WorldWideScience

Sample records for cancer conference mechanisms

  1. Conference scene: 2nd cancer epigenetics conference.

    Science.gov (United States)

    Smith, Cassandra L

    2013-04-01

    The GTC Cancer Summit: Novel Approaches to Drug Discovery was divided into two parallel tracks: the 2nd Cancer Epigenetics Conference, and the Protein Kinases and Drug Design Conference. The 2nd Cancer Epigenetics Conference focused on exciting changes in drug discovery that include an unprecedented private and public collaboration on drug discovery in epigenetics through the Structural Genomics Consortium (SGC), which has led to several major breakthroughs including: the development of small-molecule inhibitors that interfere with protein interactions, especially bromodomain-containing protein acetylation readers; the indirect but successful targeting of the elusive MYC oncogene; and the identification of epigenetic drugs that are disease-specific. Also reported were the development of clinically useful DNA methylation assays; cell, peptide and protein arrays for testing antibody- and protein-binding specificity; and tools for chromatin capture and DNA modification analysis. Several groups reported on the lack of specificity of some commercial, but unnamed, antibodies used for epigenetic studies.

  2. PREFACE: XXI Fluid Mechanics Conference

    Science.gov (United States)

    Szmyd, Janusz S.; Fornalik-Wajs, Elzbieta; Jaszczur, Marek

    2014-08-01

    This Conference Volume contains the papers presented at the 21st Fluid Mechanics Conference (XXI FMC) held at AGH - University of Science and Technology in Krakow, Poland, 15-18 June 2014, and accepted for Proceedings published in the Journal of Physics: Conference Series. The Fluid Mechanics Conferences have been taking place every two years since 1974, a total of forty years. The 21st Fluid Mechanics Conference (XXI FMC) is being organized under the auspices of the Polish Academy of Sciences, Committee of Mechanics. The goal of this conference is to provide a forum for the exposure and exchange of ideas, methods and results in fluid mechanics. Conference topics include, but are not limited to Aerodynamics, Atmospheric Science, Bio-Fluids, Combustion and Reacting Flows, Computational Fluid Dynamics, Experimental Fluid Mechanics, Flow Machinery, General Fluid Dynamics, Hydromechanics, Heat and Fluid Flow, Measurement Techniques, Micro- and Nano- Flow, Multi-Phase Flow, Non-Newtonian Fluids, Rotating and Stratified Flows, Turbulence. Within the general subjects of this conference, the Professor Janusz W. Elsner Competition for the best fluid mechanics paper presented during the Conference is organized. Authors holding a M.Sc. or a Ph.D. degree and who are not older than 35 years of age may enter the Competition. Authors with a Ph.D. degree must present individual papers; authors with a M.Sc. degree may present papers with their supervisor as coauthor, including original results of experimental, numerical or analytic research. Six state-of-the-art keynote papers were delivered by world leading experts. All contributed papers were peer reviewed. Recommendations were received from the International Scientific Committee, reviewers and the advisory board. Accordingly, of the 163 eligible extended abstracts submitted, after a review process by the International Scientific Committee, 137 papers were selected for presentation at the 21st Fluid Mechanics Conference, 68

  3. International Conference on Computational Mechanics

    CERN Document Server

    Atluri, Satya

    1986-01-01

    It is often said that these days there are too many conferences on general areas of computational mechanics. mechanics. and numer ical methods. vJhile this may be true. the his tory of scientific conferences is itself quite short. According to Abraham Pais (in "Subtle is the Lord ...• " Oxford University Press. 1982. p.80). the first international scientific conference ever held was the Karlsruhe Congress of Chemists. 3-5 September 1860 in Karlsruhe. Germany. There were 127 chemists in attendance. and the participants came from Austria. Belgium. France. Germany. Great Britain. Italy. Mexico. Poland. Russia. Spain. Sweden. and Switzerland. At the top of the agenda of the points to be discussed at this conference was the question: "Shall a difference be made between the expressions molecule and atom?" Pais goes on to note: "The conference did not at once succeed in bringing chemists closer together ... It is possible that the older men were offended by the impetuous behavior and imposing manner of the younger...

  4. Fourth European Conference on Mechanism Science (EUCOMES 2012 Conference)

    CERN Document Server

    Ceccarelli, Marco; New Trends in Mechanism and Machine Science : Theory and Applications in Engineering

    2013-01-01

    This book contains the papers of the European Conference on Mechanisms Science (EUCOMES 2012 Conference). The book presents the most recent research developments in the mechanism and machine science field and their applications. Topics addressed are theoretical kinematics, computational kinematics, mechanism design, experimental mechanics, mechanics of robots, dynamics of machinery, dynamics of multi-body systems, control issues of mechanical systems, mechanisms for biomechanics, novel designs, mechanical transmissions, linkages and manipulators, micro-mechanisms, teaching methods, history of mechanism science and industrial and non-industrial applications. This volume will also serve as an interesting reference for European activity in the fields of Mechanism and Machine Science as well as a source of inspiration for future works and developments.

  5. 6th International Conference on Mechanism Science

    CERN Document Server

    Flores, Paulo

    2017-01-01

    This book collects the most recent advances in mechanism science and machine theory with application to engineering. It contains selected peer-reviewed papers of the sixth International Conference on Mechanism Science, held in Nantes, France, 20-23 September 2016, covering topics on mechanism design and synthesis, mechanics of robots, mechanism analysis, parallel manipulators, tensegrity mechanisms, cable mechanisms, control issues in mechanical systems, history of mechanisms, mechanisms for biomechanics and surgery and industrial and nonindustrial applications.

  6. First Barcelona Conference on Epigenetics and Cancer

    Science.gov (United States)

    Palau, Anna; Perucho, Manuel; Esteller, Manel; Buschbeck, Marcus

    2014-01-01

    The Barcelona Conference on Epigenetics and Cancer (BCEC) entitled “Challenges, opportunities and perspectives” took place November 21–22, 2013 in Barcelona. The 2013 BCEC is the first edition of a series of annual conferences jointly organized by five leading research centers in Barcelona. These centers are the Institute of Predictive and Personalized Medicine of Cancer (IMPPC), the Biomedical Campus Bellvitge with its Program of Epigenetics and Cancer Biology (PEBC), the Centre for Genomic Regulation (CRG), the Institute for Biomedical Research (IRB), and the Molecular Biology Institute of Barcelona (IBMB). Manuel Perucho and Marcus Buschbeck from the Institute of Predictive and Personalized Medicine of Cancer put together the scientific program of the first conference broadly covering all aspects of epigenetic research ranging from fundamental molecular research to drug and biomarker development and clinical application. In one and a half days, 23 talks and 50 posters were presented to a completely booked out audience counting 270 participants. PMID:24413145

  7. First Barcelona Conference on Epigenetics and Cancer.

    Science.gov (United States)

    Palau, Anna; Perucho, Manuel; Esteller, Manel; Buschbeck, Marcus

    2014-03-01

    The Barcelona Conference on Epigenetics and Cancer (BCEC) entitled "Challenges, opportunities and perspectives" took place November 21-22, 2013 in Barcelona. The 2013 BCEC is the first edition of a series of annual conferences jointly organized by five leading research centers in Barcelona. These centers are the Institute of Predictive and Personalized Medicine of Cancer (IMPPC), the Biomedical Campus Bellvitge with its Program of Epigenetics and Cancer Biology (PEBC), the Centre for Genomic Regulation (CRG), the Institute for Biomedical Research (IRB), and the Molecular Biology Institute of Barcelona (IBMB). Manuel Perucho and Marcus Buschbeck from the Institute of Predictive and Personalized Medicine of Cancer put together the scientific program of the first conference broadly covering all aspects of epigenetic research ranging from fundamental molecular research to drug and biomarker development and clinical application. In one and a half days, 23 talks and 50 posters were presented to a completely booked out audience counting 270 participants.

  8. 4th International Conference on Nonlinear Mechanics

    CERN Document Server

    Maugin, G

    2003-01-01

    The mechanics of electromagnetic materials and structures has been developing rapidly with extensive applications in, e. g. , electronics industry, nuclear engineering, and smart materials and structures. Researchers in this interdisciplinary field are with diverse background and motivation. The Symposium on the Mechanics of Electromagnetic Materials and Structures of the Fourth International Conference on Nonlinear Mechanics in Shanghai, China in August 13-16, 2002 provided an opportunity for an intimate gathering of researchers and exchange of ideas. This volume contains papers based on most of the presentations at the symposium, and articles from a few invited contributors. These papers reflect some of the recent activities in the mechanics of electromagnetic materials and structures. The first twelve papers are in the order in which they were listed in the program of the conference. These are followed by six invited papers in alphabetical order of the last names of the first authors. We would like to exte...

  9. Barcelona conference on epigenetics and cancer 2016 - beyond cancer genomes.

    Science.gov (United States)

    Dumbovic, Gabrijela; Biayna, Josep; Font, Berta; Buschbeck, Marcus; Forcales, Sonia-V

    2017-03-04

    The Barcelona Conference on Epigenetics and Cancer (BCEC) entitled "Beyond Cancer Genomes" took place October 13(th) and 14(th) 2016 in Barcelona. The 2016 BCEC was the fourth edition of a series of annual conferences coordinated by Marcus Buschbeck and subsequently organized by leading research centers in Barcelona together with B•DEBATE, a joint initiative of BIOCAT and "La Caixa" Foundation. Salvador Aznar-Benitah, Eduard Batlle, and Raúl Méndez from the Institute for Research in Biomedicine in Barcelona selected the 2016 BCEC panel of speakers. As the title indicates, this year's conference expanded the epigenetic focus to include additional cancer-relevant topics, such as tumor heterogeneity and RNA regulation. Methods to develop therapeutic approaches on the basis of novel insights have been discussed in great detail. The conference has attracted 217 participants from 11 countries.

  10. International Conference on Mechanical Engineering and Technology

    CERN Document Server

    Mechanical Engineering and Technology

    2012-01-01

    The volume includes a set of selected papers extended and revised from the 2011 International Conference on Mechanical Engineering and Technology, held on London, UK, November 24-25, 2011.   Mechanical engineering technology is the application of physical principles and current technological developments to the creation of useful machinery and operation design. Technologies such as solid models may be used as the basis for finite element analysis (FEA) and / or computational fluid dynamics (CFD) of the design. Through the application of computer-aided manufacturing (CAM), the models may also be used directly by software to create "instructions" for the manufacture of objects represented by the models, through computer numerically controlled (CNC) machining or other automated processes, without the need for intermediate drawings.   This volume covers the subject areas of mechanical engineering and technology, and also covers interdisciplinary subject areas of computers, communications, control and automation...

  11. 2014 Annual Conference on Experimental and Applied Mechanics

    CERN Document Server

    Korach, Chad; Zavattieri, Pablo; Prorok, Barton; Grande-Allen, K; Carroll, Jay; Daly, Samantha; Qi, H; Antoun, Bonnie; Hall, Richard; Lu, Hongbing; Arzoumanidis, Alex; Silberstein, Meredith; Furmanski, Jevan; Amirkhizi, Alireza; Gonzalez-Gutierrez, Joamin; Jin, Helena; Sciammarella, Cesar; Yoshida, Sanichiro; Lamberti, Luciano; Sottos, Nancy; Rowlands, Robert; Dannemann, Kathryn; Tandon, Gyaneshwar; Song, Bo; Casem, Daniel; Kimberley, Jamie; Starman, LaVern; Hay, Jennifer; Shaw, Gordon

    2015-01-01

    Proceedings of the 2014 Annual Conference on Experimental and Applied Mechanics, the seventh volume of eight from the Conference, brings together contributions to this important area of research and engineering.  The collection presents early findings and case studies on a wide range of areas, including: Soft Tissues Mechanics Natural Materials & Bio-Inspiration Tissue Engineering Cells Mechanics

  12. Nuclear Mechanics in Cancer

    Science.gov (United States)

    Denais, Celine; Lammerding, Jan

    2015-01-01

    Despite decades of research, cancer metastasis remains an incompletely understood process that is as complex as it is devastating. In recent years, there has been an increasing push to investigate the biomechanical aspects of tumorigenesis, complementing the research on genetic and biochemical changes. In contrast to the high genetic variability encountered in cancer cells, almost all metastatic cells are subject to the same physical constraints as they leave the primary tumor, invade surrounding tissues, transit through the circulatory system, and finally infiltrate new tissues. Advances in live cell imaging and other biophysical techniques, including measurements of subcellular mechanics, have yielded stunning new insights into the physics of cancer cells. While much of this research has been focused on the mechanics of the cytoskeleton and the cellular microenvironment, it is now emerging that the mechanical properties of the cell nucleus and its connection to the cytoskeleton may play a major role in cancer metastasis, as deformation of the large and stiff nucleus presents a substantial obstacle during the passage through the dense interstitial space and narrow capillaries. Here, we present an overview of the molecular components that govern the mechanical properties of the nucleus and we discuss how changes in nuclear structure and composition observed in many cancers can modulate nuclear mechanics and promote metastatic processes. Improved insights into this interplay between nuclear mechanics and metastatic progression may have powerful implications in cancer diagnostics and therapy and may reveal novel therapeutic targets for pharmacological inhibition of cancer cell invasion. PMID:24563360

  13. Effect of Multidisciplinary Cancer Conference on Treatment Plan for Patients With Primary Rectal Cancer.

    Science.gov (United States)

    Snelgrove, Ryan C; Subendran, Jhananiee; Jhaveri, Kartik; Thipphavong, Seng; Cummings, Bernard; Brierley, James; Kirsch, Richard; Kennedy, Erin D

    2015-07-01

    Although multidisciplinary cancer conferences have been reported to lead to improved patient outcomes, few studies have reported results of these for rectal cancer. The purpose of this work was to assess the quality of multidisciplinary cancer conferences, the effect of the conference on the initial treatment plan, compliance with the conference treatment recommendations, and clinical outcomes for rectal cancer. This was a prospective, longitudinal study. The study was conducted at a tertiary care academic hospital. Patients with primary rectal cancer were included in this study. The intervention was a rectal cancer-specific multidisciplinary cancer conference. The quality of the multidisciplinary cancer conference was assessed using the Cancer Care Ontario Multidisciplinary Cancer Conference standards score. A change in treatment plan was defined as a change from the initial treatment plan selected by the treating physician to an alternate treatment plan recommended at the conference. Twenty-five multidisciplinary cancer conferences were conducted over a 10-month study period. The Cancer Care Ontario Multidisciplinary Cancer Conference standards score was 7 (from a maximum score of 9). Forty-two patients with primary rectal cancer were presented, and there was a 29% (12/42) change in the initial treatment plan. A total of 42% (5/12) of these changes were attributed to reinterpretation of the MRI findings. There was 100% compliance with the conference treatment recommendations. The circumferential resection margin was positive in 5.5% (2/36). Selection bias may have led to an overestimate of effect, and there is no control group for comparison of clinical outcomes. A high-quality rectal cancer-specific multidisciplinary cancer conference led to a 29% change in the treatment plan for patients with primary rectal cancer, with almost half of these changes attributed to reinterpretation of the magnetic resonance images.

  14. Third Preventing Overdiagnosis conference | Division of Cancer Prevention

    Science.gov (United States)

    Overdiagnosis Conference Early Bird Registration Open and Abstract Submission This event will be co-hosted by the National institutes of Health, National Cancer Institute in Washington DC, September 01-03, 2015. |

  15. International Conference on Research and Innovations in Mechanical Engineering

    CERN Document Server

    Singh, Paramjit; Singh, Harwinder; Brar, Gurinder

    2014-01-01

    This book comprises the proceedings of International Conference on Research and Innovations in Mechanical Engineering (ICRIME 2013) organized by Guru Nanak Dev Engineering College, Ludhiana with support from AICTE, TEQIP, DST and PTU, Jalandhar. This international conference served as a premier forum for communication of new advances and research results in the fields of mechanical engineering. The proceedings reflect the conference’s emphasis on strong methodological approaches and focus on applications within the domain of mechanical engineering. The contents of this volume aim to highlight new theoretical and experimental findings in the fields of mechanical engineering and closely related fields, including interdisciplinary fields such as robotics and mechatronics.

  16. International Conference on Differential Equations and Nonlinear Mechanics

    CERN Document Server

    2001-01-01

    The International Conference on Differential Equations and Nonlinear Mechanics was hosted by the University of Central Florida in Orlando from March 17-19, 1999. One of the conference days was dedicated to Professor V. Lakshmikantham in th honor of his 75 birthday. 50 well established professionals (in differential equations, nonlinear analysis, numerical analysis, and nonlinear mechanics) attended the conference from 13 countries. Twelve of the attendees delivered hour long invited talks and remaining thirty-eight presented invited forty-five minute talks. In each of these talks, the focus was on the recent developments in differential equations and nonlinear mechanics and their applications. This book consists of 29 papers based on the invited lectures, and I believe that it provides a good selection of advanced topics of current interest in differential equations and nonlinear mechanics. I am indebted to the Department of Mathematics, College of Arts and Sciences, Department of Mechanical, Materials and Ae...

  17. XII International Conference on the Theory of Machines and Mechanisms

    CERN Document Server

    Bílek, Martin; Žabka, Petr

    2017-01-01

    This book presents the most recent advances in the research of machines and mechanisms. It collects 54 reviewed papers presented at the XII International Conference on the Theory of Machines and mechanisms (TMM 2016) held in Liberec, Czech Republic, September 6-8, 2016. This volume offers an international selection of the most important new results and developments, grouped in six different parts, representing a well-balanced overview, and spanning the general theory of machines and mechanisms, through analysis and synthesis of planar and spatial mechanisms, linkages and cams, robots and manipulators, dynamics of machines and mechanisms, rotor dynamics, computational mechanics, vibration and noise in machines, optimization of mechanisms and machines, mechanisms of textile machines, mechatronics to the control and monitoring systems of machines. This conference is traditionally organised every four year under the auspices of the international organisation IFToMM and the Czech Society for Mechanics.

  18. The Joint International Conference of the XII International Conference on Mechanisms and Mechanical Transmissions (MTM) and the XXIII International Conference on Robotics (Robotics ’16)

    CERN Document Server

    Lovasz, Erwin-Christian; Hüsing, Mathias; Maniu, Inocentiu; Gruescu, Corina

    2017-01-01

    This volume presents the proceedings of the Joint International Conference of the XII International Conference on Mechanisms and Mechanical Transmissions (MTM) and the XXIII International Conference on Robotics (Robotics ’16), that was held in Aachen, Germany, October 26th-27th, 2016. It contains applications of mechanisms and transmissions in several modern technical fields such as mechatronics, biomechanics, machines, micromachines, robotics and apparatus. In connection with these fields, the work combines the theoretical results with experimental testing. The book presents reviewed papers developed by researchers specialized in mechanisms analysis and synthesis, dynamics of mechanisms and machines, mechanical transmissions, biomechanics, precision mechanics, mechatronics, micromechanisms and microactuators, computational and experimental methods, CAD in mechanism and machine design, mechanical design of robot architecture, parallel robots, mobile robots, micro and nano robots, sensors and actuators in ro...

  19. 2012 International Conference on Mechanical and Electronic Engineering

    CERN Document Server

    Lin, Sally; ICMEE2012; Advances in Mechanical and Electronic Engineering v.2

    2012-01-01

    This book includes the volume 2 of the proceedings of the 2012 International Conference on Mechanical and Electronic Engineering(ICMEE2012), held at June 23-24,2012 in Hefei, China. The conference provided a rare opportunity to bring together worldwide researchers who are working in the fields. This volume 2 is focusing on Mechatronic Engineering and Technology,  Electronic Engineering and Electronic Information Technology .

  20. 2012 Annual Conference on Experimental and Applied Mechanics

    CERN Document Server

    Crone, Wendy; Jin, Helena; Sciammarella, Cesar; Furlong, Cosme; Furlong, Cosme; Chalivendra, Vijay; Song, Bo; Casem, Daniel; Antoun, Bonnie; Qi, H; Hall, Richard; Tandon, GP; Lu, Hongbing; Lu, Charles; Yoshida, Sanichiro; Shaw, Gordon; Prorok, Barton; Barthelat, François; Korach, Chad; Grande-Allen, K; Lipke, Elizabeth; Lykofatitits, George; Zavattieri, Pablo; Starman, LaVern; Patterson, Eann; Backman, David; Cloud, Gary; Vol.1 Dynamic Behavior of Materials; Vol.2 Challenges in Mechanics of Time-Dependent Materials and Processes in Conventional and Multifunctional Materials; Vol.3 Imaging Methods for Novel Materials and Challenging Applications; Vol.4 Experimental and Applied Mechanics; Vol.5 Mechanics of Biological Systems and Materials; Vol.6 MEMS and Nanotechnology; Vol.7 Composite Materials and Joining Technologies for Composites

    2013-01-01

    Experimental and Applied Mechanics, Volume 4: Proceedings of the 2012 Annual Conference on Experimental and Applied Mechanics, the fourth volume of seven from the Conference, brings together 54 contributions to this important area of research and engineering. The collection presents early findings and case studies on fundamental and applied aspects of Experimental and Applied Mechanics, including papers on:  Fracture & Fatigue Microscale & Microstructural Effects in Fatigue & Fracture Material Applications Composite Characterization Using Digital Image Correlation Techniques Multi-Scale Simulation and Testing of Composites Residual Stress Inverse Problems/Hybrid Methods Nano-Composites Microstructure Material Characterization Modeling and Uncertainty Quantification Impact Behavior of Composites.

  1. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer

    Science.gov (United States)

    Colombo, Nicoletta; Creutzberg, Carien; Amant, Frederic; Bosse, Tjalling; González-Martín, Antonio; Ledermann, Jonathan; Marth, Christian; Nout, Remi; Querleu, Denis; Mirza, Mansoor Raza; Sessa, Cristiana

    2016-01-01

    Abstract The first joint European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) consensus conference on endometrial cancer was held on 11–13 December 2014 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of endometrial cancer. Before the conference, the expert panel prepared three clinically-relevant questions about endometrial cancer relating to the following four areas: prevention and screening, surgery, adjuvant treatment and advanced and recurrent disease. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. Results of this consensus conference, together with a summary of evidence supporting each recommendation, are detailed in this article. All participants have approved this final article. PMID:26645990

  2. Fifth Ovarian Cancer Consensus Conference: individualized therapy and patient factors

    NARCIS (Netherlands)

    McGee, J.; Bookman, M.; Harter, P.; Marth, C.; McNeish, I.; Moore, K.N.; Poveda, A.; Hilpert, F.; Hasegawa, K.; Bacon, M.; Gatsonis, C.; Kridelka, F.; Berek, J.; Ottevanger, N.; Levy, T.; Silverberg, S.; Kim, B.G.; Hirte, H.; Okamoto, A.; Stuart, G.; Ochiai, K.

    2017-01-01

    This manuscript reports the consensus statements regarding the design and conduct of clinical trials in patients with newly diagnosed and recurrent epithelial ovarian cancer (EOC), following deliberation at the Fifth Ovarian Cancer Consensus Conference (OCCC), held in Tokyo in November 2015. Three

  3. ESMO-ESGO-ESTRO consensus conference on endometrial cancer

    DEFF Research Database (Denmark)

    Colombo, Nicoletta; Creutzberg, Carien; Amant, Frederic

    2015-01-01

    The first joint European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) consensus conference on endometrial cancer was held on 11-13 December 2014 in Milan, Italy, and comprised a multidisciplinary...... panel of 40 leading experts in the management of endometrial cancer. Before the conference, the expert panel prepared three clinically-relevant questions about endometrial cancer relating to the following four areas: Prevention and screening, surgery, adjuvant treatment and advanced and recurrent...

  4. Epigenetic cancer prevention mechanisms in skin cancer.

    Science.gov (United States)

    Saha, Kamalika; Hornyak, Thomas J; Eckert, Richard L

    2013-10-01

    Epigenetics is an important emerging area for study of mechanisms of cancer prevention. In recent years, it has been realized that cancer prevention agents, derived from natural dietary sources, impact cancer cell survival by modulating epigenetic processes. In the present manuscript, we review key epigenetic regulatory mechanisms and examine the impact of sulforaphane and green tea polyphenols on these processes. We also discuss available information on the epigenetics in the context of skin cancer. These studies indicate that diet-derived chemopreventive agents modulate DNA methylation status and histone modification via multiple processes and point to additional areas for study of epigenetic mechanisms in skin cancer.

  5. 2016 Annual Conference on Experimental and Applied Mechanics

    CERN Document Server

    Lamberson, Leslie; Kimberley, Jamie; Korach, Chad; Tekalur, Srinivasan; Zavattieri, Pablo; Yoshida, Sanichiro; Lamberti, Luciano; Sciammarella, Cesar; Ralph, W; Singh, Raman; Tandon, Gyaneshwar; Thakre, Piyush; Zavattieri, Pablo; Zhu, Yong; Zehnder, Alan; Zehnder, Alan; Carroll, Jay; Hazeli, Kavan; Berke, Ryan; Pataky, Garrett; Cavalli, Matthew; Beese, Alison; Xia, Shuman; Starman, La; Hay, Jennifer; Karanjgaokar, Nikhil; Quinn, Simon; Balandraud, Xavier; Cloud, Gary; Patterson, Eann; Backman, David

    2017-01-01

    Dynamic Behavior of Materials, Volume 1 of the Proceedings of the 2016 SEM Annual Conference& Exposition on Experimental and Applied Mechanics, the first volume of ten from the Conference, brings together contributions to this important area of research and engineering. The collection presents early findings and case studies on fundamental and applied aspects of Experimental Mechanics, including papers on: Quantitative Visualization Fracture & Fragmentation Dynamic Behavior of Low Impedance Materials Shock & Blast Dynamic Behavior of Composites Novel Testing Techniques Hybrid Experimental & Computational Methods Dynamic Behavior of Geo-materials General Material Behavior.

  6. Conference on Mathematical Results in Quantum Mechanics

    CERN Document Server

    Exner, Pavel; Tater, Miloš; QMath-7

    1999-01-01

    At the age of almost three quarters of a century, quantum mechanics is by all accounts a mature theory. There were times when it seemed that it had borne its best fruit already and would give way to investigation of deeper levels of matter. Today this sounds like rash thinking. Modern experimental techniques have led to discoveries of numerous new quantum effects in solid state, optics and elsewhere. Quantum mechanics is thus gradually becoming a basis for many branches of applied physics, in this way entering our everyday life. While the dynamic laws of quantum mechanics are well known, a proper theoretical understanding requires methods which would allow us to de­ rive the abundance of observed quantum effects from the first principles. In many cases the rich structure hidden in the Schr6dinger equation can be revealed only using sophisticated tools. This constitutes a motivation to investigate rigorous methods which yield mathematically well-founded properties of quantum systems.

  7. 5th European Conference on Mechanisms Science (EUCOMES)

    CERN Document Server

    Viadero, Fernando; New Trends in Mechanism and Machine Science : from Fundamentals to Industrial Applications

    2015-01-01

    This work presents the most recent research in the mechanism and machine science field and its applications. The topics covered include: theoretical kinematics, computational kinematics, mechanism design, experimental mechanics, mechanics of robots, dynamics of machinery, dynamics of multi-body systems, control issues of mechanical systems, mechanisms for biomechanics, novel designs, mechanical transmissions, linkages and manipulators, micro-mechanisms, teaching methods, history of mechanism science and industrial and non-industrial applications. This volume consists of the Proceedings of the 5th European Conference on Mechanisms Science (EUCOMES), that was held in Guimarães, Portugal, from September 16 – 20, 2014. The EUCOMES is the main forum for the European community working in Mechanisms and Machine Science.

  8. Mechanisms of Cancer - Annual Plan

    Science.gov (United States)

    NCI works to understand the mechanisms of cancer cell growth, survival, and metastasis. Get more information on how NCI supports basic scientific research that will lead to new ways to prevent, detect, and treat cancer.

  9. 2nd Conference on Mechanisms, Transmissions and Applications

    CERN Document Server

    Pinto, Charles; Lovasz, Erwin-Christian

    2014-01-01

    The Second Conference on Mechanisms, Transmissions and Applications - MeTrApp 2013 was organised by the Mechanical Engineering Department of the University of the Basque Country (Spain) under the patronage of the IFToMM Technical Committees Linkages and Mechanical Controls and Micromachines and the Spanish Association of Mechanical Engineering.  The aim of the workshop was to bring together researchers, scientists, industry experts and students to provide, in a friendly and stimulating environment, the opportunity to exchange know-how and promote collaboration in the field of Mechanism and Machine Science.  The topics treated in this volume are mechanism and machine design, biomechanics, mechanical transmissions, mechatronics, computational and experimental methods, dynamics of mechanisms and micromechanisms and microactuators.

  10. 1st ESMO Consensus Conference in lung cancer; Lugano 2010: small-cell lung cancer

    DEFF Research Database (Denmark)

    Stahel, R; Thatcher, N; Früh, M

    2011-01-01

    The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21st and 22nd May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics and medical, surgical and radiation oncology. Before the conference...

  11. International Joint Conference on Mechanics, Design Engineering & Advanced Manufacturing

    CERN Document Server

    Nigrelli, Vincenzo; Oliveri, Salvatore; Peris-Fajarnes, Guillermo; Rizzuti, Sergio

    2017-01-01

    This book gathers papers presented at the International Joint Conference on Mechanics, Design Engineering and Advanced Manufacturing (JCM 2016), held on 14-16 September, 2016, in Catania, Italy. It reports on cutting-edge topics in product design and manufacturing, such as industrial methods for integrated product and process design; innovative design; and computer-aided design. Further topics covered include virtual simulation and reverse engineering; additive manufacturing; product manufacturing; engineering methods in medicine and education; representation techniques; and nautical, aeronautics and aerospace design and modeling. The book is divided into eight main sections, reflecting the focus and primary themes of the conference. The contributions presented here will not only provide researchers, engineers and experts in a range of industrial engineering subfields with extensive information to support their daily work; they are also intended to stimulate new research directions, advanced applications of t...

  12. Molecular mechanisms of cancer

    National Research Council Canada - National Science Library

    Weber, Georg F

    2007-01-01

    ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Section I. General Mechanisms of Transformation 1. Theories of Carcinogenesis...

  13. Barcelona conference on epigenetics and cancer 2016 – beyond cancer genomes

    Science.gov (United States)

    Dumbovic, Gabrijela; Biayna, Josep; Font, Berta; Buschbeck, Marcus; Forcales, Sonia-V.

    2017-01-01

    ABSTRACT The Barcelona Conference on Epigenetics and Cancer (BCEC) entitled “Beyond Cancer Genomes” took place October 13th and 14th 2016 in Barcelona. The 2016 BCEC was the fourth edition of a series of annual conferences coordinated by Marcus Buschbeck and subsequently organized by leading research centers in Barcelona together with B•DEBATE, a joint initiative of BIOCAT and “La Caixa” Foundation. Salvador Aznar-Benitah, Eduard Batlle, and Raúl Méndez from the Institute for Research in Biomedicine in Barcelona selected the 2016 BCEC panel of speakers. As the title indicates, this year's conference expanded the epigenetic focus to include additional cancer-relevant topics, such as tumor heterogeneity and RNA regulation. Methods to develop therapeutic approaches on the basis of novel insights have been discussed in great detail. The conference has attracted 217 participants from 11 countries. PMID:28121228

  14. 2013 Annual Conference on Experimental and Applied Mechanics

    CERN Document Server

    Casem, Dan; Kimberley, Jamie; Barthelat, François; Zavattieri, Pablo; Antoun, Bonnie; Qi, H; Hall, Richard; Tandon, G; Lu, Hongbing; Lu, Charles; Furmanski, Jevan; Amirkhizi, Alireza; Korach, Chad; Prorok, Barton; Grande-Allen, K; III, Gordon; Prorok, Barton; Starman, LaVern; Furlong, Cosme; Tandon, G; Tekalur, Srinivasan; Ralph, Carter; Sottos, Nancy; Blaiszik, Benjamin; Jay, Carroll; Rossi, Marco; Sasso, Marco; Connesson, Nathanael; Singh, Raman; DeWald, Adrian; Backman, David; Gloeckner, Paul; Jin, Helena; Sciammarella, Cesar; Yoshida, Sanichiro; Lamberti, Luciano; Vol.1 Dynamic Behavior of Materials; Vol.2 Challenges In Mechanics of Time-Dependent Materials and Processes in Conventional and Multifunctional Materials; Vol.3 Advancement of Optical Methods in Experimental Mechanics; Vol.4 Mechanics of Biological Systems and Materials; Vol.5 MEMS and Nanotechnology; Vol.6 Experimental Mechanics of Composite, Hybrid, and Multifunctional Materials; Vol.7 Fracture and Fatigue; Vol.8 Residual Stress, Thermomechanics & Infrared Imaging, Hybrid Techniques and Inverse Problems; SEM 2013

    2014-01-01

    This critical collection examines a range of topics in fracture and fatigue, including environmental and loading effects in fracture and fatigue and DIC and fracture, as presented in early findings and case studies from the Proceedings of the 2013 Annual Conference on Experimental and Applied Mechanics. The collection includes papers in the following general technical research areas: • Microstructural Effects in Fatigue & Fracture • Fracture of Interfaces • Fracture of Composites and Interface Cracks • Fatigue & Fracture: Environmental & Loading Eff ects • Fracture & Digital Image Correlation Fracture and Fatigue

  15. 2014 Joint Conference on Mechanical Design Engineering and Advanced Manufacturing

    CERN Document Server

    Daidie, Alain; Eynard, Benoit; Paredes, Manuel

    2016-01-01

    Covering key topics in the field such as technological innovation, human-centered sustainable engineering and manufacturing, and manufacture at a global scale in a virtual world, this book addresses both advanced techniques and industrial applications of key research in interactive design and manufacturing. Featuring the full papers presented at the 2014 Joint Conference on Mechanical Design Engineering and Advanced Manufacturing, which took place in June 2014 in Toulouse, France, it presents recent research and industrial success stories related to implementing interactive design and manufacturing solutions.

  16. Epigenetic mechanisms in gastric cancer.

    Science.gov (United States)

    Gigek, Carolina Oliveira; Chen, Elizabeth Suchi; Calcagno, Danielle Queiroz; Wisnieski, Fernanda; Burbano, Rommel Rodriguez; Smith, Marilia Arruda Cardoso

    2012-06-01

    Cancer is considered one of the major health issues worldwide, and gastric cancer accounted for 8% of total cases and 10% of total deaths in 2008. Gastric cancer is considered an age-related disease, and the total number of newly diagnosed cases has been increasing as a result of the higher life expectancy. Therefore, the basic mechanisms underlying gastric tumorigenesis is worth investigation. This review provides an overview of the epigenetic mechanisms, such as DNA methylation, histone modifications, chromatin remodeling complex and miRNA, involved in gastric cancer. As the studies in gastric cancer continue, the mapping of an epigenome code is not far for this disease. In conclusion, an epigenetic therapy might appear in the not too distant future.

  17. The Typical Metabolic Modifiers Conferring Improvement in Cancer Resistance.

    Science.gov (United States)

    Tan, Wen; Zhong, Zhangfeng; Wang, Shengpeng; Liu, Hui; Yu, Hua; Tan, Rui; Hu, Xiaodong; Pan, Tingrui; Wang, Yitao

    2017-11-17

    Cancer metabolic reprogramming rekindles enthusiasm for the research of metabolic regulation in cancer drug resistance. A growing number of metabolic modifiers combined with cancer drugs obtain the expected efficacy in in vitro or in vivo studies, also in clinical trial studies, indicating a good potential of enhancing efficacy and reducing resistance. Hence, a comprehensive review on the attenuations of metabolic modifiers in cancer drug resistance is necessary for rational drug design and clinical cancer drug research. Cancer drug resistance and cancer metabolic reprogramming were used as the key words to collect publications with reference value in bibliographic databases. Specifically, the focused question is the advances of metabolic modifiers on cancer resistance improvement. Figures and tables were applied to analyze the interventions in accordance with the inclusion criteria. This review summarized the advances of metabolic modifiers combined with cancer drugs in in vitro, in vivo and clinical trial studies, especially for cancer resistance improvement. The relationship between metabolic regulation and cancer resistance was elaborated, and the potential metabolic modifiers were embraced. Metabolic targets were also visualized in categorization in 4 figures and expatiated in 4 tables. Three typical metabolic modifiers, namely lonidamine, 2-DG and 3-BrPA, conferring attenuation to cancer resistance were elucidated systematically. Metabolic regulation is an intervention with targeted perturbation in a modest manner and reflects homeostasis balance. When combined with cancer drugs, the metabolic modifiers always show exciting potential with practical significance, enhancing activity or exerting synergism. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup

    DEFF Research Database (Denmark)

    Wilson, M K; Pujade-Lauraine, E; Aoki, D

    2017-01-01

    This manuscript reports the consensus statements regarding recurrent ovarian cancer (ROC), reached at the fifth Ovarian Cancer Consensus Conference (OCCC), which was held in Tokyo, Japan, in November 2015. Three important questions were identified: (i) What are the subgroups for clinical trials i...

  19. Telemedicine and telesurgery in cancer care: inaugural conference at MD Anderson Cancer Center.

    Science.gov (United States)

    Satcher, Robert L; Bogler, Oliver; Hyle, Laurel; Lee, Andrew; Simmons, Angela; Williams, Robert; Hawk, Ernest; Matin, Surena; Brewster, Abenaa M

    2014-09-01

    Despite the growing incidence of cancer worldwide, there are an insufficient number of primary care physicians, community oncologists, and surgeons to meet the demand for cancer care, especially in rural and other medically underserved areas. Teleoncology, including diagnostics, treatment, and supportive care, has the potential to enhance access to cancer care and to improve clinician education and training. Major cancer centers such as The University of Texas MD Anderson Cancer Center must determine how teleoncology will be used as part of strategic planning for the future. The Telemedicine and Telesurgery in Cancer Care (TTCC) conference was convened to determine technologically based strategies for addressing global access to essential cancer care services. The TTCC conference brought policy makers together with physicians, legal and regulatory experts to define strategies to optimize available resources, including teleoncology, to advance global cancer care. The TTCC conference discourse provided insight into the present state of access to care, expertise, training, technology and other interventions, including teleoncology, currently available through MD Anderson, as well as a vision of what might be achievable in the future, and proposals for moving forward with a comprehensive strategy. © 2014 Wiley Periodicals, Inc.

  20. Mechanisms Linking Obesity and Cancer

    Science.gov (United States)

    Louie, Sharon M.; Roberts, Lindsay S.; Nomura, Daniel K.

    2013-01-01

    The incidence of obesity in US adults has been steadily increasing over the past few decades. Many comorbidities associated with obesity have been well-established such as type 2 diabetes and cardiovascular diseases. However, more recently an epidemiological relationship between obesity and the prevalence of a variety of cancers has also been uncovered. The shift of the paradigm surrounding white adipose tissue function from purely an energy storage tissue, to one that has both endocrine and metabolic relevance, has led to several mechanisms implicated in how obesity drives cancer prevalence and cancer deaths. Currently, there are four categories into which these mechanisms fall – increased lipids and lipid signaling, inflammatory responses, insulin resistance, and adipokines. In this review, we examine each of these categories and the mechanisms through which they drive cancer pathogenesis. Understanding the relationship(s) between obesity and cancer and especially the nodal points of control in these cascades will be essential in developing effective therapeutics or interventions for combating this deadly combination. PMID:23470257

  1. The First Children's Cancer Hospital, Egypt International Scientific Conference.

    Science.gov (United States)

    Zaghloul, Mohamed S

    2009-10-01

    A wide gathering of scientists, clinicians, pharmacists and nurses specialized in pediatric oncology practice met to celebrate the second anniversary of Children's Cancer Hospital, Egypt (CCHE). The celebration was in the form of high-brow teaching lectures and reports presented by international experts in the fields of pediatric CNS tumors, solid tumors (neuroblastoma, nephroblastoma, soft tissue and bone tumors, lymphoma, leukemia and pediatric oncology nursing. The conference extends its activities to hospital management, clinical pharmacy and telemedicine. Furthermore, CCHE experts presented the efforts performed to establish a state-of-the-art pediatric oncology hospital equipped with all needed facilities to raise the standard of care to the highest levels.

  2. Barcelona conference on epigenetics and cancer 2016 – beyond cancer genomes

    OpenAIRE

    Dumbovic, Gabrijela; Biayna, Josep; Font, Berta; Buschbeck, Marcus; Forcales, Sonia-V.

    2017-01-01

    The Barcelona Conference on Epigenetics and Cancer (BCEC) entitled “Beyond Cancer Genomes” took place October 13th and 14th 2016 in Barcelona. The 2016 BCEC was the fourth edition of a series of annual conferences coordinated by Marcus Buschbeck and subsequently organized by leading research centers in Barcelona together with B•DEBATE, a joint initiative of BIOCAT and “La Caixa” Foundation. Salvador Aznar-Benitah, Eduard Batlle, and Raúl Méndez from the Institute for Research in Biomedicine i...

  3. Obesity and Cancer Mechanisms: Cancer Metabolism.

    Science.gov (United States)

    Hopkins, Benjamin D; Goncalves, Marcus D; Cantley, Lewis C

    2016-12-10

    Obesity is a risk factor for cancer development and is associated with poor prognosis in multiple tumor types. The positive energy balance linked with obesity induces a variety of systemic changes including altered levels of insulin, insulin-like growth factor-1, leptin, adiponectin, steroid hormones, and cytokines. Each of these factors alters the nutritional milieu and has the potential to create an environment that favors tumor initiation and progression. Although the complete ramifications of obesity as it relates to cancer are still unclear, there is convincing evidence that reducing the magnitude of the systemic hormonal and inflammatory changes has significant clinical benefits. This review will examine the changes that occur in the obese state and review the biologic mechanisms that connect these changes to increased cancer risk. Understanding the metabolic changes that occur in obese individuals may also help to elucidate more effective treatment options for these patients when they develop cancer. Moving forward, targeted clinical trials examining the effects of behavioral modifications such as reduced carbohydrate intake, caloric restriction, structured exercise, and/or pharmacologic interventions such as the use of metformin, in obese populations may help to reduce their cancer risk.

  4. Obesity and Cancer Mechanisms: Cancer Metabolism

    Science.gov (United States)

    Hopkins, Benjamin D.; Goncalves, Marcus D.

    2016-01-01

    Obesity is a risk factor for cancer development and is associated with poor prognosis in multiple tumor types. The positive energy balance linked with obesity induces a variety of systemic changes including altered levels of insulin, insulin-like growth factor-1, leptin, adiponectin, steroid hormones, and cytokines. Each of these factors alters the nutritional milieu and has the potential to create an environment that favors tumor initiation and progression. Although the complete ramifications of obesity as it relates to cancer are still unclear, there is convincing evidence that reducing the magnitude of the systemic hormonal and inflammatory changes has significant clinical benefits. This review will examine the changes that occur in the obese state and review the biologic mechanisms that connect these changes to increased cancer risk. Understanding the metabolic changes that occur in obese individuals may also help to elucidate more effective treatment options for these patients when they develop cancer. Moving forward, targeted clinical trials examining the effects of behavioral modifications such as reduced carbohydrate intake, caloric restriction, structured exercise, and/or pharmacologic interventions such as the use of metformin, in obese populations may help to reduce their cancer risk. PMID:27903152

  5. ESMO-ESGO-ESTRO consensus conference on endometrial cancer: Diagnosis, treatment and follow-up

    National Research Council Canada - National Science Library

    Colombo, Nicoletta; Creutzberg, Carien; Amant, Frederic; Bosse, Tjalling; González-Martín, Antonio; Ledermann, Jonathan; Marth, Christian; Nout, Remi; Querleu, Denis; Mirza, Mansoor Raza; Sessa, Cristiana

    2015-01-01

    ...) and European Society of Gynaecological Oncology (ESGO) consensus conference on endometrial cancer was held on 11-13 December 2014 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of endometrial cancer...

  6. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment and follow-up

    National Research Council Canada - National Science Library

    Colombo, N; Creutzberg, C; Amant, F; Bosse, T; González-Martín, A; Ledermann, J; Marth, C; Nout, R; Querleu, D; Mirza, M R; Sessa, C

    2016-01-01

    ...) and European Society of Gynaecological Oncology (ESGO) consensus conference on endometrial cancer was held on 11-13 December 2014 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of endometrial cancer...

  7. Additional mechanisms conferring genetic susceptibility to Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Miguel eCalero

    2015-04-01

    Full Text Available Familial Alzheimer's disease (AD, mostly associated with early onset, is caused by mutations in three genes (APP, PSEN1 and PSEN2 involved in the production of the amyloid  peptide. In contrast, the molecular mechanisms that trigger the most common late onset sporadic AD remain largely unknown. With the implementation of an increasing number of case-control studies and the upcoming of large-scale genome-wide association studies (GWAS there is a mounting list of genetic risk factors associated to common genetic variants that have been associated to sporadic AD. Besides APOE, that presents a strong association with the disease (OR~4, the rest of these genes have moderate or low degrees of association, with OR ranging from 0.88 to 1.23. Taking together, these genes may account only for a fraction of the attributable AD risk and therefore, rare variants and epistastic gene interactions should be taken into account in order to get the full picture of the genetic risks associated to AD. Here, we review recent whole-exome studies looking for rare variants, somatic brain mutations with a strong association to the disease, and several studies dealing with epistasis as additional mechanisms conferring genetic susceptibility to AD. Altogether, recent evidence underlines the importance of defining molecular and genetic pathways and networks rather than the contribution of specific genes.

  8. Multidisciplinary team conferences promote treatment according to guidelines in rectal cancer

    DEFF Research Database (Denmark)

    Brännström, Fredrik; Bjerregaard, Jon K; Winbladh, Anders

    2015-01-01

    BACKGROUND: Multidisciplinary team (MDT) conferences have been introduced into standard cancer care, though evidence that it benefits the patient is weak. We used the national Swedish Rectal Cancer Register to evaluate predictors for case discussion at a MDT conference and its impact on treatment...

  9. Multidisciplinary Rectal Cancer Management: 2nd European Rectal Cancer Consensus Conference (EURECA-CC2).

    NARCIS (Netherlands)

    Valentini, V.; Aristei, C.; Glimelius, B.; Minsky, B.D.; Beets-Tan, R.G.; Borras, J.M.; Haustermans, K.; Maingon, P.; Overgaard, J.; Pahlman, L.; Quirke, P.; Schmoll, H.J.; Sebag-Montefiore, D.; Taylor, I.; Cutsem, E. van; Velde, C. van de; Cellini, N.; Latini, P.

    2009-01-01

    BACKGROUND AND PURPOSE: During the first decade of the 21st century a number of important European randomized studies were published. In order to help shape clinical practice based on best scientific evidence from the literature, the International Conference on 'Multidisciplinary Rectal Cancer

  10. Recommendations for mechanical ventilation of critically ill children from the Paediatric Mechanical Ventilation Consensus Conference (PEMVECC).

    Science.gov (United States)

    Kneyber, Martin C J; de Luca, Daniele; Calderini, Edoardo; Jarreau, Pierre-Henri; Javouhey, Etienne; Lopez-Herce, Jesus; Hammer, Jürg; Macrae, Duncan; Markhorst, Dick G; Medina, Alberto; Pons-Odena, Marti; Racca, Fabrizio; Wolf, Gerhard; Biban, Paolo; Brierley, Joe; Rimensberger, Peter C

    2017-12-01

    Much of the common practice in paediatric mechanical ventilation is based on personal experiences and what paediatric critical care practitioners have adopted from adult and neonatal experience. This presents a barrier to planning and interpretation of clinical trials on the use of specific and targeted interventions. We aim to establish a European consensus guideline on mechanical ventilation of critically children. The European Society for Paediatric and Neonatal Intensive Care initiated a consensus conference of international European experts in paediatric mechanical ventilation to provide recommendations using the Research and Development/University of California, Los Angeles, appropriateness method. An electronic literature search in PubMed and EMBASE was performed using a combination of medical subject heading terms and text words related to mechanical ventilation and disease-specific terms. The Paediatric Mechanical Ventilation Consensus Conference (PEMVECC) consisted of a panel of 15 experts who developed and voted on 152 recommendations related to the following topics: (1) general recommendations, (2) monitoring, (3) targets of oxygenation and ventilation, (4) supportive measures, (5) weaning and extubation readiness, (6) normal lungs, (7) obstructive diseases, (8) restrictive diseases, (9) mixed diseases, (10) chronically ventilated patients, (11) cardiac patients and (12) lung hypoplasia syndromes. There were 142 (93.4%) recommendations with "strong agreement". The final iteration of the recommendations had none with equipoise or disagreement. These recommendations should help to harmonise the approach to paediatric mechanical ventilation and can be proposed as a standard-of-care applicable in daily clinical practice and clinical research.

  11. 2016 IFToMM Asian Conference on Mechanism and Machine Science (IFToMM Asian MMS 2016) & 2016 International Conference on Mechanism and Machine Science (CCMMS 2016)

    CERN Document Server

    Wang, Nianfeng; Huang, Yanjiang

    2017-01-01

    These proceedings collect the latest research results in mechanism and machine science, intended to reinforce and improve the role of mechanical systems in a variety of applications in daily life and industry. Gathering more than 120 academic papers, it addresses topics including: Computational kinematics, Machine elements, Actuators, Gearing and transmissions, Linkages and cams, Mechanism design, Dynamics of machinery, Tribology, Vehicle mechanisms, dynamics and design, Reliability, Experimental methods in mechanisms, Robotics and mechatronics, Biomechanics, Micro/nano mechanisms and machines, Medical/welfare devices, Nature and machines, Design methodology, Reconfigurable mechanisms and reconfigurable manipulators, and Origami mechanisms. This is the fourth installment in the IFToMM Asian conference series on Mechanism and Machine Science (ASIAN MMS 2016). The ASIAN MMS conference initiative was launched to provide a forum mainly for the Asian community working in Mechanism and Machine Science, in order to ...

  12. Cancer cachexia, mechanism and treatment

    Science.gov (United States)

    Aoyagi, Tomoyoshi; Terracina, Krista P; Raza, Ali; Matsubara, Hisahiro; Takabe, Kazuaki

    2015-01-01

    It is estimated that half of all patients with cancer eventually develop a syndrome of cachexia, with anorexia and a progressive loss of adipose tissue and skeletal muscle mass. Cancer cachexia is characterized by systemic inflammation, negative protein and energy balance, and an involuntary loss of lean body mass. It is an insidious syndrome that not only has a dramatic impact on patient quality of life, but also is associated with poor responses to chemotherapy and decreased survival. Cachexia is still largely an underestimated and untreated condition, despite the fact that multiple mechanisms are reported to be involved in its development, with a number of cytokines postulated to play a role in the etiology of the persistent catabolic state. Existing therapies for cachexia, including orexigenic appetite stimulants, focus on palliation of symptoms and reduction of the distress of patients and families rather than prolongation of life. Recent therapies for the cachectic syndrome involve a multidisciplinary approach. Combination therapy with diet modification and/or exercise has been added to novel pharmaceutical agents, such as Megestrol acetate, medroxyprogesterone, ghrelin, omega-3-fatty acid among others. These agents are reported to have improved survival rates as well as quality of life. In this review, we will discuss the emerging understanding of the mechanisms of cancer cachexia, the current treatment options including multidisciplinary combination therapies, as well an update on new and ongoing clinical trials. PMID:25897346

  13. Meeting Report of the Fifth International Cancer Epigenetics Conference in Beijing, China, October 2016.

    Science.gov (United States)

    Gao, Dan; Herman, James G; Cui, Hengmi; Jen, Jin; Fuks, Francois; Brock, Malcolm V; Ushijima, Toshikazu; Croce, Carlo; Akiyama, Yoshimitsu; Guo, Mingzhou

    2017-07-01

    Fifth International Cancer Epigenetics Conference, Beijing, China, 21-23 October 2016 This meeting reported many new findings in the field of cancer epigenetics, including basic science, translational and clinical studies. In this report, we summarize some of the main advancements and prospects in cancer epigenetics presented at this meeting.

  14. Alcohol and breast cancer: the mechanisms explained.

    Science.gov (United States)

    Al-Sader, Hassen; Abdul-Jabar, Hani; Allawi, Zahra; Haba, Yasser

    2009-08-01

    Breast cancer is a leading cause of death amongst women, several studies have shown significant association between alcohol consumption and breast cancer. The aim of this overview is to highlight some of the mechanisms by which alcohol consumption could increase the risk of developing breast cancer. Using online Medline search engine, article containing details about mechanisms which explain the link between alcohol and breast cancer were examined. A number of mechanisms were found by which alcohol could increase the risk of breast cancer, alcohol's interaction and effect on oestrogen secretion; number of oestrogen receptors; the generation of acetaldehyde and hydroxyl free radicals; cells migration and metastasis; secretion of IGF1 and interaction with HRT and folate metabolism. In conclusion, it is essential for clinicians to understand these mechanisms and inform patients of the link between alcohol and breast cancer. Breast cancer; Alcohol; Mechanisms.

  15. PREFACE: 1st International Conference on Mechanical Engineering Research 2011 (ICMER2011)

    Science.gov (United States)

    Abu Bakar, Rosli

    2012-09-01

    The year 2010 represented a significant milestone in the history of the Mechanical Engineering community with the organization of the first and second national level conferences (National Conference in Mechanical Engineering for Research, 1st and 2nd NCMER) at Universiti Malaysia Pahang on 26-27 May and 3-4 December 2010. The conferences attracted a large number of delegates from different premier academic and research institutions in the country to participate and share their research experiences at the conference. The International Conference on Mechanical Engineering Research (ICMER 2011) followed on from the first and second conferences due to good support from researchers. The ICMER 2011 is a good platform for researchers and postgraduate students to present their latest finding in research. The conference covers a wide range of topics including the internal combustion engine, machining processes, heat and mass transfer, fuel, biomechanical analysis, aerodynamic analysis, thermal comfort, computational techniques, design and simulation, automotive transmission, optimization techniques, hybrid electric vehicles, engine vibration, heat exchangers, finite element analysis, computational fluid dynamics, green energy, vehicle dynamics renewable energy, combustion, design, product development, advanced experimentation techniques, to name but a few. The international conference has helped to bridge the gap between researchers working at different institutions and in different countries to share their knowledge and has helped to motivate young scientists with their research. This has also given some clear direction for further research from the deliberations of the conference. Several people have contributed in different ways to the success of the conference. We thank the keynote speakers and all authors of the contributed papers, for the cooperation rendered to us in the publication of the CD conference proceedings. In particular, we would like to place on record our

  16. 3rd IEEE/IFToMM International Conference on Reconfigurable Mechanisms and Robots

    CERN Document Server

    Kong, Xianwen; Dai, Jian; ReMAR 2015; Advances in Reconfigurable Mechanisms and Robots II

    2016-01-01

    This book presents the most recent advances in the research and applications of reconfigurable mechanisms and robots. It collects 93 independently reviewed papers presented at the Third ASME/IFToMM International Conference on Reconfigurable Mechanisms and Robots (ReMAR 2015) held in Beijing, China, 20-22 July 2015. The conference papers are organized into seven parts to cover the reconfiguration theory, topology, kinematics and design of reconfigurable mechanisms including reconfigurable parallel mechanisms. The most recent results on reconfigurable robots are presented including their analysis, design, simulation and control. Bio-inspired mechanisms are also explored in the challenging fields of rehabilitation and minimally invasive surgery. This book further addresses deployable mechanisms and origami-inspired mechanisms and showcases a wide range of successful applications of reconfigurable mechanisms and robots. Advances in Reconfigurable Mechanisms and Robots II should be of interest for researchers, eng...

  17. BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer

    NARCIS (Netherlands)

    Shimelis, Hermela; Mesman, Romy L. S.; Von Nicolai, Catharina; Ehlen, Asa; Guidugli, Lucia; Martin, Charlotte; Calleja, Fabienne M. G. R.; Meeks, Huong; Hallberg, Emily; Hinton, Jamie; Lilyquist, Jenna; Hu, Chunling; Aalfs, Cora M.; Aittomaki, Kristiina; Andrulis, Irene; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W.; Benitez, Javier; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Borresen-Dale, Anne-Lise; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Broeks, Annegien; Brouwers, Barbara; Bruning, Thomas; Burwinkel, Barbara; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Cheng, Ching-Yu; Choi, Ji-Yeob; Collee, J. Margriet; Cox, Angela; Cross, Simon S.; Czene, Kamila; Darabi, Hatef; Dennis, Joe; Dork, Thilo; dos-Santos-Silva, Isabel; Dunning, Alison M.; Fasching, Peter A.; Figueroa, Jonine; Flyger, Henrik; Garcia-Closas, Montserrat; Giles, Graham G.; Glendon, Gord; Guenel, Pascal; Haiman, Christopher A.; Hall, Per; Hamann, Ute; Hartman, Mikael; Hogervorst, Frans B.; Hollestelle, Antoinette; Hopper, John L.; Ito, Hidemi; Jakubowska, Anna; Kang, Daehee; Kosma, Veli-Matti; Kristensen, Vessela; Lai, Kah-Nyin; Lambrechts, Diether; Le Marchand, Loic; Li, Jingmei; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Machackova, Eva; Mannermaa, Arto; Margolin, Sara; Marme, Frederik; Matsuo, Keitaro; Miao, Hui; Michailidou, Kyriaki; Milne, Roger L.; Muir, Kenneth; Neuhausen, Susan L.; Nevanlinna, Heli; Olson, Janet E.; Olswold, Curtis; Oosterwijk, Jan J. C.; Osorio, Ana; Peterlongo, Paolo; Peto, Julian; Pharoah, Pauld D. P.; Pylkas, Katri; Radice, Paolo; Rashid, Muhammad Usman; Rhenius, Valerie; Rudolph, Anja; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schmidt, Marjanka K.; Schoemaker, Minouk J.; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shrubsole, Martha; Shu, Xiao-Ou; Slager, Susan; Southey, Melissa C.; Stram, Daniel O.; Swerdlow, Anthony; Teo, Soo H.; Tomlinson, Ian; Torres, Diana; Truong, Therese; van Asperen, Christi J.; van der Kolk, Lizet E.; Wang, Qin; Winqvist, Robert; Wu, Anna H.; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Leary, Jennifer; Walker, Logan; Foretova, Lenka; Fostira, Florentia; Claes, Kathleen B. M.; Varesco, Liliana; Moghadasi, Setareh; Easton, Douglas F.; Spurdle, Amanda; Devilee, Peter; Vrieling, Harry; Monteiro, Alvaro N. A.; Goldgar, David E.; Carreira, Aura; Vreeswijk, Maaike P. G.; Couch, Fergus J.

    2017-01-01

    Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk

  18. Proceedings of the Fifth International Conference on Fluid Mechanics (Shanghai, 2007)

    CERN Document Server

    Zhuang, F. G; New Trends in Fluid Mechanics Research

    2009-01-01

    New Trends in Fluid Mechanics Research is the proceedings of the Fifth International Conference on Fluid Mechanics (ICFM-V); it is the primary forum for the presentation of technological advances and research results in the fields of theoretical, experimental, and computational Fluid Mechanics. Following the previous conferences in Beijing (1987, 1993 and 1998) and Dalian (2004) organized by the Chinese Society of Theoretical and Applied Mechanics, the Scientific Committee for ICFM presents ICFM-V to provide a forum for researchers to exchange original ideas and recent advances in Fluid Mechanics and relevant interdisciplinary subjects. Topics include: flow instability and turbulence, aerodynamics and gas dynamics, hydrodynamics, industrial and environmental fluid mechanics, biofluid mechanics, geophysical fluid mechanics, plasma and magneto-hydrodynamics, multiphase flows, non-Newtonian flows and flows in porous media, flow of reacting fluid, microscale flow and others.

  19. Cancer Cell Fusion: Mechanisms Slowly Unravel

    Directory of Open Access Journals (Sweden)

    Felicite K. Noubissi

    2016-09-01

    Full Text Available Although molecular mechanisms and signaling pathways driving invasion and metastasis have been studied for many years, the origin of the population of metastatic cells within the primary tumor is still not well understood. About a century ago, Aichel proposed that cancer cell fusion was a mechanism of cancer metastasis. This hypothesis gained some support over the years, and recently became the focus of many studies that revealed increasing evidence pointing to the possibility that cancer cell fusion probably gives rise to the metastatic phenotype by generating widespread genetic and epigenetic diversity, leading to the emergence of critical populations needed to evolve resistance to the treatment and development of metastasis. In this review, we will discuss the clinical relevance of cancer cell fusion, describe emerging mechanisms of cancer cell fusion, address why inhibiting cancer cell fusion could represent a critical line of attack to limit drug resistance and to prevent metastasis, and suggest one new modality for doing so.

  20. 6th Conference on Design and Modeling of Mechanical Systems

    CERN Document Server

    Fakhfakh, Tahar; Daly, Hachmi; Aifaoui, Nizar; Chaari, Fakher

    2015-01-01

    This book offers a collection of original peer-reviewed contributions presented at the 6th International Congress on Design and Modeling of Mechanical Systems (CMSM’2015), held in Hammamet, Tunisia, from the 23rd to the 25th of March 2015. It reports on both recent research findings and innovative industrial applications in the fields of mechatronics and robotics, dynamics of mechanical systems, fluid structure interaction and vibroacoustics, modeling and analysis of materials and structures, and design and manufacturing of mechanical systems. Since its first edition in 2005, the CMSM Congress has been held every two years with the aim of bringing together specialists from universities and industry to present the state-of-the-art in research and applications, discuss the most recent findings and exchange and develop expertise in the field of design and modeling of mechanical systems. The CMSM Congress is jointly organized by three Tunisian research laboratories: the Mechanical Engineering Laboratory of th...

  1. Phase imaging of mechanical properties of live cells (Conference Presentation)

    Science.gov (United States)

    Wax, Adam

    2017-02-01

    The mechanisms by which cells respond to mechanical stimuli are essential for cell function yet not well understood. Many rheological tools have been developed to characterize cellular viscoelastic properties but these typically require direct mechanical contact, limiting their throughput. We have developed a new approach for characterizing the organization of subcellular structures using a label free, noncontact, single-shot phase imaging method that correlates to measured cellular mechanical stiffness. The new analysis approach measures refractive index variance and relates it to disorder strength. These measurements are compared to cellular stiffness, measured using the same imaging tool to visualize nanoscale responses to flow shear stimulus. The utility of the technique is shown by comparing shear stiffness and phase disorder strength across five cellular populations with varying mechanical properties. An inverse relationship between disorder strength and shear stiffness is shown, suggesting that cell mechanical properties can be assessed in a format amenable to high throughput studies using this novel, non-contact technique. Further studies will be presented which include examination of mechanical stiffness in early carcinogenic events and investigation of the role of specific cellular structural proteins in mechanotransduction.

  2. Activating transcription factor 4 confers a multidrug resistance phenotype to gastric cancer cells through transactivation of SIRT1 expression.

    Directory of Open Access Journals (Sweden)

    Hongwu Zhu

    Full Text Available BACKGROUND: Multidrug resistance (MDR in gastric cancer remains a major challenge to clinical treatment. Activating transcription factor 4 (ATF4 is a stress response gene involved in homeostasis and cellular protection. However, the expression and function of ATF4 in gastric cancer MDR remains unknown. In this study, we investigate whether ATF4 play a role in gastric cancer MDR and its potential mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that ATF4 overexpression confered the MDR phenotype to gastric cancer cells, while knockdown of ATF4 in the MDR variants induced re-sensitization. In this study we also showed that the NAD(+-dependent histone deacetylase SIRT1 was required for ATF4-induced MDR effect in gastric cancer cells. We demonstrated that ATF4 facilitated MDR in gastric cancer cells through direct binding to the SIRT1 promoter, resulting in SIRT1 up-regulation. Significantly, inhibition of SIRT1 by small interfering RNA (siRNA or a specific inhibitor (EX-527 reintroduced therapeutic sensitivity. Also, an increased Bcl-2/Bax ratio and MDR1 expression level were found in ATF4-overexpressing cells. CONCLUSIONS/SIGNIFICANCE: We showed that ATF4 had a key role in the regulation of MDR in gastric cancer cells in response to chemotherapy and these findings suggest that targeting ATF4 could relieve therapeutic resistance in gastric cancer.

  3. Conference Scene: Epigenetic regulation: from mechanism to intervention.

    Science.gov (United States)

    Chatterjee, Aniruddha

    2012-10-01

    The Medical Research Council Clinical Sciences Centre Symposium on Epigenetic Regulation: From Mechanism to Intervention in London, UK, which was held on 20-22 June 2012, attracted 305 participants from around the globe and included 37 speakers and 85 selected poster presentations. The organizing committee, led by Niall Dillon of the Medical Research Council Clinical Sciences Centre (London, UK), consisted of several distinguished researchers in the fields of epigenetics and chromatin organization from across the UK. The meeting covered a diverse range of topics and brought together scientists carrying out fundamental research on epigenetic mechanisms and also researchers who are exploring the role of epigenetics in human diseases and its clinical applications. In addition, the meeting highlighted some emerging aspects in the rapidly evolving field of epigenetics.

  4. PREFACE: 3rd International Conference of Mechanical Engineering Research (ICMER 2015)

    Science.gov (United States)

    Mamat, Riazalman; Rahman, Mustafizur; Mohd. Zuki Nik Mohamed, Nik; Che Ghani, Saiful Anwar; Harun, Wan Sharuzi Wan

    2015-12-01

    The 3rd ICMER2015 is the continuity of the NCMER2010. The year 2010 represents a significant milestone in the history for Faculty of Mechanical Engineering, Universiti Malaysia Pahang (UMP) Malaysia with the organization of the first and second national level conferences (1st and 2nd NCMER) at UMP on May 26-27 and Dec 3-4 2010. The Faculty then changed the name from National Conference on Mechanical Engineering Research (NCMER) to International Conference on Mechanical Engineering Research (ICMER) in 2011 and this year, 2015 is our 3rd ICMER. These proceedings contain the selected scientific manuscripts submitted to the conference. It is with great pleasure to welcome you to the "International Conference on Mechanical Engineering Research (ICMER2015)" that is held at Zenith Hotel, Kuantan, Malaysia. The call for papers attracted submissions of over two hundred abstracts from twelve different countries including Japan, Iran, China, Kuwait, Indonesia, Norway, Philippines, Morocco, Germany, UAE and more. The scientific papers published in these proceedings have been revised and approved by the technical committee of the 3rd ICMER2015. All of the papers exhibit clear, concise, and precise expositions that appeal to a broad international readership interested in mechanical engineering, combustion, metallurgy, materials science as well as in manufacturing and biomechanics. The reports present original ideas or results of general significance supported by clear reasoning and compelling evidence, and employ methods, theories and practices relevant to the research. The authors clearly state the questions and the significance of their research to theory and practice, describe how the research contributes to new knowledge, and provide tables and figures that meaningfully add to the narrative. In this edition of ICMER representatives attending are from academia, industry, governmental and private sectors. The plenary and invited speakers will present, discuss, promote and

  5. Consensus on precision medicine for metastatic cancers: a report from the MAP conference

    OpenAIRE

    Swanton, C.; Soria, J.-C.; Bardelli, A.; Biankin, A.; Caldas, C.; Chandarlapaty, S.; de Koning, L.; Dive, C.; Feunteun, J.; Leung, S.-Y.; Marais, R.; Mardis, E. R.; McGranahan, N.; Middleton, G.; Quezada, S. A.

    2016-01-01

    Recent advances in biotechnologies have led to the development of multiplex genomic and proteomic analyses for clinical use. Nevertheless, guidelines are currently lacking to determine which molecular assays should be implemented in metastatic cancers. The first MAP conference was dedicated to exploring the use of genomics to better select therapies in the treatment of metastatic cancers. Sixteen consensus items were covered. There was a consensus that new technologies like next-generation se...

  6. PREFACE: International Scientific and Technical Conference ''Innovative Mechanical Engineering Technologies, Equipment and Materials-2014''

    Science.gov (United States)

    Nail, K.

    2015-06-01

    In the period from 3 to 5 December 2014 the city of Kazan hosted the International Scientific Conference ''Innovative mechanical engineering technologies, equipment and materials - 2014'' (ISC ''vIMETEM - 2014''). The event was followed by the 14th International specialized exhibition ''Engineering. Metalworking. Kazan'' The main objective of the annual conference was for participants to discuss scientific and technical achievements in the design and manufacture of engineering products, the expansion of cooperation between scientific organizations and enterprises of machine-building complex and the definition of perspective ways of creation and development of new techniques, technologies and materials. The conference ''IMETEM'' was devoted to the 90th anniversary of Fayzrahman Salahovich Yunusov, who made a great contribution in the field of aviation technology. Kashapov Nail, D.Sc., professor (Kazan Federal University)

  7. On the path to translation: Highlights from the 2010 Canadian Conference on Ovarian Cancer Research

    Directory of Open Access Journals (Sweden)

    Thériault Brigitte L

    2011-06-01

    Full Text Available Abstract Ovarian cancer continues to be the most lethal of the gynaecologic malignancies due to the lack of early detection, screening strategies and ineffective therapeutics for late-stage metastatic disease, particularly in the recurrent setting. The gathering of researchers investigating fundamental pathobiology of ovarian cancer and the clinicians who treat patients with this insidious disease is paramount to meeting the challenges we face. Since 2002, the Canadian Conference on Ovarian Cancer Research, held every two years, has served this essential purpose. The objectives of this conference have been to disseminate new information arising from the most recent ovarian cancer research and identify the most pressing challenges we still face as scientists and clinicians. This is best accomplished through direct encounters and exchanges of innovative ideas among colleagues and trainees from the realms of basic science and clinical disciplines. This meeting has and continues to successfully facilitate rapid networking and establish new collaborations from across Canada. This year, more guest speakers and participants from other countries have extended the breadth of the research on ovarian cancer that was discussed at the meeting. This report summarizes the key findings presented at the fifth biennial Canadian Conference on Ovarian Cancer Research held in Toronto, Ontario, and includes the important issues and challenges we still face in the years ahead to make a significant impact on this devastating disease.

  8. 3rd St. Gallen EORTC Gastrointestinal Cancer Conference: Consensus recommendations on controversial issues in the primary treatment of pancreatic cancer

    NARCIS (Netherlands)

    Lutz, M.P. (Manfred P.); J. Zalcberg (John); M. Ducreux (Michel); G. Aust (Gabriela); M.J. Bruno (Marco); M.W. Buchler (M.); Delpero, J.-R. (Jean-Robert); Gloor, B. (Beat); R. Glynne-Jones; Hartwig, W. (Werner); Huguet, F. (Florence); P. Laurent-Puig (Pierre); F. Lordick (Florian); P. Maisonneuve (Patrick); J. Mayerle (Julia); Martignoni, M. (Marc); J.P. Neoptolemos (John); Rhim, A.D. (Andrew D.); Schmied, B.M. (Bruno M.); T. Seufferlein (Thomas); Werner, J. (Jens); van Laethem, J.-L. (Jean-Luc); F. Otto (Florian)

    2017-01-01

    textabstractThe primary treatment of pancreatic cancer was the topic of the 3rd St. Gallen Conference 2016. A multidisciplinary panel reviewed the current evidence and discussed controversial issues in a moderated consensus session. Here we report on the key expert recommendations. It was generally

  9. Molecular pathogenesis and mechanisms of thyroid cancer

    Science.gov (United States)

    Xing, Mingzhao

    2013-01-01

    Thyroid cancer is a common endocrine malignancy. There has been exciting progress in understanding its molecular pathogenesis in recent years, as best exemplified by the elucidation of the fundamental role of several major signalling pathways and related molecular derangements. Central to these mechanisms are the genetic and epigenetic alterations in these pathways, such as mutation, gene copy-number gain and aberrant gene methylation. Many of these molecular alterations represent novel diagnostic and prognostic molecular markers and therapeutic targets for thyroid cancer, which provide unprecedented opportunities for further research and clinical development of novel treatment strategies for this cancer. PMID:23429735

  10. High serum estradiol confers no risk for breast cancer: another ...

    African Journals Online (AJOL)

    No association was found between level of estradiol and breast cancer (p 0.647). The median oestrogen levels were significantly higher than normal levels in Caucasian women. Conclusion: There was no association between level of estradiol and breast cancer. This is yet another disparity between women of African origin ...

