, are prone to DNA breakages whose restoration into functional double-strand DNA is Parp dependent. This concept has been exploited therapeutically in Brca mutated breast and ovarian tumors, where acute sensitivity to Parp inhibitors is observed. Based on in vitro and clinical studies it remains unclear to what extent Parp inhibitors can be utilized beyond treating Brca mutated tumors. This review will focus on the often overlooked roles of PARylation in chromatin remodeling, epigenetics, and transcription to explain why some cancers may be unresponsive to Parp inhibition. We predict that understanding the impact of PARylation on gene expression will lead to alternative approaches to manipulate the Parp pathway for therapeutic benefit.

  3. Is there an epigenetic component underlying the resistance of triple-negative breast cancers to PARP inhibitors?

    Directory of Open Access Journals (Sweden)

    Amanda eLovato

    2012-12-01

    Full Text Available Poly(ADP-ribosepolymerase (Parp is an enzyme responsible for catalyzing post-translational modifications through the addition of poly(ADP-ribose chains (known as PARylation. Modification by PARylation modulates numerous cellular processes including transcription, chromatin remodeling, apoptosis and DNA damage repair. In particular, the role of Parp activation in response to DNA damage has been intensely studied. Tumors bearing mutations of the breast cancer susceptibility genes, Brca1/2, are prone to DNA breakages whose restoration into functional double-strand DNA is Parp dependent. This concept has been exploited therapeutically in Brca mutated breast and ovarian tumors, where acute sensitivity to Parp inhibitors is observed. Based on in vitro and clinical studies it remains unclear to what extent Parp inhibitors can be utilized beyond treating Brca mutated tumors. This review will focus on the often overlooked roles of PARylation in chromatin remodeling, epigenetics and transcription to explain why some cancers may be unresponsive to Parp inhibition. We predict that understanding the impact of PARylation on gene expression will lead to alternative approaches to manipulate the Parp pathway for therapeutic benefit.

  4. Care provided by the father to the child with cancer under the influence of masculinities: qualitative meta-synthesis

    Directory of Open Access Journals (Sweden)

    Naiara Barros Polita

    Full Text Available ABSTRACT Objective: To synthesize and interpret findings and conclusions of qualitative research addressing the experience of the father in the care of the child with cancer. Method: Meta-synthesis of 16 qualitative studies from six databases, analyzed through taxonomic analysis. Results: Child and adolescent cancer have several repercussions on the daily life of the father, especially related to the stigma around the disease, the fear of the unknown and the social and family role. Faced with the illness and the need to care for the child, the father seeks to recover normality in the family and transitions between hegemonic masculine behaviors and practices culturally recognized as female. Final Considerations: The complex experience of the father, influenced by masculinities, was evidenced. The limitations regard the restricted understanding of the contextual specificities of the experiences, due to the limited characteristics of the parents and children described in the studies. The knowledge produced is useful to promote involvement of fathers in the care of the child, as well as to strengthen and assist him in this task.

  5. Obesity in Scotland: a persistent inequality.

    Science.gov (United States)

    Tod, Elaine; Bromley, Catherine; Millard, Andrew D; Boyd, Allan; Mackie, Phil; McCartney, Gerry

    2017-07-27

    Obesity is a health problem in its own right and a risk factor for other conditions such as cardiovascular disease. The prevalence of overweight and obesity increased in Scotland between 1995 and 2008 with socio-economic inequalities persisting in adults over time and increasing in children. This paper explores changes in the underlying distribution of body mass index (BMI) which is less well understood. Using data from the Scottish Health Survey (SHeS) between 1995 and 2014 for adults aged 18-64 years, we calculated population distributions for BMI for the population overall, and for age, sex and deprivation strata. We used SHeS data for children aged 2-15 years between 1998 and 2014, in addition to data from the Child Health Systems Programme (CHSP) collected from primary one (P1) children in participating local authorities, to describe the overall trends and to compare trends in inequalities by deprivation strata. Amongst adults, the BMI distribution shifted upwards, with a large proportion of the population gaining a small amount of weight between 1995 and 2008 before subsequently stabilising across the distribution. In men the prevalence of obesity showed a linear deprivation gradient in 1995 but over time obesity declined in the least deprived quintile while the remaining four quintiles converged (and stabilised). In contrast, a persistent and generally linear gradient is evident among women for most of the 1995-2014 period. For those aged 2-15 years, obesity increased between 1998 and 2014 for the most deprived 40% of children contrasted with stable trends for the least deprived. The surveillance data for P1 children in Scotland showed a persistent inequality between 2005/06 and 2014/15 though it was less clear if this is widening. The BMI distribution for adults increased between 1995 and 2008 with a large proportion of the population gaining a small amount of weight before stabilising across the distribution. Inequalities in obesity persist for adults

  6. Asymmetric Cationic Porphyrin as a New G-Quadruplex Probe with Wash-Free Cancer-Targeted Imaging Ability Under Acidic Microenvironments.

    Science.gov (United States)

    Zhang, Ran; Cheng, Meng; Zhang, Li-Ming; Zhu, Li-Na; Kong, De-Ming

    2018-04-16

    Porphyrins are promising candidates for nucleic acid G-quadruplex-specific optical recognition. We previously demonstrated that G-quadruplex recognition specificity of porphyrins could be improved by introducing bulky side arm substituents, but the enhanced protonation tendency limits their applications in some cases, such as under acidic conditions. Here, we demonstrated that the protonation tendency of porphyrin derivatives could be efficiently overcome by increasing molecular asymmetry. To validate this, an asymmetric, water-soluble, cationic porphyrin FA-TMPipEOPP (5-{4-[2-[[(2 E)-3-[3-methoxy-4-[2-(1-methyl-1-piperidinyl)ethoxy]phenyl]-1-oxo-2-propenyl]oxy]ethoxy]phenyl},10,15,20-tri{4-[2-(1-methyl-1-piperidinyl)ethoxy]-phenyl}porphyrin) was synthesized by introducing a ferulic acid (FA) unit at one side arm, and its structure was well-characterized. Unlike its symmetric counterpart TMPipEOPP that has a tendency to protonate under acidic conditions, FA-TMPipEOPP remained in the unprotonated monomeric form under the pH range of 2.0-8.0. Correspondingly, FA-TMPipEOPP showed better G-quadruplex recognition specificity than TMPipEOPP and thus might be used as a specific optical probe for colorimetric and fluorescent recognition of G-quadruplexes under acidic conditions. The feasibility was demonstrated by two proof-of-concept studies: probing structural competition between G-quadruplexes and duplexes and label-free and wash-free cancer cell-targeted bioimaging under an acidic tumor microenvironment. As G-quadruplex optical probes, FA-TMPipEOPP works well under acidic conditions, whereas TMPipEOPP works well under neutral conditions. This finding provides useful information for G-quadruplex probe research. That is, porphyrin-based G-quadruplex probes suitable for different pH conditions might be obtained by adjusting the molecular symmetry.

  7. Exercise, inflammation, and fatigue in cancer survivors

    OpenAIRE

    LaVoy, Emily C.P.; Fagundes, Christopher P.; Dantzer, Robert

    2016-01-01

    Cancer-related fatigue significantly disrupts normal functioning and quality of life for a substantial portion of cancer survivors, and may persist for years following cancer treatment. While the causes of persistent fatigue among cancer survivors are not yet fully understood, accumulating evidence suggests that several pathways, including chronic inflammation, autonomic imbalance, HPA-axis dysfunction, and/or mitochondrial damage, could contribute towards the disruption of normal neuronal fu...

  8. Pap smear screening in women under 30 in the Norwegian Coordinated Cervical Cancer Screening Program, with a comparison of immediate biopsy vs Pap smear triage of moderate dysplasia.

