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Sample records for tumor prevention network

  1. The Tumor Macroenvironment: Cancer-Promoting Networks Beyond Tumor Beds.

    Science.gov (United States)

    Rutkowski, Melanie R; Svoronos, Nikolaos; Perales-Puchalt, Alfredo; Conejo-Garcia, Jose R

    2015-01-01

    During tumor progression, alterations within the systemic tumor environment, or macroenvironment, result in the promotion of tumor growth, tumor invasion to distal organs, and eventual metastatic disease. Distally produced hormones, commensal microbiota residing within mucosal surfaces, myeloid cells and even the bone marrow impact the systemic immune system, tumor growth, and metastatic spread. Understanding the reciprocal interactions between the cells and soluble factors within the macroenvironment and the primary tumor will enable the design of specific therapies that have the potential to prevent dissemination and metastatic spread. This chapter will summarize recent findings detailing how the primary tumor and systemic tumor macroenvironment coordinate malignant progression. © 2015 Elsevier Inc. All rights reserved.

  2. NKT Cell Networks in the Regulation of Tumor Immunity

    Science.gov (United States)

    Robertson, Faith C.; Berzofsky, Jay A.; Terabe, Masaki

    2014-01-01

    CD1d-restricted natural killer T (NKT) cells lie at the interface between the innate and adaptive immune systems and are important mediators of immune responses and tumor immunosurveillance. These NKT cells uniquely recognize lipid antigens, and their rapid yet specific reactions influence both innate and adaptive immunity. In tumor immunity, two NKT subsets (type I and type II) have contrasting roles in which they not only cross-regulate one another, but also impact innate immune cell populations, including natural killer, dendritic, and myeloid lineage cells, as well as adaptive populations, especially CD8+ and CD4+ T cells. The extent to which NKT cells promote or suppress surrounding cells affects the host’s ability to prevent neoplasia and is consequently of great interest for therapeutic development. Data have shown the potential for therapeutic use of NKT cell agonists and synergy with immune response modifiers in both pre-clinical studies and preliminary clinical studies. However, there is room to improve treatment efficacy by further elucidating the biological mechanisms underlying NKT cell networks. Here, we discuss the progress made in understanding NKT cell networks, their consequent role in the regulation of tumor immunity, and the potential to exploit that knowledge in a clinical setting. PMID:25389427

  3. NKT cell networks in the regulation of tumor immunity.

    Science.gov (United States)

    Robertson, Faith C; Berzofsky, Jay A; Terabe, Masaki

    2014-01-01

    CD1d-restricted natural killer T (NKT) cells lie at the interface between the innate and adaptive immune systems and are important mediators of immune responses and tumor immunosurveillance. These NKT cells uniquely recognize lipid antigens, and their rapid yet specific reactions influence both innate and adaptive immunity. In tumor immunity, two NKT subsets (type I and type II) have contrasting roles in which they not only cross-regulate one another, but also impact innate immune cell populations, including natural killer, dendritic, and myeloid lineage cells, as well as adaptive populations, especially CD8(+) and CD4(+) T cells. The extent to which NKT cells promote or suppress surrounding cells affects the host's ability to prevent neoplasia and is consequently of great interest for therapeutic development. Data have shown the potential for therapeutic use of NKT cell agonists and synergy with immune response modifiers in both pre-clinical studies and preliminary clinical studies. However, there is room to improve treatment efficacy by further elucidating the biological mechanisms underlying NKT cell networks. Here, we discuss the progress made in understanding NKT cell networks, their consequent role in the regulation of tumor immunity, and the potential to exploit that knowledge in a clinical setting.

  4. NKT cell networks in the regulation of tumor immunity

    Directory of Open Access Journals (Sweden)

    Faith C Robertson

    2014-10-01

    Full Text Available CD1d-restricted natural killer T (NKT cells lie at the interface between the innate and adaptive immune systems and are important mediators of immune responses and tumor immunosurveillance. These NKT cells uniquely recognize lipid antigens, and their rapid yet specific reactions influence both innate and adaptive immunity. In tumor immunity, two NKT subsets (type I and type II have contrasting roles in which they not only cross-regulate one another, but also impact innate immune cell populations, including natural killer, dendritic and myeloid lineage cells, as well as adaptive populations, especially CD8+ and CD4+ T cells. The extent to which NKT cells promote or suppress surrounding cells affects the host’s ability to prevent neoplasia and is consequently of great interest for therapeutic development. Data have shown the potential for therapeutic use of NKT cell agonists and synergy with immune response modifiers in both pre-clinical studies and preliminary clinical studies. However, there is room to improve treatment efficacy by further elucidating the biological mechanisms underlying NKT cell networks. Here, we discuss the progress made in understanding NKT cell networks, their consequent role in the regulation of tumor immunity, and the potential to exploit that knowledge in a clinical setting.

  5. Predictive genomics: a cancer hallmark network framework for predicting tumor clinical phenotypes using genome sequencing data.

    Science.gov (United States)

    Wang, Edwin; Zaman, Naif; Mcgee, Shauna; Milanese, Jean-Sébastien; Masoudi-Nejad, Ali; O'Connor-McCourt, Maureen

    2015-02-01

    Tumor genome sequencing leads to documenting thousands of DNA mutations and other genomic alterations. At present, these data cannot be analyzed adequately to aid in the understanding of tumorigenesis and its evolution. Moreover, we have little insight into how to use these data to predict clinical phenotypes and tumor progression to better design patient treatment. To meet these challenges, we discuss a cancer hallmark network framework for modeling genome sequencing data to predict cancer clonal evolution and associated clinical phenotypes. The framework includes: (1) cancer hallmarks that can be represented by a few molecular/signaling networks. 'Network operational signatures' which represent gene regulatory logics/strengths enable to quantify state transitions and measures of hallmark traits. Thus, sets of genomic alterations which are associated with network operational signatures could be linked to the state/measure of hallmark traits. The network operational signature transforms genotypic data (i.e., genomic alterations) to regulatory phenotypic profiles (i.e., regulatory logics/strengths), to cellular phenotypic profiles (i.e., hallmark traits) which lead to clinical phenotypic profiles (i.e., a collection of hallmark traits). Furthermore, the framework considers regulatory logics of the hallmark networks under tumor evolutionary dynamics and therefore also includes: (2) a self-promoting positive feedback loop that is dominated by a genomic instability network and a cell survival/proliferation network is the main driver of tumor clonal evolution. Surrounding tumor stroma and its host immune systems shape the evolutionary paths; (3) cell motility initiating metastasis is a byproduct of the above self-promoting loop activity during tumorigenesis; (4) an emerging hallmark network which triggers genome duplication dominates a feed-forward loop which in turn could act as a rate-limiting step for tumor formation; (5) mutations and other genomic alterations have

  6. Canada-Africa Prevention Trials Network : Building African Capacity ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Canada-Africa Prevention Trials Network : Building African Capacity for HIV/AIDS Prevention Trials. The Canada-Africa Prevention Trials Network (CAPT Network) was formed through a capacity building grant from the Global Health Research Initiative (GHRI). The Network comprises eight African centres (four in Uganda, ...

  7. An Ensemble of 2D Convolutional Neural Networks for Tumor Segmentation

    DEFF Research Database (Denmark)

    Lyksborg, Mark; Puonti, Oula; Agn, Mikael

    2015-01-01

    Accurate tumor segmentation plays an important role in radiosurgery planning and the assessment of radiotherapy treatment efficacy. In this paper we propose a method combining an ensemble of 2D convolutional neural networks for doing a volumetric segmentation of magnetic resonance images....... The segmentation is done in three steps; first the full tumor region, is segmented from the background by a voxel-wise merging of the decisions of three networks learned from three orthogonal planes, next the segmentation is refined using a cellular automaton-based seed growing method known as growcut. Finally......, within-tumor sub-regions are segmented using an additional ensemble of networks trained for the task. We demonstrate the method on the MICCAI Brain Tumor Segmentation Challenge dataset of 2014, and show improved segmentation accuracy compared to an axially trained 2D network and an ensemble segmentation...

  8. Navigating cancer network attractors for tumor-specific therapy

    DEFF Research Database (Denmark)

    Creixell, Pau; Schoof, Erwin; Erler, Janine Terra

    2012-01-01

    understanding of the processes by which genetic lesions perturb these networks and lead to disease phenotypes. Network biology will help circumvent fundamental obstacles in cancer treatment, such as drug resistance and metastasis, empowering personalized and tumor-specific cancer therapies....

  9. Brain tumor segmentation in multi-spectral MRI using convolutional neural networks (CNN).

    Science.gov (United States)

    Iqbal, Sajid; Ghani, M Usman; Saba, Tanzila; Rehman, Amjad

    2018-04-01

    A tumor could be found in any area of the brain and could be of any size, shape, and contrast. There may exist multiple tumors of different types in a human brain at the same time. Accurate tumor area segmentation is considered primary step for treatment of brain tumors. Deep Learning is a set of promising techniques that could provide better results as compared to nondeep learning techniques for segmenting timorous part inside a brain. This article presents a deep convolutional neural network (CNN) to segment brain tumors in MRIs. The proposed network uses BRATS segmentation challenge dataset which is composed of images obtained through four different modalities. Accordingly, we present an extended version of existing network to solve segmentation problem. The network architecture consists of multiple neural network layers connected in sequential order with the feeding of Convolutional feature maps at the peer level. Experimental results on BRATS 2015 benchmark data thus show the usability of the proposed approach and its superiority over the other approaches in this area of research. © 2018 Wiley Periodicals, Inc.

  10. A Network-Individual-Resource Model for HIV Prevention

    Science.gov (United States)

    Johnson, Blair T.; Redding, Colleen A.; DiClemente, Ralph J.; Mustanski, Brian S.; Dodge, Brian M.; Sheeran, Paschal; Warren, Michelle R.; Zimmerman, Rick S.; Fisher, William A.; Conner, Mark T.; Carey, Michael P.; Fisher, Jeffrey D.; Stall, Ronald D.; Fishbein, Martin

    2014-01-01

    HIV is transmitted through dyadic exchanges of individuals linked in transitory or permanent networks of varying sizes. To optimize prevention efficacy, a complementary theoretical perspective that bridges key individual level elements with important network elements can be a foundation for developing and implementing HIV interventions with outcomes that are more sustainable over time and have greater dissemination potential. Toward that end, we introduce a Network-Individual-Resource (NIR) model for HIV prevention that recognizes how exchanges of resources between individuals and their networks underlies and sustains HIV-risk behaviors. Individual behavior change for HIV prevention, then, may be dependent on increasing the supportiveness of that individual's relevant networks for such change. Among other implications, an NIR model predicts that the success of prevention efforts depends on whether the prevention efforts (1) prompt behavior changes that can be sustained by the resources the individual or their networks possess; (2) meet individual and network needs and are consistent with the individual's current situation/developmental stage; (3) are trusted and valued; and (4) target high HIV-prevalence networks. PMID:20862606

  11. Brain tumor segmentation with Deep Neural Networks.

    Science.gov (United States)

    Havaei, Mohammad; Davy, Axel; Warde-Farley, David; Biard, Antoine; Courville, Aaron; Bengio, Yoshua; Pal, Chris; Jodoin, Pierre-Marc; Larochelle, Hugo

    2017-01-01

    In this paper, we present a fully automatic brain tumor segmentation method based on Deep Neural Networks (DNNs). The proposed networks are tailored to glioblastomas (both low and high grade) pictured in MR images. By their very nature, these tumors can appear anywhere in the brain and have almost any kind of shape, size, and contrast. These reasons motivate our exploration of a machine learning solution that exploits a flexible, high capacity DNN while being extremely efficient. Here, we give a description of different model choices that we've found to be necessary for obtaining competitive performance. We explore in particular different architectures based on Convolutional Neural Networks (CNN), i.e. DNNs specifically adapted to image data. We present a novel CNN architecture which differs from those traditionally used in computer vision. Our CNN exploits both local features as well as more global contextual features simultaneously. Also, different from most traditional uses of CNNs, our networks use a final layer that is a convolutional implementation of a fully connected layer which allows a 40 fold speed up. We also describe a 2-phase training procedure that allows us to tackle difficulties related to the imbalance of tumor labels. Finally, we explore a cascade architecture in which the output of a basic CNN is treated as an additional source of information for a subsequent CNN. Results reported on the 2013 BRATS test data-set reveal that our architecture improves over the currently published state-of-the-art while being over 30 times faster. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. HIV Clients as Agents for Prevention: A Social Network Solution

    Directory of Open Access Journals (Sweden)

    Sarah Ssali

    2012-01-01

    Full Text Available HIV prevention efforts to date have not explored the potential for persons living with HIV to act as change agents for prevention behaviour in their social networks. Using egocentric social network analysis, this study examined the prevalence and social network correlates of prevention advocacy behaviours (discussing HIV in general; encouraging abstinence or condom use, HIV testing, and seeking HIV care enacted by 39 HIV clients in Uganda. Participants engaged in each prevention advocacy behaviour with roughly 50–70% of the members in their network. The strongest determinant of engaging in prevention advocacy with more of one’s network members was having a greater proportion of network members who knew one’s HIV seropositive status, as this was associated with three of the four advocacy behaviours. These findings highlight the potential for PLHA to be key change agents for HIV prevention within their networks and the importance of HIV disclosure in facilitating prevention advocacy.

  13. Quantitative Analysis of Signaling Networks across Differentially Embedded Tumors Highlights Interpatient Heterogeneity in Human Glioblastoma

    Science.gov (United States)

    2015-01-01

    Glioblastoma multiforme (GBM) is the most aggressive malignant primary brain tumor, with a dismal mean survival even with the current standard of care. Although in vitro cell systems can provide mechanistic insight into the regulatory networks governing GBM cell proliferation and migration, clinical samples provide a more physiologically relevant view of oncogenic signaling networks. However, clinical samples are not widely available and may be embedded for histopathologic analysis. With the goal of accurately identifying activated signaling networks in GBM tumor samples, we investigated the impact of embedding in optimal cutting temperature (OCT) compound followed by flash freezing in LN2 vs immediate flash freezing (iFF) in LN2 on protein expression and phosphorylation-mediated signaling networks. Quantitative proteomic and phosphoproteomic analysis of 8 pairs of tumor specimens revealed minimal impact of the different sample processing strategies and highlighted the large interpatient heterogeneity present in these tumors. Correlation analyses of the differentially processed tumor sections identified activated signaling networks present in selected tumors and revealed the differential expression of transcription, translation, and degradation associated proteins. This study demonstrates the capability of quantitative mass spectrometry for identification of in vivo oncogenic signaling networks from human tumor specimens that were either OCT-embedded or immediately flash-frozen. PMID:24927040

  14. Increased frontal functional networks in adult survivors of childhood brain tumors

    Directory of Open Access Journals (Sweden)

    Hongbo Chen

    2016-01-01

    Full Text Available Childhood brain tumors and associated treatment have been shown to affect brain development and cognitive outcomes. Understanding the functional connectivity of brain many years after diagnosis and treatment may inform the development of interventions to improve the long-term outcomes of adult survivors of childhood brain tumors. This work investigated the frontal region functional connectivity of 16 adult survivors of childhood cerebellar tumors after an average of 14.9 years from diagnosis and 16 demographically-matched controls using resting state functional MRI (rs-fMRI. Independent component analysis (ICA was applied to identify the resting state activity from rs-fMRI data and to select the specific regions associated with executive functions, followed by the secondary analysis of the functional networks connecting these regions. It was found that survivors exhibited differences in the functional connectivity in executive control network (ECN, default mode network (DMN and salience network (SN compared to demographically-matched controls. More specifically, the number of functional connectivity observed in the survivors is higher than that in the controls, and with increased strength, or stronger correlation coefficient between paired seeds, in survivors compared to the controls. Observed hyperconnectivity in the selected frontal functional network thus is consistent with findings in patients with other neurological injuries and diseases.

  15. The genomic applications in practice and prevention network.

    Science.gov (United States)

    Khoury, Muin J; Feero, W Gregory; Reyes, Michele; Citrin, Toby; Freedman, Andrew; Leonard, Debra; Burke, Wylie; Coates, Ralph; Croyle, Robert T; Edwards, Karen; Kardia, Sharon; McBride, Colleen; Manolio, Teri; Randhawa, Gurvaneet; Rasooly, Rebekah; St Pierre, Jeannette; Terry, Sharon

    2009-07-01

    The authors describe the rationale and initial development of a new collaborative initiative, the Genomic Applications in Practice and Prevention Network. The network convened by the Centers for Disease Control and Prevention and the National Institutes of Health includes multiple stakeholders from academia, government, health care, public health, industry and consumers. The premise of Genomic Applications in Practice and Prevention Network is that there is an unaddressed chasm between gene discoveries and demonstration of their clinical validity and utility. This chasm is due to the lack of readily accessible information about the utility of most genomic applications and the lack of necessary knowledge by consumers and providers to implement what is known. The mission of Genomic Applications in Practice and Prevention Network is to accelerate and streamline the effective integration of validated genomic knowledge into the practice of medicine and public health, by empowering and sponsoring research, evaluating research findings, and disseminating high quality information on candidate genomic applications in practice and prevention. Genomic Applications in Practice and Prevention Network will develop a process that links ongoing collection of information on candidate genomic applications to four crucial domains: (1) knowledge synthesis and dissemination for new and existing technologies, and the identification of knowledge gaps, (2) a robust evidence-based recommendation development process, (3) translation research to evaluate validity, utility and impact in the real world and how to disseminate and implement recommended genomic applications, and (4) programs to enhance practice, education, and surveillance.

  16. Selenium prevents tumor development in a rat model for chemical carcinogenesis

    DEFF Research Database (Denmark)

    Bjorkhem-Bergman, L.; Torndal, U. B.; Eken, S.

    2005-01-01

    Previous studies in animals and humans have shown that selenium compounds can prevent cancer development. In this work we studied the tumor preventive effect of selenium supplementation, administrated as selenite, in the initiation, promotion and progression phases in a synchronized rat model for...

  17. The prevention research centers' managing epilepsy well network.

    Science.gov (United States)

    DiIorio, Colleen K; Bamps, Yvan A; Edwards, Ariele L; Escoffery, Cam; Thompson, Nancy J; Begley, Charles E; Shegog, Ross; Clark, Noreen M; Selwa, Linda; Stoll, Shelley C; Fraser, Robert T; Ciechanowski, Paul; Johnson, Erica K; Kobau, Rosemarie; Price, Patricia H

    2010-11-01

    The Managing Epilepsy Well (MEW) Network was created in 2007 by the Centers for Disease Control and Prevention's (CDC) Prevention Research Centers and Epilepsy Program to promote epilepsy self-management research and to improve the quality of life for people with epilepsy. MEW Network membership comprises four collaborating centers (Emory University, University of Texas Health Science Center at Houston, University of Michigan, and University of Washington), representatives from CDC, affiliate members, and community stakeholders. This article describes the MEW Network's background, mission statement, research agenda, and structure. Exploratory and intervention studies conducted by individual collaborating centers are described, as are Network collaborative projects, including a multisite depression prevention intervention and the development of a standard measure of epilepsy self-management. Communication strategies and examples of research translation programs are discussed. The conclusion outlines the Network's role in the future development and dissemination of evidence-based epilepsy self-management programs. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. CD8+ Tumor-Infiltrating T Cells Are Trapped in the Tumor-Dendritic Cell Network

    Directory of Open Access Journals (Sweden)

    Alexandre Boissonnas

    2013-01-01

    Full Text Available Chemotherapy enhances the antitumor adaptive immune T cell response, but the immunosuppressive tumor environment often dominates, resulting in cancer relapse. Antigen-presenting cells such as tumor-associated macrophages (TAMs and tumor dendritic cells (TuDCs are the main protagonists of tumor-infiltrating lymphocyte (TIL immuno-suppression. TAMs have been widely investigated and are associated with poor prognosis, but the immuno-suppressive activity of TuDCs is less well understood. We performed two-photon imaging of the tumor tissue to examine the spatiotemporal interactions between TILs and TuDCs after chemotherapy. In a strongly immuno-suppressive murine tumor model, cyclophosphamide-mediated chemotherapy transiently enhanced the antitumor activity of adoptively transferred ovalbumin-specific CD8+ T cell receptor transgenic T cells (OTI but barely affected TuDC compartment within the tumor. Time lapse imaging of living tumor tissue showed that TuDCs are organized as a mesh with dynamic interconnections. Once infiltrated into the tumor parenchyma, OTI T cells make antigen-specific and long-lasting contacts with TuDCs. Extensive analysis of TIL infiltration on histologic section revealed that after chemotherapy the majority of OTI T cells interact with TuDCs and that infiltration is restricted to TuDC-rich areas. We propose that the TuDC network exerts antigen-dependent unproductive retention that trap T cells and limit their antitumor effectiveness.

  19. Brain tumor segmentation using holistically nested neural networks in MRI images.

    Science.gov (United States)

    Zhuge, Ying; Krauze, Andra V; Ning, Holly; Cheng, Jason Y; Arora, Barbara C; Camphausen, Kevin; Miller, Robert W

    2017-10-01

    Gliomas are rapidly progressive, neurologically devastating, largely fatal brain tumors. Magnetic resonance imaging (MRI) is a widely used technique employed in the diagnosis and management of gliomas in clinical practice. MRI is also the standard imaging modality used to delineate the brain tumor target as part of treatment planning for the administration of radiation therapy. Despite more than 20 yr of research and development, computational brain tumor segmentation in MRI images remains a challenging task. We are presenting a novel method of automatic image segmentation based on holistically nested neural networks that could be employed for brain tumor segmentation of MRI images. Two preprocessing techniques were applied to MRI images. The N4ITK method was employed for correction of bias field distortion. A novel landmark-based intensity normalization method was developed so that tissue types have a similar intensity scale in images of different subjects for the same MRI protocol. The holistically nested neural networks (HNN), which extend from the convolutional neural networks (CNN) with a deep supervision through an additional weighted-fusion output layer, was trained to learn the multiscale and multilevel hierarchical appearance representation of the brain tumor in MRI images and was subsequently applied to produce a prediction map of the brain tumor on test images. Finally, the brain tumor was obtained through an optimum thresholding on the prediction map. The proposed method was evaluated on both the Multimodal Brain Tumor Image Segmentation (BRATS) Benchmark 2013 training datasets, and clinical data from our institute. A dice similarity coefficient (DSC) and sensitivity of 0.78 and 0.81 were achieved on 20 BRATS 2013 training datasets with high-grade gliomas (HGG), based on a two-fold cross-validation. The HNN model built on the BRATS 2013 training data was applied to ten clinical datasets with HGG from a locally developed database. DSC and sensitivity of

  20. Networks for prevention of violence: from utopia to action

    Directory of Open Access Journals (Sweden)

    Kathie Njaine

    2006-06-01

    Full Text Available This article aims to discuss the experience of networks for the protection of people exposed to situations of violence or prevention networks. It is based on the concept created by Castells, who defines the information age. This study is part of the investigation "Successful experiences in the prevention of violence", carried out by the Latin-American Center for Studies on Violence Jorge Careli/ENSP-IFF/Fiocruz, in cooperation with the Secretariat for Health Survey of the Ministry of Health. The article analyzes the possibilities and limitations in the construction of networks for the prevention of violence, seeking to understand the sense of actions and movements carried out in networks. The method we used is a case study of two network initiatives in the Southern region of the country. In terms of results, in face of the difficulties of working in networks, we found it to be necessary: to break with sectorial and vertical actions; to promote constant communication and interchange of information; to permanently train the professionals and persons involved in the network, incorporating them into the protective and preventive actions; and to promote the participation of wide social sectors. In conclusion, one can affirm that the construction of a protection network involves complex steps, looking to the same problem with new eyes and a new vision for planting solutions.

  1. A Ketogenic Formula Prevents Tumor Progression and Cancer Cachexia by Attenuating Systemic Inflammation in Colon 26 Tumor-Bearing Mice

    Directory of Open Access Journals (Sweden)

    Kentaro Nakamura

    2018-02-01

    Full Text Available Low-carbohydrate, high-fat diets (ketogenic diets might prevent tumor progression and could be used as supportive therapy; however, few studies have addressed the effect of such diets on colorectal cancer. An infant formula with a ketogenic composition (ketogenic formula; KF is used to treat patients with refractory epilepsy. We investigated the effect of KF on cancer and cancer cachexia in colon tumor-bearing mice. Mice were randomized into normal (NR, tumor-bearing (TB, and ketogenic formula (KF groups. Colon 26 cells were inoculated subcutaneously into TB and KF mice. The NR and TB groups received a standard diet, and the KF mice received KF ad libitum. KF mice preserved their body, muscle, and carcass weights. Tumor weight and plasma IL-6 levels were significantly lower in KF mice than in TB mice. In the KF group, energy intake was significantly higher than that in the other two groups. Blood ketone body concentrations in KF mice were significantly elevated, and there was a significant negative correlation between blood ketone body concentration and tumor weight. Therefore, KF may suppress the progression of cancer and the accompanying systemic inflammation without adverse effects on weight gain, or muscle mass, which might help to prevent cancer cachexia.

  2. Networking for ovarian rare tumors: a significant breakthrough improving disease management.

    Science.gov (United States)

    Chiannilkulchai, N; Pautier, P; Genestie, C; Bats, A S; Vacher-Lavenu, M C; Devouassoux-Shisheboran, M; Treilleux, I; Floquet, A; Croce, S; Ferron, G; Mery, E; Pomel, C; Penault-Llorca, F; Lefeuvre-Plesse, C; Henno, S; Leblanc, E; Lemaire, A S; Averous, G; Kurtz, J E; Ray-Coquard, I

    2017-06-01

    Rare ovarian tumors represent >20% of all ovarian cancers. Given the rarity of these tumors, natural history, prognostic factors are not clearly identified. The extreme variability of patients (age, histological subtypes, stage) induces multiple and complex therapeutic strategies. Since 2011, a national network with a dedicated system for referral, up to 22 regional and three national reference centers (RC) has been supported by the French National Cancer Institute (INCa). The network aims to prospectively monitor the management of rare ovarian tumors and provide an equal access to medical expertise and innovative treatments to all French patients through a dedicated website, www.ovaire-rare.org. Over a 5-year activity, 4612 patients have been included. Patients' inclusions increased from 553 in 2011 to 1202 in 2015. Expert pathology review and patients' files discussion in dedicated multidisciplinary tumor boards increased from 166 cases in 2011 (25%) to 538 (45%) in 2015. Pathology review consistently modified the medical strategy in 5-9% every year. The rate of patients' files discussed in RC similarly increased from 294 (53%) to 789 (66%). An increasing number (357 in 5 years) of gynecologic (non-ovarian) rare tumors were also registered by physicians seeking for pathological or medical advice from expert tumor boards. Such a nation-wide organization for rare gynecological tumors has invaluable benefits, not only for patients, but also for epidemiological, clinical and biological research. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Photodynamic therapy-generated vaccines prevent tumor recurrence after radiotherapy

    International Nuclear Information System (INIS)

    Korbelik, M.; Sun, J.

    2003-01-01

    Photodynamic therapy (PDT), an established clinical modality for a variety of malignant and non-malignant diseases, inflicts photoreactive drug-mediated oxidative stress that prompts the engagement of host inflammatory and immune responses which contribute to the therapy outcome. Recently, it has become evident that in vitro PDT-treated tumor cells or their lysates can be utilized as an effective vaccine against established tumors of the same origin. The mechanism underlying the vaccine action appears to be based on eliciting immune recognition of the tumor and developing an efficient immune response even against poorly immunogenic tumors. This study examined whether PDT-generated vaccines can be effectively combined with radiotherapy. Subcutaneous SCCVII tumors (squamous cell carcinomas) growing in syngeneic C3H/HeN mice were treated by radiotherapy (60 Gy x-ray dose). PDT-vaccine treatment, done by peritumoral injection of in vitro PDT-treated SCCVII cells (20 million/mouse), was performed either immediately after radiotherapy or ten days later. The mice were then observed for tumor regression/recurrence. The tumors treated with radiotherapy alone shrunk and became impalpable for a brief period after which they all recurred. In contrast, vaccination performed at 10 days post radiotherapy delayed tumor recurrence and prevented it in one of six mice. Even better results were obtained with mice vaccinated immediately after radiotherapy, with mice showing not only a delayed tumor recurrence but also no sign of tumor in 50% of mice. The PDT-vaccine treatment without radiotherapy produced in this trial a significant tumor growth retardation but no complete regressions. These results indicate that PDT-generated vaccines can ensure immune rejection of cancer once the lesion size is reduced by radiotherapy. Even without obtaining a systemic immunity for the elimination of disseminated malignant deposits, these findings suggest that PDT-vaccines can improve local control

  4. Social network approaches to recruitment, HIV prevention, medical care, and medication adherence.

    Science.gov (United States)

    Latkin, Carl A; Davey-Rothwell, Melissa A; Knowlton, Amy R; Alexander, Kamila A; Williams, Chyvette T; Boodram, Basmattee

    2013-06-01

    This article reviews the current issues and advancements in social network approaches to HIV prevention and care. Social network analysis can provide a method to understand health disparities in HIV rates, treatment access, and outcomes. Social network analysis is a valuable tool to link social structural factors to individual behaviors. Social networks provide an avenue for low-cost and sustainable HIV prevention interventions that can be adapted and translated into diverse populations. Social networks can be utilized as a viable approach to recruitment for HIV testing and counseling, HIV prevention interventions, optimizing HIV medical care, and medication adherence. Social network interventions may be face-to-face or through social media. Key issues in designing social network interventions are contamination due to social diffusion, network stability, density, and the choice and training of network members. There are also ethical issues involved in the development and implementation of social network interventions. Social network analyses can also be used to understand HIV transmission dynamics.

  5. Prevention of Falls Network Europe: a thematic network aimed at introducing good practice in effective falls prevention across Europe.

    Science.gov (United States)

    Skelton, D A; Becker, C; Lamb, S E; Close, J C T; Zijlstra, W; Yardley, L; Todd, C J

    2004-12-01

    The Prevention of Falls Network Europe (ProFaNE) aims to improve quality of life of the ageing population by focussing on a major cause of disability and distress: falls. The thematic network is funded by the European Commission and brings together scientists, clinicians and other health professionals from around Europe to focus on four main themes: taxonomy and coordination of trials, clinical assessment and management of falls, assessment of balance function, and psychological aspects of falling. There are 24 members across Europe as well as network associates who contribute expertise at workshops and meetings. ProFaNE, a 4-year project which started in January 2003, aims to improve and standardise health care processes, introducing and promoting good practice widely across Europe. ProFaNE undertakes workshops that bring together experts and observers around specific topics to exchange knowledge, expertise and resources on interventions that reduce falls. A key document for policy makers around Europe, written by ProFaNE members, was published by the World Health Organisation in March 2004. ProFaNE's website has both public and private areas with resources (web links to falls prevention, useful documents for policy makers, researchers and practitioners) and a discussion board to encourage informal networking between members and the public. The ultimate aim of ProFaNE is to submit a collaborative bid to undertake a multi-centre, randomised controlled trial of a multi-factorial fall prevention intervention with peripheral fracture as the primary outcome. The success of the networking and relationship building in the first year and a half of ProFaNE's work makes this an achievable goal.

  6. Numerical Modeling of Interstitial Fluid Flow Coupled with Blood Flow through a Remodeled Solid Tumor Microvascular Network.

    Science.gov (United States)

    Soltani, M; Chen, P

    2013-01-01

    Modeling of interstitial fluid flow involves processes such as fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. To date, majority of microvascular flow modeling has been done at different levels and scales mostly on simple tumor shapes with their capillaries. However, with our proposed numerical model, more complex and realistic tumor shapes and capillary networks can be studied. Both blood flow through a capillary network, which is induced by a solid tumor, and fluid flow in tumor's surrounding tissue are formulated. First, governing equations of angiogenesis are implemented to specify the different domains for the network and interstitium. Then, governing equations for flow modeling are introduced for different domains. The conservation laws for mass and momentum (including continuity equation, Darcy's law for tissue, and simplified Navier-Stokes equation for blood flow through capillaries) are used for simulating interstitial and intravascular flows and Starling's law is used for closing this system of equations and coupling the intravascular and extravascular flows. This is the first study of flow modeling in solid tumors to naturalistically couple intravascular and extravascular flow through a network. This network is generated by sprouting angiogenesis and consisting of one parent vessel connected to the network while taking into account the non-continuous behavior of blood, adaptability of capillary diameter to hemodynamics and metabolic stimuli, non-Newtonian blood flow, and phase separation of blood flow in capillary bifurcation. The incorporation of the outlined components beyond the previous models provides a more realistic prediction of interstitial fluid flow pattern in solid tumors and surrounding tissues. Results predict higher interstitial pressure, almost two times, for realistic model compared to the simplified model.

  7. Numerical Modeling of Interstitial Fluid Flow Coupled with Blood Flow through a Remodeled Solid Tumor Microvascular Network.

    Directory of Open Access Journals (Sweden)

    M Soltani

    Full Text Available Modeling of interstitial fluid flow involves processes such as fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. To date, majority of microvascular flow modeling has been done at different levels and scales mostly on simple tumor shapes with their capillaries. However, with our proposed numerical model, more complex and realistic tumor shapes and capillary networks can be studied. Both blood flow through a capillary network, which is induced by a solid tumor, and fluid flow in tumor's surrounding tissue are formulated. First, governing equations of angiogenesis are implemented to specify the different domains for the network and interstitium. Then, governing equations for flow modeling are introduced for different domains. The conservation laws for mass and momentum (including continuity equation, Darcy's law for tissue, and simplified Navier-Stokes equation for blood flow through capillaries are used for simulating interstitial and intravascular flows and Starling's law is used for closing this system of equations and coupling the intravascular and extravascular flows. This is the first study of flow modeling in solid tumors to naturalistically couple intravascular and extravascular flow through a network. This network is generated by sprouting angiogenesis and consisting of one parent vessel connected to the network while taking into account the non-continuous behavior of blood, adaptability of capillary diameter to hemodynamics and metabolic stimuli, non-Newtonian blood flow, and phase separation of blood flow in capillary bifurcation. The incorporation of the outlined components beyond the previous models provides a more realistic prediction of interstitial fluid flow pattern in solid tumors and surrounding tissues. Results predict higher interstitial pressure, almost two times, for realistic model compared to the simplified model.

  8. Alerting the immune system via stromal cells is central to the prevention of tumor growth

    DEFF Research Database (Denmark)

    Navikas, Shohreh

    2013-01-01

    Anticancer immunotherapies are highly desired. Conversely, unwanted inflammatory or immune responses contribute to oncogenesis, tumor progression, and cancer-related death. For non-immunogenic therapies to inhibit tumor growth, they must promote, not prevent, the activation of anticancer immune...

  9. Pathway Relevance Ranking for Tumor Samples through Network-Based Data Integration.

    Directory of Open Access Journals (Sweden)

    Lieven P C Verbeke

    Full Text Available The study of cancer, a highly heterogeneous disease with different causes and clinical outcomes, requires a multi-angle approach and the collection of large multi-omics datasets that, ideally, should be analyzed simultaneously. We present a new pathway relevance ranking method that is able to prioritize pathways according to the information contained in any combination of tumor related omics datasets. Key to the method is the conversion of all available data into a single comprehensive network representation containing not only genes but also individual patient samples. Additionally, all data are linked through a network of previously identified molecular interactions. We demonstrate the performance of the new method by applying it to breast and ovarian cancer datasets from The Cancer Genome Atlas. By integrating gene expression, copy number, mutation and methylation data, the method's potential to identify key pathways involved in breast cancer development shared by different molecular subtypes is illustrated. Interestingly, certain pathways were ranked equally important for different subtypes, even when the underlying (epi-genetic disturbances were diverse. Next to prioritizing universally high-scoring pathways, the pathway ranking method was able to identify subtype-specific pathways. Often the score of a pathway could not be motivated by a single mutation, copy number or methylation alteration, but rather by a combination of genetic and epi-genetic disturbances, stressing the need for a network-based data integration approach. The analysis of ovarian tumors, as a function of survival-based subtypes, demonstrated the method's ability to correctly identify key pathways, irrespective of tumor subtype. A differential analysis of survival-based subtypes revealed several pathways with higher importance for the bad-outcome patient group than for the good-outcome patient group. Many of the pathways exhibiting higher importance for the bad

  10. PRIMARY PREVENTION OF MALIGNANT SKIN TUMORS – PHOTOPROTECTION

    Directory of Open Access Journals (Sweden)

    Ana Benedičič - Pilih

    2001-12-01

    Full Text Available Background. The incidence of skin cancer is increasing in the world as well as in our country. Decades of research have increased the understanding of the ethiopathogenetic influences and risk factors for development of malignant skin tumors and stimulated efforts to promote their prevention. There are successes of prevention programs in some places in the world expressing with the reduction of mortality because of the cutaneous malignant melanoma. A primary prevention of a skin cancer attempts to change population knowledge, attitudes and beliefs about sunlight, leading to reduce of sunlight exposure.Conclusions. In this article we are discussing guidelines for photoprevention. The best approach to it is a reduction in the overall exposure to sunlight. The natural protection with the use of shade, clothing and hats is promoted as the best protection. Sunscreens are assumed as an important component of adjuvant photoprotection based on their convenience of use and also on their widespread promotion. While it has been argued that all tanning is a manifestation of skin injury, avoiding of artificial tanning devices is proposed also.

  11. Social network approaches to recruitment, HIV prevention, medical care, and medication adherence

    OpenAIRE

    Latkin, Carl A.; Davey-Rothwell, Melissa A.; Knowlton, Amy R.; Alexander, Kamila A.; Williams, Chyvette T.; Boodram, Basmattee

    2013-01-01

    This article reviews current issues and advancements in social network approaches to HIV prevention and care. Social network analysis can provide a method to understand health disparities in HIV rates and treatment access and outcomes. Social network analysis is a value tool to link social structural factors to individual behaviors. Social networks provide an avenue for low cost and sustainable HIV prevention interventions that can be adapted and translated into diverse populations. Social ne...

  12. Geometrical features assessment of liver's tumor with application of artificial neural network evolved by imperialist competitive algorithm.

    Science.gov (United States)

    Keshavarz, M; Mojra, A

    2015-05-01

    Geometrical features of a cancerous tumor embedded in biological soft tissue, including tumor size and depth, are a necessity in the follow-up procedure and making suitable therapeutic decisions. In this paper, a new socio-politically motivated global search strategy which is called imperialist competitive algorithm (ICA) is implemented to train a feed forward neural network (FFNN) to estimate the tumor's geometrical characteristics (FFNNICA). First, a viscoelastic model of liver tissue is constructed by using a series of in vitro uniaxial and relaxation test data. Then, 163 samples of the tissue including a tumor with different depths and diameters are generated by making use of PYTHON programming to link the ABAQUS and MATLAB together. Next, the samples are divided into 123 samples as training dataset and 40 samples as testing dataset. Training inputs of the network are mechanical parameters extracted from palpation of the tissue through a developing noninvasive technology called artificial tactile sensing (ATS). Last, to evaluate the FFNNICA performance, outputs of the network including tumor's depth and diameter are compared with desired values for both training and testing datasets. Deviations of the outputs from desired values are calculated by a regression analysis. Statistical analysis is also performed by measuring Root Mean Square Error (RMSE) and Efficiency (E). RMSE in diameter and depth estimations are 0.50 mm and 1.49, respectively, for the testing dataset. Results affirm that the proposed optimization algorithm for training neural network can be useful to characterize soft tissue tumors accurately by employing an artificial palpation approach. Copyright © 2015 John Wiley & Sons, Ltd.

  13. Implementation of SNS Model for Intrusion Prevention in Wireless Local Area Network

    DEFF Research Database (Denmark)

    Isah, Abdullahi

    The thesis has proposed and implemented a so-called SNS (Social network security) model for intrusion prevention in the Wireless Local Area Network of an organization. An experimental design was used to implement and test the model at a university in Nigeria.......The thesis has proposed and implemented a so-called SNS (Social network security) model for intrusion prevention in the Wireless Local Area Network of an organization. An experimental design was used to implement and test the model at a university in Nigeria....

  14. Identification of activated enhancers and linked transcription factors in breast, prostate, and kidney tumors by tracing enhancer networks using epigenetic traits.

    Science.gov (United States)

    Rhie, Suhn Kyong; Guo, Yu; Tak, Yu Gyoung; Yao, Lijing; Shen, Hui; Coetzee, Gerhard A; Laird, Peter W; Farnham, Peggy J

    2016-01-01

    Although technological advances now allow increased tumor profiling, a detailed understanding of the mechanisms leading to the development of different cancers remains elusive. Our approach toward understanding the molecular events that lead to cancer is to characterize changes in transcriptional regulatory networks between normal and tumor tissue. Because enhancer activity is thought to be critical in regulating cell fate decisions, we have focused our studies on distal regulatory elements and transcription factors that bind to these elements. Using DNA methylation data, we identified more than 25,000 enhancers that are differentially activated in breast, prostate, and kidney tumor tissues, as compared to normal tissues. We then developed an analytical approach called Tracing Enhancer Networks using Epigenetic Traits that correlates DNA methylation levels at enhancers with gene expression to identify more than 800,000 genome-wide links from enhancers to genes and from genes to enhancers. We found more than 1200 transcription factors to be involved in these tumor-specific enhancer networks. We further characterized several transcription factors linked to a large number of enhancers in each tumor type, including GATA3 in non-basal breast tumors, HOXC6 and DLX1 in prostate tumors, and ZNF395 in kidney tumors. We showed that HOXC6 and DLX1 are associated with different clusters of prostate tumor-specific enhancers and confer distinct transcriptomic changes upon knockdown in C42B prostate cancer cells. We also discovered de novo motifs enriched in enhancers linked to ZNF395 in kidney tumors. Our studies characterized tumor-specific enhancers and revealed key transcription factors involved in enhancer networks for specific tumor types and subgroups. Our findings, which include a large set of identified enhancers and transcription factors linked to those enhancers in breast, prostate, and kidney cancers, will facilitate understanding of enhancer networks and mechanisms

  15. THE TUMOR MACROENVIRONMENT: CANCER-PROMOTING NETWORKS BEYOND TUMOR BEDS

    OpenAIRE

    Rutkowski, Melanie R.; Svoronos, Nikolaos; Puchalt, Alfredo Perales; Conejo-Garcia, Jose R.

    2015-01-01

    During tumor progression, alterations within the systemic tumor environment, or macroenvironment, result in the promotion of tumor growth, tumor invasion to distal organs, and eventual metastatic disease. Distally produced hormones, commensal microbiota residing within mucosal surfaces, and myeloid cells and even the bone marrow impact the systemic immune system, tumor growth, and metastatic spread. Understanding the reciprocal interactions between the cells and soluble factors within the mac...

  16. Support surfaces for pressure ulcer prevention: A network meta-analysis

    Science.gov (United States)

    Dumville, Jo C.; Cullum, Nicky

    2018-01-01

    Background Pressure ulcers are a prevalent and global issue and support surfaces are widely used for preventing ulceration. However, the diversity of available support surfaces and the lack of direct comparisons in RCTs make decision-making difficult. Objectives To determine, using network meta-analysis, the relative effects of different support surfaces in reducing pressure ulcer incidence and comfort and to rank these support surfaces in order of their effectiveness. Methods We conducted a systematic review, using a literature search up to November 2016, to identify randomised trials comparing support surfaces for pressure ulcer prevention. Two reviewers independently performed study selection, risk of bias assessment and data extraction. We grouped the support surfaces according to their characteristics and formed evidence networks using these groups. We used network meta-analysis to estimate the relative effects and effectiveness ranking of the groups for the outcomes of pressure ulcer incidence and participant comfort. GRADE was used to assess the certainty of evidence. Main results We included 65 studies in the review. The network for assessing pressure ulcer incidence comprised evidence of low or very low certainty for most network contrasts. There was moderate-certainty evidence that powered active air surfaces and powered hybrid air surfaces probably reduce pressure ulcer incidence compared with standard hospital surfaces (risk ratios (RR) 0.42, 95% confidence intervals (CI) 0.29 to 0.63; 0.22, 0.07 to 0.66, respectively). The network for comfort suggested that powered active air-surfaces are probably slightly less comfortable than standard hospital mattresses (RR 0.80, 95% CI 0.69 to 0.94; moderate-certainty evidence). Conclusions This is the first network meta-analysis of the effects of support surfaces for pressure ulcer prevention. Powered active air-surfaces probably reduce pressure ulcer incidence, but are probably less comfortable than standard

  17. Support surfaces for pressure ulcer prevention: A network meta-analysis.

    Science.gov (United States)

    Shi, Chunhu; Dumville, Jo C; Cullum, Nicky

    2018-01-01

    Pressure ulcers are a prevalent and global issue and support surfaces are widely used for preventing ulceration. However, the diversity of available support surfaces and the lack of direct comparisons in RCTs make decision-making difficult. To determine, using network meta-analysis, the relative effects of different support surfaces in reducing pressure ulcer incidence and comfort and to rank these support surfaces in order of their effectiveness. We conducted a systematic review, using a literature search up to November 2016, to identify randomised trials comparing support surfaces for pressure ulcer prevention. Two reviewers independently performed study selection, risk of bias assessment and data extraction. We grouped the support surfaces according to their characteristics and formed evidence networks using these groups. We used network meta-analysis to estimate the relative effects and effectiveness ranking of the groups for the outcomes of pressure ulcer incidence and participant comfort. GRADE was used to assess the certainty of evidence. We included 65 studies in the review. The network for assessing pressure ulcer incidence comprised evidence of low or very low certainty for most network contrasts. There was moderate-certainty evidence that powered active air surfaces and powered hybrid air surfaces probably reduce pressure ulcer incidence compared with standard hospital surfaces (risk ratios (RR) 0.42, 95% confidence intervals (CI) 0.29 to 0.63; 0.22, 0.07 to 0.66, respectively). The network for comfort suggested that powered active air-surfaces are probably slightly less comfortable than standard hospital mattresses (RR 0.80, 95% CI 0.69 to 0.94; moderate-certainty evidence). This is the first network meta-analysis of the effects of support surfaces for pressure ulcer prevention. Powered active air-surfaces probably reduce pressure ulcer incidence, but are probably less comfortable than standard hospital surfaces. Most prevention evidence was of low or

  18. Support surfaces for pressure ulcer prevention: A network meta-analysis.

    Directory of Open Access Journals (Sweden)

    Chunhu Shi

    Full Text Available Pressure ulcers are a prevalent and global issue and support surfaces are widely used for preventing ulceration. However, the diversity of available support surfaces and the lack of direct comparisons in RCTs make decision-making difficult.To determine, using network meta-analysis, the relative effects of different support surfaces in reducing pressure ulcer incidence and comfort and to rank these support surfaces in order of their effectiveness.We conducted a systematic review, using a literature search up to November 2016, to identify randomised trials comparing support surfaces for pressure ulcer prevention. Two reviewers independently performed study selection, risk of bias assessment and data extraction. We grouped the support surfaces according to their characteristics and formed evidence networks using these groups. We used network meta-analysis to estimate the relative effects and effectiveness ranking of the groups for the outcomes of pressure ulcer incidence and participant comfort. GRADE was used to assess the certainty of evidence.We included 65 studies in the review. The network for assessing pressure ulcer incidence comprised evidence of low or very low certainty for most network contrasts. There was moderate-certainty evidence that powered active air surfaces and powered hybrid air surfaces probably reduce pressure ulcer incidence compared with standard hospital surfaces (risk ratios (RR 0.42, 95% confidence intervals (CI 0.29 to 0.63; 0.22, 0.07 to 0.66, respectively. The network for comfort suggested that powered active air-surfaces are probably slightly less comfortable than standard hospital mattresses (RR 0.80, 95% CI 0.69 to 0.94; moderate-certainty evidence.This is the first network meta-analysis of the effects of support surfaces for pressure ulcer prevention. Powered active air-surfaces probably reduce pressure ulcer incidence, but are probably less comfortable than standard hospital surfaces. Most prevention evidence was

  19. Effect of fluid friction on interstitial fluid flow coupled with blood flow through solid tumor microvascular network.

    Science.gov (United States)

    Sefidgar, Mostafa; Soltani, M; Raahemifar, Kaamran; Bazmara, Hossein

    2015-01-01

    A solid tumor is investigated as porous media for fluid flow simulation. Most of the studies use Darcy model for porous media. In Darcy model, the fluid friction is neglected and a few simplified assumptions are implemented. In this study, the effect of these assumptions is studied by considering Brinkman model. A multiscale mathematical method which calculates fluid flow to a solid tumor is used in this study to investigate how neglecting fluid friction affects the solid tumor simulation. The mathematical method involves processes such as blood flow through vessels and solute and fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. The sprouting angiogenesis model is used for generating capillary network and then fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network. Finally, the two models of porous media are used for modeling fluid flow in normal and tumor tissues in three different shapes of tumors. Simulations of interstitial fluid transport in a solid tumor demonstrate that the simplifications used in Darcy model affect the interstitial velocity and Brinkman model predicts a lower value for interstitial velocity than the values that Darcy model predicts.

  20. Assessing the efficiency of Mediterranean ditch networks in preventing vineyards soil erosion within landscape

    Science.gov (United States)

    Levavasseur, Florent; Bailly, Jean-Stéphane; Lagacherie, Philippe

    2013-04-01

    Water erosion of cultivated soils is a threat to the sustainability of agriculture, especially in Mediterranean areas. For a long time, Mediterranean farmers have thus adopted some soil conservation practices. Actual ditch networks, which are generally associated with terraces, result from historical successive farmer settlements and are one of these soil conservation practices. By intercepting surface run-off, ditches decrease slope length and prevent soil erosion on downstream plots. However, since water erosion hazard and ditch network geometries are highly variable in vineyards landscape and since ditch building and maintaining are costly, the objective of this study was to identify and map the resulting efficiency of ditch networks in preventing soil erosion. For a given area, a ditch network efficiency is defined here as the balance between the network density, i.e. network cumulated length for a given area unit, and the erosion sensitivity over an area which measures the performance of the ditch network in limiting soil erosion. The erosion efficiency of ditch networks was thus identified using both i) computer generated ditch networks with various spatial configurations and ii) the stream power index as an erosion sensitivity indicator, computed from a DTM in which each ditch network was burned. The stream power index of the actual networks were compared with a set of generated networks whose density and topology were selected to maximize the performance in preventing soil erosion thanks to the use of a self-developed optimized stochastic network generator. For four 1 km² hillslopes, we showed that the performances of actual networks to prevent soil erosion was among the best that were obtained by simulated networks with even greater densities. Furthermore, we showed that the stream power index values that accounted for the actual ditch networks to prevent soil erosion hazard was both minimal and weakly variable in the whole study area (30 km²) at

  1. Nationwide SIP Telephony Network Design to Prevent Congestion Caused by Disaster

    Science.gov (United States)

    Satoh, Daisuke; Ashitagawa, Kyoko

    We present a session initiation protocol (SIP) network design for a voice-over-IP network to prevent congestion caused by people calling friends and family after a disaster. The design increases the capacity of SIP servers in a network by using all of the SIP servers equally. It takes advantage of the fact that equipment for voice data packets is different from equipment for signaling packets in SIP networks. Furthermore, the design achieves simple routing on the basis of telephone numbers. We evaluated the performance of our design in preventing congestion through simulation. We showed that the proposed design has roughly 20 times more capacity, which is 57 times the normal load, than the conventional design if a disaster were to occur in Niigata Prefecture struck by the Chuetsu earthquake in 2004.

  2. Effect of Chemical Prevention Drugs-based MicroRNAs and Their Target Genes 
on Tumor Inhibition

    Directory of Open Access Journals (Sweden)

    Yanhui JIANG

    2015-04-01

    Full Text Available Chemopreventive drugs including natural chemopreventive drugs and synthetic chemopreventive drugs, it not only can prevent cancer, can also play a role in tumor treatment. MicroRNAs (miRNAs is a kind of short chains of non-coding RNA, regulating the expression of many genes through the way of degradation of mRNA or inhibitting mRNA translation. In recent years, more and more studies have shown that chemopreventive drugs through influence the expression of miRNAs and their target genes play a role in the prevention and treatment in a variety of tumors, and chemopreventive drugs on the experimental study of miRNAs and their target genes in tumor have demonstrated a good safety and efficacy. Effect on chemopreventive drugs-based microRNAs and their target genes into cancer cells will be expected as a new starting point for cancer research. The thesis expounds and analyzes between the natural chemopreventive drugs and synthetic chemopreventive drugs and miRNAs and their target genes in tumor research progress.

  3. [Evaluation of knowledge about colon cancer prevention versus other tumors].

    Science.gov (United States)

    Sanguinetti, José María; Henry, Nicolás; Ocaña, Domingo; Polesel, Julio Lotero

    2015-06-01

    In Argentina almost 7% of deaths are due to different cancers with screening strategies. Evaluate knowledge about cancer prevention compared with other tumors. Materials. A descriptive and comparative study. A survey between April and June 2013 in Salta City, province of Salta, Argentina. Correct answers were considered. Statistical analysis: Descriptive (mean and percentage), comparative Chi square Test (significance level Pmama and cervix. 20% (CI 0,13-0,28) knew that colon cancer has a genetic predisposition and 58% (CI 0,48-0,67) about mama. 73% (CI 0,63-0,8) received information about cancer prevention. The main source of information was the physician. 46% (CI 0,36-0,55) received medical care in private institutions. Those who had social security, higher educational levels and medical care in private institutions had better knowledge about cancer prevention except in colon cancer. The global results showed levels below 70% in general but extremely low in colon cancer. Not having social security, receiving medical care in public institutions and having a low educational level are related with poor knowledge about cancer prevention except for colon and prostate cancer.

  4. Method of image segmentation using a neural network. Application to MR imaging of brain tumors

    International Nuclear Information System (INIS)

    Engler, E.; Gautherie, M.

    1992-01-01

    An original method of numerical images segmentation has been developed. This method is based on pixel clustering using a formal neural network configurated by supervised learning of pre-classified examples. The method has been applied to series of MR images of brain tumors (gliomas) with a view to proceed with a 3D-extraction of the tumor volume. This study is part of a project on cancer thermotherapy including the development of a scan-focused ultrasound system of tumor heating and a 3D-numerical thermal model

  5. Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as tumor suppressor in T-ALL.

    Science.gov (United States)

    Della Gatta, Giusy; Palomero, Teresa; Perez-Garcia, Arianne; Ambesi-Impiombato, Alberto; Bansal, Mukesh; Carpenter, Zachary W; De Keersmaecker, Kim; Sole, Xavier; Xu, Luyao; Paietta, Elisabeth; Racevskis, Janis; Wiernik, Peter H; Rowe, Jacob M; Meijerink, Jules P; Califano, Andrea; Ferrando, Adolfo A

    2012-02-26

    The TLX1 and TLX3 transcription factor oncogenes have a key role in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). Here we used reverse engineering of global transcriptional networks to decipher the oncogenic regulatory circuit controlled by TLX1 and TLX3. This systems biology analysis defined T cell leukemia homeobox 1 (TLX1) and TLX3 as master regulators of an oncogenic transcriptional circuit governing T-ALL. Notably, a network structure analysis of this hierarchical network identified RUNX1 as a key mediator of the T-ALL induced by TLX1 and TLX3 and predicted a tumor-suppressor role for RUNX1 in T cell transformation. Consistent with these results, we identified recurrent somatic loss-of-function mutations in RUNX1 in human T-ALL. Overall, these results place TLX1 and TLX3 at the top of an oncogenic transcriptional network controlling leukemia development, show the power of network analyses to identify key elements in the regulatory circuits governing human cancer and identify RUNX1 as a tumor-suppressor gene in T-ALL.

  6. Malware Propagation and Prevention Model for Time-Varying Community Networks within Software Defined Networks

    Directory of Open Access Journals (Sweden)

    Lan Liu

    2017-01-01

    Full Text Available As the adoption of Software Defined Networks (SDNs grows, the security of SDN still has several unaddressed limitations. A key network security research area is in the study of malware propagation across the SDN-enabled networks. To analyze the spreading processes of network malware (e.g., viruses in SDN, we propose a dynamic model with a time-varying community network, inspired by research models on the spread of epidemics in complex networks across communities. We assume subnets of the network as communities and links that are dense in subnets but sparse between subnets. Using numerical simulation and theoretical analysis, we find that the efficiency of network malware propagation in this model depends on the mobility rate q of the nodes between subnets. We also find that there exists a mobility rate threshold qc. The network malware will spread in the SDN when the mobility rate q>qc. The malware will survive when q>qc and perish when qnetwork malware and provide a theoretical basis to reduce and prevent network security incidents.

  7. Perception of adult men on their preventive practices and health support networks

    Directory of Open Access Journals (Sweden)

    Guilherme Oliveira de Arruda

    2015-07-01

    Full Text Available Objectives: to know the preventive practices adopted by adult men in daily life and to identify health support networks. Methods: a descriptive qualitative study, made during the months of November and December 2012, at two emergency units, along with 32 men aged between 20 and 59 years. Data were collected through semi-structured interviews and subjected to content analysis with thematic modality. Results: men highlighted different preventive practices such as sanitizing hands, eating properly, having screening tests, avoiding psychoactive substance abuse, using personal protective equipment at work and condoms during sex. Most of the participants had nuclear family and its members were their primary support network regarding the health-disease process. Conclusion: it is for health team members to try to leverage the adoption of preventive practices by adult men from the support networks they consider significant.

  8. Technologies, Methodologies and Challenges in Network Intrusion Detection and Prevention Systems

    Directory of Open Access Journals (Sweden)

    Nicoleta STANCIU

    2013-01-01

    Full Text Available This paper presents an overview of the technologies and the methodologies used in Network Intrusion Detection and Prevention Systems (NIDPS. Intrusion Detection and Prevention System (IDPS technologies are differentiated by types of events that IDPSs can recognize, by types of devices that IDPSs monitor and by activity. NIDPSs monitor and analyze the streams of network packets in order to detect security incidents. The main methodology used by NIDPSs is protocol analysis. Protocol analysis requires good knowledge of the theory of the main protocols, their definition, how each protocol works.

  9. [Computer aided diagnosis model for lung tumor based on ensemble convolutional neural network].

    Science.gov (United States)

    Wang, Yuanyuan; Zhou, Tao; Lu, Huiling; Wu, Cuiying; Yang, Pengfei

    2017-08-01

    The convolutional neural network (CNN) could be used on computer-aided diagnosis of lung tumor with positron emission tomography (PET)/computed tomography (CT), which can provide accurate quantitative analysis to compensate for visual inertia and defects in gray-scale sensitivity, and help doctors diagnose accurately. Firstly, parameter migration method is used to build three CNNs (CT-CNN, PET-CNN, and PET/CT-CNN) for lung tumor recognition in CT, PET, and PET/CT image, respectively. Then, we aimed at CT-CNN to obtain the appropriate model parameters for CNN training through analysis the influence of model parameters such as epochs, batchsize and image scale on recognition rate and training time. Finally, three single CNNs are used to construct ensemble CNN, and then lung tumor PET/CT recognition was completed through relative majority vote method and the performance between ensemble CNN and single CNN was compared. The experiment results show that the ensemble CNN is better than single CNN on computer-aided diagnosis of lung tumor.

  10. Prevention of Human Lymphoproliferative Tumor Formation in Ovarian Cancer Patient-Derived Xenografts

    Directory of Open Access Journals (Sweden)

    Kristina A. Butler

    2017-08-01

    Full Text Available Interest in preclinical drug development for ovarian cancer has stimulated development of patient-derived xenograft (PDX or tumorgraft models. However, the unintended formation of human lymphoma in severe combined immunodeficiency (SCID mice from Epstein-Barr virus (EBV–infected human lymphocytes can be problematic. In this study, we have characterized ovarian cancer PDXs which developed human lymphomas and explore methods to suppress lymphoproliferative growth. Fresh human ovarian tumors from 568 patients were transplanted intraperitoneally in SCID mice. A subset of PDX models demonstrated atypical patterns of dissemination with mediastinal masses, hepatosplenomegaly, and CD45-positive lymphoblastic atypia without ovarian tumor engraftment. Expression of human CD20 but not CD3 supported a B-cell lineage, and EBV genomes were detected in all lymphoproliferative tumors. Immunophenotyping confirmed monoclonal gene rearrangements consistent with B-cell lymphoma, and global gene expression patterns correlated well with other human lymphomas. The ability of rituximab, an anti-CD20 antibody, to suppress human lymphoproliferation from a patient's ovarian tumor in SCID mice and prevent growth of an established lymphoma led to a practice change with a goal to reduce the incidence of lymphomas. A single dose of rituximab during the primary tumor heterotransplantation process reduced the incidence of CD45-positive cells in subsequent PDX lines from 86.3% (n = 117 without rituximab to 5.6% (n = 160 with rituximab, and the lymphoma rate declined from 11.1% to 1.88%. Taken together, investigators utilizing PDX models for research should routinely monitor for lymphoproliferative tumors and consider implementing methods to suppress their growth.

  11. [Cellular adhesion signal transduction network of tumor necrosis factor-alpha induced hepatocellular carcinoma cells].

    Science.gov (United States)

    Zheng, Yongchang; Du, Shunda; Xu, Haifeng; Xu, Yiyao; Zhao, Haitao; Chi, Tianyi; Lu, Xin; Sang, Xinting; Mao, Yilei

    2014-11-18

    To systemically explore the cellular adhesion signal transduction network of tumor necrosis factor-alpha (TNF-α)-induced hepatocellular carcinoma cells with bioinformatics tools. Published microarray dataset of TNF-α-induced HepG2, human transcription factor database HTRI and human protein-protein interaction database HPRD were used to construct and analyze the signal transduction network. In the signal transduction network, MYC and SP1 were the key nodes of signaling transduction. Several genes from the network were closely related with cellular adhesion.Epidermal growth factor receptor (EGFR) is a possible key gene of effectively regulating cellular adhesion during the induction of TNF-α. EGFR is a possible key gene for TNF-α-induced metastasis of hepatocellular carcinoma.

  12. Optimal information dissemination strategy to promote preventive behaviors in multilayer epidemic networks.

    Science.gov (United States)

    Shakeri, Heman; Sahneh, Faryad Darabi; Scoglio, Caterina; Poggi-Corradini, Pietro; Preciado, Victor M

    2015-06-01

    Launching a prevention campaign to contain the spread of infection requires substantial financial investments; therefore, a trade-off exists between suppressing the epidemic and containing costs. Information exchange among individuals can occur as physical contacts (e.g., word of mouth, gatherings), which provide inherent possibilities of disease transmission, and non-physical contacts (e.g., email, social networks), through which information can be transmitted but the infection cannot be transmitted. Contact network (CN) incorporates physical contacts, and the information dissemination network (IDN) represents non-physical contacts, thereby generating a multilayer network structure. Inherent differences between these two layers cause alerting through CN to be more effective but more expensive than IDN. The constraint for an epidemic to die out derived from a nonlinear Perron-Frobenius problem that was transformed into a semi-definite matrix inequality and served as a constraint for a convex optimization problem. This method guarantees a dying-out epidemic by choosing the best nodes for adopting preventive behaviors with minimum monetary resources. Various numerical simulations with network models and a real-world social network validate our method.

  13. Preventing lower cranial nerve injuries during fourth ventricle tumor resection by utilizing intraoperative neurophysiological monitoring.

    Science.gov (United States)

    Jahangiri, Faisal R; Minhas, Mazhar; Jane, John

    2012-12-01

    We present two cases illustrating the benefit of utilizing intraoperative neurophysiological monitoring (IONM) for prevention of injuries to the lower cranial nerves during fourth ventricle tumor resection surgeries. Multiple cranial nerve nuclei are located on the floor of the fourth ventricle with a high risk of permanent damage. Two male patients (ages 8 and 10 years) presented to the emergency department and had brain magnetic resonance imaging (MRI) scans showing brainstem/fourth ventricle tumors. During surgery, bilateral posterior tibial and median nerve somatosensory evoked potentials (SSEPs); four-limb and cranial nerves transcranial electrical motor evoked potentials (TCeMEPs); brainstem auditory evoked responses (BAERs); and spontaneous electromyography (s-EMG) were recorded. Electromyography (EMG) was monitored bilaterally from cranial nerves V VII, IX, X, XI, and XII. Total intravenous anesthesia was used. Neuromuscular blockade was used only for initial intubation. Pre-incision baselines were obtained with good morphology of waveforms. After exposure the floor of the fourth ventricle was mapped by triggered-EMG (t-EMG) using 0.4 to 1.0 mA. In both patients the tumor was entangled with cranial nerves VII to XII on the floor of the fourth ventricle. The surgeon made the decision not to resect the tumor in one case and limited the resection to 70% of the tumor in the second case on the basis of neurophysiological monitoring. This decision was made to minimize any post-operative neurological deficits due to surgical manipulation of the tumor involving the lower cranial nerves. Intraoperative spontaneous and triggered EMG was effectively utilized in preventing injuries to cranial nerves during surgical procedures. All signals remained stable during the surgical procedure. Postoperatively both patients were well with no additional cranial nerve weakness. At three months follow-up, the patients continued to have no deficits.

  14. Design of Detection and Prevention System of Unauthorized Data Sending from the Local Network

    Directory of Open Access Journals (Sweden)

    D. A. Moskvin

    2010-03-01

    Full Text Available Malware often aims at breaking confidentiality. A malicious program gets inside the local network, finds out necessary data and then illegally transfers this data to the intruder. Prevention of unauthorized data transfer requires development of a special software product, which will detect and prevent leak of information from the local network.

  15. The Rare Cancer Network: ongoing studies and future strategy

    Directory of Open Access Journals (Sweden)

    Mahmut Ozsahin

    2014-08-01

    Full Text Available The Rare Cancer Network (RCN was formed in the early 1990’s to create a global network that could pool knowledge and resources in the studies of rare malignancies whose infrequency prevented both their study with prospective clinical trials. To date, the RCN has initiated 74 studies resulting in 46 peer reviewed publications. The First International Symposium of the Rare Cancer Network took place in Nice in March of 2014. Status updates and proposals for new studies were heard for fifteen topics. Ongoing studies continue for cardiac sarcomas, thyroid cancers, glomus tumors, and adult medulloblastomas. New proposals were presented at the symposium for primary hepatic lymphoma, solitary fibrous tumors, Rosai-Dorfman disease, tumors of the ampulla of Vater, salivary gland tumors, anorectal melanoma, midline nuclear protein in testes carcinoma, pulmonary lymphoepithelioma-like carcinoma, adenoid cystic carcinoma of the trachea, osteosarcomas of the mandible, and extra-cranial hemangiopericytoma. This manuscript presents the abstracts of those proposals and updates on ongoing studies, as well a brief summary of the vision and future of the RCN.

  16. Emergence of Convolutional Neural Network in Future Medicine: Why and How. A Review on Brain Tumor Segmentation

    Science.gov (United States)

    Alizadeh Savareh, Behrouz; Emami, Hassan; Hajiabadi, Mohamadreza; Ghafoori, Mahyar; Majid Azimi, Seyed

    2018-03-01

    Manual analysis of brain tumors magnetic resonance images is usually accompanied by some problem. Several techniques have been proposed for the brain tumor segmentation. This study will be focused on searching popular databases for related studies, theoretical and practical aspects of Convolutional Neural Network surveyed in brain tumor segmentation. Based on our findings, details about related studies including the datasets used, evaluation parameters, preferred architectures and complementary steps analyzed. Deep learning as a revolutionary idea in image processing, achieved brilliant results in brain tumor segmentation too. This can be continuing until the next revolutionary idea emerging.

  17. Digital mammographic tumor classification using transfer learning from deep convolutional neural networks.

    Science.gov (United States)

    Huynh, Benjamin Q; Li, Hui; Giger, Maryellen L

    2016-07-01

    Convolutional neural networks (CNNs) show potential for computer-aided diagnosis (CADx) by learning features directly from the image data instead of using analytically extracted features. However, CNNs are difficult to train from scratch for medical images due to small sample sizes and variations in tumor presentations. Instead, transfer learning can be used to extract tumor information from medical images via CNNs originally pretrained for nonmedical tasks, alleviating the need for large datasets. Our database includes 219 breast lesions (607 full-field digital mammographic images). We compared support vector machine classifiers based on the CNN-extracted image features and our prior computer-extracted tumor features in the task of distinguishing between benign and malignant breast lesions. Five-fold cross validation (by lesion) was conducted with the area under the receiver operating characteristic (ROC) curve as the performance metric. Results show that classifiers based on CNN-extracted features (with transfer learning) perform comparably to those using analytically extracted features [area under the ROC curve [Formula: see text

  18. Identification of networks of co-occurring, tumor-related DNA copy number changes using a genome-wide scoring approach.

    Directory of Open Access Journals (Sweden)

    Christiaan Klijn

    2010-01-01

    Full Text Available Tumorigenesis is a multi-step process in which normal cells transform into malignant tumors following the accumulation of genetic mutations that enable them to evade the growth control checkpoints that would normally suppress their growth or result in apoptosis. It is therefore important to identify those combinations of mutations that collaborate in cancer development and progression. DNA copy number alterations (CNAs are one of the ways in which cancer genes are deregulated in tumor cells. We hypothesized that synergistic interactions between cancer genes might be identified by looking for regions of co-occurring gain and/or loss. To this end we developed a scoring framework to separate truly co-occurring aberrations from passenger mutations and dominant single signals present in the data. The resulting regions of high co-occurrence can be investigated for between-region functional interactions. Analysis of high-resolution DNA copy number data from a panel of 95 hematological tumor cell lines correctly identified co-occurring recombinations at the T-cell receptor and immunoglobulin loci in T- and B-cell malignancies, respectively, showing that we can recover truly co-occurring genomic alterations. In addition, our analysis revealed networks of co-occurring genomic losses and gains that are enriched for cancer genes. These networks are also highly enriched for functional relationships between genes. We further examine sub-networks of these networks, core networks, which contain many known cancer genes. The core network for co-occurring DNA losses we find seems to be independent of the canonical cancer genes within the network. Our findings suggest that large-scale, low-intensity copy number alterations may be an important feature of cancer development or maintenance by affecting gene dosage of a large interconnected network of functionally related genes.

  19. Adaptive Suspicious Prevention for Defending DoS Attacks in SDN-Based Convergent Networks.

    Science.gov (United States)

    Dao, Nhu-Ngoc; Kim, Joongheon; Park, Minho; Cho, Sungrae

    2016-01-01

    The convergent communication network will play an important role as a single platform to unify heterogeneous networks and integrate emerging technologies and existing legacy networks. Although there have been proposed many feasible solutions, they could not become convergent frameworks since they mainly focused on converting functions between various protocols and interfaces in edge networks, and handling functions for multiple services in core networks, e.g., the Multi-protocol Label Switching (MPLS) technique. Software-defined networking (SDN), on the other hand, is expected to be the ideal future for the convergent network since it can provide a controllable, dynamic, and cost-effective network. However, SDN has an original structural vulnerability behind a lot of advantages, which is the centralized control plane. As the brains of the network, a controller manages the whole network, which is attractive to attackers. In this context, we proposes a novel solution called adaptive suspicious prevention (ASP) mechanism to protect the controller from the Denial of Service (DoS) attacks that could incapacitate an SDN. The ASP is integrated with OpenFlow protocol to detect and prevent DoS attacks effectively. Our comprehensive experimental results show that the ASP enhances the resilience of an SDN network against DoS attacks by up to 38%.

  20. Celebrating 25 Years. National Dropout Prevention Center/Network Newsletter. Volume 22, Number 3

    Science.gov (United States)

    Duckenfield, Marty, Ed.