  11. Molecular Quantum Mechanics 2010: From Methylene to DNA and Beyond Conference Support

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2013-05-15

    This grant was $12500 for partial support of an international conference, Molecular Quantum Mechanics 2010, which was held on the campus of the University of California, Berkeley, from 24 to 29 May 2010. The conference involved more than 250 participants. The conference schedule ran from as early as 8:00 AM to as late as 10:30 PM at night, in order to accommodate six historical lectures, 16 plenary lectures, 42 invited talks and two very strong poster sessions containing 143 contributed posters. Since 1989, the Molecular Quantum Mechanics (MQM) series of international conferences has show- cased the frontiers of research in quantum chemistry with a strong focus on basic theory and algorithms, as well as highlights of topical applications. Both were strongly in evidence at MQM 2010. At the same time as embracing the future, the MQM conferences also honour the lifetime contributions of some of the most prominent scientists in the field of theoretical and computational quantum chemistry. MQM 2010 recognised the work of Prof. Henry F. ‘Fritz’ Schaefer of the Center for Computational Chemistry at the University of Georgia, who was previously on the faculty at Berkeley The travel of invited speakers was partially covered by sponsorships from Dell Computer, Hewlett-Packard, Journal of Chemical Theory and Computation, Virginia Tech College of Science, Molecular Physics, Q-Chem Inc and the American Institute of Physics. By contrast, the conference grant from the Department of Energy was used to provide fellowships and scholarships to enable graduate students and postdoctoral fellows to attend the meeting, and thereby broaden the participation of young scientists at a meeting where in the past most of the attendees have been more senior faculty researchers. We believe that we were very successful in this regard: 118 students and postdocs attended out of the total of 256 participants. In detail, the DOE sponsorship money was partially used for dormitory scholarships that

  12. Laser immunotherapy for metastatic pancreatic cancer (Conference Presentation)

    Science.gov (United States)

    Zhou, Feifan

    2017-02-01

    Pancreatic cancer is an extremely malignant disease with high mortality rate. Currently there is no effective therapeutic strategy for highly metastatic pancreatic cancers. Laser immunotherapy (LIT) is a combination therapeutic approach of targeted phototherapy and immunotherapy, which could destroy treated primary tumors with elimination of untreated metastases. LIT affords a remarkable efficacy in suppressing tumor growth in pancreatic tumors in mice, and results in complete tumor regression in many cases. LIT could synergize targeted phototherapy and immunological effects of immunoadjuvant, which represent a promising treatment modality to induce systemic antitumor response through a local intervention, paving the way for the treatment of highly metastatic pancreatic cancers.

  13. Management of Patients with Advanced Prostate Cancer: The Report of the Advanced Prostate Cancer Consensus Conference APCCC 2017.

    Science.gov (United States)

    Gillessen, Silke; Attard, Gerhardt; Beer, Tomasz M; Beltran, Himisha; Bossi, Alberto; Bristow, Rob; Carver, Brett; Castellano, Daniel; Chung, Byung Ha; Clarke, Noel; Daugaard, Gedske; Davis, Ian D; de Bono, Johann; Dos Reis, Rodolfo Borges; Drake, Charles G; Eeles, Ros; Efstathiou, Eleni; Evans, Christopher P; Fanti, Stefano; Feng, Felix; Fizazi, Karim; Frydenberg, Mark; Gleave, Martin; Halabi, Susan; Heidenreich, Axel; Higano, Celestia S; James, Nicolas; Kantoff, Philip; Kellokumpu-Lehtinen, Pirkko-Liisa; Khauli, Raja B; Kramer, Gero; Logothetis, Chris; Maluf, Fernando; Morgans, Alicia K; Morris, Michael J; Mottet, Nicolas; Murthy, Vedang; Oh, William; Ost, Piet; Padhani, Anwar R; Parker, Chris; Pritchard, Colin C; Roach, Mack; Rubin, Mark A; Ryan, Charles; Saad, Fred; Sartor, Oliver; Scher, Howard; Sella, Avishay; Shore, Neal; Smith, Matthew; Soule, Howard; Sternberg, Cora N; Suzuki, Hiroyoshi; Sweeney, Christopher; Sydes, Matthew R; Tannock, Ian; Tombal, Bertrand; Valdagni, Riccardo; Wiegel, Thomas; Omlin, Aurelius

    2017-06-24

    In advanced prostate cancer (APC), successful drug development as well as advances in imaging and molecular characterisation have resulted in multiple areas where there is lack of evidence or low level of evidence. The Advanced Prostate Cancer Consensus Conference (APCCC) 2017 addressed some of these topics. To present the report of APCCC 2017. Ten important areas of controversy in APC management were identified: high-risk localised and locally advanced prostate cancer; "oligometastatic" prostate cancer; castration-naïve and castration-resistant prostate cancer; the role of imaging in APC; osteoclast-targeted therapy; molecular characterisation of blood and tissue; genetic counselling/testing; side effects of systemic treatment(s); global access to prostate cancer drugs. A panel of 60 international prostate cancer experts developed the program and the consensus questions. The panel voted publicly but anonymously on 150 predefined questions, which have been developed following a modified Delphi process. Voting is based on panellist opinion, and thus is not based on a standard literature review or meta-analysis. The outcomes of the voting had varying degrees of support, as reflected in the wording of this article, as well as in the detailed voting results recorded in Supplementary data. The presented expert voting results can be used for support in areas of management of men with APC where there is no high-level evidence, but individualised treatment decisions should as always be based on all of the data available, including disease extent and location, prior therapies regardless of type, host factors including comorbidities, as well as patient preferences, current and emerging evidence, and logistical and economic constraints. Inclusion of men with APC in clinical trials should be strongly encouraged. Importantly, APCCC 2017 again identified important areas in need of trials specifically designed to address them. The second Advanced Prostate Cancer Consensus

  14. 2013 Gordon Research Conference, Inorganic reaction mechanisms, Galveston, TX, March 3-8 2013

    Energy Technology Data Exchange (ETDEWEB)

    Abu-Omar, Mahdi M. [Purdue Univ., West Lafayette, IN (United States)

    2012-12-08

    The 2013 Gordon Conference on Inorganic Reaction Mechanisms will present cutting-edge research on the molecular aspects of inorganic reactions involving elements from throughout the periodic table and state-of-the art techniques that are used in the elucidation of reaction mechanisms. The Conference will feature a wide range of topics, such as homogeneous and heterogeneous catalysis, metallobiochemistry, electron-transfer in energy reactions, polymerization, nitrogen fixation, green chemistry, oxidation, solar conversion, alkane functionalization, organotransition metal chemistry, and computational chemistry. The talks will cover themes of current interest including energy, materials, and bioinorganic chemistry. Sections cover: Electron-Transfer in Energy Reactions; Catalytic Polymerization and Oxidation Chemistry; Kinetics and Spectroscopy of Heterogeneous Catalysts; Metal-Organic Chemistry and its Application in Synthesis; Green Energy Conversion;Organometallic Chemistry and Activation of Small Molecules; Advances in Kinetics Modeling and Green Chemistry; Metals in Biology and Disease; Frontiers in Catalytic Bond Activation and Cleavage.

  15. 2nd International Conference on Mechanical, Manufacturing and Process Plant Engineering

    CERN Document Server

    2017-01-01

    This volume presents selected papers from the 2nd International Conference on Mechanical, Manufacturing and Process Plant Engineering (ICMMPE 2016) which was held from 23rd to 24th November, 2016 in Kuala Lumpur, Malaysia. The proceedings discuss genuine problems of joining technologies that are heart of manufacturing sectors. It discusses the findings of experimental and numerical works from soldering, arc welding to solid state joining technology that faced by current industry. .

  16. Cancer chemoprevention – selected molecular mechanisms

    Directory of Open Access Journals (Sweden)

    Katarzyna Walczak

    2017-03-01

    Full Text Available The effect of diet on cancer formation and prevention of carcinogenesis has attracted considerable attention for years and is the subject of several studies. Some components of the daily diet, such as resveratrol, curcumin, genistein, gingerol, can significantly reduce the risk of cancer or affect the rate of tumor progression. Cancer chemoprevention assumes the use of natural or synthetic biologically active substances in order to prevent, inhibit or reverse the progression of cancer. There are many biologically active compounds in several natural products, i.e. garlic, ginger, soy, curcuma, tomatoes, cruciferous plants or green tea. Their chemopreventive activity is based on the inhibition of processes underlying carcinogenesis (inflammation, transformation and proliferation, but also affects the final phase of carcinogenesis - angiogenesis and metastasis. Despite the relatively low toxicity of chemopreventive agents, their molecular targets often coincide with the objectives of the currently used cancer therapies. The widespread use of chemopreventive agents may contribute to reduction of the rate of cancer incidence, and increase the effectiveness of conventional cancer therapies. In the present study, selected molecular mechanisms of the chemopreventive activity have been discussed, especially their involvement in the regulation of signal transduction, cell cycle regulation, apoptosis, metastasis and angiogenesis. The role of chemopreventive agents in the inflammatory process, the metabolism of xenobiotics and multidrug resistance has been also characterized.

  17. Nanomedicines for image-guided cancer therapy (Conference Presentation)

    Science.gov (United States)

    Zheng, Jinzi

    2016-09-01

    Imaging technologies are being increasingly employed to guide the delivery of cancer therapies with the intent to increase their performance and efficacy. To date, many patients have benefited from image-guided treatments through prolonged survival and improvements in quality of life. Advances in nanomedicine have enabled the development of multifunctional imaging agents that can further increase the performance of image-guided cancer therapy. Specifically, this talk will focus on examples that demonstrate the benefits and application of nanomedicine in the context of image-guide surgery, personalized drug delivery, tracking of cell therapies and high precision radiotherapy delivery.

  18. Mueller matrix polarimetry imaging for breast cancer analysis (Conference Presentation)

    Science.gov (United States)

    Gribble, Adam; Vitkin, Alex

    2017-02-01

    Polarized light has many applications in biomedical imaging. The interaction of a biological sample with polarized light reveals information about its biological composition, both structural and functional. The most comprehensive type of polarimetry analysis is to measure the Mueller matrix, a polarization transfer function that completely describes how a sample interacts with polarized light. However, determination of the Mueller matrix requires tissue analysis under many different states of polarized light; a time consuming and measurement intensive process. Here we address this limitation with a new rapid polarimetry system, and use this polarimetry platform to investigate a variety of tissue changes associated with breast cancer. We have recently developed a rapid polarimetry imaging platform based on four photoelastic modulators (PEMs). The PEMs generate fast polarization modulations that allow the complete sample Mueller matrix to be imaged over a large field of view, with no moving parts. This polarimetry system is then demonstrated to be sensitive to a variety of tissue changes that are relevant to breast cancer. Specifically, we show that changes in depolarization can reveal tumor margins, and can differentiate between viable and necrotic breast cancer metastasized to the lymph nodes. Furthermore, the polarimetric property of linear retardance (related to birefringence) is dependent on collagen organization in the extracellular matrix. These findings indicate that our polarimetry platform may have future applications in fields such as breast cancer diagnosis, improving the speed and efficacy of intraoperative pathology, and providing prognostic information that may be beneficial for guiding treatment.

  19. Prostate cancer diagnosis with fluorescence lifetime imaging (Conference Presentation)

    Science.gov (United States)

    Sridharan, Shamira; Gandour-Edwards, Regina F.; Dall'Era, Marc; Marcu, Laura

    2017-02-01

    More than 1 million men in the United States undergo a prostate biopsy procedure annually and approximately 200,000 men receive a diagnosis of prostate cancer. 5-10% of these men have to undergo a repeat biopsy due to insufficient tissue sampling. We are studying the utility of a multi-spectral time resolved fluorescence spectroscopy (MS-TRFS) technique for real-time prostate cancer diagnosis. The MS-TRFS imaging setup, which includes a fiberoptic set-up with a 355nm excitation light source coupled with a blue (450nm) aiming beam, was used to image ex-vivo prostatectomy specimen. The prostate tissue from 11 patients was sectioned at 2mm thickness and the fluorescence lifetime information was overlaid spatially for histology and thus, diagnostic co-registration. Initial results show that fluorescence lifetime in the 390±40nm channel, which measures collagen and elastin signatures, is longer for glandular regions than in the stromal regions. Additionally, lifetime in the 452±45nm channel, corresponding to NAD redox state, is longer in the cancerous glandular region in comparison with the normal glandular regions. Current work is focused on developing real-time quantitative algorithms to combine the fluorescence signatures from the two channels for performing prostate cancer diagnosis on biopsies.

  20. PREFACE: 1st Nano-IBCT Conference 2011 - Radiation Damage of Biomolecular Systems: Nanoscale Insights into Ion Beam Cancer Therapy

    Science.gov (United States)

    Huber, Bernd A.; Malot, Christiane; Domaracka, Alicja; Solov'yov, Andrey V.

    2012-07-01

    The 1st Nano-IBCT Conference entitled 'Radiation Damage in Biomolecular Systems: Nanoscale Insights into Ion Beam Cancer Therapy' was held in Caen, France, in October 2011. The Meeting was organised in the framework of the COST Action MP1002 (Nano-IBCT) which was launched in December 2010 (http://fias.uni-frankfurt.de/nano-ibct). This action aims to promote the understanding of mechanisms and processes underlying the radiation damage of biomolecular systems at the molecular and nanoscopic level and to use the findings to improve the strategy of Ion Beam Cancer Therapy. In the hope of achieving this, participants from different disciplines were invited to represent the fields of physics, biology, medicine and chemistry, and also included those from industry and the operators of hadron therapy centres. Ion beam therapy offers the possibility of excellent dose localization for treatment of malignant tumours, minimizing radiation damage in normal healthy tissue, while maximizing cell killing within the tumour. Several ion beam cancer therapy clinical centres are now operating in Europe and elsewhere. However, the full potential of such therapy can only be exploited by better understanding the physical, chemical and biological mechanisms that lead to cell death under ion irradiation. Considering a range of spatio-temporal scales, the proposed action therefore aims to combine the unique experimental and theoretical expertise available within Europe to acquire greater insight at the nanoscopic and molecular level into radiation damage induced by ion impact. Success in this endeavour will be both an important scientific breakthrough and give great impetus to the practical improvement of this innovative therapeutic technique. Ion therapy potentially provides an important advance in cancer therapy and the COST action MP1002 will be very significant in ensuring Europe's leadership in this field, providing the scientific background, required data and mechanistic insight which

  1. 2016 International Conference on Physics and Mechanics of New Materials and Their Applications

    CERN Document Server

    Chang, Shun-Hsyung; Jani, Muaffaq

    2017-01-01

    This book presents 50 selected peer-reviewed reports from the 2016 International Conference on “Physics and Mechanics of New Materials and Their Applications”, PHENMA 2016 (Surabaya, Indonesia, 19–22 July, 2016). The Proceedings are devoted to processing techniques, physics, mechanics, and applications of advanced materials. As such, they examine a wide spectrum of nanostructures, ferroelectric crystals, materials and composites, as well as other promising materials with special properties. They present nanotechnology approaches, modern environmentally friendly piezoelectric and ferromagnetic techniques, and physical and mechanical studies of the structural and physical-mechanical properties of the materials discussed.  Further, a broad range of original mathematical and numerical methods is applied to solve various technological, mechanical and physical problems, which are inte resting for applications. Great attention is devoted to novel devices with high accuracy, longevity and extended possibilitie...

  2. [Intracellular signaling mechanisms in thyroid cancer].

    Science.gov (United States)

    Mondragón-Terán, Paul; López-Hernández, Luz Berenice; Gutiérrez-Salinas, José; Suárez-Cuenca, Juan Antonio; Luna-Ceballos, Rosa Isela; Erazo Valle-Solís, Aura

    2016-01-01

    Thyroid cancer is the most common malignancy of the endocrine system, the papillary variant accounts for 80-90% of all diagnosed cases. In the development of papillary thyroid cancer, BRAF and RAS genes are mainly affected, resulting in a modification of the system of intracellular signaling proteins known as «protein kinase mitogen-activated» (MAPK) which consist of «modules» of internal signaling proteins (Receptor/Ras/Raf/MEK/ERK) from the cell membrane to the nucleus. In thyroid cancer, these signanling proteins regulate diverse cellular processes such as differentiation, growth, development and apoptosis. MAPK play an important role in the pathogenesis of thyroid cancer as they are used as molecular biomarkers for diagnostic, prognostic and as possible therapeutic molecular targets. Mutations in BRAF gene have been correlated with poor response to treatment with traditional chemotherapy and as an indicator of poor prognosis. To review the molecular mechanisms involved in intracellular signaling of BRAF and RAS genes in thyroid cancer. Molecular therapy research is in progress for this type of cancer as new molecules have been developed in order to inhibit any of the components of the signaling pathway (RET/PTC)/Ras/Raf/MEK/ERK; with special emphasis on the (RET/PTC)/Ras/Raf section, which is a major effector of ERK pathway. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  3. 2015 International Conference on Physics and Mechanics of New Materials and their Applications

    CERN Document Server

    Chang, Shun-Hsyung; Topolov, Vitaly

    2016-01-01

    This proceedings volume presents selected and peer reviewed 50 reports of the 2015 International Conference on “Physics and Mechanics of New Materials and Their Applications” (Azov, Russia, 19-22 May, 2015), devoted to 100th Anniversary of the Southern Federal University, Russia. The book presents processing techniques, physics, mechanics, and applications of advanced materials. The book is concentrated on some nanostructures, ferroelectric crystals, materials and composites and other materials with specific properties. In this book are presented nanotechnology approaches, modern piezoelectric techniques, physical and mechanical studies of the structure-sensitive properties of the materials. A wide spectrum of mathematical and numerical methods is applied to the solution of different technological, mechanical and physical problems for applications. Great attention is devoted to novel devices with high accuracy, longevity and extended possibilities to work in a large scale of  temperatures and pressure r...

  4. Breast cancer disparities: Frontline strategies, proceedings of the 7 th annual texas conference on health disparities

    Directory of Open Access Journals (Sweden)

    Marilyne Kpetemey

    2012-01-01

    Full Text Available There are striking disparities in health status, access to health care, and risk factors among racial and ethnic minorities and the general population in Texas. The disparities are multifactorial comprising genetic, sociocultural, and environmental variables. The Texas Center for Health Disparities (TCHD, a NIMHD Center of Excellence (COE, aims to prevent, reduce, and eliminate health disparities in the communities through research, education, and community-based programs. As part of the center′s outreach activities, an annual conference is organized to build awareness and knowledge on health disparities. The overall theme for the 2012 conference was "Battling Breast Cancer Disparities: Frontline Strategies". The scientific program consisted of three sessions: "Breakthroughs in Breast Cancer", "Triple Negative Breast Cancer," and "Hormone Resistant Breast Cancer" featuring different aspects of bench-research from molecular biology, proteomics, and genetics to the clinical aspects such as detection, diagnosis, and finally to community-based approaches. This article summarizes the proceedings of the meeting providing salient strategies and best practices presented by the speakers.

  5. Rottlerin and Cancer: Novel Evidence and Mechanisms

    Directory of Open Access Journals (Sweden)

    E. Maioli

    2012-01-01

    Full Text Available Because cancers are caused by deregulation of hundreds of genes, an ideal anticancer agent should target multiple gene products or signaling pathways simultaneously. Recently, extensive research has addressed the chemotherapeutic potential of plant-derived compounds. Among the ever-increasing list of naturally occurring anticancer agents, Rottlerin appears to have great potentiality for being used in chemotherapy because it affects several cell machineries involved in survival, apoptosis, autophagy, and invasion. The underlying mechanisms that have been described are diverse, and the final, cell-specific, Rottlerin outcome appears to result from a combination of signaling pathways at multiple levels. This paper seeks to summarize the multifocal signal modulatory properties of Rottlerin, which merit to be further exploited for successful prevention and treatment of cancer.

  6. Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes

    DEFF Research Database (Denmark)

    Gudmundsson, Julius; Sulem, Patrick; Steinthorsdottir, Valgerdur

    2007-01-01

    We performed a genome-wide association scan to search for sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with prostate cancer and 11,290 controls. Follow-up studies involving three additional case-control groups replicated an association of two variants on chromoso...

  7. Cancer metastasis: Mechanisms of inhibition by melatonin.

    Science.gov (United States)

    Su, Shih-Chi; Hsieh, Ming-Ju; Yang, Wei-En; Chung, Wen-Hung; Reiter, Russel J; Yang, Shun-Fa

    2017-01-01

    Melatonin is a naturally occurring molecule secreted by the pineal gland and known as a gatekeeper of circadian clocks. Mounting evidence indicates that melatonin, employing multiple and interrelated mechanisms, exhibits a variety of oncostatic properties in a myriad of tumors during different stages of their progression. Tumor metastasis, which commonly occurs at the late stage, is responsible for the majority of cancer deaths; metastases lead to the development of secondary tumors distant from a primary site. In reference to melatonin, the vast majority of investigations have focused on tumor development and progression at the primary site. Recently, however, interest has shifted toward the role of melatonin on tumor metastases. In this review, we highlight current advances in understanding the molecular mechanisms by which melatonin counteracts tumor metastases, including experimental and clinical observations; emphasis is placed on the impact of both cancer and non-neoplastic cells within the tumor microenvironment. Due to the broad range of melatonin's actions, the mechanisms underlying its ability to interfere with metastases are numerous. These include modulation of cell-cell and cell-matrix interaction, extracellular matrix remodeling by matrix metalloproteinases, cytoskeleton reorganization, epithelial-mesenchymal transition, and angiogenesis. The evidence discussed herein will serve as a solid foundation for urging basic and clinical studies on the use of melatonin to understand and control metastatic diseases. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Barcelona conference on epigenetics and cancer 2015: Coding and non-coding functions of the genome.

    Science.gov (United States)

    Corujo, David; Mas, Gloria; Malinverni, Roberto; Di Croce, Luciano; Buschbeck, Marcus

    2016-01-01

    The Barcelona Conference on Epigenetics and Cancer (BCEC) entitled "Coding and Non-Coding functions of the Genome" took place October 29-30, 2015 in Barcelona. The 2015 BCEC was the third edition of a series of annual conferences jointly organized by 5 leading research centers in Barcelona together with B-Debate, an initiative of BioCat. Luciano Di Croce from the Center for Genomic Regulation and Marcus Buschbeck from the Josep Carreras Leukemia Research Institute put together the scientific program with a particular focus on the role of non-coding RNAs in enhancer regulation, epigenetic control by Polycomb complexes, histone variants, and nuclear organization. In one and a half days, 22 talks and 56 posters were presented to an audience of 215 participants.

  9. Mechanical properties of organic semiconductors for mechanically stable and intrinsically stretchable solar cells (Conference Presentation)

    Science.gov (United States)

    Lipomi, Darren J.

    2016-09-01

    This presentation describes my group's efforts to understand the molecular and microstructural basis for the mechanical properties of organic semiconductors for organic photovoltaic (OPV) devices. Our work is motivated by two goals. The first goal is to mitigate mechanical forms of degradation of printed modules during roll-to-roll fabrication, installation, and environmental forces—i.e., wind, rain, snow, and thermal expansion and contraction. Mechanical stability is a prerequisite for inexpensive processing on flexible substrates: to encapsulate devices in glass is to surrender this advantage. The second goal is to enable the next generation of ultra-flexible and stretchable solar cells for collapsible, portable, and wearable applications, and as low-cost sources of energy—"solar tarps"—for disaster relief and for the developing world. It may seem that organic semiconductors, due to their carbon framework, are already sufficiently compliant for these applications. We have found, however, that the mechanical properties (stiffness and brittleness) occupy a wide range of values, and can be difficult to predict from molecular structure alone. We are developing an experimental and theoretical framework for how one can combine favorable charge-transport properties and mechanical compliance in organic semiconductor films. In particular, we have explored the roles of the backbone, alkyl side chain, microstructural order, the glass transition, molecular packing with fullerenes, plasticizing effects of additives, extent of separation of [60]PCBM and [70]PCBM, structural randomness in low-bandgap polymers, and reinforcement by encapsulation, on the mechanical compliance. We are exploring the applicability of semi-empirical "back-of-the-envelope" models, along with multi-scale molecular dynamics simulations, with the ultimate goal of designing electroactive organic materials whose mechanical properties can be dialed-in. We have used the insights we have developed to

  10. Proceedings of the International Conference on Advances in Computational Mechanics 2017

    CERN Document Server

    Phung-Van, Phuc; Rabczuk, Timon

    2018-01-01

    This book provides an overview of state-of-the-art methods in computational engineering for modeling and simulation. This proceedings volume includes a selection of refereed papers presented at the International Conference on Advances in Computational Mechanics (ACOME) 2017, which took place on Phu Quoc Island, Vietnam on August 2-4, 2017. The contributions highlight recent advances in and innovative applications of computational mechanics. Subjects covered include: biological systems; damage, fracture and failure; flow problems; multiscale multiphysics problems; composites and hybrid structures; optimization and inverse problems; lightweight structures; computational mechatronics; computational dynamics; numerical methods; and high-performance computing. The book is intended for academics, including graduate students and experienced researchers interested in state-of-the-art computational methods for solving challenging problems in engineering.

  11. The 5th Conference on Asian Trends in Prostate Cancer Hormone Therapy.

    Science.gov (United States)

    Akaza, Hideyuki; Moore, Malcolm A; Chang, Shu-Jen; Cheng, Christopher; Choi, Han Yong; Esuvaranathan, Kesavan; Hinotsu, Shiro; Hong, Sung-Joon; Kim, Choung-Soo; Kim, Wun-Jae; Murai, Masaru; Naito, Seiji; Soebadi, Doddy; Song, Jae-Mann; Umbas, Rainy; Usami, Michiyuki; Xia, Shujie; Yang, Chi-Rei

    2007-01-01

    The Conference on Asian Trends in Prostate Cancer Hormone Therapy is an annual forum for Asian urologists now in its 5th year. The 2006 conference, held in Bali, Indonesia, was attended by 27 leading urologic oncologists from China, Indonesia, Japan, Korea, Singapore, and Taiwan and featured a packed program of presentations and discussions on a wide range of topics such as relationships among clinicians and the newly opened Asia Regional Office for Cancer Control of the International Union Against Cancer (UICC), detection rates of prostate cancer by biopsy in each of the 6 Asian countries, and favored treatment modalities for hormone-refractory prostate cancer (HRPC) in each country. The first session of the conference kicked off with a keynote lecture entitled "Activities of the UICC ARO". UICC's new office will be the nerve center for its activities in the Asia region. Along with the Asian Pacific Organization for Cancer Prevention (APOCP), UICC aims to shift the focus of attention to cancer control. As such APOCP's long-running publication the APJCP is to be re-launched as the Asian Pacific Journal of Cancer Control. Although UICC is primarily concerned with cancer, several risk factors for cancer are common also to other non-communicable diseases such as diabetes and heart disease, and an important strategy is to implement measures to control these various pathologic conditions as a whole. Apart from contributing to an Asian prostate cancer registry the UICC-ARO will provide training courses, working groups, and assistance in collecting and processing data. The keynote lecture was followed by a roundtable discussion on possible ways in which clinicians from each Asian country can work with UICC. A number of suggestions were put forth including better registration, epidemiology research, possible implementation of UICC prostate cancer guidelines, early detection and screening, and roles of diet and phytotherapy. The underlying reasons for the large but

  12. Recommendations for mechanical ventilation of critically ill children from the Paediatric Mechanical Ventilation Consensus Conference (PEMVECC)

    NARCIS (Netherlands)

    Kneyber, Martin C. J.; de Luca, Daniele; Calderini, Edoardo; Jarreau, Pierre-Henri; Javouhey, Etienne; Lopez-Herce, Jesus; Hammer, Jurg; Macrae, Duncan; Markhorst, Dick G.; Medina, Alberto; Pons-Odena, Marti; Racca, Fabrizio; Wolf, Gerhard; Biban, Paolo; Brierley, Joe; Rimensberger, Peter C.

    2017-01-01

    Purpose: Much of the common practice in paediatric mechanical ventilation is based on personal experiences and what paediatric critical care practitioners have adopted from adult and neonatal experience. This presents a barrier to planning and interpretation of clinical trials on the use of specific

  13. Metabolic and target-site mechanisms combine to confer strong DDT resistance in Anopheles gambiae.

    Science.gov (United States)

    Mitchell, Sara N; Rigden, Daniel J; Dowd, Andrew J; Lu, Fang; Wilding, Craig S; Weetman, David; Dadzie, Samuel; Jenkins, Adam M; Regna, Kimberly; Boko, Pelagie; Djogbenou, Luc; Muskavitch, Marc A T; Ranson, Hilary; Paine, Mark J I; Mayans, Olga; Donnelly, Martin J

    2014-01-01

    The development of resistance to insecticides has become a classic exemplar of evolution occurring within human time scales. In this study we demonstrate how resistance to DDT in the major African malaria vector Anopheles gambiae is a result of both target-site resistance mechanisms that have introgressed between incipient species (the M- and S-molecular forms) and allelic variants in a DDT-detoxifying enzyme. Sequencing of the detoxification enzyme, Gste2, from DDT resistant and susceptible strains of An. gambiae, revealed a non-synonymous polymorphism (I114T), proximal to the DDT binding domain, which segregated with strain phenotype. Recombinant protein expression and DDT metabolism analysis revealed that the proteins from the susceptible strain lost activity at higher DDT concentrations, characteristic of substrate inhibition. The effect of I114T on GSTE2 protein structure was explored through X-ray crystallography. The amino acid exchange in the DDT-resistant strain introduced a hydroxyl group nearby the hydrophobic DDT-binding region. The exchange does not result in structural alterations but is predicted to facilitate local dynamics and enzyme activity. Expression of both wild-type and 114T alleles the allele in Drosophila conferred an increase in DDT tolerance. The 114T mutation was significantly associated with DDT resistance in wild caught M-form populations and acts in concert with target-site mutations in the voltage gated sodium channel (Vgsc-1575Y and Vgsc-1014F) to confer extreme levels of DDT resistance in wild caught An. gambiae.

  14. Whole chromosome gain does not in itself confer cancer-like chromosomal instability.

    Science.gov (United States)

    Valind, Anders; Jin, Yuesheng; Baldetorp, Bo; Gisselsson, David

    2013-12-24

    Constitutional aneuploidy is typically caused by a single-event meiotic or early mitotic error. In contrast, somatic aneuploidy, found mainly in neoplastic tissue, is attributed to continuous chromosomal instability. More debated as a cause of aneuploidy is aneuploidy itself; that is, whether aneuploidy per se causes chromosomal instability, for example, in patients with inborn aneuploidy. We have addressed this issue by quantifying the level of somatic mosaicism, a proxy marker of chromosomal instability, in patients with constitutional aneuploidy by precise background-filtered dual-color FISH. In contrast to previous studies that used less precise methods, we find that constitutional trisomy, even for large chromosomes that are often trisomic in cancer, does not confer a significantly elevated rate of somatic chromosomal mosaicism in individual cases. Constitutional triploidy was associated with an increased level of somatic mosaicism, but this consisted mostly of reversion from trisomy to disomy and did not correspond to a proportionally elevated level of chromosome mis-segregation in triploids, indicating that the observed mosaicism resulted from a specific accumulation of cells with a hypotriploid chromosome number. In no case did the rate of somatic mosaicism in constitutional aneuploidy exceed that of "chromosomally stable" cancer cells. Our findings show that even though constitutional aneuploidy was in some cases associated with low-level somatic mosaicism, it was insufficient to generate the cancer-like levels expected if aneuploidy single-handedly triggered cancer-like chromosomal instability.

  15. Barcelona Conference on Epigenetics and Cancer: 50 years of histone acetylation.

    Science.gov (United States)

    Perez-Salvia, Montserrat; Simó-Riudalbas, Laia; Ausió, Juan; Esteller, Manel

    2015-01-01

    The Barcelona Conference on Epigenetics and Cancer (BCEC) was held in Barcelona, Spain, on October 1(st) and 2(nd), 2014. The meeting was co-organized by the Cancer Epigenetics and Biology Program (PEBC-IDIBELL) and B·Debate, an initiative of Biocat, with the support of "la Caixa" Foundation. The scientific committee was comprised of leading scientists in the field of epigenetics: Dr. Manel Esteller, director of PEBC-IDIBELL, Dr. Alejandro Vaquero and Dr. Esteban Ballestar, from PEBC-IDIBELL, Juan Ausió from the University of Victoria (Canada), and Marcus Buschbeck, from the Institute of Predictive and Personalized Medicine of Cancer (IMPPC), as BCEC series coordinator. This meeting was the second edition of the BCEC series, which was launched by 5 leading Barcelonan institutes to bring together leading investigators in the fields of epigenetics and chromatin research. The topics discussed during the meeting included the current challenges, opportunities, and perspectives surrounding the study of histone modifications (focusing in acetylation), chromatin structure and gene expression, and the involvement of histone acetylation in physiology and diseases, such as cancer or neurological diseases.

  16. Obesity, Inflammation, and Cancer

    OpenAIRE

    Deng, Tuo; Lyon, Christopher J.; Bergin, Stephen; Michael A. Caligiuri; Hsueh, Willa A.

    2016-01-01

    Obesity, a worldwide epidemic, confers increased risk for multiple serious conditions, including cancer, and is increasingly recognized as a growing cause of preventable cancer risk. Chronic inflammation, a well-known mediator of cancer, is a central characteristic of obesity, leading to many of its complications, and obesity-induced inflammation confers additional cancer risk beyond obesity itself. Multiple mechanisms facilitate this strong association between cancer and ob...

  17. Hexokinase 2 confers resistance to cisplatin in ovarian cancer cells by enhancing cisplatin-induced autophagy.

    Science.gov (United States)

    Zhang, Xiao-Yan; Zhang, Meng; Cong, Qing; Zhang, Ming-Xing; Zhang, Meng-Yu; Lu, Ying-Ying; Xu, Cong-Jian

    2018-02-01

    The high mortality rate of ovarian cancer is connected with the development of acquired resistance to multiple cancer drugs, especially cisplatin. Activation of cytoprotective autophagy has been implicated as a contributing mechanism for acquired cisplatin resistance in ovarian cancer cells. Hexokinase 2 (HK2) phosphorylates glucose to generate glucose-6-phosphate, the rate-limiting step in glycolysis. Higher HK2 expression has been associated with chemoresistance in ovarian cancer. However, whether HK2 functionally contributes to cisplatin resistance in ovarian cancer is unclear. In this study, we investigated the role of HK2 in regulating ovarian cancer cisplatin resistance. Increased HK2 levels were detected in drug-resistant human ovarian cancer cells and tissues. Cisplatin downregulated HK2 in cisplatin-sensitive but not in resistant ovarian cancer cells. HK2 knockdown sensitized resistant ovarian cancer cells to cisplatin-induced cell death and apoptosis. Conversely, HK2 overexpression in cisplatin-sensitive cells induced cisplatin resistance. Mechanistically, cisplatin increased ERK1/2 phosphorylation as well as autophagic activity. Blocking autophagy with the autophagy inhibitor 3-MA sensitized resistant ovarian cancer cells to cisplatin. HK2 overexpression enhanced cisplatin-induced ERK1/2 phosphorylation and autophagy while HK2 knockdown showed the opposite effects. Blocking the MEK/ERK pathway using the MEK inhibitor U0126 prevented cisplatin-induced autophagy enhanced by HK2 overexpression. Furthermore, HK2 knockdown sensitized resistance ovarian tumor xenografts to cisplatin in vivo. In conclusion, our data supported that HK2 promotes cisplatin resistance in ovarian cancer by enhancing drug-induced, ERK-mediated autophagy. Therefore, targeting HK2 may be a new therapeutic strategy to combat chemoresistance in ovarian cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Metabolic and target-site mechanisms combine to confer strong DDT resistance in Anopheles gambiae.

    Directory of Open Access Journals (Sweden)

    Sara N Mitchell

    Full Text Available The development of resistance to insecticides has become a classic exemplar of evolution occurring within human time scales. In this study we demonstrate how resistance to DDT in the major African malaria vector Anopheles gambiae is a result of both target-site resistance mechanisms that have introgressed between incipient species (the M- and S-molecular forms and allelic variants in a DDT-detoxifying enzyme. Sequencing of the detoxification enzyme, Gste2, from DDT resistant and susceptible strains of An. gambiae, revealed a non-synonymous polymorphism (I114T, proximal to the DDT binding domain, which segregated with strain phenotype. Recombinant protein expression and DDT metabolism analysis revealed that the proteins from the susceptible strain lost activity at higher DDT concentrations, characteristic of substrate inhibition. The effect of I114T on GSTE2 protein structure was explored through X-ray crystallography. The amino acid exchange in the DDT-resistant strain introduced a hydroxyl group nearby the hydrophobic DDT-binding region. The exchange does not result in structural alterations but is predicted to facilitate local dynamics and enzyme activity. Expression of both wild-type and 114T alleles the allele in Drosophila conferred an increase in DDT tolerance. The 114T mutation was significantly associated with DDT resistance in wild caught M-form populations and acts in concert with target-site mutations in the voltage gated sodium channel (Vgsc-1575Y and Vgsc-1014F to confer extreme levels of DDT resistance in wild caught An. gambiae.

  19. Metabolic and Target-Site Mechanisms Combine to Confer Strong DDT Resistance in Anopheles gambiae

    Science.gov (United States)

    Mitchell, Sara N.; Rigden, Daniel J.; Dowd, Andrew J.; Lu, Fang; Wilding, Craig S.; Weetman, David; Dadzie, Samuel; Jenkins, Adam M.; Regna, Kimberly; Boko, Pelagie; Djogbenou, Luc; Muskavitch, Marc A. T.; Ranson, Hilary; Paine, Mark J. I.; Mayans, Olga; Donnelly, Martin J.

    2014-01-01

    The development of resistance to insecticides has become a classic exemplar of evolution occurring within human time scales. In this study we demonstrate how resistance to DDT in the major African malaria vector Anopheles gambiae is a result of both target-site resistance mechanisms that have introgressed between incipient species (the M- and S-molecular forms) and allelic variants in a DDT-detoxifying enzyme. Sequencing of the detoxification enzyme, Gste2, from DDT resistant and susceptible strains of An. gambiae, revealed a non-synonymous polymorphism (I114T), proximal to the DDT binding domain, which segregated with strain phenotype. Recombinant protein expression and DDT metabolism analysis revealed that the proteins from the susceptible strain lost activity at higher DDT concentrations, characteristic of substrate inhibition. The effect of I114T on GSTE2 protein structure was explored through X-ray crystallography. The amino acid exchange in the DDT-resistant strain introduced a hydroxyl group nearby the hydrophobic DDT-binding region. The exchange does not result in structural alterations but is predicted to facilitate local dynamics and enzyme activity. Expression of both wild-type and 114T alleles the allele in Drosophila conferred an increase in DDT tolerance. The 114T mutation was significantly associated with DDT resistance in wild caught M-form populations and acts in concert with target-site mutations in the voltage gated sodium channel (Vgsc-1575Y and Vgsc-1014F) to confer extreme levels of DDT resistance in wild caught An. gambiae. PMID:24675797

  20. The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Ahmed Abdal Dayem

    2016-09-01

    Full Text Available The high incidence of breast cancer in developed and developing countries, and its correlation to cancer-related deaths, has prompted concerned scientists to discover novel alternatives to deal with this challenge. In this review, we will provide a brief overview of polyphenol structures and classifications, as well as on the carcinogenic process. The biology of breast cancer cells will also be discussed. The molecular mechanisms involved in the anti-cancer activities of numerous polyphenols, against a wide range of breast cancer cells, in vitro and in vivo, will be explained in detail. The interplay between autophagy and apoptosis in the anti-cancer activity of polyphenols will also be highlighted. In addition, the potential of polyphenols to target cancer stem cells (CSCs via various mechanisms will be explained. Recently, the use of natural products as chemotherapeutics and chemopreventive drugs to overcome the side effects and resistance that arise from using chemical-based agents has garnered the attention of the scientific community. Polyphenol research is considered a promising field in the treatment and prevention of breast cancer.

  1. Update on melanoma and non-melanoma skin cancer. Annual Skin Cancer Conference 2011, Hamilton Island, Australia, 5–6 August 2011.

    Science.gov (United States)

    Zalaudek, Iris; Whiteman, David; Rosendahl, Cliff; Menzies, Scott W; Green, Adèle C; Hersey, Peter; Argenziano, Giuseppe

    2011-12-01

    In this article, we will summarize some of the highlights of the third annual conference on skin cancer, with special emphasis on the the recent advances regarding melanoma and non-melanoma skin cancer epidemiology, diagnosis and treatment. Topics were particularly addressed to a newly developing medical branch in Australia, namely that of Primary Care Skin Cancer Practitioners, and focused on strategies to improve primary and secondary prevention and early detection of melanoma and non-melanoma skin cancer using dermoscopy. Controversies related to skin cancer screening programs and recent progresses for treating advanced melanoma were additionally discussed. Yet, besides its scientific goals, the conference aimed also to encourage research originating in primary care and relevant to primary care.

  2. Identification of the mechanism that confers superhydrophobicity on 316L stainless steel

    Energy Technology Data Exchange (ETDEWEB)

    Escobar, Ana M.; Llorca-Isern, Nuria; Rius-Ayra, Oriol

    2016-01-15

    This study develops a rapid method to confer superhydrophobicity on 316L stainless steel surfaces with an amphiphilic reagent such as dodecanoic acid. The highest contact angle (approaching 173°) was obtained after forming hierarchical structures with a non-aqueous electrolyte by an electrolytic process. Our goal was to induce superhydrophobicity directly on 316L stainless steel substrates and to establish which molecules cause the effect. The superhydrophobic behaviour is analysed by contact angle measurements, scanning electron microscopy (SEM), IR spectroscopy and atomic force microscopy (AFM). The growth mechanism is analysed using FE-SEM, TOF-SIMS and XPS in order to determine the molecules involved in the reaction and the growth. The TOF-SIMS analysis revealed that the Ni{sup 2+} ions react with lauric acid to create an ester on the stainless steel surface. - Highlights: • This study develops a rapid and facile approach to impart superhydrophobicity properties to 316L stainless steel surfaces with an amphiphilic reagent such as dodecanoic acid. Surface character changes from superhydrophilicity to superhydrophobicity. • This process changes the surface character from superhydrophilicity to superhydrophobicity. • The process based on electrolysis of a nickel salt in lauric acid provides superhydrophobic behaviour in 316L stainless steel. • The growth mechanism is proposed as a mode island (Volmert- Weber mode). • TOF-SIMS and XPS provided the identification of the molecules involved in the surface modification reaction on AISI 316L inducing superhydrophobicity.

  3. Therapeutic resistance and cancer recurrence mechanisms ...

    Indian Academy of Sciences (India)

    Cancer recurrence is believed to be one of the major reasons for the failure of cancer treatment strategies. Thisbiological phenomenon could arise from the incomplete eradication of tumour cells after chemo- and radiotherapy.Recent developments in the design of models reflecting cancer recurrence and in vivo imaging ...

  4. Therapeutic resistance and cancer recurrence mechanisms ...

    Indian Academy of Sciences (India)

    2016-07-13

    Jul 13, 2016 ... Cancer recurrence is believed to be one of the major reasons for the failure of cancer treatment strategies. This biological phenomenon could arise from the incomplete eradication of tumour cells after chemo- and radiotherapy. Recent developments in the design of models reflecting cancer recurrence and ...

  5. Loss of RASSF2 Enhances Tumorigencity of Lung Cancer Cells and Confers Resistance to Chemotherapy

    Directory of Open Access Journals (Sweden)

    Jennifer Clark

    2012-01-01

    Full Text Available RASSF2 is a novel pro-apoptotic effector of K-Ras that is frequently inactivated in a variety of primary tumors by promoter methylation. Inactivation of RASSF2 enhances K-Ras-mediated transformation and overexpression of RASSF2 suppresses tumor cell growth. In this study, we confirm that RASSF2 and K-Ras form an endogenous complex, validating that RASSF2 is a bona fide K-Ras effector. We adopted an RNAi approach to determine the effects of inactivation of RASSF2 on the transformed phenotype of lung cancer cells containing an oncogenic K-Ras. Loss of RASSF2 expression resulted in a more aggressive phenotype that was characterized by enhanced cell proliferation and invasion, decreased cell adhesion, the ability to grow in an anchorage-independent manner and cell morphological changes. This enhanced transformed phenotype of the cells correlated with increased levels of activated AKT, indicating that RASSF2 can modulate Ras signaling pathways. Loss of RASSF2 expression also confers resistance to taxol and cisplatin, two frontline therapeutics for the treatment of lung cancer. Thus we have shown that inactivation of RASSF2, a process that occurs frequently in primary tumors, enhances the transforming potential of activated K-Ras and our data suggests that RASSF2 may be a novel candidate for epigenetic-based therapy in lung cancer.

  6. [Recent history: 12th International Conference on Cancer, Buenos Aires, Argentina, 1978].

    Science.gov (United States)

    Spinelli, Hugo

    2014-04-01

    Using the approaches of history of the present, this article recovers the discussions surrounding the 12th International Conference on Cancer carried out in Buenos Aires in 1978, in reaction to which Georges Périès organized a "counter-conference" in Paris. In order to understand this discussion, the political situation of the time is described, as is the state of human rights at the time in Argentina, the role of the media - in particular the newspapers La Nación and Clarín and the magazine Gente - and the institutional position adopted by the National Academy of Medicine, as expressed in a letter sent to the presidents of the primary scientific societies of the world. The letter is reprinted in this text as a documentary source, taken from Memoria: Año 1978 (Presidencia de Dr. José E. Rivarola) [Acta: Year 1978 (Presidency of Dr. José E. Rivarola)]. The framework of the discussion makes reference to science's social policy versus science's supposed neutrality and the role of scientific societies.

  7. Mechanisms involved in breast cancer liver metastasis.

    Science.gov (United States)

    Ma, Rui; Feng, Yili; Lin, Shuang; Chen, Jiang; Lin, Hui; Liang, Xiao; Zheng, Heming; Cai, Xiujun

    2015-02-15

    Liver metastasis is a frequent occurrence in patients with breast cancer; however, the available treatments are limited and ineffective. While liver-specific homing of breast cancer cells is an important feature of metastasis, the formation of liver metastases is not random. Indeed, breast cancer cell factors contribute to the liver microenvironment. Major breakthroughs have been achieved recently in understanding breast cancer liver metastasis (BCLM). The process of liver metastasis consists of multiple steps and involves various factors from breast cancer cells and the liver microenvironment. A further understanding of the roles of breast cancer cells and the liver microenvironment is crucial to guide future work in clinical treatments. In this review we discuss the contribution of breast cancer cells and the liver microenvironment to liver metastasis, with the aim to improve therapeutic efficacy for patients with BCLM.

  8. 3rd St. Gallen EORTC Gastrointestinal Cancer Conference: Consensus recommendations on controversial issues in the primary treatment of pancreatic cancer.

    Science.gov (United States)

    Lutz, Manfred P; Zalcberg, John R; Ducreux, Michel; Aust, Daniela; Bruno, Marco J; Büchler, Markus W; Delpero, Jean-Robert; Gloor, Beat; Glynne-Jones, Rob; Hartwig, Werner; Huguet, Florence; Laurent-Puig, Pierre; Lordick, Florian; Maisonneuve, Patrick; Mayerle, Julia; Martignoni, Marc; Neoptolemos, John; Rhim, Andrew D; Schmied, Bruno M; Seufferlein, Thomas; Werner, Jens; van Laethem, Jean-Luc; Otto, Florian

    2017-07-01

    The primary treatment of pancreatic cancer was the topic of the 3rd St. Gallen Conference 2016. A multidisciplinary panel reviewed the current evidence and discussed controversial issues in a moderated consensus session. Here we report on the key expert recommendations. It was generally accepted that radical surgical resection followed by adjuvant chemotherapy offers the only evidence-based treatment with a chance for cure. Initial staging should classify localised tumours as resectable or unresectable (i.e. locally advanced pancreatic cancer) although there remains a large grey-zone of potentially resectable disease between these two categories which has recently been named as borderline resectable, a concept which was generally accepted by the panel members. However, the definition of these borderline-resectable (BR) tumours varies between classifications due to their focus on either (i) technical hurdles (e.g. the feasibility of vascular resection) or (ii) oncological outcome (e.g. predicting the risk of a R1 resection and/or occult metastases). The resulting expert discussion focussed on imaging standards as well as the value of pretherapeutic laparoscopy. Indications for biliary drainage were seen especially before neoadjuvant therapy. Following standard resection, the panel unanimously voted for the use of adjuvant chemotherapy after R0 resection and considered it as a reasonable standard of care after R1 resection, even though the optimal pathologic evaluation and the definition of R0/R1 was the issue of an ongoing debate. The general concept of BR tumours was considered as a good basis to select patients for preoperative therapy, albeit its current impact on the therapeutic strategy was far less clear. Main focus of the conference was to discuss the limits of surgical resection and to identify ways to standardise procedures and to improve curative outcome, including adjuvant and perioperative treatment. Copyright © 2017 The Authors. Published by Elsevier

  9. Epigenetic Mechanisms of Tamoxifen Resistance in Luminal Breast Cancer

    Directory of Open Access Journals (Sweden)

    Hany A. Abdel-Hafiz

    2017-07-01

    Full Text Available Breast cancer is one of the most common cancers and the second leading cause of cancer death in the United States. Estrogen receptor (ER-positive cancer is the most frequent subtype representing more than 70% of breast cancers. These tumors respond to endocrine therapy targeting the ER pathway including selective ER modulators (SERMs, selective ER downregulators (SERDs and aromatase inhibitors (AIs. However, resistance to endocrine therapy associated with disease progression remains a significant therapeutic challenge. The precise mechanisms of endocrine resistance remain unclear. This is partly due to the complexity of the signaling pathways that influence the estrogen-mediated regulation in breast cancer. Mechanisms include ER modifications, alteration of coregulatory function and modification of growth factor signaling pathways. In this review, we provide an overview of epigenetic mechanisms of tamoxifen resistance in ER-positive luminal breast cancer. We highlight the effect of epigenetic changes on some of the key mechanisms involved in tamoxifen resistance, such as tumor-cell heterogeneity, ER signaling pathway and cancer stem cells (CSCs. It became increasingly recognized that CSCs are playing an important role in driving metastasis and tamoxifen resistance. Understanding the mechanism of tamoxifen resistance will provide insight into the design of novel strategies to overcome the resistance and make further improvements in breast cancer therapeutics.

  10. Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant

    Science.gov (United States)

    Sun, Shihua; Sprenger, Cynthia C.T.; Vessella, Robert L.; Haugk, Kathleen; Soriano, Kathryn; Mostaghel, Elahe A.; Page, Stephanie T.; Coleman, Ilsa M.; Nguyen, Holly M.; Sun, Huiying; Nelson, Peter S.; Plymate, Stephen R.

    2010-01-01

    Progression of prostate cancer following castration is associated with increased androgen receptor (AR) expression and signaling despite AR blockade. Recent studies suggest that these activities are due to the generation of constitutively active AR splice variants, but the mechanisms by which these splice variants could mediate such effects are not fully understood. Here we have identified what we believe to be a novel human AR splice variant in which exons 5, 6, and 7 are deleted (ARv567es) and demonstrated that this variant can contribute to cancer progression in human prostate cancer xenograft models in mice following castration. We determined that, in human prostate cancer cell lines, ARv567es functioned as a constitutively active receptor, increased expression of full-length AR (ARfl), and enhanced the transcriptional activity of AR. In human xenografts, human prostate cancer cells transfected with ARv567es cDNA formed tumors that were resistant to castration. Furthermore, the ratio of ARv567es to ARfl expression within the xenografts positively correlated with resistance to castration. Importantly, we also detected ARv567es frequently in human prostate cancer metastases. In summary, these data indicate that constitutively active AR splice variants can contribute to the development of castration-resistant prostate cancers and may serve as biomarkers for patients who are likely to suffer from early recurrence and are candidates for therapies directly targeting the AR rather than ligand. PMID:20644256

  11. Positive coping styles and perigenual ACC volume: two related mechanisms for conferring resilience?

    Science.gov (United States)

    Holz, Nathalie E; Boecker, Regina; Jennen-Steinmetz, Christine; Buchmann, Arlette F; Blomeyer, Dorothea; Baumeister, Sarah; Plichta, Michael M; Esser, Günter; Schmidt, Martin; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

    2016-05-01

    Stress exposure has been linked to increased rates of depression and anxiety in adults, particularly in females, and has been associated with maladaptive changes in the anterior cingulate cortex (ACC), which is an important brain structure involved in internalizing disorders. Coping styles are important mediators of the stress reaction by establishing homeostasis, and may thus confer resilience to stress-related psychopathology. Anatomical scans were acquired in 181 healthy participants at age 25 years. Positive coping styles were determined using a self-report questionnaire (German Stress Coping Questionnaire, SVF78) at age 22 years. Adult anxiety and depression symptoms were assessed at ages 22, 23 and 25 years with the Young Adult Self-Report. Information on previous internalizing diagnoses was obtained by diagnostic interview (2-19 years). Positive coping styles were associated with increased ACC volume. ACC volume and positive coping styles predicted anxiety and depression in a sex-dependent manner with increased positive coping and ACC volume being related to lower levels of psychopathology in females, but not in males. These results remained significant when controlled for previous internalizing diagnoses. These findings indicate that positive coping styles and ACC volume are two linked mechanisms, which may serve as protective factors against internalizing disorders. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  12. Dormancy activation mechanism of oral cavity cancer stem cells.

    Science.gov (United States)

    Chen, Xiang; Li, Xin; Zhao, Baohong; Shang, Dehao; Zhong, Ming; Deng, Chunfu; Jia, Xinshan

    2015-07-01

    Radiotherapy and chemotherapy are targeted primarily at rapidly proliferating cancer cells and are unable to eliminate cancer stem cells in the G0 phase. Thus, these treatments cannot prevent the recurrence and metastasis of cancer. Understanding the mechanisms by which cancer stem cells are maintained in the dormant G0 phase, and how they become active is key to developing new cancer therapies. The current study found that the anti-cancer drug 5-fluorouracil, acting on the oral squamous cell carcinoma KB cell line, selectively killed proliferating cells while sparing cells in the G0 phase. Bisulfite sequencing PCR showed that demethylation of the Sox2 promoter led to the expression of Sox2. This then resulted in the transformation of cancer stem cells from the G0 phase to the division stage and suggested that the transformation of cancer stem cells from the G0 phase to the division stage is closely related to an epigenetic modification of the cell.

  13. Something going on in Milan: a review of the 4th International PhD Student Cancer Conference.

    Science.gov (United States)

    Segré, C

    2010-01-01

    The 4th International PhD Student Cancer Conference was held at the IFOM-IEO-Campus in Milan from 19-21 May 2010 http://www.semm.it/events_researchPast.phpThe Conference covered many topics related to cancer, from basic biology to clinical aspects of the disease. All attendees presented their research, by either giving a talk or presenting a poster. This conference is an opportunity to introduce PhD students to top cancer research institutes across Europe.THE CORE PARTICIPANTING INSTITUTES INCLUDED: European School of Molecular Medicine (SEMM)-IFOM-IEO Campus, MilanBeatson Institute for Cancer Research (BICR), GlasgowCambridge Research Institute (CRI), Cambridge, UKMRC Gray Institute of Radiation Biology (GIROB), OxfordLondon Research Institute (LRI), LondonPaterson Institute for Cancer Research (PICR), ManchesterThe Netherlands Cancer Institute (NKI), Amsterdam'You organizers have crushed all my prejudices towards Italians. Congratulations, I enjoyed the conference immensely!' Even if it might have sounded like rudeness for sure this was supposed to be a genuine compliment (at least, that's how we took it), also considering that it was told by a guy who himself was the fusion of two usually antithetical concepts: fashion style and English nationality.The year 2010 has marked an important event for Italian research in the international scientific panorama: the European School of Molecular Medicine (SEMM) had the honour to host the 4th International PhD Student Cancer Conference, which was held from 19-21 May 2010 at the IFOM-IEO-Campus (http://www.semm.it/events_researchPast.php) in Milan.The conference was attended by more than one hundred students, coming from a selection of cutting edge European institutes devoted to cancer research. The rationale behind it is the promotion of cooperation among young scientists across Europe to debate about science and to exchange ideas and experiences. But that is not all, it is also designed for PhD students to get in touch

  14. Survival advantages conferred to colon cancer cells by E-selectin-induced activation of the PI3K-NFκB survival axis downstream of Death receptor-3

    Directory of Open Access Journals (Sweden)

    Paquet Éric R

    2011-07-01

    Full Text Available Abstract Background Extravasation of circulating cancer cells is a key event of metastatic dissemination that is initiated by the adhesion of cancer cells to endothelial cells. It requires interactions between adhesion receptors on endothelial cells and their counter-receptors on cancer cells. Notably, E-selectin, a major endothelial adhesion receptor, interacts with Death receptor-3 present on metastatic colon carcinoma cells. This interaction confers metastatic properties to colon cancer cells by promoting the adhesion of cancer cells to endothelial cells and triggering the activation of the pro-migratory p38 and pro-survival ERK pathways in the cancer cells. In the present study, we investigated further the mechanisms by which the E-selectin-activated pathways downstream of DR3 confer a survival advantage to colon cancer cells. Methods Cell survival has been ascertained by using the WST-1 assay and by evaluating the activation of the PI3 kinase/NFκB survival axis. Apoptosis has been assayed by determining DNA fragmentation by Hoechst staining and by measuring cleavage of caspases-8 and -3. DR3 isoforms have been identified by PCR. For more precise quantification, targeted PCR reactions were carried out, and the amplified products were analyzed by automated chip-based microcapillary electrophoresis on an Agilent 2100 Bioanalyzer instrument. Results Interaction between DR3-expressing HT29 colon carcinoma cells and E-selectin induces the activation of the PI3K/Akt pathway. Moreover, p65/RelA, the anti-apoptotic subunit of NFκB, is rapidly translocated to the nucleus in response to E-selectin. This translocation is impaired by the PI3K inhibitor LY294002. Furthermore, inhibition of the PI3K/Akt pathway increases the cleavage of caspase 8 in colon cancer cells treated with E-selectin and this effect is still further increased when both ERK and PI3K pathways are concomitantly inhibited. Intriguingly, metastatic colon cancer cell lines such as HT

  15. Consensus on precision medicine for metastatic cancers: a report from the MAP conference.

    Science.gov (United States)

    Swanton, C; Soria, J-C; Bardelli, A; Biankin, A; Caldas, C; Chandarlapaty, S; de Koning, L; Dive, C; Feunteun, J; Leung, S-Y; Marais, R; Mardis, E R; McGranahan, N; Middleton, G; Quezada, S A; Rodón, J; Rosenfeld, N; Sotiriou, C; André, F

    2016-08-01

    Recent advances in biotechnologies have led to the development of multiplex genomic and proteomic analyses for clinical use. Nevertheless, guidelines are currently lacking to determine which molecular assays should be implemented in metastatic cancers. The first MAP conference was dedicated to exploring the use of genomics to better select therapies in the treatment of metastatic cancers. Sixteen consensus items were covered. There was a consensus that new technologies like next-generation sequencing of tumors and ddPCR on circulating free DNA have convincing analytical validity. Further work needs to be undertaken to establish the clinical utility of liquid biopsies and the added clinical value of expanding from individual gene tests into large gene panels. Experts agreed that standardized bioinformatics methods for biological interpretation of genomic data are needed and that precision medicine trials should be stratified based on the level of evidence available for the genomic alterations identified. © The Author 2016. 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.

  16. BRIP1 loss-of-function mutations confer high risk for familial ovarian cancer, but not familial breast cancer.

    Science.gov (United States)

    Weber-Lassalle, Nana; Hauke, Jan; Ramser, Juliane; Richters, Lisa; Groß, Eva; Blümcke, Britta; Gehrig, Andrea; Kahlert, Anne-Karin; Müller, Clemens R; Hackmann, Karl; Honisch, Ellen; Weber-Lassalle, Konstantin; Niederacher, Dieter; Borde, Julika; Thiele, Holger; Ernst, Corinna; Altmüller, Janine; Neidhardt, Guido; Nürnberg, Peter; Klaschik, Kristina; Schroeder, Christopher; Platzer, Konrad; Volk, Alexander E; Wang-Gohrke, Shan; Just, Walter; Auber, Bernd; Kubisch, Christian; Schmidt, Gunnar; Horvath, Judit; Wappenschmidt, Barbara; Engel, Christoph; Arnold, Norbert; Dworniczak, Bernd; Rhiem, Kerstin; Meindl, Alfons; Schmutzler, Rita K; Hahnen, Eric

    2018-01-24

    Germline mutations in the BRIP1 gene have been described as conferring a moderate risk for ovarian cancer (OC), while the role of BRIP1 in breast cancer (BC) pathogenesis remains controversial. To assess the role of deleterious BRIP1 germline mutations in BC/OC predisposition, 6341 well-characterized index patients with BC, 706 index patients with OC, and 2189 geographically matched female controls were screened for loss-of-function (LoF) mutations and potentially damaging missense variants. All index patients met the inclusion criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for germline testing and tested negative for pathogenic BRCA1/2 variants. BRIP1 LoF mutations confer a high OC risk in familial index patients (odds ratio (OR) = 20.97, 95% confidence interval (CI) = 12.02-36.57, P mutations with familial BC was observed (OR = 1.81 95% CI = 1.00-3.30, P = 0.0623). In the subgroup of familial BC index patients without a family history of OC there was also no apparent association (OR = 1.42, 95% CI = 0.70-2.90, P = 0.3030). In 1027 familial BC index patients with a family history of OC, the BRIP1 mutation prevalence was significantly higher than that observed in controls (OR = 3.59, 95% CI = 1.43-9.01; P = 0.0168). Based on the negative association between BRIP1 LoF mutations and familial BC in the absence of an OC family history, we conclude that the elevated mutation prevalence in the latter cohort was driven by the occurrence of OC in these families. Compared with controls, predicted damaging rare missense variants were significantly more prevalent in OC (P = 0.0014) but not in BC (P = 0.0693) patients. To avoid ambiguous results, studies aimed at assessing the impact of candidate predisposition gene mutations on BC risk might differentiate between BC index patients with an OC family history and those without. In familial cases, we suggest that BRIP1 is a high-risk gene for late

  17. Cancer epigenetics: from mechanism to therapy.

    Science.gov (United States)

    Dawson, Mark A; Kouzarides, Tony

    2012-07-06

    The epigenetic regulation of DNA-templated processes has been intensely studied over the last 15 years. DNA methylation, histone modification, nucleosome remodeling, and RNA-mediated targeting regulate many biological processes that are fundamental to the genesis of cancer. Here, we present the basic principles behind these epigenetic pathways and highlight the evidence suggesting that their misregulation can culminate in cancer. This information, along with the promising clinical and preclinical results seen with epigenetic drugs against chromatin regulators, signifies that it is time to embrace the central role of epigenetics in cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Conference on Hamiltonian Systems and Celestial Mechanics 2014 & Workshop on Virus Dynamics and Evolution : Extended Abstracts Spring 2014

    CERN Document Server

    Cors, Josep; Llibre, Jaume; Korobeinikov, Andrei

    2015-01-01

    The two parts of the present volume contain extended conference abstracts corresponding to selected talks given by participants at the "Conference on Hamiltonian Systems and Celestial Mechanics 2014" (HAMSYS2014) (15 abstracts) and at the "Workshop on Virus Dynamics and Evolution" (12 abstracts), both held at the Centre de Recerca Matemàtica (CRM) in Barcelona from June 2nd to 6th, 2014, and from June 23th to 27th, 2014, respectively. Most of them are brief articles, containing preliminary presentations of new results not yet published in regular research journals. The articles are the result of a direct collaboration between active researchers in the area after working in a dynamic and productive atmosphere. The first part is about Central Configurations, Periodic Orbits and Hamiltonian Systems with applications to Celestial Mechanics – a very modern and active field of research. The second part is dedicated to mathematical methods applied to viral dynamics and evolution. Mathematical modelling of biologi...

  19. Diversity of Molecular Mechanisms Conferring Carbapenem Resistance to Pseudomonas aeruginosa Isolates from Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Mohamed H. Al-Agamy

    2016-01-01

    Full Text Available Background. This study described various molecular and epidemiological characters determining antibiotic resistance patterns in Pseudomonas aeruginosa isolates. Methods. A total of 34 carbapenem-resistant P. aeruginosa clinical isolates were isolated from samples collected at a tertiary hospital in Riyadh, Saudi Arabia, from January to December 2011. Susceptibility testing, serotyping, molecular characterization of carbapenem resistance, and pulsed-field gel electrophoresis (PFGE were performed. Results. All isolates were resistant to ceftazidime, and more than half were highly resistant (minimum inhibitory concentration (MIC > 256 mg/L. Fifteen isolates had MIC values ≥64 mg/L for any of the carbapenems examined. Vietnamese extended-spectrum β-lactamase (VEB-1 (n=16/34 and oxacillinase (OXA-10 (n=14/34 were the most prevalent extended-spectrum β-lactamase and penicillinase, respectively. Verona imipenemase (VIM-1, VIM-2, VIM-4, VIM-11, and VIM-28 and imipenemase (IMP-7 variants were found in metallo-β-lactamase producers. A decrease in outer membrane porin gene (oprD expression was seen in nine isolates, and an increase in efflux pump gene (MexAB expression was detected in five isolates. Six serotypes (O:1, O:4, O:7, O:10, O:11, and O:15 were found among the 34 isolates. The predominant serotype was O:11 (16 isolates, followed by O:15 (nine isolates. PFGE analysis of the 34 carbapenem-resistant P. aeruginosa isolates revealed 14 different pulsotypes. Conclusions. These results revealed diverse mechanisms conferring carbapenem resistance to P. aeruginosa isolates from Saudi Arabia.

  20. Molecular Mechanisms of Prostate Cancer Progression

    National Research Council Canada - National Science Library

    Holt, Shawn E; Elmore, Lynne W

    2005-01-01

    ... increased telomerase activity. In order to determine the importance of the chaperone increase during prostate cancer progression, we have taken a 2-pronged approach, using both genetic and pharmacologic approaches...

  1. Protective mechanism against cancer found in progeria patient cells

    Science.gov (United States)

    NCI scientists have studied cells of patients with an extremely rare genetic disease that is characterized by drastic premature aging and discovered a new protective cellular mechanism against cancer. They found that cells from patients with Hutchinson Gi

  2. Maintaining success, reducing treatment burden, focusing on survivorship : highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer

    NARCIS (Netherlands)

    Beyer, J.; Albers, P.; Altena, R.; Aparicio, J.; Bokemeyer, C.; Busch, J.; Cathomas, R.; Cavallin-Stahl, E.; Clarke, N. W.; Classen, J.; Cohn-Cedermark, G.; Dahl, A. A.; Daugaard, G.; De Giorgi, U.; De Santis, M.; De Wit, M.; De Wit, R.; Dieckmann, K. P.; Fenner, M.; Fizazi, K.; Flechon, A.; Fossa, S. D.; Germa Lluch, J. R.; Gietema, J. A.; Gillessen, S.; Giwercman, A.; Hartmann, J.T.; Heidenreich, A.; Hentrich, M.; Honecker, F.; Horwich, A.; Huddart, R. A.; Kliesch, S.; Kollmannsberger, C.; Krege, S.; Laguna, M. P.; Looijenga, L. H. J.; Lorch, A.; Lotz, J. P.; Mayer, F.; Necchi, A.; Nicolai, N.; Nuver, J.; Oechsle, K.; Oldenburg, J.; Oosterhuis, J.W.; Powles, T.; Rajpert-De Meyts, E.; Rick, O.; Rosti, G.; Salvioni, R.; Schrader, M.; Schweyer, S.; Sedlmayer, F.; Sohaib, A.; Souchon, R.; Tandstad, T.; Wittekind, C.; Winter, E.

    In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European

  3. COPING MECHANISM OF CAREER WOMEN WITH BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Rosnani Rosnani

    2017-06-01

    Full Text Available Introduction: Patients with cancer may experience psychological disorders such as depression, anxiety, anger, helplessness, and unappreciated, so in certain situations require defense mechanisms (coping mechanism to oppose or resist feelings of anxiety, fear or stress that haunt her. The aim of this study was to know the coping mechanism of career women with breast cancer reviewed by phenomenology in Palembang 2016. Method: Type of this study was a qualitative study with a phenomenological approach. Total samples were 8 participants with inclusion criteria: career women, productive age range, health physic and physiologic. Independent variable was a coping mechanism, and the dependent variable was breast cancer. The instrument used the voice recorder, and interview guides. Data analyze used verbatim transcript with credibility, dependability, and confirmability. Result: The results showed that working women who have breast cancer have a coping strategy that is adjusted to the psychological condition and physical reactions of the therapy in progress. Psychologically, the coping mechanism is in the form of rejecting, drawing closer to Allah SWT, seeking the opinion of other health workers, discussing conditions with spouse and family, seeking alternative treatment and asking for doctor's direction. The coping mechanism of the body's reaction to therapy is done by taking medicine according to the rules and remember Allah SWT. Conclusions: Need the support of the coping mechanism in patients with breast cancer and nursing care approach with the pattern of coping mechanisms with the involvement of the family.

  4. The Fluid Mechanics of Cancer and Its Therapy

    Science.gov (United States)

    Koumoutsakos, Petros; Pivkin, Igor; Milde, Florian

    2013-01-01

    Fluid mechanics is involved in the growth, progression, metastasis, and therapy of cancer. Blood vessels transport oxygen and nutrients to cancerous tissues, provide a route for metastasizing cancer cells to distant organs, and deliver drugs to tumors. The irregular and leaky tumor vasculature is responsible for increased interstitial pressure in the tumor microenvironment, whereas multiscale flow-structure interaction processes control tumor growth, metastasis, and nanoparticle-mediated drug delivery. We outline these flow-mediated processes, along with related experimental and computational methods for the diagnosis, predictive modeling, and therapy of cancer.