    Science.gov (United States)

    Nygård, Jan F; Nygård, Mari; Skare, Gry Baadstrand; Thoresen, Steiner Osterbø

    2006-01-01

    Top provide population based estimates of Pap smear screening results among women under 30 and to compare the outcomes of 2 triage options for women under 30 with a moderate dysplastic Pap smear: immediate biopsy vs. Pap smear follow-up. All Pap smears, histologically verified cervical intraepithelial lesion (CIN) 2/3 and invasive cervical cancer in 1999-2002 from women in Norway under 30 in 2000-2002 were analyzed. Due to different triage recommendations in different laboratories, 836 women under 30 with a moderately dysplastic Pap smear were recommended for immediate biopsy, while 109 were recommended for a Pap smear within 6 months. Risk estimates for triage outcome were estimated by multinominal logistic regression. The prevalence of squamous intraepithelial lesion was highest around 20 years. The first moderate dysplasia was diagnosed at age 16, as was CIN 2/3. Of the women with Pap smear triage, one third were diagnosed with a CIN 2+ lesion, one third had a normal outcome, while the last third were in uncertain state 12 months later. Among those recommended for immediate biopsy, nearly 70% were diagnosed with a CIN 2+, thus having odds of 4.2 (95% CI 2.5-7.1) higher than did women with Pap smear triage of being diagnosed with CIN2+ 12 months later. The choice of triage has a profound impact on the proportion of young women diagnosed with CIN 2+ after a moderately dysplastic Pap smear.

  9. Parallel Evolution under Chemotherapy Pressure in 29 Breast Cancer Cell Lines Results in Dissimilar Mechanisms of Resistance

    DEFF Research Database (Denmark)

    Tegze, Balint; Szallasi, Zoltan Imre; Haltrich, Iren

    2012-01-01

    Background: Developing chemotherapy resistant cell lines can help to identify markers of resistance. Instead of using a panel of highly heterogeneous cell lines, we assumed that truly robust and convergent pattern of resistance can be identified in multiple parallel engineered derivatives of only...... a few parental cell lines. Methods: Parallel cell populations were initiated for two breast cancer cell lines (MDA-MB-231 and MCF-7) and these were treated independently for 18 months with doxorubicin or paclitaxel. IC50 values against 4 chemotherapy agents were determined to measure cross......-resistance. Chromosomal instability and karyotypic changes were determined by cytogenetics. TaqMan RT-PCR measurements were performed for resistance-candidate genes. Pgp activity was measured by FACS. Results: All together 16 doxorubicin-and 13 paclitaxel-treated cell lines were developed showing 2-46 fold and 3-28 fold...

  10. Recent results concerning radiation-induced cancer in the Japanese atomic bomb survivors

    International Nuclear Information System (INIS)

    Radford, E.P.

    1988-01-01

    The most recent data of the prospective study among Hiroshima and Nagasaki atomic bomb survivors support the following conclusions: (a) the dose-response relationship is consistent with a straight line through the origin, including the lowest dose group (approx. 3 rad); (b) sensitivity to cancer induction varies considerably by irradiated tissues. (c) most cancers show a radiation effect still increasing 40 years after exposure; (d) a small leukemia excess among those irradiated is still present in Hiroshima; (e) the thyroid cancer excess is declining at present; (g) smoking adds to lung cancer incidence; (g) certain benign tumors show a radiation-related effect; (h) children under 10 years old at time of bombing are presently showing the highest relative cancer risk compared to other survivors at equal attained age. If this effect persists, age-specific cancer risk coefficients are necessary [fr

  11. Quality of Life, Anxiety and Depression in Patients with Differentiated Thyroid Cancer under Short Term Hypothyroidism Induced by Levothyroxine Withdrawal.

    Science.gov (United States)

    Badihian, S; Jalalpour, P; Mirdamadi, M; Moslehi, M

    We studied quality of life (QOL), anxiety, and depression in patients with differentiated thyroid cancer (DTC) either during treatment with levothyroxine or during withdrawal from levothyroxine when whole-body scanning (WBS) needed to be performed. DTC patients projected to undergo WBS were included in the study. They were studied at two time-points - the day before levothyroxine withdrawal, and one month after levothyroxine withdrawal. They were asked to fill WHOQOL-Bref, BDI-II, and HADS questionnaires at both time-points, and blood samples were taken to measure TSH, Tg, and TgAb levels. Twenty-nine subjects (11 males) with a mean age of 42.6 ± 14.1 years entered the study. From the first to second time-point, the mean TSH level increased from 0.73 to 106.9 U/ml and the mean Tg level increased from 20.4 to 63.6 ng/ml. QOL scores decreased in four dimensions (physical health: 67.8 to 25.7; psychological: 58.9 to 38.9; social relationship: 67.5 to 56; and environment: 57.2 to 48.8). Patients also felt more depressed (48.3% to 93.2%) and anxious (65.5% to 89.6%). All changes were statistically significant (p levothyroxine withdrawal. Our findings suggest that alternative therapies, such as those employing rhTSH, should be considered for these patients. Psycho-oncological support might also be useful in helping them overcome their symptoms during short-term hypothyroidism; however, considering the reversibility of their symptoms, supportive care might be more effective.Key words: quality of life - anxiety - depression - thyroid cancer - hypothyroidism - levothyroxine - whole body scanning.

  12. The melatonin action on stromal stem cells within pericryptal area in colon cancer model under constant light

    Energy Technology Data Exchange (ETDEWEB)

    Kannen, Vinicius, E-mail: kannen71@yahoo.com.br [Department of Pathology, Medical School of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto - Sao Paulo 14049-900 (Brazil); Marini, Tassiana [Department of Pathology, Medical School of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto - Sao Paulo 14049-900 (Brazil); Zanette, Dalila L. [National Institute of Science and Technology in Stem Cell and Cell Therapy, Center for Cell Therapy and Regional Blood Center, Ribeirao Preto - Sao Paulo (Brazil); Frajacomo, Fernando T.; Silva, Gyl E.B. [Department of Pathology, Medical School of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto - Sao Paulo 14049-900 (Brazil); Silva, Wilson A. [Department of Genetics, Medical School of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto - Sao Paulo (Brazil); National Institute of Science and Technology in Stem Cell and Cell Therapy, Center for Cell Therapy and Regional Blood Center, Ribeirao Preto - Sao Paulo (Brazil); Garcia, Sergio B. [Department of Pathology, Medical School of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto - Sao Paulo 14049-900 (Brazil)

    2011-02-25

    Research highlights: {yields} We investigated melatonin against the malignant effects of constant light. {yields} Melatonin supplementation increased its serum levels and its receptor expression. {yields} Melatonin decreased cancer stem cells and dysplastic injuries in colon tissue. {yields} Melatonin controlled proliferative process and apoptosis induction. -- Abstract: Constant light (LL) is associated with high incidence of colon cancer. MLT supplementation was related to the significant control of preneoplastic patterns. We sought to analyze preneoplastic patterns in colon tissue from animals exposed to LL environment (14 days; 300 lx), MLT-supplementation (10 mg/kg/day) and DMH-treatment (1,2 dimethylhydrazine; 125 mg/kg). Rodents were sacrificed and MLT serum levels were measured by radioimmunoassay. Our results indicated that LL induced ACF development (p < 0.001) with a great potential to increase the number of CD133(+) and CD68(+) cells (p < 0.05 and p < 0.001). LL also increased the proliferative process (PCNA-Li; p < 0.001) as well as decreased caspase-3 protein (p < 0.001), related to higher COX-2 protein expression (p < 0.001) within pericryptal colonic stroma (PCCS). However, MLT-supplementation controlled the development of dysplastic ACF (p < 0.001) diminishing preneoplastic patterns into PCCS as CD133 and CD68 (p < 0.05 and p < 0.001). These events were relative to decreased PCNA-Li index and higher expression of caspase-3 protein. Thus, MLT showed a great potential to control the preneoplastic patterns induced by LL.

  13. The melatonin action on stromal stem cells within pericryptal area in colon cancer model under constant light

    International Nuclear Information System (INIS)

    Kannen, Vinicius; Marini, Tassiana; Zanette, Dalila L.; Frajacomo, Fernando T.; Silva, Gyl E.B.; Silva, Wilson A.; Garcia, Sergio B.