    2011-01-01

    The "National Dropout Prevention Newsletter" is published quarterly by the National Dropout Prevention Center/Network. This issue contains the following articles: (1) Leading the Way in Dropout Prevention; (2) The 15 Effective Strategies in Action; (3) Technology Changes 1986-2011 (Marty Duckenfield); (4) 25 Years of Research and Support…

  1. INTRUSION DETECTION PREVENTION SYSTEM (IDPS PADA LOCAL AREA NETWORK (LAN

    Directory of Open Access Journals (Sweden)

    Didit Suhartono

    2015-02-01

    Full Text Available Penelitian ini berjudul “Intrusion Detection Prevention System Local Area Network (LAN” yang bertujuan untuk memproteksi jaringan dari usaha- usaha penyusupan yang dilakukan oleh seorang intruder. Metode yang digunakan pada penelitian ini adalah menggunakan metode kerangka pikir sebagai acuan dari tahap- tahap penelitian yang penulis lakukan. IDS difungsikan sebagai pendeteksi adanya serangan sesuai rule yang ada kemudian pesan peringatan disimpan dalam database dan dikirim via sms kepada seorang network administrator, sedangkan Firewall digunakan sebagai packet filtering dengan cara menentukan security policy yang dinilai penting. Hasilnya adalah ketika IDS memberikanpesan peringatan ketika ada serangan, seorang network administrator dapat memblok adanya serangan tersebut dengan cara manual dengan firewall, ataupun firewall akan memblok sendiri serangan tersebut sesuai dengan security policy yang diterapkan oleh network adminisrator sebelumnya

  2. Service-Learning. National Dropout Prevention Center/Network Newsletter. Volume 22, Number 4

    Science.gov (United States)

    Duckenfield, Marty, Ed.

    2011-01-01

    The "National Dropout Prevention Newsletter" is published quarterly by the National Dropout Prevention Center/Network. This issue contains the following articles: (1) Dropouts and Democracy (Robert Shumer); (2) 2011 NDPN Crystal Star Winners; (3) Service-Learning as Dropout Intervention and More (Michael VanKeulen); and (4) Teacher…

  3. Using Social Network Theory to Influence the Development of State and Local Primary Prevention Capacity-Building Teams

    Science.gov (United States)

    Cook-Craig, Patricia G.

    2010-01-01

    This article examines the role that social network theory and social network analysis has played in assessing and developing effective primary prevention networks across a southeastern state. In 2004 the state began an effort to develop a strategic plan for the primary prevention of violence working with local communities across the state. The…

  4. Volumetric multimodality neural network for brain tumor segmentation

    Science.gov (United States)

    Silvana Castillo, Laura; Alexandra Daza, Laura; Carlos Rivera, Luis; Arbeláez, Pablo

    2017-11-01

    Brain lesion segmentation is one of the hardest tasks to be solved in computer vision with an emphasis on the medical field. We present a convolutional neural network that produces a semantic segmentation of brain tumors, capable of processing volumetric data along with information from multiple MRI modalities at the same time. This results in the ability to learn from small training datasets and highly imbalanced data. Our method is based on DeepMedic, the state of the art in brain lesion segmentation. We develop a new architecture with more convolutional layers, organized in three parallel pathways with different input resolution, and additional fully connected layers. We tested our method over the 2015 BraTS Challenge dataset, reaching an average dice coefficient of 84%, while the standard DeepMedic implementation reached 74%.

  5. [Social network analysis of interdisciplinary cooperation and networking in early prevention and intervention. A pilot study].

    Science.gov (United States)

    Künster, A K; Knorr, C; Fegert, J M; Ziegenhain, U

    2010-11-01

    Child protection can only be successfully solved by interdisciplinary cooperation and networking. The individual, heterogeneous, and complex needs of families cannot be met sufficiently by one profession alone. To guarantee efficient interdisciplinary cooperation, there should not be any gaps in the network. In addition, each actor in the network should be placed at an optimal position regarding function, responsibilities, and skills. Actors that serve as allocators, such as pediatricians or youth welfare officers, should be in key player positions within the network. Furthermore, successful child protection is preventive and starts early. Social network analysis is an adequate technique to assess network structures and to plan interventions to improve networking. In addition, it is very useful to evaluate the effectiveness of interventions like round tables. We present data from our pilot project which was part of "Guter Start ins Kinderleben" ("a good start into a child's life"). Exemplary network data from one community show that networking is already quite effective with a satisfactory mean density throughout the network. There is potential for improvement in cooperation, especially at the interface between the child welfare and health systems.

  6. Towards software-based signature detection for intrusion prevention on the network card

    NARCIS (Netherlands)

    Bos, H.; Huang, Kaiming

    2006-01-01

    CardGuard is a signature detection system for intrusion detection and prevention that scans the entire payload of packets for suspicious patterns and is implemented in software on a network card equiped with an Intel IXP1200 network processor. One card can be used to protect either a single host, or

  7. Creatine supplementation prevents hyperhomocysteinemia, oxidative stress and cancer-induced cachexia progression in Walker-256 tumor-bearing rats.

    Science.gov (United States)

    Deminice, Rafael; Cella, Paola Sanches; Padilha, Camila S; Borges, Fernando H; da Silva, Lilian Eslaine Costa Mendes; Campos-Ferraz, Patrícia L; Jordao, Alceu Afonso; Robinson, Jason Lorne; Bertolo, Robert F; Cecchini, Rubens; Guarnier, Flávia Alessandra

    2016-08-01

    The purpose of this study was to investigate (1) the impact of tumor growth on homocysteine (Hcy) metabolism, liver oxidative stress and cancer cachexia and, (2) the potential benefits of creatine supplementation in Walker-256 tumor-bearing rats. Three experiments were conducted. First, rats were killed on days 5 (D5), 10 (D10) and 14 (D14) after tumor implantation. In experiment 2, rats were randomly assigned to three groups designated as control (C), tumor-bearing (T) and tumor-bearing supplemented with creatine (TCr). A life span experiment was conducted as the third experiment. Creatine was supplied in drinking water for 21 days (8 g/L) in all cases. Tumor implantation consisted of a suspension of Walker-256 cells (8.0 × 10(7) cells in 0.5 mL of PBS). The progressive increase (P creatine supplementation promoted a 28 % reduction of tumor weight (P Creatine supplementation was unable to decrease Hcy concentration and to increase SAM/SAH ratio in tumor tissue. These data suggest that creatine effects on hepatic impaired Hcy metabolism promoted by tumor cell inoculation are responsible to decrease plasma Hcy in tumor-bearing rats. In conclusion, Walker-256 tumor growth is associated with progressive hyperhomocysteinemia, body weight loss and liver oxidative stress in rats. Creatine supplementation, however, prevented these tumor-associated perturbations.

  8. Percutaneous transfemoral placement of inferior vena cava filter to prevent pulmonary embolism in patients with malignant tumor

    International Nuclear Information System (INIS)

    Hu Baoshan; Li Yong; Luo Pengfei

    2005-01-01

    Objective: To evaluate the effectiveness and safety of inserting an inferior vena cava filter to prevent the pulmonary embolism (PE) due to detachment of the thrombus in the lower extremities. Methods: Inferior vena cava filter were placed in 37 patients with malignant tumor and deep venous thrombosis from 1998 to 2004. Malignancy was confirmed by pathological or cellular biological examination in all cases. The episode of pulmonary embolism was monitored during a post-intervention follow-up. Results: All the filters were placed in the inferior vena cava safely via a percutaneous femoral venous access. No serious complications such as pulmonary embolism occurred during the follow-up periods. Conclusion: The inferior vena cava filter placement is an effective and safe procedure in preventing the pulmonary embolism in patients with malignant tumor and deep venous thrombosis. (authors)

  9. Ethanol exposure induces the cancer-associated fibroblast phenotype and lethal tumor metabolism: implications for breast cancer prevention.

    Science.gov (United States)

    Sanchez-Alvarez, Rosa; Martinez-Outschoorn, Ubaldo E; Lin, Zhao; Lamb, Rebecca; Hulit, James; Howell, Anthony; Sotgia, Federica; Rubin, Emanuel; Lisanti, Michael P

    2013-01-15

    Little is known about how alcohol consumption promotes the onset of human breast cancer(s). One hypothesis is that ethanol induces metabolic changes in the tumor microenvironment, which then enhances epithelial tumor growth. To experimentally test this hypothesis, we used a co-culture system consisting of human breast cancer cells (MCF7) and hTERT-immortalized fibroblasts. Here, we show that ethanol treatment (100 mM) promotes ROS production and oxidative stress in cancer-associated fibroblasts, which is sufficient to induce myofibroblastic differentiation. Oxidative stress in stromal fibroblasts also results in the onset of autophagy/mitophagy, driving the induction of ketone body production in the tumor microenvironment. Interestingly, ethanol has just the opposite effect in epithelial cancer cells, where it confers autophagy resistance, elevates mitochondrial biogenesis and induces key enzymes associated with ketone re-utilization (ACAT1/OXCT1). During co-culture, ethanol treatment also converts MCF7 cells from an ER(+) to an ER(-) status, which is thought to be associated with "stemness," more aggressive behavior and a worse prognosis. Thus, ethanol treatment induces ketone production in cancer-associated fibroblasts and ketone re-utilization in epithelial cancer cells, fueling tumor cell growth via oxidative mitochondrial metabolism (OXPHOS). This "two-compartment" metabolic model is consistent with previous historical observations that ethanol is first converted to acetaldehyde (which induces oxidative stress) and then ultimately to acetyl-CoA (a high-energy mitochondrial fuel), or can be used to synthesize ketone bodies. As such, our results provide a novel mechanism by which alcohol consumption could metabolically convert "low-risk" breast cancer patients to "high-risk" status, explaining tumor recurrence or disease progression. Hence, our findings have clear implications for both breast cancer prevention and therapy. Remarkably, our results also show that

  10. A new method for brain tumor detection using the Bhattacharyya similarity coefficient, color conversions and neural network

    Directory of Open Access Journals (Sweden)

    Bahman Mansori

    2015-10-01

    Full Text Available Background: Magnetic resonance imaging (MRI is widely applied for examination and diagnosis of brain tumors based on its advantages of high resolution in detecting the soft tissues and especially of its harmless radiation damages to human bodies. The goal of the processing of images is automatic segmentation of brain edema and tumors, in different dimensions of the magnetic resonance images. Methods: The proposed method is based on the unsupervised method which discovers the tumor region, if there is any, by analyzing the similarities between two hemispheres and computes the image size of the goal function based on Bhattacharyya coefficient which is used in the next stage to detect the tumor region or some part of it. In this stage, for reducing the color variation, the gray brain image is segmented, then it is turned to gray again. The self-organizing map (SOM neural network is used the segmented brain image is colored and finally the tumor is detected by matching the detected region and the colored image. This method is proposed to analyze MRI images for discovering brain tumors, and done in Bu Ali Sina University, Hamedan, Iran, in 2014. Results: The results for 30 randomly selected images from data bank of MRI center in Hamedan was compared with manually segmentation of experts. The results showed that, our proposed method had the accuracy of more than 94% at Jaccard similarity index (JSI, 97% at Dice similarity score (DSS, and 98% and 99% at two measures of specificity and sensitivity. Conclusion: The experimental results showed that it was satisfactory and can be used in automatic separation of tumor from normal brain tissues and therefore it can be used in practical applications. The results showed that the use of SOM neural network to classify useful magnetic resonance imaging of the brain and demonstrated a good performance.

  11. TanZamBo Capacity Building for HIV Prevention Research Network ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    This grant will support the development of HIV/AIDS prevention trial expertise in Botswana, Tanzania and Zambia using existing collaborations between Africa, Canada and the United States. The Botswana-Tanzania-Zambia Capacity Building Network (TanZamBo) is composed of two African institutions with fairly well ...

  12. Social influence and bullying behavior: intervention-based network dynamics of the fairplayer.manual bullying prevention program.

    Science.gov (United States)

    Wölfer, Ralf; Scheithauer, Herbert

    2014-01-01

    Bullying is a social phenomenon and although preventive interventions consequently address social mechanisms, evaluations hardly consider the complexity of peer processes. Therefore, the present study analyzes the efficacy of the fairplayer.manual bullying prevention program from a social network perspective. Within a pretest-posttest control group design, longitudinal data were available from 328 middle-school students (MAge  = 13.7 years; 51% girls), who provided information on bullying behavior and interaction patterns. The revealed network parameters were utilized to examine the network change (MANCOVA) and the network dynamics (SIENA). Across both forms of analyses, findings revealed the hypothesized intervention-based decrease of bullies' social influence. Hence the present bullying prevention program, as one example of programs that successfully addresses both individual skills and social mechanisms, demonstrates the desired effect of reducing contextual opportunities for the exhibition of bullying behavior. © 2014 Wiley Periodicals, Inc.

  13. Effectiveness of school network for childhood obesity prevention (SNOCOP) in primary schools of Saraburi Province, Thailand.

    Science.gov (United States)

    Banchonhattakit, Pannee; Tanasugarn, Chanuantong; Pradipasen, Mandhana; Miner, Kathleen R; Nityasuddhi, Dechavudh

    2009-07-01

    This research was designed to test the effectiveness of a school network for childhood obesity prevention (SNOCOP) in primary schools; a program that aimed to improve student behavior in terms of knowledge, attitude, intention towards obesity prevention, and their food consumption behavior. A quasi-experimental pretest-posttest time series study was conducted. By 2-stage stratified sampling selection 180 students from 6 schools were assigned to the intervention group and 195 students from 6 schools to the control group at Saraburi Province, Thailand in 2006- 2007. In addition, thirty-one participants being school administrators, teachers, parents, and community members from six schools formed the social network initiating the intervention. The schoolchildren in the intervention group improved their eating behavior, knowledge, attitude, intention towards obesity preventive behavior. The six schools of the intervention group changed school policies and school activities aiming to reduce the proportion of obesity among their student. No such activities could be observed in the control group. These findings suggest that the School-Social Network of Childhood Obesity Prevention program is an effective means to prevent childhood obesity.

  14. A model for cell migration in non-isotropic fibrin networks with an application to pancreatic tumor islets.

    Science.gov (United States)

    Chen, Jiao; Weihs, Daphne; Vermolen, Fred J

    2018-04-01

    Cell migration, known as an orchestrated movement of cells, is crucially important for wound healing, tumor growth, immune response as well as other biomedical processes. This paper presents a cell-based model to describe cell migration in non-isotropic fibrin networks around pancreatic tumor islets. This migration is determined by the mechanical strain energy density as well as cytokines-driven chemotaxis. Cell displacement is modeled by solving a large system of ordinary stochastic differential equations where the stochastic parts result from random walk. The stochastic differential equations are solved by the use of the classical Euler-Maruyama method. In this paper, the influence of anisotropic stromal extracellular matrix in pancreatic tumor islets on T-lymphocytes migration in different immune systems is investigated. As a result, tumor peripheral stromal extracellular matrix impedes the immune response of T-lymphocytes through changing direction of their migration.

  15. Light exposure at night disrupts host/cancer circadian regulatory dynamics: impact on the Warburg effect, lipid signaling and tumor growth prevention.

    Directory of Open Access Journals (Sweden)

    David E Blask

    Full Text Available The central circadian clock within the suprachiasmatic nucleus (SCN plays an important role in temporally organizing and coordinating many of the processes governing cancer cell proliferation and tumor growth in synchrony with the daily light/dark cycle which may contribute to endogenous cancer prevention. Bioenergetic substrates and molecular intermediates required for building tumor biomass each day are derived from both aerobic glycolysis (Warburg effect and lipid metabolism. Using tissue-isolated human breast cancer xenografts grown in nude rats, we determined that circulating systemic factors in the host and the Warburg effect, linoleic acid uptake/metabolism and growth signaling activities in the tumor are dynamically regulated, coordinated and integrated within circadian time structure over a 24-hour light/dark cycle by SCN-driven nocturnal pineal production of the anticancer hormone melatonin. Dim light at night (LAN-induced melatonin suppression disrupts this circadian-regulated host/cancer balance among several important cancer preventative signaling mechanisms, leading to hyperglycemia and hyperinsulinemia in the host and runaway aerobic glycolysis, lipid signaling and proliferative activity in the tumor.

  16. The development of a network for community-based obesity prevention: the CO-OPS Collaboration

    Science.gov (United States)

    2011-01-01

    Background Community-based interventions are a promising approach and an important component of a comprehensive response to obesity. In this paper we describe the Collaboration of COmmunity-based Obesity Prevention Sites (CO-OPS Collaboration) in Australia as an example of a collaborative network to enhance the quality and quantity of obesity prevention action at the community level. The core aims of the CO-OPS Collaboration are to: identify and analyse the lessons learned from a range of community-based initiatives aimed at tackling obesity, and; to identify the elements that make community-based obesity prevention initiatives successful and share the knowledge gained with other communities. Methods Key activities of the collaboration to date have included the development of a set of Best Practice Principles and knowledge translation and exchange activities to promote the application (or use) of evidence, evaluation and analysis in practice. Results The establishment of the CO-OPS Collaboration is a significant step toward strengthening action in this area, by bringing together research, practice and policy expertise to promote best practice, high quality evaluation and knowledge translation and exchange. Future development of the network should include facilitation of further evidence generation and translation drawing from process, impact and outcome evaluation of existing community-based interventions. Conclusions The lessons presented in this paper may help other networks like CO-OPS as they emerge around the globe. It is important that networks integrate with each other and share the experience of creating these networks. PMID:21349185

  17. Modeling protective anti-tumor immunity via preventative cancer vaccines using a hybrid agent-based and delay differential equation approach.

    Science.gov (United States)

    Kim, Peter S; Lee, Peter P

    2012-01-01

    A next generation approach to cancer envisions developing preventative vaccinations to stimulate a person's immune cells, particularly cytotoxic T lymphocytes (CTLs), to eliminate incipient tumors before clinical detection. The purpose of our study is to quantitatively assess whether such an approach would be feasible, and if so, how many anti-cancer CTLs would have to be primed against tumor antigen to provide significant protection. To understand the relevant dynamics, we develop a two-compartment model of tumor-immune interactions at the tumor site and the draining lymph node. We model interactions at the tumor site using an agent-based model (ABM) and dynamics in the lymph node using a system of delay differential equations (DDEs). We combine the models into a hybrid ABM-DDE system and investigate dynamics over a wide range of parameters, including cell proliferation rates, tumor antigenicity, CTL recruitment times, and initial memory CTL populations. Our results indicate that an anti-cancer memory CTL pool of 3% or less can successfully eradicate a tumor population over a wide range of model parameters, implying that a vaccination approach is feasible. In addition, sensitivity analysis of our model reveals conditions that will result in rapid tumor destruction, oscillation, and polynomial rather than exponential decline in the tumor population due to tumor geometry.

  18. Exploring Social Networking Technologies as Tools for HIV Prevention for Men Who Have Sex With Men.

    Science.gov (United States)

    Ramallo, Jorge; Kidder, Thomas; Albritton, Tashuna; Blick, Gary; Pachankis, John; Grandelski, Valen; Grandeleski, Valen; Kershaw, Trace

    2015-08-01

    Social networking technologies are influential among men who have sex with men (MSM) and may be an important strategy for HIV prevention. We conducted focus groups with HIV positive and negative participants. Almost all participants used social networking sites to meet new friends and sexual partners. The main obstacle to effective HIV prevention campaigns in social networking platforms was stigmatization based on homosexuality as well as HIV status. Persistent stigma associated with HIV status and disclosure was cited as a top reason for avoiding HIV-related conversations while meeting new partners using social technologies. Further, social networking sites have different social etiquettes and rules that may increase HIV risk by discouraging HIV status disclosure. Overall, successful interventions for MSM using social networking technologies must consider aspects of privacy, stigma, and social norms in order to enact HIV reduction among MSM.

  19. Radiation therapy for favorable histology Wilms tumor: Prevention of flank recurrence did not improve survival on National Wilms Tumor Studies 3 and 4

    International Nuclear Information System (INIS)

    Breslow, Norman E.; Beckwith, J. Bruce; Haase, Gerald M.; Kalapurakal, John A.; Ritchey, Michael L.; Shamberger, Robert C.; Thomas, Patrick; D'Angio, Giulio J.; Green, Daniel M.

    2006-01-01

    Purpose: To determine whether radiation therapy (RT) of patients with Wilms tumor of favorable histology prevented flank recurrence and thereby improved the survival outcomes. Methods and Materials: Recurrence and mortality risks were compared among groups of patients with Stage I-IV/favorable histology Wilms tumor enrolled in the third (n = 1,640) and fourth (n = 2,066) National Wilms Tumor Study Group studies. Results: Proportions of patients with flank recurrence were 0 of 513 = 0.0% for 20 Gy, 12 of 805 = 1.5% for 10 Gy, and 44 of 2,388 = 1.8% for no flank RT (p trend 0.001 adjusted for stage and doxorubicin); for intra-abdominal (including flank) recurrence they were 5 of 513 = 1.0%, 30 of 805 = 3.7%, and 58 of 2,388 = 2.4%, respectively (p trend = 0.02 adjusted). Survival percentages at 8 years after intra-abdominal recurrence were 0 of 5 = 0% for 20 Gy, 10 of 30 = 33% for 10 Gy, and 34 of 58 = 56% for no RT (p trend = 0.0001). NWTS-4 discontinued use of 20 Gy RT, and the 8-year flank recurrence risk increased to 2.1% from 1.0% on NWTS-3 (p = 0.013). However, event-free survival was unaltered (88% vs. 86%, p = 0.39), and overall survival was better (93.8% vs. 90.8%, p = 0.036) on NWTS-4. Conclusions: Partly because of lower postrecurrence mortality among nonirradiated patients, prevention of flank recurrence by RT did not improve survival. It is important to evaluate entire treatment policies with regard to long-term outcomes

  20. E-dating, identity and HIV prevention: theorising sexualities, risk and network society.

    Science.gov (United States)

    Davis, Mark; Hart, Graham; Bolding, Graham; Sherr, Lorraine; Elford, Jonathan

    2006-05-01

    This paper addresses how London gay men use the internet to meet sexual partners, or for e-dating. Based on qualitative interviews conducted face-to-face or via the internet, this research develops an account of how information technologies mediate the negotiation of identity and risk in connection with sexual practice. E-dating itself is a bricolage, or heterogeneous DIY practice of internet-based-communication (IBC). A central aspect of IBC is "filtering" in and out prospective e-dates based on the images and texts used to depict sexual identities. Interpretations and depictions of personal HIV risk management approaches in IBC are framed by the meanings of different identities, such as the stigma associated with being HIV positive. This paper argues for a sexualities perspective in a theory of network society. Further, HIV prevention in e-dating can potentially be addressed by considering the interplay of the HIV prevention imperatives associated with different HIV serostatus identities. There is a case for encouraging more explicit IBC about risk in e-dating and incorporating the expertise of e-daters in prevention activity. There is also a need to rethink traditional conceptions of risk management in HIV prevention to make space for the risk management bricolage of network society.

  1. Preventive effect of chemical peeling on ultraviolet induced skin tumor formation.

    Science.gov (United States)

    Abdel-Daim, Mohamed; Funasaka, Yoko; Kamo, Tsuneyoshi; Ooe, Masahiko; Matsunaka, Hiroshi; Yanagita, Emmy; Itoh, Tomoo; Nishigori, Chikako

    2010-10-01

    Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photoaged skin. We assessed the photochemopreventive effect of several clinically used chemical peeling agents on the ultraviolet (UV)-irradiated skin of hairless mice. Chemical peeling was done using 35% glycolic acid dissolved in distilled water, 30% salicylic acid in ethanol, 10% or 35% trichloroacetic acid (TCA) in distilled water at the right back of UV-irradiated hairless mice every 2 weeks in case of glycolic acid, salicylic acid, and 10% TCA and every 4 weeks in case of 35% TCA for totally 18 weeks after the establishment of photoaged mice by irradiation with UVA+B range light three times a week for 10 weeks at a total dose of 420 J/cm(2) at UVA and 9.6 J/cm(2) at UVB. Tumor formation was assessed every week. Skin specimens were taken from treated and non-treated area for evaluation under microscopy, evaluation of P53 expression, and mRNA expression of cyclooxygenase (COX)-2. Serum level of prostaglandin E(2) was also evaluated. All types of chemical peeling reduced tumor formation in treated mice, mostly in the treated area but also non-treated area. Peeling suppressed clonal retention of p53 positive abnormal cells and reduced mRNA expression of COX-2 in treated skin. Further, serum prostaglandin E(2) level was decreased in chemical peeling treated mice. These results indicate that chemical peeling with glycolic acid, salicylic acid, and TCA could serve tumor prevention by removing photodamaged cells. Copyright © 2010 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  2. Plant Polyphenols and Exendin-4 Prevent Hyperactivity and TNF-α Release in LPS-Treated In vitro Neuron/Astrocyte/Microglial Networks

    Directory of Open Access Journals (Sweden)

    Francesca Gullo

    2017-09-01

    Full Text Available Increasing evidence supports a decisive role for neuroinflammation in the neurodegenerative process of several central nervous system (CNS disorders. Microglia are essential mediators of neuroinflammation and can regulate a broad spectrum of cellular responses by releasing reactive oxygen intermediates, nitric oxide, proteases, excitatory amino acids, and cytokines. We have recently shown that also in ex-vivo cortical networks of neurons, astrocytes and microglia, an increased level of tumor necrosis factor-alpha (TNF-α was detected a few hours after exposure to the bacterial endotoxin lipopolysaccharide (LPS. Simultaneously, an atypical “seizure-like” neuronal network activity was recorded by multi-electrode array (MEA electrophysiology. These effects were prevented by minocycline, an established anti-inflammatory antibiotic. We show here that the same inhibitory effect against LPS-induced neuroinflammation is exerted also by natural plant compounds, polyphenols, such as curcumin (CU, curcuma longa, crocin (CR, saffron, and resveratrol (RE, grape, as well as by the glucagon like peptide-1 receptor (GLP-1R agonist exendin-4 (EX-4. The drugs tested also caused per-se early transient (variable changes of network activity. Since it has been reported that LPS-induced neuroinflammation causes rearrangements of glutamate transporters in astrocytes and microglia, we suggest that neural activity could be putatively increased by an imbalance of glial glutamate transporter activity, leading to prolonged synaptic glutamatergic dysregulation.

  3. Tumor Blood Vessel Dynamics

    Science.gov (United States)

    Munn, Lance

    2009-11-01

    ``Normalization'' of tumor blood vessels has shown promise to improve the efficacy of chemotherapeutics. In theory, anti-angiogenic drugs targeting endothelial VEGF signaling can improve vessel network structure and function, enhancing the transport of subsequent cytotoxic drugs to cancer cells. In practice, the effects are unpredictable, with varying levels of success. The predominant effects of anti-VEGF therapies are decreased vessel leakiness (hydraulic conductivity), decreased vessel diameters and pruning of the immature vessel network. It is thought that each of these can influence perfusion of the vessel network, inducing flow in regions that were previously sluggish or stagnant. Unfortunately, when anti-VEGF therapies affect vessel structure and function, the changes are dynamic and overlapping in time, and it has been difficult to identify a consistent and predictable normalization ``window'' during which perfusion and subsequent drug delivery is optimal. This is largely due to the non-linearity in the system, and the inability to distinguish the effects of decreased vessel leakiness from those due to network structural changes in clinical trials or animal studies. We have developed a mathematical model to calculate blood flow in complex tumor networks imaged by two-photon microscopy. The model incorporates the necessary and sufficient components for addressing the problem of normalization of tumor vasculature: i) lattice-Boltzmann calculations of the full flow field within the vasculature and within the tissue, ii) diffusion and convection of soluble species such as oxygen or drugs within vessels and the tissue domain, iii) distinct and spatially-resolved vessel hydraulic conductivities and permeabilities for each species, iv) erythrocyte particles advecting in the flow and delivering oxygen with real oxygen release kinetics, v) shear stress-mediated vascular remodeling. This model, guided by multi-parameter intravital imaging of tumor vessel structure

  4. The interaction of social networks and child obesity prevention program effects: the pathways trial.

    Science.gov (United States)

    Shin, Hee-Sung; Valente, Thomas W; Riggs, Nathaniel R; Huh, Jimi; Spruijt-Metz, Donna; Chou, Chih-Ping; Ann Pentz, Mary

    2014-06-01

    Social network analysis was used to examine whether peer influence from one's social networks moderates obesity prevention program effects on obesity-related behaviors: healthful and unhealthful. Participants included 557 children residing in Southern California. The survey assessed health-promoting behaviors (i.e., physical activity at school, physical activity outside of school, and fruit and vegetable intake), as well as unhealthful behaviors (high-calorie, low-nutrient intake and sedentary activity), and peer exposure calculated from social network nominations as indicators of peer influence. Multilevel models were conducted separately on outcomes predicted by program participation, peer exposure, and program participation by peer exposure. Results indicated that peer exposure was positively associated with one's own healthful and unhealthful behaviors. Program participation effects were moderated by peer influence, but only when unhealthful peer influence was present. Results suggest that peer influence can diminish or amplify prevention programs Future interventions should consider peer-led components to promote healthful influence of peers on healthful and unhealthful behaviors, and programs should be mindful that their effects are moderated by social networks. Copyright © 2014 The Obesity Society.

  5. Review Of Prevention Techniques For Denial Of Service DOS Attacks In Wireless Sensor Network

    Directory of Open Access Journals (Sweden)

    Poonam Rolla

    2015-08-01

    Full Text Available Wireless Sensor Networks comprised of several tiny sensor nodes which are densely deployed over the region to monitor the environmental conditions. These sensor nodes have certain design issues out of which security is the main predominant factor as it effects the whole lifetime of network. DDoS Distributed denial of service attack floods unnecessary packets in the sensor network. A review on DDoS attacks and their prevention techniques have been done in this paper.

  6. Prevention of dependence on the internet and social networks among children aged 10 to 12 years.

    OpenAIRE

    ZEDNÍKOVÁ, Denisa

    2017-01-01

    This bachelor thesis deals with addiction on the internet and social networks of 10-12 years old children and subsequent prevention and treatment of this addiction. My goal was to determine whether there are children in this age addicted to the Internet and social networks and if so, are there any prevention programs and in worse cases, follow-up treatments. The first chapter is a theoretical part about the definition of addiction, particularly non-substance addiction to the internet and soci...

  7. Using literature and data to learn Bayesian networks as clinical models of ovarian tumors.

    Science.gov (United States)

    Antal, Peter; Fannes, Geert; Timmerman, Dirk; Moreau, Yves; De Moor, Bart

    2004-03-01

    Thanks to its increasing availability, electronic literature has become a potential source of information for the development of complex Bayesian networks (BN), when human expertise is missing or data is scarce or contains much noise. This opportunity raises the question of how to integrate information from free-text resources with statistical data in learning Bayesian networks. Firstly, we report on the collection of prior information resources in the ovarian cancer domain, which includes "kernel" annotations of the domain variables. We introduce methods based on the annotations and literature to derive informative pairwise dependency measures, which are derived from the statistical cooccurrence of the names of the variables, from the similarity of the "kernel" descriptions of the variables and from a combined method. We perform wide-scale evaluation of these text-based dependency scores against an expert reference and against data scores (the mutual information (MI) and a Bayesian score). Next, we transform the text-based dependency measures into informative text-based priors for Bayesian network structures. Finally, we report the benefit of such informative text-based priors on the performance of a Bayesian network for the classification of ovarian tumors from clinical data.

  8. A Red-Light Running Prevention System Based on Artificial Neural Network and Vehicle Trajectory Data

    Directory of Open Access Journals (Sweden)

    Pengfei Li

    2014-01-01

    Full Text Available The high frequency of red-light running and complex driving behaviors at the yellow onset at intersections cannot be explained solely by the dilemma zone and vehicle kinematics. In this paper, the author presented a red-light running prevention system which was based on artificial neural networks (ANNs to approximate the complex driver behaviors during yellow and all-red clearance and serve as the basis of an innovative red-light running prevention system. The artificial neural network and vehicle trajectory are applied to identify the potential red-light runners. The ANN training time was also acceptable and its predicting accurate rate was over 80%. Lastly, a prototype red-light running prevention system with the trained ANN model was described. This new system can be directly retrofitted into the existing traffic signal systems.

  9. A red-light running prevention system based on artificial neural network and vehicle trajectory data.

    Science.gov (United States)

    Li, Pengfei; Li, Yan; Guo, Xiucheng

    2014-01-01

    The high frequency of red-light running and complex driving behaviors at the yellow onset at intersections cannot be explained solely by the dilemma zone and vehicle kinematics. In this paper, the author presented a red-light running prevention system which was based on artificial neural networks (ANNs) to approximate the complex driver behaviors during yellow and all-red clearance and serve as the basis of an innovative red-light running prevention system. The artificial neural network and vehicle trajectory are applied to identify the potential red-light runners. The ANN training time was also acceptable and its predicting accurate rate was over 80%. Lastly, a prototype red-light running prevention system with the trained ANN model was described. This new system can be directly retrofitted into the existing traffic signal systems.

  10. A Red-Light Running Prevention System Based on Artificial Neural Network and Vehicle Trajectory Data

    Science.gov (United States)

    Li, Pengfei; Li, Yan; Guo, Xiucheng

    2014-01-01

    The high frequency of red-light running and complex driving behaviors at the yellow onset at intersections cannot be explained solely by the dilemma zone and vehicle kinematics. In this paper, the author presented a red-light running prevention system which was based on artificial neural networks (ANNs) to approximate the complex driver behaviors during yellow and all-red clearance and serve as the basis of an innovative red-light running prevention system. The artificial neural network and vehicle trajectory are applied to identify the potential red-light runners. The ANN training time was also acceptable and its predicting accurate rate was over 80%. Lastly, a prototype red-light running prevention system with the trained ANN model was described. This new system can be directly retrofitted into the existing traffic signal systems. PMID:25435870

  11. Reaching adolescent girls through social networking: a new avenue for smoking prevention messages.

    Science.gov (United States)

    Struik, Laura Louise; Bottorff, Joan L; Jung, Mary; Budgen, Claire

    2012-09-01

    Because adolescent girls are being targeted on social networking sites by the tobacco industry, new online tobacco control (TC) initiatives are needed. The purpose of this interpretive descriptive study was to explore adolescent girls' perspectives on the use of social networking sites to deliver TC messages targeting young women. Focus groups were conducted with 17 girls aged 16 to 19. Seven TC messages were provided for evaluation and as context for discussion about the delivery of TC messages on social networking sites. Data were analyzed for themes, which included concerns about the effectiveness of current TC messages and the stereotypical representations of gender, factors perceived to influence the effectiveness of TC messages on social networking sites, and suggestions for enhancing the effectiveness of TC messages placed on social networking sites. Endorsement of TC messaging on social networking sites suggests that this medium is an untapped resource for smoking prevention.

  12. The Italian Network for Tumor Biotherapy (NIBIT): Getting together to push the field forward

    Science.gov (United States)

    Maio, Michele; Nicolay, Hugues JM; Ascierto, Paolo; Belardelli, Filippo; Camerini, Roberto; Colombo, Mario P; Queirolo, Paola; Ridolfi, Ruggero; Russo, Vincenzo; Anzalone, Lucia; Fonsatti, Ester; Parmiani, Giorgio

    2008-01-01

    As for a consolidated tradition, the 5th annual meeting of the Italian Network for Cancer Biotherapy took place in the Certosa of Pontignano, a Tuscan monastery, on September 20–22, 2007. The congress gathered more than 40 Italian leading groups representing academia, biotechnology and pharmaceutical industry. Aim of the meeting was to share new advances in cancer bio-immunotherapy and to promote their swift translation from pre-clinical research to clinical applications. Several topics were covered including: a) molecular and cellular mechanisms of tumor escape; b) therapeutic antibodies and recombinant constructs; c) clinical trials up-date and new programs; d) National Cooperative Networks and their potential interactions; e) old and new times in cancer immunology, an "amarcord". Here, we report the main issues discussed during the meeting. PMID:18269750

  13. The Italian Network for Tumor Biotherapy (NIBIT: Getting together to push the field forward

    Directory of Open Access Journals (Sweden)

    Ridolfi Ruggero

    2008-02-01

    Full Text Available Abstract As for a consolidated tradition, the 5th annual meeting of the Italian Network for Cancer Biotherapy took place in the Certosa of Pontignano, a Tuscan monastery, on September 20–22, 2007. The congress gathered more than 40 Italian leading groups representing academia, biotechnology and pharmaceutical industry. Aim of the meeting was to share new advances in cancer bio-immunotherapy and to promote their swift translation from pre-clinical research to clinical applications. Several topics were covered including: a molecular and cellular mechanisms of tumor escape; b therapeutic antibodies and recombinant constructs; c clinical trials up-date and new programs; d National Cooperative Networks and their potential interactions; e old and new times in cancer immunology, an "amarcord". Here, we report the main issues discussed during the meeting.

  14. Study of Aided Diagnosis of Hepatic Carcinoma Based on Artificial Neural Network Combined with Tumor Marker Group

    Science.gov (United States)

    Tan, Shanjuan; Feng, Feifei; Wu, Yongjun; Wu, Yiming

    To develop a computer-aided diagnostic scheme by using an artificial neural network (ANN) combined with tumor markers for diagnosis of hepatic carcinoma (HCC) as a clinical assistant method. 140 serum samples (50 malignant, 40 benign and 50 normal) were analyzed for α-fetoprotein (AFP), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), sialic acid (SA) and calcium (Ca). The five tumor marker values were then used as ANN inputs data. The result of ANN was compared with that of discriminant analysis by receiver operating characteristic (ROC) curve (AUC) analysis. The diagnostic accuracy of ANN and discriminant analysis among all samples of the test group was 95.5% and 79.3%, respectively. Analysis of multiple tumor markers based on ANN may be a better choice than the traditional statistical methods for differentiating HCC from benign or normal.

  15. [Histological diagnosis of bone tumors: Guidelines of the French committee of bone pathologists reference network on bone tumors (RESOS)].

    Science.gov (United States)

    Galant, Christine; Bouvier, Corinne; Larousserie, Frédérique; Aubert, Sébastien; Audard, Virginie; Brouchet, Anne; Marie, Béatrice; Guinebretière, Jean-Marc; de Pinieux du Bouexic, Gonzague

    2018-04-01

    The management of patients having a bone lesion requires in many cases the realization of a histological sample in order to obtain a diagnosis. However, with the technological evolution, CT-guided biopsies are performed more frequently, often in outpatient clinics. Interpretation of these biopsies constitutes new challenges for the pathologists within the wide spectrum of bone entities. The purpose of the document is to propose guidelines based on the experience of the French committee of bone pathologists of the reference network on bone tumors (RESOS) regarding the indications and limitations of the diagnosis on restricted material. Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  16. Synthetic dosage lethality in the human metabolic network is highly predictive of tumor growth and cancer patient survival.

    Science.gov (United States)

    Megchelenbrink, Wout; Katzir, Rotem; Lu, Xiaowen; Ruppin, Eytan; Notebaart, Richard A

    2015-09-29

    Synthetic dosage lethality (SDL) denotes a genetic interaction between two genes whereby the underexpression of gene A combined with the overexpression of gene B is lethal. SDLs offer a promising way to kill cancer cells by inhibiting the activity of SDL partners of activated oncogenes in tumors, which are often difficult to target directly. As experimental genome-wide SDL screens are still scarce, here we introduce a network-level computational modeling framework that quantitatively predicts human SDLs in metabolism. For each enzyme pair (A, B) we systematically knock out the flux through A combined with a stepwise flux increase through B and search for pairs that reduce cellular growth more than when either enzyme is perturbed individually. The predictive signal of the emerging network of 12,000 SDLs is demonstrated in five different ways. (i) It can be successfully used to predict gene essentiality in shRNA cancer cell line screens. Moving to clinical tumors, we show that (ii) SDLs are significantly underrepresented in tumors. Furthermore, breast cancer tumors with SDLs active (iii) have smaller sizes and (iv) result in increased patient survival, indicating that activation of SDLs increases cancer vulnerability. Finally, (v) patient survival improves when multiple SDLs are present, pointing to a cumulative effect. This study lays the basis for quantitative identification of cancer SDLs in a model-based mechanistic manner. The approach presented can be used to identify SDLs in species and cell types in which "omics" data necessary for data-driven identification are missing.

  17. Fully convolutional networks (FCNs)-based segmentation method for colorectal tumors on T2-weighted magnetic resonance images.

    Science.gov (United States)

    Jian, Junming; Xiong, Fei; Xia, Wei; Zhang, Rui; Gu, Jinhui; Wu, Xiaodong; Meng, Xiaochun; Gao, Xin

    2018-06-01

    Segmentation of colorectal tumors is the basis of preoperative prediction, staging, and therapeutic response evaluation. Due to the blurred boundary between lesions and normal colorectal tissue, it is hard to realize accurate segmentation. Routinely manual or semi-manual segmentation methods are extremely tedious, time-consuming, and highly operator-dependent. In the framework of FCNs, a segmentation method for colorectal tumor was presented. Normalization was applied to reduce the differences among images. Borrowing from transfer learning, VGG-16 was employed to extract features from normalized images. We conducted five side-output blocks from the last convolutional layer of each block of VGG-16 along the network, these side-output blocks can deep dive multiscale features, and produced corresponding predictions. Finally, all of the predictions from side-output blocks were fused to determine the final boundaries of the tumors. A quantitative comparison of 2772 colorectal tumor manual segmentation results from T2-weighted magnetic resonance images shows that the average Dice similarity coefficient, positive predictive value, specificity, sensitivity, Hammoude distance, and Hausdorff distance were 83.56, 82.67, 96.75, 87.85%, 0.2694, and 8.20, respectively. The proposed method is superior to U-net in colorectal tumor segmentation (P colorectal tumor segmentation (P > 0.05). The results indicate that the introduction of FCNs contributed to accurate segmentation of colorectal tumors. This method has the potential to replace the present time-consuming and nonreproducible manual segmentation method.

  18. Presurgical brain mapping of the language network in patients with brain tumors using resting-state fMRI: Comparison with task fMRI.

    Science.gov (United States)

    Sair, Haris I; Yahyavi-Firouz-Abadi, Noushin; Calhoun, Vince D; Airan, Raag D; Agarwal, Shruti; Intrapiromkul, Jarunee; Choe, Ann S; Gujar, Sachin K; Caffo, Brian; Lindquist, Martin A; Pillai, Jay J

    2016-03-01

    To compare language networks derived from resting-state fMRI (rs-fMRI) with task-fMRI in patients with brain tumors and investigate variables that affect rs-fMRI vs task-fMRI concordance. Independent component analysis (ICA) of rs-fMRI was performed with 20, 30, 40, and 50 target components (ICA20 to ICA50) and language networks identified for patients presenting for presurgical fMRI mapping between 1/1/2009 and 7/1/2015. 49 patients were analyzed fulfilling criteria for presence of brain tumors, no prior brain surgery, and adequate task-fMRI performance. Rs-vs-task-fMRI concordance was measured using Dice coefficients across varying fMRI thresholds before and after noise removal. Multi-thresholded Dice coefficient volume under the surface (DiceVUS) and maximum Dice coefficient (MaxDice) were calculated. One-way Analysis of Variance (ANOVA) was performed to determine significance of DiceVUS and MaxDice between the four ICA order groups. Age, Sex, Handedness, Tumor Side, Tumor Size, WHO Grade, number of scrubbed volumes, image intensity root mean square (iRMS), and mean framewise displacement (FD) were used as predictors for VUS in a linear regression. Artificial elevation of rs-fMRI vs task-fMRI concordance is seen at low thresholds due to noise. Noise-removed group-mean DiceVUS and MaxDice improved as ICA order increased, however ANOVA demonstrated no statistically significant difference between the four groups. Linear regression demonstrated an association between iRMS and DiceVUS for ICA30-50, and iRMS and MaxDice for ICA50. Overall there is moderate group level rs-vs-task fMRI language network concordance, however substantial subject-level variability exists; iRMS may be used to determine reliability of rs-fMRI derived language networks. © 2015 Wiley Periodicals, Inc.

  19. Pre-Cancer Atlas (PCA) and Other Human Tumor Atlas Network (HTAN) Funding Opportunity Announcements (FOAs) Released | Division of Cancer Prevention

    Science.gov (United States)

    There are 3 new funding opportunity announcements about the Pre-Cancer Atlas associated with the Beau Biden Cancer MoonshotSM Initiative that are intended to accelerate cancer research. The purpose of the FOAs is to promote research that results in a comprehensive view of the dynamic, multidimensional tumor ecosystem and is a direct response to the Moonshot Blue Ribbon Panel recommendation to generate human tumor atlases. |

  20. Can social networking be used to promote engagement in child maltreatment prevention programs? Two pilot studies.

    Science.gov (United States)

    Edwards-Gaura, Anna; Whitaker, Daniel; Self-Brown, Shannon

    2014-08-01

    Child maltreatment is one of the United States' most significant public health problems. In efforts to prevent maltreatment experts recommend use of Behavioral Parent Training Programs (BPTs), which focus on teaching skills that will replace and prevent maltreating behavior. While there is research to support the effectiveness of BPTs in maltreatment prevention, the reach of such programs is still limited by several barriers, including poor retention of families in services. Recently, new technologies have emerged that offer innovative opportunities to improve family engagement. These technologies include smartphones and social networking; however, very little is known about the potential of these to aid in maltreatment prevention. The primary goal of this study was to conduct 2 pilot exploratory projects. The first project administered a survey to parents and providers to gather data about at-risk parents' use of smartphones and online social networking technologies. The second project tested a social networking-enhanced brief parenting program with 3 intervention participants and evaluated parental responses. Seventy-five percent of parents surveyed reported owning a computer that worked. Eighty-nine percent of parents reported that they had reliable Internet access at home, and 67% said they used the Internet daily. Three parents participated in the intervention with all reporting improvement in parent-child interaction skills and a positive experience participating in the social networking-enhanced SafeCare components. In general, findings suggest that smartphones, social networking, and Facebook, in particular, are now being used by individuals who show risk factors for maltreatment. Further, the majority of parents surveyed in this study said that they like Facebook, and all parents surveyed said that they use Facebook and have a Facebook account. As well, all saw it as a potentially beneficial supplement for future parents enrolling in parenting programs.

  1. Can Social Networking Be Used to Promote Engagement in Child Maltreatment Prevention Programs? Two Pilot Studies

    Directory of Open Access Journals (Sweden)

    Anna Edwards-Gaura

    2014-08-01

    Full Text Available Introduction: Child maltreatment is one of the United States’ most significant public health problems. In efforts to prevent maltreatment experts recommend use of Behavioral Parent Training Programs (BPTs, which focus on teaching skills that will replace and prevent maltreating behavior. While there is research to support the effectiveness of BPTs in maltreatment prevention, the reach of such programs is still limited by several barriers, including poor retention of families in services. Recently, new technologies have emerged that offer innovative opportunities to improve family engagement. These technologies include smartphones and social networking; however, very little is known about the potential of these to aid in maltreatment prevention. The primary goal of this study was to conduct 2 pilot exploratory projects. Methods: The first project administered a survey to parents and providers to gather data about at-risk parents’ use of smartphones and online social networking technologies. The second project tested a social networking-enhanced brief parenting program with 3 intervention participants and evaluated parental responses. Results: Seventy-five percent of parents surveyed reported owning a computer that worked. Eighty-nine percent of parents reported that they had reliable Internet access at home, and 67% said they used the Internet daily. Three parents participated in the intervention with all reporting improvement in parent-child interaction skills and a positive experience participating in the social networking-enhanced SafeCare components. Conclusion: In general, findings suggest that smartphones, social networking, and Facebook, in particular, are now being used by individuals who show risk factors formal treatment. Further, the majority of parents surveyed in this study said that they like Facebook, and all parents surveyed said that they use Facebook and have a Facebook account. As well, all saw it as a potentially

  2. [Co-author and keyword networks and their clustering appearance in preventive medicine fields in Korea: analysis of papers in the Journal of Preventive Medicine and Public Health, 1991~2006].

    Science.gov (United States)

    Jung, Minsoo; Chung, Dongjun

    2008-01-01

    This study evaluated knowledge structure and its effect factor by analysis of co-author and keyword networks in Korea's preventive medicine sector. The data was extracted from 873 papers listed in the Journal of Preventive Medicine and Public Health, and was transformed into a co-author and keyword matrix where the existence of a 'link' was judged by impact factors calculated by the weight value of the role and rate of author participation. Research achievement was dependent upon the author's status and networking index, as analyzed by neighborhood degree, multidimensional scaling, correspondence analysis, and multiple regression. Co-author networks developed as randomness network in the center of a few high-productivity researchers. In particular, closeness centrality was more developed than degree centrality. Also, power law distribution was discovered in impact factor and research productivity by college affiliation. In multiple regression, the effect of the author's role was significant in both the impact factor calculated by the participatory rate and the number of listed articles. However, the number of listed articles varied by sex. This study shows that the small world phenomenon exists in co-author and keyword networks in a journal, as in citation networks. However, the differentiation of knowledge structure in the field of preventive medicine was relatively restricted by specialization.

  3. Preventing Out-of-Sequence for Multicast Input-Queued Space-Memory-Memory Clos-Network

    DEFF Research Database (Denmark)

    Yu, Hao; Ruepp, Sarah Renée; Berger, Michael Stübert

    2011-01-01

    This paper proposes an out-of-sequence (OOS) preventative cell dispatching algorithm, the multicast flow-based round robin (MFRR), for multicast input-queued space-memory-memory (IQ-SMM) Clos-network architecture. Independently treating each incoming cell, such as the desynchronized static round...

  4. An Immune-Modulating Diet in Combination with Chemotherapy Prevents Cancer Cachexia by Attenuating Systemic Inflammation in Colon 26 Tumor-Bearing Mice.

    Science.gov (United States)

    Nakamura, Kentaro; Sasayama, Akina; Takahashi, Takeshi; Yamaji, Taketo

    2015-01-01

    Cancer cachexia is characterized by muscle wasting caused partly by systemic inflammation. We previously demonstrated an immune-modulating diet (IMD), an enteral diet enriched with immunonutrition and whey-hydrolyzed peptides, to have antiinflammatory effects in some experimental models. Here, we investigated whether the IMD in combination with chemotherapy could prevent cancer cachexia in colon 26 tumor-bearing mice. Forty tumor-bearing mice were randomized into 5 groups: tumor-bearing control (TB), low dose 5-fluorouracil (5-FU) and standard diet (LF/ST), low dose 5-FU and IMD (LF/IMD), high dose 5-FU and standard diet (HF/ST) and high dose 5-FU and IMD (HF/IMD). The ST and IMD mice received a standard diet or the IMD ad libitum for 21 days. Muscle mass in the IMD mice was significantly higher than that in the ST mice. The LF/IMD in addition to the HF/ST and HF/IMD mice preserved their body and carcass weights. Plasma prostaglandin E2 levels were significantly lower in the IMD mice than in the ST mice. A combined effect was also observed in plasma interleukin-6, glucose, and vascular endothelial growth factor levels. Tumor weight was not affected by different diets. In conclusion, the IMD in combination with chemotherapy prevented cancer cachexia without suppressing chemotherapeutic efficacy.

  5. Sci-Thur AM: YIS – 05: Prediction of lung tumor motion using a generalized neural network optimized from the average prediction outcome of a group of patients

    Energy Technology Data Exchange (ETDEWEB)

    Teo, Troy; Alayoubi, Nadia; Bruce, Neil; Pistorius, Stephen [University of Manitoba/ CancerCare Manitoba, University of Manitoba, University of Manitoba, University of Manitoba / CancerCare Manitoba (Canada)

    2016-08-15

    Purpose: In image-guided adaptive radiotherapy systems, prediction of tumor motion is required to compensate for system latencies. However, due to the non-stationary nature of respiration, it is a challenge to predict the associated tumor motions. In this work, a systematic design of the neural network (NN) using a mixture of online data acquired during the initial period of the tumor trajectory, coupled with a generalized model optimized using a group of patient data (obtained offline) is presented. Methods: The average error surface obtained from seven patients was used to determine the input data size and number of hidden neurons for the generalized NN. To reduce training time, instead of using random weights to initialize learning (method 1), weights inherited from previous training batches (method 2) were used to predict tumor position for each sliding window. Results: The generalized network was established with 35 input data (∼4.66s) and 20 hidden nodes. For a prediction horizon of 650 ms, mean absolute errors of 0.73 mm and 0.59 mm were obtained for method 1 and 2 respectively. An average initial learning period of 8.82 s is obtained. Conclusions: A network with a relatively short initial learning time was achieved. Its accuracy is comparable to previous studies. This network could be used as a plug-and play predictor in which (a) tumor positions can be predicted as soon as treatment begins and (b) the need for pretreatment data and optimization for individual patients can be avoided.

  6. Sci-Thur AM: YIS – 05: Prediction of lung tumor motion using a generalized neural network optimized from the average prediction outcome of a group of patients

    International Nuclear Information System (INIS)

    Teo, Troy; Alayoubi, Nadia; Bruce, Neil; Pistorius, Stephen

    2016-01-01

    Purpose: In image-guided adaptive radiotherapy systems, prediction of tumor motion is required to compensate for system latencies. However, due to the non-stationary nature of respiration, it is a challenge to predict the associated tumor motions. In this work, a systematic design of the neural network (NN) using a mixture of online data acquired during the initial period of the tumor trajectory, coupled with a generalized model optimized using a group of patient data (obtained offline) is presented. Methods: The average error surface obtained from seven patients was used to determine the input data size and number of hidden neurons for the generalized NN. To reduce training time, instead of using random weights to initialize learning (method 1), weights inherited from previous training batches (method 2) were used to predict tumor position for each sliding window. Results: The generalized network was established with 35 input data (∼4.66s) and 20 hidden nodes. For a prediction horizon of 650 ms, mean absolute errors of 0.73 mm and 0.59 mm were obtained for method 1 and 2 respectively. An average initial learning period of 8.82 s is obtained. Conclusions: A network with a relatively short initial learning time was achieved. Its accuracy is comparable to previous studies. This network could be used as a plug-and play predictor in which (a) tumor positions can be predicted as soon as treatment begins and (b) the need for pretreatment data and optimization for individual patients can be avoided.

  7. Improving the performance of neutral network in differentiation of breast tumors using wavelet transformation on dynamic MRI

    International Nuclear Information System (INIS)

    Abdolmaleki, P.; Abrishami-Moghddam, H.; Gity, M.; Mokhtari- Dizaji, M.; Mostafa, A.

    2005-01-01

    A computer aided diagnosis system was established using the wavelet transform and neural network to differentiate malignant from benign in a group of patients with histo-pathologically proved breast lesions based on the data derived independently from time-intensity profile. Materials and Methods: The performance of the artificial neural network was evaluated using a database with 105 patients' records each of which consisted of 8 quantitative parameters mostly derived from time- intensity profile using wavelet transform. These findings were encoded as features for a three-layered neural network to predict the outcome of biopsy. The network was trained and tested using the jackknife method and its performance was then compared to that of the radiologists in terms of sensitivity, specificity and accuracy using receiver operating characteristic curve (ROC) analysis. Results: The network was able to classify correctly the 84 original cases and yielded a comparable diagnostic accuracy (80%), compared to that of the radiologist (85%) by performing a constructive association between extracted quantitative data and corresponding pathological results (r=0.63, p<0.001). Conclusion: An artificial neural network supported by wavelet transform can be trained to differentiate malignant from benign breast tumors with a reasonable degree of accuracy

  8. Structural Network Position and Performance of Health Leaders Within an HIV Prevention Trial.

    Science.gov (United States)

    Mulawa, Marta I; Yamanis, Thespina J; Kajula, Lusajo J; Balvanz, Peter; Maman, Suzanne

    2018-04-28

    The effectiveness of peer leaders in promoting health may depend on the position they occupy within their social networks. Using sociocentric (whole network) and behavioral data from the intervention arm of a cluster-randomized HIV prevention trial in Dar es Salaam, Tanzania, we used generalized linear models with standardized predictors to examine the association between heath leaders' baseline structural network position (i.e., in-degree and betweenness centrality) and their 12-month self-reported (1) confidence in educating network members about HIV and gender-based violence (GBV) and (2) number of past-week conversations about HIV and GBV. As in-degree centrality increased, leaders reported fewer HIV-related conversations. As betweenness centrality increased, leaders reported greater number of conversations about GBV. Network position was not significantly associated with confidence in discussing either topic. Our results suggest that peer leaders who occupy spaces between sub-groups of network members may be more effective in engaging their peers in sensitive or controversial topics like GBV than more popular peer leaders.

  9. Environmental engineering and pollution prevention. European network of excellence and partnership

    International Nuclear Information System (INIS)

    Wotte, J.; Halang, W.A.; Kraemer, B.J.

    1996-01-01

    The primary purpose of the workshop was to present and discuss the main goals, contents, projects, partners, and implications of a proposed non-profit European Research Network, which aims at establishing research nodes at key locations in European NATO and CP countries. All projects are directed to solutions for the heavily polluted 'Black Triangle' Bohemia, Saxony, and Silesia, which was selected as a nucleus for the network because of its geographical location and cross-border environmental problems. Papers are presented under the following subject headings: disarmament; environment; human resources; high technology; and health. They include papers on soil remediation at manufactured gas plants, and power generation in the Czech Republic and its contribution to air pollution prevention in Central Europe

  10. Social Support Networks: An Underutilized Resource for the Prevention of HIV and other Sexually Transmitted Diseases among Hispanic/Latino Migrants and Immigrants.

    Science.gov (United States)

    Painter, Thomas M

    2018-01-01

    Hispanic/Latino migrants and immigrants are vulnerable to infection by HIV and other sexually transmitted diseases (STDs). Participation in social support networks helps them cope with circumstances in the U.S. Studies of Hispanic/Latino migrants suggest that participation may also be protective against HIV/STD infection. However the studies do not satisfactorily explain how participation leads to protective actions, and recommend externally-induced interventions for HIV/STD prevention rather than incorporating the spontaneously occurring forms of social support they describe. Given the potential protective effects of support networks, a database search was conducted to ascertain the extent to which published HIV/STD prevention interventions for these populations incorporate their support networks. Very few interventions were identified and fewer still incorporate support networks. This commentary calls for research to understand more fully how support networks affect HIV/STD risks among Hispanic/Latino migrants and immigrants and identifies potential benefits of incorporating these networks in HIV/STD prevention for these vulnerable populations.

  11. The Multi-Purpose Tool of Tumor Immunotherapy: Gene-Engineered T Cells.

    Science.gov (United States)

    Mo, Zeming; Du, Peixin; Wang, Guoping; Wang, Yongsheng

    2017-01-01

    A detailed summary of the published clinical trials of chimeric antigen receptor T cells (CAR-T) and TCR-transduced T cells (TCR-T) was constructed to understand the development trend of adoptive T cell therapy (ACT). In contrast to TCR-T, the number of CAR-T clinical trials has increased dramatically in China in the last three years. The ACT seems to be very prosperous. But, the multidimensional interaction of tumor, tumor associated antigen (TAA) and normal tissue exacerbates the uncontrolled outcome of T cells gene therapy. It reminds us the importance that optimizing treatment security to prevent the fatal serious adverse events. How to balance the safety and effectiveness of the ACT? At least six measures can potentially optimize the safety of ACT. At the same time, with the application of gene editing techniques, more endogenous receptors are disrupted while more exogenous receptors are expressed on T cells. As a multi-purpose tool of tumor immunotherapy, gene-engineered T cells (GE-T) have been given different functional weapons. A network which is likely to link radiation therapy, tumor vaccines, CAR-T and TCR-T is being built. Moreover, more and more evidences indicated that the combination of the ACT and other therapies would further enhance the anti-tumor capacity of the GE-T.

  12. Parameter estimation of brain tumors using intraoperative thermal imaging based on artificial tactile sensing in conjunction with artificial neural network

    International Nuclear Information System (INIS)

    Sadeghi-Goughari, M; Mojra, A; Sadeghi, S

    2016-01-01

    Intraoperative Thermal Imaging (ITI) is a new minimally invasive diagnosis technique that can potentially locate margins of brain tumor in order to achieve maximum tumor resection with least morbidity. This study introduces a new approach to ITI based on artificial tactile sensing (ATS) technology in conjunction with artificial neural networks (ANN) and feasibility and applicability of this method in diagnosis and localization of brain tumors is investigated. In order to analyze validity and reliability of the proposed method, two simulations were performed. (i) An in vitro experimental setup was designed and fabricated using a resistance heater embedded in agar tissue phantom in order to simulate heat generation by a tumor in the brain tissue; and (ii) A case report patient with parafalcine meningioma was presented to simulate ITI in the neurosurgical procedure. In the case report, both brain and tumor geometries were constructed from MRI data and tumor temperature and depth of location were estimated. For experimental tests, a novel assisted surgery robot was developed to palpate the tissue phantom surface to measure temperature variations and ANN was trained to estimate the simulated tumor’s power and depth. Results affirm that ITI based ATS is a non-invasive method which can be useful to detect, localize and characterize brain tumors. (paper)

  13. Brain Tumor Epidemiology Consortium (BTEC)

    Science.gov (United States)

    The Brain Tumor Epidemiology Consortium is an open scientific forum organized to foster the development of multi-center, international and inter-disciplinary collaborations that will lead to a better understanding of the etiology, outcomes, and prevention of brain tumors.

  14. An intrusion prevention system as a proactive security mechanism in network infrastructure

    Directory of Open Access Journals (Sweden)

    Dulanović Nenad

    2008-01-01

    Full Text Available A properly configured firewall is a good starting point in securing a computer network. However, complex network environments that involve higher number of participants and endpoints require better security infrastructure. Intrusion Detection Systems (IDS, proposed as a solution to perimeter defense, have many open problems and it is clear that better solutions must be found. Due to many unsolved problems associated with IDS, Intrusion Prevention Systems (IPS are introduced. The main idea in IPS is to be proactive. This paper gives an insight of Cobrador Bouncer IPS implementation. System architecture is given and three different Bouncer IPS deployment modes are presented. The Bouncer IPS as a proactive honeypot is also discussed.

  15. Tumor-Derived Exosomes and Their Role in Tumor-Induced Immune Suppression

    Directory of Open Access Journals (Sweden)

    Theresa L. Whiteside

    2016-10-01

    Full Text Available Tumor-derived exosomes (TEX are emerging as critical components of an intercellular information network between the tumor and the host. The tumor escapes from the host immune system by using a variety of mechanisms designed to impair or eliminate anti-tumor immunity. TEX carrying a cargo of immunoinhibitory molecules and factors represent one such mechanism. TEX, which are present in all body fluids of cancer patients, deliver negative molecular or genetic signals to immune cells re-programming their functions. Although TEX can also stimulate immune activity, in the microenvironments dominated by the tumor, TEX tend to mediate immune suppression thus promoting tumor progression. The TEX content, in part resembling that of the parent cell, may serve as a source of cancer biomarkers. TEX also interfere with immune therapies. A better understanding of TEX and their contribution to cancer progression and cancer patients’ response to immune therapies represents a challenging new field of investigation.

  16. Endothelial Dll4 overexpression reduces vascular response and inhibits tumor growth and metastasization in vivo.

    Science.gov (United States)

    Trindade, Alexandre; Djokovic, Dusan; Gigante, Joana; Mendonça, Liliana; Duarte, António

    2017-03-14

    The inhibition of Delta-like 4 (Dll4)/Notch signaling has been shown to result in excessive, nonfunctional vessel proliferation and significant tumor growth suppression. However, safety concerns emerged with the identification of side effects resulting from chronic Dll4/Notch blockade. Alternatively, we explored the endothelial Dll4 overexpression using different mouse tumor models. We used a transgenic mouse model of endothelial-specific Dll4 overexpression, previously produced. Growth kinetics and vascular histopathology of several types of solid tumors was evaluated, namely Lewis Lung Carcinoma xenografts, chemically-induced skin papillomas and RIP1-Tag2 insulinomas. We found that increased Dll4/Notch signaling reduces tumor growth by reducing vascular endothelial growth factor (VEGF)-induced endothelial proliferation, tumor vessel density and overall tumor blood supply. In addition, Dll4 overexpression consistently improved tumor vascular maturation and functionality, as indicated by increased vessel calibers, enhanced mural cell recruitment and increased network perfusion. Importantly, the tumor vessel normalization is not more effective than restricted vessel proliferation, but was found to prevent metastasis formation and allow for increased delivery to the tumor of concomitant chemotherapy, improving its efficacy. By reducing endothelial sensitivity to VEGF, these results imply that Dll4/Notch stimulation in tumor microenvironment could be beneficial to solid cancer patient treatment by reducing primary tumor size, improving tumor drug delivery and reducing metastization. Endothelial specific Dll4 overexpression thus appears as a promising anti-angiogenic modality that might improve cancer control.

  17. Coupled Hybrid Continuum-Discrete Model of Tumor Angiogenesis and Growth.

    Directory of Open Access Journals (Sweden)

    Jie Lyu

    Full Text Available The processes governing tumor growth and angiogenesis are codependent. To study the relationship between them, we proposed a coupled hybrid continuum-discrete model. In this model, tumor cells, their microenvironment (extracellular matrixes, matrix-degrading enzymes, and tumor angiogenic factors, and their network of blood vessels, described by a series of discrete points, were considered. The results of numerical simulation reveal the process of tumor growth and the change in microenvironment from avascular to vascular stage, indicating that the network of blood vessels develops gradually as the tumor grows. Our findings also reveal that a tumor is divided into three regions: necrotic, semi-necrotic, and well-vascularized. The results agree well with the previous relevant studies and physiological facts, and this model represents a platform for further investigations of tumor therapy.

  18. Comparative effectiveness of long term drug treatment strategies to prevent asthma exacerbations: network meta-analysis

    NARCIS (Netherlands)

    Loymans, Rik J. B.; Gemperli, Armin; Cohen, Judith; Rubinstein, Sidney M.; Sterk, Peter J.; Reddel, Helen K.; Jüni, Peter; ter Riet, Gerben

    2014-01-01

    To determine the comparative effectiveness and safety of current maintenance strategies in preventing exacerbations of asthma. Systematic review and network meta-analysis using Bayesian statistics. Cochrane systematic reviews on chronic asthma, complemented by an updated search when appropriate.

  19. Detecting and Preventing Sybil Attacks in Wireless Sensor Networks Using Message Authentication and Passing Method.

    Science.gov (United States)

    Dhamodharan, Udaya Suriya Raj Kumar; Vayanaperumal, Rajamani

    2015-01-01

    Wireless sensor networks are highly indispensable for securing network protection. Highly critical attacks of various kinds have been documented in wireless sensor network till now by many researchers. The Sybil attack is a massive destructive attack against the sensor network where numerous genuine identities with forged identities are used for getting an illegal entry into a network. Discerning the Sybil attack, sinkhole, and wormhole attack while multicasting is a tremendous job in wireless sensor network. Basically a Sybil attack means a node which pretends its identity to other nodes. Communication to an illegal node results in data loss and becomes dangerous in the network. The existing method Random Password Comparison has only a scheme which just verifies the node identities by analyzing the neighbors. A survey was done on a Sybil attack with the objective of resolving this problem. The survey has proposed a combined CAM-PVM (compare and match-position verification method) with MAP (message authentication and passing) for detecting, eliminating, and eventually preventing the entry of Sybil nodes in the network. We propose a scheme of assuring security for wireless sensor network, to deal with attacks of these kinds in unicasting and multicasting.

  20. Detecting and Preventing Sybil Attacks in Wireless Sensor Networks Using Message Authentication and Passing Method

    Directory of Open Access Journals (Sweden)

    Udaya Suriya Raj Kumar Dhamodharan

    2015-01-01

    Full Text Available Wireless sensor networks are highly indispensable for securing network protection. Highly critical attacks of various kinds have been documented in wireless sensor network till now by many researchers. The Sybil attack is a massive destructive attack against the sensor network where numerous genuine identities with forged identities are used for getting an illegal entry into a network. Discerning the Sybil attack, sinkhole, and wormhole attack while multicasting is a tremendous job in wireless sensor network. Basically a Sybil attack means a node which pretends its identity to other nodes. Communication to an illegal node results in data loss and becomes dangerous in the network. The existing method Random Password Comparison has only a scheme which just verifies the node identities by analyzing the neighbors. A survey was done on a Sybil attack with the objective of resolving this problem. The survey has proposed a combined CAM-PVM (compare and match-position verification method with MAP (message authentication and passing for detecting, eliminating, and eventually preventing the entry of Sybil nodes in the network. We propose a scheme of assuring security for wireless sensor network, to deal with attacks of these kinds in unicasting and multicasting.

  1. VA Suicide Prevention Applications Network

    Science.gov (United States)

    Stephens, Brady; Morley, Sybil; Thompson, Caitlin; Kemp, Janet; Bossarte, Robert M.

    2016-01-01

    Objectives: The US Department of Veterans Affairs’ Suicide Prevention Applications Network (SPAN) is a national system for suicide event tracking and case management. The objective of this study was to assess data on suicide attempts among people using Veterans Health Administration (VHA) services. Methods: We assessed the degree of data overlap on suicide attempters reported in SPAN and the VHA’s medical records from October 1, 2010, to September 30, 2014—overall, by year, and by region. Data on suicide attempters in the VHA’s medical records consisted of diagnoses documented with E95 codes from the International Classification of Diseases, Ninth Revision. Results: Of 50 518 VHA patients who attempted suicide during the 4-year study period, data on fewer than half (41%) were reported in both SPAN and the medical records; nearly 65% of patients whose suicide attempt was recorded in SPAN had no data on attempted suicide in the VHA’s medical records. Conclusion: Evaluation of administrative data suggests that use of SPAN substantially increases the collection of data on suicide attempters as compared with the use of medical records alone, but neither SPAN nor the VHA’s medical records identify all suicide attempters. Further research is needed to better understand the strengths and limitations of both systems and how to best combine information across systems. PMID:28123228

  2. A method for medulloblastoma tumor differentiation based on convolutional neural networks and transfer learning

    Science.gov (United States)

    Cruz-Roa, Angel; Arévalo, John; Judkins, Alexander; Madabhushi, Anant; González, Fabio

    2015-12-01

    Convolutional neural networks (CNN) have been very successful at addressing different computer vision tasks thanks to their ability to learn image representations directly from large amounts of labeled data. Features learned from a dataset can be used to represent images from a different dataset via an approach called transfer learning. In this paper we apply transfer learning to the challenging task of medulloblastoma tumor differentiation. We compare two different CNN models which were previously trained in two different domains (natural and histopathology images). The first CNN is a state-of-the-art approach in computer vision, a large and deep CNN with 16-layers, Visual Geometry Group (VGG) CNN. The second (IBCa-CNN) is a 2-layer CNN trained for invasive breast cancer tumor classification. Both CNNs are used as visual feature extractors of histopathology image regions of anaplastic and non-anaplastic medulloblastoma tumor from digitized whole-slide images. The features from the two models are used, separately, to train a softmax classifier to discriminate between anaplastic and non-anaplastic medulloblastoma image regions. Experimental results show that the transfer learning approach produce competitive results in comparison with the state of the art approaches for IBCa detection. Results also show that features extracted from the IBCa-CNN have better performance in comparison with features extracted from the VGG-CNN. The former obtains 89.8% while the latter obtains 76.6% in terms of average accuracy.

  3. System-wide analysis reveals a complex network of tumor-fibroblast interactions involved in tumorigenicity.

    Directory of Open Access Journals (Sweden)

    Megha Rajaram

    Full Text Available Many fibroblast-secreted proteins promote tumorigenicity, and several factors secreted by cancer cells have in turn been proposed to induce these proteins. It is not clear whether there are single dominant pathways underlying these interactions or whether they involve multiple pathways acting in parallel. Here, we identified 42 fibroblast-secreted factors induced by breast cancer cells using comparative genomic analysis. To determine what fraction was active in promoting tumorigenicity, we chose five representative fibroblast-secreted factors for in vivo analysis. We found that the majority (three out of five played equally major roles in promoting tumorigenicity, and intriguingly, each one had distinct effects on the tumor microenvironment. Specifically, fibroblast-secreted amphiregulin promoted breast cancer cell survival, whereas the chemokine CCL7 stimulated tumor cell proliferation while CCL2 promoted innate immune cell infiltration and angiogenesis. The other two factors tested had minor (CCL8 or minimally (STC1 significant effects on the ability of fibroblasts to promote tumor growth. The importance of parallel interactions between fibroblasts and cancer cells was tested by simultaneously targeting fibroblast-secreted amphiregulin and the CCL7 receptor on cancer cells, and this was significantly more efficacious than blocking either pathway alone. We further explored the concept of parallel interactions by testing the extent to which induction of critical fibroblast-secreted proteins could be achieved by single, previously identified, factors produced by breast cancer cells. We found that although single factors could induce a subset of genes, even combinations of factors failed to induce the full repertoire of functionally important fibroblast-secreted proteins. Together, these results delineate a complex network of tumor-fibroblast interactions that act in parallel to promote tumorigenicity and suggest that effective anti

  4. Chitosan-based nanoparticles for survivin targeted siRNA delivery in breast tumor therapy and preventing its metastasis.