  5. Changes in cellular mechanical properties during onset or progression of colorectal cancer

    Science.gov (United States)

    Ciasca, Gabriele; Papi, Massimiliano; Minelli, Eleonora; Palmieri, Valentina; De Spirito, Marco

    2016-01-01

    Colorectal cancer (CRC) development represents a multistep process starting with specific mutations that affect proto-oncogenes and tumour suppressor genes. These mutations confer a selective growth advantage to colonic epithelial cells that form first dysplastic crypts, and then malignant tumours and metastases. All these steps are accompanied by deep mechanical changes at the cellular and the tissue level. A growing consensus is emerging that such modifications are not merely a by-product of the malignant progression, but they could play a relevant role in the cancer onset and accelerate its progression. In this review, we focus on recent studies investigating the role of the biomechanical signals in the initiation and the development of CRC. We show that mechanical cues might contribute to early phases of the tumour initiation by controlling the Wnt pathway, one of most important regulators of cell proliferation in various systems. We highlight how physical stimuli may be involved in the differentiation of non-invasive cells into metastatic variants and how metastatic cells modify their mechanical properties, both stiffness and adhesion, to survive the mechanical stress associated with intravasation, circulation and extravasation. A deep comprehension of these mechanical modifications may help scientist to define novel molecular targets for the cure of CRC. PMID:27621568

  6. Deciphering the Molecular Mechanisms of Breast Cancer

    Science.gov (United States)

    2005-03-01

    together, these observations led to the hypothesis that BRCA1 mayPhiladelphia, Pennsylvania 19104 2 Department of Medical Oncology function as a...familial breast cancer (Hall BRCA1 ubiquitin E3 ligase activity has identified theet al., 1990; Narod et al., 1991; Miki et al., 1994; Wooster RING

  7. Application of Imaging Techniques to Mechanics of Materials and Structures, Volume 4 : Proceedings of the 2010 Annual Conference on Experimental and Applied Mechanics

    CERN Document Server

    2013-01-01

    This the fourth volume of six from the Annual Conference of the Society for Experimental Mechanics, 2010, brings together 58 chapters on Application of Imaging Techniques to Mechanics of Materials and Structure. It presents findings from experimental and computational investigations involving a range of imaging techniques including Recovery of 3D Stress Intensity Factors From Surface Full-field Measurements, Identification of Cohesive-zone Laws From Crack-tip Deformation Fields, Application of High Speed Digital Image Correlation for Vibration Mode Shape Analysis, Characterization of Aluminum Alloys Using a 3D Full Field Measurement, and Low Strain Rate Measurements on Explosives Using DIC.

  8. Highlights from the 13th St Gallen International Breast Cancer Conference 2013. Access to innovation for patients with breast cancer: how to speed it up?

    Science.gov (United States)

    Curigliano, Giuseppe; Criscitiello, Carmen; Andrè, Fabrice; Colleoni, Marco; Di Leo, Angelo

    2013-01-01

    The recognition that early breast cancer is a spectrum of diseases each requiring a specific systemic therapy guided the 13th St Gallen International Breast Cancer Consensus Conference [1]. The meeting assembled 3600 participants from nearly 90 countries worldwide. Educational content has been centred on the primary and multidisciplinary treatment approach of early breast cancer. The meeting culminated on the final day, with the St Gallen Breast Cancer Treatment Consensus, established by 40-50 of the world's most experienced opinion leaders in the field of breast cancer treatment. The major issue that arose during the consensus conference was the increasing gap between what is theoretically feasible in patient risk stratification, in treatment, and in daily practice management. We need to find new paths to access innovations to clinical research and daily practice. To ensure that continued innovation meets the needs of patients, the therapeutic alliance between patients and academic-led research should to be extended to include relevant pharmaceutical companies and drug regulators with a unique effort to bring innovation into clinical practice. We need to bring together major players from the world of breast cancer research to map out a coordinated strategy on an international scale, to address the disease fragmentation, to share financial resources, and to integrate scientific data. The final goal will be to improve access to an affordable, best standard of care for all patients in each country.

  9. Obesity and cancer risk: evidence, mechanisms, and recommendations.

    Science.gov (United States)

    Vucenik, Ivana; Stains, Joseph P

    2012-10-01

    Obesity, a growing health problem worldwide, has been associated with the metabolic syndrome, diabetes, cardiovascular disease, hypertension, and other chronic diseases. Recently, the obesity-cancer link has received much attention. Epidemiological studies have shown that obesity is also associated with increased risk of several cancer types, including colon, breast, endometrium, liver, kidney, esophagus, gastric, pancreatic, gallbladder, and leukemia, and can also lead to poorer treatment and increased cancer-related mortality. Biological mechanisms underlying the relationship between obesity and cancer are not well understood. They include modulation of energy balance and calorie restriction, growth factors, multiple signaling pathways, and inflammatory processes. Key among the signaling pathways linking obesity and cancer is the PI3K/Akt/mTOR cascade, which is a target of many of the obesity-associated factors and regulates cell proliferation and survival. Understanding the molecular and cellular mechanisms of the obesity-cancer connection is important in developing potential therapeutics. The link between obesity and cancer underscores the recommendation to maintain a healthy body weight throughout life as one of the most important ways to protect against cancer. © 2012 New York Academy of Sciences.

  10. Carcinogenic mechanisms of endometrial cancer: involvement of genetics and epigenetics.

    Science.gov (United States)

    Banno, Kouji; Yanokura, Megumi; Iida, Miho; Masuda, Kenta; Aoki, Daisuke

    2014-08-01

    Endometrial cancer is increasing worldwide and the number of patients with this disease is likely to continue to grow, including younger patients. Many endometrial cancers show estrogen-dependent proliferation, but the carcinogenic mechanisms are unknown or not completely explained beyond mutations of single oncogenes and tumor suppressor genes. Possible carcinogenic mechanisms include imbalance between endometrial proliferation by unopposed estrogen and the mismatch repair (MMR) system; hypermethylation of the MMR gene hMLH1; mutation of PTEN, β-catenin and K-ras genes in type I endometrial cancer and of HER-2/neu and p53 genes in type II endometrial cancer; hypermethylation of SPRY2, RASSF1A, RSK4, CHFR and CDH1; and methylation of tumor suppressor microRNAs, including miR-124, miR-126, miR-137, miR-491, miR-129-2 and miR-152. Thus, it is likely that the carcinogenic mechanisms of endometrial cancer involve both genetic and epigenetic changes. Mutations and methylation of MMR genes induce various oncogenic changes that cause carcinogenesis, and both MMR mutation in germ cells and methylation patterns may be inherited over generations and cause familial tumorigenesis. Determination of the detailed carcinogenic mechanisms will be useful for prevention and diagnosis of endometrial cancer, risk assessment, and development of new treatment strategies targeting MMR genes. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  11. Molecular Mechanisms of Prostate Cancer Progression

    National Research Council Canada - National Science Library

    Holt, Shawn

    2003-01-01

    In studies to define the mechanisms involved in the progression of immortal, non-tumorigenic prostate cells to a tumorigenic state, we have found that molecular chaperones are elevated along with telomerase activity...

  12. Molecular Mechanisms of Prostate Cancer Progression

    National Research Council Canada - National Science Library

    Holt, Shawn

    2004-01-01

    In studios to define the mechanisms involved in the progression of immortal non tumorigenic prostate cells to a tumorigenic state, we have found that molecular chaperones are elevated along with telomerase activity...

  13. Mechanisms of resistance in castration-resistant prostate cancer (CRPC).

    Science.gov (United States)

    Chandrasekar, Thenappan; Yang, Joy C; Gao, Allen C; Evans, Christopher P

    2015-06-01

    Despite advances in prostate cancer diagnosis and management, morbidity from prostate cancer remains high. Approximately 20% of men present with advanced or metastatic disease, while 29,000 men continue to die of prostate cancer each year. Androgen deprivation therapy (ADT) has been the standard of care for initial management of advanced or metastatic prostate cancer since Huggins and Hodges first introduced the concept of androgen-dependence in 1972, but progression to castration-resistant prostate cancer (CRPC) occurs within 2-3 years of initiation of ADT. CRPC, previously defined as hormone-refractory prostate cancer, is now understood to still be androgen dependent. Multiple mechanisms of resistance help contribute to the progression to castration resistant disease, and the androgen receptor (AR) remains an important driver in this progression. These mechanisms include AR amplification and hypersensitivity, AR mutations leading to promiscuity, mutations in coactivators/corepressors, androgen-independent AR activation, and intratumoral and alternative androgen production. More recently, identification of AR variants (ARVs) has been established as another mechanism of progression to CRPC. Docetaxel chemotherapy has historically been the first-line treatment for CRPC, but in recent years, newer agents have been introduced that target some of these mechanisms of resistance, thereby providing additional survival benefit. These include AR signaling inhibitors such as enzalutamide (Xtandi, ENZA, MDV-3100) and CYP17A1 inhibitors such as abiraterone acetate (Zytiga). Ultimately, these agents will also fail to suppress CRPC. While some of the mechanisms by which these agents fail are unique, many share similarities to the mechanisms contributing to CRPC progression. Understanding these mechanisms of resistance to ADT and currently approved CRPC treatments will help guide future research into targeted therapies.

  14. miR-338-3p confers 5-fluorouracil resistance in p53 mutant colon cancer cells by targeting the mammalian target of rapamycin.

    Science.gov (United States)

    Han, Jia; Li, Jie; Tang, Kaijie; Zhang, Huahua; Guo, Bo; Hou, Ni; Huang, Chen

    2017-11-15

    Evidence demonstrate that p53 mutations and microRNAs (miRs) are important components of 5-FU resistance in colorectal cancer (CRC). miR-338-3p has been reported associated with cancer prognosis. However whether or not it influences chemotherapy sensitivity and the underlying mechanisms have not been elucidated. Here, three types of human colon cancer cell lines, HT29 (mutant p53), HCT116 (wild-type p53), and HCT116 p53-/- (deficient p53), were treated with 5-FU. We showed that expression of miR-338-3p was correlated with apoptosis and 5-FU resistance in colon cancer cells. Ectopic expression of miR-338-3p conferred resistance to 5-FU in HCT116 cells. Further experiments indicated that miR-338-3p mediated 5-FU resistance through down-regulation of mTOR expression. Moreover, inhibition of miR-338-3p in HT29 and HCT116 p53-/- cells increased their sensitivity to 5-FU treatment. Furthermore, we detected autophagy changes in our experiment because mTOR was known prominently regulating autophagy and the competition between autophagy and apoptosis in response to 5-FU was a mechanism influencing 5-FU sensitivity. Our results reveal a critical and novel role of miR-338-3p in the correlation of 5-FU resistance with p53 status. Moreover, the miR-338-3p inhibitor has the potential to overcome 5-FU resistance in p53 mutant colon cancer cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. The need for public education on HPV and cervical cancer prevention in Asia. Opinions of experts at the AOGIN conference.

    Science.gov (United States)

    Garland, S; Park, S N; Ngan, H Y S; Frazer, I; Tay, E H; Chen, C J; Bhatla, N; Pitts, M; Shin, H R; Konno, R; Smith, J; Pagliusi, S; Park, J S

    2008-10-09

    Asia accounts for more than half of all cases of cervical cancer registered globally and improving prevention is urgently needed. A range of tools and strategies is now available to effectively prevent this disease, including two new prophylactic HPV vaccines approved and recommended for adolescents and young women. However, without communication these tools may have little impact on disease burden. The conferences of the Asia Oceania Research Organisation in Genital Infection and Neoplasia (AOGIN) bring together clinicians and scientists whose work is related to genital infections, particularly HPV, cervical dysplasia and neoplasia, as well as other anogenital cancers, with the aim of improving communication on prevention through human papillomavirus (HPV) vaccination and screening in Asian countries. The scope of this year's AOGIN conference was to extend education to include health workers, family doctors, paediatricians, governmental health agencies, and the general public through patients' testimonials that can reach out to women raising awareness of this silent disease. Community based initiatives and awareness campaigns were also reported, and can empower the people to engage in a dialog with local governments towards prioritization of cancer prevention programs, achieving more for the public than isolated actions. Parents and teachers are encouraged to communicate about these issues within families and schools. Evidence was discussed that males can participate in cervical cancer control as well, and prevention programs involving men should not be neglected as they may reduce genital disease burden in women. Opinion leaders proposed prevention measures to be considered for governmental decisions. While each country develops a locally appropriate policy for cervical cancer control there is a need to revise these programs regularly, as knowledge increases in response to public need, as well as to gather evidence about disease burden and the effectiveness of

  16. InCVAX, a novel in situ autologous cancer vaccine (Conference Presentation)

    Science.gov (United States)

    Lam, Samuel Siu Kit; Chen, Wei R.

    2017-02-01

    . In addition, we have extended our research of InCVAX to other tumor models and to better understand the mechanism of how GC stimulate the immune system, primarily through activation of antigen presenting cells (APCs). With our data showing therapeutic efficacy of inCVAX in animal and human models, we are confident that inCVAX can bring significant benefit to metastatic cancer patients in the near future.

  17. Trastuzumab: updated mechanisms of action and resistance in breast cancer

    Directory of Open Access Journals (Sweden)

    Francois X. Claret

    2012-06-01

    Full Text Available HER2-postitive breast cancer has the second-poorest prognosis among breast cancer subtypes. One of the most effective targeted therapies for patients with HER2-positive breast cancer is trastuzumab-based. However, primary or acquired resistance to trastuzumab has been a major obstacle in the clinical management of this disease. Therefore, to better control HER2-postitive breast cancer, it is necessary to gain a deeper understanding of trastuzumab’s actions and the pathways that cancer cells use to dodge its effects. In this review, we attempt to give an overview of the widely accepted and currently proposed molecular mechanisms for these actions and highlight recent advances in our understanding of HER2 targeted therapies.

  18. Functions and mechanisms of long noncoding RNAs in lung cancer

    Directory of Open Access Journals (Sweden)

    Peng ZZ

    2016-07-01

    Full Text Available Zhenzi Peng, Chunfang Zhang, Chaojun Duan Institute of Medical Sciences, Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, People’s Republic of China Abstract: Lung cancer is a heterogeneous disease, and there is a lack of adequate biomarkers for diagnosis. Long noncoding RNAs (lncRNAs are emerging as an important set of molecules because of their roles in various key pathophysiological pathways, including cell growth, apoptosis, and metastasis. We review the current knowledge of the lncRNAs in lung cancer. In-depth analyses of lncRNAs in lung cancer have increased the number of potential effective biomarkers, thus providing options to increase the therapeutic benefit. In this review, we summarize the functions, mechanisms, and regulatory networks of lncRNAs in lung cancer, providing a basis for further research in this field. Keywords: ncRNA, tumorigenesis, biomarker, network, proliferation, apoptosis 

  19. Epidemiological bases and molecular mechanisms linking obesity, diabetes, and cancer.

    Science.gov (United States)

    Gutiérrez-Salmerón, María; Chocarro-Calvo, Ana; García-Martínez, José Manuel; de la Vieja, Antonio; García-Jiménez, Custodia

    2017-02-01

    The association between diabetes and cancer was hypothesized almost one century ago. Today, a vast number of epidemiological studies support that obese and diabetic populations are more likely to experience tissue-specific cancers, but the underlying molecular mechanisms remain unknown. Obesity, diabetes, and cancer share many hormonal, immune, and metabolic changes that may account for the relationship between diabetes and cancer. In addition, antidiabetic treatments may have an impact on the occurrence and course of some cancers. Moreover, some anticancer treatments may induce diabetes. These observations aroused a great controversy because of the ethical implications and the associated commercial interests. We report an epidemiological update from a mechanistic perspective that suggests the existence of many common and differential individual mechanisms linking obesity and type 1 and 2 diabetes mellitus to certain cancers. The challenge today is to identify the molecular links responsible for this association. Classification of cancers by their molecular signatures may facilitate future mechanistic and epidemiological studies. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Evidence and Mechanisms of Fat Depletion in Cancer

    Science.gov (United States)

    Ebadi, Maryam; Mazurak, Vera C.

    2014-01-01

    The majority of cancer patients experience wasting characterized by muscle loss with or without fat loss. In human and animal models of cancer, body composition assessment and morphological analysis reveals adipose atrophy and presence of smaller adipocytes. Fat loss is associated with reduced quality of life in cancer patients and shorter survival independent of body mass index. Fat loss occurs in both visceral and subcutaneous depots; however, the pattern of loss has been incompletely characterized. Increased lipolysis and fat oxidation, decreased lipogenesis, impaired lipid depositionand adipogenesis, as well as browning of white adipose tissue may underlie adipose atrophy in cancer. Inflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β) produced by the tumor or adipose tissue may also contribute to adipose depletion. Identifying the mechanisms and time course of fat mass changes in cancer may help identify individuals at risk of adipose depletion and define interventions to circumvent wasting. This review outlines current knowledge of fat mass in cancer and illustrates the need for further studies to assess alterations in visceral and subcutaneous adipose depots and possible mechanisms for loss of fat during cancer progression. PMID:25415607

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

    Science.gov (United States)

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

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

  2. Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016

    DEFF Research Database (Denmark)

    Lugli, Alessandro; Kirsch, Richard; Ajioka, Yoichi

    2017-01-01

    Tumor budding is a well-established independent prognostic factor in colorectal cancer but a standardized method for its assessment has been lacking. The primary aim of the International Tumor Budding Consensus Conference (ITBCC) was to reach agreement on an international, evidence......-based standardized scoring system for tumor budding in colorectal cancer. The ITBCC included nine sessions with presentations, a pre-meeting survey and an e-book covering the key publications on tumor budding in colorectal cancer. The Grading of Recommendation Assessment, Development and Evaluation' method was used...... to determine the strength of recommendations and quality of evidence. The following 10 statements achieved consensus: Tumor budding is defined as a single tumor cell or a cell cluster consisting of four tumor cells or less (22/22, 100%). Tumor budding is an independent predictor of lymph node metastases in pT1...

  3. The molecular mechanism and regulatory pathways of cancer stem cells

    Directory of Open Access Journals (Sweden)

    Zhen Wang

    2016-01-01

    Full Text Available Malignant cancer is among the top of the life-threatening conditions, challenging humanity for a long time. Traditional methods of cancer therapy include surgery, chemotherapy, and radiotherapy, which aim to remove/destroy cancer cells. Although theoretically very promising, none of these methods can effectively eradicate cancer, the reason for which can be attributed to our incomplete understanding of the mechanism of cancer metastasis and recurrence. In recent years, researchers have proposed the theory of cancer stem cell (CSC. CSC is a small population of tumor cells that have unlimited self-renewal ability, exhibit a strong resistance to chemotherapy and radiotherapy, and have been proved to be the core reason of cancer metastasis and recurrence. CSC theory provides a deep insight into malignant tumorigenesis that brings new hope for tumor therapy. In this paper, we intend to discuss the development of CSC theory and summarize the regulatory pathways involved in CSC origin and self-renewal, which might be of assistance in the future development of malignant cancer therapy.

  4. COX-2 and PPAR-γ confer cannabidiol-induced apoptosis of human lung cancer cells.

    Science.gov (United States)

    Ramer, Robert; Heinemann, Katharina; Merkord, Jutta; Rohde, Helga; Salamon, Achim; Linnebacher, Michael; Hinz, Burkhard

    2013-01-01

    The antitumorigenic mechanism of cannabidiol is still controversial. This study investigates the role of COX-2 and PPAR-γ in cannabidiol's proapoptotic and tumor-regressive action. In lung cancer cell lines (A549, H460) and primary cells from a patient with lung cancer, cannabidiol elicited decreased viability associated with apoptosis. Apoptotic cell death by cannabidiol was suppressed by NS-398 (COX-2 inhibitor), GW9662 (PPAR-γ antagonist), and siRNA targeting COX-2 and PPAR-γ. Cannabidiol-induced apoptosis was paralleled by upregulation of COX-2 and PPAR-γ mRNA and protein expression with a maximum induction of COX-2 mRNA after 8 hours and continuous increases of PPAR-γ mRNA when compared with vehicle. In response to cannabidiol, tumor cell lines exhibited increased levels of COX-2-dependent prostaglandins (PG) among which PGD(2) and 15-deoxy-Δ(12,14)-PGJ(2) (15d-PGJ(2)) caused a translocation of PPAR-γ to the nucleus and induced a PPAR-γ-dependent apoptotic cell death. Moreover, in A549-xenografted nude mice, cannabidiol caused upregulation of COX-2 and PPAR-γ in tumor tissue and tumor regression that was reversible by GW9662. Together, our data show a novel proapoptotic mechanism of cannabidiol involving initial upregulation of COX-2 and PPAR-γ and a subsequent nuclear translocation of PPAR-γ by COX-2-dependent PGs.

  5. Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup: Recommendations on incorporating patient-reported outcomes in clinical trials in epithelial ovarian cancer.

    Science.gov (United States)

    Joly, Florence; Hilpert, Felix; Okamoto, Aikou; Stuart, Gavin; Ochiai, Kasunori; Friedlander, Michael

    2017-06-01

    Despite the support for including patient-reported outcomes (PROs) and health-related quality of life in clinical trials, there have been deficiencies in how these have been assessed and reported in epithelial ovarian cancer (EOC) clinical trials. To redress this, the 5th Ovarian Cancer Consensus Conference, included a plenary session entitled 'How to include PROs in clinical trials'. The perspective is a summary of the recommendations made by the Gynecologic Cancer InterGroup unanimously agreed on the importance of PROs and PRO end-points in EOC clinical trials. They recognised that effort must be made to ensure the integrity of collection of PRO data and to avoid missing data. PRO end-points should be based on the PRO hypotheses, be context specific and reflect the patient population and the objectives of treatment (e.g. first line, maintenance therapy, early or late relapse). The PRO end-points inform the choice of PRO measures used in the trial and how the results are analysed and reported. There was agreement that progression-free survival should be supported by PROs among patients with late relapse (platinum sensitive) and that progression-free survival alone was not sufficient as the primary end-point of clinical trials in patients with platinum resistant/refractory EOC and PROs should be included as either the primary/co-primary end-point in this subset of patients. Novel approaches to measure the benefit of palliative chemotherapy such as time until definitive deterioration of Health-Related Quality of Life were recommended. There was consensus to endorse the ISOQOL and CONSORT-PRO guidelines on the inclusion and reporting of PRO endpoints in protocols and that all future EOC Gynecologic Cancer InterGroup trials should adhere to these. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Obesity and cancer--mechanisms underlying tumour progression and recurrence.

    Science.gov (United States)

    Park, Jiyoung; Morley, Thomas S; Kim, Min; Clegg, Deborah J; Scherer, Philipp E

    2014-08-01

    Over the past several years, the field of cancer research has directed increased interest towards subsets of obesity-associated tumours, which include mammary, renal, oesophageal, gastrointestinal and reproductive cancers in both men and women. The increased risk of breast cancer that is associated with obesity has been widely reported; this has drawn much attention and as such, warrants investigation of the key mechanisms that link the obese state with cancer aetiology. For instance, the obese setting provides a unique adipose tissue microenvironment with concomitant systemic endocrine alterations that favour both tumour initiation and progression. Major metabolic differences exist within tumours that distinguish them from non-transformed healthy tissues. Importantly, considerable metabolic differences are induced by tumour cells in the stromal vascular fraction that surrounds them. The precise mechanisms that underlie the association of obesity with cancer and the accompanying metabolic changes that occur in the surrounding microenvironment remain elusive. Nonetheless, specific therapeutic agents designed for patients with obesity who develop tumours are clearly needed. This Review discusses recent advances in understanding the contributions of obesity to cancer and their implications for tumour treatment.

  7. Cisplatin in cancer therapy: molecular mechanisms of action

    Science.gov (United States)

    Dasari, Shaloam; Tchounwou, Paul Bernard

    2014-01-01

    Cisplatin, cisplatinum, or cis-diamminedichloroplatinum (II), is a well-known chemotherapeutic drug. It has been used for treatment of numerous human cancers including bladder, head and neck, lung, ovarian, and testicular cancers. It is effective against various types of cancers, including carcinomas, germ cell tumors, lymphomas, and sarcomas. Its mode of action has been linked to its ability to crosslink with the purine bases on the DNA; interfering with DNA repair mechanisms, causing DNA damage, and subsequently inducing apoptosis in cancer cells. However, because of drug resistance and numerous undesirable side effects such as severe kidney problems, allergic reactions, decrease immunity to infections, gastrointestinal disorders, hemorrhage, and hearing loss especially in younger patients, other platinum-containing anti-cancer drugs such as carboplatin, oxaliplatin and others, have also been used. Furthermore, combination therapies of cisplatin with other drugs have been highly considered to overcome drug-resistance and reduce toxicity. This comprehensive review highlights the physicochemical properties of cisplatin and related platinum-based drugs, and discusses its uses (either alone or in combination with other drugs) for the treatment of various human cancers. A special attention is given to its molecular mechanisms of action, and its undesirable side effects. PMID:25058905

  8. Pancreatic cancer in obesity: epidemiology, clinical observations, and basic mechanisms.

    Science.gov (United States)

    Zyromski, Nicholas J; White, Patrick B

    2011-06-01

    Obesity, now a worldwide epidemic, causes myriad medical problems. One of the most significant obesity-related problems is the well-recognized relationship between obesity and various malignancies, including pancreatic cancer. Pancreatic cancer is a devastating disease--the annual death rate nearly approximates its incidence. While surgical extirpation provides the best chance at long term survival, systemic therapy is largely ineffective: even those patients undergoing successful operative resection have only approximately 20% 5-year survival. These poor outcomes are largely a consequence of poor understanding of tumor biology. Clearly, identification of novel treatment strategies is of paramount importance; investigation of pancreatic cancer biology from the novel aspect of obesity offers the potential to identify unique therapeutic targets. This manuscript reviews the epidemiology, clinical findings, and putative basic science mechanisms underlying obesity-related pancreatic cancer.

  9. T cell exhaustion in cancer: mechanisms and clinical implications.

    Science.gov (United States)

    Wang, Jin-Cheng; Xu, Yong; Huang, Zheng-Ming; Lu, Xiao-Jie

    2017-12-23

    During chronic viral infection or cancer, the immune system usually induces a corresponding immune response against pathogens or cancer cells so as to prevent worsening disease. T cell exhaustion in which reduced and dysfunctional effector T cells lead to immune escape is one of the mechanisms that pathogens or cancer cells get rid of control from the immune system. In this review, we discuss some mechanisms associated with T cell exhaustion and enumerate current methods of reversing T cell exhaustion. We also summarize current targeted treatment strategies and put forward following aspects that required to research. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwen Xiao

    2014-01-01

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

  11. Cancer Chemoprevention and Piperine: Molecular Mechanisms and Therapeutic Opportunities

    Directory of Open Access Journals (Sweden)

    Rafiq A. Rather

    2018-02-01

    Full Text Available Cancer is a genetic disease characterized by unregulated growth and dissemination of malignantly transformed neoplastic cells. The process of cancer development goes through several stages of biochemical and genetic alterations in a target cell. Several dietary alkaloids have been found to inhibit the molecular events and signaling pathways associated with various stages of cancer development and therefore are useful in cancer chemoprevention. Cancer chemoprevention has long been recognized as an important prophylactic strategy to reduce the burden of cancer on health care system. Cancer chemoprevention assumes the use of one or more pharmacologically active agents to block, suppress, prevent, or reverse the development of invasive cancer. Piperine is an active alkaloid with an excellent spectrum of therapeutic activities such as anti-oxidant, anti-inflammatory, immunomodulatory, anti-asthmatic, anti-convulsant, anti-mutagenic, antimycobacterial, anti-amoebic, and anti-cancer activities. In this article, we made an attempt to sum up the current knowledge on piperine that supports the chemopreventive potential of this dietary phytochemical. Many mechanisms have been purported to understand the chemopreventive action of piperine. Piperine has been reported to inhibit the proliferation and survival of many types of cancer cells through its influence on activation of apoptotic signaling and inhibition of cell cycle progression. Piperine is known to affect cancer cells in variety of other ways such as influencing the redox homeostasis, inhibiting cancer stem cell (CSC self-renewal and modulation of ER stress and autophagy. Piperine can modify activity of many enzymes and transcription factors to inhibit invasion, metastasis, and angiogenesis. Piperine is a potent inhibitor of p-glycoprotein (P-gp and has a significant effect on the drug metabolizing enzyme (DME system. Because of its inhibitory influence on P-gp activity, piperine can reverse

  12. The Multidisciplinary Team Conference's Decision on M-Staging in Patients with Gastric- and Gastroesophageal Cancer is not Accurate without Staging Laparoscopy

    DEFF Research Database (Denmark)

    Strandby, Rune Broni; Svendsen, Lars Bo; Fallentin, E.

    2016-01-01

    BACKGROUND: The implementation of the multidisciplinary team conference has been shown to improve treatment outcome for patients with gastric- and gastroesophageal cancer. Likewise, the staging laparoscopy has increased the detection of patients with disseminated disease, that is, patients who do...... not benefit from a surgical resection. The aim of this study was to compare the multidisciplinary team conference's decision in respect of M-staging with the findings of the following staging laparoscopy. METHODS: Patients considered operable and resectable within the multidisciplinary team conference...... carcinomatosis or liver metastases on multidisciplinary team conference before staging laparoscopy. Furthermore, an evaluation with staging laparoscopy was required. RESULTS: In total, 222 patients met the inclusion criteria. Most cancers were located in the gastroesophageal junction, n = 171 (77.0%), and most...

  13. Pixel based SHG probes of extracellular matrix (ECM) alterations in ovarian cancer (Conference Presentation)

    Science.gov (United States)

    Campbell, Kirby R.; Chaudhary, Rajeev; Handel, Julia; Campagnola, Paul J.

    2017-02-01

    Remodeling of the extracellular matrix in human ovarian cancer, can be reflected in increased collagen concentration, changes in alignment and/or up-regulation of different collagen isoforms, including Col III. Using fibrillar gel models, we demonstrate that Col I and Col III can be quantitatively distinguished by 3 distinct SHG polarization specific metrics: i) determination of helical pitch angle via the single axis molecular model, ii) dipole alignment via anisotropy, and iii) chirality via SHG circular dichroism (SHG-CD). These sub-resolution differentiations are possible due to differences in the α helix angles of the two isoforms, which co-mingle in the same fibrils. We also investigated the mechanism of the SHG-CD response and show that unlike conventional CD, it is dominated by electric dipole interactions and is consistent with the two state SHG model. We further applied these 3 polarization resolved analyses to human normal, high risk, benign tumors, and malignant human ovarian tissues. We found that these tissues could all be differentiated by these metrics, where high grade tissues had analogous α-helical pitch angles to the in the Col I/Col III gel model. This confirms literature suggestions based on immunofluorescence and gene expression that Col III is up-regulated in high grade ovarian cancers. The different tissues also displayed differing anisotropies, indicating the fibril assemblies are distinct and likely do not result from remodeling of existing collagen but synthesis of new collagen. Importantly, these SHG polarization methods provide structural information not otherwise possible and can serve as label-free biomarkers for ovarian and other cancers.

  14. Abstracts of the Conference on Mechanisms of DNA Repair and Mutagenesis on the 100. Anniversary of the Discovery of Polonium and Radium

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-31

    The conference covered various aspects of mutagenesis and mechanisms of DNA repair. UV and ionizing radiation were use to induce DNA lesions in bacteria, yeast and cell cultures of higher organisms. This allows study of influence of mutations on particular processes in the cell. Mechanisms of resistance were also investigated. Biological investigations were performed using labelled compounds.

  15. Mechanical properties of normal versus cancerous breast cells.

    Science.gov (United States)

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

    2015-11-01

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

  16. Persistent organic pollutants & obesity: potential mechanisms for breast cancer promotion?

    Science.gov (United States)

    Reaves, Denise K.; Ginsburg, Erika; Bang, John J.; Fleming, Jodie M.

    2015-01-01

    Dietary ingestion of persistent organic pollutants (POPs) correlates with developing obesity. Obesity alters metabolism, induces an inflammatory tissue microenvironment, and is also linked with diabetes and breast cancer risk/promotion of the disease. However, no direct evidence exists exploring the correlation among all three of these factors (POPs, obesity, and breast cancer). Herein, we present current correlative studies suggesting a causal link between POPs exposure through diet and their bioaccumulation in adipose that promotes the development of obesity and ultimately influences breast cancer development and/or progression. Furthermore, as endocrine disruptors, POPs can potentially interfere with hormonally responsive tissue functions causing dysregulation in hormone signaling and cell function. This review highlights the critical need for advanced in vitro and in vivo model systems to understand the complex relationship between obesity, POPs, breast cancer, and, more importantly, to delineate their multifaceted molecular, cellular, and biochemical mechanisms. Comprehensive in vitro and in vivo studies directly testing the observed correlations as well as detailing their molecular mechanisms are vital to cancer research and, ultimately, public health. PMID:25624167

  17. Nuclear receptor corepressor complexes in cancer: mechanism, function and regulation

    Science.gov (United States)

    Wong, Madeline M; Guo, Chun; Zhang, Jinsong

    2014-01-01

    Nuclear receptor corepressor (NCoR) and silencing mediator for retinoid and thyroid hormone receptors (SMRT) function as corepressors for diverse transcription factors including nuclear receptors such as estrogen receptors and androgen receptors. Deregulated functions of NCoR and SMRT have been observed in many types of cancers and leukemias. NCoR and SMRT directly bind to transcription factors and nucleate the formation of stable complexes that include histone deacetylase 3, transducin b-like protein 1/TBL1-related protein 1, and G-protein pathway suppressor 2. These NCoR/SMRT-interacting proteins also show deregulated functions in cancers. In this review, we summarize the literature on the mechanism, regulation, and function of the core components of NCoR/SMRT complexes in the context of their involvement in cancers and leukemias. While the current studies support the view that the corepressors are promising targets for cancer treatment, elucidation of the mechanisms of corepressors involved in individual types of cancers is likely required for effective therapy. PMID:25374920

  18. The final checkpoint. Cancer as an adaptive evolutionary mechanism

    Directory of Open Access Journals (Sweden)

    Rumena Petkova

    2016-05-01

    Full Text Available The mechanisms for identification of DNA damage and repair usually manage DNA damage very efficiently. If damaged cells manage to bypass the checkpoints where the integrity of the genome is assessed and the decisions whether to proceed with the cell cycle are made, they may evade the imperative to stop dividing and to die. As a result, cancer may develop. Warding off the potential sequence-altering effects of DNA damage during the life of the individual or the existence span of the species is controlled by a set of larger checkpoints acting on a progressively increasing scale, from systematic removal of damaged cells from the proliferative pool by means of repair of DNA damage/programmed cell death through ageing to, finally, cancer. They serve different purposes and act at different levels of the life cycle, safeguarding the integrity of the genetic backup of the individual, the genetic diversity of the population, and, finally, the survival of the species and of life on Earth. In the light of the theory that cancer is the final checkpoint or the nature's manner to prevent complex organisms from living forever at the expense of genetic stagnation, the eventual failure of modern anti-cancer treatments is only to be expected. Nevertheless, the medicine of today and the near future has enough potential to slow down the progression to terminal cancer so that the life expectancy and the quality of life of cancer-affected individuals may be comparable to those of healthy aged individuals.

  19. Risk factors for pancreatic cancer: underlying mechanisms and potential targets

    Science.gov (United States)

    Kolodecik, Thomas; Shugrue, Christine; Ashat, Munish; Thrower, Edwin C.

    2014-01-01

    Purpose of the review: Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer. Recent findings: Intracellular activation of both pancreatic enzymes and the transcription factor NF-κB are important mechanisms that induce acute pancreatitis (AP). Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogenic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16) can ultimately lead to development of pancreatic cancer. Summary: Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions. PMID:24474939

  20. RISK FACTORS FOR PANCREATIC CANCER: UNDERLYING MECHANISMS AND POTENTIAL TARGETS

    Directory of Open Access Journals (Sweden)

    Thomas eKolodecik

    2014-01-01

    Full Text Available Purpose of the review:Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer.Recent Findings:Intracellular activation of both pancreatic enzymes and the transcription factor NF-kB are important mechanisms that induce acute pancreatitis. Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogneic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16 can ultimately lead to development of pancreatic cancer. Summary:Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions.

  1. Risk factors for pancreatic cancer: underlying mechanisms and potential targets.

    Science.gov (United States)

    Kolodecik, Thomas; Shugrue, Christine; Ashat, Munish; Thrower, Edwin C

    2013-01-01

    Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer. Intracellular activation of both pancreatic enzymes and the transcription factor NF-κB are important mechanisms that induce acute pancreatitis (AP). Recurrent pancreatic injury due to genetic susceptibility, environmental factors such as smoking, alcohol intake, and conditions such as obesity lead to increases in oxidative stress, impaired autophagy and constitutive activation of inflammatory pathways. These processes can stimulate pancreatic stellate cells, thereby increasing fibrosis and encouraging chronic disease development. Activation of oncogenic Kras mutations through inflammation, coupled with altered levels of tumor suppressor proteins (p53 and p16) can ultimately lead to development of pancreatic cancer. Although our understanding of pancreatitis and pancreatic cancer has tremendously increased over many years, much remains to be elucidated in terms of common pathways linking these conditions.

  2. The Multidisciplinary Team Conference's Decision on M-Staging in Patients with Gastric- and Gastroesophageal Cancer is not Accurate without Staging Laparoscopy.

    Science.gov (United States)

    Strandby, R B; Svendsen, L B; Fallentin, E; Egeland, C; Achiam, M P

    2016-06-01

    The implementation of the multidisciplinary team conference has been shown to improve treatment outcome for patients with gastric- and gastroesophageal cancer. Likewise, the staging laparoscopy has increased the detection of patients with disseminated disease, that is, patients who do not benefit from a surgical resection. The aim of this study was to compare the multidisciplinary team conference's decision in respect of M-staging with the findings of the following staging laparoscopy. Patients considered operable and resectable within the multidisciplinary team conference in the period 2010-2012 were retrospectively reviewed. Patient data were retrieved by searching for specific diagnosis and operation codes in the in-house system. The inclusion criteria were as follows: biopsy-verified cancer of the esophagus, gastroesophageal junction or stomach, and no suspicion of peritoneal carcinomatosis or liver metastases on multidisciplinary team conference before staging laparoscopy. Furthermore, an evaluation with staging laparoscopy was required. In total, 222 patients met the inclusion criteria. Most cancers were located in the gastroesophageal junction, n = 171 (77.0%), and most common with adenocarcinoma histology, n = 196 (88.3%). The staging laparoscopy was M1-positive for peritoneal carcinomatosis in eight patients (16.7%) with gastric cancer versus nine patients (5.3%) with gastroesophageal junction cancer. Furthermore, liver metastases were evident in zero patients (0.0%) and four patients (2.3%) with gastric- and gastroesophageal junction cancer, respectively. The staging laparoscopy findings regarding peritoneal carcinomatosis were significantly different between gastric- and gastroesophageal junction cancers, p = 0.01. No significant differences were found regarding T-/N-stage or histological tumor characteristics between the positive- and negative-staging laparoscopy group. The M-staging of the multidisciplinary team conference without staging

  3. 5th international conference on design and modeling of mechanical systems

    CERN Document Server

    Romdhane, Lotfi; Louati, Jamel; Amara, Abdelmajid

    2013-01-01

    The 5th International Congress on Design and Modeling of Mechanical Systems (CMSM) was held in Djerba, Tunisia on March 25-27, 2013 and followed four previous successful editions, which brought together international experts in the fields of design and modeling of mechanical systems, thus contributing to the exchange of information and skills and leading to a considerable progress in research among the participating teams. The fifth edition of the congress (CMSM´2013), organized by the Unit of Mechanics, Modeling and Manufacturing (U2MP) of the National School of Engineers of Sfax, Tunisia, the Mechanical Engineering Laboratory (MBL) of the National School of Engineers of Monastir, Tunisia and the Mechanics Laboratory of Sousse (LMS) of the National School of Engineers of Sousse, Tunisia, saw a significant increase of the international participation. This edition brought together nearly 300 attendees who exposed their work on the following topics: mechatronics and robotics, dynamics of mechanical systems, fl...

  4. Mechanisms of hormonal therapy resistance in breast cancer.

    Science.gov (United States)

    Hayashi, Shin-ichi; Kimura, Mariko

    2015-04-01

    Whilst estrogen receptor (ER)-positive breast cancers are preferentially treated with hormone therapy, approximately one-third of them relapse. The mechanisms of refractoriness have been investigated by numerous studies but have not been fully clarified. Hormonal therapy resistance, particularly aromatase inhibitor (AI) resistance, may be related to the acquisition of alternative intracellular ER signaling. We have been investing the mechanisms using cancer specimens and cell lines by monitoring the transcription activity of ERs. AI refractory specimens showed diverse ER activity in the adenovirus estrogen receptor element-green fluorescent protein (ERE-GFP) assay and varied sensitivity to anti-estrogens, indicating the existence of multiple resistant mechanisms. We established six different types of cell lines mimicking AI resistance from ERE-GFP-introduced ER-positive cell lines. They revealed that multiple and alternative ER activating pathways were involved in the resistance, such as phosphorylation-dependent or androgen metabolite-dependent mechanisms. The response to fulvestrant and mammalian target of rapamycin inhibitor also varied among individual resistant cell lines. These results indicate that further subclassification of ER-positive breast cancer is extremely important to decide the therapeutic management of not only hormonal therapy but also new molecular target therapy.

  5. From obesity to cancer: a review on proposed mechanisms.

    Science.gov (United States)

    Tahergorabi, Zoya; Khazaei, Majid; Moodi, Mitra; Chamani, Elham

    2016-12-01

    Nowadays, obesity is considered as a serious and growing global health problem. It is documented that the overweight and obesity are major risk factors for a series of noncommunicable diseases, and in recent years, the obesity-cancer link has received much attention. Numerous epidemiological studies have shown that obesity is associated with increased risk of several cancer types, including colon, breast, endometrium, liver, kidney, esophagus, gastric, pancreatic, gallbladder, and leukemia, and can also lead to poorer treatment. We review here the epidemiological and experimental evidences for the association between obesity and cancer. Specifically, we discuss potential mechanisms focusing how dysfunctional angiogenesis, chronic inflammation, interaction of proinflammatory cytokines, endocrine hormones, and adipokines including leptin, adiponectin insulin, growth factors, estrogen, and progesterone and strikingly, cell metabolism alteration in obesity participate in tumor development and progression, resistance to chemotherapy, and targeted therapies such as antiangiogenic and immune therapies. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Mechanisms behind the link between obesity and gastrointestinal cancers.

    Science.gov (United States)

    Tilg, Herbert; Moschen, Alexander R

    2014-08-01

    Obesity and obesity-related disorders such as non-alcoholic fatty liver disease (NAFLD), metabolic syndrome and type 2 diabetes exhibit an increased risk of developing various gastrointestinal cancers. These malignancies include mainly esophageal, gastric, colorectal, pancreatic and hepatocellular carcinoma. Whereas underlying pathomechanisms remain unclear, chronic inflammation accompanying obesity has evolved in the last years as a crucial contributing factor. Obesity is also commonly characterized by inflammation in the organ where those cancers appear. Various pathways might participate involving rather diverse components such as innate immunity, (adipo)-cytokines such as adiponectin or leptin, insulin, insulin-like growth factors, the gut's microbiota and others. An imbalance in these systems could substantially contribute to chronic inflammation and subsequent cancer development. Future studies have to elucidate in more detail underlying mechanisms in the development of obesity-related carcinogensis and potential therapeutic strategies besides weight loss. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Actomyosin tension as a determinant of metastatic cancer mechanical tropism

    Science.gov (United States)

    McGrail, Daniel J.; Kieu, Quang Minh N.; Iandoli, Jason A.; Dawson, Michelle R.

    2015-04-01

    Despite major advances in the characterization of molecular regulators of cancer growth and metastasis, patient survival rates have largely stagnated. Recent studies have shown that mechanical cues from the extracellular matrix can drive the transition to a malignant phenotype. Moreover, it is also known that the metastatic process, which results in over 90% of cancer-related deaths, is governed by intracellular mechanical forces. To better understand these processes, we identified metastatic tumor cells originating from different locations which undergo inverse responses to altered matrix elasticity: MDA-MB-231 breast cancer cells that prefer rigid matrices and SKOV-3 ovarian cancer cells that prefer compliant matrices as characterized by parameters such as tumor cell proliferation, chemoresistance, and migration. Transcriptomic analysis revealed higher expression of genes associated with cytoskeletal tension and contractility in cells that prefer stiff environments, both when comparing MDA-MB-231 to SKOV-3 cells as well as when comparing bone-metastatic to lung-metastatic MDA-MB-231 subclones. Using small molecule inhibitors, we found that blocking the activity of these pathways mitigated rigidity-dependent behavior in both cell lines. Probing the physical forces exerted by cells on the underlying substrates revealed that though force magnitude may not directly correlate with functional outcomes, other parameters such as force polarization do correlate directly with cell motility. Finally, this biophysical analysis demonstrates that intrinsic levels of cell contractility determine the matrix rigidity for maximal cell function, possibly influencing tissue sites for metastatic cancer cell engraftment during dissemination. By increasing our understanding of the physical interactions of cancer cells with their microenvironment, these studies may help develop novel therapeutic strategies.

  8. Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation.

    Science.gov (United States)

    Iyengar, Neil M; Gucalp, Ayca; Dannenberg, Andrew J; Hudis, Clifford A

    2016-12-10

    Purpose There is growing evidence that inflammation is a central and reversible mechanism through which obesity promotes cancer risk and progression. Methods We review recent findings regarding obesity-associated alterations in the microenvironment and the local and systemic mechanisms through which these changes support tumor growth. Results Locally, hyperadiposity is associated with altered adipose tissue function, adipocyte death, and chronic low-grade inflammation. Most individuals who are obese harbor inflamed adipose tissue, which resembles chronically injured tissue, with immune cell infiltration and remodeling. Within this distinctly altered local environment, several pathophysiologic changes are found that may promote breast and other cancers. Consistently, adipose tissue inflammation is associated with a worse prognosis in patients with breast and tongue cancers. Systemically, the metabolic syndrome, including dyslipidemia and insulin resistance, occurs in the setting of adipose inflammation and operates in concert with local mechanisms to sustain the inflamed microenvironment and promote tumor growth. Importantly, adipose inflammation and its protumor consequences can be found in some individuals who are not considered to be obese or overweight by body mass index. Conclusion The tumor-promoting effects of obesity occur at the local level via adipose inflammation and associated alterations in the microenvironment, as well as systemically via circulating metabolic and inflammatory mediators associated with adipose inflammation. Accurately characterizing the obese state and identifying patients at increased risk for cancer development and progression will likely require more precise assessments than body mass index alone. Biomarkers of adipose tissue inflammation would help to identify high-risk populations. Moreover, adipose inflammation is a reversible process and represents a novel therapeutic target that warrants further study to break the obesity-cancer

  9. Targeting the Androgen Receptor Confers In Vivo Cross-resistance Between Enzalutamide and Docetaxel, But Not Cabazitaxel, in Castration-resistant Prostate Cancer.

    Science.gov (United States)

    van Soest, Robert J; de Morrée, Ellen S; Kweldam, Charlotte F; de Ridder, Corrina M A; Wiemer, Erik A C; Mathijssen, Ron H J; de Wit, Ronald; van Weerden, Wytske M

    2015-06-01

    Treatment options for metastatic castration-resistant prostate cancer (CRPC) have evolved with the established benefit of the novel androgen receptor (AR)-targeted agents abiraterone and enzalutamide in the prechemotherapy setting. However, concerns regarding cross-resistance between the taxanes docetaxel and cabazitaxel and these AR-targeted agents have arisen, and the optimal drug treatment sequence is unknown. We investigated the in vivo efficacy of docetaxel and cabazitaxel in enzalutamide-resistant CRPC, and mechanisms of cross-resistance between these agents. Castrated mice harboring enzalutamide-resistant tumors and enzalutamide-naïve tumors were treated with docetaxel and cabazitaxel. Tumor growth kinetics, AR nuclear localization, AR-regulated gene expression, Ki67 expression, and serum levels of prostate-specific antigen, docetaxel, and cabazitaxel were analyzed. Docetaxel inhibited tumor growth, AR nuclear localization, and AR-regulated gene expression in enzalutamide-naïve tumors, but did not in enzalutamide-resistant tumors, demonstrating in vivo cross-resistance. By contrast, cabazitaxel remained highly effective in enzalutamide-resistant tumors and demonstrated superior antitumor activity compared to docetaxel, independent of the AR pathway. These findings demonstrate that the AR pathway is able to confer in vivo cross-resistance between enzalutamide and docetaxel, but not cabazitaxel, in CRPC. We found reduced efficacy of docetaxel, but not cabazitaxel, in enzalutamide-resistant prostate cancer. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  10. Metabolic and target-site mechanisms combine to confer strong DDT resistance in Anopheles gambiae

    National Research Council Canada - National Science Library

    Mitchell, Sara N; Rigden, Daniel J; Dowd, Andrew J; Lu, Fang; Wilding, Craig S; Weetman, David; Dadzie, Samuel; Jenkins, Adam M; Regna, Kimberly; Boko, Pelagie; Djogbenou, Luc; Muskavitch, Marc A T; Ranson, Hilary; Paine, Mark J I; Mayans, Olga; Donnelly, Martin J

    2014-01-01

    .... In this study we demonstrate how resistance to DDT in the major African malaria vector Anopheles gambiae is a result of both target-site resistance mechanisms that have introgressed between incipient species...

  11. Metastatic non-small-cell lung cancer: consensus on pathology and molecular tests, first-line, second-line, and third-line therapy: 1st ESMO Consensus Conference in Lung Cancer; Lugano 2010

    DEFF Research Database (Denmark)

    Felip, E; Gridelli, C; Baas, P

    2011-01-01

    The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21 and 22 May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics, medical oncology, surgical oncology and radiation oncology. Before the confer......The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21 and 22 May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics, medical oncology, surgical oncology and radiation oncology. Before...... the conference, the expert panel prepared clinically relevant questions concerning five areas: early and locally advanced non-small-cell lung cancer (NSCLC), first-line metastatic NSCLC, second-/third-line NSCLC, NSCLC pathology and molecular testing, and small-cell lung cancer to be addressed through discussion...... at the Consensus Conference. All relevant scientific literature for each question was reviewed in advance. During the Consensus Conference, the panel developed recommendations for each specific question. The consensus agreement on three of these areas: NSCLC pathology and molecular testing, the treatment of first...

  12. Characterization of Chronic Mechanical Irritation in Oral Cancer

    Directory of Open Access Journals (Sweden)

    Jerónimo P. Lazos

    2017-01-01

    Full Text Available Objective. Oral mucosa could host many lesions originated by chronic mechanical irritation (CMI from teeth or dentures, and it has been proposed as risk factor for oral cancer. Nevertheless, the features of CMI factors in oral cancer and other lesions are not assessed. The aim of this study is to describe CMI features regarding type (dental, prosthetic, and/or functional, localization, and time span. Materials and Methods. Three groups were studied in this cross-sectional study: Oral Cancer (OC; Chronic Traumatic Ulcer (CTU; and Benign Irritative Mechanical Lesions (BIML. All sources of mechanical irritation were included: dental, prosthetic, and functional. Results. 285 patients (176 females, 109 males were studied: OC = 38, CTU = 44, and BIML = 203. The most frequent CMI factor was dental, followed by functional and prosthetic in all groups; 76.5% (n=218 presented functional factors. Buccal mucosa (45% and tongue (42% were the most affected sites. Time of action of CMI displayed statistically significant differences between BIML, CTU, and OC groups, with a mean of 21, 33, and 49 months, respectively. Conclusions. CMI should be properly recorded with as much detail as alcohol and tobacco consumption. CMI associated lesions are produced by dental or prosthetic factors, usually in relation to functional factors, involving mainly tongue and buccal mucosa.

  13. Adaptive plasma for cancer therapy: physics, mechanism and applications

    Science.gov (United States)

    Keidar, Michael

    2017-10-01

    One of the most promising applications of cold atmospheric plasma (CAP) is the cancer therapy. The uniqueness of plasma is in its ability to change composition in situ. Plasma self-organization could lead to formation of coherent plasma structures. These coherent structures tend to modulate plasma chemistry and composition, including reactive species, the electric field and charged particles. Formation of coherent plasma structures allows the plasma to adapt to external boundary conditions, such as different cells types and their contextual tissues. In this talk we will explore possibilities and opportunities that the adaptive plasma therapeutic system might offer. We shall define such an adaptive system as a plasma device that is able to adjust the plasma composition to obtain optimal desirable outcomes through its interaction with cells and tissues. The efficacy of cold plasma in a pre-clinical model of various cancer types such as lung, bladder, breast, head, neck, brain and skin has been demonstrated. Both in-vitro and in-vivo studies revealed that cold plasmas selectively kill cancer cells. Recently mechanism of plasma selectivity based on aquaporin hypothesis has been proposed. Aquaporins (AQPs) are the confirmed membrane channels of H2O2 and other large molecules. We have demonstrated that the anti-cancer capacity of plasma could be inhibited by silencing the expression of AQPs. Additional possible cell feedback mechanism was recently discovered. It is associated with production of reactive species during direct CAP treatment by cancer cells. Selective production of hydrogen peroxide by different cells can lead to adaptation of chemistry at the plasma-cell interface based on the cellular input. In particular we have found that the discharge voltage is an important factor affecting the ratio of reactive oxygen species to reactive nitrogen species in the gas phase and this correlates well with effect of hydrogen peroxide production by cells. This work was

  14. Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016.

    Science.gov (United States)

    Lugli, Alessandro; Kirsch, Richard; Ajioka, Yoichi; Bosman, Fred; Cathomas, Gieri; Dawson, Heather; El Zimaity, Hala; Fléjou, Jean-François; Hansen, Tine Plato; Hartmann, Arndt; Kakar, Sanjay; Langner, Cord; Nagtegaal, Iris; Puppa, Giacomo; Riddell, Robert; Ristimäki, Ari; Sheahan, Kieran; Smyrk, Thomas; Sugihara, Kenichi; Terris, Benoît; Ueno, Hideki; Vieth, Michael; Zlobec, Inti; Quirke, Phil

    2017-09-01

    Tumor budding is a well-established independent prognostic factor in colorectal cancer but a standardized method for its assessment has been lacking. The primary aim of the International Tumor Budding Consensus Conference (ITBCC) was to reach agreement on an international, evidence-based standardized scoring system for tumor budding in colorectal cancer. The ITBCC included nine sessions with presentations, a pre-meeting survey and an e-book covering the key publications on tumor budding in colorectal cancer. The 'Grading of Recommendation Assessment, Development and Evaluation' method was used to determine the strength of recommendations and quality of evidence. The following 10 statements achieved consensus: tumor budding is defined as a single tumor cell or a cell cluster consisting of four tumor cells or less (22/22, 100%). Tumor budding is an independent predictor of lymph node metastases in pT1 colorectal cancer (23/23, 100%). Tumor budding is an independent predictor of survival in stage II colorectal cancer (23/23, 100%). Tumor budding should be taken into account along with other clinicopathological features in a multidisciplinary setting (23/23, 100%). Tumor budding is counted on H&E (19/22, 86%). Intratumoral budding exists in colorectal cancer and has been shown to be related to lymph node metastasis (22/22, 100%). Tumor budding is assessed in one hotspot (in a field measuring 0.785 mm(2)) at the invasive front (22/22, 100%). A three-tier system should be used along with the budding count in order to facilitate risk stratification in colorectal cancer (23/23, 100%). Tumor budding and tumor grade are not the same (23/23, 100%). Tumor budding should be included in guidelines/protocols for colorectal cancer reporting (23/23, 100%). Members of the ITBCC were able to reach strong consensus on a single international, evidence-based method for tumor budding assessment and reporting. It is proposed that this method be incorporated into colorectal cancer

  15. Non-mechanical beam control for entry, descent and landing laser radar (Conference Presentation)

    Science.gov (United States)

    Stockley, Jay E.; Kluttz, Kelly; Hosting, Lance; Serati, Steve; Bradley, Cullen P.; McManamon, Paul F.; Amzajerdian, Farzin

    2017-05-01

    Laser radar for entry, descent, and landing (EDL) applications as well as the space docking problem could benefit from a low size, weight, and power (SWaP) beam control system. Moreover, an inertia free approach employing non-mechanical beam control is also attractive for laser radar that is intended to be employed aboard space platforms. We are investigating a non-mechanical beam steering (NMBS) sub-system based on liquid crystal polarization grating (LCPG) technology with emphasis placed on improved throughput and significant weight reduction by combining components and drastically reducing substrate thicknesses. In addition to the advantages of non-mechanical, gimbal free beam control, and greatly improved SWaP, our approach also enables wide area scanning using a scalable architecture. An extraterrestrial application entails additional environmental constraints, consequently an environmental test plan tailored to an EDL mission will also be discussed. In addition, we will present advances in continuous fine steering technology which would complement the coarse steering LCPG technology. A low-SWaP, non-mechanical beam control system could be used in many laser radar remote sensing applications including meteorological studies and agricultural or environmental surveys in addition to the entry, descent, and landing application.

  16. Why Does ADHD Confer Risk for Cigarette Smoking? A Review of Psychosocial Mechanisms

    Science.gov (United States)

    Glass, Kerrie; Flory, Kate

    2010-01-01

    Research has documented that adolescents and young adults with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for cigarette smoking, but less attention has examined why this risk exists. The current paper reviews the literature on different psychosocial mechanisms [self-medication hypothesis, social factors (social modeling,…

  17. Aberrant Expression of proPTPRN2 in Cancer Cells Confers Resistance to Apoptosis.

    Science.gov (United States)

    Sorokin, Alexey V; Nair, Binoj C; Wei, Yongkun; Aziz, Kathryn E; Evdokimova, Valentina; Hung, Mien-Chie; Chen, Junjie

    2015-05-01

    The protein tyrosine phosphatase receptor PTPRN2 is expressed predominantly in endocrine and neuronal cells, where it functions in exocytosis. We found that its immature isoform proPTPRN2 is overexpressed in various cancers, including breast cancer. High proPTPRN2 expression was associated strongly with lymph node-positive breast cancer and poor clinical outcome. Loss of proPTPRN2 in breast cancer cells promoted apoptosis and blocked tumor formation in mice, whereas enforced expression of proPTPRN2 in nontransformed human mammary epithelial cells exerted a converse effect. Mechanistic investigations suggested that ProPTPRN2 elicited these effects through direct interaction with TRAF2, a hub scaffold protein for multiple kinase cascades, including ones that activate NF-κB. Overall, our results suggest PTPRN2 as a novel candidate biomarker and therapeutic target in breast cancer. ©2015 American Association for Cancer Research.

  18. Promoting Cancer Control in Africa With "Ubuntu": A Report of the African Organization for Research and Training in Africa (AORTIC) 10th Conference, 2015 in Marrakech, Morocco.

    Science.gov (United States)

    Simbiri, Kenneth O; Williams, Christopher K; Macaluso, Marcella; Giordano, Antonio

    2017-09-01

    The objectives of the African Organization for Research and Training in Cancer (AORTIC), includes bringing products of decades of advances in cancer research to African populations through local and international collaboration. The consistent and huge growth in participation in the conferences and the diversity of the nations is a witness to the success of the organization thus far. The theme for the Tenth AORTIC International Conference on Cancer in Africa in Morocco in 2015 was "Road map to Cancer Control in Africa" and topics of discussion of paramount importance for low- and middle-income African countries included childhood cancers such as BL, cancers of the cervix, breast, and prostate; cancers associated with HIV-infection such as cervical, vulvar, and anal; as well as cancer care challenges associated with palliative care. The role of environmental factors that underlie some epigenetic changes in some of the cancers was emphasized. Oral and poster presentations from various parts of the continent indicate the growth of basic and translational science of cancer in the region, with studies revealing regional diversity in the frequencies of the triple-negative breast cancer, cervical cancer, prostate cancer, HCC, and Burkitt's lymphoma. There was a sign that Africa is trying to keep pace with the paradigm shift and focusing on translational medicine. This was shown by suggestions for application of genome-wide association studies, new generation sequencing, as well as the evaluation of single nucleotide polymorphisms that may be responsible for variable susceptibility in some of the prevalent cancers in people of African descent. J. Cell. Physiol. 232: 2287-2295, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Multidisciplinary cancer conferences for gastrointestinal malignancies result in measureable treatment changes: a prospective study of 149 consecutive patients.

    Science.gov (United States)

    Oxenberg, Jacqueline; Papenfuss, Wesley; Esemuede, Iyare; Attwood, Kristopher; Simunovic, Marko; Kuvshinoff, Boris; Francescutti, Valerie

    2015-05-01

    In most jurisdictions, a minority of patients are discussed at multidisciplinary cancer conference (MCC) despite recommendations for such reviews. We assessed the impact of MCC review of gastrointestinal (GI) cancers at a stand-alone cancer center. Patient data were prospectively collected on consecutive cases presented at a GI MCC during a 6-month period. Original treatment plans were collected confidentially before presentation and compared to post-MCC treatment plans. We defined changes in management plans as major (change in treatment modality) or minor (testing prior to original plan). A total of 149 cases were evaluated: 115 upper GI (gastric/small bowel-10 %, liver-32 %, pancreaticobiliary-36 %), and 34 lower GI (23 %). Reasons for presentation were: questions regarding progression/metastases (44 %), management (26 %), diagnosis (21 %), pathology (15 %), and resectability (7 %). Physicians were certain of their original plans being the final recommendations in 84 % (n = 125). Change in management was recommended in 36 %; 72 % were major and 28 % were minor. Patients underwent all recommended treatments at our institution in 77 % of cases, a portion in 5 %, and no recommended treatments in 18 %. On multivariate analysis, physician degree of certainty for original management plan was not predictive of a change in management plan (p = 0.61). Although certainty of prediscussion treatment plan is high, changes in treatment recommendations occurred in more than one-third of patients after GI MCC. This prospective study demonstrates the value of MCC in GI cancer sites, even at a stand-alone cancer center.

  20. 14th International Conference on Acoustics and Vibration of Mechanical Structures

    CERN Document Server

    Marinca, Vasile

    2018-01-01

    This book is a collection of papers presented at Acoustics and Vibration of Mechanical Structures 2017 – AVMS 2017 – highlighting the current trends and state-of-the-art developments in the field. It covers a broad range of topics, such as noise and vibration control, noise and vibration generation and propagation, the effects of noise and vibration, condition monitoring and vibration testing, modeling, prediction and simulation of noise and vibration, environmental and occupational noise and vibration, noise and vibration attenuators, as well as biomechanics and bioacoustics. The book also presents analytical, numerical and experimental techniques for evaluating linear and non-linear noise and vibration problems (including strong nonlinearity). It is primarily intended for academics, researchers and professionals, as well as PhD students in various fields of the acoustics and vibration of mechanical structures.

  1. Pancreatic cancer study based on full field OCT and dynamic full field OCT (Conference Presentation)

    Science.gov (United States)

    Apelian, Clement; Camus, Marine; Prat, Frederic; Boccara, A. Claude

    2017-02-01

    Pancreatic cancer is one of the most feared cancer types due to high death rates and the difficulty to perform surgery. This cancer outcome could benefit from recent technological developments for diagnosis. We used a combination of standard Full Field OCT and Dynamic Full Field OCT to capture both morphological features and metabolic functions of rodents pancreas in normal and cancerous conditions with and without chemotherapy. Results were compared to histology to evaluate the performances and the specificities of the method. The comparison highlighted the importance of a number of endogenous markers like immune cells, fibrous development, architecture and more.

  2. Defective DNA repair mechanisms in prostate cancer: impact of olaparib

    Directory of Open Access Journals (Sweden)

    De Felice F

    2017-03-01

    Full Text Available Francesca De Felice,1 Vincenzo Tombolini,1 Francesco Marampon,2 Angela Musella,3 Claudia Marchetti3 1Department of Radiotherapy, Policlinico Umberto I, “Sapienza” University of Rome, Rome, 2Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L’Aquila, L’Aquila, 3Department of Gynecological and Obstetrical Sciences and Urological Sciences, “Sapienza” University of Rome, Rome, Italy Abstract: The field of prostate oncology has continued to change dramatically. It has truly become a field that is intensely linked to molecular genetic alterations, especially DNA-repair defects. Germline breast cancer 1 gene (BRCA1 and breast cancer 2 gene (BRCA2 mutations are implicated in the highest risk of prostate cancer (PC predisposition and aggressiveness. Poly adenosine diphosphate ribose polymerase (PARP proteins play a key role in DNA repair mechanisms and represent a valid target for new therapies. Olaparib is an oral PARP inhibitor that blocks DNA repair pathway and coupled with BRCA mutated-disease results in tumor cell death. In phase II clinical trials, including patients with advanced castration-resistant PC, olaparib seems to be efficacious and well tolerated. Waiting for randomized phase III trials, olaparib should be considered as a promising treatment option for PC. Keywords: prostate cancer, metastatic disease, castration resistant, BRCA, DNA-repair, PARP, olaparib

  3. Metabolic and Target-Site Mechanisms Combine to Confer Strong DDT Resistance in Anopheles gambiae

    OpenAIRE

    Mitchell, SN; Rigden, DJ; Dowd, AJ; Lu, F.; Wilding, CS; Weetman, D.; Dadzie, S.; Jenkins, AM; Regna, K; Boko, P.; Djogbenou, L.; Muskavitch, MAT.; Ranson, H; Paine, MJI; Mayans, O

    2014-01-01

    The development of resistance to insecticides has become a classic exemplar of evolution occurring within human time scales. In this study we demonstrate how resistance to DDT in the major African malaria vector Anopheles gambiae is a result of both target-site resistance mechanisms that have introgressed between incipient species (the M- and S-molecular forms) and allelic variants in a DDT-detoxifying enzyme. Sequencing of the detoxification enzyme, Gste2, from DDT resistant and susceptible ...

  4. High-throughput real-time sensing with microfluidic electro-opto-mechanical resonators (Conference Presentation)

    Science.gov (United States)

    Suh, Jeewon; Han, Kewen; Peterson, Christopher; Bahl, Gaurav

    2017-02-01

    Resonant optical sensors have enabled the label-free measurement of nanoparticles suspended in liquids, down to the resolution of individual viruses and large molecules, but are only able to quantify optical properties (refractive index, scattering, fluorescence). Additionally, these sensors are fundamentally limited by the random diffusion of particles to the sensing region, and thus only quantify a tiny fraction of the analyte. We have developed a microfluidic optomechanical resonator capable of sensing flowing nanoparticles using the action of phonons that are coupled to light. The phonon mode of the system casts a nearly perfect net for measuring density, viscoelasticity, and compressibility of the particles that flow through, without being limited by random diffusion. Information on the particle mechanical properties is encoded in the light scattered from the thermal fluctuations of the phonon mode, and measurements at a timescale of below 20 milliseconds have been demonstrated previously. In this work, we develop a new experimental method for improving the signal-to-noise ratio (SNR) and sensing speed achievable with this technique, by implementing electro-opto-mechanical transduction. We demonstrate real-time particle transit measurements as fast as 400 microseconds, a factor of 50x improvement in speed, without any post-processing. We discuss how this novel technique can be used for ultra-high throughput analysis of mechanical properties of biological particles in liquids, enabling a new form of flow cytometry.

  5. End-stage head and neck cancer coping mechanisms

    Directory of Open Access Journals (Sweden)

    Bogdan Popescu

    2017-10-01

    Full Text Available Coping mechanisms are patients’ means of adapting to stressful situations and involve psychological and physical changes in behavior. Patients adapt to head and neck cancer in a variety of ways. Head and neck cancers are extremely debilitating, especially in advanced stages of the disease or in end-of-life situations. While an oncology team needs to address the needs of all oncology patients, the advanced terminal patients require special attention. Most of these patients do not cope well with their situation and have a tendency to cease social interactions. Pain is the most frequentlyexperienced medical disability in patients having an end-stage illness experience, and thus an important medical endeavor is to afford dignity to the dying patient facingan incurable disease. In such cases, the medical community should never refuse therapy or to assist a dying patient.In some instances, the patient and family may derive benefit from their religious beliefs.

  6. Aberrant expression of STYK1 and E-cadherin confer a poor prognosis for pancreatic cancer patients.

    Science.gov (United States)

    Chen, Luguang; Ma, Chao; Bian, Yun; Shao, Chengwei; Wang, Tiegong; Li, Jing; Chong, Xiaodan; Su, Li; Lu, Jianping

    2017-12-19

    Previous studies showed that aberrant Serine/threonine/tyrosine kinase 1 (STYK1, also known as NOK) or/and E-cadherin were involved in the progression of some types of human cancers. However, whether they contributed to the development of pancreatic cancer was unknown. Here, we investigated the prognostic significance of aberrant STYK1 and E-cadherin in pancreatic cancer. Our results showed that STYK1 expression increased while E-cadherin decreased in pancreatic cancer tissues compared with normal pancreas tissues. STYK1 level was positively correlated with lymph node metastasis and clinical stage in pancreatic cancer patients. E-cadherin expression was inversely correlated with STYK1 expression in pancreatic cancer tissue samples. Patients with high STYK1 and low E-cadherin expression had the worst prognosis. In addition, STYK1 knockdown in pancreatic cancer cell lines inhibited cell proliferation, enhanced cell apoptosis, induced cell cycle arrest, and prohibited cell migration, while STYK1 over-expression showed the opposite effects. Silencing STYK1 also increased E-cadherin expression and inhibited epithelial-to-mesenchymal transition (EMT) and p-p38 expression in vitro. Over-expression had showed the opposite trends, and treatment with p38 inhibitor, SB203580, could reverse the trends. Thus, STYK1 repressed E-cadherin expression and promoted EMT, mediated by p38 MAPK signaling pathway, which was the possible mechanism for STYK1-mediated pancreatic cancer cell proliferation and migration. In summary, our results showed that STYK1 might be a prognostic marker for pancreatic cancer patients and might be a novel strategy for the treatment of pancreatic cancer.

  7. Utilising non-linear elasticity to increase mechanical contrast in quantitative optical coherence elastography (Conference Presentation)

    Science.gov (United States)

    Allen, Wes M.; Wijesinghe, Philip; Chin, Lixin; Hamzah, Juliana; Ganss, Ruth; Sampson, David D.; Kennedy, Brendan F.

    2017-02-01

    Compression optical coherence elastography (OCE) enables rapid acquisition with high resolution over fields of view relevant to many clinical applications. Compression OCE typically provides a relative measure of mechanical properties; however, we have recently demonstrated a technique which quantifies stiffness via a compliant layer, termed quantitative OCE. In quantitative OCE, stiffness is reported as a tangent modulus, which is a surrogate for Young's modulus at a given preload in non-linear elastic material. In biological tissues, which are typically non-linear elastic, values of stiffness reported through quantitative OCE could be over- or under-estimated, and are heavily biased by the arbitrary bulk preload applied to that region. We present a method to measure tissue nonlinearity locally, by preforming compression OCE at multiple preloads ranging from 2% to 40%. We show, through presentation of 2D quantitative elastograms, that compression OCE has the potential to measure the non-linear stiffness in tissue mimicking phantoms and biological tissue. Further, intrinsic mechanical contrast in tissue is dependent upon its preload. By tailoring tissue preload, we demonstrate improved contrast between benign and tumor tissue in a murine liver carcinoma model.

  8. National Institutes of Health State-of-the-Science Conference Statement: Symptom management in cancer: pain, depression, and fatigue, July 15-17, 2002.