    2011-01-01

    Research highlights: → We investigated melatonin against the malignant effects of constant light. → Melatonin supplementation increased its serum levels and its receptor expression. → Melatonin decreased cancer stem cells and dysplastic injuries in colon tissue. → Melatonin controlled proliferative process and apoptosis induction. -- Abstract: Constant light (LL) is associated with high incidence of colon cancer. MLT supplementation was related to the significant control of preneoplastic patterns. We sought to analyze preneoplastic patterns in colon tissue from animals exposed to LL environment (14 days; 300 lx), MLT-supplementation (10 mg/kg/day) and DMH-treatment (1,2 dimethylhydrazine; 125 mg/kg). Rodents were sacrificed and MLT serum levels were measured by radioimmunoassay. Our results indicated that LL induced ACF development (p < 0.001) with a great potential to increase the number of CD133(+) and CD68(+) cells (p < 0.05 and p < 0.001). LL also increased the proliferative process (PCNA-Li; p < 0.001) as well as decreased caspase-3 protein (p < 0.001), related to higher COX-2 protein expression (p < 0.001) within pericryptal colonic stroma (PCCS). However, MLT-supplementation controlled the development of dysplastic ACF (p < 0.001) diminishing preneoplastic patterns into PCCS as CD133 and CD68 (p < 0.05 and p < 0.001). These events were relative to decreased PCNA-Li index and higher expression of caspase-3 protein. Thus, MLT showed a great potential to control the preneoplastic patterns induced by LL.

  14. Current outlook of childhood cancer epidemiology in a middle-income country under a public health insurance program.

    Science.gov (United States)

    Rivera-Luna, Roberto; Velasco-Hidalgo, Liliana; Zapata-Tarrés, Marta; Cárdenas-Cardos, Rocío; Aguilar-Ortiz, Marco R

    2017-02-01

    In Mexico, childhood cancer (0-18 years) is treated in a multidisciplinary way while providing care for more than half of the affected children through a public medical insurance. This insurance is given to all children who do not have any health care coverage in Mexico. This program is offered to the poorest of all Mexicans. All the children with this disease are submitted to pathology diagnosis and treatment according to national treatment protocols from 57 accredited medical institutions. From 2007 to 2015, a total of 24,039 children with cancer have been registered; the male gender predominates by 55%. The highest incidence was in the group aged between 0 and 4 years. Every year, there has been an increment in registration. In 2015, there were 3,433 new patients with an incidence of 150.1/million. In the same year, the incidence for all types of leukemia increased to 89.5/million. But for acute lymphoblastic leukemia, the incidence was found to be 79.8/million, which is extremely high. The mortality rate for all these patients in 2015 was 5.3/100,000. However, with regard to children aged between 15 and 18 years, the mortality rate was 8.5/100,000. Abandonment rate was 10%, and there were nine state institutions that had a mortality rate between 25% and 50% among their patients. Coincidentally, as per the Human Development Index, the parameters for education, health, and income were low for those nine institutions. The purpose of this work is to show the epidemiology and the burden we are facing due to this disease.

  15. Persistent Homology of Collaboration Networks

    Directory of Open Access Journals (Sweden)

    C. J. Carstens

    2013-01-01

    Full Text Available Over the past few decades, network science has introduced several statistical measures to determine the topological structure of large networks. Initially, the focus was on binary networks, where edges are either present or not. Thus, many of the earlier measures can only be applied to binary networks and not to weighted networks. More recently, it has been shown that weighted networks have a rich structure, and several generalized measures have been introduced. We use persistent homology, a recent technique from computational topology, to analyse four weighted collaboration networks. We include the first and second Betti numbers for the first time for this type of analysis. We show that persistent homology corresponds to tangible features of the networks. Furthermore, we use it to distinguish the collaboration networks from similar random networks.

  16. Esophageal Cancer

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All Cancer Types A to ...

  17. Dermatomyositis with anti-TIF-1γ antibodies as a presenting symptom of underlying triple-negative breast cancer: a case report.

    Science.gov (United States)

    Kubeček, Ondřej; Soukup, Tomáš; Paulík, Adam; Kopecký, Jindřich

    2016-08-25

    Dermatomyositis is an autoimmune myopathy characterized by proximal muscle weakness, muscle inflammation, and typical skin findings. It is a rare disease with an incidence of ~1/100 000. About 15-30 % of adult-onset cases are caused by underlying malignancy and dermatomyositis can be the first symptom of undiagnosed cancer, mainly in the case of anti-transcription intermediary factor 1γ (anti-TIF-1γ) antibodies presence. TIF-1γ is a transcriptional cofactor which is implicated in TGFβ signaling pathway that controls cell proliferation, differentiation, apoptosis, and tumorigenesis. Its expression was shown to be associated with younger age, higher tumor grade, more estrogen receptor negativity, tumors larger than 2 cm, and tendency towards poor outcome in early breast cancer. No association between anti-TIF-1γ antibodies and prognosis has been proposed yet. We report a case of a 43-year-old premenopausal woman presenting with the symptoms of systemic rheumatic disease, the most prominent being a typical skin rash and muscle pain. After a series of investigations, the patient was diagnosed with anti-TIF-1γ positive dermatomyositis and concurrent triple-negative breast cancer (cT1c N3c M0) as an underlying cause. Immediate intravenous corticosteroid therapy relieved the symptoms and enabled anticancer therapy to be commenced. Considering the tumor stage, neoadjuvant therapy with 4 courses of AC (Doxorubicin/Cyclophosphamide) followed by 4 courses of Paclitaxel/Carboplatin was administered. However, no tumor regression was documented and radiotherapy was chosen as the definitive treatment. Early detection of anti-TIF-1γ autoantibodies can contribute to a rapid diagnosis of tumor-associated dermatomyositis and enable immediate anticancer treatment. We demonstrate the emerging role of anti-TIF-1γ antibodies in the diagnostics of tumor-associated dermatomyositis. Furthermore, we propose a potential role of anti-TIF-1γ antibodies as a prognostic marker in

  18. Incidence of leukemia, lymphoma and thyroid cancers in children under 15 years old in the vicinity of Marcoule nuclear plant, 1985-95

    International Nuclear Information System (INIS)

    Bouges, S.; Daures, J.P.; Hebrard, M.

    1999-01-01

    The aim of this investigation was to report incidence of childhood leukemia, lymphoma and thyroid neoplasms in children under 15 years of age living in the vicinity of the French Marcoule nuclear reprocessing plant. This exhaustive and retrospective survey was carried out between 1985 and 1995 in children aged under 14 at the time of diagnosis and living inside a 35 kilometer zone around the nuclear site. 656 practitioners, 109 medical analysis laboratories and 5 hospitals or cancer institutes were investigated. A panel of experts checked each case. 48 cases of acute leukemia (39 acute lymphoid leukemia and 9 acute myeloid leukemia), 15 cases of lymphoma (8 Hodgkin lymphomas - 53 % - and 7 non hodgkinian lymphomas including 5 Burkitt lymphomas), 1 case of chronic myeloid leukemia and 1 case of papillary thyroid cancer, appeared among the 1,116,442 children-years followed. The total incidences of leukemias and lymphomas were respectively 4.12 and 1.29.10 -5 . Standardised Incidence Ratios, calculated according to Poisson methods and Bayesian inference, with various reference rates did not show any excess of risk: 100.67 (95 % confidence interval 72-131) for leukemia. Children under 5 years old and living in non exposed areas to dominant winds or downstream Rhodanian water drawing presented a 3 or 4 fold decreased risk of leukemia than others (the latter still having an identical risk to that of the general population). This was not true for lymphomas, nor for the other age groups. Over the entire zone, children do not have an increased risk of malignant hematology disease but health monitoring by a systematic collection of cases remains useful around Marcoule. The assumption of aquiferous or air contamination thus still remains questionable: further studies investigating models of contamination are needed to take into account all other nonionizing leukemogenic factors (benzene and viral infection in particular) or correlation studies between health indicators and

  19. Long memory and changing persistence

    DEFF Research Database (Denmark)

    Kruse, Robinson; Sibbertsen, Philipp

    We study the empirical behaviour of semi-parametric log-periodogram estimation for long memory models when the true process exhibits a change in persistence. Simulation results confirm theoretical arguments which suggest that evidence for long memory is likely to be found. A recently proposed test...... by Sibbertsen and Kruse (2009) is shown to exhibit noticeable power to discriminate between long memory and a structural change in autoregressive parameters....

