The "magic" of tutorial centres in Hong Kong: An analysis of media marketing and pedagogy in a tutorial centre

Science.gov (United States)

Koh, Aaron

2014-12-01

Why do more than three-quarters of Hong Kong's senior secondary students flock to tutorial centres like moths to light? What is the "magic" that is driving the popularity of the tutorial centre enterprise? Indeed, looking at the ongoing boom of tutorial centres in Hong Kong (there are almost 1,000 of them), it is difficult not to ask these questions. This paper examines the phenomenon of tutorial centres in Hong Kong and seeks to understand what draws students to these centres. Combining theories of marketing semiotics and emotion studies, the author investigates the pivotal role of media marketing in generating the "magic" of tutorial centres, whose advertising strategy includes, for example, a display of billboard posters featuring stylishly-dressed "celebrity teachers". The author reviews some of the literature available on the subject of tutorial centres. In a case study approach, he then maps out the pedagogy he observed in an English tutorial class, seeking heuristic insights into the kind of teaching students in the study were looking for. He argues that part of the "magical" attraction of what are essentially "cram schools" is their formulaic pedagogy of teaching and reinforcing exam skills. Finally, the paper considers the social implications of the tutorial centre industry in terms of media marketing of education and unequal access to tutorial services.

[Resistance to target-based therapy and its circumvention].

Science.gov (United States)

Nishio, Kazuto

2004-07-01

Intrinsic and acquired resistance to molecular target therapy critically limits the outcome of cancer treatments. Target levels including quantitative and gene alteration should be determinants for the resistance. Downstream of the target molecules, drug metabolism, and drug transport influences the tumor sensitivity to molecular target therapy. The mechanisms of resistance to antibody therapy have not been fully clarified. Correlative clinical studies using these biomarkers of resistance are extremely important for circumvention of clinical resistance to target based therapy.

A Multimedia Tutorial for Charged-Particle Beam Dynamics. Final report

International Nuclear Information System (INIS)

Silbar, Richard R.

1999-01-01

In September 1995 WhistleSoft, Inc., began developing a computer-based multimedia tutorial for charged-particle beam dynamics under Phase II of a Small Business Innovative Research grant from the U.S. Department of Energy. In Phase I of this project (see its Final Report) we had developed several prototype multimedia modules using an authoring system on NeXTStep computers. Such a platform was never our intended target, and when we began Phase II we decided to make the change immediately to develop our tutorial modules for the Windows and Macintosh microcomputer market. This Report details our progress and accomplishments. It also gives a flavor of the look and feel of the presently available and upcoming modules

A Multimedia Tutorial for Charged-Particle Beam Dynamics. Final report

Energy Technology Data Exchange (ETDEWEB)

Silbar, Richard R.

1999-07-26

In September 1995 WhistleSoft, Inc., began developing a computer-based multimedia tutorial for charged-particle beam dynamics under Phase II of a Small Business Innovative Research grant from the U.S. Department of Energy. In Phase I of this project (see its Final Report) we had developed several prototype multimedia modules using an authoring system on NeXTStep computers. Such a platform was never our intended target, and when we began Phase II we decided to make the change immediately to develop our tutorial modules for the Windows and Macintosh microcomputer market. This Report details our progress and accomplishments. It also gives a flavor of the look and feel of the presently available and upcoming modules.

Targeted Radionuclide Therapy

Directory of Open Access Journals (Sweden)

David Cheng

2011-10-01

Full Text Available Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose.

Targeted Radionuclide Therapy

Energy Technology Data Exchange (ETDEWEB)

Ersahin, Devrim, E-mail: devrimersahin@yahoo.com; Doddamane, Indukala; Cheng, David [Department of Diagnostic Radiology, School of Medicine, Yale University, 333 Cedar St., New Haven, CT 06520 (United States)

2011-10-11

Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose.

Targeted Radionuclide Therapy

International Nuclear Information System (INIS)

Ersahin, Devrim; Doddamane, Indukala; Cheng, David

2011-01-01

Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose

TMVA tutorial

CERN Multimedia

CERN. Geneva; VOSS, Helge

2015-01-01

This tutorial will both give an introduction on how to use TMVA in root6 and showcase some new features, such as modularity, variable importance, interfaces to R and python. After explaining the basic functionality, the typical steps required during a real life application (such as variable selection, pre-processing, tuning and classifier evaluation) will be demonstrated on simple examples. First part of the tutorial will use the usual Root interface (please make sure you have Root 6.04 installed somewhere). The second part will utilize the new server notebook functionality of Root as a Service. If you are within CERN but outside the venue or outside CERN please consult the notes attached.

Gene transfer technology and genetic radioisotope targeting therapy

International Nuclear Information System (INIS)

Wang Jiaqiong; Wang Zizheng

2004-01-01

With deeper cognition about mechanisms of disease at the cellular and molecular level, gene therapy has become one of the most important research fields in medical molecular biology at present. Gene transfer technology plays an important role during the course of gene therapy, and further improvement should be made about vectors carrying target gene sequences. Also, gene survey is needed during gene therapy, and gene imaging is the most effective method. The combination of gene therapy and targeted radiotherapy, that is, 'Genetic Radioisotope Targeting Therapy', will be a novel approach to tumor gene therapy

Molecular Targets for Targeted Radionuclide Therapy

International Nuclear Information System (INIS)

Mather, S.J.

2009-01-01

Molecular targeted radionuclide cancer therapy is becoming of increasing importance, especially for disseminated diseases. Systemic chemotherapies often lack selectivity while targeted radionuclide therapy has important advantages as the radioactive cytotoxic unit of the targeting vector is specifically directed to the cancer, sparing normal tissues. The principle strategy to improve cancer selectivity is to couple therapeutic agents to tumour-targeting vectors. In targeted radionuclide therapy (TRT), the cytotoxic portion of the conjugates normally contains a therapeutic radiometal immobilised by a bifunctional chelator. The aim is therefore to use as ligand-targeted therapeutics vectors coupled to Auger-, alpha- and/or beta-emitting radionuclides. An advantage of using radiation instead of chemotherapeutics as the cytotoxic agent is the so called 'crossfire effect'. This allows sterilisation of tumour cells that are not directly targeted due to heterogeneity in target molecule expression or inhomogeneous vector delivery. However, before the targeting ligands can be selected, the target molecule on the tumour has to be selected. It should be uniquely expressed, or at least highly overexpressed, on or in the target cells relative to normal tissues. The target should be easily accessible for ligand delivery and should not be shed or down- regulated after ligand binding. An important property of a receptor (or antigen) is its potential to be internalized upon binding of the ligand. This provides an active uptake mechanism and allows the therapeutic agent to be trapped within the tumour cells. Molecular targets of current interest include: Receptors: G-protein coupled receptors are overexpressed on many major human tumours. The prototype of these receptors are somatostatin receptors which show very high density in neuroendocrine tumours, but there are many other most interesting receptors to be applied for TRT. The targeting ligands for these receptors are

OAI-PMH basics Tutorial 3

CERN Document Server

CERN. Geneva

2007-01-01

This tutorial is aimed at those who are new to the area of repositories and who want to learn more about key advocacy and policy issues. The tutorial will include information and advice on putting together an institutional advocacy campaign and developing policies for your repository. There will be opportunities for participants to share experiences and to ask questions. The tutorial will include a practical exercise in developing an advocacy presentation. Participants with experience of advocacy are welcome to attend the session to share their experiences, but should bear in mind that it is aimed primarily at those looking for help and advice in advocacy matters.

Gene therapy and radionuclides targeting therapy in mammary carcinoma

International Nuclear Information System (INIS)

Song Jinhua

2003-01-01

Breast carcinoma's gene therapy is a hotspot in study of the tumor's therapy in the recent years. Currently the major therapy methods that in the experimentative and primary clinical application phases include immunological gene therapy, multidrug resistance gene therapy, antisense oligonucleotide therapy and suicide gene therapy. The gene targeting brachytherapy, which is combined with gene therapy and radiotherapy has enhanced the killer effects of the suicide gene and nuclide in tumor cells. That has break a new path in tumor's gene therapy. The further study in this field will step up it's space to the clinical application

Karibu Tutorials

DEFF Research Database (Denmark)

Christensen, Henrik Bærbak

These tutorials demonstrate how to use Karibu for high quality data collection, in particular how to setup a distributed Karibu system and how to adapt Karibu to your particular data collection needs....

Teaching Game Programming using Video Tutorials

DEFF Research Database (Denmark)

Majgaard, Gunver

. & Squire K. (2004). Design-Based Research: Putting a Stake in the Ground. Journal of Learning Sciences Vol. 13-1. Lave, J., & Wenger, E. (1991). Situated Learning: Legitimate Peripheral Participation, Cambridge: Cambridge Univ. Majgaard, G. (2014). Teaching Design of Emerging Embodied Technologies......Background. What are the learning potentials of using online video tutorials as educational tools in game programming of Mixed Reality? The paper reports on the first experiences of teaching third semester engineering students design of Mixed Reality using online step-by-step programming video...... production makes video tutorials a promising alternative to paper tutorials. Software and game engine companies such as Unity has already switched to video and other online materials as the primary medium for their tutorials. It is often hard to find up to date thoroughly worked through textbooks on new...

Quantitative Microbial Risk Assessment Tutorial - Primer

Science.gov (United States)

This document provides a Quantitative Microbial Risk Assessment (QMRA) primer that organizes QMRA tutorials. The tutorials describe functionality of a QMRA infrastructure, guide the user through software use and assessment options, provide step-by-step instructions for implementi...

Indico MEETING tutorial

CERN Multimedia

CERN. Geneva; Manzoni, Alex Marc; Dimou, Maria

2017-01-01

This short tutorial explains how to create a MEETING in indico, how to populate the timetable, write minutes and how to add material. If you are only interested in the timetable part, please slide to 03.39, for the minutes to 07.46 and for adding material to 08.29.   Tell us what you think via e-learning.support at cern.ch More tutorials in the e-learning collection of the CERN Document Server (CDS) http://cds.cern.ch/collection/E-learning%20modules?ln=en All info about the CERN rapid e-learning project is linked from http://twiki.cern.ch/ELearning  

Tutorials in university students with a disability

Directory of Open Access Journals (Sweden)

Joaquín Gairín Sallán

2013-10-01

Full Text Available This article places an emphasis on the importance of tutorials for students with a disability in universities. It presented the most significant results of the study of tutorials carried out in help services, units or offices for students with a disability inmore than 45 Spanish universities, in relation to promotion, reception, completion and graduation. The contributions highlight the importance of organising a response through a Tutorial Action Plan made up of the stages of motivation and awareness-raisin, planning, execution, evaluation and institutionalisation. Among the principle conclusions, the importance of moving towards a truly inclusive university through tutorial activity is highlighted, thereby providing a guide for providing assistance to university students with a disability.

Progress Report--Microsoft Office 2003 Lynchburg College Tutorials

Science.gov (United States)

Murray, Tom

2004-01-01

For the past several years Lynchburg College has developed Microsoft tutorials for use with academic classes and faculty, student and staff training. The tutorials are now used internationally. Last year Microsoft and Verizon sponsored a tutorial web site at http://www.officetutorials.com. This website recognizes ASCUE members for their wonderful…

Tutorial Instruction in Science Education

Directory of Open Access Journals (Sweden)

Rhea Miles

2015-06-01

Full Text Available The purpose of the study is to examine the tutorial practices of in-service teachers to address the underachievement in the science education of K-12 students. Method: In-service teachers in Virginia and North Carolina were given a survey questionnaire to examine how they tutored students who were in need of additional instruction. Results: When these teachers were asked, “How do you describe a typical one-on-one science tutorial session?” the majority of their responses were categorized as teacher-directed. Many of the teachers would provide a science tutorial session for a student after school for 16-30 minutes, one to three times a week. Respondents also indicated they would rely on technology, peer tutoring, scientific inquiry, or themselves for one-on-one science instruction. Over half of the in-service teachers that responded to the questionnaire stated that they would never rely on outside assistance, such as a family member or an after school program to provide tutorial services in science. Additionally, very few reported that they incorporated the ethnicity, culture, or the native language of ELL students into their science tutoring sessions.

Tutorials in university students with a disability

OpenAIRE

Joaquín Gairín Sallán; José Luís Muñoz Moreno

2013-01-01

This article places an emphasis on the importance of tutorials for students with a disability in universities. It presented the most significant results of the study of tutorials carried out in help services, units or offices for students with a disability inmore than 45 Spanish universities, in relation to promotion, reception, completion and graduation. The contributions highlight the importance of organising a response through a Tutorial Action Plan made up of the stages of motivation and ...

NVidia Tutorial

CERN Document Server

CERN. Geneva; MESSMER, Peter; DEMOUTH, Julien

2015-01-01

This tutorial will present Caffee, a powerful Python library to implement solutions working on CPUs and GPUs, and explain how to use it to build and train Convolutional Neural Networks using NVIDIA GPUs. The session requires no prior experience with GPUs or Caffee.

The Development of e-tutorial on Implementation National Curriculum 2013 for Mathematics Teacher

Science.gov (United States)

Roza, Yenita; Satria, Gita; Nur Siregar, Syarifah

2017-06-01

Curriculum 2013 is the new national Curriculum in Indonesia that is targeted to be used in all Indonesian schools in 2019. At this time the teacher training continues but the number and locations of teachers very diffuse and time constraints to be an obstacle for the government to be able to conduct training for teachers. This research resulted in the e-tutorial which is designed for mathematics teachers in studying the process of Curriculum implementation. This product will assist the government in accelerating the preparation of teachers in implementation of Curriculum 2013. This e-tutorial contains the dynamics of Curriculum development, learning model, learning assessment, lesson plan, curriculum stages of implementation and government regulation that is relevant to the implementation of Curriculum 2013. The product development started with a needs analysis through discussions with mathematics teachers about their difficulties in the implementation of the Curriculum 2013. This e-tutorial was developed using Application of Adobe Director 11. This paper discusses the results of need analysis, process development and results of product revisions made based on input from teachers during the FGD. From the discussion, it can be concluded that this e-tutorial easily understood by teachers and help them to understand the implementation of Curriculum 2013

Heart failure—potential new targets for therapy

Science.gov (United States)

Nabeebaccus, Adam; Zheng, Sean; Shah, Ajay M.

2016-01-01

Abstract Introduction/background Heart failure is a major cause of cardiovascular morbidity and mortality. This review covers current heart failure treatment guidelines, emerging therapies that are undergoing clinical trial, and potential new therapeutic targets arising from basic science advances. Sources of data A non-systematic search of MEDLINE was carried out. International guidelines and relevant reviews were searched for additional articles. Areas of agreement Angiotensin-converting enzyme inhibitors and beta-blockers are first line treatments for chronic heart failure with reduced left ventricular function. Areas of controversy Treatment strategies to improve mortality in heart failure with preserved left ventricular function are unclear. Growing points Many novel therapies are being tested for clinical efficacy in heart failure, including those that target natriuretic peptides and myosin activators. A large number of completely novel targets are also emerging from laboratory-based research. Better understanding of pathophysiological mechanisms driving heart failure in different settings (e.g. hypertension, post-myocardial infarction, metabolic dysfunction) may allow for targeted therapies. Areas timely for developing research Therapeutic targets directed towards modifying the extracellular environment, angiogenesis, cell viability, contractile function and microRNA-based therapies. PMID:27365454

Advocacy and policy issues Tutorial 2

CERN Document Server

CERN. Geneva

2007-01-01

This tutorial is aimed at those who are new to the area of repositories and who want to learn more about key advocacy and policy issues. The tutorial will include information and advice on putting together an institutional advocacy campaign and developing policies for your repository. There will be opportunities for participants to share experiences and to ask questions. The tutorial will include a practical exercise in developing an advocacy presentation. Participants with experience of advocacy are welcome to attend the session to share their experiences, but should bear in mind that it is aimed primarily at those looking for help and advice in advocacy matters.

Solidaridad en la relación tutorial

Directory of Open Access Journals (Sweden)

Arturo G Rillo

Full Text Available Introducción. La tutoría académica concreta el proceso educativo sustentado en estándares de calidad, características y necesidades de aprendizaje del estudiante; se desenvuelve confrontando actividades pedagógicas y consolida solidaridades. En este contexto, el estudio se realizó con el propósito de realizar la analítica de la solidaridad que surge de la relación tutorial. Método. Desde el ámbito de la hermenéutica, se realizó un estudio en cuatro fases: analítica, comprensiva, reconstructiva, crítica. Se construyó el concepto de solidaridad en la relación tutorial con propuestas de Gadamer, Habermas, Adela Cortina y Edgar Morín. Las categorías de análisis fueron: construcción social del sentido en la relación tutorial, relación tutorial de naturaleza epistémica, compleja, infinita y cambiante; y práctica tutorial generadora de solidaridades. Resultados. La solidaridad como praxis humana orientada al cuidado del otro (Fürsorge promueve el encuentro con el estudiante. La tutoría académica regula la experiencia vital de la dualidad enseñar-aprender; articula la decisión del docente y alumno con la responsabilidad solidaria. El docente concreta un asentimiento aconsejado por la amistad de estar-ahí-con el estudiante, acompañándolo, posibilitando elecciones y decisiones entre posibilidades para una vida sustentable mediante la virtud de la phrónesis. Conclusiones. La solidaridad en la relación tutorial como horizonte de sentido engarza la cosmovisión del binomio docente-estudiante en la relación tutorial. Dado el vínculo social, se ubica en el escenario de la relación tutorial el sentido originario de la amistad y la solidaridad con los siguientes baremos: compasión, saber hacer, confidencialidad, confianza, conciencia de sí mismo y del otro, tacto, escucha atenta y solícita, comprensión del otro.

First year clinical tutorials: students’ learning experience

Directory of Open Access Journals (Sweden)

Burgess A

2014-11-01

Full Text Available Annette Burgess,1 Kim Oates,2 Kerry Goulston,2 Craig Mellis1 1Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; 2Sydney Medical School, The University of Sydney, Sydney, NSW, Australia Background: Bedside teaching lies at the heart of medical education. The learning environment afforded to students during clinical tutorials contributes substantially to their knowledge, thinking, and learning. Situated cognition theory posits that the depth and breadth of the students' learning experience is dependent upon the attitude of the clinical teacher, the structure of the tutorial, and the understanding of tutorial and learning objectives. This theory provides a useful framework to conceptualize how students' experience within their clinical tutorials impacts their knowledge, thinking, and learning. Methods: The study was conducted with one cohort (n=301 of students who had completed year 1 of the medical program at Sydney Medical School in 2013. All students were asked to complete a three-part questionnaire regarding their perceptions of their clinical tutor's attributes, the consistency of the tutor, and the best features of the tutorials and need for improvement. Both quantitative and qualitative data were collected and analyzed using descriptive statistics. Results: The response rate to the questionnaire was 88% (265/301. Students perceived that their tutors displayed good communication skills and enthusiasm, encouraged their learning, and were empathetic toward patients. Fifty-two percent of students reported having the same communications tutor for the entire year, and 28% reported having the same physical examination tutor for the entire year. Students would like increased patient contact, greater structure within their tutorials, and greater alignment of teaching with the curriculum. Conclusion: Situated cognition theory provides a valuable lens to view students' experience of learning within the

Targeted Therapies in Epithelial Ovarian Cancer

Directory of Open Access Journals (Sweden)

Jurjees Hasan

2010-02-01

Full Text Available Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.

Targeted Therapies in Epithelial Ovarian Cancer

Energy Technology Data Exchange (ETDEWEB)

Dean, Emma; El-Helw, Loaie; Hasan, Jurjees, E-mail: jurjees.hasan@christie.nhs.uk [Christie Hospital NHS Foundation Trust / Wilmslow Road, Manchester, M20 4BX (United Kingdom)

2010-02-23

Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.

Individualized therapies in colorectal cancer: KRAS as a marker for response to EGFR-targeted therapy

Directory of Open Access Journals (Sweden)

Li Kuiyuan

2009-04-01

Full Text Available Abstract Individualized therapies that are tailored to a patient's genetic composition will be of tremendous value for treatment of cancer. Recently, Kirsten ras (KRAS status has emerged as a predictor of response to epidermal growth factor receptor (EGFR targeted therapies. In this article, we will discuss targeted therapies for colorectal cancers (CRC based on EGFR signaling pathway and review published data about the potential usefulness of KRAS as a biological marker for response to these therapies. Results from relevant studies published since 2005 and unpublished results presented at national meetings were retrieved and summarized. These studies reflected response (or lack of response to EGFR-targeted therapies in patients with metastatic CRC as a function of KRAS status. It has become clear that patients with colorectal cancer whose tumor has an activating mutation in KRAS do not respond to monoclonal antibody therapies targeting EGFR. It should now become a standard practice that any patients being considered for EGFR targeted therapies have their tumors tested for KRAS status and only those with wild-type KRAS being offered such therapies.

Tutorial on beam current monitoring

International Nuclear Information System (INIS)

Webber, Robert C.

2000-01-01

This paper is a tutorial level review covering a wide range of aspects related to charged particle beam current measurement. The tutorial begins with a look at the characteristics of the beam as a signal source, the associated electromagnetic fields, the influence of the typical accelerator environment on those fields, and the usual means of modifying and controlling that environment to facilitate beam current measurement. Short descriptions of three quite different types of current monitors are presented and a quantitative review of the classical transformer circuit is given. Recognizing that environmental noise pick-up may present a large source of error in quantitative measurements, signal handling considerations are given considerable attention using real-life examples. An example of a successful transport line beam current monitor implementation is presented and the tutorial concludes with a few comments about signal processing and current monitor calibration issues

Targeted Therapy for Melanoma

International Nuclear Information System (INIS)

Quinn, Thomas; Moore, Herbert

2016-01-01

The research project, entitled ''Targeted Therapy for Melanoma,'' was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the "2"1"2"P"b"/"2"0"3Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg"1"1)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of "2"1"2Pb labeled DOTA-Re(Arg"1"1)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter "2"1"2Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

Targeted Therapy for Melanoma

Energy Technology Data Exchange (ETDEWEB)

Quinn, Thomas [Alphamed, Jackson, TN (United States); Moore, Herbert [Alphamed, Jackson, TN (United States)

2016-12-05

The research project, entitled ”Targeted Therapy for Melanoma,” was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the ^212Pb/203Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg¹¹)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of ²¹²Pb labeled DOTA-Re(Arg¹¹)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter ²¹²Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

Online Hotseat Tutorials

DEFF Research Database (Denmark)

Bengtsen, Søren Smedegaard; Nørgård, Rikke Toft; Dalsgaard, Christian

. On the grounds of the developed pedagogical format, students elicit advanced academic competences such as being facilitators of critical dialogue, exhibiting knowledge stewardship, and taking on responsibility of relationship formation between students. These are traits we normally see only teachers......We present a design-based research experiment for developing a pedagogical format for supervision collectives called ’online hotseat tutorials.’ The format has been developed and tested within the MA Programme ICT-based educational design, Aarhus University 2014-2018. It has affinity to traditional......-up as well as the pedagogical intentions behind it is presented. Finally, we analyse the emerging forms of partnership within online hot seat tutorials, and we discuss the pedagogical implications for how to further inform, qualify and develop pedagogical formats for team-based supervision in higher...

Research progess on treatment of cancer with targeted radionuclide therapy

International Nuclear Information System (INIS)

Luo Jiawen; Zhang Caixia

2008-01-01

The new development and situation of targeted radionuclide therapy in oncology is described, which include radioimmunotherapy, peptide receptor radionuclide therapy, gene therapy and radionuclide labled chemotherapeutics therapy. The application research on labled carrier of those therapy is emphasized. Meanwhile, the research progess of indomethacin and its combined with targeted radionuclide therapy is also described. (authors)

Metastatic gastric cancer – focus on targeted therapies

Directory of Open Access Journals (Sweden)

Meza-Junco J

2012-06-01

Full Text Available Judith Meza-Junco, Michael B SawyerDepartment of Oncology, Cross Cancer Institute, Edmonton, Alberta, CanadaAbstract: Gastric cancer (GC is currently the second leading cause of cancer death worldwide; unfortunately, most patients will present with locally advanced or metastatic disease. Despite recent progress in diagnosis, surgery, chemotherapy, and radiotherapy, prognosis remains poor. A better understanding of GC biology and signaling pathways is expected to improve GC therapy, and the integration of targeted therapies has recently become possible and appears to be promising. This article focuses on anti-Her-2 therapy, specifically trastuzumab, as well as other epidermal growth factor receptor antagonists such as cetuximab, panitumub, matuzumab, nimotzumab, gefitinib, and erlotinib. Additionally, drugs that target angiogenesis pathways are also under investigation, particulary bevacizumab, ramucirumab, sorafenib, sunitinib, and cediranib. Other targeted agents in preclinical or early clinical development include mTOR inhibitors, anti c-MET, polo-like kinase 1 inhibitors, anti-insulin-like growth factor, anti-heat shock proteins, and small molecules targeting Hedgehog signaling.Keywords: gastric cancer, targeted therapy, antiangiogenesis drugs, anti-EGFR drugs

Advocacy and IPR, tutorial 4

CERN Multimedia

CERN. Geneva

2005-01-01

With open access and repositories assuming a high profile some may question whether advocacy is still necessary. Those involved in the business of setting up and populating repositories are aware that in the majority of institutions there is still a great need for advocacy. This tutorial will give participants an opportunity to discuss different advocacy methods and approaches, including the 'top down' and 'bottom up' approach, publicity methods and the opportunities offered by funding body positions on open access. Participants will have the opportunity to share experiences of what works and what doesn't. The advocacy role often encompasses responsibility for advising academics on IPR issues. This is a particularly critical area where repository staff are engaged in depositing content on behalf of academics. The tutorial will offer an opportunity to discuss the IPR issues encountered by those managing repositories. The tutorial will draw on the experience of participants who have been engaged in advocacy act...

Targeted Therapies for Lung Cancer.

Science.gov (United States)

Stinchcombe, Thomas E

Targeted therapies have become standard therapies for patients with non-small cell lung cancer (NSCLC). A phase III trial of carboplatin and paclitaxel with and without bevacizumab in patients with advanced NSCLC with non-squamous histology demonstrated a statistically significant improvement in efficacy. In patients with NSCLC with an activating epidermal growth factor receptor (EGFR) mutation (defined as exon 19 deletion and exon 21 L858R point mutation), phase III trials of EGFR tyrosine kinase inhibitors (TKI) compared to platinum-based chemotherapy have demonstrated superior efficacy in the first-line setting. In patients with NSCLC with anaplastic lymphoma kinase (ALK) rearrangements, phase III trials of crizotinib have demonstrated superior efficacy compared to platinum-pemetrexed in the first-line setting and standard chemotherapy in the second-line setting. A second-generation ALK inhibitor, ceritinib, is available for patients who have progressed after or were intolerant of crizotinib. Crizotinib has also demonstrated activity on patients with ROS1 rearrangements, and BRAF inhibitors (dabrafenib, vemurafenib) have demonstrated activity in patients with NSCLC with BRAF V600E mutation. The oncogenic mutations that are susceptible to targeted therapy are mainly found in non-squamous NSCLC. The development of targeted therapy in patients with squamous NSCLC has been more challenging due to the genomic complexity observed in the squamous histology and the low prevalence of EGFR, ALK, and ROS1 molecular alterations. A phase III trial of cisplatin and gemcitabine with and without necitumumab in patients with advanced NSCLC with squamous histology demonstrated a statistically significant improvement in progression-free and overall survival.

Medical imaging informatics simulators: a tutorial.

Science.gov (United States)

Huang, H K; Deshpande, Ruchi; Documet, Jorge; Le, Anh H; Lee, Jasper; Ma, Kevin; Liu, Brent J

2014-05-01

A medical imaging informatics infrastructure (MIII) platform is an organized method of selecting tools and synthesizing data from HIS/RIS/PACS/ePR systems with the aim of developing an imaging-based diagnosis or treatment system. Evaluation and analysis of these systems can be made more efficient by designing and implementing imaging informatics simulators. This tutorial introduces the MIII platform and provides the definition of treatment/diagnosis systems, while primarily focusing on the development of the related simulators. A medical imaging informatics (MII) simulator in this context is defined as a system integration of many selected imaging and data components from the MIII platform and clinical treatment protocols, which can be used to simulate patient workflow and data flow starting from diagnostic procedures to the completion of treatment. In these processes, DICOM and HL-7 standards, IHE workflow profiles, and Web-based tools are emphasized. From the information collected in the database of a specific simulator, evidence-based medicine can be hypothesized to choose and integrate optimal clinical decision support components. Other relevant, selected clinical resources in addition to data and tools from the HIS/RIS/PACS and ePRs platform may also be tailored to develop the simulator. These resources can include image content indexing, 3D rendering with visualization, data grid and cloud computing, computer-aided diagnosis (CAD) methods, specialized image-assisted surgical, and radiation therapy technologies. Five simulators will be discussed in this tutorial. The PACS-ePR simulator with image distribution is the cradle of the other simulators. It supplies the necessary PACS-based ingredients and data security for the development of four other simulators: the data grid simulator for molecular imaging, CAD-PACS, radiation therapy simulator, and image-assisted surgery simulator. The purpose and benefits of each simulator with respect to its clinical relevance

Auger radiation targeted into DNA: a therapy perspective

Energy Technology Data Exchange (ETDEWEB)

Buchegger, Franz [University Hospital of Lausanne CHUV, Service of Nuclear Medicine, Lausanne (Switzerland); University Hospital of Lausanne, Service of Nuclear Medicine, Lausanne (Switzerland); Perillo-Adamer, Florence; Bischof Delaloye, Angelika [University Hospital of Lausanne CHUV, Service of Nuclear Medicine, Lausanne (Switzerland); Dupertuis, Yves M. [University Hospital of Geneva, Service of Nutrition, Geneva (Switzerland)

2006-11-15

Auger electron emitters that can be targeted into DNA of tumour cells represent an attractive systemic radiation therapy goal. In the situation of DNA-associated decay, the high linear energy transfer (LET) of Auger electrons gives a high relative biological efficacy similar to that of {alpha} particles. In contrast to {alpha} radiation, however, Auger radiation is of low toxicity when decaying outside the cell nucleus, as in cytoplasm or outside cells during blood transport. The challenge for such therapies is the requirement to target a high percentage of all cancer cells. An overview of Auger radiation therapy approaches of the past decade shows several research directions and various targeting vehicles. The latter include hormones, peptides, halogenated nucleotides, oligonucleotides and internalising antibodies. Here, we will discuss the basic principles of Auger electron therapy as compared with vector-guided {alpha} and {beta} radiation. We also review some radioprotection issues and briefly present the main advantages and disadvantages of the different targeting modalities that are under investigation. (orig.)

Auger radiation targeted into DNA: a therapy perspective

International Nuclear Information System (INIS)

Buchegger, Franz; Perillo-Adamer, Florence; Bischof Delaloye, Angelika; Dupertuis, Yves M.

2006-01-01

Auger electron emitters that can be targeted into DNA of tumour cells represent an attractive systemic radiation therapy goal. In the situation of DNA-associated decay, the high linear energy transfer (LET) of Auger electrons gives a high relative biological efficacy similar to that of α particles. In contrast to α radiation, however, Auger radiation is of low toxicity when decaying outside the cell nucleus, as in cytoplasm or outside cells during blood transport. The challenge for such therapies is the requirement to target a high percentage of all cancer cells. An overview of Auger radiation therapy approaches of the past decade shows several research directions and various targeting vehicles. The latter include hormones, peptides, halogenated nucleotides, oligonucleotides and internalising antibodies. Here, we will discuss the basic principles of Auger electron therapy as compared with vector-guided α and β radiation. We also review some radioprotection issues and briefly present the main advantages and disadvantages of the different targeting modalities that are under investigation. (orig.)

Oligonucleotide Aptamers: New Tools for Targeted Cancer Therapy

Directory of Open Access Journals (Sweden)

Hongguang Sun

2014-01-01

Full Text Available Aptamers are a class of small nucleic acid ligands that are composed of RNA or single-stranded DNA oligonucleotides and have high specificity and affinity for their targets. Similar to antibodies, aptamers interact with their targets by recognizing a specific three-dimensional structure and are thus termed “chemical antibodies.” In contrast to protein antibodies, aptamers offer unique chemical and biological characteristics based on their oligonucleotide properties. Hence, they are more suitable for the development of novel clinical applications. Aptamer technology has been widely investigated in various biomedical fields for biomarker discovery, in vitro diagnosis, in vivo imaging, and targeted therapy. This review will discuss the potential applications of aptamer technology as a new tool for targeted cancer therapy with emphasis on the development of aptamers that are able to specifically target cell surface biomarkers. Additionally, we will describe several approaches for the use of aptamers in targeted therapeutics, including aptamer-drug conjugation, aptamer-nanoparticle conjugation, aptamer-mediated targeted gene therapy, aptamer-mediated immunotherapy, and aptamer-mediated biotherapy.

Targeted Therapy in Nonmelanoma Skin Cancers

International Nuclear Information System (INIS)

Spallone, Giulia; Botti, Elisabetta; Costanzo, Antonio

2011-01-01

Nonmelanoma skin cancer (NMSC) is the most prevalent cancer in light-skinned populations, and includes mainly Basal Cell Carcinomas (BCC), representing around 75% of NMSC and Squamous Cell Carcinomas (SCC). The incidence of these tumors is continuously growing. It was found that the overall number of procedures for NMSC in US rose by 76%, from 1,158,298 in 1992 to 2,048,517 in 2006. Although mortality from NMSC tends to be very low, clearly the morbidity related to these skin cancers is very high. Treatment options for NMSC include both surgical and nonsurgical interventions. Surgery was considered the gold standard therapy, however, advancements in the knowledge of pathogenic mechanisms of NMSCs led to the identification of key targets for drug intervention and to the consequent development of several targeted therapies. These represent the future in treatment of these common forms of cancer ensuring a high cure rate, preservation of the maximal amount of normal surrounding tissue and optimal cosmetic outcome. Here, we will review recent advancements in NMSC targeted therapies focusing on BCC and SCC

Targeted Therapy in Nonmelanoma Skin Cancers

Directory of Open Access Journals (Sweden)

Giulia Spallone

2011-05-01

Full Text Available Nonmelanoma skin cancer (NMSC is the most prevalent cancer in light-skinned populations, and includes mainly Basal Cell Carcinomas (BCC, representing around 75% of NMSC and Squamous Cell Carcinomas (SCC. The incidence of these tumors is continuously growing. It was found that the overall number of procedures for NMSC in US rose by 76%, from 1,158,298 in 1992 to 2,048,517 in 2006. Although mortality from NMSC tends to be very low, clearly the morbidity related to these skin cancers is very high. Treatment options for NMSC include both surgical and nonsurgical interventions. Surgery was considered the gold standard therapy, however, advancements in the knowledge of pathogenic mechanisms of NMSCs led to the identification of key targets for drug intervention and to the consequent development of several targeted therapies. These represent the future in treatment of these common forms of cancer ensuring a high cure rate, preservation of the maximal amount of normal surrounding tissue and optimal cosmetic outcome. Here, we will review recent advancements in NMSC targeted therapies focusing on BCC and SCC.

Historical Text Comprehension Reflective Tutorial Dialogue System

Science.gov (United States)

Grigoriadou, Maria; Tsaganou, Grammatiki; Cavoura, Theodora

2005-01-01

The Reflective Tutorial Dialogue System (ReTuDiS) is a system for learner modelling historical text comprehension through reflective dialogue. The system infers learners' cognitive profiles and constructs their learner models. Based on the learner model the system plans the appropriate--personalized for learners--reflective tutorial dialogue in…

Targeted therapy in the treatment of malignant gliomas

Directory of Open Access Journals (Sweden)

Rimas V Lukas

2009-05-01

Full Text Available Rimas V Lukas1, Adrienne Boire2, M Kelly Nicholas1,2 1Department of Neurology; 2Department of Medicine, University of Chicago, Chicago, IL, USAAbstract: Malignant gliomas are invasive tumors with the potential to progress through current available therapies. These tumors are characterized by a number of abnormalities in molecular signaling that play roles in tumorigenesis, spread, and survival. These pathways are being actively investigated in both the pre-clinical and clinical settings as potential targets in the treatment of malignant gliomas. We will review many of the therapies that target the cancer cell, including the epidermal growth factor receptor, mammalian target of rapamycin, histone deacetylase, and farnesyl transferase. In addition, we will discuss strategies that target the extracellular matrix in which these cells reside as well as angiogenesis, a process emerging as central to tumor development and growth. Finally, we will briefly touch on the role of neural stem cells as both potential targets as well as delivery vectors for other therapies. Interdependence between these varied pathways, both in maintaining health and in causing disease, is clear. Thus, attempts to easily classify some targeted therapies are problematic.Keywords: glioma, EGFR, mTOR, HDAC, Ras, angiogenesis

The genre tutorial and social networks terminology

Directory of Open Access Journals (Sweden)

Márcio Sales Santiago

2014-02-01

Full Text Available This paper analyzes the terminology in the Internet social networks tutorials. A tutorial is a specialized text, full of terms, aiming to teach an individual or group of individuals who need some guidelines to operationalize a computerized tool, such as a social network. It is necessary to identify linguistic and terminological characteristics from the specialized lexical units in this digital genre. Social networks terminology is described and exemplified here. The results show that it is possible to refer to two specific terminologies in tutorials which help to determine the terminological profile of the thematic area, specifically from the point of view of denomination.

Novel Targeted Therapies for Inflammatory Breast Cancer

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-16-1-0461 TITLE: Novel Targeted Therapies for Inflammatory Breast Cancer PRINCIPAL INVESTIGATOR: Jose Silva CONTRACTING...CONTRACT NUMBER Novel Targeted Therapies for Inflammatory Breast Cancer 5b. GRANT NUMBER W81XWH-16-1-0461 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) l 5d...NOTES 14. ABSTRACT Inflammatory breast cancer (IBC, ~5% of all breast cancers ) is the most lethal form of breast cancer , presenting a 5- year

Writing learning cases for an information literacy tutorial

OpenAIRE

Gunhild Austrheim

2010-01-01

The research and writing processes are often hidden mysteries to our students. A key point in the online tutorial Search and Write (Søk and Skriv) has been to supply our students with tools to handle these processes. Learning cases embedded in the tutorial allow us to demonstrate a variety of working techniques and to better cater for a diverse student population. The tutorial can be used as an independent resource for students and as a teaching aid for both library sessions on inform...

The SIKS/BiGGrid Big Data Tutorial

NARCIS (Netherlands)

Hiemstra, Djoerd; Lammerts, Evert; de Vries, A.P.

2011-01-01

The School for Information and Knowledge Systems SIKS and the Dutch e-science grid BiG Grid organized a new two-day tutorial on Big Data at the University of Twente on 30 November and 1 December 2011, just preceding the Dutch-Belgian Database Day. The tutorial is on top of some exciting new

Neoadjuvant targeted therapy in patients with renal cell carcinoma

Directory of Open Access Journals (Sweden)

B. Ya. Alekseev

2015-01-01

Full Text Available Cytoreductive nephrectomy as an independent option in patients with metastatic renal cell carcinoma (mRCC cannot be considered as the only effective method, with rare exception, of a few patients with solitary metastases. Cytoreductive nephrectomy is now part of a multimodal approach encompassing surgical treatment and systemic drug therapy. Many retrospective and two prospective studies have demonstrated that it is expedient to perform cytoreductive nephrectomy. Immunotherapy should not be used as preoperatively in the era of cytokine therapy for mRCC due to that fact that it has no impact on primary tumor. In the current targeted therapy era, many investigators have concentrated attentionon the role of neoadjuvant targeted therapy for the treatment of patients with both localized and locally advanced mRCC. The potential benefits of neoadjuvant therapy for localized and locally advanced RCC include to make surgery easier and to increase the possibility of organsparing treatment, by decreasing the stage of primary tumor and the size of tumors. The possible potential advantages of neoadjuvant targeted therapy in patients with mRCC include prompt initiation of necessary systemic therapy; identification of patients with primary refractory tumors; and a preoperative reduction in the stage of primary tumor. Numerous retrospective and some prospective phase II studies have shown that neoadjuvant targeted therapy in patients with localized and locally advanced RCC is possible and tolerable and surgical treatment after neoadjuvant targeted therapy is safe and executable with a low incidence of complications. If neoadjuvant therapy is to be performed, it should be done within 2–4 months before surgery. Sorafenib and sunitinib are now most tested and suitable for neoadjuvant targeted therapy. Sorafenib is a more preferred drug due to its shorter half-life and accordingly to the possibility of discontinuing the drug immediately prior to

Audio-Tutorial Instruction: A Strategy For Teaching Introductory College Geology.

Science.gov (United States)

Fenner, Peter; Andrews, Ted F.

The rationale of audio-tutorial instruction is discussed, and the history and development of the audio-tutorial botany program at Purdue University is described. Audio-tutorial programs in geology at eleven colleges and one school are described, illustrating several ways in which programs have been developed and integrated into courses. Programs…

Captivate MenuBuilder: Creating an Online Tutorial for Teaching Software

Science.gov (United States)

Yelinek, Kathryn; Tarnowski, Lynn; Hannon, Patricia; Oliver, Susan

2008-01-01

In this article, the authors, students in an instructional technology graduate course, describe a process to create an online tutorial for teaching software. They created the tutorial for a cyber school's use. Five tutorial modules were linked together through one menu screen using the MenuBuilder feature in the Adobe Captivate program. The…

Video and HTML: Testing Online Tutorial Formats with Biology Students

Science.gov (United States)

Craig, Cindy L.; Friehs, Curt G.

2013-01-01

This study compared two common types of online information literacy tutorials: a streaming media tutorial using animation and narration and a text-based tutorial with static images. Nine sections of an undergraduate biology lab class (234 students total) were instructed by a librarian on how to use the BIOSIS Previews database. Three sections…

Caregiver's satisfaction with a video tutorial for shoulder dystocia management algorithm.