    Science.gov (United States)

    Patrick, Daniel L; Ferketich, Sandra L; Frame, Paul S; Harris, Jesse J; Hendricks, Carolyn B; Levin, Bernard; Link, Michael P; Lustig, Craig; McLaughlin, Joseph; Reid, L Douglas; Turrisi, Andrew T; Unützer, Jürgen; Vernon, Sally W

    2004-01-01

    Despite advances in early detection and effective treatment, cancer remains one of the most feared diseases. Among the most common side effects of cancer and treatments for cancer are pain, depression, and fatigue. Although research is producing increasingly hopeful insights into the causes and cures for cancer, efforts to manage the side effects of the disease and its treatments have not kept pace. The challenge that faces us is how to increase awareness of the importance of recognizing and actively addressing cancer-related distress. The National Institutes of Health (NIH) convened a State-of-the-Science Conference on Symptom Management in Cancer: Pain, Depression, and Fatigue to examine the current state of knowledge regarding the management of pain, depression, and fatigue in individuals with cancer and to identify directions for future research. Specifically, the conference examined how to identify individuals who are at risk for cancer-related pain, depression, and/or fatigue; what treatments work best to address these symptoms when they occur; and what is the best way to deliver interventions across the continuum of care. STATE-OF-THE-SCIENCE PROCESS: A non-advocate, non-Federal, 14-member panel of experts representing the fields of oncology, radiology, psychology, nursing, public health, social work, and epidemiology prepared the statement. In addition, 24 experts in medical oncology, geriatrics, pharmacology, psychology, and neurology presented data to the panel and to the conference audience during the first 1.5 days of the conference. The panel then prepared its statement, addressing the five predetermined questions and drawing on submitted literature, the speakers' presentations, and discussions held at the conference. The statement was presented to the conference audience, followed by a press conference to allow the panel to respond to questions from the media. After its release at the conference, the draft statement was made available on the Internet

  9. Ciprofloxacin mediates cancer stem cell phenotypes in lung cancer cells through caveolin-1-dependent mechanism.

    Science.gov (United States)

    Phiboonchaiyanan, Preeyaporn Plaimee; Kiratipaiboon, Chayanin; Chanvorachote, Pithi

    2016-04-25

    Cancer stem cells (CSCs), a subpopulation of cancer cells with high aggressive behaviors, have been identified in many types of cancer including lung cancer as one of the key mediators driving cancer progression and metastasis. Here, we have reported for the first time that ciprofloxacin (CIP), a widely used anti-microbial drug, has a potentiating effect on CSC-like features in human non-small cell lung cancer (NSCLC) cells. CIP treatment promoted CSC-like phenotypes, including enhanced anchorage-independent growth and spheroid formation. The known lung CSC markers: CD133, CD44, ABCG2 and ALDH1A1 were found to be significantly increased, while the factors involving in epithelial to mesenchymal transition (EMT): Slug and Snail, were depleted. Also, self-renewal transcription factors Oct-4 and Nanog were found to be up-regulated in CIP-treated cells. The treatment of CIP on CSC-rich populations obtained from secondary spheroids resulted in the further increase of CSC markers. In addition, we have proven that the mechanistic insight of the CIP induced stemness is through Caveolin-1 (Cav-1)-dependent mechanism. The specific suppression of Cav-1 by stably transfected Cav-1 shRNA plasmid dramatically reduced the effect of CIP on CSC markers as well as the CIP-induced spheroid formation ability. Cav-1 was shown to activate protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) pathways in CSC-rich population; however, such an effect was rarely found in the main lung cancer cells population. These findings reveal a novel effect of CIP in positively regulating CSCs in lung cancer cells via the activation of Cav-1, Akt and ERK, and may provoke the awareness of appropriate therapeutic strategy in cancer patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Mapping the mechanical heterogeneity of the brain, and why this matters (Conference Presentation)

    Science.gov (United States)

    Guck, Jochen R.

    2017-02-01

    It is increasingly recognized that cells measure and respond to the mechanics of their environment. We are especially interested in this mechanosensing during CNS development and pathologies. Using quantitative scanning force microscopy we have shown that various neural tissues are very compliant (shear modulus root of foreign body reactions. Also oligodendrocytes are mechanosensitive as their survival, proliferation, migration, and differentiation capacity in vitro depend on substrate stiffness. This finding might be linked to the failure of remyelination in chronic demyelinating diseases such as multiple sclerosis. And finally, we have also shown retinal ganglion axon pathfinding in the early embryonic Xenopus brain development to be instructed by stiffness gradients. These results form the basis for further investigations into the mechanobiology of cell function in the CNS. Ultimately, this research could help treating previously incurable neuropathologies such as spinal cord injuries and neurodegenerative disorders.

  11. Skin cancer margin analysis within minutes with full-field OCT (Conference Presentation)

    Science.gov (United States)

    Dalimier, Eugénie; Ogrich, Lauren; Morales, Diego; Cusack, Carrie Ann; Abdelmalek, Mark; Boccara, Claude; Durkin, John

    2017-02-01

    Non-melanoma skin cancer (NMSC) is the most common cancer. Treatment consists of surgical removal of the skin cancer. Traditional excision involves the removal of the visible skin cancer with a significant margin of normal skin. On cosmetically sensitive areas, Mohs micrographic tissue is the standard of care. Mohs uses intraoperative microscopic margin assessment which minimizes the surgical defect and can help reduce the recurrence rate by a factor of 3. The current Mohs technique relies on frozen section tissue slide preparation which significantly lengthens operative time and requires on-site trained histotechnicians. Full-Field Optical Coherence Tomography (FFOCT) is a novel optical imaging technique which provides a quick and efficient method to visualize cancerous areas in minutes, without any preparation or destruction of the tissue. This study aimed to evaluate the potential of FFOCT for the analysis of skin cancer margins during Mohs surgery. Over 150 images of Mohs specimens were acquired intraoperatively with FFOCT before frozen section analysis. The imaging procedure took less than 5 minutes for each specimen. No artifacts on histological preparation were found arising from FFOCT manipulation; however frozen section artifact was readily seen on FFOCT. An atlas was established with FFOCT images and corresponding histological slides to reveal FFOCT reading criteria of normal and cancerous structures. Blind analysis showed high concordance between FFOCT and histology. FFOCT can potentially reduce recurrence rates while maintaining short surgery times, optimize clinical workflow, and decrease healthcare costs. For the patient, this translates into smaller infection risk, decreased stress, and better comfort.

  12. Functional genetic polymorphisms in PP2A subunit genes confer increased risks of lung cancer in southern and eastern Chinese.

    Directory of Open Access Journals (Sweden)

    Rongrong Yang

    Full Text Available Protein phosphatase-2A (PP2A is one of the major cellular serine-threonine phosphatases and functions as a tumor suppressor that negatively regulates the activity of some oncogenic kinases. Recent studies have reported that PP2A expression was suppressed during lung carcinogenesis, we there hypothesized that the single nucleotide polymorphisms (SNPs in PP2A subunit genes may affect PP2A function and thus contribute to lung cancer susceptibility. In a two-stage case-control study with a total of 1559 lung cancer patients and 1679 controls, we genotyped eight putative functional SNPs and one identified functional SNP (i.e., rs11453459 in seven major PP2A subunits (i.e., PPP2R1A, PPP2R1B, PPP2CA, PPP2R2A, PPP2R2B, PPP2R5C, PPP2R5E in southern and eastern Chinese. We found that rs11453459G (-G/GG variant genotypes of PPP2R1A and the rs1255722AA variant genotype of PPP2R5E conferred increased risks of lung cancer (rs11453459, -G/GG vs. -: OR = 1.31, 95% CI = 1.13-1.51; rs1255722, AA vs.OR = 1.27, 95% CI = 1.07-1.51. After combined the two variants, the number of the adverse genotypes was positively associated with lung cancer risk in a dose-response manner (P trend = 5.63 × 10(-6. Further functional assay showed that lung cancer tissues carrying rs1255722AA variant genotype had a significantly lower mRNA level of PPP2R5E compared with tissues carrying GG/GA genotypes. However, such effect was not observed for the other SNPs and other combinations. Our findings suggested that the two functional variants in PPP2R1A and PPP2R5E and their combination are associated with lung cancer risk in Chinese, which may be valuable biomarkers to predict risk of lung cancer.

  13. BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer

    DEFF Research Database (Denmark)

    Shimelis, Hermela; Mesman, Romy L S; Von Nicolai, Catharina

    2017-01-01

    were investigated through a breast cancer case-control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A>C, p.Tyr3035Ser (OR = 2.52; P = 0.04), and BRCA......, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants. Cancer Res; 77(11); 2789-99. ©2017 AACR....

  14. Autophagic Mechanism in Anti-Cancer Immunity: Its Pros and Cons for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Ying-Ying Li

    2017-06-01

    Full Text Available Autophagy, a self-eating machinery, has been reported as an adaptive response to maintain metabolic homeostasis when cancer cells encounter stress. It has been appreciated that autophagy acts as a double-edge sword to decide the fate of cancer cells upon stress factors, molecular subtypes, and microenvironmental conditions. Currently, the majority of evidence support that autophagy in cancer cells is a vital mechanism bringing on resistance to current and prospective treatments, yet whether autophagy affects the anticancer immune response remains unclear and controversial. Accumulated studies have demonstrated that triggering autophagy is able to facilitate anticancer immunity due to an increase in immunogenicity, whereas other studies suggested that autophagy is likely to disarm anticancer immunity mediated by cytotoxic T cells and nature killer (NK cells. Hence, this contradiction needs to be elucidated. In this review, we discuss the role of autophagy in cancer cells per se and in cancer microenvironment as well as its dual regulatory roles in immune surveillance through modulating presentation of tumor antigens, development of immune cells, and expression of immune checkpoints. We further focus on emerging roles of autophagy induced by current treatments and its impact on anticancer immune response, and illustrate the pros and cons of utilizing autophagy in cancer immunotherapy based on preclinical references.

  15. Mechanisms of right heart disease in pulmonary hypertension (2017 Grover Conference Series).

    Science.gov (United States)

    Asosingh, Kewal; Erzurum, Serpil

    2018-01-01

    Current dogma is that pathological hypertrophy of the right ventricle is a direct consequence of pulmonary vascular remodeling. However, progression of right ventricle dysfunction is not always lung-dependent. Increased afterload caused by pulmonary vascular remodeling initiates the right ventricle hypertrophy, but determinants leading to adaptive or maladaptive hypertrophy and failure remain unknown. Ischemia in a hypertrophic right ventricle may directly contribute to right heart failure. Rapidly enlarging cardiomyocytes switch from aerobic to anaerobic energy generation resulting in cell growth under relatively hypoxic conditions. Cardiac muscle reacts to an increased afterload by over-activation of the sympathetic system and uncoupling and downregulation of β-adrenergic receptors. Recent studies suggest that β blocker therapy in PH is safe, well tolerated, and preserves right ventricle function and cardiac output by reducing right ventricular glycolysis. Fibrosis, an evolutionary conserved process in host defense and wound healing, is dysregulated in maladaptive cardiac tissue contributing directly to right ventricle failure. Despite several mechanisms having been suggested in right heart disease, the causes of maladaptive cardiac remodeling remain unknown and require further research.

  16. Novel coupled-cavity sensing mechanism for on-chip detection of microparticles (Conference Presentation)

    Science.gov (United States)

    Gillgrass, Sara-Jayne; Thomas, Robert; Smowton, Peter M.

    2017-02-01

    Coupled-cavity lasers have attracted wide attention in the past, in particular for telecommunication applications where their wavelength tunability and ability for side mode suppression are desirable. The inherent sensitivity of these devices to changes in the optical coupling has also led to their proposed use in optical sensing systems. Small changes to the refractive index of the coupler section can lead to shifts in the resonance frequency of the laser. Here we present an alternative approach to coupled-cavity sensing that exploits changes to the imaginary part of the refractive index of the coupler. An optical loss, introduced to the cavity by the passage of micro-particles, influences the optical loss of the lasing mode and changes the threshold gain requirement of the laser. The sub-linear nature of the gain-current density characteristics of the quantum confined gain medium amplifies this effect, producing an even larger perturbation in output power. We demonstrate this sensing mechanism using a monolithic coupled-cavity particle detector with on-chip capillary fill microfluidics and an in-line photo-detector section for photo-voltage transduction. Both laser and detector are pulsed allowing for a time-resolved measurement to be taken.

  17. Dana-Farber Cancer Institute: Discovery of Resistance Mechanisms | Office of Cancer Genomics

    Science.gov (United States)

    Resistance to targeted therapy is emerging as a bottleneck to achieving durable drug responses in cancer. The goal of the CTD2 Center at Dana Farber Cancer Institute is to identify mechanisms of resistance for both existing therapeutics as well as for emerging targets even prior to the identification of lead compounds. They aim to use this information to inform combinatorial treatments. In representative examples they have found that YAP1 leads to resistance after KRAS targeting and that PRKACA mediates resistance to HER2 therapy.

  18. Harnessing Raman spectroimmunoassay for detection of serological breast cancer markers (Conference Presentation)

    Science.gov (United States)

    Barman, Ishan; Li, Ming

    2017-02-01

    Two critical, unmet needs in breast cancer are the early detection of cancer metastasis and recurrence, and the sensitive assessment of temporal changes in tumor burden in response to therapy. The present research is directed towards developing a non-invasive, ultrasensitive and specific tool that provides a comprehensive real-time picture of the metastatic tumor burden and provides a radically new route to address these overarching challenges. As the continuing search for better diagnostic and prognostic clues has shifted away from a singular focus on primary tumor lesions, circulating and disseminated biomarkers have surfaced as attractive candidates due to the intrinsic advantages of a non-invasive, repeatable "liquid biopsy" procedure. However, a reproducible, facile blood-based test for diagnosis and follow-up of breast cancer has yet to be incorporated into a clinical laboratory assay due to the limitations of existing assays in terms of sensitivity, extensive sample processing requirements and, importantly, multiplexing capability. Here, by architecting nano-structured probes for detection of specific molecular species, we engineer a novel plasmon-enhanced Raman spectroscopic platform that offers a paradigmatic shift from the capabilities of today's diagnostic test platforms. Specifically, quantitative single-droplet serum tests reveal ultrasensitive and multiplexed detection of three key breast cancer biomarkers, cancer antigen 15-3 (CA15-3), CA27-29 and carcinoembryonic antigen (CEA), over several order of magnitude range of biomarker concentration and clear segmentation of the sera between normal and metastatic cancer levels.

  19. A THz plasmonics perfect absorber and Fabry-Perot cavity mechanism (Conference Presentation)

    Science.gov (United States)

    Zhou, Jiangfeng; Bhattarai, Khagendra; Silva, Sinhara; Jeon, Jiyeon; Kim, Junoh; Lee, Sang Jun; Ku, Zahyun

    2016-10-01

    The plasmonic metamaterial perfect absorber (MPA) is a recently developed branch of metamaterial which exhibits nearly unity absorption within certain frequency range.[1-6] The optically thin MPA possesses characteristic features of angular-independence, high Q-factor and strong field localization that have inspired a wide range of applications including electromagnetic wave absorption,[3, 7, 8] spatial[6] and spectral[5] modulation of light,[9] selective thermal emission,[9] thermal detecting[10] and refractive index sensing for gas[11] and liquid[12, 13] targets. In this work, we demonstrate a MPA working at terahertz (THz) regime and characterize it using an ultrafast THz time-domain spectroscopy (THz-TDS). Our study reveal an ultra-thin Fabry-Perot cavity mechanism compared to the impedance matching mechanism widely adopted in previous study [1-6]. Our results also shows higher-order resonances when the cavities length increases. These higher order modes exhibits much larger Q-factor that can benefit potential sensing and imaging applications. [1] C. M. Watts, X. L. Liu, and W. J. Padilla, "Metamaterial Electromagnetic Wave Absorbers," Advanced Materials, vol. 24, pp. 98-120, Jun 19 2012. [2] M. Hedayati, F. Faupel, and M. Elbahri, "Review of Plasmonic Nanocomposite Metamaterial Absorber," Materials, vol. 7, pp. 1221-1248, 2014. [3] N. I. Landy, S. Sajuyigbe, J. J. Mock, D. R. Smith, and W. J. Padilla, "Perfect metamaterial absorber," Physical Review Letters, vol. 100, p. 207402, May 23 2008. [4] H. R. Seren, G. R. Keiser, L. Cao, J. Zhang, A. C. Strikwerda, K. Fan, et al., "Optically Modulated Multiband Terahertz Perfect Absorber," Advanced Optical Materials, vol. 2, pp. 1221-1226, 2014. [5] D. Shrekenhamer, J. Montoya, S. Krishna, and W. J. Padilla, "Four-Color Metamaterial Absorber THz Spatial Light Modulator," Advanced Optical Materials, vol. 1, pp. 905-909, 2013. [6] S. Savo, D. Shrekenhamer, and W. J. Padilla, "Liquid Crystal Metamaterial Absorber Spatial

  20. Possibilities of Bragg filtering structures based on subwavelength grating guiding mechanism (Conference Presentation)

    Science.gov (United States)

    Kwiecien, Pavel; Litvik, Ján.; Richter, Ivan; Ctyroký, Jirí; Cheben, Pavel

    2017-05-01

    Silicon-on-insulator (SOI), as the most promising platform, for advanced photonic integrated structures, employs a high refractive index contrast between the silicon "core" and surrounding media. One of the recent new ideas within this field is based on the alternative formation of the subwavelength sized (quasi)periodic structures, manifesting as an effective medium with respect to propagating light. Such structures relay on Bloch wave propagation concept, in contrast to standard index guiding mechanism. Soon after the invention of such subwavelength grating (SWG) waveguides, the scientists concentrated on various functional elements such as couplers, crossings, mode transformers, convertors, MMI couplers, polarization converters, resonators, Bragg filters, and others. Our contribution is devoted to a detailed numerical analysis and design considerations of Bragg filtering structures based on SWG idea. Based on our previous studies where we have shown impossibility of application of various 2 and "2.5" dimensional methods for the proper numerical analysis, here we effectively use two independent but similar in-house approaches based on 3D Fourier modal methods, namely aperiodic rigorous coupled wave analysis (aRCWA) and bidirectional expansion and propagation method based on Fourier series (BEX) tools. As it was recently demonstrated, SWG Bragg filters are feasible. Based on this idea, we propose, simulate, and optimize spectral characteristics of such filters. In particular, we have investigated several possibilities of modifications of original SWG waveguides towards the Bragg filtering, including firstly - simple single-segment changes in position, thickness, and width, and secondly - several types of Si inclusions, in terms of perturbed width and thickness (and their combinations). The leading idea was to obtain required (e.g. sufficiently narrow) spectral characteristic while keeping the minimum size of Si features large enough. We have found that the second

  1. Origami-based mechanical metamaterials with tunable frequency band structures (Conference Presentation)

    Science.gov (United States)

    Yasuda, Hiromi; Pratt, Riley; Yang, Jinkyu

    2017-04-01

    We investigate wave dynamics in origami-based mechanical metamaterials composed of bellows-like origami structures, specifically the Tachi-Miura Polyhedron (TMP). One of the unique features of the TMP is that its structural deformations take place only along the crease lines, therefore the structure can be made of rigid plates and hinges. By utilizing this feature, we introduce linear torsional springs to model the crease lines and derive the force and displacement relationship of the TMP structure along the longitudinal direction. Our analysis shows strain softening/hardening behaviors in compression/tensile regions respectively, and the force-displacement curve can be manipulated by altering the initial configuration of the TMP (e.g., the initial folding angle). We also fabricate physical prototypes and measure the force-displacement behavior to verify our analytical model. Based on this static analysis on the TMP, we simplify the TMP structure into a linkage model, preserving the tunable strain softening/hardening behaviors. Dynamic analysis is also conducted numerically to analyze the frequency response of the simplified TMP unit cell under harmonic excitations. The simplified TMP exhibits a transition between linear and nonlinear behaviors, which depends on the amplitude of the excitation and the initial configuration. In addition, we design a 1D system composed of simplified TMP unit cells and analyze the relationship between frequency and wave number. If two different configurations of the unit cell (e.g., different initial folding angles) are connected in an alternating arrangement, the system develops frequency bandgaps. These unique static/dynamic behaviors can be exploited to design engineering devices which can handle vibrations and impact in an efficient manner.

  2. Disulfide-crosslinked nanomicelles confer cancer-specific drug delivery and improve efficacy of paclitaxel in bladder cancer

    Science.gov (United States)

    Pan, Amy; Zhang, Hongyong; Li, Yuanpei; Lin, Tzu-yin; Wang, Fuli; Lee, Joyce; Cheng, Mingshan; Dall'Era, Marc; Li, Tianhong; deVere White, Ralph; Pan, Chong-Xian; Lam, Kit S.

    2016-10-01

    Chemotherapy commonly used in the treatment of advanced bladder cancer is only moderately effective and associated with significant toxicity. There has been no appreciable improvement in overall survival over the last three decades. The goal of this project is to develop and characterize bladder cancer-specific nanometer-scale micelles loaded with the chemotherapeutic drug paclitaxel (PTX) and determine the anti-tumor activity and toxicity. Micelle-building-material telodendrimers were synthesized through the stepwise conjugation of eight cholic acid units at one terminus of polyethylene glycol (PEG) and a bladder cancer-specific targeting peptide named PLZ4 at the other terminus. To synthesize disulfide-crosslinked PLZ4 nanomicelles (DC-PNM), cysteine was introduced between the cholic acid and PEG. DC-PNM-PTX was synthesized through the evaporation method by loading PTX in the core. The loading capacity of PTX in DC-PNM was 25% (W/W). The loading efficiency was over 99%. DC-PNM-PTX was spherical with the median size of 25 nm. The stability of DC-PNM-PTX was determined in a solution containing sodium docecyl sulfate (SDS). It was stable in a SDS solution, but dissolved within 5 min after the addition of glutathione at the physiological intracellular concentration of 10 mM. In vivo targeting and anti-tumor activity were determined in immunodeficient mice carrying patient-derived bladder cancer xenografts (PDXs). After intravenous administration, DC-PNM specifically targeted the bladder cancer PDXs, but very little to the lung cancer xenografts in the same mice (p < 0.001). DC-PNM loaded with PTX overcame cisplatin resistance, and improved the median survival from 55 d with free PTX to 69.5 d (p = 0.03) of mice carrying PDXs. In conclusion, DC-PNM remained stable in the SDS solution, specifically targeted the bladder cancer xenografts in vivo, and improved the anti-cancer efficacy of PTX.

  3. Pain in Breast Cancer Treatment: Aggravating Factors and Coping Mechanisms

    Directory of Open Access Journals (Sweden)

    Maria de Fatima Guerreiro Godoy

    2014-01-01

    Full Text Available The objective of this study was to evaluate pain in women with breast cancer-related lymphedema and the characteristics of aggravating factors and coping mechanisms. The study was conducted in the Clinica Godoy, São Jose do Rio Preto, with a group of 46 women who had undergone surgery for the treatment of breast cancer. The following variables were evaluated: type and length of surgery; number of radiotherapy and chemotherapy sessions; continued feeling of the removed breast (phantom limb, infection, intensity of pain, and factors that improve and worsen the pain. The percentage of events was used for statistical analysis. About half the participants (52.1% performed modified radical surgery, with 91.3% removing only one breast; 82.6% of the participants did not perform breast reconstruction surgery. Insignificant pain was reported by 32.60% of the women and 67.3% said they suffered pain; it was mild in 28.8% of the cases (scale 1–5, moderate in 34.8% (scale 6–9, and severe in 4.3%. The main mechanisms used to cope with pain were painkillers in 41.30% of participants, rest in 21.73%, religious ceremonies in 17.39%, and chatting with friends in 8.69%. In conclusion, many mastectomized patients with lymphedema complain of pain, but pain is often underrecognized and undertreated.

  4. Photothermal therapy to damage PC3 cancer cells: in vitro studies of a pulsed laser (Conference Presentation)

    Science.gov (United States)

    Zamora-Romero, Noe; Aguilar, Guillermo; Devia-Cruz, Luis F.; Banks, Darren; Zhang, Bin; Halaney, David L.

    2017-02-01

    Laser-nanoparticles interactions have been widely used for several years. In biomedicine, several in vitro and in vivo experiments have shown promising results for the detection and treatment of cancer. One of the techniques of interest to us, is the nanoparticle-assisted photothermal therapy (PTT), which consists of irradiating cancer cells incubated with nanoparticles with either a pulsed or continuous (cw) laser in order to damage the cells. However, there is still a debate over which type of laser is most effective for PTT for cancer treatment. On the one hand, cw lasers are minimally invasive and can be used for both detection and treatment of tumors. On the other hand, pulsed lasers offer great spatial precision and can deposit higher energy fluences than cw lasers, making them very efficient for inducing cavitation to damage cancer cells and tumors mechanically. The aim of this study is to investigate whether simultaneous application of cw and pulsed laser could offer a synergetic enhancement of PTT efficacy to damage cancer cells in vitro, compared to either laser applied individually. PTT efficacy is evaluated through cell viability tests following the irradiation of prostate cancer (PC3) cells incubated with gold nanorods (5.7 X10 10 p/ml). By irradiating the PC3-nanorod solution with the cw laser at 808 nm for 60 seconds, the temperature increases from 37.5 to 45°C, which damages some cancer cells via the heat shock response within the cells, and also could increase their sensitivity to the mechanical stress caused by the shock wave generated from inducing cavitation in the solution by the pulsed laser irradiation.

  5. Beclin 1 and UVRAG confer protection from radiation-induced DNA damage and maintain centrosome stability in colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Jae Myung Park

    Full Text Available Beclin 1 interacts with UV-irradiation-resistance-associated gene (UVRAG to form core complexes that induce autophagy. While cells with defective autophagy are prone to genomic instability that contributes to tumorigenesis, it is unknown whether Beclin1 or UVRAG can regulate the DNA damage/repair response to cancer treatment in established tumor cells. We found that siRNA knockdown of Beclin 1 or UVRAG can increase radiation-induced DNA double strand breaks (DSBs, shown by pATM and γH2Ax, and promote colorectal cancer cell death. Furthermore, knockdown of Beclin 1, UVRAG or ATG5 increased the percentage of irradiated cells with nuclear foci expressing 53BP1, a marker of nonhomologous end joining but not RAD51 (homologous recombination, compared to control siRNA. Beclin 1 siRNA was shown to attenuate UVRAG expression. Cells with a UVRAG deletion mutant defective in Beclin 1 binding showed increased radiation-induced DSBs and cell death compared to cells with ectopic wild-type UVRAG. Knockdown of Beclin 1 or UVRAG, but not ATG5, resulted in a significant increase in centrosome number (γ-tubulin staining in irradiated cells compared to control siRNA. Taken together, these data indicate that Beclin 1 and UVRAG confer protection against radiation-induced DNA DSBs and may maintain centrosome stability in established tumor cells.

  6. Improved cancer risk stratification and diagnosis via quantitative phase microscopy (Conference Presentation)

    Science.gov (United States)

    Liu, Yang; Uttam, Shikhar; Pham, Hoa V.; Hartman, Douglas J.

    2017-02-01

    Pathology remains the gold standard for cancer diagnosis and in some cases prognosis, in which trained pathologists examine abnormality in tissue architecture and cell morphology characteristic of cancer cells with a bright-field microscope. The limited resolution of conventional microscope can result in intra-observer variation, missed early-stage cancers, and indeterminate cases that often result in unnecessary invasive procedures in the absence of cancer. Assessment of nanoscale structural characteristics via quantitative phase represents a promising strategy for identifying pre-cancerous or cancerous cells, due to its nanoscale sensitivity to optical path length, simple sample preparation (i.e., label-free) and low cost. I will present the development of quantitative phase microscopy system in transmission and reflection configuration to detect the structural changes in nuclear architecture, not be easily identifiable by conventional pathology. Specifically, we will present the use of transmission-mode quantitative phase imaging to improve diagnostic accuracy of urine cytology and the nuclear dry mass is progressively correlate with negative, atypical, suspicious and positive cytological diagnosis. In a second application, we will present the use of reflection-mode quantitative phase microscopy for depth-resolved nanoscale nuclear architecture mapping (nanoNAM) of clinically prepared formalin-fixed, paraffin-embedded tissue sections. We demonstrated that the quantitative phase microscopy system detects a gradual increase in the density alteration of nuclear architecture during malignant transformation in animal models of colon carcinogenesis and in human patients with ulcerative colitis, even in tissue that appears histologically normal according to pathologists. We evaluated the ability of nanoNAM to predict "future" cancer progression in patients with ulcerative colitis.

  7. Stress and Coping Mechanisms Among Breast Cancer Patients and ...

    African Journals Online (AJOL)

    Background: Breast cancer is the most common malignancy of women worldwide accounting for 23% of all newly diagnosed cancer cases. It is also the leading cause of cancer mortality, representing 14.1%. In Zambia, it is second to cervical cancer and its incidence is steadily increasing. A diagnosis of cancer regardless of ...

  8. Photoacoustic physio-chemical analysis for prostate cancer diagnosis (Conference Presentation)

    Science.gov (United States)

    Xu, Guan; Cheng, Qian; Huang, Shengsong; Qin, Ming; Hopkins, Thomas; Lee, Chang H.; Kopelman, Raoul; Chao, Wan-yu; Keller, Evan T.; Wu, Denglong; Wang, Xueding

    2017-03-01

    Photoacoustic physio-chemical analysis (PAPCA) is a recently developed technology capable of simultaneously quantifying the content of molecular components and the corresponding microarchitectures in biological tissue. We have successfully quantified the diagnostic information in livers with PAPCA. In this study, we implemented PAPCA to the diagnosis of prostate cancers. 4 human prostates were scanned ex vivo. The PA signals from normal and cancerous regions in the prostates were acquired by an interstitial needle PA probe. A total of 14 interstitial measurements, including 6 within the normal regions and 8 in the cancerous regions, were acquired. The observed changes in molecular components, including lipid, collagen and hemoglobin were consistent with the findings by other research groups. The changes were quantified by PA spectral analysis (PASA) at wavelengths where strong optical absorption of the relevant molecular components was found. Statistically significant differences among the PASA parameters were observed (p=0.025 at significance of 0.05). A support vector machine model for differentiating the normal and cancerous tissue was established. With the limited number of samples, an 85% diagnostic accuracy was found. The diagnostic information in the PCPCA can be further enriched by targeted optical contrast agents visualizing the microarchitecture in PCa tissues. F3 PAA-PEG nanoparticles was employed to stain the PCa cells in a transgenic mouse model, in which the microarchitectures of normal and cancerous prostate tissues are comparable to that in human. Statistically significant differences were observed between the contrast-enhanced normal and cancerous regions (p=0.038 at a significance of 0.05).

  9. Near infrared photoimmunotherapy rapidly elicits specific host immunity against cancer cells (Conference Presentation)

    Science.gov (United States)

    Kobayashi, Hisataka

    2017-02-01

    Near infrared photoimmunotherapy (NIR-PIT) is a new molecularly-targeted cancer photo-therapy based on conjugating a near infrared silica-phthalocyanine dye, IR700, to a monoclonal antibody (mAb) targeting cell-surface molecules. When exposed to NIR light, the conjugate induces a highly-selective necrotic/immunogenic cell death (ICD) only in target-positive, mAb-IR700-bound cancer cells. This cell death occurs as early as 1 minute after exposure to NIR light. Meanwhile, immediately adjacent target-negative cells are unharmed. Dynamic 3D-microscopy of live tumor cells undergoing NIR-PIT showed rapid swelling in treated cells immediately after light exposure, followed by irreversible morphologic changes such as bleb formation, and rupture of vesicles within several minutes. Furthermore, biological markers of ICD including relocation of HSP70/90 and calreticulin, and release of ATP and High Mobility Group Box 1 (HMGB1), were clearly detected immediately after NIR-PIT. When NIR-PIT was performed in a mixture of cancer cells and immature dendritic cells, maturation of immature dendritic cells was strongly induced rapidly after NIR-PIT. Alternatively, NIR-PIT can also target negative regulatory immune cells such as Treg only in the tumor bed. Treg targeting NIR-PIT against CD25 can deplete >80% of Treg in tumor bed within 20 min that induces activation of tumor cell-specific CD8+-T and NK cells within 1.5 hour, and then these activated cells killed cancer cells in local tumor within 1 day and also in distant tumors of the same cell origin within 2 days. In summary, cancer cell-targeting and immuno-suppressor cell-targeting NIR-PITs effectively induce innate and acquired immunity specifically against cancer cells growing in patients, respectively.

  10. A truncating mutation of HDAC2 in human cancers confers resistance to histone deacetylase inhibition

    DEFF Research Database (Denmark)

    Ropero, S; Fraga, MF; Ballestar, E

    2006-01-01

    Disruption of histone acetylation patterns is a common feature of cancer cells, but very little is known about its genetic basis. We have identified truncating mutations in one of the primary human histone deacetylases, HDAC2, in sporadic carcinomas with microsatellite instability and in tumors...... arising in individuals with hereditary nonpolyposis colorectal cancer syndrome. The presence of the HDAC2 frameshift mutation causes a loss of HDAC2 protein expression and enzymatic activity and renders these cells more resistant to the usual antiproliferative and proapoptotic effects of histone...

  11. A coding variant in RARG confers susceptibility to anthracycline-induced cardiotoxicity in childhood cancer

    NARCIS (Netherlands)

    Aminkeng, Folefac; Bhavsar, Amit P.; Visscher, Henk; Rassekh, Shahrad R.; Li, Yuling; Lee, Jong W.; Brunham, Liam R.; Caron, Huib N.; van Dalen, Elvira C.; Kremer, Leontien C.; van der Pal, Helena J.; Amstutz, Ursula; Rieder, Michael J.; Bernstein, Daniel; Carleton, Bruce C.; Hayden, Michael R.; Ross, Colin J. D.; MacLeod, Stuart; Smith, Anne; Hildebrand, Claudette; Ghannadan, Reza; Miao, Fudan; Higginson, Michelle; Massah, Nasim; Borrie, Adrienne; Hughes, Shevaun; Shaw, Kaitlyn; Dhoot, Satvir; Kowalec, Kaarina; Stortz, Jessica; Bendyshe-Walton, Tessa; Waltrip, Duncan; Bader, Rachel; Nijssen-Jordan, Cheri; Johnson, David; Verbeek, Linda; Kaczowka, Rick; Stevenson, Patti; Zhuwaki, Carnation; Grundy, Paul; Stobart, Kent; Wilson, Bev; Desai, Sunil; Spavor, Maria; Churcher, Linda; Chow, Terence; Hall, Kevin; Honcharik, Nick; Israels, Sara; Chan, Shanna; Garnham, Byron; Staub, Michelle; 't Jong, Geert; Malkin, Becky; Portwine, Carol; Cranston, Amy; Koren, Gideon; Ito, Shinya; Nathan, Paul; Greenberg, Mark; Bournissen, Facundo Garcia; Inoue, Miho; Sakaguchi, Sachi; Tanaka, Toshihiro; Fujii, Hisaki; Ogawa, Mina; Ingram, Ryoko; Kamiya, Taro; Karande, Smita; Ghayoori, Sholeh; Silva, Mariana; Willing, Stephanie; Vaillancourt, Régis; Johnston, Donna; Mankoo, Herpreet; Wong, Elaine; Wilson, Brenda; O'Connor, Lauren; Hui, Caleb; Yuen, Cindy; Bussières, Jean-Francois; Lebel, Denis; Barret, Pierre; Clauson, Aurélie; Courbon, Eve; Cerruti, Léna; Jabado, Nada; Santo, Anelise Espirito; Nagy, Martine; Murray, Margaret; Boliver, Darlene; Tiller, Marilyn; Osborne, Carol-Anne; Goodyear, Lisa; Bowes, Lynette; Kean, Norma; Hand, Jack

    2015-01-01

    Anthracyclines are used in over 50% of childhood cancer treatment protocols, but their clinical usefulness is limited by anthracycline-induced cardiotoxicity (ACT) manifesting as asymptomatic cardiac dysfunction and congestive heart failure in up to 57% and 16% of patients, respectively. Candidate

  12. Quantum dot nanoprobe-based quantitative analysis for prostate cancer (Conference Presentation)

    Science.gov (United States)

    Kang, Benedict J.; Jang, Gun Hyuk; Park, Sungwook; Lee, Kwan Hyi

    2016-09-01

    Prostate cancer causes one of the leading cancer-related deaths among the Caucasian adult males in Europe and the United State of America. However, it has a high recovery rate indicating when a proper treatment is delivered to a patient. There are cases of over- or under-treatments which exacerbate the disease states indicating the importance of proper therapeutic approach depending on stage of the disease. Recognition of the unmet needs has raised a need for stratification of the disease. There have been attempts to stratify based on biomarker expression patterns in the course of disease progression. To closely observe the biomarker expression patterns, we propose the use of quantitative imaging method by using fabricated quantum dot-based nanoprobe to quantify biomarker expression on the surface of prostate cancer cells. To characterize the cell line and analyze the biomarker levels, cluster of differentiation 44 (CD 44), prostate specific membrane antigen (PSMA), and epithelial cell adhesion molecule (EpCAM) are used. Each selected biomarker per cell line has been quantified from which we established a signature of biomarkers of a prostate cancer cell line.

  13. Metastatic non-small-cell lung cancer: consensus on pathology and molecular tests, first-line, second-line, and third-line therapy: 1st ESMO Consensus Conference in Lung Cancer; Lugano 2010

    DEFF Research Database (Denmark)

    Felip, E; Gridelli, C; Baas, P

    2011-01-01

    The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21 and 22 May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics, medical oncology, surgical oncology and radiation oncology. Before the confer......The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21 and 22 May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics, medical oncology, surgical oncology and radiation oncology. Before......-line, and second-line/third-line therapy in metastatic NSCLC are reported in this article. The recommendations detailed here are based on an expert consensus after careful review of published data. All participants have approved this final update....

  14. Pancreatic adenocarcinoma upregulated factor (PAUF) confers resistance to pancreatic cancer cells against oncolytic parvovirus H-1 infection through IFNA receptor-mediated signaling

    Energy Technology Data Exchange (ETDEWEB)

    Kaowinn, Sirichat; Cho, Il-Rae; Moon, Jeong; Jun, Seung Won; Kim, Chang Seok [BK21+, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-736 (Korea, Republic of); Kang, Ho Young [Department of Microbiology, Pusan National University, Busan 609-736 (Korea, Republic of); Kim, Manbok [Department of Medical Science, Dankook University College of Medicine, Cheonan 330-714 (Korea, Republic of); Koh, Sang Seok [Department of Biological Sciences, Dong-A University, Busan 604-714 (Korea, Republic of); Chung, Young-Hwa, E-mail: younghc@pusan.ac.kr [BK21+, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-736 (Korea, Republic of)

    2015-04-03

    Pancreatic adenocarcinoma upregulated factor (PAUF), a novel oncogene, plays a crucial role in the development of pancreatic cancer, including its metastasis and proliferation. Therefore, PAUF-expressing pancreatic cancer cells could be important targets for oncolytic virus-mediated treatment. Panc-1 cells expressing PAUF (Panc-PAUF) showed relative resistance to parvovirus H-1 infection compared with Panc-1 cells expressing an empty vector (Panc-Vec). Of interest, expression of type I IFN-α receptor (IFNAR) was higher in Panc-PAUF cells than in Panc-Vec cells. Increased expression of IFNAR in turn increased the activation of Stat1 and Tyk2 in Panc-PAUF cells compared with that in Panc-Vec cells. Suppression of Tyk2 and Stat1, which are important downstream molecules for IFN-α signaling, sensitized pancreatic cancer cells to parvovirus H-1-mediated apoptosis. Further, constitutive suppression of PAUF sensitized Bxpc3 pancreatic cancer cells to parvovirus H-1 infection. Taken together, these results suggested that PAUF conferred resistance to pancreatic cancer cells against oncolytic parvovirus H-1 infection through IFNAR-mediated signaling. - Highlights: • PAUF confers resistance against oncolytic parvovirus H-1 infection. • PAUF enhances the expression of IFNAR in Panc-1 cells. • Increased activation of Tyk2 or Stat1 by PAUF provides resistance to parvovirus H-1-mediated apoptosis. • Constitutive inhibition of PAUF enhances parvovirus H-1-mediated oncolysis of Bxpc3 pancreatic cancer cells.

  15. Nanoscale metal-organic frameworks for photodynamic therapy and cancer immunotherapy (Conference Presentation)

    Science.gov (United States)

    Lin, Wenbin

    2017-02-01

    Photodynamic therapy (PDT) is an effective anticancer procedure that relies on tumor localization of a photosensitizer followed by light activation to generate cytotoxic reactive oxygen species. We recently reported the rational design of a Hf-porphyrin nanoscale metal-organic framework, DBP-UiO, as an exceptionally effective photosensitizer for PDT of resistant head and neck cancer. DBP-UiO efficiently generates singlet oxygen owing to site isolation of porphyrin ligands, enhanced intersystem crossing by heavy Hf centers, and facile singlet oxygen diffusion through porous DBP-UiO nanoplates. Consequently, DBP-UiO displayed greatly enhanced PDT efficacy both in vitro and in vivo, leading to complete tumor eradication in half of the mice receiving a single DBP-UiO dose and a single light exposure. The photophysical properties of DBP-UiO are however not optimum with the lowest energy absorption at 634 nm and a relatively small extinction coefficient of 2200 M-1·cm-1. We recently designed a chlorin-based NMOF, DBC-UiO, with much improved photophysical properties and PDT efficacy in two colon cancer mouse models. Reduction of the DBP ligands in DBP-UiO to the DBC ligands in DBC-UiO led to a 13 nm red-shift and an 11-fold extinction coefficient increase of the lowest energy Q-band. While inheriting the crystallinity, stability, porosity, and nanoplate morphology of DBP-UiO, DBC-UiO sensitizes more efficient singlet oxygen generation and exhibits much enhanced photodynamic therapy (PDT) efficacy on two colon cancer mouse models as a result of its improved photophysical properties. Both apoptosis and immunogenic cell death contributed to cancer cell-killing in DBC-UiO induced PDT. Our work has thus demonstrated that NMOFs represent a new class of highly potent PDT agents and hold great promise in treating resistant cancers in the clinic.

  16. Visualization and tissue classification of human breast cancer images using ultrahigh-resolution OCT (Conference Presentation)

    Science.gov (United States)

    Yao, Xinwen; Gan, Yu; Chang, Ernest W.; Hibshoosh, Hanina; Feldman, Sheldon; Hendon, Christine P.

    2017-02-01

    We employed a home-built ultrahigh resolution (UHR) OCT system at 800nm to image human breast cancer sample ex vivo. The system has an axial resolution of 2.72µm and a lateral resolution of 5.52µm with an extended imaging range of 1.78mm. Over 900 UHR OCT volumes were generated on specimens from 23 breast cancer cases. With better spatial resolution, detailed structures in the breast tissue were better defined. Different types of breast cancer as well as healthy breast tissue can be well delineated from the UHR OCT images. To quantitatively evaluate the advantages of UHR OCT imaging of breast cancer, features derived from OCT intensity images were used as inputs to a machine learning model, the relevance vector machine. A trained machine learning model was employed to evaluate the performance of tissue classification based on UHR OCT images for differentiating tissue types in the breast samples, including adipose tissue, healthy stroma and cancerous region. For adipose tissue, grid-based local features were extracted from OCT intensity data, including standard deviation, entropy, and homogeneity. We showed that it was possible to enhance the classification performance on distinguishing fat tissue from non-fat tissue by using the UHR images when compared with the results based on OCT images from a commercial 1300 nm OCT system. For invasive ductal carcinoma (IDC) and normal stroma differentiation, the classification was based on frame-based features that portray signal penetration depth and tissue reflectivity. The confusing matrix indicated a sensitivity of 97.5% and a sensitivity of 77.8%.

  17. Label free aggressive prostate cancer identification with ultraviolet photoacoustic spectral analysis (Conference Presentation)

    Science.gov (United States)

    Xu, Guan; Davis, Mandy A.; Siddiqui, Javed; Chao, Wan-yu; Tomlins, Scott A.; Wei, John T.; Wang, Xueding

    2017-03-01

    Prostate cancer (PCa) is the most commonly diagnosed cancer in American men for the past decades. PCa has a relatively low progression rate but the 5 year survival rate decreases dramatically once the cancer has metastasized. Differentiating aggressive from indolent PCa is critical for improving PCa patient outcomes and preventing metastasis and death. Prostate biopsy is the standard procedure for evaluating the presence and aggressiveness of PCa. The microarchitecture of the biopsied tissues visualized by histology process is evaluated by pathologists and assigned a Gleason score as a quantification of the aggressiveness. In our previous study, we have shown that photoacoustic spectral analysis (PASA) is capable of quantifying the Gleason scores of the H&E stained human prostate tissues. In this study, we attempt to assess the Gleason scores without any staining by taking advantage of the strong optical absorption of nucleic acid at ultraviolet wavelengths. PA signals were generated by wide field illumination at 266 nm and received by a hydrophone with a bandwidth of 0-20 MHz. DU145 prostate cancer cells at the concentrations of 0.8, 0.4, 0.05, 0.025 and 0.0125 million per cm3 simulating those in cancerous and normal tissues were first attempted. The measurements were repeated for 10 times at each concentration. A correlation of 0.86 was observed between the PA signal intensities and the cell concentrations. Human PCa tissues with Gleason score 6, 7 and 8 and normal tissues were assessed. With 11 samples, a correlation of 0.89 was found between the Gleason scores and PASA slopes.

  18. miR-199a-5p confers tumor-suppressive role in triple-negative breast cancer.

    Science.gov (United States)

    Chen, Jiawei; Shin, Vivian Y; Siu, Man T; Ho, John C W; Cheuk, Isabella; Kwong, Ava

    2016-11-14

    Triple-negative breast cancer (TNBC) remains a poor prognostic factor for breast cancer since no effective targeted therapy is readily available. Our previous studies confirmed miR-199a-5p is a TNBC-specific circulating biomarker, however, its functional roles in breast cancer is largely unknown. Thus, we investigated the functional implication of miR-199a-5p in TNBC and its potential underlying mechanisms. MTT assay was performed to investigate the cell proliferation after transient transfection of miR-199a-5p in MDA-MB-231 cell line, followed by cell cycle analysis. Transwell invasion assay and wound healing assay were used to study the invasion and migration ability respectively. To further investigate the stemness-related characteristics of miR-199a-5p in breast cancer cells, single-cell clonogenic assay and aldehyde dehydrogenase (ALDH) assay were performed. 32 normal and 100 breast cancer patients' plasma were recruited to identify the potential circulating markers by qPCR. Cell proliferation assay revealed significant inhibition after miR-199a-5p ectopic expression (p breast cancer plasma especially in TNBC (p = 0.0248). PIK3CD was identified as a potential downstream target of miR-199a-5p. Taken together, we unraveled, for the first time, the tumor-suppressive role of miR-199a-5p in TNBC, which attributed to EMT and cancer stemness properties, providing a novel therapeutic options towards this aggressive disease.

  19. Epigenetic mechanisms of breast cancer: an update of the current knowledge.

    Science.gov (United States)

    Karsli-Ceppioglu, Seher; Dagdemir, Aslihan; Judes, Gaëlle; Ngollo, Marjolaine; Penault-Llorca, Frédérique; Pajon, Amaury; Bignon, Yves-Jean; Bernard-Gallon, Dominique

    2014-01-01

    Epigenetic alterations are heritable changes in gene expression that occur without causing any change in DNA sequence. They are important key factors for cancer development and prognosis. Breast cancer is induced by the accumulation of altered gene regulation. Besides genetic mutations, epigenetics mechanisms have an important role in breast cancer tumorigenesis. Investigations related with aberrant epigenetic regulations in breast cancer focus on initiating molecular mechanisms in cancer development, identification of new biomarkers to predict breast cancer aggressiveness and the potential of epigenetic therapy. In this review, we will summarize the recent knowledge about the role of epigenetic alterations related with DNA methylation and histone modification in breast cancer. In addition, altered regulation of breast cancer specific genes and the potential of epigenetic therapy will be discussed according to epigenetic mechanisms.

  20. The gut microbiome and liver cancer: mechanisms and clinical translation.

    Science.gov (United States)

    Yu, Le-Xing; Schwabe, Robert F

    2017-09-01

    Hepatocellular carcinoma (HCC) is the third leading cause of worldwide cancer mortality. HCC almost exclusively develops in patients with chronic liver disease, driven by a vicious cycle of liver injury, inflammation and regeneration that typically spans decades. Increasing evidence points towards a key role of the bacterial microbiome in promoting the progression of liver disease and the development of HCC. Here, we will review mechanisms by which the gut microbiota promotes hepatocarcinogenesis, focusing on the leaky gut, bacterial dysbiosis, microbe-associated molecular patterns and bacterial metabolites as key pathways that drive cancer-promoting liver inflammation, fibrosis and genotoxicity. On the basis of accumulating evidence from preclinical studies, we propose the intestinal-microbiota-liver axis as a promising target for the simultaneous prevention of chronic liver disease progression and HCC development in patients with advanced liver disease. We will review in detail therapeutic modalities and discuss clinical settings in which targeting the gut-microbiota-liver axis for the prevention of disease progression and HCC development seems promising.

  1. [Advance in studies on anti-cancer activity and mechanism of flavonoids].

    Science.gov (United States)

    Yang, Nan; Jia, Xiao-bin; Zhang, Zhen-hai; Sun, E; Yan, Hong-mei

    2015-02-01

    Flavonoids are natural products that are ubiquitous in the natural world, with wide physiological activities and low toxic and side effects. In recent years, their anti-tumor effect has caused widespread concern and studies. According to the findings, flavonoids have prominent effects in preventing and treating lung cancer, breast cancer, colon cancer, prostate cancer, liver cancer, leukemia, ovarian cancer, gastric cancer and so on. Their anti-tumor mechanisms mainly include anti-oxidation, anti-free radical, induction of apoptosis of cancer cells, impact on cell cycle, immune regulation, inhibition of tumor angiogenesis, inhibition of COX-2, inhibition of telomerase activity and so on. This article focuses on the advance in domestic and foreign studies on anti-cancer activity and mechanism of flavonoids, in order to provide theoretical basis and research ideas for the further development and clinical application of flavonoids.

  2. Mechanisms Linking Obesity and Thyroid Cancer Development and Progression in Mouse Models.

    Science.gov (United States)

    Kim, Won Gu; Cheng, Sheue-Yann

    2018-01-19

    Recent compelling epidemiological studies indicate a strong association of obesity with thyroid cancer. Obesity has been shown to promote thyroid cancer progression and exacerbate poor outcome in thyroid cancer patients. However, the molecular mechanisms by which obesity increases thyroid cancer risk and facilitates cancer progression are not completely understood. Obesity induces complex pathological changes including hyperglycemia, hyperinsulinemia, hyperlipidemia, oxidative stress, adipokines, and inflammatory responses. These changes can affect the development and progression of cancer through highly complex interactions in vivo. The deleterious effect of obesity may differ according to the different cancer types. In view of the increased incidence of thyroid cancer in parallel with the widespread occurrence of obesity in the past decades, it is imperative to clarify how obesity affects thyroid carcinogenesis. This review focuses on molecular mechanisms by which obesity aggravates thyroid carcinogenesis as elucidated by mouse models of thyroid cancer.

  3. Adapting biomodulatory strategies for treatment in new contexts: pancreatic and oral cancers (Conference Presentation)

    Science.gov (United States)

    Anbil, Sriram R.; Rizvi, Imran; Khan, Amjad P.; Celli, Jonathan P.; Maytin, Edward V.; Hasan, Tayyaba

    2016-03-01

    Biomodulation of cancer cell metabolism represents a promising approach to overcome tumor heterogeneity and poor selectivity, which contribute significantly to treatment resistance. To date, several studies have demonstrated that modulation of cell metabolism including the heme synthesis pathway serves as an elegant approach to improve the efficacy of aminolevulinic acid (ALA) based photodynamic therapy (PDT). However, the ability of biomodulation-enhanced PDT to improve outcomes in low resource settings and to address challenges in treating lethal tumors with exogenous photosensitizers remains underexplored. The ability of vitamin D or methotrexate to enhance PDT efficacy in a carcinogen-induced hamster cheek pouch model of oral squamous cell carcinoma and in 3D cell-based models for pancreatic ductal adenocarcinoma is evaluated. Challenges associated with adapting PDT regimens to low resource settings, understanding the effects of biomodulatory agents on the metabolism of cancer cells, and the differential effects of biomodulatory agents on tumor and stromal cells will be discussed.

  4. Partial wave spectroscopic microscopy can predict prostate cancer progression and mitigate over-treatment (Conference Presentation)

    Science.gov (United States)

    Zhang, Di; Graff, Taylor; Crawford, Susan; Subramanian, Hariharan; Thompson, Sebastian; Derbas, Justin R.; Lyengar, Radha; Roy, Hemant K.; Brendler, Charles B.; Backman, Vadim

    2016-02-01

    Prostate Cancer (PC) is the second leading cause of cancer deaths in American men. While prostate specific antigen (PSA) test has been widely used for screening PC, >60% of the PSA detected cancers are indolent, leading to unnecessary clinical interventions. An alternative approach, active surveillance (AS), also suffer from high expense, discomfort and complications associated with repeat biopsies (every 1-3 years), limiting its acceptance. Hence, a technique that can differentiate indolent from aggressive PC would attenuate the harms from over-treatment. Combining microscopy with spectroscopy, our group has developed partial wave spectroscopic (PWS) microscopy, which can quantify intracellular nanoscale organizations (e.g. chromatin structures) that are not accessible by conventional microscopy. PWS microscopy has previously been shown to predict the risk of cancer in seven different organs (N ~ 800 patients). Herein we use PWS measurement of label-free histologically-normal prostatic epithelium to distinguish indolent from aggressive PC and predict PC risk. Our results from 38 men with low-grade PC indicated that there is a significant increase in progressors compared to non-progressors (p=0.002, effect size=110%, AUC=0.80, sensitivity=88% and specificity=72%), while the baseline clinical characteristics were not significantly different. We further improved the diagnostic power by performing nuclei-specific measurements using an automated system that separates in real-time the cell nuclei from the remaining prostate epithelium. In the long term, we envision that the PWS based prognostication can be coupled with AS without any change to the current procedure to mitigate the harms caused by over-treatment.

  5. Molecular Mechanisms Linking Exercise to Cancer Prevention and Treatment

    DEFF Research Database (Denmark)

    Hojman, Pernille; Gehl, Julie; Christensen, Jesper F.

    2018-01-01

    The benefits of exercise training for cancer patients are becoming increasingly evident. Physical exercise has been shown to reduce cancer incidence and inhibit tumor growth. Here we provide the status of the current molecular understanding of the effect of exercise on cancer. We propose...... that exercise has a role in controlling cancer progression through a direct effect on tumor-intrinsic factors, interplay with whole-body exercise effects, alleviation of cancer-related adverse events, and improvement of anti-cancer treatment efficacy. These findings have wide-ranging societal implications......, as this understanding may lead to changes in cancer treatment strategies. Hojman et al. discuss the role of exercise in controlling cancer progression through direct effects on tumor-intrinsic factors, interplay with whole-body exercise effects, alleviation of cancer-related adverse events, and improvement of cancer...

  6. DNA Repair Mechanisms in Cancer Development and Therapy

    Directory of Open Access Journals (Sweden)

    Alessandro eTorgovnick

    2015-04-01

    Full Text Available DNA damage has been long recognized as causal factor for cancer development. When erroneous DNA repair leads to mutations or chromosomal aberrations affecting oncogenes and tumor suppressor genes, cells undergo malignant transformation resulting in cancerous growth. Genetic defects can predispose to cancer: Mutations in distinct DNA repair systems elevate the susceptibility to various cancer types. However, DNA damage not only comprises a root cause for cancer development but also continues to provide an important avenue for chemo- and radiotherapy. Since the beginning of cancer therapy, genotoxic agents have been applied that trigger DNA damage checkpoints that halt the growth and trigger the apoptotic demise of cancer cells. We provide an overview about the involvement of DNA repair systems in cancer prevention and the classes of genotoxins that are commonly used for the treatment of cancer. A better understanding of the roles and interactions of the highly complex DNA repair machineries will lead to important improvements in cancer therapy.

  7. MUSME Conference

    CERN Document Server

    Martinez, Eusebio

    2015-01-01

    This volume contains the Proceedings of MUSME 2014, held at Huatulco in Oaxaca, Mexico, October 2014. Topics include analysis and synthesis of mechanisms; dynamics of multibody systems; design algorithms for mechatronic systems; simulation procedures and results; prototypes and their performance; robots and micromachines; experimental validations; theory of mechatronic simulation; mechatronic systems; and control of mechatronic systems. The MUSME symposium on Multibody Systems and Mechatronics was held under the auspices of IFToMM, the International Federation for Promotion of Mechanism and Machine Science, and FeIbIM, the Iberoamerican Federation of Mechanical Engineering. Since the first symposium in 2002, MUSME events have been characterised by the way they stimulate the integration between the various mechatronics and multibody systems dynamics disciplines, present a forum for facilitating contacts among researchers and students mainly in South American countries, and serve as a joint conference for the ...

  8. Body fatness as a cause of cancer: epidemiologic clues to biologic mechanisms.

    Science.gov (United States)

    Byers, Tim; Sedjo, Rebecca L

    2015-06-01

    Carrying excess body fat is a leading cause of cancer. Epidemiologic evidence gives strong clues about the mechanisms that link excess adiposity to risk for several cancer sites. For postmenopausal breast cancer and endometrial cancer, the hyper-estrogenic state that is induced by excess body fatness is the likely cause. For esophageal cancer and gallbladder cancer, chronic local inflammation induced by acid reflux and gallstones is the likely cause, and for liver cancer, local inflammation induced by hepatic fatty infiltration is the likely cause. However, for several other cancers known to be associated with excess adiposity, including cancers of the colon, pancreas, ovary, kidney, and prostate, specific causes are not known. Possible candidates include elevated systemic or local tissue inflammation induced by adiposity and effects of the elevated levels of leptin, insulin, IGFs, and depressed immune function that are seen with excess adiposity. There is growing evidence that intentional weight loss not only reduces circulating levels of cancer-associated factors but that it also reduces cancer incidence and recurrence. Better research is needed to understand the mechanisms that link excess body fat to cancer risk as well as to understand the amount of weight loss needed for substantial cancer risk reduction. Finally, as we develop better understanding of the mediators of the effects of excess body fatness on cancer risk, we should identify pharmacologic interventions that target those mediators so that they can be used to complement weight loss in order to reduce cancer risk. © 2015 Society for Endocrinology.

  9. Physical Activity and Gastrointestinal Cancers: Primary and Tertiary Preventive Effects and Possible Biological Mechanisms

    Directory of Open Access Journals (Sweden)

    Karen Steindorf

    2015-07-01

    Full Text Available Gastrointestinal cancers account for 37% of all cancer deaths worldwide, underlining the need to further investigate modifiable factors for gastrointestinal cancer risk and prognosis. This review summarizes the corresponding evidence for physical activity (PA, including, briefly, possible biological mechanisms. Despite high public health relevance, there is still a scarcity of studies, especially for tertiary prevention. Besides the convincing evidence of beneficial effects of PA on colon cancer risk, clear risk reduction for gastroesophageal cancer was identified, as well as weak indications for pancreatic cancer. Inverse associations were observed for liver cancer, yet based on few studies. Only for rectal cancer, PA appeared to be not associated with cancer risk. With regard to cancer-specific mortality of the general population, published data were rare but indicated suggestive evidence of protective effects for colon and liver cancer, and to a lesser extent for rectal and gastroesophageal cancer. Studies in cancer patients on cancer-specific and total mortality were published for colorectal cancer only, providing good evidence of inverse associations with post-diagnosis PA. Overall, evidence of associations of PA with gastrointestinal cancer risk and progression is promising but still limited. However, the already available knowledge further underlines the importance of PA to combat cancer.

  10. Meeting Report From the 2016 11th Biennial Ovarian Cancer Research Symposium: Mechanisms of Initiation and Progression of Ovarian Cancers.

    Science.gov (United States)

    Chien, Jeremy; Mehta, Geeta

    2017-11-01

    The aim of this study was to review the latest research advances on the mechanisms of initiation and progression of ovarian cancer. At the 11th Biennial Ovarian Cancer Research Symposium, which was held in Seattle, Washington in September 2016, leaders in ovarian cancer research convened to present and discuss current advances and future directions in ovarian cancer research. One session was dedicated to Mechanisms of Initiation and Progression of Ovarian Cancer, and included a keynote presentation from Dr Ronny Drapkin, MD (University of Pennsylvania), and an invited oral presentation from Laising Yen, PhD (Baylor College of Medicine). Nine additional oral presentations were selected from abstract submissions. Thirty-three abstracts were presented in poster format and were grouped into the categories of mechanisms of the genesis of genomic instability, tumor initiation, metastases of ovarian cancers, innate and acquired chemotherapy resistance, tumor progression, tumor-initiating cell and chemotherapy resistance, and immunomodulation. Eradication of ovarian cancers requires clear understanding of molecular mechanisms of ovarian cancer initiation and progression. These mechanisms will not only drive the precision of early detection, but also discovery of new therapies to target precursor lesions and more advanced stage disease.

  11. Fluorescence lifetime imaging of endogenous molecules in live mouse cancer models (Conference Presentation)

    Science.gov (United States)

    Svindrych, Zdenek; Wang, Tianxiong; Hu, Song; Periasamy, Ammasi

    2017-02-01

    NADH and FAD are important endogenous fluorescent coenzymes participating in key enzymatic reactions of cellular metabolism. While fluorescence intensities of NADH and FAD have been used to determine the redox state of cells and tissues, this simple approach breaks down in the case of deep-tissue intravital imaging due to depth- and wavelength-dependent light absorption and scattering. To circumvent this limitation, our research focuses on fluorescence lifetimes of two-photon excited NADH and FAD emission to study the metabolic state of live tissues. In our custom-built scanning microscope we combine tunable femtosecond Ti:sapphire laser (operating at 740 nm for NADH excitation and 890 nm for FAD excitation), two GaAsP hybrid detectors for registering individual fluorescence photons and two Becker and Hickl time correlator boards for high precision lifetime measurements. Together with our rigorous FLIM analysis approach (including image segmentation, multi-exponential decay fitting and detailed statistical analysis) we are able to detect metabolic changes in cancer xenografts (human pancreatic cancer MPanc96 cells injected subcutaneously into the ear of an immunodeficient nude mouse), relative to surrounding healthy tissue. Advantageously, with the same instrumentation we can also take high-resolution and high-contrast images of second harmonic signal (SHG) originating from collagen fibers of both the healthy skin and the growing tumor. The combination of metabolic measurements (NADH and FAD lifetime) and morphological information (collagen SHG) allows us to follow the tumor growth in live mouse model and the changes in tumor microenvironment.

  12. Optical metabolic imaging measures early drug response in an allograft murine breast cancer model (Conference Presentation)

    Science.gov (United States)

    Sharick, Joe T.; Cook, Rebecca S.; Skala, Melissa C.

    2017-02-01

    Previous work has shown that cellular-level Optical Metabolic Imaging (OMI) of organoids derived from human breast cancer cell-line xenografts accurately and rapidly predicts in vivo response to therapy. To validate OMI as a predictive measure of treatment response in an immune-competent model, we used the polyomavirus middle-T (PyVmT) transgenic mouse breast cancer model. The PyVmT model includes intra-tumoral heterogeneity and a complex tumor microenvironment that can influence treatment responses. Three-dimensional organoids generated from primary PyVmT tumor tissue were treated with a chemotherapy (paclitaxel) and a PI3K inhibitor (XL147), each alone or in combination. Cellular subpopulations of response were measured using the OMI Index, a composite endpoint of metabolic response comprised of the optical redox ratio (ratio of the fluorescence intensities of metabolic co-enzymes NAD(P)H to FAD) as well as the fluorescence lifetimes of NAD(P)H and FAD. Combination treatment significantly decreased the OMI Index of PyVmT tumor organoids (padaptive immunity. Thus, this method is promising for use in humans to predict long-term treatment responses accurately and rapidly, and could aid in clinical treatment planning.

  13. Pluripotent Stem Cell Protein Sox2 Confers Sensitivity to LSD1 Inhibition in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Xiaoming Zhang

    2013-10-01

    Full Text Available Gene amplification of Sox2 at 3q26.33 is a common event in squamous cell carcinomas (SCCs of the lung and esophagus, as well as several other cancers. Here, we show that the expression of LSD1/KDM1 histone demethylase is significantly elevated in Sox2-expressing lung SCCs. LSD1-specific inhibitors selectively impair the growth of Sox2-expressing lung SCCs, but not that of Sox2-negative cells. Sox2 expression is associated with sensitivity to LSD1 inhibition in lung, breast, ovarian, and other carcinoma cells. Inactivation of LSD1 reduces Sox2 expression, promotes G1 cell-cycle arrest, and induces genes for differentiation by selectively modulating the methylation states of histone H3 at lysines 4 (H3K4 and 9 (H3K9. Reduction of Sox2 further suppresses Sox2-dependent lineage-survival oncogenic potential, elevates trimethylation of histone H3 at lysine 27 (H3K27 and enhances growth arrest and cellular differentiation. Our studies suggest that LSD1 serves as a selective epigenetic target for therapy in Sox2-expressing cancers.

  14. Epigenetics and genetics in endometrial cancer: new carcinogenic mechanisms and relationship with clinical practice.

    Science.gov (United States)

    Banno, Kouji; Kisu, Iori; Yanokura, Megumi; Masuda, Kenta; Ueki, Arisa; Kobayashi, Yusuke; Susumu, Nobuyuki; Aoki, Daisuke

    2012-04-01

    Endometrial cancer is the seventh most common cancer worldwide among females. An increased incidence and a younger age of patients are also predicted to occur, and therefore elucidation of the pathological mechanisms is important. However, several aspects of the mechanism of carcinogenesis in the endometrium remain unclear. Associations with genetic mutations of cancer-related genes have been shown, but these do not provide a complete explanation. Therefore, epigenetic mechanisms have been examined. Silencing of genes by DNA hypermethylation, hereditary epimutation of DNA mismatch repair genes and regulation of gene expression by miRNAs may underlie carcinogenesis in endometrial cancer. New therapies include targeting epigenetic changes using histone deacetylase inhibitors. Some cases of endometrial cancer may also be hereditary. Thus, patients with Lynch syndrome which is a hereditary disease, have a higher risk for developing endometrial cancer than the general population. Identification of such disease-related genes may contribute to early detection and prevention of endometrial cancer.

  15. Comparative Proteomic Analysis of Anti-Cancer Mechanism by Periplocin Treatment in Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Zejun Lu

    2014-03-01

    Full Text Available Background: Periplocin is used for treatment of rheumatoid arthritis, reinforcement of bones and tendons, palpitations or shortness of breath and lower extremity edema in traditional medicine. Our previous findings suggested that periplocin could inhibit the growth of lung cancer both in vitro and in vivo. But the biological processes and molecular pathways by which periplocin induces these beneficial effects remain largely undefined. Methods: To explore the molecular mechanisms of periplocin involved in anti-cancer activity, in the present study the protein profile changes of human lung cancer cell lines A549 in response to periplocin treatment were investigated using the proteomics approaches (2-DE combined with MS/MS. Western blot was employed to verify the changed proteins. Interactions between changed proteins were analyzed by STRING. Results: 29 down-regulated protein species named GTP-binding nuclear protein Ran (RAN, Rho GDP-dissociation inhibitor 1 (ARHGDIA, eukaryotic translation initiation factor 5A-1 (EIF5A and Profilin-1(PFN1, and 10 up-regulated protein species named Heat shock cognate 71 kDa protein (HSPA8,10 kDa heat shock protein (HSPE1, and Cofilin-1(CFL-1 were identified. Among them, GTP-binding nuclear protein Ran (RAN and Rho GDP-dissociation inhibitor 1 (ARHGDIA were the most significantly changed (over tenfold. The proteasome subunit beta type-6 (PSMB6, ATP synthase ecto-α-subunit (ATP5A1, Aldehyde dehydrogenase 1 (ALDH1 and EIF5A were verified by immunoblot assays to be dramatically down-regulated. By STRING bioinformatics analysis revealing interactions and signaling networks it became apparent that the proteins changed they are primarily involved in transcription and proteolysis. Conclusion: Periplocin inhibited growth of lung cancer by down-regulating proteins, such as ATP5A1, EIF5A, ALDH1 and PSMB6. These findings may improve our understanding of the molecular mechanisms underlying the anti-cancer effects of

  16. Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1.

    Science.gov (United States)

    Au Yeung, Chi Lam; Co, Ngai-Na; Tsuruga, Tetsushi; Yeung, Tsz-Lun; Kwan, Suet-Ying; Leung, Cecilia S; Li, Yong; Lu, Edward S; Kwan, Kenny; Wong, Kwong-Kwok; Schmandt, Rosemarie; Lu, Karen H; Mok, Samuel C

    2016-03-29

    Advanced ovarian cancer usually spreads to the visceral adipose tissue of the omentum. However, the omental stromal cell-derived molecular determinants that modulate ovarian cancer growth have not been characterized. Here, using next-generation sequencing technology, we identify significantly higher levels of microRNA-21 (miR21) isomiRNAs in exosomes and tissue lysates isolated from cancer-associated adipocytes (CAAs) and fibroblasts (CAFs) than in those from ovarian cancer cells. Functional studies reveal that miR21 is transferred from CAAs or CAFs to the cancer cells, where it suppresses ovarian cancer apoptosis and confers chemoresistance by binding to its direct novel target, APAF1. These data suggest that the malignant phenotype of metastatic ovarian cancer cells can be altered by miR21 delivered by exosomes derived from neighbouring stromal cells in the omental tumour microenvironment, and that inhibiting the transfer of stromal-derived miR21 is an alternative modality in the treatment of metastatic and recurrent ovarian cancer.

  17. A lipid-based nano-regulator for cancer immunotherapy (Conference Presentation)

    Science.gov (United States)

    Qian, Yuan; Qiao, Sha; Zhang, Zhihong

    2017-02-01

    In the application of nanotechnology in cancer immunotherapy, antigen presenting cells (APCs, dendritic cells and macrophages) are preferable target due to their endocytic capacity and suppressed phenotype. Recently, we developed a lipid-based core-shell nanocarrier, which is stabilized by changeable fusion peptides and possesses a sub-30 diameter. With the different peptides, the nanoparticles (NPs) could either target to dendritic cells (DCs) in lymph nodes (LNs) or tumor associated macrophages (TAMs) in tumor environment. After subcutaneous injection, the NPs could targeted deliver the encapsulated antigen peptides (APs) and adjuvants (CpG-ODN) to dendritic cells in LNs, and lead to the antigen presenting and activation of cytotoxic T lymphocytes against tumor. In other case, after systemic administration, the immune regulatory molecules were carried by NPs and targeting delivered to specific immunocytes in tumor microenvironment resulting in the immunosuppressive state broken and tumor growth inhibition.

  18. EFFECT OF MINDFULLNESS MEDITATION ON STRESS LEVEL AND COPING MECHANISM IN CANCER PATIENTS

    OpenAIRE

    Wahyu Werdani, Yesiana Dwi

    2017-01-01

    Cancer patients have a tendency to experience mental disorders, because the physical changes cause frustration and despair. It impacts on anxiety, depression, and social isolation. The purpose of this study was to analyze the influence of mindfullness meditation to stress levels and coping mechanisms in cancer patients. This study used pre experimental approach with one group pre-test post-test design. Samples were 32 cancer patients with composmentis condition in Indonesian Cancer Foundation...

  19. Synergistic interactions among flavonoids and acetogenins in Graviola (Annona muricata) leaves confer protection against prostate cancer.