  20. Persistent Authentication in Smart Environments

    DEFF Research Database (Denmark)

    Hansen, Mads Syska; Kirschmeyer, Martin; Jensen, Christian D.

    2008-01-01

    present a proof-of-concept implementation of the proposed mechanism, which employs camera based tracking with a single stationary 3D camera that uses the "time of flight" principle. A preliminary evaluation of the proposed mechanism indicates that persistent authentication is technically possible...... with the proposed hardware. The proposed model is sufficiently general to allow the addition of more cameras or supplemental tracking technologies, which will improve the robustness and scalability of the proposed mechanism....

  1. Radar interferometry persistent scatterer technique

    CERN Document Server

    Kampes, Bert M

    2014-01-01

    This volume is devoted to the Persistent Scatterer Technique, the latest development in radar interferometric data processing. It is the only book on Permanent Scatterer (PS) technique of radar interferometry, and it details a newly developed stochastic model and estimator algorithm to cope with possible problems for the application of the PS technique. The STUN (spatio-temporal unwrapping network) algorithm, developed to cope with these issues in a robust way, is presented and applied to two test sites.

  2. Is Farm Management Skill Persistent?

    OpenAIRE

    Li, Xin; Paulson, Nicholas

    2014-01-01

    Farm management skills can affect farm managers' performance. In this article, farm management performance is analyzed based on yearly Illinois Farm Business Farm Management (FBFM) panel data across 6,760 farms from 1996 through 2011. Two out-of-sample measures of skill are used to analyze the ability of farm managers that consistently perform well over yearly and longer time horizons. Persistence tests show management skills are consistent and predictable. Results also suggest that the most ...

  3. Effects of meropenem exposure in persister cells of Acinetobacter calcoaceticus-baumannii.

    Science.gov (United States)

    Gallo, Stephanie Wagner; Donamore, Bruna Kern; Pagnussatti, Vany Elisa; Ferreira, Carlos Alexandre Sanchez; de Oliveira, Sílvia Dias

    2017-02-01

    To evaluate the influence of meropenem in the Acinetobacter calcoaceticus-baumannii (ACB) persister levels. Persister levels in planktonic and biofilm cultures from ACB isolates were evaluated after exposure to different meropenem concentrations. A high variability of persister fractions was observed among the isolates cultured under planktonic and biofilm conditions. Meropenem concentration did not influence persister fractions, even when far above the MIC. No correlation was found between persister levels and biofilm biomass. The magnitude of persister levels from ACB planktonic and, particularly, biofilm cultures exposed to meropenem was independent of the antibiotic concentration, dosing regimen and biofilm biomass. These findings, in a context of meropenem failure to treat chronic infections, strengthen the importance of understanding persister behavior.

  4. The role of metabolism in bacterial persistence

    Directory of Open Access Journals (Sweden)

    Stephanie M. Amato

    2014-03-01

    Full Text Available Bacterial persisters are phenotypic variants with extraordinary tolerances toward antibiotics. Persister survival has been attributed to inhibition of essential cell functions during antibiotic stress, followed by reversal of the process and resumption of growth upon removal of the antibiotic. Metabolism plays a critical role in this process, since it participates in the entry, maintenance, and exit from the persister phenotype. Here, we review the experimental evidence that demonstrates the importance of metabolism to persistence, highlight the successes and potential for targeting metabolism in the search for anti-persister therapies, and discuss the current methods and challenges to understand persister physiology.

  5. The persistence of gender inequality in Zimbabwe: factors that ...

    African Journals Online (AJOL)

    Gender stereotypes were shown to be one of the major causes of persistent under-representation of women in primary school headship. The influence of gender role stereotypes was found to manifest in the form of low self esteem; lack of confidence; women's perception that their role in the family overrides all other roles; ...

  6. Determination of the Persistence of Non-Spore-Forming ...

    Science.gov (United States)

    Report This report presents the results of an investigation to evaluate the persistence (or natural attenuation) of Yersinia pestis (Y. pestis), Francisella tularensis (F. tularensis), and Burkholderia mallei (B. mallei) on glass and soil under multiple environmental conditions and time points.

  7. A minimally invasive option for the treatment of persistent ...

    African Journals Online (AJOL)

    drainage, and antibiotics were started. The esophageal leak persisted for 76 days. Under general anesthesia with ... 6 Rakocz M, Mazar A, Varon D, Spierer S, Blinder D, Martinowitz U. Dental extractions in patients with bleeding disorders. The use of fibrin glue. Oral Surg Oral Med Oral Pathol 1993; 75:280–282. 7 Ochsner ...

  8. Persistence and vulnerability: retaining biodiversity in the landscape ...

    Indian Academy of Sciences (India)

    The application of information on vulnerability and persistence to conservation planning and management is discussed under the headings of natural dynamics, replication of protection, levels of representation, source and sink population structures, refuges and critical resources, reserve design, habitat fragmentation and ...

  9. The role of visual functions in persisting developmental coordination ...

    African Journals Online (AJOL)

    Children with Developmental Coordination Disorder (DCD) are a heterogeneous group regarding underlying problems. They struggle with a range of problems, including gross motor skills, fine motor skills and learning related problems which also seem to persist into adolescence. The aim of this study was to determine ...

  10. Persistence of high-risk human papillomavirus infection in a population-based cohort of Danish women

    DEFF Research Database (Denmark)

    Nielsen, Ann; Kjaer, Susanne K; Munk, Christian

    2010-01-01

    rarely in cancer cases were also likely to persist. The number of high-risk HPV types and detection of HPV 16 infection at baseline and ever use of oral contraceptives increased the risk for persistence. The risk factor analyses also showed that use of an intrauterine device decreased the risk...

  11. Distributed design approach in persistent identifiers systems

    Science.gov (United States)

    Golodoniuc, Pavel; Car, Nicholas; Klump, Jens

    2017-04-01

    The need to identify both digital and physical objects is ubiquitous in our society. Past and present persistent identifier (PID) systems, of which there is a great variety in terms of technical and social implementations, have evolved with the advent of the Internet, which has allowed for globally unique and globally resolvable identifiers. PID systems have catered for identifier uniqueness, integrity, persistence, and trustworthiness, regardless of the identifier's application domain, the scope of which has expanded significantly in the past two decades. Since many PID systems have been largely conceived and developed by small communities, or even a single organisation, they have faced challenges in gaining widespread adoption and, most importantly, the ability to survive change of technology. This has left a legacy of identifiers that still exist and are being used but which have lost their resolution service. We believe that one of the causes of once successful PID systems fading is their reliance on a centralised technical infrastructure or a governing authority. Golodoniuc et al. (2016) proposed an approach to the development of PID systems that combines the use of (a) the Handle system, as a distributed system for the registration and first-degree resolution of persistent identifiers, and (b) the PID Service (Golodoniuc et al., 2015), to enable fine-grained resolution to different information object representations. The proposed approach solved the problem of guaranteed first-degree resolution of identifiers, but left fine-grained resolution and information delivery under the control of a single authoritative source, posing risk to the long-term availability of information resources. Herein, we develop these approaches further and explore the potential of large-scale decentralisation at all levels: (i) persistent identifiers and information resources registration; (ii) identifier resolution; and (iii) data delivery. To achieve large-scale decentralisation

  12. MOOCs and Persistence: Definitions and Predictors

    Science.gov (United States)

    Evans, Brent J.; Baker, Rachel B.

    2016-01-01

    The chapter argues for redefining the term "persistence" as it relates to MOOCs and considers how different measures produce different results in the research; it closes with a review of research on persistence in MOOCs.

  13. Persistent junctional reciprocating tachycardia in the fetus

    NARCIS (Netherlands)

    Oudijk, M. A.; Stoutenbeek, P.; Sreeram, N.; Visser, G. H. A.; Meijboom, E. J.