    Science.gov (United States)

    Sun, Ping; Huang, Wei; Jin, Mingji; Wang, Qiming; Fan, Bo; Kang, Lin; Gao, Zhonggao

    Nanoparticle-mediated small interfering RNA (siRNA) delivery is a promising therapeutic strategy in various cancers. However, it is difficult to deliver degradative siRNA to tumor tissue, and thus a safe and efficient vector for siRNA delivery is essential for cancer therapy. In this study, poly(ethylene glycol)-modified chitosan (PEG-CS) was synthesized successfully for delivering nucleic acid drug. We deemed that PEGylated CS could improve its solubility by forming a stable siRNA loaded in nanoparticles, and enhancing transfection efficiency of siRNA-loaded CS nanoparticles in cancer cell line. The research results showed that siRNA loaded in PEGylated CS (PEG-CS/siRNA) nanoparticles with smaller particle size had superior structural stability in the physical environment compared to CS nanoparticles. The data of in vitro antitumor activity revealed that 4T1 tumor cell growth was significantly inhibited and cellular uptake of PEG-CS/siRNA nanoparticles in 4T1 cells was dramatically enhanced compared to naked siRNA groups. The results from flow cytometry and confocal laser scanning microscopy showed that PEG-CS/siRNA nanoparticles were more easily taken up than naked siRNA. Importantly, PEG-CS/siRNA nanoparticles significantly reduced the growth of xenograft tumors of 4T1 cells in vivo. It has been demonstrated that the PEG-CS is a safe and efficient vector for siRNA delivery, and it can effectively reduce tumor growth and prevent metastasis.

  5. Understanding social and sexual networks of sexual minority men and transgender women in Guatemala city to improve HIV prevention efforts.

    Science.gov (United States)

    Tucker, C; Arandi, C Galindo; Bolaños, J Herbert; Paz-Bailey, G; Barrington, C

    2014-11-01

    Sexual minority men and transgender women are disproportionately affected by HIV in Guatemala. Innovative prevention strategies are urgently needed to address these disparities. While social network approaches are frequently used to reach sexual minorities, little is known about the unique network characteristics among sub-groups. We conducted in-depth qualitative interviews with 13 gay-identifying men, eight non-gay-identifying men who have sex with men (MSM) and eight transgender women in Guatemala City. Using narrative and thematic coding procedures, we identified distinct patterns in the size, composition, and overlap between social and sexual networks across groups. Gay-identifying men had the largest, most supportive social networks, predominantly comprising family. For both non-gay-identifying MSM and transgender women, friends and sex clients provided more support. Transgender women reported the smallest social networks, least social support, and the most discrimination. HIV prevention efforts should be tailored to the specific sexual minority population and engage with strong ties.

  6. Understanding Social and Sexual Networks of Sexual Minority Men and Transgender Women in Guatemala City to Improve HIV Prevention Efforts

    Science.gov (United States)

    Tucker, C.; Arandi, C. Galindo; Bolaños, J. Herbert; Paz-Bailey, G.; Barrington, C.

    2015-01-01

    Sexual minority men and transgender women are disproportionately affected by HIV in Guatemala. Innovative prevention strategies are urgently needed to address these disparities. While social network approaches are frequently used to reach sexual minorities, little is known about the unique network characteristics among sub-groups. We conducted in-depth qualitative interviews with 13 gay-identifying men, eight non-gay-identifying men who have sex with men (MSM) and eight transgender women in Guatemala City. Using narrative and thematic coding procedures, we identified distinct patterns in the size, composition, and overlap between social and sexual networks across groups. Gay-identifying men had the largest, most supportive social networks, predominantly comprising family. For both non-gay-identifying MSM and transgender women, friends and sex clients provided more support. Transgender women reported the smallest social networks, least social support, and the most discrimination. HIV prevention efforts should be tailored to the specific sexual minority population and engage with strong ties. PMID:25418236

  7. Angiogenesis and anti-angiogenesis: Perspectives for the treatment of solid tumors

    NARCIS (Netherlands)

    Hinsbergh, V.W.M. van; Collen, A.; Koolwijk, P.

    1999-01-01

    Angiogenesis is the formation of new blood vessels from preexisting ones. Many solid tumors depend on an extensive newly formed vascular network to become nourished and to expand. Tumor cells induce the formation of an extensive but aberrant vascular network by the secretion of angiogenic factors. A

  8. [Prevention and Treatment of Eating Disorders: The Health Care Network Anorexia and Bulimia nervosa].

    Science.gov (United States)

    Weigel, Angelika; Gumz, Antje; Kästner, Denise; Romer, Georg; Wegscheider, Karl; Löwe, Bernd

    2015-07-01

    The "Health care network anorexia and bulimia nervosa", a subproject of psychenet - the Hamburg network for mental health - aims to decrease the incidence of eating disorders as well as the risk for chronic illness courses. One focal project, therefore, evaluates a school-based prevention manual in a randomized controlled trial. The other one examines the impact of a systemic public health intervention on early treatment initiation in anorexia nervosa. The present article provides an overview about study design and interventions in both focal projects as well as preliminary results. © Georg Thieme Verlag KG Stuttgart · New York.

  9. The role of succinylcholine in the prevention of the obturator nerve reflex during transurethral resection of bladder tumors

    International Nuclear Information System (INIS)

    Cesur, M.; Erdem, Ali F.; Alici, Haci A.; Yuksek, Mustafa S.; Yapanoglu, T.; Aksoy, Y.

    2008-01-01

    Objective was to present our 8 year experience in the prevention of the obturator nerve reflex during transurethral resection of bladder tumors. This study was performed in Ataturk University Hospital between 1999 and 2007. We retrospectively reviewed the records of 89 patients with inferolateral bladder tumors, who underwent transurethral resection under epidural or general anesthesia and requested obturator nerve reflex inhibition. Epidural anesthesia was administered to 57 patients, while the remaining 32 patients underwent general anesthesia via mask; and succinylcholine was administered prior to resection. Of the 57 patients received epidural anesthesia, 18 were diagnosed as inferolateral bladder tumors during endoscopy and had to undergo general anesthesia. Obturator nerve block was attempted preoperatively in 39 patients. However, a nerve identification failure, hematoma and 4 obturator nerve reflex events, despite the block, were observed and these patients were subjected to general anesthesia with succinylcholine. Fifty-six patients (32 patients initially had general anesthesia and 24 converted from epidural to general anesthesia) were all given succinylcholine prior to resection. Due to its mechanisms of action, succinylcholine is completely effective and represents a simple alternative to obturator nerve block. No contraction was observed in any patient given succinylcholine. (author)

  10. Preventative vaccine-loaded mannosylated chitosan nanoparticles intended for nasal mucosal delivery enhance immune responses and potent tumor immunity.

    Science.gov (United States)

    Yao, Wenjun; Peng, Yixing; Du, Mingzhu; Luo, Juan; Zong, Li

    2013-08-05

    Chitosan (CS) has been extensively used as a protein drug and gene delivery carrier, but its delivery efficiency is unsatisfactory. In this study, a mannose ligand was used to modify CS, which could enhance the delivery efficiency of CS via mannose receptor-mediated endocytosis. A preventative anti-GRP DNA vaccine (pCR3.1-VS-HSP65-TP-GRP6-M2, pGRP) was condensed with mannosylated chitosan (MCS) to form MCS/pGRP nanoparticles. Nanoparticles were intranasally administered in a subcutaneous mice prostate carcinoma model to evaluate the efficacy on inhibition of the growth of tumor cells. The titers of anti-GRP IgG that lasted for 11 weeks were significantly higher than that for administration of CS/pGRP nanoparticles (p intramuscular administration of a pGRP solution (p nanoparticles could suppress the growth of tumor cells. The average tumor weight (0.79 ± 0.30 g) was significantly lower than that in the CS/pGRP nanoparticle group (1.69 ± 0.15 g) (p nanoparticles bound with C-type lectin receptors on macrophages. MCS was an efficient targeting gene delivery carrier and could be used in antitumor immunotherapy.

  11. Illustration, detection and prevention of sleep deprivation anomaly in mobile ad hoc networks

    International Nuclear Information System (INIS)

    Nadeem, A.; Ahsan, K.; Sarim, M.

    2017-01-01

    MANETs (Mobile Ad Hoc Networks) have applications in various walks of life from rescue operations to battle field operations, personal and commercial. However, routing operations in MANETs are still vulnerable to anomalies and DoS (Denial of Service) attacks such as sleep deprivation. In SD (Sleep Deprivation) attack malicious node exploits the vulnerability in the route discovery function of the reactive routing protocol for example AODV (Ad Hoc On-Demand Distance Vector). In this paper, we first illustrate the SD anomaly in MANETs and then propose a SD detection and prevention algorithm which efficiently deals with this attack. We assess the performance of our proposed approach through simulation, evaluating its successfulness using different network scenarios. (author)

  12. The microbiome modulates the tumor macroenvironment.

    Science.gov (United States)

    Erdman, Susan E; Poutahidis, Theofilos

    2014-01-01

    Earlier investigations of the tumor microenvironment unveiled systemic networks presenting novel therapeutic opportunities. It has been recently shown that gut microbes modulate whole host immune and neuroendocrine factors impacting the fate of distant preneoplastic lesions toward malignancy or regression. These findings establish a new paradigm of holobiont therapeutic engineering in emerging tumor macroenvironments.

  13. Liver Tumor Segmentation from MR Images Using 3D Fast Marching Algorithm and Single Hidden Layer Feedforward Neural Network

    Directory of Open Access Journals (Sweden)

    Trong-Ngoc Le

    2016-01-01

    Full Text Available Objective. Our objective is to develop a computerized scheme for liver tumor segmentation in MR images. Materials and Methods. Our proposed scheme consists of four main stages. Firstly, the region of interest (ROI image which contains the liver tumor region in the T1-weighted MR image series was extracted by using seed points. The noise in this ROI image was reduced and the boundaries were enhanced. A 3D fast marching algorithm was applied to generate the initial labeled regions which are considered as teacher regions. A single hidden layer feedforward neural network (SLFN, which was trained by a noniterative algorithm, was employed to classify the unlabeled voxels. Finally, the postprocessing stage was applied to extract and refine the liver tumor boundaries. The liver tumors determined by our scheme were compared with those manually traced by a radiologist, used as the “ground truth.” Results. The study was evaluated on two datasets of 25 tumors from 16 patients. The proposed scheme obtained the mean volumetric overlap error of 27.43% and the mean percentage volume error of 15.73%. The mean of the average surface distance, the root mean square surface distance, and the maximal surface distance were 0.58 mm, 1.20 mm, and 6.29 mm, respectively.

  14. Harnessing and blending the power of two research networks to improve prevention science and public health practice

    Science.gov (United States)

    Vanderpool, Robin C.; Brownson, Ross C.; Mays, Glen P.; Crosby, Richard A.; Wyatt, Stephen W.

    2015-01-01

    Strategic collaborations are essential in moving public health research and practice forward1, particularly in light of escalating fiscal and environmental challenges facing the public health community. This commentary provides background and context for an emerging partnership between two national networks, Prevention Research Centers (PRCs) and Public Health Practice-Based Research Networks (PBRNs), to impact public health practice. Supported by CDC, PRCs are celebrating over 25 years of transdisciplinary applied prevention research grounded in community and stakeholder engagement. Public Health PBRNs, funded by the Robert Wood Johnson Foundation, conduct innovative public health services and systems research with public health agencies and community partners to improve public health decision-making. By utilizing each of the networks’ respective strengths and resources, collaborative ventures between PRCs and Public Health PBRNs can enhance the translation of applied prevention research to evidence-based practice and empirically investigate novel public health practices developed in the field. Three current PRC-Public Health PBRNs projects are highlighted and future research directions are discussed. Improving the interconnectedness of prevention research and public health practice is essential to improve the health of the Nation. PMID:24237918

  15. Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells

    Science.gov (United States)

    2011-01-01

    essential oil hydrodistilled at 100 oC was more potent than the essential oil prepared at 78 oC in inducing cancer cell death, preventing the cellular network formation (MDA-MB-231) cells on Matrigel, causing the breakdown of multicellular tumor spheroids (T47D cells), and regulating molecules involved in apoptosis, signal transduction, and cell cycle progression. Conclusions Similar to our previous observations in human bladder cancer cells, Boswellia sacra essential oil induces breast cancer cell-specific cytotoxicity. Suppression of cellular network formation and disruption of spheroid development of breast cancer cells by Boswellia sacra essential oil suggest that the essential oil may be effective for advanced breast cancer. Consistently, the essential oil represses signaling pathways and cell cycle regulators that have been proposed as therapeutic targets for breast cancer. Future pre-clinical and clinical studies are urgently needed to evaluate the safety and efficacy of Boswellia sacra essential oil as a therapeutic agent for treating breast cancer. PMID:22171782

  16. Shenlingbaishusan, a chines herbal medicine, in the prevention and treatment of colo-rectal radiation reactions during pelvic tumor radiotherapy

    International Nuclear Information System (INIS)

    Hu Yueran; Liu Yajie; Wu Chaoquan; Chen Chuping; Wang Yaobang; Li Xianming; Zhong Heli; Wu Dong

    2005-01-01

    Objective: To study the effect of traditional Chinese herbal medicine-Shenlingbaishusan in preventing and treating colon and rectum radiation reactions. Methods: Ninty-six patients with female pelvic tumor (cervical and endometrial cancer) were randomly divided into two groups: radiotherapy (RT) alone group (47 patients) and RT+ Shenlingbaishusan group(49 patients). RT in both groups, being similar, 1.8-2.0 Gy/per fraction, five fractions/per week, to a total dose of 48-50 Gy/5-6 weeks to the whole pelvis by external irradiation plus brachytherapy: to a total dose of 42-49 Gy/6-7 weeks for cervix carcinoma, and 10-15 Gy/1-2 weeks for endometrial cancer. Results: All patients have been were followed for more than one year after radiotherapy. The incidence of acute and late colon and rectum radiation reactions. was:15 patients in the RT + Shenlingbaishusan group: grade I10 patients, Grade II3 patients, grade III2 patients incontrast to the 47 patients in the RT group: grade I 24 patients, grade II 14 patients and grade III 9 patients (P<0.01). Conclusions: The traditional Chinese medicine-Shenlingbaishusan is effective in preventing and treating colon and rectum radiation reactions during pelvic tumor radiotherapy.(authors)

  17. Out-of-Sequence Preventative Cell Dispatching for Multicast Input-Queued Space-Memory-Memory Clos-Network

    DEFF Research Database (Denmark)

    Yu, Hao; Ruepp, Sarah Renée; Berger, Michael Stübert

    2011-01-01

    This paper proposes two out-of-sequence (OOS) preventative cell dispatching algorithms for the multicast input-queued space-memory-memory (IQ-SMM) Clos-network switch architecture, i.e. the multicast flow-based DSRR (MF-DSRR) and the multicast flow-based round-robin (MFRR). Treating each cell...

  18. SU-F-R-44: Modeling Lung SBRT Tumor Response Using Bayesian Network Averaging

    International Nuclear Information System (INIS)

    Diamant, A; Ybarra, N; Seuntjens, J; El Naqa, I

    2016-01-01

    Purpose: The prediction of tumor control after a patient receives lung SBRT (stereotactic body radiation therapy) has proven to be challenging, due to the complex interactions between an individual’s biology and dose-volume metrics. Many of these variables have predictive power when combined, a feature that we exploit using a graph modeling approach based on Bayesian networks. This provides a probabilistic framework that allows for accurate and visually intuitive predictive modeling. The aim of this study is to uncover possible interactions between an individual patient’s characteristics and generate a robust model capable of predicting said patient’s treatment outcome. Methods: We investigated a cohort of 32 prospective patients from multiple institutions whom had received curative SBRT to the lung. The number of patients exhibiting tumor failure was observed to be 7 (event rate of 22%). The serum concentration of 5 biomarkers previously associated with NSCLC (non-small cell lung cancer) was measured pre-treatment. A total of 21 variables were analyzed including: dose-volume metrics with BED (biologically effective dose) correction and clinical variables. A Markov Chain Monte Carlo technique estimated the posterior probability distribution of the potential graphical structures. The probability of tumor failure was then estimated by averaging the top 100 graphs and applying Baye’s rule. Results: The optimal Bayesian model generated throughout this study incorporated the PTV volume, the serum concentration of the biomarker EGFR (epidermal growth factor receptor) and prescription BED. This predictive model recorded an area under the receiver operating characteristic curve of 0.94(1), providing better performance compared to competing methods in other literature. Conclusion: The use of biomarkers in conjunction with dose-volume metrics allows for the generation of a robust predictive model. The preliminary results of this report demonstrate that it is possible

  19. SU-F-R-44: Modeling Lung SBRT Tumor Response Using Bayesian Network Averaging

    Energy Technology Data Exchange (ETDEWEB)

    Diamant, A; Ybarra, N; Seuntjens, J [McGill University, Montreal, Quebec (Canada); El Naqa, I [University of Michigan, Ann Arbor, MI (United States)

    2016-06-15

    Purpose: The prediction of tumor control after a patient receives lung SBRT (stereotactic body radiation therapy) has proven to be challenging, due to the complex interactions between an individual’s biology and dose-volume metrics. Many of these variables have predictive power when combined, a feature that we exploit using a graph modeling approach based on Bayesian networks. This provides a probabilistic framework that allows for accurate and visually intuitive predictive modeling. The aim of this study is to uncover possible interactions between an individual patient’s characteristics and generate a robust model capable of predicting said patient’s treatment outcome. Methods: We investigated a cohort of 32 prospective patients from multiple institutions whom had received curative SBRT to the lung. The number of patients exhibiting tumor failure was observed to be 7 (event rate of 22%). The serum concentration of 5 biomarkers previously associated with NSCLC (non-small cell lung cancer) was measured pre-treatment. A total of 21 variables were analyzed including: dose-volume metrics with BED (biologically effective dose) correction and clinical variables. A Markov Chain Monte Carlo technique estimated the posterior probability distribution of the potential graphical structures. The probability of tumor failure was then estimated by averaging the top 100 graphs and applying Baye’s rule. Results: The optimal Bayesian model generated throughout this study incorporated the PTV volume, the serum concentration of the biomarker EGFR (epidermal growth factor receptor) and prescription BED. This predictive model recorded an area under the receiver operating characteristic curve of 0.94(1), providing better performance compared to competing methods in other literature. Conclusion: The use of biomarkers in conjunction with dose-volume metrics allows for the generation of a robust predictive model. The preliminary results of this report demonstrate that it is possible

  20. Lack of evidence to favor specific preventive interventions in psychosis: a network meta‐analysis

    Science.gov (United States)

    Davies, Cathy; Cipriani, Andrea; Ioannidis, John P.A.; Radua, Joaquim; Stahl, Daniel; Provenzani, Umberto; McGuire, Philip; Fusar‐Poli, Paolo

    2018-01-01

    Preventing psychosis in patients at clinical high risk may be a promising avenue for pre‐emptively ameliorating outcomes of the most severe psychiatric disorder. However, information on how each preventive intervention fares against other currently available treatment options remains unavailable. The aim of the current study was to quantify the consistency and magnitude of effects of specific preventive interventions for psychosis, comparing different treatments in a network meta‐analysis. PsycINFO, Web of Science, Cochrane Central Register of Controlled Trials, and unpublished/grey literature were searched up to July 18, 2017, to identify randomized controlled trials conducted in individuals at clinical high risk for psychosis, comparing different types of intervention and reporting transition to psychosis. Two reviewers independently extracted data. Data were synthesized using network meta‐analyses. The primary outcome was transition to psychosis at different time points and the secondary outcome was treatment acceptability (dropout due to any cause). Effect sizes were reported as odds ratios and 95% confidence intervals (CIs). Sixteen studies (2,035 patients, 57% male, mean age 20.1 years) reported on risk of transition. The treatments tested were needs‐based interventions (NBI); omega‐3 + NBI; ziprasidone + NBI; olanzapine + NBI; aripiprazole + NBI; integrated psychological interventions; family therapy + NBI; D‐serine + NBI; cognitive behavioural therapy, French & Morrison protocol (CBT‐F) + NBI; CBT‐F + risperidone + NBI; and cognitive behavioural therapy, van der Gaag protocol (CBT‐V) + CBT‐F + NBI. The network meta‐analysis showed no evidence of significantly superior efficacy of any one intervention over the others at 6 and 12 months (insufficient data were available after 12 months). Similarly, there was no evidence for intervention differences in acceptability at either time point. Tests

  1. Outcomes of Interorganizational Networks in Canada for Chronic Disease Prevention: Insights From a Concept Mapping Study, 2015.

    Science.gov (United States)

    Willis, Cameron; Kernoghan, Alison; Riley, Barbara; Popp, Janice; Best, Allan; Milward, H Brinton

    2015-11-19

    We conducted a mixed methods study from June 2014 to March 2015 to assess the perspectives of stakeholders in networks that adopt a population approach for chronic disease prevention (CDP). The purpose of the study was to identify important and feasible outcome measures for monitoring network performance. Participants from CDP networks in Canada completed an online concept mapping exercise, which was followed by interviews with network stakeholders to further understand the findings. Nine concepts were considered important outcomes of CDP networks: enhanced learning, improved use of resources, enhanced or increased relationships, improved collaborative action, network cohesion, improved system outcomes, improved population health outcomes, improved practice and policy planning, and improved intersectoral engagement. Three themes emerged from participant interviews related to measurement of the identified concepts: the methodological difficulties in measuring network outcomes, the dynamic nature of network evolution and function and implications for outcome assessment, and the challenge of measuring multisectoral engagement in CDP networks. Results from this study provide initial insights into concepts that can be used to describe the outcomes of networks for CDP and may offer foundations for strengthening network outcome-monitoring strategies and methodologies.

  2. Prevention of photoimmunosuppression and photocarcinogenesis by topical nicotinamide

    International Nuclear Information System (INIS)

    Gensler, H.L.

    1997-01-01

    Ultraviolet (UV) B irradiation leads to a potent immunosuppression of the capacity to reject syngeneic, antigenic tumors. If this immunosuppression is critical for the development of most skin tumors, then its prevention should result in prevention of photocarcinogenesis. We previously showed a correlation between the inhibition of photoimmunosuppression and prevention of photocarcinogenesis by dl-alpha-tocopherol, tannic acid, or alpha-difluoro methylornithine. The current study was designed to determine whether topical nicotinamide, the active form of vitamin B-3, or niacin, prevents immunosuppression and skin cancer in UV-irradiated mice. In a passive transfer assay for immunosuppression, splenocytes from UV-irradiated mice enhanced the growth of antigenic tumor challenges in recipient mice. Treatment of the UV-irradiated mice with 40 micromoles of nicotinamide twice weekly starting two weeks before UV irradiation and throughout the experiment prevented this immunosuppresion. UVB irradiation consisted of five weekly 30-minute exposures to banks of six FS40 Westinghouse fluorescent sunlamps. Mice received approximatety 6.2 x 10(5) J/m(2) in the passive transfer assays and 1.09 x 10(6) J/m(2) in the photocarcinogenesis studies. Application of nicotinamide to UV-irradiated mice reduced skin tumor incidence from 75% to 42.5% (p = 0.016, Cox proportional hazards analysis). Thus topical nicotinamide prevented the immunosuppression and skin tumor induction by UVB irradiation

  3. Social network characteristics and HIV vulnerability among transgender persons in San Salvador: identifying opportunities for HIV prevention strategies.

    Science.gov (United States)

    Barrington, Clare; Wejnert, Cyprian; Guardado, Maria Elena; Nieto, Ana Isabel; Bailey, Gabriela Paz

    2012-01-01

    The purpose of this study is to improve understanding of HIV vulnerability and opportunities for HIV prevention within the social networks of male-to-female transgender persons in San Salvador, El Salvador. We compare HIV prevalence and behavioral data from a sample of gay-identified men who have sex with men (MSM) (n = 279), heterosexual or bisexual identified MSM (n = 229) and transgender persons (n = 67) recruited using Respondent Driven Sampling. Transgender persons consistently reported higher rates of HIV risk behavior than the rest of the study population and were significantly more likely to be involved in sex work. While transgender persons reported the highest rates of exposure to HIV educational activities they had the lowest levels of HIV-related knowledge. Transgender respondents' social networks were homophilous and efficient at recruiting other transgender persons. Findings suggest that transgender social networks could provide an effective and culturally relevant opportunity for HIV prevention efforts in this vulnerable population.

  4. Malignant renal tumors in pediatrics

    International Nuclear Information System (INIS)

    Pena, C.; Torterolo, J.; Irigoyen, B.; Bel, M.; Elias, E.

    2004-01-01

    Introduction: Professionals who work in pediatric oncology, we see childhood cancer as a common disease, but in fact constitutes about 2% of all cancers diagnosed worldwide. Wilms tumor accounts for 6% of all childhood tumors and presentation bilateral accounts for 4-6% of all Wilms tumors diagnosed. Theoretical Framework: In the period between the year 1994-2003 period were attended in the Pediatric Hematology-Oncology Center, a total of 29 cases of malignant renal tumors, corresponding to 86% (25 cases) to Wilms tumor or nephroblastoma tumor. The Wilms is of embryonic origin, capable of metastatic spread, (85% lungs 15% liver). Very sensitive to chemotherapy and radiotherapy, which confers high cure rates (85%); having a multidisciplinary treatment model, combining surgery, chemotherapy, and radiotherapy. The role of nursing in comprehensive cancer care child is essential in the prevention and early detection of side effects or complications. Case report: S.D. currently 10 years old. In 10/1994, at 8 months of age, was diagnosed with bilateral Wilms tumor. On admission her weight was 8200gr with abdominal circumference 50cm. Conducted pre-operative MDT and 02/1995 nephrectomy of the left kidney and right kidney lumpectomy (tumor nodule 420gr. and a 250gr.). MDT begins in 03/1995 01/1996 ending. 09/2003 with abdominal pain and vomiting, and kidney failure. 10/2003 lumpectomy biopsy (sclerotic nodule associated with maturation nephroblastoma). Currently severe renal insufficiency plan enters dialysis. Nursing process: Objectives: 1) To prepare the child and family to the side effects and possible complications of chemotherapy and / or radiotherapy 2) Prevent and minimize related complications tumor and / or treatment. Care Plan comprises four stages: A) rating and customer income. B) Implement care chemotherapy C) post-operative Care D) Implement radiation care

  5. Building African Capacity for HIV/AIDS Prevention Trials

    International Development Research Centre (IDRC) Digital Library (Canada)

    Canada-Africa Prevention Trials Network : Building African Capacity for HIV/AIDS Prevention Trials. The Canada-Africa Prevention Trials Network (CAPT Network) was formed through a capacity building grant from the Global Health Research Initiative (GHRI). The Network comprises eight African centres (four in Uganda, ...

  6. The EUVAC-NET project: creation and operation of a surveillance community network for vaccine preventable infectious diseases.

    Science.gov (United States)

    Glismann, S; Rønne, T; Tozzi, A

    2001-06-01

    The EUVAC-NET network is in charge of the epidemiological surveillance and control of vaccine preventable diseases. It is coordinated by the SSI in Denmark, in collaboration with the ISS in Italy. The two main diseases targeted by the network are measles and pertussis. A collaboration is planned with the PHLS for the monitoring of Haemophilus influenzae b. EUVAC-NET includes the Member States of the European Union, and Iceland, Norway and Switzerland.

  7. Leveraging Hypoxia-Activated Prodrugs to Prevent Drug Resistance in Solid Tumors.

    Directory of Open Access Journals (Sweden)

    Danika Lindsay

    2016-08-01

    Full Text Available Experimental studies have shown that one key factor in driving the emergence of drug resistance in solid tumors is tumor hypoxia, which leads to the formation of localized environmental niches where drug-resistant cell populations can evolve and survive. Hypoxia-activated prodrugs (HAPs are compounds designed to penetrate to hypoxic regions of a tumor and release cytotoxic or cytostatic agents; several of these HAPs are currently in clinical trial. However, preliminary results have not shown a survival benefit in several of these trials. We hypothesize that the efficacy of treatments involving these prodrugs depends heavily on identifying the correct treatment schedule, and that mathematical modeling can be used to help design potential therapeutic strategies combining HAPs with standard therapies to achieve long-term tumor control or eradication. We develop this framework in the specific context of EGFR-driven non-small cell lung cancer, which is commonly treated with the tyrosine kinase inhibitor erlotinib. We develop a stochastic mathematical model, parametrized using clinical and experimental data, to explore a spectrum of treatment regimens combining a HAP, evofosfamide, with erlotinib. We design combination toxicity constraint models and optimize treatment strategies over the space of tolerated schedules to identify specific combination schedules that lead to optimal tumor control. We find that (i combining these therapies delays resistance longer than any monotherapy schedule with either evofosfamide or erlotinib alone, (ii sequentially alternating single doses of each drug leads to minimal tumor burden and maximal reduction in probability of developing resistance, and (iii strategies minimizing the length of time after an evofosfamide dose and before erlotinib confer further benefits in reduction of tumor burden. These results provide insights into how hypoxia-activated prodrugs may be used to enhance therapeutic effectiveness in the

  8. Discriminating between benign and malignant breast tumors using 3D convolutional neural network in dynamic contrast enhanced-MR images

    Science.gov (United States)

    Li, Jing; Fan, Ming; Zhang, Juan; Li, Lihua

    2017-03-01

    Convolutional neural networks (CNNs) are the state-of-the-art deep learning network architectures that can be used in a range of applications, including computer vision and medical image analysis. It exhibits a powerful representation learning mechanism with an automated design to learn features directly from the data. However, the common 2D CNNs only use the two dimension spatial information without evaluating the correlation between the adjoin slices. In this study, we established a method of 3D CNNs to discriminate between malignant and benign breast tumors. To this end, 143 patients were enrolled which include 66 benign and 77 malignant instances. The MRI images were pre-processed for noise reduction and breast tumor region segmentation. Data augmentation by spatial translating, rotating and vertical and horizontal flipping is applied to the cases to reduce possible over-fitting. A region-of-interest (ROI) and a volume-of-interest (VOI) were segmented in 2D and 3D DCE-MRI, respectively. The enhancement ratio for each MR series was calculated for the 2D and 3D images. The results for the enhancement ratio images in the two series are integrated for classification. The results of the area under the ROC curve(AUC) values are 0.739 and 0.801 for 2D and 3D methods, respectively. The results for 3D CNN which combined 5 slices for each enhancement ratio images achieved a high accuracy(Acc), sensitivity(Sens) and specificity(Spec) of 0.781, 0.744 and 0.823, respectively. This study indicates that 3D CNN deep learning methods can be a promising technology for breast tumor classification without manual feature extraction.

  9. Pituitary Tumors: Condition Information

    Science.gov (United States)

    ... hormones. They can press on or damage the pituitary gland and prevent it from secreting adequate levels of hormones. National Institute of Neurological Disorders and Stroke. (2010). NINDS pituitary tumors information page . ...

  10. Dentists’ practice patterns regarding caries prevention: results from a dental practice-based research network

    Science.gov (United States)

    Yokoyama, Yoko; Kakudate, Naoki; Sumida, Futoshi; Matsumoto, Yuki; Gilbert, Gregg H; Gordan, Valeria V

    2013-01-01

    Objective The purposes of this study were to (1) quantify dentists' practice patterns regarding caries prevention and (2) test the hypothesis that certain dentists' characteristics are associated with these practice patterns. Design The study used a cross-sectional study design consisting of a questionnaire survey. Participants The study queried dentists who worked in outpatient dental practices who were affiliated with the Dental Practice-Based Research Network Japan, which seeks to engage dentists in investigating research questions and sharing experiences and expertise (n=282). Measurement Dentists were asked about their practice patterns regarding caries preventive dentistry. Background data on patients, practice and dentist were also collected. Results 38% of dentists (n=72) provided individualised caries prevention to more than 50% of their patients. Overall, 10% of the time in daily practice was spent on caries preventive dentistry. Dentists who provided individualised caries prevention to more than 50% of their patients spent significantly more time on preventive care and less time on removable prosthetics treatment, compared to dentists who did not provide individualised caries prevention. Additionally, they provided oral hygiene instruction, patient education, fluoride recommendations, intraoral photographs taken and diet counselling to their patients significantly more often than dentists who did not provide individualised caries prevention. Multiple logistic regression analysis suggested that the percentage of patients interested in caries prevention and the percentage of patients who received hygiene instruction, were both associated with the percentage of patients who receive individualised caries prevention. Conclusions We identified substantial variation in dentists' practice patterns regarding preventive dentistry. Individualised caries prevention was significantly related to provision of other preventive services and to having a higher percentage

  11. Cancer stem cells and the tumor microenvironment: interplay in tumor heterogeneity.

    Science.gov (United States)

    Albini, Adriana; Bruno, Antonino; Gallo, Cristina; Pajardi, Giorgio; Noonan, Douglas M; Dallaglio, Katiuscia

    2015-01-01

    Tumor cells able to recapitulate tumor heterogeneity have been tracked, isolated and characterized in different tumor types, and are commonly named Cancer Stem Cells or Cancer Initiating Cells (CSC/CIC). CSC/CIC are disseminated in the tumor mass and are resistant to anti-cancer therapies and adverse conditions. They are able to divide into another stem cell and a "proliferating" cancer cell. They appear to be responsible for disease recurrence and metastatic dissemination even after apparent eradication of the primary tumor. The modulation of CSC/CIC activities by the tumor microenvironment (TUMIC) is still poorly known. CSC/CIC may mutually interact with the TUMIC in a special and unique manner depending on the TUMIC cells or proteins encountered. The TUMIC consists of extracellular matrix components as well as cellular players among which endothelial, stromal and immune cells, providing and responding to signals to/from the CSC/CIC. This interplay can contribute to the mechanisms through which CSC/CIC may reside in a dormant state in a tissue for years, later giving rise to tumor recurrence or metastasis in patients. Different TUMIC components, including the connective tissue, can differentially activate CIC/CSC in different areas of a tumor and contribute to the generation of cancer heterogeneity. Here, we review possible networking activities between the different components of the tumor microenvironment and CSC/CIC, with a focus on its role in tumor heterogeneity and progression. We also summarize novel therapeutic options that could target both CSC/CIC and the microenvironment to elude resistance mechanisms activated by CSC/CIC, responsible for disease recurrence and metastases.

  12. The effectiveness of different interventions to promote poison prevention behaviours in households with children: a network meta-analysis.

    Science.gov (United States)

    Achana, Felix A; Sutton, Alex J; Kendrick, Denise; Wynn, Persephone; Young, Ben; Jones, David R; Hubbard, Stephanie J; Cooper, Nicola J

    2015-01-01

    There is evidence from 2 previous meta-analyses that interventions to promote poison prevention behaviours are effective in increasing a range of poison prevention practices in households with children. The published meta-analyses compared any intervention against a "usual care or no intervention" which potentially limits the usefulness of the analysis to decision makers. We aim to use network meta-analysis to simultaneously evaluate the effectiveness of different interventions to increase prevalence of safe storage of i) Medicines only, ii) Other household products only, iii) Poisons (both medicines and non-medicines), iv) Poisonous plants; and v) Possession of poison control centre (PCC) telephone number in households with children. Data on the effectiveness of poison prevention interventions was extracted from primary studies identified in 2 newly-undertaken systematic reviews. Effect estimates were pooled across studies using a random effects network meta-analysis model. 28 of the 47 primary studies identified were included in the analysis. Compared to usual care intervention, the intervention with education and low cost/free equipment elements was most effective in promoting safe storage of medicines (odds ratio 2.51, 95% credible interval 1.01 to 6.00) while interventions with education, low cost/free equipment, home safety inspection and fitting components were most effective in promoting safe storage of other household products (2.52, 1.12 to 7.13), safe storage of poisons (11.10, 1.60 to 141.50) and possession of PCC number (38.82, 2.19 to 687.10). No one intervention package was more effective than the others in promoting safe storage of poisonous plants. The most effective interventions varied by poison prevention practice, but education alone was not the most effective intervention for any poison prevention practice. Commissioners and providers of poison prevention interventions should tailor the interventions they commission or provide to the poison

  13. The Structure of Policy Networks for Injury and Violence Prevention in 15 US Cities.

    Science.gov (United States)

    Harris, Jenine K; Jonson-Reid, Melissa; Carothers, Bobbi J; Fowler, Patrick

    Changes in policy can reduce violence and injury; however, little is known about how partnerships among organizations influence policy development, adoption, and implementation. To understand partnerships among organizations working on injury and violence prevention (IVP) policy, we examined IVP policy networks in 15 large US cities. In summer 2014, we recruited 15 local health departments (LHDs) to participate in the study. They identified an average of 28.9 local partners (SD = 10.2) working on IVP policy. In late 2014, we sent survey questionnaires to 434 organizations, including the 15 LHDs and their local partners, about their partnerships and the importance of each organization to local IVP policy efforts; 319 participated. We used network methods to examine the composition and structure of the policy networks. Each IVP policy network included the LHD and an average of 21.3 (SD = 6.9) local partners. On average, nonprofit organizations constituted 50.7% of networks, followed by government agencies (26.3%), schools and universities (11.8%), coalitions (11.2%), voluntary organizations (9.6%), hospitals (8.5%), foundations (2.2%), and for-profit organizations (0.7%). Government agencies were perceived as important by the highest proportion of partners. Perceived importance was significantly associated with forming partnerships in most networks; odds ratios ranged from 1.07 (95% CI, 1.02-1.13) to 2.35 (95% CI, 1.68-3.28). Organization type was significantly associated with partnership formation in most networks after controlling for an organization's importance to the network. Several strategies could strengthen local IVP policy networks, including (1) developing connections with partners from sectors that are not well integrated into the networks and (2) encouraging indirect or less formal connections with important but missing partners and partner types.

  14. The Structure of Policy Networks for Injury and Violence Prevention in 15 US Cities

    Science.gov (United States)

    Jonson-Reid, Melissa; Carothers, Bobbi J.; Fowler, Patrick

    2017-01-01

    Objectives: Changes in policy can reduce violence and injury; however, little is known about how partnerships among organizations influence policy development, adoption, and implementation. To understand partnerships among organizations working on injury and violence prevention (IVP) policy, we examined IVP policy networks in 15 large US cities. Methods: In summer 2014, we recruited 15 local health departments (LHDs) to participate in the study. They identified an average of 28.9 local partners (SD = 10.2) working on IVP policy. In late 2014, we sent survey questionnaires to 434 organizations, including the 15 LHDs and their local partners, about their partnerships and the importance of each organization to local IVP policy efforts; 319 participated. We used network methods to examine the composition and structure of the policy networks. Results: Each IVP policy network included the LHD and an average of 21.3 (SD = 6.9) local partners. On average, nonprofit organizations constituted 50.7% of networks, followed by government agencies (26.3%), schools and universities (11.8%), coalitions (11.2%), voluntary organizations (9.6%), hospitals (8.5%), foundations (2.2%), and for-profit organizations (0.7%). Government agencies were perceived as important by the highest proportion of partners. Perceived importance was significantly associated with forming partnerships in most networks; odds ratios ranged from 1.07 (95% CI, 1.02-1.13) to 2.35 (95% CI, 1.68-3.28). Organization type was significantly associated with partnership formation in most networks after controlling for an organization’s importance to the network. Conclusions: Several strategies could strengthen local IVP policy networks, including (1) developing connections with partners from sectors that are not well integrated into the networks and (2) encouraging indirect or less formal connections with important but missing partners and partner types. PMID:28426291

  15. Effects of different anticoagulant drugs on the prevention of complications in patients after arthroplasty: A network meta-analysis.

    Science.gov (United States)

    Gao, Ji-Hai; Chu, Xiu-Cheng; Wang, Lin-Liang; Ning, Bo; Zhao, Chuan-Xin

    2017-10-01

    After arthroplasty treatment, some complications commonly occur, such as early revision, infection/dislocation, and venous thromboembolism (VTE). This study aims to use a network meta-analysis to compare effects of 9 anticoagulant drugs (edoxaban, dabigatan, apixaban, rivaroxaban, warfarin, heparin, bemiparin, ximelagatran, and enoxaparin) in preventing postoperative complications in arthroplasty patients. After retrieving PubMed, Embase, and Cochrane Library database from the inception to November 2016, randomized controlled trials were enrolled. The integration of direct and indirect evidences was performed to calculate odd ratios and the surface under the cumulative ranking curves. Nineteen eligible randomized controlled trials were included. The network meta-analysis results showed that compared with warfarin, edoxaban, apixaban, and rivaroxaban had a lower incidence rate in asymptomatic deep venous thrombosis, which indicated that edoxaban, apixaban, and rivaroxaban had better effects on prevention. Similarly, in comparison to enoxaparin, edoxaban and rivaroxaban had better effect; rivaroxaban was better than ximelagatran in preventive effects. Compared with apixaban, edoxaban, dabigatan, rivaroxaban, and enoxaparin had a higher incidence rate in clinically relevant non-major bleeding, which showed that preventive effects were relatively poor. In addition, the results of the surface under the cumulative ranking curves showed that rivaroxaban and bemiparin worked best on symptomatic deep venous thrombosis and pulmonary embolism. In terms of bleeding, apixaban and warfarin had better preventive effects. Our findings suggested that rivaroxaban may work better in terms of symptomatic deep venous thrombosis and pulmonary embolism, whereas apixaban had better preventive effects in bleeding.

  16. 15-Hydroxyprostaglandin dehydrogenase inactivation as a mechanism of resistance to celecoxib chemoprevention of colon tumors.

    LENUS (Irish Health Repository)

    Yan, Min

    2009-06-09

    Pharmacologic inhibitors of the prostaglandin-synthesizing COX-2 oncogene prevent the development of premalignant human colon adenomas. However, resistance to treatment is common. In this study, we show that the adenoma prevention activity of the COX-2 inhibitor celecoxib requires the concomitant presence of the 15-hydroxyprostaglandin dehydrogenase (15-PGDH) tumor suppressor gene, and that loss of 15-PGDH expression imparts resistance to celecoxib\\'s anti-tumor effects. We first demonstrate that the adenoma-preventive activity of celecoxib is abrogated in mice genetically lacking 15-PGDH. In FVB mice, celecoxib prevents 85% of azoxymethane-induced tumors >1 mm in size, but is essentially inactive in preventing tumor induction in 15-PGDH-null animals. Indeed, celecoxib treated 15-PGDH null animals develop more tumors than do celecoxib naive WT mice. In parallel with the loss of tumor prevention activity, celecoxib-mediated suppression of colonic PGE(2) levels is also markedly attenuated in 15-PGDH-null versus WT mice. Finally, as predicted by the murine models, humans with low colonic 15-PGDH levels also exhibit celecoxib resistance. Specifically, in a colon adenoma prevention trial, in all cases tested, individuals who developed new adenomas while receiving celecoxib treatment were also found as having low colonic 15-PGDH levels.

  17. Síndrome de lise tumoral: uma revisão abrangente da literatura Acute tumor lysis syndrome: a comprehensive review

    Directory of Open Access Journals (Sweden)

    Michael Darmon

    2008-09-01

    égias baseadas no risco dos pacientes são necessários para limitar a alta morbidade e mortalidade desta complicação.Tumor lysis syndrome is characterized by the massive destruction of malignant cells and the release in the extra-cellular space of their content. While Tumor lysis syndrome may occur spontaneously before treatment, it usually develops shortly after the initiation of cytotoxic chemotherapy. These metabolites can overwhelm the homeostatic mechanisms with development of hyperuricaemia, hyperkalaemia, hyperphosphataemia, and hypocalcaemia. These biological manifestations may lead to clinical manifestations including, acute kidney injury, seizure, or sudden death that require intensive care. Since clinical tumor lysis syndrome is associated with a poor prognosis both prevention of tumor lysis syndrome and prevention of clinical consequences of tumor lysis syndrome are mandatory. The objective of this review is to describe pathophysiological mechanisms, biological and clinical manifestations of tumor Lysis syndrome, and to provide upto-date guidelines to ensure prevention of tumor lysis syndrome. Review of selected studies on tumor lysis syndrome published at the PubMed database www.pubmed.gov during the last 20 years. Additional references were retrieved from the studies initially selected. Tumor lysis syndrome is a frequent and life-threatening complication of the newly diagnosed malignancies. Preventive measures, including hydration, uricolytic agents, eviction of factors predisposing to acute kidney injury and, in the more severe patients, on prophylactic renal replacement therapy, are required to prevent or limit clinical consequences of Tumor lysis syndrome. However optimal timing and modalities of prevention remains unknown and may be modified by the changing spectrum of patients at risk of tumor lysis syndrome. Development and validation of risk based strategies is required to limit the high morbidity and mortality of this complication.

  18. Antioxidant intervention of smoking-induced lung tumor in mice by vitamin E and quercetin

    International Nuclear Information System (INIS)

    Yang, Jie; Li, Jun-Wen; Wang, Lu; Chen, Zhaoli; Shen, Zhi-Qiang; Jin, Min; Wang, Xin-Wei; Zheng, Yufei; Qiu, Zhi-Gang; Wang, Jing-feng

    2008-01-01

    Epidemiological and in vitro studies suggest that antioxidants such as quercetin and vitamin E (VE) can prevent lung tumor caused by smoking; however, there is limited evidence from animal studies. In the present study, Swiss mouse was used to examine the potential of quercetin and VE for prevention lung tumor induced by smoking. Our results suggest that the incidence of lung tumor and tumor multiplicity were 43.5% and 1.00 ± 0.29 in smoking group; Quercetin has limited effects on lung tumor prevention in this in vivo model, as measured by assays for free radical scavenging, reduction of smoke-induced DNA damage and inhibition of apoptosis. On the other hand, vitamin E drastically decreased the incidence of lung tumor and tumor multiplicity which were 17.0% and 0.32 ± 0.16, respectively (p < 0.05); and demonstrated prominent antioxidant effects, reduction of DNA damage and decreased cell apoptosis (p < 0.05). Combined treatment with quercetin and VE in this animal model did not demonstrate any effect greater than that due to vitamin E alone. In addition, gender differences in the occurrence of smoke induced-lung tumor and antioxidant intervention were also observed. We conclude that VE might prevent lung tumor induced by smoking in Swiss mice

  19. Exploratory Network Meta Regression Analysis of Stroke Prevention in Atrial Fibrillation Fails to Identify Any Interactions with Treatment Effect.

    Science.gov (United States)

    Batson, Sarah; Sutton, Alex; Abrams, Keith

    2016-01-01

    Patients with atrial fibrillation are at a greater risk of stroke and therefore the main goal for treatment of patients with atrial fibrillation is to prevent stroke from occurring. There are a number of different stroke prevention treatments available to include warfarin and novel oral anticoagulants. Previous network meta-analyses of novel oral anticoagulants for stroke prevention in atrial fibrillation acknowledge the limitation of heterogeneity across the included trials but have not explored the impact of potentially important treatment modifying covariates. To explore potentially important treatment modifying covariates using network meta-regression analyses for stroke prevention in atrial fibrillation. We performed a network meta-analysis for the outcome of ischaemic stroke and conducted an exploratory regression analysis considering potentially important treatment modifying covariates. These covariates included the proportion of patients with a previous stroke, proportion of males, mean age, the duration of study follow-up and the patients underlying risk of ischaemic stroke. None of the covariates explored impacted relative treatment effects relative to placebo. Notably, the exploration of 'study follow-up' as a covariate supported the assumption that difference in trial durations is unimportant in this indication despite the variation across trials in the network. This study is limited by the quantity of data available. Further investigation is warranted, and, as justifying further trials may be difficult, it would be desirable to obtain individual patient level data (IPD) to facilitate an effort to relate treatment effects to IPD covariates in order to investigate heterogeneity. Observational data could also be examined to establish if there are potential trends elsewhere. The approach and methods presented have potentially wide applications within any indication as to highlight the potential benefit of extending decision problems to include additional

  20. Exploratory Network Meta Regression Analysis of Stroke Prevention in Atrial Fibrillation Fails to Identify Any Interactions with Treatment Effect.

    Directory of Open Access Journals (Sweden)

    Sarah Batson

    Full Text Available Patients with atrial fibrillation are at a greater risk of stroke and therefore the main goal for treatment of patients with atrial fibrillation is to prevent stroke from occurring. There are a number of different stroke prevention treatments available to include warfarin and novel oral anticoagulants. Previous network meta-analyses of novel oral anticoagulants for stroke prevention in atrial fibrillation acknowledge the limitation of heterogeneity across the included trials but have not explored the impact of potentially important treatment modifying covariates.To explore potentially important treatment modifying covariates using network meta-regression analyses for stroke prevention in atrial fibrillation.We performed a network meta-analysis for the outcome of ischaemic stroke and conducted an exploratory regression analysis considering potentially important treatment modifying covariates. These covariates included the proportion of patients with a previous stroke, proportion of males, mean age, the duration of study follow-up and the patients underlying risk of ischaemic stroke.None of the covariates explored impacted relative treatment effects relative to placebo. Notably, the exploration of 'study follow-up' as a covariate supported the assumption that difference in trial durations is unimportant in this indication despite the variation across trials in the network.This study is limited by the quantity of data available. Further investigation is warranted, and, as justifying further trials may be difficult, it would be desirable to obtain individual patient level data (IPD to facilitate an effort to relate treatment effects to IPD covariates in order to investigate heterogeneity. Observational data could also be examined to establish if there are potential trends elsewhere. The approach and methods presented have potentially wide applications within any indication as to highlight the potential benefit of extending decision problems to

  1. Tumor-associated antigens identified by mRNA expression profiling as tumor rejection epitopes

    DEFF Research Database (Denmark)

    Andersen, Marie; Ruhwald, Morten; Thorn, Mette

    2003-01-01

    , suggesting that SM7 thymoma cells are recognized by the adaptive immune system of the host. However, prophylactic vaccination with RAD23-31 and RAD24-31 peptides combined with anti-CTLA4 Ab treatment and did not improve tumor resistance. Our data would indicate that vaccination with immunogenic peptides......Thirteen H-2b-binding peptides derived from six potentially overexpressed proteins in p53-/- thymoma (SM7) cells were studied for immunogenecity and vaccine-induced prevention of tumor growth in mice inoculated with SM7 tumor cells. Six of the peptides generated specific CTL responses after...... immunization, but only two of these peptides (RAD23-31 and RAD24-31) were capable of generating a weak vaccination-induced protection against adoptive tumor growth. SM7 inoculated mice treated with a blocking antibody against the inhibitory T cell signal transducing molecule CTLA4 appeared to delay tumor take...

  2. Bone tumor mimickers: A pictorial essay

    International Nuclear Information System (INIS)

    Mhuircheartaigh, Jennifer Ni; Lin, Yu-Ching; Wu, Jim S

    2014-01-01

    Focal lesions in bone are very common and many of these lesions are not bone tumors. These bone tumor mimickers can include numerous normal anatomic variants and non-neoplastic processes. Many of these tumor mimickers can be left alone, while others can be due to a significant disease process. It is important for the radiologist and clinician to be aware of these bone tumor mimickers and understand the characteristic features which allow discrimination between them and true neoplasms in order to avoid unnecessary additional workup. Knowing which lesions to leave alone or which ones require workup can prevent misdiagnosis and reduce patient anxiety

  3. Commensal bacteria modulate the tumor microenvironment.

    Science.gov (United States)

    Poutahidis, Theofilos; Erdman, Susan E

    2016-09-28

    It has been recently shown that gut microbes modulate whole host immune and hormonal factors impacting the fate of distant preneoplastic lesions toward malignancy or regression. This raises the possibility that the tumor microenvironment interacts with broader systemic microbial-immune networks. These accumulated findings suggest novel therapeutic opportunities for holobiont engineering in emerging tumor microenvironments. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Tumor immunology.

    Science.gov (United States)

    Mocellin, Simone; Lise, Mario; Nitti, Donato

    2007-01-01

    Advances in tumor immunology are supporting the clinical implementation of several immunological approaches to cancer in the clinical setting. However, the alternate success of current immunotherapeutic regimens underscores the fact that the molecular mechanisms underlying immune-mediated tumor rejection are still poorly understood. Given the complexity of the immune system network and the multidimensionality of tumor/host interactions, the comprehension of tumor immunology might greatly benefit from high-throughput microarray analysis, which can portrait the molecular kinetics of immune response on a genome-wide scale, thus accelerating the discovery pace and ultimately catalyzing the development of new hypotheses in cell biology. Although in its infancy, the implementation of microarray technology in tumor immunology studies has already provided investigators with novel data and intriguing new hypotheses on the molecular cascade leading to an effective immune response against cancer. Although the general principles of microarray-based gene profiling have rapidly spread in the scientific community, the need for mastering this technique to produce meaningful data and correctly interpret the enormous output of information generated by this technology is critical and represents a tremendous challenge for investigators, as outlined in the first section of this book. In the present Chapter, we report on some of the most significant results obtained with the application of DNA microarray in this oncology field.

  5. SAR405, a PIK3C3/Vps34 inhibitor that prevents autophagy and synergizes with MTOR inhibition in tumor cells.

    Science.gov (United States)

    Pasquier, Benoit

    2015-04-03

    Autophagy plays an important role in cancer and it has been suggested that it functions not only as a tumor suppressor pathway to prevent tumor initiation, but also as a prosurvival pathway that helps tumor cells endure metabolic stress and resist death triggered by chemotherapeutic agents. We recently described the discovery of inhibitors of PIK3C3/Vps34 (phosphatidylinositol 3-kinase, catalytic subunit type 3), the lipid kinase component of the class III phosphatidylinositol 3-kinase (PtdIns3K). This PtdIns3K isoform has attracted significant attention in recent years because of its role in autophagy. Following chemical optimization we identified SAR405, a low molecular mass kinase inhibitor of PIK3C3, highly potent and selective with regard to other lipid and protein kinases. We demonstrated that inhibiting the catalytic activity of PIK3C3 disrupts vesicle trafficking from late endosomes to lysosomes. SAR405 treatment also inhibits autophagy induced either by starvation or by MTOR (mechanistic target of rapamycin) inhibition. Finally our results show that combining SAR405 with everolimus, the FDA-approved MTOR inhibitor, results in a significant synergy on the reduction of cell proliferation using renal tumor cells. This result indicates a potential therapeutic application for PIK3C3 inhibitors in cancer.

  6. Prognostic factors in urothelial renal pelvis and ureter tumors: a multicenter rare cancer network study

    International Nuclear Information System (INIS)

    Ozsahin, M.; Zouhair, A.; Villa, S.; Storme, G.; Chauvet, B.; Taussky, D.; Houtte, P. van; Ries, G.; Bontemps, P.; Coucke, P.; Mirimanoff, R.O.

    1997-01-01

    Purpose: To assess the prognostic factors and the outcome in patients with transitional-cell carcinoma of the renal pelvis and/or ureter. Materials and Methods: A series of 138 patients treated between 1971 and 1996 for transitional-cell carcinoma of the renal pelvis and/or ureter was collected in a retrospective multicenter study of the Rare Cancer Network. Twelve patients with distant metastases were excluded from the statistical evaluation. In the remaining 126 patients, median age was 66 years (range: 41-87). The male to female ratio was 2.5 ((90(36))). All but 3 patients underwent a radical surgery: nephroureterectomy (n = 71), nephroureterectomy and lymphadenectomy (n = 20), nephroureterectomy and partial bladder resection or transurethral resection (n = 20), nephrectomy (n = 8), and ureterectomy (n = 4). There were 6 stage pTa, 22 pT1, 17 pT2, 37 pT3, 37 pT4, and 7 pTx tumors. The pN-stage distribution was as follows: 69 pN0, 8 pN1, 14 pN2, 4 pN3, and 31 pNx. Sixty-one percent (n = 77) of the tumors were located in the renal pelvis, and 21% (n = 27) in the ureter. Renal pelvis and ureter localization was present together in 22 (17%) patients. There were 4 grade 1, 37 grade 2, 42 grade 3 tumors (grade was not registered in 43). Following surgery, microscopic (n = 16) or macroscopic (n = 17) tumor rest was detected in 33 patients. Postoperative radiotherapy was given in 45 (36%) patients with a median total dose of 50 Gy (range: 20-66) in median 25 fractions (range: 4-33). Adjuvant systemic chemotherapy was administered in 12 (10%) patients. The median follow-up period was 39 months (range: 5-220). Results: In a median period of 9 months (range: 1-141), 66% (n = 81) of the patients relapsed (local in 34, locoregional in 7, regional in 16, and distant in 24). The 5- and 10-year overall survival (Kaplan-Meier product-limit estimates) was respectively 29% (± 5) and 19% (± 5) in all patients. In univariate analyses (logrank test), statistically significant

  7. Targeting of the tumor suppressor GRHL3 by a miR-21-dependent proto-oncogenic network results in PTEN loss and tumorigenesis.

    Science.gov (United States)

    Darido, Charbel; Georgy, Smitha R; Wilanowski, Tomasz; Dworkin, Sebastian; Auden, Alana; Zhao, Quan; Rank, Gerhard; Srivastava, Seema; Finlay, Moira J; Papenfuss, Anthony T; Pandolfi, Pier Paolo; Pearson, Richard B; Jane, Stephen M

    2011-11-15

    Despite its prevalence, the molecular basis of squamous cell carcinoma (SCC) remains poorly understood. Here, we identify the developmental transcription factor Grhl3 as a potent tumor suppressor of SCC in mice, and demonstrate that targeting of Grhl3 by a miR-21-dependent proto-oncogenic network underpins SCC in humans. Deletion of Grhl3 in adult epidermis evokes loss of expression of PTEN, a direct GRHL3 target, resulting in aggressive SCC induced by activation of PI3K/AKT/mTOR signaling. Restoration of Pten expression completely abrogates SCC formation. Reduced levels of GRHL3 and PTEN are evident in human skin, and head and neck SCC, associated with increased expression of miR-21, which targets both tumor suppressors. Our data define the GRHL3-PTEN axis as a critical tumor suppressor pathway in SCC. 2011 Elsevier Inc. All rights reserved.

  8. Diabetes Prevention Program (DPP)

    Science.gov (United States)

    ... Recruiting Patients & Families Consortia, Networks & Centers Reports & Planning Diabetes Prevention Program (DPP) The NIDDK-sponsored Diabetes Prevention ... Diabetes Prevention Program for those who are eligible. Diabetes Prevention Program (DPP) DPP Goal The DPP looked ...

  9. Road Accident Prevention with Instant Emergency Warning Message Dissemination in Vehicular Ad-Hoc Network.

    Directory of Open Access Journals (Sweden)

    P Gokulakrishnan

    Full Text Available A Road Accident Prevention (RAP scheme based on Vehicular Backbone Network (VBN structure is proposed in this paper for Vehicular Ad-hoc Network (VANET. The RAP scheme attempts to prevent vehicles from highway road traffic accidents and thereby reduces death and injury rates. Once the possibility of an emergency situation (i.e. an accident is predicted in advance, instantly RAP initiates a highway road traffic accident prevention scheme. The RAP scheme constitutes the following activities: (i the Road Side Unit (RSU constructs a Prediction Report (PR based on the status of the vehicles and traffic in the highway roads, (ii the RSU generates an Emergency Warning Message (EWM based on an abnormal PR, (iii the RSU forms a VBN structure and (iv the RSU disseminates the EWM to the vehicles that holds the high Risk Factor (RF and travels in High Risk Zone (HRZ. These vehicles might reside either within the RSU's coverage area or outside RSU's coverage area (reached using VBN structure. The RAP scheme improves the performance of EWM dissemination in terms of increase in notification and decrease in end-to-end delay. The RAP scheme also reduces infrastructure cost (number of RSUs by formulating and deploying the VBN structure. The RAP scheme with VBN structure improves notification by 19 percent and end-to-end delay by 14.38 percent for a vehicle density of 160 vehicles. It is also proved from the simulation experiment that the performance of RAP scheme is promising in 4-lane highway roads.

  10. Road Accident Prevention with Instant Emergency Warning Message Dissemination in Vehicular Ad-Hoc Network.

    Science.gov (United States)

    Gokulakrishnan, P; Ganeshkumar, P

    2015-01-01

    A Road Accident Prevention (RAP) scheme based on Vehicular Backbone Network (VBN) structure is proposed in this paper for Vehicular Ad-hoc Network (VANET). The RAP scheme attempts to prevent vehicles from highway road traffic accidents and thereby reduces death and injury rates. Once the possibility of an emergency situation (i.e. an accident) is predicted in advance, instantly RAP initiates a highway road traffic accident prevention scheme. The RAP scheme constitutes the following activities: (i) the Road Side Unit (RSU) constructs a Prediction Report (PR) based on the status of the vehicles and traffic in the highway roads, (ii) the RSU generates an Emergency Warning Message (EWM) based on an abnormal PR, (iii) the RSU forms a VBN structure and (iv) the RSU disseminates the EWM to the vehicles that holds the high Risk Factor (RF) and travels in High Risk Zone (HRZ). These vehicles might reside either within the RSU's coverage area or outside RSU's coverage area (reached using VBN structure). The RAP scheme improves the performance of EWM dissemination in terms of increase in notification and decrease in end-to-end delay. The RAP scheme also reduces infrastructure cost (number of RSUs) by formulating and deploying the VBN structure. The RAP scheme with VBN structure improves notification by 19 percent and end-to-end delay by 14.38 percent for a vehicle density of 160 vehicles. It is also proved from the simulation experiment that the performance of RAP scheme is promising in 4-lane highway roads.

  11. [Factors regarding awareness of preventive care exercises: Distance to exercise facilities and their social networks].

    Science.gov (United States)

    Soma, Yuki; Tsunoda, Kenji; Kitano, Naruki; Jindo, Takashi; Okura, Tomohiro

    2015-01-01

    The present study examines factors affecting individuals' awareness of certain types of preventive care exercises, particularly the distance from their home to an exercise facility and their social networks. Participants were 3206 men (age, 73.0±6.2 years) and 3395 women (age, 73.2±6.4 years) aged ≥65 years who had not been certified as persons with care needs and who had responded to an inventory survey conducted in Kasama City, Japan, in 2013. We performed multiple logistic regression analysis to assess the characteristics associated with participants' awareness of two types of exercises for preventive care: "silver rehabili taisou" (SRT) and "square-stepping exercise" (SSE). Independent variables were distance from home to the exercise facility, social networks, transportation availability, physical function, cognitive function, and neighborhood population density. Older adults who were aware of the exercises lived significantly closer to an exercise facility (SRT, aware: 1,148.5±961.3 m vs. unaware: 1,284.2±1,027.4 m; SSE, aware: 1,415.9±1104.1 m vs. unaware: 1,615.7±1,172.2 m). Multiple logistic regression analysis showed that participation in community activities (men, SRT-odds ratio [OR]=2.54 and SSE-OR=2.19; women, SRT-OR=4.14 and SSE-OR=3.34] and visiting friends (men, SRT-OR=1.45 and SSE-OR=1.49; women SRT-OR=1.44 and SSE-OR=1.73) were promoting factors for awareness of both types of exercises. In men and women, low physical function (SRT-OR=0.73 and SSE-OR=0.56) and dependence on another person to drive them to the destination (SRT-OR=0.79 and SSE-OR=0.78) were inhibiting factors, respectively. A distance of >500 m between their home and the facility tended to be an inhibiting factor. A shorter distance from home to an exercise facility and better social networks increased awareness of preventive care exercises in both sexes and for both types of exercise. Establishing exercise centers and devising effective methods of imparting information to

  12. Tumor lysis syndrome in children

    International Nuclear Information System (INIS)

    Suarez, Amaranto

    2004-01-01

    Tumor lysis syndrome is a metabolic emergency characterized by electrolyte alteration with or without acute renal failure. It occurs mainly in patients with malignant tumors that have a high growth fraction, or after cytotoxic therapy, as a result of the massive degradation of malignant cells and the release of high amounts of intracellular elements that exceed the capacity of renal excretion. The objective of the treatment is the prevention of nephropathy due to uric acid deposits, and the correction of metabolic acidosis and electrolyte alterations. This paper reviews the incidence, the physiopathology, and the treatment of tumor lysis syndrome in children

  13. Uncertainces in tumor target definition using PET

    International Nuclear Information System (INIS)

    Kirov, A.

    2013-01-01

    Full text: Introduction: PET entered into the clinics for radiation therapy as a means of displaying the metabolically active part of the tumor. However this advantage, PET has a number of shortcomings that prevent its use for precise determination of the tumor boundaries. What you will learn: The aim of the lecture is to present: the requirements for the accuracy of the determination of tumor boundaries in radiation therapy; the main phenomena which bring uncertainty using PET and a brief overview of methods for segmentation of tumors and their problems

  14. Efficacy of Supplementation with B Vitamins for Stroke Prevention: A Network Meta-Analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Dong, Hongli; Pi, Fuhua; Ding, Zan; Chen, Wei; Pang, Shaojie; Dong, Wenya; Zhang, Qingying

    2015-01-01

    Supplementation with B vitamins for stroke prevention has been evaluated over the years, but which combination of B vitamins is optimal for stroke prevention is unclear. We performed a network meta-analysis to assess the impact of different combinations of B vitamins on risk of stroke. A total of 17 trials (86 393 patients) comparing 7 treatment strategies and placebo were included. A network meta-analysis combined all available direct and indirect treatment comparisons to evaluate the efficacy of B vitamin supplementation for all interventions. B vitamin supplementation was associated with reduced risk of stroke and cerebral hemorrhage. The risk of stroke was lower with folic acid plus vitamin B6 as compared with folic acid plus vitamin B12 and was lower with folic acid plus vitamin B6 plus vitamin B12 as compared with placebo or folic acid plus vitamin B12. The treatments ranked in order of efficacy for stroke, from higher to lower, were folic acid plus vitamin B6 > folic acid > folic acid plus vitamin B6 plus vitamin B12 > vitamin B6 plus vitamin B12 > niacin > vitamin B6 > placebo > folic acid plus vitamin B12. B vitamin supplementation was associated with reduced risk of stroke; different B vitamins and their combined treatments had different efficacy on stroke prevention. Folic acid plus vitamin B6 might be the optimal therapy for stroke prevention. Folic acid and vitamin B6 were both valuable for stroke prevention. The efficacy of vitamin B12 remains to be studied.

  15. Efficacy of Supplementation with B Vitamins for Stroke Prevention: A Network Meta-Analysis of Randomized Controlled Trials.

    Directory of Open Access Journals (Sweden)

    Hongli Dong

    Full Text Available Supplementation with B vitamins for stroke prevention has been evaluated over the years, but which combination of B vitamins is optimal for stroke prevention is unclear. We performed a network meta-analysis to assess the impact of different combinations of B vitamins on risk of stroke.A total of 17 trials (86 393 patients comparing 7 treatment strategies and placebo were included. A network meta-analysis combined all available direct and indirect treatment comparisons to evaluate the efficacy of B vitamin supplementation for all interventions.B vitamin supplementation was associated with reduced risk of stroke and cerebral hemorrhage. The risk of stroke was lower with folic acid plus vitamin B6 as compared with folic acid plus vitamin B12 and was lower with folic acid plus vitamin B6 plus vitamin B12 as compared with placebo or folic acid plus vitamin B12. The treatments ranked in order of efficacy for stroke, from higher to lower, were folic acid plus vitamin B6 > folic acid > folic acid plus vitamin B6 plus vitamin B12 > vitamin B6 plus vitamin B12 > niacin > vitamin B6 > placebo > folic acid plus vitamin B12.B vitamin supplementation was associated with reduced risk of stroke; different B vitamins and their combined treatments had different efficacy on stroke prevention. Folic acid plus vitamin B6 might be the optimal therapy for stroke prevention. Folic acid and vitamin B6 were both valuable for stroke prevention. The efficacy of vitamin B12 remains to be studied.

  16. Inference of cancer-specific gene regulatory networks using soft computing rules.

    Science.gov (United States)

    Wang, Xiaosheng; Gotoh, Osamu

    2010-03-24

    Perturbations of gene regulatory networks are essentially responsible for oncogenesis. Therefore, inferring the gene regulatory networks is a key step to overcoming cancer. In this work, we propose a method for inferring directed gene regulatory networks based on soft computing rules, which can identify important cause-effect regulatory relations of gene expression. First, we identify important genes associated with a specific cancer (colon cancer) using a supervised learning approach. Next, we reconstruct the gene regulatory networks by inferring the regulatory relations among the identified genes, and their regulated relations by other genes within the genome. We obtain two meaningful findings. One is that upregulated genes are regulated by more genes than downregulated ones, while downregulated genes regulate more genes than upregulated ones. The other one is that tumor suppressors suppress tumor activators and activate other tumor suppressors strongly, while tumor activators activate other tumor activators and suppress tumor suppressors weakly, indicating the robustness of biological systems. These findings provide valuable insights into the pathogenesis of cancer.

  17. Wireless sensor network-based greenhouse environment monitoring and automatic control system for dew condensation prevention.

    Science.gov (United States)

    Park, Dae-Heon; Park, Jang-Woo

    2011-01-01

    Dew condensation on the leaf surface of greenhouse crops can promote diseases caused by fungus and bacteria, affecting the growth of the crops. In this paper, we present a WSN (Wireless Sensor Network)-based automatic monitoring system to prevent dew condensation in a greenhouse environment. The system is composed of sensor nodes for collecting data, base nodes for processing collected data, relay nodes for driving devices for adjusting the environment inside greenhouse and an environment server for data storage and processing. Using the Barenbrug formula for calculating the dew point on the leaves, this system is realized to prevent dew condensation phenomena on the crop's surface acting as an important element for prevention of diseases infections. We also constructed a physical model resembling the typical greenhouse in order to verify the performance of our system with regard to dew condensation control.

  18. Role of chemical carcinogens in epithelial and mesenchymal neoplasms with tumor initiation-promotion protocol and the effect of 13-cis retinoic acid in chemo prevention

    International Nuclear Information System (INIS)

    Bukhari, S.M.H.; Shahzad, S.Q.; Naeem, S.; Qureshi, G.R.; Naveed, I.A.