    Science.gov (United States)

    Yang, Chunhua; Gundala, Sushma Reddy; Mukkavilli, Rao; Vangala, Subrahmanyam; Reid, Michelle D; Aneja, Ritu

    2015-06-01

    Phytochemical complexity of plant extracts may offer health-promoting benefits including chemotherapeutic and chemopreventive effects. Isolation of 'most-active fraction' or single constituents from whole extracts may not only compromise the therapeutic efficacy but also render toxicity, thus emphasizing the importance of preserving the natural composition of whole extracts. The leaves of Annona muricata, commonly known as Graviola, are known to be rich in flavonoids, isoquinoline alkaloids and annonaceous acetogenins. Here, we demonstrate phytochemical synergy among the constituents of Graviola leaf extract (GLE) compared to its flavonoid-enriched (FEF) and acetogenin-enriched (AEF) fractions. Comparative quantitation of flavonoids revealed enrichment of rutin (~7-fold) and quercetin-3-glucoside (Q-3-G, ~3-fold) in FEF compared to GLE. In vivo pharmacokinetics and in vitro absorption kinetics of flavonoids revealed enhanced bioavailability of rutin in FEF compared to GLE. However, GLE was more effective in inhibiting in vitro prostate cancer proliferation, viability and clonogenic capacity compared to FEF. Oral administration of 100mg/kg bw GLE showed ~1.2-fold higher tumor growth-inhibitory efficacy than FEF in human prostate tumor xenografts although the concentration of rutin and Q-3-G was more in FEF. Contrarily, AEF, despite its superior in vitro and in vivo efficacy, resulted in death of the mice due to toxicity. Our data indicate that despite lower absorption and bioavailability of rutin, maximum efficacy was achieved in the case of GLE, which also comprises of other phytochemical groups including acetogenins that make up its natural complex environment. Hence, our study emphasizes on evaluating the nature of interactions among Graviola leaf phytochemcials for developing favorable dose regimen for prostate cancer management to achieve optimal therapeutic benefits. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions

  20. Dual-modality smartphone endoscope for cervical pre-cancer detection (Conference Presentation)

    Science.gov (United States)

    Hong, Xiangqian; Yu, Bing

    2017-02-01

    Early detection is the key to the prevention of cervical cancer. There is an urgent need for a portable, affordable, and easy-to-use device for cervical pre-cancer detection, especially in low-resource settings. We have developed a dual-modality fiber-optic endoscope system (SmartME) that integrates high-resolution fluorescence imaging (FLI) and quantitative diffuse reflectance spectroscopy (DRS) onto a smartphone platform. The SmartME consists of a smartphone, a miniature fiber-optic endoscope, a phone attachment containing imaging optics, and a smartphone application (app). FLI is obtained by painting the tissue with a contrast agent (e.g., proflavine), illuminating the tissue and collecting its fluorescence images through an imaging bundle that is coupled to the phone camera. DRS is achieved by using a white LED, attaching additional source and detection fibers to the imaging bundle, and converting the phone camera into a spectrometer. The app collects images/spectra and transmits them to a remote server for analysis to extract the tissue parameters, including nuclear-to-cytoplasm ratio (calculated from FLI), concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) as well as scattering (measured by DRS). These parameters can be used to detect cervical dysplasia. Our preliminary studies have demonstrated that the SmartME can clearly visualize the nuclei in living cells and in vivo biological samples, with a high spatial resolution of 3.1μm. The device can also measure tissue absorption and scattering properties with comparable accuracy to those of a benchtop DRS system. The SmartME has great potential to provide a compact, affordable, and `smart' solution for early detection of neoplastic changes in cervix.

  1. ISOCT study of collagen crosslinking of collagen in cancer models (Conference Presentation)

    Science.gov (United States)

    Spicer, Graham; Young, Scott T.; Yi, Ji; Shea, Lonnie D.; Backman, Vadim

    2016-03-01

    The role of extracellular matrix modification and signaling in cancer progression is an increasingly recognized avenue for the progression of the disease. Previous study of field effect carcinogenesis with Inverse Spectroscopic Optical Coherence Tomography (ISOCT) has revealed pronounced changes in the nanoscale-sensitive mass fractal dimension D measured from field effect tissue when compared to healthy tissue. However, the origin of this difference in tissue ultrastructure in field effect carcinogenesis has remained poorly understood. Here, we present findings supporting the idea that enzymatic crosslinking of the extracellular matrix is an effect that presents at the earliest stages of carcinogenesis. We use a model of collagen gel with crosslinking induced by lysyl oxidase (LOXL4) to recapitulate the difference in D previously reported from healthy and cancerous tissue biopsies. Furthermore, STORM imaging of this collagen gel model verifies the morphologic effects of enzymatic crosslinking at length scales as small as 40 nm, close to the previously reported lower length scale sensitivity threshold of 35 nm for ISOCT. Analysis of the autocorrelation function from STORM images of collagen gels and subsequent fitting to the Whittle-Matérn correlation function shows a similar effect of LOXL4 on D from collagen measured with ISOCT and STORM. We extend this to mass spectrometric study of tissue to directly measure concentrations of collagen crosslink residues. The validation of ISOCT as a viable tool for non-invasive rapid quantification of collagen ultrastructure lends it to study other physiological phenomena involving ECM restructuring such as atherosclerotic plaque screening or cervical ripening during pregnancy.

  2. Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance

    DEFF Research Database (Denmark)

    Alvero, Ayesha B; Chen, Rui; Fu, Han-Hsuan

    2009-01-01

    of the tumor and may be the primary source of recurrence. We describe the characterization of human ovarian cancer stem cells (OCSCs). These cells have a distinctive genetic profile that confers them with the capacity to recapitulate the original tumor, proliferate with chemotherapy, and promote recurrence...... to form spheroids in suspension, and the ability to recapitulate in vivo the original tumor. Chemotherapy eliminates the bulk of the tumor but it leaves a core of cancer cells with high capacity for repair and renewal. The molecular properties identified in these cells may explain some of the unique......A major burden in the treatment of ovarian cancer is the high percentage of recurrence and chemoresistance. Cancer stem cells (CSCs) provide a reservoir of cells that can self-renew, can maintain the tumor by generating differentiated cells [non-stem cells (non-CSCs)] which make up the bulk...

  3. Risk factors for pancreatic cancer: underlying mechanisms and potential targets

    OpenAIRE

    Thomas eKolodecik; Christine eShugrue; Munish eAshat; Edwin Charles Thrower

    2014-01-01

    Purpose of the review:Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer.Recent Findings:Intracellular activation of both pancreatic enzymes and the transcri...

  4. Risk factors for pancreatic cancer: underlying mechanisms and potential targets

    OpenAIRE

    Kolodecik, Thomas; Shugrue, Christine; Ashat, Munish; Thrower, Edwin C.

    2014-01-01

    Purpose of the review: Pancreatic cancer is extremely aggressive, forming highly chemo-resistant tumors, and has one of the worst prognoses. The evolution of this cancer is multi-factorial. Repeated acute pancreatic injury and inflammation are important contributing factors in the development of pancreatic cancer. This article attempts to understand the common pathways linking pancreatitis to pancreatic cancer. Recent findings: Intracellular activation of both pancreatic enzymes and the trans...

  5. Annexin II-Dependent Mechanism of Breast Cancer Progression

    Science.gov (United States)

    2010-11-01

    of Annexin-II in GI cancers: interaction with gastrins /progastrins. Cancer Lett. 252, 19–35. Stack, M.S., et al., 1999. Angiostatin inhibits...ytokine t hat c ontributes t o cancer is interleukin 6 (IL -6). Al ong w ith IL -4 and IL -10, IL-6 is highly expressed in hormone refractory prostate

  6. Stress and Coping Mechanisms Among Breast Cancer Patients and ...

    African Journals Online (AJOL)

    Sitwala

    the leading cause of cancer mortality, representing. 14.1%. In Zambia, it is second to cervical cancer and its incidence is steadily increasing. A diagnosis of cancer regardless of stage is a stressful event impacting on all facets of the patient's life and that of her family caregivers. To minimize the impact, adaptive coping ...

  7. Linc-RoR promotes MAPK/ERK signaling and confers estrogen-independent growth of breast cancer.

    Science.gov (United States)

    Peng, Wan-Xin; Huang, Jian-Guo; Yang, Liu; Gong, Ai-Hua; Mo, Yin-Yuan

    2017-10-17

    The conversion from estrogen-dependent to estrogen-independent state of ER+ breast cancer cells is the key step to promote resistance to endocrine therapies. Although the crucial role of MAPK/ERK signaling pathway in estrogen-independent breast cancer cell growth is well established, the underlying mechanism is not fully understood. In this study, we profiled lncRNA expression against a focused group of lncRNAs selected from lncRNA database. CRISPR/Cas9 was employed to knockout (KO) linc-RoR in MCF-7 cells, while rescue experiments were carried out to re-express linc-RoR in KO cells. Colony formation and MTT assays were used to examine the role of linc-RoR in estrogen-independent growth and tamoxifen resistance. Western blot and qRT-PCR were used to determine the change of protein and lncRNA levels, respectively. The expression of DUSP7 in clinical specimens was downloaded from Oncomine ( www.oncomine.org ) and the dataset from Kaplan-Meier Plotter ( http://kmplot.com ) was used to analyze the clinical outcomes in relation to DUSP7. We identified that linc-RoR functions as an onco-lncRNA to promote estrogen-independent growth of ER+ breast cancer. Under estrogen deprivation, linc-RoR causes the upregulation of phosphorylated MAPK/ERK pathway which in turn activates ER signaling. Knockout of linc-RoR abrogates estrogen deprivation-induced ERK activation as well as ER phosphorylation, whereas re-expression of linc-RoR restores all above phenotypes. Moreover, we show that the ERK-specific phosphatase Dual Specificity Phosphatase 7 (DUSP7), also known as MKP-X, is involved in linc-RoR KO-induced repression of MAPK/ERK signaling. Interestingly, linc-RoR KO increases the protein stability of DUSP7, resulting in repression of ERK phosphorylation. Clinical data analysis reveal that DUSP7 expression is lower in ER+ breast cancer samples than that in ER- breast cancer. Moreover, downregulation of DUSP7 expression is associated with poor patient survival. Taken together

  8. A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer.

    Science.gov (United States)

    Kiemeney, Lambertus A; Sulem, Patrick; Besenbacher, Soren; Vermeulen, Sita H; Sigurdsson, Asgeir; Thorleifsson, Gudmar; Gudbjartsson, Daniel F; Stacey, Simon N; Gudmundsson, Julius; Zanon, Carlo; Kostic, Jelena; Masson, Gisli; Bjarnason, Hjordis; Palsson, Stefan T; Skarphedinsson, Oskar B; Gudjonsson, Sigurjon A; Witjes, J Alfred; Grotenhuis, Anne J; Verhaegh, Gerald W; Bishop, D Timothy; Sak, Sei Chung; Choudhury, Ananya; Elliott, Faye; Barrett, Jennifer H; Hurst, Carolyn D; de Verdier, Petra J; Ryk, Charlotta; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Vineis, Paolo; Polidoro, Silvia; Guarrera, Simonetta; Sacerdote, Carlotta; Campagna, Marcello; Placidi, Donatella; Arici, Cecilia; Zeegers, Maurice P; Kellen, Eliane; Gutierrez, Berta Saez; Sanz-Velez, José I; Sanchez-Zalabardo, Manuel; Valdivia, Gabriel; Garcia-Prats, Maria D; Hengstler, Jan G; Blaszkewicz, Meinolf; Dietrich, Holger; Ophoff, Roel A; van den Berg, Leonard H; Alexiusdottir, Kristin; Kristjansson, Kristleifur; Geirsson, Gudmundur; Nikulasson, Sigfus; Petursdottir, Vigdis; Kong, Augustine; Thorgeirsson, Thorgeir; Mungan, N Aydin; Lindblom, Annika; van Es, Michael A; Porru, Stefano; Buntinx, Frank; Golka, Klaus; Mayordomo, José I; Kumar, Rajiv; Matullo, Giuseppe; Steineck, Gunnar; Kiltie, Anne E; Aben, Katja K H; Jonsson, Eirikur; Thorsteinsdottir, Unnur; Knowles, Margaret A; Rafnar, Thorunn; Stefansson, Kari

    2010-05-01

    Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.

  9. Oncogenic activation of ERG: A predominant mechanism in prostate cancer

    Directory of Open Access Journals (Sweden)

    Taduru L Sreenath

    2011-01-01

    Full Text Available Prevalent gene fusions involving regulatory sequences of the androgen receptor (AR regulated genes (primarily TMPRSS2 and protein coding sequences of nuclear transcription factors of the ETS gene family (predominantly ERG result in unscheduled androgen dependent ERG expression in prostate cancer (CaP.Cumulative data from a large number of studies in the past six years accentuate ERG alterations in more than half of all CaP patients in Western countries. Studies underscore that ERG functions are involved in the biology of CaP. ERG expression in normal context is selective to endothelial cells, specific hematopoetic cells and pre-cartilage cells. Normal functions of ERG are highlighted in hematopoetic stem cells. Emerging data continues to unravel molecular and cellular mechanisms by which ERG may contribute to CaP. Herein, we focus on biological and clinical aspects of ERG oncogenic alterations, potential of ERG-based stratification of CaP and the possibilities of targeting the ERG network in developing new therapeutic strategies for the disease.

  10. Optical coherence tomography (OCT) guided smart laser knife for cancer surgery (Conference Presentation)

    Science.gov (United States)

    Katta, Nitesh; Mcelroy, Austin; Estrada, Arnold; Milner, Thomas E.

    2017-02-01

    Neurological cancer surgeries require specialized tools that enhance imaging for precise cutting and removal of tissue without damaging adjacent neurological structures. The novel combination of high-resolution fast optical coherence tomography (OCT) alongside short pulsed nanosecond thulium (Tm) lasers offers stark advantages utilizing the superior beam quality, high volumetric tissue removal rates of thulium lasers with minimal residual thermal footprint in the tissue and avoiding damage to delicate sub-surface structures (e.g., nerves and microvessels); which has not been showcased before. A bench-top system is constructed, using a 15W 1940nm nanosecond pulsed Tm fiber laser (500uJ pulse energy, 100ns pulse duration, 30kHz repetition rate) for removing tissue and a swept source laser (1310±70nm, 100kHz sweep rate) is utilized for OCT imaging, forming a combined Tm/OCT system - a smart laser knife. The OCT image-guidance informs the Tm laser for cutting/removal of targeted tissue structures. Tissue phantoms were constructed to demonstrate surgical incision with blood vessel avoidance on the surface where 2mm wide 600um deep cuts are executed around the vessel using OCT to guide the procedure. Cutting up to delicate subsurface blood vessels (2mm deep) is demonstrated while avoiding damage to their walls. A tissue removal rate of 5mm^3/sec is obtained from the bench-top system. We constructed a blow-off model to characterize Tm cut depths taking into account the absorption coefficients and beam delivery systems to compute Arrhenius damage integrals. The model is used to compare predicted tissue removal rate and residual thermal injury with experimental values in response to Tm laser-tissue modification.

  11. Lung cancer-associated brain metastasis: Molecular mechanisms and therapeutic options.

    Science.gov (United States)

    Yousefi, Meysam; Bahrami, Tayyeb; Salmaninejad, Arash; Nosrati, Rahim; Ghaffari, Parisa; Ghaffari, Seyed H

    2017-10-01

    Lung cancer is the most common cause of cancer-related mortality in humans. There are several reasons for this high rate of mortality, including metastasis to several organs, especially the brain. In fact, lung cancer is responsible for approximately 50% of all brain metastases, which are very difficult to manage. Understanding the cellular and molecular mechanisms underlying lung cancer-associated brain metastasis brings up novel therapeutic promises with the hope to ameliorate the severity of the disease. Here, we provide an overview of the molecular mechanisms underlying the pathogenesis of lung cancer dissemination and metastasis to the brain, as well as promising horizons for impeding lung cancer brain metastasis, including the role of cancer stem cells, the blood-brain barrier, interactions of lung cancer cells with the brain microenvironment and lung cancer-driven systemic processes, as well as the role of growth factor/receptor tyrosine kinases, cell adhesion molecules and non-coding RNAs. In addition, we provide an overview of current and novel therapeutic approaches, including radiotherapy, surgery and stereotactic radiosurgery, chemotherapy, as also targeted cancer stem cell and epithelial-mesenchymal transition (EMT)-based therapies, micro-RNA-based therapies and other small molecule or antibody-based therapies. We will also discuss the daunting potential of some combined therapies. The identification of molecular mechanisms underlying lung cancer metastasis has opened up new avenues towards their eradication and provides interesting opportunities for future research aimed at the development of novel targeted therapies.

  12. Techniques for thyroid FNA: a synopsis of the National Cancer Institute Thyroid Fine-Needle Aspiration State of the Science Conference.

    Science.gov (United States)

    Pitman, Martha Bishop; Abele, John; Ali, Syed Z; Duick, Dan; Elsheikh, Tarik M; Jeffrey, R Brooke; Powers, Celeste N; Randolph, Gregory; Renshaw, Andrew; Scoutt, Leslie

    2008-06-01

    The National Cancer Institute (NCI) sponsored the NCI Thyroid fine-needle aspiration (FNA) State of the Science Conference on October 22-23, 2007 in Bethesda, MD. The 2-day meeting was accompanied by a permanent informational website and several on-line discussion periods between May 1 and December 15, 2007 (http://thyroidfna.cancer.gov). This document summarizes matters addressing manual and ultrasound guided FNA technique and related issues. Specific topics covered include details regarding aspiration needles, devices, and methods, including the use of core needle biopsy; the pros and cons of anesthesia; the influence of thyroid lesion location, size, and characteristics on technique; the role of ultrasound in the FNA of a palpable thyroid nodule; the advantages and disadvantages of various specialists performing a biopsy; the optimal number of passes and tissue preparation methods; sample adequacy criteria for solid and cystic nodules, and management of adverse reactions from the procedure. (http://thyroidfna.cancer.gov/pages/info/agenda/)

  13. Novel mechanism for obesity-induced colon cancer progression

    OpenAIRE

    Birmingham, Janette M; Busik, Julia V.; Hansen-Smith, Fay M.; Fenton, Jenifer I

    2009-01-01

    Adipose tissue secretes factors linked to colon cancer risk including leptin. A hallmark of cancer is sustained angiogenesis. While leptin promotes angiogenesis in adipose tissue, it is unknown whether leptin can induce epithelial cells to produce factors that may drive angiogenesis, vascular development and therefore cancer progression. The purpose of this study was to compare the effects of leptin-stimulated colon epithelial cells differing in adenomatous polyposis coli (Apc) genotype (gate...

  14. Pancreatic cancer cachexia: a review of mechanisms and therapeutics

    Science.gov (United States)

    Tan, Carlyn R.; Yaffee, Patrick M.; Jamil, Laith H.; Lo, Simon K.; Nissen, Nicholas; Pandol, Stephen J.; Tuli, Richard; Hendifar, Andrew E.

    2014-01-01

    Over the last decade, we have gained new insight into the pathophysiology of cachexia associated with pancreatic cancer. Unfortunately, its treatment is complex and remains a challenge. Pancreatic cancer cachexia is a multifactorial syndrome characterized by uncompensated adipose tissue and skeletal muscle loss in the setting of anorexia that leads to progressive functional impairment. This paper will review the current concepts of pancreatic cancer cachexia, its assessment and pathophysiology as well as current and future treatments. The successful management of pancreatic cancer cachexia will likely require a multimodal approach that includes nutritional support and combination pharmaceutical interventions. PMID:24624094

  15. Combinatorial epigenetic mechanisms and efficacy of early breast cancer inhibition by nutritive botanicals

    Science.gov (United States)

    Li, Yuanyuan; Buckhaults, Phillip; Cui, Xiangqin; Tollefsbol, Trygve O

    2016-01-01

    Aim: Aberrant epigenetic events are important contributors to the pathogenesis of different types of cancers and dietary botanicals with epigenetic properties can influence early cancer development leading to cancer prevention effects. We sought to investigate potential combinatorial effects of bioactive dietary components including green tea polyphenols (GTPs) and broccoli sprouts (BSp) on neutralizing epigenetic aberrations during breast tumorigenesis. Materials & methods: The combinatorial effects were evaluated in a breast cancer transformation cellular system and breast cancer mouse xenografts. Results & conclusion: Combined treatment with epigallocatechin-3-gallate in GTPs and sulforaphane in BSp resulted in a synergistic inhibition of breast cancer cellular growth. Further studies revealed this combination led to genome-wide epigenetic alterations. Combinatorial diets significantly inhibited tumor growth in breast cancer mouse xenografts. Collectively, these studies indicate that combined GTPs and BSp are highly effective in inhibiting early breast cancer development by, at least in part, regulating epigenetic mechanisms. PMID:27478970

  16. Combinatorial epigenetic mechanisms and efficacy of early breast cancer inhibition by nutritive botanicals.

    Science.gov (United States)

    Li, Yuanyuan; Buckhaults, Phillip; Cui, Xiangqin; Tollefsbol, Trygve O

    2016-08-01

    Aberrant epigenetic events are important contributors to the pathogenesis of different types of cancers and dietary botanicals with epigenetic properties can influence early cancer development leading to cancer prevention effects. We sought to investigate potential combinatorial effects of bioactive dietary components including green tea polyphenols (GTPs) and broccoli sprouts (BSp) on neutralizing epigenetic aberrations during breast tumorigenesis. The combinatorial effects were evaluated in a breast cancer transformation cellular system and breast cancer mouse xenografts. Combined treatment with epigallocatechin-3-gallate in GTPs and sulforaphane in BSp resulted in a synergistic inhibition of breast cancer cellular growth. Further studies revealed this combination led to genome-wide epigenetic alterations. Combinatorial diets significantly inhibited tumor growth in breast cancer mouse xenografts. Collectively, these studies indicate that combined GTPs and BSp are highly effective in inhibiting early breast cancer development by, at least in part, regulating epigenetic mechanisms.

  17. Obesity-associated digestive cancers: A review of mechanisms and interventions.

    Science.gov (United States)

    Zheng, Jiachen; Zhao, Ming; Li, Jiahui; Lou, Guoying; Yuan, Yanyan; Bu, Shizhong; Xi, Yang

    2017-03-01

    The prevalence of obesity has steadily increased over the past few decades. Previous studies suggest that obesity is an oncogenic factor and that over 20% of all cancers are obesity-related. Among such cancers, digestive system malignancies (including esophageal adenocarcinomas, colorectal cancers, and cancers of the gastric cardia, liver, and pancreas) are reported most frequently. While the 5-year survival rates of cancers of the breast and prostate are 90%, that rate is only 45% for digestive cancers. In this review, the mechanisms of obesity-associated digestive cancers are discussed, with an emphasis on obesity-related gene mutations, insulin and insulin-like growth factor signaling pathways, chronic inflammation, and altered adipokine levels. Evidence that these factors often function interdependently rather than independently in carcinogenesis is presented. Recommended interventions that may reduce the burden of obesity-associated digestive cancers, such as participation in physical activity, diet modulation, and calorie restriction, are also described.

  18. Conference Interpreters

    DEFF Research Database (Denmark)

    Leal Lobato, Ana Isabel

    2017-01-01

    Conference Interpreters: How to serve the cause of minorized communities in the new postmonolingual / ‘postmonodiscoursive’ order,......Conference Interpreters: How to serve the cause of minorized communities in the new postmonolingual / ‘postmonodiscoursive’ order,...

  19. CONFERENCE CALENDAR

    National Research Council Canada - National Science Library

    2014-01-01

    .... 2nd Annual Integrated Health Conference March 20-22, 2015-Town and Country Resort and Convention Center, San Diego, California The Integrated Health Conference provides the latest in integrative...

  20. Mechanisms of disease: The epidemiology of bladder cancer.

    Science.gov (United States)

    Pelucchi, Claudio; Bosetti, Cristina; Negri, Eva; Malvezzi, Matteo; La Vecchia, Carlo

    2006-06-01

    Mortality from bladder cancer has shown downward trends over the last 2 decades in several western European countries (albeit 10-15 years later than similar trends in the US), but is still increasing in some eastern European countries. Tobacco smoking and occupational exposure to aromatic amines are the two major established environmental risk factors for bladder cancer. Controlling exposure to these factors has been an important contributor to the reduction in bladder cancer mortality, particularly among men. Diet could influence bladder carcinogenesis, as many compounds contained in foods--and their metabolites--are excreted through the urinary tract. Fruit and vegetable consumption was inversely related with bladder cancer in many studies, but no consistent association has emerged between intake of related micronutrients and reduced risk of bladder cancer. Other widely investigated lifestyle habits are probably not associated with risk of developing bladder cancer (e.g. coffee consumption, artificial sweetener use, hair dyes) or are difficult to assess (e.g. fluid intake). Infections and stones in the urinary tract might cause chronic irritation of the bladder epithelium, and thus increase bladder cancer risk. First-degree relatives of bladder cancer patients have a 50-100% increased relative risk of developing the disease, a risk that could be even higher when the proband is diagnosed at an early age.

  1. 3rd Cryocooler Conference

    CERN Document Server

    Louie, Berverly; McCarthy, Sandy

    1985-01-01

    Cryocoolers 3 documents the output of the Third Cryocooler Conference, held at the National Bureau of Standards, Boulder, Colorado, on September 17-18, 1984. About 140 people from 10 countries attended the conference representing industry, government, and academia. A total of 26 papers were presented orally at the conference and all appear in written form in the proceedings. The focus of this conference was on small cryocoolers in the temperature range of 4 - 80 K. Mechanical and nonmechanical types are discussed in the various papers. Applications of these small cryocoolers include the cooling of infrared detectors, cryopumps, small superconducting devices and magnets, and electronic devices. The conference proceedings reproduced here was published by the National Bureau of Standards in Boulder, Colorado as NBS Special Publication #698.

  2. Cancer-associated venous thromboembolism: Burden, mechanisms, and management.

    Science.gov (United States)

    Ay, Cihan; Pabinger, Ingrid; Cohen, Alexander T

    2017-01-26

    Venous thromboembolism (VTE) is a significant health problem in the general population but especially in cancer patients. In this review, we discuss the epidemiology and burden of the disease, the pathophysiology of cancer-associated VTE, and the clinical treatment options for both primary prevention and acute treatment. Overall, the development of VTE in cancer patients is related to increases in morbidity, mortality, and medical costs. However, the incidence of cancer-associated VTE varies due to patient-related factors (e.g. thrombophilia, comorbidities, performance status, history of venous diseases), tumour-related factors (e.g. cancer site, stage, grade), and treatment-related factors (e.g. surgery, chemotherapy, anti-angiogenesis treatment, hormonal and supportive treatment). Furthermore, blood count parameters (e.g. platelets and leukocytes) and biomarkers (e.g. soluble P-selectin and D-dimer) are predictive markers for the risk of VTE in cancer patients and have been used to enhance risk stratification. Evidence suggests that cancer itself is associated with a state of hypercoagulability, driven in part by the release of procoagulant factors, such as tissue factor, from malignant tissue as well as by inflammation-driven activation of endothelial cells, platelets, and leukocytes. In general, low-molecular-weight heparin (LWMH) monotherapy is the standard of care for the management of cancer-associated VTE, as vitamin K antagonists are less effective in cancer patients. Direct oral anticoagulants (DOACs) offer a potentially promising treatment option for cancer patients with VTE, but recommendations concerning the routine use of DOACs should await head-to-head studies with LMWH.

  3. Cancer Data and Statistics Tools

    Science.gov (United States)

    ... National Cancer Conference Stay Informed Cancer Data and Statistics Tools Recommend on Facebook Tweet Share Compartir United States Cancer Statistics The United States Cancer Statistics (USCS): Incidence and ...

  4. Translating Mechanism-Based Strategies to Break the Obesity-Cancer Link: A Narrative Review.

    Science.gov (United States)

    Smith, Laura A; O'Flanagan, Ciara H; Bowers, Laura W; Allott, Emma H; Hursting, Stephen D

    2017-11-01

    Prevalence of obesity, an established risk factor for many cancers, has increased dramatically over the past 50 years in the United States and across the globe. Relative to normoweight cancer patients, obese cancer patients often have poorer prognoses, resistance to chemotherapies, and are more likely to develop distant metastases. Recent progress on elucidating the mechanisms underlying the obesity-cancer connection suggests that obesity exerts pleomorphic effects on pathways related to tumor development and progression and, thus, there are multiple opportunities for primary prevention and treatment of obesity-related cancers. Obesity-associated alterations, including systemic metabolism, adipose inflammation, growth factor signaling, and angiogenesis, are emerging as primary drivers of obesity-associated cancer development and progression. These obesity-associated host factors interact with the intrinsic molecular characteristics of cancer cells, facilitating several of the hallmarks of cancer. Each is considered in the context of potential preventive and therapeutic strategies to reduce the burden of obesity-related cancers. In addition, this review focuses on emerging mechanisms behind the obesity-cancer link, as well as relevant dietary interventions, including calorie restriction, intermittent fasting, low-fat diet, and ketogenic diet, that are being implemented in preclinical and clinical trials, with the ultimate goal of reducing incidence and progression of obesity-related cancers. Copyright © 2017 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  5. Conference Planning.

    Science.gov (United States)

    Burke, W. Warner, Ed.; Beckhard, Richard, Ed.

    This book, written to instruct in the use of a conference as a medium of social intercourse, is divided into four sections. Section I, which contains five articles, deals with factors to be considered in planning a conference. Specific techniques one can employ to improve a conference and several different techniques for evaluating the…

  6. 217 YAP Is Ready to Rac and Rho: Elucidation of a Novel YAP-Driven Network That Potentiates Brain Cancer Cell Dispersal and Confers Poor Survival in Patients.

    Science.gov (United States)

    Shah, Sagar R; Tippens, Nathaniel; Park, JinSeok; Mohyeldin, Ahmed; Vela, Guillermo; Martinez-Gutierrez, Juan Carlos; Margolis, Seth S; Schmidt, Susanne; Levchenko, Andre; Quinones-Hinojosa, Alfredo

    2016-08-01

    Molecular pathways linking cell polarization and migration to extracellular cues regulate many pathological processes, including progression of aggressive and infiltrative cancers. Glioblastoma (GBM), the most common and lethal form of primary brain cancer, is characterized by its pronounced ability to disseminate into the intricate microenvironment of the human brain, confounding surgical excision and radiotherapy, leading to a median patient survival of 14 months. Progression results from defects in molecular pathways linking cell migration and invasion into surrounding tissue. However, the molecular engines are not known. Using patient-derived GBM tissues and cells, we profiled the expression of network moieties via Western blotting, quantitative real-time polymerase chain reaction and performed live cell time-lapse microscopy, bioinformatics analyses, in vivo intracranial GBM experiments using genetic and pharmacological inhibitors to delineate a prodispersal mechanism for management and treatment of GBMs. Yes-associated protein (YAP), a transcriptional coactivator, is overexpressed and hyperactive in 78% of GBMs and 50% of metastatic tumors to the brain (P < .05). Our studies demonstrate that YAP activates a Rho-GTPase switch to potentiate migratory speed by interacting with canonical pathways through direct transcriptional control. In addition, YAP mediates a proinvasive genetic network by direct posttranslational regulation. By coupling the regulation of migration and invasion, YAP drives tumor cell dispersal in vitro and in vivo (P < .05). Hyperactivation of this YAP-driven network in GBM confers poor patient outcome in clinical biopsies and The Cancer Genome Atlas (P < .05), suggesting a new signature in clinical prognosis of this aggressive and infiltrative cancer. Targeting this network using a proprietary pharmacological inhibitor attenuates tumor dispersal and growth (P < .05). YAP can critically control cellular locomotion through direct interaction

  7. Intrinsic and Acquired Resistance to HER2-Targeted Therapies in HER2 Gene-Amplified Breast Cancer: Mechanisms and Clinical Implications

    Science.gov (United States)

    Rexer, Brent N.; Arteaga, Carlos L.

    2012-01-01

    Approximately 25% of human breast cancers overexpress the HER2 (ErbB2) proto-oncogene, which confers a more aggressive tumor phenotype and associates with a poor prognosis in patients with this disease. Two approved therapies targeting HER2, the monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib, are clinically active against this type of breast cancer. However, a significant fraction of patients with HER2+ breast cancer treated with these agents eventually relapse or develop progressive disease. This suggests that tumors acquire or possess intrinsic mechanisms of resistance that allow escape from HER2 inhibition. This review focuses on mechanisms of intrinsic and/or acquired resistance to HER2-targeted therapies that have been identified in preclinical and clinical studies. These mechanisms involve alterations to HER2 itself, coexpression or acquisition of bypass signaling through other receptor or intracellular signaling pathways, defects in mechanisms of cell cycle regulation or apoptosis, and host factors that may modulate drug response. Emerging clinical evidence already suggests that combinations of therapies targeting HER2 as well as these resistance pathways will be effective in overcoming or preventing resistance. PMID:22471661

  8. Molecular mechanisms of chemopreventive phytochemicals against gastroenterological cancer development

    Science.gov (United States)

    Chung, Min-Yu; Lim, Tae Gyu; Lee, Ki Won

    2013-01-01

    Cancer is one of the leading causes of death worldwide. Commonly used cancer treatments, including chemotherapy and radiation therapy, often have side effects and a complete cure is sometimes impossible. Therefore, prevention, suppression, and/or delaying the onset of the disease are important. The onset of gastroenterological cancers is closely associated with an individual’s lifestyle. Thus, changing lifestyle, specifically the consumption of fruits and vegetables, can help to protect against the development of gastroenterological cancers. In particular, naturally occurring bioactive compounds, including curcumin, resveratrol, isothiocyanates, (-)-epigallocatechin gallate and sulforaphane, are regarded as promising chemopreventive agents. Hence, regular consumption of these natural bioactive compounds found in foods can contribute to prevention, suppression, and/or delay of gastroenterological cancer development. In this review, we will summarize natural phytochemicals possessing potential antioxidant and/or anti-inflammatory and anti-carcinogenic activities, which are exerted by regulating or targeting specific molecules against gastroenterological cancers, including esophageal, gastric and colon cancers. PMID:23467658

  9. Mechanisms of metabolic dysfunction in cancer-associated cachexia

    Science.gov (United States)

    Petruzzelli, Michele; Wagner, Erwin F.

    2016-01-01

    Metabolic dysfunction contributes to the clinical deterioration observed in advanced cancer patients and is characterized by weight loss, skeletal muscle wasting, and atrophy of the adipose tissue. This systemic syndrome, termed cancer-associated cachexia (CAC), is a major cause of morbidity and mortality. While once attributed solely to decreased food intake, the present description of cancer cachexia is a disorder of multiorgan energy imbalance. Here we review the molecules and pathways responsible for metabolic dysfunction in CAC and the ideas that led to the current understanding. PMID:26944676

  10. Shear-wave elastographic features of breast cancers: comparison with mechanical elasticity and histopathologic characteristics.

    Science.gov (United States)

    Lee, Su Hyun; Moon, Woo Kyung; Cho, Nariya; Chang, Jung Min; Moon, Hyeong-Gon; Han, Wonshik; Noh, Dong-Young; Lee, Jung Chan; Kim, Hee Chan; Lee, Kyoung-Bun; Park, In-Ae

    2014-03-01

    The objective of this study was to compare the quantitative and qualitative shear-wave elastographic (SWE) features of breast cancers with mechanical elasticity and histopathologic characteristics. This prospective study was conducted with institutional review board approval, and written informed consent was obtained. Shear-wave elastography was performed for 30 invasive breast cancers in 30 women before surgery. The mechanical elasticity of a fresh breast tissue section, correlated with the ultrasound image, was measured using an indentation system. Quantitative (maximum, mean, minimum, and standard deviation of elasticity in kilopascals) and qualitative (color heterogeneity and presence of signal void areas in the mass) SWE features were compared with mechanical elasticity and histopathologic characteristics using the Pearson correlation coefficient and the Wilcoxon signed rank test. Maximum SWE values showed a moderate correlation with maximum mechanical elasticity (r = 0.530, P = 0.003). There were no significant differences between SWE values and mechanical elasticity in histologic grade I or II cancers (P = 0.268). However, SWE values were significantly higher than mechanical elasticity in histologic grade III cancers (P elasticity (r = 0.469, P = 0.009). Signal void areas in the masses were present in 43% of breast cancers (13 of 30) and were correlated with dense collagen depositions (n = 11) or intratumoral necrosis (n = 2). Quantitative and qualitative SWE features reflect both the mechanical elasticity and histopathologic characteristics of breast cancers.

  11. Clinical assessment of human breast cancer margins with wide-field optical coherence micro-elastography (Conference Presentation)

    Science.gov (United States)

    Allen, Wes M.; Chin, Lixin; Wijesinghe, Philip; Kirk, Rodney W.; Latham, Bruce; Sampson, David D.; Saunders, Christobel M.; Kennedy, Brendan F.

    2017-02-01

    Breast cancer has the second highest mortality rate of all cancers in females. Surgical excision of malignant tissue forms a central component of breast-conserving surgery (BCS) procedures. Incomplete excision of malignant tissue is a major issue in BCS with typically 20 - 30% cases requiring a second surgical procedure due to postoperative detection of tumor in the margin. A major challenge for surgeons during BCS is the lack of effective tools to assess the surgical margin intraoperatively. Such tools would enable the surgeon to more effectively remove all tumor during the initial surgery, hence reducing re-excision rates. We report advances in the development of a new tool, optical coherence micro-elastography, which forms images, known as elastograms, based on mechanical contrast within the tissue. We demonstrate the potential of this technique to increase contrast between malignant tumor and healthy stroma in elastograms over OCT images. We demonstrate a key advance toward clinical translation by conducting wide-field imaging in intraoperative time frames with a wide-field scanning system, acquiring mosaicked elastograms with overall dimensions of 50 × 50 mm, large enough to image an entire face of most lumpectomy specimens. We describe this wide-field imaging system, and demonstrate its operation by presenting wide-field optical coherence tomography images and elastograms of a tissue mimicking silicone phantom and a number of representative freshly excised human breast specimens. Our results demonstrate the feasibility of scanning large areas of lumpectomies, which is an important step towards practical intraoperative margin assessment.

  12. Molecular Mechanisms of Metastatic Progression in Breast Cancer

    National Research Council Canada - National Science Library

    Flanagan, Louise A

    2004-01-01

    .... In our studies, we have focused on determining whether clusterin plays a causative role in the progression of human breast cancer by promoting cell survival, increasing cell motility and resistance to cytotoxic drugs...

  13. Effects and potential mechanisms of exercise training on cancer progression: A translational perspective

    Science.gov (United States)

    Betof, Allison S.; Dewhirst, Mark W.; Jones, Lee W.

    2013-01-01

    Over the past decade there has been increasing research and clinical interest in the role of exercise therapy/rehabilitation as an adjunct therapy to improve symptom control and management following a cancer diagnosis. More recently, the field of ‘exercise – oncology’ has broadened in scope to investigate whether the benefits extend beyond symptom control to modulate cancer-specific outcomes (i.e., cancer progression and metastasis). Here we review the extant epidemiological evidence examining the association between exercise behavior, functional capacity/exercise capacity, and cancer-specific recurrence and mortality as well as all-cause mortality individuals following a cancer diagnosis. We also evaluate evidence from clinical studies investigating the effects of structured exercise on blood-based biomarkers associated with cancer progression/metastasis as well findings from preclinical investigations examining the effects and molecular mechanisms of exercise in mouse models of cancer. Current gaps in knowledge are also discussed. PMID:22610066

  14. Mechanical Stress Downregulates MHC Class I Expression on Human Cancer Cell Membrane

    DEFF Research Database (Denmark)

    La Rocca, Rosanna; Tallerico, Rossana; Hassan, Almosawy Talib

    2014-01-01

    In our body, cells are continuously exposed to physical forces that can regulate different cell functions such as cell proliferation, differentiation and death. In this work, we employed two different strategies to mechanically stress cancer cells. The cancer and healthy cell populations were tre...

  15. In-depth Investigation of Genetic Region Identifies Mechanism that Contributes to Cancer Risk

    Science.gov (United States)

    Investigators in the Laboratory of Translational Genomics have identified a genetic variant in a multi-cancer risk locus at chromosome 5p15.33 that explains, at least in part, the molecular mechanism through which this variant influences cancer risk.

  16. Obesity and cancer risk: evidence, mechanisms, and recommendations

    OpenAIRE

    Vucenik, Ivana; Stains, Joseph P.

    2012-01-01

    Obesity, a growing health problem worldwide, has been associated with the metabolic syndrome, diabetes, cardiovascular disease, hypertension, and other chronic diseases. Recently, the obesity–cancer link has received much attention. Epidemiological studies have shown that obesity is also associated with increased risk of several cancer types, including colon, breast, endometrium, liver, kidney, esophagus, gastric, pancreatic, gallbladder, and leukemia, and can also lead to poorer treatment an...

  17. Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer

    Science.gov (United States)

    1997-07-01

    role in cancer etiology is required. Thus positional cloning is a reasonable approach if strong, well-characterized pedigrees are available. However...experimental animals. Besides the ethical consider- function of immune components that, in turn, ations, large tumor burdens can complicate experi...1990, Spontaneous tumors in dogs ance of positive and negative regulation. Cell, 64, and cats: models for the study of cancer biology and 327-36

  18. Molecular mechanisms of garlic‐derived allyl sulfides in the inhibition of skin cancer progression

    National Research Council Canada - National Science Library

    Wang, Hsiao‐Chi; Pao, Jung; Lin, Shuw‐Yuan; Sheen, Lee‐Yan

    2012-01-01

    .... Allyl sulfides—i.e., sulfur metabolites in garlic oil—have been demonstrated to have anticancer activity against several cancer types, although the mechanisms underlying these effects remain enigmatic...

  19. Mechanisms Down-Regulating Sprouty1, a Growth Inhibitor in Prostate Cancer

    National Research Council Canada - National Science Library

    Kwabi-Addo, Bernard

    2006-01-01

    .... I have demonstrated that Sprouty1 is down-regulated in human prostate cancer (PCa). The purpose of the present study is to characterize the molecular mechanisms regulating Sprouty1 expression in the human PCa. Results...

  20. 75 FR 2552 - NIH State-of-the-Science Conference: Enhancing Use and Quality of Colorectal Cancer Screening

    Science.gov (United States)

    2010-01-15

    ... Quality of Colorectal Cancer Screening Notice is hereby given by the National Institutes of Health (NIH... one type of polyp, known as an adenoma, can develop into colorectal cancer. Screening tests for... early cancer in people who have no symptoms. A range of colorectal cancer screening tests is available...

  1. Molecular Mechanisms and Metabolomics of Natural Polyphenols Interfering with Breast Cancer Metastasis.

    Science.gov (United States)

    Ci, Yingqian; Qiao, Jinping; Han, Mei

    2016-12-17

    Metastatic cancers are the main cause of cancer-related death. In breast primary cancer, the five-year survival rate is close to 100%; however, for metastatic breast cancer, that rate drops to a mere 25%, due in part to the paucity of effective therapeutic options for treating metastases. Several in vitro and in vivo studies have indicated that consumption of natural polyphenols significantly reduces the risk of cancer metastasis. Therefore, this review summarizes the research findings involving the molecular mechanisms and metabolomics of natural polyphenols and how they may be blocking breast cancer metastasis. Most natural polyphenols are thought to impair breast cancer metastasis through downregulation of MMPs expression, interference with the VEGF signaling pathway, modulation of EMT regulator, inhibition of NF-κB and mTOR expression, and other related mechanisms. Intake of natural polyphenols has been shown to impact endogenous metabolites and complex biological metabolic pathways in vivo. Breast cancer metastasis is a complicated process in which each step is modulated by a complex network of signaling pathways. We hope that by detailing the reported interactions between breast cancer metastasis and natural polyphenols, more attention will be directed to these promising candidates as effective adjunct therapies against metastatic breast cancer in the clinic.

  2. Breast cancer prevention: lessons to be learned from mechanisms of early pregnancy-mediated breast cancer protection.

    Science.gov (United States)

    Meier-Abt, Fabienne; Bentires-Alj, Mohamed; Rochlitz, Christoph

    2015-03-01

    Pregnancy at early, but not late age, has a strong and life-long protective effect against breast cancer. The expected overall increase in breast cancer incidence demands the development of a pharmaceutical mimicry of early-age pregnancy-mediated protection. Recently, converging results from rodent models and women on molecular and cellular mechanisms underlying the protective effect of early-age pregnancy have opened the door for translational studies on pharmacologic prevention against breast cancer. In particular, alterations in Wnt and TGFβ signaling in mammary stem/progenitor cells reveal new potential targets for preventive interventions, and thus might help to significantly reduce the incidence of breast cancer in the future. ©2015 American Association for Cancer Research.

  3. Targeting the Cancer Biomarker CD47: A Review on the Diverse Mechanisms of the CD47 Pathway in Cancer Treatment.

    Science.gov (United States)

    Zhang, Liang; Huang, He

    2016-01-01

    CD47 is a widely expressed cell membrane receptor belonging to the immunoglobulin (Ig) superfamily. CD47 is involved in a number of cellular processes, including proliferation, apoptosis, adhesion and migration through interacting with integrin, thrombospondins and SIRPα. CD47 also plays an important role in the immune system and homeostasis. In recent few years, numerous studies have demonstrated that targeting CD47 exhibits noticeable effects on inhibition of tumor growth and prevention of metastasis in various types of cancers, while the mechanisms is complicated. In this review, we stated three possible mechanisms of targeting CD47 for cancer treatment. First, blockade of CD47 interrupts the CD47-SIRPα pathway which helps cancer cells escape from phagocytosis by macrophages. Second, ligation of CD47 induces cancer cells apoptosis. Third, targeting CD47 improves the tumor microenvironment. We also described several prospective strategies that have been used for targeting CD47 in cancer therapy, including antibodies, miRNA/siRNA and recombinant protein, etc. In conclusion, CD47 is a promising cancer biomarker, and targeting CD47 presents an effective and potential therapeutic strategy through synthesized mechanisms.

  4. TRPV6 calcium channel translocates to the plasma membrane via Orai1-mediated mechanism and controls cancer cell survival.

    Science.gov (United States)

    Raphaël, Maylis; Lehen'kyi, V'yacheslav; Vandenberghe, Matthieu; Beck, Benjamin; Khalimonchyk, Sergiy; Vanden Abeele, Fabien; Farsetti, Leonardo; Germain, Emmanuelle; Bokhobza, Alexandre; Mihalache, Adriana; Gosset, Pierre; Romanin, Christoph; Clézardin, Philippe; Skryma, Roman; Prevarskaya, Natalia

    2014-09-16

    Transient receptor potential vanilloid subfamily member 6 (TRPV6) is a highly selective calcium channel that has been considered as a part of store-operated calcium entry (SOCE). Despite its first discovery in the early 2000s, the role of this channel in prostate cancer (PCa) remained, until now, obscure. Here we show that TRPV6 mediates calcium entry, which is highly increased in PCa due to the remodeling mechanism involving the translocation of the TRPV6 channel to the plasma membrane via the Orai1/TRPC1-mediated Ca(2+)/Annexin I/S100A11 pathway, partially contributing to SOCE. The TRPV6 calcium channel is expressed de novo by the PCa cell to increase its survival by enhancing proliferation and conferring apoptosis resistance. Xenografts in nude mice and bone metastasis models confirmed the remarkable aggressiveness of TRPV6-overexpressing tumors. Immunohistochemical analysis of these demonstrated the increased expression of clinical markers such as Ki-67, prostate specific antigen, synaptophysin, CD31, and CD56, which are strongly associated with a poor prognosis. Thus, the TRPV6 channel acquires its oncogenic potential in PCa due to the remodeling mechanism via the Orai1-mediated Ca(2+)/Annexin I/S100A11 pathway.

  5. TRPV6 calcium channel translocates to the plasma membrane via Orai1-mediated mechanism and controls cancer cell survival

    Science.gov (United States)

    Raphaël, Maylis; Lehen’kyi, V’yacheslav; Vandenberghe, Matthieu; Beck, Benjamin; Khalimonchyk, Sergiy; Vanden Abeele, Fabien; Farsetti, Leonardo; Germain, Emmanuelle; Bokhobza, Alexandre; Mihalache, Adriana; Gosset, Pierre; Romanin, Christoph; Clézardin, Philippe; Skryma, Roman; Prevarskaya, Natalia

    2014-01-01

    Transient receptor potential vanilloid subfamily member 6 (TRPV6) is a highly selective calcium channel that has been considered as a part of store-operated calcium entry (SOCE). Despite its first discovery in the early 2000s, the role of this channel in prostate cancer (PCa) remained, until now, obscure. Here we show that TRPV6 mediates calcium entry, which is highly increased in PCa due to the remodeling mechanism involving the translocation of the TRPV6 channel to the plasma membrane via the Orai1/TRPC1-mediated Ca2+/Annexin I/S100A11 pathway, partially contributing to SOCE. The TRPV6 calcium channel is expressed de novo by the PCa cell to increase its survival by enhancing proliferation and conferring apoptosis resistance. Xenografts in nude mice and bone metastasis models confirmed the remarkable aggressiveness of TRPV6-overexpressing tumors. Immunohistochemical analysis of these demonstrated the increased expression of clinical markers such as Ki-67, prostate specific antigen, synaptophysin, CD31, and CD56, which are strongly associated with a poor prognosis. Thus, the TRPV6 channel acquires its oncogenic potential in PCa due to the remodeling mechanism via the Orai1-mediated Ca2+/Annexin I/S100A11 pathway. PMID:25172921

  6. ERBB receptors: from oncogene discovery to basic science to mechanism-based cancer therapeutics.

    Science.gov (United States)

    Arteaga, Carlos L; Engelman, Jeffrey A

    2014-03-17

    ERBB receptors were linked to human cancer pathogenesis approximately three decades ago. Biomedical investigators have since developed substantial understanding of the biology underlying the dependence of cancers on aberrant ERBB receptor signaling. An array of cancer-associated genetic alterations in ERBB receptors has also been identified. These findings have led to the discovery and development of mechanism-based therapies targeting ERBB receptors that have improved outcome for many cancer patients. In this Perspective, we discuss current paradigms of targeting ERBB receptors with cancer therapeutics and our understanding of mechanisms of action and resistance to these drugs. As current strategies still have limitations, we also discuss challenges and opportunities that lie ahead as basic scientists and clinical investigators work toward more breakthroughs. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Hvidtfeldt, Ulla Arthur

    2014-10-01

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

  8. Myxoma and vaccinia virus exploit different mechanisms to enter and infect human cancer cells

    Science.gov (United States)

    Villa, Nancy Y.; Bartee, Eric; Mohamed, Mohamed R.; Rahman, Masmudur M.; Barrett, John W.; McFadden, Grant

    2010-01-01

    Myxoma (MYXV) and vaccinia virus (VACV) have recently emerged as potential oncolytic agents that can infect and kill different human cancer cells. Although both are structurally similar, it is unknown whether the pathway(s) used by these poxviruses to enter and cause oncolysis in cancer cells are mechanistically similar. Here, we compared the entry of MYXV and VACV-WR into various human cancer cells and observed significant differences: 1- Low pH treatment accelerates fusion-mediated entry of VACV but not MYXV, 2- The tyrosine kinase inhibitor genistein inhibits entry of VACV, but not MYXV, 3- Knockdown of PAK1 revealed that it is required for a late stage downstream of MYXV entry into cancer cells, whereas PAK1 is required for VACV entry into the same target cells. These results suggest that VACV and MYXV exploit different mechanisms to enter into human cancer cells, thus providing some rationale for their divergent cancer cell tropisms. PMID:20334889

  9. Mechanisms linking dietary fiber, gut microbiota and colon cancer prevention

    Science.gov (United States)

    Many epidemiological and experimental studies have suggested that dietary fiber plays an important role in colon cancer prevention. These findings may relate to the ability of fiber to reduce the contact time of carcinogens within the intestinal lumen and to promote healthy gut microbiota, which mod...

  10. Mechanisms of CTC Biomarkers in Breast Cancer Brain Metastasis

    Science.gov (United States)

    2015-10-01

    bioinformatics.istge.it/ clima /) and from each other (Fig. 2b). Third, we interrogated CTC subsets by their abilities to be viable and expand in vitro. We...employing cancer cell lines from available databases (http://bioinfor- matics.istge.it/ clima /) and from each other (Fig. 2b). Third, we interrogated CTC

  11. Mechanisms of Hepatocyte Growth Factor Activation in Cancer Tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kawaguchi, Makiko; Kataoka, Hiroaki, E-mail: mejina@med.miyazaki-u.ac.jp [Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan)

    2014-09-29

    Hepatocyte growth factor/scatter factor (HGF/SF) plays critical roles in cancer progression through its specific receptor, MET. HGF/SF is usually synthesized and secreted as an inactive proform (pro-HGF/SF) by stromal cells, such as fibroblasts. Several serine proteases are reported to convert pro-HGF/SF to mature HGF/SF and among these, HGF activator (HGFA) and matriptase are the most potent activators. Increased activities of both proteases have been observed in various cancers. HGFA is synthesized mainly by the liver and secreted as an inactive pro-form. In cancer tissues, pro-HGFA is likely activated by thrombin and/or human kallikrein 1-related peptidase (KLK)-4 and KLK-5. Matriptase is a type II transmembrane serine protease that is expressed by most epithelial cells and is also synthesized as an inactive zymogen. Matriptase activation is likely to be mediated by autoactivation or by other trypsin-like proteases. Recent studies revealed that matriptase autoactivation is promoted by an acidic environment. Given the mildly acidic extracellular environment of solid tumors, matriptase activation may, thus, be accelerated in the tumor microenvironment. HGFA and matriptase activities are regulated by HGFA inhibitor (HAI)-1 (HAI-1) and/or HAI-2 in the pericellular microenvironment. HAIs may have an important role in cancer cell biology by regulating HGF/SF-activating proteases.

  12. Sustained proliferation in cancer: mechanisms and novel therapeutic targets

    Science.gov (United States)

    Arzumanyan, Alla; Kulathinal, Rob J.; Blain, Stacy W.; Holcombe, Randall F.; Mahajna, Jamal; Marino, Maria; Martinez-Chantar, Maria L.; Nawroth, Roman; Sanchez-Garcia, Isidro; Sharma, Dipali; Saxena, Neeraj K.; Singh, Neetu; Vlachostergios, Panagiotis J.; Guo, Shanchun; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Amedei, Amedeo; Niccolai, Elena; Amin, Amr; Ashraf, S. Salman; Boosani, Chandra S.; Guha, Gunjan; Ciriolo, Maria Rosa; Aquilano, Katia; Chen, Sophie; Mohammed, Sulma I.; Azmi, Asfar S.; Bhakta, Dipita; Halicka, Dorota; Nowsheen, Somaira

    2016-01-01

    Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). This data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression. PMID:25892662

  13. Personalized integrative oncology: targeted approaches for optimal outcomes: the 11th International Conference of the Society for Integrative Oncology.

    Science.gov (United States)

    Lee, Richard T; Yang, Peiying; Greenlee, Heather; Bauer-Wu, Susan; Balneaves, Lynda G; Zick, Suzanna

    2015-01-01

    The 11th International Conference of the Society for Integrative Oncology (SIO) brought together more than 300 clinicians, researchers, patients, and advocates to hear and interact with world-leading experts about the latest research in the areas of nutrition, exercise, acupuncture, health services research, meditation, and other integrative disciplines. The conference theme, "Personalized Integrative Oncology: Targeted Approaches for Optimal Outcomes," highlighted innovations in personalized medicine and ways this growing field will advance the evolution of individualized integrative cancer care to the next level. This year's conference also featured a clinical track focusing on clinical information for the practicing health care professional. The conference's rigorous schedule included 3 keynotes, 4 plenary sessions, 2 interdisciplinary tumor boards, 5 workshops, 45 concurrent oral sessions, and 106 posters. In addition to the conference theme, keynote and plenary sessions presented topics on stress and cancer, the importance of sleep for cancer patients, epigenetic mechanisms of lifestyle and natural products, recently published Journal of the National Cancer Institute monograph on integrative oncology, SIO's clinical practice guidelines for breast cancer survivors, and a joint session of the American Academy of Hospice and Palliative Medicine and SIO about supportive care and symptom management. This highly successful conference helped further the mission of the SIO to advance evidence-based, comprehensive, integrative health care to improve the lives of people affected by cancer. © The Author(s) 2014.

  14. PHYSICS FOR HEALTH: CONFERENCE

    CERN Multimedia

    2016-01-01

    ICTR-PHE 2016 - International Conference on Translational Research in Radio-Oncology and Physics for Health -, co organized by CERN, aims at developing new strategies to better diagnose and treat cancer, by uniting biology and physics with clinics. Through the various sessions and symposia, the scientific programme offers the delegates the opportunity to discuss, in a friendly atmosphere, the latest progress in physics breakthroughs for health applications. The third edition of this conference took place at CICG (Centre International de Conférence Genève) from 15 to 19 Feb 2016.

  15. Nostradamus conference

    CERN Document Server

    Rössler, Otto; Snášel, Václav; Abraham, Ajith; Corchado, Emilio; Nostradamus: Modern Methods of Prediction, Modeling and Analysis of Nonlinear Systems

    2013-01-01

    This proceeding book of Nostradamus conference (http://nostradamus-conference.org) contains accepted papers presented at this event in 2012. Nostradamus conference was held in the one of the biggest and historic city of Ostrava (the Czech Republic, http://www.ostrava.cz/en), in September 2012. Conference topics are focused on classical as well as modern methods for prediction of dynamical systems with applications in science, engineering and economy. Topics are (but not limited to): prediction by classical and novel methods, predictive control, deterministic chaos and its control, complex systems, modelling and prediction of its dynamics and much more.

  16. Crowdsourcing awareness: exploration of the ovarian cancer knowledge gap through Amazon Mechanical Turk.

    Directory of Open Access Journals (Sweden)

    Rebecca R Carter

    Full Text Available BACKGROUND: Ovarian cancer is the most lethal gynecologic disease in the United States, with more women dying from this cancer than all gynecological cancers combined. Ovarian cancer has been termed the "silent killer" because some patients do not show clear symptoms at an early stage. Currently, there is a lack of approved and effective early diagnostic tools for ovarian cancer. There is also an apparent severe knowledge gap of ovarian cancer in general and of its indicative symptoms among both public and many health professionals. These factors have significantly contributed to the late stage diagnosis of most ovarian cancer patients (63% are diagnosed at Stage III or above, where the 5-year survival rate is less than 30%. The paucity of knowledge concerning ovarian cancer in the United States is unknown. METHODS: The present investigation examined current public awareness and knowledge about ovarian cancer. The study implemented design strategies to develop an unbiased survey with quality control measures, including the modern application of multiple statistical analyses. The survey assessed a reasonable proxy of the US population by crowdsourcing participants through the online task marketplace Amazon Mechanical Turk, at a highly condensed rate of cost and time compared to traditional recruitment methods. CONCLUSION: Knowledge of ovarian cancer was compared to that of breast cancer using repeated measures, bias control and other quality control measures in the survey design. Analyses included multinomial logistic regression and categorical data analysis procedures such as correspondence analysis, among other statistics. We confirmed the relatively poor public knowledge of ovarian cancer among the US population. The simple, yet novel design should set an example for designing surveys to obtain quality data via Amazon Mechanical Turk with the associated analyses.

  17. Exercise and Prostate Cancer: Evidence and Proposed Mechanisms for Disease Modification.

    Science.gov (United States)

    Hayes, Brian D; Brady, Lauren; Pollak, Michael; Finn, Stephen P

    2016-09-01

    Exercise has many potential benefits in relation to cancer. Apart from primary prevention, these include improvement of nonspecific cancer-related symptoms, amelioration of symptoms and cardiovascular risk factors related to cancer treatment, and improvements in various quality-of-life-related factors. Increasing evidence also points toward improved cancer-free and overall survival in cancer patients who undertake regular exercise, findings which should encourage further research in this area. Obesity is known to be associated with a proinflammatory, prothrombotic humoral milieu, which may promote aggressiveness in prostate cancer through interactions with NK-cell-mediated killing of circulating tumor cells, through platelet-circulating tumor cell interactions, and through alterations in adipokine and myokine profile among others. Physical activity reduces levels of systemic inflammatory mediators and so exercise may represent an accessible and cost-effective means of ameliorating the proinflammatory effects of obesity in cancer patients. This review outlines the evidence for the benefits of exercise in these patients, focusing on prostate cancer, and delineates current theories of the underlying biological mechanisms. Cancer Epidemiol Biomarkers Prev; 25(9); 1281-8. ©2016 AACR. ©2016 American Association for Cancer Research.

  18. Comparative membrane proteomics analyses of breast cancer cell lines to understand the molecular mechanism of breast cancer brain metastasis.

    Science.gov (United States)

    Peng, Wenjing; Zhang, Yu; Zhu, Rui; Mechref, Yehia

    2017-09-01

    Breast cancer is the leading type of cancer in women. Breast cancer brain metastasis is currently considered an issue of concern among breast cancer patients. Membrane proteins play important roles in breast cancer brain metastasis, involving cell adhesion and penetration of blood-brain barrier. To understand the mechanism of breast cancer brain metastasis, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed in conjunction with enrichment of membrane proteins to analyze the proteomes from five different breast cancer and a brain cancer cell lines. Quantitative proteomic data of all cell lines were compared with MDA-MB-231BR which is a brain seeking breast cancer cell line, thus representing brain metastasis characteristics. Label-free proteomics of the six cell lines facilitates the identification of 1238 proteins and the quantification of 899 proteins of which more than 70% were membrane proteins. Unsupervised principal component analysis (PCA) of the label-free proteomics data resulted in a distinct clustering of cell lines, suggesting quantitative differences in the expression of several proteins among the different cell lines. Unique protein expressions in 231BR were observed for 28 proteins. The up-regulation of STAU1, AT1B3, NPM1, hnRNP Q, and hnRNP K and the down-regulation of TUBB4B and TUBB5 were noted in 231BR relative to 231 (precursor cell lines from which 231BR is derived). These proteins might contribute to the breast cancer brain metastasis. Ingenuity pathway analysis (IPA) supported the great brain metastatic propensity of 231BR and suggested the importance of the up-regulation of integrin proteins and down-regulation of EPHA2 in brain metastasis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Tylosis with oesophageal cancer: Diagnosis, management and molecular mechanisms.

    Science.gov (United States)

    Ellis, Anthony; Risk, Janet M; Maruthappu, Thiviyani; Kelsell, David P

    2015-09-29

    Tylosis (hyperkeratosis palmaris et plantaris) is characterised by focal thickening of the skin of the hands and feet and is associated with a very high lifetime risk of developing squamous cell carcinoma of the oesophagus. This risk has been calculated to be 95% at the age of 65 in one large family, however the frequency of the disorder in the general population is not known and is likely to be less than one in 1,000,000. Oesophageal lesions appear as small (2-5 mm), white, polyploid lesions dotted throughout the oesophagus and oral leukokeratosis has also been described. Although symptoms of oesophageal cancer can include dysphagia, odynophagia, anorexia and weight loss, there may be an absence of symptoms in early disease, highlighting the importance of endoscopic surveillance in these patients. Oesophageal cancer associated with tylosis usually presents in middle to late life (from mid-fifties onwards) and shows no earlier development than the sporadic form of the disease. Tylosis with oesophageal cancer is inherited as an autosomal dominant trait with complete penetrance of the cutaneous features, usually by 7 to 8 years of age but can present as late as puberty. Mutations in RHBDF2 located on 17q25.1 have recently been found to be causative. A diagnosis of tylosis with oesophageal cancer is made on the basis of a positive family history, characteristic clinical features, including cutaneous and oesophageal lesions, and genetic analysis for mutations in RHBDF2. The key management goal is surveillance for early detection and treatment of oesophageal dysplasia. Surveillance includes annual gastroscopy with biopsy of any suspicious lesion together with quadratic biopsies from the upper, middle and lower oesophagus. This is coupled with dietary and lifestyle modification advice and symptom education. Symptomatic management of the palmoplantar keratoderma includes regular application of emollients, specialist footwear and early treatment of fissures and super

  20. Mechanisms of Reactive Stroma-Induced Tumorigenesis in Prostate Cancer

    Science.gov (United States)

    2016-11-01

    coculture Epithelial cell (LNCaP cell engineered to express active TGF- 1) Stromal cell (hP-MSC) Porous membrane ( Cell culture plate insert) Cell culture...myofibroblasts with a reactive stroma signature. (A) Schematic diagram of 3D organoid coculture. LNCaP cells engineered to express active TGF-β1 were cultured...factors in regulating the biology of myofibroblast progenitor cells in the tumor microenvironment of prostate cancer. Task 1 used novel 3D organoid

  1. Mechanism of Selenium Chemoprevention and Therapy in Prostate Cancer

    Science.gov (United States)

    2010-11-01

    Cancer. Edited by Tindall D and Mohler J. Springer Science and Business Media and Humana Press, 2009 Abstract: 1. Lee SO, Chun JY, Nadiminty...antiproliferative effects of selenium, including antioxidant effects, enhance- ment of immune function, stimulation of apoptosis, and induction of cell...were obtained from the American Type Culture Collection (Manassas, VA) and maintained in RPMI 1640 supple- mented with 10% fetal bovine serum. The

  2. Molecular Mechanisms in Compromised Endothelial Barrier during Breast Cancer Metastasis

    Science.gov (United States)

    2009-03-01

    those working in breast cancer, but for any investigators who need to expand their FRET imaging repertoire to study dynamic signaling, protein ...processing, protein - protein interactions as well as protein conformational changes in three dimension either in single cells or in thicker tissue specimens...Obtain FRET-based biosensors for MLCK, Rho, and Rac [accomplished] • Standardizing simultaneous CFP /YFP FRET imaging techniques [accomplished

  3. Molecular Mechanism by Which Retinoids Prevent Breast Cancer Development

    Science.gov (United States)

    2007-06-01

    204078_at synaptonemal complex protein SC65 -2.9 203881_s_at dystrophin ( muscular dystrophy , Duchenne and Becker types) -2.88 209717_at ecotropic viral...for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection...and therapeutic role in cervical cancer. Lancet Oncol. 2005 Sep;6(9):712-20. Review . 4. De Luca LM, Darwiche N, Celli G, Kosa K, Jones C, Ross S

  4. Platinum and taxane chemoresistance mechanisms in ovarian cancer cells

    OpenAIRE

    Busschots, Steven

    2015-01-01

    Ovarian cancer is the leading cause of death from a gynaecological malignancy, typically presenting at late stage due to difficult diagnosis and lack of suitable screening tools. The standard treatment of combination taxol/carboplatin chemotherapy often fails and patients relapse with chemoresistant disease. Patients have a median survival of two years following recurrence and will all eventually die from their disease. Patients with BRCA1 deficiencies have an increased lifetime risk of appro...

  5. Molecular mechanisms and theranostic potential of miRNAs in drug resistance of gastric cancer.

    Science.gov (United States)

    Yang, Wanli; Ma, Jiaojiao; Zhou, Wei; Cao, Bo; Zhou, Xin; Yang, Zhiping; Zhang, Hongwei; Zhao, Qingchuan; Fan, Daiming; Hong, Liu

    2017-11-01

    Systemic chemotherapy is a curative approach to inhibit gastric cancer cells proliferation. Despite the great progress in anti-cancer treatment achieved during the last decades, drug resistance and treatment refractoriness still extensively persists. Recently, accumulating studies have highlighted the role of miRNAs in drug resistance of gastric cancers by modulating some drug resistance-related proteins and genes expression. Pre-clinical reports indicate that miRNAs might serve as ideal biomarkers and potential targets, thus holding great promise for developing targeted therapy and personalized treatment for the patients with gastric cancer. Areas covered: This review provide a comprehensive overview of the current advances of miRNAs and molecular mechanisms underlying miRNA-mediated drug resistance in gastric cancer. We particularly focus on the potential values of drug resistance-related miRNAs as biomarkers and novel targets in gastric cancer therapy and envisage the future research developments of these miRNAs and challenges in translating the new findings into clinical applications. Expert opinion: Although the concrete mechanisms of miRNAs in drug resistance of gastric cancer have not been fully clarified, miRNA may be a promising theranostic approach. Further studies are still needed to facilitate the clinical applications of miRNAs in drug resistant gastric cancer.

  6. Multiple Mechanisms of Anti-Cancer Effects Exerted by Astaxanthin

    Directory of Open Access Journals (Sweden)

    Li Zhang

    2015-07-01

    Full Text Available Astaxanthin (ATX is a xanthophyll carotenoid which has been approved by the United States Food and Drug Administration (USFDA as food colorant in animal and fish feed. It is widely found in algae and aquatic animals and has powerful anti-oxidative activity. Previous studies have revealed that ATX, with its anti-oxidative property, is beneficial as a therapeutic agent for various diseases without any side effects or toxicity. In addition, ATX also shows preclinical anti-tumor efficacy both in vivo and in vitro in various cancer models. Several researches have deciphered that ATX exerts its anti-proliferative, anti-apoptosis and anti-invasion influence via different molecules and pathways including signal transducer and activator of transcription 3 (STAT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and peroxisome proliferator-activated receptor gamma (PPARγ. Hence, ATX shows great promise as chemotherapeutic agents in cancer. Here, we review the rapidly advancing field of ATX in cancer therapy as well as some molecular targets of ATX.

  7. Multiple Mechanisms of Anti-Cancer Effects Exerted by Astaxanthin.

    Science.gov (United States)

    Zhang, Li; Wang, Handong

    2015-07-14

    Astaxanthin (ATX) is a xanthophyll carotenoid which has been approved by the United States Food and Drug Administration (USFDA) as food colorant in animal and fish feed. It is widely found in algae and aquatic animals and has powerful anti-oxidative activity. Previous studies have revealed that ATX, with its anti-oxidative property, is beneficial as a therapeutic agent for various diseases without any side effects or toxicity. In addition, ATX also shows preclinical anti-tumor efficacy both in vivo and in vitro in various cancer models. Several researches have deciphered that ATX exerts its anti-proliferative, anti-apoptosis and anti-invasion influence via different molecules and pathways including signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and peroxisome proliferator-activated receptor gamma (PPARγ). Hence, ATX shows great promise as chemotherapeutic agents in cancer. Here, we review the rapidly advancing field of ATX in cancer therapy as well as some molecular targets of ATX.

  8. Mechanisms and Targets Involved in Dissemination of Ovarian Cancer

    Science.gov (United States)

    H. WEIDLE, ULRICH; BIRZELE, FABIAN; KOLLMORGEN, GWENDLYN; RUEGER, RÜDIGER

    2016-01-01

    Ovarian carcinoma is associated with the highest death rate of all gynecological tumors. On one hand, its aggressiveness is based on the rapid dissemination of ovarian cancer cells to the peritoneum, the omentum, and organs located in the peritoneal cavity, and on the other hand, on the rapid development of resistance to chemotherapeutic agents. In this review, we focus on the metastatic process of ovarian cancer, which involves dissemination of, homing to and growth of tumor cells in distant organs, and describe promising molecular targets for possible therapeutic intervention. We provide an outline of the interaction of ovarian cancer cells with the microenvironment such as mesothelial cells, adipocytes, fibroblasts, endothelial cells, and other stromal components in the context of approaches for therapeutic interference with dissemination. The targets described in this review are discussed with respect to their validity as drivers of metastasis and to the availability of suitable efficient agents for their blockage, such as small molecules, monoclonal antibodies or antibody conjugates as emerging tools to manage this disease. PMID:27807064

  9. Cellular and molecular mechanisms underlying alcohol-induced aggressiveness of breast cancer.

    Science.gov (United States)

    Wang, Yongchao; Xu, Mei; Ke, Zun-Ji; Luo, Jia

    2017-01-01

    Breast cancer is a leading cause of morbidity and mortality in women. Both Epidemiological and experimental studies indicate a positive correlation between alcohol consumption and the risk of breast cancer. While alcohol exposure may promote the carcinogenesis or onset of breast cancer, it may as well enhance the progression and aggressiveness of existing mammary tumors. Recent progress in this line of research suggests that alcohol exposure is associated with invasive breast cancer and promotes the growth and metastasis of mammary tumors. There are multiple potential mechanisms involved in alcohol-stimulated progression and aggressiveness of breast cancer. Alcohol may increase the mobility of cancer cells by inducing cytoskeleton reorganization and enhancing the cancer cell invasion by causing degradation and reconstruction of the extracellular matrix (ECM). Moreover, alcohol may promote the epithelial-mesenchymal transition (EMT), a hallmark of malignancy, and impair endothelial integrity, thereby increasing the dissemination of breast cancer cells and facilitating metastasis. Furthermore, alcohol may stimulate tumor angiogenesis through the activation of cytokines and chemokines which promotes tumor growth. Additionally, alcohol may increase the cancer stem cell population which affects neoplastic cell behavior, aggressiveness, and the therapeutic response. Alcohol can be metabolized in the mammary tissues and breast cancer cells which produces reactive oxygen species (ROS), causing oxidative stress. Recent studies suggest that the epidermal growth factor receptor (EGFR) family, particularly ErbB2 (a member of this family), is involved in alcohol-mediated tumor promotion. Breast cancer cells or mammary epithelial cells over-expressing ErbB2 are more sensitive to alcohol's tumor promoting effects. There is considerable cross-talk between oxidative stress and EGFR/ErbB2 signaling. This review further discusses how the interaction between oxidative stress and EGFR

  10. Effect of process control agent (PCA) on the characteristics of mechanically alloyed Ti-Mg powders [Conference paper

    CSIR Research Space (South Africa)

    Machio, Christopher N

    2010-10-01

    Full Text Available in the milling process. 1.0 Introduction: The production of alloy powders through mechanical milling has advantages such as increasing solid solubility limits. Alloying occurs through repeated cold welding and fracturing resulting from impacts from... the milling media. The fracturing process exposes new surfaces over which atomic diffusion occurs leading to alloying. Mechanical alloying has been applied to titanium (Ti) and magnesium (Mg) powders in order to produce Ti-Mg alloy powders. Ti-Mg alloys...