Science.gov (United States)

Youssef, A; Salsi, G; Ragusa, A; Ghi, T; Pacella, G; Rizzo, N; Pilu, G

2015-01-01

In our questionnaire, a video tutorial illustrating the management of shoulder dystocia was considered by health personnel as a useful complementary training tool. We prepared a 5-min video tutorial on the management of shoulder dystocia, using a simulator that includes maternal pelvic and baby models. We performed a survey among obstetric personnel in order to assess their opinion on the tutorial by inviting them to watch the video tutorial and answer an online questionnaire. Five multiple-choice questions were set, focusing on the video's main objectives: clarity, simplicity and usefulness. Following the collection of answers, global and category-weighted analyses were conducted for each question. Out of 956 invitations sent, 482 (50.4%) answered the survey. More than 90% of all categories found the video tutorial to be clinically relevant and clear. For revising the management of shoulder dystocia most obstetric personnel would use the video tutorial together with traditional textbooks. In conclusion, our video tutorial was considered by health personnel as a useful complementary training tool.

Mail2Print online tutorial

CERN Multimedia

CERN. Geneva

2016-01-01

Mail2print is a feature which allows you to send documents to a printer by mail. This tutorial (text attached to the event page) explains how to use this service. Content owner: Vincent Nicolas Bippus Presenter: Pedro Augusto de Freitas Batista Tell us what you think via e-learning.support at cern.ch More tutorials in the e-learning collection of the CERN Document Server (CDS) https://cds.cern.ch/collection/E-learning%20modules?ln=en All info about the CERN rapid e-learning project is linked from http://twiki.cern.ch/ELearning  

Research and Teaching: Correlations between Students' Written Responses to Lecture-Tutorial Questions and Their Understandings of Key Astrophysics Concepts

Science.gov (United States)

Eckenrode, Jeffrey; Prather, Edward E.; Wallace, Colin S.

2016-01-01

This article reports on an investigation into the correlations between students' understandings of introductory astronomy concepts and the correctness and coherency of their written responses to targeted Lecture-Tutorial questions.

Hadoop Tutorials - Hadoop Foundations

CERN Multimedia

CERN. Geneva; Lanza Garcia, Daniel

2016-01-01

The Hadoop ecosystem is the leading opensource platform for distributed storage and processing of "big data". The Hadoop platform is available at CERN as a central service provided by the IT department. This tutorial organized by the IT Hadoop service, aims to introduce the main concepts about Hadoop technology in a practical way and is targeted to those who would like to start using the service for distributed parallel data processing. The main topics that will be covered are: Hadoop architecture and available components How to perform distributed parallel processing in order to explore and create reports with SQL (with Apache Impala) on example data. Using a HUE - Hadoop web UI for presenting the results in user friendly way. How to format and/or structure data in order to make data processing more efficient - by using various data formats/containers and partitioning techniques (Avro, Parquet, HBase). ...

Dynamical systems on networks a tutorial

CERN Document Server

Porter, Mason A

2016-01-01

This volume is a tutorial for the study of dynamical systems on networks. It discusses both methodology and models, including spreading models for social and biological contagions. The authors focus especially on “simple” situations that are analytically tractable, because they are insightful and provide useful springboards for the study of more complicated scenarios. This tutorial, which also includes key pointers to the literature, should be helpful for junior and senior undergraduate students, graduate students, and researchers from mathematics, physics, and engineering who seek to study dynamical systems on networks but who may not have prior experience with graph theory or networks. Mason A. Porter is Professor of Nonlinear and Complex Systems at the Oxford Centre for Industrial and Applied Mathematics, Mathematical Institute, University of Oxford, UK. He is also a member of the CABDyN Complexity Centre and a Tutorial Fellow of Somerville College. James P. Gleeson is Professor of Industrial and Appli...

Web-tutorials in context

DEFF Research Database (Denmark)

Lund, Haakon; Pors, Niels Ole

2012-01-01

Purpose – The purpose of the research is to investigate Norwegian web‐tutorials in contexts consisting of organizational issues and different forms of usability in relation to students’ perception and use of the system. Further, the research investigates the usefulness of the concepts concerning...... affordances and different forms of usability. Design/methodology/approach – The research has employed a variety of data‐collection methods including interviews with librarians, interviews and focus group interviews with students, coupled with tests of their capabilities using the systems. A detailed research...... the tutorials as part of the requirements. Further, examples of organizational amnesia are discussed, pointing to the necessity for leadership support and systematic knowledge sharing. System Usability Scores are analysed in relation to solution of tasks and interesting relations are analysed. The perceptions...

Online Pedagogical Tutorial Tactics Optimization Using Genetic-Based Reinforcement Learning.

Science.gov (United States)

Lin, Hsuan-Ta; Lee, Po-Ming; Hsiao, Tzu-Chien

2015-01-01

Tutorial tactics are policies for an Intelligent Tutoring System (ITS) to decide the next action when there are multiple actions available. Recent research has demonstrated that when the learning contents were controlled so as to be the same, different tutorial tactics would make difference in students' learning gains. However, the Reinforcement Learning (RL) techniques that were used in previous studies to induce tutorial tactics are insufficient when encountering large problems and hence were used in offline manners. Therefore, we introduced a Genetic-Based Reinforcement Learning (GBML) approach to induce tutorial tactics in an online-learning manner without basing on any preexisting dataset. The introduced method can learn a set of rules from the environment in a manner similar to RL. It includes a genetic-based optimizer for rule discovery task by generating new rules from the old ones. This increases the scalability of a RL learner for larger problems. The results support our hypothesis about the capability of the GBML method to induce tutorial tactics. This suggests that the GBML method should be favorable in developing real-world ITS applications in the domain of tutorial tactics induction.

Target marketing strategies for occupational therapy entrepreneurs.

Science.gov (United States)

Kautzmann, L N; Kautzmann, F N; Navarro, F H

1989-01-01

Understanding marketing techniques is one of the skills needed by successful entre renews. Target marketing is an effective method for occupational therapy entrepreneurs to use in determining when and where to enter the marketplace. The two components of target marketing, market segmentation and the development of marketing mix strategies for each identified market segment, are described. The Profife of Attitudes Toward Health Care (PATH) method of psychographic market segmentation of health care consumers is presented. Occupational therapy marketing mix strategies for each PATH consumer group are delineated and compatible groupings of market segments are suggested.

ROOT Tutorial for Summer Students

CERN Multimedia

CERN. Geneva; Piparo, Danilo

2015-01-01

ROOT is a "batteries-included" tool kit for data analysis, storage and visualization. It is widely used in High Energy Physics and other disciplines such as Biology, Finance and Astrophysics. This event is an introductory tutorial to ROOT and comprises a front lecture and hands on exercises. IMPORTANT NOTE: The tutorial is based on ROOT 6.04 and NOT on the ROOT5 series.  IMPORTANT NOTE: if you have ROOT 6.04 installed on your laptop, you will not need to install any virtual machine. The instructions showing how to install the virtual machine on which you can find ROOT 6.04 can be found under "Material" on this page.

Interdisciplinary, Application-Oriented Tutorials: Design, Implementation, and Evaluation

Science.gov (United States)

Herman, Carolyn; Casiday, Rachel E.; Deppe, Roberta K.; Gilbertson, Michelle; Spees, William M.; Holten, Dewey; Frey, Regina F.

2005-01-01

Fifteen application-oriented chemical tutorials were developed out of which thirteen are currently in use in the general chemistry lab rotary curriculum for chemistry students at Washington University from 1998 to 2000. The central philosophy of the tutorial that the students learn to combine information from variety of sources like science…

A Web-Based Interactive Homework Quiz and Tutorial Package To Motivate Undergraduate Chemistry Students and Improve Learning

Science.gov (United States)

Freasier, Ben; Collins, Grant; Newitt, Paula

2003-11-01

This study presents a Web-based interactive homework quiz and tutorial package that we have devised to improve the learning of first-year undergraduate chemistry students. We developed this automated scheme, based on WWWAssign, to produce randomly generated quizzes from a large database of questions, instantaneously grade that homework, give a fully-worked solution, and provide individually targeted tutorial assistance. Success in these quizzes was a necessary requirement before taking supervised tests. We found a positive correlation at the p= 0.1 level (90%) between voluntary extra use of the quizzes in the interactive package and the final course grade. All students undertook more quizzes than the base course requirement even though the quiz grades did not contribute to the total course grades. We suggest that students were motivated to pursue additional practice with the quizzes and associated tutorial information, as they perceived some benefit in this student-centered study tool and could access it at any time.

Targeted therapies for bone sarcomas

International Nuclear Information System (INIS)

Mudry, P.

2011-01-01

Therapy success in bone sarcoma is significantly better compared to history cohorts with 60 - 70 % overall survival to date. Unfortunately, there is yet no shift and movement in better survival of patients with relapsed and refractory bone sarcomas during last twenty years. This article reviews targeted therapeutics for bone sarcomas which are under investigation and which could give chance to patients suffering from relapsed and chemo resistant bone sarcomas. Majority of the targeted drugs are given as part of phase 1 or 2 studies. (author)

Targeted Radiation Therapy for Cancer Initiative

Science.gov (United States)

2017-11-01

AWARD NUMBER: W81XWH-08-2-0174 TITLE: Targeted Radiation Therapy for Cancer Initiative PRINCIPAL INVESTIGATOR: Dusten Macdonald, MD...for Cancer Initiative 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Dusten Macdonald, MD 5d. PROJECT NUMBER...Cancer Initiative Final Report INTRODUCTION: The full potential of radiation therapy has not been realized due to the inability to locate and

Dealing with Conflicts on Knowledge in Tutorial Groups

Science.gov (United States)

Aarnio, Matti; Lindblom-Ylanne, Sari; Nieminen, Juha; Pyorala, Eeva

2013-01-01

The aim of our study was to gain understanding of different types of conflicts on knowledge in the discussions of problem-based learning tutorial groups, and how such conflicts are dealt with. We examined first-year medical and dental students' (N = 33) conflicts on knowledge in four videotaped reporting phase tutorials. A coding scheme was…

Developing and Testing a Video Tutorial for Software Training

NARCIS (Netherlands)

van der Meij, Hans

2014-01-01

Purpose: Video tutorials for software training are rapidly becoming popular. A set of dedicated guidelines for the construction of such tutorials was recently advanced in Technical Communication (Van der Meij & Van der Meij, 2013). The present study set out to assess the cognitive and motivational

Targeting Herpetic Keratitis by Gene Therapy

Directory of Open Access Journals (Sweden)

Hossein Mostafa Elbadawy

2012-01-01

Full Text Available Ocular gene therapy is rapidly becoming a reality. By November 2012, approximately 28 clinical trials were approved to assess novel gene therapy agents. Viral infections such as herpetic keratitis caused by herpes simplex virus 1 (HSV-1 can cause serious complications that may lead to blindness. Recurrence of the disease is likely and cornea transplantation, therefore, might not be the ideal therapeutic solution. This paper will focus on the current situation of ocular gene therapy research against herpetic keratitis, including the use of viral and nonviral vectors, routes of delivery of therapeutic genes, new techniques, and key research strategies. Whereas the correction of inherited diseases was the initial goal of the field of gene therapy, here we discuss transgene expression, gene replacement, silencing, or clipping. Gene therapy of herpetic keratitis previously reported in the literature is screened emphasizing candidate gene therapy targets. Commonly adopted strategies are discussed to assess the relative advantages of the protective therapy using antiviral drugs and the common gene therapy against long-term HSV-1 ocular infections signs, inflammation and neovascularization. Successful gene therapy can provide innovative physiological and pharmaceutical solutions against herpetic keratitis.

Writing learning cases for an information literacy tutorial

Directory of Open Access Journals (Sweden)

Gunhild Austrheim

2010-09-01

Full Text Available The research and writing processes are often hidden mysteries to our students. A key point in the online tutorial Search and Write (Søk and Skriv has been to supply our students with tools to handle these processes. Learning cases embedded in the tutorial allow us to demonstrate a variety of working techniques and to better cater for a diverse student population. The tutorial can be used as an independent resource for students and as a teaching aid for both library sessions on information literacy and for faculty-led sessions on academic writing. Our tutorial is available in Norwegian and in English and thereby the tutorial can be used with both local and international students. An online tutorial is aimed at all students and therefore the information literacy content is of a general kind. The pedagogical foundation for the Search and Write tutorial is in contextual learning. Adding context to our general content has been important to us and we decided to develop learning cases for this purpose. In our online tutorial we have developed three sample student blogs, Kuhlthau’s information search process functions as a template in structuring the students’ stories. The blogs are learning cases, developed with the intent of illustrating various aspects of academic writing tasks. The blog stories are idealized and touch upon many of the known stumbling stones for student writers. Contextualising the search and write process like this let us explore the diversity of student assignments and from various fields of study. When our real-life students use Search and Write they may use their own research question as a point of departure. They can read the blog stories and relate these stories to their own experiences. They can use the How to brainstorm-tips provided in Sofie’s blog. Christian’s use of tutors, library staff and his writing group can provide guidance on who to ask for help. For students writing literature reviews Oda’s systematic

Effectiveness of Tutorials for Introductory Physics in Argentinean high schools

Science.gov (United States)

Benegas, J.; Flores, J. Sirur

2014-06-01

This longitudinal study reports the results of a replication of Tutorials in Introductory Physics in high schools of a Latin-American country. The main objective of this study was to examine the suitability of Tutorials for local science education reform. Conceptual learning of simple resistive electric circuits was determined by the application of the single-response multiple-choice test "Determining and Interpreting Resistive Electric Circuits Concepts Test" (DIRECT) to high school classes taught with Tutorials and traditional instruction. The study included state and privately run schools of different socioeconomic profiles, without formal laboratory space and equipment, in classes of mixed-gender and female-only students, taught by novice and experienced instructors. Results systematically show that student learning is significantly higher in the Tutorials classes compared with traditional teaching for all of the studied conditions. The results also show that long-term learning (one year after instruction) in the Tutorials classes is highly satisfactory, very similar to the performance of the samples of college students used to develop the test DIRECT. On the contrary, students following traditional instruction returned one year after instruction to the poor performance (students attending seven universities in Spain and four Latin-American countries. Some replication and adaptation problems and difficulties of this experience are noted, as well as recommendations for successful use of Tutorials in high schools of similar educational systems.

Targeted alpha therapy: Applications and current status

International Nuclear Information System (INIS)

Bruchertseifer, Frank

2017-01-01

Full text: The field of targeted alpha therapy has been developed rapidly in the last decade. Besides 223 Ra, 211 At and 212 Pb/ 212 Bi the alpha emitters 225 Ac and 213 Bi are promising therapeutic radionuclides for application in targeted alpha therapy of cancer and infectious diseases. The presentation will give a short overview about the current clinical treatments with alpha emitting radionuclides and will place an emphasis on the most promising clinical testing of peptides and antibodies labelled with 225 Ac and 213 Bi for treatment of metastatic castration-resistant prostate cancer patients with glioma and glioblastoma multiform, PSMA-positive tumor phenotype and bladder carcinoma in situ. (author)

Targeting Apoptosis Signaling Pathways for Anticancer Therapy

Energy Technology Data Exchange (ETDEWEB)

Fulda, Simone, E-mail: simone.fulda@kgu.de [Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Frankfurt (Germany)

2011-08-29

Treatment approaches for cancer, for example chemotherapy, radiotherapy, or immunotherapy, primarily act by inducing cell death in cancer cells. Consequently, the inability to trigger cell death pathways or alternatively, evasion of cancer cells to the induction of cell death pathways can result in resistance of cancers to current treatment protocols. Therefore, in order to overcome treatment resistance a better understanding of the underlying mechanisms that regulate cell death and survival pathways in cancers and in response to cancer therapy is necessary to develop molecular-targeted therapies. This strategy should lead to more effective and individualized treatment strategies that selectively target deregulated signaling pathways in a tumor type- and patient-specific manner.

Targeting Apoptosis Signaling Pathways for Anticancer Therapy

International Nuclear Information System (INIS)

Fulda, Simone

2011-01-01

Treatment approaches for cancer, for example chemotherapy, radiotherapy, or immunotherapy, primarily act by inducing cell death in cancer cells. Consequently, the inability to trigger cell death pathways or alternatively, evasion of cancer cells to the induction of cell death pathways can result in resistance of cancers to current treatment protocols. Therefore, in order to overcome treatment resistance a better understanding of the underlying mechanisms that regulate cell death and survival pathways in cancers and in response to cancer therapy is necessary to develop molecular-targeted therapies. This strategy should lead to more effective and individualized treatment strategies that selectively target deregulated signaling pathways in a tumor type- and patient-specific manner.

Comparison of two interactive tutorial methods: results from a medical college in Karachi.

Science.gov (United States)

Rehan, Rabiya; Farooqi, Lubna; Khan, Hira; Rehman, Rehana

2017-02-01

To compare perception of students on usefulness of interactive tutorials and clinically-oriented problem-solving tutorials. The cross-sectional study was carried out from January 2012 to November 2013 at Bahria University Medical and Dental College, Karachi. The perception of medical students on usefulness of interactive tutorials and clinically-oriented problem-solving tutorials was acquired through a questionnaire distributed to medical students having completed the first two years of studies. The responses on various aspects of learning of physiology were acquired on a scale of poor, good or excellent. The learning abilities and acquired skills were compared in terms of not at all, to some extent, and to great extent. Data was analysed using SPSS 15. Of the hundred students initially enrolled, complete response was obtained from 83(83%). Of them, 47(57%) were females. There was significant difference in understanding of structure and function by clinically-oriented problem-solving tutorials (p=0.04). The students preferred clinically-oriented problem-solving tutorials as far as understating of difficult concepts was concerned (pskills were improved by interactive tutorials (p=0.02) whereas clinical reasoning skills acquired by clinically-oriented problem-solving tutorials was found to be significantly better (pskills were acquired more by clinically-oriented problem-solving tutorials that helped in better understanding of structure and functions.

MacSelfService online tutorial

CERN Multimedia

CERN. Geneva

2016-01-01

Mac Self-Service is a functionality within the Mac Desktop Service built and maintained to empower CERN users by giving them easy access to applications and configurations through the Self-Service application. This tutorial (text attached to the event page) explains how to install Mac Self-Service and how to use it to install applications and printers. Content owner: Vincent Nicolas Bippus Presenter: Pedro Augusto de Freitas Batista Tell us what you think via e-learning.support at cern.ch More tutorials in the e-learning collection of the CERN Document Server (CDS) https://cds.cern.ch/collection/E-learning%20modules?ln=en All info about the CERN rapid e-learning project is linked from http://twiki.cern.ch/ELearning  

A test of the design of a video tutorial for software training

NARCIS (Netherlands)

van der Meij, Jan; van der Meij, Hans

2015-01-01

The effectiveness of a video tutorial versus a paper-based tutorial for software training has yet to be established. Mixed outcomes from the empirical studies to date suggest that for a video tutorial to outperform its paper-based counterpart, the former should be crafted so that it addresses the

Radiation therapy following targeted therapy in oligometastatic renal cell carcinoma.

Science.gov (United States)

Gravis, Gwenaelle; Faure, Marjorie; Rybikowski, Stanislas; Dermeche, Slimane; Tyran, Marguerite; Calderon, Benoit; Thomassin, Jeanne; Walz, Jochen; Salem, Naji

2015-11-01

Up to 40% of patients with renal cell carcinoma (RCC) with initially localized disease eventually develop metastasis following nephrectomy. The current standard of care for metastatic RCC (mRCC) is targeted therapy. However, complete response remains rare. A state of oligometastatic disease may exist, in which metastases are present in a limited number of locations; such cases may benefit from metastasis-directed local therapy, based on the evidence supporting resection of limited-volume metastases, allowing for improved disease control. We retrospectively analyzed 7 cases of response of RCC metastases, in patients treated with targeted therapies followed by radiation therapy (RT) of residual metastatic lesions in Paoli-Calmettes Institute (Marseille, France). We analyzed disease response rates, response to sequential strategy, relapse at the irradiated locations and disease evolution. The median follow-up was 34.1 months (range, 19.2-54.5 months). No progression at the irradiated sites was observed. A total of 5 patients had stable disease at the irradiated locations at the last follow-up; 3 remained in complete remission at the assessment, and 2 were stable. Excellent local response and clinical benefit may be achieved without added toxicity. In conclusion, sequential therapeutic strategies with RT following systemic treatment using sunitinib appear to be highly effective in patients with progressive mRCC and prompt the conduction of further confirmatory trials.

Improving the University Tutorial.

Science.gov (United States)

Stanton, Harry E.

1982-01-01

Frequently, tutorial or seminar members take no part in discussion, a feature considered essential to this teaching method. Tutors may be largely responsible by dominating discussion. Student participation can be increased by varying teaching methods; reducing discussion group size, brainstorming, idea development techniques, and student…

Tutorial to SARAH

CERN Document Server

Staub, Florian

2016-01-01

I give in this brief tutorial a short practical introduction to the Mathematica package SARAH. First, it is shown how an existing model file can be changed to implement a new model in SARAH. In the second part, masses, vertices and renormalisation group equations are calculated with SARAH. Finally, the main commands to generate model files and output for other tools are summarised.

Treatment outcome of radiation therapy and concurrent targeted molecular therapy in spinal metastasis from renal cell carcinoma

Energy Technology Data Exchange (ETDEWEB)

Park, Sang Joon; Kim, Kyung Hwan; Rhee, Woo Joong; Lee, Jeong Shin; Cho, Yeo Na; Koom, Woong Sub [Dept. of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

2016-06-15

To evaluate the clinical outcomes of patients who underwent radiation therapy with or without targeted molecular therapy for the treatment of spinal metastasis from renal cell carcinoma (RCC). A total of 28 spinal metastatic lesions from RCC patients treated with radiotherapy between June 2009 and June 2015 were retrospectively reviewed. Thirteen lesions were treated concurrently with targeted molecular therapy (concurrent group) and 15 lesions were not (nonconcurrent group). Local control was defined as lack of radiographically evident local progression and neurological deterioration. At a median follow-up of 11 months (range, 2 to 58 months), the 1-year local progression-free rate (LPFR) was 67.0%. The patients with concurrent targeted molecular therapy showed significantly higher LPFR than those without (p = 0.019). After multivariate analysis, use of concurrent targeted molecular therapy showed a tendency towards improved LPFR (hazard ratio, 0.13; 95% confidence interval, 0.01 to 1.16). There was no difference in the incidence of systemic progression between concurrent and nonconcurrent groups. No grade ≥2 toxicities were observed during or after radiotherapy. Our study suggests the possibility that concurrent use of targeted molecular therapy during radiotherapy may improve LPFR. Further study with a large population is required to confirm these results.

Treatment outcome of radiation therapy and concurrent targeted molecular therapy in spinal metastasis from renal cell carcinoma

International Nuclear Information System (INIS)

Park, Sang Joon; Kim, Kyung Hwan; Rhee, Woo Joong; Lee, Jeong Shin; Cho, Yeo Na; Koom, Woong Sub

2016-01-01

To evaluate the clinical outcomes of patients who underwent radiation therapy with or without targeted molecular therapy for the treatment of spinal metastasis from renal cell carcinoma (RCC). A total of 28 spinal metastatic lesions from RCC patients treated with radiotherapy between June 2009 and June 2015 were retrospectively reviewed. Thirteen lesions were treated concurrently with targeted molecular therapy (concurrent group) and 15 lesions were not (nonconcurrent group). Local control was defined as lack of radiographically evident local progression and neurological deterioration. At a median follow-up of 11 months (range, 2 to 58 months), the 1-year local progression-free rate (LPFR) was 67.0%. The patients with concurrent targeted molecular therapy showed significantly higher LPFR than those without (p = 0.019). After multivariate analysis, use of concurrent targeted molecular therapy showed a tendency towards improved LPFR (hazard ratio, 0.13; 95% confidence interval, 0.01 to 1.16). There was no difference in the incidence of systemic progression between concurrent and nonconcurrent groups. No grade ≥2 toxicities were observed during or after radiotherapy. Our study suggests the possibility that concurrent use of targeted molecular therapy during radiotherapy may improve LPFR. Further study with a large population is required to confirm these results

Targeted therapies in the treatment of urothelial cancers.

Science.gov (United States)

Aragon-Ching, Jeanny B; Trump, Donald L

2017-07-01

Progress has been slow in systemic management of locally advanced and metastatic bladder cancer over the past 20 years. However, the recent approval of immunotherapy with atezolizumab and nivolumab for second-line salvage therapy may usher in an era of more rapid improvement. Systemic treatment is suboptimal and is an area of substantial unmet medical need. The recent findings from The Cancer Genome Atlas project revealed promising pathways that may be amenable to targeted therapies. Promising results with treatment using vascular endothelial growth factor inhibitors such as ramucirumab, sunitinib or bevacizumab, and human epidermal growth factor receptor 2 targeted therapies, epidermal growth factor receptor inhibitors, and fibroblast growth factor receptor inhibitors, are undergoing clinical trials and are discussed later. Copyright © 2017 Elsevier Inc. All rights reserved.

Introduction to radiobiology of targeted radionuclide therapy

Directory of Open Access Journals (Sweden)

Jean-Pierre ePOUGET

2015-03-01

Full Text Available During the last decades, new radionuclide-based targeted therapies have emerged as efficient tools for cancer treatment. Targeted radionuclide therapies (TRT are based on a multidisciplinary approach that involves the cooperation of specialists in several research fields. Among them, radiobiologists investigate the biological effects of ionizing radiation, specifically the molecular and cellular mechanisms involved in the radiation response. Most of the knowledge about radiation effects concerns external beam radiation therapy (EBRT and radiobiology has then strongly contributed to the development of this therapeutic approach. Similarly, radiobiology and dosimetry are also assumed to be ways for improving TRT, in particular in the therapy of solid tumors which are radioresistant. However, extrapolation of EBRT radiobiology to TRT is not straightforward. Indeed, the specific physical characteristics of TRT (heterogeneous and mixed irradiation, protracted exposure and low absorbed dose rate differ from those of conventional EBRT (homogeneous irradiation, short exposure and high absorbed dose rate, and consequently the response of irradiated tissues might be different. Therefore, specific TRT radiobiology needs to be explored. Determining dose-effect correlation is also a prerequisite for rigorous preclinical radiobiology studies because dosimetry provides the necessary referential to all TRT situations. It is required too for developing patient-tailored TRT in the clinic in order to estimate the best dose for tumor control, while protecting the healthy tissues, thereby improving therapeutic efficacy. Finally, it will allow to determine the relative contribution of targeted effects (assumed to be dose-related and non-targeted effects (assumed to be non-dose-related of ionizing radiation. However, conversely to EBRT where it is routinely used, dosimetry is still challenging in TRT. Therefore, it constitutes with radiobiology, one of the main

Cardiotoxicity of novel HER2-targeted therapies.

Science.gov (United States)

Sendur, Mehmet A N; Aksoy, Sercan; Altundag, Kadri

2013-08-01

Trastuzumab, an anti-HER2 humanized monoclonal antibody, is the standard treatment for both early and metastatic HER2-positive breast cancer. In addition to other chemotherapeutic agents, trastuzumab significantly improves response rate and survival in HER2-positive early and metastatic breast cancer. Although it is well known that trastuzumab therapy is closely associated with both symptomatic and asymptomatic cardiotoxicity, less is known about novel HER2-targeted therapies. The aim of this review is to discuss the cardiac safety data from recent studies of novel anti-HER2 drugs other than trastuzumab. Novel HER2-targeted therapies showed favorable results in HER2 positive metastatic breast cancer patients. Pubmed database, ASCO and San Antonio Breast Cancer Symposium Meeting abstracts were searched until January 2013 using the following search keywords; 'trastuzumab, trastuzumab cardiotoxicity, HER-2 targeted therapies, lapatinib, pertuzumab, trastuzumab emtansine, afatinib and neratinib'; papers which were considered relevant for the aim of this review were selected by the authors. Lapatinib, pertuzumab, T-DM1, neratinib and afatinib molecules are evaluated in the study. In a comprehensive analysis, 3689 lapatinib treated patients enrolled in 49 trials; asymptomatic cardiac events were reported in 53 patients (1.4%) and symptomatic grade III and IV systolic dysfunction was observed only in 7 patients (0.2%) treated with lapatinib. In phase I-III trials of pertuzumab, cardiac dysfunction was seen in 4.5-14.5% of patients with pertuzumab treatment and cardiac dysfunction was usually grade I and II. Cardiotoxicity of pertuzumab was usually reported with the trastuzumab combination and no additive cardiotoxicity was reported with addition of pertuzumab to trastuzumab. T-DM1 had a better safety profile compared to trastuzumab, no significant cardiotoxicity was observed with T-DM1 in heavily pre-treated patients. In the EMILIA study, only in 1.7% of patients in the T

Computer Tutorial Programs in Physics.

Science.gov (United States)

Faughn, Jerry; Kuhn, Karl

1979-01-01

Describes a series of computer tutorial programs which are intended to help college students in introductory physics courses. Information about these programs, which are either calculus or algebra-trig based, is presented. (HM)

Targeting therapy-resistant cancer stem cells by hyperthermia

DEFF Research Database (Denmark)

Oei, A L; Vriend, L E M; Krawczyk, P M

2017-01-01

Eradication of all malignant cells is the ultimate but challenging goal of anti-cancer treatment; most traditional clinically-available approaches fail because there are cells in a tumour that either escape therapy or become therapy-resistant. A subpopulation of cancer cells, the cancer stem cells...... are limited. Here, we argue that hyperthermia - a therapeutic approach based on local heating of a tumour - is potentially beneficial for targeting CSCs in solid tumours. First, hyperthermia has been described to target cells in hypoxic and nutrient-deprived tumour areas where CSCs reside and ionising...

Targeted alpha therapy: Applications and current status

Energy Technology Data Exchange (ETDEWEB)

Bruchertseifer, Frank, E-mail: frank.bruchertseifer@ec.europa.eu [European Commission, Joint Research Centre, Karlsruhe (Germany)

2017-07-01

Full text: The field of targeted alpha therapy has been developed rapidly in the last decade. Besides {sup 223}Ra, {sup 211}At and {sup 212}Pb/{sup 212}Bi the alpha emitters {sup 225}Ac and {sup 213}Bi are promising therapeutic radionuclides for application in targeted alpha therapy of cancer and infectious diseases. The presentation will give a short overview about the current clinical treatments with alpha emitting radionuclides and will place an emphasis on the most promising clinical testing of peptides and antibodies labelled with {sup 225}Ac and {sup 213}Bi for treatment of metastatic castration-resistant prostate cancer patients with glioma and glioblastoma multiform, PSMA-positive tumor phenotype and bladder carcinoma in situ. (author)

Biology and Nursing Students’ Perceptions of a Web-based Information Literacy Tutorial

Directory of Open Access Journals (Sweden)

Sharon Weiner

2012-04-01

Full Text Available This study assessed student perceptions about an online information literacy tutorial, CORE (Comprehensive Online Research Education, to plan for the next generation of tutorials. The CORE tutorial includes seven modules: “Planning Your Project,” “Topic Exploration,” “Types of Information,” “Search Tools,” “Search Strategies,” “Evaluating Sources,” and “Copyright, Plagiarism, and Citing Sources.” First-year students in biology and nursing courses responded to a survey after they completed the CORE modules. The students liked learning through an online tutorial. They thought that the tutorial could be improved with shorter modules and the addition of video and audio content. Few students reported learning important information from the “Copyright, Plagiarism, and Citing Sources,” “Evaluating Resources,” and “Types of Information” modules. They suggested topics for additional tutorials: how to use library databases and Microsoft Excel; how to evaluate the quality of information, how to cite references in a bibliography, and how to find statistics.

Evaluating the role of web-based tutorials in educational practice

DEFF Research Database (Denmark)

Moring, Camilla; Schreiber, Trine

The paper describes and discusses a two step analysis for evaluating web based information literacy tutorials in educational practice. In a recent evaluation project the authors used the analysis to examine three web based tutorials developed by three different academic libraries in Norway. Firstly...... of the analysis focuses on user reception and meaning negotiation. In combination the two different analyses strengthen the evaluation of how web-tutorials as communicative acts become meaningful to users, and how this meaning is negotiated in relation to an educational practice. This approach can be recommended...

Making Accounting Tutorials Enjoyable

Science.gov (United States)

Bargate, Karen

2018-01-01

This paper emanates from a case study which focussed on 15 Managerial Accounting and Financial Management (MAFM) students' "enjoyment" of learning MAFM in an 18-week Writing Intensive Tutorial (WIT) programme. Interactive Qualitative Analysis (IQA) was used for the research design and as a data analysis tool. Following IQA protocols…

Effectiveness of Tutorials for Introductory Physics in Argentinean high schools

Directory of Open Access Journals (Sweden)

J. Benegas

2014-03-01

Full Text Available This longitudinal study reports the results of a replication of Tutorials in Introductory Physics in high schools of a Latin-American country. The main objective of this study was to examine the suitability of Tutorials for local science education reform. Conceptual learning of simple resistive electric circuits was determined by the application of the single-response multiple-choice test “Determining and Interpreting Resistive Electric Circuits Concepts Test” (DIRECT to high school classes taught with Tutorials and traditional instruction. The study included state and privately run schools of different socioeconomic profiles, without formal laboratory space and equipment, in classes of mixed-gender and female-only students, taught by novice and experienced instructors. Results systematically show that student learning is significantly higher in the Tutorials classes compared with traditional teaching for all of the studied conditions. The results also show that long-term learning (one year after instruction in the Tutorials classes is highly satisfactory, very similar to the performance of the samples of college students used to develop the test DIRECT. On the contrary, students following traditional instruction returned one year after instruction to the poor performance (<20% shown before instruction, a result compatible with the very low level of conceptual knowledge of basic physics recently determined by a systematic study of first-year students attending seven universities in Spain and four Latin-American countries. Some replication and adaptation problems and difficulties of this experience are noted, as well as recommendations for successful use of Tutorials in high schools of similar educational systems.

Familial breast cancer - targeted therapy in secondary and tertiary prevention.

Science.gov (United States)

Kast, Karin; Rhiem, Kerstin

2015-02-01

The introduction of an increasing number of individualized molecular targeted therapies into clinical routine mirrors their importance in modern cancer prevention and treatment. Well-known examples for targeted agents are the monoclonal antibody trastuzumab and the selective estrogen receptor modulator tamoxifen. The identification of an unaltered gene in tumor tissue in colon cancer (KRAS) is a predictor for the patient's response to targeted therapy with a monoclonal antibody (cetuximab). Targeted therapy for hereditary breast and ovarian cancer has become a reality with the approval of olaparib for platin-sensitive late relapsed BRCA-associated ovarian cancer in December 2014. This manuscript reviews the status quo of poly-ADP-ribose polymerase inhibitors (PARPi) in the therapy of breast and ovarian cancer as well as the struggle for carboplatin as a potential standard of care for triple-negative and, in particular, BRCA-associated breast cancer. Details of the mechanism of action with information on tumor development are provided, and an outlook for further relevant research is given. The efficacy of agents against molecular targets together with the identification of an increasing number of cancer-associated genes will open the floodgates to a new era of treatment decision-making based on molecular tumor profiles. Current clinical trials involving patients with BRCA-associated cancer explore the efficacy of the molecular targeted therapeutics platinum and PARPi.

Chromatin-regulating proteins as targets for cancer therapy

International Nuclear Information System (INIS)

Oike, Takahiro; Ogiwara, Hideaki; Kohno, Takashi; Amornwichet, Napapat; Nakano, Takashi

2014-01-01

Chromatin-regulating proteins represent a large class of novel targets for cancer therapy. In the context of radiotherapy, acetylation and deacetylation of histones by histone acetyltransferases (HATs) and histone deacetylases (HDACs) play important roles in the repair of DNA double-strand breaks generated by ionizing irradiation, and are therefore attractive targets for radiosensitization. Small-molecule inhibitors of HATs (garcinol, anacardic acid and curcumin) and HDACs (vorinostat, sodium butyrate and valproic acid) have been shown to sensitize cancer cells to ionizing irradiation in preclinical models, and some of these molecules are being tested in clinical trials, either alone or in combination with radiotherapy. Meanwhile, recent large-scale genome analyses have identified frequent mutations in genes encoding chromatin-regulating proteins, especially in those encoding subunits of the SWI/SNF chromatin-remodeling complex, in various human cancers. These observations have driven researchers toward development of targeted therapies against cancers carrying these mutations. DOT1L inhibition in MLL-rearranged leukemia, EZH2 inhibition in EZH2-mutant or MLL-rearranged hematologic malignancies and SNF5-deficient tumors, BRD4 inhibition in various hematologic malignancies, and BRM inhibition in BRG1-deficient tumors have demonstrated promising anti-tumor effects in preclinical models, and these strategies are currently awaiting clinical application. Overall, the data collected so far suggest that targeting chromatin-regulating proteins is a promising strategy for tomorrow's cancer therapy, including radiotherapy and molecularly targeted chemotherapy. (author)

Metastasis Targeted Therapies in Renal Cell Cancer

OpenAIRE

K. Fehmi Narter; Bora Özveren

2018-01-01

Metastatic renal cell cancer is a malignant disease and its treatment has been not been described clearly yet. These patients are generally symptomatic and resistant to current treatment modalities. Radiotherapy, chemotherapy, and hormonal therapy are not curative in many of these patients. A multimodal approach consisting of cytoreductive nephrectomy, systemic therapy (immunotherapy or targeted molecules), and metastasectomy has been shown to be hopeful in prolonging the survival and improvi...

New perspectives on biological HDL-targeted therapies

OpenAIRE

Muthuramu, Ilayaraja; Amin, Md Ruhul; De Geest, Bart

2017-01-01

According to a modified high-density lipoprotein (HDL) hypothesis, improving HDL function will lead to a decrease of coronary events. The stringent requirement for proving or refuting this hypothesis is that the causal pathway between the therapeutic intervention and a clinically meaningful endpoint obligatory passes through HDL. Infusion therapy of reconstituted HDL particles and human apolipoprotein A-I gene transfer are biological HDL-targeted therapies that are distinguished by HDL specif...

Design and Assessment of Online, Interactive Tutorials That Teach Science Process Skills.

Science.gov (United States)

Kramer, Maxwell; Olson, Dalay; Walker, J D

2018-06-01

Explicit emphasis on teaching science process skills leads to both gains in the skills themselves and, strikingly, deeper understanding of content. Here, we created and tested a series of online, interactive tutorials with the goal of helping undergraduate students develop science process skills. We designed the tutorials in accordance with evidence-based multimedia design principles and student feedback from usability testing. We then tested the efficacy of the tutorials in an introductory undergraduate biology class. On the basis of a multivariate ordinary least-squares regression model, students who received the tutorials are predicted to score 0.82 points higher on a 15-point science process skill assessment than their peers who received traditional textbook instruction on the same topic. This moderate but significant impact indicates that well-designed online tutorials can be more effective than traditional ways of teaching science process skills to undergraduate students. We also found trends that suggest the tutorials are especially effective for nonnative English-speaking students. However, due to a limited sample size, we were unable to confirm that these trends occurred due to more than just variation in the student group sampled.

Hazardous Solvent Substitution Data System tutorial

International Nuclear Information System (INIS)

Twitchell, K.E.; Skinner, N.L.

1993-07-01

This manual is the tutorial for the Hazardous Solvent Substitution Data System (HSSDS), an online, comprehensive system of information on alternatives to hazardous solvents and related subjects. The HSSDS data base contains product information, material safety data sheets, toxicity reports, usage reports, biodegradable data, product chemical element lists, and background information on solvents. HSSDS use TOPIC reg-sign to search for information based on a query defined by the user. TOPIC provides a full text retrieval of unstructured source documents. In this tutorial, a series of lessons is provided that guides the user through basic steps common to most queries performed with HSSDS. Instructions are provided for both window-based and character-based applications

New series of ORACLE tutorials, March-June 2006

CERN Multimedia

Catherine Delamare

2006-01-01

The IT DES Oracle Support team is pleased to announce the new series of Oracle tutorials with the proposed schedule: Thursday 20 April - SQL I - Eva Dafonte Perez Thursday 27 April - SQL II - Lucia Moreno Lopez Thursday 4 May - Architecture - Montse Collados Thursday 11 May - Tuning - Michal Kwiatek Thursday 1 June - PL/SQL I - Eva Dafonte Perez Thursday 8 June - PL/SQL II - Nilo Segura Thursday 15 June - Oracle Tools and Bindings with languages - Eric Grancher, Nilo Segura These tutorials will take place in the IT Auditorium (bldg. 31/3-004) starting at 10:00. The average duration will be 1 hour plus time for questions. There is no need to register in advance. You can access the previous 2002-2003 sessions at http://it-des.web.cern.ch/IT-DES/DIS/oracle/tutorials.html If you need more information, please contact Catherine.Delamare@cern.ch

Understanding Medical Words: A Tutorial from the National Library of Medicine

Science.gov (United States)

... page: https://medlineplus.gov/medicalwords.html Understanding Medical Words: A Tutorial from the National Library of Medicine ... enable JavaScript. This tutorial teaches you about medical words. You'll learn about how to put together ...

A tutorial on Fisher information

NARCIS (Netherlands)

Ly, A.; Marsman, M.; Verhagen, J.; Grasman, R.P.P.P.; Wagenmakers, E.-M.

2017-01-01

In many statistical applications that concern mathematical psychologists, the concept of Fisher information plays an important role. In this tutorial we clarify the concept of Fisher information as it manifests itself across three different statistical paradigms. First, in the frequentist paradigm,

Palliative chemotherapy and targeted therapies for esophageal and gastroesophageal junction cancer.