    2002-01-01

    Objective: To study the effects of chemical carcinogens on epithelial and mesenchymal tumorigenesis with tumor initiation-promotion protocol and the use of 13-cis retinoic acid as a chemo preventive agent. Design: It was an experimental study. Place and Duration of Study: The study was conducted at Postgraduate Medical Institute (PGML) Lahore for 20 weeks. Materials and Methods: Sixty albino rats were divided into six groups of ten of animals each. First group of animals (control) was not given carcinogens and 13-cis retinoic acid in second group DMBA was applied on the dorsal skin in repeated dos of 100 mu g/ml in acetone, twice a weak. In the third group DMBA was given 100 mu g/ml as single dose while TPA was given 10 mu g//ml in acetone, twice a weak after two weeks of DMBA applications. In fourth group only DMBA 100 mu g/ml in acetone was applied as a single dose. In fifth and sixth groups 13-cis retinoic acid was given topically before and after the application of DMBA and TPA. Results: First and fourth groups did not develop any tumor. In second groups 2 animals developed malignant fibrous histiocytoma, 4 squamous cell carcinoma while 1 dysphasia and 1 carcinoma in situ. Third group developed osteoma (3 animals), papilloma (3 animals, squamous cell carcinoma (01) and dysplasia (01). Conclusion: Our results showed that DMBA acts as tumor initiator while TPA as promoter. DMBA also produces tumors itself when given alone in repeated doses. The chemical carcinogens are not only a cause of epithelial carcinogenesis but also responsible for mesenchymal tumorigenesis. 13 cis retinoic acid was equally effective in both stages of tumorigenesis. It also prevents malignant conversion of chemically induced benign tumors. (author)

  19. Identifying diabetes knowledge network nodes as sites for a diabetes prevention program.

    Science.gov (United States)

    Gesler, Wilbert M; Arcury, Thomas A; Skelly, Anne H; Nash, Sally; Soward, April; Dougherty, Molly

    2006-12-01

    This paper reports on the methods used and results of a study that identified specific places within a community that have the potential to be sites for a diabetes prevention program. These sites, termed diabetes knowledge network nodes (DKNNs), are based on the concept of socio-spatial knowledge networks (SSKNs), the web of social relationships within which people obtain knowledge about type 2 diabetes. The target population for the study was working poor African Americans, Latinos, and European Americans of both sexes in a small rural southern town who had not been diagnosed with diabetes. Information was collected from a sample of 121 respondents on the places they visited in carrying out their daily activities. Data on number of visits to specific sites, degree of familiarity with these sites, and ratings of sites as places to receive diabetes information were used to develop three categories of DKNNs for six subgroups based on ethnicity and sex. Primary potential sites of importance to one or more subgroups included churches, grocery stores, drugstores, the local library, a beauty salon, laundromats, a community service agency, and a branch of the County Health Department. Secondary potential sites included gas stations, restaurants, banks, and post offices. Latent potential sites included three medical facilities. Most of the DKNNs were located either in the downtown area or in one of two shopping areas along the most used highway that passed through the town. The procedures used in this study can be generalized to other communities and prevention programs for other chronic diseases.

  20. [Rare tumors of the head and neck; on behalf of the REFCOR, the French Network of rare head and neck tumors].

    Science.gov (United States)

    Baujat, Bertrand; Thariat, Juliette; Baglin, Anne Catherine; Costes, Valérie; Testelin, Sylvie; Reyt, Emile; Janot, François

    2014-05-01

    Malignant tumors of the upper aerodigestive tract may be rare by their histology (sarcoma, variants of conventional squamous cell carcinomas) and/or location (sinuses, salivary glands, ear, of various histologies themselves). They represent less than 10% of head and neck neoplasms. The confirmation of their diagnosis often requires a medical expertise and sometimes biomolecular techniques complementary to classical histology and immunohistochemistry. Due to their location, their treatment often requires a specific surgical technique. Radiation therapy is indicated based on histoclinical characteristics common to other head and neck neoplasms but also incorporate grade. Further, the technique must often be adapted to take into account the proximity of organs at risk. For most histologies, chemotherapy is relatively inefficient but current molecular advances may allow to consider pharmaceutical developments in the coming years. The REFCOR, the French Network of head and neck cancers aims to organize and promote the optimal management of these rare and heterogeneous diseases, to promote research and clinical trials.

  1. Viral infection of implanted meningeal tumors induces antitumor memory T-cells to travel to the brain and eliminate established tumors.

    Science.gov (United States)

    Gao, Yanhua; Whitaker-Dowling, Patricia; Barmada, Mamdouha A; Basse, Per H; Bergman, Ira

    2015-04-01

    Leptomeningeal metastases occur in 2%-5% of patients with breast cancer and have an exceptionally poor prognosis. The blood-brain and blood-meningeal barriers severely inhibit successful chemotherapy. We have developed a straightforward method to induce antitumor memory T-cells using a Her2/neu targeted vesicular stomatitis virus. We sought to determine whether viral infection of meningeal tumor could attract antitumor memory T-cells to eradicate the tumors. Meningeal implants in mice were studied using treatment trials and analyses of immune cells in the tumors. This paper demonstrates that there is a blood-meningeal barrier to bringing therapeutic memory T-cells to meningeal tumors. The barrier can be overcome by viral infection of the tumor. Viral infection of the meningeal tumors followed by memory T-cell transfer resulted in 89% cure of meningeal tumor in 2 different mouse strains. Viral infection produced increased infiltration and proliferation of transferred memory T-cells in the meningeal tumors. Following viral infection, the leukocyte infiltration in meninges and tumor shifted from predominantly macrophages to predominantly T-cells. Finally, this paper shows that successful viral therapy of peritoneal tumors generates memory CD8 T-cells that prevent establishment of tumor in the meninges of these same animals. These results support the hypothesis that a virally based immunization strategy can be used to both prevent and treat meningeal metastases. The meningeal barriers to cancer therapy may be much more permeable to treatment based on cells than treatment based on drugs or molecules. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Improving Suicide Prevention in Dutch Regions by Creating Local Suicide Prevention Action Networks (SUPRANET): A Study Protocol.

    Science.gov (United States)

    Gilissen, Renske; De Beurs, Derek; Mokkenstorm, Jan; Mérelle, Saskia; Donker, Gé; Terpstra, Sanne; Derijck, Carla; Franx, Gerdien

    2017-03-28

    The European Alliance against Depression (EAAD) program is to be introduced in The Netherlands from 2017 onwards. This program to combat suicide consists of interventions on four levels: (1) increasing the awareness of suicide by local media campaigns; (2) training local gatekeepers, such as teachers or police officers; (3) targeting high-risk persons in the community; and (4) training and support of professionals in primary care settings. The implementation starts in seven Dutch pilot regions. Each region is designated as a Suicide Prevention Action NETwork (SUPRANET). This paper describes the SUPRANET program components and the evaluation of its feasibility and impact. The findings will be used to facilitate the national implementation of EAAD in The Netherlands and to add new findings to the existing literature on EAAD.

  3. Protein Kinase C Epsilon and Genetic Networks in Osteosarcoma Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Goudarzi, Atta, E-mail: atta.goudarzi@utoronto.ca [Department of Molecular Genetics, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8 (Canada); Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, ON M5G 1X5 (Canada); Gokgoz, Nalan; Gill, Mona; Pinnaduwage, Dushanthi [Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, ON M5G 1X5 (Canada); Merico, Daniele [The Centre for Applied Genomics, The Hospital for Sick Children, MaRS Centre-East Tower, 101 College Street Rm.14-701, Toronto, ON M5G 1L7 (Canada); Wunder, Jay S. [Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, ON M5G 1X5 (Canada); Andrulis, Irene L. [Department of Molecular Genetics, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8 (Canada); Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, ON M5G 1X5 (Canada)

    2013-04-08

    Osteosarcoma (OS) is the most common primary malignant tumor of the bone, and pulmonary metastasis is the most frequent cause of OS mortality. The aim of this study was to discover and characterize genetic networks differentially expressed in metastatic OS. Expression profiling of OS tumors, and subsequent supervised network analysis, was performed to discover genetic networks differentially activated or organized in metastatic OS compared to localized OS. Broad trends among the profiles of metastatic tumors include aberrant activity of intracellular organization and translation networks, as well as disorganization of metabolic networks. The differentially activated PRKCε-RASGRP3-GNB2 network, which interacts with the disorganized DLG2 hub, was also found to be differentially expressed among OS cell lines with differing metastatic capacity in xenograft models. PRKCε transcript was more abundant in some metastatic OS tumors; however the difference was not significant overall. In functional studies, PRKCε was not found to be involved in migration of M132 OS cells, but its protein expression was induced in M112 OS cells following IGF-1 stimulation.

  4. Protein Kinase C Epsilon and Genetic Networks in Osteosarcoma Metastasis

    International Nuclear Information System (INIS)

    Goudarzi, Atta; Gokgoz, Nalan; Gill, Mona; Pinnaduwage, Dushanthi; Merico, Daniele; Wunder, Jay S.; Andrulis, Irene L.

    2013-01-01

    Osteosarcoma (OS) is the most common primary malignant tumor of the bone, and pulmonary metastasis is the most frequent cause of OS mortality. The aim of this study was to discover and characterize genetic networks differentially expressed in metastatic OS. Expression profiling of OS tumors, and subsequent supervised network analysis, was performed to discover genetic networks differentially activated or organized in metastatic OS compared to localized OS. Broad trends among the profiles of metastatic tumors include aberrant activity of intracellular organization and translation networks, as well as disorganization of metabolic networks. The differentially activated PRKCε-RASGRP3-GNB2 network, which interacts with the disorganized DLG2 hub, was also found to be differentially expressed among OS cell lines with differing metastatic capacity in xenograft models. PRKCε transcript was more abundant in some metastatic OS tumors; however the difference was not significant overall. In functional studies, PRKCε was not found to be involved in migration of M132 OS cells, but its protein expression was induced in M112 OS cells following IGF-1 stimulation

  5. Sex Venue-Based Network Analysis to Identify HIV Prevention Dissemination Targets for Men Who Have Sex with Men.

    Science.gov (United States)

    Patel, Rupa R; Luke, Douglas A; Proctor, Enola K; Powderly, William G; Chan, Philip A; Mayer, Kenneth H; Harrison, Laura C; Dhand, Amar

    2018-01-01

    The aim of this study was to identify sex venue-based networks among men who have sex with men (MSM) to inform HIV preexposure prophylaxis (PrEP) dissemination efforts. Using a cross-sectional design, we interviewed MSM about the venues where their recent sexual partners were found. Venues were organized into network matrices grouped by condom use and race. We examined network structure, central venues, and network subgroups. Among 49 participants, the median age was 27 years, 49% were Black and 86% reported condomless anal sex (ncAS). Analysis revealed a map of 54 virtual and physical venues with an overlap in the ncAS and with condom anal sex (cAS) venues. In the ncAS network, virtual and physical locations were more interconnected. The ncAS venues reported by Blacks were more diffusely organized than those reported by Whites. The network structures of sex venues for at-risk MSM differed by race. Network information can enhance HIV prevention dissemination efforts among subpopulations, including PrEP implementation.

  6. Wireless Sensor Network-Based Greenhouse Environment Monitoring and Automatic Control System for Dew Condensation Prevention

    Science.gov (United States)

    Park, Dae-Heon; Park, Jang-Woo

    2011-01-01

    Dew condensation on the leaf surface of greenhouse crops can promote diseases caused by fungus and bacteria, affecting the growth of the crops. In this paper, we present a WSN (Wireless Sensor Network)-based automatic monitoring system to prevent dew condensation in a greenhouse environment. The system is composed of sensor nodes for collecting data, base nodes for processing collected data, relay nodes for driving devices for adjusting the environment inside greenhouse and an environment server for data storage and processing. Using the Barenbrug formula for calculating the dew point on the leaves, this system is realized to prevent dew condensation phenomena on the crop’s surface acting as an important element for prevention of diseases infections. We also constructed a physical model resembling the typical greenhouse in order to verify the performance of our system with regard to dew condensation control. PMID:22163813

  7. Epidemiological features of brain tumors

    Directory of Open Access Journals (Sweden)

    Živković Nenad

    2013-01-01

    Full Text Available Brain tumors account for 1.4% of all cancers and 2.4% of all cancer-related deaths. The incidence of brain tumors varies and it is higher in developed countries of Western Europe, North America, Australia and New Zealand. In Serbia, according to data from 2009, malignant brain tumors account for 2. 2 of all tumors, and from all cancer­related deaths, 3.2% is caused by malignant brain tumors. According to recent statistical reports, an overall incidence of brain tumors for benign and malignant tumors combined is 18.71 per 100,000 persons/year. The most common benign brain tumor in adults is meningioma, which is most present in women, and the most common malignant tumor is glioblastoma, which is most present in adult men. Due to high mortality, especially in patients diagnosed with glioblastoma and significant brain tumor morbidity, there is a constant interest in understanding its etiology in order to possibly prevent tumor occurrence in future and enable more efficient treatment strategies for this fatal brain disease. Despite the continuously growing number of epidemiological studies on possible factors of tumor incidence, the etiology remains unclear. The only established environmental risk factor of gliomas is ionizing radiation exposure. Exposure to radiofrequency electromagnetic fields via cell phone use has gained a lot of attention as a potential risk factor of brain tumor development. However, studies have been inconsistent and inconclusive, so more definite results are still expected.

  8. Inference of Cancer-specific Gene Regulatory Networks Using Soft Computing Rules

    Directory of Open Access Journals (Sweden)

    Xiaosheng Wang

    2010-03-01

    Full Text Available Perturbations of gene regulatory networks are essentially responsible for oncogenesis. Therefore, inferring the gene regulatory networks is a key step to overcoming cancer. In this work, we propose a method for inferring directed gene regulatory networks based on soft computing rules, which can identify important cause-effect regulatory relations of gene expression. First, we identify important genes associated with a specific cancer (colon cancer using a supervised learning approach. Next, we reconstruct the gene regulatory networks by inferring the regulatory relations among the identified genes, and their regulated relations by other genes within the genome. We obtain two meaningful findings. One is that upregulated genes are regulated by more genes than downregulated ones, while downregulated genes regulate more genes than upregulated ones. The other one is that tumor suppressors suppress tumor activators and activate other tumor suppressors strongly, while tumor activators activate other tumor activators and suppress tumor suppressors weakly, indicating the robustness of biological systems. These findings provide valuable insights into the pathogenesis of cancer.

  9. A quantitative theory of solid tumor growth, metabolic rate and vascularization.

    Directory of Open Access Journals (Sweden)

    Alexander B Herman

    Full Text Available The relationships between cellular, structural and dynamical properties of tumors have traditionally been studied separately. Here, we construct a quantitative, predictive theory of solid tumor growth, metabolic rate, vascularization and necrosis that integrates the relationships between these properties. To accomplish this, we develop a comprehensive theory that describes the interface and integration of the tumor vascular network and resource supply with the cardiovascular system of the host. Our theory enables a quantitative understanding of how cells, tissues, and vascular networks act together across multiple scales by building on recent theoretical advances in modeling both healthy vasculature and the detailed processes of angiogenesis and tumor growth. The theory explicitly relates tumor vascularization and growth to metabolic rate, and yields extensive predictions for tumor properties, including growth rates, metabolic rates, degree of necrosis, blood flow rates and vessel sizes. Besides these quantitative predictions, we explain how growth rates depend on capillary density and metabolic rate, and why similar tumors grow slower and occur less frequently in larger animals, shedding light on Peto's paradox. Various implications for potential therapeutic strategies and further research are discussed.

  10. National Suicide Prevention Lifeline

    Science.gov (United States)

    ... Initiatives Best Practices Our Network Media Resources National Suicide Prevention Lifeline We can all help prevent suicide. The ... Call The Lifeline Everyone Plays A Role In Suicide Prevention Here are some helpful links: GET HELP NOW ...

  11. Epigenetic Biomarkers of Breast Cancer Risk: Across the Breast Cancer Prevention Continuum.

    Science.gov (United States)

    Terry, Mary Beth; McDonald, Jasmine A; Wu, Hui Chen; Eng, Sybil; Santella, Regina M

    2016-01-01

    Epigenetic biomarkers, such as DNA methylation, can increase cancer risk through altering gene expression. The Cancer Genome Atlas (TCGA) Network has demonstrated breast cancer-specific DNA methylation signatures. DNA methylation signatures measured at the time of diagnosis may prove important for treatment options and in predicting disease-free and overall survival (tertiary prevention). DNA methylation measurement in cell free DNA may also be useful in improving early detection by measuring tumor DNA released into the blood (secondary prevention). Most evidence evaluating the use of DNA methylation markers in tertiary and secondary prevention efforts for breast cancer comes from studies that are cross-sectional or retrospective with limited corresponding epidemiologic data, raising concerns about temporality. Few prospective studies exist that are large enough to address whether DNA methylation markers add to the prediction of tertiary and secondary outcomes over and beyond standard clinical measures. Determining the role of epigenetic biomarkers in primary prevention can help in identifying modifiable pathways for targeting interventions and reducing disease incidence. The potential is great for DNA methylation markers to improve cancer outcomes across the prevention continuum. Large, prospective epidemiological studies will provide essential evidence of the overall utility of adding these markers to primary prevention efforts, screening, and clinical care.

  12. Preventative topical diclofenac treatment differentially decreases tumor burden in male and female Skh-1 mice in a model of UVB-induced cutaneous squamous cell carcinoma

    Science.gov (United States)

    Oberyszyn, Tatiana M.

    2013-01-01

    Ultraviolet B (UVB) light is the major environmental carcinogen contributing to non-melanoma skin cancer (NMSC) development. There are over 3.5 million NMSC diagnoses in two million patients annually, with men having a 3-fold greater incidence of squamous cell carcinoma (SCC) compared with women. Chronic inflammation has been linked to tumorigenesis, with a key role for the cyclooxygenase-2 (COX-2) enzyme. Diclofenac, a COX-2 inhibitor and non-steroidal anti-inflammatory drug, currently is prescribed to patients as a short-term therapeutic agent to induce SCC precursor lesion regression. However, its efficacy as a preventative agent in patients without evidence of precursor lesions but with significant UVB-induced cutaneous damage has not been explored. We previously demonstrated in a murine model of UVB-induced skin carcinogenesis that when exposed to equivalent UVB doses, male mice had lower levels of inflammation but developed increased tumor multiplicity, burden and grade compared with female mice. Because of the discrepancy in the degree of inflammation between male and female skin, we sought to determine if topical treatment of previously damaged skin with an anti-inflammatory COX-2 inhibitor would decrease tumor burden and if it would be equally effective in the sexes. Our results demonstrated that despite observed sex differences in the inflammatory response, prolonged topical diclofenac treatment of chronically UVB-damaged skin effectively reduced tumor multiplicity in both sexes. Unexpectedly, tumor burden was significantly decreased only in male mice. Our data suggest a new therapeutic use for currently available topical diclofenac as a preventative intervention for patients predisposed to cutaneous SCC development before lesions appear. PMID:23125227

  13. Robust gene network analysis reveals alteration of the STAT5a network as a hallmark of prostate cancer.

    Science.gov (United States)

    Reddy, Anupama; Huang, C Chris; Liu, Huiqing; Delisi, Charles; Nevalainen, Marja T; Szalma, Sandor; Bhanot, Gyan

    2010-01-01

    We develop a general method to identify gene networks from pair-wise correlations between genes in a microarray data set and apply it to a public prostate cancer gene expression data from 69 primary prostate tumors. We define the degree of a node as the number of genes significantly associated with the node and identify hub genes as those with the highest degree. The correlation network was pruned using transcription factor binding information in VisANT (http://visant.bu.edu/) as a biological filter. The reliability of hub genes was determined using a strict permutation test. Separate networks for normal prostate samples, and prostate cancer samples from African Americans (AA) and European Americans (EA) were generated and compared. We found that the same hubs control disease progression in AA and EA networks. Combining AA and EA samples, we generated networks for low low (cancer (e.g. possible turning on of oncogenes). (ii) Some hubs reduced their degree in the tumor network compared to their degree in the normal network, suggesting that these genes are associated with loss of regulatory control in cancer (e.g. possible loss of tumor suppressor genes). A striking result was that for both AA and EA tumor samples, STAT5a, CEBPB and EGR1 are major hubs that gain neighbors compared to the normal prostate network. Conversely, HIF-lα is a major hub that loses connections in the prostate cancer network compared to the normal prostate network. We also find that the degree of these hubs changes progressively from normal to low grade to high grade disease, suggesting that these hubs are master regulators of prostate cancer and marks disease progression. STAT5a was identified as a central hub, with ~120 neighbors in the prostate cancer network and only 81 neighbors in the normal prostate network. Of the 120 neighbors of STAT5a, 57 are known cancer related genes, known to be involved in functional pathways associated with tumorigenesis. Our method is general and can easily

  14. Malignant tumors of gastrointestinal tract

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    International histological classification and classification according to TNM systems, domestic clinical classification according to stages of carcinoma of stomach, large intestine and rectum are presented. Diagnosis of tumoral processes of the given localizations should be based on complex application of diagnostic methods: clinical, ultrasonic, radiological and others. Surgical method and variants of surgical method with preoperative radiotherapy play a leading role in treatment of mentioned tumors. Combined method of treatment-surgical intervention with postoperation intravenous injection of colloid 198 Au - is applied for preventing propagation of stomach cancer metastases. Advisability of combining operations with radiological and antitumoral medicamentous therapy is shown. Reliable results of treatment of malignant tumors of gastrointestinal tract are presented

  15. Understanding Collagen Organization in Breast Tumors to Predict and Prevent Metastasis

    Science.gov (United States)

    2015-11-01

    mouse mammary tumor virus polyoma middle T (MMTV-PyMT) mice crossed with MMP13 KO mice, noted proportionately more “thin collagen fibers” (rela- tive to...mammary gland gene expression and increased tumor growth following social isolation. Cancer Prev. Res. 2, 850–861. Wohleb, E.S., Hanke, M.L., Corona , A.W...1:100 dilution of mouse anti-Collagen II (II-II6B3; Developmental Studies Hybridoma Bank, Iowa City, IA) or a mouse monoclonal anti-Collagen I ( Cat

  16. Understanding the Social Networks That Form within the Context of an Obesity Prevention Intervention

    Directory of Open Access Journals (Sweden)

    Sabina B. Gesell

    2012-01-01

    Full Text Available Background. Antiobesity interventions have generally failed. Research now suggests that interventions must be informed by an understanding of the social environment. Objective. To examine if new social networks form between families participating in a group-level pediatric obesity prevention trial. Methods. Latino parent-preschool child dyads (N=79 completed the 3-month trial. The intervention met weekly in consistent groups to practice healthy lifestyles. The control met monthly in inconsistent groups to learn about school readiness. UCINET and SIENA were used to examine network dynamics. Results. Children’s mean age was 4.2 years (SD=0.9, and 44% were overweight/obese (BMI≥85th percentile. Parents were predominantly mothers (97%, with a mean age of 31.4 years (SD=5.4, and 81% were overweight/obese (BMI≥25. Over the study, a new social network evolved among participating families. Parents selectively formed friendship ties based on child BMI z-score, (t=2.08; P<.05. This reveals the tendency for mothers to form new friendships with mothers whose children have similar body types. Discussion. Participating in a group-level intervention resulted in new social network formation. New ties were greatest with mothers who had children of similar body types. This finding might contribute to the known inability of parents to recognize child overweight.

  17. Neuroendocrine tumors and smoking

    Directory of Open Access Journals (Sweden)

    Tanja Miličević

    2016-12-01

    Full Text Available Neuroendocrine cells are dispersed around the body and can be found within the gastrointestinal system, lungs, larynx, thymus, thyroid, adrenal, gonads, skin and other tissues. These cells form the so-called ''diffuse neuroendocrine system'' and tumors arising from them are defined as neuroendocrine tumors (NETs. The traditional classification of NETs based on their embryonic origin includes foregut tumors (lung, thymus, stomach, pancreas and duodenum, midgut tumors (beyond the ligament of Treitz of the duodenum to the proximal transverse colon and hindgut tumors (distal colon and rectum. NETs at each site are biologically and clinically distinct from their counterparts at other sites. Symptoms in patients with early disease are often insidious in onset, leading to a delay in diagnosis. The majority of these tumors are thus diagnosed at a stage at which the only curative treatment, radical surgical intervention, is no longer an option. Due to the increasing incidence and mortality, many studies have been conducted in order to identify risk factors for the development of NETs. Still, little is known especially when it comes to preventable risk factors such as smoking. This review will focus on smoking and its contribution to the development of different subtypes of NETs.

  18. Electrocatalysis aqueous phenol with carbon nanotubes networks as anodes: Electrodes passivation and regeneration and prevention

    International Nuclear Information System (INIS)

    Gao, Guandao; Vecitis, Chad D.

    2013-01-01

    Highlights: ► The electrochemical filtration used carbon nanotube network is effective to remove aqueous pollutants. ► Electrodes passivation is one of the most urgent challenges to overcome to 3-D electrode technology. ► Generally running system at higher potential can avoid generating polymer. ► Washing electrodes with suitable solvents is an effective alternative for removing polymer if it is not the best. -- Abstract: Electrochemical filtration using three-dimensional carbon nanotube (CNT) networks has been reported to increase the electrooxidation rate of aqueous pollutants due to convective mass transfer enhancements resulting from the flow through the electrode. In regards to the long term application of this novel electrochemical technology, electrode passivation is one of the most important challenges to overcome. Here, electrochemical filtration of aqueous phenol in a sodium sulfate electrolyte is utilized to investigate the primary passivation mechanisms and electrode regeneration methodologies, in which chronoamperometry and effluent total organic carbon measurements are utilized to monitor the passivation process in real-time, and electrochemical impedance spectroscopy, linear sweep voltammetry, and scanning electron microscopy are utilized to examine the CNT networks before passivation, after passivation and after regeneration. Finnaly, the carbon nanotube electrode passivation mechanisms and regeneration methods are discussed. Generally it is better choice to run system at higher potential in order to avoid generating polymer firstly other than regenerate complicatedly it after its passivation. Polymer formation can be prevented by application of an anode potential ≥2.1 V, which can completely mineralize phenol to carbon dioxide etc. and prevent polymerization of phenol. If there is still a bit of polymer formed inevitably, washing electrodes with suitable solvents is an effective alternative

  19. Investigating Contingency Risk Factors of Brain Tumor in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    A Nazemi

    2014-12-01

    Conclusion: According to research results, several preventable and predictable factors are linked to pediatric brain tumors. Therefore, children prone to brain tumors are recommended to be examined and screened for these risk factors.

  20. Forum: social network for the surveillance and prevention of workplace accidents.

    Science.gov (United States)

    Vilela, R A G; Almeida, I M; Nunes da Silva, A; Gomes, M H P; Prado, H; Buoso, E; Dias, M D; Cavalcante, S; Lacorte, L E

    2012-01-01

    In 2008, academic researchers and public service officials created a university extension studies platform based on online and on-site meetings denominated "Work-Related Accidents Forum: Analysis, Prevention, and Other Relevant Aspects. Its aim was to help public agents and social partners to propagate a systemic approach that would be helpful in the surveillance and prevention of work-related accidents. This article describes and analyses such a platform. Online access is free and structured to: support dissemination of updated concepts; support on-site meetings and capacity to build educational activities; and keep a permanent space for debate among the registered participants. The desired result is the propagation of a social-technical-systemic view of work-related accidents that replaces the current traditional view that emphasizes human error and results in blaming the victims. The Forum uses an educational approach known as permanent health education, which is based on the experience and needs of workers and encourages debate among participants. The forum adopts a problematizing pedagogy that starts from the requirements and experiences of the social actors and stimulates support and discussions among them in line with an ongoing health educational approach. The current challenge is to turn the platform into a social networking website in order to broaden its links with society.

  1. A selective androgen receptor modulator that reduces prostate tumor size and prevents orchidectomy-induced bone loss in rats.

    Science.gov (United States)

    Allan, George; Lai, Muh-Tsann; Sbriscia, Tifanie; Linton, Olivia; Haynes-Johnson, Donna; Bhattacharjee, Sheela; Dodds, Robert; Fiordeliso, James; Lanter, James; Sui, Zhihua; Lundeen, Scott

    2007-01-01

    The pharmacological activity of JNJ-26146900 is described. JNJ-26146900 is a nonsteroidal androgen receptor (AR) ligand with tissue-selective activity in rats. The compound was evaluated in in vitro and in vivo models of AR activity. It binds to the rat AR with a K(i) of 400nM and acts as a pure androgen antagonist in an in vitro cell-based assay. Its in vitro profile is similar to the androgen antagonist bicalutamide (Casodex). In intact rats, JNJ-26146900 reduces ventral prostate weight with an oral potency (ED(50)) of 20-30mg/kg, again comparable to that of bicalutamide. JNJ-26146900 prevented prostate tumor growth in the Dunning rat model, maximally inhibiting growth at a dose of 10mg/kg. It slowed tumor growth significantly in a CWR22-LD1 mouse xenograft model of human prostate cancer. It was tested in aged male rats for its ability to prevent bone loss and loss of lean body mass following orchidectomy. After 6 weeks of dosing, bone volume decreased by 33% in orchidectomized versus intact vehicle-treated rats with a probability (P) of less than 0.05, as measured by micro-computerized tomography analysis. At a dose of 30mg/kg, JNJ-26146900 significantly reduced castration-induced tibial bone loss as indicated by the following parameters: bone volume, trabecular connectivity, trabecular number and spacing between trabeculae. Bone mineral density decreased from 229+/-34mg/cm(3) of hydroxyapatite to 166+/-26mg/cm(3) following orchidectomy, and was maintained at 194+/-20mg/cm(3) with JNJ-26146900 treatment (Pselective androgen receptor modulators (SARMs) have the potential for anabolic effects on bone and muscle while maintaining therapeutic efficacy in prostate cancer.

  2. Use of caries-preventive agents in children: findings from the dental practice-based research network.

    Science.gov (United States)

    Riley, J L; Richman, Joshua S; Rindal, D Brad; Fellows, Jeffrey L; Qvist, Vibeke; Gilbert, Gregg H; Gordan, Valeria V

    2010-01-01

    Scientific evidence supports the application of caries-preventive agents in children and adolescents, and this knowledge must be applied to the practice of dentistry. There are few multi-region data that allow for comparisons of practice patterns between types of dental practices and geographical regions. The objective of the present study was to characterise the use of specific caries-preventive agents for paediatric patients in a large multi-region sample of practising clinicians. The present study surveyed clinicians from the Dental Practice-based Research Network who perform restorative dentistry in their practices. The survey consisted of a questionnaire that presented a range of questions about caries risk assessment and the use of preventive techniques in children aged 6 to 18 years. Dental sealants (69%) or in-office fluoride (82%) were the most commonly used caries-preventive agents of the caries preventive regimens. The recommendation of at-home caries-preventive agents ranged from 36% to 7%,with the most commonly used agent being non-prescription fluoride rinse. Clinicians who practised in a large group practice model and clinicians who come from the Scandinavian region use caries risk assessment more frequently compared to clinicians who come from regions that had, predominantly, clinicians in private practice. Whether or not clinicians used caries risk assessment with their paediatric patients was poorly correlated with the likelihood of actually using caries-preventive treatments on patients. Although clinicians reported the use of some form of in-office caries-preventive agent, there was considerable variability across practices. These differences could represent a lack of consensus across practising clinicians about the benefits of caries-preventive agents, or a function of differing financial incentives, or patient pools with differing levels of overall caries risk.

  3. Migratory neighbors and distant invaders: tumor-associated niche cells

    Science.gov (United States)

    Wels, Jared; Kaplan, Rosandra N.; Rafii, Shahin; Lyden, David

    2008-01-01

    The cancer environment is comprised of tumor cells as well as a wide network of stromal and vascular cells participating in the cellular and molecular events necessary for invasion and metastasis. Tumor secretory factors can activate the migration of host cells, both near to and far from the primary tumor site, as well as promote the exodus of cells to distant tissues. Thus, the migration of stromal cells and tumor cells among specialized microenvironments takes place throughout tumor and metastatic progression, providing evidence for the systemic nature of a malignancy. Investigations of the tumor–stromal and stromal–stromal cross-talk involved in cellular migration in cancer may lead to the design of novel therapeutic strategies. PMID:18316475

  4. Neem leaf glycoprotein prophylaxis transduces immune dependent stop signal for tumor angiogenic switch within tumor microenvironment.

    Directory of Open Access Journals (Sweden)

    Saptak Banerjee

    Full Text Available We have reported that prophylactic as well as therapeutic administration of neem leaf glycoprotein (NLGP induces significant restriction of solid tumor growth in mice. Here, we investigate whether the effect of such pretreatment (25µg/mice; weekly, 4 times benefits regulation of tumor angiogenesis, an obligate factor for tumor progression. We show that NLGP pretreatment results in vascular normalization in melanoma and carcinoma bearing mice along with downregulation of CD31, VEGF and VEGFR2. NLGP pretreatment facilitates profound infiltration of CD8+ T cells within tumor parenchyma, which subsequently regulates VEGF-VEGFR2 signaling in CD31+ vascular endothelial cells to prevent aberrant neovascularization. Pericyte stabilization, VEGF dependent inhibition of VEC proliferation and subsequent vascular normalization are also experienced. Studies in immune compromised mice confirmed that these vascular and intratumoral changes in angiogenic profile are dependent upon active adoptive immunity particularly those mediated by CD8+ T cells. Accumulated evidences suggest that NLGP regulated immunomodulation is active in tumor growth restriction and normalization of tumor angiogenesis as well, thereby, signifying its clinical translation.

  5. Local and systemic tumor immune dynamics

    Science.gov (United States)

    Enderling, Heiko

    Tumor-associated antigens, stress proteins, and danger-associated molecular patterns are endogenous immune adjuvants that can both initiate and continually stimulate an immune response against a tumor. In retaliation, tumors can hijack intrinsic immune regulatory programs that are intended to prevent autoimmune disease, thereby facilitating continued growth despite the activated antitumor immune response. In metastatic disease, this ongoing tumor-immune battle occurs at each site. Adding an additional layer of complexity, T cells activated at one tumor site can cycle through the blood circulation system and extravasate in a different anatomic location to surveil a distant metastasis. We propose a mathematical modeling framework that incorporates the trafficking of activated T cells between metastatic sites. We extend an ordinary differential equation model of tumor-immune system interactions to multiple metastatic sites. Immune cells are activated in response to tumor burden and tumor cell death, and are recruited from tumor sites elsewhere in the body. A model of T cell trafficking throughout the circulatory system can inform the tumor-immune interaction model about the systemic distribution and arrival of T cells at specific tumor sites. Model simulations suggest that metastases not only contribute to immune surveillance, but also that this contribution varies between metastatic sites. Such information may ultimately help harness the synergy of focal therapy with the immune system to control metastatic disease.

  6. The state of the art in intrusion prevention and detection

    CERN Document Server

    Pathan, Al-Sakib Khan

    2013-01-01

    The State of the Art in Intrusion Prevention and Detection analyzes the latest trends and issues surrounding intrusion detection systems in computer networks, especially in communications networks. Its broad scope of coverage includes wired, wireless, and mobile networks; next-generation converged networks; and intrusion in social networks.Presenting cutting-edge research, the book presents novel schemes for intrusion detection and prevention. It discusses tracing back mobile attackers, secure routing with intrusion prevention, anomaly detection, and AI-based techniques. It also includes infor

  7. Prevention of spontaneous and radiation-induced tumors in rats by reduction of food intake

    International Nuclear Information System (INIS)

    Gross, L.; Dreyfuss, Y.

    1990-01-01

    In our previous studies carried out on inbred Sprague-Dawley rats, we reported a striking increase in the incidence of tumors following total-body gamma-irradiation [150 rads (1.5 Gy) five times at weekly intervals]. Subsequently, we observed that two or three irradiations, and to a lesser extent even a single irradiation, were sufficient to induce an impressive increase in the incidence of tumors, particularly in females. A significant reduction of the incidence of radiation-induced tumors resulted when the rats were placed on calorically restricted diet. In experiments reported here, we increased slightly the amount of food given to animals on restricted diet. In the new study, among 102 irradiated females on full diet, 91 (89%) developed tumors, as compared with 29 out of 128 female rats (23%) also irradiated but maintained on restricted diet and 43 out of 89 (48%) untreated control females. None of 77 nonirradiated females on restricted diet developed tumors. Among 65 irradiated male rats, 29 (45%) developed tumors, as compared with 5 out of 74 (7%) rats also irradiated but maintained on restricted diet. Of the 49 males in the nonirradiated groups, 2 (4%) developed tumors. There was a significant weight reduction in both females and males maintained on restricted diet; animals on restricted diet lived longer than those on full diet

  8. Treatment of malignant brain tumor. Today and tomorrow. Image-guided neurosurgery for brain tumor. A current perspective

    International Nuclear Information System (INIS)

    Kajita, Yasukazu; Fujii, Masazumi; Yoshida, Jun; Maesawa, Satoshi

    2008-01-01

    Although usefulness of the image-guided neurosurgery is well documented, there are scarce facilities having the actually operating system in Japan. Since 2006, authors' Nagoya University Hospital has had an operating room named ''Brain THEATER'', where an open MRI system APERTO (Hitachi-Medical Co.) and a navigation system Vector Vision (BrainLAB) are connected to conduct the complete image-guided neurosurgery for brain tumor by using the intraoperative MRI for continuously updating the residual tumor tissue to be dissected out. The room is pre- and intra-operatively supported by Departments of image analysis and of radiation technology in the University, and as well, is connected by net-working with another image-guided surgical room ''Brain Suite'' (Siemens 1.5 T MRI system: BrainLAB) in the neighboring facility, Nagoya Central Hospital. This paper describes the circumstances of the introduction of these systems in the Hospital, details of the image-guided surgery in the operation rooms with illustration of actual photos of the rooms and of pre-, intra- and post-operative images, outcomes of image-guided neurosurgery for brain tumor reported hitherto, image-guided neurosurgery for brain tumor's future perspectives involving robotic surgery and operation on the virtual 3D image including the net-worked one. Efforts should be made to further spread the system for performing the more non-invasive and precise surgery, and for conducting the diagnosis united with treatment. (R.T.)

  9. Invasive species information networks: Collaboration at multiple scales for prevention, early detection, and rapid response to invasive alien species

    Science.gov (United States)

    Simpson, Annie; Jarnevich, Catherine S.; Madsen, John; Westbrooks, Randy G.; Fournier, Christine; Mehrhoff, Les; Browne, Michael; Graham, Jim; Sellers, Elizabeth A.

    2009-01-01

    Accurate analysis of present distributions and effective modeling of future distributions of invasive alien species (IAS) are both highly dependent on the availability and accessibility of occurrence data and natural history information about the species. Invasive alien species monitoring and detection networks (such as the Invasive Plant Atlas of New England and the Invasive Plant Atlas of the MidSouth) generate occurrence data at local and regional levels within the United States, which are shared through the US National Institute of Invasive Species Science. The Inter-American Biodiversity Information Network's Invasives Information Network (I3N), facilitates cooperation on sharing invasive species occurrence data throughout the Western Hemisphere. The I3N and other national and regional networks expose their data globally via the Global Invasive Species Information Network (GISIN). International and interdisciplinary cooperation on data sharing strengthens cooperation on strategies and responses to invasions. However, limitations to effective collaboration among invasive species networks leading to successful early detection and rapid response to invasive species include: lack of interoperability; data accessibility; funding; and technical expertise. This paper proposes various solutions to these obstacles at different geographic levels and briefly describes success stories from the invasive species information networks mentioned above. Using biological informatics to facilitate global information sharing is especially critical in invasive species science, as research has shown that one of the best indicators of the invasiveness of a species is whether it has been invasive elsewhere. Data must also be shared across disciplines because natural history information (e.g. diet, predators, habitat requirements, etc.) about a species in its native range is vital for effective prevention, detection, and rapid response to an invasion. Finally, it has been our

  10. Tumor cell-derived PDGF-B potentiates mouse mesenchymal stem cells-pericytes transition and recruitment through an interaction with NRP-1

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    Haque Inamul

    2010-08-01

    Full Text Available Abstract Background New blood vessel formation, or angiogenic switch, is an essential event in the development of solid tumors and their metastatic growth. Tumor blood vessel formation and remodeling is a complex and multi-step processes. The differentiation and recruitment of mural cells including vascular smooth muscle cells and pericytes are essential steps in tumor angiogenesis. However, the role of tumor cells in differentiation and recruitment of mural cells has not yet been fully elucidated. This study focuses on the role of human tumor cells in governing the differentiation of mouse mesenchymal stem cells (MSCs to pericytes and their recruitment in the tumor angiogenesis process. Results We show that C3H/10T1/2 mouse embryonic mesenchymal stem cells, under the influence of different tumor cell-derived conditioned media, differentiate into mature pericytes. These differentiated pericytes, in turn, are recruited to bind with capillary-like networks formed by endothelial cells on the matrigel under in vitro conditions and recruited to bind with blood vessels on gel-foam under in vivo conditions. The degree of recruitment of pericytes into in vitro neo-angiogenesis is tumor cell phenotype specific. Interestingly, invasive cells recruit less pericytes as compared to non-invasive cells. We identified tumor cell-secreted platelet-derived growth factor-B (PDGF-B as a crucial factor controlling the differentiation and recruitment processes through an interaction with neuropilin-1 (NRP-1 in mesenchymal stem cells. Conclusion These new insights into the roles of tumor cell-secreted PDGF-B-NRP-1 signaling in MSCs-fate determination may help to develop new antiangiogenic strategies to prevent the tumor growth and metastasis and result in more effective cancer therapies.

  11. Performance analysis and implementation of proposed mechanism for detection and prevention of security attacks in routing protocols of vehicular ad-hoc network (VANET

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    Parul Tyagi

    2017-07-01

    Full Text Available Next-generation communication networks have become widely popular as ad-hoc networks, broadly categorized as the mobile nodes based on mobile ad-hoc networks (MANET and the vehicular nodes based vehicular ad-hoc networks (VANET. VANET is aimed at maintaining safety to vehicle drivers by begin autonomous communication with the nearby vehicles. Each vehicle in the ad-hoc network performs as an intelligent mobile node characterized by high mobility and formation of dynamic networks. The ad-hoc networks are decentralized dynamic networks that need efficient and secure communication requirements due to the vehicles being persistently in motion. These networks are more susceptible to various attacks like Warm Hole attacks, denial of service attacks and Black Hole Attacks. The paper is a novel attempt to examine and investigate the security features of the routing protocols in VANET, applicability of AODV (Ad hoc On Demand protocol to detect and tackle a particular category of network attacks, known as the Black Hole Attacks. A new algorithm is proposed to enhance the security mechanism of AODV protocol and to introduce a mechanism to detect Black Hole Attacks and to prevent the network from such attacks in which source node stores all route replies in a look up table. This table stores the sequences of all route reply, arranged in ascending order using PUSH and POP operations. The priority is calculated based on sequence number and discard the RREP having presumably very high destination sequence number. The result show that proposed algorithm for detection and prevention of Black Hole Attack increases security in Intelligent Transportation System (ITS and reduces the effect of malicious node in the VANET. NCTUNs simulator is used in this research work.

  12. Composite implants coated with biodegradable polymers prevent stimulating tumor progression

    Energy Technology Data Exchange (ETDEWEB)

    Litviakov, N. V., E-mail: nvlitv72@yandex.ru; Tsyganov, M. M., E-mail: TsyganovMM@yandex.ru; Cherdyntseva, N. V., E-mail: nvch@oncology.tomsk.ru [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); National Research Tomsk State University, Tomsk, 634050 (Russian Federation); Tverdokhlebov, S. I., E-mail: tverd@tpu.ru; Bolbasov, E. N., E-mail: ebolbasov@gmail.com [National Research Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation); Perelmuter, V. M., E-mail: pvm@ngs.ru; Kulbakin, D. E., E-mail: kulbakin2012@gmail.com [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Zheravin, A. A., E-mail: zheravin2010@yandex.ru [Tomsk Cancer Research Institute, Tomsk, 634050 (Russian Federation); Academician E.N. Meshalkin Novosibirsk State Research Institute of Circulation Pathology, Novosibirsk (Russian Federation); Svetlichnyi, V. A., E-mail: v-svetlichnyi@bk.ru [National Research Tomsk State University, Tomsk, 634050 (Russian Federation)

    2016-08-02

    In this experiment we studied oncologic safety of model implants created using the solution blow spinning method with the use of the PURASORB PL-38 polylactic acid polymer and organic mineral filler which was obtained via laser ablation of a solid target made of dibasic calcium phosphate dihydrate. For this purpose the implant was introduced into the area of Wistar rats’ iliums, and on day 17 after the surgery the Walker sarcoma was transplanted into the area of the implant. We evaluated the implant’s influence on the primary tumor growth, hematogenous and lymphogenous metastasis of the Walker sarcoma. In comparison with sham operated animals the implant group demonstrated significant inhibition of hematogenous metastasis on day 34 after the surgery. The metastasis inhibition index (MII) equaled 94% and the metastases growth inhibition index (MGII) equaled 83%. The metastasis frequency of the Walker sarcoma in para aortic lymph nodes in the implant group was not statistically different from the control frequency; there was also no influence of the implant on the primary tumor growth noted. In case of the Walker sarcoma transplantation into the calf and the palmar pad of the ipsilateral limb to the one with the implant in the ilium, we could not note any attraction of tumor cells to the implant area, i.e. stimulation of the Walker sarcoma relapse by the implant. Thus, the research concluded that the studied implant meets the requirements of oncologic safety.

  13. Composite implants coated with biodegradable polymers prevent stimulating tumor progression

    International Nuclear Information System (INIS)

    Litviakov, N. V.; Tsyganov, M. M.; Cherdyntseva, N. V.; Tverdokhlebov, S. I.; Bolbasov, E. N.; Perelmuter, V. M.; Kulbakin, D. E.; Zheravin, A. A.; Svetlichnyi, V. A.

    2016-01-01

    In this experiment we studied oncologic safety of model implants created using the solution blow spinning method with the use of the PURASORB PL-38 polylactic acid polymer and organic mineral filler which was obtained via laser ablation of a solid target made of dibasic calcium phosphate dihydrate. For this purpose the implant was introduced into the area of Wistar rats’ iliums, and on day 17 after the surgery the Walker sarcoma was transplanted into the area of the implant. We evaluated the implant’s influence on the primary tumor growth, hematogenous and lymphogenous metastasis of the Walker sarcoma. In comparison with sham operated animals the implant group demonstrated significant inhibition of hematogenous metastasis on day 34 after the surgery. The metastasis inhibition index (MII) equaled 94% and the metastases growth inhibition index (MGII) equaled 83%. The metastasis frequency of the Walker sarcoma in para aortic lymph nodes in the implant group was not statistically different from the control frequency; there was also no influence of the implant on the primary tumor growth noted. In case of the Walker sarcoma transplantation into the calf and the palmar pad of the ipsilateral limb to the one with the implant in the ilium, we could not note any attraction of tumor cells to the implant area, i.e. stimulation of the Walker sarcoma relapse by the implant. Thus, the research concluded that the studied implant meets the requirements of oncologic safety.

  14. Usage of Probabilistic and General Regression Neural Network for Early Detection and Prevention of Oral Cancer

    Directory of Open Access Journals (Sweden)

    Neha Sharma

    2015-01-01

    Full Text Available In India, the oral cancers are usually presented in advanced stage of malignancy. It is critical to ascertain the diagnosis in order to initiate most advantageous treatment of the suspicious lesions. The main hurdle in appropriate treatment and control of oral cancer is identification and risk assessment of early disease in the community in a cost-effective fashion. The objective of this research is to design a data mining model using probabilistic neural network and general regression neural network (PNN/GRNN for early detection and prevention of oral malignancy. The model is built using the oral cancer database which has 35 attributes and 1025 records. All the attributes pertaining to clinical symptoms and history are considered to classify malignant and non-malignant cases. Subsequently, the model attempts to predict particular type of cancer, its stage and extent with the help of attributes pertaining to symptoms, gross examination and investigations. Also, the model envisages anticipating the survivability of a patient on the basis of treatment and follow-up details. Finally, the performance of the PNN/GRNN model is compared with that of other classification models. The classification accuracy of PNN/GRNN model is 80% and hence is better for early detection and prevention of the oral cancer.

  15. Usage of Probabilistic and General Regression Neural Network for Early Detection and Prevention of Oral Cancer.

    Science.gov (United States)

    Sharma, Neha; Om, Hari

    2015-01-01

    In India, the oral cancers are usually presented in advanced stage of malignancy. It is critical to ascertain the diagnosis in order to initiate most advantageous treatment of the suspicious lesions. The main hurdle in appropriate treatment and control of oral cancer is identification and risk assessment of early disease in the community in a cost-effective fashion. The objective of this research is to design a data mining model using probabilistic neural network and general regression neural network (PNN/GRNN) for early detection and prevention of oral malignancy. The model is built using the oral cancer database which has 35 attributes and 1025 records. All the attributes pertaining to clinical symptoms and history are considered to classify malignant and non-malignant cases. Subsequently, the model attempts to predict particular type of cancer, its stage and extent with the help of attributes pertaining to symptoms, gross examination and investigations. Also, the model envisages anticipating the survivability of a patient on the basis of treatment and follow-up details. Finally, the performance of the PNN/GRNN model is compared with that of other classification models. The classification accuracy of PNN/GRNN model is 80% and hence is better for early detection and prevention of the oral cancer.

  16. General practice and the Internet revolution. Use of an Internet social network to communicate information on prevention in France.

    Science.gov (United States)

    Veuillotte, Isabelle; Morel, Gilles; Pitois, Stephane; Haler, Renaud; Mercier, Patricia; Aubry, Catherine; Cannet, Didier

    2015-03-01

    The popularity of social networks and the huge number of exchanges have made them immensely important for the communication of information. This French study explored prevention in hereditary breast cancer using a social Internet network to communicate information. The principal objective was to inform French women aged from 20 to 50 years, using the social network Facebook, about the warning signs of breast cancer in cases of a predisposition to the disease due to a genetic mutation. The secondary objectives were to inform people about screening. An information page entitled "hereditary breast cancer: and if I was concerned?" was distributed in 3 different ways: from friend to friend, via groups of persons, and by targeted advertising. Four articles and 11 messages were distributed over 27 days. The total number of visits for this period amounted to 1019. A total of 81 percent of the Internauts were women and 55 percent of the visitors were aged between 25 and 44 years. Other information campaigns concerning public health issues could be conducted using this tool. A legal framework is necessary to preserve the quality of the medical information provided. This new means of communication, used for prevention purposes, will add to other frequently used methods of communication. © The Author(s) 2013.

  17. A Case of Malignant Peripheral Nerve Sheath Tumor with Rhabdomyoblastic Differentiation: Malignant Triton Tumor

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    Kenichiro Mae

    2013-12-01

    Full Text Available Malignant peripheral nerve sheath tumors (MPNST constitute a rare variety of soft tissue sarcomas thought to originate from Schwann cells or pluripotent cells of the neural crest. Malignant triton tumor (MTT, a very rare, highly aggressive soft tissue tumor, is a subgroup of MPNST and is comprised of malignant Schwann cells coexisting with malignant rhabdomyoblasts. We herein report the case of a 24-year-old man who presented a subcutaneous mass in his right thigh. The mass was removed surgically in its entirety and radiation therapy was applied locally to prevent tumor regrowth. Nonetheless, the patient died 10 months after surgery from metastases to the lung and brain. He presented neither cafe-au-lait spots nor cutaneous neurofibromas. The histopathology showed a transition from a neurofibroma to an MTT, making this the second report of an MTT arising from a neurofibroma without neurofibromatosis type 1, an autosomal dominant disorder with which 50-70% of tumors reported in previous studies were associated. A histopathological examination using immunostaining with desmin confirmed this diagnosis. MTT has a poorer prognosis than MPNST and should therefore be regarded as a distinct clinical entity.

  18. Novel Therapeutic Strategies for Solid Tumor Based on Body's Intrinsic Antitumor Immune System.

    Science.gov (United States)

    Duan, Haifeng

    2018-05-22

    The accumulation of mutated somatic cells due to the incompetency of body's immune system may lead to tumor onset. Therefore, enhancing the ability of the system to eliminate such cells should be the core of tumor therapy. The intrinsic antitumor immunity is triggered by tumor-specific antigens (TSA) or TSA-sensitized dendritic cells (DC). Once initiated, specific anti-tumor antibodies are produced and tumor-specific killer immune cells, including cytotoxic T lymphocytes (CTL), NK cells, and macrophages, are raised or induced. Several strategies may enhance antitumor action of immune system, such as supplying tumor-targeted antibody, activating T cells, enhancing the activity and tumor recognition of NK cells, promoting tumor-targeted phagocytosis of macrophages, and eliminating the immunosuppressive myeloid-derived suppressor cells (MDSCs) and Treg cells. Apart from the immune system, the removal of tumor burden still needs to be assisted by drugs, surgery or radiation. And the body's internal environment and tumor microenvironment should be improved to recover immune cell function and prevent tumor growth. Multiple microenvironment modulatory therapies may be applied, including addressing hypoxia and oxidative stress, correcting metabolic disorders, and controlling chronic inflammation. Finally, to cure tumor and prevent tumor recurrence, repairing or supporting therapy that consist of tissue repair and nutritional supplement should be applied properly. © 2018 The Author(s). Published by S. Karger AG, Basel.

  19. [Network Prevention of Accidents at Work: a strategy for distance education].

    Science.gov (United States)

    Marziale, Maria Helena; Zapparoli, Amanda dos Santos; Felli, Vanda Elisa; Anabuki, Marina Hideko

    2010-01-01

    Quasi-experimental study that aimed at evaluating the proposed interactive training, as a strategy for change in the behavior of workers, seeking the appropriate use of gloves in the administration of intravenous drugs. The interactive training was structured in the Model of Health Promotion of Pender, conducted through access to the web site of the Network Prevention of Accidents at Work (REPAT) available from: http://repat.eerp.usp.br/estrategia/index.php and applied in 60 workers nursing from two hospitals in the state of Sao Paulo. On the week before the training 58.3% of the workers were wearing gloves to administrate intravenous drugs and 83.3% of the workers informed the intention of wearing gloves after the training. the use of interactive tool facilitated the implementation of educational strategy in work and showed that training can help in changing behavior.

  20. Goniothalamin prevents the development of chemically induced and spontaneous colitis in rodents and induces apoptosis in the HT-29 human colon tumor cell line

    Energy Technology Data Exchange (ETDEWEB)

    Vendramini-Costa, Débora Barbosa, E-mail: vendramini.debora@gmail.com [Department of Organic Chemistry, Institute of Chemistry, University of Campinas, Campinas, SP (Brazil); Chemical, Biological and Agricultural Pluridisciplinary Research Center (CPQBA), University of Campinas, Campinas, SP (Brazil); Alcaide, Antonio [Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville (Spain); Pelizzaro-Rocha, Karin Juliane [Department of Biochemistry, Institute of Biology, University of Campinas, Campinas, SP (Brazil); Talero, Elena; Ávila-Román, Javier [Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville (Spain); Garcia-Mauriño, Sofia [Department of Plant Biology and Ecology, Faculty of Biology, University of Seville, Seville (Spain); Pilli, Ronaldo Aloise [Department of Organic Chemistry, Institute of Chemistry, University of Campinas, Campinas, SP (Brazil); Carvalho, João Ernesto de [Chemical, Biological and Agricultural Pluridisciplinary Research Center (CPQBA), University of Campinas, Campinas, SP (Brazil); Faculty of Pharmaceutical Sciences, University of Campinas, Campinas, SP (Brazil); Motilva, Virginia [Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville (Spain)

    2016-06-01

    Colon cancer is the third most incident type of cancer worldwide. One of the most important risk factors for colon cancer development are inflammatory bowel diseases (IBD), thus therapies focusing on IBD treatment have great potential to be used in cancer prevention. Nature has been a source of new therapeutic and preventive agents and the racemic form of the styryl-lactone goniothalamin (GTN) has been shown to be a promising antiproliferative agent, with gastroprotective, antinociceptive and anti-inflammatory effects. As inflammation is a well-known tumor promoter, the major goal of this study was to evaluate the therapeutic and preventive potentials of GTN on chemically induced and spontaneous colitis, as well as the cytotoxic effects of GTN on a human colon tumor cell line (HT-29). GTN treatments inhibited TNBS-induced acute and chronic colitis development in Wistar rats, reducing myeloperoxidase levels and inflammatory cells infiltration in the mucosa. In spontaneous-colitis using IL-10 deficient mice (C57BL/6 background), GTN prevented colitis development through downregulation of TNF-α, upregulation of SIRT-1 and inhibition of proliferation (PCNA index), without signs of toxicity after three months of treatment. In HT-29 cells, treatment with 10 μM of GTN induced apoptosis by increasing BAX/BCL2, p-JNK1/JNK1, p-P38/P38 ratios as well as through ROS generation. Caspase 8, 9 and 3 activation also occurred, suggesting caspase-dependent apoptotic pathway, culminating in PARP-1 cleavage. Together with previous data, these results show the importance of GTN as a pro-apoptotic, preventive and therapeutic agent for IBD and highlight its potential as a chemopreventive agent for colon cancer. - Highlights: • Goniothalamin (GTN) inhibits the development of TNBS-induced colitis in rats. • Moreover, GTN prevents the development of spontaneous colitis in IL-10 deficient mice. • This activity relies on downregulation of TNF-α and upregulation of SIRT-1 expression

  1. Comparative Analysis of Neural Network Training Methods in Real-time Radiotherapy

    Directory of Open Access Journals (Sweden)

    Nouri S.

    2017-03-01

    Full Text Available Background: The motions of body and tumor in some regions such as chest during radiotherapy treatments are one of the major concerns protecting normal tissues against high doses. By using real-time radiotherapy technique, it is possible to increase the accuracy of delivered dose to the tumor region by means of tracing markers on the body of patients. Objective: This study evaluates the accuracy of some artificial intelligence methods including neural network and those of combination with genetic algorithm as well as particle swarm optimization (PSO estimating tumor positions in real-time radiotherapy. Method: One hundred recorded signals of three external markers were used as input data. The signals from 3 markers thorough 10 breathing cycles of a patient treated via a cyber-knife for a lung tumor were used as data input. Then, neural network method and its combination with genetic or PSO algorithms were applied determining the tumor locations using MATLAB© software program. Results: The accuracies were obtained 0.8%, 12% and 14% in neural network, genetic and particle swarm optimization algorithms, respectively. Conclusion: The internal target volume (ITV should be determined based on the applied neural network algorithm on training steps.

  2. Optimizing the dosing schedule of l-asparaginase improves its anti-tumor activity in breast tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    Shoya Shiromizu

    2018-04-01

    Full Text Available Proliferation of acute lymphoblastic leukemic cells is nutritionally dependent on the external supply of asparagine. l-asparaginase, an enzyme hydrolyzing l-asparagine in blood, is used for treatment of acute lymphoblastic leukemic and other related blood cancers. Although previous studies demonstrated that l-asparaginase suppresses the proliferation of cultured solid tumor cells, it remains unclear whether this enzyme prevents the growth of solid tumors in vivo. In this study, we demonstrated the importance of optimizing dosing schedules for the anti-tumor activity of l-asparaginase in 4T1 breast tumor-bearing mice. Cultures of several types of murine solid tumor cells were dependent on the external supply of asparagine. Among them, we selected murine 4T1 breast cancer cells and implanted them into BALB/c female mice kept under standardized light/dark cycle conditions. The growth of 4T1 tumor cells implanted in mice was significantly suppressed by intravenous administration of l-asparaginase during the light phase, whereas its administration during the dark phase failed to show significant anti-tumor activity. Decreases in plasma asparagine levels due to the administration of l-asparaginase were closely related to the dosing time-dependency of its anti-tumor effects. These results suggest that the anti-tumor efficacy of l-asparaginase in breast tumor-bearing mice is improved by optimizing the dosing schedule. Keywords: l-asparaginase, Asparagine, Solid tumor, Chrono-pharmacotherapy

  3. Multifunctional Nanoparticles for Brain Tumor Diagnosis and Therapy

    Science.gov (United States)

    Cheng, Yu; Morshed, Ramin; Auffinger, Brenda; Tobias, Alex L.; Lesniak, Maciej S.

    2013-01-01

    Brain tumors are a diverse group of neoplasms that often carry a poor prognosis for patients. Despite tremendous efforts to develop diagnostic tools and therapeutic avenues, the treatment of brain tumors remains a formidable challenge in the field of neuro-oncology. Physiological barriers including the blood-brain barrier result in insufficient accumulation of therapeutic agents at the site of a tumor, preventing adequate destruction of malignant cells. Furthermore, there is a need for improvements in brain tumor imaging to allow for better characterization and delineation of tumors, visualization of malignant tissue during surgery, and tracking of response to chemotherapy and radiotherapy. Multifunctional nanoparticles offer the potential to improve upon many of these issues and may lead to breakthroughs in brain tumor management. In this review, we discuss the diagnostic and therapeutic applications of nanoparticles for brain tumors with an emphasis on innovative approaches in tumor targeting, tumor imaging, and therapeutic agent delivery. Clinically feasible nanoparticle administration strategies for brain tumor patients are also examined. Furthermore, we address the barriers towards clinical implementation of multifunctional nanoparticles in the context of brain tumor management. PMID:24060923

  4. Comparison of pharmacological and non-pharmacological interventions to prevent delirium in critically ill patients: a protocol for a systematic review incorporating network meta-analyses.

    Science.gov (United States)

    Burry, L D; Hutton, B; Guenette, M; Williamson, D; Mehta, S; Egerod, I; Kanji, S; Adhikari, N K; Moher, D; Martin, C M; Rose, L

    2016-09-08

    Delirium is characterized by acute changes in mental status including inattention, disorganized thinking, and altered level of consciousness, and is highly prevalent in critically ill adults. Delirium has adverse consequences for both patients and the healthcare system; however, at this time, no effective treatment exists. The identification of effective prevention strategies is therefore a clinical and research imperative. An important limitation of previous reviews of delirium prevention is that interventions were considered in isolation and only direct evidence was used. Our systematic review will synthesize all existing data using network meta-analysis, a powerful statistical approach that enables synthesis of both direct and indirect evidence. We will search Ovid MEDLINE, CINAHL, Embase, PsycINFO, and Web of Science from 1980 to March 2016. We will search the PROSPERO registry for protocols and the Cochrane Library for published systematic reviews. We will examine reference lists of pertinent reviews and search grey literature and the International Clinical Trials Registry Platform for unpublished studies and ongoing trials. We will include randomized and quasi-randomized trials of critically ill adults evaluating any pharmacological, non-pharmacological, or multi-component intervention for delirium prevention, administered in or prior to (i.e., peri-operatively) transfer to the ICU. Two authors will independently screen search results and extract data from eligible studies. Risk of bias assessments will be completed on all included studies. To inform our network meta-analysis, we will first conduct conventional pair-wise meta-analyses for primary and secondary outcomes using random-effects models. We will generate our network meta-analysis using a Bayesian framework, assuming a common heterogeneity parameter across all comparisons, and accounting for correlations in multi-arm studies. We will perform analyses using WinBUGS software. This systematic review

  5. Neem leaf glycoprotein optimizes effector and regulatory functions within tumor microenvironment to intervene therapeutically the growth of B16 melanoma in C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Subhasis Barik

    2015-01-01

    Full Text Available Therapy with neem leaf glycoprotein (NLGP inhibits murine B16-melanoma in vivo and improves survivability. Studies on tumor-microenvironment (TME from NLGP treated mice (NLGP-TME suggests that anti-tumor effect is directly associated with enhanced CD8+T cell activity, dominance of type 1 cytokines/chemokine network with downregulation of suppressive cellular functions. NLGP-TME educated CD8+T cells showed higher perforin and granzymeB expression with greater in vitro cytotoxicity against B16 melanoma. These CD8+T cells showed proportionally lower FasR expression, denotes prevention from activation induced cell death by NLGP. Accumulated evidences strongly suggest NLGP influenced normalized TME allows CD8+T cells to perform optimally to inhibit melanoma growth.

  6. INFLAMMATION AS A THERAPEUTIC TARGET IN THE COMPLEX TREATMENT OF MALIGNANT TUMORS

    Directory of Open Access Journals (Sweden)

    O. E. Savelieva

    2017-01-01

    Full Text Available In this review, we analyzed the role of inflammation in carcinogenesis, tumor development, and metastasis. In addition, the mechanisms of non-steroidal anti-inflammatory drugs (NSAIDs and the reasons of their contradictory influence on cancers were discussed. We summarized the numerous data about effectiveness of anti-inflammatory drugs for the prevention and additional therapy of tumor diseases. In particular, divergent effects of NSAIDs may be due to the peculiarities of immune-inflammatory responses that are realized in carcinogenesis and tumor development that have yet to be studied. We also discussed the selectivity of NSAID effects on different cancers and opposite effects of anticancer drugs with similar mechanisms of action. Apparently, the unsuccessful use of NSAIDs in cancer prevention and therapy are more specific for squamous cell carcinomas. Based on the literature, we provided significant clinical findings regarding the need of NSAID use in the current therapy of certain cancers and the determination of molecular predictors of the drug effect. In fact, anti-inflammatory therapy could eliminate the factors that contribute to the appearance of invasive and metastatic tumor cells, cancer and premetastatic niches and thus prevent metastasis and recurrence. At present, some non-selective (aspirin and selective (celecoxib NSAIDs are highly promising in the therapy of solid tumors

  7. Effects of a Social Network HIV/STD Prevention Intervention for Men Who Have Sex with Men in Russia and Hungary: A Randomized Controlled Trial

    Science.gov (United States)

    Amirkhanian, Yuri A.; Kelly, Jeffrey A.; Takacs, Judit; McAuliffe, Timothy L.; Kuznetsova, Anna V.; Toth, Tamas P.; Mocsonaki, Laszlo; DiFranceisco, Wayne J.; Meylakhs, Anastasia

    2015-01-01

    Objective To test a novel social network HIV risk reduction intervention for MSM in Russia and Hungary, where same-sex behavior is stigmatized and men may best be reached through their social network connections. Design A 2-arm trial with 18 sociocentric networks of MSM randomized to the social network intervention or standard HIV/STD testing/counseling. Setting St. Petersburg, Russia and Budapest, Hungary. Participants 18 “seeds” from community venues invited the participation of their MSM friends who, in turn, invited their own MSM friends into the study, a process that continued outward until eighteen 3-ring sociocentric networks (mean size=35 members, n=626) were recruited. Intervention Empirically-identified network leaders were trained and guided to convey HIV prevention advice to other network members. Main Outcome and Measures Changes in sexual behavior from baseline to 3- and 12-month followup, with composite HIV/STD incidence measured at 12-months to corroborate behavior changes. Results There were significant reductions between baseline, first followup, and second followup in the intervention versus comparison arm for proportion of men engaging in any unprotected anal intercourse (P=.04); UAI with a nonmain partner (P=.04); and UAI with multiple partners (P=.002). The mean percentage of unprotected AI acts significantly declined (P=.001), as well as the mean number of UAI acts among men who initially had multiple partners (P=.05). Biological HIV/STD incidence was 15% in comparison condition networks and 9% in intervention condition networks. Conclusions Even where same-sex behavior is stigmatized, it is possible to reach MSM and deliver HIV prevention through their social networks. PMID:25565495

  8. Convolutional Neural Network for Histopathological Analysis of Osteosarcoma.

    Science.gov (United States)

    Mishra, Rashika; Daescu, Ovidiu; Leavey, Patrick; Rakheja, Dinesh; Sengupta, Anita

    2018-03-01

    Pathologists often deal with high complexity and sometimes disagreement over osteosarcoma tumor classification due to cellular heterogeneity in the dataset. Segmentation and classification of histology tissue in H&E stained tumor image datasets is a challenging task because of intra-class variations, inter-class similarity, crowded context, and noisy data. In recent years, deep learning approaches have led to encouraging results in breast cancer and prostate cancer analysis. In this article, we propose convolutional neural network (CNN) as a tool to improve efficiency and accuracy of osteosarcoma tumor classification into tumor classes (viable tumor, necrosis) versus nontumor. The proposed CNN architecture contains eight learned layers: three sets of stacked two convolutional layers interspersed with max pooling layers for feature extraction and two fully connected layers with data augmentation strategies to boost performance. The use of a neural network results in higher accuracy of average 92% for the classification. We compare the proposed architecture with three existing and proven CNN architectures for image classification: AlexNet, LeNet, and VGGNet. We also provide a pipeline to calculate percentage necrosis in a given whole slide image. We conclude that the use of neural networks can assure both high accuracy and efficiency in osteosarcoma classification.

  9. A Review of HIV Prevention Studies that Use Social Networking Sites: Implications for Recruitment, Health Promotion Campaigns, and Efficacy Trials.

    Science.gov (United States)

    Jones, Jamal; Salazar, Laura F

    2016-11-01

    This review describes the use of social networking sites (SNS) in the context of primary prevention of HIV. A review was conducted to assess the published literature for HIV interventions using SNS. Sixteen articles describing twelve interventions were included. SNS were instrumental in recruiting hard-to-reach populations within a short amount of time; were able to reach wide audiences beyond the targeted population for HIV prevention campaigns; and helped to significantly reduce sexual risk behaviors and increase HIV testing. SNS are a viable option to recruit hidden populations, engage the target audience, and disseminate HIV prevention messages. Researchers should use SNS to generate sampling frames that can be used to select participants. Practitioners should use SNS to post images of preventive behavior within health promotion campaigns. Researchers should use multiple SNS platforms to engage participants. As more studies are published using SNS for HIV prevention, meta-analyses will be needed.

  10. Optimizing the dosing schedule of l-asparaginase improves its anti-tumor activity in breast tumor-bearing mice.

    Science.gov (United States)

    Shiromizu, Shoya; Kusunose, Naoki; Matsunaga, Naoya; Koyanagi, Satoru; Ohdo, Shigehiro

    2018-04-01

    Proliferation of acute lymphoblastic leukemic cells is nutritionally dependent on the external supply of asparagine. l-asparaginase, an enzyme hydrolyzing l-asparagine in blood, is used for treatment of acute lymphoblastic leukemic and other related blood cancers. Although previous studies demonstrated that l-asparaginase suppresses the proliferation of cultured solid tumor cells, it remains unclear whether this enzyme prevents the growth of solid tumors in vivo. In this study, we demonstrated the importance of optimizing dosing schedules for the anti-tumor activity of l-asparaginase in 4T1 breast tumor-bearing mice. Cultures of several types of murine solid tumor cells were dependent on the external supply of asparagine. Among them, we selected murine 4T1 breast cancer cells and implanted them into BALB/c female mice kept under standardized light/dark cycle conditions. The growth of 4T1 tumor cells implanted in mice was significantly suppressed by intravenous administration of l-asparaginase during the light phase, whereas its administration during the dark phase failed to show significant anti-tumor activity. Decreases in plasma asparagine levels due to the administration of l-asparaginase were closely related to the dosing time-dependency of its anti-tumor effects. These results suggest that the anti-tumor efficacy of l-asparaginase in breast tumor-bearing mice is improved by optimizing the dosing schedule. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  11. Endoscopic Management of Tumor Bleeding from Inoperable Gastric Cancer

    Science.gov (United States)

    Kim, Young-Il

    2015-01-01

    Tumor bleeding is not a rare complication in patients with inoperable gastric cancer. Endoscopy has important roles in the diagnosis and primary treatment of tumor bleeding, similar to its roles in other non-variceal upper gastrointestinal bleeding cases. Although limited studies have been performed, endoscopic therapy has been highly successful in achieving initial hemostasis. One or a combination of endoscopic therapy modalities, such as injection therapy, mechanical therapy, or ablative therapy, can be used for hemostasis in patients with endoscopic stigmata of recent hemorrhage. However, rebleeding after successful hemostasis with endoscopic therapy frequently occurs. Endoscopic therapy may be a treatment option for successfully controlling this rebleeding. Transarterial embolization or palliative surgery should be considered when endoscopic therapy fails. For primary and secondary prevention of tumor bleeding, proton pump inhibitors can be prescribed, although their effectiveness to prevent bleeding remains to be investigated. PMID:25844339

  12. A tumor suppressor role of the Bub3 spindle checkpoint protein after apoptosis inhibition

    Science.gov (United States)

    Moutinho-Santos, Tatiana

    2013-01-01

    Most solid tumors contain aneuploid cells, indicating that the mitotic checkpoint is permissive to the proliferation of chromosomally aberrant cells. However, mutated or altered expression of mitotic checkpoint genes accounts for a minor proportion of human tumors. We describe a Drosophila melanogaster tumorigenesis model derived from knocking down spindle assembly checkpoint (SAC) genes and preventing apoptosis in wing imaginal discs. Bub3-deficient tumors that were also deficient in apoptosis displayed neoplastic growth, chromosomal aneuploidy, and high proliferative potential after transplantation into adult flies. Inducing aneuploidy by knocking down CENP-E and preventing apoptosis does not induce tumorigenesis, indicating that aneuploidy is not sufficient for hyperplasia. In this system, the aneuploidy caused by a deficient SAC is not driving tumorigenesis because preventing Bub3 from binding to the kinetochore does not cause hyperproliferation. Our data suggest that Bub3 has a nonkinetochore-dependent function that is consistent with its role as a tumor suppressor. PMID:23609535

  13. Novel real-time tumor-contouring method using deep learning to prevent mistracking in X-ray fluoroscopy.

    Science.gov (United States)

    Terunuma, Toshiyuki; Tokui, Aoi; Sakae, Takeji

    2018-03-01

    Robustness to obstacles is the most important factor necessary to achieve accurate tumor tracking without fiducial markers. Some high-density structures, such as bone, are enhanced on X-ray fluoroscopic images, which cause tumor mistracking. Tumor tracking should be performed by controlling "importance recognition": the understanding that soft-tissue is an important tracking feature and bone structure is unimportant. We propose a new real-time tumor-contouring method that uses deep learning with importance recognition control. The novelty of the proposed method is the combination of the devised random overlay method and supervised deep learning to induce the recognition of structures in tumor contouring as important or unimportant. This method can be used for tumor contouring because it uses deep learning to perform image segmentation. Our results from a simulated fluoroscopy model showed accurate tracking of a low-visibility tumor with an error of approximately 1 mm, even if enhanced bone structure acted as an obstacle. A high similarity of approximately 0.95 on the Jaccard index was observed between the segmented and ground truth tumor regions. A short processing time of 25 ms was achieved. The results of this simulated fluoroscopy model support the feasibility of robust real-time tumor contouring with fluoroscopy. Further studies using clinical fluoroscopy are highly anticipated.