    2003-01-01

    Persistent junctional reciprocating tachycardia (PJRT) tends to be a persistent arrhythmia and requires aggressive therapeutic management. Diagnosis and management of this infrequently occurring tachycardia in the fetus at an early stage is of importance for the prevention of congestive heart

  14. High Persister Mutants in Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Heather L Torrey

    Full Text Available Mycobacterium tuberculosis forms drug-tolerant persister cells that are the probable cause of its recalcitrance to antibiotic therapy. While genetically identical to the rest of the population, persisters are dormant, which protects them from killing by bactericidal antibiotics. The mechanism of persister formation in M. tuberculosis is not well understood. In this study, we selected for high persister (hip mutants and characterized them by whole genome sequencing and transcriptome analysis. In parallel, we identified and characterized clinical isolates that naturally produce high levels of persisters. We compared the hip mutants obtained in vitro with clinical isolates to identify candidate persister genes. Genes involved in lipid biosynthesis, carbon metabolism, toxin-antitoxin systems, and transcriptional regulators were among those identified. We also found that clinical hip isolates exhibited greater ex vivo survival than the low persister isolates. Our data suggest that M. tuberculosis persister formation involves multiple pathways, and hip mutants may contribute to the recalcitrance of the infection.

  15. Single-cell protein induction dynamics reveals a period of vulnerability to antibiotics in persister bacteria

    OpenAIRE

    Gefen, Orit; Gabay, Chana; Mumcuoglu, Michael; Engel, Giora; Balaban, Nathalie Q.

    2008-01-01

    Phenotypic variability in populations of cells has been linked to evolutionary robustness to stressful conditions. A remarkable example of the importance of cell-to-cell variability is found in bacterial persistence, where subpopulations of dormant bacteria, termed persisters, were shown to be responsible for the persistence of the population to antibiotic treatments. Here, we use microfluidic devices to monitor the induction of fluorescent proteins under synthetic promoters and characterize ...

  16. Quantification of temperature persistence over the Northern Hemisphere land-area

    Science.gov (United States)

    Pfleiderer, Peter; Coumou, Dim

    2017-10-01

    Extreme weather events such as heat waves and floods are damaging to society and their contribution to future climate impacts is expected to be large. Such extremes are often related to persistent local weather conditions. Weather persistence is linked to sea surface temperatures, soil-moisture (especially in summer) and large-scale circulation patterns and these factors can alter under past and future climate change. Though persistence is a key characteristic for extreme weather events, to date the climatology and potential changes in persistence have only been poorly documented. Here, we present a systematic analysis of temperature persistence for the northern hemisphere land area. We define persistence as the length of consecutive warm or cold days and use spatial clustering techniques to create regional persistence distributions. We find that persistence is longest in the Arctic and shortest in the mid-latitudes. Parameterizations of the regional persistence distributions show that they are characterized by an exponential decay with a drop in the decay rate for very persistent events, implying that feedback mechanisms are important in prolonging these events. For the mid-latitudes, we find that persistence in summer has increased over the past 60 years. The changes are particularly pronounced for prolonged events suggesting a lengthening in the duration of heat waves.

  17. Endobronchial ultrasound-guided biopsy performed under optimal conditions in patients with known or suspected lung cancer may render mediastinoscopy unnecessary

    DEFF Research Database (Denmark)

    Clementsen, Paul F; Skov, Birgit G; Vilmann, Peter

    2014-01-01

    BACKGROUND: Mediastinoscopy is the gold standard for preoperative mediastinal staging of patients with suspected or proven lung cancer. Since the development of endoscopic ultrasound-guided biopsy via the trachea (EBUS-TBNA), this status has been challenged. The purpose of the study was to examine...... patients were operated, resulting in 9 benign and 67 malignant diagnoses; spread was found to station 4R, 5, and 5 and 6 in 4 patients. The negative predictive value (NPV) was 63/67=0.94. However, if you exclude station 5 and 6, as they cannot be reached by neither EBUS nor mediastinoscopy, NPV was 66....../67=0.99. The sensitivity was 0.76, and the specificity was 1.0. CONCLUSIONS: When EBUS-TBNA is performed under optimal conditions including general anesthesia and "bed side" microscopy performed by a pathologist resulting in representative biopsies from station 4R, 7, and 4L, the NPV is so high that mediastinoscopy seems...

  18. Endobronchial Ultrasound-guided Biopsy Performed Under Optimal Conditions in Patients With Known or Suspected Lung Cancer May Render Mediastinoscopy Unnecessary

    DEFF Research Database (Denmark)

    Clementsen, Paul F; Skov, Birgit G; Vilmann, Peter

    2014-01-01

    BACKGROUND: Mediastinoscopy is the gold standard for preoperative mediastinal staging of patients with suspected or proven lung cancer. Since the development of endoscopic ultrasound-guided biopsy via the trachea (EBUS-TBNA), this status has been challenged. The purpose of the study was to examine...... patients were operated, resulting in 9 benign and 67 malignant diagnoses; spread was found to station 4R, 5, and 5 and 6 in 4 patients. The negative predictive value (NPV) was 63/67=0.94. However, if you exclude station 5 and 6, as they cannot be reached by neither EBUS nor mediastinoscopy, NPV was 66....../67=0.99. The sensitivity was 0.76, and the specificity was 1.0. CONCLUSIONS: When EBUS-TBNA is performed under optimal conditions including general anesthesia and "bed side" microscopy performed by a pathologist resulting in representative biopsies from station 4R, 7, and 4L, the NPV is so high that mediastinoscopy seems...

  19. Persistence of high-risk human papillomavirus infection in a population-based cohort of Danish women

    DEFF Research Database (Denmark)

    Nielsen, Ann; Kjaer, Susanne K; Munk, Christian

    2010-01-01

    rarely in cancer cases were also likely to persist. The number of high-risk HPV types and detection of HPV 16 infection at baseline and ever use of oral contraceptives increased the risk for persistence. The risk factor analyses also showed that use of an intrauterine device decreased the risk......Persisting human papillomavirus (HPV) infection is a critical step in cervical carcinogenesis. This study was conducted to determine the type-specific HPV persistence and risk factors for persistence of high-risk HPV infections in a large cohort of Danish women. The study was based on a population...... high-risk HPV type at both examinations. Overall, 4.2% of the women had persistent HPV infection, accounting for 26.9% of the initially HPV-positive women. HPV 16, HPV 58, and HPV 31, all from species group alpha 9, were the most persistent types; however, other high-risk HPV types that are detected...

  20. Persistent Ambivalence: Theorizing Queer East German Studies.

    Science.gov (United States)

    Frackman, Kyle

    2018-01-16

    The German Democratic Republic (GDR, East Germany) had an ambivalent relationship with homosexuality. Under the principles of socialism, everyone was welcome to contribute to the greater good. The situation for queer people, here lesbians and gay men, was different: one of illegality and invisibility. A difficulty in analyzing these experiences is the theory and methodology necessary to find them and draw them together in an historical narrative. This essay offers a mode of analysis in which theories of affect illustrate long-term trends in East German conceptualizations of same-sex sexuality. By discussing a 1950 court ruling and a 1989 film, the essay demonstrates the persistence of homophobic prejudice and fear of homosexual seduction of young people and the links to historical and legal developments.

  1. Persistence of malathion residues in stored wheat

    International Nuclear Information System (INIS)

    Farghaly, M.; Zayed, S.M.A.D.