Science.gov (United States)

Janmaat, Vincent T; Steyerberg, Ewout W; van der Gaast, Ate; Mathijssen, Ron Hj; Bruno, Marco J; Peppelenbosch, Maikel P; Kuipers, Ernst J; Spaander, Manon Cw

2017-11-28

Almost half of people with esophageal or gastroesophageal junction cancer have metastatic disease at the time of diagnosis. Chemotherapy and targeted therapies are increasingly used with a palliative intent to control tumor growth, improve quality of life, and prolong survival. To date, and with the exception of ramucirumab, evidence for the efficacy of palliative treatments for esophageal and gastroesophageal cancer is lacking. To assess the effects of cytostatic or targeted therapy for treating esophageal or gastroesophageal junction cancer with palliative intent. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Web of Science, PubMed Publisher, Google Scholar, and trial registries up to 13 May 2015, and we handsearched the reference lists of studies. We did not restrict the search to publications in English. Additional searches were run in September 2017 prior to publication, and they are listed in the 'Studies awaiting assessment' section. We included randomized controlled trials (RCTs) on palliative chemotherapy and/or targeted therapy versus best supportive care or control in people with esophageal or gastroesophageal junction cancer. Two authors independently extracted data. We assessed the quality and risk of bias of eligible studies according to the Cochrane Handbook for Systematic Reviews of Interventions. We calculated pooled estimates of effect using an inverse variance random-effects model for meta-analysis. We identified 41 RCTs with 11,853 participants for inclusion in the review as well as 49 ongoing studies. For the main comparison of adding a cytostatic and/or targeted agent to a control arm, we included 11 studies with 1347 participants. This analysis demonstrated an increase in overall survival in favor of the arm with an additional cytostatic or targeted therapeutic agent with a hazard ratio (HR) of 0.75 (95% confidence interval (CI) 0.68 to 0.84, high-quality evidence). The median increased

Would You Watch It? Creating Effective and Engaging Video Tutorials

Science.gov (United States)

Martin, Nichole A.; Martin, Ross

2015-01-01

Video tutorials are a common form of library instruction used with distance learners. This paper combines professional experience and literature reviews from multiple disciplines to provide a contextual overview of recommendations and findings for effective and engaging videos. The tools for tutorials appear in five main categories: screencasts,…

Online interactive tutorials for creating graphs with excel 2007 or 2010.

Science.gov (United States)

Vanselow, Nicholas R; Bourret, Jason C

2012-01-01

Graphic display of clinical data is a useful tool for the behavior-analytic clinician. However, graphs can sometimes be difficult to create. We describe how to access and use an online interactive tutorial that teaches the user to create a variety of graphs often used by behavior analysts. Three tutorials are provided that cover the basics of Microsoft Excel 2007 or 2010, creating graphs for clinical purposes, and creating graphs for research purposes. The uses for this interactive tutorial and other similar programs are discussed.

You Tube Video Genres. Amateur how-to Videos Versus Professional Tutorials

Directory of Open Access Journals (Sweden)

Andreea Mogoș

2015-12-01

Full Text Available In spite of the fact that there is a vast literature on traditional textual and visual genre classifications, the categorization of web content is still a difficult task, because this medium is fluid, unstable and fast-paced on one hand and, on the other hand, the genre classifications are socially constructed through the tagging process and the interactions (commenting, rating, chatting. This paper focuses on YouTube tutorials and aims to compare video tutorials produced by professionals with amateur video tutorials.

Subtitled video tutorials, an accessible teaching material

Directory of Open Access Journals (Sweden)

Luis Bengochea

2012-11-01

Full Text Available The use of short-lived audio-visual tutorials constitutes an educational resource very attractive for young students, widely familiar with this type of format similar to YouTube clips. Considered as "learning pills", these tutorials are intended to strengthen the understanding of complex concepts that because their dynamic nature can’t be represented through texts or diagrams. However, the inclusion of this type of content in eLearning platforms presents accessibility problems for students with visual or hearing disabilities. This paper describes this problem and shows the way in which a teacher could add captions and subtitles to their videos.

Success of the Tutorial Program in Biochemistry at The Federal University of Vi

Directory of Open Access Journals (Sweden)

M.C. Baracat-Pereira

2004-05-01

Full Text Available Institutionalized at UFV in 2001, the Tutorial Program in Biochemistry aims to reduce the une-venness of basic prior knowledge among the students enrolled in regular Biochemistry courses. Thework methodology has been periodically evaluated and rened in order to overcome identied pro-blems. Thus, the objective of this study was to evaluate the Tutorial Program based on the stu-dentsachievement, to show implemented modications and proposed alternatives to adjust methodo-logies. The student-nal-grades were obtained from UFV les. Questionnaires were applied to thePrograms students at the end of each semester. Suggestions and criticism from tutors and coordinatingprofessors were discussed at weekly meetings. Along six semesters (2001-2003, a leveling o of thetutorial students was observed with the attending students (S, minimum of 75% attendance, averagegrade 71.3 that got grades close to the average of no-tutorial students (average grade 71.5. For thetutorial students with attendance below the required minimum (N, the average grade was 58.8. Thefailure rate for grade S students (7.4% was lower then that for no-tutorial students (9.9% and forgrade N students (27.9%. Based on the lled out questionnaire from tutorial students, we observeas follows: 96.7% stated that it is eective to participate in the Program and 79.9% modied theirstudy approach. Among the modications implemented in the Program, are as folows: 1 Increase inthe number of tutorial groups (from 4 to 6; 2 Reduction in the number of volunteer-students, givingpriority to students with decient prior knowledge in pre-requisite-disciplines; and 3 Time reductionof tutorial sessions (from 3 to 2h weekly, with smaller groups and exercise classes. Thus, the observedmotivation, the leveling o and the lower failure rate of the S grade tutorial students indicated that theTutorial Program at UFV is improving and reaching its objectives.

Low temperature plasma biomedicine: A tutorial review

International Nuclear Information System (INIS)

Graves, David B.

2014-01-01

Gas discharge plasmas formed at atmospheric pressure and near room temperature have recently been shown to be potentially useful for surface and wound sterilization, antisepsis, bleeding cessation, wound healing, and cancer treatment, among other biomedical applications. This tutorial review summarizes the field, stressing the likely role of reactive oxygen and nitrogen species created in these plasmas as the biologically and therapeutically active agents. Reactive species, including radicals and non-radical compounds, are generated naturally within the body and are now understood to be essential for normal biological functions. These species are known to be active agents in existing therapies for wound healing, infection control, and cancer treatment. But they are also observed at elevated levels in persons with many diseases and are associated with aging. The physical and chemical complexity of plasma medical devices and their associated biochemical effects makes the development of safe, effective plasma medical devices and procedures a challenge, but encouragingly rapid progress has been reported around the world in the last several years

Low temperature plasma biomedicine: A tutorial review

Energy Technology Data Exchange (ETDEWEB)

Graves, David B., E-mail: graves@berkeley.edu [University of California at Berkeley, Berkeley, California 94720 (United States)

2014-08-15

Gas discharge plasmas formed at atmospheric pressure and near room temperature have recently been shown to be potentially useful for surface and wound sterilization, antisepsis, bleeding cessation, wound healing, and cancer treatment, among other biomedical applications. This tutorial review summarizes the field, stressing the likely role of reactive oxygen and nitrogen species created in these plasmas as the biologically and therapeutically active agents. Reactive species, including radicals and non-radical compounds, are generated naturally within the body and are now understood to be essential for normal biological functions. These species are known to be active agents in existing therapies for wound healing, infection control, and cancer treatment. But they are also observed at elevated levels in persons with many diseases and are associated with aging. The physical and chemical complexity of plasma medical devices and their associated biochemical effects makes the development of safe, effective plasma medical devices and procedures a challenge, but encouragingly rapid progress has been reported around the world in the last several years.

Low temperature plasma biomedicine: A tutorial reviewa)

Science.gov (United States)

Graves, David B.

2014-08-01

Gas discharge plasmas formed at atmospheric pressure and near room temperature have recently been shown to be potentially useful for surface and wound sterilization, antisepsis, bleeding cessation, wound healing, and cancer treatment, among other biomedical applications. This tutorial review summarizes the field, stressing the likely role of reactive oxygen and nitrogen species created in these plasmas as the biologically and therapeutically active agents. Reactive species, including radicals and non-radical compounds, are generated naturally within the body and are now understood to be essential for normal biological functions. These species are known to be active agents in existing therapies for wound healing, infection control, and cancer treatment. But they are also observed at elevated levels in persons with many diseases and are associated with aging. The physical and chemical complexity of plasma medical devices and their associated biochemical effects makes the development of safe, effective plasma medical devices and procedures a challenge, but encouragingly rapid progress has been reported around the world in the last several years.

Radiotherapy in combination with vascular-targeted therapies

International Nuclear Information System (INIS)

Ciric, Eva; Sersa, Gregor

2010-01-01

Given the critical role of tumor vasculature in tumor development, considerable efforts have been spent on developing therapeutic strategies targeting the tumor vascular network. A variety of agents have been developed, with two general approaches being pursued. Antiangiogenic agents (AAs) aim to interfere with the process of angiogenesis, preventing new tumor blood vessel formation. Vascular-disrupting agents (VDAs) target existing tumor vessels causing tumor ischemia and necrosis. Despite their great therapeutic potential, it has become clear that their greatest clinical utility may lie in combination with conventional anticancer therapies. Radiotherapy is a widely used treatment modality for cancer with its distinct therapeutic challenges. Thus, combining the two approaches seems reasonable. Strong biological rationale exist for combining vascular-targeted therapies with radiation. AAs and VDAs were shown to alter the tumor microenvironment in such a way as to enhance responses to radiation. The results of preclinical and early clinical studies have confirmed the therapeutic potential of this new treatment strategy in the clinical setting. However, concerns about increased normal tissue toxicity, have been raised

Palliative nephrectomy until targeted therapy of disseminated kidney cancer patients

Directory of Open Access Journals (Sweden)

A. V. Klimov

2015-01-01

Full Text Available Objective: to assess the role of palliative nephrectomy in disseminated kidney cancer patients planned to undergo targeted antiangiogenic treatment.Subjects and methods. The investigation included data on 83 patients with T1-4N0 / +M1 disseminated renal cell carcinoma (RCC who had received at least 2 targeted therapy cycles in 2009 to 2011. In 48 (57.8 % patients, the treatment was preceded by palliative nephrectomy that was not carried out in 35 (42.2 %. Before starting targeted therapy, all the cases were confirmed to be diagnosed with clear cell RCC, with a sarcomatoid component being in 7 (8.4 % patients. The median follow-up of all the patients was 21 (12–36 months.Results. The unremoved affected kidney in disseminated kidney cancer patients receiving targeted antiangiogenic therapy is an independent factor for the poor prognosis of progression-free (odds ratio (OR, 2.4; 95 % confidence interval (CI, 1.2–4.7 and overall (OR, 2.8; 95 % CI, 1.3–6.3 survival. Palliative nephrectomy does not improve the prognosis in patients with a low somatic status, the N+ category, and metastases into the bones and nonregional lymph nodes.Conclusion. Palliative nephrectomy in the selected patients with disseminated kidney cancer on targeted antiangiogenic therapy increases progression-free and overall survival.

New series of ORACLE tutorials, March-June 2006

CERN Multimedia

Catherine Delamare

2006-01-01

The IT DES Oracle Support team is pleased to announce the new series of Oracle tutorials with the proposed schedule: Thursday 30 March - Design - Arash Khodabandeh Thursday 20 April - SQL I - Eva Dafonte Perez Thursday 27 April - SQL II - Lucia Moreno Lopez Thursday 4 May - Architecture - Montse Collados Thursday 11 May - Tuning - Michal Kwiatek Thursday 1 June - PL/SQL I - Eva Dafonte Perez Thursday 8 June - PL/SQL II - Nilo Segura Thursday 15 June - Oracle Tools and Bindings with languages - Eric Grancher, Nilo Segura These tutorials will take place in the IT Auditorium (bldg. 31/3-004) starting at 10:00. The average duration will be 1 hour plus time for questions. There is no need to register in advance. You can access the previous 2002-2003 sessions at http://it-des.web.cern.ch/IT-DES/DIS/oracle/tutorials.html If you need more information, please contact Catherine.Delamare@cern.ch

A Web-Based Comparative Genomics Tutorial for Investigating Microbial Genomes

Directory of Open Access Journals (Sweden)

Michael Strong

2009-12-01

Full Text Available As the number of completely sequenced microbial genomes continues to rise at an impressive rate, it is important to prepare students with the skills necessary to investigate microorganisms at the genomic level. As a part of the core curriculum for first-year graduate students in the biological sciences, we have implemented a web-based tutorial to introduce students to the fields of comparative and functional genomics. The tutorial focuses on recent computational methods for identifying functionally linked genes and proteins on a genome-wide scale and was used to introduce students to the Rosetta Stone, Phylogenetic Profile, conserved Gene Neighbor, and Operon computational methods. Students learned to use a number of publicly available web servers and databases to identify functionally linked genes in the Escherichia coli genome, with emphasis on genome organization and operon structure. The overall effectiveness of the tutorial was assessed based on student evaluations and homework assignments. The tutorial is available to other educators at http://www.doe-mbi.ucla.edu/~strong/m253.php.

Gene Therapy Targeting HIV Entry

Directory of Open Access Journals (Sweden)

Chuka Didigu

2014-03-01

Full Text Available Despite the unquestionable success of antiretroviral therapy (ART in the treatment of HIV infection, the cost, need for daily adherence, and HIV-associated morbidities that persist despite ART all underscore the need to develop a cure for HIV. The cure achieved following an allogeneic hematopoietic stem cell transplant (HSCT using HIV-resistant cells, and more recently, the report of short-term but sustained, ART-free control of HIV replication following allogeneic HSCT, using HIV susceptible cells, have served to both reignite interest in HIV cure research, and suggest potential mechanisms for a cure. In this review, we highlight some of the obstacles facing HIV cure research today, and explore the roles of gene therapy targeting HIV entry, and allogeneic stem cell transplantation in the development of strategies to cure HIV infection.

Catching moving targets: cancer stem cell hierarchies, therapy-resistance & considerations for clinical intervention.

LENUS (Irish Health Repository)

Gasch, Claudia

2017-01-01

It is widely believed that targeting the tumour-initiating cancer stem cell (CSC) component of malignancy has great therapeutic potential, particularly in therapy-resistant disease. However, despite concerted efforts, CSC-targeting strategies have not been efficiently translated to the clinic. This is partly due to our incomplete understanding of the mechanisms underlying CSC therapy-resistance. In particular, the relationship between therapy-resistance and the organisation of CSCs as Stem-Progenitor-Differentiated cell hierarchies has not been widely studied. In this review we argue that modern clinical strategies should appreciate that the CSC hierarchy is a dynamic target that contains sensitive and resistant components and expresses a collection of therapy-resisting mechanisms. We propose that the CSC hierarchy at primary presentation changes in response to clinical intervention, resulting in a recurrent malignancy that should be targeted differently. As such, addressing the hierarchical organisation of CSCs into our bench-side theory should expedite translation of CSC-targeting to bed-side practice. In conclusion, we discuss strategies through which we can catch these moving clinical targets to specifically compromise therapy-resistant disease.

Targeted therapies for diarrhea-predominant irritable bowel syndrome

Directory of Open Access Journals (Sweden)

Olden KW

2012-05-01

Full Text Available Kevin W OldenDepartment of Medicine, St Joseph's Hospital and Medical Center, Phoenix, AZ, USAAbstract: Irritable bowel syndrome (IBS causes gastrointestinal symptoms such as abdominal pain, bloating, and bowel pattern abnormalities, which compromise patients' daily functioning. Common therapies address one or two IBS symptoms, while others offer wider symptom control, presumably by targeting pathophysiologic mechanisms of IBS. The aim of this targeted literature review was to capture clinical trial reports of agents receiving the highest recommendation (Grade 1 for treatment of IBS from the 2009 American College of Gastroenterology IBS Task Force, with an emphasis on diarrhea-predominant IBS. Literature searches in PubMed captured articles detailing randomized placebo-controlled trials in IBS/diarrhea-predominant IBS for agents receiving Grade I (strong 2009 American College of Gastroenterology IBS Task Force recommendations: tricyclic antidepressants, nonabsorbable antibiotics, and the 5-HT3 receptor antagonist alosetron. Studies specific for constipation-predominant IBS were excluded. Tricyclic antidepressants appear to improve global IBS symptoms but have variable effects on abdominal pain and uncertain tolerability; effects on stool consistency, frequency, and urgency were not adequately assessed. Nonabsorbable antibiotics show positive effects on global symptoms, abdominal pain, bloating, and stool consistency but may be most efficacious in patients with altered intestinal microbiota. Alosetron improves global symptoms and abdominal pain and normalizes bowel irregularities, including stool frequency, consistency, and fecal urgency. Both the nonabsorbable antibiotic rifaximin and the 5-HT3 receptor antagonist alosetron improve quality of life. Targeted therapies provide more complete relief of IBS symptoms than conventional agents. Familiarization with the quantity and quality of evidence of effectiveness can facilitate more individualized

Tutorial on architectural acoustics

Science.gov (United States)

Shaw, Neil; Talaske, Rick; Bistafa, Sylvio

2002-11-01

This tutorial is intended to provide an overview of current knowledge and practice in architectural acoustics. Topics covered will include basic concepts and history, acoustics of small rooms (small rooms for speech such as classrooms and meeting rooms, music studios, small critical listening spaces such as home theatres) and the acoustics of large rooms (larger assembly halls, auditoria, and performance halls).

Cancer Nanomedicine: From Targeted Delivery to Combination Therapy

Science.gov (United States)

Xu, Xiaoyang; Ho, William; Zhang, Xueqing; Bertrand, Nicolas; Farokhzad, Omid

2015-01-01

The advent of nanomedicine marks an unparalleled opportunity to advance the treatment of a variety of diseases, including cancer. The unique properties of nanoparticles, such as large surface-to volume ratio, small size, the ability to encapsulate a variety of drugs, and tunable surface chemistry, gives them many advantages over their bulk counterparts. This includes multivalent surface modification with targeting ligands, efficient navigation of the complex in vivo environment, increased intracellular trafficking, and sustained release of drug payload. These advantages make nanoparticles a mode of treatment potentially superior to conventional cancer therapies. This article highlights the most recent developments in cancer treatment using nanoparticles as drug-delivery vehicles, including promising opportunities in targeted and combination therapy. PMID:25656384

Communicating Big Data with the Public via Tutorials

Science.gov (United States)

Montgomery, Michele

2015-08-01

Although numerical models that researchers use to analyze large astronomy data sets may be easily found on NASA websites, tutorials on how to use these models and understanding the products of the models are lacking. Thus, communication with the public is ineffective. Where the public could easily engage with data and models to determine if their work and lives could be impacted, and if so, to plan accordingly, a lack of good tutorials typically results in the public waiting for a tweet, a post on Facebook, an announcement on a NASA webpage, an alert sent via text message or email, etc. An example is a solar flare or coronal mass ejection event that may impact GPS devices, the precision of which is heavily relied upon by several sectors of the public and military. To allow the public to engage in real time with solar data and NASA developed heliophysics software, we have developed tutorials. In this work, we present our tutorials made for NASA's Living With a Star Program on the such as Integrated Space Weather Analysis (ISWA) layout and the WSA-ENLIL-CONE Model to analyze a CME Evolution that occurred in 2010. We present our results and our analysis of the public's ability to understand the model's predictions of whether the event will impact Earth. By training the public to use the data and to understand model predictions, we turn passive recipients into engaged and self-supporting users of NASA data of space weather events.

Engaging undergraduate nursing students in face-to-face tutorials.

Science.gov (United States)

Elder, Ruth L; Lewis, Peter A; Windsor, Carol A; Wheeler, Margaret; Forster, Elizabeth; Foster, Joanne; Chapman, Helen

2011-09-01

Chronic nursing shortages have placed increasing pressure on many nursing schools to recruit greater numbers of students with the consequence of larger class sizes. Larger class sizes have the potential to lead to student disengagement. This paper describes a case study that examined the strategies used by a group of nursing lecturers to engage students and to overcome passivity in a Bachelor of Nursing programme. A non-participant observer attended 20 tutorials to observe five academics deliver four tutorials each. Academics were interviewed both individually and as a group following the completion of all tutorial observations. All observations, field notes, interviews and focus groups were coded separately and major themes identified. From this analysis two broad categories emerged: getting students involved; and engagement as a struggle. Academics used a wide variety of techniques to interest and involve students. Additionally, academics desired an equal relationship with students. They believed that both they and the students had some power to influence the dynamics of tutorials and that neither party had ultimate power. The findings of this study serve to re-emphasise past literature which suggests that to engage students, the academics must also engage. Copyright © 2011 Elsevier Ltd. All rights reserved.

Nanobody-photosensitizer conjugates for targeted photodynamic therapy

NARCIS (Netherlands)

Heukers, Raimond; van Bergen en Henegouwen, P; Oliveira, Sabrina

2014-01-01

Photodynamic therapy (PDT) induces cell death through light activation of a photosensitizer (PS). Targeted delivery of PS via monoclonal antibodies has improved tumor selectivity. However, these conjugates have long half-lives, leading to relatively long photosensitivity in patients. In an attempt

Targeted Therapy for Medullary Thyroid Cancer: A Review

Directory of Open Access Journals (Sweden)

S. R. Priya

2017-10-01

Full Text Available Medullary thyroid cancers (MTCs constitute between 2 and 5% of all thyroid cancers. The 10-year overall survival (OS rate of patients with localized disease is around 95% while that of patients with regional stage disease is about 75%. Only 20% of patients with distant metastases at diagnosis survive 10 years which is significantly lower than for differentiated thyroid cancers. Cases with regional metastases at presentation have high recurrence rates. Adjuvant external radiation confers local control but not improved OS. The management of residual, recurrent, or metastatic disease till a few years ago was re-surgery with local measures such as radiation. Chemotherapy was used with marginal benefit. The development of targeted therapy has brought in a major advantage in management of such patients. Two drugs—vandetanib and cabozantinib—have been approved for use in progressive or metastatic MTC. In addition, several drugs acting on other steps of the molecular pathway are being investigated with promising results. Targeted radionuclide therapy also provides an effective treatment option with good quality of life. This review covers the rationale of targeted therapy for MTC, present treatment options, drugs and methods under investigation, as well as an outline of the adverse effects and their management.

A tutorial on the principles of harmonic intonation for trombonists

Science.gov (United States)

Keener, Michael Kenneth

A Tutorial on the Principles of Harmonic Intonation for Trombonists includes a manual containing background information, explanations of the principles of harmonic intonation, and printed musical examples for use in learning and practicing the concepts of harmonic intonation. An audio compact disk containing music files corresponding to the printed music completes the set. This tutorial is designed to allow performing musicians and students to practice intonation skills with the pitch-controlled music on the compact disc. The music on the CD was recorded in movable-comma just intonation, replicating performance parameters of wind, string, and vocal ensembles. The compact disc includes sixty tracks of ear-training exercises and interval studies with which to practice intonation perception and adjustment. Tuning notes and examples of equal-tempered intervals and just intervals are included on the CD. The intonation exercises consist of musical major scales, duets, trios, and quartet phrases to be referenced while playing the printed music. The CD tracks allow the performer to play scales in unison (or practice other harmonic intervals) or the missing part of the corresponding duet, trio, or quartet exercise. Instructions in the manual guide the user through a process that can help prepare musicians for more accurate musical ensemble performance. The contextual essay that accompanies the tutorial includes a description of the tutorial, a review of related literature, methodology of construction of the tutorial, evaluations and outcomes, conclusions and recommendations for further research, and a selected bibliography.

Proposal for tutorial: Resilience in carrier Ethernet transport

DEFF Research Database (Denmark)

Berger, Michael Stübert; Wessing, Henrik; Ruepp, Sarah Renée

2009-01-01

This tutorial addresses how Carrier Ethernet technologies can be used in the transport network to provide resilience to the packet layer. Carrier Ethernet networks based on PBB-TE and T-MPLS/MPLS-TP are strong candidates for reliable transport of triple-play services. These technologies offer...... of enhancements are still required to make Carrier Ethernet ready for large scale deployments of reliable point-to-multipoint services. The tutorial highlights the necessary enhancements and shows possible solutions and directions towards reliable multicast. Explicit focus is on OAM for multicast, where...

Targeted drugs in radiation therapy

International Nuclear Information System (INIS)

Favaudon, V.; Hennequin, C.; Hennequin, C.

2004-01-01

New drugs aiming at the development of targeted therapies have been assayed in combination with ionizing radiation over the past few years. The rationale of this concept comes from the fact that the cytotoxic potential of targeted drugs is limited, thus requiring concomitant association with a cytotoxic agent for the eradication of tumor cells. Conversely a low level of cumulative toxicity is expected from targeted drugs. Most targeted drugs act through inhibition of post-translational modifications of proteins, such as dimerization of growth factor receptors, prenylation reactions, or phosphorylation of tyrosine or serine-threonine residues. Many systems involving the proteasome, neo-angiogenesis promoters, TGF-β, cyclooxygenase or the transcription factor NF-κB, are currently under investigation in hopes they will allow a control of cell proliferation, apoptosis, cell cycle progression, tumor angiogenesis and inflammation. A few drugs have demonstrated an antitumor potential in particular phenotypes. In most instances, however, radiation-drug interactions proved to be strictly additive in terms of cell growth inhibition or induced cell death. Strong potentiation of the response to radiotherapy is expected to require interaction with DNA repair mechanisms. (authors)

The undergraduate physics tutorial program at CSU Los Angeles assessment of utility and areas of interest

Science.gov (United States)

Avetyan, Smbat

The Physics Education Research (PER) group at the University of Washington have researched traditional teaching methods and found that students in introductory physics are lacking a conceptual understanding of the physics material. The solution they put forth is an interactive tutorial program designed to meet the lack of conceptual understanding. Since the tutorial programs inception at CSU Los Angeles in Fall 2006 no evaluation has been successfully undertaken therefore the effect of the tutorial program in the physics 200 series is deeply obscure to the department. The research has shed light on the tutorial program and brought into context its effectiveness on the overall physics 200 series courses at CSU Los Angeles. The researcher has addressed the following research questions, what overall effect does the tutorial program have on the Physics 200 series curriculum? What is the size and significance of gains attributable to the undergraduate calculus based Physics 200 series tutorial program at CSU Los Angeles? What can we learn from gains about individual weekly lessons from the Physics 200 series tutorial courses? What is the correlation of tutorial gains with student final course grades? Are the gains from the tutorial program different for genders? Is there a difference in gains based on the different students' colleges?

A Tutorial Design Process Applied to an Introductory Materials Engineering Course

Science.gov (United States)

Rosenblatt, Rebecca; Heckler, Andrew F.; Flores, Katharine

2013-01-01

We apply a "tutorial design process", which has proven to be successful for a number of physics topics, to design curricular materials or "tutorials" aimed at improving student understanding of important concepts in a university-level introductory materials science and engineering course. The process involves the identification…

Folate-targeted nanoparticles for rheumatoid arthritis therapy.

Science.gov (United States)

Nogueira, Eugénia; Gomes, Andreia C; Preto, Ana; Cavaco-Paulo, Artur

2016-05-01

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease, affecting almost 1% of the world population. Although the cause of RA remains unknown, the complex interaction between immune mediators (cytokines and effector cells) is responsible for the joint damage that begins at the synovial membrane. Activated macrophages are critical in the pathogenesis of RA and showed specifically express a receptor for the vitamin folic acid (FA), folate receptor β (FRβ). This particular receptor allows internalization of FA-coupled cargo. In this review we will address the potential of nanoparticles as an effective drug delivery system for therapies that will directly target activated macrophages. Special attention will be given to stealth degree of the nanoparticles as a strategy to avoid clearance by macrophages of the mononuclear phagocytic system (MPS). This review summarizes the application of FA-target nanoparticles as drug delivery systems for RA and proposes prospective future directions. Rheumatoid arthritis is a debilitating autoimmune disease of the joints which affects many people worldwide. Up till now, there is a lack of optimal therapy against this disease. In this review article, the authors outlined in depth the current mechanism of disease for rheumatoid arthritis and described the latest research in using folic acid-targeted nanoparticles to target synovial macrophages in the fight against rheumatoid arthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

Opportunity of interventional radiology: advantages and application of interventional technique in biological target therapy

International Nuclear Information System (INIS)

Teng Gaojun; Lu Qin

2007-01-01

Interventional techniques not only provide opportunity of treatment for many diseases, but also alter the traditional therapeutic pattern. With the new century of wide application of biological therapies, interventional technique also shows extensive roles. The current biological therapy, including gene therapy, cell transplantation therapy, immunobiologic molecule therapy containing cell factors, tumor antibody or vaccine, recombined proteins, radioactive-particles and targeting materials therapy, can be locally administrated by interventional techniques. The combination of targeting biological therapies and high-targeted interventional technique holds advantages of minimal invasion, accurate delivery, vigorous local effect, and less systemic adverse reactions. Authors believe that the biological therapy may arise a great opportunity for interventional radiology, therefore interventional colleagues should grasp firmly and promptly for the development and extension in this field. (authors)

The Nature of Reflective Practice and Emotional Intelligence in Tutorial Settings

Science.gov (United States)

Gill, Gobinder Singh

2014-01-01

The purpose of this paper was to assess the nature of reflective practice and emotional intelligence in tutorial settings. Following the completion of a self-report measure of emotional intelligence, practitioners incorporated a model of reflective practice into their tutorial sessions. Practitioners were instructed to utilise reflective practice…

Prognostics 101: A tutorial for particle filter-based prognostics algorithm using Matlab

International Nuclear Information System (INIS)

An, Dawn; Choi, Joo-Ho; Kim, Nam Ho

2013-01-01

This paper presents a Matlab-based tutorial for model-based prognostics, which combines a physical model with observed data to identify model parameters, from which the remaining useful life (RUL) can be predicted. Among many model-based prognostics algorithms, the particle filter is used in this tutorial for parameter estimation of damage or a degradation model. The tutorial is presented using a Matlab script with 62 lines, including detailed explanations. As examples, a battery degradation model and a crack growth model are used to explain the updating process of model parameters, damage progression, and RUL prediction. In order to illustrate the results, the RUL at an arbitrary cycle are predicted in the form of distribution along with the median and 90% prediction interval. This tutorial will be helpful for the beginners in prognostics to understand and use the prognostics method, and we hope it provides a standard of particle filter based prognostics. -- Highlights: ► Matlab-based tutorial for model-based prognostics is presented. ► A battery degradation model and a crack growth model are used as examples. ► The RUL at an arbitrary cycle are predicted using the particle filter

Targeted therapy using nanotechnology: focus on cancer.

Science.gov (United States)

Sanna, Vanna; Pala, Nicolino; Sechi, Mario

2014-01-01

Recent advances in nanotechnology and biotechnology have contributed to the development of engineered nanoscale materials as innovative prototypes to be used for biomedical applications and optimized therapy. Due to their unique features, including a large surface area, structural properties, and a long circulation time in blood compared with small molecules, a plethora of nanomaterials has been developed, with the potential to revolutionize the diagnosis and treatment of several diseases, in particular by improving the sensitivity and recognition ability of imaging contrast agents and by selectively directing bioactive agents to biological targets. Focusing on cancer, promising nanoprototypes have been designed to overcome the lack of specificity of conventional chemotherapeutic agents, as well as for early detection of precancerous and malignant lesions. However, several obstacles, including difficulty in achieving the optimal combination of physicochemical parameters for tumor targeting, evading particle clearance mechanisms, and controlling drug release, prevent the translation of nanomedicines into therapy. In spite of this, recent efforts have been focused on developing functionalized nanoparticles for delivery of therapeutic agents to specific molecular targets overexpressed on different cancer cells. In particular, the combination of targeted and controlled-release polymer nanotechnologies has resulted in a new programmable nanotherapeutic formulation of docetaxel, namely BIND-014, which recently entered Phase II clinical testing for patients with solid tumors. BIND-014 has been developed to overcome the limitations facing delivery of nanoparticles to many neoplasms, and represents a validated example of targeted nanosystems with the optimal biophysicochemical properties needed for successful tumor eradication.

Targeted Alpha Therapy: From Alpha to Omega

International Nuclear Information System (INIS)

Allen, Barry J; Clarke, Raymond; Huang Chenyu

2013-01-01

This review covers the broad spectrum of Targeted Alpha Therapy (TAT) research in Australia; from in vitro and in vivo studies to clinical trials. The principle of tumour anti-vascular alpha therapy (TAVAT) is discussed in terms of its validation by Monte Carlo calculations of vascular models and the potential role of biological dosimetry is examined. Summmary of this review is as follows: 1. The essence of TAT 2. Therapeutic objectives 3. TAVAT and Monte Carlo microdosimetry 4. Biological dosimetry 5. Preclinical studies 6. Clinical trials 7. What next? 8. Obstacles. (author)

RANKL-Targeted Therapies: The Next Frontier in the Treatment of Male Osteoporosis

Directory of Open Access Journals (Sweden)

Alicia K. Morgans

2011-01-01

Full Text Available Male osteoporosis is an increasingly recognized problem in aging men. A common cause of male osteoporosis is hypogonadism. Thousands of men with prostate cancer are treated with androgen deprivation therapy, a treatment that dramatically reduces serum testosterone and causes severe hypogonadism. Men treated with androgen deprivation therapy experience a decline in bone mineral density and have an increased rate of fracture. This paper describes prostate cancer survivors as a model of hypogonadal osteoporosis and discusses the use of RANKL-targeted therapies in osteoporosis. Denosumab, the only RANKL-targeted therapy currently available, increases bone mineral density and decreases fracture rate in men with prostate cancer. Denosumab is also associated with delayed time to first skeletal-related event and an increase in bone metastasis-free survival in these men. It is reasonable to investigate the use of RANKL-targeted therapy in male osteoporosis in the general population.

The roles of pathology in targeted therapy of women with gynecologic cancers.

Science.gov (United States)

Murali, Rajmohan; Grisham, Rachel N; Soslow, Robert A

2018-01-01

The role of the pathologist in the multidisciplinary management of women with gynecologic cancer has evolved substantially over the past decade. Pathologists' evaluation of parameters such as pathologic stage, histologic subtype, grade and microsatellite instability, and their identification of patients at risk for Lynch syndrome have become essential components of diagnosis, prognostic assessment and determination of optimal treatment of affected women. Despite the use of multimodality treatment and combination cytotoxic chemotherapy, the prognosis of women with advanced-stage gynecologic cancer is often poor. Therefore, expanding the arsenal of available systemic therapies with targeted therapeutic agents is appealing. Anti-angiogenic therapies, immunotherapy and poly ADP ribose polymerase (PARP) inhibitors are now routinely used for the treatment of advanced gynecologic cancer, and many more are under investigation. Pathologists remain important in the clinical management of patients with targeted therapy, by identifying potentially targetable tumors on the basis of their pathologic phenotype, by assessing biomarkers that are predictive of response to targeted therapy (e.g. microsatellite instability, PD1/PDL1 expression), and by monitoring treatment response and resistance. Pathologists are also vital to research efforts exploring novel targeted therapies by identifying homogenous subsets of tumors for more reliable and meaningful analyses, and by confirming expression in tumor tissues of novel targets identified in genomic, epigenetic or other screening studies. In the era of precision gynecologic oncology, the roles of pathologists in the discovery, development and implementation of targeted therapeutic strategies remain as central as they are for traditional (surgery-chemotherapy-radiotherapy) management of women with gynecologic cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

New Molecular Targets of Anticancer Therapy - Current Status and Perspectives.

Science.gov (United States)

Zajac, Marianna; Muszalska, Izabela; Jelinska, Anna

2016-01-01

Molecularly targeted anticancer therapy involves the use of drugs or other substances affecting specific molecular targets that play a part in the development, progression and spread of a given neoplasm. By contrast, the majority of classical chemotherapeutics act on all rapidly proliferating cells, both healthy and cancerous ones. Target anticancer drugs are designed to achieve a particular aim and they usually act cytostatically, not cytotoxically like classical chemotherapeutics. At present, more than 300 biological molecular targets have been identified. The proteins involved in cellular metabolism include (among others) receptor proteins, signal transduction proteins, mRNA thread matrix synthesis proteins participating in neoplastic transformation, cell cycle control proteins, functional and structural proteins. The receptor proteins that are targeted by currently used anticancer drugs comprise the epithelial growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor(VEGFR). Target anticancer drugs may affect extracellular receptor domains (antibodies) or intracellular receptor domains (tyrosine kinase inhibitors). The blocking of the mRNA thread containing information about the structure of oncogenes (signal transduction proteins) is another molecular target of anticancer drugs. That type of treatment, referred to as antisense therapy, is in clinical trials. When the synthesis of genetic material is disturbed, in most cases the passage to the next cycle phase is blocked. The key proteins responsible for the blockage are cyclines and cycline- dependent kinases (CDK). Clinical trials are focused on natural and synthetic substances capable of blocking various CDKs. The paper discusses the molecular targets and chemical structure of target anticancer drugs that have been approved for and currently applied in antineoplastic therapy together with indications and contraindications for their

Financial relationships in economic analyses of targeted therapies in oncology.

Science.gov (United States)

Valachis, Antonis; Polyzos, Nikolaos P; Nearchou, Andreas; Lind, Pehr; Mauri, Davide

2012-04-20

A potential financial relationship between investigators and pharmaceutical manufacturers has been associated with an increased likelihood of reporting favorable conclusions about a sponsor's proprietary agent in pharmacoeconomic studies. The purpose of this study is to investigate whether there is an association between financial relationships and outcome in economic analyses of new targeted therapies in oncology. We searched PubMed (last update June 2011) for economic analyses of targeted therapies (including monoclonal antibodies, tyrosine-kinase inhibitors, and mammalian target of rapamycin inhibitors) in oncology. The trials were qualitatively rated regarding the cost assessment as favorable, neutral, or unfavorable on the basis of prespecified criteria. Overall, 81 eligible studies were identified. Economic analyses that were funded by pharmaceutical companies were more likely to report favorable qualitative cost estimates (28 [82%] of 34 v 21 [45%] of 47; P = .003). The presence of an author affiliated with manufacturer was not associated with study outcome. Furthermore, if only studies including a conflict of interest statement were included (66 of 81), studies that reported any financial relationship with manufacturers (author affiliation and/or funding and/or other financial relationship) were more likely to report favorable results of targeted therapies compared with studies without financial relationship (32 [71%] of 45 v nine [43%] of 21; P = .025). Our study reveals a potential threat for industry-related bias in economic analyses of targeted therapies in oncology in favor of analyses with financial relationships between authors and manufacturers. A more balanced funding of economic analyses from other sources may allow greater confidence in the interpretation of their results.

Using Structure-Based Organic Chemistry Online Tutorials with Automated Correction for Student Practice and Review

Science.gov (United States)

O'Sullivan, Timothy P.; Hargaden, Gra´inne C.

2014-01-01

This article describes the development and implementation of an open-access organic chemistry question bank for online tutorials and assessments at University College Cork and Dublin Institute of Technology. SOCOT (structure-based organic chemistry online tutorials) may be used to supplement traditional small-group tutorials, thereby allowing…

A Knock-in Reporter for a Novel AR-Targeted Therapy

Science.gov (United States)

2016-05-01

AWARD NUMBER: W81XWH-15-1-0049 TITLE: A Knock -in Reporter for a Novel AR-Targeted Therapy PRINCIPAL INVESTIGATOR: Chunhong Yan, Ph.D...5a. CONTRACT NUMBER A Knock -in Reporter for a Novel AR-Targeted Therapy 5b. GRANT NUMBER W81XWH-15-1-0049 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...enhancer. While the knock -in reporter is expected to faithfully reproduce chemical responses of the endogenous AR gene, we carried out a pilot screen

Targeted Therapies for Myeloma and Metastatic Bone Cancers

Science.gov (United States)

2010-09-01

Cancer J Clin 2003; 53:5. Kasugai S, Fujisawa R, Waki Y, Miyamoto K, Ohya K 2000 Selective drug delivery system to bone: small peptide (Asp)6...page. Bone targeted nanoparticles , bone cancer myeloma, mice studies, PLGA , Biodegradable materials. Targeted Therapies for Myeloma and Metastatic Bone...present results from this program at talk at the Particles 2006 –Medical/Biochemical Diagnostic , Pharmaceutical, and Drug Delivery . 3

Targeted therapies for diarrhea-predominant irritable bowel syndrome

OpenAIRE

Olden, Kevin W

2012-01-01

Kevin W OldenDepartment of Medicine, St Joseph's Hospital and Medical Center, Phoenix, AZ, USAAbstract: Irritable bowel syndrome (IBS) causes gastrointestinal symptoms such as abdominal pain, bloating, and bowel pattern abnormalities, which compromise patients' daily functioning. Common therapies address one or two IBS symptoms, while others offer wider symptom control, presumably by targeting pathophysiologic mechanisms of IBS. The aim of this targeted literature review was t...

Inducement of radionuclides targeting therapy by gene transfection

International Nuclear Information System (INIS)

Luo Quanyong

2001-01-01

The author presents an overview of gene transfection methods to genetically induce tumor cells to express enhanced levels of cell surface antigens and receptors to intake radiolabeled antibody and peptide targeting and thus increase their therapeutic effect in radiotherapy. The current research include inducement of radioimmunotherapy through CEA gene transfection, inducement of iodine-131 therapy by sodium iodide symporter gene transfection and inducement of MIBG therapy by noradrenaline transporter gene transfection. These studies raise the prospect that gene-therapy techniques could be used to enable the treatment of a wide range of tumors with radiopharmaceuticals of established clinical acceptability

Tutorial on nuclear thermal propulsion safety for Mars

International Nuclear Information System (INIS)

Buden, D.