  14. Perception of Communication Network Fraud Dynamics by Network ...

    African Journals Online (AJOL)

    In considering the implications of the varied nature of the potential targets, the paper identifies the view to develop effective intelligence analysis methodologies for network fraud detection and prevention by network administrators and stakeholders. The paper further notes that organizations are fighting an increasingly ...

  15. Prevention of violence against women: challenges in the articulation of an intersetorial network

    Directory of Open Access Journals (Sweden)

    Patrícia Krieger Grossi

    2012-11-01

    Full Text Available This article has the objective of highlighting the importance of sectoriality action in the prevention of violence against women through the articulation of different social actors concerned and committed to the reduction of the violence against women rates, and consequently with a more fair and equal society. These challenges in the articulation of the network of protection services for women in domestic violence are illustrated by the managers of the social welfare policies, coordinators of women´s policies and professionals that work in Reference Centers for Women, Reference Centers of Social Welfare (CRAS and Specialized Reference Center of Social Welfare (CREAS in municipalities of the State of Rio Grande do Sul.

  16. Iatrogenic giant cell tumor at bone graft harvesting site

    Directory of Open Access Journals (Sweden)

    Zile S Kundu

    2013-01-01

    Full Text Available 30 year old female patient with giant cell tumor of the distal tibia initially treated at a peripheral nononcological center by curettage and autologous bone grafting from the ipsilateral iliac crest reported to us with local recurrence and an implantation giant cell tumor at the graft harvesting site which required extensive surgeries at both sites. The risk of iatrogenic direct implantation of tumor, often attributable to inadequate surgical planning or poor surgical techniques, and the steps to prevent such complication is reported here.

  17. Attitude of the Italian general population towards prevention and screening of the most common tumors, with special emphasis on colorectal malignancies.

    Science.gov (United States)

    Domati, Federica; Travlos, Estratios; Cirilli, Claudia; Rossi, Giuseppina; Benatti, Piero; Marino, Massimiliano; Ponti, Giovanni; Vandelli, Maria; Valmori, Simone; Oursana, Amal; Pezzi, Annalisa; Ponz de Leon, Maurizio

    2009-06-01

    Screening and early diagnosis of cancer represent relatively recent tools in the long-lasting battle against tumors. If the American public opinion manifests its enthusiasm towards screening, the attitude of European is less well known. The purpose of the present study was to assess the level of knowledge and awareness of cancer screening (with particular emphasis on colorectal neoplasms) among middle-aged individuals. The study group consisted of 945 healthy individuals (489 men, 456 women, average age 57 +/- 12.4 years) who were asked to answer a series of questions about cancer screening and surveillance through a questionnaire presented by trained residents. Each interview lasted 20-30 min. Middle-aged Italians of both sexes seem to be aware of the fact that cancer is a frequent disease; moreover, many of the interviewed subjects believe almost all neoplasms are incurable. Diet, style of life, other environmental factors and familial factors are fully appreciated as relevant risk factors. The exact meaning of prevention was clear to less than half of the subjects. When various cancer sites were analyzed, the existence of preventive measures was well known for breast, cervical and prostate tumors, but their role was less clear for colorectal cancer. Only a fraction of the interviewed individuals were willing to undergo screening; the main reasons for refusal were lack of usefulness and fear of results. Among various tests, ultrasound and endoscopy were usually carried out in the presence of symptoms. Finally, multivariate analysis showed that the two factors significantly associated with the decision to undergo screening procedures were increasing age and level of education. The results of the study suggest that middle-aged Italian individuals, predominantly from Northern regions, have a correct perception of some aspects (frequency, risk factors) of cancer biology, whereas the knowledge of other aspects (outcome, prevention) remains poor or approximate. It

  18. A study of spinal cord tumors by magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gushiken, Isao; Nishihira, Takeshi; Nakasone, Tomohiro [Ryukyu Univ., Nishihara, Okinawa (Japan). School of Medicine; Takara, Hiroaki; Oshiro, Yutaka; Oshiro, Takashi; Isa, Makoto; Kinjo, Yukio; Ibaraki, Kunio

    1989-10-01

    We studied 17 cases of spinal cord tumors using magnetic resonance imaging. According to the intensity of image and histological feature of spinal cord tumors, we identified two groups in T2 weighted imaging. One was a hypointensity group showing cystic or vascular tumors, and the other was hyperintensity group of solid tumors. Preoperative images of swelling, narrowing, deviation of the spinal cord were remained after the operations. Grafted free fatty tissue for the prevention of adhesion was recognized well also after the operation. Postoperative imagings sometime showed pseudo-deviation of the spinal cord which was easy to be mistaken as the remains of tumors and narrowing of the spinal cord. In conclusion, the magnetic resonance imaging makes very early detection of spinal cord tumors possible, and it is valuable for a diagnosis of the spinal cord tumor associated with brain tumor. (author).

  19. A study of spinal cord tumors by magnetic resonance imaging

    International Nuclear Information System (INIS)

    Gushiken, Isao; Nishihira, Takeshi; Nakasone, Tomohiro; Takara, Hiroaki; Oshiro, Yutaka; Oshiro, Takashi; Isa, Makoto; Kinjo, Yukio; Ibaraki, Kunio.

    1989-01-01

    We studied 17 cases of spinal cord tumors using magnetic resonance imaging. According to the intensity of image and histological feature of spinal cord tumors, we identified two groups in T2 weighted imaging. One was a hypointensity group showing cystic or vascular tumors, and the other was hyperintensity group of solid tumors. Preoperative images of swelling, narrowing, deviation of the spinal cord were remained after the operations. Grafted free fatty tissue for the prevention of adhesion was recognized well also after the operation. Postoperative imagings sometime showed pseudo-deviation of the spinal cord which was easy to be mistaken as the remains of tumors and narrowing of the spinal cord. In conclusion, the magnetic resonance imaging makes very early detection of spinal cord tumors possible, and it is valuable for a diagnosis of the spinal cord tumor associated with brain tumor. (author)

  20. Modulation of Tumor Tolerance in Primary Central Nervous System Malignancies

    Directory of Open Access Journals (Sweden)

    Theodore S. Johnson

    2012-01-01

    Full Text Available Central nervous system tumors take advantage of the unique immunology of the CNS and develop exquisitely complex stromal networks that promote growth despite the presence of antigen-presenting cells and tumor-infiltrating lymphocytes. It is precisely this immunological paradox that is essential to the survival of the tumor. We review the evidence for functional CNS immune privilege and the impact it has on tumor tolerance. In this paper, we place an emphasis on the role of tumor-infiltrating myeloid cells in maintaining stromal and vascular quiescence, and we underscore the importance of indoleamine 2,3-dioxygenase activity as a myeloid-driven tumor tolerance mechanism. Much remains to be discovered regarding the tolerogenic mechanisms by which CNS tumors avoid immune clearance. Thus, it is an open question whether tumor tolerance in the brain is fundamentally different from that of peripheral sites of tumorigenesis or whether it simply stands as a particularly strong example of such tolerance.

  1. Biopsy in Musculoskeletal Tumors

    Directory of Open Access Journals (Sweden)

    Mohammad Gharehdaghi

    2014-09-01

    other anatomic structures? (4 Carcinomas are homogeneous, and a simple CNB is usually sufficient for diagnosis, but in soft tissue sarcomas, the periphery of the tumor is the growing part and usually represents the authentic underlying malignancy. The center of the tumor may be hemorrhagic or necrotic, thus taking biopsy from this part may distract from the correct diagnosis.Extraosseus part of a bone sarcoma is as representative as bony component of the tumor. Violating the bone and weakening the cortex may predispose it to pathologic fracture, so biopsy of an extraosseus part is sufficient for the diagnosis if present (3. The biopsy tract “open or CNB” is contaminated by tumor cells and should be widely excised if a wide excision or amputation is performed. For this reason, excision of the biopsy incision or needle entrance should be planned along with the definitive tumor excision to prevent complications and the need for altering the treatment strategy (Figure A, B, C. Open incisional biopsy provides sufficient material for microscopic diagnosis as well as immune- histochemical, cytogenetic, or electron microscopic studies. It has some disadvantages such as wound healing problems, infection, tumor cell contamination, and nerve and vessel injuries (1. For open biopsies, the incision should be as small as necessary and longitudinal. Transverse incisions are not advisable. To perform an intraosseus biopsy, the window should be circular or oblong, and as small as needed to prevent a pathologic fracture. Closing this window by PMMA prevents tumor cell contamination. Compressing the PMMA exceeds the chance of metastasis. As a rule, culture what you biopsy and biopsy what you culture. Use of a tourniquet without exsanguinations helps better visualization and meticulous hemostasis which prevents spreading of the tumor cells in hematoma. Importantly, it should be deflated before closing the wound (3. The port of entry of drains, if necessary, must be in line and

  2. Sclerosing stromal tumor of the ovary: A case report

    Directory of Open Access Journals (Sweden)

    Navjot Kaur

    2014-01-01

    Full Text Available Sclerosing stromal tumors are benign ovarian neoplasms of the sex cord-stromal category, occurring predominantly in the second and third decades of life. Herein, we report a 23-year-old female who presented with pelvic pain, irregular menses but normal hormonal status and was diagnosed as having a right ovarian tumor. A right oophorectomy was performed, and microscopic examination revealed a sclerosing stromal tumor of the right ovary. We stress the importance of being familiar with sclerosing stromal tumors when evaluating ovarian neoplasms in young women, in order to contribute to the appropriate clinical management, preventing extensive and unnecessary surgery, and preserving fertility.

  3. Labeled bleomycin as a tumor localizing agent

    International Nuclear Information System (INIS)

    Vos, C.M.

    1982-01-01

    The antitumor antibiotics bleomycins labeled with 57 Co are known to possess excellent tumor localizing properties but the rather long halflife of 57 Co prevents its use in clinical routine. It is therefore desirable to label cobalt-bleomycin with a more suitable radionuclide, e.g. 123 I. This thesis reports on further studies on cobalt-bleomycin. It appears from the studies on the structure of cobalt-bleomycin described in this thesis (Chapter B), that cobalt is able to form different complexes with bleomycin (the forms I and II). The difference in structure is not clear, but the biological behavior of both forms is studied (Chapter C). In Chapter D the iodination of cobalt-bleomycin is described. Iodination of free bleomycin yields a product with bad tumor localizing properties, and straight-on iodination of cobalt-bleomycin is prevented by the presence of cobalt. To retain the good tumor-localizing properties of cobalt-bleomycin, possibilities were explored to incorporate the iodine in the terminal amine (a side chain, not involved in complexation). Alkylation of cobalt-bleomycin demethyl A 2 with N-bromoacetyl-3-iodoaniline yielded a product; unfortunately this product possessed bad tumor localizing properties and moreover, was not stable in vivo. The structure of a possibly successful iodinated cobalt-bleomycin is outlined but could not be realized during this research. (Auth.)

  4. Reoxygenation of hypoxic cells by tumor shrinkage during irradiation. A computer simulation

    International Nuclear Information System (INIS)

    Kocher, M.; Treuer, H.

    1995-01-01

    A 3-dimensional computer simulation was developed in order to estimate the impact of tumor shrinkage on reoxygenation of chronic hypoxic tumor cells during a full course of fractionated irradiation. The growth of a small tumor situated in a vascularized stroma with 350 capillary cross-sections/mm 3 which were displaced by the growing tumor was simulated. Tumors contained 10 4 cells when irradiation started, intrinsic radiosensitivity was set to either low (α=0.3 Gy -1 , β=0.03 Gy -2 ) or high (α=0.4 Gy -1 , β=0.04 Gy -2 ) values. Oxygen enhancement ratio was 3.0, potential tumor doubling time T pot =1, 2 or 5 days. A simulated fractionated radiotherapy was carried out with daily fractions of 2.0 Gy, total dose 50 to 70 Gy. The presence or absence of factors preventing tumor cord shrinkage was also included. During the growth phase, all tumors developed a necrotic core with a hypoxic cell fraction of 25% under these conditions. During irradiation, the slower growing tumors (T pot =2 to 5 days) showed complete reoxygenation of the hypoxic cells after 30 to 40 Gy independent from radiosensitivity, undisturbed tumor shrinkage provided. If shrinkage was prevented, the hypoxic fraction rose to 100% after 30 to 50 Gy. Local tumor control, defined as the destruction of all clonogenic and hypoxic tumor cells increased by 20 to 100% due to reoxygenation and 50 Gy were enough in order to sterilize the tumors in these cases. In the fast growing tumors (T pot =1 day), reoxygenation was only observed in the case of high radiosensitivity and undisturbed tumor shrinkage. In these tumors reoxygenation increased the control rates by up to 60%. (orig./MG) [de

  5. Vision and Relevant Risk Factor Interventions for Preventing Falls among Older People: A Network Meta-analysis.

    Science.gov (United States)

    Zhang, Xin-Yi; Shuai, Jian; Li, Li-Ping

    2015-05-28

    Our study objective was to determine the effect of vision intervention and combinations of different intervention components on preventing falls and fall-related injuries among older people. Six electronic databases were searched to identify seven articles published before May, 2014. We conducted a systematic review of data from seven randomized controlled trails and identified eight regimens: vision intervention alone (V), vision plus exercise (referred to as physical exercise) interventions (V + E), vision plus home hazard interventions (V + HH), vision plus exercise plus home hazard interventions (V + E + HH), vision plus exercise plus sensation interventions (V + E + S), vision plus hearing interventions (V + H), vision plus various risk factor assessment and interventions (V + VRF), and the control group (C, no intervention group). The main outcome was the incidence of falls during the follow-up period. Seven papers included 2723 participants. Network meta-analysis of seven trials, using pairwise comparisons between each intervention, indicated there was no significant difference. However, there was a trend in which intervention incorporating V + VRF had more advantages than any other combination of interventions. In conclusion, V + VRF proves to be more effective than other V combination interventions in preventing falls in older people (≥65 years of age). V alone appears less effective in our network meta-analysis.

  6. Acceptability of HIV Prevention Information Delivered Through Established Geosocial Networking Mobile Applications to Men Who Have Sex With Men.

    Science.gov (United States)

    Czarny, Heather N; Broaddus, Michelle R

    2017-11-01

    Geosocial networking (GSN) applications could disseminate HIV prevention information to thousands of men who have sex with men (MSM); however, acceptability of the type of information, methods, and frequency of information delivery are unknown. Acceptability of these constructs were assessed through a survey of 224 MSM at the Milwaukee Pridefest. All types of information were found acceptable. A sexual health section and self-seeking information were the most acceptable method and frequency of delivery. Demographics and differences in app usage did not correlate to acceptability. Continued research focusing on the feasibility of incorporating HIV prevention information into GSN applications is needed.

  7. Expression signature based on TP53 target genes doesn't predict response to TP53-MDM2 inhibitor in wild type TP53 tumors

    OpenAIRE

    Sonkin, Dmitriy

    2015-01-01

    eLife digest Damaged cells in the human body can develop into tumors if left unchecked. TP53 (also called p53) is a protein that normally helps to repair or eliminate these damaged cells and prevent tumors from forming. About half of all cancerous tumors have mutations that prevent TP53 from working. In tumors with normal TP53 (called TP53 wild type tumors), another protein that acts to keep TP53 in check is often overly active. This overactive protein (called MDM2) prevents TP53 from suppres...

  8. Minocycline attenuates cardiac dysfunction in tumor-burdened mice.

    Science.gov (United States)

    Devine, Raymond D; Eichenseer, Clayton M; Wold, Loren E

    2016-11-01

    Cardiovascular dysfunction as a result of tumor burden is becoming a recognized complication; however, the mechanisms remain unknown. A murine model of cancer cachexia has shown marked increases of matrix metalloproteinases (MMPs), known mediators of cardiac remodeling, in the left ventricle. The extent to which MMPs are involved in remodeling remains obscured. To this end a common antibiotic, minocycline, with MMP inhibitory properties was used to elucidate MMP involvement in tumor induced cardiovascular dysfunction. Tumor-bearing mice showed decreased cardiac function with reduced posterior wall thickness (PWTs) during systole, increased MMP and collagen expression consistent with fibrotic remodeling. Administration of minocycline preserved cardiac function in tumor bearing mice and decreased collagen RNA expression in the left ventricle. MMP protein levels were unaffected by minocycline administration, with the exception of MMP-9, indicating minocycline inhibition mechanisms are directly affecting MMP activity. Cancer induced cardiovascular dysfunction is an increasing concern; novel therapeutics are needed to prevent cardiac complications. Minocycline is a well-known antibiotic and recently has been shown to possess MMP inhibitory properties. Our findings presented here show that minocycline could represent a novel use for a long established drug in the prevention and treatment of cancer induced cardiovascular dysfunction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Prevention of bladder tumor implantion after fluorescence-guided TUR with photodynamic therapy

    Science.gov (United States)

    Berrahmoune, Saoussen; Bezdetnaya, Lina; de Witte, Peter; Leroux, Agnès; Dumas, Dominique; Guillemin, François; D'Hallewin, Marie Ange

    2009-06-01

    The prevalence of bladder cancer is very high, due to its high recurrence rate in superficial bladder cancer (30 to 85%), which is the staging of approximately 80% of the patients at first diagnosis. Risk of recurrence and progression is associated with grade, stage, presence of concomitant carcinoma in situ, size and number of lesions, as well as time to first recurrence. Recurrences can be partly attributed to new occurrences but also to residual tumors after resection. Incomplete tumor removal has been observed in 30 to 50% of TUR's, especially when dealing with T1 or poorly visible malignant or pre-malignant disease1. Fluorescence guided resection with 5 amino levulinic acid (ALA) or its hexyl ester derivative (Hexvix, has now unequivocally been demonstrated to increase detection rate and a growing number of studies indicate this has a positive impact on recurrence and progression ratesImplantation of viable tumor cells, dispersed during resection, is a third factor influencing bladder cancer recurrence. The aim of early intravesical therapy is to interfere with cell viability and thus reduce implantation risks.

  10. Solitary Fibrous Tumor of Retromolar Pad; a Rare Challenging Case

    Science.gov (United States)

    Lotfi, Ali; Mokhtari, Sepideh; Moshref, Mohammad; Shahla, Maryam; Atarbashi Moghadam, Saede

    2017-01-01

    Solitary fibrous tumor has a wide spectrum of histopathologic features and many tumors show similar microscopic features. This similarity poses diagnostic challenges to the pathologists and immunohistochemical analysis is required in many cases. Moreover, it is a rare entity in orofacial region which consequently would make its diagnosis more challenging in oral cavity. The knowledge of various microscopic patterns of this tumor contributes to a proper diagnosis and prevents unnecessary treatment. This study reports a case of solitary fibrous tumor in the retromolar pad area and discusses its various histological features and differential diagnoses. PMID:28620640

  11. Multiscale CNNs for Brain Tumor Segmentation and Diagnosis.

    Science.gov (United States)

    Zhao, Liya; Jia, Kebin

    2016-01-01

    Early brain tumor detection and diagnosis are critical to clinics. Thus segmentation of focused tumor area needs to be accurate, efficient, and robust. In this paper, we propose an automatic brain tumor segmentation method based on Convolutional Neural Networks (CNNs). Traditional CNNs focus only on local features and ignore global region features, which are both important for pixel classification and recognition. Besides, brain tumor can appear in any place of the brain and be any size and shape in patients. We design a three-stream framework named as multiscale CNNs which could automatically detect the optimum top-three scales of the image sizes and combine information from different scales of the regions around that pixel. Datasets provided by Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized by MICCAI 2013 are utilized for both training and testing. The designed multiscale CNNs framework also combines multimodal features from T1, T1-enhanced, T2, and FLAIR MRI images. By comparison with traditional CNNs and the best two methods in BRATS 2012 and 2013, our framework shows advances in brain tumor segmentation accuracy and robustness.

  12. INTERFACING VISIBLE LIGHT COMMUNICATION WITH GSM NETWORKS TO PREVENT THE THEFT OF THE VEHICLE

    Directory of Open Access Journals (Sweden)

    P. Prabu

    2015-09-01

    Full Text Available Visible Light Communication (VLC by means of white Light Emitting Diode (LED is an alternate and most promising technology for existing Radio Frequency (RF communication. We proposed one of the important applications of VLC to prevent the theft of the vehicle. Every year approximately 36,000 vehicles worth Rs.115 crores are stolen in India. In critical road condition, only 15,000 are traced and many spare parts of vehicle are found missing. Even the existing technologies have some disadvantages related to the problem stated. In our paper, we dealt with the data communication through LED. One of the optical wireless communication having short range is called as VLC whose visible light spectrum starts from 380 nm and ends at 780 nm and it has an incomparable data rate of 10GB/s whereas the speed is 1MB/s on Bluetooth and for Infra Red (IR the speed is 4MB/s. We try to achieve the communication through VLC between 1 car - car to prevent the accident and 2 car - tollgate and received signal from tollgate is transmitted to Global System for Mobile communication (GSM network using microcontroller to prevent the theft of vehicle. To enhance the security of VLC, Advanced Encryption Standard (AES algorithm is used and the result is illustrated with the help of LabVIEW.

  13. Creating an African HIV clinical research and prevention trials network: HIV prevalence, incidence and transmission.

    Directory of Open Access Journals (Sweden)

    Anatoli Kamali

    Full Text Available HIV epidemiology informs prevention trial design and program planning. Nine clinical research centers (CRC in sub-Saharan Africa conducted HIV observational epidemiology studies in populations at risk for HIV infection as part of an HIV prevention and vaccine trial network. Annual HIV incidence ranged from below 2% to above 10% and varied by CRC and risk group, with rates above 5% observed in Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria fishing communities, men who have sex with men, and several cohorts of women. HIV incidence tended to fall after the first three months in the study and over calendar time. Among suspected transmission pairs, 28% of HIV infections were not from the reported partner. Volunteers with high incidence were successfully identified and enrolled into large scale cohort studies. Over a quarter of new cases in couples acquired infection from persons other than the suspected transmitting partner.

  14. Creating an African HIV Clinical Research and Prevention Trials Network: HIV Prevalence, Incidence and Transmission

    Science.gov (United States)

    Kamali, Anatoli; Price, Matt A.; Lakhi, Shabir; Karita, Etienne; Inambao, Mubiana; Sanders, Eduard J.; Anzala, Omu; Latka, Mary H.; Bekker, Linda-Gail; Kaleebu, Pontiano; Asiki, Gershim; Ssetaala, Ali; Ruzagira, Eugene; Allen, Susan; Farmer, Paul; Hunter, Eric; Mutua, Gaudensia; Makkan, Heeran; Tichacek, Amanda; Brill, Ilene K.; Fast, Pat; Stevens, Gwynn; Chetty, Paramesh; Amornkul, Pauli N.; Gilmour, Jill

    2015-01-01

    HIV epidemiology informs prevention trial design and program planning. Nine clinical research centers (CRC) in sub-Saharan Africa conducted HIV observational epidemiology studies in populations at risk for HIV infection as part of an HIV prevention and vaccine trial network. Annual HIV incidence ranged from below 2% to above 10% and varied by CRC and risk group, with rates above 5% observed in Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria fishing communities, men who have sex with men, and several cohorts of women. HIV incidence tended to fall after the first three months in the study and over calendar time. Among suspected transmission pairs, 28% of HIV infections were not from the reported partner. Volunteers with high incidence were successfully identified and enrolled into large scale cohort studies. Over a quarter of new cases in couples acquired infection from persons other than the suspected transmitting partner. PMID:25602351

  15. [Punish or cherish: p53, metabolism and tumor suppression].

    Science.gov (United States)

    Albagli, Olivier

    2015-10-01

    The p53 gene is essential for tumor suppression, but how it does so remains unclear. Upon genotoxic or oncogenic stresses, increased p53 activity induces transient cell cycle arrest, senescence or apoptosis, the three cornerstones of the so-called triumvirate. Accordingly, it has long been thought that p53 suppresses tumorigenesis by somehow counteracting cell proliferation or survival. However, several recently described genetically modified mice indicate that p53 can suppress tumorigenesis without triggering these three responses. Rather, as an important mechanism for tumor suppression, these mutant mice point to the ability of p53 to prevent the Warburg effect, that is to dampen glycolysis and foster mitochondrial respiration. Interestingly, these metabolic functions of p53 rely, in part, on its "unstressed" (basal) expression, a feature shared by its mechanistically linked anti-oxydant function. Together, these "conservative" activities of p53 may prevent tumor initiation by promoting and maintaining a normal oxidative metabolism and hence underly the "daily" tumor suppression by p53 in most cells. Conversely, destructive activities elicited by high p53 levels and leading to senescence or apoptosis provide a shield against partially or overtly transformed cells. This last situation, although relatively infrequent throughout life, is usual in experimental settings, which could explain the disproportionally high number of data implicating the triumvirate in tumor suppression by p53. © 2015 médecine/sciences – Inserm.

  16. GLI1 is a central mediator of EWS/FLI1 signaling in Ewing tumors.

    Directory of Open Access Journals (Sweden)

    Jay Joo

    2009-10-01

    Full Text Available The Ewing Sarcoma Family Tumors (ESFT consist of the classical pathologic entities of Ewing Sarcoma and peripheral Primitive Neuroectodermal Tumor. Occurring largely in the childhood through young adult years, these tumors have an unsurpassed propensity for metastasis and have no defined cell of origin. The biology of these aggressive malignancies centers around EWS/FLI1 and related EWS/ETS chimeric transcription factors, which are largely limited to this tumor class. Much progress has been made in the identification of a network of loci whose expression is modulated by EWS/FLI1 and its congeners. To date, little progress has been made in reconstructing the sequence of direct and indirect events that produce this network of modulated loci. The recent identification of GLI1 as an upregulated target of EWS/ETS transcription factors suggests a target which may be a more central mediator in the ESFT signaling network. In this paper, we further define the relationship of EWS/FLI1 expression and GLI1 upregulation in ESFT. This relationship is supported with data from primary tumor specimens. It is consistently observed across multiple ESFT cell lines and with multiple means of EWS/FLI1 inhibition. GLI1 inhibition affects tumor cell line phenotype whether shRNA or endogenous or pharmacologic inhibitors are employed. As is seen in model transformation systems, GLI1 upregulation by EWS/FLI1 appears to be independent of Hedgehog stimulation. Consistent with a more central role in ESFT pathogenesis, several known EWS/FLI1 targets appear to be targeted through GLI1. These findings further establish a central role for GLI1 in the pathogenesis of Ewing Tumors.

  17. State of infection prevention in US hospitals enrolled in the National Health and Safety Network.

    Science.gov (United States)

    Stone, Patricia W; Pogorzelska-Maziarz, Monika; Herzig, Carolyn T A; Weiner, Lindsey M; Furuya, E Yoko; Dick, Andrew; Larson, Elaine

    2014-02-01

    This report provides a national cross-sectional snapshot of infection prevention and control programs and clinician compliance with the implementation of processes to prevent health care-associated infections (HAIs) in intensive care units (ICUs). All hospitals, except Veterans Affairs hospitals, enrolled in the National Healthcare Safety Network (NHSN) were eligible to participate. Participation involved completing a survey assessing the presence of evidence-based prevention policies and clinician adherence and joining our NHSN research group. Descriptive statistics were computed. Facility characteristics and HAI rates by ICU type were compared between respondents and nonrespondents. Of the 3,374 eligible hospitals, 975 provided data (29% response rate) on 1,653 ICUs, and there were complete data on the presence of policies in 1,534 ICUs. The average number of infection preventionists (IPs) per 100 beds was 1.2. Certification of IP staff varied across institutions, and the average hours per week devoted to data management and secretarial support were generally low. There was variation in the presence of policies and clinician adherence to these policies. There were no differences in HAI rates between respondents and nonrespondents. Guidelines for IP staffing in acute care hospitals need to be updated. In future work, we will analyze the associations between HAI rates and infection prevention and control program characteristics, as well as the inplementation of and clinician adherence to evidence-based policies. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

  18. Understanding the poultry trade network in Kenya: Implications for regional disease prevention and control.

    Science.gov (United States)

    McCarron, Margaret; Munyua, Peninah; Cheng, Po-Yung; Manga, Thomas; Wanjohi, Cathryn; Moen, Ann; Mounts, Anthony; Katz, Mark A

    2015-07-01

    Infectious diseases in poultry can spread quickly and lead to huge economic losses. In the past decade, on multiple continents, the accelerated spread of highly pathogenic avian Influenza A (H5N1) virus, often through informal trade networks, has led to the death and culling of hundreds of millions of poultry. Endemic poultry diseases like Newcastle disease and fowl typhoid can also be devastating in many parts of the world. Understanding trade networks in unregulated systems can inform policy decisions concerning disease prevention and containment. From June to December 2008 we conducted a cross-sectional survey of backyard farmers, market traders, and middlemen in 5/8 provinces in Kenya. We administered a standardized questionnaire to each type of actor using convenience, random, snowball, and systematic sampling. Questionnaires addressed frequency, volume, and geography of trade, as well as biosecurity practices. We created a network diagram identifying the most important locations for trade. Of 380 respondents, 51% were backyard farmers, 24% were middlemen and 25% were market traders. Half (50%) of backyard farmers said they raised poultry both for household consumption and for sale. Compared to market traders, middlemen bought their poultry from a greater number of villages (median 4.2 villages for middlemen vs. 1.9 for market traders). Traders were most likely to purchase poultry from backyard farmers. Of the backyard farmers who sold poultry, 51% [CI 40-63] reported selling poultry to market traders, and 54% [CI 44-63] sold to middlemen. Middlemen moved the largest volume of poultry on a weekly basis (median purchases: 187 birds/week [IQR 206]; median sales: 188 birds/week [IQR 412.5]). The highest numbers of birds were traded in Nairobi - Kenya's capital city. Nairobi was the most prominent trading node in the network (61 degrees of centrality). Many smaller sub-networks existed as a result of clustered local trade. Market traders were also integral to the

  19. Exosome-Based Cell-Cell Communication in the Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Joana Maia

    2018-02-01

    Full Text Available Tumors are not isolated entities, but complex systemic networks involving cell-cell communication between transformed and non-transformed cells. The milieu created by tumor-associated cells may either support or halt tumor progression. In addition to cell-cell contact, cells communicate through secreted factors via a highly complex system involving characteristics such as ligand concentration, receptor expression and integration of diverse signaling pathways. Of these, extracellular vesicles, such as exosomes, are emerging as novel cell-cell communication mediators in physiological and pathological scenarios. Exosomes, membrane vesicles of endocytic origin released by all cells (both healthy and diseased, ranging in size from 30 to 150 nm, transport all the main biomolecules, including lipids, proteins, DNAs, messenger RNAs and microRNA, and perform intercellular transfer of components, locally and systemically. By acting not only in tumor cells, but also in tumor-associated cells such as fibroblasts, endothelium, leukocytes and progenitor cells, tumor- and non-tumor cells-derived exosomes have emerged as new players in tumor growth and invasion, tumor-associated angiogenesis, tissue inflammation and immunologic remodeling. In addition, due to their property of carrying molecules from their cell of origin to the peripheral circulation, exosomes have been increasingly studied as sources of tumor biomarkers in liquid biopsies. Here we review the current literature on the participation of exosomes in the communication between tumor and tumor-associated cells, highlighting the role of this process in the setup of tumor microenvironments that modulate tumor initiation and metastasis.

  20. Kidney cancer progression linked to shifts in tumor metabolism

    Science.gov (United States)

    Investigators in The Cancer Genome Atlas Research Network have uncovered a connection between how tumor cells use energy from metabolic processes and the aggressiveness of the most common form of kidney cancer, clear cell renal cell carcinoma.

  1. HUMAN NK CELLS: FROM SURFACE RECEPTORS TO THE THERAPY OF LEUKEMIAS AND SOLID TUMORS

    Directory of Open Access Journals (Sweden)

    LORENZO eMORETTA

    2014-03-01

    Full Text Available Natural Killer (NK cells are major effector cells of the innate immunity. The discovery, over two decades ago, of MHC-class I specific NK receptors and subsequently of activating receptors, recognizing ligands expressed by tumor or virus-infected cells, paved the way to our understanding of the mechanisms of selective recognition and killing of tumor cells. Although NK cells can efficiently kill tumor cells of different histotypes in vitro, their activity may be limited in vivo by their inefficient trafficking to tumor lesions and by the inhibition of their function induced by tumor cells themselves and by the tumor microenvironment. On the other hand, the important role of NK cells has been clearly demonstrated in the therapy of high risk leukemias in the haploidentical hematopoietic cell (HSC transplantation setting. NK cells derived from donor HSC kill leukemic cells residual after the conditioning regimen, thus preventing leukemia relapses. In addition, they also kill residual dendritic cells and T lymphocytes, thus preventing both GvHD and graft rejection.

  2. Anti- and pro-tumor functions of autophagy.

    Science.gov (United States)

    Morselli, Eugenia; Galluzzi, Lorenzo; Kepp, Oliver; Vicencio, José-Miguel; Criollo, Alfredo; Maiuri, Maria Chiara; Kroemer, Guido

    2009-09-01

    Autophagy constitutes one of the major responses to stress in eukaryotic cells, and is regulated by a complex network of signaling cascades. Not surprisingly, autophagy is implicated in multiple pathological processes, including infection by pathogens, inflammatory bowel disease, neurodegeneration and cancer. Both oncogenesis and tumor survival are influenced by perturbations of the molecular machinery that controls autophagy. Numerous oncoproteins, including phosphatidylinositol 3-kinase, Akt1 and anti-apoptotic members of the Bcl-2 family suppress autophagy. Conversely, several tumor suppressor proteins (e.g., Atg4c; beclin 1; Bif-1; BH3-only proteins; death-associated protein kinase 1; LKB1/STK11; PTEN; UVRAG) promote the autophagic pathway. This does not entirely apply to p53, one of the most important tumor suppressor proteins, which regulates autophagy in an ambiguous fashion, depending on its subcellular localization. Irrespective of the controversial role of p53, basal levels of autophagy appear to inhibit tumor development. On the contrary, chemotherapy- and metabolic stress-induced activation of the autophagic pathway reportedly contribute to the survival of formed tumors, thereby favoring resistance. In this context, autophagy inhibition would represent a major therapeutic target for chemosensitization. Here, we will review the current knowledge on the dual role of autophagy as an anti- and pro-tumor mechanism.

  3. Antigen localization controls T cell-mediated tumor immunity.

    Science.gov (United States)

    Zeelenberg, Ingrid S; van Maren, Wendy W C; Boissonnas, Alexandre; Van Hout-Kuijer, Maaike A; Den Brok, Martijn H M G M; Wagenaars, Jori A L; van der Schaaf, Alie; Jansen, Eric J R; Amigorena, Sebastian; Théry, Clotilde; Figdor, Carl G; Adema, Gosse J

    2011-08-01

    Effective antitumor immunotherapy requires the identification of suitable target Ags. Interestingly, many of the tumor Ags used in clinical trials are present in preparations of secreted tumor vesicles (exosomes). In this study, we compared T cell responses elicited by murine MCA101 fibrosarcoma tumors expressing a model Ag at different localizations within the tumor cell in association with secreted vesicles (exosomes), as a nonsecreted cell-associated protein, or as secreted soluble protein. Remarkably, we demonstrated that only the tumor-secreting vesicle-bound Ag elicited a strong Ag-specific CD8(+) T cell response, CD4(+) T cell help, Ag-specific Abs, and a decrease in the percentage of immunosuppressive regulatory T cells in the tumor. Moreover, in a therapeutic tumor model of cryoablation, only in tumors secreting vesicle-bound Ag could Ag-specific CD8(+) T cells still be detected up to 16 d after therapy. We concluded that the localization of an Ag within the tumor codetermines whether a robust immunostimulatory response is elicited. In vivo, vesicle-bound Ag clearly skews toward a more immunogenic phenotype, whereas soluble or cell-associated Ag expression cannot prevent or even delay outgrowth and results in tumor tolerance. This may explain why particular immunotherapies based on these vesicle-bound tumor Ags are potentially successful. Therefore, we conclude that this study may have significant implications in the discovery of new tumor Ags suitable for immunotherapy and that their location should be taken into account to ensure a strong antitumor immune response.

  4. Pollution Prevention Information Network (PPIN) Grant Summaries 2014

    Science.gov (United States)

    The Office of Pollution Prevention and Toxics is responsible for overseeing several grant programs for tribes and states which promote pollution prevention through source reduction and resource conservation.

  5. Spices for Prevention and Treatment of Cancers.

    Science.gov (United States)

    Zheng, Jie; Zhou, Yue; Li, Ya; Xu, Dong-Ping; Li, Sha; Li, Hua-Bin

    2016-08-12

    Spices have been widely used as food flavorings and folk medicines for thousands of years. Numerous studies have documented the antioxidant, anti-inflammatory and immunomodulatory effects of spices, which might be related to prevention and treatment of several cancers, including lung, liver, breast, stomach, colorectum, cervix, and prostate cancers. Several spices are potential sources for prevention and treatment of cancers, such as Curcuma longa (tumeric), Nigella sativa (black cumin), Zingiber officinale (ginger), Allium sativum (garlic), Crocus sativus (saffron), Piper nigrum (black pepper) and Capsicum annum (chili pepper), which contained several important bioactive compounds, such as curcumin, thymoquinone, piperine and capsaicin. The main mechanisms of action include inducing apoptosis, inhibiting proliferation, migration and invasion of tumors, and sensitizing tumors to radiotherapy and chemotherapy. This review summarized recent studies on some spices for prevention and treatment of cancers, and special attention was paid to bioactive components and mechanisms of action.

  6. Spices for Prevention and Treatment of Cancers

    Science.gov (United States)

    Zheng, Jie; Zhou, Yue; Li, Ya; Xu, Dong-Ping; Li, Sha; Li, Hua-Bin

    2016-01-01

    Spices have been widely used as food flavorings and folk medicines for thousands of years. Numerous studies have documented the antioxidant, anti-inflammatory and immunomodulatory effects of spices, which might be related to prevention and treatment of several cancers, including lung, liver, breast, stomach, colorectum, cervix, and prostate cancers. Several spices are potential sources for prevention and treatment of cancers, such as Curcuma longa (tumeric), Nigella sativa (black cumin), Zingiber officinale (ginger), Allium sativum (garlic), Crocus sativus (saffron), Piper nigrum (black pepper) and Capsicum annum (chili pepper), which contained several important bioactive compounds, such as curcumin, thymoquinone, piperine and capsaicin. The main mechanisms of action include inducing apoptosis, inhibiting proliferation, migration and invasion of tumors, and sensitizing tumors to radiotherapy and chemotherapy. This review summarized recent studies on some spices for prevention and treatment of cancers, and special attention was paid to bioactive components and mechanisms of action. PMID:27529277

  7. Establishing HIV treatment as prevention in the HIV Prevention Trials Network 052 randomized trial: an ethical odyssey.

    Science.gov (United States)

    Cohen, Myron S; McCauley, Marybeth; Sugarman, Jeremy

    2012-06-01

    Obtaining the definitive data necessary to determine the safety and efficacy of using antiretroviral treatment (ART) to reduce the sexual transmission of HIV in heterosexual couples encountered an array of ethical challenges that threatened to compromise HIV Prevention Trials Network (HPTN) 052, the multinational clinical trial addressing this issue that has profound public health implications. To describe and analyze the major ethical challenges faced in HPTN 052. The ethical issues and modifications of HPTN 052 in response to these issues were cataloged by the principal investigator, the lead coordinator, and the ethicist working on the trial. The major ethical issues that were unique to the trial were then described and analyzed in light of the published literature as well as guidances and policies. The ethical challenges that must be addressed in many clinical trials, such as those related to obtaining informed consent and making provisions for ancillary care, are not described. When HPTN 052 was being designed, ethical questions emerged related to the relevance of the research question itself given data from observational research and a range of beliefs about the appropriate means of preventing and treating HIV infection and AIDS. Furthermore, ethical challenges were faced regarding site selection since there was a scientific need to conduct the research in settings where HIV incidence was high, but alternatives to study participation should be available. As in most HIV-prevention research, ethical questions surrounded the determination of the appropriate prevention package for all of those enrolled. During the course of the trial, guidance documents and policies emerged that were of direct relevance to the research questions, calling for a balancing of concerns for the research subjects and trial integrity. When the study results were made public, there was a need to ensure access to the treatment shown to be effective that in some cases differed from the

  8. Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    International Nuclear Information System (INIS)

    Tonelli, Francesco; Giudici, Francesco; Giusti, Francesca; Brandi, Maria Luisa

    2012-01-01

    We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present

  9. Multiscale CNNs for Brain Tumor Segmentation and Diagnosis

    Directory of Open Access Journals (Sweden)

    Liya Zhao

    2016-01-01

    Full Text Available Early brain tumor detection and diagnosis are critical to clinics. Thus segmentation of focused tumor area needs to be accurate, efficient, and robust. In this paper, we propose an automatic brain tumor segmentation method based on Convolutional Neural Networks (CNNs. Traditional CNNs focus only on local features and ignore global region features, which are both important for pixel classification and recognition. Besides, brain tumor can appear in any place of the brain and be any size and shape in patients. We design a three-stream framework named as multiscale CNNs which could automatically detect the optimum top-three scales of the image sizes and combine information from different scales of the regions around that pixel. Datasets provided by Multimodal Brain Tumor Image Segmentation Benchmark (BRATS organized by MICCAI 2013 are utilized for both training and testing. The designed multiscale CNNs framework also combines multimodal features from T1, T1-enhanced, T2, and FLAIR MRI images. By comparison with traditional CNNs and the best two methods in BRATS 2012 and 2013, our framework shows advances in brain tumor segmentation accuracy and robustness.

  10. Selenium for the Prevention of Cutaneous Melanoma

    Science.gov (United States)

    Cassidy, Pamela B.; Fain, Heidi D.; Cassidy, James P.; Tran, Sally M.; Moos, Philip J.; Boucher, Kenneth M.; Gerads, Russell; Florell, Scott R.; Grossman, Douglas; Leachman, Sancy A.

    2013-01-01

    The role of selenium (Se) supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to study two unique therapeutic windows for intervention in the process of cutaneous melanomagenisis, and to examine the utility of two different chemical forms of Se for prevention and treatment of melanoma. We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts. Our findings suggest that modestly elevation of selenium levels in the skin might risk acceleration of growth of incipient tumors. Additionally, certain Se compounds administered at very high doses could have utility for the treatment of fully-malignant tumors or prevention of recurrence. PMID:23470450

  11. The emerging potential for network analysis to inform precision cancer medicine.

    Science.gov (United States)

    Ozturk, Kivilcim; Dow, Michelle; Carlin, Daniel E; Bejar, Rafael; Carter, Hannah

    2018-06-14

    Precision cancer medicine promises to tailor clinical decisions to patients using genomic information. Indeed, successes of drugs targeting genetic alterations in tumors, such as imatinib that targets BCR-ABL in chronic myelogenous leukemia, have demonstrated the power of this approach. However biological systems are complex, and patients may differ not only by the specific genetic alterations in their tumor, but by more subtle interactions among such alterations. Systems biology and more specifically, network analysis, provides a framework for advancing precision medicine beyond clinical actionability of individual mutations. Here we discuss applications of network analysis to study tumor biology, early methods for N-of-1 tumor genome analysis and the path for such tools to the clinic. Copyright © 2018. Published by Elsevier Ltd.

  12. Modeling In-Network Aggregation in VANETs

    NARCIS (Netherlands)

    Dietzel, Stefan; Kargl, Frank; Heijenk, Geert; Schaub, Florian

    2011-01-01

    The multitude of applications envisioned for vehicular ad hoc networks requires efficient communication and dissemination mechanisms to prevent network congestion. In-network data aggregation promises to reduce bandwidth requirements and enable scalability in large vehicular networks. However, most

  13. Ketoconazole attenuates radiation-induction of tumor necrosis factor

    Energy Technology Data Exchange (ETDEWEB)

    Hallahan, D.E.; Virudachalam, S.; Kufe, D.W.; Weichselbaum, R.R. [Dana Farber Cancer Institute, Boston, MA (United States)

    1994-07-01

    Previous work has demonstrated that inhibitors of phospholipase A2 attenuate ionizing radiation-induced arachidonic acid production, protein kinase C activation, and prevent subsequent induction of the tumor necrosis factor gene. Because arachidonic acid contributes to radiation-induced tumor necrosis factor expression, the authors analyzed the effects of agents which alter arachidonate metabolism on the regulation of this gene. Phospholipase A2 inhibitors quinicrine, bromphenyl bromide, and pentoxyfylline or the inhibitor of lipoxygenase (ketoconazole) or the inhibitor of cycloxygenase (indomethacine) were added to cell culture 1 h prior to irradiation. Radiation-induced tumor necrosis factor gene expression was attenuated by each of the phospholipase A2 inhibitors (quinicrine, bromphenylbromide, and pentoxyfylline). Furthermore, ketoconazole attenuated X ray induced tumor necrosis factor gene expression. Conversely, indomethacin enhanced tumor necrosis factor expression following irradiation. The finding that radiation-induced tumor necrosis factor gene expression was attenuated by ketoconazole suggests that the lipoxygenase pathway participates in signal transduction preceding tumor necrosis factor induction. Enhancement of tumor necrosis factor expression by indomethacin following irradiation suggests that prostaglandins produced by cyclooxygenase act as negative regulators of tumor necrosis factor expression. Inhibitors of tumor necrosis factor induction ameliorate acute and subacute sequelae of radiotherapy. The authors propose therefore, that ketoconazole may reduce acute radiation sequelae such as mucositis and esophagitis through a reduction in tumor necrosis factor induction or inhibition of phospholipase A2 in addition to its antifungal activity. 25 refs., 2 figs.

  14. Hypoxia alters the physical properties of the tumor microenvironment

    Science.gov (United States)

    Gilkes, Daniele

    Of all the deaths attributed to cancer, 90% are due to metastasis, or the spread of cancer cells from a primary tumor to distant organs, and treatments that prevent or cure metastasis remain elusive. Emerging data indicate that low oxygen states within a tumor, termed hypoxia, can alter the chemical and physical parameters of the extracellular matrix (ECM), or scaffold of the tumor tissue. These changes generate a microenvironment that may be more conducive for promoting metastasis. During tumor evolution, changes in the composition and the overall content of the ECM reflect both its biophysical and biological properties and these strongly influence the cells properties, such as cellular proliferation and cell motility. The talk will cover how hypoxia arises within normal tissue and also in tumors. We will cover the role of hypoxia in collagen biogenesis which influences compositional changes to the tumor microenvironment and discuss how these changes lead to a stiffer tumor stroma. The challenges in determining the influence of chemical versus physical cues on cancer progression will also be considered.

  15. ONCOLYTIC VIRUS-MEDIATED REVERSAL OF IMPAIRED TUMOR ANTIGEN PRESENTATION

    Directory of Open Access Journals (Sweden)

    Shashi Ashok Gujar

    2014-04-01

    Full Text Available Anti-tumor immunity can eliminate existing cancer cells and also maintain a constant surveillance against possible relapse. Such an antigen-specific adaptive response begins when tumor-specific T cells become activated. T cell activation requires two signals on antigen presenting cells (APCs: antigen presentation through MHC molecules and co-stimulation. In the absence of one or both of these signals, T cells remain inactivated or can even become tolerized. Cancer cells and their associated microenvironment strategically hinder the processing and presentation of tumor antigens and consequently prevent the development of anti-tumor immunity. Many studies, however, demonstrate that interventions that overturn tumor-associated immune evasion mechanisms can establish anti-tumor immune responses of therapeutic potential. One such intervention is oncolytic virus (OV-based anti-cancer therapy. Here we discuss how OV-induced immunological events override tumor-associated antigen presentation impairment and promote appropriate T cell:APC interaction. Detailed understanding of this phenomenon is pivotal for devising the strategies that will enhance the efficacy of OV-based anti-cancer therapy by complementing its inherent oncolytic

  16. Market analyses of livestock trade networks to inform the prevention of joint economic and epidemiological risks.

    Science.gov (United States)

    Moslonka-Lefebvre, Mathieu; Gilligan, Christopher A; Monod, Hervé; Belloc, Catherine; Ezanno, Pauline; Filipe, João A N; Vergu, Elisabeta

    2016-03-01

    Conventional epidemiological studies of infections spreading through trade networks, e.g., via livestock movements, generally show that central large-size holdings (hubs) should be preferentially surveyed and controlled in order to reduce epidemic spread. However, epidemiological strategies alone may not be economically optimal when costs of control are factored in together with risks of market disruption from targeting core holdings in a supply chain. Using extensive data on animal movements in supply chains for cattle and swine in France, we introduce a method to identify effective strategies for preventing outbreaks with limited budgets while minimizing the risk of market disruptions. Our method involves the categorization of holdings based on position along the supply chain and degree of market share. Our analyses suggest that trade has a higher risk of propagating epidemics through cattle networks, which are dominated by exchanges involving wholesalers, than for swine. We assess the effectiveness of contrasting interventions from the perspectives of regulators and the market, using percolation analysis. We show that preferentially targeting minor, non-central agents can outperform targeting of hubs when the costs to stakeholders and the risks of market disturbance are considered. Our study highlights the importance of assessing joint economic-epidemiological risks in networks underlying pathogen propagation and trade. © 2016 The Authors.

  17. Market analyses of livestock trade networks to inform the prevention of joint economic and epidemiological risks

    Science.gov (United States)

    Gilligan, Christopher A.; Belloc, Catherine; Filipe, João A. N.; Vergu, Elisabeta

    2016-01-01

    Conventional epidemiological studies of infections spreading through trade networks, e.g. via livestock movements, generally show that central large-size holdings (hubs) should be preferentially surveyed and controlled in order to reduce epidemic spread. However, epidemiological strategies alone may not be economically optimal when costs of control are factored in together with risks of market disruption from targeting core holdings in a supply chain. Using extensive data on animal movements in supply chains for cattle and swine in France, we introduce a method to identify effective strategies for preventing outbreaks with limited budgets while minimizing the risk of market disruptions. Our method involves the categorization of holdings based on position along the supply chain and degree of market share. Our analyses suggest that trade has a higher risk of propagating epidemics through cattle networks, which are dominated by exchanges involving wholesalers, than for swine. We assess the effectiveness of contrasting interventions from the perspectives of regulators and the market, using percolation analysis. We show that preferentially targeting minor, non-central agents can outperform targeting of hubs when the costs to stakeholders and the risks of market disturbance are considered. Our study highlights the importance of assessing joint economic–epidemiological risks in networks underlying pathogen propagation and trade. PMID:26984191

  18. Fractional laser exposure induces neutrophil infiltration (N1 phenotype into the tumor and stimulates systemic anti-tumor immune response.

    Directory of Open Access Journals (Sweden)

    Masayoshi Kawakubo

    Full Text Available Ablative fractional photothermolysis (aFP using a CO2 laser generates multiple small diameter tissue lesions within the irradiation field. aFP is commonly used for a wide variety of dermatological indications, including treatment of photodamaged skin and dyschromia, drug delivery and modification of scars due to acne, surgical procedures and burns. In this study we explore the utility of aFP for treating oncological indications, including induction of local tumor regression and inducing anti-tumor immunity, which is in marked contrast to current indications of aFP.We used a fractional CO2 laser to treat a tumor established by BALB/c colon carcinoma cell line (CT26.CL25, which expressed a tumor antigen, beta-galactosidase (beta-gal. aFP treated tumors grew significantly slower as compared to untreated controls. Complete remission after a single aFP treatment was observed in 47% of the mice. All survival mice from the tumor inoculation rejected re-inoculation of the CT26.CL25 colon carcinoma cells and moreover 80% of the survival mice rejected CT26 wild type colon carcinoma cells, which are parental cells of CT26.CL25 cells. Histologic section of the FP-treated tumors showed infiltrating neutrophil in the tumor early after aFP treatment. Flow cytometric analysis of tumor-infiltrating lymphocytes showed aFP treatment abrogated the increase in regulatory T lymphocyte (Treg, which suppresses anti-tumor immunity and elicited the expansion of epitope-specific CD8+ T lymphocytes, which were required to mediate the tumor-suppressing effect of aFP.We have demonstrated that aFP is able to induce a systemic anti-tumor adaptive immunity preventing tumor recurrence in a murine colon carcinoma in a mouse model. This study demonstrates a potential role of aFP treatments in oncology and further studies should be performed.

  19. Resistance exercise attenuates skeletal muscle oxidative stress, systemic pro-inflammatory state, and cachexia in Walker-256 tumor-bearing rats.

    Science.gov (United States)

    Padilha, Camila Souza; Borges, Fernando Henrique; Costa Mendes da Silva, Lilian Eslaine; Frajacomo, Fernando Tadeu Trevisan; Jordao, Alceu Afonso; Duarte, José Alberto; Cecchini, Rubens; Guarnier, Flávia Alessandra; Deminice, Rafael

    2017-09-01

    The aim of this study was to investigate the effects of resistance exercise training (RET) on oxidative stress, systemic inflammatory markers, and muscle wasting in Walker-256 tumor-bearing rats. Male (Wistar) rats were divided into 4 groups: sedentary controls (n = 9), tumor-bearing (n = 9), exercised (n = 9), and tumor-bearing exercised (n = 10). Exercised and tumor-bearing exercised rats were exposed to resistance exercise of climbing a ladder apparatus with weights tied to their tails for 6 weeks. The physical activity of control and tumor-bearing rats was confined to the space of the cage. After this period, tumor-bearing and tumor-bearing exercised animals were inoculated subcutaneously with Walker-256 tumor cells (11.0 × 10 7 cells in 0.5 mL of phosphate-buffered saline) while control and exercised rats were injected with vehicle. Following inoculation, rats maintained resistance exercise training (exercised and tumor-bearing exercised) or sedentary behavior (control and tumor-bearing) for 12 more days, after which they were euthanized. Results showed muscle wasting in the tumor-bearing group, with body weight loss, increased systemic leukocytes, and inflammatory interleukins as well as muscular oxidative stress and reduced mTOR signaling. In contrast, RET in the tumor-bearing exercised group was able to mitigate the reduced body weight and muscle wasting with the attenuation of muscle oxidative stress and systemic inflammatory markers. RET also prevented loss of muscle strength associated with tumor development. RET, however, did not prevent the muscle proteolysis signaling via FBXO32 gene messenger RNA expression in the tumor-bearing group. In conclusion, RET performed prior tumor implantation prevents cachexia development by attenuating tumor-induced systemic pro-inflammatory condition with muscle oxidative stress and muscle damage.

  20. Phenotypic and Functional Properties of Tumor-Infiltrating Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Gap Ryol Lee

    2017-01-01

    Full Text Available Regulatory T (Treg cells maintain immune homeostasis by suppressing excessive immune responses. Treg cells induce tolerance against self- and foreign antigens, thus preventing autoimmunity, allergy, graft rejection, and fetus rejection during pregnancy. However, Treg cells also infiltrate into tumors and inhibit antitumor immune responses, thus inhibiting anticancer therapy. Depleting whole Treg cell populations in the body to enhance anticancer treatments will produce deleterious autoimmune diseases. Therefore, understanding the precise nature of tumor-infiltrating Treg cells is essential for effectively targeting Treg cells in tumors. This review summarizes recent results relating to Treg cells in the tumor microenvironment, with particular emphasis on their accumulation, phenotypic, and functional properties, and targeting to enhance the efficacy of anticancer treatment.

  1. Vulnerability of network of networks

    Science.gov (United States)

    Havlin, S.; Kenett, D. Y.; Bashan, A.; Gao, J.; Stanley, H. E.

    2014-10-01

    Our dependence on networks - be they infrastructure, economic, social or others - leaves us prone to crises caused by the vulnerabilities of these networks. There is a great need to develop new methods to protect infrastructure networks and prevent cascade of failures (especially in cases of coupled networks). Terrorist attacks on transportation networks have traumatized modern societies. With a single blast, it has become possible to paralyze airline traffic, electric power supply, ground transportation or Internet communication. How, and at which cost can one restructure the network such that it will become more robust against malicious attacks? The gradual increase in attacks on the networks society depends on - Internet, mobile phone, transportation, air travel, banking, etc. - emphasize the need to develop new strategies to protect and defend these crucial networks of communication and infrastructure networks. One example is the threat of liquid explosives a few years ago, which completely shut down air travel for days, and has created extreme changes in regulations. Such threats and dangers warrant the need for new tools and strategies to defend critical infrastructure. In this paper we review recent advances in the theoretical understanding of the vulnerabilities of interdependent networks with and without spatial embedding, attack strategies and their affect on such networks of networks as well as recently developed strategies to optimize and repair failures caused by such attacks.

  2. Automatic Semantic Segmentation of Brain Gliomas from MRI Images Using a Deep Cascaded Neural Network.

    Science.gov (United States)

    Cui, Shaoguo; Mao, Lei; Jiang, Jingfeng; Liu, Chang; Xiong, Shuyu

    2018-01-01

    Brain tumors can appear anywhere in the brain and have vastly different sizes and morphology. Additionally, these tumors are often diffused and poorly contrasted. Consequently, the segmentation of brain tumor and intratumor subregions using magnetic resonance imaging (MRI) data with minimal human interventions remains a challenging task. In this paper, we present a novel fully automatic segmentation method from MRI data containing in vivo brain gliomas. This approach can not only localize the entire tumor region but can also accurately segment the intratumor structure. The proposed work was based on a cascaded deep learning convolutional neural network consisting of two subnetworks: (1) a tumor localization network (TLN) and (2) an intratumor classification network (ITCN). The TLN, a fully convolutional network (FCN) in conjunction with the transfer learning technology, was used to first process MRI data. The goal of the first subnetwork was to define the tumor region from an MRI slice. Then, the ITCN was used to label the defined tumor region into multiple subregions. Particularly, ITCN exploited a convolutional neural network (CNN) with deeper architecture and smaller kernel. The proposed approach was validated on multimodal brain tumor segmentation (BRATS 2015) datasets, which contain 220 high-grade glioma (HGG) and 54 low-grade glioma (LGG) cases. Dice similarity coefficient (DSC), positive predictive value (PPV), and sensitivity were used as evaluation metrics. Our experimental results indicated that our method could obtain the promising segmentation results and had a faster segmentation speed. More specifically, the proposed method obtained comparable and overall better DSC values (0.89, 0.77, and 0.80) on the combined (HGG + LGG) testing set, as compared to other methods reported in the literature. Additionally, the proposed approach was able to complete a segmentation task at a rate of 1.54 seconds per slice.

  3. "Mixed germ cell testicular tumor" in an adult female

    Directory of Open Access Journals (Sweden)

    Udasimath Shivakumarswamy

    2012-01-01

    Full Text Available The androgen insensitivity (testicular feminization syndrome was described by Morris in phenotypic females with 46XY karyotype, presenting with primary amenorrhea, adequate breast development, and absent or scanty pubic or axillary hair. Gonads consist usually of seminiferous tubules without spermatogenesis. These patients have a 5-10% risk of developing germ cell tumors, usually after the complete development of secondary female sexual characteristics. We hereby report a case considered as a female with married life of 15 years, who was operated for severe abdominal pain. Phenotype characters were that of female. Microscopic examination of the tumor from the abdomen revealed germinoma and yolk sac tumor with adjacent seminiferous tubules. Karyotyping showed 46XY. Final diagnosis of malignant mixed germ cell tumor in androgen insensitivity syndrome was made. Surveillance may be the most appropriate option when these conditions are initially diagnosed in adulthood to prevent development of germ cell tumors.

  4. Building secure network by integrated technology

    International Nuclear Information System (INIS)

    An Dehai; Xu Rongsheng; Liu Baoxu

    2000-01-01

    The author introduces a method which can realize the most powerful network security prevention by the network security integrated technologies such as firewall, realtime monitor, network scanner, Web detection and security, etc

  5. Locally aggressive and multifocal phosphaturic mesenchymal tumors: two unusual cases of tumor-induced osteomalacia.

    Science.gov (United States)

    Higley, Meghan; Beckett, Brooke; Schmahmann, Sandra; Dacey, Elizabeth; Foss, Erik

    2015-12-01

    Tumor-induced osteomalacia (TIO) has long been recognized as a clinical paraneoplastic syndrome. The identification of a unique histopathologic entity, the phosphaturic mesenchymal tumor (PMT), as a distinct etiology for TIO has been a more recent discovery. The majority of published cases describe a solitary, non-aggressive appearing soft tissue or osseous lesions in patients with osteomalacia; aggressive appearing or multifocal lesions appear to be exceedingly rare. These tumors characteristically secrete fibroblast growth factor 23 (FGF23). Elevated serum levels of FGF23 result in phosphate wasting and osteomalacia. In the majority of cases, laboratory abnormalities and clinical signs and symptoms of osteomalacia precede identification of the causative lesion by years. Following diagnosis, complete resection with wide margins to prevent local recurrence is most often curative. Imaging characteristics of PMT are diverse and remain incompletely defined, as the majority of previous publications are outside of the radiologic literature. We present multiple imaging modalities in two cases of patients with debilitating osteomalacia and unusual appearing PMTs: one with a locally aggressive lesion leading to pathologic fracture, the second presenting with exceedingly rare multifocal PMT.

  6. Tumor-educated myeloid cells: impact the micro- and macroenvironment.

    Science.gov (United States)

    Becker, Jürgen C

    2014-03-01

    Immune escape mechanisms of cancers include some of the mechanisms normally used for immune homeostasis, particular those preventing autoimmunity; one of these is the polarisation of myeloid cells. Thereby, tumors, i.e. the cancerous and stromal cells, also condition distant sites like spleen and bone marrow via soluble factors and membrane vesicles such as exosomes in order to create a tumor-educated macroenvironment. Albeit these mechanisms are currently in the focus of (tumor-)immunologic research, the first evidence had been published almost 40 years ago. One of these early reports will be discussed here. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Moving Toward Bioadjuvant Approaches to Head and Neck Cancer Prevention

    International Nuclear Information System (INIS)

    Saba, Nabil F.; Hammond, Anthea; Shin, Dong M.; Khuri, Fadlo R.

    2007-01-01

    Head and neck squamous cell carcinoma affects >45,000 Americans annually. Patients who are successfully treated for their primary tumor are at high risk of developing a second primary tumor, making effective preventive strategies highly desirable for this disease. Although a landmark study in 1990 suggested some benefit of high-dose retinoids in head and neck cancer prevention, subsequent trials using more tolerable doses have shown limited clinical success. Newer preventive strategies have included bioadjuvant therapy combining retinoids with interferon and α-tocopherol, combinations of molecularly targeted agents, and oncolytic viruses. Furthermore, considerable evidence has supported a cancer protective role for several nutrients, including green tea and curcumin analogs. Natural compounds such as these with favorable long-term safety profiles might be particularly suited to the cancer prevention setting, in which patients will usually tolerate only moderate risk and toxicity

  8. The relationship between community nutritionists' use of policy, systems and environmental strategies to prevent obesity and its determinants depends on networking.

    Science.gov (United States)

    Lu, Angela H; Dickin, Katherine L; Constas, Mark A; Dollahite, Jamie S

    2017-08-01

    To apply the Theory of Planned Behaviour to examine the relationship between the constructs of background factors and beliefs towards using policy, systems and environmental (PSE) strategies and reported use of PSE strategies to prevent obesity by a group of professional nutrition educators. Cross-sectional study using self-reported survey. Cooperative Extension in New York, USA. Nutrition educators (n 58); survey response rate 100 %. Nutrition educators' reported use of PSE strategies to prevent obesity were positively associated with background factors of their community networking and number of staff they managed, their belief of other people's expectations of them to make PSE changes and the belief that their communities were ready to use PSE strategies; and negatively associated with their belief that individual-level factors contributed to obesity. The relationships among these variables were complicated and their use of PSE strategies occurred only when they utilized their professional networks at a moderately high level (above mean of 5·3 on a scale of 1-7), given that their community was also ready to use PSE strategies. Nutrition educators' use of PSE strategies depends on several internal and external factors. Community networking needs to be emphasized as one of the most significant factors contributing to nutrition educators' work in this area. Organizational and community support should be in place in order to facilitate nutrition educators' effective use of PSE strategies.

  9. Naked DNA Immunization for Prevention of Prostate Cancer in a Dunning Rat Prostate Tumor Model

    National Research Council Canada - National Science Library

    Mincheff, Milcho

    2003-01-01

    ...: H-PSMA-T, R-"PSMA"-T, H-PSA, H-PSA-T, H-PAP-T and R"PSMA"-S. Preliminary studies using the Copenhagen rat tumor prostate model showed uniform tumor development in rats that were injected subcutaneously with 100 000 AT3B-lPSMA,PSA cells...

  10. Social networks and their role in preventing dementia

    OpenAIRE

    Pillai, Jagan A.; Verghese, Joe

    2009-01-01

    Interest in the role of social networks as a protective factor in the development of dementia over the last decade has increased with a number of longitudinal studies being published on the possible association of different lifestyles with dementia. This review examines and provides a summary of the published longitudinal studies exploring the effect of social network on dementia, with particular focus on their relevance to the Indian society. Potential cognitive and biological mechanisms med...

  11. PENGOBATAN PENYAKIT TUMOR MAMMAE MELALAUI OPERASI (MATEKTOMI DAN OVARIOHISTEREKTOMI DAN KOMBINASINYA (TANAMAN HERBAL PADA HEWAN

    Directory of Open Access Journals (Sweden)

    Gunanati Soedjono

    2009-04-01

    Full Text Available Tumor or neuplasm can be meant as a abnormal and uncontrol growth of the transformation tissue or the change of one or main location of the body. This degenerative desease is one of the deseases in the animal pet especially dog and cat. Generaly this tumor deseases can be used with therapy using surgery and usually will relapse after six months. From our previous research had succeded to examp by using activity in vitro antiproliverati from extract plant (nusa indah, blustru and temu putih combined with recombinanct interferon dog ( rCaIFN. The above phenomenon indicate a new hope to make a therapy for tumor desease, especially for dog and cat and may be in the future can be used for human. In this research we used 21 female rabbits and divided into 7 treatment groups, consisted of 3 rabits ie : group A. negative control; B. surgery, preventive and curative curcumine; C. positive control; D. positive control and surgery; E. surgery and preventive zedoaria capsul; F. surgery , preventive and curative zedoaria capsule and G. surgery and curative zedoaria capsule . Induction with carcinogen (MNU treated every weeks during 3 weeks. Surgery is executed in the 5 weeks and giving capsule zedoaria is executed every day for 4 weeks (preventive or curative and 8 weeks (preventive and curative. Result of the research indicated that mammae tumor has been made successfully by MNU (n-metil-n-nitrosuria induction to rabit and capsule zedoaria and it has been treated by doing surgery therapy (mastectomy and ovariohisterectomy. Also decombination of zedoaria capsule. The result of the research indicated lindrance of tumorgenesis to the group which is given by zedoaria capsule. From the clinical picture shows that zedoaria capsule does not give negative effect to clinical picture (temperature, respiratory frequency and heart rate/ still normal to all the groups. Tumor induction with (MNO at mammary gland will occur allegic reaction inflammatory which is the

  12. Muscle wasting and impaired myogenesis in tumor bearing mice are prevented by ERK inhibition.

    Directory of Open Access Journals (Sweden)

    Fabio Penna

    Full Text Available BACKGROUND: The onset of cachexia is a frequent feature in cancer patients. Prominent characteristic of this syndrome is the loss of body and muscle weight, this latter being mainly supported by increased protein breakdown rates. While the signaling pathways dependent on IGF-1 or myostatin were causally involved in muscle atrophy, the role of the Mitogen-Activated-Protein-Kinases is still largely debated. The present study investigated this point on mice bearing the C26 colon adenocarcinoma. METHODOLOGY/PRINCIPAL FINDINGS: C26-bearing mice display a marked loss of body weight and muscle mass, this latter associated with increased phosphorylated (p-ERK. Administration of the ERK inhibitor PD98059 to tumor bearers attenuates muscle depletion and weakness, while restoring normal atrogin-1 expression. In C26 hosts, muscle wasting is also associated with increased Pax7 expression and reduced myogenin levels. Such pattern, suggestive of impaired myogenesis, is reversed by PD98059. Increased p-ERK and reduced myosin heavy chain content can be observed in TNFα-treated C2C12 myotubes, while decreased myogenin and MyoD levels occur in differentiating myoblasts exposed to the cytokine. All these changes are prevented by PD98059. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that ERK is involved in the pathogenesis of muscle wasting in cancer cachexia and could thus be proposed as a therapeutic target.

  13. Clinical results of BNCT for malignant brain tumors in children

    International Nuclear Information System (INIS)

    Nakagawa, Yoshinobu; Kageji, Teruyoshi; Mizobuchi, Yoshifumi; Kumada, Hiroaki; Nakagawa, Yoshiaki

    2009-01-01

    It is very difficult to treat the patients with malignant brain tumor in children, especially under 3 years, because the conventional irradiation cannot be applied due to the damage of normal brain tissue. However, boron neutron capture therapy (BNCT) has tumor selectivity such that it can make damage only in tumor cells. We evaluated the clinical results and courses in patients with malignant glioma under 15 years. Among 183 patients with brain tumors treated by our group using BSH-based intra-operative BNCT, 23 patients were under 15 years. They included 4 patients under 3 years. There were 3 glioblastomas (GBM), 6 anaplastic astrocytomas(AAS), 7 primitive neuroectodermal tumors (PNET), 6 pontine gliomas and 1 anaplastic ependymoma. All GBM and PNET patients died due to CSF and/or CNS dissemination without local tumor regrowth. All pontine glioma patients died due to regrowth of the tumor. Four of 6 anaplastic astrocytoma and 1 anaplastic ependymoma patients alive without tumor recurrence. BNCT can be applied to malignant brain tumors in children, especially under 3 years instead of conventional radiation. Although it can achieve the local control in the primary site, it cannot prevent CSF dissemination in patients with glioblastoma.

  14. Integrating a suicide prevention program into the primary health care network: a field trial study in Iran.

    Science.gov (United States)

    Malakouti, Seyed Kazem; Nojomi, Marzieh; Poshtmashadi, Marjan; Hakim Shooshtari, Mitra; Mansouri Moghadam, Fariba; Rahimi-Movaghar, Afarin; Afghah, Susan; Bolhari, Jafar; Bazargan-Hejazi, Shahrzad

    2015-01-01

    To describe and evaluate the feasibility of integrating a suicide prevention program with Primary Health Care services and evaluate if such system can improve screening and identification of depressive disorder, reduce number of suicide attempters, and lower rate of suicide completion. This was a quasi-experimental trial in which one community was exposed to the intervention versus the control community with no such exposure. The study sites were two counties in Western Iran. The intervention protocol called for primary care and suicide prevention collaboration at different levels of care. The outcome variables were the number of suicides committed, the number of documented suicide attempts, and the number of identified depressed cases. We identified a higher prevalence of depressive disorders in the intervention site versus the control site (χ (2) = 14.8, P suicide completion in the intervention region compared to the control, but a higher prevalence of suicide attempts in both the intervention and the control sites. Integrating a suicide prevention program with the Primary Health Care network enhanced depression and suicide surveillance capacity and subsequently reduced the number of suicides, especially in rural areas.