    1990-01-01

    The persistence of succinate- 14 C-malathion in stored wheat was investigated under local conditions during a storage period of 32 weeks. The insecticide penetrated readily into the seed and up to 16% of the applied dose was found to be bound after 32 weeks in storage. Total terminal residues declined to 9.3 and 21.0 mg/kg from initially applied doses of 12.2 and 24.4 mg/kg respectively. A small percentage of malaoxon was detected only during the early weeks after treatment (3-5%). Malathion was the major constituent of the extractable residues. In addition, seven degradation products were detected and identified. (author). 6 refs, 2 figs, 2 tabs

  2. Oral Mirtazapine in Persistent Chronic Urticaria

    Directory of Open Access Journals (Sweden)

    Mustafa Kulaç

    2008-05-01

    Full Text Available Chronic urticaria accounts for up to 75% of patients with urticaria attending dermatology clinics and can persist for many years. Chronic urticaria often causes significant quality of life issues due to pruritus and urticarial lesions resistant to treatment. Patients attending urticaria clinics have a similar impairment of quality of life as those with eczema or those with coronary disease awaiting by pass surgery. A good response to standard treatment with oral H1 receptor antagonists occurs in under 50%. Immunomodulatory or immunosuppression therapy might therefore required in patients with severe refractory chronic urticaria. But these treatments have too many adverse effects and difficulties in their using. In two current reports, three cases of severe chronic urticaria, unresponsive to conventional therapy, with a successful response to antidepressant mirtazapine were presented. Herein we present three cases responding oral mirtazapine, resistant combination therapies including antihistaminics, leucotrien antagonists and systemic corticosteroids. (Turkderm 2008; 42: 31-3

  3. Distributed Persistent Identifiers System Design

    Directory of Open Access Journals (Sweden)

    Pavel Golodoniuc

    2017-06-01

    Full Text Available The need to identify both digital and physical objects is ubiquitous in our society. Past and present persistent identifier (PID systems, of which there is a great variety in terms of technical and social implementation, have evolved with the advent of the Internet, which has allowed for globally unique and globally resolvable identifiers. PID systems have, by in large, catered for identifier uniqueness, integrity, and persistence, regardless of the identifier’s application domain. Trustworthiness of these systems has been measured by the criteria first defined by Bütikofer (2009 and further elaborated by Golodoniuc 'et al'. (2016 and Car 'et al'. (2017. Since many PID systems have been largely conceived and developed by a single organisation they faced challenges for widespread adoption and, most importantly, the ability to survive change of technology. We believe that a cause of PID systems that were once successful fading away is the centralisation of support infrastructure – both organisational and computing and data storage systems. In this paper, we propose a PID system design that implements the pillars of a trustworthy system – ensuring identifiers’ independence of any particular technology or organisation, implementation of core PID system functions, separation from data delivery, and enabling the system to adapt for future change. We propose decentralisation at all levels — persistent identifiers and information objects registration, resolution, and data delivery — using Distributed Hash Tables and traditional peer-to-peer networks with information replication and caching mechanisms, thus eliminating the need for a central PID data store. This will increase overall system fault tolerance thus ensuring its trustworthiness. We also discuss important aspects of the distributed system’s governance, such as the notion of the authoritative source and data integrity

  4. Ten-year estimated risk of bone fracture in women with differentiated thyroid cancer under TSH-suppressive levothyroxine therapy.

    Science.gov (United States)

    Vera, Lara; Gay, Stefano; Campomenosi, Claudia; Paolino, Sabrina; Pera, Giorgia; Monti, Eleonora; Mortara, Lorenzo; Seriolo, Bruno; Giusti, Massimo

    2016-01-01

    After thyroidectomy and radioiodine therapy, patients with differentiated thyroid cancer (DTC) are indefinitely treated with levothyroxine (L-T4). Osteoporosis is a debated consequence of hypothyroxinaemia. The aim of this study was to evaluate bone mineral density (BMD) and fracture risk assessed by FRAX in a cohort of DTC women. Seventy-four women with DTC (aged 56.5 ± 9.9 years) treated at the mean age of 51.9 ± 12.0 years were studied. Baseline BMD and FRAX were evaluated after 3.0 years (median). BMD and FRAX were further evaluated 5.5 years (median) after the baseline evaluation. A cohort of 120 euthyroid women, matched for age, BMI, and menopausal status, were evaluated as controls. L-T4 dosages were 813.6 ± 208.8 μg/week and 782.1 ± 184.4 μg/week at the baseline and second evaluation, respectively. The risks of major osteoporotic fracture (MOF) and hip fracture (HF) were similar in DTC patients and in controls. In DTC women, significant changes in FRAX were found, with a higher increase in the probability of HF than of MOF. A similar change was found in controls. A significant inverse correlation (P < 0.001) between L-T4 dosage and HF/MOF probability on both first and second evaluations was found. A significant inverse correlation (P = 0.05) was found between fT4, TSH and duration of therapy and HF/MOF probability only on the second evaluation. FRAX increase is a multi-factorial, age-related phenomenon. The absence of correlations between L-T4 dosage, length of therapy or fT4 levels and FRAX does not enable us to attribute an increased fracture risk to DTC women with well-controlled disease on therapy. (Endokrynol Pol 2016; 67 (4): 350-358).

  5. Thêta-Cream versus Bepanthol lotion in breast cancer patients under radiotherapy. A new prophylactic agent in skin care?

    Science.gov (United States)

    Röper, Barbara; Kaisig, Danielle; Auer, Florian; Mergen, Ertan; Molls, Michael

    2004-05-01

    In radiotherapy of the breast following breast-conserving surgery, the adverse reaction predominantly found is confined to the skin. After phase II studies, Thêta-Cream, containing CM Glucan, Hydroxyprolisilan C und Matrixyl as active substances, was said to have prophylactic properties of preventing acute radiation side effects in skin tissue. In a prospective randomized study, Thêta-cream was compared with standard skin care using Bepanthol lotion. 20 breast cancer patients were randomly assigned to use Thêta-Cream or Bepanthol lotion during radiotherapy. At 0, 30, and 50 Gy, acute skin toxicity was scored with a modified RTOG scoring system. The patients' content with the skin care and the technical assistants' content with the skin marks were recorded. For single aspects of toxicity and their sums in defined skin areas, no differences in median and range between study groups were found. The maximal toxicity anywhere in the breast averaged in a moderate erythema, mild elevation of skin temperature, no desquamation in both groups. Mild itchiness and sporadic efflorescences were more frequently seen with Thêta-Cream. According to a ranking of anonymized breast photos at 50 Gy by independent investigators, side effects were equal. Patients' content was high with both skin care regimens (1.25 on a scale from 0 to 10). With Thêta-Cream a trend toward worse skin marks was noted. Adverse events exclusively occurred in Thêta-Cream users: suspected allergic reaction once, and the necessity for resimulation twice. In direct comparison with dexpanthenol-containing lotion, no advantage for Thêta-Cream was found. Higher costs and problems with skin marks prevent a general recommendation.

  6. Immune Evasion Strategies and Persistence of Helicobacter pylori.

    Science.gov (United States)

    Mejías-Luque, Raquel; Gerhard, Markus

    Helicobacter pylori infection is commonly acquired during childhood, can persist lifelong if not treated, and can cause different gastric pathologies, including chronic gastritis, peptic ulcer disease, and eventually gastric cancer. H. pylori has developed a number of strategies in order to cope with the hostile conditions found in the human stomach as well as successful mechanisms to evade the strong innate and adaptive immune responses elicited upon infection. Thus, by manipulating innate immune receptors and related signaling pathways, inducing tolerogenic dendritic cells and inhibiting effector T cell responses, H. pylori ensures low recognition by the host immune system as well as its persistence in the gastric epithelium. Bacterial virulence factors such as cytotoxin-associated gene A, vacuolating cytotoxin A, or gamma-glutamyltranspeptidase have been extensively studied in the context of bacterial immune escape and persistence. Further, the bacterium possesses other factors that contribute to immune evasion. In this chapter, we discuss in detail the main evasion and persistence strategies evolved by the bacterium as well as the specific bacterial virulence factors involved.