1992-01-01

Safety is the prime design requirement for nuclear thermal propulsion (NTP). It must be built in at the initiation of the design process. An understanding of safety concerns is fundamental to the development of nuclear rockets for manned missions to Mars and many other applications that will be enabled or greatly enhanced by the use of nuclear propulsion. To provide an understanding of the basic issues, a tutorial has been prepared. This tutorial covers a range of topics including safety requirements and approaches to meet these requirements, risk and safety analysis methodology, NERVA reliability and safety approach, and life cycle risk assessments

An example of using CASPER tutorials for teaching knowledge of firmware development for FPGAs

International Nuclear Information System (INIS)

Pollak, A.W.

2015-01-01

We present an example of using CASPER tutorials for teaching purposes in Summer Schools and Workshops with participants from a variety of different academic backgrounds. Using the tutorials for laboratory exercises at the INFIERI Summer School 2014, we showed that the flexible nature provided by these tutorials has the advantage of providing high quality laboratory exercises for participants independent of their prior knowledge

Action perception and imitation : a tutorial

NARCIS (Netherlands)

Bekkering, H; Wohlschlager, A; Prinz, W; Hommel, B

2002-01-01

Currently, imitation, or performing an act after perceiving it, is in the focus of attention of researchers from many different disciplines. Although this tutorial attempts to provide some interdisciplinary background, it will concentrate on possible cognitive mechanisms that underlie imitation

CERN Technical Training 2007: IT3T - IT Technical Training Tutorials (Autumn 2007)

CERN Multimedia

2007-01-01

CERN Technical Training and the Internet Services group of the IT department (IT/IS) are jointly organizing a series of free tutorials, addressing some topics of common interest: the IT Technical Training Tutorials (IT3T). The first IT3T series will be offered in October 2007, in French, with the following schedule: IT3T/2007/1 "Introduction to Collaboration Workspaces using SharePoint", October 23rd , 14:30-16:00, Alexandre Lossent IT3T/2007/2 "What is new in Office 2007", October 25th, 14:30-15:30, Emmanuel Ormancey IT3T/2007/3 "Working with Windows Vista at CERN", October 30th, 14:30-15:30, Michal Kwiatek IT3T/2007/4 "Read your mail and more with Outlook 2007", November 1st, 14:30-15:30, Sebastien Dellabella All IT Technical Training Tutorials will take place in the Training Centre Auditorium (building 593, room 11), at 14h30. The tutorials are free of charge, but separate registration to each is required. Participation to any of the tutorials is open: attendance to any ...

Targeting Strategies for Multifunctional Nanoparticles in Cancer Imaging and Therapy

Science.gov (United States)

Yu, Mi Kyung; Park, Jinho; Jon, Sangyong

2012-01-01

Nanomaterials offer new opportunities for cancer diagnosis and treatment. Multifunctional nanoparticles harboring various functions including targeting, imaging, therapy, and etc have been intensively studied aiming to overcome limitations associated with conventional cancer diagnosis and therapy. Of various nanoparticles, magnetic iron oxide nanoparticles with superparamagnetic property have shown potential as multifunctional nanoparticles for clinical translation because they have been used asmagnetic resonance imaging (MRI) constrast agents in clinic and their features could be easily tailored by including targeting moieties, fluorescence dyes, or therapeutic agents. This review summarizes targeting strategies for construction of multifunctional nanoparticles including magnetic nanoparticles-based theranostic systems, and the various surface engineering strategies of nanoparticles for in vivo applications. PMID:22272217

Magnetic chitosan nanoparticles as a drug delivery system for targeting photodynamic therapy

International Nuclear Information System (INIS)

Sun Yun; Chen Zhilong; Yang Xiaoxia; Huang Peng; Zhou Xinping; Du Xiaoxia

2009-01-01

Photodynamic therapy (PDT) has become an increasingly recognized alternative to cancer treatment in clinic. However, PDT therapy agents, namely photosensitizer (PS), are limited in application as a result of prolonged cutaneous photosensitivity, poor water solubility and inadequate selectivity, which are encountered by numerous chemical therapies. Magnetic chitosan nanoparticles provide excellent biocompatibility, biodegradability, non-toxicity and water solubility without compromising their magnetic targeting. Nevertheless, no previous attempt has been reported to develop an in vivo magnetic drug delivery system with chitosan nanoparticles for magnetic resonance imaging (MRI) monitored targeting photodynamic therapy. In this study, magnetic targeting chitosan nanoparticles (MTCNPs) were prepared and tailored as a drug delivery system and imaging agents for PS, designated as PHPP. Results showed that PHPP-MTCNPs could be used in MRI monitored targeting PDT with excellent targeting and imaging ability. Non-toxicity and high photodynamic efficacy on SW480 carcinoma cells both in vitro and in vivo were achieved with this method at the level of 0-100 μM. Notably, localization of nanoparticles in skin and hepatic tissue was significantly less than in tumor tissue, therefore photosensitivity and hepatotoxicity can be attenuated.

Hyperspectral image analysis. A tutorial

International Nuclear Information System (INIS)

Amigo, José Manuel; Babamoradi, Hamid; Elcoroaristizabal, Saioa

2015-01-01

This tutorial aims at providing guidelines and practical tools to assist with the analysis of hyperspectral images. Topics like hyperspectral image acquisition, image pre-processing, multivariate exploratory analysis, hyperspectral image resolution, classification and final digital image processing will be exposed, and some guidelines given and discussed. Due to the broad character of current applications and the vast number of multivariate methods available, this paper has focused on an industrial chemical framework to explain, in a step-wise manner, how to develop a classification methodology to differentiate between several types of plastics by using Near infrared hyperspectral imaging and Partial Least Squares – Discriminant Analysis. Thus, the reader is guided through every single step and oriented in order to adapt those strategies to the user's case. - Highlights: • Comprehensive tutorial of Hyperspectral Image analysis. • Hierarchical discrimination of six classes of plastics containing flame retardant. • Step by step guidelines to perform class-modeling on hyperspectral images. • Fusion of multivariate data analysis and digital image processing methods. • Promising methodology for real-time detection of plastics containing flame retardant.

Intelligent tutorial system for selftraining in tuning of control systems; Sistema tutorial inteligente para el autoentrenamiento en sintonizacion de sistemas de control

Energy Technology Data Exchange (ETDEWEB)

Romero Jimenez, Guillermo; Perez Ocampo, Maria Concepcion [Instituto de Investigaciones Electricas, Temixco, Morelos (Mexico)

1999-07-01

In this paper the design, development and validation of an intelligent tutorial system oriented to the instruction of techniques of tuning of control systems is described. This system is based on systems previously developed in the Simulation Unit of the Instituto de Investigaciones Electricas (IIE). The designed system accounts with four modules: of knowledge, the student model, of tutor and of interface, basic characteristics that allows to locate this system in the context of the intelligent tutorial systems. In this system in particular, the knowledge module was only modified, because advantage is taken of the existing structure to incorporate a new dominion of application: the one of the techniques of tuning of control systems. The system maintains the characteristic that it can also be used as a consultation system. In addition to the design and validation of the tutorial system, when following the methodology of processing the degree of generality of the developed system, was evaluated, taking into account the evaluation and quantification of metrics that the engineering software proposes. [Spanish] En este trabajo se describen el diseno, el desarrollo y la validacion de un sistema tutorial inteligente orientado a la instruccion de tecnicas de sintonizacion de sistemas de control. Este sistema esta basado en sistemas desarrollados anteriormente en la Unidad de Simulacion del Instituto de Investigaciones Electricas (IIE). El sistema disenado cuenta con cuatro modulos: de conocimiento, del modelo del estudiante, de tutor y de interfaz, caracteristica principal que permite ubicar a este sistema en el contexto de los sistemas tutoriales inteligentes. En este sistema en particular solo se modifica el modulo de conocimiento, pues se aprovecha la estructura existente para incorporar un nuevo dominio de aplicacion: el de las tecnicas de sintonizacion de sistemas de control. El sistema mantiene la caracteristica de que tambien puede utilizarse como un sistema de

RNA-Targeted Therapies and Amyotrophic Lateral Sclerosis

Directory of Open Access Journals (Sweden)

Stéphane Mathis

2018-01-01

Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal motor disease in adults. Its pathophysiology remains mysterious, but tremendous advances have been made with the discovery of the most frequent mutations of its more common familial form linked to the C9ORF72 gene. Although most cases are still considered sporadic, these genetic mutations have revealed the role of RNA production, processing and transport in ALS, and may be important players in all ALS forms. There are no disease-modifying treatments for adult human neurodegenerative diseases, including ALS. As in spinal muscular atrophy, RNA-targeted therapies have been proposed as potential strategies for treating this neurodegenerative disorder. Successes achieved in various animal models of ALS have proven that RNA therapies are both safe and effective. With careful consideration of the applicability of such therapies in humans, it is possible to anticipate ongoing in vivo research and clinical trial development of RNA therapies for treating ALS.

RNA-Targeted Therapies and Amyotrophic Lateral Sclerosis.

Science.gov (United States)

Mathis, Stéphane; Le Masson, Gwendal

2018-01-15

Amyotrophic lateral sclerosis (ALS) is a fatal motor disease in adults. Its pathophysiology remains mysterious, but tremendous advances have been made with the discovery of the most frequent mutations of its more common familial form linked to the C9ORF72 gene. Although most cases are still considered sporadic, these genetic mutations have revealed the role of RNA production, processing and transport in ALS, and may be important players in all ALS forms. There are no disease-modifying treatments for adult human neurodegenerative diseases, including ALS. As in spinal muscular atrophy, RNA-targeted therapies have been proposed as potential strategies for treating this neurodegenerative disorder. Successes achieved in various animal models of ALS have proven that RNA therapies are both safe and effective. With careful consideration of the applicability of such therapies in humans, it is possible to anticipate ongoing in vivo research and clinical trial development of RNA therapies for treating ALS.

Tutorial Continuing Education: Innovative Strategy in a Tertiary Specialized Health Unit

Directory of Open Access Journals (Sweden)

Flaviana Maciel

2017-06-01

Full Text Available Hospital Pelopidas Silveira-IMIP/SES/SUS is a tertiary-unit, specialized in cardiology, neurology, neurosurgery and interventional radiology. It is the only hospital of Brazilian Public-Health-System (SUS with this profile and a 24h-acute-cardio/neurovascular facility. Challenges of Continuing-Education include a guaranteeing appropriate level of basic knowledge, b empowering clinical staff to remain up to date in current knowledge. HPS Continuing-Education Program is based on three branches: a Classroom-Tutorials (CT, b Online-Tutorials at "Pelopidas Digital" Virtual-Teaching-Platform (PD-VTP and c Daily-Practice Evaluation (DPE. This paper presents logistic details of HPS Continuing-Education Program. Training team coordinates tutorial meetings and performs continuous statistical analysis. Evaluation team visit hospital departments daily, observing in practice the incorporation of information provided, and retraining individuals in their work scenarios. Both teams perform curriculum development, meeting planning and creation of digital-training-modules. Tutorial meetings have pre/post-tests, allowing monitoring of attendance, topic significance and short-term retention. Tutorial groups are formed by 6-12 employees sharing similarities in training needs. CT is offered to 4 groups-of-interest: a nurses, b nursing assistants, c administrative staff, porters, drivers, d cleaning, laundry and security staff. Problematization and active strategies have resulted into an attractive, structured educational program customized to produce short-term results. The strategy is of interest to institutions sharing similar challenges.

Tutorial on X-ray photon counting detector characterization.

Science.gov (United States)

Ren, Liqiang; Zheng, Bin; Liu, Hong

2018-01-01

Recent advances in photon counting detection technology have led to significant research interest in X-ray imaging. As a tutorial level review, this paper covers a wide range of aspects related to X-ray photon counting detector characterization. The tutorial begins with a detailed description of the working principle and operating modes of a pixelated X-ray photon counting detector with basic architecture and detection mechanism. Currently available methods and techniques for charactering major aspects including energy response, noise floor, energy resolution, count rate performance (detector efficiency), and charge sharing effect of photon counting detectors are comprehensively reviewed. Other characterization aspects such as point spread function (PSF), line spread function (LSF), contrast transfer function (CTF), modulation transfer function (MTF), noise power spectrum (NPS), detective quantum efficiency (DQE), bias voltage, radiation damage, and polarization effect are also remarked. A cadmium telluride (CdTe) pixelated photon counting detector is employed for part of the characterization demonstration and the results are presented. This review can serve as a tutorial for X-ray imaging researchers and investigators to understand, operate, characterize, and optimize photon counting detectors for a variety of applications.

An interactive tutorial on radiation protection for medical students

International Nuclear Information System (INIS)

Sendra-Portero, F.; Martinez-Morillo, M.

2003-01-01

The aim of this project is to develop an interactive tutorial designed for medical students training in radiation protection in order to use its definitive version in a collaborative group of medical schools. The contents of the tutorial matchers the outlines proposed by the EC guidelines on education and training in Radiation Protection for Medical exposures (RP118), for medical and dental schools. The tutorial is organised in virtual lectures, following a similar structure than the traditional lectures, slides and explanations. There is a central script for each theme with a forward-return interaction. Additionally, branches with deeper explanations (drawings, images, videos,...) are provided to the user. The tutorial is being developed on a set of power Point presentations, linked between them. The user can choose two ways sto launch each lecture, based either on spoken (audio) or written explanations. We present the initial version of a useful tool for pre-graduate training of general practitioners in Radiation Protection, which is a complementary tool for personally adapted computed-based education. Most of the contents can be easily adapted for other students of health related careers (i. e. nurses, technologists...) The use of multimedia tools has been recommended in the field of radiation protection, but developing these tools is time consuming and needs expertise in both, educative and multimedia resources. This projects takes part of more than a dozen multimedia projects on different radiology related subjects developed in our department. (Author) 6 refs

Emerging hematological targets and therapy for cardiovascular disease: From bench to bedside

Directory of Open Access Journals (Sweden)

Ana Villegas

2008-09-01

Full Text Available Ana Villegas, Fernando A Gonzalez, Leopoldo Llorente, Santiago RedondoService of Hematology and Hemotherapy, Hospital Clinico Universitario San Carlos, Madrid, SpainAbstract: Atherosclerotic cardiovascular disease is the leading cause of death and a major part of its pathophysiology remains obscure. Some hematological targets have been related to the development and clinical outcome of this disease, especially soluble cytokines, leukocytes, red blood cells, hemostatic factors and platelets, and bone-marrow vascular progenitors. These emerging factors may be modulated by current antiatherosclerotic pharmacotherapy, target-designed novel drugs or progenitor cell therapy. The aim of current review article is to comprehensively review the role of these antiatherosclerotic targets and therapy.Keywords: atherosclerosis, blood, progenitor cells, cytokines, therapy

Discontinuing VEGF-targeted Therapy for Progression Versus Toxicity Affects Outcomes of Second-line Therapies in Metastatic Renal Cell Carcinoma

DEFF Research Database (Denmark)

De Velasco, Guillermo; Xie, Wanling; Donskov, Frede

2017-01-01

BACKGROUND: A significant subgroup of metastatic renal cell carcinoma (mRCC) patients discontinue vascular endothelial growth factor-targeted therapies (VEGF-TT) because of toxicity. Whether clinical outcomes differ in patients who receive second-line (2L) targeted therapy on the basis of reason ...

Prostate Specific Membrane Antigen (PSMA) Targeted Bio-orthogonal Therapy for Metastatic Prostate Cancer

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-16-1-0595 TITLE: Prostate-Specific Membrane Antigen (PSMA) Targeted Bio -orthogonal Therapy for Metastatic Prostate Cancer...Sep 2016 - 14 Sep 2017 4. TITLE AND SUBTITLE Prostate-Specific Membrane Antigen (PSMA) Targeted Bio -orthogonal Therapy for Metastatic Prostate

Adaptive Tutorials Versus Web-Based Resources in Radiology: A Mixed Methods Comparison of Efficacy and Student Engagement.

Science.gov (United States)

Wong, Vincent; Smith, Ariella J; Hawkins, Nicholas J; Kumar, Rakesh K; Young, Noel; Kyaw, Merribel; Velan, Gary M

2015-10-01

Diagnostic imaging is under-represented in medical curricula globally. Adaptive tutorials, online intelligent tutoring systems that provide a personalized learning experience, have the potential to bridge this gap. However, there is limited evidence of their effectiveness for learning about diagnostic imaging. We performed a randomized mixed methods crossover trial to determine the impact of adaptive tutorials on perceived engagement and understanding of the appropriate use and interpretation of common diagnostic imaging investigations. Although concurrently engaged in disparate blocks of study, 99 volunteer medical students (from years 1-4 of the 6-year program) were randomly allocated to one of two groups. In the first arm of the trial on chest X-rays, one group received access to an adaptive tutorial, whereas the other received links to an existing peer-reviewed Web resource. These two groups crossed over in the second arm of the trial, which focused on computed tomography scans of the head, chest, and abdomen. At the conclusion of each arm of the trial, both groups completed an examination-style assessment, comprising questions both related and unrelated to the topics covered by the relevant adaptive tutorial. Online questionnaires were used to evaluate student perceptions of both learning resources. In both arms of the trial, the group using adaptive tutorials obtained significantly higher assessment scores than controls. This was because of higher assessment scores by senior students in the adaptive tutorial group when answering questions related to topics covered in those tutorials. Furthermore, students indicated significantly better engagement with adaptive tutorials than the Web resource and rated the tutorials as a significantly more valuable tool for learning. Medical students overwhelmingly accept adaptive tutorials for diagnostic imaging. The tutorials significantly improve the understanding of diagnostic imaging by senior students. Crown Copyright �

New perspectives on targeted therapy in ovarian cancer

Directory of Open Access Journals (Sweden)

Coward JIG

2015-02-01

Full Text Available Jermaine IG Coward,1–3 Kathryn Middleton,1 Felicity Murphy1 1Mater Health Services, Raymond Terrace, South Brisbane, QLD, Australia; 2Inflammtion and Cancer Therapeutics Group, Mater Research, University of Queensland, Translational Research Institute, Woolloongabba, Brisbane, QLD, Australia; 3School of Medicine, University of Queensland, Brisbane, QLD, Australia Abstract: Epithelial ovarian cancer remains the most lethal gynecologic malignancy. During the last 15 years, there has been only marginal improvement in 5 year overall survival. These daunting statistics are compounded by the fact that despite all subtypes exhibiting striking heterogeneity, their systemic management remains identical. Although changes to the scheduling and administration of chemotherapy have improved outcomes to a degree, a therapeutic ceiling is being reached with this approach, resulting in a number of trials investigating the efficacy of targeted therapies alongside standard treatment algorithms. Furthermore, there is an urge to develop subtype-specific studies in an attempt to improve outcomes, which currently remain poor. This review summarizes the key studies with antiangiogenic agents, poly(adenosine diphosphate [ADP]-ribose inhibitors, and epidermal growth factor receptor/human epidermal growth factor receptor family targeting, in addition to folate receptor antagonists and insulin growth factor receptor inhibitors. The efficacy of treatment paradigms used in non-ovarian malignancies for type I tumors is also highlighted, in addition to recent advances in appropriate patient stratification for targeted therapies in epithelial ovarian cancer. Keywords: antiangiogenic therapy, high-grade serous, low grade ovarian cancer, PARP inhibition, cancer-related inflammation

An Online Tutorial vs. Pre-Recorded Lecture for Reducing Incidents of Plagiarism

Science.gov (United States)

Henslee, Amber M.; Goldsmith, Jacob; Stone, Nancy J.; Krueger, Merilee

2015-01-01

The current study compared an online academic integrity tutorial modified from Belter & du Pre (2009) to a pre-recorded online academic integrity lecture in reducing incidents of plagiarism among undergraduate students at a science and technology university. Participants were randomized to complete either the tutorial or the pre-recorded…

Psychosemiotics and Libraries: Identifying Signways in Library Informational Guides, Games, and Tutorials

Science.gov (United States)

Laster, Barbara; Blummer, Barbara; Kenton, Jeffrey M.

2010-01-01

Tutorials and digital learning objects provide librarians a quick, concise mechanism for delivering information and training on a wide range of library topics. The semiotic theory promoted by Charles Sanders Peirce (Wiener, 1958) and Howard Smith (2005) contains implications for enhancing the effectiveness of library tutorials through the…

Epithelioid Sarcoma: Opportunities for Biology-Driven Targeted Therapy.

Science.gov (United States)

Noujaim, Jonathan; Thway, Khin; Bajwa, Zia; Bajwa, Ayeza; Maki, Robert G; Jones, Robin L; Keller, Charles

2015-01-01

Epithelioid sarcoma (ES) is a soft tissue sarcoma of children and young adults for which the preferred treatment for localized disease is wide surgical resection. Medical management is to a great extent undefined, and therefore for patients with regional and distal metastases, the development of targeted therapies is greatly desired. In this review, we will summarize clinically relevant biomarkers (e.g., SMARCB1, CA125, dysadherin, and others) with respect to targeted therapeutic opportunities. We will also examine the role of EGFR, mTOR, and polykinase inhibitors (e.g., sunitinib) in the management of local and disseminated disease. Toward building a consortium of pharmaceutical, academic, and non-profit collaborators, we will discuss the state of resources for investigating ES with respect to cell line resources, tissue banks, and registries so that a roadmap can be developed toward effective biology-driven therapies.

Why Targeted Therapies are Necessary for Systemic Lupus Erythematosus

Science.gov (United States)

Durcan, Laura; Petri, Michelle

2016-01-01

Systemic lupus erythematosus (SLE) continues to have important morbidity and accelerated mortality despite therapeutic advances. Targeted therapies offer the possibility of improved efficacy with fewer side-effects. Current management strategies rely heavily on non-specific immunosuppressive agents. Prednisone, in particular, is responsible for a considerable burden of later organ damage. There are a multitude of diverse mechanisms of disease activity, immunogenic abnormalities and clinical manifestations to take into consideration in SLE. Many targeted agents with robust mechanistic pre-clinical data and promising early phase studies have ultimately been disappointing in phase III randomized controlled studies. Recent efforts have focused on B cell therapies, in particular given the success of belimumab in clinical trials, with limited success. We remain optimistic regarding other specific therapies being evaluated including interferon alpha blockade. It is likely that in SLE, given the heterogeneity of the population involved, precision medicine is needed, rather than expecting that any single biologic will be universally effective. PMID:27497251

Transcript for Understanding Medical Words: A Tutorial

Science.gov (United States)

... medlineplus.gov/medicalwordstranscript.html Transcript for Understanding Medical Words: A Tutorial To use the sharing features on ... get to what those mean in a minute. Word Roots Word Roots. Let's begin with body parts. ...

Advances in the targeted therapy of liposarcoma

Directory of Open Access Journals (Sweden)

Guan Z

2015-01-01

Full Text Available Zhonghai Guan,1 Xiongfei Yu,1 Haohao Wang,1 Haiyong Wang,1 Jing Zhang,1 Guangliang Li,2 Jiang Cao,3 Lisong Teng1 1Department of Surgical Oncology, First Affiliated Hospital, College of Medicine, Zhejiang University, 2Department of Medicine Oncology, Zhejiang Cancer Hospital, 3Clinical Research Center, The 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China Abstract: Liposarcoma (LPS is the most common type of soft-tissue sarcoma. Complete surgical resection is the only curative means for localized disease; however, both radiation and conventional cytotoxic chemotherapy remain controversial for metastatic or unresectable disease. An increasing number of trials with novel targeted therapy of LPS have provided encouraging data during recent years. This review will provide an overview of the advances in our understanding of LPS and summarize the results of recent trials with novel therapies targeting different genetic and molecular aberrations for different subtypes of LPS. Keywords: well-/dedifferentiated, myxoid/round cell, pleomorphic, soft-tissue sarcoma

Suicide genes or p53 gene and p53 target genes as targets for cancer gene therapy by ionizing radiation

International Nuclear Information System (INIS)

Liu Bing; Chinese Academy of Sciences, Beijing; Zhang Hong

2005-01-01

Radiotherapy has some disadvantages due to the severe side-effect on the normal tissues at a curative dose of ionizing radiation (IR). Similarly, as a new developing approach, gene therapy also has some disadvantages, such as lack of specificity for tumors, limited expression of therapeutic gene, potential biological risk. To certain extent, above problems would be solved by the suicide genes or p53 gene and its target genes therapies targeted by ionizing radiation. This strategy not only makes up the disadvantage from radiotherapy or gene therapy alone, but also promotes success rate on the base of lower dose. By present, there have been several vectors measuring up to be reaching clinical trials. This review focused on the development of the cancer gene therapy through suicide genes or p53 and its target genes mediated by IR. (authors)

Indico CONFERENCE tutorial

CERN Multimedia

CERN. Geneva; Manzoni, Alex Marc

2017-01-01

This short tutorial explains how to create a CONFERENCE in indico and how to handle abstracts and registration forms, in detail: Timestamps: 1:01 - Programme  2:28 - Call for abstracts  11:50 - Abstract submission  13:41 - Abstract Review 15:41 - The Judge's Role 17:23 - Registration forms' creation 23:34 - Candidate participant's registration/application 25:54 - Customisation of Indico pages - Layout 28:08 - Customisation of Indico pages - Menus 29:47 - Configuring Event reminders and import into calendaring tools   See HERE a recent presentation by Pedro about the above steps in the life of an indico CONFERENCE event.

Cancer gene therapy with targeted adenoviruses.

Science.gov (United States)

Bachtarzi, Houria; Stevenson, Mark; Fisher, Kerry

2008-11-01

Clinical experience with adenovirus vectors has highlighted the need for improved delivery and targeting. This manuscript aims to provide an overview of the techniques currently under development for improving adenovirus delivery to malignant cells in vivo. Primary research articles reporting improvements in adenoviral gene delivery are described. Strategies include genetic modification of viral coat proteins, non-genetic modifications including polymer encapsulation approaches and pharmacological interventions. Reprogramming adenovirus tropism in vitro has been convincingly demonstrated using a range of genetic and physical strategies. These studies have provided new insights into our understanding of virology and the field is progressing. However, there are still some limitations that need special consideration before adenovirus-targeted cancer gene therapy emerges as a routine treatment in the clinical setting.

Solar Tutorial and Annotation Resource (STAR)

Science.gov (United States)

Showalter, C.; Rex, R.; Hurlburt, N. E.; Zita, E. J.

2009-12-01

We have written a software suite designed to facilitate solar data analysis by scientists, students, and the public, anticipating enormous datasets from future instruments. Our “STAR" suite includes an interactive learning section explaining 15 classes of solar events. Users learn software tools that exploit humans’ superior ability (over computers) to identify many events. Annotation tools include time slice generation to quantify loop oscillations, the interpolation of event shapes using natural cubic splines (for loops, sigmoids, and filaments) and closed cubic splines (for coronal holes). Learning these tools in an environment where examples are provided prepares new users to comfortably utilize annotation software with new data. Upon completion of our tutorial, users are presented with media of various solar events and asked to identify and annotate the images, to test their mastery of the system. Goals of the project include public input into the data analysis of very large datasets from future solar satellites, and increased public interest and knowledge about the Sun. In 2010, the Solar Dynamics Observatory (SDO) will be launched into orbit. SDO’s advancements in solar telescope technology will generate a terabyte per day of high-quality data, requiring innovation in data management. While major projects develop automated feature recognition software, so that computers can complete much of the initial event tagging and analysis, still, that software cannot annotate features such as sigmoids, coronal magnetic loops, coronal dimming, etc., due to large amounts of data concentrated in relatively small areas. Previously, solar physicists manually annotated these features, but with the imminent influx of data it is unrealistic to expect specialized researchers to examine every image that computers cannot fully process. A new approach is needed to efficiently process these data. Providing analysis tools and data access to students and the public have proven

Assimilation of contents and learning through the use of video tutorials

Directory of Open Access Journals (Sweden)

David JIMÉNEZ CASTILLO

2013-01-01

Full Text Available The need for a change in the university educational model promoted by the establishment of the European Higher Education Area (EHEA has promoted the implementation of numerous proposals for innovation in university teaching. These innovative practices that are based on a process of reflection and analysis of past teaching experience, are helping to improve qualitatively the teaching practice and, consequently, the learning process and outcomes of students, from a process of reflection and analysis of the teaching experience. In this context, this paper focuses on analyzing a specific teaching tool for innovation, the video tutorial, in order to assess its influence on the processes of assimilation of contents and self-learning. In particular, we attempt to show if the video tutorial allows reinforcing the understanding of practical contents that have been previously given by the classical method of masterly exposition. From the analysis of data obtained through a survey directed to a sample of students after experimenting with the teaching tool, it is shown that the video tutorial is considered a very suitable tool to improve the assimilation capacity of the contents taught previously and to acquire higher learning. After performing a regression analysis, the research also shows that students’ attitudes toward multimedia tools and the perceived utility of video tutorial positively influence these capacities. On the contrary, we find that the attitude towards individual learning and the attention paid by the student to the contents of the video tutorial do not affect the level of learning obtained from this tool.

DNA repair in cancer: emerging targets for personalized therapy

International Nuclear Information System (INIS)

Abbotts, Rachel; Thompson, Nicola; Madhusudan, Srinivasan

2014-01-01

Genomic deoxyribonucleic acid (DNA) is under constant threat from endogenous and exogenous DNA damaging agents. Mammalian cells have evolved highly conserved DNA repair machinery to process DNA damage and maintain genomic integrity. Impaired DNA repair is a major driver for carcinogenesis and could promote aggressive cancer biology. Interestingly, in established tumors, DNA repair activity is required to counteract oxidative DNA damage that is prevalent in the tumor microenvironment. Emerging clinical data provide compelling evidence that overexpression of DNA repair factors may have prognostic and predictive significance in patients. More recently, DNA repair inhibition has emerged as a promising target for anticancer therapy. Synthetic lethality exploits intergene relationships where the loss of function of either of two related genes is nonlethal, but loss of both causes cell death. Exploiting this approach by targeting DNA repair has emerged as a promising strategy for personalized cancer therapy. In the current review, we focus on recent advances with a particular focus on synthetic lethality targeting in cancer

Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer

Science.gov (United States)

2017-12-01

deprivation therapy (ADT) or androgen receptor (AR) pathway inhibition (ARPI) but eventually develops into lethal castration resistance prostate cancer ...AWARD NUMBER: W81XWH-14-1-0553 TITLE: Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer PRINCIPAL INVESTIGATOR: Martin Gleave...Siah2 as Novel Therapy for Metastatic Prostate Cancer 5b. GRANT NUMBER W81XWH-14-1-0553 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Martin Gleave 5d

Tutorial: Digital microfluidic biochips: Towards hardware/software co-design and cyber-physical system integration

DEFF Research Database (Denmark)

Ho, Tsung-Yi; Huang, Juinn-Dar; Pop, Paul

2013-01-01

This tutorial will first provide an overview of typical bio-molecular applications (market drivers) such as immunoassays, DNA sequencing, clinical chemistry, etc. Next, microarrays and various microfluidic platforms will be discussed. The next part of the tutorial will focus on electro-wetting-ba......This tutorial will first provide an overview of typical bio-molecular applications (market drivers) such as immunoassays, DNA sequencing, clinical chemistry, etc. Next, microarrays and various microfluidic platforms will be discussed. The next part of the tutorial will focus on electro......-wetting-based digital micro-fluidic biochips. The key idea here is to manipulate liquids as discrete droplets. A number of case studies based on representative assays and laboratory procedures will be interspersed in appropriate places throughout the tutorial. Basic concepts in micro-fabrication techniques will also...... be discussed. Attendees will next learn about CAD and reconfiguration aspects of digital microfluidic biochips. Synthesis tools will be described to map assay protocols from the lab bench to a droplet-based microfluidic platform and generate an optimized schedule of bioassay operations, the binding of assay...

Erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy

Science.gov (United States)

Zhu, Dao-Ming; Xie, Wei; Xiao, Yu-Sha; Suo, Meng; Zan, Ming-Hui; Liao, Qing-Quan; Hu, Xue-Jia; Chen, Li-Ben; Chen, Bei; Wu, Wen-Tao; Ji, Li-Wei; Huang, Hui-Ming; Guo, Shi-Shang; Zhao, Xing-Zhong; Liu, Quan-Yan; Liu, Wei

2018-02-01

Recently, red blood cell (RBC) membrane-coated nanoparticles have attracted much attention because of their excellent immune escapability; meanwhile, gold nanocages (AuNs) have been extensively used for cancer therapy due to their photothermal effect and drug delivery capability. The combination of the RBC membrane coating and AuNs may provide an effective approach for targeted cancer therapy. However, few reports have shown the utilization of combining these two technologies. Here, we design erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy. First, anti-EpCam antibodies were used to modify the RBC membranes to target 4T1 cancer cells. Second, the antitumor drug paclitaxel (PTX) was encapsulated into AuNs. Then, the AuNs were coated with the modified RBC membranes. These new nanoparticles were termed EpCam-RPAuNs. We characterized the capability of the EpCam-RPAuNs for selective tumor targeting via exposure to near-infrared irradiation. The experimental results demonstrate that EpCam-RPAuNs can effectively generate hyperthermia and precisely deliver the antitumor drug PTX to targeted cells. We also validated the biocompatibility of the EpCam-RAuNs in vitro. By combining the molecularly modified targeting RBC membrane and AuNs, our approach provides a new way to design biomimetic nanoparticles to enhance the surface functionality of nanoparticles. We believe that EpCam-RPAuNs can be potentially applied for cancer diagnoses and therapies.

Individualization of anticancer therapy; molecular targets of novel drugs in oncology

Directory of Open Access Journals (Sweden)

Katarzyna Regulska

2012-11-01

Full Text Available Deregulation of cellular signal transduction, caused by gene mutations, has been recognized as a basic factor of cancer initiation, promotion and progression. Thus, the ability to control the activity of overstimulated signal molecules by the use of appropriate inhibitors became the idea of targeted cancer therapy, which has provided an effective tool to normalize the molecular disorders in malignant cells and to treat certain types of cancer. The molecularly targeted drugs are divided into two major pharmaceutical classes: monoclonal antibodies and small-molecule kinase inhibitors. This review presents a summary of their characteristics, analyzing their chemical structures, specified molecular targets, mechanisms of action and indications for use. Also the molecules subjected to preclinical trials or phase I, II and III clinical trials evaluating their efficiency and safety are presented. Moreover, the article discusses further perspectives for development of targeted therapies focusing on three major directions: systematic searching and discovery of new targets that are oncogenic drivers, improving the pharmacological properties of currently known drugs, and developing strategies to overcome drug resistance. Finally, the role of proper pharmacodiagnostics as a key to rational anticancer therapy has been emphasized since the verification of reliable predictive biomarkers is a basis of individualized medicine in oncology. 

Epithelioid Sarcoma: Opportunities for Biology-driven Targeted Therapy

Directory of Open Access Journals (Sweden)

Jonathan eNoujaim

2015-08-01

Full Text Available Epithelioid sarcoma is a soft tissue sarcoma of children and young adults for which the preferred treatment for localised disease is wide surgical resection. Medical management is to a great extent undefined, and therefore for patients with regional and distal metastases, the development of targeted therapies is greatly desired. In this review we will summarize clinically-relevant biomarkers (e.g., SMARCB1, CA125, dysadherin and others with respect to targeted therapeutic opportunities. We will also examine the role of EGFR, mTOR and polykinase inhibitors (e.g., sunitinib in the management of local and disseminated disease. Towards building a consortium of pharmaceutical, academic and non-profit collaborators, we will discuss the state of resources for investigating epithelioid sarcoma with respect to cell line resources, tissue banks, and registries so that a roadmap can be developed towards effective biology-driven therapies.

Design of a cryogenic deuterium gas target for neutron therapy

International Nuclear Information System (INIS)

Kuchnir, F.T.; Waterman, F.M.; Forsthoff, H.; Skaggs, L.S.; Vander Arend, P.C.; Stoy, S.

1976-01-01

A cryogenic deuterium gas target operating at 80 0 K and 10 atm pressure has been designed for use with a small cyclotron; the D(d,n) reaction is used to produce a neutron beam suitable for radiation therapy. The target is cooled by circulation of the gas in a closed loop between the target and an external heat exchanger immersed in liquid nitrogen

From DIY tutorials to DIY recipes

NARCIS (Netherlands)

Dalton, M.; Desjardins, A.; Wakkary, R.L.

2014-01-01

While online DIY (do-it-yourself) tutorials have increasingly gained interest both at CHI and in the DIY and Maker communities, there is not a lot of research concerning the qualities and drawbacks of the current formats used to share DIY knowledge online. Drawing on our current study of DIY

The Web Lecture Archive Project: Archiving ATLAS Presentations and Tutorials

CERN Multimedia

Herr, J

2004-01-01

The geographical diversity of the ATLAS Collaboration presents constant challenges in the communication between and training of its members. One important example is the need for training of new collaboration members and/or current members on new developments. The Web Lecture Archive Project (WLAP), a joint project between the University of Michigan and CERN Technical Training, has addressed this challenge by recording ATLAS tutorials in the form of streamed "Web Lectures," consisting of synchronized audio, video and high-resolution slides, available on demand to anyone in the world with a Web browser. ATLAS software tutorials recorded by WLAP include ATHENA, ATLANTIS, Monte Carlo event generators, Object Oriented Analysis and Design, GEANT4, and Physics EDM and tools. All ATLAS talks, including both tutorials and meetings are available at http://www.wlap.org/browser.php?ID=atlas. Members of the University of Michigan Physics Department and Media Union, under the framework of the ATLAS Collaboratory Project ...

SFO-Project: The New Generation of Sharable, Editable and Open-Access CFD Tutorials

Science.gov (United States)

Javaherchi, Teymour; Javaherchi, Ardeshir; Aliseda, Alberto

2016-11-01

One of the most common approaches to develop a Computational Fluid Dynamic (CFD) simulation for a new case study of interest is to search for the most similar, previously developed and validated CFD simulation among other works. A simple search would result into a pool of written/visual tutorials. However, users should spend significant amount of time and effort to find the most correct, compatible and valid tutorial in this pool and further modify it toward their simulation of interest. SFO is an open-source project with the core idea of saving the above-mentioned time and effort. This is done via documenting/sharing scientific and methodological approaches to develop CFD simulations for a wide spectrum of fundamental and industrial case studies in three different CFD solvers; STAR-CCM +, FLUENT and Open FOAM (SFO). All of the steps and required files of these tutorials are accessible and editable under the common roof of Github (a web-based Git repository hosting service). In this presentation we will present the current library of 20 + developed CFD tutorials, discuss the idea and benefit of using them, their educational values and explain how the next generation of open-access and live resource of CFD tutorials can be built further hand-in-hand within our community.

Educational Tutorial Video with Aspects of Psychological Sensation and Perception in Academic Achievement

Directory of Open Access Journals (Sweden)

Martha Jiménez García

2015-09-01

Full Text Available In Mexico 75.5% of children and young students in elementary and secondary school are at insufficient and elementary levels in mathematics. The purpose of this research is to join the UNESCO initiative by granting quality education, boosted by technology (Rose, 2013. Specifically, the objective is to analyze the impact of using a tutorial video on academic achievement, based on Gestalt psychology stimulating the sensation and perception cognitive capabilities. Using a 50 student sample was used, which was divided into two groups (experimental and control we test whether students that use a tutorial video based on sensation and perception increase their attention and interest to increase academic achievement. The experimental group was a virtual class with tutorial videos on the use of slopes, explanation of the equation, and a virtual graph generator. Both groups were a survey and an exam. The results show that a high impact on the grades and on the perception of knowledge in the experimental group; the average academic achievement of the experimental group was 9.31, against 2 in the control group. Thus, we conclude that the tutorial video presented stimulates cognitive capabilities and improves academic achievement with a 7.3 impact per additional unit of tutorial video, presented as reinforcement of the class.

Tutorials in endovascular neurosurgery and interventional neuroradiology

International Nuclear Information System (INIS)

Byrne, James Vincent

2012-01-01

This book aims to provide the trainee and practicing minimally invasive neurological therapist with a comprehensive understanding of the background science and theory that forms the foundation of their work. The contents are based on the tutorial teaching techniques used at the University of Oxford and are authored by the MSc Course Director. The tutorial is a learning episode focussed on a particular topic and intended to guide the student/reader through the background literature, to highlight the research on which standard practices are based and to provide the insights of an experienced practitioner. Each chapter of the book covers a different topic to build a complete review of the subspecialty, with in-depth discussion of all currently used techniques. The literature is reviewed and presented in context to illustrate its importance to the practice of this rapidly expanding field of medical treatment.

Tutorials in endovascular neurosurgery and interventional neuroradiology

Energy Technology Data Exchange (ETDEWEB)

Byrne, James Vincent [Univ. of Oxford, Oxford (United Kingdom). Dept. of Neuroradiology

2012-07-01

This book aims to provide the trainee and practicing minimally invasive neurological therapist with a comprehensive understanding of the background science and theory that forms the foundation of their work. The contents are based on the tutorial teaching techniques used at the University of Oxford and are authored by the MSc Course Director. The tutorial is a learning episode focussed on a particular topic and intended to guide the student/reader through the background literature, to highlight the research on which standard practices are based and to provide the insights of an experienced practitioner. Each chapter of the book covers a different topic to build a complete review of the subspecialty, with in-depth discussion of all currently used techniques. The literature is reviewed and presented in context to illustrate its importance to the practice of this rapidly expanding field of medical treatment.

Targeted Alpha Therapy Approach to the Management of Pancreatic Cancer

International Nuclear Information System (INIS)

Allen, Barry J.; Abbas Rizvi, Syed M.; Qu, Chang F.; Smith, Ross C.