  15. Magnetic resonance imaging of tumor oxygenation and metabolic profile

    DEFF Research Database (Denmark)

    Krishna, Murali C.; Matsumoto, Shingo; Saito, Keita

    2013-01-01

    The tumor microenvironment is distinct from normal tissue as a result of abnormal vascular network characterized by hypoxia, low pH, high interstitial fluid pressure and elevated glycolytic activity. This poses a barrier to treatments including radiation therapy and chemotherapy. Imaging methods...... spectroscopic imaging. Imaging pO2 in tumors is now a robust pre-clinical imaging modality with potential for implementation clinically. Pre-clinical studies and an initial clinical study with hyperpolarized metabolic MR have been successful and suggest that the method may be part of image-guided radiotherapy...

  16. Overview of gastrointestinal cancer prevention in Asia.

    Science.gov (United States)

    Park, Jong-Min; Lee, Ho-Jae; Yoo, Jun Hwan; Ko, Weon Jin; Cho, Joo Young; Hahm, Ki Baik

    2015-12-01

    "War on cancer" was declared through the National Cancer Act by President Richard Nixon in 1971, but cancer statistics from the American Cancer Society and other sources indicated the failure of this war, suggesting instead focus on the message that a "prevention strategy" might be much more effective than cancer treatment. While cancer statistics notoriously showed sharp increases in incidence as well as in mortality concurrent with economic growth in Asia, fortunately Asian countries benefit from plentiful resources of natural compounds, which can prevent cancer. Just like cancer chemotherapeutics targeted to kill cancer cells in Western countries, natural agents activating molecular mechanisms for cancer prevention, reversion of premalignant tumors, and even ablation of cancer stem cells, are very abundant in Asia. Currently, these natural agents are under very active investigations targeting the hallmarks of cancer prevention, including selective induction of apoptosis in cancer cells, suppression of growth factors or their signaling, suppression of cell proliferation and of cancer-promoting angiogenesis, induction of mesenchymal-epithelial transition, and disruption of the tumor microenvironment, developing promising cancer preventive agents. However, Asia is the most populous continent in the world and some Asian countries do not have the resources to implement cancer screening programs for early detection or treatment. In addition, despite the excellent cancer preventive screening strategies in some Asian countries, well-designed clinical trials for cancer prevention are somewhat delayed compared to Western countries. In this review article, several phytochemicals/phytoceuticals produced and studied in different Asian countries will be introduced, including Korean red ginseng (pride of Korea), curcumin (Indian spice for life), black or green tea (popular in Japan/Sri Lanka), genistein from tofu (famous Chinese food), diallylsulfide or S-allylcysteine (garlic

  17. The behavior of the vascular system in the experimental tumor radiotherapy

    International Nuclear Information System (INIS)

    Yamaura, Hirotsugu; Matsuzawa, Taiju; Sato, Haruo; Ito, Yasuhiko.

    1975-01-01

    The rat ascites hepatoma AH109A transplanted and grown in the rat transparent chamber developed a tumor specific vascular system, the process of which was quantitatively studied because of the vascular length, surface area, and volume per mm 3 of tissue. The values changed characteristically in each stage of the course. The tumor was irradiated in a chamber with 3000 R of 60 Co γ-rays, and the tumor cells died leaving behind highly dense capillary networks, which gradually returned to normal level by 7 days after irradiation. The blood vessels, either preformed or newly formed, in the control tissue without tumor were not damaged by this dose. But the proliferation of capillary buds were inhibited slightly with 400 R and completely with 4000 R. (auth.)

  18. Increasing the endogenous NO level causes catalase inactivation and reactivation of intercellular apoptosis signaling specifically in tumor cells.

    Science.gov (United States)

    Bauer, Georg

    2015-12-01

    Tumor cells generate extracellular superoxide anions and are protected against intercellular apoptosis-inducing HOCl- and NO/peroxynitrite signaling through the expression of membrane-associated catalase. This enzyme decomposes H2O2 and thus prevents HOCl synthesis. It efficiently interferes with NO/peroxynitrite signaling through oxidation of NO and decomposition of peroxynitrite. The regulatory potential of catalase at the crosspoint of ROS and RNS chemical biology, as well as its high local concentration on the outside of the cell membrane of tumor cells, establish tight control of intercellular signaling and thus prevent tumor cell apoptosis. Therefore, inhibition of catalase or its inactivation by singlet oxygen reactivate intercellular apoptosis-inducing signaling. Nitric oxide and peroxynitrite are connected with catalase in multiple and meaningful ways, as (i) NO can be oxidated by compound I of catalase, (ii) NO can reversibly inhibit catalase, (iii) peroxynitrite can be decomposed by catalase and (iv) the interaction between peroxynitrite and H2O2 leads to the generation of singlet oxygen that inactivates catalase. Therefore, modulation of the concentration of free NO through addition of arginine, inhibition of arginase, induction of NOS expression or inhibition of NO dioxygenase triggers an autoamplificatory biochemical cascade that is based on initial formation of singlet oxygen, amplification of superoxide anion/H2O2 and NO generation through singlet oxygen dependent stimulation of the FAS receptor and caspase-8. Finally, singlet oxygen is generated at sufficiently high concentration to inactivate protective catalase and to reactivate intercellular apoptosis-inducing ROS signaling. This regulatory network allows to establish several pathways for synergistic interactions, like the combination of modulators of NO metabolism with enhancers of superoxide anion generation, modulators of NO metabolism that act at different targets and between modulators of

  19. Increasing the endogenous NO level causes catalase inactivation and reactivation of intercellular apoptosis signaling specifically in tumor cells

    Science.gov (United States)

    Bauer, Georg

    2015-01-01

    Tumor cells generate extracellular superoxide anions and are protected against intercellular apoptosis-inducing HOCl- and NO/peroxynitrite signaling through the expression of membrane-associated catalase. This enzyme decomposes H2O2 and thus prevents HOCl synthesis. It efficiently interferes with NO/peroxynitrite signaling through oxidation of NO and decomposition of peroxynitrite. The regulatory potential of catalase at the crosspoint of ROS and RNS chemical biology, as well as its high local concentration on the outside of the cell membrane of tumor cells, establish tight control of intercellular signaling and thus prevent tumor cell apoptosis. Therefore, inhibition of catalase or its inactivation by singlet oxygen reactivate intercellular apoptosis-inducing signaling. Nitric oxide and peroxynitrite are connected with catalase in multiple and meaningful ways, as (i) NO can be oxidated by compound I of catalase, (ii) NO can reversibly inhibit catalase, (iii) peroxynitrite can be decomposed by catalase and (iv) the interaction between peroxynitrite and H2O2 leads to the generation of singlet oxygen that inactivates catalase. Therefore, modulation of the concentration of free NO through addition of arginine, inhibition of arginase, induction of NOS expression or inhibition of NO dioxygenase triggers an autoamplificatory biochemical cascade that is based on initial formation of singlet oxygen, amplification of superoxide anion/H2O2 and NO generation through singlet oxygen dependent stimulation of the FAS receptor and caspase-8. Finally, singlet oxygen is generated at sufficiently high concentration to inactivate protective catalase and to reactivate intercellular apoptosis-inducing ROS signaling. This regulatory network allows to establish several pathways for synergistic interactions, like the combination of modulators of NO metabolism with enhancers of superoxide anion generation, modulators of NO metabolism that act at different targets and between modulators of

  20. The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

    International Nuclear Information System (INIS)

    Rymaszewski, Amy L.; Tate, Everett; Yimbesalu, Joannes P.; Gelman, Andrew E.; Jarzembowski, Jason A.; Zhang, Hao; Pritchard, Kirkwood A. Jr.; Vikis, Haris G.

    2014-01-01

    Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting

  1. The role of neutrophil myeloperoxidase in models of lung tumor development.

    Science.gov (United States)

    Rymaszewski, Amy L; Tate, Everett; Yimbesalu, Joannes P; Gelman, Andrew E; Jarzembowski, Jason A; Zhang, Hao; Pritchard, Kirkwood A; Vikis, Haris G

    2014-05-09

    Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

  2. The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

    Energy Technology Data Exchange (ETDEWEB)

    Rymaszewski, Amy L.; Tate, Everett; Yimbesalu, Joannes P. [Department of Pharmacology and Toxicology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Gelman, Andrew E. [Department of Surgery, Washington University in St. Louis, St. Louis, MO 63130 (United States); Jarzembowski, Jason A. [Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Zhang, Hao; Pritchard, Kirkwood A. Jr. [Department of Surgery and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Vikis, Haris G., E-mail: hvikis@mcw.edu [Department of Pharmacology and Toxicology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States)

    2014-05-09

    Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

  3. The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

    Directory of Open Access Journals (Sweden)

    Amy L. Rymaszewski

    2014-05-01

    Full Text Available Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA-initiated, butylated hydroxytoluene (BHT-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC, a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

  4. Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance.

    Science.gov (United States)

    Khdair, Ayman; Chen, Di; Patil, Yogesh; Ma, Linan; Dou, Q Ping; Shekhar, Malathy P V; Panyam, Jayanth

    2010-01-25

    Tumor drug resistance significantly limits the success of chemotherapy in the clinic. Tumor cells utilize multiple mechanisms to prevent the accumulation of anticancer drugs at their intracellular site of action. In this study, we investigated the anticancer efficacy of doxorubicin in combination with photodynamic therapy using methylene blue in a drug-resistant mouse tumor model. Surfactant-polymer hybrid nanoparticles formulated using an anionic surfactant, Aerosol-OT (AOT), and a naturally occurring polysaccharide polymer, sodium alginate, were used for synchronized delivery of the two drugs. Balb/c mice bearing syngeneic JC tumors (mammary adenocarcinoma) were used as a drug-resistant tumor model. Nanoparticle-mediated combination therapy significantly inhibited tumor growth and improved animal survival. Nanoparticle-mediated combination treatment resulted in enhanced tumor accumulation of both doxorubicin and methylene blue, significant inhibition of tumor cell proliferation, and increased induction of apoptosis. These data suggest that nanoparticle-mediated combination chemotherapy and photodynamic therapy using doxorubicin and methylene blue has significant therapeutic potential against drug-resistant tumors. Copyright 2009 Elsevier B.V. All rights reserved.

  5. CS2164, a novel multi-target inhibitor against tumor angiogenesis, mitosis and chronic inflammation with anti-tumor potency.

    Science.gov (United States)

    Zhou, You; Shan, Song; Li, Zhi-Bin; Xin, Li-Jun; Pan, De-Si; Yang, Qian-Jiao; Liu, Ying-Ping; Yue, Xu-Peng; Liu, Xiao-Rong; Gao, Ji-Zhou; Zhang, Jin-Wen; Ning, Zhi-Qiang; Lu, Xian-Ping

    2017-03-01

    Although inhibitors targeting tumor angiogenic pathway have provided improvement for clinical treatment in patients with various solid tumors, the still very limited anti-cancer efficacy and acquired drug resistance demand new agents that may offer better clinical benefits. In the effort to find a small molecule potentially targeting several key pathways for tumor development, we designed, discovered and evaluated a novel multi-kinase inhibitor, CS2164. CS2164 inhibited the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα and c-Kit), mitosis-related kinase Aurora B and chronic inflammation-related kinase CSF-1R in a high potency manner with the IC 50 at a single-digit nanomolar range. Consequently, CS2164 displayed anti-angiogenic activities through suppression of VEGFR/PDGFR phosphorylation, inhibition of ligand-dependent cell proliferation and capillary tube formation, and prevention of vasculature formation in tumor tissues. CS2164 also showed induction of G2/M cell cycle arrest and suppression of cell proliferation in tumor tissues through the inhibition of Aurora B-mediated H3 phosphorylation. Furthermore, CS2164 demonstrated the inhibitory effect on CSF-1R phosphorylation that led to the suppression of ligand-stimulated monocyte-to-macrophage differentiation and reduced CSF-1R + cells in tumor tissues. The in vivo animal efficacy studies revealed that CS2164 induced remarkable regression or complete inhibition of tumor growth at well-tolerated oral doses in several human tumor xenograft models. Collectively, these results indicate that CS2164 is a highly selective multi-kinase inhibitor with potent anti-tumor activities against tumor angiogenesis, mitosis and chronic inflammation, which may provide the rationale for further clinical assessment of CS2164 as a therapeutic agent in the treatment of cancer. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  6. Energy and Redox Homeostasis in Tumor Cells

    Directory of Open Access Journals (Sweden)

    Marcus Fernandes de Oliveira

    2012-01-01

    Full Text Available Cancer cells display abnormal morphology, chromosomes, and metabolism. This review will focus on the metabolism of tumor cells integrating the available data by way of a functional approach. The first part contains a comprehensive introduction to bioenergetics, mitochondria, and the mechanisms of production and degradation of reactive oxygen species. This will be followed by a discussion on the oxidative metabolism of tumor cells including the morphology, biogenesis, and networking of mitochondria. Tumor cells overexpress proteins that favor fission, such as GTPase dynamin-related protein 1 (Drp1. The interplay between proapoptotic members of the Bcl-2 family that promotes Drp 1-dependent mitochondrial fragmentation and fusogenic antiapoptotic proteins such as Opa-1 will be presented. It will be argued that contrary to the widespread belief that in cancer cells, aerobic glycolysis completely replaces oxidative metabolism, a misrepresentation of Warburg’s original results, mitochondria of tumor cells are fully viable and functional. Cancer cells also carry out oxidative metabolism and generally conform to the orthodox model of ATP production maintaining as well an intact electron transport system. Finally, data will be presented indicating that the key to tumor cell survival in an ROS rich environment depends on the overexpression of antioxidant enzymes and high levels of the nonenzymatic antioxidant scavengers.

  7. Advancing Strategies for Agenda Setting by Health Policy Coalitions: A Network Analysis of the Canadian Chronic Disease Prevention Survey.

    Science.gov (United States)

    McGetrick, Jennifer Ann; Raine, Kim D; Wild, T Cameron; Nykiforuk, Candace I J

    2018-06-11

    Health in all policies can address chronic disease morbidity and mortality by increasing population-level physical activity and healthy eating, and reducing tobacco and alcohol use. Both governmental and nongovernmental policy influencers are instrumental for health policy that modifies political, economic, and social environments. Policy influencers are informed and persuaded by coalitions that support or oppose changing the status quo. Empirical research examining policy influencers' contact with coalitions, as a social psychological exposure with health policy outcomes, can benefit from application of health communication theories. Accordingly, we analyzed responses to the 2014 Chronic Disease Prevention Survey for 184 Canadian policy influencers employed in provincial governments, municipalities, large workplaces, school boards, and the media. In addition to contact levels with coalitions, respondents' jurisdiction, organization, and ideology were analyzed as potential moderators. Calculating authority score centrality using network analysis, we determined health policy supporters to be more central in policy influencer networks, and theorized their potential to impact health policy public agenda setting via priming and framing processes. We discuss the implications of our results as presenting opportunities to more effectively promote health policy through priming and framing by coordinating coalitions across risk behaviors to advance a societal imperative for chronic disease prevention.

  8. Nuclear Magnetic Resonance-Based Metabolomics Approach to Evaluate the Prevention Effect of Camellia nitidissima Chi on Colitis-Associated Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Ming-Hui Li

    2017-07-01

    Full Text Available Colorectal cancer (CRC is one of the most common malignant tumors worldwide, occurring in the colon or rectum portion of large intestine. With marked antioxidant, anti-inflammation and anti-tumor activities, Camellia nitidissima Chi has been used as an effective treatment of cancer. The azoxymethane/dextran sodium sulfate (AOM/DSS induced CRC mice model was established and the prevention effect of C. nitidissima Chi extracts on the evolving of CRC was evaluated by examination of neoplastic lesions, histopathological inspection, serum biochemistry analysis, combined with nuclear magnetic resonance (NMR-based metabolomics and correlation network analysis. C. nitidissima Chi extracts could significantly inhibit AOM/DSS induced CRC, relieve the colonic pathology of inflammation and ameliorate the serum biochemistry, and could significantly reverse the disturbed metabolic profiling toward the normal state. Moreover, the butanol fraction showed a better efficacy than the water-soluble fraction of C. nitidissima Chi. Further development of C. nitidissima Chi extracts as a potent CRC inhibitor was warranted.

  9. Preventing Alcohol Abuse Through Social Networking Sites: A First Assessment of a Two-Year Ecological Approach.

    Science.gov (United States)

    Flaudias, Valentin; de Chazeron, Ingrid; Zerhouni, Oulmann; Boudesseul, Jordane; Begue, Laurent; Bouthier, Renaud; Lévrier, Christel; Llorca, Pierre Michel; Brousse, Georges

    2015-12-10

    Prevention strategies to reduce alcohol use/consumption among young people are crucial to reducing alcohol-related deaths and preventing disease. This paper focuses on the effectiveness of a social networking site (SNS) alcohol prevention program targeted toward young people. We hypothesized that the program would diminish the relation made by participants between alcohol and festive moments, and would result in a reduction of their declared consumption of alcohol at festive moments during the program. We also explored the interaction with the prevention program that was the most efficient. The prevention program took the form of 3 lotteries over 2 years. The participants periodically received prevention messages, particularly on alcohol and festive moments (eg, videos on Facebook and short message service [SMS] text messages on their mobile phones). For the 3 periods, the participants had to answer questions exploring the level of their belief that alcohol consumption and festive moments are highly associated. A control group that did not participate in the prevention program was asked the same questions over the same number of days for the first 2 periods. During the second period, the participants were asked to answer questions about their alcohol consumption during parties. During the third period, we explored the interaction with the prevention program on the reduction of their belief that alcohol consumption and festive moments are associated. A total of 651 participants (age: mean 22.24, SD 4.10 years; women: n=430) during the first period, 301 participants (age: mean 21.27, SD 3.07 years; women n=199) during the second period, and 305 (age: mean 22.41, SD 4.65 years; women: n=190) during the third period correctly completed the survey. For the control group, 69 students completed the survey during the first period (age: mean 18.93, SD 1.14 years; women: n=59) and 50 during the second (age: mean 20.78, SD 1.94 years; women: n=45). We observed a significant

  10. Principles of Practical Training Organization in a Networking (Development of the Module "Psychological Prevention of Behavioral Disorders and Abnormalities in Development" as Example

    Directory of Open Access Journals (Sweden)

    Bogdanovich N. V.

    2016-01-01

    Full Text Available The article presents principles of inserting study subjects and practices in educational modules running with network organizations (internship sites. We proposed a methodological basis of the modular organization of educational process in the framework of the master's program, combied the activity, competence and psychotechnical approaches. Networking of leading chair and specially selected organizations providing the base for practical training solves the problem of organizing activity-related content of educational module. We discussed the main options for networking with the databases of practice and offered methodological principles of designing the educational practice-oriented module, wherein the main principle is the reflexive and activity character of networking. We proposed activity-based content of educational module "Psychological prevention of behavioral disorders and abnormalities in development", based on the substantial psychological definition of psychoprophylaxis as a directions of professional activity of the psychologist.

  11. Selenium for the Prevention of Cutaneous Melanoma

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    Douglas Grossman

    2013-03-01

    Full Text Available The role of selenium (Se supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to study two unique therapeutic windows for intervention in the process of cutaneous melanomagenisis, and to examine the utility of two different chemical forms of Se for prevention and treatment of melanoma. We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts. Our findings suggest that modestly elevation of selenium levels in the skin might risk acceleration of growth of incipient tumors. Additionally, certain Se compounds administered at very high doses could have utility for the treatment of fully-malignant tumors or prevention of recurrence.

  12. Knowledge sharing in infection prevention in routine and outbreak situations: a survey of the Society for Healthcare Epidemiology of America Research Network

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    Rami Sommerstein

    2017-08-01

    Full Text Available Abstract In this cross-sectional Society for Healthcare Epidemiology of America Research Network survey on knowledge sharing in infection prevention we identified a rudimentary understanding of how to communicate and share knowledge within healthcare institutions. Our data support the need of further research in this important field.

  13. Detection and Prevention of Denial of Service (DoS Attacks in Mobile Ad Hoc Networks using Reputation-based Incentive Schemes

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    Mieso, K Denko

    2005-08-01

    Full Text Available Mobile ad hoc networks (MANETs are dynamic mobile networks that can be formed in the absence of any pre-existing communication infrastructure. In addition to node mobility, a MANET is characterized by limited resources such as bandwidth, battery power, and storage space. The underlying assumption in MANETs is that the intermediate nodes cooperate in forwarding packets. However, this assumption does not hold in commercial and emerging civilian applications. MANETs are vulnerable to Denial of Service (DoS due to their salient characteristics. There is a need to provide an incentive mechanism that can provide cooperation among nodes in the network and improve overall network performance by reducing DoS attacks. In this paper, we propose a reputation-based incentive mechanism for detecting and preventing DoS attacks. DoS attacks committed by selfish and malicious nodes were investigated. Our scheme motivates nodes to cooperate and excludes them from the network only if they fail to do so. We evaluated the performance of our scheme using the packet delivery ratio, the routing and communication overhead, and misbehaving node detection in a discrete event-simulation environment. The results indicate that a reputation-based incentive mechanism can significantly reduce the effect of DoS attacks and improve performance in MANETs.

  14. Repurposing of bisphosphonates for the prevention and therapy of nonsmall cell lung and breast cancer.

    Science.gov (United States)

    Stachnik, Agnes; Yuen, Tony; Iqbal, Jameel; Sgobba, Miriam; Gupta, Yogesh; Lu, Ping; Colaianni, Graziana; Ji, Yaoting; Zhu, Ling-Ling; Kim, Se-Min; Li, Jianhua; Liu, Peng; Izadmehr, Sudeh; Sangodkar, Jaya; Scherer, Thomas; Mujtaba, Shiraz; Galsky, Matthew; Gomez, Jorge; Epstein, Solomon; Buettner, Christoph; Bian, Zhuan; Zallone, Alberta; Aggarwal, Aneel K; Haider, Shozeb; New, Maria I; Sun, Li; Narla, Goutham; Zaidi, Mone

    2014-12-16

    A variety of human cancers, including nonsmall cell lung (NSCLC), breast, and colon cancers, are driven by the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases. Having shown that bisphosphonates, a class of drugs used widely for the therapy of osteoporosis and metastatic bone disease, reduce cancer cell viability by targeting HER1, we explored their potential utility in the prevention and therapy of HER-driven cancers. We show that bisphosphonates inhibit colony formation by HER1(ΔE746-A750)-driven HCC827 NSCLCs and HER1(wt)-expressing MB231 triple negative breast cancers, but not by HER(low)-SW620 colon cancers. In parallel, oral gavage with bisphosphonates of mice xenografted with HCC827 or MB231 cells led to a significant reduction in tumor volume in both treatment and prevention protocols. This result was not seen with mice harboring HER(low) SW620 xenografts. We next explored whether bisphosphonates can serve as adjunctive therapies to tyrosine kinase inhibitors (TKIs), namely gefitinib and erlotinib, and whether the drugs can target TKI-resistant NSCLCs. In silico docking, together with molecular dynamics and anisotropic network modeling, showed that bisphosphonates bind to TKIs within the HER1 kinase domain. As predicted from this combinatorial binding, bisphosphonates enhanced the effects of TKIs in reducing cell viability and driving tumor regression in mice. Impressively, the drugs also overcame erlotinib resistance acquired through the gatekeeper mutation T790M, thus offering an option for TKI-resistant NSCLCs. We suggest that bisphosphonates can potentially be repurposed for the prevention and adjunctive therapy of HER1-driven cancers.

  15. Brief Report: HIV Drug Resistance in Adults Failing Early Antiretroviral Treatment: Results From the HIV Prevention Trials Network 052 Trial.

    Science.gov (United States)

    Fogel, Jessica M; Hudelson, Sarah E; Ou, San-San; Hart, Stephen; Wallis, Carole; Morgado, Mariza G; Saravanan, Shanmugam; Tripathy, Srikanth; Hovind, Laura; Piwowar-Manning, Estelle; Sabin, Devin; McCauley, Marybeth; Gamble, Theresa; Zhang, Xinyi C; Eron, Joseph J; Gallant, Joel E; Kumwenda, Johnstone; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James; Badal-Faesen, Sharlaa; Akelo, Victor; Hosseinipour, Mina C; Santos, Breno R; Godbole, Sheela V; Pilotto, Jose H; Grinsztejn, Beatriz; Panchia, Ravindre; Mayer, Kenneth H; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H

    2016-07-01

    Early initiation of antiretroviral treatment (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HIV Prevention Trials Network 052 trial who started ART at CD4 counts of 350-550 cells per cubic millimeter and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7 of 8 (87.5%) participants who started ART at lower CD4 cell counts.

  16. Bibliometric investigation on preventive medicine in North Korea: a coauthor and keyword network analysis.

    Science.gov (United States)

    Jung, Minsoo

    2013-01-01

    This study examined the 2 preventive medicine journals in North Korea by using coauthor and keyword network analysis on the basis of medical informatics and bibliometrics. Used were the Journal of Chosun Medicine (JCM) and the Journal of Preventive Medicine (JPM) (from the first volume of 1997 to the fourth volume of 2006) as data. Extracted were 1734 coauthors from 1104 articles and 1567 coauthors from 1172 articles, respectively. Huge single components were extracted in the coauthor analysis, which indicated a tendency toward structuralization. However, the 2 journals differed in that JPM showed a relative tendency toward specialization, whereas JCM showed one toward generalization. Seventeen and 33 keywords were extracted from each journal in the keyword analysis; JCM mainly concerned pathological research, whereas JPM mainly concerned virus and basic medicine studies that were based on infection and immunity. In contrast to South Korea, North Korea has developed Juche medicine, which came from self-reliance ideology and gratuitous medical service. According to the present study, their ideology was embodied by the discovery of bacteria, study on immune system, and emphasis on pathology, on the basis of experimental epidemiology. However, insufficient research has been conducted thus far on population health and its related determinants.

  17. The burden of chronic pain after major head and neck tumor therapy

    Directory of Open Access Journals (Sweden)

    Abdullah Sulieman Terkawi

    2017-01-01

    Conclusion: Our study highlighted the high burden of chronic pain after therapy for major head and neck tumors. We identified demographic and clinical factors that are associated with the presence of chronic pain. Further studies are required to better understand the risk factors to implement strategies to prevent, alleviate, and treat chronic pain associated with major head and neck tumor therapies.

  18. Induction of highly immunogenic variants of Lewis lung carcinoma tumor by ultraviolet irradiation

    International Nuclear Information System (INIS)

    Peppoloni, S.; Herberman, R.B.; Gorelik, E.

    1985-01-01

    This study was undertaken to determine whether in vitro treatment of Lewis lung carcinoma (3LL) cells with ultraviolet (UV) radiation could increase their immunogenicity. Tumor cells were irradiated with UV light from a germicidal lamp (254 nm; UV-C) at a dose of 720 J/sq m. After 2 weeks of culture, the surviving cell population was cloned by limiting dilution. Cell suspensions of each clone were injected intrafootpad in C57BL/6 mice at a dose of 2.5 X 10(5) cells per mouse. Eighty independent clones were tested. Fifty-one clones showed decreased tumorigenicity and failed to grow in 20 to 95% of immunocompetent mice, whereas they produced tumors in 100% of irradiated (550 R) and athymic nude mice. These clones were designated tum- (nontumorigenic) clones. In contrast, all 25 clones selected from the untreated parental 3LL induced progressively growing tumors in 100% of the mice. After two courses of UV treatment, the uncloned 3LL population was rejected in 45% of inoculated mice. Mice rejecting an inoculum of a tum- clone were completely resistant to subsequent challenge with higher doses of the same or unrelated tum- clones. This resistance was fully expressed even after irradiation of immune mice with 550 R. Mice immune to a tum- clone also were able to prevent the growth of various tum+ clones or untreated 3LL tumor cells. When tum- and tum+ clone cells were simultaneously inoculated intrafootpad in opposite legs, rejection of tum- clone resulted also in the prevention of the growth of tum+ clone. Spleen cells of immune mice caused rapid elimination of radiolabeled 3LL tumor cells from the place of their inoculation (intrafootpad) and prevented tumor growth

  19. The behavior of the vascular system in the experimental tumor radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Yamaura, H; Matsuzawa, T; Sato, H [Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis, Leprosy and Cancer; Ito, Yasuhiko

    1975-07-01

    The rat ascites hepatoma AH109A transplanted and grown in the rat transparent chamber developed a tumor specific vascular system, the process of which was quantitatively studied because of the vascular length, surface area, and volume per mm/sup 3/ of tissue. The values changed characteristically in each stage of the course. The tumor was irradiated in a chamber with 3000 R of /sup 60/Co ..gamma..-rays, and the tumor cells died leaving behind highly dense capillary networks, which gradually returned to normal level by 7 days after irradiation. The blood vessels, either preformed or newly formed, in the control tissue without tumor were not damaged by this dose. But the proliferation of capillary buds were inhibited slightly with 400 R and completely with 4000 R.

  20. Inhibition of tumor angiogenesis and tumor growth by the DSL domain of human Delta-like 1 targeted to vascular endothelial cells.

    Science.gov (United States)

    Zhao, Xing-Cheng; Dou, Guo-Rui; Wang, Li; Liang, Liang; Tian, Deng-Mei; Cao, Xiu-Li; Qin, Hong-Yan; Wang, Chun-Mei; Zhang, Ping; Han, Hua

    2013-07-01

    The growth of solid tumors depends on neovascularization. Several therapies targeting tumor angiogenesis have been developed. However, poor response in some tumors and emerging resistance necessitate further investigations of new drug targets. Notch signal pathway plays a pivotal role in vascular development and tumor angiogenesis. Either blockade or forced activation of this pathway can inhibit angiogenesis. As blocking Notch pathway results in the formation of vascular neoplasm, activation of Notch pathway to prevent tumor angiogenesis might be an alternative choice. However, an in vivo deliverable reagent with highly efficient Notch-activating capacity has not been developed. Here, we generated a polypeptide, hD1R, which consists of the Delta-Serrate-Lag-2 fragment of the human Notch ligand Delta-like 1 and an arginine-glycine-aspartate (RGD) motif targeting endothelial cells (ECs). We showed that hD1R could bind to ECs specifically through its RGD motif and effectively triggered Notch signaling in ECs. We demonstrated both in vitro and in vivo that hD1R inhibited angiogenic sprouting and EC proliferation. In tumor-bearing mice, the injection of hD1R effectively repressed tumor growth, most likely through increasing tumor hypoxia and tissue necrosis. The amount and width of vessels reduced remarkably in tumors of mice treated with hD1R. Moreover, vessels in tumors of mice treated with hD1R recruited more NG2(+) perivascular cells and were better perfused. Combined application of hD1R and chemotherapy with cisplatin and teniposide revealed that these two treatments had additive antitumor effects. Our study provided a new strategy for antiangiogenic tumor therapy.

  1. Inhibition of Tumor Angiogenesis and Tumor Growth by the DSL Domain of Human Delta-Like 1 Targeted to Vascular Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Xing-Cheng Zhao

    2013-07-01

    Full Text Available The growth of solid tumors depends on neovascularization. Several therapies targeting tumor angiogenesis have been developed. However, poor response in some tumors and emerging resistance necessitate further investigations of newdrug targets. Notch signal pathway plays a pivotal role in vascular development and tumor angiogenesis. Either blockade or forced activation of this pathway can inhibit angiogenesis. As blocking Notch pathway results in the formation of vascular neoplasm, activation of Notch pathway to prevent tumor angiogenesis might be an alternative choice. However, an in vivo deliverable reagent with highly efficient Notch-activating capacity has not been developed. Here, we generated a polypeptide, hD1R, which consists of the Delta-Serrate-Lag-2 fragment of the human Notch ligand Delta-like 1 and an arginine-glycine-aspartate (RGD motif targeting endothelial cells (ECs. We showed that hD1R could bind to ECs specifically through its RGD motif and effectively triggered Notch signaling in ECs. We demonstrated both in vitro and in vivo that hD1R inhibited angiogenic sprouting and EC proliferation. In tumor-bearing mice, the injection of hD1R effectively repressed tumor growth, most likely through increasing tumor hypoxia and tissue necrosis. The amount and width of vessels reduced remarkably in tumors of mice treated with hD1R. Moreover, vessels in tumors of mice treated with hD1R recruited more NG2+ perivascular cells and were better perfused. Combined application of hD1R and chemotherapy with cisplatin and teniposide revealed that these two treatments had additive antitumor effects. Our study provided a new strategy for antiangiogenic tumor therapy.

  2. Label-free LC-MSe in tissue and serum reveals protein networks underlying differences between benign and malignant serous ovarian tumors.

    Directory of Open Access Journals (Sweden)

    Wouter Wegdam

    Full Text Available PURPOSE: To identify proteins and (molecular/biological pathways associated with differences between benign and malignant epithelial ovarian tumors. EXPERIMENTAL PROCEDURES: Serum of six patients with a serous adenocarcinoma of the ovary was collected before treatment, with a control group consisting of six matched patients with a serous cystadenoma. In addition to the serum, homogeneous regions of cells exhibiting uniform histology were isolated from benign and cancerous tissue by laser microdissection. We subsequently employed label-free liquid chromatography tandem mass spectrometry (LC-MSe to identify proteins in these serum and tissues samples. Analyses of differential expression between samples were performed using Bioconductor packages and in-house scripts in the statistical software package R. Hierarchical clustering and pathway enrichment analyses were performed, as well as network enrichment and interactome analysis using MetaCore. RESULTS: In total, we identified 20 and 71 proteins that were significantly differentially expressed between benign and malignant serum and tissue samples, respectively. The differentially expressed protein sets in serum and tissue largely differed with only 2 proteins in common. MetaCore network analysis, however inferred GCR-alpha and Sp1 as common transcriptional regulators. Interactome analysis highlighted 14-3-3 zeta/delta, 14-3-3 beta/alpha, Alpha-actinin 4, HSP60, and PCBP1 as critical proteins in the tumor proteome signature based on their relative overconnectivity. The data have been deposited to the ProteomeXchange with identifier PXD001084. DISCUSSION: Our analysis identified proteins with both novel and previously known associations to ovarian cancer biology. Despite the small overlap between differentially expressed protein sets in serum and tissue, APOA1 and Serotransferrin were significantly lower expressed in both serum and cancer tissue samples, suggesting a tissue-derived effect in serum

  3. The redox biology network in cancer pathophysiology and therapeutics

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    Gina Manda

    2015-08-01

    Full Text Available The review pinpoints operational concepts related to the redox biology network applied to the pathophysiology and therapeutics of solid tumors. A sophisticated network of intrinsic and extrinsic cues, integrated in the tumor niche, drives tumorigenesis and tumor progression. Critical mutations and distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation and efficient repair mechanisms. Additionally, the complex inter-cellular crosstalk within the tumor niche, mediated by cytokines, redox-sensitive danger signals (HMGB1 and exosomes, under the pressure of multiple stresses (oxidative, inflammatory, metabolic, greatly contributes to the malignant phenotype. The tumor-associated inflammatory stress and its suppressive action on the anti-tumor immune response are highlighted. We further emphasize that ROS may act either as supporter or enemy of cancer cells, depending on the context. Oxidative stress-based therapies, such as radiotherapy and photodynamic therapy, take advantage of the cytotoxic face of ROS for killing tumor cells by a non-physiologically sudden, localized and intense oxidative burst. The type of tumor cell death elicited by these therapies is discussed. Therapy outcome depends on the differential sensitivity to oxidative stress of particular tumor cells, such as cancer stem cells, and therefore co-therapies that transiently down-regulate their intrinsic antioxidant system hold great promise. We draw attention on the consequences of the damage signals delivered by oxidative stress-injured cells to neighboring and distant cells, and emphasize the benefits of therapeutically triggered immunologic cell death in metastatic cancer. An integrative approach should be applied when designing therapeutic strategies in cancer, taking into consideration the mutational, metabolic, inflammatory and oxidative status of tumor cells, cellular

  4. Generative adversarial networks for brain lesion detection

    Science.gov (United States)

    Alex, Varghese; Safwan, K. P. Mohammed; Chennamsetty, Sai Saketh; Krishnamurthi, Ganapathy

    2017-02-01

    Manual segmentation of brain lesions from Magnetic Resonance Images (MRI) is cumbersome and introduces errors due to inter-rater variability. This paper introduces a semi-supervised technique for detection of brain lesion from MRI using Generative Adversarial Networks (GANs). GANs comprises of a Generator network and a Discriminator network which are trained simultaneously with the objective of one bettering the other. The networks were trained using non lesion patches (n=13,000) from 4 different MR sequences. The network was trained on BraTS dataset and patches were extracted from regions excluding tumor region. The Generator network generates data by modeling the underlying probability distribution of the training data, (PData). The Discriminator learns the posterior probability P (Label Data) by classifying training data and generated data as "Real" or "Fake" respectively. The Generator upon learning the joint distribution, produces images/patches such that the performance of the Discriminator on them are random, i.e. P (Label Data = GeneratedData) = 0.5. During testing, the Discriminator assigns posterior probability values close to 0.5 for patches from non lesion regions, while patches centered on lesion arise from a different distribution (PLesion) and hence are assigned lower posterior probability value by the Discriminator. On the test set (n=14), the proposed technique achieves whole tumor dice score of 0.69, sensitivity of 91% and specificity of 59%. Additionally the generator network was capable of generating non lesion patches from various MR sequences.

  5. To avoid operating on pseudo tumoral pulmonary infarctions ...

    African Journals Online (AJOL)

    Pulmonary infarction usually appears as a hump-shaped triangular opacity with its base applied to a pleural surface. In some cases, pulmonary infarctions may appear as a pseudo tumoral opacity mimicking lung cancer. Thoracotomy could be prevented by repeating CT scan in properly selected patients. Pan African ...

  6. The study on linac stereotactic radiosurgery for acoustic tumors

    International Nuclear Information System (INIS)

    Ohishi, Hitoshi

    1995-01-01

    We have designed and manufactured a new type of device for stereotactic radiosurgery characterized by the combined use of a rotatory chair and a linear accelerator. In this study, 20 acoustic tumors treated by our modality were evaluated by serial neuroimaging, neurofunctional outcome and, in a few cases, pathological findings of surgical specimens. Because tumor size usually changed very slowly after radiosurgery, 12 cases that had a minimum of 12 months of follow-up were employed in the analysis of tumor size. Serial neuroimaging studies revealed the reduction of tumor size in 3 cases and prevention of tumor growth in 7 cases, therefore, the rate of tumor control was evaluated as 83%. Growth of tumor size occurred in 3 cases, two were cases harbouring a large cyst in the tumor and another was a case of neurofibromatosis type 2. In 13 cases (68%), loss of the gadolinium enhancement effect inside the tumor was observed. This is a characteristic change after radiosurgery for acoustic tumors, and attributable to a necrotic change. Cranial nerve neuropathies as a complication also occurred (facial nerve palsy in 2 and trigeminal nerve dysfunction in 1). Adjacent parenchymal change appeared in 1 case. This patient had two prior operations and the tumor had an irregular shape, therefore, planning for radiosurgery encountered some difficulty. Hydrocephalus occurred in 1 case. Surgical specimens in 2 cases in which microsurgery was undertaken for growing tumors, revealed a necrotic tumor tissue and proliferation of fibrous tissue. In conclusion, our new device for stereotactic radiosurgery is particularly useful for the treatment of acoustic tumors. Similar therapeutic results of the gamma knife have been achieved. Radiosurgery is a recommendable treatment for acoustic tumors. However, the superiority of radiosurgery over microsurgery is still controversial and needs a longer term follow-up and multivariate analysis for a final conclusion. (author)

  7. MURC/cavin-4 Is Co-Expressed with Caveolin-3 in Rhabdomyosarcoma Tumors and Its Silencing Prevents Myogenic Differentiation in the Human Embryonal RD Cell Line.

    Science.gov (United States)

    Faggi, Fiorella; Codenotti, Silvia; Poliani, Pietro Luigi; Cominelli, Manuela; Chiarelli, Nicola; Colombi, Marina; Vezzoli, Marika; Monti, Eugenio; Bono, Federica; Tulipano, Giovanni; Fiorentini, Chiara; Zanola, Alessandra; Lo, Harriet P; Parton, Robert G; Keller, Charles; Fanzani, Alessandro

    2015-01-01

    The purpose of this study was to investigate whether MURC/cavin-4, a plasma membrane and Z-line associated protein exhibiting an overlapping distribution with Caveolin-3 (Cav-3) in heart and muscle tissues, may be expressed and play a role in rhabdomyosarcoma (RMS), an aggressive myogenic tumor affecting childhood. We found MURC/cavin-4 to be expressed, often concurrently with Cav-3, in mouse and human RMS, as demonstrated through in silico analysis of gene datasets and immunohistochemical analysis of tumor samples. In vitro expression studies carried out using human cell lines and primary mouse tumor cultures showed that expression levels of both MURC/cavin-4 and Cav-3, while being low or undetectable during cell proliferation, became robustly increased during myogenic differentiation, as detected via semi-quantitative RT-PCR and immunoblotting analysis. Furthermore, confocal microscopy analysis performed on human RD and RH30 cell lines confirmed that MURC/cavin-4 mostly marks differentiated cell elements, colocalizing at the cell surface with Cav-3 and labeling myosin heavy chain (MHC) expressing cells. Finally, MURC/cavin-4 silencing prevented the differentiation in the RD cell line, leading to morphological cell impairment characterized by depletion of myogenin, Cav-3 and MHC protein levels. Overall, our data suggest that MURC/cavin-4, especially in combination with Cav-3, may play a consistent role in the differentiation process of RMS.

  8. MURC/cavin-4 Is Co-Expressed with Caveolin-3 in Rhabdomyosarcoma Tumors and Its Silencing Prevents Myogenic Differentiation in the Human Embryonal RD Cell Line.

    Directory of Open Access Journals (Sweden)

    Fiorella Faggi

    Full Text Available The purpose of this study was to investigate whether MURC/cavin-4, a plasma membrane and Z-line associated protein exhibiting an overlapping distribution with Caveolin-3 (Cav-3 in heart and muscle tissues, may be expressed and play a role in rhabdomyosarcoma (RMS, an aggressive myogenic tumor affecting childhood. We found MURC/cavin-4 to be expressed, often concurrently with Cav-3, in mouse and human RMS, as demonstrated through in silico analysis of gene datasets and immunohistochemical analysis of tumor samples. In vitro expression studies carried out using human cell lines and primary mouse tumor cultures showed that expression levels of both MURC/cavin-4 and Cav-3, while being low or undetectable during cell proliferation, became robustly increased during myogenic differentiation, as detected via semi-quantitative RT-PCR and immunoblotting analysis. Furthermore, confocal microscopy analysis performed on human RD and RH30 cell lines confirmed that MURC/cavin-4 mostly marks differentiated cell elements, colocalizing at the cell surface with Cav-3 and labeling myosin heavy chain (MHC expressing cells. Finally, MURC/cavin-4 silencing prevented the differentiation in the RD cell line, leading to morphological cell impairment characterized by depletion of myogenin, Cav-3 and MHC protein levels. Overall, our data suggest that MURC/cavin-4, especially in combination with Cav-3, may play a consistent role in the differentiation process of RMS.

  9. Human Tumor Antigens Yesterday, Today, and Tomorrow.

    Science.gov (United States)

    Finn, Olivera J

    2017-05-01

    The question of whether human tumors express antigens that can be recognized by the immune system has been answered with a resounding YES. Most were identified through spontaneous antitumor humoral and cellular immune responses found in cancer patients and include peptides, glycopeptides, phosphopeptides, viral peptides, and peptides resulting from common mutations in oncogenes and tumor-suppressor genes, or common gene fusion events. Many have been extensively tested as candidates for anticancer vaccines. More recently, attention has been focused on the potentially large number of unique tumor antigens, mutated neoantigens, that are the predicted products of the numerous mutations revealed by exome sequencing of primary tumors. Only a few have been confirmed as targets of spontaneous immunity and immunosurveillance, and even fewer have been tested in preclinical and clinical settings. The field has been divided for a long time on the relative importance of shared versus mutated antigens in tumor surveillance and as candidates for vaccines. This question will eventually need to be answered in a head to head comparison in well-designed clinical trials. One advantage that shared antigens have over mutated antigens is their potential to be used in vaccines for primary cancer prevention. Cancer Immunol Res; 5(5); 347-54. ©2017 AACR . ©2017 American Association for Cancer Research.

  10. Ets2 in tumor fibroblasts promotes angiogenesis in breast cancer.

    Directory of Open Access Journals (Sweden)

    Julie A Wallace

    Full Text Available Tumor fibroblasts are active partners in tumor progression, but the genes and pathways that mediate this collaboration are ill-defined. Previous work demonstrates that Ets2 function in stromal cells significantly contributes to breast tumor progression. Conditional mouse models were used to study the function of Ets2 in both mammary stromal fibroblasts and epithelial cells. Conditional inactivation of Ets2 in stromal fibroblasts in PyMT and ErbB2 driven tumors significantly reduced tumor growth, however deletion of Ets2 in epithelial cells in the PyMT model had no significant effect. Analysis of gene expression in fibroblasts revealed a tumor- and Ets2-dependent gene signature that was enriched in genes important for ECM remodeling, cell migration, and angiogenesis in both PyMT and ErbB2 driven-tumors. Consistent with these results, PyMT and ErbB2 tumors lacking Ets2 in fibroblasts had fewer functional blood vessels, and Ets2 in fibroblasts elicited changes in gene expression in tumor endothelial cells consistent with this phenotype. An in vivo angiogenesis assay revealed the ability of Ets2 in fibroblasts to promote blood vessel formation in the absence of tumor cells. Importantly, the Ets2-dependent gene expression signatures from both mouse models were able to distinguish human breast tumor stroma from normal stroma, and correlated with patient outcomes in two whole tumor breast cancer data sets. The data reveals a key function for Ets2 in tumor fibroblasts in signaling to endothelial cells to promote tumor angiogenesis. The results highlight the collaborative networks that orchestrate communication between stromal cells and tumor cells, and suggest that targeting tumor fibroblasts may be an effective strategy for developing novel anti-angiogenic therapies.

  11. Interstitial fluid flow and drug delivery in vascularized tumors: a computational model.

    Directory of Open Access Journals (Sweden)

    Michael Welter

    Full Text Available Interstitial fluid is a solution that bathes and surrounds the human cells and provides them with nutrients and a way of waste removal. It is generally believed that elevated tumor interstitial fluid pressure (IFP is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, but the complex interplay of extravasation, permeabilities, vascular heterogeneities and diffusive and convective drug transport remains poorly understood. Here we consider-with the help of a theoretical model-the tumor IFP, interstitial fluid flow (IFF and its impact upon drug delivery within tumor depending on biophysical determinants such as vessel network morphology, permeabilities and diffusive vs. convective transport. We developed a vascular tumor growth model, including vessel co-option, regression, and angiogenesis, that we extend here by the interstitium (represented by a porous medium obeying Darcy's law and sources (vessels and sinks (lymphatics for IFF. With it we compute the spatial variation of the IFP and IFF and determine its correlation with the vascular network morphology and physiological parameters like vessel wall permeability, tissue conductivity, distribution of lymphatics etc. We find that an increased vascular wall conductivity together with a reduction of lymph function leads to increased tumor IFP, but also that the latter does not necessarily imply a decreased extravasation rate: Generally the IF flow rate is positively correlated with the various conductivities in the system. The IFF field is then used to determine the drug distribution after an injection via a convection diffusion reaction equation for intra- and extracellular concentrations with parameters guided by experimental data for the drug Doxorubicin. We observe that the interplay of convective and diffusive drug transport can lead to quite unexpected effects in the presence of a heterogeneous, compartmentalized vasculature. Finally we discuss

  12. Interstitial fluid flow and drug delivery in vascularized tumors: a computational model.

    Science.gov (United States)

    Welter, Michael; Rieger, Heiko

    2013-01-01

    Interstitial fluid is a solution that bathes and surrounds the human cells and provides them with nutrients and a way of waste removal. It is generally believed that elevated tumor interstitial fluid pressure (IFP) is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, but the complex interplay of extravasation, permeabilities, vascular heterogeneities and diffusive and convective drug transport remains poorly understood. Here we consider-with the help of a theoretical model-the tumor IFP, interstitial fluid flow (IFF) and its impact upon drug delivery within tumor depending on biophysical determinants such as vessel network morphology, permeabilities and diffusive vs. convective transport. We developed a vascular tumor growth model, including vessel co-option, regression, and angiogenesis, that we extend here by the interstitium (represented by a porous medium obeying Darcy's law) and sources (vessels) and sinks (lymphatics) for IFF. With it we compute the spatial variation of the IFP and IFF and determine its correlation with the vascular network morphology and physiological parameters like vessel wall permeability, tissue conductivity, distribution of lymphatics etc. We find that an increased vascular wall conductivity together with a reduction of lymph function leads to increased tumor IFP, but also that the latter does not necessarily imply a decreased extravasation rate: Generally the IF flow rate is positively correlated with the various conductivities in the system. The IFF field is then used to determine the drug distribution after an injection via a convection diffusion reaction equation for intra- and extracellular concentrations with parameters guided by experimental data for the drug Doxorubicin. We observe that the interplay of convective and diffusive drug transport can lead to quite unexpected effects in the presence of a heterogeneous, compartmentalized vasculature. Finally we discuss various

  13. Integrating a Suicide Prevention Program into the Primary Health Care Network: A Field Trial Study in Iran

    Directory of Open Access Journals (Sweden)

    Seyed Kazem Malakouti

    2015-01-01

    Full Text Available Objective. To describe and evaluate the feasibility of integrating a suicide prevention program with Primary Health Care services and evaluate if such system can improve screening and identification of depressive disorder, reduce number of suicide attempters, and lower rate of suicide completion. Methodology. This was a quasi-experimental trial in which one community was exposed to the intervention versus the control community with no such exposure. The study sites were two counties in Western Iran. The intervention protocol called for primary care and suicide prevention collaboration at different levels of care. The outcome variables were the number of suicides committed, the number of documented suicide attempts, and the number of identified depressed cases. Results. We identified a higher prevalence of depressive disorders in the intervention site versus the control site (χ2=14.8, P<0.001. We also found a reduction in the rate of suicide completion in the intervention region compared to the control, but a higher prevalence of suicide attempts in both the intervention and the control sites. Conclusion. Integrating a suicide prevention program with the Primary Health Care network enhanced depression and suicide surveillance capacity and subsequently reduced the number of suicides, especially in rural areas.

  14. A non-equilibrium thermodynamic model for tumor extracellular matrix with enzymatic degradation

    Science.gov (United States)

    Xue, Shi-Lei; Li, Bo; Feng, Xi-Qiao; Gao, Huajian

    2017-07-01

    The extracellular matrix (ECM) of a solid tumor not only affords scaffolding to support tumor architecture and integrity but also plays an essential role in tumor growth, invasion, metastasis, and therapeutics. In this paper, a non-equilibrium thermodynamic theory is established to study the chemo-mechanical behaviors of tumor ECM, which is modeled as a poroelastic polyelectrolyte consisting of a collagen network and proteoglycans. By using the principle of maximum energy dissipation rate, we deduce a set of governing equations for drug transport and mechanosensitive enzymatic degradation in ECM. The results reveal that osmosis is primarily responsible for the compression resistance of ECM. It is suggested that a well-designed ECM degradation can effectively modify the tumor microenvironment for improved efficiency of cancer therapy. The theoretical predictions show a good agreement with relevant experimental observations. This study aimed to deepen our understanding of tumor ECM may be conducive to novel anticancer strategies.

  15. Occupational contact urticaria: lessons from the French National Network for Occupational Disease Vigilance and Prevention (RNV3P).

    Science.gov (United States)

    Bensefa-Colas, L; Telle-Lamberton, M; Faye, S; Bourrain, J-L; Crépy, M-N; Lasfargues, G; Choudat, D; Momas, I

    2015-12-01

    Occupational contact urticaria (OCU) is an occupational contact dermatitis that can cause serious health consequences and disability at work. To describe OCU and its temporal trends by the main causal agents and activity sectors in a nationwide scheme in France. Using data from the French National Network for Occupational Disease Vigilance and Prevention (RNV3P), we described OCU reported during the period 2001-10 and analysed the temporal trends of OCU and OCU attributed to the most frequent agents over the study period. Trends analyses were supported by reporting odds ratios using a logistic regression model with reference to 2001, or with time as a continuous variable. During the study period, 251 cases of OCU were reported in RNV3P, half of which were due to natural rubber latex, in particular in the health and social work activity sector (HSW). The number of these cases declined significantly over the study period (19% per year), and particularly after 2006. Conversely, the other causes of OCU did not decrease. Using surveillance data from a French national network, this study has found that there was a significant decline in OCU due to natural rubber latex, particularly in the HSW, when powdered latex gloves were banned from French hospitals. Our results show the effectiveness of this preventive measure, and suggest that this practice should be extended to other sectors. © 2015 British Association of Dermatologists.

  16. Botnet detection and prevention in anonymous networks

    NARCIS (Netherlands)

    Kuhnert, Katharina; Steinberger, Jessica; Baier, Harald

    Botnets are a major threat to the Internet landscape and have been responsible for large scale distributed attacks on online services. To make take down measures more difficult, Botnet operators started to incorporate anonymous networks into their software to protect their users and their Botnets.

  17. An Approach for Prevention of MitM Attack Based on Rogue AP in Wireless Network

    Directory of Open Access Journals (Sweden)

    Zhendong Wu

    2014-12-01

    Full Text Available With the rapid development of WLAN, more and more schools and businesses have begun to provide the WLAN for users. However, WLAN is considerably more susceptible to MitM (man- in-the-middle attack. To overcome it, we propose a dynamic password technology named Two-way Dynamic Authentication Technology (TDAT. It uses two-factor during the initial authentication, and uses a two-way hash chain during the cross-domain authentication. TDAT effectively protects users' authentication credentials and improves users' experience. In an actual wireless network environment, we implement a MitM attack framework based on Rogue AP. Then we effectively prevent this MitM attack by using TDAT. Moreover we analyze the security of TDAT by using BAN logic.

  18. Software-defined network abstractions and configuration interfaces for building programmable quantum networks

    Energy Technology Data Exchange (ETDEWEB)

    Dasari, Venkat [U.S. Army Research Laboratory, Aberdeen Proving Ground, MD; Sadlier, Ronald J [ORNL; Geerhart, Mr. Billy [U.S. Army Research Laboratory, Aberdeen Proving Ground, MD; Snow, Nikolai [U.S. Army Research Laboratory, Aberdeen Proving Ground, MD; Williams, Brian P [ORNL; Humble, Travis S [ORNL

    2017-01-01

    Well-defined and stable quantum networks are essential to realize functional quantum applications. Quantum networks are complex and must use both quantum and classical channels to support quantum applications like QKD, teleportation, and superdense coding. In particular, the no-cloning theorem prevents the reliable copying of quantum signals such that the quantum and classical channels must be highly coordinated using robust and extensible methods. We develop new network abstractions and interfaces for building programmable quantum networks. Our approach leverages new OpenFlow data structures and table type patterns to build programmable quantum networks and to support quantum applications.

  19. Conservative multimodal management of a primitive neuroectodermal tumor of the thyroid

    Directory of Open Access Journals (Sweden)

    Juliette Haudebourg

    2013-04-01

    Full Text Available Primitive neuroectodermal tumors (PNET represent 1% of sarcomas. Head and neck peripheral PNETs have an intermediate prognosis between abdominopelvic disease and extremities. We here report the case of a 40-year old male who presented with primitive neuroectodermal tumor of the thyroid and was treated by multimodal treatment, including surgery, chemotherapy and intermediate dose radiotherapy. The patient is alive and fit with a functional larynx at 27 months. Multimodal treatments yield five-year survival rates of about 60%. Major drug regimens use vincristine, doxorubicin, ifosfamide or cyclophosphamide, dactinomycin and/or etoposide. Complete surgical excision is undertaken whenever possible to improve long-term survival. However, the relative radiosensitivity of tumors of the Ewing family, suggest multimodal treatment including adjuvant conformal radiotherapy in case of positive margins or poor response to chemotherapy rather than resection with 2-3 cm margins, which would imply laryngeal sacrifice for thyroid tumors. The role of expert rare tumor networks is crucial for optimal decision-making and management of such rare tumors on a case by case basis.

  20. Polaprezinc reduces paclitaxel-induced peripheral neuropathy in rats without affecting anti-tumor activity

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    Kuniaki Tsutsumi

    2016-06-01

    Full Text Available Paclitaxel, an anticancer drug, frequently causes painful peripheral neuropathy. In this study, we investigated the preventive effect of polaprezinc on paclitaxel-induced peripheral neuropathy in rats. Polaprezinc (3 mg/kg, p.o., once daily inhibited the development of mechanical allodynia induced by paclitaxel (4 mg/kg, i.p., on days 1, 3, 5 and 7 and suppressed the paclitaxel-induced increase in macrophage migration in dorsal root ganglion cells. In addition, polaprezinc did not affect the anti-tumor activity of paclitaxel in cultured cell lines or tumor-bearing mice. These results suggest a clinical indication for polaprezinc in the prevention of paclitaxel-induced neuropathy.

  1. Prevention of radiochemotherapy-induced toxicity with amifostine in patients with malignant orbital tumors involving the lacrimal gland: a pilot study

    International Nuclear Information System (INIS)

    Goldblum, David; Ghadjar, Pirus; Curschmann, Juergen; Greiner, Richard; Aebersold, Daniel

    2008-01-01

    To use amifostine concurrently with radiochemotherapy (CT-RT) or radiotherapy (RT) alone in order to prevent dry eye syndrome in patients with malignancies located in the fronto-orbital region. Five patients (2 males, 3 females) with diagnosed malignancies (Non-Hodgkin B-cell Lymphoma, neuroendocrine carcinoma) involving the lacrimal gland, in which either combined CT-RT or local RT were indicated, were prophylactically treated with amifostine (500 mg sc). Single RT fraction dose, total dose and treatment duration were individually adjusted to the patient's need. Acute and late adverse effects were recorded using the RTOG score. Subjective and objective dry eye assessment was performed for the post-treatment control of lacrimal gland function. All patients have completed CT-RT or RT as indicated. The median total duration of RT was 29 days (range, 23 – 39 days) and the median total RT dose was 40 Gy (range, 36 – 60 Gy). Median lacrimal gland exposure was 35.9 Gy (range, 16.8 – 42.6 Gy). Very good partial or complete tumor remission was achieved in all patients. The treatment was well tolerated without major toxic reactions. Post-treatment control did not reveal in any patient either subjective or objective signs of a dry eye syndrome. The addition of amifostine to RT/CT-RT of patients with tumors localized in orbital region was found to be associated with absence of dry eye syndrome

  2. Preventive but Not Curative Efficacy of Celecoxib on Bladder Carcinogenesis in a Rat Model

    Directory of Open Access Journals (Sweden)

    José Sereno

    2010-01-01

    Full Text Available To evaluate the effect of a cyclooxygenase 2 inhibitor, celecoxib (CEL, on bladder cancer inhibition in a rat model, when used as preventive versus as curative treatment. The study comprised 52 male Wistar rats, divided in 5 groups, during a 20-week protocol: control: vehicle, carcinogen: 0.05% of N-butyl-N-(4-hydroxybutyl nitrosamine (BBN, CEL: 10 mg/kg/day of the selective COX-2 inhibitor Celebrex, preventive CEL (CEL+BBN-P, and curative CEL (BBN+CEL-C groups. Although tumor growth was markedly inhibited by the preventive application of CEL, it was even aggravated by the curative treatment. The incidence of gross bladder carcinoma was: control 0/8(0%, BBN 13/20(65%, CEL 0/8(0%, CEL+BBN-P 1/8(12.5%, and BBN+CEL-C 6/8(75%. The number and volume of carcinomas were significantly lower in the CEL+BBN-P versus BBN, accompanied by an ample reduction in hyperplasia, dysplasia, and papillary tumors as well as COX-2 immunostaining. In spite of the reduction of tumor volumes in the curative BBN+CEL-C group, tumor malignancy was augmented. An anti-inflammatory and antioxidant profile was encountered only in the group under preventive treatment. In conclusion, preventive, but not curative, celecoxib treatment promoted a striking inhibitory effect on bladder cancer development, reinforcing the potential role of chemopreventive strategies based on cyclooxygenase 2 inhibition.

  3. Tumor SHB gene expression affects disease characteristics in human acute myeloid leukemia.

    Science.gov (United States)

    Jamalpour, Maria; Li, Xiujuan; Cavelier, Lucia; Gustafsson, Karin; Mostoslavsky, Gustavo; Höglund, Martin; Welsh, Michael

    2017-10-01

    The mouse Shb gene coding for the Src Homology 2-domain containing adapter protein B has recently been placed in context of BCRABL1-induced myeloid leukemia in mice and the current study was performed in order to relate SHB to human acute myeloid leukemia (AML). Publicly available AML databases were mined for SHB gene expression and patient survival. SHB gene expression was determined in the Uppsala cohort of AML patients by qPCR. Cell proliferation was determined after SHB gene knockdown in leukemic cell lines. Despite a low frequency of SHB gene mutations, many tumors overexpressed SHB mRNA compared with normal myeloid blood cells. AML patients with tumors expressing low SHB mRNA displayed longer survival times. A subgroup of AML exhibiting a favorable prognosis, acute promyelocytic leukemia (APL) with a PMLRARA translocation, expressed less SHB mRNA than AML tumors in general. When examining genes co-expressed with SHB in AML tumors, four other genes ( PAX5, HDAC7, BCORL1, TET1) related to leukemia were identified. A network consisting of these genes plus SHB was identified that relates to certain phenotypic characteristics, such as immune cell, vascular and apoptotic features. SHB knockdown in the APL PMLRARA cell line NB4 and the monocyte/macrophage cell line MM6 adversely affected proliferation, linking SHB gene expression to tumor cell expansion and consequently to patient survival. It is concluded that tumor SHB gene expression relates to AML survival and its subgroup APL. Moreover, this gene is included in a network of genes that plays a role for an AML phenotype exhibiting certain immune cell, vascular and apoptotic characteristics.

  4. Comprehensive characterization of lncRNA-mRNA related ceRNA network across 12 major cancers

    Science.gov (United States)

    Feng, Li; Li, Feng; Sun, Zeguo; Wu, Tan; Shi, Xinrui; Li, Jing; Li, Xia

    2016-01-01

    Recent studies indicate that long noncoding RNAs (lncRNAs) can act as competing endogenous RNAs (ceRNAs) to indirectly regulate mRNAs through shared microRNAs, which represents a novel layer of RNA crosstalk and plays critical roles in the development of tumor. However, the global regulation landscape and characterization of these lncRNA related ceRNA crosstalk in cancers is still largely unknown. Here, we systematically characterized the lncRNA related ceRNA interactions across 12 major cancers and the normal physiological states by integrating multidimensional molecule profiles of more than 5000 samples. Our study suggest the large difference of ceRNA regulation between normal and tumor states and the higher similarity across similar tissue origin of tumors. The ceRNA related molecules have more conserved features in tumor networks and they play critical roles in both the normal and tumorigenesis processes. Besides, lncRNAs in the pan-cancer ceRNA network may be potential biomarkers of tumor. By exploring hub lncRNAs, we found that these conserved key lncRNAs dominate variable tumor hallmark processes across pan-cancers. Network dynamic analysis highlights the critical roles of ceRNA regulation in tumorigenesis. By analyzing conserved ceRNA interactions, we found that miRNA mediate ceRNA regulation showed different patterns across pan-cancer; while analyzing the cancer specific ceRNA interactions reveal that lncRNAs synergistically regulated tumor driver genes of cancer hallmarks. Finally, we found that ceRNA modules have the potential to predict patient survival. Overall, our study systematically dissected the lncRNA related ceRNA networks in pan-cancer that shed new light on understanding the molecular mechanism of tumorigenesis. PMID:27580177

  5. Networks for prevention of violence: from utopia to action Redes de prevenção à violência: da utopia à ação

    Directory of Open Access Journals (Sweden)

    Kathie Njaine

    2006-06-01

    Full Text Available This article aims to discuss the experience of networks for the protection of people exposed to situations of violence or prevention networks. It is based on the concept created by Castells, who defines the information age. This study is part of the investigation "Successful experiences in the prevention of violence", carried out by the Latin-American Center for Studies on Violence Jorge Careli/ENSP-IFF/Fiocruz, in cooperation with the Secretariat for Health Survey of the Ministry of Health. The article analyzes the possibilities and limitations in the construction of networks for the prevention of violence, seeking to understand the sense of actions and movements carried out in networks. The method we used is a case study of two network initiatives in the Southern region of the country. In terms of results, in face of the difficulties of working in networks, we found it to be necessary: to break with sectorial and vertical actions; to promote constant communication and interchange of information; to permanently train the professionals and persons involved in the network, incorporating them into the protective and preventive actions; and to promote the participation of wide social sectors. In conclusion, one can affirm that the construction of a protection network involves complex steps, looking to the same problem with new eyes and a new vision for planting solutions.Este artigo objetiva discutir a experiência de redes de proteção a pessoas em situação de violência ou redes de prevenção. Baseia-se no conceito de rede de Castells, que define a sociedade da informação. O estudo é parte da pesquisa "Experiências exitosas em prevenção da violência", realizada pelo Centro Latino-Americano de Estudos de Violência e Saúde Jorge Careli/ENSP-IFF/ Fiocruz, em convênio com a Secretaria de Vigilância à Saúde do Ministério da Saúde. O presente artigo analisa as potencialidades e os limites para a construção de redes de prevenção

  6. How many molecular subtypes? Implications of the unique tumor principle in personalized medicine.

    Science.gov (United States)

    Ogino, Shuji; Fuchs, Charles S; Giovannucci, Edward

    2012-07-01

    Cancers are complex multifactorial diseases. For centuries, conventional organ-based classification system (i.e., breast cancer, lung cancer, colon cancer, colorectal cancer, prostate cancer, lymphoma, leukemia, and so on) has been utilized. Recently, molecular diagnostics has become an essential component in clinical decision-making. However, tumor evolution and behavior cannot accurately be predicted, despite numerous research studies reporting promising tumor biomarkers. To advance molecular diagnostics, a better understanding of intratumor and intertumor heterogeneity is essential. Tumor cells interact with the extracellular matrix and host non-neoplastic cells in the tumor microenvironment, which is influenced by genomic variation, hormones, and dietary, lifestyle and environmental exposures, implicated by molecular pathological epidemiology. Essentially, each tumor possesses its own unique characteristics in terms of molecular make-up, tumor microenvironment and interactomes within and between neoplastic and host cells. Starting from the unique tumor concept and paradigm, we can better classify tumors by molecular methods, and move closer toward personalized cancer medicine and prevention.

  7. A histological evaluation and in vivo assessment of intratumoral near infrared photothermal nanotherapy-induced tumor regression

    Directory of Open Access Journals (Sweden)

    Green HN

    2014-11-01

    Full Text Available Hadiyah N Green,1,2 Stephanie D Crockett,3 Dmitry V Martyshkin,1 Karan P Singh,2,4 William E Grizzle,2,5 Eben L Rosenthal,2,6 Sergey B Mirov11Department of Physics, Center for Optical Sensors and Spectroscopies, 2Comprehensive Cancer Center, 3Department of Pediatrics, Division of Neonatology, 4Department of Medicine, Division of Preventive Medicine, Biostatistics and Bioinformatics Shared Facility, 5Department of Pathology, 6Department of Surgery, Division of Otolaryngology, Head and Neck Surgery, The University of Alabama at Birmingham, Birmingham, AL, USAPurpose: Nanoparticle (NP-enabled near infrared (NIR photothermal therapy has realized limited success in in vivo studies as a potential localized cancer therapy. This is primarily due to a lack of successful methods that can prevent NP uptake by the reticuloendothelial system, especially the liver and kidney, and deliver sufficient quantities of intravenously injected NPs to the tumor site. Histological evaluation of photothermal therapy-induced tumor regression is also neglected in the current literature. This report demonstrates and histologically evaluates the in vivo potential of NIR photothermal therapy by circumventing the challenges of intravenous NP delivery and tumor targeting found in other photothermal therapy studies.Methods: Subcutaneous Cal 27 squamous cell carcinoma xenografts received photothermal nanotherapy treatments, radial injections of polyethylene glycol (PEG-ylated gold nanorods and one NIR 785 nm laser irradiation for 10 minutes at 9.5 W/cm2. Tumor response was measured for 10–15 days, gross changes in tumor size were evaluated, and the remaining tumors or scar tissues were excised and histologically analyzed.Results: The single treatment of intratumoral nanorod injections followed by a 10 minute NIR laser treatment also known as photothermal nanotherapy, resulted in ~100% tumor regression in ~90% of treated tumors, which was statistically significant in a

  8. Complementary roles in cancer prevention: protease inhibitor makes the cancer preventive peptide lunasin bioavailable.

    Directory of Open Access Journals (Sweden)

    Chia-Chien Hsieh

    Full Text Available BACKGROUND: The lower incidence of breast cancer among Asian women compared with Western countries has been partly attributed to soy in the Asian diet, leading to efforts to identify the bioactive components that are responsible. Soy Bowman Birk Inhibitor Concentrate (BBIC is a known cancer preventive agent now in human clinical trials. METHODOLOGY/PRINCIPAL FINDINGS: The objectives of this work are to establish the presence and delineate the in vitro activity of lunasin and BBI found in BBIC, and study their bioavailability after oral administration to mice and rats. We report that lunasin and BBI are the two main bioactive ingredients of BBIC based on inhibition of foci formation, lunasin being more efficacious than BBI on an equimolar basis. BBI and soy Kunitz Trypsin Inhibitor protect lunasin from in vitro digestion with pancreatin. Oral administration of (3H-labeled lunasin with lunasin-enriched soy results in 30% of the peptide reaching target tissues in an intact and bioactive form. In a xenograft model of nude mice transplanted with human breast cancer MDA-MB-231 cells, intraperitoneal injections of lunasin, at 20 mg/kg and 4 mg/kg body weight, decrease tumor incidence by 49% and 33%, respectively, compared with the vehicle-treated group. In contrast, injection with BBI at 20 mg/kg body weight shows no effect on tumor incidence. Tumor generation is significantly reduced with the two doses of lunasin, while BBI is ineffective. Lunasin inhibits cell proliferation and induces cell death in the breast tumor sections. CONCLUSIONS/SIGNIFICANCE: We conclude that lunasin is actually the bioactive cancer preventive agent in BBIC, and BBI simply protects lunasin from digestion when soybean and other seed foods are eaten by humans.

  9. Electrophysiology of glioma: a Rho GTPase-activating protein reduces tumor growth and spares neuron structure and function.