  7. A critical analysis of test-retest reliability in instrument validation studies of cancer patients under palliative care: a systematic review

    Science.gov (United States)

    2014-01-01

    Background Patient-reported outcome validation needs to achieve validity and reliability standards. Among reliability analysis parameters, test-retest reliability is an important psychometric property. Retested patients must be in a clinically stable condition. This is particularly problematic in palliative care (PC) settings because advanced cancer patients are prone to a faster rate of clinical deterioration. The aim of this study was to evaluate the methods by which multi-symptom and health-related qualities of life (HRQoL) based on patient-reported outcomes (PROs) have been validated in oncological PC settings with regards to test-retest reliability. Methods A systematic search of PubMed (1966 to June 2013), EMBASE (1980 to June 2013), PsychInfo (1806 to June 2013), CINAHL (1980 to June 2013), and SCIELO (1998 to June 2013), and specific PRO databases was performed. Studies were included if they described a set of validation studies. Studies were included if they described a set of validation studies for an instrument developed to measure multi-symptom or multidimensional HRQoL in advanced cancer patients under PC. The COSMIN checklist was used to rate the methodological quality of the study designs. Results We identified 89 validation studies from 746 potentially relevant articles. From those 89 articles, 31 measured test-retest reliability and were included in this review. Upon critical analysis of the overall quality of the criteria used to determine the test-retest reliability, 6 (19.4%), 17 (54.8%), and 8 (25.8%) of these articles were rated as good, fair, or poor, respectively, and no article was classified as excellent. Multi-symptom instruments were retested over a shortened interval when compared to the HRQoL instruments (median values 24 hours and 168 hours, respectively; p = 0.001). Validation studies that included objective confirmation of clinical stability in their design yielded better results for the test-retest analysis with regard to both

  8. Persisting eicosanoid pathways in rheumatic diseases.

    Science.gov (United States)

    Korotkova, Marina; Jakobsson, Per-Johan

    2014-04-01

    An unmet clinical need exists for early treatment of rheumatic diseases and improved treatment strategies that can better maintain remission with reduced ongoing subclinical inflammation and bone destruction. Eicosanoids form one of the most complex networks in the body controlling many physiological and pathophysiological processes, including inflammation, autoimmunity and cancer. Persisting eicosanoid pathways are thought to be involved in the development of rheumatic diseases, and targeting this pathway might enable improved treatment strategies. Several enzymes of the arachidonic acid cascade as well as eicosanoid receptors (all part of the eicosanoid pathway) are today well-recognized targets for anti-inflammatory drugs that can reduce symptoms of inflammation in rheumatic diseases. In this Review, we outline the evidence supporting pivotal roles of eicosanoid signalling in the pathogenesis of rheumatic diseases and discuss findings from studies in animals and humans. We focus first on rheumatoid arthritis and discuss the upregulation of the cyclooxygenase and lipoxygenase pathways as most data are available in this condition. Research into the roles of eicosanoids in other rheumatic diseases (osteoarthritis, idiopathic inflammatory myopathies, systemic lupus erythematosus and gout) is also progressing rapidly and is discussed. Finally, we summarize the prospects of targeting eicosanoid pathways as anti-inflammatory treatment strategies for patients with rheumatic diseases.

  9. Immune persistence after pertussis vaccination.

    Science.gov (United States)

    Chen, Zhiyun; He, Qiushui

    2017-04-03

    Pertussis is one of the most prevalent vaccine-preventable diseases worldwide. The true infection rate is significantly higher than the reported incidence rate. An increased prevalence of pertussis in older populations has been found, mainly caused by waning immunity after vaccination. Vaccine-induced immunity differs due to variation in vaccine content, schedule and coverage. Protection following acellular pertussis vaccines has been suggested to wane faster than whole cell pertussis vaccines. However, long-term immune persistence of whole cell pertussis vaccines may be confounded by a progressive acquisition of natural immunity. The World Health Organization has recommended that a switch from whole cell to acellular pertussis vaccines for primary immunization in infants should only be considered if additional periodic boosters or maternal immunization can be ensured and sustained in the national immunization schedules. In this review, we present data on immune persistence after different pertussis vaccinations and compare the findings from countries with different vaccination strategies. Future aspects in serological studies are briefly discussed.

  10. The structure and stability of persistence modules

    CERN Document Server

    Chazal, Frédéric; Glisse, Marc; Oudot, Steve

    2016-01-01

    This book is a comprehensive treatment of the theory of persistence modules over the real line. It presents a set of mathematical tools to analyse the structure and to establish the stability of such modules, providing a sound mathematical framework for the study of persistence diagrams. Completely self-contained, this brief introduces the notion of persistence measure and makes extensive use of a new calculus of quiver representations to facilitate explicit computations. Appealing to both beginners and experts in the subject, The Structure and Stability of Persistence Modules provides a purely algebraic presentation of persistence, and thus complements the existing literature, which focuses mainly on topological and algorithmic aspects.

  11. New-found fundamentals of bacterial persistence.

    Science.gov (United States)

    Kint, Cyrielle I; Verstraeten, Natalie; Fauvart, Maarten; Michiels, Jan

    2012-12-01

    Persister cells display tolerance to high doses of bactericidal antibiotics and typically comprise a small fraction of a bacterial population. Recently, evidence was provided for a causal link between therapy failure and the presence of persister cells in chronic infections, underscoring the need for research on bacterial persistence. A series of recent breakthroughs have shed light on the multiplicity of persister genes, the contribution of gene expression noise to persister formation, the importance of active responses to antibiotic tolerance and heterogeneity among persister cells. Moreover, the development of in vivo model systems has highlighted the clinical relevance of persistence. This review discusses these recent advances and how this knowledge fundamentally changes the way in which we will perceive the problem of antibiotic tolerance in years to come. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Burden of acute, persistent and chronic diarrhea, Thailand, 2010.

    Science.gov (United States)

    Sutra, Sumitr; Kosuwon, Pensri; Chirawatkul, Aroon; Thepsuthammarat, Kaewjai

    2012-07-01

    The incidence of diarrhea in Thai children under five years of age increased over the last decade while mortality dramatically decreased. To evaluate the effectiveness of MCH services under Universal Coverage Schemes, health outcomes should be performed. To assess the burden and pattern of childhood diarrheal diseases in Thai children under five. The information on Intestinal Infectious Diseases ICD10: A00-A09 was divided into two groups: 1. Infectious diarrhea: A04, A05, A08, A09 and 2. Dysentery: A02, A03. The authors investigated the number of OPD visits, IPD, mortality, length of hospital stay and co-morbidity of severe cases. The burden of diarrhea was: 3.7 million (1:1) episodes, 756,552 OPD visits (1:5), 124, 403 IPD admissions (1:30), 202 (1:18,460) persistent diarrhea and 48 (1:77, 685) deaths. Diarrheal incidence had two peaks: cool season and early rainy season. Admissions lasted a collective 309,398 days. Diarrhea was persistent in 202 episodes (1.6 per 1,000 admissions) and the associated factors included: age, sepsis, anemia, chronic diseases, malnutrition and HIV. The risks for diarrhea-related mortality included: infant, septicemia and dehydration. The incidence of diarrhea was higher than expected albeit mortality was low. The mortality rate was associated with age under one year persistent diarrhea, septicemia, chronic and underlying diseases.

  13. Persistent cough in an adolescent.

    Science.gov (United States)

    Stein, M T; Harper, G; Chen, J

    1999-12-01

    Jessica, a 14-year-old girl with a history of asthma, went to her pediatrician's office because of a persistent cough. She had been coughing for at least 3 months with occasional cough-free periods of less than a few days. The cough was nonproductive and was not accompanied by fever, rhinorrhea, or facial or chest pain. Jessica and her mother observed that the cough increased with exercise and typically was not present during sleep. She has used two metered-dose inhalers--albuterol and cromolyn--without any change in the cough pattern. For the past 5 years, Jessica has had mild asthma responsive to albuterol. She enjoys running on the cross-country team, soccer, and dancing. She is an average student and denies any change in academic performance. She has never been hospitalized or had an emergency department visit for asthma or pneumonia. There has been no recent travel or exposure to a person with a chronic productive cough, tobacco smoke, or a live-in pet. Jessica lives with her mother and younger sister in a 10-year-old, carpeted apartment without any evidence of mold or recent renovation. In the process of taking the history, the pediatrician noticed that Jessica coughed intermittently, with two or three coughs during each episode. At times, the cough was harsh; at other times, it was a quiet cough, as if she were clearing her throat. She was cooperative, without overt anxiety or respiratory distress. After a complete physical examination with normal findings, the pediatrician interviewed Jessica and her mother alone. Jessica's parents had been divorced for the past 6 years. She lived with her mother but visited her father, and his new family with two young children, every weekend. She spoke about this arrangement comfortably and said that she loved her father and mother but didn't like the tension she experienced at her father's home. "I don't like adults arguing when kids are around." When asked why she thought the cough persisted so long, she commented in a