2011-01-01

Evidence for the efficacy of targeted alpha therapy for the control of pancreatic cancer in preclinical models is reviewed. Results are given for in vitro pancreatic cancer cells and clusters and micro-metastatic cancer lesions in vivo. Two complementary targeting vectors are examined. These are the C595 monoclonal antibody that targets the MUC1 antigen and the PAI2 ligand that targets the uPA receptor. The expression of the tumor-associated antigen MUC-1 and the uPA receptor on three pancreatic cancer cell lines is reported for cell clusters, human mouse xenografts and lymph node metastases, as well as for human pancreatic cancer tissues, using immuno-histochemistry, confocal microscopy and flow cytometry. The targeting vectors C595 and PAI2 were labeled with the alpha emitting radioisotope 213 Bi using the chelators cDTPA and CHX-A″ to form the alpha-conjugates (AC). Cell clusters were incubated with the AC and examined at 48 hours. Apoptosis was documented using the TUNEL assay. In vivo, the anti-proliferative effect for tumors was tested at two days post-subcutaneous cell inoculation. Mice were injected with different concentrations of AC by local or systemic administration. Changes in tumor progression were assessed by tumor size. MUC-1 and uPA are strongly expressed on CFPAC-1, PANC-1 and moderate expression was found CAPAN-1 cell clusters and tumor xenografts. The ACs can target pancreatic cells and regress cell clusters (∼100 μm diameter), causing apoptosis in some 70–90 % of cells. At two days post-cell inoculation in mice, a single local injection of 74 MBq/kg of AC causes complete inhibition of tumor growth. Systemic injections of 111, 222 and 333 MBq/kg of alpha-conjugate caused significant tumor growth delay in a dose dependent manner after 16 weeks, compared with the non-specific control at 333 MBq/kg. Cytotoxicity was assessed by the MTS and TUNEL assays. The C595 and PAI2-alpha conjugates are indicated for the treatment of micro

Ovarian cancer and the immune system - The role of targeted therapies.

Science.gov (United States)

Turner, Taylor B; Buchsbaum, Donald J; Straughn, J Michael; Randall, Troy D; Arend, Rebecca C

2016-08-01

The majority of patients with epithelial ovarian cancer are diagnosed with advanced disease. While many of these patients will respond initially to chemotherapy, the majority will relapse and die of their disease. Targeted therapies that block or activate specific intracellular signaling pathways have been disappointing. In the past 15years, the role of the immune system in ovarian cancer has been investigated. Patients with a more robust immune response, as documented by the presence of lymphocytes infiltrating within their tumor, have increased survival and better response to chemotherapy. In addition, a strong immunosuppressive environment often accompanies ovarian cancer. Recent research has identified potential therapies that leverage the immune system to identify and destroy tumor cells that previously evaded immunosurveillance mechanisms. In this review, we discuss the role of the immune system in ovarian cancer and focus on specific pathways and molecules that show a potential for targeted therapy. We also review the ongoing clinical trials using targeted immunotherapy in ovarian cancer. The role of targeted immunotherapy in patients with ovarian cancer represents a field of growing research and clinical importance. Copyright © 2016 Elsevier Inc. All rights reserved.

Design and Analysis of simulation experiments : Tutorial

NARCIS (Netherlands)

Kleijnen, J.P.C.

2017-01-01

This tutorial reviews the design and analysis of simulation experiments. These experiments may have various goals: validation, prediction, sensitivity analysis, optimization (possibly robust), and risk or uncertainty analysis. These goals may be realized through metamodels. Two types of metamodels

Understanding the molecular target therapy and it's approved synchronous use with radiation therapy in current Indian oncology practice

International Nuclear Information System (INIS)

Gupta, Puneet; Dohhen, Umesh Kumar; Romana; Srivastava, Priyanka

2012-01-01

The molecular targeted drugs (MTD) are of two types; large and small. The large molecular targeted drugs (LMTD) cannot cross the cancer cell membrane whereas those that cross the cancer cell membrane are nicknamed small molecular target drugs (SMTD). India has availability of almost all MTD originals approved by USA Food and Drug administration. However a few LMTD like inj vectibix, inj Zevalin, Inj Bexar etc.; and SMTD like cap Tipifarnib approved for AML, are not available in India currently although approved and available in USA. The MTD may he used alone as singlet; along with chemotherapy as doublet or triplet; or along with radiation and chemotherapy combo (nicknamed chemo-radiation-bio therapy). The molecular target therapy approved by USA and/or European FDA and currently available in India and used along with radiation therapy with or without chemotherapy, indication wise are; Brain Tumor Inj Nimotuzumab (LMTD) and Inj bevacizumab (LMTD) in Glioblasoma Multiforme; for Carcinoma Head and neck Inj Cetuximab and Inj Nimotuzumab (LMTT), Tab Geftinib (SMTD). (author)

Adverse Renal Effects of Novel Molecular Oncologic Targeted Therapies: A Narrative Review

Directory of Open Access Journals (Sweden)

Kenar D. Jhaveri

2017-01-01

Full Text Available Novel targeted anti-cancer therapies have resulted in improvement in patient survival compared to standard chemotherapy. Renal toxicities of targeted agents are increasingly being recognized. The incidence, severity, and pattern of renal toxicities may vary according to the respective target of the drug. Here we review the adverse renal effects associated with a selection of currently approved targeted cancer therapies, directed to EGFR, HER2, BRAF, MEK, ALK, PD1/PDL1, CTLA-4, and novel agents targeted to VEGF/R and TKIs. In summary, electrolyte disorders, renal impairment and hypertension are the most commonly reported events. Of the novel targeted agents, ipilumumab and cetuximab have the most nephrotoxic events reported. The early diagnosis and prompt recognition of these renal adverse events are essential for the general nephrologist taking care of these patients.

Target Therapies for Uterine Carcinosarcomas: Current Evidence and Future Perspectives

Directory of Open Access Journals (Sweden)

Salvatore Giovanni Vitale

2017-05-01

Full Text Available Carcinosarcomas (CS in gynecology are very infrequent and represent only 2–5% of uterine cancers. Despite surgical cytoreduction and subsequent chemotherapy being the primary treatment for uterine CS, the overall five-year survival rate is 30 ± 9% and recurrence is extremely common (50–80%. Due to the poor prognosis of CS, new strategies have been developed in the last few decades, targeting known dysfunctional molecular pathways for immunotherapy. In this paper, we aimed to gather the available evidence on the latest therapies for the treatment of CS. We performed a systematic review using the terms “uterine carcinosarcoma”, “uterine Malignant Mixed Müllerian Tumors”, “target therapies”, “angiogenesis therapy”, “cancer stem cell therapy”, “prognostic biomarker”, and “novel antibody-drug”. Based on our results, the differential expression and accessibility of epithelial cell adhesion molecule-1 on metastatic/chemotherapy-resistant CS cells in comparison to normal tissues and Human Epidermal Growth Factor Receptor 2 (HER2 open up new possibilities in the field of target therapy. Nevertheless, future investigations are needed to clarify the impact of these new therapies on survival rate and medium-/long-term outcomes.

Targeted radionuclide therapy for solid tumors: An overview

International Nuclear Information System (INIS)

De Nardo, Sally J.; De Nardo, Gerald L.

2006-01-01

Although radioimmunotherapy (RIT) has been effective in non-Hodgkin's lymphoma (NHL) as a single agent, solid tumors have shown less clinically significant therapeutic response to RIT alone. The clinical impact of RIT or other forms of targeted radionuclide therapy for solid tumors depends on the development of a high therapeutic index (TI) for the tumor vs. normal tissue effect, and the implementation of RIT as part of synergistic combined modality therapy (CMRIT). Preclinical and clinical studies have provided a wealth of information, and new prototypes or paradigms have shed light on future possibilities in many instances. Evidence suggests that combination and sequencing of RIT in CMRIT appropriately can provide effective treatment for many solid tumors. Vascular targets provide RIT enhancement opportunities and nanoparticles may prove to be effective carriers for RIT combined with intracellular drug delivery or alternating magnetic frequency (AMF) induced thermal tumor necrosis. The sequence and timing of combined modality treatments will be of critical importance to achieve synergy for therapy while minimizing toxicity. Fortunately, the radionuclide used for RIT also provides a signal useful for nondestructive quantitation of the influence of sequence and timing of CMRIT on events in animals and patients. This can be readily accomplished clinically using quantitative high-resolution imaging (e.g., positron emission tomography [PET])

A Pilot Evaluation of a Tutorial to Teach Clients and Clinicians About Gambling Game Design.

Science.gov (United States)

Turner, Nigel E; Robinson, Janine; Harrigan, Kevin; Ferentzy, Peter; Jindani, Farah

2018-01-01

This paper describes the pilot evaluation of an Internet-based intervention, designed to teach counselors and problem gamblers about how electronic gambling machines (EGMs) work. This study evaluated the tutorial using assessment tools, such as rating scales and test of knowledge about EGMs and random chance. The study results are based on a number of samples, including problem gambling counselors ( n  = 25) and problem gamblers ( n  = 26). The interactive tutorial was positively rated by both clients and counselors. In addition, we found a significant improvement in scores on a content test about EGM games for both clients and counselors. An analysis of the specific items suggests that the effects of the tutorial were mainly on those items that were most directly related to the content of the tutorial and did not always generalize to other items. This tutorial is available for use with clients and for education counselors. The data also suggest that the tutorial is equally effective in group settings and in individual settings. These results are promising and illustrate that the tool can be used to teach counselors and clients about game design. Furthermore, research is needed to evaluate its impact on gambling behavior.

Radionuclide molecular target therapy for lung cancer

International Nuclear Information System (INIS)

Zhang Fuhai; Meng Zhaowei; Tan Jian

2012-01-01

Lung cancer harms people's health or even lives severely. Currently, the morbidity and mortality of lung cancer are ascending all over the world. Accounting for 38.08% of malignant tumor caused death in male and 16% in female in cities,ranking top in both sex. Especially, the therapy of non-small cell lung cancer has not been obviously improved for many years. Recently, sodium/iodide transporter gene transfection and the therapy of molecular target drugs mediated radionuclide are being taken into account and become the new research directions in treatment of advanced lung cancer patients with the development of technology and theory for medical molecular biology and the new knowledge of lung cancer's pathogenesis. (authors)

Interaction Patterns in Synchronous Chinese Tutorials

Science.gov (United States)

Shi, Lijing; Stickler, Ursula

2018-01-01

Speaking in Chinese is problematic for all learners, particularly for beginners and more so during online interaction. Despite the fact that interaction has been identified as crucial for the development of speaking skills, it can be hindered by students' lack of language competence or their anxiety. Teacher-centred practices in tutorials can…

TRAIL, Wnt, Sonic Hedgehog, TGFβ, and miRNA Signalings Are Potential Targets for Oral Cancer Therapy.

Science.gov (United States)

Farooqi, Ammad Ahmad; Shu, Chih-Wen; Huang, Hurng-Wern; Wang, Hui-Ru; Chang, Yung-Ting; Fayyaz, Sundas; Yuan, Shyng-Shiou F; Tang, Jen-Yang; Chang, Hsueh-Wei

2017-07-14

Clinical studies and cancer cell models emphasize the importance of targeting therapies for oral cancer. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is highly expressed in cancer, and is a selective killing ligand for oral cancer. Signaling proteins in the wingless-type mouse mammary tumor virus (MMTV) integration site family (Wnt), Sonic hedgehog (SHH), and transforming growth factor β (TGFβ) pathways may regulate cell proliferation, migration, and apoptosis. Accordingly, the genes encoding these signaling proteins are potential targets for oral cancer therapy. In this review, we focus on recent advances in targeting therapies for oral cancer and discuss the gene targets within TRAIL, Wnt, SHH, and TGFβ signaling for oral cancer therapies. Oncogenic microRNAs (miRNAs) and tumor suppressor miRNAs targeting the genes encoding these signaling proteins are summarized, and the interactions between Wnt, SHH, TGFβ, and miRNAs are interpreted. With suitable combination treatments, synergistic effects are expected to improve targeting therapies for oral cancer.

TRAIL, Wnt, Sonic Hedgehog, TGFβ, and miRNA Signalings Are Potential Targets for Oral Cancer Therapy

Science.gov (United States)

Farooqi, Ammad Ahmad; Shu, Chih-Wen; Huang, Hurng-Wern; Wang, Hui-Ru; Chang, Yung-Ting; Fayyaz, Sundas; Yuan, Shyng-Shiou F.; Tang, Jen-Yang

2017-01-01

Clinical studies and cancer cell models emphasize the importance of targeting therapies for oral cancer. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is highly expressed in cancer, and is a selective killing ligand for oral cancer. Signaling proteins in the wingless-type mouse mammary tumor virus (MMTV) integration site family (Wnt), Sonic hedgehog (SHH), and transforming growth factor β (TGFβ) pathways may regulate cell proliferation, migration, and apoptosis. Accordingly, the genes encoding these signaling proteins are potential targets for oral cancer therapy. In this review, we focus on recent advances in targeting therapies for oral cancer and discuss the gene targets within TRAIL, Wnt, SHH, and TGFβ signaling for oral cancer therapies. Oncogenic microRNAs (miRNAs) and tumor suppressor miRNAs targeting the genes encoding these signaling proteins are summarized, and the interactions between Wnt, SHH, TGFβ, and miRNAs are interpreted. With suitable combination treatments, synergistic effects are expected to improve targeting therapies for oral cancer. PMID:28708091

Recent advances in targeted drug therapy for hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

FAN Yongqiang

2018-02-01

Full Text Available More and more clinical trials have proved the efficacy of targeted drugs in the treatment of hepatocellular carcinoma (HCC. With the development of science and technology, more and more targeted drugs have appeared. In recent years, targeted drugs such as regorafenib and ramucirumab have shown great potential in related clinical trials. In addition, there are ongoing clinical trials for second-line candidate drugs, such as c-Met inhibitors tivantinib and cabozantinib and a VEGFR-2 inhibitor ramucirumab. This article summarizes the advances in targeted drug therapy for HCC and related trial data, which provides a reference for further clinical trials and treatment.

Interactive Intragroup Tutorials: A Need-Based Modification to Enhance Learning in Physiology

Science.gov (United States)

Srivastava, Tripti K.; Waghmare, Lalitbhushan S.; Jagzape, Arunita; Mishra, Vedprakash

2015-01-01

A tutorial is a period of instruction given by a university or college tutor to an individual or a very small group. Essentially, it is a small class of a few students in which the tutor (a lecturer or other academic staff member) gives individual attention to every learner. The tutorial focuses on certain subject areas and generally proceeds with…

Tutorial on Online Partial Evaluation

Directory of Open Access Journals (Sweden)

William R. Cook

2011-09-01

Full Text Available This paper is a short tutorial introduction to online partial evaluation. We show how to write a simple online partial evaluator for a simple, pure, first-order, functional programming language. In particular, we show that the partial evaluator can be derived as a variation on a compositionally defined interpreter. We demonstrate the use of the resulting partial evaluator for program optimization in the context of model-driven development.

Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia

Science.gov (United States)

Satake, Noriko; Lee, Joyce; Xiao, Kai; Luo, Juntao; Sarangi, Susmita; Chang, Astra; McLaughlin, Bridget; Zhou, Ping; Kenney, Elaina; Kraynov, Liliya; Arnott, Sarah; McGee, Jeannine; Nolta, Jan; Lam, Kit

2011-06-01

The goal of our project is to develop a unique ligand-conjugated nanoparticle (NP) therapy against childhood acute lymphoblastic leukemia (ALL). LLP2A, discovered by Dr. Kit Lam, is a high-affinity and high-specificity peptidomimetic ligand against an activated α4β1 integrin. Our study using 11 fresh primary ALL samples (10 precursor B ALL and 1 T ALL) showed that childhood ALL cells expressed activated α4β1 integrin and bound to LLP2A. Normal hematopoietic cells such as activated lymphocytes and monocytes expressed activated α4β1 integrin; however, normal hematopoietic stem cells showed low expression of α4β1 integrin. Therefore, we believe that LLP2A can be used as a targeted therapy for childhood ALL. The Lam lab has developed novel telodendrimer-based nanoparticles (NPs) which can carry drugs efficiently. We have also developed a human leukemia mouse model using immunodeficient NOD/SCID/IL2Rγ null mice engrafted with primary childhood ALL cells from our patients. LLP2A-conjugated NPs will be evaluated both in vitro and in vivo using primary leukemia cells and this mouse model. NPs will be loaded first with DiD near infra-red dye, and then with the chemotherapeutic agents daunorubicin or vincristine. Both drugs are mainstays of current chemotherapy for childhood ALL. Targeting properties of LLP2A-conjugated NPs will be evaluated by fluorescent microscopy, flow cytometry, MTS assay, and mouse survival after treatment. We expect that LLP2A-conjugated NPs will be preferentially delivered and endocytosed to leukemia cells as an effective targeted therapy.

IMPLEMENTASI MODEL TUTORIAL BERBASIS KOMPUTER FISIOLOGI HEWAN UNTUK MEMBEKALI KEMAMPUAN REKONSTRUKSI KONSEP MAHASISWA CALON GURU BIOLOGI

Directory of Open Access Journals (Sweden)

Adeng Slamet

2015-03-01

Full Text Available Penelitian ini bertujuan untuk membandingkan model perkuliahan fisiologi hewan yang diharapkan mampu membekali kemampuan rekonstruksi konsep bagi mahasiswa calon guru biologi. Strategi perkuliahan ditempuh melalui implementasi model tutorial berbasis komputer. Sebanyak 80 orang mahasiswa S1 calon guru biologi dibagi ke dalam dua kelompok, 41 mahasiswa mengikuti perkuliahan model tutorial komputer, dan 39 mahasiswa mengikuti perkuliahan konvensional. Kemampuan rekonstruksi konsep diukur dengan membandingkan skor sebelum pembelajaran (pretes dengan setelah implementasi model (postes di antara kedua kelompok belajar. Selain itu, untuk mengungkap pandangan mahasiswa mengenai pengalaman belajarnya, seperangkat angket disebarkan kepada mahasiswa yang mengikuti model perkuliahan.  Efektivitas program perkuliahan dievaluasi dengan tes tertulis bentuk respon terbatas pada mahasiswa yang mengikuti program perkuliahan model tutorial komputer dibandingkan dengan mahasiswa dari kelompok konvensional. Hasil penelitian menunjukkan secara keseluruhan terjadi peningkatan  kemampuan rekonstruksi konsep pada kedua kelompok belajar, namun mahasiswa yang mengikuti perkuliahan model tutorial berbasis komputer menunjukkan peningkatan yang lebih tinggi dibandingkan kelompok mahasiswa peserta perkuliahan konvensional. Mahasiswa menanggapi positif implementasi model tutorial berbasis komputer dalam perkuliahan fisiologi hewan. Dapat disimpulkan bahwa penerapan model tutorial berbasis komputer pada penelitian ini dinyatakan lebih efektif dan mampu  membekali mahasiwa calon guru biologi dalam meningkatkan kemampuan  rekonstruksi konsep.

Assessing the Effectiveness of Web-Based Tutorials Using Pre-and Post-Test Measurements

Science.gov (United States)

Guy, Retta Sweat; Lownes-Jackson, Millicent

2012-01-01

Computer technology in general and the Internet in particular have facilitated as well as motivated the development of Web-based tutorials (MacKinnon & Williams, 2006). The current research study describes a pedagogical approach that exploits the use of self-paced, Web-based tutorials for assisting students with reviewing grammar and mechanics…

Non-small cell lung cancer: the era of targeted therapy

Directory of Open Access Journals (Sweden)

Antonoff MB

2012-07-01

Full Text Available Mara B Antonoff, Jonathan D'CunhaDivision of Thoracic and Foregut Surgery, Department of Surgery, University of Minnesota, Minneapolis, MN, USAAbstract: In this review, the authors aim to provide an overview of current molecular targeted therapies for NSCLC, to propose an algorithm for clinical application of presently available treatment strategies, and to identify future directions for this important area of research. Historically, choice of treatment algorithm for the management of non-small cell lung cancer (NSCLC has relied heavily upon histology and clinical staging information, typically assigning patients to surgery, chemotherapy, radiation, or a combination thereof. However, previous treatment strategies have been fraught with disappointing response rates and significant systemic toxicities. The concept of personalized therapy for NSCLC involves characterization of each individual patient's tumor, in terms of genetic aberrations and expected biologic behavior, and using this information to tailor subsequent clinical management. Several driver mutations have been identified to date in subsets of patients with NSCLC, and, by focusing on specific molecular targets, new agents have been developed with the intent of treating the cancer cells while causing minimal toxicity to benign, healthy cells. In particular, current strategies exist to identify patients with epidermal growth factor receptor gene mutations and anaplastic lymphoma kinase rearrangements, with promising results upon clinical application of agents targeting these abnormalities. Moving forward, attempts are being made to determine comprehensive genetic and biologic characterization of individuals' NSCLC tumors and to incorporate these findings into everyday practice. The era of targeted therapy is upon us. As we seek to expand our knowledge of the specific molecular and cellular derangements leading to growth and proliferation of NSCLC tumors, our efforts bring us closer to

The effectiveness of web-based, multimedia tutorials for teaching methods of human body composition analysis.

Science.gov (United States)

Buzzell, Paul R; Chamberlain, Valerie M; Pintauro, Stephen J

2002-12-01

This study examined the effectiveness of a series of Web-based, multimedia tutorials on methods of human body composition analysis. Tutorials were developed around four body composition topics: hydrodensitometry (underwater weighing), dual-energy X-ray absorptiometry, bioelectrical impedance analysis, and total body electrical conductivity. Thirty-two students enrolled in the course were randomly assigned to learn the material through either the Web-based tutorials only ("Computer"), a traditional lecture format ("Lecture"), or lectures supplemented with Web-based tutorials ("Both"). All students were administered a validated pretest before randomization and an identical posttest at the completion of the course. The reliability of the test was 0.84. The mean score changes from pretest to posttest were not significantly different among the groups (65.4 plus minus 17.31, 78.82 plus minus 21.50, and 76 plus minus 21.22 for the Computer, Both, and Lecture groups, respectively). Additionally, a Likert-type assessment found equally positive attitudes toward all three formats. The results indicate that Web-based tutorials are as effective as the traditional lecture format for teaching these topics.

Engineering liposomal nanoparticles for targeted gene therapy.

Science.gov (United States)

Zylberberg, C; Gaskill, K; Pasley, S; Matosevic, S

2017-08-01

Recent mechanistic studies have attempted to deepen our understanding of the process by which liposome-mediated delivery of genetic material occurs. Understanding the interactions between lipid nanoparticles and cells is still largely elusive. Liposome-mediated delivery of genetic material faces systemic obstacles alongside entry into the cell, endosomal escape, lysosomal degradation and nuclear uptake. Rational design approaches for targeted delivery have been developed to reduce off-target effects and enhance transfection. These strategies, which have included the modification of lipid nanoparticles with target-specific ligands to enhance intracellular uptake, have shown significant promise at the proof-of-concept stage. Control of physical and chemical specifications of liposome composition, which includes lipid-to-DNA charge, size, presence of ester bonds, chain length and nature of ligand complexation, is integral to the performance of targeted liposomes as genetic delivery agents. Clinical advances are expected to rely on such systems in the therapeutic application of liposome nanoparticle-based gene therapy. Here, we discuss the latest breakthroughs in the development of targeted liposome-based agents for the delivery of genetic material, paying particular attention to new ligand and cationic lipid design as well as recent in vivo advances.

Stem cells’ guided gene therapy of cancer: New frontier in personalized and targeted therapy

Directory of Open Access Journals (Sweden)

Mavroudi M

2014-01-01

Full Text Available Diagnosis and therapy of cancer remain to be the greatest challenges for all physicians working in clinical oncology and molecular medicine. The grim statistics speak for themselves with reports of 1,638,910 men and women diagnosed with cancer and nearly 577,190 patients passed away due to cancer in the USA in 2012. For practicing clinicians, who treat patients suffering from advanced cancers with contemporary systemic therapies, the main challenge is to attain therapeutic efficacy, while minimizing side effects. Unfortunately, all contemporary systemic therapies cause side effects. In treated patients, these side effects may range from nausea to damaged tissues. In cancer survivors, the iatrogenic outcomes of systemic therapies may include genomic mutations and their consequences. Therefore, there is an urgent need for personalized and targeted therapies. Recently, we reviewed the current status of suicide gene therapy for cancer. Herein, we discuss the novel strategy: genetically engineered stem guided gene therapy. Stem cells have the unique potential for self-renewal and differentiation. This potential is the primary reason for introducing them into medicine to regenerate injured or degenerated organs, as well as to rejuvenate aging tissues. Recent advances in genetic engineering and stem cell research have created the foundations for genetic engineering of stem cells as the vectors for delivery of therapeutic transgenes. Specifically in oncology, the stem cells are genetically engineered to deliver the cell suicide inducing genes selectively to the cancer cells. Expression of the transgenes kills the cancer cells, while leaving healthy cells unaffected. Herein, we present various strategies to bioengineer suicide inducing genes and stem cell vectors. Moreover, we review results of the main preclinical studies and clinical trials. However, the main risk for therapeutic use of stem cells is their cancerous transformation. Therefore, we

You Tube Video Genres. Amateur how-to Videos Versus Professional Tutorials

OpenAIRE

Andreea Mogoș; Constantin Trofin

2015-01-01

In spite of the fact that there is a vast literature on traditional textual and visual genre classifications, the categorization of web content is still a difficult task, because this medium is fluid, unstable and fast-paced on one hand and, on the other hand, the genre classifications are socially constructed through the tagging process and the interactions (commenting, rating, chatting). This paper focuses on YouTube tutorials and aims to compare video tutorials produced by professionals wi...

A view on EGFR-targeted therapies from the oncogene-addiction perspective.

Science.gov (United States)

Perez, Rolando; Crombet, Tania; de Leon, Joel; Moreno, Ernesto

2013-01-01

Tumor cell growth and survival can often be impaired by inactivating a single oncogen- a phenomenon that has been called as "oncogene addiction." It is in such scenarios that molecular targeted therapies may succeed. among known oncogenes, the epidermal growth factor receptor (EGFR) has become the target of different cancer therapies. So far, however, the clinical benefit from EGFR-targeted therapies has been rather limited. a critical review of the large amount of clinical data obtained with anti-EGFR agents, carried out from the perspective of the oncogene addiction concept, may help to understand the causes of the unsatisfactory results. In this article we intend to do such an exercise taking as basis for the analysis a few case studies of anti-EGFR agents that are currently in the clinic. There, the "EGFR addiction" phenomenon becomes apparent in high-responder patients. We further discuss how the concept of oncogene addiction needs to be interpreted on the light of emerging experimental evidences and ideas; in particular, that EGFR addiction may reflect the interconnection of several cellular pathways. In this regard we set forth several hypotheses; namely, that requirement of higher glucose uptake by hypoxic tumor cells may reinforce EGFR addiction; and that chronic use of EGFR-targeted antibodies in EGFR-addicted tumors would induce stable disease by reversing the malignant phenotype of cancer stem cells and also by sustaining an anti-tumor T cell response. Finally, we discuss possible reasons for the failure of certain combinatorial therapies involving anti-EGFR agents, arguing that some of these agents might produce either a negative or a positive trans-modulation effect on other oncogenes. It becomes evident that we need operational definitions of EGFR addiction in order to determine which patient populations may benefit from treatment with anti-EGFR drugs, and to improve the design of these therapies.

A view on EGFR-targeted therapies from the oncogene-addiction perspective

Directory of Open Access Journals (Sweden)

Rolando ePerez

2013-04-01

Full Text Available Tumor cell growth and survival can often be impaired by inactivating a single oncogen – a phenomenon that has been called as 'oncogene addiction'. It is in such scenarios that molecular targeted therapies may succeed. Among known oncogenes, the epidermal growth factor receptor (EGFR has become the target of different cancer therapies. So far, however, the clinical benefit from EGFR-targeted therapies has been rather limited. A critical review of the large amount of clinical data obtained with anti-EGFR agents, carried out from the perspective of the oncogene addiction concept, may help to understand the causes of the unsatisfactory results. In this article we intend to do such an exercise taking as basis for the analysis a few case studies of anti-EGFR agents that are currently in the clinic. There, the 'EGFR addiction' phenomenon becomes apparent in high-responder patients. We further discuss how the concept of oncogene addiction needs to be interpreted on the light of emerging experimental evidences and ideas; in particular, that EGFR addiction may reflect the interconnection of several cellular pathways. In this regard we set forth several hypotheses; namely, that requirement of higher glucose uptake by hypoxic tumor cells may reinforce EGFR addiction; and that chronic use of EGFR-targeted antibodies in EGFR-addicted tumors would induce stable disease by reversing the malignant phenotype of cancer stem cells and also by sustaining an anti-tumor T cell response. Finally, we discuss possible reasons for the failure of certain combinatorial therapies involving anti-EGFR agents, arguing that some of these agents might produce either a negative or a positive trans-modulation effect on other oncogenes. It becomes evident that we need operational definitions of EGFR addiction in order to determine which patient populations may benefit from treatment with anti-EGFR drugs, and to improve the design of these therapies.

Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy

Directory of Open Access Journals (Sweden)

Han-Chung Wu

2010-01-01

Full Text Available Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

Energy Technology Data Exchange (ETDEWEB)

Fillat, Cristina, E-mail: cristina.fillat@crg.es; Jose, Anabel; Ros, Xavier Bofill-De; Mato-Berciano, Ana; Maliandi, Maria Victoria; Sobrevals, Luciano [Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG, UPF, Parc de Recerca Biomedica de Barcelona-PRBB and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona (Spain)

2011-01-18

The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

Translational research: precision medicine, personalized medicine, targeted therapies: marketing or science?

Science.gov (United States)

Marquet, Pierre; Longeray, Pierre-Henry; Barlesi, Fabrice; Ameye, Véronique; Augé, Pascale; Cazeneuve, Béatrice; Chatelut, Etienne; Diaz, Isabelle; Diviné, Marine; Froguel, Philippe; Goni, Sylvia; Gueyffier, François; Hoog-Labouret, Natalie; Mourah, Samia; Morin-Surroca, Michèle; Perche, Olivier; Perin-Dureau, Florent; Pigeon, Martine; Tisseau, Anne; Verstuyft, Céline

2015-01-01

Personalized medicine is based on: 1) improved clinical or non-clinical methods (including biomarkers) for a more discriminating and precise diagnosis of diseases; 2) targeted therapies of the choice or the best drug for each patient among those available; 3) dose adjustment methods to optimize the benefit-risk ratio of the drugs chosen; 4) biomarkers of efficacy, toxicity, treatment discontinuation, relapse, etc. Unfortunately, it is still too often a theoretical concept because of the lack of convenient diagnostic methods or treatments, particularly of drugs corresponding to each subtype of pathology, hence to each patient. Stratified medicine is a component of personalized medicine employing biomarkers and companion diagnostics to target the patients likely to present the best benefit-risk balance for a given active compound. The concept of targeted therapy, mostly used in cancer treatment, relies on the existence of a defined molecular target, involved or not in the pathological process, and/or on the existence of a biomarker able to identify the target population, which should logically be small as compared to the population presenting the disease considered. Targeted therapies and biomarkers represent important stakes for the pharmaceutical industry, in terms of market access, of return on investment and of image among the prescribers. At the same time, they probably represent only the first generation of products resulting from the combination of clinical, pathophysiological and molecular research, i.e. of translational research. © 2015 Société Française de Pharmacologie et de Thérapeutique.

Targeted therapy in lung and breast cancer: a big deal

OpenAIRE

Caffarra, Cristina

2015-01-01

Great strides have been done in treating cancer. For decades, the hallmark of medical treatment for cancer has been intravenous cytotoxic chemotherapy which targets all dividing cells. In the last ten years the identification of different driver oncogenic mutations has allowed the development of targeted drugs. Targeted cancer therapies are based on the use of drugs that block the growth and spread of cancer by interfering with specific molecules involved in tumor growth and progression. The ...

Targeted Therapies in Hematology and Their Impact on Patient Care: Chronic and Acute Myeloid Leukemia

Science.gov (United States)

Cortes, Elias Jabbour Jorge; Ravandi, Farhad; O’Brien, Susan; Kantarjian, Hagop

2014-01-01

Advances in the genetic and molecular characterizations of leukemias have enhanced our capabilities to develop targeted therapies. The most dramatic examples of targeted therapy in cancer to date are the use of targeted BCR-ABL protein tyrosine kinase inhibitors (TKI) which has revolutionized the treatment of chronic myeloid leukemia (CML). Inhibition of the signaling activity of this kinase has proved to be a highly successful treatment target, transforming the prognosis of patients with CML. In contrast, acute myeloid leukemia (AML) is an extremely heterogeneous disease with outcomes that vary widely according to subtype of the disease. Targeted therapy with monoclonal antibodies and small molecule kinase inhibitors are promising strategies to help improve the cure rates in AML. In this review, we will highlight the results of recent clinical trials in which outcomes of CML and AML have been influenced significantly. Also, novel approaches to sequencing and combining available therapies will be covered. PMID:24246694

Colorectal cancer heterogeneity and targeted therapy: a case for molecular disease subtypes

NARCIS (Netherlands)

Linnekamp, Janneke F.; Wang, Xin; Medema, Jan Paul; Vermeulen, Louis

2015-01-01

Personalized cancer medicine is becoming increasingly important in colorectal cancer treatment. Especially for targeted therapies, large variations between individual treatment responses exist. Predicting therapy response is of utmost significance, as it prevents overtreatment and adverse effects in

Targeted Therapy of Cancer Using Photodynamic Therapy in Combination with Multi-faceted Anti-Tumor Modalities

Directory of Open Access Journals (Sweden)

Malini Olivo

2010-05-01

Full Text Available Photodynamic therapy (PDT has emerged as one of the important therapeutic options in the management of cancer and other diseases. PDT involves a tumor-localized photosensitizer (PS, which when appropriately illuminated by visible light converts oxygen into cytotoxic reactive oxygen species (ROS, that attack key structural entities within the targeted cells, ultimately resulting in necrosis or apoptosis. Though PDT is a selective modality, it can be further enhanced by combining other targeted therapeutic strategies that include the use of synthetic peptides and nanoparticles for selective delivery of photosensitizers. Another potentially promising strategy is the application of targeted therapeutics that exploit a myriad of critical pathways involved in tumorigenesis and metastasis. Vascular disrupting agents that eradicate tumor vasculature during PDT and anti-angiogenic agents that targets specific molecular pathways and prevent the formation of new blood vessels are novel therapeutic approaches that have been shown to improve treatment outcome. In addition to the well-documented mechanisms of direct cell killing and damage to the tumor vasculature, PDT can also activate the body’s immune response against tumors. Numerous pre-clinical studies and clinical observations have demonstrated the immuno-stimulatory capability of PDT. Herein, we aim to integrate the most important findings with regard to the combination of PDT and other novel targeted therapy approaches, detailing its potential in cancer photomedicine.

Targeted Gene Therapy of Cancer: Second Amendment toward Holistic Therapy.

Science.gov (United States)

Barar, Jaleh; Omidi, Yadollah

2013-01-01

It seems solid tumors are developing smart organs with specialized cells creating specified bio-territory, the so called "tumor microenvironment (TME)", in which there is reciprocal crosstalk among cancer cells, immune system cells and stromal cells. TME as an intricate milieu also consists of cancer stem cells (CSCs) that can resist against chemotherapies. In solid tumors, metabolism and vascularization appears to be aberrant and tumor interstitial fluid (TIF) functions as physiologic barrier. Thus, chemotherapy, immunotherapy and gene therapy often fail to provide cogent clinical outcomes. It looms that it is the time to accept the fact that initiation of cancer could be generation of another form of life that involves a cluster of thousands of genes, while we have failed to observe all aspects of it. Hence, the current treatment modalities need to be re-visited to cover all key aspects of disease using combination therapy based on the condition of patients. Perhaps personalized cluster of genes need to be simultaneously targeted.

Targeted Gene Therapy of Cancer: Second Amendment toward Holistic Therapy

Directory of Open Access Journals (Sweden)

Jaleh Barar

2013-02-01

Full Text Available It seems solid tumors are developing smart organs with specialized cells creating specified bio-territory, the so called “tumor microenvironment (TME”, in which there is reciprocal crosstalk among cancer cells, immune system cells and stromal cells. TME as an intricate milieu also consists of cancer stem cells (CSCs that can resist against chemotherapies. In solid tumors, metabolism and vascularization appears to be aberrant and tumor interstitial fluid (TIF functions as physiologic barrier. Thus, chemotherapy, immunotherapy and gene therapy often fail to provide cogent clinical outcomes. It looms that it is the time to accept the fact that initiation of cancer could be generation of another form of life that involves a cluster of thousands of genes, while we have failed to observe all aspects of it. Hence, the current treatment modalities need to be re-visited to cover all key aspects of disease using combination therapy based on the condition of patients. Perhaps personalized cluster of genes need to be simultaneously targeted.

Systemic sclerosis and localized scleroderma--current concepts and novel targets for therapy.

Science.gov (United States)

Distler, Oliver; Cozzio, Antonio

2016-01-01

Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Skin and organ fibrosis are key manifestations of SSc, for which no generally accepted therapy is available. Thus, there is a high unmet need for novel anti-fibrotic therapeutic strategies in SSc. At the same time, important progress has been made in the identification and characterization of potential molecular targets in fibrotic diseases over the recent years. In this review, we have selected four targeted therapies, which are tested in clinical trials in SSc, for in depths discussion of their preclinical characterization. Soluble guanylate cyclase (sGC) stimulators such as riociguat might target both vascular remodeling and tissue fibrosis. Blockade of interleukin-6 might be particularly promising for early inflammatory stages of SSc. Inhibition of serotonin receptor 2b signaling links platelet activation to tissue fibrosis. Targeting simultaneously multiple key molecules with the multityrosine kinase-inhibitor nintedanib might be a promising approach in complex fibrotic diseases such as SSc, in which many partially independent pathways are activated. Herein, we also give a state of the art overview of the current classification, clinical presentation, diagnostic approach, and treatment options of localized scleroderma. Finally, we discuss whether the novel targeted therapies currently tested in SSc could be used for localized scleroderma.

IGF1 Receptor Targeted Theranostic Nanoparticles for Targeted and Image-Guided Therapy of Pancreatic Cancer.

Science.gov (United States)

Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M; Wang, Liya; Wang, Y Andrew; Chen, Hongyu; Kooby, David; Yu, Qian; Lipowska, Malgorzata; Staley, Charles A; Mao, Hui; Yang, Lily

2015-08-25

Overcoming resistance to chemotherapy is a major and unmet medical challenge in the treatment of pancreatic cancer. Poor drug delivery due to stromal barriers in the tumor microenvironment and aggressive tumor biology are additional impediments toward a more successful treatment of pancreatic cancer. In attempts to address these challenges, we developed IGF1 receptor (IGF1R)-directed, multifunctional theranostic nanoparticles for targeted delivery of therapeutic agents into IGF1R-expressing drug-resistant tumor cells and tumor-associated stromal cells. These nanoparticles were prepared by conjugating recombinant human IGF1 to magnetic iron oxide nanoparticles (IONPs) carrying the anthracycline doxorubicin (Dox) as the chemotherapeutic payload. Intravenously administered IGF1-IONPs exhibited excellent tumor targeting and penetration in an orthotopic patient-derived xenograft (PDX) model of pancreatic cancer featuring enriched tumor stroma and heterogeneous cancer cells. IGF1R-targeted therapy using the theranostic IGF1-IONP-Dox significantly inhibited the growth of pancreatic PDX tumors. The effects of the intratumoral nanoparticle delivery and therapeutic responses in the orthotopic pancreatic PDX tumors could be detected by magnetic resonance imaging (MRI) with IONP-induced contrasts. Histological analysis showed that IGF1R-targeted delivery of Dox significantly inhibited cell proliferation and induced apoptotic cell death of pancreatic cancer cells. Therefore, further development of IGF1R-targeted theranostic IONPs and MRI-guided cancer therapy as a precision nanomedicine may provide the basis for more effective treatment of pancreatic cancer.

Introduction to OAI and harvesting, tutorial 3

CERN Multimedia

CERN. Geneva

2005-01-01

1. Coverage: - Overview of key Open Archives Initiative (OAI) concepts. - Development of the OAI Protocol for Metadata Harvesting (OAI-PMH). - Non-technical introduction to main underlying technical ideas. - Some considerations regarding implementation of OAI-PMH, with particular focus on harvesting issues. For those who would like an introduction to, or revision of, the main concepts associated with OAI then this session will provide an ideal foundation for the rest of the OAI4 workshop. 2. Audience: Decision-makers, Managers, Technical staff with no previous OAI-PMH knowledge. This is a tutorial for those who may not themselves do hands-on technical implementation, but might make or advise on decisions whether or not to implement particular solutions. They may have staff who are implementers, or may work with them. Technical staff are likely to prefer the technical tutorials, but may want to attend this one if they are at the very early stage of simply requiring background information. 3. At the end of the ...

Using Visual Assessments and Tutorials to Teach Solar System Concepts in Introductory Astronomy

Science.gov (United States)

LoPresto, Michael C.

2010-01-01

Visual assessments and tutorials are instruments that rely on student construction and/or examination of pictures and/or diagrams rather than multiple choice and/or short answer questions. Being a very visual subject, astronomy lends itself to assessments and tutorials of this type. What follows is a report on the results of the use of visual…

L'ajuda tutorial en els MOOCs: un nou enfocament en l'acció tutorial

Directory of Open Access Journals (Sweden)

Rosario Medina-Salguero

2013-12-01

Full Text Available En el present treball s'expon un analisis de l'accio tutorial en una nova modalitat d'ensenyança-aprenentage, els MOOCS. Per a açò, hem portat a veta un estudi de material documental que permet reconstruir els acontenyiments que estan succeint en l'actualitat en els MOOCS. Els resultats mos indiquen com se configura esta nova tendencia d'aprenentage a nivell internacional i nacional i com s'establix l'ajuda pedagogica en els MOOCS.