    Science.gov (United States)

    Vannini, Eleonora; Olimpico, Francesco; Middei, Silvia; Ammassari-Teule, Martine; de Graaf, Erik L; McDonnell, Liam; Schmidt, Gudula; Fabbri, Alessia; Fiorentini, Carla; Baroncelli, Laura; Costa, Mario; Caleo, Matteo

    2016-12-01

    Glioblastomas are the most aggressive type of brain tumor. A successful treatment should aim at halting tumor growth and protecting neuronal cells to prevent functional deficits and cognitive deterioration. Here, we exploited a Rho GTPase-activating bacterial protein toxin, cytotoxic necrotizing factor 1 (CNF1), to interfere with glioma cell growth in vitro and vivo. We also investigated whether this toxin spares neuron structure and function in peritumoral areas. We performed a microarray transcriptomic and in-depth proteomic analysis to characterize the molecular changes triggered by CNF1 in glioma cells. We also examined tumor cell senescence and growth in vehicle- and CNF1-treated glioma-bearing mice. Electrophysiological and morphological techniques were used to investigate neuronal alterations in peritumoral cortical areas. Administration of CNF1 triggered molecular and morphological hallmarks of senescence in mouse and human glioma cells in vitro. CNF1 treatment in vivo induced glioma cell senescence and potently reduced tumor volumes. In peritumoral areas of glioma-bearing mice, neurons showed a shrunken dendritic arbor and severe functional alterations such as increased spontaneous activity and reduced visual responsiveness. CNF1 treatment enhanced dendritic length and improved several physiological properties of pyramidal neurons, demonstrating functional preservation of the cortical network. Our findings demonstrate that CNF1 reduces glioma volume while at the same time maintaining the physiological and structural properties of peritumoral neurons. These data indicate a promising strategy for the development of more effective antiglioma therapies. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Jaehong Kim

    2016-01-01

    Full Text Available Distinct tumor microenvironment forms in each progression step of cancer and has diverse capacities to induce both adverse and beneficial consequences for tumorigenesis. It is now known that immune cells can be activated to favor tumor growth and progression, most probably influenced by the tumor microenvironment. Tumor-associated macrophages and tumor-associated neutrophils can exert protumoral functions, enhancing tumor cell invasion and metastasis, angiogenesis, and extracellular matrix remodeling, while inhibiting the antitumoral immune surveillance. Considering that neutrophils in inflammatory environments recruit macrophages and that recruited macrophages affect neutrophil functions, there may be various degrees of interaction between tumor-associated macrophages and tumor-associated neutrophils. Platelets also play an important role in the recruitment and regulation of monocytic and granulocytic cells in the tumor tissues, suggesting that platelet function may be essential for generation of tumor-associated macrophages and tumor-associated neutrophils. In this review, we will explore the biology of tumor-associated macrophages and tumor-associated neutrophils and their possible interactions in the tumor microenvironment. Special attention will be given to the recruitment and activation of these tumor-associated cells and to the roles they play in maintenance of the tumor microenvironment and progression of tumors.

  11. Non osseous intra-spinal tumors in children and adolescents: spinal column deformity (in french)

    International Nuclear Information System (INIS)

    Ghanem, I.; Zeller, R.; Dubousset, J.

    1997-01-01

    Purpose of the study. The delay in diagnosis of spinal tumors is not rare. The chief complaint may include pain, walking disability and spinal or limb deformities. The purpose of our study is to analyze the spinal deformities associated with non osseous intra-spinal tumors, to assess the complications of treatment, and to set out a preventive protocol. Methods. The incidence and pattern of spinal deformity was assessed before tumor treatment and ultimately after laminectomy or osteoplastic laminotomy (or lamino-plasty). Results. Among the 9 cases with preexisting spinal deformity, the curve magnitude increased after laminectomy in 4. A kyphotic, kyphoscoliotic or scoliotic deformity developed in 18 cases after surgery for tumor resection. Among these 18 patients, only one had bad an adequate osteoplastic laminotomy. The treatment of spinal deformities was surgical in 12 cases, and done by either posterior or anterior and posterior combined arthrodesis. Discussion. Spinal deformity may be the main complaint of a patient who has intraspinal tumor. Prevention of post-laminectomy spinal deformity is mandatory, and could be done by osteoplastic laminotomy and the use of a brace during a minimum period of 4 to 6 months after surgery. Conclusion. Diagnosis of intraspinal tumors in children and adolescents should be done early, and lamino-arthrectomy should be replaced by osteoplastic laminotomy. (authors)

  12. Gleditsia Saponin C Induces A549 Cell Apoptosis via Caspase-Dependent Cascade and Suppresses Tumor Growth on Xenografts Tumor Animal Model

    Directory of Open Access Journals (Sweden)

    Ye Cheng

    2018-01-01

    Full Text Available Saponins are natural compounds and possess the most promising anti-cancer function. Here, a saponin gleditsia saponin C (GSC, extracted from gleditsiae fructus abnormalis, could induce apoptosis of lung tumor cell line A549 via caspase dependent cascade and this effect could be prevented by the caspase inhibitors. In addition, GSC induced cell death companied with an increase ratio of Bax:Bcl-2 and inhibition of ERK and Akt signaling pathways. Meanwhile, GSC suppressed TNFα inducing NF-κB activation and increased the susceptibility of lung cancer cell to TNFα induced apoptosis. Furthermore, on mouse xenograft model, GSC significantly suppressed tumor growth and induced cancer cell apoptosis, which validated the anti-tumor effect of GSC. Based on these results, GSC might be a promising drug candidate of anti-lung cancer for its potential clinical applications.

  13. The dependence receptor Ret induces apoptosis in somatotrophs through a Pit-1/p53 pathway, preventing tumor growth.

    Science.gov (United States)

    Cañibano, Carmen; Rodriguez, Noela L; Saez, Carmen; Tovar, Sulay; Garcia-Lavandeira, Montse; Borrello, Maria Grazia; Vidal, Anxo; Costantini, Frank; Japon, Miguel; Dieguez, Carlos; Alvarez, Clara V

    2007-04-18

    Somatotrophs are the only pituitary cells that express Ret, GFRalpha1 and GDNF. This study investigated the effects of Ret in a somatotroph cell line, in primary pituitary cultures and in Ret KO mice. Ret regulates somatotroph numbers by inducing Pit-1 overexpression, leading to increased p53 expression and apoptosis, both of which can be prevented with Ret or Pit-1 siRNA. The Pit-1 overexpression is mediated by sustained activation of PKCdelta, JNK, c/EBPalpha and CREB induced by a complex of Ret, caspase 3 and PKCdelta. In the presence of GDNF, Akt is activated, and the Pit-1 overexpression and resulting apoptosis are blocked. The adenopituitary of Ret KO mice is larger than normal, showing Pit-1 and somatotroph hyperplasia. In normal animals, activation of the Ret/Pit-1/p53 pathway by retroviral introduction of Ret blocked tumor growth in vivo. Thus, somatotrophs have an intrinsic mechanism for controlling Pit-1/GH production through an apoptotic/survival pathway. Ret might be of value for treatment of pituitary adenomas.

  14. The network approach for prevention of healthcare-associated infections: long-term effect of participation in the Duke Infection Control Outreach Network.

    Science.gov (United States)

    Anderson, Deverick J; Miller, Becky A; Chen, Luke F; Adcock, Linda H; Cook, Evelyn; Cromer, A Lynn; Louis, Susan; Thacker, Paul A; Sexton, Daniel J

    2011-04-01

    To describe the rates of several key outcomes and healthcare-associated infections (HAIs) among hospitals that participated in the Duke Infection Control Outreach Network (DICON). Prospective, observational cohort study of patients admitted to 24 community hospitals from 2003 through 2009. The following data were collected and analyzed: incidence of central line-associated bloodstream infections (CLABSIs), ventilator-associated pneumonia (VAP), catheter-associated urinary tract infections (CAUTIs), and HAIs caused by methicillin-resistant Staphylococcus aureus (MRSA); employee exposures to bloodborne pathogens (EBBPs); physician EBBPs; patient-days; central line-days; ventilator-days; and urinary catheter-days. Poisson regression was used to determine whether incidence rates of these HAIs and exposures changed during the first 5 and 7 years of participation in DICON; nonrandom clustering of each outcome was controlled for. Cost saved and lives saved were calculated on the basis of published estimates. In total, we analyzed 6.5 million patient-days, 4,783 EBPPs, 2,948 HAIs due to MRSA, and 2,076 device-related infections. Rates of employee EBBPs, HAIs due to MRSA, and device-related infections decreased significantly during the first 5 years of participation in DICON (Pprevented. Each hospital saved approximately $100,000 per year of participation, and collectively the hospitals may have prevented 52-105 deaths from CLABSI or VAP. The 7-year analysis demonstrated that these trends continued with further participation. Hospitals with long-term participation in an infection control network decreased rates of significant HAIs by approximately 50%, decreased costs, and saved lives.

  15. International Workshop on Mathematical Modeling of Tumor-Immune Dynamics

    CERN Document Server

    Kim, Peter; Mallet, Dann

    2014-01-01

    This collection of papers offers a broad synopsis of state-of-the-art mathematical methods used in modeling the interaction between tumors and the immune system. These papers were presented at the four-day workshop on Mathematical Models of Tumor-Immune System Dynamics held in Sydney, Australia from January 7th to January 10th, 2013. The workshop brought together applied mathematicians, biologists, and clinicians actively working in the field of cancer immunology to share their current research and to increase awareness of the innovative mathematical tools that are applicable to the growing field of cancer immunology. Recent progress in cancer immunology and advances in immunotherapy suggest that the immune system plays a fundamental role in host defense against tumors and could be utilized to prevent or cure cancer. Although theoretical and experimental studies of tumor-immune system dynamics have a long history, there are still many unanswered questions about the mechanisms that govern the interaction betwe...

  16. A pilot study to image the vascular network of small melanocytic choroidal tumors with speckle noise-free 1050-nm swept source optical coherence tomography (OCT choroidal angiography).

    Science.gov (United States)

    Maloca, Peter; Gyger, Cyrill; Hasler, Pascal W

    2016-06-01

    To visualize and measure the vascular network of melanocytic choroidal tumors with speckle noise-free swept source optical coherence tomography (SS-OCT choroidal angiography). Melanocytic choroidal tumors from 24 eyes were imaged with 1050-nm optical coherence tomography (Topcon DRI OCT-1 Atlantis). A semi-automated algorithm was developed to remove speckle noise and to extract and measure the volume of the choroidal vessels from the obtained OCT data. In all cases, analysis of the choroidal vessels could be performed with SS-OCT without the need for pupillary dilation. The proposed method allows speckle noise-free, structure-guided visualization and measurement of the larger choroidal vessels in three dimensions. The obtained data suggest that speckle noise-free OCT may be more effective at identifying choroidal structures than traditional OCT methods. The measured volume of the extracted choroidal vessels of Haller's layer and Sattler's layer in the examined tumorous eyes was on average 0.982463955 mm(3) /982463956 μm(3) (range of 0.209764406 mm(3) /209764405.9 μm(3)to 1.78105544 mm(3) /1781055440 μm(3)). Full thickness obstruction of the choroidal vasculature by the tumor was found in 18 cases (72 %). In seven cases (18 %), choroidal vessel architecture did not show pronounced morphological abnormalities (18 %). Speckle noise-free OCT may serve as a new illustrative imaging technology and enhance visualization of the choroidal vessels without the need for dye injection. OCT can be used to identify and evaluate the choroidal vessels of melanocytic choroidal tumors, and may represent a potentially useful tool for imaging and monitoring of choroidal nevi and melanoma.

  17. Endocrine tumors other than thyroid tumors

    International Nuclear Information System (INIS)

    Takeichi, Norio; Dohi, Kiyohiko

    1992-01-01

    This paper discusses the tendency for the occurrence of tumors in the endocrine glands, other than the thyroid gland, in A-bomb survivors using both autopsy and clinical data. ABCC-RERF sample data using 4136 autopsy cases (1961-1977) revealed parathyroid tumors in 13 A-bomb survivors, including 3 with the associated hyperparathyroidism, with the suggestion of dose-dependent increase in the occurrence of tumors. Based on clinical data from Hiroshima University, 7 (46.7%) of 15 parathyroid tumors cases were A-bomb survivors. Data (1974-1987) from the Tumor Registry Committee (TRC) in Hiroshima Prefecture revealed that a relative risk of parathyroid tumors was 5.6 times higher in the entire group of A-bomb survivors and 16.2 times higher in the group of heavily exposed A-bomb survivors, suggesting the dose-dependent increase in their occurrence. Adrenal tumors were detected in 47 of 123 cases from the TRC data, and 15 (31.5%) of these 47 were A-bomb survivors. Particularly, 11 cases of adrenal tumors associated with Cushing syndrome included 6 A-bomb survivors (54.5%). The incidence of multiple endocrine gonadial tumors (MEGT) tended to be higher with increasing exposure doses; and the 1-9 rad group, the 10-99 rad group, and the 100 or more rad group had a risk of developing MEGT of 4.1, 5.7, and 7.1, respectively, relative to both the not-in the city group and the 0 rad group. These findings suggested that there is a correlation between A-bomb radiation and the occurrence of parathyroid tumors (including hyperparathyroidism), adrenal tumors associated with Cushing syndrome and MEGT (especially, the combined thyroid and ovarian tumors and the combined thyroid and parathyroid tumors). (N.K.)

  18. A new intrusion prevention model using planning knowledge graph

    Science.gov (United States)

    Cai, Zengyu; Feng, Yuan; Liu, Shuru; Gan, Yong

    2013-03-01

    Intelligent plan is a very important research in artificial intelligence, which has applied in network security. This paper proposes a new intrusion prevention model base on planning knowledge graph and discuses the system architecture and characteristics of this model. The Intrusion Prevention based on plan knowledge graph is completed by plan recognition based on planning knowledge graph, and the Intrusion response strategies and actions are completed by the hierarchical task network (HTN) planner in this paper. Intrusion prevention system has the advantages of intelligent planning, which has the advantage of the knowledge-sharing, the response focused, learning autonomy and protective ability.

  19. Thioredoxin and Cancer: A Role for Thioredoxin in all States of Tumor Oxygenation

    International Nuclear Information System (INIS)

    Karlenius, Therese Christina; Tonissen, Kathryn Fay

    2010-01-01

    Thioredoxin is a small redox-regulating protein, which plays crucial roles in maintaining cellular redox homeostasis and cell survival and is highly expressed in many cancers. The tumor environment is usually under either oxidative or hypoxic stress and both stresses are known up-regulators of thioredoxin expression. These environments exist in tumors because their abnormal vascular networks result in an unstable oxygen delivery. Therefore, the oxygenation patterns in human tumors are complex, leading to hypoxia/re-oxygenation cycling. During carcinogenesis, tumor cells often become more resistant to hypoxia or oxidative stress-induced cell death and most studies on tumor oxygenation have focused on these two tumor environments. However, recent investigations suggest that the hypoxic cycling occurring within tumors plays a larger role in the contribution to tumor cell survival than either oxidative stress or hypoxia alone. Thioredoxin is known to have important roles in both these cellular responses and several studies implicate thioredoxin as a contributor to cancer progression. However, only a few studies exist that investigate the regulation of thioredoxin in the hypoxic and cycling hypoxic response in cancers. This review focuses on the role of thioredoxin in the various states of tumor oxygenation

  20. The Healthy Aging Research Network: Modeling Collaboration for Community Impact.

    Science.gov (United States)

    Belza, Basia; Altpeter, Mary; Smith, Matthew Lee; Ory, Marcia G

    2017-03-01

    As the first Centers for Disease Control and Prevention (CDC) Prevention Research Centers Program thematic network, the Healthy Aging Research Network was established to better understand the determinants of healthy aging within older adult populations, identify interventions that promote healthy aging, and assist in translating research into sustainable community-based programs throughout the nation. To achieve these goals requires concerted efforts of a collaborative network of academic, community, and public health organizational partnerships. For the 2001-2014 Prevention Research Center funding cycles, the Healthy Aging Research Network conducted prevention research and promoted the wide use of practices known to foster optimal health. Organized around components necessary for successful collaborations (i.e., governance and infrastructure, shaping focus, community involvement, and evaluation and improvement), this commentary highlights exemplars that demonstrate the Healthy Aging Research Network's unique contributions to the field. The Healthy Aging Research Network's collaboration provided a means to collectively build capacity for practice and policy, reduce fragmentation and duplication in health promotion and aging research efforts, maximize the efficient use of existing resources and generate additional resources, and ultimately, create synergies for advancing the healthy aging agenda. This collaborative model was built upon a backbone organization (coordinating center); setting of common agendas and mutually reinforcing activities; and continuous communications. Given its successes, the Healthy Aging Research Network model could be used to create new and evaluate existing thematic networks to guide the translation of research into policy and practice. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  1. Heterogeneity maintenance in glioblastoma: a social network.

    Science.gov (United States)

    Bonavia, Rudy; Inda, Maria-del-Mar; Cavenee, Webster K; Furnari, Frank B

    2011-06-15

    Glioblastoma multiforme (GBM), the most common intracranial tumor in adults, is characterized by extensive heterogeneity at the cellular and molecular levels. This insidious feature arises inevitably in almost all cancers and has great significance for the general outcome of the malignancy, because it confounds our understanding of the disease and also intrinsically contributes to the tumor's aggressiveness and poses an obstacle to the design of effective therapies. The classic view that heterogeneity arises as the result of a tumor's "genetic chaos" and the more contemporary cancer stem cell (CSC) hypothesis tend to identify a single cell population as the therapeutic target: the prevailing clone over time in the first case and the CSC in the latter. However, there is growing evidence that the different tumor cell populations may not be simple bystanders. Rather, they can establish a complex network of interactions between each other and with the tumor microenvironment that eventually strengthens tumor growth and increases chances to escape therapy. These differing but complementary ideas about the origin and maintenance of tumor heterogeneity and its importance in GBM are reviewed here.

  2. Tumor-associated mesenchymal stem cells inhibit naïve T cell expansion by blocking cysteine export from dendritic cells.

    Science.gov (United States)

    Ghosh, Tithi; Barik, Subhasis; Bhuniya, Avishek; Dhar, Jesmita; Dasgupta, Shayani; Ghosh, Sarbari; Sarkar, Madhurima; Guha, Ipsita; Sarkar, Koustav; Chakrabarti, Pinak; Saha, Bhaskar; Storkus, Walter J; Baral, Rathindranath; Bose, Anamika

    2016-11-01

    Mesenchymal stem cells (MSCs) represent an important cellular constituent of the tumor microenvironment, which along with tumor cells themselves, serve to regulate protective immune responses in support of progressive disease. We report that tumor MSCs prevent the ability of dendritic cells (DC) to promote naïve CD4(+) and CD8(+) T cell expansion, interferon gamma secretion and cytotoxicity against tumor cells, which are critical to immune-mediated tumor eradication. Notably, tumor MSCs fail to prevent DC-mediated early T cell activation events or the ability of responder T cells to produce IL-2. The immunoregulatory activity of tumor MSCs is IL-10- and STAT3-dependent, with STAT3 repressing DC expression of cystathionase, a critical enzyme that converts methionine-to-cysteine. Under cysteine-deficient priming conditions, naïve T cells exhibit defective cellular metabolism and proliferation. Bioinformatics analyses as well as in vitro observations suggest that STAT3 may directly bind to a GAS-like motif within the cystathionase promoter (-269 to -261) leading to IL-10-STAT3 mediated repression of cystathionase gene transcription. Our collective results provide evidence for a novel mechanism of tumor MSC-mediated T cell inhibition within tumor microenvironment. © 2016 UICC.

  3. Stress Prevention@Work: a study protocol for the evaluation of a multifaceted integral stress prevention strategy to prevent employee stress in a healthcare organization: a cluster controlled trial.

    Science.gov (United States)

    Hoek, Rianne J A; Havermans, Bo M; Houtman, Irene L D; Brouwers, Evelien P M; Heerkens, Yvonne F; Zijlstra-Vlasveld, Moniek C; Anema, Johannes R; van der Beek, Allard J; Boot, Cécile R L

    2017-07-17

    Adequate implementation of work-related stress management interventions can reduce or prevent work-related stress and sick leave in organizations. We developed a multifaceted integral stress-prevention strategy for organizations from several sectors that includes a digital platform and collaborative learning network. The digital platform contains a stepwise protocol to implement work-related stress-management interventions. It includes stress screeners, interventions and intervention providers to facilitate access to and the selection of matching work-related stress-management interventions. The collaborative learning network, including stakeholders from various organizations, plans meetings focussing on an exchange of experiences and good practices among organizations for the implementation of stress prevention measures. This paper describes the design of an integral stress-prevention strategy, Stress Prevention@Work, and the protocol for the evaluation of: 1) the effects of the strategy on perceived stress and work-related outcomes, and 2) the barriers and facilitators for implementation of the strategy. The effectiveness of Stress Prevention@Work will be evaluated in a cluster controlled trial, in a large healthcare organization in the Netherlands, at six and 12 months. An independent researcher will match teams on working conditions and size and allocate the teams to the intervention or control group. Teams in the intervention group will be offered Stress Prevention@Work. For each intervention team, one employee is responsible for applying the strategy within his/her team using the digital platform and visiting the collaborative learning network. Using a waiting list design, the control group will be given access to the strategy after 12 months. The primary outcome is the employees' perceived stress measured by the stress subscale of the Depression, Anxiety, and Stress Scale (DASS-21). Secondary outcome measures are job demands, job resources and the number

  4. Tumor cell-derived microparticles polarize M2 tumor-associated macrophages for tumor progression.

    Science.gov (United States)

    Ma, Ruihua; Ji, Tiantian; Chen, Degao; Dong, Wenqian; Zhang, Huafeng; Yin, Xiaonan; Ma, Jingwei; Liang, Xiaoyu; Zhang, Yi; Shen, Guanxin; Qin, Xiaofeng; Huang, Bo

    2016-04-01

    Despite identification of macrophages in tumors (tumor-associated macrophages, TAM) as potential targets for cancer therapy, the origin and function of TAM in the context of malignancy remain poorly characterized. Here, we show that microparticles (MPs), as a by-product, released by tumor cells act as a general mechanism to mediate M2 polarization of TAM. Taking up tumor MPs by macrophages is a very efficient process, which in turn results in the polarization of macrophages into M2 type, not only leading to promoting tumor growth and metastasis but also facilitating cancer stem cell development. Moreover, we demonstrate that the underlying mechanism involves the activation of the cGAS/STING/TBK1/STAT6 pathway by tumor MPs. Finally, in addition to murine tumor MPs, we show that human counterparts also possess consistent effect on human M2 polarization. These findings provide new insights into a critical role of tumor MPs in remodeling of tumor microenvironment and better understanding of the communications between tumors and macrophages.

  5. Developing a network: the PMM process.

    Science.gov (United States)

    Kamara, A

    1997-11-01

    Since 1988, the Prevention of Maternal Mortality (PMM) Network has developed, implemented and evaluated projects that focus directly on prevention of maternal deaths. The Network, which consists of 11 multidisciplinary teams in West Africa and one at Columbia University, grew from discussions between the Carnegie Corporation of New York and researchers at Columbia School of Public Health. Its goals are: to strengthen capacities in developing countries; to provide program models for preventing maternal deaths; and to inform policymakers about the importance of maternal mortality. This paper describes the development and functioning of the Network. The initial steps included identifying interested partners in Africa and encouraging them to form multidisciplinary teams. Each African team received two grants: one to perform a needs assessment and then another to develop and implement projects based on the results. The Columbia team provided technical assistance in a variety of ways, including site visits, workshops and correspondence. Teams tested program models and reported findings both to local policymakers and in international fora. Collaboration with government and community leaders helped facilitate progress at all stages. At the PMM Network Results Conference in 1996, the teams decided to continue their work by forming the Regional PMM (RPMM) Network, an entirely African entity.

  6. Is oxygen important in the radiocurability of human tumors

    International Nuclear Information System (INIS)

    Withers, H.R.; Suit, H.D.

    1974-01-01

    It is quite likely that untreated human tumors contain hypoxic cells. Frequently, perhaps usually, the presence of these hypoxic cells does not influence radiocurability. If hypoxia limits radiocurability, it is more likely to do so in the treatment of large tumors and maybe with greater likelihood in tumors in certain sites. Hypoxia would also be more likely to affect response to a small number of fractions, since reoxygenation would need to be more complete in order that cell killing by the larger dose fractions used would not be prejudiced by the hypoxia of a small proportion of cells. Hyperbaric oxygen is disappointing as an adjuvant to radiotherapy. Results obtained are not better than those obtained using the best conventional fractionation regimes in air. This does not prove, however, that hypoxia is not a cause of failure to control tumors locally, since physiological adaptive mechanisms against HPO such as vasoconstriction may prevent better oxygenation of the tumor. If other methods such as high LET beams are to be used to reduce any effect hypoxia may have on radiocurability, their greatest benefit would be expected in the local control of late-stage disease and this benefit may be greater in some tumor sites than others. (U.S.)

  7. Keratocystic Odontogenic Tumor: Case Reports and Review of Literature

    Directory of Open Access Journals (Sweden)

    Mukta B Motwani

    2011-01-01

    Full Text Available The lesion traditionally known as odontogenic keratocyst has been renamed by WHO in 2005, as "keratocystic" odontogenic tumor as it is more appropriate and reflects its potential for local, destructive behavior. It is a benign intraosseous neoplasm of jaw, which is unusual due to its characteristic histopathological and clinical features, including potentially aggressive behavior, high recurrence rate and association with the nevoid basal cell carcinoma syndrome. The purpose of this review is to highlight the importance of proper diagnosis of keratocystic odontogenic tumor in order to prevent the recurrence due to improper surgical excision of the lesion.

  8. Dissecting microregulation of a master regulatory network

    Directory of Open Access Journals (Sweden)

    Kaimal Vivek

    2008-02-01

    Full Text Available Abstract Background The master regulator p53 tumor-suppressor protein through coordination of several downstream target genes and upstream transcription factors controls many pathways important for tumor suppression. While it has been reported that some of the p53's functions are microRNA-mediated, it is not known as to how many other microRNAs might contribute to the p53-mediated tumorigenesis. Results Here, we use bioinformatics-based integrative approach to identify and prioritize putative p53-regulated miRNAs, and unravel the miRNA-based microregulation of the p53 master regulatory network. Specifically, we identify putative microRNA regulators of a transcription factors that are upstream or downstream to p53 and b p53 interactants. The putative p53-miRs and their targets are prioritized using current knowledge of cancer biology and literature-reported cancer-miRNAs. Conclusion Our predicted p53-miRNA-gene networks strongly suggest that coordinated transcriptional and p53-miR mediated networks could be integral to tumorigenesis and the underlying processes and pathways.

  9. The milk protein α-casein functions as a tumor suppressor via activation of STAT1 signaling, effectively preventing breast cancer tumor growth and metastasis

    Science.gov (United States)

    Bonuccelli, Gloria; Castello-Cros, Remedios; Capozza, Franco; Martinez-Outschoorn, Ubaldo E.; Lin, Zhao; Tsirigos, Aristotelis; Xuanmao, Jiao; Whitaker-Menezes, Diana; Howell, Anthony; Lisanti, Michael P.; Sotgia, Federica

    2012-01-01

    Here, we identified the milk protein α-casein as a novel suppressor of tumor growth and metastasis. Briefly, Met-1 mammary tumor cells expressing α-casein showed a ~5-fold reduction in tumor growth and a near 10-fold decrease in experimental metastasis. To identify the molecular mechanism(s), we performed genome-wide transcriptional profiling. Interestingly, our results show that α-casein upregulates gene transcripts associated with interferon/STAT1 signaling and downregulates genes associated with “stemness.” These findings were validated by immunoblot and FACS analysis, which showed the upregulation and hyperactivation of STAT1 and a decrease in the number of CD44(+) “cancer stem cells.” These gene signatures were also able to predict clinical outcome in human breast cancer patients. Thus, we conclude that a lactation-based therapeutic strategy using recombinant α-casein would provide a more natural and non-toxic approach to the development of novel anticancer therapies. PMID:23047602

  10. A three-dimensional computational model of collagen network mechanics.

    Directory of Open Access Journals (Sweden)

    Byoungkoo Lee

    Full Text Available Extracellular matrix (ECM strongly influences cellular behaviors, including cell proliferation, adhesion, and particularly migration. In cancer, the rigidity of the stromal collagen environment is thought to control tumor aggressiveness, and collagen alignment has been linked to tumor cell invasion. While the mechanical properties of collagen at both the single fiber scale and the bulk gel scale are quite well studied, how the fiber network responds to local stress or deformation, both structurally and mechanically, is poorly understood. This intermediate scale knowledge is important to understanding cell-ECM interactions and is the focus of this study. We have developed a three-dimensional elastic collagen fiber network model (bead-and-spring model and studied fiber network behaviors for various biophysical conditions: collagen density, crosslinker strength, crosslinker density, and fiber orientation (random vs. prealigned. We found the best-fit crosslinker parameter values using shear simulation tests in a small strain region. Using this calibrated collagen model, we simulated both shear and tensile tests in a large linear strain region for different network geometry conditions. The results suggest that network geometry is a key determinant of the mechanical properties of the fiber network. We further demonstrated how the fiber network structure and mechanics evolves with a local formation, mimicking the effect of pulling by a pseudopod during cell migration. Our computational fiber network model is a step toward a full biomechanical model of cellular behaviors in various ECM conditions.

  11. Antibacterial activity of probiotics in bladder tumor patients

    Directory of Open Access Journals (Sweden)

    Molchanov R.N.

    2014-09-01

    Full Text Available The chronic urinary tract infection (UTI is a risk factor that worsens a natural course of bladder tumors. Using of probiotics, possessing antagonistic influence on pathogenic microflora and immunocorrection effect, for preventive maintenance and treat¬ment of a chronic UTI in bladder tumor patients is an actual and perspective direction. The goal of the research was studying antimicrobial and anti-inflammatory effect of a single bladder instillation of either lactobacilli or aerococci in bladder tumor patients. In the preoperative period a single bladder instillation with either lactobacterin or a-bacterin preparation to 35 bladder tumor patients was done. Bacteriuria, leucocyturia, lactobacilli and aerococci count in urine were measured before and in 1, 3, 6 and 24 hours after instillation. Decrease in bacteriuria level in both groups of patients was revealed. Lactobacilli and aerococci count in urine gradually decreased up to complete elimination in 24 hours (in 1 patient who received lactobacterin (12,5 % and in 9 patients who received a-bacterin. (40,9 %. Leucocyturia study did not show statistically confidence dynamics throughout the observation period in both groups. Thus, bladder instillation with lactobacterin or a-bacterin leads to suppression of uropathogenic microflora in bladder tumor patients; in the majority of patients spontaneous elimination of lactobacilli and aerococci occurs within 24 hours.

  12. Differential diagnosis between benign and malignant soft tissue tumors utilizing ultrasound parameters.

    Science.gov (United States)

    Morii, Takeshi; Kishino, Tomonori; Shimamori, Naoko; Motohashi, Mitsue; Ohnishi, Hiroaki; Honya, Keita; Aoyagi, Takayuki; Tajima, Takashi; Ichimura, Shoichi

    2018-01-01

    Preoperative discrimination between benign and malignant soft tissue tumors is critical for the prevention of excess application of magnetic resonance imaging and biopsy as well as unplanned resection. Although ultrasound, including power Doppler imaging, is an easy, noninvasive, and cost-effective modality for screening soft tissue tumors, few studies have investigated reliable discrimination between benign and malignant soft tissue tumors. To establish a modality for discrimination between benign and malignant soft tissue tumors using ultrasound, we extracted the significant risk factors for malignancy based on ultrasound information from 40 malignant and 56 benign pathologically diagnosed soft tissue tumors and established a scoring system based on these risk factors. The maximum size, tumor margin, and vascularity evaluated using ultrasound were extracted as significant risk factors. Using the odds ratio from a multivariate regression model, a scoring system was established. Receiver operating characteristic analyses revealed a high area under the curve value (0.85), confirming the accuracy of the scoring system. Ultrasound is a useful modality for establishing the differential diagnosis between benign and malignant soft tissue tumors.

  13. Herbal Medicine Goshajinkigan Prevents Paclitaxel-Induced Mechanical Allodynia without Impairing Antitumor Activity of Paclitaxel

    Directory of Open Access Journals (Sweden)

    Muh. Akbar Bahar

    2013-01-01

    Full Text Available Chemotherapy-induced peripheral neuropathy is a major dose-limiting side effect of commonly used chemotherapeutic agents. However, there are no effective strategies to treat the neuropathy. We examined whether Goshajinkigan, a herbal medicine, would prevent paclitaxel-induced allodynia without affecting the anticancer action in mice. Murine breast cancer 4T1 cells were inoculated into the mammary fat pad. Paclitaxel (10 and 20 mg/kg, intraperitoneal, alternate day from day 7 postinoculation inhibited the tumor growth, and Goshajinkigan (1 g/kg, oral, daily from day 2 postinoculation did not affect the antitumor action of paclitaxel. Mechanical allodynia developed in the inoculated region due to tumor growth and in the hind paw due to paclitaxel-induced neuropathy. Paclitaxel-induced allodynia was markedly prevented by Goshajinkigan, although tumor-associated allodynia was not inhibited by Goshajinkigan. These results suggest that Goshajinkigan prevents paclitaxel-induced peripheral neuropathy without interfering with the anti-cancer action of paclitaxel.

  14. Healthcare worker contact networks and the prevention of hospital-acquired infections.

    Directory of Open Access Journals (Sweden)

    Donald E Curtis

    Full Text Available We present a comprehensive approach to using electronic medical records (EMR for constructing contact networks of healthcare workers in a hospital. This approach is applied at the University of Iowa Hospitals and Clinics (UIHC--a 3.2 million square foot facility with 700 beds and about 8,000 healthcare workers--by obtaining 19.8 million EMR data points, spread over more than 21 months. We use these data to construct 9,000 different healthcare worker contact networks, which serve as proxies for patterns of actual healthcare worker contacts. Unlike earlier approaches, our methods are based on large-scale data and do not make any a priori assumptions about edges (contacts between healthcare workers, degree distributions of healthcare workers, their assignment to wards, etc. Preliminary validation using data gathered from a 10-day long deployment of a wireless sensor network in the Medical Intensive Care Unit suggests that EMR logins can serve as realistic proxies for hospital-wide healthcare worker movement and contact patterns. Despite spatial and job-related constraints on healthcare worker movement and interactions, analysis reveals a strong structural similarity between the healthcare worker contact networks we generate and social networks that arise in other (e.g., online settings. Furthermore, our analysis shows that disease can spread much more rapidly within the constructed contact networks as compared to random networks of similar size and density. Using the generated contact networks, we evaluate several alternate vaccination policies and conclude that a simple policy that vaccinates the most mobile healthcare workers first, is robust and quite effective relative to a random vaccination policy.

  15. Complex microcirculation patterns detected by confocal indocyanine green angiography predict time to growth of small choroidal melanocytic tumors: MuSIC Report II.

    Science.gov (United States)

    Mueller, Arthur J; Freeman, William R; Schaller, Ulrich C; Kampik, Anselm; Folberg, Robert

    2002-12-01

    Multiple independent laboratories have confirmed the histologic observation that some tumor microcirculation patterns (MCPs) in uveal melanomas are associated strongly with death resulting from metastatic disease. Because these patterns are imageable with confocal indocyanine green angiography (ICG), we designed a prospective study to evaluate whether these angiographically detectable MCPs predict time to tumor growth. Observational case series, prospective, non-randomized. Ninety-eight patients with unilateral, small, choroidal melanocytic tumors. The following information and tumor characteristics were recorded for each patient: demographic parameters, best-corrected visual acuity, intraocular pressure, related visual symptoms, location and dimension of tumor, pigmentation, orange pigment, drusen, tumor-associated hemorrhage, subretinal fluid, and confocal ICG angiographically determined microcirculation patterns-silent (avascularity), normal (preexisting normal choroidal vessels within the tumor), straight vessels, parallel without and with cross-linking, arcs without and with branching, loops, and networks. Time to growth of the tumor, with growth defined as an increase in the maximal apical tumor height of 0.5 mm measured by standardized A-scan ultrasonography, photographic documentation of an increase of the largest basal diameter of at least 1.5 mm, advancement of one tumor border of at least 0.75 mm, or a combination thereof. Twenty-eight of the 98 tumors in this study (29%) met the predetermined criteria for tumor growth. The median time to growth was 127 days (range, 51-625 days). The following tumor characteristics were significantly associated with time to tumor growth: flashes (P = 0.0224), orange pigment (P = 0.012), subretinal fluid (P < 0.001), maximum basal tumor diameter at initial examination (P = 0.015), maximum apical tumor height (P < 0.001), parallel with cross-linking MCP (P < 0.001), arcs with branching MCP (P = 0.006), loops (P < 0

  16. Influence networks based on coexpression improve drug target discovery for the development of novel cancer therapeutics

    Science.gov (United States)

    2014-01-01

    Background The demand for novel molecularly targeted drugs will continue to rise as we move forward toward the goal of personalizing cancer treatment to the molecular signature of individual tumors. However, the identification of targets and combinations of targets that can be safely and effectively modulated is one of the greatest challenges facing the drug discovery process. A promising approach is to use biological networks to prioritize targets based on their relative positions to one another, a property that affects their ability to maintain network integrity and propagate information-flow. Here, we introduce influence networks and demonstrate how they can be used to generate influence scores as a network-based metric to rank genes as potential drug targets. Results We use this approach to prioritize genes as drug target candidates in a set of ER + breast tumor samples collected during the course of neoadjuvant treatment with the aromatase inhibitor letrozole. We show that influential genes, those with high influence scores, tend to be essential and include a higher proportion of essential genes than those prioritized based on their position (i.e. hubs or bottlenecks) within the same network. Additionally, we show that influential genes represent novel biologically relevant drug targets for the treatment of ER + breast cancers. Moreover, we demonstrate that gene influence differs between untreated tumors and residual tumors that have adapted to drug treatment. In this way, influence scores capture the context-dependent functions of genes and present the opportunity to design combination treatment strategies that take advantage of the tumor adaptation process. Conclusions Influence networks efficiently find essential genes as promising drug targets and combinations of targets to inform the development of molecularly targeted drugs and their use. PMID:24495353

  17. Mapping one strong 'Ohana: using network analysis and GIS to enhance the effectiveness of a statewide coalition to prevent child abuse and neglect.

    Science.gov (United States)

    Cardazone, Gina; U Sy, Angela; Chik, Ivan; Corlew, Laura Kate

    2014-06-01

    Network analysis and GIS enable the presentation of meaningful data about organizational relationships and community characteristics, respectively. Together, these tools can provide a concrete representation of the ecological context in which coalitions operate, and may help coalitions identify opportunities for growth and enhanced effectiveness. This study uses network analysis and GIS mapping as part of an evaluation of the One Strong 'Ohana (OSO) campaign. The OSO campaign was launched in 2012 via a partnership between the Hawai'i Children's Trust Fund (HCTF) and the Joyful Heart Foundation. The OSO campaign uses a collaborative approach aimed at increasing public awareness of child maltreatment and protective factors that can prevent maltreatment, as well as enhancing the effectiveness of the HCTF Coalition. This study focuses on three elements of the OSO campaign evaluation: (1) Network analysis exploring the relationships between 24 active Coalition member organizations, (2) GIS mapping of responses to a randomized statewide phone survey (n = 1,450) assessing awareness of factors contributing to child maltreatment, and (3) Combined GIS maps and network data, illustrating opportunities for geographically-targeted coalition building and public awareness activities.

  18. Transfer of allogeneic CD4+ T cells rescues CD8+ T cells in anti-PD-L1–resistant tumors leading to tumor eradication

    Science.gov (United States)

    Arina, Ainhoa; Karrison, Theodore; Galka, Eva; Schreiber, Karin; Weichselbaum, Ralph R.; Schreiber, Hans

    2017-01-01

    Adoptively transferred CD8+ T cells can stabilize the size of solid tumors over long periods of time by exclusively recognizing antigen cross-presented on tumor stroma. However, these tumors eventually escape T cell–mediated growth control. The aim of this study was to eradicate such persistent cancers. In our model, the SIYRYYGL antigen is expressed by cancer cells that lack the MHC-I molecule Kb needed for direct presentation, but the antigen is picked up and cross-presented by tumor stroma. A single injection of antigen-specific 2C CD8+ T cells caused long-term inhibition of tumor growth, but without further intervention, tumors started to progress after approximately 3 months. Escape was associated with reduced numbers of circulating 2C cells. Tumor-infiltrating 2C cells produced significantly less TNFα and expressed more of the “exhaustion” markers PD-1 and Tim-3 than T cells from lymphoid organs. High-dose local ionizing radiation, depletion of myeloid-derived suppressor cells, infusions of additional 2C cells, and antibodies blocking PD-L1 did not prevent tumor escape. In contrast, adoptive transfer of allogeneic CD4+ T cells restored the numbers of circulating Ag-specific CD8+ T cells and their intratumoral function, resulting in tumor eradication. These CD4+ T cells had no antitumor effects in the absence of CD8+ T cells and recognized the alloantigen cross-presented on tumor stroma. CD4+ T cells might also be effective in cancer patients when PD1/PD-L1 blockade does not rescue intratumoral CD8+ T-cell function and tumors persist. PMID:28077434

  19. In Vivo Loss of Function Screening Reveals Carbonic Anhydrase IX as a Key Modulator of Tumor Initiating Potential in Primary Pancreatic Tumors

    Directory of Open Access Journals (Sweden)

    Nabendu Pore

    2015-06-01

    Full Text Available Reprogramming of energy metabolism is one of the emerging hallmarks of cancer. Up-regulation of energy metabolism pathways fuels cell growth and division, a key characteristic of neoplastic disease, and can lead to dependency on specific metabolic pathways. Thus, targeting energy metabolism pathways might offer the opportunity for novel therapeutics. Here, we describe the application of a novel in vivo screening approach for the identification of genes involved in cancer metabolism using a patient-derived pancreatic xenograft model. Lentiviruses expressing short hairpin RNAs (shRNAs targeting 12 different cell surface protein transporters were separately transduced into the primary pancreatic tumor cells. Transduced cells were pooled and implanted into mice. Tumors were harvested at different times, and the frequency of each shRNA was determined as a measure of which ones prevented tumor growth. Several targets including carbonic anhydrase IX (CAIX, monocarboxylate transporter 4, and anionic amino acid transporter light chain, xc- system (xCT were identified in these studies and shown to be required for tumor initiation and growth. Interestingly, CAIX was overexpressed in the tumor initiating cell population. CAIX expression alone correlated with a highly tumorigenic subpopulation of cells. Furthermore, CAIX expression was essential for tumor initiation because shRNA knockdown eliminated the ability of cells to grow in vivo. To the best of our knowledge, this is the first parallel in vivo assessment of multiple novel oncology target genes using a patient-derived pancreatic tumor model.

  20. Dynamics of tumor growth and combination of anti-angiogenic and cytotoxic therapies

    Science.gov (United States)

    Kohandel, M.; Kardar, M.; Milosevic, M.; Sivaloganathan, S.

    2007-07-01

    Tumors cannot grow beyond a certain size (about 1-2 mm in diameter) through simple diffusion of oxygen and other essential nutrients into the tumor. Angiogenesis, the formation of blood vessels from pre-existing vessels, is a crucial and observed step, through which a tumor obtains its own blood supply. Thus, strategies that interfere with the development of this tumor vasculature, known as anti-angiogenic therapy, represent a novel approach to controlling tumor growth. Several pre-clinical studies have suggested that currently available angiogenesis inhibitors are unlikely to yield significant sustained improvements in tumor control on their own, but rather will need to be used in combination with conventional treatments to achieve maximal benefit. Optimal sequencing of anti-angiogenic treatment and radiotherapy or chemotherapy is essential to the success of these combined treatment strategies. Hence, a major challenge to mathematical modeling and computer simulations is to find appropriate dosages, schedules and sequencing of combination therapies to control or eliminate tumor growth. Here, we present a mathematical model that incorporates tumor cells and the vascular network, as well as their interplay. We can then include the effects of two different treatments, conventional cytotoxic therapy and anti-angiogenic therapy. The results are compared with available experimental and clinical data.

  1. Radiation as an inducer of in-situ autologous vaccine in the treatment of solid tumors

    International Nuclear Information System (INIS)

    Ahmed, Mansoor M.

    2013-01-01

    Radiation therapy (RT) is conventionally used for local tumor control. Although local control of the primary tumor can prevent the development of subsequent systemic metastases, tumor irradiation is not effective in controlling pre-existing systemic disease. The concept of radiation-enhanced antigen presentation and immunomodulation allows the harnessing of tumor cell death induced by radiation as a potential source of tumor antigens for immunotherapy. Immunomodulation using RT is a novel strategy of in situ tumor vaccination where primary tumor irradiation can contribute to the control of pre-existing systemic metastatic disease. The absence of systemic immunosuppression (often associated with chemotherapy) and the generally lower toxicity makes radiation a desirable adjuvant regimen for immunotherapy and tumor vaccination strategies. Increased understanding of tumor immunology and the biology of radiation-mediated immune modulation should enhance the efficacy of combining these therapeutic modalities. Here we aim to provide an overview of the biology of radiation-induced immune modulation. (author)

  2. Anti-tumor effects of (1→3)-β-d-glucan from Saccharomyces cerevisiae in S180 tumor-bearing mice.

    Science.gov (United States)

    Mo, Li; Chen, Yafei; Li, Wenjian; Guo, Shuai; Wang, Xuzhao; An, Hailong; Zhan, Yong

    2017-02-01

    (1→3)-β-d-Glucan from Saccharomyces cerevisiae is a typical polysaccharide with various biological effects and is considered a candidate for the prevention and treatment of cancer in vitro. Research into the function of (1→3)-β-d-glucan in tumor-bearing animals in vivo, however, is limited. Here, we investigated the effects of (1→3)-β-d-glucan from S. cerevisiae on S180 tumor-bearing mice and on the immunity of the tumor-bearing host. The molecular mechanisms underlying the observed effects were investigated. (1→3)-β-d-Glucan was shown to exert anti-tumor effects without toxicity in normal mouse cells. The volume and weight of S180 tumors decreased dramatically following treatment with (1→3)-β-d-glucan, and treatment with the polysaccharide was furthermore shown to increase the tumor inhibition rate in a dose-dependent manner. Spleen index, T lymphocyte subsets (CD 4 and CD 8 ), as well as interleukins (IL)-2, (IL-2, IL-6), and tumor necrosis factor-α were assayed to detect the immunoregulatory and anti-tumor effects after (1→3)-β-d-glucan intragastrical administration. (1→3)-β-d-Glucan was shown to significantly potentiate the mouse immune responses by, among other effects, decreasing the ratio of CD 4 to CD 8 . The expression levels of IL-2, IL-6, and TNF-α were also significantly increased by (1→3)-β-d-glucan. These results suggest that (1→3)-β-d-glucan enhances the host's immune function during the tumor inhibition process. S180 tumor cells treated with (1→3)-β-d-glucan also exhibited significant apoptotic characteristics. (1→3)-β-d-glucan increased the ratio of Bax to Bcl-2 at the translation level by up-regulating Bax expression and down-regulating Bcl-2 expression, resulting in the initiation of cell apoptosis in S180 tumor-bearing mice. Taken together, these results indicate that the anti-tumor effects exerted by (1→3)-β-d-glucan may be attributed to the polysaccharide's immunostimulating properties and apoptosis

  3. Preventing Childhood obesity. EPODE European Network Recommendations

    NARCIS (Netherlands)

    Borys, J.M.; Le Bodo, Y.; De Henauw, S.; Moreno, L.A.; Romon, M.; Seidell, J.C.; Visscher, T.L.S.

    2011-01-01

    Childhood obesity is a complex issue and needs multistakeholder involvement at all levels to foster healthier lifestyles in a sustainable way. 'Ensemble Prévenons l'ObésitéDes Enfants' (EPODE, Together Let's Prevent Childhood Obesity) is a large-scale, coordinated, capacity-building approach for

  4. Surgery of language-eloquent tumors in patients not eligible for awake surgery: the impact of a protocol based on navigated transcranial magnetic stimulation on presurgical planning and language outcome, with evidence of tumor-induced intra-hemispheric plasticity.

    Science.gov (United States)

    Raffa, Giovanni; Quattropani, Maria C; Scibilia, Antonino; Conti, Alfredo; Angileri, Filippo Flavio; Esposito, Felice; Sindorio, Carmela; Cardali, Salvatore Massimiliano; Germanò, Antonino; Tomasello, Francesco

    2018-05-01

    Awake surgery and intraoperative monitoring represent the gold standard for surgery of brain tumors located in the perisylvian region of the dominant hemisphere due to their ability to map and preserve the language network during surgery. Nevertheless, in some cases awake surgery is not feasible. This could increase the risk of postoperative language deficit. Navigated transcranial magnetic stimulation (nTMS) and nTMS-based DTI fiber tracking (DTI-FT) provide a preoperative mapping and reconstruction of the cortico-subcortical language network. This can be used to plan and guide the surgical strategy to preserve the language function. The objective if this study is to describe the impact of a non-invasive preoperative protocol for mapping the language network through the nTMS and nTMS-based DTI-FT in patients not eligible for awake surgery and thereby operated under general anesthesia for suspected language-eloquent brain tumors. We reviewed clinical data of patients not eligible for awake surgery and operated under general anaesthesia between 2015 and 2016. All patients underwent nTMS language cortical mapping and nTMS-based DTI-FT of subcortical language fascicles. The nTMS findings were used to plan and guide the maximal safe resection of the tumor. The impact on postoperative language outcome and the accuracy of the nTMS-based mapping in predicting language deficits were evaluated. Twenty patients were enrolled in the study. The nTMS-based reconstruction of the language network was successful in all patients. Interestingly, we observed a significant association between tumor localization and the cortical distribution of the nTMS errors (p = 0.004), thereby suggesting an intra-hemispheric plasticity of language cortical areas, probably induced by the tumor itself. The nTMS mapping disclosed the true-eloquence of lesions in 12 (60%) of all suspected cases. In the remaining 8 cases (40%) the suspected eloquence of the lesion was disproved. The n

  5. Alternative polyadenylation of tumor suppressor genes in small intestinal neuroendocrine tumors.

    Science.gov (United States)

    Rehfeld, Anders; Plass, Mireya; Døssing, Kristina; Knigge, Ulrich; Kjær, Andreas; Krogh, Anders; Friis-Hansen, Lennart

    2014-01-01

    The tumorigenesis of small intestinal neuroendocrine tumors (SI-NETs) is poorly understood. Recent studies have associated alternative polyadenylation (APA) with proliferation, cell transformation, and cancer. Polyadenylation is the process in which the pre-messenger RNA is cleaved at a polyA site and a polyA tail is added. Genes with two or more polyA sites can undergo APA. This produces two or more distinct mRNA isoforms with different 3' untranslated regions. Additionally, APA can also produce mRNAs containing different 3'-terminal coding regions. Therefore, APA alters both the repertoire and the expression level of proteins. Here, we used high-throughput sequencing data to map polyA sites and characterize polyadenylation genome-wide in three SI-NETs and a reference sample. In the tumors, 16 genes showed significant changes of APA pattern, which lead to either the 3' truncation of mRNA coding regions or 3' untranslated regions. Among these, 11 genes had been previously associated with cancer, with 4 genes being known tumor suppressors: DCC, PDZD2, MAGI1, and DACT2. We validated the APA in three out of three cases with quantitative real-time-PCR. Our findings suggest that changes of APA pattern in these 16 genes could be involved in the tumorigenesis of SI-NETs. Furthermore, they also point to APA as a new target for both diagnostic and treatment of SI-NETs. The identified genes with APA specific to the SI-NETs could be further tested as diagnostic markers and drug targets for disease prevention and treatment.

  6. Is primary prevention with antiepileptic drugs effective in brain tumors or brain metastases?

    Directory of Open Access Journals (Sweden)

    Diego Lobos-Urbina

    2017-03-01

    Full Text Available Resumen Los pacientes con tumores cerebrales, primarios o metastásicos, presentan riego de desarrollar convulsiones durante la evolución de su enfermedad, por lo que se ha propuesto el uso profiláctico de anticonvulsivantes. Sin embargo, el efecto de esta intervención no está claro. Para responder esta pregunta utilizamos la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en múltiples bases de datos. Identificamos 12 revisiones sistemáticas que en conjunto incluyen ochenta estudios primarios. Doce corresponden a estudios aleatorizados, pero sólo dos responden la pregunta de interés. Extrajimos los datos, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Concluimos que la prevención primaria con anticonvulsivantes podría no disminuir el riesgo de convulsiones en tumores o metástasis cerebrales, y se asocia a efectos adversos frecuentes.

  7. Psychology and social networks: a dynamic network theory perspective.

    Science.gov (United States)

    Westaby, James D; Pfaff, Danielle L; Redding, Nicholas

    2014-04-01

    Research on social networks has grown exponentially in recent years. However, despite its relevance, the field of psychology has been relatively slow to explain the underlying goal pursuit and resistance processes influencing social networks in the first place. In this vein, this article aims to demonstrate how a dynamic network theory perspective explains the way in which social networks influence these processes and related outcomes, such as goal achievement, performance, learning, and emotional contagion at the interpersonal level of analysis. The theory integrates goal pursuit, motivation, and conflict conceptualizations from psychology with social network concepts from sociology and organizational science to provide a taxonomy of social network role behaviors, such as goal striving, system supporting, goal preventing, system negating, and observing. This theoretical perspective provides psychologists with new tools to map social networks (e.g., dynamic network charts), which can help inform the development of change interventions. Implications for social, industrial-organizational, and counseling psychology as well as conflict resolution are discussed, and new opportunities for research are highlighted, such as those related to dynamic network intelligence (also known as cognitive accuracy), levels of analysis, methodological/ethical issues, and the need to theoretically broaden the study of social networking and social media behavior. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  8. Osteoprotegerin inhibits bone resorption and prevents tumor development in a xenogenic model of Ewing's sarcoma by inhibiting RANKL

    Science.gov (United States)

    Picarda, Gaëlle; Matous, Etienne; Amiaud, Jérôme; Charrier, Céline; Lamoureux, François; Heymann, Marie-Françoise; Tirode, Franck; Pitard, Bruno; Trichet, Valérie; Heymann, Dominique; Redini, Françoise

    2013-01-01

    Ewing's sarcoma (ES) associated with high osyeolytic lesions typically arises in the bones of children and adolescents. The development of multi-disciplinary therapy has increased current long-term survival rates to greater than 50% but only 20% for high risk group patients (relapse, metastases, etc.). Among new therapeutic approaches, osteoprotegerin (OPG), an anti-bone resorption molecule may represent a promising candidate to inhibit RANKL-mediated osteolytic component of ES and consequently to limit the tumor development. Xenogenic orthotopic models of Ewing's sarcoma were induced by intra-osseous injection of human TC-71 ES cells. OPG was administered in vivo by non-viral gene transfer using an amphiphilic non ionic block copolymer. ES bearing mice were assigned to controls (no treatment, synthetic vector alone or F68/empty pcDNA3.1 plasmid) and hOPG treated groups. A substantial but not significant inhibition of tumor development was observed in the hOPG group as compared to control groups. Marked bone lesions were revealed by micro-computed tomography analyses in control groups whereas a normal bone micro-architecture was preserved in the hOPG treated group. RANKL over-expressed in ES animal model was expressed by tumor cells rather than by host cells. However, TRAIL present in the tumor microenvironment may interfere with OPG effect on tumor development and bone remodeling via RANKL inhibition. In conclusion, the use of a xenogenic model of Ewing's sarcoma allowed discriminating between the tumor and host cells responsible for the elevation of RANKL production observed in this tumor and demonstrated the relevance of blocking RANKL by OPG as a promising therapy in ES. PMID:26909278

  9. Control patterns in an healthcare network

    NARCIS (Netherlands)

    Kartseva, V.; Hulstijn, J.; Gordijn, J.; Tan, Y.H.

    2010-01-01

    To keep a network of enterprises sustainable, inter-organizational control measures are needed to detect or prevent opportunistic behaviour of network participants. We present a requirements engineering method for understanding control problems and designing solutions, based on an economic value

  10. Dietary supplement use and colorectal tumors : from prevention to diagnosis

    NARCIS (Netherlands)

    Bröring, R.C.

    2015-01-01

    Background: Expert guidelines formulated by the World Cancer Research Fund and the American Institute for Cancer Research (WCRF/AICR) advised no use of dietary supplements for cancer prevention. However, it is unclear whether those recommendations also apply to populations at

  11. Anti-tumor bioactivities of curcumin on mice loaded with gastric carcinoma.

    Science.gov (United States)

    Wang, Xiao-Ping; Wang, Qiao-Xia; Lin, Huan-Ping; Chang, Na

    2017-09-20

    Curcumin, a derivative from the dried rhizome of curcuma longa, has been proven to possess anti-tumor effects. However, the detailed molecular mechanisms have not been fully elucidated. In this study, we aimed to explore the anti-tumor mechanisms of curcumin in treating gastric cancer. BALB/C mice grafted with a mouse gastric adenocarcinoma cell line (MFC) were used as the experimental model. Mice received different doses of curcumin after grafting. Tumor size was measured and tumor weight was determined after tumor inoculation. TUNEL assay and flow cytometric analysis were applied to evaluate the apoptosis of the cancer cells. Serum cytokines IFN-γ, TNF-α, granzyme B and perforin were detected by ELISA assay. The anti-tumor effect was determined using cytotoxic T-lymphocyte (CTL) assays and in vivo tumor prevention tests. The expression of DEC1, HIF-1α, STAT3 and VEGF in tumor tissues was examined by immunostaining and analyzed using an Image J analysis system. Compared with controls, tumor growth (size and weight) was significantly inhibited by curcumin treatment (P curcumin treatment group. Splenocyte cells from mice treated with curcumin exhibited higher cytolytic effects on MFC cancer cells than those from mice treated with saline (P curcumin treatment. Our results indicate that curcumin inhibits the proliferation of gastric carcinoma by inducing the apoptosis of tumor cells, activating immune cells to secrete a large amount of cytokines, and down-regulating the DEC1, HIF-1α, VEGF and STAT3 signal transduction pathways.

  12. Determinates of tumor response to radiation: Tumor cells, tumor stroma and permanent local control

    International Nuclear Information System (INIS)

    Li, Wende; Huang, Peigen; Chen, David J.; Gerweck, Leo E.

    2014-01-01

    Background and purpose: The causes of tumor response variation to radiation remain obscure, thus hampering the development of predictive assays and strategies to decrease resistance. The present study evaluates the impact of host tumor stromal elements and the in vivo environment on tumor cell kill, and relationship between tumor cell radiosensitivity and the tumor control dose. Material and methods: Five endpoints were evaluated and compared in a radiosensitive DNA double-strand break repair-defective (DNA-PKcs −/− ) tumor line, and its DNA-PKcs repair competent transfected counterpart. In vitro colony formation assays were performed on in vitro cultured cells, on cells obtained directly from tumors, and on cells irradiated in situ. Permanent local control was assessed by the TCD 50 assay. Vascular effects were evaluated by functional vascular density assays. Results: The fraction of repair competent and repair deficient tumor cells surviving radiation did not substantially differ whether irradiated in vitro, i.e., in the absence of host stromal elements and factors, from the fraction of cells killed following in vivo irradiation. Additionally, the altered tumor cell sensitivity resulted in a proportional change in the dose required to achieve permanent local control. The estimated number of tumor cells per tumor, their cloning efficiency and radiosensitivity, all assessed by in vitro assays, were used to predict successfully, the measured tumor control doses. Conclusion: The number of clonogens per tumor and their radiosensitivity govern the permanent local control dose

  13. Oleuropein, a non-toxic olive iridoid, is an anti-tumor agent and cytoskeleton disruptor

    International Nuclear Information System (INIS)

    Hamdi, Hamdi K.; Castellon, Raquel

    2005-01-01

    Oleuropein, a non-toxic secoiridoid derived from the olive tree, is a powerful antioxidant and anti-angiogenic agent. Here, we show it to be a potent anti-cancer compound, directly disrupting actin filaments in cells and in a cell-free assay. Oleuropein inhibited the proliferation and migration of advanced-grade tumor cell lines in a dose-responsive manner. In a novel tube-disruption assay, Oleuropein irreversibly rounded cancer cells, preventing their replication, motility, and invasiveness; these effects were reversible in normal cells. When administered orally to mice that developed spontaneous tumors, Oleuropein completely regressed tumors in 9-12 days. When tumors were resected prior to complete regression, they lacked cohesiveness and had a crumbly consistency. No viable cells could be recovered from these tumors. These observations elevate Oleuropein from a non-toxic antioxidant into a potent anti-tumor agent with direct effects against tumor cells. Our data may also explain the cancer-protective effects of the olive-rich Mediterranean diet

  14. Highly efficient elimination of colorectal tumor-initiating cells by an EpCAM/CD3-bispecific antibody engaging human T cells.

    Directory of Open Access Journals (Sweden)

    Ines Herrmann

    2010-10-01

    Full Text Available With their resistance to genotoxic and anti-proliferative drugs and potential to grow tumors and metastases from very few cells, cancer stem or tumor-initiating cells (TICs are a severe limitation for the treatment of cancer by conventional therapies. Here, we explored whether human T cells that are redirected via an EpCAM/CD3-bispecific antibody called MT110 can lyse colorectal TICs and prevent tumor growth from TICs. MT110 recognizes EpCAM, a cell adhesion molecule expressed on TICs from diverse human carcinoma, which was recently shown to promote tumor growth through engagement of elements of the wnt pathway. MT110 was highly potent in mediating complete redirected lysis of KRAS-, PI3 kinase- and BRAF-mutated colorectal TICs, as demonstrated in a soft agar assay. In immunodeficient mice, MT110 prevented growth of tumors from a 5,000-fold excess of a minimally tumorigenic TIC dose. T cells engaged by MT110 may provide a potent therapeutic means to eradicate TICs and bulk tumor cells derived thereof.

  15. What factors influence the provision of preventive care by general dental practitioners?

    Science.gov (United States)

    Sbaraini, A

    2012-06-08

    What factors influence a general dental practitioner to offer preventive care to patients? A potential answer to this question is presented based on the findings of a qualitative study recently undertaken in general dental practice in Australia. A model of how practices come to be oriented towards preventive or restorative care is described, condensing all of the findings of the study into a single framework. Eight practices were studied and highlighted the interaction between two factors: leadership in practice and prioritisation of cultural, social and economic resources. In this model, dentists' leadership to reorient the prioritisation of resources towards preventive care was crucial. Ideally a whole practice changed to preventive philosophy, but change was also possible in a single dentist within a practice. Prioritisation of resources was also key and interacted with dentist leadership. Prioritisation could be seen in the reorganisation of space, routines and fee schedules. During this process, one key support factor for dentists was their external networks of trusted peers and respected practicing dentists. These peers were crucial for transferring preventive knowledge within small networks of dentists who trusted one another; their influence was reportedly more important than centrally produced guidelines or academic advice. In order to help dentists change their practices towards preventive care, the findings from our study suggest that it is important to intervene in these local networks by identifying local dental opinion leaders. During this study, the key conditions needed for practices to reorient to preventive care included the presence of a committed leader with a prevention-supportive peer network, and the reorientation of space, routines and fee schedules to support preventive practice.

  16. Altered tumor growth in vivo after immunization of mice with antitumor antibodies

    International Nuclear Information System (INIS)

    Gorczynski, R.M.; Kennedy, M.; Polidoulis, I.; Price, G.B.

    1984-01-01

    A comparison has been made between the growth patterns of two spontaneously appearing mammary adenocarcinomas in murine bone marrow radiation chimeras and in mice preimmunized with monoclonal antibodies (MAb) detecting embryo-associated antigenic determinants. A correlation was seen between the ability of the embryo-immunized chimeras to produce cytotoxic antibody to the tumors, as assessed by an antibody-dependent cellular cytotoxic assay, and the permissiveness of the mice for growth of a tumor transplant. In addition, mice deliberately preimmunized with cytotoxic MAb (antibody-dependent cellular cytotoxic assay) allowed more rapid growth specifically of that tumor earlier found to be most sensitive to the MAb used for immunization. By comparing the changing antigenic phenotype of tumor cells serially passaged through different immunized, nonimmunized mice, evidence was found suggesting that immunization could cause either antigen modulation of transferred tumor cells or a (transient) selective advantage to antigenically discrete subpopulations within the heterogeneous tumor population. Finally, a study has been made of the growth pattern of tumor cells transplanted into mice immunized with rabbit antibodies directed against the murine MAb. In this case, tumor growth was slowed preferentially for the tumor reactive with the specific MAb, and again, predictable changes in the antigenic spectrum of tumor cells harvested from these animals were observed. Our overall findings are interpreted in terms of the involvement of networks of antibodies reacting with embryo-associated antigens in the regulation of growth of the murine mammary adenocarcinomas studied

  17. Chimeric Antigen Receptors T Cell Therapy in Solid Tumor: Challenges and Clinical Applications

    Directory of Open Access Journals (Sweden)

    Hamid R. Mirzaei

    2017-12-01

    Full Text Available Adoptive cellular immunotherapy (ACT employing engineered T lymphocytes expressing chimeric antigen receptors (CARs has demonstrated promising antitumor effects in advanced hematologic cancers, such as relapsed or refractory acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma, supporting the translation of ACT to non-hematological malignancies. Although CAR T cell therapy has made remarkable strides in the treatment of patients with certain hematological cancers, in solid tumors success has been limited likely due to heterogeneous antigen expression, immunosuppressive networks in the tumor microenvironment limiting CAR T cell function and persistence, and suboptimal trafficking to solid tumors. Here, we outline specific approaches to overcome barriers to CAR T cell effectiveness in the context of the tumor microenvironment and offer our perspective on how expanding the use of CAR T cells in solid tumors may require modifications in CAR T cell design. We anticipate these modifications will further expand CAR T cell therapy in clinical practice.

  18. Stress Prevention@Work: a study protocol for the evaluation of a multifaceted integral stress prevention strategy to prevent employee stress in a healthcare organization: a cluster controlled trial

    Directory of Open Access Journals (Sweden)

    Rianne J. A. Hoek

    2017-07-01

    Full Text Available Abstract Background Adequate implementation of work-related stress management interventions can reduce or prevent work-related stress and sick leave in organizations. We developed a multifaceted integral stress-prevention strategy for organizations from several sectors that includes a digital platform and collaborative learning network. The digital platform contains a stepwise protocol to implement work-related stress-management interventions. It includes stress screeners, interventions and intervention providers to facilitate access to and the selection of matching work-related stress-management interventions. The collaborative learning network, including stakeholders from various organizations, plans meetings focussing on an exchange of experiences and good practices among organizations for the implementation of stress prevention measures. This paper describes the design of an integral stress-prevention strategy, Stress Prevention@Work, and the protocol for the evaluation of: 1 the effects of the strategy on perceived stress and work-related outcomes, and 2 the barriers and facilitators for implementation of the strategy. Methods The effectiveness of Stress Prevention@Work will be evaluated in a cluster controlled trial, in a large healthcare organization in the Netherlands, at six and 12 months. An independent researcher will match teams on working conditions and size and allocate the teams to the intervention or control group. Teams in the intervention group will be offered Stress Prevention@Work. For each intervention team, one employee is responsible for applying the strategy within his/her team using the digital platform and visiting the collaborative learning network. Using a waiting list design, the control group will be given access to the strategy after 12 months. The primary outcome is the employees’ perceived stress measured by the stress subscale of the Depression, Anxiety, and Stress Scale (DASS-21. Secondary outcome measures

  19. Regional and temporal differences in gene expression of LH(BETA)T(AG) retinoblastoma tumors.

    Science.gov (United States)

    Houston, Samuel K; Pina, Yolanda; Clarke, Jennifer; Koru-Sengul, Tulay; Scott, William K; Nathanson, Lubov; Schefler, Amy C; Murray, Timothy G

    2011-07-23

    The purpose of this study was to evaluate by microarray the hypothesis that LH(BETA)T(AG) retinoblastoma tumors exhibit regional and temporal variations in gene expression. LH(BETA)T(AG) mice aged 12, 16, and 20 weeks were euthanatized (n = 9). Specimens were taken from five tumor areas (apex, anterior lateral, center, base, and posterior lateral). Samples were hybridized to gene microarrays. The data were preprocessed and analyzed, and genes with a P 2.5 were considered to be differentially expressed. Differentially expressed genes were analyzed for overlap with known networks by using pathway analysis tools. There were significant temporal (P regional differences in gene expression for LH(BETA)T(AG) retinoblastoma tumors. At P 2.5, there were significant changes in gene expression of 190 genes apically, 84 genes anterolaterally, 126 genes posteriorly, 56 genes centrally, and 134 genes at the base. Differentially expressed genes overlapped with known networks, with significant involvement in regulation of cellular proliferation and growth, response to oxygen levels and hypoxia, regulation of cellular processes, cellular signaling cascades, and angiogenesis. There are significant temporal and regional variations in the LH(BETA)T(AG) retinoblastoma model. Differentially expressed genes overlap with key pathways that may play pivotal roles in murine retinoblastoma development. These findings suggest the mechanisms involved in tumor growth and progression in murine retinoblastoma tumors and identify pathways for analysis at a functional level, to determine significance in human retinoblastoma. Microarray analysis of LH(BETA)T(AG) retinal tumors showed significant regional and temporal variations in gene expression, including dysregulation of genes involved in hypoxic responses and angiogenesis.

  20. Adoptively transferred immune T cells eradicate established tumors in spite of cancer-induced immune suppression

    Science.gov (United States)

    Arina, Ainhoa; Schreiber, Karin; Binder, David C.; Karrison, Theodore; Liu, Rebecca B.; Schreiber, Hans

    2014-01-01

    Myeloid-derived CD11b+Gr1+ suppressor cells (MDSC) and tumor-associated macrophages (TAM) are considered a major obstacle for effective adoptive T cell therapy. Myeloid cells suppress naive T cell proliferation ex vivo and can prevent the generation of T cell responses in vivo. We find, however, that immune T cells adoptively transferred eradicate well-established tumors in the presence of MDSC and TAM which are strongly immunosuppressive ex vivo. These MDSC and TAM were comparable in levels and immunosuppression among different tumor models. Longitudinal microscopy of tumors in vivo revealed that after T cell transfer tumor vasculature and cancer cells disappeared simultaneously. During T-cell mediated tumor destruction, the tumor stroma contained abundant myeloid cells (mainly TAM) that retained their suppressive properties. Preimmunized but not naive mice resisted immune suppression caused by an unrelated tumor-burden supporting the idea that in vivo, myeloid immunosuppressive cells can suppress naive but not memory T cell responses. PMID:24367029

  1. Impact of anemia prevention by recombinant human erythropoietin on the sensitivity of xenografted glioblastomas to fractionated irradiation

    International Nuclear Information System (INIS)

    Stueben, G.; Poettgen, C.; Knuehmann, K.; Sack, H.; Stuschke, M.; Thews, O.; Vaupel, P.

    2003-01-01

    Background: Pronounced oxygen deficiency in tumors which might be caused by a diminished oxygen transport capacity of the blood (e.g., in anemia) reduces the efficacy of ionizing radiation. The aim of this study was to analyze whether anemia prevention by recombinant human erythropoietin (rHuEPO) affects the radiosensitivity of human glioblastoma xenografts during fractionated irradiation. Material and Methods: Anemia was induced by total body irradiation (TBI, 2 x 4 Gy) of mice prior to tumor implantation into the subcutis of the hind leg. In one experimental group, the development of anemia was prevented by rHuEPO (750 U/kg s.c.) given three times weekly starting 10 days prior to TBI. 13 days after tumor implantation (tumor volume approx. 40 mm 3 ), fractionated irradiation (4 x 7 Gy, one daily fraction) of the glioblastomas was performed resulting in a growth delay with subsequent regrowth of the tumors. Results: Compared to nonanemic control animals (hemoglobin concentration cHb = 14.7 g/dl), the growth delay in anemic mice (cHb = 9.9 g/dl) was significantly shorter (49 ± 5 days vs. 79 ± 4 days to reach four times the initial tumor volume) upon fractionated radiation. The prevention of anemia by rHuEPO treatment (cHb = 13.3 g/dl) resulted in a significantly prolonged growth delay (61 ± 5 days) compared to the anemia group, even though the growth inhibition found in control animals was not completely achieved. Conclusions: These data indicate that moderate anemia significantly reduces the efficacy of radiotherapy. Prevention of anemia with rHuEPO partially restores the radiosensitivity of xenografted glioblastomas to fractionated irradiation. (orig.)