  11. Breast Reconstruction Affects Coping Mechanisms in Breast Cancer Survivors

    National Research Council Canada - National Science Library

    Blossom Lake; Heidi R Fuller; Sarah Rastall; Tamoor Usman

    2017-01-01

    .... Whilst it is clear that factors such as age at diagnosis, social support and ethnicity can influence coping mechanisms, there is currently no information about whether breast reconstruction changes...

  12. Mechanisms for the induction of gastric cancer by Helicobacter pylori infection: aberrant DNA methylation pathway.

    Science.gov (United States)

    Maeda, Masahiro; Moro, Hiroshi; Ushijima, Toshikazu

    2017-03-01

    Multiple pathogenic mechanisms by which Helicobacter pylori infection induces gastric cancer have been established in the last two decades. In particular, aberrant DNA methylation is induced in multiple driver genes, which inactivates them. Methylation profiles in gastric cancer are associated with specific subtypes, such as microsatellite instability. Recent comprehensive and integrated analyses showed that many cancer-related pathways are more frequently altered by aberrant DNA methylation than by mutations. Aberrant DNA methylation can even be present in noncancerous gastric mucosae, producing an "epigenetic field for cancerization." Mechanistically, H. pylori-induced chronic inflammation, but not H. pylori itself, plays a direct role in the induction of aberrant DNA methylation. The expression of three inflammation-related genes, Il1b, Nos2, and Tnf, is highly associated with the induction of aberrant DNA methylation. Importantly, the degree of accumulated aberrant DNA methylation is strongly correlated with gastric cancer risk. A recent multicenter prospective cohort study demonstrated the utility of epigenetic cancer risk diagnosis for metachronous gastric cancer. Suppression of aberrant DNA methylation by a demethylating agent was shown to inhibit gastric cancer development in an animal model. Induction of aberrant DNA methylation is the major pathway by which H. pylori infection induces gastric cancer, and this can be utilized for translational opportunities.

  13. Fatigue mechanisms in patients with cancer: effects of tumor necrosis factor and exercise on skeletal muscle

    Science.gov (United States)

    St Pierre, B. A.; Kasper, C. E.; Lindsey, A. M.

    1992-01-01

    Fatigue is a common adverse effect of cancer and its therapy. However, the specific mechanisms underlying cancer fatigue are unclear. One physiologic mechanism may involve changes in skeletal muscle protein stores or metabolite concentration. A reduction in skeletal muscle protein stores may result from endogenous tumor necrosis factor (TNF) or from TNF administered as antineoplastic therapy. This muscle wasting would require patients to exert an unusually high amount of effort to generate adequate contractile force during exercise performance or during extended periods of sitting or standing. This additional effort could result in the onset of fatigue. Additionally, cancer fatigue may develop or become exacerbated during exercise as a consequence of changes in the concentration of skeletal muscle metabolites. These biochemical alterations may interfere with force that is produced by the muscle contractile proteins. These physiologic changes may play a role in the decision to include exercise in the rehabilitation plans of patients with cancer. They also may affect ideas about fatigue.

  14. Novel flavonoids as anti-cancer agents: mechanisms of action and promise for their potential application in breast cancer.

    Science.gov (United States)

    Martinez-Perez, Carlos; Ward, Carol; Cook, Graeme; Mullen, Peter; McPhail, Donald; Harrison, David J; Langdon, Simon P

    2014-08-01

    Flavonoids are a large group of ubiquitous polyphenolic secondary metabolites in plants with a wide range of properties, including a widely reported anti-cancer effect. The present review focuses on the different known mechanisms partaking in said anti-tumour effects, with particular emphasis on breast cancer. Their structure and reactivity allows flavonoids to work as antioxidant agents and phyto-oestrogens, modulating oestrogen signalling and metabolism to induce an overall anti-proliferative response. Other effects include the ability of flavonoids to modulate the CYP1 (cytochrome P450 1) and ABC (ATP-binding cassette) protein families, involved in carcinogenesis and drug delivery respectively. They can also induce apoptosis and cell cycle arrest and regulate other signalling pathways involved in the development and progression of cancer. In conclusion, there is accumulating evidence on the versatility of flavonoids and the numerous activities contributing to their anti-tumour effect. The complex, yet effective, mechanism of action of flavonoids, together with their interesting pharmacological properties, is the basis for their potential application in breast and other cancers. This rationale has led to the current interest in the application of flavonoids, including clinical trials currently underway and the development of novel flavonoids with improved properties, which hold great promise for tackling breast cancer.

  15. The Role and Mechanism of Epithelial-to-Mesenchymal Transition in Prostate Cancer Progression

    Science.gov (United States)

    Lo, U-Ging; Lee, Cheng-Fan; Lee, Ming-Shyue; Hsieh, Jer-Tsong

    2017-01-01

    In prostate cancer (PCa), similar to many other cancers, distant organ metastasis symbolizes the beginning of the end disease, which eventually leads to cancer death. Many mechanisms have been identified in this process that can be rationalized into targeted therapy. Among them, epithelial-to-mesenchymal transition (EMT) is originally characterized as a critical step for cell trans-differentiation during embryo development and now recognized in promoting cancer cells invasiveness because of high mobility and migratory abilities of mesenchymal cells once converted from carcinoma cells. Nevertheless, the underlying pathways leading to EMT appear to be very diverse in different cancer types, which certainly represent a challenge for developing effective intervention. In this article, we have carefully reviewed the key factors involved in EMT of PCa with clinical correlation in hope to facilitate the development of new therapeutic strategy that is expected to reduce the disease mortality. PMID:28973968

  16. The mechanisms of genetically modified vaccinia viruses for the treatment of cancer.

    Science.gov (United States)

    Jefferson, Artrish; Cadet, Valerie E; Hielscher, Abigail

    2015-09-01

    The use of oncolytic viruses for the treatment of cancer is an emerging field of cancer research and therapy. Oncolytic viruses are designed to induce tumor specific immunity while replicating selectively within cancer cells to cause lysis of the tumor cells. While there are several forms of oncolytic viruses, the use of vaccinia viruses for oncolysis may be more beneficial than other forms of oncolytic viruses. For example, vaccinia viruses have been shown to exert their anti-tumor effects through genetic engineering strategies which enhance their therapeutic efficacy. This paper will address some of the most common forms of genetically modified vaccinia viruses and will explore the mechanisms whereby they selectively target, enter and destroy cancer cells. Furthermore, this review will highlight how vaccinia viruses activate host immune responses against cancer cells and will address clinical trials evaluating the tumor-directed and killing efficacy of these viruses against solid tumors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

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

  18. Roles of Ubiquitination and SUMOylation on Prostate Cancer: Mechanisms and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Zhenbang Chen

    2015-02-01

    Full Text Available The initiation and progression of human prostate cancer are highly associated with aberrant dysregulations of tumor suppressors and proto-oncogenes. Despite that deletions and mutations of tumor suppressors and aberrant elevations of oncogenes at the genetic level are reported to cause cancers, emerging evidence has revealed that cancer progression is largely regulated by posttranslational modifications (PTMs and epigenetic alterations. PTMs play critical roles in gene regulation, cellular functions, tissue development, diseases, malignant progression and drug resistance. Recent discoveries demonstrate that ubiquitination and SUMOylation are complicated but highly-regulated PTMs, and make essential contributions to diseases and cancers by regulation of key factors and signaling pathways. Ubiquitination and SUMOylation pathways can be differentially modulated under various stimuli or stresses in order to produce the sustained oncogenic potentials. In this review, we discuss some new insights about molecular mechanisms on ubiquitination and SUMOylation, their associations with diseases, oncogenic impact on prostate cancer (PCa and clinical implications for PCa treatment.

  19. Molecular mechanisms for chemoprevention of colorectal cancer by natural dietary compounds.

    Science.gov (United States)

    Pan, Min-Hsiung; Lai, Ching-Shu; Wu, Jia-Ching; Ho, Chi-Tang

    2011-01-01

    Colorectal cancer is one of the major causes of cancer-related mortality in both men and women worldwide. This review focuses on preventing the initiation and promotion of neoplastic growth in colorectal cancer, particularly with natural dietary compounds. Chemoprevention is defined as the use of natural dietary compounds and/or synthetic substances that can delay, prevent, or even reverse the development of adenomas, as well as the progression from adenoma to carcinoma. The molecular mechanisms of their chemopreventive action are associated with the modulation of signaling cascades, gene expressions involved in the regulation of cell proliferation, differentiation, and apoptosis and the suppression of chronic inflammation, metastasis, and angiogenesis. Here, we summarize the currently known targets and signaling pathways whereby natural dietary compounds interfere with the development of colorectal cancer, and thus providing evidence for these substances in colonic cancer chemopreventive action. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. New insights into Vinca alkaloids resistance mechanism and circumvention in lung cancer.

    Science.gov (United States)

    Zhang, Ying; Yang, Shao-Hui; Guo, Xiu-Li

    2017-10-13

    Nowadays, lung cancer, as a health problem in worldwide, has high mortality both in men and women. Despite advances in diagnosis and surgical techniques of lung cancer in recent decades, chemotherapy is still a fundamentally and extensively useful strategy. Vinca alkaloids are a class of important and widely used drugs in the treatment of lung cancer, targeting on the Vinca binding site at the exterior of microtubule plus ends. Either intrinsic or acquired resistance to chemotherapy of Vinca alkaloids has been a major obstacle to the treatment of lung cancer, which arose great interests in studies of understanding and overcoming resistance. In this review, we focused on the application and resistance mechanisms of the Vinca alkaloids such as vinblastine, vincristine, vinorelbine and vinflunine in lung cancer. We reviewed characteristic resistance mechanisms in lung cancer including over-expression of ATP-binding cassette (ABC) transporters P-glycoprotein and structural, functional or expression alterations of β-tubulin (βII, βIII, βIV) which may devote to the development of acquired resistance to the Vinca alkaloids; multidrug-resistance proteins (MRP1, MRP2, MRP3) and RLIP76 protein have also been identified that probably play a significant role in intrinsic resistance. Lung resistance-related protein (LRP) is contributed to lung cancer therapy resistance, but is not deal with the Vinca alkaloids resistance in lung cancer. Understanding the principle of the Vinca alkaloids in clinical application and mechanisms of drug resistance will support individualized lung cancer therapy and improve future therapies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Linc-ROR confers gemcitabine resistance to pancreatic cancer cells via inducing autophagy and modulating the miR-124/PTBP1/PKM2 axis.

    Science.gov (United States)

    Li, Chenggang; Zhao, Zhiming; Zhou, Zhipeng; Liu, Rong

    2016-12-01

    In this study, we investigated the regulation of linc-ROR on autophagy and gemcitabine resistance of pancreatic cancer cells and further studied the underlying involvement of the miR-124/PTBP1/PKM2 axis in this regulation. Pancreatic cancer cell lines PANC-1 and MIAPaCa-2 cells were used as in vitro model. Autophagy was assessed by western blot of LC3 I/II and observation GFP-LC3 puncta. Cell viability was examined using CCK-8 assay. Cell apoptosis was examined by flow cytometric analysis of Annexin V/PI staining. QRT-PCR, RNA fluorescence in situ hybridization and dual luciferase assay were used to study the expression and the binding between linc-ROR and miR-124. Linc-ROR siRNA significantly sensitized PANC-1 and MIAPaCa-2 cells to gemcitabine, while linc-ROR overexpression significantly reduced the sensitivity. Linc-ROR knockdown reduced basal autophagy, while linc-ROR overexpression markedly increased basal autophagy in the cells. Linc-ROR siRNA showed similar effect as 3-MA on enhancing gemcitabine-induced cell apoptosis and also reduced PKM2 expression. MiR-124 overexpression restored PKM1 and reduced PKM2 levels in the cells. In addition, miR-124 mimics also alleviated autophagy in pancreatic cancer cells. Both miR-124 mimics and PKM2 siRNA enhanced gemcitabine-induced cell apoptosis. In both pancreatic cell lines and PADC tissues, linc-ROR is negatively correlated with miR-124 expression. In addition, dual luciferase assay verified two 8mer binding sites between miR-124 and linc-ROR. Linc-ROR confers gemcitabine resistance to pancreatic cancer cells at least partly via inducing autophagy. There is a linc-ROR/miR-124/PTBP1/PKM2 axis involved in regulation of gemcitabine resistance in pancreatic cancer cells.

  2. Natural Products as Promising Antitumoral Agents in Breast Cancer: Mechanisms of Action and Molecular Targets.

    Science.gov (United States)

    Bonofiglio, Daniela; Giordano, Cinzia; De Amicis, Francesca; Lanzino, Marilena; Andò, Sebastiano

    2016-01-01

    Extensive research over the past several decades has identified numerous dietary and phytochemical compounds that have chemopreventive potential and could represent an important source of anti-cancer lead molecules. In this scenario several nutritional factors have attracted considerable attention as modifiable risk factor in the prevention of breast cancer, the most frequently diagnosed cancer and a major cause of death among women worldwide. There is an immediate need for more effective and less toxic therapeutic and preventive strategies for breast cancers able also to counteract the recurrent phenomenon of resistance to hormonal and targeted therapy that represent the first-line treatment in the management of breast cancer patients. The present review focuses on chemopreventive and anti-cancer activities of different bioactive compounds obtained from dietary sources such as Omega-3 fatty acids, naturally present in fish, Resveratrol (3,5,40-trihydroxy-transstilbene), a phytoalexin found in grapes and Epigallocatechin Gallate, a polyphenolic compound found in green tea, or purified from medicinal plant (Oldenlandia Diffusa) and fruits (Ziziphus Jujube) highlighting their potential use in breast cancer treatment. Herein, we discuss the molecular mechanisms by which the bioactive compounds can inhibit carcinogenesis by regulating antioxidant enzyme activities, and inducing antiproliferative and apoptotic effects in different breast cancer cell lines. Understanding the mechanism of action of dietary compounds or traditionally used herbs having potential preventive and therapeutic effects on cancer may provide a rationale for further translational studies. This review emphasizes the importance, in the next future, of a proper scientific validation of these natural bioactive compounds for clinical use in the therapeutic portfolio for breast cancer.

  3. How changes in extracellular matrix mechanics and gene expression variability might combine to drive cancer progression.

    Directory of Open Access Journals (Sweden)

    Justin Werfel

    Full Text Available Changes in extracellular matrix (ECM structure or mechanics can actively drive cancer progression; however, the underlying mechanism remains unknown. Here we explore whether this process could be mediated by changes in cell shape that lead to increases in genetic noise, given that both factors have been independently shown to alter gene expression and induce cell fate switching. We do this using a computer simulation model that explores the impact of physical changes in the tissue microenvironment under conditions in which physical deformation of cells increases gene expression variability among genetically identical cells. The model reveals that cancerous tissue growth can be driven by physical changes in the microenvironment: when increases in cell shape variability due to growth-dependent increases in cell packing density enhance gene expression variation, heterogeneous autonomous growth and further structural disorganization can result, thereby driving cancer progression via positive feedback. The model parameters that led to this prediction are consistent with experimental measurements of mammary tissues that spontaneously undergo cancer progression in transgenic C3(1-SV40Tag female mice, which exhibit enhanced stiffness of mammary ducts, as well as progressive increases in variability of cell-cell relations and associated cell shape changes. These results demonstrate the potential for physical changes in the tissue microenvironment (e.g., altered ECM mechanics to induce a cancerous phenotype or accelerate cancer progression in a clonal population through local changes in cell geometry and increased phenotypic variability, even in the absence of gene mutation.

  4. Molecular mechanisms of heptaplatin effective against cisplatin-resistant cancer cell lines: less involvement of metallothionein

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    Moon Sung-Pyo

    2004-10-01

    Full Text Available Abstract Background Heptaplatin is a new platinum derivative with anticancer activity against various cancer cell lines, including cisplatin-resistant cancer cell lines (Cancer Chemother Pharmacol 1995; 35: 441. Methods Molecular mechanisms of heptaplatin effective against cisplatin-resistant cancer cell lines has been investigated in connection with metallothionein (MT. Cytotoxicity was determined by an MTT assay. MT mRNA, was determined by RT-PCR assay. Transfection study was carried out to examine the function of MT. Results Of various gastric cancer cell lines, SNU-638 and SNU-601 showed the highest and lowest levels of MT mRNA, respectively, showing 80-fold difference. The IC50 values of SNU-638 to cisplatin, carboplatin and heptaplatin were 11.2-fold, 5.1-fold and 2.0-fold greater than those of SNU-601, respectively. Heptaplatin was more effective against cisplatin-resistant and MT-transfected gastric cancer sublines than cisplatin or carboplatin was. In addition, heptaplatin attenuated cadmium, but not zinc, induction of MT. Conclusion These results indicate that molecular mechanisms of heptaplatin effective against cisplatin-resistant gastric cancer sublines is at least in part due to the less involvement of MT in heptaplatin resistance as well as its attenuation of MT induction.

  5. Empowerment beliefs and intention to uptake cervical cancer screening: three psychosocial mediating mechanisms.

    Science.gov (United States)

    Luszczynska, Aleksandra; Durawa, Alicja B; Scholz, Urte; Knoll, Nina

    2012-01-01

    Three studies tested if the associations between women's empowerment beliefs and intentions to attend cervical cancer screening could be explained by mediating psychological mechanisms: control-related beliefs, well being-related beliefs, and beliefs and evaluations referring to social functioning. Data were collected from January to March 2011 in the rural and urban areas across regions of Poland. Study 1 (N = 386) indicated that women with strong empowerment harbored stronger self-efficacy and beliefs that screening participation would make them feel in control of their own health and body. These two types of cognitions were, in turn, associated with stronger cervical cancer screening intentions. Results of Study 2 (N = 527) confirmed three significant well being-related mediators in the relationship between empowerment beliefs and cervical cancer screening: perceived benefits of screening related to well being, appearance satisfaction, discomfort- and shame-related barriers for screening. Finally, Study 3 (N = 424) showed that empowerment enabled receiving higher social support for cervical cancer screening, promoted perceiving fewer barriers for cervical cancer screening-related communication and more social benefits of engaging in cervical cancer screening. Support for cervical cancer screening, social barriers, and benefits were, in turn, related to screening intentions. Across the studies similar shares of intention variance were explained, and thus the hypothesized mediating mechanisms may have similar explanatory power.

  6. Anticancer effects of lactoferrin: underlying mechanisms and future trends in cancer therapy.

    Science.gov (United States)

    Zhang, Yunlei; Lima, Cristovao F; Rodrigues, Ligia R

    2014-12-01

    Lactoferrin has been widely studied over the last 70 years, and its role in diverse biological functions is now well known and generally accepted by the scientific community. Usually, alterations of the lactoferrin gene in cells are associated with an increased incidence of cancer. Several studies suggest that exogenous treatment with lactoferrin and its derivatives can efficiently inhibit the growth of tumors and reduce susceptibility to cancer. None of these studies, however, reported a consistent outcome with regard to the mechanisms underlying the anticancer effects of lactoferrin. In this review, the association of lactoferrin with cancer is thoroughly discussed, from lactoferrin gene expression to the potential use of lactoferrin in cancer therapy. Lactoferrin cytotoxicity against several cancers is reported to occur in distinct ways under different conditions, namely by cell membrane disruption, apoptosis induction, cell cycle arrest, and cell immunoreaction. Based on these mechanisms, new strategies to improve the anticancer effects of the lactoferrin protein and/or its derivatives are proposed. The potential for lactoferrin in the field of cancer research (including as a chemotherapeutic agent in cancer therapy) is also discussed. © 2014 International Life Sciences Institute.

  7. Mechanical stress as the common denominator between chronic inflammation, cancer and Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Marcel eLevy Nogueira

    2015-09-01

    Full Text Available The pathogenesis of common diseases such as Alzheimer’s disease (AD and cancer are currently poorly understood. Inflammation is a common risk factor for cancer and AD. Recent data, provided by our group and from others, demonstrate that increased pressure and inflammation are synonymous. There is a continuous increase in pressure from inflammation to fibrosis and then cancer. This in line with the numerous papers reporting high interstitial pressure in cancer. But most authors focus on the role of pressure in the lack of delivery of chemotherapy in the center of the tumor. Pressure may also be a key factor in carcinogenesis. Increased pressure is responsible for oncogene activation and cytokine secretion. Accumulation of mechanical stress plays a key role in the development of diseases of old age such as cardiomyopathy, atherosclerosis and osteoarthritis. Growing evidence suggest also a possible link between mechanical stress in the pathogenesis of AD. The aim of this review is to describe environmental and endogenous mechanical factors possibly playing a pivotal role in the mechanism of chronic inflammation, AD and cancer.

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

    Directory of Open Access Journals (Sweden)

    Anna Jarosz

    2016-01-01

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

  9. Gordon Research Conference on Genetic Toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Project Director Penelope Jeggo

    2003-02-15

    Genetic toxicology represents a study of the genetic damage that a cell can incur, the agents that induce such damage, the damage response mechanisms available to cells and organisms, and the potential consequences of such damage. Genotoxic agents are abundant in the environment and are also induced endogenously. The consequences of such damage can include carcinogenesis and teratogenesis. An understanding of genetic toxicology is essential to carry out risk evaluations of the impact of genotoxic agents and to assess how individual genetic differences influence the response to genotoxic damage. In recent years, the importance of maintaining genomic stability has become increasingly recognized, in part by the realization that failure of the damage response mechanisms underlies many, if not all, cancer incidence. The importance of these mechanisms is also underscored by their remarkable conservation between species, allowing the study of simple organisms to provide significant input into our understanding of the underlying mechanisms. It has also become clear that the damage response mechanisms interface closely with other aspects of cellular metabolism including replication, transcription and cell cycle regulation. Moreover, defects in many of these mechanisms, as observed for example in ataxia telangiectasia patients, confer disorders with associated developmental abnormalities demonstrating their essential roles during growth and development. In short, while a decade ago, a study of the impact of DNA damage was seen as a compartmentalized area of cellular research, it is now appreciated to lie at the centre of an array of cellular responses of crucial importance to human health. Consequently, this has become a dynamic and rapidly advancing area of research. The Genetic Toxicology Gordon Research Conference is biannual with an evolving change in the emphasis of the meetings. From evaluating the nature of genotoxic chemicals, which lay at the centre of the early

  10. Effects of Honey and Its Mechanisms of Action on the Development and Progression of Cancer

    Directory of Open Access Journals (Sweden)

    Omotayo O. Erejuwa

    2014-02-01

    Full Text Available Honey is a natural product known for its varied biological or pharmacological activities—ranging from anti-inflammatory, antioxidant, antibacterial, antihypertensive to hypoglycemic effects. This review article focuses on the role of honey in modulating the development and progression of tumors or cancers. It reviews available evidence (some of which is very recent with regards to the antimetastatic, antiproliferative and anticancer effects of honey in various forms of cancer. These effects of honey have been thoroughly investigated in certain cancers such as breast, liver and colorectal cancer cell lines. In contrast, limited but promising data are available for other forms of cancers including prostate, bladder, endometrial, kidney, skin, cervical, oral and bone cancer cells. The article also underscores the various possible mechanisms by which honey may inhibit growth and proliferation of tumors or cancers. These include regulation of cell cycle, activation of mitochondrial pathway, induction of mitochondrial outer membrane permeabilization, induction of apoptosis, modulation of oxidative stress, amelioration of inflammation, modulation of insulin signaling and inhibition of angiogenesis. Honey is highly cytotoxic against tumor or cancer cells while it is non-cytotoxic to normal cells. The data indicate that honey can inhibit carcinogenesis by modulating the molecular processes of initiation, promotion, and progression stages. Thus, it may serve as a potential and promising anticancer agent which warrants further experimental and clinical studies.

  11. Robotic palpation-based mechanical property mapping for diagnosis of prostate cancer.

    Science.gov (United States)

    Ahn, Bummo; Lorenzo, Enrique Ian S; Rha, Koon Ho; Kim, Hyung Joo; Kim, Jung

    2011-05-01

    The aim of this study was to estimate the mechanical properties (elasticity) of normal and cancer prostate tissues and to develop a tissue elasticity map for the diagnosis and localization of prostate cancer. A total of 735 sites from 35 radical prostatectomy specimens were used in the experiments using a robotic palpation system, and the elasticities of the specimens were estimated by a tissue characterization algorithm. The estimated elasticities from 21 regions were separated into normal and cancer tissues using the pathological information, and a tissue elasticity map was developed using numerical functions and a nonlinear surface-fitting method. The mean elastic moduli of the normal and cancer tissues were 15.25 ± 5.88 and 28.80 ± 11.20 kPa, respectively. The base region had the highest elasticity, followed by the medial and apex regions. These results demonstrated the ability to separate the cancer tissue from the normal tissue based on its elastic modulus. The tissue elasticity mapping was carried out using the estimated elasticity and nonlinear surface fitting. The proposed map showed the elasticity and was used to estimate the elastic modulus of the prostate at any given region. Tissue elasticity may be an important indicator of prostate cancer because the pathologic changes alter the tissue properties, including cell integrity and intercellular matrix. This work provides quantitative and objective information for the diagnosis of prostate cancer. In addition, these results may have implications for the localization of prostate cancers.

  12. The association between type 2 diabetes mellitus and women cancer: the epidemiological evidences and putative mechanisms.

    Science.gov (United States)

    Joung, Kyong Hye; Jeong, Jae-Wook; Ku, Bon Jeong

    2015-01-01

    Type 2 diabetes mellitus (T2DM), a chronic disease increasing rapidly worldwide, is well established as an important risk factor for various types of cancer. Although many factors impact the development of T2DM and cancer including sex, age, ethnicity, obesity, diet, physical activity levels, and environmental exposure, many epidemiological and experimental studies are gradually contributing to knowledge regarding the interrelationship between DM and cancer. The insulin resistance, hyperinsulinemia, and chronic inflammation associated with diabetes mellitus are all associated strongly with cancer. The changes in bioavailable ovarian steroid hormone that occur in diabetes mellitus (the increasing levels of estrogen and androgen and the decreasing level of progesterone) are also considered potentially carcinogenic conditions for the breast, endometrium, and ovaries in women. In addition, the interaction among insulin, insulin-like growth factors (IGFs), and ovarian steroid hormones, such as estrogen and progesterone, could act synergistically during cancer development. Here, we review the cancer-related mechanisms in T2DM, the epidemiological evidence linking T2DM and cancers in women, and the role of antidiabetic medication in these cancers.

  13. Role of a novel I1781T mutation and other mechanisms in conferring resistance to acetyl-CoA carboxylase inhibiting herbicides in a black-grass population.

    Directory of Open Access Journals (Sweden)

    Shiv Shankhar Kaundun

    Full Text Available BACKGROUND: Knowledge of the mechanisms of herbicide resistance is important for designing long term sustainable weed management strategies. Here, we have used an integrated biology and molecular approach to investigate the mechanisms of resistance to acetyl-CoA carboxylase inhibiting herbicides in a UK black-grass population (BG2. METHODOLOGY/PRINCIPAL FINDINGS: Comparison between BG2 phenotypes using single discriminant rates of herbicides and genotypes based on ACCase gene sequencing showed that the I1781L, a novel I1781T, but not the W2027C mutations, were associated with resistance to cycloxydim. All plants were killed with clethodim and a few individuals containing the I1781L mutation were partially resistant to tepraloxydim. Whole plant dose response assays demonstrated that a single copy of the mutant T1781 allele conferred fourfold resistance levels to cycloxydim and clodinafop-propargyl. In contrast, the impact of the I1781T mutation was low (Rf = 1.6 and non-significant on pinoxaden. BG2 was also characterised by high levels of resistance, very likely non-target site based, to the two cereal selective herbicides clodinafop-propargyl and pinoxaden and not to the poorly metabolisable cyclohexanedione herbicides. Analysis of 480 plants from 40 cycloxydim resistant black grass populations from the UK using two very effective and high throughput dCAPS assays established for detecting any amino acid changes at the 1781 ACCase codon and for positively identifying the threonine residue, showed that the occurrence of the T1781 is extremely rare compared to the L1781 allele. CONCLUSION/SIGNIFICANCE: This study revealed a novel mutation at ACCase codon position 1781 and adequately assessed target site and non-target site mechanisms in conferring resistance to several ACCase herbicides in a black-grass population. It highlights that over time the level of suspected non-target site resistance to some cereal selective ACCase herbicides have in some

  14. Role of a novel I1781T mutation and other mechanisms in conferring resistance to acetyl-CoA carboxylase inhibiting herbicides in a black-grass population.

    Science.gov (United States)

    Kaundun, Shiv Shankhar; Hutchings, Sarah-Jane; Dale, Richard P; McIndoe, Eddie

    2013-01-01

    Knowledge of the mechanisms of herbicide resistance is important for designing long term sustainable weed management strategies. Here, we have used an integrated biology and molecular approach to investigate the mechanisms of resistance to acetyl-CoA carboxylase inhibiting herbicides in a UK black-grass population (BG2). Comparison between BG2 phenotypes using single discriminant rates of herbicides and genotypes based on ACCase gene sequencing showed that the I1781L, a novel I1781T, but not the W2027C mutations, were associated with resistance to cycloxydim. All plants were killed with clethodim and a few individuals containing the I1781L mutation were partially resistant to tepraloxydim. Whole plant dose response assays demonstrated that a single copy of the mutant T1781 allele conferred fourfold resistance levels to cycloxydim and clodinafop-propargyl. In contrast, the impact of the I1781T mutation was low (Rf = 1.6) and non-significant on pinoxaden. BG2 was also characterised by high levels of resistance, very likely non-target site based, to the two cereal selective herbicides clodinafop-propargyl and pinoxaden and not to the poorly metabolisable cyclohexanedione herbicides. Analysis of 480 plants from 40 cycloxydim resistant black grass populations from the UK using two very effective and high throughput dCAPS assays established for detecting any amino acid changes at the 1781 ACCase codon and for positively identifying the threonine residue, showed that the occurrence of the T1781 is extremely rare compared to the L1781 allele. This study revealed a novel mutation at ACCase codon position 1781 and adequately assessed target site and non-target site mechanisms in conferring resistance to several ACCase herbicides in a black-grass population. It highlights that over time the level of suspected non-target site resistance to some cereal selective ACCase herbicides have in some instances surpassed that of target site resistance, including the one endowed by the

  15. Optimization of voltage output of energy harvesters with continuous mechanical rotation extracted from human motion (Conference Presentation)

    Science.gov (United States)

    Rashid, Evan; Hamidi, Armita; Tadesse, Yonas

    2017-04-01

    With increasing popularity of portable devices for outdoor activities, portable energy harvesting devices are coming into spot light. The next generation energy harvester which is called hybrid energy harvester can employ more than one mechanism in a single device to optimize portion of the energy that can be harvested from any source of waste energy namely motion, vibration, heat and etc. In spite of few recent attempts for creating hybrid portable devices, the level of output energy still needs to be improved with the intention of employing them in commercial electronic systems or further applications. Moreover, implementing a practical hybrid energy harvester in different application for further investigation is still challenging. This proposal is projected to incorporate a novel approach to maximize and optimize the voltage output of hybrid energy harvesters to achieve a greater conversion efficiency normalized by the total mass of the hybrid device than the simple arithmetic sum of the individual harvesting mechanisms. The energy harvester model previously proposed by Larkin and Tadesse [1] is used as a baseline and a continuous unidirectional rotation is incorporated to maximize and optimize the output. The device harvest mechanical energy from oscillatory motion and convert it to electrical energy through electromagnetic and piezoelectric systems. The new designed mechanism upgrades the device in a way that can harvest energy from both rotational and linear motions by using magnets. Likewise, the piezoelectric section optimized to harvest at least 10% more energy. To the end, the device scaled down for tested with different sources of vibrations in the immediate environment, including machinery operation, bicycle, door motion while opening and closing and finally, human motions. Comparing the results from literature proved that current device has capability to be employed in commercial small electronic devices for enhancement of battery usage or as a backup

  16. The 4th Bi-annual international African-Caribbean Cancer Consortium conference: building capacity to address cancer health disparities in populations of African descent.

    Science.gov (United States)

    Blackman, Elizabeth; Campbell, Jasmine; Bowen, Carlene; Delmoor, Ernestine; Jean-Louis, Gilda; Noumbissi, Raphiatou; O'Garro, Yvonne; Richards-Waritay, Oni; Straughter, Stanley; Tolbert, Vera; Wilson, Barbara; Ragin, Camille

    2014-01-01

    This is a brief summary of the 4(th) International Meeting of the African-Caribbean Cancer Consortium (AC3), organized and sponsored by Fox Chase Cancer Center (FCCC), and held on July 21-22, 2012 at the Lincoln University Graduate Center, Lincoln Plaza, Philadelphia, Pennsylvania. AC3 investigators gathered in Philadelphia, PA to present the results of our ongoing collaborative research efforts throughout the African Diaspora. The general theme addressed cancer health disparities and presentations represented all cancer types. However, there was particular emphasis on women's cancers, related to human papillomavirus (HPV) and human immunodeficiency virus (HIV) infections.

  17. G-quadruplex oligonucleotide AS1411 as a cancer-targeting agent: Uses and mechanisms.

    Science.gov (United States)

    Bates, Paula J; Reyes-Reyes, Elsa M; Malik, Mohammad T; Murphy, Emily M; O'Toole, Martin G; Trent, John O

    2017-05-01

    AS1411 is a 26-mer G-rich DNA oligonucleotide that forms a variety of G-quadruplex structures. It was identified based on its cancer-selective antiproliferative activity and subsequently determined to be an aptamer to nucleolin, a multifunctional protein that preferentially binds quadruplex nucleic acids and which is present at high levels on the surface of cancer cells. AS1411 has exceptionally efficient cellular internalization compared to non-quadruplex DNA sequences. Recent developments related to AS1411 will be examined, with a focus on its use for targeted delivery of therapeutic and imaging agents. Numerous research groups have used AS1411 as a targeting agent to deliver nanoparticles, oligonucleotides, and small molecules into cancer cells. Studies in animal models have demonstrated that AS1411-linked materials can accumulate selectively in tumors following systemic administration. The mechanism underlying the cancer-targeting ability of AS1411 is not completely understood, but recent studies suggest a model that involves: (1) initial uptake by macropinocytosis, a form of endocytosis prevalent in cancer cells; (2) stimulation of macropinocytosis by a nucleolin-dependent mechanism resulting in further uptake; and (3) disruption of nucleolin-mediated trafficking and efflux leading to cargoes becoming trapped inside cancer cells. Human trials have indicated that AS1411 is safe and can induce durable remissions in a few patients, but new strategies are needed to maximize its clinical impact. A better understanding of the mechanisms by which AS1411 targets and kills cancer cells may hasten the development of promising technologies using AS1411-linked nanoparticles or conjugates for cancer-targeted therapy and imaging. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio. Copyright © 2016. Published by Elsevier B.V.

  18. Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans.

    Science.gov (United States)

    Abegglen, Lisa M; Caulin, Aleah F; Chan, Ashley; Lee, Kristy; Robinson, Rosann; Campbell, Michael S; Kiso, Wendy K; Schmitt, Dennis L; Waddell, Peter J; Bhaskara, Srividya; Jensen, Shane T; Maley, Carlo C; Schiffman, Joshua D

    2015-11-03

    Evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n = 644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro in the laboratory for DNA damage response. The study included African and Asian elephants (n = 8), patients with LFS (n = 10), and age-matched human controls (n = 11). Human samples were collected at the University of Utah between June 2014 and July 2015. Ionizing radiation and doxorubicin. Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95% CI, 0%-5%]; African wild dog, 8% [95% CI, 0%-16%]; lion, 2% [95% CI, 0%-7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95% CI, 3.14%-6.49%), compared with humans, who have 11% to 25% cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction. In response to DNA damage, elephant lymphocytes underwent p53-mediated apoptosis

  19. Centrosome-Based Mechanisms, Prognostics and Therapeutics in Prostate Cancer

    Science.gov (United States)

    2006-12-01

    and time. J. Cell. Biol. 157:1139–49 Rajagopalan S, Bimbo A, Balasubramanian MK, Oliferenko S. 2004. A potential tension-sensing mechanism that...cytoplasmic dynein light intermediate chain contributes to mitotic spindle organization. J. Cell Biol. 147, 481–491. Rajagopalan, S., Bimbo , A., Balasubramanian...organization. J. Cell Biol. 147, 481–491. Rajagopalan, S., Bimbo , A., Balasubramanian, M.K., and Oliferenko, S. (2004). A potential tension-sensing

  20. Characterizing Mechanisms of Resistance to Androgen Deprivation in Prostate Cancer

    Science.gov (United States)

    2015-11-01

    have been intensely studied over the past years [3]. It is well established that the AR pathway plays a central role in the progression of PCa [4...have been achieved by treatment with abiraterone, which inhibits the enzyme (CYP17) that catalyzes the formation of testosterone precursors [7, 8...suppressor screen drive castration resistance through AR-dependent or -independent mechanisms. Major task 1: Analysis of AR pathway activation in cells

  1. Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer

    Science.gov (United States)

    2000-07-01

    Church of Harrisburg 1999 Development Team - Finance, Church Plant - Harrisburg Area Evangelical Free Church 1997 Environmental Health Advisory...Washington, DC 1988 Screening Systems for Anti-invasive and Anti-metastatic Drugs. Bioassay -directed Discovery of Anti-tumor and Anti-viral Agents...the cell lines did not maintain transgene expression levels following in vivo growth. The mechanism of action of Kail is not completely understood

  2. Skin Cancer Chemoprevention by Silibinin: Mechanisms and Efficacy | Division of Cancer Prevention

    Science.gov (United States)

    Project Summary Abstract Basal cell carcinoma (BCC), a non-melanoma skin cancer (NMSC) type, is a major health problem in the United States (US); annual BCC incidences alone are higher than all other cancer incidences combined (1.67 million/year). Most BCC cases are curable by surgery/radiation, but these can be painful and highly disfiguring and are not viable treatment options for BCC patients with locally advanced and metastatic disease where chemotherapy has also not proven effective. |

  3. CONFERENCE REPORTS

    African Journals Online (AJOL)

    Test

    imagining. Psychology in Africa. She asserted that psychology is very important in society because it brings out human perceptions and attitudes. In a unique keynote presentation, Sean Hagen, a lecturer at UNISA who organised the conference ...

  4. Cytokines, obesity, and cancer: new insights on mechanisms linking obesity to cancer risk and progression.

    Science.gov (United States)

    Gilbert, Candace A; Slingerland, Joyce M

    2013-01-01

    Obesity is a problem of epidemic proportions in many developed nations. Increased body mass index and obesity are associated with a significantly worse outcome for many cancers. Breast cancer risk in the postmenopausal setting and poor disease outcome for all patients is significantly augmented in overweight and obese individuals. The expansion of fat tissue involves a complex interaction of endocrine factors known as adipokines and cytokines. High cytokine levels in primary breast cancers and in the circulation of affected patients have been associated with poor outcome. This review summarizes the how cytokine production in obese adipose tissue creates a chronic inflammatory microenvironment that favors tumor cell motility, invasion, and epithelial-mesenchymal transition to enhance the metastatic potential of tumor cells. Many of the cytokines associated with a proinflammatory state are not only upregulated in obese adipose tissue but may also stimulate the self-renewal of cancer stem cells. Thus, enhanced cytokine production in obese adipose tissue may serve both as a chemoattractant for invading cancers and to augment their malignant potential. These new mechanistic insights suggest that the current obesity epidemic will presage a significant increase in cancer incidence, morbidity, and mortality in the next few decades.

  5. The BRAF{sup T1799A} mutation confers sensitivity of thyroid cancer cells to the BRAF{sup V600E} inhibitor PLX4032 (RG7204)

    Energy Technology Data Exchange (ETDEWEB)

    Xing, Joanna [Division of Head and Neck Cancer Research, Department of Otolaryngology and Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21231 (United States); Liu, Ruixin; Xing, Mingzhao [Laboratory for Cellular and Molecular Thyroid Research, Division of Endocrinology and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, MD 21287 (United States); Trink, Barry, E-mail: btrink@jhmi.edu [Division of Head and Neck Cancer Research, Department of Otolaryngology and Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21231 (United States)

    2011-01-28

    Research highlights: {yields} Exciting therapeutic potential has been recently reported for the BRAF{sup V600E} inhibitor PLX4032 in melanoma. {yields} We tested the effects of PLX4032 on the growth of thyroid cancer cells which often harbor the BRAF{sup V600E} mutation. {yields} We observed a potent BRAF{sup V600E}-dependent inhibition of thyroid cancer cells by PLX4032. {yields} We thus demonstrated an important therapeutic potential of PLX4032 for thyroid cancer. -- Abstract: Aberrant signaling of the Ras-Raf-MEK-ERK (MAP kinase) pathway driven by the mutant kinase BRAF{sup V600E}, as a result of the BRAF{sup T1799A} mutation, plays a fundamental role in thyroid tumorigenesis. This study investigated the therapeutic potential of a BRAF{sup V600E}-selective inhibitor, PLX4032 (RG7204), for thyroid cancer by examining its effects on the MAP kinase signaling and proliferation of 10 thyroid cancer cell lines with wild-type BRAF or BRAF{sup T1799A} mutation. We found that PLX4032 could effectively inhibit the MAP kinase signaling, as reflected by the suppression of ERK phosphorylation, in cells harboring the BRAF{sup T1799A} mutation. PLX4032 also showed a potent and BRAF mutation-selective inhibition of cell proliferation in a concentration-dependent manner. PLX4032 displayed low IC{sub 50} values (0.115-1.156 {mu}M) in BRAF{sup V600E} mutant cells, in contrast with wild-type BRAF cells that showed resistance to the inhibitor with high IC{sub 50} values (56.674-1349.788 {mu}M). Interestingly, cells with Ras mutations were also sensitive to PLX4032, albeit moderately. Thus, this study has confirmed that the BRAF{sup T1799A} mutation confers cancer cells sensitivity to PLX4032 and demonstrated its specific potential as an effective and BRAF{sup T1799A} mutation-selective therapeutic agent for thyroid cancer.

  6. ATRA mechanically reprograms pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion

    Science.gov (United States)

    Chronopoulos, Antonios; Robinson, Benjamin; Sarper, Muge; Cortes, Ernesto; Auernheimer, Vera; Lachowski, Dariusz; Attwood, Simon; García, Rebeca; Ghassemi, Saba; Fabry, Ben; del Río Hernández, Armando

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a dismal survival rate. Persistent activation of pancreatic stellate cells (PSCs) can perturb the biomechanical homoeostasis of the tumour microenvironment to favour cancer cell invasion. Here we report that ATRA, an active metabolite of vitamin A, restores mechanical quiescence in PSCs via a mechanism involving a retinoic acid receptor beta (RAR-β)-dependent downregulation of actomyosin (MLC-2) contractility. We show that ATRA reduces the ability of PSCs to generate high traction forces and adapt to extracellular mechanical cues (mechanosensing), as well as suppresses force-mediated extracellular matrix remodelling to inhibit local cancer cell invasion in 3D organotypic models. Our findings implicate a RAR-β/MLC-2 pathway in peritumoural stromal remodelling and mechanosensory-driven activation of PSCs, and further suggest that mechanical reprogramming of PSCs with retinoic acid derivatives might be a viable alternative to stromal ablation strategies for the treatment of PDAC. PMID:27600527

  7. Exploring the FGFR3-related oncogenic mechanism in bladder cancer using bioinformatics strategy.

    Science.gov (United States)

    Cao, Wei; Ma, Enguang; Zhou, Li; Yuan, Tan; Zhang, Chunying

    2017-03-20

    Aberrant activation of fibroblast growth factor receptor 3 (FGFR3) is frequently observed in bladder cancer, but how it involved in carcinogenesis is not well understood. The current study was aimed to investigate the underlying mechanism on the progression of bladder cancer. The GSE41035 dataset downloaded from Gene Expression Omnibus was used to identify the differentially expressed genes (DEGs) between bladder cancer cell line RT112 with or without depletion of FGFR3, and gene ontology enrichment analysis was performed. Then, FGFR3-centered protein-protein interaction (PPI) and regulatory networks were constructed. Combined with the data retrieved from GSE31684, prognostic makers for bladder cancer were predicted. We identified a total of 2855 DEGs, and most of them were associated with blood vessel morphogenesis and cell division. In addition, KIAA1377, POLA2, FGFR3, and EPHA4 were the hub genes with high degree in the FGFR3-centered PPI network. Besides, 17 microRNAs (miRNAs) and 6 transcriptional factors (TFs) were predicted to be the regulators of the nodes in PPI network. Moreover, CSTF2, POLA1, HMOX2, and EFNB2 may be associated with the prognosis of bladder cancer patient. The current study may provide some insights into the molecular mechanism of FGFR3 as a mediator in bladder cancer.

  8. Molecular mechanisms of anti-cancer action of garlic compounds in neuroblastoma.

    Science.gov (United States)

    Karmakar, Surajit; Choudhury, Subhasree Roy; Banik, Naren L; Ray, Swapan K

    2011-05-01

    The medicinal properties of garlic (Allium sativum) have been well known and widely used since historical times. Garlic compounds have received increasing attention during the last few years due to their cancer chemopreventive properties. The anti-cancer activity of garlic-derived organosulfur compounds (OSCs) are extensively reported in many cancers but only a few in the pediatric tumor neuroblastoma, which warrants exploration of new therapy for its management. There are some recent reports suggesting that garlic-derived OSCs cause cell cycle arrest, generate reactive oxygen species (ROS), activate stress kinases, and also stimulate the mitochondrial pathway for apoptosis in malignant neuroblastoma. The comprehensive mechanisms of anti-cancer action of OSCs still remain unclear and require more studies in neuroblastoma. This review is designed to highlight the molecular mechanisms of anti-cancer actions of garlic-derived OSCs in neuroblastoma and as well as in several other cancers. Further studies should be conducted to establish the clinical expediency of garlic-derived OSCs for treatment of malignant neuroblastoma in humans.

  9. [Mechanisms smoothing deglutition disorders after oral cancer surgery].

    Science.gov (United States)

    Halczy-Kowalik, L; Wysocki, R; Domański, Z; Kowalik, S; Bielawiec, A

    1999-01-01

    Compensatory treatment for oropharyngeal dysphagia includes postural changes and reducing the risk of aspiration. Some of compensatory maneuvers are introduced spontaneously by the ill at first weeks after oral cavity tumour resection. On the basis of roentgenotelevision examination of deglutition in 82 patients we detected mechanisms with intention to minimize swallowing disturbances. Variability of their occurrence and differences in their efficiency should be emphasized, as well as essential synchronization of laryngeal closure with emptying of pharynx and opening upper oesophageal sphincter for swallowing efficiency. The valuation of compensatory maneuvers introduced spontaneously by the ill was defined as an important part of swallowing rehabilitation.

  10. Herceptin Resistance Database for Understanding Mechanism of Resistance in Breast Cancer Patients

    OpenAIRE

    Sahil Ahmad; Sudheer Gupta; Rahul Kumar; Grish C. Varshney; Gajendra P. S. Raghava

    2014-01-01

    Monoclonal antibody Trastuzumab/Herceptin is considered as frontline therapy for Her2-positive breast cancer patients. However, it is not effective against several patients due to acquired or de novo resistance. In last one decade, several assays have been performed to understand the mechanism of Herceptin resistance with/without supplementary drugs. This manuscript describes a database HerceptinR, developed for understanding the mechanism of resistance at genetic level. HerceptinR maintains ...

  11. Proceedings of the Midwestern Mechanics Conference (22nd) Held in Rolla, Missouri on 6-9 October 1991. Developments in Mechanics. Volume 16.

    Science.gov (United States)

    1991-10-01

    253 FREE VIBRATION OF LAMINATED PLATES OF RECTANGULAR PLANFORM WITH MULTIPLE INTERMEDIATE LINE SUPPORTS Serge Abrate Department of Mechanical and...shear layer, Lang and Dimotakis (1985], Balint, et. al. (1989), Kim [1989], and Foss and Haw (1990]. The outcome of this comparative measurements program...Berlin, (Prof. Dr. H. Fiedler). Lang , D. B. and P.E. Dimotakis (1985] "Laser Doppler Velocity and Vorticity Measurements in Turbulent Shear Layers

  12. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Events Scientific Meetings & Lectures Conferences Advisory Board Meetings Social Media Events Cancer Currents Blog All Press Releases 2017 ... Events Scientific Meetings & Lectures Conferences Advisory Board Meetings Social Media Cancer Currents Blog About NCI NCI Overview History ...

  13. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Events Scientific Meetings & Lectures Conferences Advisory Board Meetings Social Media Events Cancer Currents Blog All Press Releases 2018 ... Events Scientific Meetings & Lectures Conferences Advisory Board Meetings Social Media Cancer Currents Blog About NCI NCI Overview History ...

  14. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Events Scientific Meetings & Lectures Conferences Advisory Board Meetings Social Media Events Cancer Currents Blog All Press Releases ... Events Scientific Meetings & Lectures Conferences Advisory Board Meetings Social Media Cancer Currents Blog About NCI NCI Overview ...

  15. Label-free vascular imaging in a spontaneous hamster cheek pouch carcinogen model for pre-cancer detection (Conference Presentation)

    Science.gov (United States)

    Hu, Fangyao; Morhard, Robert; Liu, Heather; Murphy, Helen; Farsiu, Sina; Ramanujam, Nimmi

    2016-03-01

    Inducing angiogenesis is one hallmark of cancer. Tumor induced neovasculature is often characterized as leaky, tortuous and chaotic, unlike a highly organized normal vasculature. Additionally, in the course of carcinogenesis, angiogenesis precedes a visible lesion. Tumor cannot grow beyond 1-2 mm in diameter without inducing angiogenesis. Therefore, capturing the event of angiogenesis may aid early detection of pre-cancer -important for better treatment prognoses in regions that lack the resources to manage invasive cancer. In this study, we imaged the neovascularization in vivo in a spontaneous hamster cheek pouch carcinogen model using a, non-invasive, label-free, high resolution, reflected-light spectral darkfield microscope. Hamsters' cheek pouches were painted with 7,12-Dimethylbenz[a]anthracene (DMBA) to induce pre-cancerous to cancerous changes, or mineral oil as control. High resolution spectral darkfield images were obtained over the course of pre-cancer development and in control cheek pouches. The vasculature was segmented with a multi-scale Gabor filter with an 85% accuracy compared with manually traced masks. Highly tortuous vasculature was observed only in the DMBA treated cheek pouches as early as 6 weeks of treatment. In addition, the highly tortuous vessels could be identified before a visible lesion occurred later during the treatment. The vessel patterns as determined by the tortuosity index were significantly different from that of the control cheek pouch. This preliminary study suggests that high-resolution darkfield microscopy is promising tool for pre-cancer and early cancer detection in low resource settings.

  16. Role of epigenetic mechanisms in epithelial-to-mesenchymal transition of breast cancer cells.

    Science.gov (United States)

    Nickel, Annina; Stadler, Sonja C

    2015-01-01

    The epithelial-to-mesenchymal transition (EMT) is a crucial process during normal development that allows dynamic and reversible shifts between epithelial and mesenchymal cell states. Cancer cells take advantage of the complex, interrelated cellular networks that regulate EMT to promote their migratory and invasive capabilities. During the past few years, evidence has accumulated that indicates that genetic mutations and changes to epigenetic mechanisms are key drivers of EMT in cancer cells. Recent studies have begun to shed light on the epigenetic reprogramming in cancer cells that enables them to switch from a noninvasive form to an invasive, metastatic form. The authors review the current knowledge of alterations of epigenetic machinery, including DNA methylation, histone modifications, nucleosome remodeling and expression of microRNAs, associated with EMT and tumor progression of breast cancer cells. Last, existing and upcoming drug therapies targeting epigenetic regulators and their potential benefit for developing novel treatment strategies are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. NADPH Oxidases: Insights into Selected Functions and Mechanisms of Action in Cancer and Stem Cells

    Directory of Open Access Journals (Sweden)

    Magdalena Skonieczna

    2017-01-01

    Full Text Available NADPH oxidases (NOX are reactive oxygen species- (ROS- generating enzymes regulating numerous redox-dependent signaling pathways. NOX are important regulators of cell differentiation, growth, and proliferation and of mechanisms, important for a wide range of processes from embryonic development, through tissue regeneration to the development and spread of cancer. In this review, we discuss the roles of NOX and NOX-derived ROS in the functioning of stem cells and cancer stem cells and in selected aspects of cancer cell physiology. Understanding the functions and complex activities of NOX is important for the application of stem cells in tissue engineering, regenerative medicine, and development of new therapies toward invasive forms of cancers.

  18. Mechanisms of Cancer Induction by Tobacco-Specific NNK and NNN

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Jiaping [Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612 (United States); Yang, Suping; Seng, Seyha, E-mail: sseng@bidmc.harvard.edu [Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215 (United States)

    2014-05-14

    Tobacco use is a major public health problem worldwide. Tobacco-related cancers cause millions of deaths annually. Although several tobacco agents play a role in the development of tumors, the potent effects of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are unique. Metabolically activated NNK and NNN induce deleterious mutations in oncogenes and tumor suppression genes by forming DNA adducts, which could be considered as tumor initiation. Meanwhile, the binding of NNK and NNN to the nicotinic acetylcholine receptor promotes tumor growth by enhancing and deregulating cell proliferation, survival, migration, and invasion, thereby creating a microenvironment for tumor growth. These two unique aspects of NNK and NNN synergistically induce cancers in tobacco-exposed individuals. This review will discuss various types of tobacco products and tobacco-related cancers, as well as the molecular mechanisms by which nitrosamines, such as NNK and NNN, induce cancer.

  19. Association of 12 polymorphic variants conferring genetic risk to lung cancer in Indian population: An extensive meta-analysis.

    Science.gov (United States)

    Sengupta, Debmalya; Guha, Udayan; Bhattacharjee, Samsiddhi; Sengupta, Mainak

    2017-12-01

    Candidate gene as well as genome-wide association studies identified several polymorphic variants to be associated with lung cancer worldwide including in India. However, contradictory results have failed to estimate the overall effect of the polymorphic variants on the disease. Textmining was conducted on PubMed following specific search strings to gather all the publications related to genetic association with lung cancer in India. Out of 211 PubMed hits only 30 studies were selected for meta-analysis following specific inclusion criteria. Heterogeneity between studies was calculated by Cochran's Q-test (P associated with lung cancer. However, after multiple testing correction, only rs1048943 was found to be significantly associated (P value = 0.0321) with lung cancer. None of the polymorphic variants showed any evidence of heterogeneity between studies or of publication bias. Our meta-analysis revealed strong association of rs1048943 in CYP1A1, but a suggestive association of deletion polymorphisms in GSTT1 and GSTM1 with lung cancer, which provides a comprehensive insight on the overall effect of the polymorphic variants, reported in various case-control studies on Indian population, on the risk of lung cancer development. Environ. Mol. Mutagen. 58:688-700, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. In vivo detection of oral epithelial cancer using endogenous fluorescence lifetime imaging: a pilot human study (Conference Presentation)

    Science.gov (United States)

    Jo, Javier A.; Hwang, Dae Yon; Palma, Jorge; Cheng, Shuna; Cuenca, Rodrigo; Malik, Bilal; Jabbour, Joey; Cheng, Lisa; Wright, John; Maitland, Kristen

    2016-03-01

    Endogenous fluorescence lifetime imaging (FLIM) provides direct access to the concomitant functional and biochemical changes accompanying tissue transition from benign to precancerous and cancerous. Since FLIM can noninvasively measure different and complementary biomarkers of precancer and cancer, we hypothesize that it will aid in clinically detecting early oral epithelial cancer. Our group has recently demonstrated the detection of benign from premalignant and malignant lesions based on endogenous multispectral FLIM in the hamster cheek-pouch model. Encouraged by these positive preliminary results, we have developed a handheld endoscope capable of acquiring multispectral FLIM images in real time from the oral mucosa. This novel FLIM endoscope is being used for imaging clinically suspicious pre-malignant and malignant lesions from patients before undergoing tissue biopsy for histopathological diagnosis of oral epithelial cancer. Our preliminary results thus far are already suggesting the potential of endogenous FLIM for distinguishing a variety of benign lesions from advanced dysplasia and squamous cell carcinoma (SCC). To the best of out knowledge, this is the first in vivo human study aiming to demonstrate the ability to predict the true malignancy of clinically suspicious lesions using endogenous FLIM. If successful, the resulting clinical tool will allow noninvasive real-time detection of epithelial precancerous and cancerous lesions in the oral mucosa and could potentially be used to assist at every step involved on the clinical management of oral cancer patients, from early screening and diagnosis, to treatment and monitoring of recurrence.

  1. Label-free biomolecular characterization of human breast cancer tissue with stimulated Raman scattering (SRS) spectral imaging (Conference Presentation)

    Science.gov (United States)

    Lu, Fa-Ke F.; Calligaris, David; Suo, Yuanzhen; Santagata, Sandro; Golby, Alexandra J.; Xie, X. Sunney; Mallory, Melissa A.; Golshan, Mehra; Dillon, Deborah A.; Agar, Nathalie Y. R.

    2017-02-01

    Stimulated Raman scattering (SRS) microscopy has been used for rapid label-free imaging of various biomolecules and drugs in living cells and tissues (Science, doi:10.1126/science.aaa8870). Our recent work has demonstrated that lipid and protein mapping of cancer tissue renders pathology-like images, providing essential histopathological information with subcellular resolution of the entire specimen (Cancer Research, doi: 10.1158/0008-5472.CAN-16-027). We have also established the first SRS imaging Atlas of human brain tumors (Harvard Dataverse, doi: (doi:10.7910/DVN/EZW4EK). SRS imaging of tissue could provide invaluable information for cancer diagnosis and surgical guidance in two aspects: rapid surgical pathology and quantitative biomolecular characterization. In this work, we present the use of SRS microscopy for characterization of a few essential biomolecules in breast cancer. Human breast cancer tissue specimens at the tumor core, tumor margin and normal area (5 cm away from the tumor) from surgical cases will be imaged with SRS at multiple Raman shifts, including the peaks for lipid, protein, blood (absorption), collagen, microcalcification (calcium phosphates and calcium oxalate) and carotenoids. Most of these Raman shifts have relatively strong Raman cross sections, which ensures high-quality and fast imaging. This proof-of-principle study is sought to demonstrate the feasibility and potential of SRS imaging for ambient diagnosis and surgical guidance of breast cancer.

  2. Folate-Chitosan Nanoparticles Loaded with Ursolic Acid Confer Anti-Breast Cancer Activities in vitro and in vivo

    Science.gov (United States)

    Jin, Hua; Pi, Jiang; Yang, Fen; Jiang, Jinhuan; Wang, Xiaoping; Bai, Haihua; Shao, Mingtao; Huang, Lei; Zhu, Haiyan; Yang, Peihui; Li, Lihua; Li, Ting; Cai, Jiye; Chen, Zheng W.

    2016-07-01

    Ursolic acid (UA) has proved to have broad-spectrum anti-tumor effects, but its poor water solubility and incompetent targeting property largely limit its clinical application and efficiency. Here, we synthesized a nanoparticle-based drug carrier composed of chitosan, UA and folate (FA-CS-UA-NPs) and demonstrated that FA-CS-UA-NPs could effectively diminish off-target effects and increase local drug concentrations of UA. Using MCF-7 cells as in vitro model for anti-cancer mechanistic studies, we found that FA-CS-UA-NPs could be easily internalized by cancer cells through a folate receptor-mediated endocytic pathway. FA-CS-UA-NPs entered into lysosome, destructed the permeability of lysosomal membrane, and then got released from lysosomes. Subsequently, FA-CS-UA-NPs localized into mitochondria but not nuclei. The prolonged retention of FA-CS-UA-NPs in mitochondria induced overproduction of ROS and destruction of mitochondrial membrane potential, and resulted in the irreversible apoptosis in cancer cells. In vivo experiments showed that FA-CS-UA-NPs could significantly reduce breast cancer burden in MCF-7 xenograft mouse model. These results suggested that FA-CS-UA-NPs could further be explored as an anti-cancer drug candidate and that our approach might provide a platform to develop novel anti-cancer drug delivery system.

  3. Molecular programs induced by heat acclimation confer neuroprotection against TBI and hypoxic insults via cross-tolerance mechanisms

    Directory of Open Access Journals (Sweden)

    Michal eHorowitz

    2015-07-01

    Full Text Available Neuroprotection following prolonged exposure to high ambient temperatures (heat acclimation HA develops via altered molecular programs such as cross-tolerance (Heat Acclimation -Neuroprotection Cross-Tolerance -HANCT. The mechanisms underlying cross-tolerance depend on enhanced on-demand protective pathways evolving during acclimation. The protection achieved is long lasting and limits the need for de novo recruitment of cytoprotective pathways upon exposure to novel stressors. Using mouse and rat acclimated phenotypes, we will focus on the impact of heat acclimation on Angiotensin II-AT2 receptors in neurogenesis and on HIF-1 as key mediators in spontaneous recovery and HANCT after traumatic brain injury (TBI. The neuroprotective consequences of heat acclimation on NMDA and AMPA receptors will be discussed using the global hypoxia model. A behavioral-molecular link will be crystallized. The differences between HANCT and consensus preconditioning will be reviewed.

  4. Decreased glucose uptake by hyperglycemia is regulated by different mechanisms in human cancer cells and monocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chae Kyun; Chung, June Key; Lee, Yong Jin; Hong, Mee Kyoung; Jeong, Jae Min; Lee, Dong Soo; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    2002-04-01

    To clarify the difference in glucose uptake between human cancer cells and monocytes, we studied ({sup 18}F) fluorodeoxyglucose (FDG) uptake in three human colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5), one human lung cancer cell line (NCI-H522), and human peripheral blood monocytes. The FDG uptake of both cancer cells and monocytes was increased in glucose-free medium, but decreased in the medium containing 16.7 mM glucose (hyperglycemic). The level of Glut1 mRNA decreased in human colon cancer cells and NCI-H522 under hyperglycemic condition. Glut1 protein expression was also decreased in the four human cancer cell lines under hyperglycemic condition, whereas it was consistently undetectable in monocytes. SNU-C2A, SNU-C4 and NCI-H522 showed a similar level of hexokinase activity (7.5-10.8 mU/mg), while SNU-C5 and moncytes showed lower range of hexokinase activity (4.3-6.5 mU/mg). These data suggest that glucose uptake is regulated by different mechanisms in human cancer cells and monocytes.

  5. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism

    Directory of Open Access Journals (Sweden)

    Bryan G. Allen

    2014-01-01

    Full Text Available Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS such as O2•−and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses.

  6. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism.

    Science.gov (United States)

    Allen, Bryan G; Bhatia, Sudershan K; Anderson, Carryn M; Eichenberger-Gilmore, Julie M; Sibenaller, Zita A; Mapuskar, Kranti A; Schoenfeld, Joshua D; Buatti, John M; Spitz, Douglas R; Fath, Melissa A

    2014-01-01

    Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS) such as O2(•-)and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses. © 2014 Published by Elsevier Ltd.

  7. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism

    Science.gov (United States)

    Allen, Bryan G.; Bhatia, Sudershan K.; Anderson, Carryn M.; Eichenberger-Gilmore, Julie M.; Sibenaller, Zita A.; Mapuskar, Kranti A.; Schoenfeld, Joshua D.; Buatti, John M.; Spitz, Douglas R.; Fath, Melissa A.

    2014-01-01

    Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS) such as O2•−and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses. PMID:25460731

  8. Diabetes mellitus and gynecologic cancer: molecular mechanisms, epidemiological, clinical and prognostic perspectives.

    Science.gov (United States)

    Vrachnis, Nikolaos; Iavazzo, Christos; Iliodromiti, Zoe; Sifakis, Stavros; Alexandrou, Andreas; Siristatidis, Charalambos; Grigoriadis, Charalambos; Botsis, Dimitrios; Creatsas, George

    2016-02-01

    Diabetes mellitus, the prevalence of which has increased dramatically worldwide, may put patients at a higher risk of cancer. The aim of our study is the clarification of the possible mechanisms linking diabetes mellitus and gynecological cancer and their epidemiological relationship. This is a narrative review of the current literature, following a search on MEDLINE and the Cochrane Library, from their inception until January 2012. Articles investigating gynecologic cancer (endometrial, ovarian, and breast) incidence in diabetic patients were extracted. The strong evidence for a positive association between diabetes mellitus and the risk for cancer indicates that energy intake in excess to energy expenditure, or the sequelae thereof, is involved in gynecological carcinogenesis. This risk may be further heightened by glucose which can directly promote the production of tumor cells by functioning as a source of energy. Insulin resistance accompanied by secondary hyperinsulinemia is hypothezised to have a mitogenic effect. Steroid hormones are in addition potent regulators of the balance between cellular differentiation, proliferation, and apoptosis. Inflammatory pathways may also be implicated, as a correlation seems to exist between diabetes mellitus and breast or endometrial carcinoma pathogenesis, although an analogous correlation with ovarian carcinoma is still under investigation. Antidiabetic agents have been correlated with elevated cancer risk, while metformin seems to lower the risk. Diabetes mellitus is associated with an elevation in gynecologic cancer risk. Moreover, there are many studies exploring the prognosis of patients with diabetes and gynecological cancer, the outcome and the overall survival in well-regulated patients.

  9. Trolox inhibits osteolytic bone metastasis of breast cancer through both PGE2-dependent and independent mechanisms.

    Science.gov (United States)

    Lee, Jong-Ho; Kim, Bongjun; Jin, Won Jong; Kim, Jung-Wook; Kim, Hong-Hee; Ha, Hyunil; Lee, Zang Hee

    2014-09-01

    Bone is a preferred site of metastasis from breast cancer, and increased osteoclast activity is implicated in breast cancer outgrowth in the bone microenvironment. Our previous observation of an anti-osteoclastic activity of Trolox, a vitamin E analog, led us to investigate whether Trolox inhibits bone metastasis and osteolysis caused by breast cancer. Administration of Trolox markedly inhibited osteolytic bone metastasis in an experimental metastasis model by intracardiac injection of 4T1 breast cancer cells. Trolox inhibited proliferation of 4T1 cells in the bone marrow but not in the mammary fat pad. In addition, Trolox could reduce tumor burden, osteolysis, and prostaglandin E2 (PGE2) production induced by direct inoculation of 4T1 cells into the marrow cavity of the tibia. Trolox decreased the migratory and invasive activities of 4T1 cells via PGE2-dependent and independent mechanisms. It also inhibited the ability of 4T1 cells to stimulate the expression of receptor activator of nuclear factor-κB ligand (RANKL), a key cytokine for osteoclast differentiation factor, in osteoblasts. In addition, Trolox suppressed RANKL expression in osteoblasts induced by soluble factors from 4T1 cells. Furthermore, Trolox suppressed 4T1 cell-induced osteoclast differentiation in the co-culture of bone marrow cells and osteoblasts via both PGE2-dependent and independent mechanisms. Taken together, these results suggest that Trolox inhibits breast cancer cell-induced osteoclast differentiation and the invasive behavior of cancer cells through PGE2-dependent and independent mechanisms, thereby suppressing osteolytic bone metastasis of breast cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Chromothripsis is a common mechanism driving genomic rearrangements in primary and metastatic colorectal cancer

    NARCIS (Netherlands)

    Kloosterman, W.P.; Hoogstraat, M.; Paling, O.; Tavakoli-Yaraki, M.; Renkens, I.; Vermaat, J.S.; Roosmalen, van M.J.; Lieshout, van S.; Nijman, I.J.; Roessingh, W.; Slot, van 't R.; Belt, van de J.

    2011-01-01

    Background - Structural rearrangements form a major class of somatic variation in cancer genomes. Local chromosome shattering, termed chromothripsis, is a mechanism proposed to be the cause of clustered chromosomal rearrangements and was recently described to occur in a small percentage of tumors.

  11. Antibody therapy of cancer : Fc receptor-mediated mechanisms of action

    NARCIS (Netherlands)

    Overdijk, M.B.

    2013-01-01

    Cancer, a class of malignant diseases characterized by unregulated cell growth, is still a leading cause of death worldwide. The high specificity of antibodies combined with the ability to engage multiple mechanisms of action (MoA) and minimal side-effects makes them attractive agents for targeted

  12. Metastasis Suppressor Gene Inactivates Actin-Based Mechanism of Tumor Cell Motility | Center for Cancer Research

    Science.gov (United States)

    Metastasis is responsible for up to 90 percent of all cancer-related deaths. Though proteins derived from nearly a dozen metastasis suppressor genes have been discovered over the past 15 years, strategies for exploiting the proteins in metastasis-prevention therapies has been hampered by the lack of knowledge regarding the mechanisms underlying the proteins’ interactions with other proteins.

  13. Epigenetic mechanisms and cancer: an interface between the environment and the genome.

    Science.gov (United States)

    Herceg, Zdenko; Vaissière, Thomas

    2011-07-01

    Although epidemiological studies support the role of environment in a wide range of human cancers, the precise mechanisms by which environmental exposures promote cancer development and progression remain poorly understood. Environmental factors have been proposed to promote the development of malignancies by eliciting epigenetic changes; however, it is only with recent advances in epigenetics and epigenomics that target genes and the mechanisms underlying environmental influences are beginning to be elucidated. Because epigenetic mechanisms may function as an interface between environmental factors and the genome, deregulation of the epigenome by environmental stressors is likely to disrupt different cellular processes and contribute to cancer risk. In addition, the early appearance and ubiquity of epigenetic changes in virtually all steps of tumor development and progression in most, if not all, human neoplasms, make them attractive targets for biomarker discovery and targeted prevention. At the cellular level, aberrant epigenetic changes associated with environmental exposures may deregulate key cellular processes (including transcriptional control, DNA repair, cell cycle control, and carcinogen detoxification), which can be further modulated by environmental stressors, thus defining not only the phenotype of the disease but also potential biomarkers. This review summarizes recent progress in our understanding of the epigenetic mechanisms through which environmental factors may promote tumor development, with a particular focus on human lung cancer.