Tutorial: Speech Assessment for Multilingual Children Who Do Not Speak the Same Language(s) as the Speech-Language Pathologist.

Science.gov (United States)

McLeod, Sharynne; Verdon, Sarah

2017-08-15

The aim of this tutorial is to support speech-language pathologists (SLPs) undertaking assessments of multilingual children with suspected speech sound disorders, particularly children who speak languages that are not shared with their SLP. The tutorial was written by the International Expert Panel on Multilingual Children's Speech, which comprises 46 researchers (SLPs, linguists, phoneticians, and speech scientists) who have worked in 43 countries and used 27 languages in professional practice. Seventeen panel members met for a 1-day workshop to identify key points for inclusion in the tutorial, 26 panel members contributed to writing this tutorial, and 34 members contributed to revising this tutorial online (some members contributed to more than 1 task). This tutorial draws on international research evidence and professional expertise to provide a comprehensive overview of working with multilingual children with suspected speech sound disorders. This overview addresses referral, case history, assessment, analysis, diagnosis, and goal setting and the SLP's cultural competence and preparation for working with interpreters and multicultural support workers and dealing with organizational and government barriers to and facilitators of culturally competent practice. The issues raised in this tutorial are applied in a hypothetical case study of an English-speaking SLP's assessment of a multilingual Cantonese- and English-speaking 4-year-old boy. Resources are listed throughout the tutorial.

From Single Target to Multitarget/Network Therapeutics in Alzheimer’s Therapy

Directory of Open Access Journals (Sweden)

Hailin Zheng

2014-01-01

Full Text Available Brain network dysfunction in Alzheimer’s disease (AD involves many proteins (enzymes, processes and pathways, which overlap and influence one another in AD pathogenesis. This complexity challenges the dominant paradigm in drug discovery or a single-target drug for a single mechanism. Although this paradigm has achieved considerable success in some particular diseases, it has failed to provide effective approaches to AD therapy. Network medicines may offer alternative hope for effective treatment of AD and other complex diseases. In contrast to the single-target drug approach, network medicines employ a holistic approach to restore network dysfunction by simultaneously targeting key components in disease networks. In this paper, we explore several drugs either in the clinic or under development for AD therapy in term of their design strategies, diverse mechanisms of action and disease-modifying potential. These drugs act as multi-target ligands and may serve as leads for further development as network medicines.

Toxins and derivatives in molecular pharmaceutics: Drug delivery and targeted therapy.

Science.gov (United States)

Zhan, Changyou; Li, Chong; Wei, Xiaoli; Lu, Wuyuan; Lu, Weiyue

2015-08-01

Protein and peptide toxins offer an invaluable source for the development of actively targeted drug delivery systems. They avidly bind to a variety of cognate receptors, some of which are expressed or even up-regulated in diseased tissues and biological barriers. Protein and peptide toxins or their derivatives can act as ligands to facilitate tissue- or organ-specific accumulation of therapeutics. Some toxins have evolved from a relatively small number of structural frameworks that are particularly suitable for addressing the crucial issues of potency and stability, making them an instrumental source of leads and templates for targeted therapy. The focus of this review is on protein and peptide toxins for the development of targeted drug delivery systems and molecular therapies. We summarize disease- and biological barrier-related toxin receptors, as well as targeted drug delivery strategies inspired by those receptors. The design of new therapeutics based on protein and peptide toxins is also discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

The Effectiveness of a 3D Computerized Tutorial to Enhance Learning of the Canine Larynx and Hyoid Apparatus.

Science.gov (United States)

Nemanic, Sarah; Mills, Serena; Viehdorfer, Matt; Clark, Terri; Bailey, Mike

Teaching the anatomy of the canine larynx and hyoid apparatus is challenging because dissection disassembles and/or damages these structures, making it difficult to understand their three-dimensional (3D) anatomy and spatial interrelationships. This study assessed the effectiveness of an interactive, computerized 3D tutorial for teaching the anatomy of the canine larynx and hyoid apparatus using a randomized control design with students enrolled in the first-year professional program at Oregon State University College of Veterinary Medicine. All first-year students from 2 consecutive years were eligible. All students received the traditional methods of didactic teaching and dissection to learn the anatomy of the canine larynx and hyoid apparatus, after which they were divided into two statistically equal groups based on their cumulative anatomy test scores from the prior term. The tutorial group received an interactive, computerized tutorial developed by the investigators containing 3D images of the canine larynx and hyoid apparatus, while the control group received the same 3D images without the computerized tutorial. Both groups received the same post-learning assessment and survey. Sixty-three first-year students participated in the study, 28 in the tutorial group, and 35 in the control group. Post-learning assessment and survey scores were both significantly higher among students in the computerized tutorial group than those in the control group. This study demonstrates that a 3D computerized tutorial is more effective in teaching the anatomy of the canine hyoid apparatus and larynx than 3D images without a tutorial. Students likewise rated their learning experience higher when using the 3D computerized tutorial.

Statistical Tutorial | Center for Cancer Research

Science.gov (United States)

Recent advances in cancer biology have resulted in the need for increased statistical analysis of research data.  ST is designed as a follow up to Statistical Analysis of Research Data (SARD) held in April 2018.  The tutorial will apply the general principles of statistical analysis of research data including descriptive statistics, z- and t-tests of means and mean

Effectiveness of interactive tutorials in promoting "which-path" information reasoning in advanced quantum mechanics

Science.gov (United States)

Maries, Alexandru; Sayer, Ryan; Singh, Chandralekha

2017-12-01

Research suggests that introductory physics students often have difficulty using a concept in contexts different from the ones in which they learned it without explicit guidance to help them make the connection between the different contexts. We have been investigating advanced students' learning of quantum mechanics concepts and have developed interactive tutorials which strive to help students learn these concepts. Two such tutorials, focused on the Mach-Zehnder interferometer (MZI) and the double-slit experiment (DSE), help students learn how to use the concept of "which-path" information to reason about the presence or absence of interference in these two experiments in different situations. After working on a pretest that asked students to predict interference in the MZI with single photons and polarizers of various orientations placed in one or both paths of the MZI, students worked on the MZI tutorial which, among other things, guided them to reason in terms of which-path information in order to predict interference in similar situations. We investigated the extent to which students were able to use reasoning related to which-path information learned in the MZI tutorial to answer analogous questions on the DSE (before working on the DSE tutorial). After students worked on the DSE pretest they worked on a DSE tutorial in which they learned to use the concept of which-path information to answer questions about interference in the DSE with single particles with mass sent through the two slits and a monochromatic lamp placed between the slits and the screen. We investigated if this additional exposure to the concept of which-path information promoted improved learning and performance on the DSE questions with single photons and polarizers placed after one or both slits. We find evidence that both tutorials promoted which-path information reasoning and helped students use this reasoning appropriately in contexts different from the ones in which they had learned

The MAGIC of Web Tutorials: How One Library (Re)Focused Its Delivery of Online Learning Objects on Users

Science.gov (United States)

Hess, Amanda Nichols

2013-01-01

Oakland University (OU) Libraries undertook an assessment of how to leverage its resources to make online tutorials more focused on users' needs. A multi-part assessment process reconsidered Web tutorials offerings through the lenses of faculty and staff feedback, literature review, and an analysis of other universities' online tutorial offerings.…

Online Bioinformatics Tutorials | Office of Cancer Genomics

Science.gov (United States)

Bioinformatics is a scientific discipline that applies computer science and information technology to help understand biological processes. The NIH provides a list of free online bioinformatics tutorials, either generated by the NIH Library or other institutes, which includes introductory lectures and "how to" videos on using various tools.

Cancer gene therapy targeting angiogenesis: An updated Review

Science.gov (United States)

Liu, Ching-Chiu; Shen, Zan; Kung, Hsiang-Fu; Lin, Marie CM

2006-01-01

Since the relationship between angiogenesis and tumor growth was established by Folkman in 1971, scientists have made efforts exploring the possibilities in treating cancer by targeting angiogenesis. Inhibition of angiogenesis growth factors and administration of angiogenesis inhibitors are the basics of anti-angiogenesis therapy. Transfer of anti-angiogenesis genes has received attention recently not only because of the advancement of recombinant vectors, but also because of the localized and sustained expression of therapeutic gene product inside the tumor after gene transfer. This review provides the up-to-date information about the strategies and the vectors studied in the field of anti-angiogenesis cancer gene therapy. PMID:17109514

MAIN MOLECULAR TARGETS FOR PROSTATE CANCER THERAPY

Directory of Open Access Journals (Sweden)

G. S. Krasnov

2014-01-01

Full Text Available Androgenic pathway plays a pivotal role in the development of benign and malignant prostate tumors. Most of the prostate neoplasms are hormone-dependent at the time of diagnosis. Therapeutic interventions aimed at reducing the level of testosterone in the blood allow to stop progression of the disease. But over time, the tumor almost inevitably starts to progress, moving in the castration-resistant state (CRPC, representing a serious problem of oncourology. In recent years, the possibility of CRRPC therapy increased significantly – there was developed a number of new drugs that effectively inhibit the development of castration-resistant tumors and significantly push back the start of chemotherapy. This review describes the major drug targets and mechanisms of action of abiraterone, enzalutamide, galeterone, VT-464 and other approved and promising CRPC therapies.

Current Molecular Targeted Therapies for Bone and Soft Tissue Sarcomas

Directory of Open Access Journals (Sweden)

Kenji Nakano

2018-03-01

Full Text Available Systemic treatment options for bone and soft tissue sarcomas remained unchanged until the 2000s. These cancers presented challenges in new drug development partly because of their rarity and heterogeneity. Many new molecular targeting drugs have been tried in the 2010s, and some were approved for bone and soft tissue sarcoma. As one of the first molecular targeted drugs approved for solid malignant tumors, imatinib’s approval as a treatment for gastrointestinal stromal tumors (GISTs has been a great achievement. Following imatinib, other tyrosine kinase inhibitors (TKIs have been approved for GISTs such as sunitinib and regorafenib, and pazopanib was approved for non-GIST soft tissue sarcomas. Olaratumab, the monoclonal antibody that targets platelet-derived growth factor receptor (PDGFR-α, was shown to extend the overall survival of soft tissue sarcoma patients and was approved in 2016 in the U.S. as a breakthrough therapy. For bone tumors, new drugs are limited to denosumab, a receptor activator of nuclear factor κB ligand (RANKL inhibitor, for treating giant cell tumors of bone. In this review, we explain and summarize the current molecular targeting therapies approved and in development for bone and soft tissue sarcomas.

The Role of High Dose Interleukin-2 in the Era of Targeted Therapy.

Science.gov (United States)

Gills, Jessie; Parker, William P; Pate, Scott; Niu, Sida; Van Veldhuizen, Peter; Mirza, Moben; Holzbeierlein, Jeffery M; Lee, Eugene K

2017-09-01

We assessed survival outcomes following high dose interleukin-2 in a contemporary cohort of patients during the era of targeted agents. We retrospectively reviewed the records of patients with metastatic renal cell carcinoma treated with high dose interleukin-2 between July 2007 and September 2014. Clinicopathological data were abstracted and patient response to therapy was based on RECIST (Response Evaluation Criteria In Solid Tumors), version 1.1 criteria. The Kaplan-Meier method was used to estimate progression-free and overall survival in the entire cohort, the response to high dose interleukin-2 in regard to previous targeted agent therapy and the response to the targeted agent in relation to the response to high dose interleukin-2. We identified 92 patients, of whom 87 had documentation of a response to high dose interleukin-2. Median overall survival was 34.4 months from the initiation of high dose interleukin-2 therapy in the entire cohort. Patients who received targeted therapy before high dose interleukin-2 had overall survival (median 34.4 and 30.0 months, p = 0.88) and progression-free survival (median 1.5 and 1.7 months, p = 0.8) similar to those in patients who received no prior therapy, respectively. Additionally, patients with a complete or partial response to high dose interleukin-2 had similar outcomes for subsequent targeted agents compared to patients whose best response was stable or progressive disease (median overall survival 30.1 vs 25.4 months, p = 0.4). Our data demonstrate that patient responses to high dose interleukin-2 and to targeted agents before and after receiving high dose interleukin-2 are independent. As such, carefully selected patients should be offered high dose interleukin-2 for the possibility of a complete and durable response without the fear of limiting the treatment benefit of targeted agents. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Oracle support provides a range of new tutorials

CERN Multimedia

2012-01-01

The IT DB is pleased to announce a new series of Oracle tutorials, with the proposed schedule. Note that these tutorials will take place in the Filtration Plant (Building 222) and that no registration is required.   4 June (Monday) 09:00 Oracle Architecture, Przemyslaw Adam Radowiecki The objective is to go through Oracle database physical and logical structures, highlighting the consequences of some of Oracle's internal design choices for developers of database applications. The presentation defines Oracle-related basic terms and illustrates them based on the database architecture. The following topics will be discussed: • Database with its physical and logical structures (tablespace, segment, extent, block, database user, schema, user's quota) • Single instance (significant memory structures: buffer cache, shared pool) • Real Application Cluster (RAC) • Connecting to the database (TNS, database service) • SQL statement processing (h...

A dual-targeting upconversion nanoplatform for two-color fluorescence imaging-guided photodynamic therapy.

Science.gov (United States)

Wang, Xu; Yang, Cheng-Xiong; Chen, Jia-Tong; Yan, Xiu-Ping

2014-04-01

The targetability of a theranostic probe is one of the keys to assuring its theranostic efficiency. Here we show the design and fabrication of a dual-targeting upconversion nanoplatform for two-color fluorescence imaging-guided photodynamic therapy (PDT). The nanoplatform was prepared from 3-aminophenylboronic acid functionalized upconversion nanocrystals (APBA-UCNPs) and hyaluronated fullerene (HAC60) via a specific diol-borate condensation. The two specific ligands of aminophenylboronic acid and hyaluronic acid provide synergistic targeting effects, high targetability, and hence a dramatically elevated uptake of the nanoplatform by cancer cells. The high generation yield of (1)O2 due to multiplexed Förster resonance energy transfer between APBA-UCNPs (donor) and HAC60 (acceptor) allows effective therapy. The present nanoplatform shows great potential for highly selective tumor-targeted imaging-guided PDT.

Using Active-Learning Pedagogy to Develop Essay-Writing Skills in Introductory Political Theory Tutorials

Science.gov (United States)

Murphy, Michael P. A.

2017-01-01

Building on prior research into active learning pedagogy in political science, I discuss the development of a new active learning strategy called the "thesis-building carousel," designed for use in political theory tutorials. This use of active learning pedagogy in a graduate student-led political theory tutorial represents the overlap…

Effects of implementation of problem-based learning tutorials on fifth-year pharmacy students and future issues.

Science.gov (United States)

Sato, Atsuko; Morone, Mieko; Azuma, Yutaka

2011-01-01

At Tohoku Pharmaceutical University, problem-based learning (PBL) tutorials were incorporated into "prescription analysis" and "case analysis" for fifth-year students in 2010 with the following objectives: ① application and confirmation of acquired knowledge and skills, and acquisition of ② communication ability, ③ presentation ability, ④ cooperativeness through groupwork, and ⑤ information collecting ability. In the present study, we conducted a questionnaire survey on a total of 158 fifth-year students in order to investigate the educational benefits of PBL tutorials. The results showed that the above five objectives of PBL tutorials were being achieved, and confirmed the educational benefits expected of PBL tutorials. In contrast, it was found to be necessary to improve the contents of scenarios and lectures, time allocation regarding schedules, the learning environment, the role of tutors, and other matters. In order to maximize the educational benefits of PBL tutorials, it will be necessary in the future to continue to conduct surveys on students and make improvements to the curriculum based on survey results.

Cutaneous Adverse Events of Targeted Therapies for Hematolymphoid Malignancies.

Science.gov (United States)

Ransohoff, Julia D; Kwong, Bernice Y

2017-12-01

The identification of oncogenic drivers of liquid tumors has led to the rapid development of targeted agents with distinct cutaneous adverse event (AE) profiles. The diagnosis and management of these skin toxicities has motivated a novel partnership between dermatologists and oncologists in developing supportive oncodermatology clinics. In this article we review the current state of knowledge of clinical presentation, mechanisms, and management of the most common and significant cutaneous AEs observed during treatment with targeted therapies for hematologic and lymphoid malignancies. We systematically review according to drug-targeting pathway the cutaneous AE profiles of these drugs, and offer insight when possible into whether pharmacologic target versus immunologic modulation primarily underlie presentation. We include discussion of tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib, bosutinib, ponatinib), blinatumomab, ibrutinib, idelalisib, anti-B cell antibodies (rituximab, ibritumomab, obinutuzumab, ofatumumab, tositumomab), immune checkpoint inhibitors (nivolumab, pembrolizumab), alemtuzumab, brentuximab, and proteasome inhibitors (bortezomib, carfilzomib, ixazomib). We highlight skin reactions seen with antiliquid but not solid tumor agents, draw attention to serious cutaneous AEs that might require therapy modification or cessation, and offer management strategies to permit treatment tolerability. We emphasize the importance of early diagnosis and treatment to minimize disruptions to care, optimize prognosis and quality of life, and promptly address life-threatening skin or infectious events. This evolving partnership between oncologists and dermatologists in the iterative characterization and management of skin toxicities will contribute to a better understanding of these drugs' cutaneous targets and improved patient care. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessing the Response to Targeted Therapies in Renal Cell Carcinoma: Technical Insights and Practical Considerations

NARCIS (Netherlands)

Bex, A.; Fournier, L.; Lassau, N.; Mulders, P.F.A.; Nathan, P.; Oyen, W.J.G.; Powles, T.

2014-01-01

CONTEXT: The introduction of targeted agents for the treatment of renal cell carcinoma (RCC) has resulted in new challenges for assessing response to therapy, and conventional response criteria using computed tomography (CT) are limited. It is widely recognised that targeted therapies may lead to

Generation of Tutorial Dialogues: Discourse Strategies for Active Learning

National Research Council Canada - National Science Library

Evans, Martha

1998-01-01

With the support of the Cognitive Science Program of ONR, we are developing the capability to generate complex natural language tutorial dialogues for an intelligent tutoring system designed to help...

Automated problem generation in Learning Management Systems: a tutorial

Directory of Open Access Journals (Sweden)

Jaime Romero

2016-07-01

Full Text Available The benefits of solving problems have been widely acknowledged by literature. Its implementation in e–learning platforms can make easier its management and the learning process itself. However, its implementation can also become a very time–consuming task, particularly when the number of problems to generate is high. In this tutorial we describe a methodology that we have developed aiming to alleviate the workload of producing a great deal of problems in Moodle for an undergraduate business course. This methodology follows a six-step process and allows evaluating student’s skills in problem solving, minimizes plagiarism behaviors and provides immediate feedback. We expect this tutorial encourage other educators to apply our six steps process, thus benefiting themselves and their students of its advantages.

Staying on Top of Your Game and Scoring Big with Adobe Presenter Multimedia Tutorials

Science.gov (United States)

Koury, Regina; Francis, Marcia J.; Gray, Catherine J.; Jardine, Spencer J.; Guo, Ruiling

2010-01-01

In order to reach distance students in times of financial uncertainty, librarians must be creative. While much has been written about Camtasia, Captivate and Jing tutorial software, Adobe Presenter, a Microsoft PowerPoint plug-in, has not been discussed. This article describes how our library team created multimedia tutorial projects at Idaho…

Development of a Novel Targeted RNAi Delivery Technology inTherapies for Metabolic Diseases

Science.gov (United States)

2017-10-01

report Impact on other disciplines: Nothing to report Impact on technology transfer: Nothing to report Impact on society : Nothing to report 5. CHANGES...AWARD NUMBER: W81XWH-15-1-0569 TITLE: Development of a Novel Targeted RNAi Delivery Technology in Therapies for Metabolic Diseases PRINCIPAL...COVERED 30Sep2016 - 29Sep2017 4. TITLE AND SUBTITLE Development of a Novel Targeted RNAi Delivery Technology in Therapies for Metabolic Diseases 5a

Assessing the flexibility of research-based instructional strategies: Implementing tutorials in introductory physics in the lecture environment

Science.gov (United States)

Kryjevskaia, Mila; Boudreaux, Andrew; Heins, Dustin

2014-03-01

Materials from Tutorials in Introductory Physics, originally designed and implemented by the Physics Education Group at the University of Washington, were used in modified form as interactive lectures under conditions significantly different from those suggested by the curriculum developers. Student learning was assessed using tasks drawn from the physics education research literature. Use of tutorials in the interactive lecture format yielded gains in student understanding comparable to those obtained through the canonical tutorial implementation at the University of Washington, suggesting that student engagement with the intellectual steps laid out in the tutorials, rather than the specific strategies used in facilitating such engagement, plays the central role in promoting student learning. We describe the implementation details and assessment of student learning for two different tutorials: one focused on mechanical waves, used at North Dakota State University, and one on Galilean relativity, used at Western Washington University. Also discussed are factors that may limit the generalizability of the results.

The Implementation of Blended Learning Using Android-Based Tutorial Video in Computer Programming Course II

Science.gov (United States)

Huda, C.; Hudha, M. N.; Ain, N.; Nandiyanto, A. B. D.; Abdullah, A. G.; Widiaty, I.

2018-01-01

Computer programming course is theoretical. Sufficient practice is necessary to facilitate conceptual understanding and encouraging creativity in designing computer programs/animation. The development of tutorial video in an Android-based blended learning is needed for students’ guide. Using Android-based instructional material, students can independently learn anywhere and anytime. The tutorial video can facilitate students’ understanding about concepts, materials, and procedures of programming/animation making in detail. This study employed a Research and Development method adapting Thiagarajan’s 4D model. The developed Android-based instructional material and tutorial video were validated by experts in instructional media and experts in physics education. The expert validation results showed that the Android-based material was comprehensive and very feasible. The tutorial video was deemed feasible as it received average score of 92.9%. It was also revealed that students’ conceptual understanding, skills, and creativity in designing computer program/animation improved significantly.

An Audit of the Effectiveness of Large Group Neurology Tutorials for Irish Undergraduate Medical Students

LENUS (Irish Health Repository)

Kearney, H

2016-07-01

The aim of this audit was to determine the effectiveness of large group tutorials for teaching neurology to medical students. Students were asked to complete a questionnaire rating their confidence on a ten point Likert scale in a number of domains in the undergraduate education guidelines from the Association of British Neurologists (ABN). We then arranged a series of interactive large group tutorials for the class and repeated the questionnaire one month after teaching. In the three core domains of neurological: history taking, examination and differential diagnosis, none of the students rated their confidence as nine or ten out of ten prior to teaching. This increased to 6% for history taking, 12 % in examination and 25% for differential diagnosis after eight weeks of tutorials. This audit demonstrates that in our centre, large group tutorials were an effective means of teaching, as measured by the ABN guidelines in undergraduate neurology.

Tutorial de calcul poromécanique avec le logiciel Abaqus

OpenAIRE

Bonelli, S.

2011-01-01

/ Ce tutorial est destiné à apprendre à réaliser avec Abaqus, sous CAE, un calcul de poroélasticité linéaire. Il est écrit de telle sorte que quelqu'un n'ayant jamais utilisé Abaqus, mais ayant des connaissances de base en mécanique des milieux poreux d'une part, et en éléments-finis d'autre part, puisse réaliser un tel calcul en partant de zéro. Toutefois, il ne s'agit en aucun cas d'un tutorial sur Abaqus ui-même, ni sur la méthode des éléments-finis.

Cytopathology whole slide images and adaptive tutorials for postgraduate pathology trainees: a randomized crossover trial.

Science.gov (United States)

Van Es, Simone L; Kumar, Rakesh K; Pryor, Wendy M; Salisbury, Elizabeth L; Velan, Gary M

2015-09-01

To determine whether cytopathology whole slide images and virtual microscopy adaptive tutorials aid learning by postgraduate trainees, we designed a randomized crossover trial to evaluate the quantitative and qualitative impact of whole slide images and virtual microscopy adaptive tutorials compared with traditional glass slide and textbook methods of learning cytopathology. Forty-three anatomical pathology registrars were recruited from Australia, New Zealand, and Malaysia. Online assessments were used to determine efficacy, whereas user experience and perceptions of efficiency were evaluated using online Likert scales and open-ended questions. Outcomes of online assessments indicated that, with respect to performance, learning with whole slide images and virtual microscopy adaptive tutorials was equivalent to using traditional methods. High-impact learning, efficiency, and equity of learning from virtual microscopy adaptive tutorials were strong themes identified in open-ended responses. Participants raised concern about the lack of z-axis capability in the cytopathology whole slide images, suggesting that delivery of z-stacked whole slide images online may be important for future educational development. In this trial, learning cytopathology with whole slide images and virtual microscopy adaptive tutorials was found to be as effective as and perceived as more efficient than learning from glass slides and textbooks. The use of whole slide images and virtual microscopy adaptive tutorials has the potential to provide equitable access to effective learning from teaching material of consistently high quality. It also has broader implications for continuing professional development and maintenance of competence and quality assurance in specialist practice. Copyright © 2015 Elsevier Inc. All rights reserved.

Variation in use of targeted therapies for metastatic renal cell carcinoma: Results from a Dutch population-based registry

International Nuclear Information System (INIS)

De Groot, S.; Sleijfer, S.; Redekop, W. K.; Oosterwijk, E.; Haanen, J. B. A. G.; Kiemeney, L. A. L. M.; Uyl-de Groot, C. A.

2016-01-01

For patients with metastatic renal cell carcinoma (mRCC), targeted therapies have entered the market since 2006. The aims of this study were to evaluate the uptake and use of targeted therapies for mRCC in The Netherlands, examine factors associated with the prescription of targeted therapies in daily clinical practice and study their effectiveness in terms of overall survival (OS). Two cohorts from PERCEPTION, a population-based registry of mRCC patients, were used: a 2008–2010 Cohort (n = 645) and a 2011–2013 Cohort (n = 233). Chi-squared tests for trend were used to study time trends in the use of targeted therapy. Patients were grouped based on the eligibility criteria of the SUTENT trial, the trial that led to sunitinib becoming standard of care, to investigate the use of targeted therapies amongst patients fulfilling those criteria. Multi-level logistic regression was used to identify patient subgroups that are less likely to receive targeted therapies. Approximately one-third of patients fulfilling SUTENT trial eligibility criteria did not receive any targeted therapy (29 % in the 2008–2010 Cohort; 35 % in the 2011–2013 Cohort). Patients aged 65+ years were less likely to receive targeted therapy in both cohorts and different risk groups (odds ratios range between 0.84–0.92); other factors like number of metastatic sites were of influence in some subgroups. Amongst treated patients, there was a decreasing trend in sunitinib use over time (p = 0.0061), and an increasing trend in pazopanib use (p = 0.0005). Targeted therapies have largely replaced interferon-alfa as first-line standard of care. Nevertheless, many eligible patients in Dutch daily practice did not receive targeted therapies despite their ability to improve survival. Reasons for their apparent underutilisation should be examined more carefully. The online version of this article (doi:10.1186/s12885-016-2395-x) contains supplementary material, which is available to authorized users

Online Job Tutorials @ the Public Library: Best Practices from Carnegie Library of Pittsburgh's Job & Career Education Center

Directory of Open Access Journals (Sweden)

Rhea M. Hebert

2013-09-01

Full Text Available This article describes the Job & Career Education Center (JCEC tutorial project completed in September of 2012. The article also addresses the website redesign implemented to highlight the tutorials and improve user engagement with JCEC online resources. Grant monies made it possible for a Digital Outreach Librarian to create a series of tutorials with the purpose of providing job-related assistance beyond the JCEC in the Carnegie Library of Pittsburgh—Main location. Benchmarking, planning, implementation, and assessment are addressed. A set of best practices for all libraries (public, academic, school, special are presented. Best practices are applicable to tutorials created with software other than Camtasia, the software used by the JCEC project.

Approximating Literacy Practices in Tutorials: What Is Learned and What Matters for Teacher Preparation

Science.gov (United States)

Hoffman, James V.; Wetzel, Melissa Mosley; Peterson, Katie

2016-01-01

In this study, we examined the learning of preservice teachers associated with the features of a literacy tutorial experience. Our qualitative study focused on the close inspection of the experiences of 7 focus cases out of the 19 preservice teachers enrolled in our program across a one-semester tutorial experience. Through our research we…

The Purpose of Tutorial Groups: Social Influence and the Group as Means and Objective

Science.gov (United States)

Rosander, Michael; Chiriac, Eva Hammar

2016-01-01

The aim of this study was to investigate how first-year students view the purpose of tutorial groups in problem-based learning. In all, 147 students from 24 groups participated, providing 399 statements. Data were analysed using thematic analysis. The results showed a focus on both learning and social influence. Learning involved the tutorial as…

Targeted therapies and radiation for the treatment of head and neck cancer

International Nuclear Information System (INIS)

Kim, Gwi Eon

2004-01-01

The purpose of this review is to provide an update on novel radiation treatments for head and neck cancer. Despite the remarkable advances in chemotherapy and radiotherapy techniques, the management of advanced head and neck cancer remains challenging. Epidermal growth factor receptor (EGFR) is an appealing target for novel therapies in head and neck cancer because not only EGFR activation stimulates many important signaling pathways associated with cancer development and progression, and importantly, resistance to radiation. Furthermore, EGFR overexpression is known to be portended for a worse outcome in patients with advanced head and neck cancer. Two categories of compounds designed to abrogate EGFR signaling, such as monoclonal antibodies (Cetuximab) and tyrosine kinase inhibitors (ZD1839 and OSI-774) have been assessed and have been most extensively studied in preclinical models and clinical trials. Additional TKIs in clinical trials include a reversible agent, Cl-1033, which blocks activation of all erbB receptors. Encouraging preclinical data for head and neck cancers resulted in rapid translation into the clinic. Results from initial clinical trials show rather surprisingly that only minority of patients benefited from EGFR inhibition as monotherapy or in combination with chemotherapy. In this review, we begin with a brief summary of erbB-mediated signal transduction. Subsequently, we present data on prognostic-predictive value of erbB receptor expression in HNC followed by preclinical and clinical data on the role of EGFR antagonists alone or in combination with radiation in the treatment of HNC. Finally, we discuss the emerging thoughts on resistance to EGFR blockade and efforts in the development of multiple-targeted therapy for combination with chemotherapy or radiation. Current challenges for investigators are to determine (1) who will benefit from targeted agents and which agents are most appropriate to combine with radiation and/or chemotherapy, (2

Targeting chemotherapy-resistant leukemia by combining DNT cellular therapy with conventional chemotherapy.

Science.gov (United States)

Chen, Branson; Lee, Jong Bok; Kang, Hyeonjeong; Minden, Mark D; Zhang, Li

2018-04-24

While conventional chemotherapy is effective at eliminating the bulk of leukemic cells, chemotherapy resistance in acute myeloid leukemia (AML) is a prevalent problem that hinders conventional therapies and contributes to disease relapse, and ultimately patient death. We have recently shown that allogeneic double negative T cells (DNTs) are able to target the majority of primary AML blasts in vitro and in patient-derived xenograft models. However, some primary AML blast samples are resistant to DNT cell therapy. Given the differences in the modes of action of DNTs and chemotherapy, we hypothesize that DNT therapy can be used in combination with conventional chemotherapy to further improve their anti-leukemic effects and to target chemotherapy-resistant disease. Drug titration assays and flow-based cytotoxicity assays using ex vivo expanded allogeneic DNTs were performed on multiple AML cell lines to identify therapy-resistance. Primary AML samples were also tested to validate our in vitro findings. Further, a xenograft model was employed to demonstrate the feasibility of combining conventional chemotherapy and adoptive DNT therapy to target therapy-resistant AML. Lastly, blocking assays with neutralizing antibodies were employed to determine the mechanism by which chemotherapy increases the susceptibility of AML to DNT-mediated cytotoxicity. Here, we demonstrate that KG1a, a stem-like AML cell line that is resistant to DNTs and chemotherapy, and chemotherapy-resistant primary AML samples both became more susceptible to DNT-mediated cytotoxicity in vitro following pre-treatment with daunorubicin. Moreover, chemotherapy treatment followed by adoptive DNT cell therapy significantly decreased bone marrow engraftment of KG1a in a xenograft model. Mechanistically, daunorubicin increased the expression of NKG2D and DNAM-1 ligands on KG1a; blocking of these pathways attenuated DNT-mediated cytotoxicity. Our results demonstrate the feasibility and benefit of using DNTs as

Position paper: Web tutorials and Information Literacy research

DEFF Research Database (Denmark)

Hyldegård, Jette

2011-01-01

Position paper on future research challenges regarding web tutorials with the aim of supporting and facilitating Information Literacy in an academic context. Presented and discussed at the workshop: Social media & Information Practices, track on Information literacy practices, University of Borås...

University tutorials in the setting of the European Higher Education Area: current profiles

Directory of Open Access Journals (Sweden)

Carolina FERNÁNDEZ-SALINERO MIGUEL

2014-07-01

Full Text Available In the new setting promoted by the European Higher Education Area, university guidance and tutorials have become more important than ever. We understand tutorials as part of the teaching responsibility in which a more personal interaction between professor and student, professor and novice teacher, or student and student is established, and whose goal is to guide learning according to the individual characteristics and learning styles of the individuals involved. Now is the time to set up guidance and tutorials systems for students –both during the training process and in their first professional steps– and for novice teachers also. Among such systems we can mention professor coaching, peer mentoring, professional tutoring in training centres or mentoring of an experienced university professor on the novice teacher.

Targeting the EGFR pathway for cancer therapy

DEFF Research Database (Denmark)

Johnston, JB; Navaratnam, S; Pitz, MW

2006-01-01

.g.: Trastuzumab/Herceptin, Pertuzumab/Omnitarg/rhuMab-2C4, Cetuximab/Erbitux/IMC-C225, Panitumumab/Abenix/ABX-EGF, and also ZD6474). In addition, we summarize, both current therapy development driven by antibody-based targeting of the EGFR-dependent signaling pathways, and furthermore, we provide a background...

A Tutorial on the Cross-Entropy Method

NARCIS (Netherlands)

de Boer, Pieter-Tjerk; Kroese, Dirk; Mannor, Shie; Rubinstein, Reuven Y.

The cross-entropy (CE) method is a new generic approach to combinatorial and multi-extremal optimization and rare event simulation. The purpose of this tutorial is to give a gentle introduction to the CE method. We present the CE methodology, the basic algorithm and its modi��?cations, and

Chemoradiotherapy in head and neck squamous cell carcinoma: focus on targeted therapies

International Nuclear Information System (INIS)

Bozec, A.; Thariat, J.; Bensadoun, R.J.; Milano, G.

2008-01-01

Radiotherapy is an essential treatment for many patients with head and neck squamous cell carcinoma. Its association with molecular targeted therapies represents a real progress. Among the recent advances in the molecular targeted therapy of cancer, the applications centred on E.G.F.R. are currently the most promising and the most advanced at clinical level. Considering the set of therapeutic tools targeting E.G.F.R., there are at present two well-identified emerging categories of drugs with monoclonal antibodies, on the one hand, and tyrosine kinase inhibitors, on the other. In many preclinical studies, the combination of anti-E.G.F.R. drugs with irradiation has led to additive or supra-additive cytotoxic effects. Furthermore, anti-angiogenic agents have shown promising results in association with anti-E.G.F.R. drugs and radiotherapy. This research effort has recently produced encouraging clinical results in advanced head and neck cancer with combination of cetuximab (an anti-E.G.F.R. monoclonal antibody) with irradiation with a significant impact on patient survival. Active and efficient clinical research is currently ongoing to determine the place of molecular targeted therapies in the treatment of head and neck cancer, particularly in association with radiotherapy. (authors)

Immuno-Oncology-The Translational Runway for Gene Therapy: Gene Therapeutics to Address Multiple Immune Targets.

Science.gov (United States)

Weß, Ludger; Schnieders, Frank

2017-12-01

Cancer therapy is once again experiencing a paradigm shift. This shift is based on extensive clinical experience demonstrating that cancer cannot be successfully fought by addressing only single targets or pathways. Even the combination of several neo-antigens in cancer vaccines is not sufficient for successful, lasting tumor eradication. The focus has therefore shifted to the immune system's role in cancer and the striking abilities of cancer cells to manipulate and/or deactivate the immune system. Researchers and pharma companies have started to target the processes and cells known to support immune surveillance and the elimination of tumor cells. Immune processes, however, require novel concepts beyond the traditional "single-target-single drug" paradigm and need parallel targeting of diverse cells and mechanisms. This review gives a perspective on the role of gene therapy technologies in the evolving immuno-oncology space and identifies gene therapy as a major driver in the development and regulation of effective cancer immunotherapy. Present challenges and breakthroughs ranging from chimeric antigen receptor T-cell therapy, gene-modified oncolytic viruses, combination cancer vaccines, to RNA therapeutics are spotlighted. Gene therapy is recognized as the most prominent technology enabling effective immuno-oncology strategies.

Targeted Therapy for Biliary Tract Cancer

International Nuclear Information System (INIS)

Furuse, Junji; Okusaka, Takuji

2011-01-01

It is necessary to establish effective chemotherapy to improve the survival of patients with biliary tract cancer, because most of these patients are unsuitable candidates for surgery, and even patients undergoing curative surgery often have recurrence. Recently, the combination of cisplatin plus gemcitabine was reported to show survival benefits over gemcitabine alone in randomized clinical trials conducted in the United Kingdom and Japan. Thus, the combination of cisplatin plus gemcitabine is now recognized as the standard therapy for unresectable biliary tract cancer. One of the next issues that need to be addressed is whether molecular targeted agents might also be effective against biliary tract cancer. Although some targeted agents have been investigated as monotherapy for first-line chemotherapy, none were found to exert satisfactory efficacy. On the other hand, monoclonal antibodies such as bevacizumab and cetuximab have also been investigated in combination with a gemcitabine-based regimen and have been demonstrated to show promising activity. Furthermore, clinical trials using new targeted agents for biliary tract cancer are also proposed. This cancer is a relatively rare and heterogeneous tumor consisting of cholangiocarcinoma and gallbladder carcinoma. Therefore, a large randomized clinical trial is necessary to confirm the efficacy of chemotherapy, and international collaboration is important

Molecular strategies targeting the host component of cancer to enhance tumor response to radiation therapy

International Nuclear Information System (INIS)

Kim, Dong Wook; Huamani, Jessica; Fu, Allie; Hallahan, Dennis E.

2006-01-01

The tumor microenvironment, in particular, the tumor vasculature, as an important target for the cytotoxic effects of radiation therapy is an established paradigm for cancer therapy. We review the evidence that the phosphoinositide 3-kinase (PI3K)/Akt pathway is activated in endothelial cells exposed to ionizing radiation (IR) and is a molecular target for the development of novel radiation sensitizing agents. On the basis of this premise, several promising preclinical studies that targeted the inhibition of the PI3K/Akt activation as a potential method of sensitizing the tumor vasculature to the cytotoxic effects of IR have been conducted. An innovative strategy to guide cytotoxic therapy in tumors treated with radiation and PI3K/Akt inhibitors is presented. The evidence supports a need for further investigation of combined-modality therapy that involves radiation therapy and inhibitors of PI3K/Akt pathway as a promising strategy for improving the treatment of patients with cancer

Challenge of engaging all students via self-paced interactive electronic learning tutorials for introductory physics

Directory of Open Access Journals (Sweden)

Seth DeVore

2017-05-01

Full Text Available As research-based, self-paced electronic learning tools become increasingly available, a critical issue educators encounter is implementing strategies to ensure that all students engage with them as intended. Here, we first discuss the effectiveness of electronic learning tutorials as self-paced learning tools in large enrollment brick and mortar introductory physics courses and then propose a framework for helping students engage effectively with the learning tools. The tutorials were developed via research in physics education and were found to be effective for a diverse group of introductory physics students in one-on-one implementation. Instructors encouraged the use of these tools in a self-paced learning environment by telling students that they would be helpful for solving the assigned homework problems and that the underlying physics principles in the tutorial problems would be similar to those in the in-class quizzes (which we call paired problems. We find that many students in the courses in which these interactive electronic learning tutorials were assigned as a self-study tool performed poorly on the paired problems. In contrast, a majority of student volunteers in one-on-one implementation greatly benefited from the tutorials and performed well on the paired problems. The significantly lower overall performance on paired problems administered as an in-class quiz compared to the performance of student volunteers who used the research-based tutorials in one-on-one implementation suggests that many students enrolled in introductory physics courses did not effectively engage with the tutorials outside of class and may have only used them superficially. The findings suggest that many students in need of out-of-class remediation via self-paced learning tools may have difficulty motivating themselves and may lack the self-regulation and time-management skills to engage effectively with tools specially designed to help them learn at their

Challenge of engaging all students via self-paced interactive electronic learning tutorials for introductory physics

Science.gov (United States)

DeVore, Seth; Marshman, Emily; Singh, Chandralekha

2017-06-01

As research-based, self-paced electronic learning tools become increasingly available, a critical issue educators encounter is implementing strategies to ensure that all students engage with them as intended. Here, we first discuss the effectiveness of electronic learning tutorials as self-paced learning tools in large enrollment brick and mortar introductory physics courses and then propose a framework for helping students engage effectively with the learning tools. The tutorials were developed via research in physics education and were found to be effective for a diverse group of introductory physics students in one-on-one implementation. Instructors encouraged the use of these tools in a self-paced learning environment by telling students that they would be helpful for solving the assigned homework problems and that the underlying physics principles in the tutorial problems would be similar to those in the in-class quizzes (which we call paired problems). We find that many students in the courses in which these interactive electronic learning tutorials were assigned as a self-study tool performed poorly on the paired problems. In contrast, a majority of student volunteers in one-on-one implementation greatly benefited from the tutorials and performed well on the paired problems. The significantly lower overall performance on paired problems administered as an in-class quiz compared to the performance of student volunteers who used the research-based tutorials in one-on-one implementation suggests that many students enrolled in introductory physics courses did not effectively engage with the tutorials outside of class and may have only used them superficially. The findings suggest that many students in need of out-of-class remediation via self-paced learning tools may have difficulty motivating themselves and may lack the self-regulation and time-management skills to engage effectively with tools specially designed to help them learn at their own pace. We

Reimbursement of targeted cancer therapies within 3 different European health care systems

NARCIS (Netherlands)

Mihajlović, Jovan; Dolk, Christiaan; Tolley, Keith; Simoens, Steven; Postma, Maarten J.