  2. Modeling the live-pig trade network in Georgia: Implications for disease prevention and control.

    Directory of Open Access Journals (Sweden)

    Esther Andrea Kukielka

    Full Text Available Live pig trade patterns, drivers and characteristics, particularly in backyard predominant systems, remain largely unexplored despite their important contribution to the spread of infectious diseases in the swine industry. A better understanding of the pig trade dynamics can inform the implementation of risk-based and more cost-effective prevention and control programs for swine diseases. In this study, a semi-structured questionnaire elaborated by FAO and implemented to 487 farmers was used to collect data regarding basic characteristics about pig demographics and live-pig trade among villages in the country of Georgia, where very scarce information is available. Social network analysis and exponential random graph models were used to better understand the structure, contact patterns and main drivers for pig trade in the country. Results indicate relatively infrequent (a total of 599 shipments in one year and geographically localized (median Euclidean distance between shipments = 6.08 km; IQR = 0-13.88 km pig movements in the studied regions. The main factors contributing to live-pig trade movements among villages were being from the same region (i.e., local trade, usage of a middleman or a live animal market to trade live pigs by at least one farmer in the village, and having a large number of pig farmers in the village. The identified villages' characteristics and structural network properties could be used to inform the design of more cost-effective surveillance systems in a country which pig industry was recently devastated by African swine fever epidemics and where backyard production systems are predominant.

  3. Biophysical force regulation in 3D tumor cell invasion

    Science.gov (United States)

    Wu, Mingming

    When embedded within 3D extracellular matrices (ECM), animal cells constantly probe and adapt to the ECM locally (at cell length scale) and exert forces and communicate with other cells globally (up to 10 times of cell length). It is now well accepted that mechanical crosstalk between animal cells and their microenvironment critically regulate cell function such as migration, proliferation and differentiation. Disruption of the cell-ECM crosstalk is implicated in a number of pathologic processes including tumor progression and fibrosis. Central to the problem of cell-ECM crosstalk is the physical force that cells generate. By measuring single cell generated force within 3D collagen matrices, we revealed a mechanical crosstalk mechanism between the tumor cells and the ECM. Cells generate sufficient force to stiffen collagen fiber network, and stiffer matrix, in return promotes larger cell force generation. Our work highlights the importance of fibrous nonlinear elasticity in regulating tumor cell-ECM interaction, and results may have implications in the rapid tissue stiffening commonly found in tumor progression and fibrosis. This work is partially supported by NIH Grants R21RR025801 and R21GM103388.

  4. SegAN: Adversarial Network with Multi-scale L1 Loss for Medical Image Segmentation.

    Science.gov (United States)

    Xue, Yuan; Xu, Tao; Zhang, Han; Long, L Rodney; Huang, Xiaolei

    2018-05-03

    Inspired by classic Generative Adversarial Networks (GANs), we propose a novel end-to-end adversarial neural network, called SegAN, for the task of medical image segmentation. Since image segmentation requires dense, pixel-level labeling, the single scalar real/fake output of a classic GAN's discriminator may be ineffective in producing stable and sufficient gradient feedback to the networks. Instead, we use a fully convolutional neural network as the segmentor to generate segmentation label maps, and propose a novel adversarial critic network with a multi-scale L 1 loss function to force the critic and segmentor to learn both global and local features that capture long- and short-range spatial relationships between pixels. In our SegAN framework, the segmentor and critic networks are trained in an alternating fashion in a min-max game: The critic is trained by maximizing a multi-scale loss function, while the segmentor is trained with only gradients passed along by the critic, with the aim to minimize the multi-scale loss function. We show that such a SegAN framework is more effective and stable for the segmentation task, and it leads to better performance than the state-of-the-art U-net segmentation method. We tested our SegAN method using datasets from the MICCAI BRATS brain tumor segmentation challenge. Extensive experimental results demonstrate the effectiveness of the proposed SegAN with multi-scale loss: on BRATS 2013 SegAN gives performance comparable to the state-of-the-art for whole tumor and tumor core segmentation while achieves better precision and sensitivity for Gd-enhance tumor core segmentation; on BRATS 2015 SegAN achieves better performance than the state-of-the-art in both dice score and precision.

  5. [Strategies for cardiovascular disease prevention].

    Science.gov (United States)

    Gabus, Vincent; Wuerzner, Grégoire; Saubade, Mathieu; Favre, Lucie; Jacot Sadowski, Isabelle; Nanchen, David

    2018-02-28

    Atherosclerosis is a disease which develops very gradually over decades. Under the influence of modifiable cardiovascular risk factors, such as blood pressure, LDL-cholesterol level, smoking or lifestyle, clinical symptoms of atherosclerosis manifest more or less early in life. When cardiovascular risk factors accumulate, the risk of having a cardiovascular event increases and the benefits of prevention measures are greater. This article summarizes existing strategies for controlling modifiable cardiovascular risk factors in primary prevention. The physician can rely on an interprofessional network of cardiovascular prevention. Managing risk factors while respecting the autonomy and priorities of the patient will bring the greatest benefit.

  6. A 40 GHz fully integrated circuit with a vector network analyzer and a coplanar-line-based detection area for circulating tumor cell analysis using 65 nm CMOS technology

    Science.gov (United States)

    Nakanishi, Taiki; Matsunaga, Maya; Kobayashi, Atsuki; Nakazato, Kazuo; Niitsu, Kiichi

    2018-03-01

    A 40-GHz fully integrated CMOS-based circuit for circulating tumor cells (CTC) analysis, consisting of an on-chip vector network analyzer (VNA) and a highly sensitive coplanar-line-based detection area is presented in this paper. In this work, we introduce a fully integrated architecture that eliminates unwanted parasitic effects. The proposed analyzer was designed using 65 nm CMOS technology, and SPICE and MWS simulations were used to validate its operation. The simulation confirmed that the proposed circuit can measure S-parameter shifts resulting from the addition of various types of tumor cells to the detection area, the data of which are provided in a previous study: the |S 21| values for HepG2, A549, and HEC-1-A cells are -0.683, -0.580, and -0.623 dB, respectively. Additionally, the measurement demonstrated an S-parameters reduction of -25.7% when a silicone resin was put on the circuit. Hence, the proposed system is expected to contribute to cancer diagnosis.

  7. Glioma Cells in the Tumor Periphery Have a Stem Cell Phenotype

    DEFF Research Database (Denmark)

    Munthe, Sune; Petterson, Stine Asferg; Dahlrot, Rikke Hedegaard

    2016-01-01

    and a panel of markers was used. The panel comprised of six stem cell-related markers (CD133, Musashi-1, Bmi-1, Sox-2, Nestin and Glut-3), a proliferation marker (Ki-67) as well as a chemo-resistance marker (MGMT). Computer-based automated classifiers were designed to measure the mIDH1 positive nucleus area......-fraction of the chosen markers. Moreover, orthotopic glioblastoma xenografts from five different patient-derived spheroid cultures were obtained and the tumor cells identified by human specific immunohistochemical markers. The results showed that tumor cells in the periphery of patient gliomas expressed stem cell...... in the periphery of patient gliomas have a stem cell phenotype, although it is less pronounced than in the tumor core. Novel therapies aiming at preventing recurrence should therefore take tumor stemness into account. Migrating cells in orthotopic glioblastoma xenografts preserve expression and stem cell markers...

  8. Radioprotection of normal tissues in tumor-bearing mice by troxerutin

    International Nuclear Information System (INIS)

    Maurya, D.K.; Salvi, V.P.; Krishnan Nair, C.K.

    2004-01-01

    The flavanoid derivative troxerutin, used clinically for treating venous disorders, protected biomembranes and cellular DNA against the deleterious effects of γ-radiation. The peroxidation of lipids (measured as thiobarbituric acid-reacting substances, or TBARS) in rat liver microsomal and mitochondrial membranes resulting from γ-irradiation up to doses of 500 Gy in vitro was prevented by 0.2 mM troxerutin. The administration of troxerutin (175 mg/kg body weight) to tumor-bearing mice by intraperitoneal (ip) one hour prior to 4 Gy whole-body γ-irradiation significantly decreased the radiation-induced peroxidation of lipids in tissues such as liver and spleen, but there was no reduction of lipid peroxidation in tumor. The effect of troxerutin in γ-radiation-induced DNA strand breaks in different tissues of tumor-bearing mice was studied by comet assay. The administration of troxerutin to tumor-bearing animals protected cellular DNA against radiation-induced strand breaks. This was evidenced from decreases in comet tail length, tail moment, and percent of DNA in the tails in cells of normal tissues such as blood leukocytes and bone marrow, and these parameters were not altered in cells of fibrosarcoma tumor. The results revealed that troxerutin could preferentially protect normal tissues against radiation-induced damages in tumor-bearing animals. (author)

  9. Cellular solitary fibrous tumor (hemangiopericytoma) with anaplasia at cerebellopontine angle--a case report.

    Science.gov (United States)

    Zeng, Jianying; Ogera, Patricia; Benardete, Ethan A; Nicastri, Anthony D; Rao, Chandrakant

    2012-08-15

    Cellular solitary fibrous tumor is currently considered a synonym for hemangiopericytoma, as it became increasingly clear that the morphological and immunohistochemical features that separate these two entities have become tenuous, and evidence for a unifying concept has emerged. Furthermore, as no evidence of pericytic differentiation is given in most cases of hemangiopericytoma, this diagnostic term is waning in popularity. We present here a case of cellular solitary fibrous tumor in a 22-year-old man. Neuroimaging revealed a right cerebellopontine angle tumor. Most of the tumor was cellular although some less cellular areas were seen. Sinusoidally dilated large vessels, including staghorn type, were seen. Nuclear pleomorphism and increased mitotic activity (5 mitosis/10 high power field) were regarded as evidence of anaplasia. Diffuse CD34 immunoreactivity and focal positivity for Factor XIIIa were seen in the tumor, which was negative for EMA and S100. The tumor also displayed rich reticulin network. Solitary fibrous tumor at cerebellopontine angle is rare, and 20 such cases (five reported as hemangiopericytoma) have been reported in the English literature. Copyright © 2012 Elsevier GmbH. All rights reserved.

  10. Wavelet-enhanced convolutional neural network: a new idea in a deep learning paradigm.

    Science.gov (United States)

    Savareh, Behrouz Alizadeh; Emami, Hassan; Hajiabadi, Mohamadreza; Azimi, Seyed Majid; Ghafoori, Mahyar

    2018-05-29

    Manual brain tumor segmentation is a challenging task that requires the use of machine learning techniques. One of the machine learning techniques that has been given much attention is the convolutional neural network (CNN). The performance of the CNN can be enhanced by combining other data analysis tools such as wavelet transform. In this study, one of the famous implementations of CNN, a fully convolutional network (FCN), was used in brain tumor segmentation and its architecture was enhanced by wavelet transform. In this combination, a wavelet transform was used as a complementary and enhancing tool for CNN in brain tumor segmentation. Comparing the performance of basic FCN architecture against the wavelet-enhanced form revealed a remarkable superiority of enhanced architecture in brain tumor segmentation tasks. Using mathematical functions and enhancing tools such as wavelet transform and other mathematical functions can improve the performance of CNN in any image processing task such as segmentation and classification.

  11. Beta-endorphin cell therapy for cancer prevention.

    Science.gov (United States)

    Zhang, Changqing; Murugan, Sengottuvelan; Boyadjieva, Nadka; Jabbar, Shaima; Shrivastava, Pallavi; Sarkar, Dipak K

    2015-01-01

    β-Endorphin (BEP)-producing neuron in the hypothalamus plays a key role in bringing the stress axis to a state of homeostasis and maintaining body immune defense system. Long-term delivery of BEP to obtain beneficial effect on chemoprevention is challenging, as the peptides rapidly develop tolerance. Using rats as animal models, we show here that transplantation of BEP neurons into the hypothalamus suppressed carcinogens- and hormone-induced cancers in various tissues and prevented growth and metastasis of established tumors via activation of innate immune functions. In addition, we show that intracerebroventricular administration of nanosphere-attached dibutyryl cyclic adenosine monophosphate (dbcAMP) increased the number of BEP neurons in the hypothalamus, reduced the stress response, enhanced the innate immune function, and prevented tumor cell growth, progression, and metastasis. BEP neuronal supplementation did not produce any deleterious effects on general health but was beneficial in suppressing age-induced alterations in physical activity, metabolic, and immune functions. We conclude that the neuroimmune system has significant control over cancer growth and progression, and that activation of the neuroimmune system via BEP neuronal supplementation/induction may have therapeutic value for cancer prevention and improvement of general health. ©2014 American Association for Cancer Research.

  12. Multiple Delivery of siRNA against Endoglin into Murine Mammary Adenocarcinoma Prevents Angiogenesis and Delays Tumor Growth

    Science.gov (United States)

    Dolinsek, Tanja; Markelc, Bostjan; Sersa, Gregor; Coer, Andrej; Stimac, Monika; Lavrencak, Jaka; Brozic, Andreja; Kranjc, Simona; Cemazar, Maja

    2013-01-01

    Endoglin is a transforming growth factor-β (TGF- β) co-receptor that participates in the activation of a signaling pathway that mediates endothelial cell proliferation and migration in angiogenic tumor vasculature. Therefore, silencing of endoglin expression is an attractive approach for antiangiogenic therapy of tumors. The aim of our study was to evaluate the therapeutic potential of small interfering RNA (siRNA) molecules against endoglin in vitro and in vivo. Therapeutic potential in vitro was assessed in human and murine endothelial cells (HMEC-1, 2H11) by determining endoglin expression level, cell proliferation and tube formation. In vivo, the therapeutic potential of siRNA molecules was evaluated in TS/A mammary adenocarcinoma growing in BALB/c mice. Results of our study showed that siRNA molecules against endoglin have a good antiangiogenic therapeutic potential in vitro, as expression of endoglin mRNA and protein levels in mouse and human microvascular endothelial cells after lipofection were efficiently reduced, which resulted in the inhibition of endothelial cell proliferation and tube formation. In vivo, silencing of endoglin with triple electrotransfer of siRNA molecules into TS/A mammary adenocarcinoma also significantly reduced the mRNA levels, number of tumor blood vessels and the growth of tumors. The obtained results demonstrate that silencing of endoglin is a promising antiangiogenic therapy of tumors that could not be used as single treatment, but as an adjunct to the established cytotoxic treatment approaches. PMID:23593103

  13. Multiple delivery of siRNA against endoglin into murine mammary adenocarcinoma prevents angiogenesis and delays tumor growth.

    Directory of Open Access Journals (Sweden)

    Tanja Dolinsek

    Full Text Available Endoglin is a transforming growth factor-β (TGF- β co-receptor that participates in the activation of a signaling pathway that mediates endothelial cell proliferation and migration in angiogenic tumor vasculature. Therefore, silencing of endoglin expression is an attractive approach for antiangiogenic therapy of tumors. The aim of our study was to evaluate the therapeutic potential of small interfering RNA (siRNA molecules against endoglin in vitro and in vivo. Therapeutic potential in vitro was assessed in human and murine endothelial cells (HMEC-1, 2H11 by determining endoglin expression level, cell proliferation and tube formation. In vivo, the therapeutic potential of siRNA molecules was evaluated in TS/A mammary adenocarcinoma growing in BALB/c mice. Results of our study showed that siRNA molecules against endoglin have a good antiangiogenic therapeutic potential in vitro, as expression of endoglin mRNA and protein levels in mouse and human microvascular endothelial cells after lipofection were efficiently reduced, which resulted in the inhibition of endothelial cell proliferation and tube formation. In vivo, silencing of endoglin with triple electrotransfer of siRNA molecules into TS/A mammary adenocarcinoma also significantly reduced the mRNA levels, number of tumor blood vessels and the growth of tumors. The obtained results demonstrate that silencing of endoglin is a promising antiangiogenic therapy of tumors that could not be used as single treatment, but as an adjunct to the established cytotoxic treatment approaches.

  14. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  15. Effect of x irradiation on the vascularization of experimental animal tumors

    Energy Technology Data Exchange (ETDEWEB)

    Saeki, Y; Ogawa, F; Nishiguchi, H; Tanaka, N; Murakami, K [Kyoto Prefectural Univ. of Medicine (Japan)

    1975-03-01

    The authors studied the effect of ionizing radiation on blood vessels and tumor growth in two animal tumor systems: a third generation isoplants of a mammary cancer and a spontaneously arising squamous cell carcinoma. Single cell suspensions were transplanted into a C3H and a C3Hf mouse respectively. They were irradiated once with 2000 rad when the tumors reached about 8 mm in diameter. Microangiography was performed at a constant temperature and pressure, and a contrast medium containing lead-oxide and gelatin was flushed the vena cava for 10 min. at 120 mmHg. Tumor shrinkage was followed by continuous regrowth. The basic vasculature of the mammary carcinoma consisted of abundant large and fine blood vessels corkscrewed or stretched from the periphery of the tumor to its center in complex reticular networks. One day after irradiation there were small scattered avascular areas which, by the third day formed a large central necrosis. Supervascularization was also observed, indicating that some hypoxic tumor cells could be reoxygenized. In 5 days vascularization was similar to that of a nonirradiated tumor. Conversely, The squamous cell carcinoma showed peripheral and central vascularization with abundant vascular and avascular areas and extravasion in the large avascular area. Two days after irradiation the vessels were dilated. At 3 days peripheral fine vessels were damaged but the central vasculature remained intact. Unlike the mammary carcinoma, supervascularization was not the typical finding. At 5 days, vascularization was similar to that of a nonirradiated tumor.

  16. Tumor immunology

    International Nuclear Information System (INIS)

    Otter, W. den

    1987-01-01

    Tumor immunology, the use of immunological techniques for tumor diagnosis and approaches to immunotherapy of cancer are topics covered in this multi-author volume. Part A, 'Tumor Immunology', deals with present views on tumor-associated antigens, the initiation of immune reactions of tumor cells, effector cell killing, tumor cells and suppression of antitumor immunity, and one chapter dealing with the application of mathematical models in tumor immunology. Part B, 'Tumor Diagnosis and Imaging', concerns the use of markers to locate the tumor in vivo, for the histological diagnosis, and for the monitoring of tumor growth. In Part C, 'Immunotherapy', various experimental approaches to immunotherapy are described, such as the use of monoclonal antibodies to target drugs, the use of interleukin-2 and the use of drugs inhibiting suppression. In the final section, the evaluation, a pathologist and a clinician evaluate the possibilities and limitations of tumor immunology and the extent to which it is useful for diagnosis and therapy. refs.; figs.; tabs

  17. A SURVEY ON DELAY AND NEIGHBOR NODE MONITORING BASED WORMHOLE ATTACK PREVENTION AND DETECTION

    Directory of Open Access Journals (Sweden)

    Sudhir T Bagade

    2016-12-01

    Full Text Available In Mobile Ad-hoc Networks (MANET, network layer attacks, for example wormhole attacks, disrupt the network routing operations and can be used for data theft. Wormhole attacks are of two types: hidden and exposed wormhole. There are various mechanisms in literature which are used to prevent and detect wormhole attacks. In this paper, we survey wormhole prevention and detection techniques and present our critical observations for each. These techniques are based on cryptographic mechanisms, monitoring of packet transmission delay and control packet forwarding behavior of neighbor nodes. We compare the techniques using the following criteria- extra resources needed applicability to different network topologies and routing protocols, prevention/detection capability, etc. We conclude the paper with potential research directions.

  18. Preventing surgery-induced NK cell dysfunction and cancer metastases with influenza vaccination

    Science.gov (United States)

    Tai, Lee-Hwa; Zhang, Jiqing; Auer, Rebecca C

    2013-01-01

    Surgical resection is the mainstay of treatment for solid tumors, but the postoperative period is uniquely inclined to the formation of metastases, largely due to the suppression of natural killer (NK) cells. We found that preoperative influenza vaccination prevents postoperative NK-cell dysfunction, attenuating tumor dissemination in murine models and promoting the activation of NK cells in cancer patients. PMID:24404430

  19. Awareness of pre-exposure prophylaxis (PrEP) among women who inject drugs in NYC: the importance of networks and syringe exchange programs for HIV prevention.

    Science.gov (United States)

    Walters, Suzan M; Reilly, Kathleen H; Neaigus, Alan; Braunstein, Sarah

    2017-06-29

    Women who inject drugs (WWID) are at heightened risk for HIV due to biological, behavioral, and structural factors. Pre-exposure prophylaxis (PrEP) could aid in HIV prevention for WWID. However, little is known about WWID awareness of PrEP, which is a necessary step that must occur before PrEP uptake. We report factors associated with greater awareness among WWID to identify efficient means of awareness dissemination. Data from the 2015 National HIV Behavioral Surveillance (NHBS) system cycle on injection drug use collected in New York City (NYC) were used. Bivariable analyses, using chi-squared statistics, were conducted to examine correlates of awareness of PrEP with socio-demographic, behavioral, and health care variables. Multivariable logistic regression was used to estimate adjusted associations and determine differences in awareness of PrEP. The analysis consisted of 118 WWID. Awareness of PrEP was relatively low (31%), and risk factors were high. In the last 12 months, almost two thirds (65%) reported condomless sex, approximately one third (31%) reported transactional sex, and one third (32%) reported sharing injection equipment. In multivariable logistic regression, increased PrEP awareness was associated with reported transactional sex (AOR 3.32, 95% CI 1.22-9.00) and having a conversation about HIV prevention at a syringe exchange program (SEP) (AOR 7.61, 95% CI 2.65-21.84). We did not find race, education, household income, age, binge drinking, or sexual identity to be significantly associated with PrEP awareness. Large proportions of WWID were unaware of PrEP. These findings suggest that social networks (specifically sex work and SEP networks) are an efficient means for disseminating messaging about prevention materials such as PrEP. We recommend that SEP access increase, SEP processes be adopted in other health care settings, and WWID networks be utilized to increase PrEP awareness.

  20. Adaptive Suspicious Prevention for Defending DoS Attacks in SDN-Based Convergent Networks

    OpenAIRE

    Dao, Nhu-Ngoc; Kim, Joongheon; Park, Minho; Cho, Sungrae

    2016-01-01

    The convergent communication network will play an important role as a single platform to unify heterogeneous networks and integrate emerging technologies and existing legacy networks. Although there have been proposed many feasible solutions, they could not become convergent frameworks since they mainly focused on converting functions between various protocols and interfaces in edge networks, and handling functions for multiple services in core networks, e.g., the Multi-protocol Label Switchi...

  1. Enalapril and ASS inhibit tumor growth in a transgenic mouse model of islet cell tumors.

    Science.gov (United States)

    Fendrich, V; Lopez, C L; Manoharan, J; Maschuw, K; Wichmann, S; Baier, A; Holler, J P; Ramaswamy, A; Bartsch, D K; Waldmann, J

    2014-10-01

    Accumulating evidence suggests a role for angiotensin-converting enzymes involving the angiotensin II-receptor 1 (AT1-R) and the cyclooxygenase pathway in carcinogenesis. The effects of ASS and enalapril were assessed in vitro and in a transgenic mouse model of pancreatic neuroendocrine neoplasms (pNENs). The effects of enalapril and ASS on proliferation and expression of the AGTR1A and its target gene vascular endothelial growth factor (Vegfa) were assessed in the neuroendocrine cell line BON1. Rip1-Tag2 mice were treated daily with either 0.6 mg/kg bodyweight of enalapril i.p., 20 mg/kg bodyweight of ASS i.p., or a vehicle in a prevention (weeks 5-12) and a survival group (week 5 till death). Tumor surface, weight of pancreatic glands, immunostaining for AT1-R and nuclear factor kappa beta (NFKB), and mice survival were analyzed. In addition, sections from human specimens of 20 insulinomas, ten gastrinomas, and 12 non-functional pNENs were evaluated for AT1-R and NFKB (NFKB1) expression and grouped according to the current WHO classification. Proliferation was significantly inhibited by enalapril and ASS in BON1 cells, with the combination being the most effective. Treatment with enalapril and ASS led to significant downregulation of known target genes Vegf and Rela at RNA level. Tumor growth was significantly inhibited by enalapril and ASS in the prevention group displayed by a reduction of tumor size (84%/67%) and number (30%/45%). Furthermore, daily treatment with enalapril and ASS prolonged the overall median survival compared with vehicle-treated Rip1-Tag2 (107 days) mice by 9 and 17 days (P=0.016 and P=0.013). The AT1-R and the inflammatory transcription factor NFKB were abolished completely upon enalapril and ASS treatment. AT1-R and NFKB expressions were observed in 80% of human pNENs. Enalapril and ASS may provide an approach for chemoprevention and treatment of pNENs. © 2014 Society for Endocrinology.

  2. Characterization of the live salmonid movement network in Ireland: Implications for disease prevention and control.

    Science.gov (United States)

    Yatabe, T; More, S J; Geoghegan, F; McManus, C; Hill, A E; Martínez-López, B

    2015-11-01

    Live fish movement is considered as having an important role in the transmission of infectious diseases. For that reason, interventions for cost-effective disease prevention and control rely on a sound understanding of the patterns of live fish movements in a region or country. Here, we characterize the network of live fish movements in the Irish salmonid farming industry during 2013, using social network analysis and spatial epidemiology methods, and identify interventions to limit the risk of disease introduction and spread. In the network there were 62 sites sending and/or receiving fish, with a total of 130 shipments (84 arcs) comprising approx. 17.2 million fish during the year. Atlantic salmon shipments covered longer distances than trout shipments, with some traversing the entire country. The average shipment of Atlantic salmon was 146,186 (SD 194,344) fish, compared to 77,928 (127,009) for trout, however, variability was high. There were 3 periods where shipments peaked (February-April, June-September, and November), which were related to specific stages of fish. The network was disconnected and had two major weak components, the first one with 39 nodes (mostly Atlantic salmon sites), and the second one with 10 nodes (exclusively trout sites). Correlation between in and out-degree at each site and assortativity coefficient were slightly low and non-significant: -0.08 (95% CI: -0.22, 0.06) and -0.13 (95% CI: -0.36, 0.08), respectively, indicating random mixing with regard to node degree. Although competing models also produced a good fit to degree distribution, it is likely that the network possesses both small-world and scale-free topology. This would facilitate the spread and persistence of infection in the salmon production system, but would also facilitate the design of risk-based surveillance strategies by targeting hubs, bridges or cut-points. Using Infomap community detection algorithms, 2 major communities were identified within the giant weak

  3. A Secure Network Coding-based Data Gathering Model and Its Protocol in Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Qian Xiao

    2012-09-01

    Full Text Available To provide security for data gathering based on network coding in wireless sensor networks (WSNs, a secure network coding-based data gathering model is proposed, and a data-privacy preserving and pollution preventing (DPPaamp;PP protocol using network coding is designed. DPPaamp;PP makes use of a new proposed pollution symbol selection and pollution (PSSP scheme based on a new obfuscation idea to pollute existing symbols. Analyses of DPPaamp;PP show that it not only requires low overhead on computation and communication, but also provides high security on resisting brute-force attacks.

  4. Teratoid Wilms′ tumor - A rare renal tumor

    Directory of Open Access Journals (Sweden)

    Biswanath Mukhopadhyay

    2011-01-01

    Full Text Available Teratoid Wilms′ tumor is an extremely rare renal tumor. We report a case of unilateral teratoid Wilms′ tumor in a 4-year-old girl. The patient was admitted with a right-sided abdominal mass. The mass was arising from the right kidney. Radical nephrectomy was done and the patient had an uneventful recovery. Histopathology report showed teratoid Wilms′ tumor.

  5. Cycling hypoxia: A key feature of the tumor microenvironment.

    Science.gov (United States)

    Michiels, Carine; Tellier, Céline; Feron, Olivier

    2016-08-01

    A compelling body of evidence indicates that most human solid tumors contain hypoxic areas. Hypoxia is the consequence not only of the chaotic proliferation of cancer cells that places them at distance from the nearest capillary but also of the abnormal structure of the new vasculature network resulting in transient blood flow. Hence two types of hypoxia are observed in tumors: chronic and cycling (intermittent) hypoxia. Most of the current work aims at understanding the role of chronic hypoxia in tumor growth, response to treatment and metastasis. Only recently, cycling hypoxia, with spatial and temporal fluctuations in oxygen levels, has emerged as another key feature of the tumor environment that triggers different responses in comparison to chronic hypoxia. Either type of hypoxia is associated with distinct effects not only in cancer cells but also in stromal cells. In particular, cycling hypoxia has been demonstrated to favor, to a higher extent than chronic hypoxia, angiogenesis, resistance to anti-cancer treatments, intratumoral inflammation and tumor metastasis. These review details these effects as well as the signaling pathway it triggers to switch on specific transcriptomic programs. Understanding the signaling pathways through which cycling hypoxia induces these processes that support the development of an aggressive cancer could convey to the emergence of promising new cancer treatments. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Smart social adaptation prevents catastrophic ecological regime shifts in networks of myopic harvesters

    Science.gov (United States)

    Donges, Jonathan; Lucht, Wolfgang; Wiedermann, Marc; Heitzig, Jobst; Kurths, Jürgen

    2015-04-01

    In the anthropocene, the rise of global social and economic networks with ever increasing connectivity and speed of interactions, e.g., the internet or global financial markets, is a key challenge for sustainable development. The spread of opinions, values or technologies on these networks, in conjunction with the coevolution of the network structures themselves, underlies nexuses of current concern such as anthropogenic climate change, biodiversity loss or global land use change. To isolate and quantitatively study the effects and implications of network dynamics for sustainable development, we propose an agent-based model of information flow on adaptive networks between myopic harvesters that exploit private renewable resources. In this conceptual model of a network of socio-ecological systems, information on management practices flows between agents via boundedly rational imitation depending on the state of the resource stocks involved in an interaction. Agents can also adapt the structure of their social network locally by preferentially connecting to culturally similar agents with identical management practices and, at the same time, disconnecting from culturally dissimilar agents. Investigating in detail the statistical mechanics of this model, we find that an increasing rate of information flow through faster imitation dynamics or growing density of network connectivity leads to a marked increase in the likelihood of environmental resource collapse. However, we show that an optimal rate of social network adaptation can mitigate this negative effect without loss of social cohesion through network fragmentation. Our results highlight that seemingly immaterial network dynamics of spreading opinions or values can be of large relevance for the sustainable management of socio-ecological systems and suggest smartly conservative network adaptation as a strategy for mitigating environmental collapse. Hence, facing the great acceleration, these network dynamics should

  7. Spinal tumors

    International Nuclear Information System (INIS)

    Goethem, J.W.M. van; Hauwe, L. van den; Oezsarlak, Oe.; Schepper, A.M.A. de; Parizel, P.M.

    2004-01-01

    Spinal tumors are uncommon lesions but may cause significant morbidity in terms of limb dysfunction. In establishing the differential diagnosis for a spinal lesion, location is the most important feature, but the clinical presentation and the patient's age and gender are also important. Magnetic resonance (MR) imaging plays a central role in the imaging of spinal tumors, easily allowing tumors to be classified as extradural, intradural-extramedullary or intramedullary, which is very useful in tumor characterization. In the evaluation of lesions of the osseous spine both computed tomography (CT) and MR are important. We describe the most common spinal tumors in detail. In general, extradural lesions are the most common with metastasis being the most frequent. Intradural tumors are rare, and the majority is extramedullary, with meningiomas and nerve sheath tumors being the most frequent. Intramedullary tumors are uncommon spinal tumors. Astrocytomas and ependymomas comprise the majority of the intramedullary tumors. The most important tumors are documented with appropriate high quality CT or MR images and the characteristics of these tumors are also summarized in a comprehensive table. Finally we illustrate the use of the new World Health Organization (WHO) classification of neoplasms affecting the central nervous system

  8. A Hyperactive Signalosome in Acute Myeloid Leukemia Drives Addiction to a Tumor-Specific Hsp90 Species

    Directory of Open Access Journals (Sweden)

    Hongliang Zong

    2015-12-01

    Full Text Available Acute myeloid leukemia (AML is a heterogeneous and fatal disease with an urgent need for improved therapeutic regimens given that most patients die from relapsed disease. Irrespective of mutation status, the development of aggressive leukemias is enabled by increasing dependence on signaling networks. We demonstrate that a hyperactive signalosome drives addiction of AML cells to a tumor-specific Hsp90 species (teHsp90. Through genetic, environmental, and pharmacologic perturbations, we demonstrate a direct and quantitative link between hyperactivated signaling pathways and apoptotic sensitivity of AML to teHsp90 inhibition. Specifically, we find that hyperactive JAK-STAT and PI3K-AKT signaling networks are maintained by teHsp90 and, in fact, gradual activation of these networks drives tumors increasingly dependent on teHsp90. Thus, although clinically aggressive AML survives via signalosome activation, this addiction creates a vulnerability that can be exploited with Hsp90-directed therapy.

  9. Drug-selected human lung cancer stem cells: cytokine network, tumorigenic and metastatic properties.

    Directory of Open Access Journals (Sweden)

    Vera Levina

    2008-08-01

    Full Text Available Cancer stem cells (CSCs are thought to be responsible for tumor regeneration after chemotherapy, although direct confirmation of this remains forthcoming. We therefore investigated whether drug treatment could enrich and maintain CSCs and whether the high tumorogenic and metastatic abilities of CSCs were based on their marked ability to produce growth and angiogenic factors and express their cognate receptors to stimulate tumor cell proliferation and stroma formation.Treatment of lung tumor cells with doxorubicin, cisplatin, or etoposide resulted in the selection of drug surviving cells (DSCs. These cells expressed CD133, CD117, SSEA-3, TRA1-81, Oct-4, and nuclear beta-catenin and lost expression of the differentiation markers cytokeratins 8/18 (CK 8/18. DSCs were able to grow as tumor spheres, maintain self-renewal capacity, and differentiate. Differentiated progenitors lost expression of CD133, gained CK 8/18 and acquired drug sensitivity. In the presence of drugs, differentiation of DSCs was abrogated allowing propagation of cells with CSC-like characteristics. Lung DSCs demonstrated high tumorogenic and metastatic potential following inoculation into SCID mice, which supported their classification as CSCs. Luminex analysis of human and murine cytokines in sonicated lysates of parental- and CSC-derived tumors revealed that CSC-derived tumors contained two- to three-fold higher levels of human angiogenic and growth factors (VEGF, bFGF, IL-6, IL-8, HGF, PDGF-BB, G-CSF, and SCGF-beta. CSCs also showed elevated levels of expression of human VEGFR2, FGFR2, CXCR1, 2 and 4 receptors. Moreover, human CSCs growing in SCID mice stimulated murine stroma to produce elevated levels of angiogenic and growth factors.These findings suggest that chemotherapy can lead to propagation of CSCs and prevention of their differentiation. The high tumorigenic and metastatic potentials of CSCs are associated with efficient cytokine network production that may represent

  10. Disaster prevention surveillance system

    International Nuclear Information System (INIS)

    Nara, Satoru; Kamiya, Eisei

    2001-01-01

    Fuji Electric Co., Ltd. has supplied many management systems to nuclear reactor institution. 'The nuclear countermeasures-against-calamities special-measures' was enforced. A nuclear entrepreneur has devised the measure about expansion prevention and restoration of a calamity while it endeavors after prevention of generating of a nuclear calamity. Our company have supplied the 'disaster prevention surveillance system' to the Japan Atomic Energy Research Institute Tokai Research Establishment aiming at strengthening of the monitoring function at the time (after the accident) of the accident used as one of the above-mentioned measures. A 'disaster prevention surveillance system' can share the information on the accident spot in an on-site command place, an activity headquarters, and support organizations, when the serious accident happens. This system is composed of various sensors (temperature, pressure and radiation), cameras, computers and network. (author)

  11. Tumor control probability after a radiation of animal tumors

    International Nuclear Information System (INIS)

    Urano, Muneyasu; Ando, Koichi; Koike, Sachiko; Nesumi, Naofumi

    1975-01-01

    Tumor control and regrowth probability of animal tumors irradiated with a single x-ray dose were determined, using a spontaneous C3H mouse mammary carcinoma. Cellular radiation sensitivity of tumor cells and tumor control probability of the tumor were examined by the TD 50 and TCD 50 assays respectively. Tumor growth kinetics were measured by counting the percentage of labelled mitosis and by measuring the growth curve. A mathematical analysis of tumor control probability was made from these results. A formula proposed, accounted for cell population kinetics or division probability model, cell sensitivity to radiation and number of tumor cells. (auth.)

  12. An exceptional collision tumor: gastric calcified stromal tumor and ...

    African Journals Online (AJOL)

    The authors report an exceptional case of collision tumor comprised of a gastric calcified stromal tumor and a pancreatic adenocarcinoma. The pancreatic tumor was detected fortuitously on the histological exam of resection specimen. Key words: Collision tumor, stromal tumor, adenocarcinoma ...

  13. Sunlight suppressing rejection of 280- to 320-nm UV-radiation-induced skin tumors in mice

    International Nuclear Information System (INIS)

    Morison, W.L.; Kelley, S.P.

    1985-01-01

    Repeated exposure of female C3H/HeNCR- mice to sunlight prevented the normal immunologic rejection of a UV-induced tumor. This systemic immunologic alteration was transferred to syngeneic lethally X-irradiated animals with lymphoid cells from mice exposed to sunlight. The lymphoid cells also were able to suppress the capacity of lymphoid cells from normal animals to reject a UV-induced tumor. The 295- to 320-nm wave band appeared to be responsible for this immunosuppressive effect of sunlight because suppression was prevented by filtration of the radiation through Mylar and by application of a sunscreen containing para-aminobenzoic acid. These observations may have importance in understanding the pathogenesis of sunlight-induced skin cancer in humans

  14. The influence of arachidonic acid metabolites on cell division in the intestinal epithelium and in colonic tumors.

    Science.gov (United States)

    Petry, F M; Tutton, P J; Barkla, D H

    1984-09-01

    Various metabolites of arachidonic acid are now known to influence cell division. In this paper the effects on cell proliferation of arachidonic acid, some inhibitors of arachidonic acid metabolism and some analogs of arachidonic acid metabolites is described. The epithelial cell proliferation rate in the jejunum, in the descending colon and in dimethylhydrazine-induced tumors of rat colon was measured using a stathmokinetic technique. Administration of arachidonic acid resulted in retardation of cell proliferation in each of the tissues examined. A cyclooxygenase inhibitor (Flurbiprofen) prevented this effect of arachidonic acid in the jejunal crypts and in colonic tumors, but not in colonic crypts. In contrast, inhibitors of both cyclooxygenase and lipoxygenase (Benoxaprofen and BW755c) prevented the effect of arachidonic acid in the colonic crypts and reduced its effect on colonic tumours but did not alter its effect on the jejunum. An inhibitor of thromoboxane A2 synthetase (U51,605) was also able to prevent the inhibitory effect of arachidonic acid on colonic tumors. Treatment with 16,16-dimethyl PGE2 inhibited cell proliferation in jejunal crypts and in colonic tumors, as did a thromboxane A2 mimicking agent, U46619. Nafazatrom, an agent that stimulates prostacyclin synthesis and inhibits lypoxygenase, promoted cell proliferation in the jejunal crypts and colonic crypts, but inhibited cell proliferation in colonic tumours.

  15. Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types.

    Science.gov (United States)

    Iliopoulos, Dimitrios; Hirsch, Heather A; Struhl, Kevin

    2011-05-01

    Metformin, the first-line drug for treating diabetes, selectively kills the chemotherapy resistant subpopulation of cancer stem cells (CSC) in genetically distinct types of breast cancer cell lines. In mouse xenografts, injection of metformin and the chemotherapeutic drug doxorubicin near the tumor is more effective than either drug alone in blocking tumor growth and preventing relapse. Here, we show that metformin is equally effective when given orally together with paclitaxel, carboplatin, and doxorubicin, indicating that metformin works together with a variety of standard chemotherapeutic agents. In addition, metformin has comparable effects on tumor regression and preventing relapse when combined with a four-fold reduced dose of doxorubicin that is not effective as a monotherapy. Finally, the combination of metformin and doxorubicin prevents relapse in xenografts generated with prostate and lung cancer cell lines. These observations provide further evidence for the CSC hypothesis for cancer relapse, an experimental rationale for using metformin as part of combinatorial therapy in a variety of clinical settings, and for reducing the chemotherapy dose in cancer patients.

  16. Taming dendritic cells with TIM-3: Another immunosuppressive strategy by tumors

    Science.gov (United States)

    Patel, Jaina; Bozeman, Erica N.; Selvaraj, Periasamy

    2013-01-01

    The identification of TIM-3 expression on tumor associated dendritic cells (TADCs) provides insight into another aspect of tumor-mediated immunosuppression. The role of TIM-3 has been well characterized on tumor-infiltrating T cells, however its role on TADCs was not previously known. The current paper demonstrated that TIM-3 was predominantly expressed by TADCs and its interaction with the nuclear protein HMGB1 suppressed nucleic acid mediated activation of an effective antitumor immune response. The authors were able to show that TIM-3 interaction with HMGB1 prevented the localization of nucleic acids into endosomal vesicles. Furthermore, chemotherapy was found to be more effective in anti-TIM-3 mAb treated mice or mice depleted of all DCs which indicated that significant role played by TADCs inhibiting tumor regression. Taken together, these findings identify TIM-3 as a potential target for inducing antitumor immunity in conjunction with DNA vaccines and/or immunogenic chemotherapy in clinical settings. PMID:23240746

  17. [Mixed odontogenic tumors in children and adolescents].

    Science.gov (United States)

    Gyulai-Gaál, Szabolcs; Takács, Daniel; Barabás, József; Tarján, Ildikó; Martonffy, Katalin; Szabó, György; Suba, Zsuzsanna

    2007-04-01

    Mixed odontogenic tumors in the jaws of children and adolescents usually cause dentition anomalies. The typical forms of these are ameloblastic fibroma, ameloblastic fibroodontoma, complex odontoma and compound odontoma. In the present study mixed odontogenic tumor cases are presented in patients under 20 years of age. All of them were associated with tooth eruption disturbances. Further aim of this study was to discuss the nature and interrelationships of this group of lesions. Ameloblastic fibromas (AFs) are true, mixed, soft tissue neoplasms, deriving from the proliferation of both odontogenic epithelium and mesenchyma. They have a potential to both recurrence and malignant transformation. Ameloblastic fibroodontomas (AFOs) may be regarded as hamartomas, which exhibit epithelial, mesenchymal and abundant hard tissue components of the developing teeth. Odontomas are calcifying benign hamartomas, and represent the most common type of odontogenic jaw tumors among patients less than 20y, having complex and compound variants. Complex odontomas (CXOs) are built up from amorphous hard tissue elements, and generally occur in the premolar or molar regions of the maxilla. Compound odontomas (CDOs) usually appear in the maxilla, in the region of the incisors and canines, and contain small, radio-opaque structures reminiscent of rudimentary teeth. Early diagnosis and treatment of mixed odontogenic jaw tumors in children may prevent the serious orthodontic complications and jaw deformations.

  18. Canada-Africa grants spur novel ideas, networks | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2016-06-22

    Jun 22, 2016 ... Canada-Africa grants spur novel ideas, networks ... networks involving African and Canadian academic researchers. ... Remarkable new research into HIV prevention among the "choice disabled" — vulnerable groups less ...

  19. [HIV prevention program for young people--the WYSH Project as a model of "combination prevention"].

    Science.gov (United States)

    Ono-Kihara, Masako

    2010-03-01

    In face of the HIV pandemic that still grows, unsuccessful efforts of developing biomedical control measures or the failure of cognitive-behavioral approach to show sustained social level effectiveness, behavioral strategy is now expected to evolve into a structural prevention ("combination prevention") that involves multiple behavioral goals and multilevel approaches. WYSH Project is a combination prevention project for youth developed through socio-epidemiological approach that integrates epidemiology with social science such as social marketing and mixed method. WYSH Project includes mass education programs for youth in schools and programs for out-of-school youth through cyber network and peer communication. Started in 2002, it expanded nationwide with supports from related ministries and parent-teacher associations and has grown into a single largest youth prevention project in Japan.

  20. Increased Serotonin Signaling Contributes to the Warburg Effect in Pancreatic Tumor Cells Under Metabolic Stress and Promotes Growth of Pancreatic Tumors in Mice.

    Science.gov (United States)

    Jiang, Shu-Heng; Li, Jun; Dong, Fang-Yuan; Yang, Jian-Yu; Liu, De-Jun; Yang, Xiao-Mei; Wang, Ya-Hui; Yang, Min-Wei; Fu, Xue-Liang; Zhang, Xiao-Xin; Li, Qing; Pang, Xiu-Feng; Huo, Yan-Miao; Li, Jiao; Zhang, Jun-Feng; Lee, Ho-Young; Lee, Su-Jae; Qin, Wen-Xin; Gu, Jian-Ren; Sun, Yong-Wei; Zhang, Zhi-Gang

    2017-07-01

    of 5-HT to be increased in human PDAC tissues compared with non-tumor pancreatic tissues, and PDAC cell lines compared with non-transformed pancreatic cells. Incubation of PDAC cell lines with 5-HT increased proliferation and prevented apoptosis. Agonists of HTR2B, but not other 5-HT receptors, promoted proliferation and prevented apoptosis of PDAC cells. Knockdown of HTR2B in PDAC cells, or incubation of cells with HTR2B inhibitors, reduced their growth as xenograft tumors in mice. We observed a correlation between 5-HT and glycolytic flux in PDAC cells; levels of metabolic enzymes involved in glycolysis, the phosphate pentose pathway, and hexosamine biosynthesis pathway increased significantly in PDAC cells following 5-HT stimulation. 5-HT stimulation led to formation of the HTR2B-LYN-p85 complex, which increased PI3K-Akt-mTOR signaling and the Warburg effect by increasing protein levels of MYC and HIF1A. Administration of SB204741 to KPC mice slowed growth and metabolism of established pancreatic tumors and prolonged survival of the mice. Human PDACs have increased levels of 5-HT, and PDAC cells increase expression of its receptor, HTR2B. These increases allow for tumor glycolysis under metabolic stress and promote growth of pancreatic tumors and PDAC xenograft tumors in mice. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  1. MR findings of ovarian tumors with hormonal activity, with emphasis on tumors other than sex cord-stromal tumors

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Yumiko Oishi [Department of Radiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan)]. E-mail: ytanaka@md.tsukuba.ac.jp; Saida, Tsukasa Sasaki [Department of Diagnostic and Interventional Radiology, Tsukuba University Hospital (Japan); Minami, Rie [Department of Obstetrics and Gynecology, Graduate School of Comprehensive Human Sciences, University of Tsukuba (Japan); Yagi, Takako [Department of Diagnostic and Interventional Radiology, Tsukuba University Hospital (Japan); Tsunoda, Hajime [Department of Obstetrics and Gynecology, Kanto Medical Center, Nippon Telegraph and Telephone East Corporation (Japan); Yoshikawa, Hiroyuki [Department of Obstetrics and Gynecology, Graduate School of Comprehensive Human Sciences, University of Tsukuba (Japan); Minami, Manabu [Department of Radiology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan)

    2007-06-15

    Sex cord-stromal tumors including granulosa cell tumor, thecoma, Sertoli stromal cell tumor and steroid cell tumor are noted for their hormonal activity. However, there are many kinds of ovarian tumors other than sex cord-stromal tumors and tumor-like conditions with endocrine manifestations. Cross-sectional imaging, especially MR, can provide precise features of ovarian tumors and uterine morphological change even in a clinically latent excess of estrogen. In this article, we demonstrate typical imaging findings of ovarian tumors with hormonal activity. We also shortly explain the mechanism of the virilization and hyperestrogenism caused by ovarian tumors and tumor-like conditions.

  2. MR findings of ovarian tumors with hormonal activity, with emphasis on tumors other than sex cord-stromal tumors

    International Nuclear Information System (INIS)

    Tanaka, Yumiko Oishi; Saida, Tsukasa Sasaki; Minami, Rie; Yagi, Takako; Tsunoda, Hajime; Yoshikawa, Hiroyuki; Minami, Manabu

    2007-01-01

    Sex cord-stromal tumors including granulosa cell tumor, thecoma, Sertoli stromal cell tumor and steroid cell tumor are noted for their hormonal activity. However, there are many kinds of ovarian tumors other than sex cord-stromal tumors and tumor-like conditions with endocrine manifestations. Cross-sectional imaging, especially MR, can provide precise features of ovarian tumors and uterine morphological change even in a clinically latent excess of estrogen. In this article, we demonstrate typical imaging findings of ovarian tumors with hormonal activity. We also shortly explain the mechanism of the virilization and hyperestrogenism caused by ovarian tumors and tumor-like conditions

  3. Tumor-Associated Antigens for Specific Immunotherapy of Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kiessling, Andrea [Biologics Safety and Disposition, Preclinical Safety, Translational Sciences, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Werk Klybeck, Klybeckstraße 141, Basel CH-4057 (Switzerland); Wehner, Rebekka [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Füssel, Susanne [Department of Urology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Bachmann, Michael [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Wirth, Manfred P. [Department of Urology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Schmitz, Marc, E-mail: marc.schmitz@tu-dresden.de [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany)

    2012-02-22

    Prostate cancer (PCa) is the most common noncutaneous cancer diagnosis and the second leading cause of cancer-related deaths among men in the United States. Effective treatment modalities for advanced metastatic PCa are limited. Immunotherapeutic strategies based on T cells and antibodies represent interesting approaches to prevent progression from localized to advanced PCa and to improve survival outcomes for patients with advanced disease. CD8{sup +} cytotoxic T lymphocytes (CTLs) efficiently recognize and destroy tumor cells. CD4{sup +} T cells augment the antigen-presenting capacity of dendritic cells and promote the expansion of tumor-reactive CTLs. Antibodies mediate their antitumor effects via antibody-dependent cellular cytotoxicity, activation of the complement system, improving the uptake of coated tumor cells by phagocytes, and the functional interference of biological pathways essential for tumor growth. Consequently, several tumor-associated antigens (TAAs) have been identified that represent promising targets for T cell- or antibody-based immunotherapy. These TAAs comprise proteins preferentially expressed in normal and malignant prostate tissues and molecules which are not predominantly restricted to the prostate, but are overexpressed in various tumor entities including PCa. Clinical trials provide evidence that specific immunotherapeutic strategies using such TAAs represent safe and feasible concepts for the induction of immunological and clinical responses in PCa patients. However, further improvement of the current approaches is required which may be achieved by combining T cell- and/or antibody-based strategies with radio-, hormone-, chemo- or antiangiogenic therapy.

  4. Gamma knife radiosurgery for metastatic brain tumors from lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Serizawa, Toru; Ono, Junichi; Iuchi, Toshihiko [Chiba Cardiovascular Center, Ichihara (Japan). Chiba Cancer Center] (and others)

    2003-01-01

    The purpose of this retrospective study is to evaluate the effectiveness of gamma knife radiosurgery (GKS) alone for metastatic brain tumors from lung cancer. Two hundred thirty-one consecutive patients with metastatic brain tumors from lung cancer filling the following 4 criteria were analyzed for this study; no prior brain tumor treatment, 25 or fewer lesions, a maximum 5 tumors with diameter of 2 cm or more, no surgically inaccessible tumor 3 cm or greater in diameter. According to the same treatment protocol, large tumors ({>=} 3 cm) were surgically removed and all the other small lesions (<3 cm) were treated with GKS. New lesions were treated with repeated GKS. The tumor-progression-free, overall, neurological, lowered-QOL (quality of life)-free and new-lesion-free survivals were calculated with the Kaplan-Meier method. The poor prognostic factors for each survival were also analyzed with the Cox's proportional hazard model. The tumor control rate at 1 year was 96.5%. The estimated median overall survival time was 7.7 months. The first-year survival rates were 83.0% in neurological survival and 76.0% in lowered-QOL-free survival. The new-lesion-free survival at 1 year was 27.9%. Multivariate analysis revealed significant poor prognostic factors for neurological and lowered-QOL-free survivals were carcinomatous meningitis and >10 brain lesions. This study suggests the results of GKS for metastatic brain tumors from lung cancer are quite satisfactory considering prevention of neurological death and maintenance of QOL. But cases with carcinomatous meningitis and/or >10 brain lesions are not good candidates for GKS alone. (author)

  5. The anti-tumor effect of bee honey in Ehrlich ascite tumor model of mice is coincided with stimulation of the immune cells.

    Science.gov (United States)

    Attia, W Y; Gabry, M S; El-Shaikh, K A; Othman, G A

    2008-01-01

    Honey is thought to exhibit a broad spectrum of therapeutic properties including antibacterial, antifungal, cytostatic and anti-inflammatory activity and has been used for the treatment of gastric ulcers, burns, and for storage of skin grafts. The present study investigated the antitumor effect of bee honey against Ehrlich ascites tumor in mice and the possible mode of antitumor action. Peroral administration of mice with honey (10, 100 or 1000 mg/ 100 g BW) every other day for 4 weeks before intraperitoneal inoculation with Ehrlich ascites tumor (EAT, 1 x 10(6) cells) increased the number bone marrow cells as well as peritoneal macrophages, but not peripheral blood leukocytes nor splenocytes. The phagocytic function of macrophages as well as the T- and B-cell functions were also increased. Honey pre-treatment also recovered the total lipids, total proteins, as well as liver and kidney enzyme activities in EAT-bearing mice. In vitro studies on EAT cells demonstrated inhibitory effect of honey on tumor cell proliferation, viability % of tumor cells as well as the size of solid tumor. The present results indicate that the preventive treatment with honey is considerably effective against EAT in mice both in vivo and in vitro. The antitumor activity of honey may occur through the activation of macrophages, T-cells and B-cells.

  6. Tumor hypoxia and reoxygenation: the yin and yang for radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Beom Ju; Kim, Jong Woo; Jeong, Hoi Bin; Bok, Seo Yeon; Kim, Young Eun; Ahn, G One [Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang (Korea, Republic of)

    2016-12-15

    Tumor hypoxia, a common feature occurring in nearly all human solid tumors is a major contributing factor for failures of anticancer therapies. Because ionizing radiation depends heavily on the presence of molecular oxygen to produce cytotoxic effect, the negative impact of tumor hypoxia had long been recognized. In this review, we will highlight some of the past attempts to overcome tumor hypoxia including hypoxic radiosensitizers and hypoxia-selective cytotoxin. Although they were (still are) a very clever idea, they lacked clinical efficacy largely because of ‘reoxygenation’ phenomenon occurring in the conventional low dose hyperfractionation radiotherapy prevented proper activation of these compounds. Recent meta-analysis and imaging studies do however indicate that there may be a significant clinical benefit in lowering the locoregional failures by using these compounds. Latest technological advancement in radiotherapy has allowed to deliver high doses of radiation conformally to the tumor volume. Although this technology has brought superb clinical responses for many types of cancer, recent modeling studies have predicted that tumor hypoxia is even more serious because ‘reoxygenation’ is low thereby leaving a large portion of hypoxic tumor cells behind. Wouldn’t it be then reasonable to combine hypoxic radiosensitizers and/or hypoxia-selective cytotoxin with the latest radiotherapy? We will provide some preclinical and clinical evidence to support this idea hoping to revamp an enthusiasm for hypoxic radiosensitizers or hypoxia-selective cytotoxins as an adjunct therapy for radiotherapy.

  7. Jnk2 effects on tumor development, genetic instability and replicative stress in an oncogene-driven mouse mammary tumor model.

    Directory of Open Access Journals (Sweden)

    Peila Chen

    2010-05-01

    Full Text Available Oncogenes induce cell proliferation leading to replicative stress, DNA damage and genomic instability. A wide variety of cellular stresses activate c-Jun N-terminal kinase (JNK proteins, but few studies have directly addressed the roles of JNK isoforms in tumor development. Herein, we show that jnk2 knockout mice expressing the Polyoma Middle T Antigen transgene developed mammary tumors earlier and experienced higher tumor multiplicity compared to jnk2 wildtype mice. Lack of jnk2 expression was associated with higher tumor aneuploidy and reduced DNA damage response, as marked by fewer pH2AX and 53BP1 nuclear foci. Comparative genomic hybridization further confirmed increased genomic instability in PyV MT/jnk2-/- tumors. In vitro, PyV MT/jnk2-/- cells underwent replicative stress and cell death as evidenced by lower BrdU incorporation, and sustained chromatin licensing and DNA replication factor 1 (CDT1 and p21(Waf1 protein expression, and phosphorylation of Chk1 after serum stimulation, but this response was not associated with phosphorylation of p53 Ser15. Adenoviral overexpression of CDT1 led to similar differences between jnk2 wildtype and knockout cells. In normal mammary cells undergoing UV induced single stranded DNA breaks, JNK2 localized to RPA (Replication Protein A coated strands indicating that JNK2 responds early to single stranded DNA damage and is critical for subsequent recruitment of DNA repair proteins. Together, these data support that JNK2 prevents replicative stress by coordinating cell cycle progression and DNA damage repair mechanisms.

  8. Bone tumors

    International Nuclear Information System (INIS)

    Unni, K.K.

    1988-01-01

    This book contains the proceedings on bone tumors. Topics covered include: Bone tumor imaging: Contribution of CT and MRI, staging of bone tumors, perind cell tumors of bone, and metastatic bone disease

  9. Effects of Acanthus ebracteatus Vahl on tumor angiogenesis and on tumor growth in nude mice implanted with cervical cancer

    International Nuclear Information System (INIS)

    Mahasiripanth, Taksanee; Hokputsa, Sanya; Niruthisard, Somchai; Bhattarakosol, Parvapan; Patumraj, Suthiluk

    2012-01-01

    The aim of this study was to examine the effects of the crude extract of Acanthus ebracteatus Vahl (AE) on tumor growth and angiogenesis by utilizing a tumor model in which nude mice were implanted with cervical cancer cells containing human papillomavirus 16 DNA (HPV-16 DNA). The growth-inhibitory effect of AE was investigated in four different cell types: CaSki (HPV-16 positive), HeLa (HPV-18 positive), hepatocellular carcinoma cells (HepG2), and human dermal fibroblast cells (HDFs). The cell viabilities and IC 50 values of AE were determined in cells incubated with AE for different lengths of time. To conduct studies in vivo, female BALB/c nude mice (aged 6–7 weeks, weighing 20–25 g) were used. A cervical cancer-derived cell line (CaSki) with integrated HPV-16 DNA was injected subcutaneously (1 × 10 7 cells/200 μL) in the middle dorsum of each animal (HPV group). One week after injection, mice were fed orally with AE crude extract at either 300 or 3000 mg/kg body weight/day for 14 or 28 days (HPV-AE groups). Tumor microvasculature and capillary vascularity were determined using laser scanning confocal microscopy. Tumor tissue was collected from each mouse to evaluate tumor histology and vascular endothelial growth factor (VEGF) immunostaining. The time-response curves of AE and the dose-dependent effect of AE on growth inhibition were determined. After a 48-hour incubation period, the IC 50 of AE in CaSki was discovered to be significantly different from that of HDFs (P < 0.05). A microvascular network was observed around the tumor area in the HPV group on days 21 and 35. Tumor capillary vascularity in the HPV group was significantly increased compared with the control group (P < 0.001). High-dose treatment of AE extract (HPV-3000AE group) significantly attenuated the increase in VEGF expression and tumor angiogenesis in mice that received either the 14- or 28-day treatment period (P < 0.001). Our novel findings demonstrated that AE crude extract could

  10. Radiation Therapy Induces Macrophages to Suppress Immune Responses Against Pancreatic Tumors in Mice

    Science.gov (United States)

    Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Ly, Nancy Ngoc Giao; Nguy, Susanna; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Daley, Donnele; Barilla, Rocky; Tippens, Daniel; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R.; Hajdu, Cristina; Pellicciotta, Ilenia; Oh, Philmo; Du, Kevin; Miller, George

    2016-01-01

    Background & Aims The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcome, compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of pre-invasive foci. Methods We investigated the effects of radiation in p48Cre;LSL-KrasG12D (KC) and p48Cre;LSLKrasG12D;LSL-Trp53R172H (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2–12 Gy and analyzed by flow cytometry. Results Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from invasive and pre-invasive pancreatic tumors had an immune-suppressive, M2-like phenotype, compared with control mice. Pancreata from mice exposed to radiation had fewer CD8+ T cells than controls and greater numbers of CD4+ T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. An antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. Conclusions Radiation exposure causes macrophages in PDAs

  11. Photocarcinogenesis and Skin Cancer Prevention Strategies.

    Science.gov (United States)

    Seebode, Christina; Lehmann, Janin; Emmert, Steffen

    2016-03-01

    In this review the basic principles of UV-induced carcinogenesis are summarized and the state of the art diagnosis and therapeutic strategies are discussed. The prevalent keratinocyte-derived neoplasms of the skin are basal cell and squamous cell carcinomas. Cutaneous melanoma is less frequent but associated with high mortality. Common risk factors for all three tumor entities include sun exposure and DNA-repair deficiencies. Photocarcinogenesis follows a multistep model of cancer development in which ultraviolet-induced DNA damage leads to mutations resulting in activation of oncogenes or silencing of tumor-suppressor genes. This ends in a cellular mutator phenotype even more prone to mutation acquisition. DNA repair, especially the nucleotide excision repair (NER) pathway, counteracts mutation formation and skin cancer development. This is vividly demonstrated by the NER-defective disorder xeroderma pigmentosum. Primary skin cancer preventative strategies, therefore, include reduction of DNA photodamage by protection from the sun. Secondary preventative strategies include skin cancer screening. This implies standard examination techniques with the naked eye, an epiluminescence microscope, or digital epiluminescence microscopy. More advanced techniques include confocal laser scan microscopy. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. SEADE: Countering the Futility of Network Security

    Science.gov (United States)

    2015-10-01

    guards, and computer cages) and logical security measures (network firewall and intrusion detection). However, no matter how many layers of network...security built-in and with minimal security dependence on network security appliances (e.g., firewalls ). As Secretary of Defense Ashton Carter...based analysis that assumes nothing bad will happen to applications/data if those defenses prevent malware transactions at the entrance. The

  13. Tumor-Associated Macrophages as Incessant Builders and Destroyers of the Cancer Stroma

    International Nuclear Information System (INIS)

    Liguori, Manuela; Solinas, Graziella; Germano, Giovanni; Mantovani, Alberto; Allavena, Paola

    2011-01-01

    Tumor-Associated Macrophages (TAM) are key components of the reactive stroma of tumors. In most, although not all cancers, their presence is associated with poor patient prognosis. In addition to releasing cytokines and growth factors for tumor and endothelial cells, a distinguished feature of TAM is their high-rate degradation of the extra-cellular matrix. This incessant stroma remodelling favours the release of matrix-bound growth factors and promotes tumor cell motility and invasion. In addition, TAM produce matrix proteins, some of which are typical of the neoplastic tissues. The gene expression profile of TAM isolated from human tumors reveals a matrix-related signature with the up-regulation of genes coding for different matrix proteins, as well as several proteolytic enzymes. Among ECM components are: osteopontin, osteoactivin, collagens and fibronectin, including also a truncated isoform of fibronectin termed migration stimulation factor. In addition to serve as structural proteins, these matrix components have key functions in the regulation of the vessel network, in the inductionof tumor cell motility and degradation of cellular debris. Among proteolytic enzymes are: matrix metalloproteases, cathepsins, lysosomal and ADAM proteases, and the urokinase-type plasminogen activator. The degrading activity of TAM, coupled to the production of bio-active ECM proteins, co-operate to the build-up and maintenance of an inflammatory micro-environment which eventually promotes tumor progression

  14. Tumor-Associated Macrophages as Incessant Builders and Destroyers of the Cancer Stroma

    Energy Technology Data Exchange (ETDEWEB)

    Liguori, Manuela; Solinas, Graziella; Germano, Giovanni [Department of Immunology and Inflammation Istituto Clinico Humanitas, Via Manzoni 113, Rozzano-Milano 20089 (Italy); Mantovani, Alberto [Department of Immunology and Inflammation Istituto Clinico Humanitas, Via Manzoni 113, Rozzano-Milano 20089 (Italy); Department of Translational Medicine, University of Milano, Milano 20089 (Italy); Allavena, Paola, E-mail: paola.allavena@humanitasresearch.it [Department of Immunology and Inflammation Istituto Clinico Humanitas, Via Manzoni 113, Rozzano-Milano 20089 (Italy)

    2011-09-28

    Tumor-Associated Macrophages (TAM) are key components of the reactive stroma of tumors. In most, although not all cancers, their presence is associated with poor patient prognosis. In addition to releasing cytokines and growth factors for tumor and endothelial cells, a distinguished feature of TAM is their high-rate degradation of the extra-cellular matrix. This incessant stroma remodelling favours the release of matrix-bound growth factors and promotes tumor cell motility and invasion. In addition, TAM produce matrix proteins, some of which are typical of the neoplastic tissues. The gene expression profile of TAM isolated from human tumors reveals a matrix-related signature with the up-regulation of genes coding for different matrix proteins, as well as several proteolytic enzymes. Among ECM components are: osteopontin, osteoactivin, collagens and fibronectin, including also a truncated isoform of fibronectin termed migration stimulation factor. In addition to serve as structural proteins, these matrix components have key functions in the regulation of the vessel network, in the inductionof tumor cell motility and degradation of cellular debris. Among proteolytic enzymes are: matrix metalloproteases, cathepsins, lysosomal and ADAM proteases, and the urokinase-type plasminogen activator. The degrading activity of TAM, coupled to the production of bio-active ECM proteins, co-operate to the build-up and maintenance of an inflammatory micro-environment which eventually promotes tumor progression.

  15. Poster - 51: A tumor motion-compensating system with tracking and prediction – a proof-of-concept study

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Kaiming; Teo, Peng; Kawalec, Philip; Pistorius, Stephen [CancerCare Manitoba (Canada)

    2016-08-15

    Purpose: This work reports on the development of a mechanical slider system for the counter-steering of tumor motion in adaptive Radiation Therapy (RT). The tumor motion was tracked using a weighted optical flow algorithm and its position is being predicted with a neural network (NN). Methods: The components of the proposed mechanical counter-steering system includes: (1) an actuator which provides the tumor motion, (2) the motion detection using an optical flow algorithm, (3) motion prediction using a neural network, (4) a control module and (5) a mechanical slider to counter-steer the anticipated motion of the tumor phantom. An asymmetrical cosine function and five patient traces (P1–P5) were used to evaluate the tracking of a 3D printed lung tumor. In the proposed mechanical counter-steering system, both actuator (Zaber NA14D60) and slider (Zaber A-BLQ0070-E01) were programed to move independently with LabVIEW and their positions were recorded by 2 potentiometers (ETI LCP12S-25). The accuracy of this counter-steering system is given by the difference between the two potentiometers. Results: The inherent accuracy of the system, measured using the cosine function, is −0.15 ± 0.06 mm. While the errors when tracking and prediction were included, is (0.04 ± 0.71) mm. Conclusion: A prototype tumor motion counter-steering system with tracking and prediction was implemented. The inherent errors are small in comparison to the tracking and prediction errors, which in turn are small in comparison to the magnitude of tumor motion. The results show that this system is suited for evaluating RT tracking and prediction.

  16. Real-Time Communication in Wireless Home Networks

    NARCIS (Netherlands)

    Scholten, Johan; Jansen, P.G.

    This paper describes a medium access protocol for real-time communication in wireless networks. Medium access is controlled by a scheduler, which utilizes a pre-emptive earliest deadline first (PEDF) scheduling algorithm. The scheduler prevents collisions in the network, where normally only

  17. Captopril improves tumor nanomedicine delivery by increasing tumor blood perfusion and enlarging endothelial gaps in tumor blood vessels.

    Science.gov (United States)

    Zhang, Bo; Jiang, Ting; Tuo, Yanyan; Jin, Kai; Luo, Zimiao; Shi, Wei; Mei, Heng; Hu, Yu; Pang, Zhiqing; Jiang, Xinguo

    2017-12-01

    Poor tumor perfusion and unfavorable vessel permeability compromise nanomedicine drug delivery to tumors. Captopril dilates blood vessels, reducing blood pressure clinically and bradykinin, as the downstream signaling moiety of captopril, is capable of dilating blood vessels and effectively increasing vessel permeability. The hypothesis behind this study was that captopril can dilate tumor blood vessels, improving tumor perfusion and simultaneously enlarge the endothelial gaps of tumor vessels, therefore enhancing nanomedicine drug delivery for tumor therapy. Using the U87 tumor xenograft with abundant blood vessels as the tumor model, tumor perfusion experiments were carried out using laser Doppler imaging and lectin-labeling experiments. A single treatment of captopril at a dose of 100 mg/kg significantly increased the percentage of functional vessels in tumor tissues and improved tumor blood perfusion. Scanning electron microscopy of tumor vessels also indicated that the endothelial gaps of tumor vessels were enlarged after captopril treatment. Immunofluorescence-staining of tumor slices demonstrated that captopril significantly increased bradykinin expression, possibly explaining tumor perfusion improvements and endothelial gap enlargement. Additionally, imaging in vivo, imaging ex vivo and nanoparticle distribution in tumor slices indicated that after a single treatment with captopril, the accumulation of 115-nm nanoparticles in tumors had increased 2.81-fold with a more homogeneous distribution pattern in comparison to non-captopril treated controls. Finally, pharmacodynamics experiments demonstrated that captopril combined with paclitaxel-loaded nanoparticles resulted in the greatest tumor shrinkage and the most extensive necrosis in tumor tissues among all treatment groups. Taken together, the data from the present study suggest a novel strategy for improving tumor perfusion and enlarging blood vessel permeability simultaneously in order to improve

  18. Ethanol exposure induces the cancer-associated fibroblast phenotype and lethal tumor metabolism

    Science.gov (United States)

    Sanchez-Alvarez, Rosa; Martinez-Outschoorn, Ubaldo E.; Lin, Zhao; Lamb, Rebecca; Hulit, James; Howell, Anthony; Sotgia, Federica; Rubin, Emanuel; Lisanti, Michael P.

    2013-01-01

    Little is known about how alcohol consumption promotes the onset of human breast cancer(s). One hypothesis is that ethanol induces metabolic changes in the tumor microenvironment, which then enhances epithelial tumor growth. To experimentally test this hypothesis, we used a co-culture system consisting of human breast cancer cells (MCF7) and hTERT-immortalized fibroblasts. Here, we show that ethanol treatment (100 mM) promotes ROS production and oxidative stress in cancer-associated fibroblasts, which is sufficient to induce myofibroblastic differentiation. Oxidative stress in stromal fibroblasts also results in the onset of autophagy/mitophagy, driving the induction of ketone body production in the tumor microenvironment. Interestingly, ethanol has just the opposite effect in epithelial cancer cells, where it confers autophagy resistance, elevates mitochondrial biogenesis and induces key enzymes associated with ketone re-utilization (ACAT1/OXCT1). During co-culture, ethanol treatment also converts MCF7 cells from an ER(+) to an ER(-) status, which is thought to be associated with “stemness,” more aggressive behavior and a worse prognosis. Thus, ethanol treatment induces ketone production in cancer-associated fibroblasts and ketone re-utilization in epithelial cancer cells, fueling tumor cell growth via oxidative mitochondrial metabolism (OXPHOS). This “two-compartment” metabolic model is consistent with previous historical observations that ethanol is first converted to acetaldehyde (which induces oxidative stress) and then ultimately to acetyl-CoA (a high-energy mitochondrial fuel), or can be used to synthesize ketone bodies. As such, our results provide a novel mechanism by which alcohol consumption could metabolically convert “low-risk” breast cancer patients to “high-risk” status, explaining tumor recurrence or disease progression. Hence, our findings have clear implications for both breast cancer prevention and therapy. Remarkably, our results

  19. Local anesthetics for brain tumor resection: current perspectives

    Directory of Open Access Journals (Sweden)

    Potters JW

    2018-02-01

    Full Text Available Jan-Willem Potters, Markus Klimek Department of Anesthesiology, Erasmus MC, Rotterdam, The Netherlands Abstract: This review summarizes the added value of local anesthetics in patients undergoing craniotomy for brain tumor resection, which is a procedure that is carried out frequently in neurosurgical practice. The procedure can be carried out under general anesthesia, sedation with local anesthesia or under local anesthesia only. Literature shows a large variation in the postoperative pain intensity ranging from no postoperative analgesia requirement in two-thirds of the patients up to a rate of 96% of the patients suffering from severe postoperative pain. The only identified causative factor predicting higher postoperative pain scores is infratent