  14. Persistently better treatment planning results of intensity-modulated (IMRT) over conformal radiotherapy (3D-CRT) in prostate cancer patients with significant variation of clinical target volume and/or organs-at-risk

    International Nuclear Information System (INIS)

    Fenoglietto, Pascal; Laliberte, Benoit; Allaw, Ali; Ailleres, Norbert; Idri, Katia; Hay, Meng Huor; Moscardo, Carmen Llacer; Gourgou, Sophie; Dubois, Jean-Bernard; Azria, David

    2008-01-01

    Purpose: To compare the dose coverage of planning and clinical target volume (PTV, CTV), and organs-at-risk (OAR) between intensity-modulated (3D-IMRT) and conventional conformal radiotherapy (3D-CRT) before and after internal organ variation in prostate cancer. Methods and materials: We selected 10 patients with clinically significant interfraction volume changes. Patients were treated with 3D-IMRT to 80 Gy (minimum PTV dose of 76 Gy, excluding rectum). Fictitious, equivalent 3D-CRT plans (80 Gy at isocenter, with 95% isodose (76 Gy) coverage of PTV, with rectal blocking above 76 Gy) were generated using the same planning CT data set ('CT planning'). The plans were then also applied to a verification CT scan ('CT verify') obtained at a different moment. PTV, CTV, and OAR dose coverage were compared using non-parametric tests statistics for V95, V90 (% of the volume receiving ≥95 or 90% of the dose) and D50 (dose to 50% of the volume). Results: Mean V95 of the PTV for 'CT planning' was 94.3% (range, 88-99) vs 89.1% (range, 84-94.5) for 3D-IMRT and 3D-CRT (p = 0.005), respectively. Mean V95 of the CTV for 'CT verify' was 97% for both 3D-IMRT and 3D-CRT. Mean D50 of the rectum for 'CT planning' was 26.8 Gy (range, 22-35) vs 43.5 Gy (range, 33.5-50.5) for 3D-IMRT and 3D-CRT (p = 0.0002), respectively. For 'CT verify', this D50 was 31.1 Gy (range, 16.5-44) vs 44.2 Gy (range, 34-55) for 3D-IMRT and 3D-CRT (p = 0.006), respectively. V95 of the rectum was 0% for both plans for 'CT planning', and 2.3% (3D-IMRT) vs 2.1% (3D-CRT) for 'CT verify' (p = non-sig.). Conclusion: Dose coverage of the PTV and OAR was better with 3D-IMRT for each patient and remained so after internal volume changes

  15. Does the Androgen Receptor (AR)-Regulated Map Kinase Phosphatase 1 (MKP-1) Enhance Castration-Resistant Prostate Cancer Survival under Therapeutic Stress?

    Science.gov (United States)

    2016-03-01

    in breast cancer models, and is inversely associated with apoptosis in preclinical prostate cancer models. Androgen and glucocorticoid signaling can... effects of both hormonal and chemotherapies. To date, significant progress has been made including optimization of MKP-1 protein detection...with apoptosis in preclinical prostate cancer models. Androgen and glucocorticoid signaling can induce MKP-1 expression; as mCRPC remains driven by

  16. Is administration of trastuzumab an independent risk factor for developing osteonecrosis of the jaw among metastatic breast cancer patients under zoledronic acid treatment?

    Science.gov (United States)

    Pilanci, Kezban Nur; Alco, Gul; Ordu, Cetin; Sarsenov, Dauren; Celebi, Filiz; Erdogan, Zeynep; Agacayak, Filiz; Ilgun, Serkan; Tecimer, Coskun; Demir, Gokhan; Eralp, Yesim; Okkan, Sait; Ozmen, Vahit

    2015-05-01

    One of the most important adverse effects of zoledronic acid (ZA) is osteonecrosis of the jaw (ONJ). In previous literature, several risk factors have been identified in the development of ONJ. In this study, we aimed to determine the role of trastuzumab, an antiangiogenic agent, as an independent risk factor for the development of this serious side effect.Our study included 97 patients (mean age: 54 ± 10 years) with breast cancer, recorded in the archives of the Istanbul Florence Nightingale Breast Study Group, who received ZA therapy due to bone metastases between March 2006 and December 2013. We recorded the patients' ages, weights, duration of treatment with ZA, number of ZA infusions, dental procedures, anticancer treatments (chemotherapy, aromatase inhibitor, trastuzumab), the presence of diabetes mellitus or renal dysfunction, and smoking habits.Thirteen patients (13.40%) had developed ONJ. Among the patients with ONJ, the mean time of exposure to ZA was 41 months (range: 13-82) and the mean number of ZA infusions was 38 (range: 15-56). The duration of treatment with ZA and the use of trastuzumab were observed to be 2 factors that influenced the development of ONJ (P = 0.049 and P = 0.028, respectively).The development of ONJ under ZA treatment may be associated solely with the duration of ZA treatment and the concurrent administration of trastuzumab. These findings show that patients who are administered trastuzumab for metastatic breast cancer while undergoing ZA treatment are prone to developing ONJ. Therefore, we recommend intense clinical observation to avoid this particular condition in patients receiving ZA and trastuzumab.

  17. Persistent homology and string vacua

    Energy Technology Data Exchange (ETDEWEB)

    Cirafici, Michele [Center for Mathematical Analysis, Geometry and Dynamical Systems,Instituto Superior Técnico, Universidade de Lisboa,Av. Rovisco Pais, 1049-001 Lisboa (Portugal); Institut des Hautes Études Scientifiques,Le Bois-Marie, 35 route de Chartres, F-91440 Bures-sur-Yvette (France)

    2016-03-08

    We use methods from topological data analysis to study the topological features of certain distributions of string vacua. Topological data analysis is a multi-scale approach used to analyze the topological features of a dataset by identifying which homological characteristics persist over a long range of scales. We apply these techniques in several contexts. We analyze N=2 vacua by focusing on certain distributions of Calabi-Yau varieties and Landau-Ginzburg models. We then turn to flux compactifications and discuss how we can use topological data analysis to extract physical information. Finally we apply these techniques to certain phenomenologically realistic heterotic models. We discuss the possibility of characterizing string vacua using the topological properties of their distributions.

  18. Persistence of antimuscarinic drug use

    DEFF Research Database (Denmark)

    Brostrøm, Søren; Hallas, Jesper

    2009-01-01

    PURPOSE: Evidence suggests antimuscarinic drugs for the overactive-bladder syndrome only confer modest improvements in quality of life. We wanted to describe the persistence of therapy, including an extended analysis beyond the 1-year follow-up employed in other studies. METHODS: All prescriptions...... for drugs in ATC category G04BD were retrieved for the period 1999-2006 from a regional database with complete capture of all reimbursed prescriptions. Kaplan-Meyer curves were generated for duration of treatment for each substance and analyzed for determinants of termination. RESULTS: With the exception...... of trospium chloride, all drugs had continuation rates of less than 50% at 6 months, less than 25% at 1 year, and less than 10% at 2 years and longer. Trospium chloride, however, exhibited continuation rates of 46% at 6 months, 36% at 1 year, 22% at 2 years, and 16% at 3 years. CONCLUSIONS: In a setting...

  19. Persistence Mechanisms of Conjugative Plasmids

    DEFF Research Database (Denmark)

    Bahl, Martin Iain; Hansen, Lars H.; Sørensen, Søren Johannes

    2009-01-01

    maintenance in the host cell. These importantly include the ability to self-mobilize in a process termed conjugative transfer, which may occur across species barriers. Other plasmid stabilizing mechanisms include the multimer resolution system, active partitioning, and post-segregational-killing of plasmid......Are plasmids selfish parasitic DNA molecules or an integrated part of the bacterial genome? This chapter reviews the current understanding of the persistence mechanisms of conjugative plasmids harbored by bacterial cells and populations. The diversity and intricacy of mechanisms affecting...... the successful propagation and long-term continued existence of these extra-chromosomal elements is extensive. Apart from the accessory genetic elements that may provide plasmid-harboring cells a selective advantage, special focus is placed on the mechanisms conjugative