2015-01-01

PURPOSE: Targeted cancer therapies (TCTs) are drugs that specifically act on molecular targets within the cancer cell, causing its regression and/or destruction. Although TCTs offer clinically important gains in survival in one of the most challenging therapeutic areas, these gains are followed by

Molecular targeted therapy for advanced gastric cancer.

Science.gov (United States)

Kim, Jong Gwang

2013-03-01

Although medical treatment has been shown to improve quality of life and prolong survival, no significant progress has been made in the treatment of advanced gastric cancer (AGC) within the last two decades. Thus, the optimum standard first-line chemotherapy regimen for AGC remains debatable, and most responses to chemotherapy are partial and of short duration; the median survival is approximately 7 to 11 months, and survival at 2 years is exceptionally > 10%. Recently, remarkable progress in tumor biology has led to the development of new agents that target critical aspects of oncogenic pathways. For AGC, many molecular targeting agents have been evaluated in international randomized studies, and trastuzumab, an anti-HER-2 monoclonal antibody, has shown antitumor activity against HER-2-positive AGC. However, this benefit is limited to only ~20% of patients with AGC (patients with HER-2-positive AGC). Therefore, there remains a critical need for both the development of more effective agents and the identification of molecular predictive and prognostic markers to select those patients who will benefit most from specific chemotherapeutic regimens and targeted therapies.

Instructional and regulative discourse in language tutorials: An ...

African Journals Online (AJOL)

The research is situated in the context of literature tutorials. To achieve this goal Bernstein's (1990; 1996) pedagogic discourse is employed, as it was used by Buzzelli and Johnston (2001). Keywords: language learning, learning process, teacher-student interaction, participation, potentially offensive views, pedagogic ...

Professionalizing tutors and tutorials in higher education

Directory of Open Access Journals (Sweden)

Colunga, Silvia

2012-01-01

Full Text Available The paper analyzes the necessity of professionalizing training of university teachers performing tutorial activities in higher education as a response to the demands of pupils following a part-time model. Permanent training of tutor is emphasized as a way to enhance professional and personal accomplishments. This training gives priority to educative orientation and interventional actions.

Mesenchymal Stem Cell-Based Tumor-Targeted Gene Therapy in Gastrointestinal Cancer

Science.gov (United States)

Bao, Qi; Zhao, Yue; Niess, Hanno; Conrad, Claudius; Schwarz, Bettina; Jauch, Karl-Walter; Huss, Ralf; Nelson, Peter J.

2012-01-01

Mesenchymal stem (or stromal) cells (MSCs) are nonhematopoietic progenitor cells that can be obtained from bone marrow aspirates or adipose tissue, expanded and genetically modified in vitro, and then used for cancer therapeutic strategies in vivo. Here, we review available data regarding the application of MSC-based tumor-targeted therapy in gastrointestinal cancer, provide an overview of the general history of MSC-based gene therapy in cancer research, and discuss potential problems associated with the utility of MSC-based therapy such as biosafety, immunoprivilege, transfection methods, and distribution in the host. PMID:22530882

Targeted Therapy for Breast Cancer Prevention

Science.gov (United States)

den Hollander, Petra; Savage, Michelle I.; Brown, Powel H.

2013-01-01

With a better understanding of the etiology of breast cancer, molecularly targeted drugs have been developed and are being testing for the treatment and prevention of breast cancer. Targeted drugs that inhibit the estrogen receptor (ER) or estrogen-activated pathways include the selective ER modulators (tamoxifen, raloxifene, and lasofoxifene) and aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) have been tested in preclinical and clinical studies. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer and promising results of AIs in breast cancer trials, suggest that AIs might be even more effective in the prevention of ER-positive breast cancer. However, these agents only prevent ER-positive breast cancer. Therefore, current research is focused on identifying preventive therapies for other forms of breast cancer such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC, breast cancer that does express ER, progesterone receptor, or HER2). HER2-positive breast cancers are currently treated with anti-HER2 therapies including trastuzumab and lapatinib, and preclinical and clinical studies are now being conducted to test these drugs for the prevention of HER2-positive breast cancers. Several promising agents currently being tested in cancer prevention trials for the prevention of TNBC include poly(ADP-ribose) polymerase inhibitors, vitamin D, and rexinoids, both of which activate nuclear hormone receptors (the vitamin D and retinoid X receptors). This review discusses currently used breast cancer preventive drugs, and describes the progress of research striving to identify and develop more effective preventive agents for all forms of breast cancer. PMID:24069582

Targeting embryonic signaling pathways in cancer therapy.

Science.gov (United States)

Harris, Pamela Jo; Speranza, Giovanna; Dansky Ullmann, Claudio

2012-01-01

The embryonic signaling pathways (ESP), Hedgehog, Notch and Wnt, are critical for the regulation of normal stem cells and cellular development processes. They are also activated in the majority of cancers. ESP are operational in putative cancer stem cells (CSC), which drive initial tumorigenesis and sustain cancer progression and recurrence in non-CSC bulk subpopulations. ESP represent novel therapeutic targets. A variety of inhibitors and targeting strategies are being developed. This review discusses the rationale for targeting ESP for cancer treatment, as well as specific inhibitors under development; mainly focusing on those approaching clinical use and the challenges that lie ahead. The data sources utilized are several database search engines (PubMed, Google, Clinicaltrials.gov), and the authors' involvement in the field. CSC research is rapidly evolving. Expectations regarding their therapeutic targeting are rising quickly. Further definition of what constitutes a true CSC, proper validation of CSC markers, a better understanding of cross-talk among ESP and other pathways, and interactions with tumor non-CSC and the tumor microenvironment are needed. The appropriate patient population, the right clinical setting and combination strategies to test these therapies, as well as the proper pharmacodynamic markers to measure, need to be further established.

Antibody-drug conjugates: Promising and efficient tools for targeted cancer therapy.

Science.gov (United States)

Nasiri, Hadi; Valedkarimi, Zahra; Aghebati-Maleki, Leili; Majidi, Jafar

2018-09-01

Over the recent decades, the use of antibody-drug conjugates (ADCs) has led to a paradigm shift in cancer chemotherapy. Antibody-based treatment of various human tumors has presented dramatic efficacy and is now one of the most promising strategies used for targeted therapy of patients with a variety of malignancies, including hematological cancers and solid tumors. Monoclonal antibodies (mAbs) are able to selectively deliver cytotoxic drugs to tumor cells, which express specific antigens on their surface, and has been suggested as a novel category of agents for use in the development of anticancer targeted therapies. In contrast to conventional treatments that cause damage to healthy tissues, ADCs use mAbs to specifically attach to antigens on the surface of target cells and deliver their cytotoxic payloads. The therapeutic success of future ADCs depends on closely choosing the target antigen, increasing the potency of the cytotoxic cargo, improving the properties of the linker, and reducing drug resistance. If appropriate solutions are presented to address these issues, ADCs will play a more important role in the development of targeted therapeutics against cancer in the next years. We review the design of ADCs, and focus on how ADCs can be exploited to overcome multiple drug resistance (MDR). © 2018 Wiley Periodicals, Inc.

Influence of androgen deprivation therapy on the uptake of PSMA-targeted agents: Emerging opportunities challenges

Energy Technology Data Exchange (ETDEWEB)

Bakht, Martin K.; Oh, So Won; Youn, Hye Won; Cheon, Gi Jeong; Kwak, Cheol; Kang, Keon Wook [Seoul National University College of Medicine, Seoul (Korea, Republic of)

2017-09-15

Prostate-specific membrane antigen (PSMA) is an attractive target for both diagnosis and therapy because of its high expression in the vast majority of prostate cancers. Development of small molecules for targeting PSMA is important for molecular imaging and radionuclide therapy of prostate cancer. Recent evidence implies that androgen-deprivation therapy increase PSMA-ligand uptake in some cases. The reported upregulations in PSMA-ligand uptake after exposure to second-generation antiandrogens such as enzalutamide and abiraterone might disturb PSMA-targeted imaging for staging and response monitoring of patients undergoing treatment with antiandrogen-based drugs. On the other hand, second-generation antiandrogens are emerging as potential endoradio-/chemosensitizers. Therefore, the enhancement of the therapeutic efficiency of PSMA-targeted theranostic methods can be listed as a new capability of antiandrogens. In this manuscript, we will present what is currently known about the mechanism of increasing PSMA uptake following exposure to antiandrogens. In addition, we will discuss whether these above-mentioned antiandrogens could play the role of endoradio-/chemosensitizers in combination with the well-established PSMA-targeted methods for pre-targeting of prostate cancer.

Influence of androgen deprivation therapy on the uptake of PSMA-targeted agents: Emerging opportunities challenges

International Nuclear Information System (INIS)

Bakht, Martin K.; Oh, So Won; Youn, Hye Won; Cheon, Gi Jeong; Kwak, Cheol; Kang, Keon Wook

2017-01-01

Prostate-specific membrane antigen (PSMA) is an attractive target for both diagnosis and therapy because of its high expression in the vast majority of prostate cancers. Development of small molecules for targeting PSMA is important for molecular imaging and radionuclide therapy of prostate cancer. Recent evidence implies that androgen-deprivation therapy increase PSMA-ligand uptake in some cases. The reported upregulations in PSMA-ligand uptake after exposure to second-generation antiandrogens such as enzalutamide and abiraterone might disturb PSMA-targeted imaging for staging and response monitoring of patients undergoing treatment with antiandrogen-based drugs. On the other hand, second-generation antiandrogens are emerging as potential endoradio-/chemosensitizers. Therefore, the enhancement of the therapeutic efficiency of PSMA-targeted theranostic methods can be listed as a new capability of antiandrogens. In this manuscript, we will present what is currently known about the mechanism of increasing PSMA uptake following exposure to antiandrogens. In addition, we will discuss whether these above-mentioned antiandrogens could play the role of endoradio-/chemosensitizers in combination with the well-established PSMA-targeted methods for pre-targeting of prostate cancer

Histone lysine demethylases as targets for anticancer therapy

DEFF Research Database (Denmark)

Højfeldt, Jonas W; Agger, Karl; Helin, Kristian

2013-01-01

It has recently been demonstrated that the genes controlling the epigenetic programmes that are required for maintaining chromatin structure and cell identity include genes that drive human cancer. This observation has led to an increased awareness of chromatin-associated proteins as potentially...... interesting drug targets. The successful introduction of DNA methylation and histone deacetylase (HDAC) inhibitors for the treatment of specific subtypes of cancer has paved the way for the use of epigenetic therapy. Here, we highlight key biological findings demonstrating the roles of members of the histone...... lysine demethylase class of enzymes in the development of cancers, discuss the potential and challenges of therapeutically targeting them, and highlight emerging small-molecule inhibitors of these enzymes....

Advances in targeting strategies for nanoparticles in cancer imaging and therapy.

Science.gov (United States)

Yhee, Ji Young; Lee, Sangmin; Kim, Kwangmeyung

2014-11-21

In the last decade, nanoparticles have offered great advances in diagnostic imaging and targeted drug delivery. In particular, nanoparticles have provided remarkable progress in cancer imaging and therapy based on materials science and biochemical engineering technology. Researchers constantly attempted to develop the nanoparticles which can deliver drugs more specifically to cancer cells, and these efforts brought the advances in the targeting strategy of nanoparticles. This minireview will discuss the progress in targeting strategies for nanoparticles focused on the recent innovative work for nanomedicine.

Engineering of magnetic DNA nanoparticles for tumor-targeted therapy

International Nuclear Information System (INIS)

Hosseinkhani, Hossein; Chen Yiru; He Wenjie; Hong Poda; Yu, Dah-Shyong; Domb, Abraham J.

2013-01-01

This study aims to engineer novel targeted delivery system composed of magnetic DNA nanoparticles to be effective as an efficient targeted gene therapy vehicle for tumor therapy. A polysaccharide, dextran, was chosen as the vector of plasmid DNA-encoded NK4 that acts as an HGF-antagonist and anti-angiogenic regulator for inhibitions of tumor growth, invasion, and metastasis. Spermine (Sm) was chemically introduced to the hydroxyl groups of dextran to obtain dextran-Sm. When Fe 2+ solution was added to the mixture of dextran-Sm and a plasmid DNA, homogenous DNA nanoparticles were formed via chemical metal coordination bonding with average size of 230 nm. Characterization of DNA nanoparticles was performed via dynamic light scattering measurement, electrophoretic light scattering measurement, as well as transmission electron microscope. DNA nanoparticles effectively condensed plasmid DNA into nanoparticles and enhanced the stability of DNA, while significantly improved transfection efficiency in vitro and tumor accumulation in vivo. In addition, magnetic DNA nanoparticles exhibited high efficiency in antitumor therapy with regards to tumor growth as well as survival of animals evaluated in the presence of external magnetic field. We conclude that the magnetic properties of these DNA nanoparticles would enhance the tracking of non-viral gene delivery systems when administrated in vivo in a test model. These findings suggest that DNA nanoparticles effectively deliver DNA to tumor and thereby inhibiting tumor growth.

Engineering of magnetic DNA nanoparticles for tumor-targeted therapy

Energy Technology Data Exchange (ETDEWEB)

Hosseinkhani, Hossein, E-mail: hosseinkhani@yahoo.com [Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology (Taiwan Tech) (China); Chen Yiru [National Yang-Ming University, Department of Biomedical Engineering (China); He Wenjie; Hong Poda [Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology (Taiwan Tech) (China); Yu, Dah-Shyong [Nanomedicine Research Center, National Defense Medical Center (China); Domb, Abraham J. [Institute of Drug Research, The Center for Nanoscience and Nanotechnology, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem (Israel)

2013-01-15

This study aims to engineer novel targeted delivery system composed of magnetic DNA nanoparticles to be effective as an efficient targeted gene therapy vehicle for tumor therapy. A polysaccharide, dextran, was chosen as the vector of plasmid DNA-encoded NK4 that acts as an HGF-antagonist and anti-angiogenic regulator for inhibitions of tumor growth, invasion, and metastasis. Spermine (Sm) was chemically introduced to the hydroxyl groups of dextran to obtain dextran-Sm. When Fe{sup 2+} solution was added to the mixture of dextran-Sm and a plasmid DNA, homogenous DNA nanoparticles were formed via chemical metal coordination bonding with average size of 230 nm. Characterization of DNA nanoparticles was performed via dynamic light scattering measurement, electrophoretic light scattering measurement, as well as transmission electron microscope. DNA nanoparticles effectively condensed plasmid DNA into nanoparticles and enhanced the stability of DNA, while significantly improved transfection efficiency in vitro and tumor accumulation in vivo. In addition, magnetic DNA nanoparticles exhibited high efficiency in antitumor therapy with regards to tumor growth as well as survival of animals evaluated in the presence of external magnetic field. We conclude that the magnetic properties of these DNA nanoparticles would enhance the tracking of non-viral gene delivery systems when administrated in vivo in a test model. These findings suggest that DNA nanoparticles effectively deliver DNA to tumor and thereby inhibiting tumor growth.

Comparing the Effectiveness of a Supplemental Online Tutorial to Traditional Instruction with Nutritional Science Students

Science.gov (United States)

Zubas, Patrice; Heiss, Cindy; Pedersen, Mary

2006-01-01

The purpose of this study was to ascertain if an online computer tutorial on diabetes mellitus, supplemented to traditional classroom lecture, is an effective tool in the education of nutrition students. Students completing a web-based tutorial as a supplement to classroom lecture displayed greater improvement in pre- vs. post-test scores compared…

Targeted therapies for diarrhea-predominant irritable bowel syndrome

Science.gov (United States)

Olden, Kevin W

2012-01-01

Irritable bowel syndrome (IBS) causes gastrointestinal symptoms such as abdominal pain, bloating, and bowel pattern abnormalities, which compromise patients’ daily functioning. Common therapies address one or two IBS symptoms, while others offer wider symptom control, presumably by targeting pathophysiologic mechanisms of IBS. The aim of this targeted literature review was to capture clinical trial reports of agents receiving the highest recommendation (Grade 1) for treatment of IBS from the 2009 American College of Gastroenterology IBS Task Force, with an emphasis on diarrhea-predominant IBS. Literature searches in PubMed captured articles detailing randomized placebo-controlled trials in IBS/diarrhea-predominant IBS for agents receiving Grade I (strong) 2009 American College of Gastroenterology IBS Task Force recommendations: tricyclic antidepressants, nonabsorbable antibiotics, and the 5-HT3 receptor antagonist alosetron. Studies specific for constipation-predominant IBS were excluded. Tricyclic antidepressants appear to improve global IBS symptoms but have variable effects on abdominal pain and uncertain tolerability; effects on stool consistency, frequency, and urgency were not adequately assessed. Nonabsorbable antibiotics show positive effects on global symptoms, abdominal pain, bloating, and stool consistency but may be most efficacious in patients with altered intestinal microbiota. Alosetron improves global symptoms and abdominal pain and normalizes bowel irregularities, including stool frequency, consistency, and fecal urgency. Both the nonabsorbable antibiotic rifaximin and the 5-HT3 receptor antagonist alosetron improve quality of life. Targeted therapies provide more complete relief of IBS symptoms than conventional agents. Familiarization with the quantity and quality of evidence of effectiveness can facilitate more individualized treatment plans for patients with this heterogeneous disorder. PMID:22754282

A possible usage of a CDK4 inhibitor for breast cancer stem cell-targeted therapy

International Nuclear Information System (INIS)

Han, Yu Kyeong; Lee, Jae Ho; Park, Ga-Young; Chun, Sung Hak; Han, Jeong Yun; Kim, Sung Dae; Lee, Janet; Lee, Chang-Woo; Yang, Kwangmo; Lee, Chang Geun

2013-01-01

Highlights: ► A CDK4 inhibitor may be used for breast cancer stem cell-targeted therapy. ► The CDK4 inhibitor differentiated the cancer stem cell population (CD24 − /CD44 + ) of MDA-MB-231. ► The differentiation of the cancer stem cells by the CDK4 inhibitor radiosensitized MDA-MB-231. -- Abstract: Cancer stem cells (CSCs) are one of the main reasons behind cancer recurrence due to their resistance to conventional anti-cancer therapies. Thus, many efforts are being devoted to developing CSC-targeted therapies to overcome the resistance of CSCs to conventional anti-cancer therapies and decrease cancer recurrence. Differentiation therapy is one potential approach to achieve CSC-targeted therapies. This method involves inducing immature cancer cells with stem cell characteristics into more mature or differentiated cancer cells. In this study, we found that a CDK4 inhibitor sensitized MDA-MB-231 cells but not MCF7 cells to irradiation. This difference appeared to be associated with the relative percentage of CSC-population between the two breast cancer cells. The CDK4 inhibitor induced differentiation and reduced the cancer stem cell activity of MDA-MB-231 cells, which are shown by multiple marker or phenotypes of CSCs. Thus, these results suggest that radiosensitization effects may be caused by reducing the CSC-population of MDA-MB-231 through the use of the CDK4 inhibitor. Thus, further investigations into the possible application of the CDK4 inhibitor for CSC-targeted therapy should be performed to enhance the efficacy of radiotherapy for breast cancer

LHC@home online tutorial for Windows users - recording

CERN Multimedia

CERN. Geneva

2016-01-01

A step-by-step online tutorial about LHC@home for Windows users by Karolina Bozek. It contains detailed instructions on how-to-join this volunteer computing project.  This 5' video is linked from http://lhcathome.web.cern.ch/join-us Also from the CDS e-learning category.

Acquaintanceship, Familiarity, and Coordinated Laughter in Writing Tutorials

Science.gov (United States)

Thonus, Terese

2008-01-01

This study compared the frequency, structure, and purposes of laughter in writing tutorials between 46 acquainted and unacquainted tutor-student pairs. Of particular interest were instances of shared, or coordinated laughter, which took the form of sequenced, simultaneous, and extended laughter. Familiarity, viewed as a continuum, was also…

Nanobody-Based Delivery Systems for Diagnosis and Targeted Tumor Therapy

Directory of Open Access Journals (Sweden)

Yaozhong Hu

2017-11-01

Full Text Available The development of innovative targeted therapeutic approaches are expected to surpass the efficacy of current forms of treatments and cause less damage to healthy cells surrounding the tumor site. Since the first development of targeting agents from hybridoma’s, monoclonal antibodies (mAbs have been employed to inhibit tumor growth and proliferation directly or to deliver effector molecules to tumor cells. However, the full potential of such a delivery strategy is hampered by the size of mAbs, which will obstruct the targeted delivery system to access the tumor tissue. By serendipity, a new kind of functional homodimeric antibody format was discovered in camelidae, known as heavy-chain antibodies (HCAbs. The cloning of the variable domain of HCAbs produces an attractive minimal-sized alternative for mAbs, referred to as VHH or nanobodies (Nbs. Apart from their dimensions in the single digit nanometer range, the unique characteristics of Nbs combine a high stability and solubility, low immunogenicity and excellent affinity and specificity against all possible targets including tumor markers. This stimulated the development of tumor-targeted therapeutic strategies. Some autonomous Nbs have been shown to act as antagonistic drugs, but more importantly, the targeting capacity of Nbs has been exploited to create drug delivery systems. Obviously, Nb-based targeted cancer therapy is mainly focused toward extracellular tumor markers, since the membrane barrier prevents antibodies to reach the most promising intracellular tumor markers. Potential strategies, such as lentiviral vectors and bacterial type 3 secretion system, are proposed to deliver target-specific Nbs into tumor cells and to block tumor markers intracellularly. Simultaneously, Nbs have also been employed for in vivo molecular imaging to diagnose diseased tissues and to monitor the treatment effects. Here, we review the state of the art and focus on recent developments with Nbs as

Combined analgesics in (headache pain therapy: shotgun approach or precise multi-target therapeutics?

Directory of Open Access Journals (Sweden)

Fiebich Bernd L

2011-03-01

Full Text Available Abstract Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix" are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA, paracetamol (acetaminophen and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

Science.gov (United States)

2011-01-01

Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden the array of therapeutic

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

Science.gov (United States)

Straube, Andreas; Aicher, Bernhard; Fiebich, Bernd L; Haag, Gunther

2011-03-31

Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.As an example the fixed-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness

Multimedia Tutorial In Physics For Foreign Students Of the Engineering Faculty Preparatory Department

Directory of Open Access Journals (Sweden)

P. G. Matukhin

2016-05-01

Full Text Available Foreign students study physics and Russian as a foreign language at the preparatory Department. They are to be trained to study different courses. During only one year the teachers of physics and Russian should help students from Asia, Africa and Latin America to get ready to study in the university. To help students in a short time to learn physical terms, to understand physics by ear, to read and write, teachers are developing the online multimedia tutorial. It is placed on the cloud OneDrive. Tutorial includes the main themes in the Mechanics. They are physical processes and phenomena, units, physical quantities, kinematics, laws of mechanics and others. The Power Point presentation slides contain information on the topics. These slides help students learn to read Russian texts on physics. There are hyperlinks to sound files on slides. Listening to those recordings, students gain the skills of physical texts listening. After each module we placed the test. Students can prepare for it using the simulator. Tests and exercise equipment made in the form of EXCEL spreadsheets. We provide our students the opportunity to view, read and listen, the tutorial files via their own mobile devices. Thus they can study physics in Russian in the classroom, or at home, but in the library, in the Park etc. Also they have access to it when they are not in Russia, and in their native countries. The tutorial presented seems to be considered as the first attempt to develop the online multimedia aimed to assist foreign students to get success in their efforts to study physics in Russian. It helps our students to learn physics in Russian faster and better. Determined are the directions of further development and improvement of the tutorial.

TARGETED NANOPARTICLES FOR PEDIATRIC LEUKEMIA THERAPY

Directory of Open Access Journals (Sweden)

Riyaz eBasha

2014-05-01

Full Text Available The two major forms of leukemia, acute lymphoblastic leukemia (ALL and acute myeloid leukemia (AML account for about one third of the malignancies diagnosed in children. Despite the marked successes in ALL and AML treatment, concerns remain regarding the occurrence of resistant disease in subsets of patients the residual effects of therapy that often persist for decades beyond the cessation of treatment. Therefore, new approaches are needed to reduce or to avoid off target toxicities, associated with chemotherapy and their long term residual effects. Recently, nanotechnology has been employed to enhance cancer therapy, via improving the bioavailability and therapeutic efficacy of anti-cancer agents. While in the last several years, numerous review articles appeared detailing the size, composition, assembly and performance evaluation of different types of drug carrying nanoparticles, the description and evaluation of lipoprotein based drug carriers have been conspicuously absent from most of these major reviews. The current review focuses on such information regarding nanoparticles with an emphasis on high density lipoprotein (HDL-based drug delivery systems to examine their potential role(s in the enhanced treatment of children with leukemia.

Mitochondria and Mitochondrial ROS in Cancer: Novel Targets for Anticancer Therapy.

Science.gov (United States)

Yang, Yuhui; Karakhanova, Svetlana; Hartwig, Werner; D'Haese, Jan G; Philippov, Pavel P; Werner, Jens; Bazhin, Alexandr V

2016-12-01

Mitochondria are indispensable for energy metabolism, apoptosis regulation, and cell signaling. Mitochondria in malignant cells differ structurally and functionally from those in normal cells and participate actively in metabolic reprogramming. Mitochondria in cancer cells are characterized by reactive oxygen species (ROS) overproduction, which promotes cancer development by inducing genomic instability, modifying gene expression, and participating in signaling pathways. Mitochondrial and nuclear DNA mutations caused by oxidative damage that impair the oxidative phosphorylation process will result in further mitochondrial ROS production, completing the "vicious cycle" between mitochondria, ROS, genomic instability, and cancer development. The multiple essential roles of mitochondria have been utilized for designing novel mitochondria-targeted anticancer agents. Selective drug delivery to mitochondria helps to increase specificity and reduce toxicity of these agents. In order to reduce mitochondrial ROS production, mitochondria-targeted antioxidants can specifically accumulate in mitochondria by affiliating to a lipophilic penetrating cation and prevent mitochondria from oxidative damage. In consistence with the oncogenic role of ROS, mitochondria-targeted antioxidants are found to be effective in cancer prevention and anticancer therapy. A better understanding of the role played by mitochondria in cancer development will help to reveal more therapeutic targets, and will help to increase the activity and selectivity of mitochondria-targeted anticancer drugs. In this review we summarized the impact of mitochondria on cancer and gave summary about the possibilities to target mitochondria for anticancer therapies. J. Cell. Physiol. 231: 2570-2581, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

C595 antibody: A potential vector for targeted alpha therapy

International Nuclear Information System (INIS)

Perkins, A.C.; Allen, B.J.

2005-01-01

Full text: Mucins are high molecular-weight heavily glycosylated glycoproteins with many oligosaccharide side-chains, linked to a protein backbone called apomucin. A total of 19 different mucin genes (MUC1-MUC4, MUC5B, MUC5AC, MUC6-MUC18) have been identified to date. Mucins are present on the surface of most epithelial cells and play a role in their protection and lubrication. In cancer cells the mucin molecule becomes altered, thus representing an important target for diagnosis and therapy. Urinary epithelial mucin1 (MUC1) is found to be frequently up-regulated and abnormally glycosylated in a number of common malignancies, including breast, bladder, colon, ovarian and gastric cancer. The monoclonal antibody C595 is an IgG3 murine MAb raised against the protein core of human MUC1. Epitope mapping has shown that C595 recognizes a tetrapeptide motif (RPAP) within the protein core of MUC1 mucin that contains a large domain of multiples of a highly conserved 20-amino-acid-repeat sequence (PDTRPAPGSTAPPAHGVTSA). This antibody has previously been radiolabelled with 99m Tc and 111 In and used for imaging a range of tumour types including ovary, breast and bladder. The antibody has also been radiolabelled with 67 Cu and 188 Re for the therapy of superficial bladder cancer. More recently we have investigated the pre-clinical use of the C595 antibody for targeted alpha therapy using 213 Bi which emits alpha particles with high linear energy transfer (LET), short range (80 m) radiation and has a short physical half-life of 45.6 minutes. Alpha particles are some 7300 times heavier than beta particles and in theory, following binding of an alpha immunocongugates to the target, a large fraction of the alpha particle energy is delivered to cancer cells, with minimal concomitant radiation of normal tissues. 213 Bi was produced from the 225 Ac/ 213 Bi generator. For antibody conjugation the chelator, cyclic diethylenetriaminepentacetic acid anhydride (DTPA) was used. Initial

Mesenchymal Stem Cell-Based Tumor-Targeted Gene Therapy in Gastrointestinal Cancer

OpenAIRE

Bao, Qi; Zhao, Yue; Niess, Hanno; Conrad, Claudius; Schwarz, Bettina; Jauch, Karl-Walter; Huss, Ralf; Nelson, Peter J.; Bruns, Christiane J.

2012-01-01

Mesenchymal stem (or stromal) cells (MSCs) are nonhematopoietic progenitor cells that can be obtained from bone marrow aspirates or adipose tissue, expanded and genetically modified in vitro, and then used for cancer therapeutic strategies in vivo. Here, we review available data regarding the application of MSC-based tumor-targeted therapy in gastrointestinal cancer, provide an overview of the general history of MSC-based gene therapy in cancer research, and discuss potential problems associa...

Targeted therapy for localized non-small-cell lung cancer: a review

Directory of Open Access Journals (Sweden)

Paleiron N

2016-07-01

Full Text Available Nicolas Paleiron,1 Olivier Bylicki,2 Michel André,1 Emilie Rivière,1 Frederic Grassin,1 Gilles Robinet,3 Christos Chouaïd4 On behalf of the GFPC Group 1Chest Department, HIA Clermont Tonnerre, Brest, 2Chest Department, HIA Percy, Clamart, 3Chest Department, CHU de Brest, Brest, 4GRC OncoEst, Université Paris XII, Paris, France Abstract: Targeted therapies have markedly improved the management of patients with advanced non-small-cell lung cancer (NSCLC, but their efficacy in localized NSCLC is less well established. The aim of this review is to analyze trials of targeted therapies in localized NSCLC. In patients with wild-type EGFR, tyrosine kinase inhibitors have shown no efficacy in Phase III trials. Few data are available for EGFR-mutated localized NSCLC, as routine biological profiling is not recommended. Available studies are small, often retrospectives, and/or conducted in a single-center making it difficult to draw firm conclusions. Ongoing prospective Phase III trials are comparing adjuvant tyrosine kinase inhibitor administration versus adjuvant chemotherapy. By analogy with the indication of bevacizumab in advanced NSCLC, use of antiangiogenic agents in the perioperative setting is currently restricted to nonsquamous NSCLC. Several trials of adjuvant or neoadjuvant bevacizumab are planned or ongoing, but for the moment there is no evidence of efficacy. Data on perioperative use of biomarkers in early-stage NSCLC come mainly from small, retrospective, uncontrolled studies. Assessment of customized adjuvant or neoadjuvant therapy in localized NSCLC (with or without oncogenic driver mutations is a major challenge. Keywords: targeted therapy, non-small-cell lung cancer, adjuvant, neo-adjuvant, surgery 

The development of molecularly targeted anticancer therapies: an Eli Lilly and Company perspective.

Science.gov (United States)

Perry, William L; Weitzman, Aaron

2005-03-01

The ability to identify activated pathways that drive the growth and progression of cancer and to develop specific and potent inhibitors of key proteins in these pathways promises to dramatically change the treatment of cancer: A patient's cancer could be characterized at the molecular level and the information used to select the best treatment options. The development of successful therapies not only requires extensive target validation, but also new approaches to evaluating drug efficacy in animal models and in the clinic compared to the development of traditional cytotoxic agents. This article highlights Eli Lilly and Company's approach to developing targeted therapies, from target identification and validation through evaluation in the clinic. A selection of drugs in the Lilly Oncology pipeline is also discussed.

Oncolytic viral therapy: targeting cancer stem cells

Directory of Open Access Journals (Sweden)

Smith TT

2014-02-01

Full Text Available Tyrel T Smith,1 Justin C Roth,1 Gregory K Friedman,1 G Yancey Gillespie2 1Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL, USA; 2Department of Neurosurgery, The University of Alabama at Birmingham, Birmingham, AL, USA Abstract: Cancer stem cells (CSCs are defined as rare populations of tumor-initiating cancer cells that are capable of both self-renewal and differentiation. Extensive research is currently underway to develop therapeutics that target CSCs for cancer therapy, due to their critical role in tumorigenesis, as well as their resistance to chemotherapy and radiotherapy. To this end, oncolytic viruses targeting unique CSC markers, signaling pathways, or the pro-tumor CSC niche offer promising potential as CSCs-destroying agents/therapeutics. We provide a summary of existing knowledge on the biology of CSCs, including their markers and their niche thought to comprise the tumor microenvironment, and then we provide a critical analysis of the potential for targeting CSCs with oncolytic viruses, including herpes simplex virus-1, adenovirus, measles virus, reovirus, and vaccinia virus. Specifically, we review current literature regarding first-generation oncolytic viruses with their innate ability to replicate in CSCs, as well as second-generation viruses engineered to enhance the oncolytic effect and CSC-targeting through transgene expression. Keywords: oncolytic virotherapy, cancer stem cell niche

Reactive Oxygen Species-Mediated Mechanisms of Action of Targeted Cancer Therapy

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Hanna-Riikka Teppo

2017-01-01

Full Text Available Targeted cancer therapies, involving tyrosine kinase inhibitors and monoclonal antibodies, for example, have recently led to substantial prolongation of survival in many metastatic cancers. Compared with traditional chemotherapy and radiotherapy, where reactive oxygen species (ROS have been directly linked to the mediation of cytotoxic effects and adverse events, the field of oxidative stress regulation is still emerging in targeted cancer therapies. Here, we provide a comprehensive review regarding the current evidence of ROS-mediated effects of antibodies and tyrosine kinase inhibitors, use of which has been indicated in the treatment of solid malignancies and lymphomas. It can be concluded that there is rapidly emerging evidence of ROS-mediated effects of some of these compounds, which is also relevant in the context of drug resistance and how to overcome it.

A Surgical Perspective on Targeted Therapy of Hepatocellular Carcinoma

Science.gov (United States)

Faltermeier, Claire; Busuttil, Ronald W.; Zarrinpar, Ali

2015-01-01

Hepatocellular carcinoma (HCC), the second leading cause of cancer deaths worldwide, is difficult to treat and highly lethal. Since HCC is predominantly diagnosed in patients with cirrhosis, treatment planning must consider both the severity of liver disease and tumor burden. To minimize the impact to the patient while treating the tumor, techniques have been developed to target HCC. Anatomical targeting by surgical resection or locoregional therapies is generally reserved for patients with preserved liver function and minimal to moderate tumor burden. Patients with decompensated cirrhosis and small tumors are optimal candidates for liver transplantation, which offers the best chance of long-term survival. Yet, only 20%–30% of patients have disease amenable to anatomical targeting. For the majority of patients with advanced HCC, chemotherapy is used to target the tumor biology. Despite these treatment options, the five-year survival of patients in the United States with HCC is only 16%. In this review we provide a comprehensive overview of current approaches to target HCC. We also discuss emerging diagnostic and prognostic biomarkers, novel therapeutic targets identified by recent genomic profiling studies, and potential applications of immunotherapy in the treatment of HCC. PMID:28943622

A Surgical Perspective on Targeted Therapy of Hepatocellular Carcinoma

Directory of Open Access Journals (Sweden)

Claire Faltermeier

2015-09-01

Full Text Available Hepatocellular carcinoma (HCC, the second leading cause of cancer deaths worldwide, is difficult to treat and highly lethal. Since HCC is predominantly diagnosed in patients with cirrhosis, treatment planning must consider both the severity of liver disease and tumor burden. To minimize the impact to the patient while treating the tumor, techniques have been developed to target HCC. Anatomical targeting by surgical resection or locoregional therapies is generally reserved for patients with preserved liver function and minimal to moderate tumor burden. Patients with decompensated cirrhosis and small tumors are optimal candidates for liver transplantation, which offers the best chance of long-term survival. Yet, only 20%–30% of patients have disease amenable to anatomical targeting. For the majority of patients with advanced HCC, chemotherapy is used to target the tumor biology. Despite these treatment options, the five-year survival of patients in the United States with HCC is only 16%. In this review we provide a comprehensive overview of current approaches to target HCC. We also discuss emerging diagnostic and prognostic biomarkers, novel therapeutic targets identified by recent genomic profiling studies, and potential applications of immunotherapy in the treatment of HCC.

Targeted therapy of multiple myeloma.

Science.gov (United States)

Dolloff, Nathan G; Talamo, Giampaolo

2013-01-01

Multiple myeloma (MM) is a plasma cell malignancy and the second most common hematologic cancer. MM is characterized by the accumulation of malignant plasma cells within the bone marrow, and presents clinically with a broad range of symptoms, including hypercalcemia, renal insufficiency, anemia, and lytic bone lesions. MM is a heterogeneous disease associated with genomic instability, where patients may express multiple genetic abnormalities that affect several oncogenic pathways. Commonly detected genetic aberrations are translocations involving immunoglobulin heavy chain (IgH) switch regions (chromosome 14q32) and oncogenes such as c-maf [t(14:16)], cyclin D1 [t(11:14)], and FGFR3/MMSET [t(4:14)]. Advances in the basic understanding of MM and the development of novel agents, such as the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide and the proteasome inhibitor bortezomib, have increased therapeutic response rates and prolonged patient survival. Despite these advances MM remains incurable in the majority of patients, and it is therefore critical to identify additional therapeutic strategies and targets for its treatment. In this chapter, we review the underlying genetic components of MM and discuss the results of recent clinical trials that demonstrate the effectiveness of targeted agents in the management of MM. In addition, we discuss experimental therapies that are currently in clinical development along with their molecular rationale in the treatment of MM.

Molecular targeted therapy in ovarian cancer: what is on the horizon?

LENUS (Irish Health Repository)

Kalachand, Roshni

2012-02-01

Over the past two decades, empirical optimization of cytotoxic chemotherapy combinations and surgical debulking procedures have improved outcomes and survival in epithelial ovarian cancer. Yet, this disease remains the fifth leading cause of cancer-related deaths in the US, as cure rates seem to have reached a plateau at approximately 20% with conventional chemotherapy. Novel high-throughput genomic and proteomic analyses have improved the molecular understanding of ovarian carcinogenesis, thereby providing a vast array of new potential drug targets with complex signalling interactions. In order to yield the most significant impact on disease outcome, it is necessary to carefully select, and subsequently target, the driving molecular pathway(s) within a tumour or tumour subtype, which are most likely to correspond to high-frequency mutations and genomic aberrations. The identification of biomarkers predictive of response to targeted therapy is essential to avoid poor responses to potentially useful drugs in unselected trial populations. With some promising, albeit early, phase III data on the angiogenesis inhibitor bevacizumab, exciting new opportunities lie ahead with the ultimate goal of personalizing therapies to individual tumour profiles.

Molecular Targeted Therapy in Ovarian Cancer: What is on the Horizon?

LENUS (Irish Health Repository)

Kalachand, Roshni

2011-05-28

Over the past two decades, empirical optimization of cytotoxic chemotherapy combinations and surgical debulking procedures have improved outcomes and survival in epithelial ovarian cancer. Yet, this disease remains the fifth leading cause of cancer-related deaths in the US, as cure rates seem to have reached a plateau at approximately 20% with conventional chemotherapy. Novel high-throughput genomic and proteomic analyses have improved the molecular understanding of ovarian carcinogenesis, thereby providing a vast array of new potential drug targets with complex signalling interactions. In order to yield the most significant impact on disease outcome, it is necessary to carefully select, and subsequently target, the driving molecular pathway(s) within a tumour or tumour subtype, which are most likely to correspond to high-frequency mutations and genomic aberrations. The identification of biomarkers predictive of response to targeted therapy is essential to avoid poor responses to potentially useful drugs in unselected trial populations. With some promising, albeit early, phase III data on the angiogenesis inhibitor bevacizumab, exciting new opportunities lie ahead with the ultimate goal of personalizing therapies to individual tumour profiles.

Neutrophils, a candidate biomarker and target for radiation therapy?