  14. Quantum Interactomics and Cancer Molecular Mechanisms: I. Report Outline

    CERN Document Server

    Baianu, I C

    2004-01-01

    Single cell interactomics in simpler organisms, as well as somatic cell interactomics in multicellular organisms, involve biomolecular interactions in complex signalling pathways that were recently represented in modular terms by quantum automata with ‘reversible behavior’ representing normal cell cycling and division. Other implications of such quantum automata, modular modeling of signaling pathways and cell differentiation during development are in the fields of neural plasticity and brain development leading to quantum-weave dynamic patterns and specific molecular processes underlying extensive memory, learning, anticipation mechanisms and the emergence of human consciousness during the early brain development in children. Cell interactomics is here represented for the first time as a mixture of ‘classical’ states that determine molecular dynamics subject to Boltzmann statistics and ‘steady-state’, metabolic (multi-stable) manifolds, together with ‘configuration’ spaces of metastable quant...

  15. Obesity, Inflammation, and Cancer.

    Science.gov (United States)

    Deng, Tuo; Lyon, Christopher J; Bergin, Stephen; Caligiuri, Michael A; Hsueh, Willa A

    2016-05-23

    Obesity, a worldwide epidemic, confers increased risk for multiple serious conditions, including cancer, and is increasingly recognized as a growing cause of preventable cancer risk. Chronic inflammation, a well-known mediator of cancer, is a central characteristic of obesity, leading to many of its complications, and obesity-induced inflammation confers additional cancer risk beyond obesity itself. Multiple mechanisms facilitate this strong association between cancer and obesity. Adipose tissue is an important endocrine organ, secreting several hormones, including leptin and adiponectin, and chemokines that can regulate tumor behavior, inflammation, and the tumor microenvironment. Excessive adipose expansion during obesity causes adipose dysfunction and inflammation to increase systemic levels of proinflammatory factors. Cells from adipose tissue, such as cancer-associated adipocytes and adipose-derived stem cells, enter the cancer microenvironment to enhance protumoral effects. Dysregulated metabolism that stems from obesity, including insulin resistance, hyperglycemia, and dyslipidemia, can further impact tumor growth and development. This review describes how adipose tissue becomes inflamed in obesity, summarizes ways these mechanisms impact cancer development, and discusses their role in four adipose-associated cancers that demonstrate elevated incidence or mortality in obesity.

  16. Mechanism and applications of new fluorescent compounds produced by femtosecond laser surgery in biological tissue (Conference Presentation)

    Science.gov (United States)

    Qu, Jianan Y.; Sun, Qiqi

    2017-02-01

    The single or multi-photon microscopy based on fluorescent labelling and staining is a sensitive and quantitative method that is widely used in molecular biology and medical research for a variety of experimental, analytical, and quality control applications. However, label-free method is highly desirable in biology and medicine when performing long term live imaging of biological system and obtaining instant tissue examination during surgery procedures. Recently, our group found that femtosecond laser surgery turned a variety of biological tissues and protein samples into highly fluorescent substances. The newly formed fluorescent compounds produced during the laser surgery can be excited via single- and two-photon processes over broad wavelength ranges. We developed a combined confocal and two-photon spectroscopic microscope to characterize the fluorescence from the new compound systematically. The structures of the femtosecond laser treated tissue were studied using Raman spectroscopy and transmission electron microscopy. Our study revealed the mechanisms of the fluorescence emission form the new compound. Furthermore, we demonstrated the applications of the fluorescent compounds for instant evaluation of femtosecond laser microsurgery, study of stem cell responses to muscle injury and neuro-regeneration after spinal cord injury.

  17. Clinical trial involving sufferers and non-sufferers of cervicogenic headache (CGH): potential mechanisms of action of photobiomodulation (Conference Presentation)

    Science.gov (United States)

    Liebert, Ann D.; Bicknell, Brian

    2017-02-01

    Photobiomodulation (PBM) is an effective tool for the management of spinal pain including inflammation of facet joints. Apart from cervical and lumbar joint pain the upper cervical spine facet joint inflammation can result in the CGH (traumatic or atraumatic in origin). This condition affects children, adults and elders and is responsible for 19% of chronic headache and up to 33% of patients in pain clinics. The condition responds well to physiotherapy, facet joint injection, radiofrequency neurotomy and surgery at a rate of 75%. The other 25% being unresponsive to treatment with no identified features of unresponsiveness. In other conditions of chronic unresponsive cervical pain have responded to photobiomodulation at a level of 80% in the short and medium term. A clinical trial was therefore conducted on a cohort of atraumatic patients from the ages of 5-93 (predominantly Neurologist referred / familial sufferers 2/3 generations vertically and laterally) who had responded to a course of PBM and physiotherapy. The CGH sufferers and their non CGH suffering relatives over these generations were then compared for features that distinguish the two groups. Fifty parameters were tested (anthropmetric, movement and neural tension tests included) and there was a noted difference in tandem stance between the groups (.04 significance with repeated measures). As this impairment is common to benign ataxia and migrainous vertigo and in these conditions there is an ion channelopathy (especially potassium channelopathy). A postulated mechanism of action of PBM would involve modulation of ion channels and this is discussed in this presentation.

  18. International Conference on Risk Analysis

    CERN Document Server

    Oliveira, Teresa; Rigas, Alexandros; Gulati, Sneh

    2015-01-01

    This book covers the latest results in the field of risk analysis. Presented topics include probabilistic models in cancer research, models and methods in longevity, epidemiology of cancer risk, engineering reliability and economical risk problems. The contributions of this volume originate from the 5th International Conference on Risk Analysis (ICRA 5). The conference brought together researchers and practitioners working in the field of risk analysis in order to present new theoretical and computational methods with applications in biology, environmental sciences, public health, economics and finance.

  19. DNA amplification is a ubiquitous mechanism of oncogene activation in lung and other cancers

    Science.gov (United States)

    Lockwood, WW; Chari, R; Coe, BP; Girard, L; MacAulay, C; Lam, S; Gazdar, AF; Minna, JD; Lam, WL

    2009-01-01

    Chromosomal translocation is the best-characterized genetic mechanism for oncogene activation. However, there are documented examples of activation by alternate mechanisms, for example gene dosage increase, though its prevalence is unclear. Here, we answered the fundamental question of the contribution of DNA amplification as a molecular mechanism driving oncogenesis. Comparing 104 cancer lines representing diverse tissue origins identified genes residing in amplification ‘hotspots’ and discovered an unexpected frequency of genes activated by this mechanism. The 3431 amplicons identified represent ~10 per hematological and ~36 per epithelial cancer genome. Many recurrently amplified oncogenes were previously known to be activated only by disease-specific translocations. The 135 hotspots identified contain 538 unique genes and are enriched for proliferation, apoptosis and linage-dependency genes, reflecting functions advantageous to tumor growth. Integrating gene dosage with expression data validated the downstream impact of the novel amplification events in both cell lines and clinical samples. For example, multiple downstream components of the EGFR-family-signaling pathway, including CDK5, AKT1 and SHC1, are overexpressed as a direct result of gene amplification in lung cancer. Our findings suggest that amplification is far more common a mechanism of oncogene activation than previously believed and that specific regions of the genome are hotspots of amplification. PMID:18391978

  20. Cancers of the Esophagus and Stomach: Potential Mechanisms Behind the Beneficial Influence of Physical Activity.

    Science.gov (United States)

    Shephard, Roy J

    2017-07-01

    To compare findings from several recent meta-analyses showing a reduced risk of gastric and esophageal cancers in physically active individuals, to assess the magnitude of this benefit, and to seek information on potential underlying mechanisms. A comprehensive search of Ovid/Medline from 1996 to February 2016, using the terms physical activity or exercise or training and esophageal or gastric cancer, and supplementing the articles identified by material from references lists and personal files. Moderate-to-vigorous physical activity is associated with a 20% to 30% reduction in the risk of gastroesophageal adenocarcinomas, with a significant dose/response relationship. Benefit is greater in women than in men, and greater for noncardia than for cardia or esophageal tumors. Mechanisms could include a reduction of visceral fat (with a lesser production of cancer promoting hormones and reduced gastroesophageal reflux) and/or a lesser likelihood of smoking and excessive alcohol consumption. Physical activity does not protect against Helicobacter pylori infections or gastric ulceration, but mechanisms related to the impact of exercise on immune function, antioxidant mechanisms, and gastroesophageal reflux remain to be explored. Regular, moderate-to-vigorous physical activity is associated with a clinically significant reduction in the risk of gastroesophageal adenocarcinomas, but mechanisms are as yet unclear, and a causal relationship remains to be proven.

  1. A mechanically-induced colon cancer cell population shows increased metastatic potential

    KAUST Repository

    Tang, Xin

    2014-05-29

    Background: Metastasis accounts for the majority of deaths from cancer. Although tumor microenvironment has been shown to have a significant impact on the initiation and/or promotion of metastasis, the mechanism remains elusive. We previously reported that HCT-8 colon cancer cells underwent a phenotypic transition from an adhesive epithelial type (E-cell) to a rounded dissociated type (R-cell) via soft substrate culture, which resembled the initiation of metastasis. The objective of current study was to investigate the molecular and metabolic mechanisms of the E-R transition.Methods: Global gene expressions of HCT-8 E and R cells were measured by RNA Sequencing (RNA-seq); and the results were further confirmed by real-time PCR. Reactive oxygen species (ROS), anoikis resistance, enzyme activity of aldehyde dehydrogenase 3 family, member A1 (ALDH3A1), and in vitro invasion assay were tested on both E and R cells. The deformability of HCT-8 E and R cells was measured by atomic force microscopy (AFM). To study the in vivo invasiveness of two cell types, athymic nude mice were intra-splenically injected with HCT-8 E or R cells and sacrificed after 9 weeks. Incidences of tumor development and metastasis were histologically evaluated and analyzed with Fisher\\'s exact test.Results: Besides HCT-8, E-R transition on soft substrates was also seen in three other cancer cell lines (HCT116, SW480 colon and DU145 prostate cancer). The expression of some genes, such as ALDH3A1, TNS4, CLDN2, and AKR1B10, which are known to play important roles in cancer cell migration, invasion, proliferation and apoptosis, were increased in HCT-8 R cells. R cells also showed higher ALDH3A1 enzyme activity, higher ROS, higher anoikis resistance, and higher softness than E cells. More importantly, in vitro assay and in vivo animal models revealed that HCT-8 R cells were more invasive than E cells.Conclusions: Our comprehensive comparison of HCT-8 E and R cells revealed differences of molecular

  2. A mechanically-induced colon cancer cell population shows increased metastatic potential.

    Science.gov (United States)

    Tang, Xin; Kuhlenschmidt, Theresa B; Li, Qian; Ali, Shahjahan; Lezmi, Stephane; Chen, Hong; Pires-Alves, Melissa; Laegreid, William W; Saif, Taher A; Kuhlenschmidt, Mark S

    2014-05-29

    Metastasis accounts for the majority of deaths from cancer. Although tumor microenvironment has been shown to have a significant impact on the initiation and/or promotion of metastasis, the mechanism remains elusive. We previously reported that HCT-8 colon cancer cells underwent a phenotypic transition from an adhesive epithelial type (E-cell) to a rounded dissociated type (R-cell) via soft substrate culture, which resembled the initiation of metastasis. The objective of current study was to investigate the molecular and metabolic mechanisms of the E-R transition. Global gene expressions of HCT-8 E and R cells were measured by RNA Sequencing (RNA-seq); and the results were further confirmed by real-time PCR. Reactive oxygen species (ROS), anoikis resistance, enzyme activity of aldehyde dehydrogenase 3 family, member A1 (ALDH3A1), and in vitro invasion assay were tested on both E and R cells. The deformability of HCT-8 E and R cells was measured by atomic force microscopy (AFM). To study the in vivo invasiveness of two cell types, athymic nude mice were intra-splenically injected with HCT-8 E or R cells and sacrificed after 9 weeks. Incidences of tumor development and metastasis were histologically evaluated and analyzed with Fisher's exact test. Besides HCT-8, E-R transition on soft substrates was also seen in three other cancer cell lines (HCT116, SW480 colon and DU145 prostate cancer). The expression of some genes, such as ALDH3A1, TNS4, CLDN2, and AKR1B10, which are known to play important roles in cancer cell migration, invasion, proliferation and apoptosis, were increased in HCT-8 R cells. R cells also showed higher ALDH3A1 enzyme activity, higher ROS, higher anoikis resistance, and higher softness than E cells. More importantly, in vitro assay and in vivo animal models revealed that HCT-8 R cells were more invasive than E cells. Our comprehensive comparison of HCT-8 E and R cells revealed differences of molecular, phenotypical, and mechanical signatures

  3. Development of InCVAX as a novel in situ autologous vaccine for metastatic cancers (Conference Presentation)

    Science.gov (United States)

    Hode, Tomas; Alleruzzo, Luciano; Raker, Joseph; Lam, Samuel Siu Kit; Nordquist, Robert E.; Chen, Wei R.

    2016-03-01

    A novel method, an in situ autologous whole-cell cancer vaccine (inCVAX), is being developed by Immunophotonics, Inc., for the treatment of metastatic cancers. inCVAX combines phototherapy and immunotherapy to potentially induce a systemic anti-tumor immune response in the hosts. Immunophotonics and its academic partners have spent years conducting nonclinical research, developing CMC techniques and conducting clinical research. In 2015 the company initiated a late-stage (II/III) clinical trial in South America for advanced breast cancer patients. The process of developing the inCVAX approach from a laboratory setting into clinical trials requires significant efforts from a group of dedicated engineers, scientists, and physicians. The growth of the company and its business advances demonstrated the determination of a group of visionary investors, entrepreneurs, and business leaders. This talk will chronicle the milestones of the scientific achievement, medical progress, and business development of Immunophotonics.

  4. Molecular mechanism of anti-cancer activity of phycocyanin in triple-negative breast cancer cells.

    Science.gov (United States)

    Ravi, Mathangi; Tentu, Shilpa; Baskar, Ganga; Rohan Prasad, Surabhi; Raghavan, Swetha; Jayaprakash, Prajisha; Jeyakanthan, Jeyaraman; Rayala, Suresh K; Venkatraman, Ganesh

    2015-10-23

    Triple-negative breast cancers represent an important clinical challenge, as these cancers do not respond to conventional endocrine therapies or other available targeted agents. Phycocyanin (PC), a natural, water soluble and non-toxic molecule is shown to have potent anti-cancer property. In this study, we determined the efficacy of PC as an anti-neoplastic agent in vitro on a series of breast cancer cell lines. We studied effects of PC in inducing DNA damage and apoptosis through western blot and qPCR. Also, anti-metastatic and anti-angiogenic properties were studied by classic wound healing and vasculogenic mimicry assays. We found that triple negative MDA-MB-231 cells were most sensitive to PC (IC50 : 5.98 ± 0.95 μM) as compared to other cells. They also showed decreased cell proliferation and reduced colony formation ability upon treatment with PC. Profile of Cell cycle analysis showed that PC caused G1 arrest which could be attributed to decreased mRNA levels of Cyclin E and CDK-2 and increased p21 levels. Mechanistic studies revealed that PC induced apoptosis as evident by increase in percentage of annexin positive cells, increase in γ-H2AX levels, and by changing the Bcl-2/Bax ratio followed by release of cytochrome C and increased Caspase 9 levels. MDA MB 231 cells treated with PC resulted in decreased cell migration and increased cell adhesive property and also showed anti-angiogenic effects. We also observed that PC suppressed cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) production. All these biological effects of phycocyanin on MDA MB 231 cells could be attributed to decreased MAPK signaling pathway. We also observed that PC is non-toxic to non-malignant cells, platelets and RBC's. Taken together, these findings demonstrate, for the first time, that PC may be a promising anti-neoplastic agent for treatment of triple negative breast cancers.

  5. Bcl-2 confers survival in cisplatin treated cervical cancer cells: circumventing cisplatin dose-dependent toxicity and resistance.

    Science.gov (United States)

    Leisching, Gina; Loos, Benjamin; Botha, Matthys; Engelbrecht, Anna-Mart

    2015-10-16

    Cisplatin is the main chemotherapeutic drug for the treatment of cervical cancers, however resistance to cisplatin is increasingly common and therefore has limited the efficacy and use of this drug in the clinic. Dose-dependent toxicity poses an additional challenge since patients suffer long-term and often permanent side-effects after treatment. Bcl-2 up-regulation has been implicated in the resistance to cisplatin in a variety of cancer cell lines, however its role in cervical cancer is confounding. A low, non-cytotoxic concentration of cisplatin was used in the treatment of HeLa and CaSki cells. Bcl-2 expression was determined through Western blotting and immunocytochemistry before and after treatment with cisplatin. To assess the reliance of the cervical cancer cells on Bcl-2 in the presence of cisplatin, Bcl-2 knock-down was achieved through RNA interference, where after apoptosis was assessed through PARP cleavage (Western blotting), Caspase activity (Caspase-Glo(©)) and PI inclusion analysis (Flow cytometry). Finally, pre-malignant and malignant cervical tissue was analysed for the presence of Bcl-2 through Western blotting and immunofluorescence. Cervical cancer cells upregulate Bcl-2 when treated with a non-cytotoxic concentration of cisplatin, which when silenced, effectively enhanced cisplatin sensitivity, and therefore significantly induced apoptosis. Analysis of the expression profile of Bcl-2 in cervical tissue revealed its up-regulation in cervical carcinoma, which agrees with results obtained from the in vitro data. Our data strongly suggest that utilising a lower dose of cisplatin is feasible when combined with Bcl-2 silencing as an adjuvant treatment, thereby improving both the dose-dependent toxicity, as well as cervical cancer resistance.

  6. COX-independent mechanisms of cancer chemoprevention by anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Evrim eGurpinar

    2013-07-01

    Full Text Available Epidemiological and clinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs, including cyclooxygenase (COX-2 selective inhibitors, reduce the risk of developing cancer. Experimental studies in human cancer cell lines and rodent models of carcinogenesis support these observations by providing strong evidence for the antineoplastic properties of NSAIDs. The involvement of COX-2 in tumorigenesis and its overexpression in various cancer tissues suggest that inhibition of COX-2 is responsible for the chemopreventive efficacy of these agents. However, the precise mechanisms by which NSAIDs exert their antiproliferative effects are still a matter of debate. Numerous other studies have shown that NSAIDs can act through COX-independent mechanisms. This review provides a detailed description of the major COX-independent molecular targets of NSAIDs and discusses how these targets may be involved in their anticancer effects. Toxicities resulting from COX inhibition and the suppression of prostaglandin synthesis preclude the long-term use of NSAIDs for cancer chemoprevention. Furthermore, chemopreventive efficacy is incomplete and treatment often leads to the development of resistance. Identification of alternative NSAID targets and elucidation of the biochemical processes by which they inhibit tumor growth could lead to the development of safer and more efficacious drugs for cancer chemoprevention.

  7. Risk of gastrointestinal malignancies and mechanisms of cancer development with obesity and its treatment.

    Science.gov (United States)

    Freeman, Hugh J

    2004-12-01

    Gastrointestinal malignancies may be associated with obesity, defined specifically by increased body-mass index, and based largely on environmental factors rather than genetics. In particular, there seems to be a definite increase in the incidence of both oesophageal and colorectal cancer. Mechanisms associated with obesity include a particular metabolic state characterized by hyperinsulinemia, or insulin resistance, along with elevated serum leptin. Leptin is derived from adipocytes and appears to play a role in the regulation of ghrelin, a peptide derived from the stomach and small intestine that stimulates appetite and weight gain. In addition to these metabolic changes, there are other anatomical alterations that may indirectly predispose to cancer, including the predisposition of obesity to gastroesophageal reflux and, possibly, oesophageal cancer. Other mechanisms may involve adipocyte-derived cytokines, or adipokines, that may serve as signalling devices in the pathogenesis of cancer. Finally, pharmacologic and surgical avenues available for treatment of obesity, including lipase inhibitors and gastric or jejuno-ileal bypass procedures may set the stage for subsequent gastric or intestinal tract cancer.

  8. Genetic Alterations in the PI3K/Akt Signaling Pathway Confer Sensitivity of Thyroid Cancer Cells to Therapeutic Targeting of Akt and mTOR

    Science.gov (United States)

    Liu, Dingxie; Hou, Peng; Liu, Zhi; Wu, Guojun; Xing, Mingzhao

    2009-01-01

    We investigated the genotype-dependent therapeutic potential of targeting the PI3K/Akt pathway for thyroid cancer. Proliferation of TPC1, Hth7, FTC133, OCUT1, K1, and BCPAP cells that harbored PI3K/Akt-activating genetic alterations was potently inhibited by the Akt inhibitor perifosine whereas SW1736, Hth74, WRO, KAT18, and TAD2 cells that harbored no genetic alterations had no or only modest responses. Inhibition of Akt phosphorylation by perifosine was seen in these cells. Genetic-dependent apoptosis was induced by perifosine in cells selectively tested. Similarly, potent inhibition of cell proliferation by the mTOR inhibitor temsirolimus occurred in virtually all the cells harboring genetic alterations whereas modest inhibition was seen in some of the cells not harboring genetic alterations. Temsirolimus inhibited the phosphorylation of p70S6K, a substrate of mTOR. Knockdown of Akt1/2 or mTOR by shRNA approach inhibited the proliferation and colony formation of FTC133 and OCUT1 cells that harbored genetic alterations in the PI3K/Akt pathway but had no effect on SW1736 and KAT18 cells that did not. Transfection with PIK3CA mutants greatly sensitized SW1736 cells to perifosine and temsirolimus. Growth of xenograft tumors derived from FTC133 cells but not SW1736 cells in nude mice was dramatically inhibited by perifosine. Thus, this work for the first time demonstrates that genetic alterations in the PI3K/Akt pathway confer thyroid cancer cells addiction to this pathway and their sensitivity to inhibition by targeting Akt and mTOR. This genotype-based targeting of the PI3K/Akt pathway using Akt and mTOR inhibitors may offer an effective therapeutic strategy for thyroid cancer and warrants further studies. PMID:19706758

  9. Mendel conference

    CERN Document Server

    2015-01-01

    This book is a collection of selected accepted papers of Mendel conference that has been held in Brno, Czech Republic in June 2015. The book contents three chapters which represent recent advances in soft computing including intelligent image processing and bio-inspired robotics.: Chapter 1: Evolutionary Computing, and Swarm intelligence, Chapter 2: Neural Networks, Self-organization, and Machine Learning, and Chapter3: Intelligent Image Processing, and Bio-inspired Robotics. The Mendel conference was established in 1995, and it carries the name of the scientist and Augustinian priest Gregor J. Mendel who discovered the famous Laws of Heredity. In 2015 we are commemorating 150 years since Mendel's lectures, which he presented in Brno on February and March 1865. The main aim of the conference was to create a periodical possibility for students, academics and researchers to exchange their ideas and novel research methods.  .

  10. Mutations in human DNA polymerase γ confer unique mechanisms of catalytic deficiency that mirror the disease severity in mitochondrial disorder patients

    Science.gov (United States)

    Sohl, Christal D.; Kasiviswanathan, Rajesh; Copeland, William C.; Anderson, Karen S.

    2013-01-01

    Human mitochondrial DNA polymerase γ (pol γ) is solely responsible for the replication and repair of the mitochondrial genome. Unsurprisingly, alterations in pol γ activity have been associated with mitochondrial diseases such as Alpers syndrome and progressive external ophthalmoplegia. Thus far, predicting the severity of mitochondrial disease based the magnitude of deficiency in pol γ activity has been difficult. In order to understand the relationship between disease severity in patients and enzymatic defects in vitro, we characterized the molecular mechanisms of four pol γ mutations, A957P, A957S, R1096C and R1096H, which have been found in patients suffering from aggressive Alpers syndrome to mild progressive external ophthalmoplegia. The A957P mutant showed the most striking deficiencies in the incorporation efficiency of a correct deoxyribonucleotide triphosphate (dNTP) relative to wild-type pol γ, with less, but still significant incorporation efficiency defects seen in R1096H and R1096C, and only a small decrease in incorporation efficiency observed for A957S. Importantly, this trend matches the disease severity observed in patients very well (approximated as , from most severe disease to least severe). Further, the A957P mutation conferred a two orders of magnitude loss of fidelity relative to wild-type pol γ, indicating that a buildup of mitochondrial genomic mutations may contribute to the death in infancy seen with these patients. We conclude that characterizing the unique molecular mechanisms of pol γ deficiency for physiologically important mutant enzymes is important for understanding mitochondrial disease and for predicting disease severity. PMID:23208208

  11. A Novel Mechanism for CTCF in the Epigenetic Regulation of Bax in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Claudia Fabiola Méndez-Catalá

    2013-08-01

    Full Text Available We previously reported the association of elevated levels of the multifunctional transcription factor, CCCTC binding factor (CTCF, in breast cancer cells with the specific anti-apoptotic function of CTCF. To understand the molecular mechanisms of this phenomenon, we investigated regulation of the human Bax gene by CTCF in breast and non-breast cells. Two CTCF binding sites (CTSs within the Bax promoter were identified. In all cells, breast and non-breast, active histone modifications were present at these CTSs, DNA harboring this region was unmethylated, and levels of Bax mRNA and protein were similar. Nevertheless, up-regulation of Bax mRNA and protein and apoptotic cell death were observed only in breast cancer cells depleted of CTCF. We proposed that increased CTCF binding to the Bax promoter in breast cancer cells, by comparison with non-breast cells, may be mechanistically linked to the specific apoptotic phenotype in CTCF-depleted breast cancer cells. In this study, we show that CTCF binding was enriched at the Bax CTSs in breast cancer cells and tumors; in contrast, binding of other transcription factors (SP1, WT1, EGR1, and c-Myc was generally increased in non-breast cells and normal breast tissues. Our findings suggest a novel mechanism for CTCF in the epigenetic regulation of Bax in breast cancer cells, whereby elevated levels of CTCF support preferential binding of CTCF to the Bax CTSs. In this context, CTCF functions as a transcriptional repressor counteracting influences of positive regulatory factors; depletion of breast cancer cells from CTCF therefore results in the activation of Bax and apoptosis.

  12. Mechanisms of Resistance to NTRK Inhibitors and Therapeutic Strategies in NTRK1-Rearranged Cancers.

    Science.gov (United States)

    Fuse, Miho J; Okada, Koutaroh; Oh-Hara, Tomoko; Ogura, Hayato; Fujita, Naoya; Katayama, Ryohei

    2017-10-01

    Neurotrophic receptor tyrosine kinase 1 ( NTRK1 ) gene rearrangement leads to constitutive activation of NTRK1, which induces high-transforming ability. NTRK-rearranged cancers have been identified in several cancer types, such as glioblastoma, non-small cell lung cancer, and colorectal cancer. Although there are currently no clinically approved inhibitors that target NTRK1, several tyrosine kinase inhibitors (TKI), such as entrectinib and LOXO-101, are in clinical trials. The purpose of this study was to identify potential mechanisms of resistance to NTRK inhibitors and find potential therapeutic strategies to overcome the resistance. We examined the sensitivity of TPM3-NTRK1-transformed Ba/F3 cells and TPM3-NTRK1-harboring KM12 cells to multiple NTRK inhibitors. Acquired NTRK inhibitor-resistant mutations were screened by N-ethyl-N-nitrosourea mutagenesis with Ba/F3-TPM3-NTRK1 cells or by the establishment of NTRK-TKI-resistant cells from KM12 cells continuously treated with NTRK-TKIs. We identified multiple novel NTRK-TKI resistance mutations in the NTRK1 kinase domain, including G595R, and insulin growth factor receptor type 1 (IGF1R) bypass pathway-mediated resistance. After identifying the resistance mechanisms, we performed drug screening with small-molecule inhibitors to overcome the resistance. As a result, we found that ponatinib and nintedanib effectively inhibited the survival of TPM3-NTRK1-G667C but not G595R mutants, both of which showed resistance to entrectinib or larotrectinib (LOXO-101). Furthermore, cabozantinib with an IGF1R inhibitor such as OSI-906 could overcome bypass pathway-mediated resistance. We developed a comprehensive model of acquired resistance to NTRK inhibitors in cancer with NTRK1 rearrangement and identified cabozantinib as a therapeutic strategy to overcome the resistance. Mol Cancer Ther; 16(10); 2130-43. ©2017 AACR . ©2017 American Association for Cancer Research.

  13. Brown seaweed fucoidan: biological activity and apoptosis, growth signaling mechanism in cancer.

    Science.gov (United States)

    Senthilkumar, Kalimuthu; Manivasagan, Panchanathan; Venkatesan, Jayachandran; Kim, Se-Kwon

    2013-09-01

    Seaweeds, being abundant sources of bioactive components have much interest in recent times. The complex polysaccharides from the brown, red and green seaweeds possess broad spectrum therapeutic properties. The sulfated polysaccharides are routinely used in biomedical research and have known biological activities. Fucoidan, a fucose-rich polysaccharide extracted from brown seaweed has various biological functions including anticancer effects. Cellular damage induces growth arrest and tumor suppression by inducing apoptosis, the mechanism of cell death depends on the magnitude of DNA damage following exposure to anticancer agents. Apoptosis is mainly regulated by cell growth signaling molecules. Number of research studies evidenced that fucoidan shown to induce cytotoxicity of various cancer cells, induces apoptosis, and inhibits invasion, metastasis and angiogenesis of cancer cells. There are few articles discussing on fucoidan biological activity but no specific review on cancer and its signaling mechanism. Hence, this review discusses the brown seaweed fucoidan structure and some biological function and role in apoptosis, invasion, metastasis, angiogenesis and growth signal mechanism on cancer. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Biophysical Approach to Mechanisms of Cancer Prevention and Treatment with Green Tea Catechins.

    Science.gov (United States)

    Suganuma, Masami; Takahashi, Atsushi; Watanabe, Tatsuro; Iida, Keisuke; Matsuzaki, Takahisa; Yoshikawa, Hiroshi Y; Fujiki, Hirota

    2016-11-18

    Green tea catechin and green tea extract are now recognized as non-toxic cancer preventives for humans. We first review our brief historical development of green tea cancer prevention. Based on exciting evidence that green tea catechin, (-)-epigallocatechin gallate (EGCG) in drinking water inhibited lung metastasis of B16 melanoma cells, we and other researchers have studied the inhibitory mechanisms of metastasis with green tea catechins using biomechanical tools, atomic force microscopy (AFM) and microfluidic optical stretcher. Specifically, determination of biophysical properties of cancer cells, low cell stiffness, and high deformability in relation to migration, along with biophysical effects, were studied by treatment with green tea catechins. The study with AFM revealed that low average values of Young's moduli, indicating low cell stiffness, are closely associated with strong potential of cell migration and metastasis for various cancer cells. It is important to note that treatments with EGCG and green tea extract elevated the average values of Young's moduli resulting in increased stiffness (large elasticity) of melanomas and various cancer cells. We discuss here the biophysical basis of multifunctions of green tea catechins and green tea extract leading to beneficial effects for cancer prevention and treatment.

  15. Obesity and pancreatic cancer: overview of epidemiologic evidence and biologic mechanisms.

    Science.gov (United States)

    Bracci, Paige M

    2012-01-01

    In the United States, pancreatic cancer is characterized by a low 5-yr survival rate of approximately 6%, fewer than 10% of patients diagnosed with localized disease and thus candidates for "curative" surgical resection, increasing incidence and few established risk factors. Similar statistics are observed for other industrialized nations. With new evidence to suggest that pancreatic cancer develops over a number of years, markers that can better identify high risk patients and are applicable to earlier diagnosis hold promise for improving these dire statistics. Obesity is one of the few modifiable risk factors that has been associated with increased risk of pancreatic cancer and also is related to increased risk of diabetes, a condition that in turn has been associated with pancreatic cancer development. Given recent data that nearly 70% of United States adults are overweight or obese, a clarification of the complex association between obesity and pancreatic cancer may disclose targets for prevention and intervention to decrease incidence and improve prognosis of this highly fatal disease. An overview of the current epidemiology and hypothesized biological mechanisms involved in the obesity-pancreatic cancer association are presented. Copyright © 2011 Wiley Periodicals, Inc.

  16. Multiple Molecular and Cellular Mechanisms of Action of Lycopene in Cancer Inhibition

    Directory of Open Access Journals (Sweden)

    Cristina Trejo-Solís

    2013-01-01

    Full Text Available Epidemiological studies suggest that including fruits, vegetables, and whole grains in regular dietary intake might prevent and reverse cellular carcinogenesis, reducing the incidence of primary tumours. Bioactive components present in food can simultaneously modulate more than one carcinogenic process, including cancer metabolism, hormonal balance, transcriptional activity, cell-cycle control, apoptosis, inflammation, angiogenesis and metastasis. Some studies have shown an inverse correlation between a diet rich in fruits, vegetables, and carotenoids and a low incidence of different types of cancer. Lycopene, the predominant carotenoid found in tomatoes, exhibits a high antioxidant capacity and has been shown to prevent cancer, as evidenced by clinical trials and studies in cell culture and animal models. In vitro studies have shown that lycopene treatment can selectively arrest cell growth and induce apoptosis in cancer cells without affecting normal cells. In vivo studies have revealed that lycopene treatment inhibits tumour growth in the liver, lung, prostate, breast, and colon. Clinical studies have shown that lycopene protects against prostate cancer. One of the main challenges in cancer prevention is the integration of new molecular findings into clinical practice. Thus, the identification of molecular biomarkers associated with lycopene levels is essential for improving our understanding of the mechanisms underlying its antineoplastic activity.

  17. Myxoma and vaccinia viruses exploit different mechanisms to enter and infect human cancer cells.

    Science.gov (United States)

    Villa, Nancy Y; Bartee, Eric; Mohamed, Mohamed R; Rahman, Masmudur M; Barrett, John W; McFadden, Grant

    2010-06-05

    Myxoma (MYXV) and vaccinia (VACV) viruses have recently emerged as potential oncolytic agents that can infect and kill different human cancer cells. Although both are structurally similar, it is unknown whether the pathway(s) used by these poxviruses to enter and cause oncolysis in cancer cells are mechanistically similar. Here, we compared the entry of MYXV and VACV-WR into various human cancer cells and observed significant differences: 1--low-pH treatment accelerates fusion-mediated entry of VACV but not MYXV, 2--the tyrosine kinase inhibitor genistein inhibits entry of VACV, but not MYXV, 3--knockdown of PAK1 revealed that it is required for a late stage event downstream of MYXV entry into cancer cells, whereas PAK1 is required for VACV entry into the same target cells. These results suggest that VACV and MYXV exploit different mechanisms to enter into human cancer cells, thus providing some rationale for their divergent cancer cell tropisms. 2010 Elsevier Inc. All rights reserved.

  18. Moderate alcohol consumption and breast cancer in women: from epidemiology to mechanisms and interventions.

    Science.gov (United States)

    Brooks, Philip J; Zakhari, Samir

    2013-01-01

    Epidemiologic studies indicate that moderate alcohol consumption increases breast cancer risk in women. Understanding the mechanistic basis of this relationship has important implications for women's health and breast cancer prevention. In this commentary, we focus on some recent epidemiologic studies linking moderate alcohol consumption to breast cancer risk and place the results of those studies within the framework of our current understanding of the temporal and mechanistic basis of human carcinogenesis. This analysis supports the hypothesis that alcohol acts as a weak cumulative breast carcinogen and may also be a tumor promoter. We discuss the implications of these mechanisms for the prevention and treatment of alcohol-related breast cancer and present some considerations for future studies. Moderate alcohol consumption has been shown to benefit cardiovascular health and recently been associated with healthy aging. Therefore, a better understanding of how moderate alcohol consumption impacts breast cancer risk will allow women to make better informed decisions about the risks and benefits of alcohol consumption in the context of their overall health and at different stages of their life. Such mechanistic information is also important for the development of rational clinical interventions to reduce ethanol-related breast cancer mortality. Copyright © 2012 by the Research Society on Alcoholism.

  19. The Redox Status of Cancer Cells Supports Mechanisms behind the Warburg Effect

    Directory of Open Access Journals (Sweden)

    Jorgelindo da Veiga Moreira

    2016-10-01

    Full Text Available To better understand the energetic status of proliferating cells, we have measured the intracellular pH (pHi and concentrations of key metabolites, such as adenosine triphosphate (ATP, nicotinamide adenine dinucleotide (NAD, and nicotinamide adenine dinucleotide phosphate (NADP in normal and cancer cells, extracted from fresh human colon tissues. Cells were sorted by elutriation and segregated in different phases of the cell cycle (G0/G1/S/G2/M in order to study their redox (NAD, NADP and bioenergetic (ATP, pHi status. Our results show that the average ATP concentration over the cell cycle is higher and the pHi is globally more acidic in normal proliferating cells. The NAD+/NADH and NADP+/NADPH redox ratios are, respectively, five times and ten times higher in cancer cells compared to the normal cell population. These energetic differences in normal and cancer cells may explain the well-described mechanisms behind the Warburg effect. Oscillations in ATP concentration, pHi, NAD+/NADH, and NADP+/NADPH ratios over one cell cycle are reported and the hypothesis addressed. We also investigated the mitochondrial membrane potential (MMP of human and mice normal and cancer cell lines. A drastic decrease of the MMP is reported in cancer cell lines compared to their normal counterparts. Altogether, these results strongly support the high throughput aerobic glycolysis, or Warburg effect, observed in cancer cells.

  20. MicroRNA-519a is a novel oncomir conferring tamoxifen resistance by targeting a network of tumour-suppressor genes in ER+ breast cancer.

    Science.gov (United States)

    Ward, Aoife; Shukla, Kirti; Balwierz, Aleksandra; Soons, Zita; König, Rainer; Sahin, Ozgür; Wiemann, Stefan

    2014-08-01

    Tamoxifen is an endocrine therapy which is administered to up to 70% of all breast cancer patients with oestrogen receptor alpha (ERα) expression. Despite the initial response, most patients eventually acquire resistance to the drug. MicroRNAs (miRNAs) are a class of small non-coding RNAs which have the ability to post-transcriptionally regulate genes. Although the role of a few miRNAs has been described in tamoxifen resistance at the single gene/target level, little is known about how concerted actions of miRNAs targeting biological networks contribute to resistance. Here we identified the miRNA cluster, C19MC, which harbours around 50 mature miRNAs, to be up-regulated in resistant cells, with miRNA-519a being the most highly up-regulated. We could demonstrate that miRNA-519a regulates tamoxifen resistance using gain- and loss-of-function testing. By combining functional enrichment analysis and prediction algorithms, we identified three central tumour-suppressor genes (TSGs) in PI3K signalling and the cell cycle network as direct target genes of miR-519a. Combined expression of these target genes correlated with disease-specific survival in a cohort of tamoxifen-treated patients. We identified miRNA-519a as a novel oncomir in ER+ breast cancer cells as it increased cell viability and cell cycle progression as well as resistance to tamoxifen-induced apoptosis. Finally, we could show that elevated miRNA-519a levels were inversely correlated with the target genes' expression and that higher expression of this miRNA correlated with poorer survival in ER+ breast cancer patients. Hence we have identified miRNA-519a as a novel oncomir, co-regulating a network of TSGs in breast cancer and conferring resistance to tamoxifen. Using inhibitors of such miRNAs may serve as a novel therapeutic approach to combat resistance to therapy as well as proliferation and evasion of apoptosis in breast cancer. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons

  1. Mechanisms Regulating Acid-Base Transporter Expression in Breast- and Pancreatic Cancer

    DEFF Research Database (Denmark)

    Gorbatenko, Andrej

    , characteristics of which are a shift towards glycolytic metabolism and increased acid production. HER2 receptor overexpression in breast cancer leads to further increased glycolysis, invasion and metastasis, drug resistance and poor prognosis. Increased tumor glycolysis requires acquisition of mechanisms...... for dealing with excess acid production. In this light, evidence accumulates on the importance of pH regulatory proteins to cancer cell survival and motility. Our group previously demonstrated upregulation of the Na+/HCO3 - co-transporter NBCn1 (SLC4A7) by a constitutively active form of HER2 receptor (p95HER...

  2. Akt-dependent and independent mechanisms of mTOR regulation in cancer

    OpenAIRE

    Memmott, Regan M.; Dennis, Phillip A.

    2009-01-01

    The protein kinase mTOR (mammalian target of rapamycin) is a critical regulator of cellular metabolism, growth, and proliferation. These processes contribute to tumor formation, and many cancers are characterized by aberrant activation of mTOR. Although activating mutations in mTOR itself have not been identified, deregulation of upstream components that regulate mTOR are prevalent in cancer. The prototypic mechanism of mTOR regulation in cells is through activation of the PI3K/Akt pathway, b...

  3. European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): part II

    DEFF Research Database (Denmark)

    Krege, Susanne; Beyer, Jörg; Souchon, Rainer

    2007-01-01

    OBJECTIVES: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology...... trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged Udgivelsesdato: 2008/3...

  4. BRCA1 R1699Q variant displaying ambiguous functional abrogation confers intermediate breast and ovarian cancer risk

    DEFF Research Database (Denmark)

    Spurdle, Amanda B; Whiley, Phillip J; Thompson, Bryony

    2012-01-01

    Clinical classification of rare sequence changes identified in the breast cancer susceptibility genes BRCA1 and BRCA2 is essential for appropriate genetic counselling of individuals carrying these variants. We previously showed that variant BRCA1 c.5096G>A p.Arg1699Gln in the BRCA1 transcriptional...

  5. Metabolic autofluorescence imaging of head and neck cancer organoids quantifies cellular heterogeneity and treatment response (Conference Presentation)

    Science.gov (United States)

    Shah, Amy T.; Heaster, Tiffany M.; Skala, Melissa C.

    2017-02-01

    Treatment options for head and neck cancer are limited, and can cause an impaired ability to eat, talk, and breathe. Therefore, optimized and personalized therapies could reduce unnecessary toxicities from ineffective treatments. Organoids are generated from primary tumor tissue and provide a physiologically-relevant in vitro model to measure drug response. Additionally, multiphoton fluorescence lifetime imaging (FLIM) of the metabolic cofactors NAD(P)H and FAD can resolve dynamic cellular response to anti-cancer treatment. This study applies FLIM of NAD(P)H and FAD to head and neck cancer organoids. Head and neck cancer tissue was digested and grown in culture as three-dimensional organoids. Gold standard measures of therapeutic response in vivo indicate stable disease after treatment with cetuximab (antibody therapy) or cisplatin (chemotherapy), and treatment response after combination treatment. In parallel, organoids were treated with cetuximab, cisplatin, or combination therapy for 24 hours. Treated organoids exhibit decreased NAD(P)H lifetime (p<0.05) and increased FAD lifetime (p<0.05) compared with control organoids. Additionally, analysis of cellular heterogeneity identifies distinct subpopulations of cells in response to treatment. A quantitative heterogeneity index predicts in vivo treatment response and demonstrates increased cellular heterogeneity in organoids treated with cetuximab or cisplatin compared with combination treatment. Mapping of cell subpopulations enables characterization of spatial relationships between cell subpopulations. Ultimately, an organoid model combined with metabolic fluorescence imaging could provide a high-throughput platform for drug discovery. Organoids grown from patient tissue could enable individualized treatment planning. These achievements could optimize quality of life and treatment outcomes for head and neck cancer patients.

  6. Modeling extracellular matrix (ECM) alterations in ovarian cancer by multiphoton excited fabrication of stromal models (Conference Presentation)

    Science.gov (United States)

    Campagnola, Paul J.; Ajeti, Visar; Lara, Jorge; Eliceiri, Kevin W.; Patankar, Mansh

    2016-04-01

    A profound remodeling of the extracellular matrix (ECM) occurs in human ovarian cancer but it unknown how this affects tumor growth, where this understanding could lead to better diagnostics and therapeutic approaches. We investigate the role of these ECM alterations by using multiphoton excited (MPE) polymerization to fabricate biomimetic models to investigate operative cell-matrix interactions in invasion/metastasis. First, we create nano/microstructured gradients mimicking the basal lamina to study adhesion/migration dynamics of ovarian cancer cells of differing metastatic potential. We find a strong haptotactic response that depends on both contact guidance and ECM binding cues. While we found enhanced migration for more invasive cells, the specifics of alignment and directed migration also depend on cell polarity. We further use MPE fabrication to create collagen scaffolds with complex, 3D submicron morphology. The stromal scaffold designs are derived directly from "blueprints" based on SHG images of normal, high risk, and malignant ovarian tissues. The models are seeded with different cancer cell lines and this allows decoupling of the roles of cell characteristics (metastatic potential) and ECM structure and composition (normal vs cancer) on adhesion/migration dynamics. We found the malignant stroma structure promotes enhanced migration and proliferation and also cytoskeletal alignment. Creating synthetic models based on fibers patterns further allows decoupling the topographic roles of the fibers themselves vs their alignment within the tissue. These models cannot be synthesized by other conventional fabrication methods and we suggest the MPE image-based fabrication method will enable a variety of studies in cancer biology.

  7. Cancer pain: A critical review of mechanism-based classification and physical therapy management in palliative care

    Directory of Open Access Journals (Sweden)

    Senthil P Kumar

    2011-01-01

    Full Text Available Mechanism-based classification and physical therapy management of pain is essential to effectively manage painful symptoms in patients attending palliative care. The objective of this review is to provide a detailed review of mechanism-based classification and physical therapy management of patients with cancer pain. Cancer pain can be classified based upon pain symptoms, pain mechanisms and pain syndromes. Classification based upon mechanisms not only addresses the underlying pathophysiology but also provides us with an understanding behind patient′s symptoms and treatment responses. Existing evidence suggests that the five mechanisms - central sensitization, peripheral sensitization, sympathetically maintained pain, nociceptive and cognitive-affective - operate in patients with cancer pain. Summary of studies showing evidence for physical therapy treatment methods for cancer pain follows with suggested therapeutic implications. Effective palliative physical therapy care using a mechanism-based classification model should be tailored to suit each patient′s findings, using a biopsychosocial model of pain.

  8. European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus group (EGCCCG): part I

    DEFF Research Database (Denmark)

    Krege, Susanne; Beyer, Jörg; Souchon, Rainer

    2007-01-01

    OBJECTIVES: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the A......OBJECTIVES: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology...... in 2004 remain valid 3 yr later, refinements in the treatment of early- and advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer...

  9. [Distribution of fibronectin and other plasma proteins in gastric cancer tissues: investigation of mechanisms of desmoplasia of the stroma].

    Science.gov (United States)

    Maeda, M

    1984-11-01

    To elucidate the mechanisms of desmoplasia of gastric cancer tissues, distribution of fibronectin (FN), fibrinogen (Fbg), alpha 2-plasmin inhibitor (alpha 2PI) and factor XIII (XIIIA) in fresh 49 gastric cancer tissues and 5 gastric ulcer tissues was studied by indirect immunofluorescent technique. FN existed scarcely in the basement membrane area of gastric cancer tubuli. FN and Fbg were distributed in same patterns abundantly in the stroma of all gastric cancer tissues regardless of their histological types. Neither alpha 2PI nor XIIIA was demonstrated in gastric cancer tissues. Autofluorescence of the cross-linked collagen fibers, which were seen in many gastric cancer cases, were surrounded with FN and Fbg. These results were well identical with those obtained from gastric ulcer tissues. These facts indicate that such a mechanism as non-specific wound healing process participates in desmoplasia of gastric cancer stroma as well as in fibrosis of gastric ulcer.

  10. Mechanical stress downregulates MHC class I expression on human cancer cell membrane.

    Directory of Open Access Journals (Sweden)

    Rosanna La Rocca

    Full Text Available In our body, cells are continuously exposed to physical forces that can regulate different cell functions such as cell proliferation, differentiation and death. In this work, we employed two different strategies to mechanically stress cancer cells. The cancer and healthy cell populations were treated either with mechanical stress delivered by a micropump (fabricated by deep X-ray nanolithography or by ultrasound wave stimuli. A specific down-regulation of Major Histocompatibility Complex (MHC class I molecules expression on cancer cell membrane compared to different kinds of healthy cells (fibroblasts, macrophages, dendritic and lymphocyte cells was observed, stimulating the cells with forces in the range of nano-newton, and pressures between 1 and 10 bar (1 bar = 100.000 Pascal, depending on the devices used. Moreover, Raman spectroscopy analysis, after mechanical treatment, in the range between 700-1800 cm(-1, indicated a relative concentration variation of MHC class I. PCA analysis was also performed to distinguish control and stressed cells within different cell lines. These mechanical induced phenotypic changes increase the tumor immunogenicity, as revealed by the related increased susceptibility to Natural Killer (NK cells cytotoxic recognition.

  11. Mechanical Stress Downregulates MHC Class I Expression on Human Cancer Cell Membrane

    KAUST Repository

    La Rocca, Rosanna

    2014-12-26

    In our body, cells are continuously exposed to physical forces that can regulate different cell functions such as cell proliferation, differentiation and death. In this work, we employed two different strategies to mechanically stress cancer cells. The cancer and healthy cell populations were treated either with mechanical stress delivered by a micropump (fabricated by deep X-ray nanolithography) or by ultrasound wave stimuli. A specific down-regulation of Major Histocompatibility Complex (MHC) class I molecules expression on cancer cell membrane compared to different kinds of healthy cells (fibroblasts, macrophages, dendritic and lymphocyte cells) was observed, stimulating the cells with forces in the range of nano-newton, and pressures between 1 and 10 bar (1 bar = 100.000 Pascal), depending on the devices used. Moreover, Raman spectroscopy analysis, after mechanical treatment, in the range between 700–1800 cm−1, indicated a relative concentration variation of MHC class I. PCA analysis was also performed to distinguish control and stressed cells within different cell lines. These mechanical induced phenotypic changes increase the tumor immunogenicity, as revealed by the related increased susceptibility to Natural Killer (NK) cells cytotoxic recognition.

  12. AFM Bio-Mechanical Investigation of the Taxol Treatment of Breast Cancer Cells

    Science.gov (United States)

    Smith, Dylan; Patel, Dipika; Monjaraz, Fernando; Park, Soyeun

    2009-10-01

    Cancerous cells are known to be softer and easier to deform than normal cells. Changes in mechanical properties originate from the alteration of the actin cytoskeleton. The mechanism of cancer treatment using Taxol is related to the stabilization of microtubules. It has been shown that Taxol binds to polymerized tublin, stabilizes it against disassembly, and consequently inhibits cell division. An accurate quantitative study still lacks to relate the microtubule stabilizing effect with the cellular mechanical properties. We utilized our AFM to study changes in elastic properties of treated breast cancer cells. The AFM has several advantages for precise force measurements on a localized region with nanometer lateral dimension. In previous AFM studies, measurable contributions from the underlying hard substrate have been an obstacle to accurately determine the properties on thin samples. We modified our AFM tip to obtain the exact deformation profile as well as reducing the high stresses produced. We have probed depth profiles of mechanical properties of the taxol-treated and untreated cells by varying the indentation depth of the AFM-nanoindenting experiments.

  13. Conference Report: CAQD Conference 2013

    Directory of Open Access Journals (Sweden)

    Christina Silver

    2013-05-01

    Full Text Available Nestled on the banks of the river Lahn in central Germany, the 15th CAQD conference was held at Marburg. A beautiful provincial town, it is one of very few that was spared the bombings of WWII; now providing the perfect backdrop for meeting to discuss developments in qualitative technology. This was the second international conference in the series with more than 140 delegates from 14 countries, including: Canada, Brazil, Portugal, the UK, as well as Germany. Hosted by MAGMA, the Marburg Research Group for Methodology and Evaluation, in partnership with Philipps-University Marburg, CAQD prioritizes a user-focus which balances practical and methodological workshops with conference presentations. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs1302249

  14. 4th European Turbulence Conference

    CERN Document Server

    1993-01-01

    The European Turbulence Conferences have been organized under the auspices of the European Mechanics Committee (Euromech) to provide a forum for discussion and exchange of recent and new results in the field of turbulence. The first conference was organized in Lyon in 1986 with 152 participants. The second and third conferences were held in Berlin (1988) and Stockholm (1990) with 165 and 172 participants respectively. The fourth was organized in Delft from 30 June to 3 July 1992 by the J.M. Burgers Centre. There were 214 participants from 22 countries. This steadily growing number of participants demonstrates both the success and need for this type of conference. The main topics of the Fourth European Turbulence Conference were: Dynamical Systems and Transition; Statistical Physics and Turbulence; Experiments and Novel Experimental Techniques; Particles and Bubbles in Turbulence; Simulation Methods; Coherent Structures; Turbulence Modelling and Compressibility Effects. In addition a special session was held o...

  15. Consensus conferences

    DEFF Research Database (Denmark)

    Nielsen, Annika Porsborg; Lassen, Jesper

    , the differing perceptions are each in their own way rooted in an argument for democratic legitimacy. We therefore argue that national interpretations of consensus conferences, and of their ability to functions as a tool for public participation, depend to a great extent on the dominant ideals of democratic...

  16. Conference Summary

    Science.gov (United States)

    Harrington, James L., Jr.

    2000-01-01

    Celebrations and special events were in order this year as the Minority University-Space Interdisciplinary Network (MU-SPIN) Program and NASA's Minority University Research and Education Division (MURED) both reached their 10th anniversaries. In honor of this occasion, the 2000 Annual Users' Conference held at Morris Brown College (MBC) in Atlanta, Georgia, September 11-15, 2000, was the first to be jointly hosted by MU-SPIN and MURED. It was particularly fitting that this anniversary should fall in the year 2000. The start of the new millennium propelled us to push bold new ideas and renew our commitment to minority university participation in all areas of NASA. With the theme 'Celebrating Our Tenth Year With Our Eyes on the Prize,' the conference provided a national forum for showcasing successful MU-SPIN and MURED Program (MUREP) experiences to enhance faculty/student development in areas of scientific and technical research and education. Our NASA-relevant conference agenda resulted in a record-breaking 220 registered attendees. Using feedback from past participants, we designed a track of student activities closely tailored to their interests. The resulting showcase of technical assistance and best practices set a new standard for our conferences in the years to come. This year's poster session was our largest ever, with over 50 presentations from students, faculty, and teachers. Posters covered a broad range of NASA activities from 'A Study of the Spiral Galaxy M101' to 'Network Cabling Characteristics.'

  17. Conference report

    African Journals Online (AJOL)

    Tamara Shefer

    poster presentations on numerous disciplines, including: epidemiology, preventive medicine, public health, social ... The conference theme “from research to implementation” emphasised the importance of ... sustainable implementation were addressed in an honest and nuanced manner, leaving me with a sense of trouble ...

  18. CONFERENCE REPORTS

    African Journals Online (AJOL)

    Dr. Marfo

    dinner and, at this dinner, socialization was at its best, with some music and dancing and presentation of gifts from the host university. Some members of the .... Jean Monnet, a student hostel with conference facilities where most of the participants also stayed. The third and fourth days' sessions were held at the INALCO ...

  19. Prevalence, putative mechanisms, and current management of sleep problems during chemotherapy for cancer

    Directory of Open Access Journals (Sweden)

    Palesh O

    2012-12-01

    Full Text Available Oxana Palesh,1 Luke Peppone,2 Pasquale F Innominato,3–5 Michelle Janelsins,2 Monica Jeong,1 Lisa Sprod,7 Josee Savard,6 Max Rotatori,1 Shelli Kesler,1 Melinda Telli,1 Karen Mustian21Stanford University School of Medicine, Stanford, CA, USA; 2University of Rochester School of Medicine and Dentistry, Rochester, NY, USA; 3INSERM, UMRS 776, Biological Rhythms and Cancers, Villejuif, France; 4Faculty of Medicine, Universite Paris Sud, le Kremlin-Bicêtre, France; 5APHP, Chronotherapy Unit, Department of Oncology, Paul Brousse Hospital, Villejuif, France; 6Laval University, Quebec, Canada; 7University of North Carolina, Wilmington, NC, USAAbstract: Sleep problems are highly prevalent in cancer patients undergoing chemotherapy. This article reviews existing evidence on etiology, associated symptoms, and management of sleep problems associated with chemotherapy treatment during cancer. It also discusses limitations and methodological issues of current research. The existing literature suggests that subjectively and objectively measured sleep problems are the highest during the chemotherapy phase of cancer treatments. A possibly involved mechanism reviewed here includes the rise in the circulating proinflammatory cytokines and the associated disruption in circadian rhythm in the development and maintenance of sleep dysregulation in cancer patients during chemotherapy. Various approaches to the management of sleep problems during chemotherapy are discussed with behavioral intervention showing promise. Exercise, including yoga, also appear to be effective and safe at least for subclinical levels of sleep problems in cancer patients. Numerous challenges are associated with conducting research on sleep in cancer patients during chemotherapy treatments and they are discussed in this review. Dedicated intervention trials, methodologically sound and sufficiently powered, are needed to test current and novel treatments of sleep problems in cancer patients

  20. To Infection and Beyond: The Multi-Pronged Anti-Cancer Mechanisms of Oncolytic Viruses.

    Science.gov (United States)

    Cassady, Kevin A; Haworth, Kellie B; Jackson, Josh; Markert, James M; Cripe, Timothy P

    2016-02-04

    Over the past 1-2 decades we have witnessed a resurgence of efforts to therapeutically exploit the attributes of lytic viruses to infect and kill tumor cells while sparing normal cells. We now appreciate that the utility of viruses for treating cancer extends far beyond lytic cell death. Viruses are also capable of eliciting humoral and cellular innate and adaptive immune responses that may be directed not only at virus-infected cells but also at uninfected cancer cells. Here we review our current understanding of this bystander effect, and divide the mechanisms into lytic, cytokine, innate cellular, and adaptive phases. Knowing the key pathways and molecular players during virus infection in the context of the cancer microenvironment will be critical to devise strategies to maximize the therapeutic effects of oncolytic viroimmunotherapy.

  1. 2004 Mutagenesis Gordon Conference

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Sue Jinks-Robertson

    2005-09-16

    Mutations are genetic alterations that drive biological evolution and cause many, if not all, human diseases. Mutation originates via two distinct mechanisms: ''vertical'' variation is de novo change of one or few bases, whereas ''horizontal'' variation occurs by genetic recombination, which creates new mosaics of pre-existing sequences. The Mutagenesis Conference has traditionally focused on the generation of mutagenic intermediates during normal DNA synthesis or in response to environmental insults, as well as the diverse repair mechanisms that prevent the fixation of such intermediates as permanent mutations. While the 2004 Conference will continue to focus on the molecular mechanisms of mutagenesis, there will be increased emphasis on the biological consequences of mutations, both in terms of evolutionary processes and in terms of human disease. The meeting will open with two historical accounts of mutation research that recapitulate the intellectual framework of this field and thereby place the current research paradigms into perspective. The two introductory keynote lectures will be followed by sessions on: (1) mutagenic systems, (2) hypermutable sequences, (3) mechanisms of mutation, (4) mutation avoidance systems, (5) mutation in human hereditary and infectious diseases, (6) mutation rates in evolution and genotype-phenotype relationships, (7) ecology, mutagenesis and the modeling of evolution and (8) genetic diversity of the human population and models for human mutagenesis. The Conference will end with a synthesis of the meeting as the keynote closing lecture.

  2. Modulatory effects and molecular mechanisms of olive oil and other dietary lipids in breast cancer.

    Science.gov (United States)

    Escrich, Eduard; Solanas, Montserrat; Moral, Raquel; Escrich, Raquel

    2011-01-01

    Breast cancer is the most common cancer among women worldwide. In addition to genetic and endocrine factors, the environment, and specifically dietary habits, plays a key role in the aetiology of this malignancy. Epidemiological and, especially, experimental studies have shown a relationship between dietary lipids and breast cancer although there are conflicting results concerning their potential to modify cancer risk in humans. Abundant data have attributed a potential chemopreventive effect to extra-virgin olive oil (EVOO), the main source of fat in the Mediterranean diet, which is associated with low incidence and mortality rates from cardiovascular disease and some cancers, including that of the breast. It is well-established that the healthy effects of EVOO can be attributed both to its particular fatty acid composition (a high content in oleic acid (OA), a suitable quantity of essential polyunsaturated fatty acids (PUFA) and a relatively low n-6 PUFA/n-3 PUFA ratio) and its richness in minor bioactive compounds such as squalene and phenolic antioxidants. The specific mechanisms by which EVOO and other dietary lipids may exert their modulatory effects on cancer are not fully understood although abundant research has proposed the following: They influence in the stages of the carcinogenesis process, oxidative stress, alteration of the hormonal status, modification of the structure and function of cell membranes, modulation of cell signalling transduction pathways, regulation of gene expression and influence in the immune system. This article will explore the current knowledge of these mechanisms, including our own results in the context of the international literature.

  3. Breast conservation in early breast cancer - indication and consequences. Results of a multidisciplinary consensus development conference. Brusterhaltende Therapie beim Mammakarzinom - Indikation und Konsequenzen. Ergebnisse einer multidisziplinaeren Konsensus-Tagung

    Energy Technology Data Exchange (ETDEWEB)

    Hellriegel, K.P. (Krankenhaus Moabit, Berlin (Germany, F.R.). Innere Abt.)

    1991-02-01

    A multidisciplinary consensus development conference on the management of breast preserving treatment in early breast cancer was organized in November 1989 in Berlin. Following a two-day discussion of data presented, conclusions and recommendations were achieved on the indication and limitation of breast conservation, the optimal technique as well as the diagnostic requirements and therapeutic strategies in context with breast conservation including follow-up. (orig.).

  4. Functionalized magnetic nanowires for chemical and magneto-mechanical induction of cancer cell death

    KAUST Repository

    Martinez Banderas, Aldo Isaac

    2016-10-24

    Exploiting and combining different properties of nanomaterials is considered a potential route for next generation cancer therapies. Magnetic nanowires (NWs) have shown good biocompatibility and a high level of cellular internalization. We induced cancer cell death by combining the chemotherapeutic effect of doxorubicin (DOX)-functionalized iron NWs with the mechanical disturbance under a low frequency alternating magnetic field. (3-aminopropyl)triethoxysilane (APTES) and bovine serum albumin (BSA) were separately used for coating NWs allowing further functionalization with DOX. Internalization was assessed for both formulations by confocal reflection microscopy and inductively coupled plasma-mass spectrometry. From confocal analysis, BSA formulations demonstrated higher internalization and less agglomeration. The functionalized NWs generated a comparable cytotoxic effect in breast cancer cells in a DOX concentration-dependent manner, (~60% at the highest concentration tested) that was significantly different from the effect produced by free DOX and non-functionalized NWs formulations. A synergistic cytotoxic effect is obtained when a magnetic field (1 mT, 10 Hz) is applied to cells treated with DOX-functionalized BSA or APTES-coated NWs, (~70% at the highest concentration). In summary, a bimodal method for cancer cell destruction was developed by the conjugation of the magneto-mechanical properties of iron NWs with the effect of DOX producing better results than the individual effects.

  5. Mechanisms of Indomethacin-Induced Alterations in the Choline Phospholipid Metabolism of Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Kristine Glunde

    2006-09-01

    Full Text Available Human mammary epithelial cells (HMECs exhibit an increase in phosphocholine (PC and total cholinecontaining compounds, as well as a switch from high glycerophosphocholine (GPC/low PC to low GPC/high PC, with progression to malignant phenotype. The treatment of human breast cancer cells with a nonsteroidal anti-inflammatory agent, indomethacin, reverted the high PC/low GPC pattern to a low PC/high GPC pattern indicative of a less malignant phenotype, supported by decreased invasion. Here, we have characterized mechanisms underlying indomethacininduced alterations in choline membrane metabolism in malignant breast cancer cells and nonmalignant HMECs labeled with [1,2-13C]choline using 1H and 13C magnetic resonance spectroscopy. Microarray gene expression analysis was performed to understand the molecular mechanisms underlying these changes. In breast cancer cells, indomethacin treatment activated phospholipases that, combined with an increased choline phospholipid biosynthesis, led to increased GPC and decreased PC levels. However, in nonmalignant HMECs, activation of the anabolic pathway alone was detected following indomethacin treatment. Following indomethacin treatment in breast cancer cells, several candidate genes, such as interleukin 8, NGFB, CSF2, RHOB, EDN1, and JUNB, were differentially expressed, which may have contributed to changes in choline metabolism through secondary effects or signaling cascades leading to changes in enzyme activity.

  6. An Ancient, Unified Mechanism for Metformin Growth Inhibition in C. elegans and Cancer.

    Science.gov (United States)

    Wu, Lianfeng; Zhou, Ben; Oshiro-Rapley, Noriko; Li, Man; Paulo, Joao A; Webster, Christopher M; Mou, Fan; Kacergis, Michael C; Talkowski, Michael E; Carr, Christopher E; Gygi, Steven P; Zheng, Bin; Soukas, Alexander A

    2016-12-15

    Metformin has utility in cancer prevention and treatment, though the mechanisms for these effects remain elusive. Through genetic screening in C. elegans, we uncover two metformin response elements: the nuclear pore complex (NPC) and acyl-CoA dehydrogenase family member-10 (ACAD10). We demonstrate that biguanides inhibit growth by inhibiting mitochondrial respiratory capacity, which restrains transit of the RagA-RagC GTPase heterodimer through the NPC. Nuclear exclusion renders RagC incapable of gaining the GDP-bound state necessary to stimulate mTORC1. Biguanide-induced inactivation of mTORC1 subsequently inhibits growth through transcriptional induction of ACAD10. This ancient metformin response pathway is conserved from worms to humans. Both restricted nuclear pore transit and upregulation of ACAD10 are required for biguanides to reduce viability in melanoma and pancreatic cancer cells, and to extend C. elegans lifespan. This pathway provides a unified mechanism by which metformin kills cancer cells and extends lifespan, and illuminates potential cancer targets. PAPERCLIP. Copyright © 2016. Published by Elsevier Inc.

  7. Akt-dependent and independent mechanisms of mTOR regulation in cancer

    Science.gov (United States)

    Memmott, Regan M.; Dennis, Phillip A.

    2009-01-01

    The protein kinase mTOR (mammalian target of rapamycin) is a critical regulator of cellular metabolism, growth, and proliferation. These processes contribute to tumor formation, and many cancers are characterized by aberrant activation of mTOR. Although activating mutations in mTOR itself have not been identified, deregulation of upstream components that regulate mTOR are prevalent in cancer. The prototypic mechanism of mTOR regulation in cells is through activation of the PI3K/Akt pathway, but mTOR receives input from multiple signaling pathways. This review will discuss Akt-dependent and independent mechanisms of mTOR regulation in response to mitogenic signals, as well as its regulation in response to energy and nutrient-sensing pathways. Preclinical and clinical studies have demonstrated that tumors bearing genetic alterations that activate mTOR are sensitive to pharmacologic inhibition of mTOR. Elucidation of novel pathways that regulate mTOR may help identify predictive factors for sensitivity to mTOR inhibitors and could provide new therapeutic targets for inhibiting the mTOR pathway in cancer. This review will also highlight pharmacologic approaches that inhibit mTOR via activation of the AMP-activated protein kinase (AMPK), an important inhibitor of the mTOR pathway and an emerging target in cancer. PMID:19166931

  8. Human tumor-associated viruses and new insights into the molecular mechanisms of cancer.

    Science.gov (United States)

    Martin, D; Gutkind, J S

    2008-12-01

    The study of acute-transforming retroviruses and their oncogenes and of the multiple mechanisms deployed by DNA viruses to circumvent the growth-suppressive and proapoptotic function of tumor suppressor genes has provided the foundation of our current understanding of cancer biology. Unlike acute-transforming animal viruses, however, human tumor-associated viruses lead to malignancies with a prolonged latency and in conjunction with other environmental and host-related cooperating events. The relevance of viral infection to human cancer development has often been debated. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), human papilloma virus (HPV), human T-cell lymphotropic virus (HTLV-1) and Kaposi's associated sarcoma virus (KSHV) contribute to 10-15% of the cancers worldwide. Hence, the opportunity exists to fight cancer at the global scale by preventing the spread of these viruses, by the development and distribution of effective and safe antiviral vaccines, and by identifying their oncogenic mechanism. Here, we discuss the molecular events underlying the neoplastic potential of the human tumor-associated viruses, with emphasis on the enigmatic KSHV and its numerous virally hijacked proangiogenic, immune-evasive and tumor-promoting genes. The emerging information may facilitate the development of new molecular-targeted approaches to prevent and treat virally associated human malignancies.

  9. Are immunological mechanisms involved in colon cancer and are they possible markers for biotherapy improvement?

    Science.gov (United States)

    Berghella, Anna Maria; Contasta, Ida; Pellegrini, Patrizia; Del Beato, Tiziana; Adorno, Domenico

    2006-10-01

    This paper focuses on our data on colon cancer patients. Our overall results lead us to believe that the suppressive effect of specific cytokines in colon cancer patients alters the functionality of TH1 and TH2 subsets of CD4+ T-cells, with an expansion of TH2 cells and a malfunctioning of TH1 cells. This immunological disregulation appears to increase with stage progression, suggesting a direct role in the mechanisms that allow the tumour to locate and expand within the host. It is also clear that in order to identify disease markers and generate an in vivo immune response that corrects the imbalance between TH1 and TH2 cells, we need to understand how tumour mechanisms cause this imbalance to begin with.

  10. The Mechanism by Which MYCN Amplification Confers an Enhanced Sensitivity to a PCNA-Derived Cell Permeable Peptide in Neuroblastoma Cells

    Directory of Open Access Journals (Sweden)

    Long Gu

    2015-12-01

    Full Text Available Dysregulated expression of MYC family genes is a hallmark of many malignancies. Unfortunately, these proteins are not amenable to blockade by small molecules or protein-based therapeutic agents. Therefore, we must find alternative approaches to target MYC-driven cancers. Amplification of MYCN, a MYC family member, predicts high-risk neuroblastoma (NB disease. We have shown that R9-caPep blocks the interaction of PCNA with its binding partners and selectively kills human NB cells, especially those with MYCN amplification, and we now show the mechanism. We found elevated levels of DNA replication stress in MYCN-amplified NB cells. R9-caPep exacerbated DNA replication stress in MYCN-amplified NB cells and NB cells with an augmented level of MYC by interfering with DNA replication fork extension, leading to Chk1 dependence and susceptibility to Chk1 inhibition. We describe how these effects may be exploited for treating NB.

  11. A covalent PIN1 inhibitor selectively targets cancer cells by a dual mechanism of action

    Science.gov (United States)

    Campaner, Elena; Rustighi, Alessandra; Zannini, Alessandro; Cristiani, Alberto; Piazza, Silvano; Ciani, Yari; Kalid, Ori; Golan, Gali; Baloglu, Erkan; Shacham, Sharon; Valsasina, Barbara; Cucchi, Ulisse; Pippione, Agnese Chiara; Lolli, Marco Lucio; Giabbai, Barbara; Storici, Paola; Carloni, Paolo; Rossetti, Giulia; Benvenuti, Federica; Bello, Ezia; D'Incalci, Maurizio; Cappuzzello, Elisa; Rosato, Antonio; Del Sal, Giannino

    2017-06-01

    The prolyl isomerase PIN1, a critical modifier of multiple signalling pathways, is overexpressed in the majority of cancers and its activity strongly contributes to tumour initiation and progression. Inactivation of PIN1 function conversely curbs tumour growth and cancer stem cell expansion, restores chemosensitivity and blocks metastatic spread, thus providing the rationale for a therapeutic strategy based on PIN1 inhibition. Notwithstanding, potent PIN1 inhibitors are still missing from the arsenal of anti-cancer drugs. By a mechanism-based screening, we have identified a novel covalent PIN1 inhibitor, KPT-6566, able to selectively inhibit PIN1 and target it for degradation. We demonstrate that KPT-6566 covalently binds to the catalytic site of PIN1. This interaction results in the release of a quinone-mimicking drug that generates reactive oxygen species and DNA damage, inducing cell death specifically in cancer cells. Accordingly, KPT-6566 treatment impairs PIN1-dependent cancer phenotypes in vitro and growth of lung metastasis in vivo.

  12. Neuroendorine differentiation in prostate cancer: A mechanism of radioresistance and treatment failure

    Directory of Open Access Journals (Sweden)

    Chang-Deng eHu

    2015-04-01

    Full Text Available Neuroendocrine differentiation (NED in prostate cancer is a well recognized phenotypic change by which prostate cancer cells transdifferentiate into neuroendocrine-like (NE-like cells. NE-like cells lack the expression of androgen receptor and prostate specific antigen, and are resistant to treatments. In addition, NE-like cells secrete peptide hormones and growth factors to support the growth of surrounding tumor cells in a paracrine manner. Accumulated evidence has suggested that NED is associated with disease progression and poor prognosis. The importance of NED in prostate cancer progression and therapeutic response is further supported by the fact that therapeutic agents, including androgen deprivation therapy, chemotherapeutic agents, and radiotherapy, also induce NED. We will review the work supporting the overall hypothesis that therapy-induced NED is a mechanism of resistance to treatments, as well as discuss the relationship between therapy-induced NED and therapy-induced senescence, epithelial-to-mesenchymal transition, and cancer stem cells. Furthermore, we will use radiation-induced NED as a model to explore several NED-based targeting strategies for development of novel therapeutics. Finally, we propose future studies that will specifically address therapy-induced NED in the hope that a better treatment regimen for prostate cancer can be developed.

  13. Fucoxanthin: A Marine Carotenoid Exerting Anti-Cancer Effects by Affecting Multiple Mechanisms

    Directory of Open Access Journals (Sweden)

    Sangeetha Ravi Kumar

    2013-12-01

    Full Text Available Fucoxanthin is a marine carotenoid exhibiting several health benefits. The anti-cancer effect of fucoxanthin and its deacetylated metabolite, fucoxanthinol, is well documented. In view of its potent anti-carcinogenic activity, the need to understand the underlying mechanisms has gained prominence. Towards achieving this goal, several researchers have carried out studies in various cell lines and in vivo and have deciphered that fucoxanthin exerts its anti-proliferative and cancer preventing influence via different molecules and pathways including the Bcl-2 proteins, MAPK, NFκB, Caspases, GADD45, and several other molecules that are involved in either cell cycle arrest, apoptosis, or metastasis. Thus, in addition to decreasing the frequency of occurrence and growth of tumours, fucoxanthin has a cytotoxic effect on cancer cells. Some studies show that this effect is selective, i.e., fucoxanthin has the capability to target cancer cells only, leaving normal physiological cells unaffected/less affected. Hence, fucoxanthin and its metabolites show great promise as chemotherapeutic agents in cancer.

  14. Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans

    Science.gov (United States)

    Abegglen, Lisa M.; Caulin, Aleah F.; Chan, Ashley; Lee, Kristy; Robinson, Rosann; Campbell, Michael S.; Kiso, Wendy K.; Schmitt, Dennis L.; Waddell, Peter J; Bhaskara, Srividya; Jensen, Shane T.; Maley, Carlo C.; Schiffman, Joshua D.

    2016-01-01

    IMPORTANCE Evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology. OBJECTIVE To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS). DESIGN, SETTING, AND PARTICIPANTS A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n = 644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro in the laboratory for DNA damage response. The study included African and Asian elephants (n = 8), patients with LFS (n = 10), and age-matched human controls (n = 11). Human samples were collected at the University of Utah between June 2014 and July 2015. EXPOSURES Ionizing radiation and doxorubicin. MAIN OUTCOMES AND MEASURES Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes. RESULTS Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95%CI, 0%–5%]; African wild dog, 8%[95%CI, 0%–16%]; lion, 2%[95%CI, 0% –7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95%CI, 3.14%–6.49%), compared with humans, who have 11% to 25%cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain

  15. Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer

    Directory of Open Access Journals (Sweden)

    Yiwen Fang

    2016-02-01

    Full Text Available Long non-coding RNAs (lncRNAs play important roles in cancer. They are involved in chromatin remodeling, as well as transcriptional and post-transcriptional regulation, through a variety of chromatin-based mechanisms and via cross-talk with other RNA species. lncRNAs can function as decoys, scaffolds, and enhancer RNAs. This review summarizes the characteristics of lncRNAs, including their roles, functions, and working mechanisms, describes methods for identifying and annotating lncRNAs, and discusses future opportunities for lncRNA-based therapies using antisense oligonucleotides.

  16. Crosstalk between Apoptosis and Autophagy: Molecular Mechanisms and Therapeutic Strategies in Cancer

    Directory of Open Access Journals (Sweden)

    Abdelouahid El-Khattouti

    2013-01-01

    Full Text Available Both apoptosis and autophagy are highly conserved processes that besides their role in the maintenance of the organismal and cellular homeostasis serve as a main target of tumor therapeutics. Although their important roles in the modulation of tumor therapeutic strategies have been widely reported, the molecular actions of both apoptosis and autophagy are counteracted by cancer protective mechanisms. While apoptosis is a tightly regulated process that is implicated in the removal of damaged or unwanted cells, autophagy is a cellular catabolic pathway that is involved in lysosomal degradation and recycling of proteins and organelles, and thereby is considered an important survival/protective mechanism for cancer cells in response to metabolic stress or chemotherapy. Although the relationship between autophagy and cell death is very complicated and has not been characterized in detail, the molecular mechanisms that control this relationship are considered to be a relevant target for the development of a therapeutic strategy for tumor treatment. In this review, we focus on the molecular mechanisms of apoptosis, autophagy, and those of the crosstalk between apoptosis and autophagy in order to provide insight into the molecular mechanisms that may be essential for the balance between cell survival and death as well as their role as targets for the development of novel therapeutic approaches.

  17. Endogenous molecular network reveals two mechanisms of heterogeneity within gastric cancer

    Science.gov (United States)

    Li, Site; Zhu, Xiaomei; Liu, Bingya; Wang, Gaowei; Ao, Ping

    2015-01-01

    Intratumor heterogeneity is a common phenomenon and impedes cancer therapy and research. Gastric cancer (GC) cells have generally been classified into two heterogeneous cellular phenotypes, the gastric and intestinal types, yet the mechanisms of maintaining two phenotypes and controlling phenotypic transition are largely unknown. A qualitative systematic framework, the endogenous molecular network hypothesis, has recently been proposed to understand cancer genesis and progression. Here, a minimal network corresponding to such framework was found for GC and was quantified via a stochastic nonlinear dynamical system. We then further extended the framework to address the important question of intratumor heterogeneity quantitatively. The working network characterized main known features of normal gastric epithelial and GC cell phenotypes. Our results demonstrated that four positive feedback loops in the network are critical for GC cell phenotypes. Moreover, two mechanisms that contribute to GC cell heterogeneity were identified: particular positive feedback loops are responsible for the maintenance of intestinal and gastric phenotypes; GC cell progression routes that were revealed by the dynamical behaviors of individual key components are heterogeneous. In this work, we constructed an endogenous molecular network of GC that can be expanded in the future and would broaden the known mechanisms of intratumor heterogeneity. PMID:25962957

  18. Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity at high sensitivity levels (Conference Presentation)

    Science.gov (United States)

    Zhao, Jianhua; Zeng, Haishan; Kalia, Sunil; Lui, Harvey

    2017-02-01

    Background: Raman spectroscopy is a non-invasive optical technique which can measure molecular vibrational modes within tissue. A large-scale clinical study (n = 518) has demonstrated that real-time Raman spectroscopy could distinguish malignant from benign skin lesions with good diagnostic accuracy; this was validated by a follow-up independent study (n = 127). Objective: Most of the previous diagnostic algorithms have typically been based on analyzing the full band of the Raman spectra, either in the fingerprint or high wavenumber regions. Our objective in this presentation is to explore wavenumber selection based analysis in Raman spectroscopy for skin cancer diagnosis. Methods: A wavenumber selection algorithm was implemented using variably-sized wavenumber windows, which were determined by the correlation coefficient between wavenumbers. Wavenumber windows were chosen based on accumulated frequency from leave-one-out cross-validated stepwise regression or least and shrinkage selection operator (LASSO). The diagnostic algorithms were then generated from the selected wavenumber windows using multivariate statistical analyses, including principal component and general discriminant analysis (PC-GDA) and partial least squares (PLS). A total cohort of 645 confirmed lesions from 573 patients encompassing skin cancers, precancers and benign skin lesions were included. Lesion measurements were divided into training cohort (n = 518) and testing cohort (n = 127) according to the measurement time. Result: The area under the receiver operating characteristic curve (ROC) improved from 0.861-0.891 to 0.891-0.911 and the diagnostic specificity for sensitivity levels of 0.99-0.90 increased respectively from 0.17-0.65 to 0.20-0.75 by selecting specific wavenumber windows for analysis. Conclusion: Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity at high sensitivity levels.

  19. 1999 Gordon Research Conference on Mammalian DNA Repair. Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-02-12

    This Conference will examine DNA repair as the key component in genomic surveillance that is so crucial to the overall integrity and function of mammalian cells. Recent discoveries have catapulted the field of DNA repair into a pivotal position for fundamental investigations into oncology, aging, environmental health, and developmental biology. We hope to highlight the most promising and exciting avenues of research in robust discussions at this conference. This Mammalian DNA Repair Gordon Conference differs from the past conferences in this series, in which the programs were broader in scope, with respect to topics and biological systems covered. A conference sponsored by the Genetics Society in April 1998 emphasized recombinational mechanisms for double-strand break repair and the role of mismatch repair deficiency in colorectal cancer. These topics will therefore receive somewhat less emphasis in the upcoming Conference. In view of the recent mechanistic advances in mammalian DNA repair, an upcoming comprehensive DNA repair meeting next autumn at Hilton Head; and the limited enrollment for Gordon Conferences we have decided to focus session-by-session on particular areas of controversy and/or new developments specifically in mammalian systems. Thus, the principal presentations will draw upon results from other cellular systems only to the extent that they impact our understanding of mammalian DNA repair.

  20. SIGEF Conference

    CERN Document Server

    Terceño-Gómez, Antonio; Ferrer-Comalat, Joan; Merigó-Lindahl, José; Linares-Mustarós, Salvador

    2015-01-01

    This book is a collection of selected papers presented at the SIGEF conference, held at the Faculty of Economics and Business of the University of Girona (Spain), 06-08 July, 2015. This edition of the conference has been presented with the slogan “Scientific methods for the treatment of uncertainty in social sciences”. There are different ways for dealing with uncertainty in management. The book focuses on soft computing theories and their role in assessing uncertainty in a complex world. It gives a comprehensive overview of quantitative management topics and discusses some of the most recent developments in all the areas of business and management in soft computing including Decision Making, Expert Systems and Forgotten Effects Theory, Forecasting Models, Fuzzy Logic and Fuzzy Sets, Modelling and Simulation Techniques, Neural Networks and Genetic Algorithms and Optimization and Control. The book might be of great interest for anyone working in the area of management and business economics and might be es...

  1. European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus group (EGCCCG): part I.

    NARCIS (Netherlands)

    Krege, S.; Beyer, J.; Souchon, R.; Albers, P.; Albrecht, W.; Algaba, F.; Bamberg, M.; Bodrogi, I.; Bokemeyer, C.; Cavallin-Stahl, E.; Classen, J.; Clemm, C.; Cohn-Cedermark, G.; Culine, S.; Daugaard, G.; Mulder, P.H.M. de; Santis, M. de; Wit, M. de; Wit, R. de; Derigs, H.G.; Dieckmann, K.P.; Dieing, A.; Droz, J.P.; Fenner, M.; Fizazi, K.; Flechon, A.; Fossa, S.D.; Muro, X.G. del; Gauler, T.; Geczi, L.; Gerl, A.; Germa-Lluch, J.R.; Gillessen, S.; Hartmann, J.T.; Hartmann, M.; Heidenreich, A.; Hoeltl, W.; Horwich, A.; Huddart, R.; Jewett, M.; Joffe, J.; Jones, W.G.; Kisbenedek, L.; Klepp, O.; Kliesch, S.; Koehrmann, K.U.; Kollmannsberger, C.; Kuczyk, M.; Laguna, P.; Galvis, O.L.; Loy, V.; Mason, M.D.; Mead, G.M.; Mueller, R.; Nichols, C.; Nicolai, N.; Oliver, T.; Ondrus, D.; Oosterhof, G.O.; Ares, L.P.; Pizzocaro, G.; Pont, J.; Pottek, T.; Powles, T.; Rick, O.; Rosti, G.; Salvioni, R.; Scheiderbauer, J.; Schmelz, H.U.; Schmidberger, H.; Schmoll, H.J.; Schrader, M.; Sedlmayer, F.; Skakkebaek, N.E.; Sohaib, A.; Tjulandin, S.; Warde, P.; Weinknecht, S.; Weissbach, L.; Wittekind, C.; Winter, E.; Wood, L.; Maase, H. von der

    2008-01-01

    OBJECTIVES: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the

  2. European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): part II.

    NARCIS (Netherlands)

    Krege, S.; Beyer, J.; Souchon, R.; Albers, P.; Albrecht, W.; Algaba, F.; Bamberg, M.; Bodrogi, I.; Bokemeyer, C.; Cavallin-Stahl, E.; Classen, J.; Clemm, C.; Cohn-Cedermark, G.; Culine, S.; Daugaard, G.; Mulder, P.H.M. de; Santis, M. De; Wit, M. de; Wit, R. de; Derigs, H.G.; Dieckmann, K.P.; Dieing, A.; Droz, J.P.; Fenner, M.; Fizazi, K.; Flechon, A.; Fossa, S.D.; Muro, X.G. del; Gauler, T.; Geczi, L.; Gerl, A.; Germa-Lluch, J.R.; Gillessen, S.; Hartmann, J.T.; Hartmann, M.; Heidenreich, A.; Hoeltl, W.; Horwich, A.; Huddart, R.; Jewett, M.; Joffe, J.; Jones, W.G.; Kisbenedek, L.; Klepp, O.; Kliesch, S.; Koehrmann, K.U.; Kollmannsberger, C.; Kuczyk, M.; Laguna, P.; Galvis, O.L.; Loy, V.; Mason, M.D.; Mead, G.M.; Mueller, R.; Nichols, C.; Nicolai, N.; Oliver, T.; Ondrus, D.; Oosterhof, G.O.; Paz-Ares, L.; Pizzocaro, G.; Pont, J.; Pottek, T.; Powles, T.; Rick, O.; Rosti, G.; Salvioni, R.; Scheiderbauer, J.; Schmelz, H.U.; Schmidberger, H.; Schmoll, H.J.; Schrader, M.; Sedlmayer, F.; Skakkebaek, N.E.; Sohaib, A.; Tjulandin, S.; Warde, P.; Weinknecht, S.; Weissbach, L.; Wittekind, C.; Winter, E.; Wood, L.; Maase, H. von der

    2008-01-01

    OBJECTIVES: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the

  3. Melatonin as a promising agent to treat ovarian cancer: molecular mechanisms.

    Science.gov (United States)

    Chuffa, Luiz Gustavo de Almeida; Reiter, Russel J; Lupi, Luiz Antonio

    2017-10-01

    Ovarian cancer (OC) has the highest mortality rate of all gynecological cancers, and most patients develop chemoresistance after first-line treatments. Despite recent advances, the 5-year relative survival is ~45% for all OC subtypes, and invasive epithelial OC has only a 17% survival rate when diagnosed at a late stage. Identification of new efficacious molecules or biomarkers represents important opportunities in the treatment of OC. The pharmacological and physiological properties of melatonin indicate this agent could be useful against OC progression and metastasis. In normal cells, melatonin has potent antioxidant and anti-apoptotic actions. Conversely, melatonin has pro-oxidant as well as anti-proliferative, anti-angiogenic and immunomodulatory properties in many cancer types including hormone-dependent cancers. Although melatonin receptors have been identified in OC cells, the exact mechanism by which melatonin induces anticancer activities remains incompletely understood. Clinical studies have reported negative correlation between aggressiveness of OC and serum levels of melatonin, reinforcing the idea that melatonin may be a critical factor determining OC development. In vitro and in vivo studies suggest melatonin differentially regulates multiple signaling pathways in OC cells. This focused review explores the potential mechanisms of action of melatonin on cultured OC cells and in experimental models of OC in an attempt to clarify how melatonin modulates the signaling pathways involved in cancer cell apoptosis, survival, inflammation, proliferation and metabolic processes. Based on the evidence presented, we feel that melatonin, as an agent that controls cellular signals associated with malignancy, may be beneficial in combination with other therapeutics for OC treatment. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Bypass mechanisms of the androgen receptor pathway in therapy-resistant prostate cancer cell models.

    Directory of Open Access Journals (Sweden)

    Rute B Marques

    Full Text Available BACKGROUND: Prostate cancer is initially dependent on androgens for survival and growth, making hormonal therapy the cornerstone treatment for late-stage tumors. However, despite initial remission, the cancer will inevitably recur. The present study was designed to investigate how androgen-dependent prostate cancer cells eventually survive and resume growth under androgen-deprived and antiandrogen supplemented conditions. As model system, we used the androgen-responsive PC346C cell line and its therapy-resistant sublines: PC346DCC, PC346Flu1 and PC346Flu2. METHODOLOGY/PRINCIPAL FINDINGS: Microarray technology was used to analyze differences in gene expression between the androgen-responsive and therapy-resistant PC346 cell lines. Microarray analysis revealed 487 transcripts differentially-expressed between the androgen-responsive and the therapy-resistant cell lines. Most of these genes were common to all three therapy-resistant sublines and only a minority (∼5% was androgen-regulated. Pathway analysis revealed enrichment in functions involving cellular movement, cell growth and cell death, as well as association with cancer and reproductive system disease. PC346DCC expressed residual levels of androgen receptor (AR and showed significant down-regulation of androgen-regulated genes (p-value = 10(-7. Up-regulation of VAV3 and TWIST1 oncogenes and repression of the DKK3 tumor-suppressor was observed in PC346DCC, suggesting a potential AR bypass mechanism. Subsequent validation of these three genes in patient samples confirmed that expression was deregulated during prostate cancer progression. CONCLUSIONS/SIGNIFICANCE: Therapy-resistant growth may result from adaptations in the AR pathway, but androgen-independence may also be achieved by alternative survival mechanisms. Here we identified TWIST1, VAV3 and DKK3 as potential players in the bypassing of the AR pathway, making them good candidates as biomarkers and novel therapeutical targets.

  5. Aspirin in the 21st century-common mechanisms of disease and their modulation by aspirin: a report from the 2015 scientific conference of the international aspirin foundation, 28 August, London, UK.

    Science.gov (United States)

    Smith, Tom; Hutchison, Pippa; Schrör, Karsten; Clària, Joan; Lanas, Angel; Patrignani, Paola; Chan, Andrew T; Din, Farhat; Langley, Ruth; Elwood, Peter; Freedman, Andrew; Eccles, Ron

    2015-01-01

    Professor Peter Rothwell of Oxford University chaired the annual Scientific Conference of the International Aspirin Foundation in London on 28 August 2015. It took the form of four sessions. Aspirin has more than one action in its effects on disease. Its acetylation of cyclooxygenase 2 (COX-2) in platelets leads to the blockade of pro-inflammatory chemicals and generation of anti-inflammatory mediators and increase in nitrous oxide (NO) production, which helps to preserve arterial endothelium. But platelets are not its only target. There is now evidence that aspirin has a direct antitumour effect on intestinal mucosal cells that block their potential transformation into cancer cells. Randomised placebo-controlled trials (RCTs) in people with histories of colorectal neoplasia have shown that aspirin reduces the risk of recurrent adenomas and reduces long-term cancer incidence in patients with Lynch syndrome. Among women given aspirin for cardiovascular disease, there were fewer cancers than in those given placebo. Epidemiological evidence has suggested that aspirin treatment after cancer is diagnosed reduces the incidence of metastases and prolongs survival, and long-term studies of anticancer treatment with aspirin are under way to confirm this. Apart from cancer studies, aspirin use is now firmly established as treatment for antiphospholipid syndrome (Hughes syndrome) and is being used to prevent and treat the heightened risk of cardiovascular disease in diabetes mellitus and in patients with HIV.

  6. Aspirin in the 21st century—common mechanisms of disease and their modulation by aspirin: a report from the 2015 scientific conference of the international aspirin foundation, 28 August, London, UK

    Science.gov (United States)

    Smith, Tom; Hutchison, Pippa; Schrör, Karsten; Clària, Joan; Lanas, Angel; Patrignani, Paola; Chan, Andrew T; Din, Farhat; Langley, Ruth; Elwood, Peter; Freedman, Andrew; Eccles, Ron

    2015-01-01

    Professor Peter Rothwell of Oxford University chaired the annual Scientific Conference of the International Aspirin Foundation in London on 28 August 2015. It took the form of four sessions. Aspirin has more than one action in its effects on disease. Its acetylation of cyclooxygenase 2 (COX-2) in platelets leads to the blockade of pro-inflammatory chemicals and generation of anti-inflammatory mediators and increase in nitrous oxide (NO) production, which helps to preserve arterial endothelium. But platelets are not its only target. There is now evidence that aspirin has a direct antitumour effect on intestinal mucosal cells that block their potential transformation into cancer cells. Randomised placebo-controlled trials (RCTs) in people with histories of colorectal neoplasia have shown that aspirin reduces the risk of recurrent adenomas and reduces long-term cancer incidence in patients with Lynch syndrome. Among women given aspirin for cardiovascular disease, there were fewer cancers than in those given placebo. Epidemiological evidence has suggested that aspirin treatment after cancer is diagnosed reduces the incidence of metastases and prolongs survival, and long-term studies of anticancer treatment with aspirin are under way to confirm this. Apart from cancer studies, aspirin use is now firmly established as treatment for antiphospholipid syndrome (Hughes syndrome) and is being used to prevent and treat the heightened risk of cardiovascular disease in diabetes mellitus and in patients with HIV. PMID:26557879

  7. Effects and mechanism of flavonoids from Astragalus complanatus on breast cancer growth.

    Science.gov (United States)

    Zhu, Jinhai; Zhang, Hui; Zhu, Zhengzhi; Zhang, Qiong; Ma, Xiaokai; Cui, Zhen; Yao, Tingjing

    2015-09-01

    Flavonoids from Astragalus complanatus R.Br (FAC) had anticancer effects on many tumor cells. The current study was performed to evaluate the effects of FAC on human breast cell proliferation, apoptosis, and metastasis, as well as their active mechanism. Cell viability and growth were detected using the cell counting kit (CCK)-8 assay in vitro. Assay of FAC on induced breast cancer mortality was counted as survival time of nude mice after breast cell line inoculation. The effect of FAC on cell invasion was investigated by an optimization assay that contains a 96-well Boyden chamber with wells precoated with BME at three different concentrations. The mechanism of its action on apoptosis and metastasis was determined by related gene detection. Proliferation of three breast cell lines was inhibited with FAC treatment in a dose-dependent manner. Survival time of nude mice with breast cancer cell inoculation also was prolonged with increasing FAC dose. Metastasis in FAC-treated breast cells was also significantly inhibited. Real-time polymerase chain reaction (PCR) assay demonstrated that apoptosis-related BCL-2 and caspase-9 gene expression was consistent with their phenotype change. Metastasis-related FAK and BRCA1 gene expression was inversely related to FAC treatment. Western blot analysis indicated that BCL-2 and FAK proteins were reduced, whereas caspase-9 and BRCA1 proteins were increased with a higher dose of FAC treatment. These data suggested that FAC has an important role in breast cancer growth and metastasis suppression in vitro and in vivo. Its active mechanism involves promoting programmed cancer cell death and regulates metastasis-related gene expression.

  8. Robust spinal neuroinflammation mediates mechanical allodynia in Walker 256 induced bone cancer rats

    Directory of Open Access Journals (Sweden)

    Mao-Ying Qi-Liang

    2012-05-01

    Full Text Available Abstract It has been reported that remarkable and sustained activation of astrocytes and/or microglia occurs in cancer induced pain (CIP, which is different from neuropathic and inflammatory pain. The present study was designed to investigate the role of spinal Toll-like receptor 4 (TLR4 induced glial neuroinflammation in cancer induced pain using a modified rat model of bone cancer. The rat model of CIP consisted of unilateral intra-tibial injection with Walker 256 mammary gland carcinoma. Nine days after Walker 256 inoculation, a robust activation of both astrocytes and microglia in bilateral spinal dorsal horn was observed together with significant bilateral mechanical allodynia. This neuroinflammation was characterized by enhanced immunostaining of both glial fibrillary acidic protein (GFAP, astrocyte marker and OX-42 (microglia marker, and an elevated level of IL-1β, IL-6 and TNF-α mRNA. I.t. administration of fluorocitrate (an inhibitor of glial metabolism, 1 nmol or minocycline (an inhibitor of microglia, 100 μg has significant anti-allodynic effects on day 12 after Walker 256 inoculation. Naloxone (a nonstereoselective TLR4 signaling blocker, 60 μg, i.t. also significantly alleviated mechanical allodynia and simultaneously blocked the increased inflammatory cytokine mRNA. The results suggested that spinal TLR4 might play an important role in the sustained glial activation that critically contributed to the robust and sustained spinal neuroinflammation in CIP. This result could potentially help clinicians and researchers to better understand the mechanism of complicated cancer pain.

  9. Psychosocial factors and psychophysiological mechanisms in the aetiology and development of cancers.

    Science.gov (United States)

    Cox, T; Mackay, C

    1982-01-01

    Socio-cultural factors which may play a contributory role in the aetiology of cancer have been extensively investigated and it is well established that the incidence rates of different forms and sites of the disease are not equally distributed throughout the population. Social class, occupational, environmental and 'life-style' differences, amongst others, have been found to be associated with an excess risk of cancer, although the argument concerning the relative importance of these various factors remains a controversial one. It seems increasingly clear however, that there are large behavioural components which govern exposure to potential carcinogens and there is growing interest in the extent to which social and psychological demands may be associated with these agents or may operate as contributory factors in their own right. A number of early studies of psychological approaches to the study of cancer aetiology are reviewed from a methodological perspective. Much of the early work suffered from the problem that psychological characteristics of individuals who already had cancer were used to construct models concerned with aetiological factors. A number of the more recent studies which have attempted to overcome these difficulties are discussed. Tentatively, these later investigations suggest that two main groups of factors are related to an increased risk of cancer. First, the loss of, or lack of closeness or attachment to an important relation (often a parent) early in life, and second, the inability to express hostile feelings or more generally the abnormal release of emotion. Several psychophysiological mechanisms are reviewed which have attempted to account for the relationship between psychological disturbances and the onset of cancer, particularly the growing evidence which implicated a role for the immune system as a link between the central nervous system and disease processes.

  10. Inhibitory effect and mechanism of metformin on human ovarian cancer cells SKOV-3 and A2780.

    Science.gov (United States)

    Huo, J; Bian, X-H; Huang, Y; Miao, Z-C; Song, L-H

    2017-02-01

    Ovarian cancer is the most common malignant tumor in female reproductive system. Metformin is an orally taken hypoglycemic agent, which is extensively applied in the clinic. Clinical trials find that there may be a certain degree of action of the metformin in inhibiting malignant tumors. This paper aims to investigate the inhibitory effect and mechanism of metformin on human ovarian cancer cells. Through in vitro cell experiment, the influences of metformin on the proliferation, colony formation and apoptosis of ovarian carcinoma cells were studied. Ovarian cancer cells SKOV-3 and A2780 in logarithmic growth phase were selected and cell proliferation was measured by MTT method. The metformin was processed for 48 h to calculate the survival rate of cells. Also, metformin was processed for 24 h and two weeks or stained with crystal violet, after which Quantity One (Bio-Rad, Hercules, CA, USA) method was used to quantitatively analyze the cell clone formation, meanwhile, the FCM (flow cytometry) was used for the detection and analysis. Intervened by metformin with different concentrations for 48 h, the cell viabilities of SKOV-3 and A2780 cells were respectively reduced by 19.49 ± 2.92%, 45.41 ± 7.95%, 53.84 ± 5.53%, 64.04 ± 4.36% and 11.45 ± 3.12%, 35.42 ± 7.55%, 43.77 ± 5.77%, 53.05 ± 5.55% as compared with that in the control group with statistical significances. After processed by metformin with different concentrations for two weeks, the cells clone numbers of SKOV-3 and A2780 were significantly reduced. Treatment of metformin on SKOV-3 and A2780 cells of human ovarian cancer showed significant apoptosis. The metformin has the inhibitory effect on the cells of human ovarian cancer, which may be through inducing ovarian cancer cell apoptosis.

  11. Mechanism of microRNAs Regulation and Function them in Recognition and Treatment of Cancer

    Directory of Open Access Journals (Sweden)

    Atefeh Zamani

    2017-07-01

    Full Text Available Background: Despite of all the efforts and studies conducted on diagnosis and treatment of cancer, this disease still has many of losses annually. Cancer is a multifactorial disease that is incidence of genetic and environmental factors are involved. MicroRNA of (micro ribonucleic acid group of non-coding RNA that have been preserved during evolution. miRNA also like that mRNA By the enzyme RNA polymerase II transcription and after the capping mechanism and Polyadenylation (Pre-miRNA obtained that by two cutting successive reactions, mature miRNA produced and through the connection to 3'UTR, mRNA target gene affects on it.Methods: For investigate from the articles in the database such as pubmed, Google Scholar ,…. Were taken to this study we used.Results: MicroRNA can be alter gene expression after transcription that is action in most cases performed through two way decomposition and or inhibit the translation of target gene mRNA. MIR in various cancers could have role oncogenes and tumor suppressor genes (Tumor suppressor and also in cell cycle, cell death, apoptosis, differentiation and cell proliferation and drug resistance have an important role and can stop the progression of cancer and Hence as biomarkers for the diagnosis and treatment of cancer are available.Conclusion: MIR expression in various cancers decreases or increases, which in most cases increase the expression of a MIR cause to reduce expression of a gene targeting and vice versa. Hence further studies about this great group of micro RNA are important and can be investigated.

  12. Mechanisms of microsatellite instability in colorectal cancer patients in different age groups.

    Science.gov (United States)

    Yiu, Raymond; Qiu, Hongming; Lee, Suk-Hwan; García-Aguilar, Julio

    2005-11-01

    The proportion of colorectal cancers located proximal to the splenic flexure increases with age. Colorectal cancers of the microsatellite instability phenotype are preferentially located in the proximal colon. We investigated the location of colorectal cancer with this phenotype in different age groups to determine whether different molecular mechanisms could account for the changes in distribution of colorectal cancers. A representative sample of 230 colorectal cancers from three age groups (87 years) was selected from a subset of The Upper Midwest Oncology Medical Registries database. Microsatellite instability was determined by polymerase chain reaction using a panel of five microsatellite markers. The presence of new microsatellite alleles at two or more loci was scored as microsatellite instability. Tumors were otherwise considered microsatellite stable. MLH1 and MSH2 expression was determined by immunohistochemistry. Methylation of the MLH1 gene promotor was determined by methylation-specific polymerase chain reaction assay. The proportion of tumors of the microsatellite instability phenotype was 21 percent in the young group, 15 percent in the middle group, and 33 percent in the old group. More tumors of the microsatellite instability phenotype were proximal compared with microsatellite-stable tumors in all three age groups, but the differences were significant only for the old group. Tumors of the microsatellite instability phenotype in the older group were associated with MLH1 inactivation (24/29 or 83 percent), MLH1 promoter methylation (18/29 or 62 percent), and proximal location (25/29 or 86 percent), while tumors in the young group were associated with MSH2 inactivation (8/18 or 44 percent) and distal location (11/18 or 62 percent). The age-related proximal shift of colorectal cancers is associated with the microsatellite instability phenotype, MLH1 inactivation, and MLH1 promoter hypermethylation.

  13. Mechanisms of Anorexia Cancer Cachexia Syndrome and Potential Benefits of Traditional Medicine and Natural Herbs.

    Science.gov (United States)

    Ming-Hua, Cong; Bao-Hua, Zou; Lei, Yu

    Anorexia cancer cachexia syndrome is prevalent in advanced cancer patients, which is featured by anorexia, decreased dietary intake, body weight loss (skeletal muscle mass loss), and is unable to be reversed by routine nutritional support therapy. Up to now, the main mechanisms involved in cancer cachexia include excessive systemic inflammation, which is represented by increased plasma levels of IL-1, IL-6, TNF-alpha, tumor-induced factors, such as PIF and LMF. These factors eventually act on orexigenic and anorexigenicneurons located in the hypothalamus or protein and lipid metabolism of peripheral tissues, which lead to anorexia, decreased dietary intake, enhanced basic metabolism rate and hypercatabolism. The treatment modality includes early nutritional intervention, physical activity and drug treatment. However, studies about drugs used to treat cachexia are always controversial or merely effective in stimulating appetite and increasing body weight, though not lean body mass. The main target of pharmaceutical treatment is to improve appetite, decrease systemic inflammation and promote anabolic metabolism. Nevertheless, the treatment effectiveness of chemical drugs are not reaching consensus by existing cachexia guidelines. Complementary and alternative medicine (CAM) is recently known as a promising treatment to improve cachaxia status and quality of life of cancer patients. Traditional Chinese medicine (TCM) and natural herbal medicines have been used in the treatment of cancer for thousands of years worldwide, particularly in China. More and more research show that traditional Hanfang (Chinese medicines) and some natural herbs with less side reactions, have the effects of antagonizing pro-inflammatory cytokines, enhancing immune system, inhibiting protein catabolism, boosting the appetite and body weight, which maybe a promising treatment strategy and development tendency for anorexia cancer cachexia syndrome.

  14. Nucleotide selectivity defect and mutator phenotype conferred by a colon cancer-associated DNA polymerase δ mutation in human cells.

    Science.gov (United States)

    Mertz, T M; Baranovskiy, A G; Wang, J; Tahirov, T H; Shcherbakova, P V

    2017-08-01

    Mutations in the POLD1 and POLE genes encoding DNA polymerases δ (Polδ) and ɛ (Polɛ) cause hereditary colorectal cancer (CRC) and have been found in many sporadic colorectal and endometrial tumors. Much attention has been focused on POLE exonuclease domain mutations, which occur frequently in hypermutated DNA mismatch repair (MMR)-proficient tumors and appear to be responsible for the bulk of genomic instability in these tumors. In contrast, somatic POLD1 mutations are seen less frequently and typically occur in MMR-deficient tumors. Their functional significance is often unclear. Here we demonstrate that expression of the cancer-associated POLD1-R689W allele is strongly mutagenic in human cells. The mutation rate increased synergistically when the POLD1-R689W expression was combined with a MMR defect, indicating that the mutator effect of POLD1-R689W results from a high rate of replication errors. Purified human Polδ-R689W has normal exonuclease activity, but the nucleotide selectivity of the enzyme is severely impaired, providing a mechanistic explanation for the increased mutation rate in the POLD1-R689W-expressing cells. The vast majority of mutations induced by the POLD1-R689W are GC→︀TA transversions and GC→︀AT transitions, with transversions showing a strong strand bias and a remarkable preference for polypurine/polypyrimidine sequences. The mutational specificity of the Polδ variant matches that of the hypermutated CRC cell line, HCT15, in which this variant was first identified. The results provide compelling evidence for the pathogenic role of the POLD1-R689W mutation in the development of the human tumor and emphasize the need to experimentally determine the significance of Polδ variants present in sporadic tumors.

  15. Wavelength dependent SHG imaging and scattering probes of extracellular matrix (ECM) alterations in ovarian cancer (Conference Presentation)

    Science.gov (United States)

    Campagnola, Paul J.; Tilbury, Karissa B.; Campbell, Kirby R.; Eliceiri, Kevin W.; Patankar, Manish

    2017-02-01

    Ovarian cancer remains the most deadly gynecological cancer with a poor aggregate survival rate. To improve upon this situation, we utilized collagen-specific Second Harmonic Generation (SHG) imaging microscopy and optical scattering measurements to probe structural differences in the extracellular matrix of normal stroma, benign tumors, endometrioid tumors, and low and high-grade serous (LGS and HGS) tumors. The SHG signatures of the emission directionality and conversion efficiency as well as the optical scattering are related to the organization of collagen on the sub-micron size. The wavelength dependence of these readouts adds additional characterization of the size and distribution of collagen fibrils/fibers relative to the interrogating wavelengths. We found strong wavelength dependent dependencies of these metrics that were different between the different tumors that are related to respective structural attributes in the collagen organization. These sub-resolution determinations are consistent with the dualistic classification of type I and II serous tumors. However, type I endometrioid tumors have strongly differing ECM architecture than the serous malignancies. Moreover, our analyses are further consistent with LGS and benign tumors having similar etiology. We identified optimal wavelengths for the SHG metrics as well as optical scattering measurements. The SHG metrics and optical scattering measurements were then used to form a linear discriminant model to classify the tissues, and we obtained high accuracy ( 90%) between the tissue types. This delineation is superior to current clinical performance and has potential applicability in supplementing histological analysis, understanding the etiology, as well as development of an in vivo screening tool.

  16. Green tea catechins: Proposed mechanisms of action in breast cancer focusing on the interplay between survival and apoptosis.

    Science.gov (United States)

    Yiannakopoulou, Eugenia Ch

    2014-02-01

    Recent data have shown strong chemopreventive and possibly cancer chemotherapeutic effects of green tea polyphenols against cancer. Despite advances in breast cancer treatment, mortality from breast cancer is still high. Undoubtedly novel treatment strategies are needed for chemoprevention of high risk women and for the treatment of receptor negative breast cancer. Green tea catechins have been shown to inhibit proliferation of breast cancer cells and to block carcinogenesis. This review attempts a critical presentation of the mechanisms of action of green tea catechins in breast cancer. Several mechanisms of action of green tea catechins in breast cancer have been proposed including modulation of extracellular signalling, induction of apoptosis through redox regulation, or through modulation of epigenetic alterations. A number of molecular targets of green tea catechins have been suggested i.e molecular chaperones, telomerase, apoptotic cascade. Although the molecular links among the proposed mechanisms of action of green tea catechins are often missing, it must be emphasized that all the proposed mechanisms indicate that green tea catechins inhibit growth and /or promote apoptosis. It would be interesting if future experimental trials could take into account that green tea catechins are multi-target agents and attempt to link every novel proposed target with the other already proposed targets of green tea catechins.

  17. MicroRNA-21 links epithelial-to-mesenchymal transition and inflammatory signals to confer resistance to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer patients.

    Science.gov (United States)

    De Mattos-Arruda, Leticia; Bottai, Giulia; Nuciforo, Paolo G; Di Tommaso, Luca; Giovannetti, Elisa; Peg, Vicente; Losurdo, Agnese; Pérez-Garcia, José; Masci, Giovanna; Corsi, Fabio; Cortés, Javier; Seoane, Joan; Calin, George A; Santarpia, Libero

    2015-11-10

    Patients with primary HER2-positive breast cancer benefit from HER2-targeted therapies. Nevertheless, a significant proportion of these patients die of disease progression due to mechanisms of drug resistance. MicroRNAs (miRNAs) are emerging as critical core regulators of drug resistance that act by modulating the epithelial-to-mesenchymal transition (EMT) and cancer-related immune responses. In this study, we investigated the association between the expression of a specific subset of 14 miRNAs involved in EMT processes and immune functions and the response to neoadjuvant trastuzumab and chemotherapy in 52 patients with HER2-overexpressing breast tumors. The expression of only a single miRNA, miR-21, was significantly associated with residual disease (p = 0.030) and increased after trastuzumab-chemotherapy (p = 0.012). A target prediction analysis coupled with in vitro and in vivo validations revealed that miR-21 levels inversely correlated with the expression of PTEN (rs = -0.502; p = 0.005) and PDCD4 (rs = -0.426; p = 0.019), which differentially influenced the drug sensitivity of HER2-positive breast cancer cells. However, PTEN expression was only marginally associated with residual disease. We further demonstrated that miR-21 was able to affect the response to both trastuzumab and chemotherapy, triggering an IL-6/STAT3/NF-κB-mediated signaling loop and activating the PI3K pathway. Our findings support the ability of miR-21 signaling to sustain EMT and shape the tumor immune microenvironment in HER2-positive breast cancer. Collectively, these data provide a rationale for using miR-21 expression as a biomarker to select trastuzumab-chemotherapy-resistant HER2-positive breast cancer patients who may benefit from treatments containing PI3K inhibitors or immunomodulatory drugs.

  18. Mechanisms of apoptosis in irradiated and sunitinib-treated follicular thyroid cancer cells.

    Science.gov (United States)

    Grosse, Jirka; Warnke, Elisabeth; Wehland, Markus; Pietsch, Jessica; Pohl, Fabian; Wise, Petra; Magnusson, Nils E; Eilles, Christoph; Grimm, Daniela

    2014-03-01

    The multikinase inhibitor sunitinib (S) seems to have promising potential in the treatment of thyroid cancer. We focused on the impact of S and/or irradiation (R) on mechanisms of apoptosis in follicular thyroid cancer cells. The effects of R, S and their combination were evaluated 2 and 4 days after treatment, using the human thyroid cancer cell line CGTH W-1. The transcription of genes involved in the regulation of apoptosis was investigated using quantitative real-time PCR. Western blot analyses of caspases and survivin were also performed. S elevated BAX (day 4), CASP9, CASP3, BIRC5 (day 4) and PRKACA (day 4) gene expression, whereas the mRNAs of BCL2, CASP8, PRKCA, ERK1, and ERK2 were not significantly changed. S, R and R+S clearly induced caspase-9 protein and elevated caspase-3 activity. Survivin was down-regulated at day 4 in control cells and the expression was blunted by S treatment. R+S induced survivin expression at day 2 followed by a reduction at day 4 of treatment. Sunitinib and the combined application with radiation induced apoptosis in follicular thyroid cancer cells via the intrinsic pathway of apoptosis. In addition, sunitinib might induce apoptosis via decreased expression of the anti-apoptotic protein survivin. These findings suggest the potential use of sunitinib for the treatment of poorly differentiated follicular thyroid carcinomas.

  19. Research progress on chemopreventive effects of phytochemicals on colorectal cancer and their mechanisms.

    Science.gov (United States)

    Yin, Teng-Fei; Wang, Min; Qing, Ying; Lin, Ying-Min; Wu, Dong

    2016-08-21

    Colorectal cancer (CRC) is a type of cancer with high morbidity and mortality rates worldwide and has become a global health problem. The conventional radiotherapy and chemotherapy regimen for CRC not only has a low cure rate but also causes side effects. Many studies have shown that adequate intake of fruits and vegetables in the diet may have a protective effect on CRC occurrence, possibly due to the special biological protective effect of the phytochemicals in these foods. Numerous in vitro and in vivo studies have demonstrated that phytochemicals play strong antioxidant, anti-inflammatory and anti-cancer roles by regulating specific signaling pathways and molecular markers to inhibit the occurrence and development of CRC. This review summarizes the progress on CRC prevention using the phytochemicals sulforaphane, curcumin and resveratrol, and elaborates on the specific underlying mechanisms. Thus, we believe that phytochemicals might provide a novel therapeutic approach for CRC prevention, but future clinical studies are needed to confirm the specific preventive effect of phytochemicals on cancer.

  20. Detection of cancer biomarkers in serum using a hybrid mechanical and optoplasmonic nanosensor

    Science.gov (United States)

    Kosaka, P. M.; Pini, V.; Ruz, J. J.; da Silva, R. A.; González, M. U.; Ramos, D.; Calleja, M.; Tamayo, J.

    2014-12-01

    Blood contains a range of protein biomarkers that could be used in the early detection of disease. To achieve this, however, requires sensors capable of detecting (with high reproducibility) biomarkers at concentrations one million times lower than the concentration of the other blood proteins. Here, we show that a sandwich assay that combines mechanical and optoplasmonic transduction can detect cancer biomarkers in serum at ultralow concentrations. A biomarker is first recognized by a surface-anchored antibody and then by an antibody in solution that identifies a free region of the captured biomarker. This second antibody is tethered to a gold nanoparticle that acts as a mass and plasmonic label; the two signatures are detected by means of a silicon cantilever that serves as a mechanical resonator for ‘weighing’ the mass of the captured nanoparticles and as an optical cavity that boosts the plasmonic signal from the nanoparticles. The capabilities of the approach are illustrated with two cancer biomarkers: the carcinoembryonic antigen and the prostate specific antigen, which are currently in clinical use for the diagnosis, monitoring and prognosis of colon and prostate cancer, respectively. A detection limit of 1 × 10-16 g ml-1 in serum is achieved with both biomarkers, which is at least seven orders of magnitude lower than that achieved in routine clinical practice. Moreover, the rate of false positives and false negatives at this concentration is extremely low, ˜10-4.

  1. Cannabinoids Modulate Neuronal Activity and Cancer by CB1 and CB2 Receptor-Independent Mechanisms.

    Science.gov (United States)

    Soderstrom, Ken; Soliman, Eman; Van Dross, Rukiyah

    2017-01-01

    Cannabinoids include the active constituents of Cannabis or are molecules that mimic the structure and/or function of these Cannabis-derived molecules. Cannabinoids produce many of their cellular and organ system effects by interacting with the well-characterized CB1 and CB2 receptors. However, it has become clear that not all effects of cannabinoid drugs are attributable to their interaction with CB1 and CB2 receptors. Evidence now demonstrates that cannabinoid agents produce effects by modulating activity of the entire array of cellular macromolecules targeted by other drug classes, including: other receptor types; ion channels; transporters; enzymes, and protein- and non-protein cellular structures. This review summarizes evidence for these interactions in the CNS and in cancer, and is organized according to the cellular targets involved. The CNS represents a well-studied area and cancer is emerging in terms of understanding mechanisms by which cannabinoids modulate their activity. Considering the CNS and cancer together allow identification of non-cannabinoid receptor targets that are shared and divergent in both systems. This comparative approach allows the identified targets to be compared and contrasted, suggesting potential new areas of investigation. It also provides insight into the diverse sources of efficacy employed by this interesting class of drugs. Obtaining a comprehensive understanding of the diverse mechanisms of cannabinoid action may lead to the design and development of therapeutic agents with greater efficacy and specificity for their cellular targets.

  2. Cannabinoids Modulate Neuronal Activity and Cancer by CB1 and CB2 Receptor-Independent Mechanisms

    Directory of Open Access Journals (Sweden)

    Ken Soderstrom

    2017-10-01

    Full Text Available Cannabinoids include the active constituents of Cannabis or are molecules that mimic the structure and/or function of these Cannabis-derived molecules. Cannabinoids produce many of their cellular and organ system effects by interacting with the well-characterized CB1 and CB2 receptors. However, it has become clear that not all effects of cannabinoid drugs are attributable to their interaction with CB1 and CB2 receptors. Evidence now demonstrates that cannabinoid agents produce effects by modulating activity of the entire array of cellular macromolecules targeted by other drug classes, including: other receptor types; ion channels; transporters; enzymes, and protein- and non-protein cellular structures. This review summarizes evidence for these interactions in the CNS and in cancer, and is organized according to the cellular targets involved. The CNS represents a well-studied area and cancer is emerging in terms of understanding mechanisms by which cannabinoids modulate their activity. Considering the CNS and cancer together allow identification of non-cannabinoid receptor targets that are shared and divergent in both systems. This comparative approach allows the identified targets to be compared and contrasted, suggesting potential new areas of investigation. It also provides insight into the diverse sources of efficacy employed by this interesting class of drugs. Obtaining a comprehensive understanding of the diverse mechanisms of cannabinoid action may lead to the design and development of therapeutic agents with greater efficacy and specificity for their cellular targets.

  3. Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism

    Science.gov (United States)

    Donadelli, M; Dando, I; Zaniboni, T; Costanzo, C; Dalla Pozza, E; Scupoli, M T; Scarpa, A; Zappavigna, S; Marra, M; Abbruzzese, A; Bifulco, M; Caraglia, M; Palmieri, M

    2011-01-01

    Gemcitabine (GEM, 2′,2′-difluorodeoxycytidine) is currently used in advanced pancreatic adenocarcinoma, with a response rate of cannabinoids. Here, we show that GEM induces both cannabinoid receptor-1 (CB1) and cannabinoid receptor-2 (CB2) receptors by an NF-κB-dependent mechanism and that its association with cannabinoids synergistically inhibits pancreatic adenocarcinoma cell growth and increases reactive oxygen species (ROS) induced by single treatments. The antiproliferative synergism is prevented by the radical scavenger N-acetyl--cysteine and by the specific NF-κB inhibitor BAY 11-7085, demonstrating that the induction of ROS by GEM/cannabinoids and of NF-κB by GEM is required for this effect. In addition, we report that neither apoptotic nor cytostatic mechanisms are responsible for the synergistic cell growth inhibition, which is strictly associated with the enhancement of endoplasmic reticulum stress and autophagic cell death. Noteworthy, the antiproliferative synergism is stronger in GEM-resistant pancreatic cancer cell lines compared with GEM-sensitive pancreatic cancer cell lines. The combined treatment strongly inhibits growth of human pancreatic tumor cells xenografted in nude mice without apparent toxic effects. These findings support a key role of the ROS-dependent activation of an autophagic program in the synergistic growth inhibition induced by GEM/cannabinoid combination in human pancreatic cancer cells. PMID:21525939

  4. Mechanical properties of metastatic breast cancer cells invading into collagen I matrices

    Science.gov (United States)

    Ros, Robert

    2014-03-01

    Mechanical interactions between cells and the extracellular matrix (ECM) are critical to the metastasis of cancer cells. To investigate the mechanical interplay between the cells and ECM during invasion, we created thin bovine collagen I hydrogels ranging from 0.1-5 kPa in Young's modulus that were seeded with highly metastatic MDA-MB-231 breast cancer cells. Significant population fractions invaded the matrices either partially or fully within 24 h. We then combined confocal fluorescence microscopy and indentation with an atomic force microscope to determine the Young's moduli of individual embedded cells and the pericellular matrix using novel analysis methods for heterogeneous samples. In partially embedded cells, we observe a statistically significant correlation between the degree of invasion and the Young's modulus, which was up to an order of magnitude greater than that of the same cells measured in 2D. ROCK inhibition returned the cells' Young's moduli to values similar to 2D and diminished but did not abrogate invasion. This provides evidence that Rho/ROCK-dependent acto-myosin contractility is employed for matrix reorganization during initial invasion, and suggests the observed cell stiffening is due to an attendant increase in actin stress fibers. This work was supported by the National Cancer Institute under the grant U54 CA143862.

  5. Shp2 confers cisplatin resistance in small cell lung cancer via an AKT-mediated increase in CA916798.

    Science.gov (United States)

    Yang, Xuemei; Tang, Chunlan; Luo, Hu; Wang, Haijing; Zhou, Xiangdong

    2017-04-04

    The tyrosine phosphatase Shp2 is associated with tumorigenesis in small cell lung cancer (SCLC). However, the relationship between Shp2 and resistance to chemotherapy remains unclear. Here, we show that Shp2 plays an important role in inducing resistance to cisplatin-based chemotherapy via the SHP2-AKT-CA916798 pathway. In an SCLC cell line, overexpression of Shp2 induced cisplatin resistance and the increased expression of AKT, pAKT, pmTOR, and CA916798. Conversely, depletion of Shp2 in a cisplatin-resistant cell line via RNA interference increased cisplatin sensitivity and decreased AKT, pAKT, pmTOR, and CA916798 expression levels. Activation of AKT stimulated CA916798 expression and altered the level of Shp2. A mouse xenograft model verified the results obtained from the in vitro experiments. In addition, we collected and analyzed clinical SCLC specimens and found that Shp2 levels correlated with CA916798 expression in tumor tissues. Importantly, higher levels of Shp2 or CA916798 were associated with a poorer prognosis in SCLC patients who received chemotherapy. Together, our findings indicate that Shp2 induces cisplatin resistance in SCLC patients via the SHP2-AKT-CA916798 pathway. Therefore, Shp2 and CA916798 may be promising biomarkers for predicting resistance to chemotherapy and may function as targets for enhancing treatments.

  6. Anti-EGFR Therapy: Mechanism and Advances in Clinical Efficacy in Breast Cancer

    Directory of Open Access Journals (Sweden)

    John F. Flynn

    2009-01-01

    Full Text Available This review will focus on recent advances in the application of antiepidermal growth factor receptor (anti-EGFR for the treatment of breast cancer. The choice of EGFR, a member of the ErbB tyrosine kinase receptor family, stems from evidence pinpointing its role in various anti-EGFR therapies. Therefore, an increase in our understanding of EGFR mechanism and signaling might reveal novel targets amenable to intervention in the clinic. This knowledge base might also improve existing medical treatment options and identify research gaps in the design of new therapeutic agents. While the approved use of drugs like the dual kinase inhibitor Lapatinib represents significant advances in the clinical management of breast cancer, confirmatory studies must be considered to foster the use of anti-EGFR therapies including safety, pharmacokinetics, and clinical efficacy.

  7. Daily application of low magnitude mechanical stimulus inhibits the growth of MDA-MB-231 breast cancer cells in vitro.

    Science.gov (United States)

    Olcum, Melis; Ozcivici, Engin

    2014-01-01

    Mechanical loads can regulate cell proliferation and differentiation at various stages of development and homeostasis. However, the extension of this regulatory effect of mechanical loads on cancer cells is largely unknown. Increased physical compliance is one of the key features of cancer cells, which may hamper the transmission of mechanical loads to these cells within tumor microenvironment. Here we tested whether brief daily application of an external low magnitude mechanical stimulus (LMMS), would impede the growth of MDA-MB-231 aggressive type breast cancer cells in vitro for 3 wks of growth. The signal was applied in oscillatory form at 90 Hz and 0.15 g, a regimen that would induce mechanical loads on MDA-MB-231 cells via inertial properties of cells rather than matrix deformations. Experimental cells were exposed to LMMS 15 min/day, 5 days/week in ambient conditions while control cells were sham loaded. Cell proliferation, viability, cycle, apoptosis, morphology and migration were tested via Trypan Blue dye exclusion, MTT, PI, Annexin V, Calcein-AM and phalloidin stains and scratch wound assays. Compared to sham controls, daily application of LMMS reduced the number and viability of cancerous MDA-MB-231 cells significantly after first week in the culture, while non-cancerous MCF10A cells were found to be unaffected. Flow cytomety analyses suggested that the observed decrease for the cancer cells in the LMMS group was due to a cell cycle arrest rather than apoptosis. LMMS further reduced cancer cell circularity and increased cytoskeletal actin in MDA-MB-231 cells. Combined, results suggest that direct application of mechanical loads negatively regulate the proliferation of aggressive type cancer cells. If confirmed, this non-invasive approach may be integrated to the efforts for the prevention and/or treatment of cancer.

  8. PHYSICS FOR HEALTH: CONFERENCE HIGHLIGHTS

    CERN Multimedia

    2016-01-01

    Highlights of ICTR-PHE 2016 - International Conference on Translational Research in Radio-Oncology and Physics for Health -, co organized by CERN, aims at developing new strategies to better diagnose and treat cancer, by uniting biology and physics with clinics. Through the various sessions and symposia, the scientific programme offers the delegates the opportunity to discuss, in a friendly atmosphere, the latest progress in physics breakthroughs for health applications. The third edition of this conference took place at CICG (Centre International de Conférence Genève) from 15 to 19 Feb 2016.

  9. Fumarates and Cancer.

    Science.gov (United States)

    Fuhler, Gwenny M; Eppinga, Hester; Peppelenbosch, Maikel P

    2017-01-01

    Accumulation of intermediate metabolites of the tricarboxylic acid (TCA) cycle in tumor cells can cause epithelial-to-mesenchymal transition (EMT), although the exact mechanisms remain elusive. Recent studies show that the oncometabolite fumarate, which accumulates in fumarate hydratase-deficient renal cancers, confers tumor aggressiveness by causing epigenetic changes in the antimetastatic miRNA cluster mir-200ba429. This may have important implications for the use of fumarates in the clinic. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Mechanisms of intestinal inflammation and development of associated cancers: Lessons learned from mouse models

    Science.gov (United States)

    Westbrook, Aya M.; Szakmary, Akos; Schiestl, Robert H.

    2010-01-01

    Chronic inflammation is strongly associated with approximately 1/5th of all human cancers. Arising from combinations of factors such as environmental exposures, diet, inherited gene polymorphisms, infections, or from dysfunctions of the immune response, chronic inflammation begins as an attempt of the body to remove injurious stimuli; however, over time, this results in continuous tissue destruction and promotion and maintenance of carcinogenesis. Here we focus on intestinal inflammation and its associated cancers, a group of diseases on the rise and affecting millions of people worldwide. Intestinal inflammation can be widely grouped into inflammatory bowel diseases (ulcerative colitis and Crohn's disease) and celiac disease. Long-standing intestinal inflammation is associated with colorectal cancer and small-bowel adenocarcinoma, as well as extraintestinal manifestations, including lymphomas and autoimmune diseases. This article highlights potential mechanisms of pathogenesis in inflammatory bowel diseases and celiac disease, as well as those involved in the progression to associated cancers, most of which have been identified from studies utilizing mouse models of intestinal inflammation. Mouse models of intestinal inflammation can be widely grouped into chemically induced models; genetic models, which make up the bulk of the studied models; adoptive transfer models; and spontaneous models. Studies in these models have lead to the understanding that persistent antigen exposure in the intestinal lumen, in combination with loss of epithelial barrier function, and dysfunction and dysregulation of the innate and adaptive immune responses lead to chronic intestinal inflammation. Transcriptional changes in this environment leading to cell survival, hyperplasia, promotion of angiogenesis, persistent DNA damage, or insufficient repair of DNA damage due to an excess of proinflammatory mediators are then thought to lead to sustained malignant transformation. With regards

  11. Purified Essential Oil from Ocimum sanctum Linn. Triggers the Apoptotic Mechanism in Human Breast Cancer Cells.

    Science.gov (United States)

    Manaharan, Thamilvaani; Thirugnanasampandan, Ramaraj; Jayakumar, Rajarajeswaran; Kanthimathi, M S; Ramya, Gunasekar; Ramnath, Madhusudhanan Gogul

    2016-05-01

    Essential oil of Ocimum sanctum Linn. exhibited various pharmacological activities including antifungal and antimicrobial activities. In this study, we analyzed the anticancer and apoptosis mechanisms of Ocimum sanctum essential oil (OSEO). To trigger the apoptosis mechanism in human breast cancer cells using OSEO. OSEO was extracted using hydrodistillation of the leaves. Cell proliferation was determined using different concentrations of OSEO. Apoptosis studies were carried out in human breast cancer cells using propidium iodide (PI) and Hoechst staining. We found that OSEO inhibited proliferation (IC50 = 170 μg/ml) of Michigan cancer foundation-7 (MCF-7) cells in a dose-dependent manner. The OSEO also induced apoptosis as evidenced by the increasing number of PI-stained apoptotic nucleic of MCF-7 cells. Flow cytometry analysis revealed that treatment with OSEO (50-500 μg/ml) increased the apoptotic cells population (16-84%) dose dependently compared to the control. OSEO has the ability to up-regulate the apoptotic genes p53 and Bid and as well as elevates the ratio of Bax/Bcl-2. Our findings indicate that OSEO has the ability as proapoptotic inducer and it could be developed as an anticancer agent. OSEO inhibited proliferation of MCF-7 cells with an IC50 of 170 μg/mLOSEO at 500 μg/mL increased the population of apoptotic cells by 84%OSEO up-regulated the expression of apoptotic genes and as well increased the Bax/Bcl2 ratio. Abbreviations used: BAX: BAX BCL2-associated X protein; BCL2: B-cell CLL/lymphoma 2; BID: BH3 Interacting domain death agonist; OSEO: Ocimum sanctum essential oil; DMSO: Dimethyl sulfoxide; DMEM: Dulbecco's modified Eagle medium; MCF-7: Michigan cancer foundation-7; Real Time Polymerase Chain Reaction.

  12. Emerging Cytotoxic Alkaloids in the Battle against Cancer: Overview of Molecular Mechanisms

    Directory of Open Access Journals (Sweden)

    Zeina Habli

    2017-02-01

    Full Text Available Considered as the second deadliest disease globally, cancer has captured the attention of researchers who have been trying with perseverance to decode its hidden aspects, to find new prognosis methods, and to develop better and more effective treatments. Plants have continuously offered an excess of unique secondary metabolites with remarkable biological applications. Alkaloids, one of the most abundant metabolites, constitute a large conglomerate of basic heterocyclic nitrogen-containing natural compounds which are normally produced by plants as toxic substances. Out of the 27,000 different alkaloids, more than 17,000 have displayed diversified pharmacological properties including anticancer activities. These metabolites have been classified either according to their chemical structures or their taxonomic origin. None of the researched alkaloids have been classified according to their molecular mechanism of action against cancer. In fact, only a fraction of the tremendous number of anticancer alkaloids has been copiously mentioned in journals. Here, we aim to provide a summary of the literature on some of the promising anticancer alkaloids that have not been well discussed previously and to classify them according to their molecular mechanisms of action. This review will provide a better understanding of the anticancer mechanisms of these promising natural products that are a rich reservoir for drug discovery.

  13. [Mechanisms of resistance to CYP17A1 inhibitors in castrate resistant prostate cancer].

    Science.gov (United States)

    Ripert, T; Crouzet, S; Ploussard, G; De La Taille, A; Robert, G

    2013-10-01

    Abiraterone acetate has increased the overall survival of patients with metastatic castration-resistant prostate cancer. However, despite an initial response to treatment, many patients develop resistance to the drug. In this paper we present different hypotheses that may explain the emergence of resistance. This review was conducted from the PubMed database. The most relevant articles were selected and analyzed. The molecular mechanisms of resistance to abiraterone acetate remain largely elusive. We detailed some of them including the reactivation of the androgen receptor through alternative biosynthesis of androgens, over expression or mutation of the androgen receptor gene, or the action of co-activators. The over expression of CYP17A1 or the alteration of other genes' expression involved in steroidogenesis could also contribute to the resistance. Some of the molecular mechanisms involved in the resistance to abiraterone acetate were detailed. Better understanding of these mechanisms is a key step to allow the emergence of new therapeutic options and personalized treatments of castration resistant prostate cancer. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  14. Troxerutin with copper generates oxidative stress in cancer cells: Its possible chemotherapeutic mechanism against hepatocellular carcinoma.

    Science.gov (United States)

    Subastri, Ariraman; Suyavaran, Arumugam; Preedia Babu, Ezhuthupurakkal; Nithyananthan, Subramaniyam; Barathidasan, Rajamani; Thirunavukkarasu, Chinnasamy

    2018-03-01

    Troxerutin (TXER) a rutin derivative is known for its anticancer effect against hepatocellular carcinoma (HCC). As part of large study, recently we have shown TXER interact with genetic material and its anti-mutagenic property. In the present study we have explored its possible mode of action in HCC. Since TXER alone did not show significant anticancer effect on Huh-7 cells, in vitro biochemical assays were performed for determining anticancer efficacy of TXER + metal complex using transition metals such as Cu, Zn, and Fe. The anticancer efficacy of TXER + Cu on Huh-7 cells were evaluated using MTT assay, DCFDA, JC-1 staining, comet assay, cell cycle analysis, immunocytochemistry, and Western blotting. Non-toxic nature of TXER was analyzed on primary rat hepatocytes. The in vivo efficacy of TXER was tested in N-nitrosodiethylamine initiated and γ-benzene hexachloride and partial hepatectomy promoted rat liver cancer. Liver markers, transition metal levels, histopathological examination, and expression levels of GST-P, 8-OHdG and Ki-67 were studied to assess the in vivo anticancer effect of TXER. We observed that TXER + Cu induced extensive cellular death on Huh-7 cells through generating free radicals and did not possess any toxic effect on normal hepatocytes. The in vivo studies revealed that TXER possess significant anti-cancer effect as assessed through improved liver markers and suppressed GST-P, 8-OHdG, and Ki-67 expression. TXER treatment reduced the hepatic Cu level in cancer bearing animals. Current study brings the putative mechanism involved in anti-cancer effect of TXER, further it will help to formulate phytoconstituents coupled anti-cancer drug for effective treatment of HCC. © 2017 Wiley Periodicals, Inc.

  15. Target-oriented mechanisms of novel herbal therapeutics in the chemotherapy of gastrointestinal cancer and inflammation.

    Science.gov (United States)

    Ko, Joshua K; Auyeung, Kathy K

    2013-01-01

    A prominent group of effective cancer chemopreventive drugs has been derived from natural products having low toxicity while possessing apparent benefit in the disease process. It is plausible that there are multiple target molecules critical to cancer cell survival. Herbal terpenoids have demonstrated excellent target-specific anti-neoplastic functions by suppression of cell proliferation and induction of apoptosis. Transcriptional molecules in the NF-κB, MEK/ERK and PI3K/Akt/mTOR pathways are important molecular targets of chemotherapy that play distinctive roles in modulating the apoptosis cascades. It is recently suggested that NSAID-activated gene (NAG-1), a novel proapoptotic protein, is the upstream anti-carcinogenic target of NSAIDs, PPAR ligands and herbal chemotherapeutic agents that triggers some of the events mentioned above. Besides, angiogenesis, oxidative stress as well as inflammation are important factors that contribute to the development and metastasis of cancer, which could be actively modulated by novel agents of plant origin. The aim of the present review is to discuss and summarize the contemporary use of herbal therapeutics and phytochemicals in the treatment of human cancers, in particular that of the colon. The major events and signaling pathways in the carcinogenesis process being potentially modulated by natural products and novel herbal compounds will be evaluated, with emphasis on some terpenoids. Advances in eliciting the precise cellular and molecular mechanisms during the anti-tumorigenic process of novel herbal therapeutics will be of imperative clinical significance to increase the efficacy and reduce prominent adverse drug effects in cancer patients through target-specific therapy.

  16. Intra-operative label-free multimodal multiphoton imaging of breast cancer margins and microenvironment (Conference Presentation)

    Science.gov (United States)

    Sun, Yi; You, Sixian; Tu, Haohua; Spillman, Darold R.; Marjanovic, Marina; Chaney, Eric J.; Liu, George Z.; Ray, Partha S.; Higham, Anna; Boppart, Stephen A.

    2017-02-01

    Label-free multi-photon imaging has been a powerful tool for studying tissue microstructures and biochemical distributions, particularly for investigating tumors and their microenvironments. However, it remains challenging for traditional bench-top multi-photon microscope systems to conduct ex vivo tumor tissue imaging in the operating room due to their bulky setups and laser sources. In this study, we designed, built, and clinically demonstrated a portable multi-modal nonlinear label-free microscope system that combined four modalities, including two- and three- photon fluorescence for studying the distributions of FAD and NADH, and second and third harmonic generation, respectively, for collagen fiber structures and the distribution of micro-vesicles found in tumors and the microenvironment. Optical realignments and switching between modalities were motorized for more rapid and efficient imaging and for a light-tight enclosure, reducing ambient light noise to only 5% within the brightly lit operating room. Using up to 20 mW of laser power after a 20x objective, this system can acquire multi-modal sets of images over 600 μm × 600 μm at an acquisition rate of 60 seconds using galvo-mirror scanning. This portable microscope system was demonstrated in the operating room for imaging fresh, resected, unstained breast tissue specimens, and for assessing tumor margins and the tumor microenvironment. This real-time label-free nonlinear imaging system has the potential to uniquely characterize breast cancer margins and the microenvironment of tumors to intraoperatively identify structural, functional, and molecular changes that could indicate the aggressiveness of the tumor.

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

    Directory of Open Access Journals (Sweden)

    Han Yan

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

  18. EGC Conferences

    CERN Document Server

    Ritschard, Gilbert; Pinaud, Bruno; Venturini, Gilles; Zighed, Djamel; Advances in Knowledge Discovery and Management

    This book is a collection of representative and novel works done in Data Mining, Knowledge Discovery, Clustering and Classification that were originally presented in French at the EGC'2012 Conference held in Bordeaux, France, on January 2012. This conference was the 12th edition of this event, which takes place each year and which is now successful and well-known in the French-speaking community. This community was structured in 2003 by the foundation of the French-speaking EGC society (EGC in French stands for ``Extraction et Gestion des Connaissances'' and means ``Knowledge Discovery and Management'', or KDM). This book is intended to be read by all researchers interested in these fields, including PhD or MSc students, and researchers from public or private laboratories. It concerns both theoretical and practical aspects of KDM. The book is structured in two parts called ``Knowledge Discovery and Data Mining'' and ``Classification and Feature Extraction or Selection''. The first part (6 chapters) deals with...

  19. NATO Conference

    CERN Document Server

    Lynn, W

    1975-01-01

    The contents of this volume involve selection, emendation and up-dating of papers presented at the NATO Conference "Mathe­ matical Analysis of Decision problems in Ecology" in Istanbul, Turkey, July 9-13, 1973. It was sponsored by the System Sciences Division of NATO directed by Dr. B. Bayraktar with local arrange­ ments administered by Dr. Ilhami Karayalcin, professor of the Department of Industrial Engineering at the Technical University of Istanbul. It was organized by A. Charnes, University professor across the University of Texas System, and Walter R.Lynn, Di­ rector of the School of Civil and Environmental Engineering at Cornell Unjversity. The objective of the conference was to bring together a group of leading researchers from the major sciences involved in eco­ logical problems and to present the current state of progress in research of a mathematical nature which might assist in the solu­ tion of these problems. Although their presentations are not herein recorded, the key­ note address of Dr....

  20. Epigenetic Mechanisms of Human Papillomavirus-Associated Head and Neck Cancer.

    Science.gov (United States)

    Anayannis, Nicole V J; Schlecht, Nicolas F; Belbin, Thomas J

    2015-11-01

    Growing evidence suggests that as many as half of all oropharyngeal squamous cell carcinomas (OPSCCs) harbor human papillomavirus (HPV) infections. Despite being more advanced at diagnosis, HPV-positive OPSCCs are associated with a better response to therapy and longer patient survival than HPV-negative OPSCCs. Human papillomavirus-positive OPSCC has also been shown to have distinct host gene expression profiles compared with HPV-negative OPSCC. Recently, this distinction has been shown to include the epigenome. It is well supported that cancers are epigenetically deregulated. This review highlights epigenetic differences between HPV-positive and HPV-negative OPSCCs. The epigenetic mechanisms highlighted include methylation changes to host and viral DNA, and host chromatin modification. We also review the current evidence regarding host DNA methylation changes associated with smoking, and deregulation of microRNA expression in HPV-positive OPSCC. To provide an overview of epigenetic mechanisms reported in HPV-positive OPSCC, with analogies to cervical cancer, and discussion of the challenges involved in studying epigenetic changes in HPV-associated OPSCC in combination with changes associated with smoking. Sources were a literature review of peer-reviewed articles in PubMed on HPV and either OPSCC or head and neck squamous cell carcinoma, and related epigenetic mechanisms. Epigenetic changes are reported to be a contributing factor to maintaining a malignant phenotype in HPV-positive OPSCC. The epigenetic mechanisms highlighted in this review can be studied for potential as biomarkers or as drug targets. Furthermore, continued research on the deregulation of epigenetic mechanisms in HPV-positive OPSCC (compared with HPV-negative OPSCC) may contribute to our understanding of the clinical and biologic differences between HPV-positive and HPV-negative OPSCC.