Science.gov (United States)

Schernberg, Antoine; Blanchard, Pierre; Chargari, Cyrus; Deutsch, Eric

2017-11-01

Neutrophils are the most abundant blood-circulating white blood cells, continuously generated in the bone marrow. Growing evidence suggests they regulate the innate and adaptive immune system during tumor evolution. This review will first summarize the recent findings on neutrophils as a key player in cancer evolution, then as a potential biomarker, and finally as therapeutic targets, with respective focuses on the interplay with radiation therapy. A complex interplay: Neutrophils have been associated with tumor progression through multiple pathways. Ionizing radiation has cytotoxic effects on cancer cells, but the sensitivity to radiation therapy in vivo differ from isolated cancer cells in vitro, partially due to the tumor microenvironment. Different microenvironmental states, whether baseline or induced, can modulate or even attenuate the effects of radiation, with consequences for therapeutic efficacy. Inflammatory biomarkers: Inflammation-based scores have been widely studied as prognostic biomarkers in cancer patients. We have performed a large retrospective cohort of patients undergoing radiation therapy (1233 patients), with robust relationship between baseline blood neutrophil count and 3-year's patient's overall survival in patients with different cancer histologies. (Pearson's correlation test: p = .001, r = -.93). Therapeutic approaches: Neutrophil-targeting agents are being developed for the treatment of inflammatory and autoimmune diseases. Neutrophils either can exert antitumoral (N1 phenotype) or protumoral (N2 phenotype) activity, depending on the Tumor Micro Environment. Tumor associated N2 neutrophils are characterized by high expression of CXCR4, VEGF, and gelatinase B/MMP9. TGF-β within the tumor microenvironment induces a population of TAN with a protumor N2 phenotype. TGF-β blockade slows tumor growth through activation of CD8 + T cells, macrophages, and tumor associated neutrophils with an antitumor N1 phenotype. This supports

Gradient Boosting Machines, A Tutorial

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Alexey eNatekin

2013-12-01

Full Text Available Gradient boosting machines are a family of powerful machine-learning techniques that have shown considerable success in a wide range of practical applications. They are highly customizable to the particular needs of the application, like being learned with respect to different loss functions. This article gives a tutorial introduction into the methodology of gradient boosting methods. A theoretical information is complemented with many descriptive examples and illustrations which cover all the stages of the gradient boosting model design. Considerations on handling the model complexity are discussed. A set of practical examples of gradient boosting applications are presented and comprehensively analyzed.

Multistage Targeting Strategy Using Magnetic Composite Nanoparticles for Synergism of Photothermal Therapy and Chemotherapy.

Science.gov (United States)

Wang, Yi; Wei, Guoqing; Zhang, Xiaobin; Huang, Xuehui; Zhao, Jingya; Guo, Xing; Zhou, Shaobing

2018-03-01

Mitochondrial-targeting therapy is an emerging strategy for enhanced cancer treatment. In the present study, a multistage targeting strategy using doxorubicin-loaded magnetic composite nanoparticles is developed for enhanced efficacy of photothermal and chemical therapy. The nanoparticles with a core-shell-SS-shell architecture are composed of a core of Fe 3 O 4 colloidal nanocrystal clusters, an inner shell of polydopamine (PDA) functionalized with triphenylphosphonium (TPP), and an outer shell of methoxy poly(ethylene glycol) linked to the PDA by disulfide bonds. The magnetic core can increase the accumulation of nanoparticles at the tumor site for the first stage of tumor tissue targeting. After the nanoparticles enter the tumor cells, the second stage of mitochondrial targeting is realized as the mPEG shell is detached from the nanoparticles by redox responsiveness to expose the TPP. Using near-infrared light irradiation at the tumor site, a photothermal effect is generated from the PDA photosensitizer, leading to a dramatic decrease in mitochondrial membrane potential. Simultaneously, the loaded doxorubicin can rapidly enter the mitochondria and subsequently damage the mitochondrial DNA, resulting in cell apoptosis. Thus, the synergism of photothermal therapy and chemotherapy targeting the mitochondria significantly enhances the cancer treatment. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Internal and External Triggering Mechanism of "Smart" Nanoparticle-Based DDSs in Targeted Tumor Therapy.

Science.gov (United States)

Qiana, Xian-Ling; Li, Jun; Wei, Ran; Lin, Hui; Xiong, Li-Xia

2018-05-09

Anticancer chemotherapeutics have a lot of problems via conventional drug delivery systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the tumor site in three ways: "passive", "active", and "smart" targeting. To summarize the mechanisms of various internal and external "smart" stimulating factors on the basis of findings from in vivo and in vitro studies. A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel articles related to the subject. Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors (temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), "smart" DDSs exhibit targeted delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes. In this review article, we summarize and classify the internal and external triggering mechanism of "smart" nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated for better understanding. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Multifunctional nanoparticle-EpCAM aptamer bioconjugates: a paradigm for targeted drug delivery and imaging in cancer therapy.

Science.gov (United States)

Das, Manasi; Duan, Wei; Sahoo, Sanjeeb K

2015-02-01

The promising proposition of multifunctional nanoparticles for cancer diagnostics and therapeutics has inspired the development of theranostic approach for improved cancer therapy. Moreover, active targeting of drug carrier to specific target site is crucial for providing efficient delivery of therapeutics and imaging agents. In this regard, the present study investigates the theranostic capabilities of nutlin-3a loaded poly (lactide-co-glycolide) nanoparticles, functionalized with a targeting ligand (EpCAM aptamer) and an imaging agent (quantum dots) for cancer therapy and bioimaging. A wide spectrum of in vitro analysis (cellular uptake study, cytotoxicity assay, cell cycle and apoptosis analysis, apoptosis associated proteins study) revealed superior therapeutic potentiality of targeted NPs over other formulations in EpCAM expressing cells. Moreover, our nanotheranostic system served as a superlative bio-imaging modality both in 2D monolayer culture and tumor spheroid model. Our result suggests that, these aptamer-guided multifunctional NPs may act as indispensable nanotheranostic approach toward cancer therapy. This study investigated the theranostic capabilities of nutlin-3a loaded poly (lactide-co-glycolide) nanoparticles functionalized with a targeting ligand (EpCAM aptamer) and an imaging agent (quantum dots) for cancer therapy and bioimaging. It was concluded that the studied multifunctional targeted nanoparticle may become a viable and efficient approach in cancer therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Intermittent targeted therapies and stochastic evolution in patients affected by chronic myeloid leukemia

Science.gov (United States)

Pizzolato, N.; Persano Adorno, D.; Valenti, D.; Spagnolo, B.

2016-05-01

Front line therapy for the treatment of patients affected by chronic myeloid leukemia (CML) is based on the administration of tyrosine kinase inhibitors, namely imatinib or, more recently, axitinib. Although imatinib is highly effective and represents an example of a successful molecular targeted therapy, the appearance of resistance is observed in a proportion of patients, especially those in advanced stages. In this work, we investigate the appearance of resistance in patients affected by CML, by modeling the evolutionary dynamics of cancerous cell populations in a simulated patient treated by an intermittent targeted therapy. We simulate, with the Monte Carlo method, the stochastic evolution of initially healthy cells to leukemic clones, due to genetic mutations and changes in their reproductive behavior. We first present the model and its validation with experimental data by considering a continuous therapy. Then, we investigate how fluctuations in the number of leukemic cells affect patient response to the therapy when the drug is administered with an intermittent time scheduling. Here we show that an intermittent therapy (IT) represents a valid choice in patients with high risk of toxicity, despite an associated delay to the complete restoration of healthy cells. Moreover, a suitably tuned IT can reduce the probability of developing resistance.

Targeted radionuclide therapy for neuroendocrine tumours: principles and application.

Science.gov (United States)

Druce, Maralyn R; Lewington, Val; Grossman, Ashley B

2010-01-01

Neuroendocrine tumours comprise a group of neoplasms with variable clinical behaviour. Their growth and spread is often very slow and initially asymptomatic, and thus they are often metastatic at the time of diagnosis and incurable by surgery. An exciting therapeutic strategy for cytoreduction, both for stabilisation of tumour growth and inhibition of hormone production, is the use of targeted radionuclide therapy. Evidence from large-scale, randomised, placebo-controlled trials is very difficult to obtain in these rare diseases, but current data appear promising. It is timely to review the principles underlying the use of these therapies, together with the clinical outcomes to date and potential directions for future research. Copyright 2009 S. Karger AG, Basel.

Key Elements of the Tutorial Support Management Model

Science.gov (United States)

Lynch, Grace; Paasuke, Philip

2011-01-01

In response to an exponential growth in enrolments the "Tutorial Support Management" (TSM) model has been adopted by Open Universities Australia (OUA) after a two-year project on the provision of online tutor support in first year, online undergraduate units. The essential focus of the TSM model was the development of a systemic approach…

An Evaluation of a Biological Slide-Tutorial Program.

Science.gov (United States)

Chan, Gordon L.

Described is an auto-tutorial slide program for zoology students. A self-paced system was devised for observing the subject matter covered in the twelve study units of a zoology course. The post-testing evaluation revealed that students with lower grade point averages achieved scores comparable with students of higher grade point averages.…

LHC@home online tutorial for Linux users - recording

CERN Multimedia

CERN. Geneva

2016-01-01

A step-by-step online tutorial for LHC@home by Karolina Bozek It contains detailed instructions for Linux users on how-to-join this volunteer computing project.  This 5' linked from http://lhcathome.web.cern.ch/join-us CLICK Here to see the commands to copy/paste for installing BOINC and the VirtualBox.

Pemetrexed With Platinum Combination as a Backbone for Targeted Therapy in Non-Small-Cell Lung Cancer.

Science.gov (United States)

Stinchcombe, Thomas E; Borghaei, Hossein; Barker, Scott S; Treat, Joseph Anthony; Obasaju, Coleman

2016-01-01

Standard platinum-based chemotherapy combinations for advanced non-small-cell lung cancer (NSCLC) have reached a plateau in terms of the survival benefit they offer for patients. In addition, the emerging clinical trend of tailored treatment based on patient characteristics has led to the development of therapeutic strategies that target specific cancer-related molecular pathways, including epidermal growth factor receptor (EGFR), angiogenesis, and anaplastic lymphoma kinase inhibitors. Current research is focused on combining targeted therapy with platinum-based chemotherapy in an endeavor to achieve an additional benefit in specific patient populations. Currently, pemetrexed is indicated for use in the first-line, maintenance, and second-line settings for the treatment of nonsquamous NSCLC. The combination of pemetrexed and cisplatin is well tolerated and is the approved standard first-line therapy. Thus, the pemetrexed-platinum backbone provides an attractive option for combination with targeted therapies. This review aims to summarize the current knowledge and future prospects of the use of pemetrexed-platinum as a backbone for combination with targeted therapies for NSCLC. Copyright © 2016 Elsevier Inc. All rights reserved.

How Levels of Interactivity in Tutorials Affect Students' Learning of Modeling Transportation Problems in a Spreadsheet

Science.gov (United States)

Seal, Kala Chand; Przasnyski, Zbigniew H.; Leon, Linda A.

2010-01-01

Do students learn to model OR/MS problems better by using computer-based interactive tutorials and, if so, does increased interactivity in the tutorials lead to better learning? In order to determine the effect of different levels of interactivity on student learning, we used screen capture technology to design interactive support materials for…

Drug design with Cdc7 kinase: a potential novel cancer therapy target

Directory of Open Access Journals (Sweden)

Masaaki Sawa

2008-11-01

Full Text Available Masaaki Sawa1, Hisao Masai21Carna Biosciences, Inc., Kobe, Japan; 2Genome Dynamics Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, JapanAbstract: Identification of novel molecular targets is critical in development of new and efficient cancer therapies. Kinases are one of the most common drug targets with a potential for cancer therapy. Cell cycle progression is regulated by a number of kinases, some of which are being developed to treat cancer. Cdc7 is a serine-threonine kinase originally discovered in budding yeast, which has been shown to be necessary to initiate the S phase. Inhibition of Cdc7 in cancer cells retards the progression of the S phase, accumulates DNA damage, and induces p53-independent cell death, but the same treatment in normal cells does not significantly affect viability. Low-molecular-weight compounds that inhibit Cdc7 kinase with an IC50 of less than 10 nM have been identified, and shown to be effective in the inhibition of tumor growth in animal models. Thus Cdc7 kinase can be recognized as a novel molecular target for cancer therapy.Keywords: Cdc7 kinase, cell cycle, replication fork, genome stability, DNA damages, ATP-binding pocket, kinase inhibitor

Osteosarcoma: Cells-of-Origin, Cancer Stem Cells, and Targeted Therapies

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Ander Abarrategi

2016-01-01

Full Text Available Osteosarcoma (OS is the most common type of primary solid tumor that develops in bone. Although standard chemotherapy has significantly improved long-term survival over the past few decades, the outcome for those patients with metastatic or recurrent OS remains dismally poor and, therefore, novel agents and treatment regimens are urgently required. A hypothesis to explain the resistance of OS to chemotherapy is the existence of drug resistant CSCs with progenitor properties that are responsible of tumor relapses and metastasis. These subpopulations of CSCs commonly emerge during tumor evolution from the cell-of-origin, which are the normal cells that acquire the first cancer-promoting mutations to initiate tumor formation. In OS, several cell types along the osteogenic lineage have been proposed as cell-of-origin. Both the cell-of-origin and their derived CSC subpopulations are highly influenced by environmental and epigenetic factors and, therefore, targeting the OS-CSC environment and niche is the rationale for many recently postulated therapies. Likewise, some strategies for targeting CSC-associated signaling pathways have already been tested in both preclinical and clinical settings. This review recapitulates current OS cell-of-origin models, the properties of the OS-CSC and its niche, and potential new therapies able to target OS-CSCs.

Text Mining for Information Systems Researchers: An Annotated Topic Modeling Tutorial

DEFF Research Database (Denmark)

Debortoli, Stefan; Müller, Oliver; Junglas, Iris

2016-01-01

, such as manual coding. Yet, the size of text data setsobtained from the Internet makes manual analysis virtually impossible. In this tutorial, we discuss the challengesencountered when applying automated text-mining techniques in information systems research. In particular, weshowcase the use of probabilistic...... researchers,this tutorial provides some guidance for conducting text mining studies on their own and for evaluating the quality ofothers.......t is estimated that more than 80 percent of today’s data is stored in unstructured form (e.g., text, audio, image, video);and much of it is expressed in rich and ambiguous natural language. Traditionally, the analysis of natural languagehas prompted the use of qualitative data analysis approaches...

A tutorial on Palm distributions for spatial point processes

DEFF Research Database (Denmark)

Coeurjolly, Jean-Francois; Møller, Jesper; Waagepetersen, Rasmus Plenge

2017-01-01

This tutorial provides an introduction to Palm distributions for spatial point processes. Initially, in the context of finite point processes, we give an explicit definition of Palm distributions in terms of their density functions. Then we review Palm distributions in the general case. Finally, we...

Tabletted guar gum microspheres of piroxicam for targeted adjuvant therapy for colonic adenocarcinomas.

Science.gov (United States)

Vats, Anima; Pathak, Kamla

2012-11-01

In recent years, nonsteroidal anti-inflammatory drugs have been found to be cogent as an adjuvant therapeutic agent in mitigating colorectal cancer. Thus, this present investigation was aimed to formulate an oral, targeted tablet of piroxicam microspheres for sustained and targeted adjuvant therapy for colonic adenocarcinomas. Crosslinked guar gum microspheres of piroxicam were directly compressed into matrix tablet and coated with Eudragit S100. The optimized tablet that displayed 0% release in simulated gastric fluid, 15% in simulated intestinal fluid and 97.1% in simulated colonic fluid underwent roentgenographic study in rabbits to check its safe transit to the colon. x-ray images revealed intactness of the tablet until it reached the colon where the tablet matrix eroded. The designed, conceptual formulation emerged as potential carrier for targeted adjuvant therapy of piroxicam.

Cellular Energy Pathways as Novel Targets for the Therapy of Autosomal Dominant Polycystic Kidney Disease

Science.gov (United States)

2017-09-01

AWARD NUMBER: W81XWH-15-1-0419 TITLE: Cellular Energy Pathways as Novel Targets for the Therapy of Autosomal Dominant Polycystic Kidney Disease...COVERED 1 Sep 2016 - 31 Aug 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Cellular Energy Pathways as Novel Targets for the Therapy of Autosomal...inappropriate cell growth, fluid secretion, and dysregulation of cellular energy metabolism. The enzyme AMPK regulates a number of cellular pathways, including

Autoradiography Imaging in Targeted Alpha Therapy with Timepix Detector

Directory of Open Access Journals (Sweden)

Ruqaya AL Darwish

2015-01-01

Full Text Available There is a lack of data related to activity uptake and particle track distribution in targeted alpha therapy. These data are required to estimate the absorbed dose on a cellular level as alpha particles have a limited range and traverse only a few cells. Tracking of individual alpha particles is possible using the Timepix semiconductor radiation detector. We investigated the feasibility of imaging alpha particle emissions in tumour sections from mice treated with Thorium-227 (using APOMAB, with and without prior chemotherapy and Timepix detector. Additionally, the sensitivity of the Timepix detector to monitor variations in tumour uptake based on the necrotic tissue volume was also studied. Compartmental analysis model was used, based on the obtained imaging data, to assess the Th-227 uptake. Results show that alpha particle, photon, electron, and muon tracks were detected and resolved by Timepix detector. The current study demonstrated that individual alpha particle emissions, resulting from targeted alpha therapy, can be visualised and quantified using Timepix detector. Furthermore, the variations in the uptake based on the tumour necrotic volume have been observed with four times higher uptake for tumours pretreated with chemotherapy than for those without chemotherapy.

New Targets for End-Stage Chronic Kidney Disease Therapy

Directory of Open Access Journals (Sweden)

Prakoura Niki

2015-05-01

Full Text Available Severe forms of chronic kidney disease can lead to a critical, end-stage condition, requiring renal replacement therapy, which may involve a form of dialysis or renal transplantation. Identification and characterization of novel markers and/or targets of therapy that could be applied in these critically ill patients remains the focus of the current research in the field of critical care medicine and has been the objective of our studies for some years past. To this end, we used models of renal vascular disease, Ang II, L-NAME or mice overexpressing renin, treated with AT1 antagonists at different stages of progression, to create cohorts of animals during progression, reversal or escape from therapy. Transcriptomic analysis and comparisons were performed and genes were selected according to the following criteria: a not previously described in the kidney, b highly upregulated during progression and returning to the normal levels during reversal, and c producing proteins that are either circulating or membrane receptors.

Efficacy of Multimedia Learning Modules as Preparation for Lecture-Based Tutorials in Electromagnetism

Directory of Open Access Journals (Sweden)

James Christopher Moore

2018-02-01

Full Text Available We have investigated the efficacy of on-line, multimedia learning modules (MLMs as preparation for in-class, lecture-based tutorials in electromagnetism in a physics course for natural science majors (biology and marine science. Specifically, we report the results of a multiple-group pre/post-test research design comparing two groups receiving different treatments with respect to activities preceding participation in Tutorials in Introductory Physics. The different pre-tutorial activities were as follows: (1 students were assigned reading from a traditional textbook, followed by a traditional lecture; and (2 students completed on-line MLMs developed by the Physics Education Research Group at the University of Illinois at Urbana Champaign (UIUC, and commercially known as FlipItPhysics. The MLM treatment group earned significantly higher mid-term examination scores and larger gains in content knowledge as measured by the Conceptual Survey of Electricity and Magnetism (CSEM. Student attitudes towards “reformed” instruction in the form of active-engagement tutorials were also improved. Specifically, post-course surveys showed that MLM-group students believed class time was more effective and the instructor was more clear than reported by non-MLM students, even though there was no significant difference between groups with respect to in-class activities and the same instructor taught both groups. MLM activities can be a highly effective tool for some student populations, especially when student preparation and buy-in are important for realizing significant gains.

Emerging Glycolysis Targeting and Drug Discovery from Chinese Medicine in Cancer Therapy

Directory of Open Access Journals (Sweden)

Zhiyu Wang

2012-01-01

Full Text Available Molecular-targeted therapy has been developed for cancer chemoprevention and treatment. Cancer cells have different metabolic properties from normal cells. Normal cells mostly rely upon the process of mitochondrial oxidative phosphorylation to produce energy whereas cancer cells have developed an altered metabolism that allows them to sustain higher proliferation rates. Cancer cells could predominantly produce energy by glycolysis even in the presence of oxygen. This alternative metabolic characteristic is known as the “Warburg Effect.” Although the exact mechanisms underlying the Warburg effect are unclear, recent progress indicates that glycolytic pathway of cancer cells could be a critical target for drug discovery. With a long history in cancer treatment, traditional Chinese medicine (TCM is recognized as a valuable source for seeking bioactive anticancer compounds. A great progress has been made to identify active compounds from herbal medicine targeting on glycolysis for cancer treatment. Herein, we provide an overall picture of the current understanding of the molecular targets in the cancer glycolytic pathway and reviewed active compounds from Chinese herbal medicine with the potentials to inhibit the metabolic targets for cancer treatment. Combination of TCM with conventional therapies will provide an attractive strategy for improving clinical outcome in cancer treatment.

Organic molecule-based photothermal agents: an expanding photothermal therapy universe.

Science.gov (United States)

Jung, Hyo Sung; Verwilst, Peter; Sharma, Amit; Shin, Jinwoo; Sessler, Jonathan L; Kim, Jong Seung

2018-04-03

Over the last decade, organic photothermal therapy (PTT) agents have attracted increasing attention as a potential complement for, or alternative to, classical drugs and sensitizers involving inorganic nanomaterials. In this tutorial review, we provide a structured description of the main classes of organic photothermal agents and their characteristics. Representative agents that have been studied in the context of photothermal therapy since 2000 are summarized and recent advances in using PTT agents to address various cancers indications are highlighted.

HER3 signaling and targeted therapy in cancer

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Rosalin Mishra

2018-05-01

Full Text Available ERBB family members including epidermal growth factor receptor (EGFR also known as HER1, ERBB2/HER2/Neu, ERBB3/HER3 and ERBB4/HER4 are aberrantly activated in multiple cancers and hence serve as drug targets and biomarkers in modern precision therapy. The therapeutic potential of HER3 has long been underappreciated, due to impaired kinase activity and relatively low expression in tumors. However, HER3 has received attention in recent years as it is a crucial heterodimeric partner for other EGFR family members and has the potential to regulate EGFR/HER2-mediated resistance. Upregulation of HER3 is associated with several malignancies where it fosters tumor progression via interaction with different receptor tyrosine kinases (RTKs. Studies also implicate HER3 contributing significantly to treatment failure, mostly through the activation of PI3K/AKT, MAPK/ERK and JAK/STAT pathways. Moreover, activating mutations in HER3 have highlighted the role of HER3 as a direct therapeutic target. Therapeutic targeting of HER3 includes abrogating its dimerization partners’ kinase activity using small molecule inhibitors (lapatinib, erlotinib, gefitinib, afatinib, neratinib or direct targeting of its extracellular domain. In this review, we focus on HER3-mediated signaling, its role in drug resistance and discuss the latest advances to overcome resistance by targeting HER3 using mono- and bispecific antibodies and small molecule inhibitors.

Rational Design of Iron Oxide Nanoparticles as Targeted Nanomedicines for Cancer Therapy

Science.gov (United States)

Kievit, Forrest M.

2011-07-01

Nanotechnology provides a flexible platform for the development of effective therapeutic nanomaterials that can interact specifically with a target in a biological system and provoke a desired biological response. Of the nanomaterials studied, superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as one of top candidates for cancer therapy due to their intrinsic superparamagnetism that enables non-invasive magnetic resonance imaging (MRI) and biodegradability favorable for in vivo application. This dissertation is aimed at development of SPION-based nanomedicines to overcome the current limitations in cancer therapy. These limitations include non-specificity of therapy which can harm healthy tissue, the difficulty in delivering nucleic acids for gene therapy, the formation of drug resistance, and the inability to detect and treat micrometastases. First, a SPION-based non-viral gene delivery vehicle was developed through functionalization of the SPION core with a co-polymer designed to provide stable binding of DNA and low toxicity which showed excellent gene delivery in vitro and in vivo. This SPION-based non-viral gene delivery vehicle was then activated with a targeting agent to improve gene delivery throughout a xenograft tumor of brain cancer. It was found that targeting did not promote the accumulation of SPIONs at the tumor site, but rather improved the distribution of SPIONs throughout the tumor so a higher proportion of cells received treatment. Next, the high surface area of SPIONs was utilized for loading large amounts of drug which was shown to overcome the multidrug resistance acquired by many cancer cells. Drug bound to SPIONs showed significantly higher multidrug resistant cell uptake as compared to free drug which translated into improved cell kill. Also, an antibody activated SPION was developed and was shown to be able to target micrometastases in a transgenic animal model of metastatic breast cancer. These SPION-based nanomedicines

Target volume delineation and field setup. A practical guide for conformal and intensity-modulated radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Lee, Nancy Y. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States). Radiation Oncology; Lu, Jiade J. (eds.) [National Univ. Health System, Singapore (Singapore). Dept. of Radiation Oncology; National Univ. of Singapore (Singapore). Dept. of Medicine

2013-03-01

Practical handbook on selection and delineation of tumor volumes and fields for conformal radiation therapy, including IMRT. Helpful format facilitating use on a step-by-step basis in daily practice. Designed to ensure accurate coverage of commonly encountered tumors along their routes of spread. This handbook is designed to enable radiation oncologists to appropriately and confidently delineate tumor volumes/fields for conformal radiation therapy, including intensity-modulated radiation therapy (IMRT), in patients with commonly encountered cancers. The orientation of this handbook is entirely practical, in that the focus is on the illustration of clinical target volume (CTV) delineation for each major malignancy. Each chapter provides guidelines and concise knowledge on CTV selection for a particular disease, explains how the anatomy of lymphatic drainage shapes the selection of the target volume, and presents detailed illustrations of volumes, slice by slice, on planning CT images. While the emphasis is on target volume delineation for three-dimensional conformal therapy and IMRT, information is also provided on conventional radiation therapy field setup and planning for certain malignancies for which IMRT is not currently suitable.

Targeting DNA Replication Stress for Cancer Therapy

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Jun Zhang

2016-08-01

Full Text Available The human cellular genome is under constant stress from extrinsic and intrinsic factors, which can lead to DNA damage and defective replication. In normal cells, DNA damage response (DDR mediated by various checkpoints will either activate the DNA repair system or induce cellular apoptosis/senescence, therefore maintaining overall genomic integrity. Cancer cells, however, due to constitutive growth signaling and defective DDR, may exhibit “replication stress” —a phenomenon unique to cancer cells that is described as the perturbation of error-free DNA replication and slow-down of DNA synthesis. Although replication stress has been proven to induce genomic instability and tumorigenesis, recent studies have counterintuitively shown that enhancing replicative stress through further loosening of the remaining checkpoints in cancer cells to induce their catastrophic failure of proliferation may provide an alternative therapeutic approach. In this review, we discuss the rationale to enhance replicative stress in cancer cells, past approaches using traditional radiation and chemotherapy, and emerging approaches targeting the signaling cascades induced by DNA damage. We also summarize current clinical trials exploring these strategies and propose future research directions including the use of combination therapies, and the identification of potential new targets and biomarkers to track and predict treatment responses to targeting DNA replication stress.

[The opinion of teachers about tutorial problem based learning].

Science.gov (United States)

Navarro H, Nancy; Zamora S, José

2014-08-01

In 2004 the Faculty of Medicine of Universidad de La Frontera in Chile implemented curricular changes, incorporating small group problem based learning in different carriers. To explore aspects that hamper or facilitate tutorial problem based learning from the perspective of tutors. Six in depth interviews and a focus group with tutors were carried out in 2010 and 2011. Data were analyzed through constant comparisons using the program ATLAS ti, guaranteeing credibility, reliance, validation and transferability. Five hundred and twenty eight (528) significance units were identified and 25 descriptive categories emerged. The categories of tutor motivation, methodological domain, tutor responsibility, tutor critical capacity, disciplinary domain, student participation and tutor-student interaction were emphasized. Three qualitative domains were generated, namely tutor skills, transformation of student roles and institutional commitment. Tutorial teaching is favored by teachers when the institutions train them in the subject, when there is administrative support and an adequate infrastructure and coordination.

Targeted therapy of advanced non-small cell lung cancer: the role of bevacizumab.

Science.gov (United States)

Stinchcombe, Thomas E

2007-09-01

Lung cancer is the leading cause of cancer death in the United States. The majority of patients present with advanced stage disease, and treatment with standard cytotoxic chemotherapy agents have been shown to provide a modest improvement in survival, reduce disease-related symptoms, and improve quality of life. However, with standard chemotherapy treatments the prognosis is poor with the majority of patients dying in less than a year from diagnosis. Treatment with standard chemotherapy agents has reached a therapeutic plateau, and recent investigations have focused on therapies that target a specific pathway within the malignant cell or related to angiogenesis. The most promising of the targeted therapies are agents that target the process of angiogenesis. Bevacizuamab is a monoclonal antibody that binds to circulating vascular endothelial growth factor (VEGF)-A, and prevents binding of VEGF to vascular endothelial growth factor receptors, thus inhibiting activation of the VEGF pathway and angiogenesis. A recent phase III trial of first-line treatment of advanced non-small cell lung cancer revealed a statistically significant improvement in response, progression-free survival, and overall survival with the combination of bevacizumab and standard chemotherapy in comparison to standard chemotherapy alone. Bevacizumab is the only targeted therapy that has been shown to improve survival when combined with standard chemotherapy in the first-line setting.

Outcomes of Patients with Renal Cell Carcinoma and Sarcomatoid Dedifferentiation Treated with Nephrectomy and Systemic Therapies: Comparison between the Cytokine and Targeted Therapy Eras.

Science.gov (United States)

Keskin, Sarp K; Msaouel, Pavlos; Hess, Kenneth R; Yu, Kai-Jie; Matin, Surena F; Sircar, Kanishka; Tamboli, Pheroze; Jonasch, Eric; Wood, Christopher G; Karam, Jose A; Tannir, Nizar M

2017-09-01

We studied overall survival and prognostic factors in patients with sarcomatoid renal cell carcinoma treated with nephrectomy and systemic therapy in the cytokine and targeted therapy eras. This is a retrospective study of patients with sarcomatoid renal cell carcinoma who underwent nephrectomy and received systemic therapy at our center in the cytokine era (1987 to 2005) or the targeted therapy era (2006 to 2015). Multivariate regression models were used to determine the association of covariables with survival. Of the 199 patients with sarcomatoid renal cell carcinoma 167 (83.9%) died (median overall survival 16.5 months, 95% CI 15.2-20.9). Survival of patients with clear cell histology was significantly longer vs those with nonclear cell histology (p = 0.034). Patients with synchronous metastatic disease had significantly shorter survival than patients with metachronous metastatic disease (median 12.1 vs 23.3 months, p = 0.0064). Biopsy of the primary tumor or a metastatic site could detect the presence of sarcomatoid features in only 7.5% of cases. Although a significant improvement in survival rate was observed in the first year in patients treated in the targeted therapy era (p = 0.011), this effect was attenuated at year 2, disappeared at years 3 to 5 after diagnosis and was not evident in patients with poor risk features. Patients with sarcomatoid renal cell carcinoma still have poor prognosis with no clear long-term benefit of targeted therapy. This underscores the need to develop more effective systemic therapies for these patients. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Statistical Shape Modelling and Markov Random Field Restoration (invited tutorial and exercise)

DEFF Research Database (Denmark)

Hilger, Klaus Baggesen

This tutorial focuses on statistical shape analysis using point distribution models (PDM) which is widely used in modelling biological shape variability over a set of annotated training data. Furthermore, Active Shape Models (ASM) and Active Appearance Models (AAM) are based on PDMs and have proven...... deformation field between shapes. The tutorial demonstrates both generative active shape and appearance models, and MRF restoration on 3D polygonized surfaces. ''Exercise: Spectral-Spatial classification of multivariate images'' From annotated training data this exercise applies spatial image restoration...... using Markov random field relaxation of a spectral classifier. Keywords: the Ising model, the Potts model, stochastic sampling, discriminant analysis, expectation maximization....

Targeting SR-BI for cancer diagnostics, imaging and therapy

Directory of Open Access Journals (Sweden)

Maneesha Amrita Rajora

2016-09-01

Full Text Available Scavenger receptor class B type I (SR-BI plays an important role in trafficking cholesteryl esters between the core of high density lipoprotein and the liver. Interestingly, this integral membrane protein receptor is also implicated in the metabolism of cholesterol by cancer cells, whereby overexpression of SR-BI has been observed in a number of tumours and cancer cell lines, including breast and prostate cancers. Consequently, SR-BI has recently gained attention as a cancer biomarker and exciting target for the direct cytosolic delivery of therapeutic agents. This brief review highlights these key developments in SR-BI-targeted cancer therapies and imaging probes. Special attention is given to the exploration of high density lipoprotein nanomimetic platforms that take advantage of upregulated SR-BI expression to facilitate targeted drug-delivery and cancer diagnostics, and promising future directions in the development of these agents.

[50 years of hepatology - from therapeutic nihilism to targeted therapies].

Science.gov (United States)

Manns, Michael P

2013-04-01

Over the past 50 years significant progress has been made in the whole field of hepatology. Part of this is translation of basic research (biochemistry, immunology, virology, molecular biology and others) into clinical hepatology. This enabled us to understand more about the pathogenesis of liver diseases and led to the discovery of the five major hepatotropic viruses, the identification of hepatocellular autoantigens, and to the development of specific therapies for chronic hepatitis B, C and D. In addition, the molecular basis of most genetic liver diseases has been identified. Significant progress was made in the development of medical therapies for various liver diseases with different underlying etiologies. Surgery significantly contributed to the progress in the management of liver diseases; examples are laparoscopic cholecystectomy and the development of liver transplantation. A multimodal therapeutic algorithm has been established for the therapy of hepatocelluar carcinoma (HCC); with Sorafenib "targeted therapy" has entered the area of HCC. The progress made over the last 50 years not only led to an aetiological differentiation of acute and chronic liver diseases but also to specific therapies based on the identification and understanding of the underlying etiology. © Georg Thieme Verlag KG Stuttgart · New York.

The impact of maths support tutorials on mathematics confidence and academic performance in a cohort of HE Animal Science students.

Science.gov (United States)

van Veggel, Nieky; Amory, Jonathan

2014-01-01

Students embarking on a bioscience degree course, such as Animal Science, often do not have sufficient experience in mathematics. However, mathematics forms an essential and integral part of any bioscience degree and is essential to enhance employability. This paper presents the findings of a project looking at the effect of mathematics tutorials on a cohort of first year animal science and management students. The results of a questionnaire, focus group discussions and academic performance analysis indicate that small group tutorials enhance students' confidence in maths and improve students' academic performance. Furthermore, student feedback on the tutorial programme provides a deeper insight into student experiences and the value students assign to the tutorials.

Auto-Tutorial Instruction in Entomology: Principles of Entomology (Orders).

Science.gov (United States)

Minnick, D. R.; Steele, K. L.

Auto-tutorial instruction was compared to traditional lecture instruction in a university entomology course. In seven consecutive terms, undergraduate students enrolled in an introductory entomology course were divided into two groups: Group I received only lecture instruction on insect orders, while Group II was dismissed for three consecutive…

Tutorial : service-oriented architecture (SOA) development for serious games

NARCIS (Netherlands)

Carvalho, M.B.; Hu, J.; Bellotti, F.; de Gloria, A.; Rauterberg, G.W.M.; Chorianopoulos, K.; Divitini, M.; Hauge, J.; Jaccheri, L.; Malaka, R.

2015-01-01

This tutorial aims to introduce the benefits of applying a service-oriented architecture (SOA) approach to serious games developers. For that end, we propose a hands-on session in which we will provide information on state-of-the-art services for serious games and guide developers in rethinking one

Negative feedback and adaptive resistance to the targeted therapy of cancer.

Science.gov (United States)

Chandarlapaty, Sarat

2012-04-01

Mutational activation of growth factor signaling pathways is commonly observed and often necessary for oncogenic transformation. Under physiologic conditions, these pathways are subject to tight regulation through negative feedback, which limits the extent and duration of signaling events after physiologic stimulation. Until recently, the role of these negative feedback pathways in oncogene-driven cancers has been poorly understood. In this review, I discuss the evidence for the existence and relevance of negative feedback pathways within oncogenic signaling networks, the selective advantages such feedback pathways may confer, and the effects such feedback might have on therapies aimed at inhibiting oncogenic signaling. Negative feedback pathways are ubiquitous features of growth factor signaling networks. Because growth factor signaling networks play essential roles in the majority of cancers, their therapeutic targeting has become a major emphasis of clinical oncology. Drugs targeting these networks are predicted to inhibit the pathway but also to relieve the negative feedback. This loss of negative feedback can itself promote oncogenic signals and cancer cell survival. Drug-induced relief of feedback may be viewed as one of the major consequences of targeted therapy and a key contributor to therapeutic resistance.

Adoptive T cell therapy targeting CD1 and MR1

Directory of Open Access Journals (Sweden)

Tingxi eGuo

2015-05-01

Full Text Available Adoptive T cell immunotherapy has demonstrated clinically relevant efficacy in treating malignant and infectious diseases. However, much of these therapies have been focused on enhancing, or generating de novo, effector functions of conventional T cells recognizing HLA molecules. Given the heterogeneity of HLA alleles, mismatched patients are ineligible for current HLA-restricted adoptive T cell therapies. CD1 and MR1 are class I-like monomorphic molecules and their restricted T cells possess unique T cell receptor specificity against entirely different classes of antigens. CD1 and MR1 molecules present lipid and vitamin B metabolite antigens, respectively, and offer a new front of targets for T cell therapies. This review will cover the recent progress in the basic research of CD1, MR1, and their restricted T cells that possess translational potential.

Trojan horses and guided missiles: targeted therapies in the war on arthritis.

Science.gov (United States)

Ferrari, Mathieu; Onuoha, Shimobi C; Pitzalis, Costantino

2015-06-01

Despite major advances in the treatment of rheumatoid arthritis (RA) led by the success of biologic therapies, the lack of response to therapy in a proportion of patients, as well as therapy discontinuation owing to systemic toxicity, are still unsolved issues. Unchecked RA might develop into progressive structural joint damage, loss of function and long-term disability, disorders which are associated with a considerable health-economic burden. Therefore, new strategies are required to actively target and deliver therapeutic agents to disease sites in order to promote in situ activity and decrease systemic toxicity. Polymer-drug conjugates can improve the pharmacokinetics of therapeutic agents, conferring desirable properties such as increased solubility and tissue penetration at sites of active disease. Additionally, nanotechnology is an exciting modality in which drugs are encapsulated to protect them from degradation or early activation in the circulation, as well as to reduce systemic toxicity. Together with the targeting capacity of antibodies and site-specific peptides, these approaches will facilitate selective accumulation of therapeutic agents in the inflamed synovium, potentially improving drug efficacy at disease sites without affecting healthy tissues. This Review aims to summarize key developments in the past 5 years in polymer conjugation, nanoparticulate drug delivery and antibody or peptide-based targeting--strategies that might constitute the platform for the next generation of RA therapeutics.

Tutorial on nonlinear backstepping: Applications to ship control

Directory of Open Access Journals (Sweden)

Thor I. Fossen

1999-04-01

Full Text Available The theoretical foundation of nonlinear backstepping designs is presented in a tutorial setting. This includes a brief review of integral backstepping, extensions to SISO and MIMO systems in strict feedback form and physical motivated case studies. Parallels and differences to feedback linearization where it is shown how so-called "good nonlincarities" can be exploited in the design are also made.

A MSLN-targeted multifunctional nanoimmunoliposome for MRI and targeting therapy in pancreatic cancer

Directory of Open Access Journals (Sweden)

Deng L

2012-09-01

Full Text Available Li Deng,1,# Xingfa Ke,4,# Zhiying He,3,# Daoqiu Yang,5 Hai Gong,6 Yingying Zhang,1 Xiaolong Jing,4 Jianzhong Yao,2 Jianming Chen11Department of Pharmaceutics, 2Department of Medicinal Chemistry, School of Pharmacy, 3Department of Cell Biology, Second Military Medical University, Shanghai, People's Republic of China; 4Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fujian, People's Republic of China; 5Department of Dermatology, 107th Hospital of PLA, Yantai, People's Republic of China; 6Department of Radiation Oncology, General Hospital of Jinan Military Region, Jinan, People’s Republic of China#These authors contributed equally to this workAbstract: Pancreatic cancer is a highly lethal disease with a 5-year survival rate less than 5% due to the lack of an early diagnosis method and effective therapy. To provide a novel early diagnostic method and targeted therapy for pancreatic cancer, a multifunctional nanoimmunoliposome with high loading of ultrasmall superparamagnetic iron oxides (USPIOs and doxorubicin (DOX was prepared by transient binding and reverse-phase evaporation method, and was conjugated with anti-mesothelin monoclonal antibody by post-insertion method to target anti-mesothelin-overexpressed pancreatic cancer cells. The in vitro and in vivo properties of this anti-mesothelin antibody-conjugated PEGlyated liposomal DOX and USPIOs (M-PLDU; and PEGlyated nanoimmunoliposome without antibody conjugation [PLDU] were evaluated both in human pancreatic cancer cell line Panc-1 cell and in a pancreatic cancer xenograft animal model. Results showed that M-PLDUs were spherical and uniform with a diameter about ~180 nm, with a zeta potential of about −28~−30 mV, and had good efficacy encapsulating DOX and USPIOs. The in vitro study demonstrated that M-PLDUs possessed good magnetic resonance imaging (MRI capability with a transverse relaxivity (r2 of about 58.5 mM–1 • s–1. Confocal microscopy showed more

Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer.

Science.gov (United States)

Matsuda, Naoko; Lim, Bora; Wang, Xiaoping; Ueno, Naoto T

2017-04-01

Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered: This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion: Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted.

[Management of side effects of targeted therapies in renal cancer: stomatological side effects (mucositis, epistaxis)].

Science.gov (United States)

Agbo-Godeau, Scarlette; Nicolas-Virelizier, Emmanuelle; Scotté, Florian

2011-01-01

The advent of targeted therapies in the treatment of renal cancer has shown different types of lesions of the oral cavity, which appear to be specific to the drug classes used (mTOR inhibitors, anti-angiogenic agents and conventional cytotoxic drugs). Before starting treatment with targeted therapy, it is essential to have an oral and a dental examination. The treatment of mucositis induced by targeted therapies is based on bicarbonate-based mouthwash, with the optional addition of an antifungal or a local antiseptic. It is possible to use topical or systemic analgesics for the pain. Dietary advice for patients is also useful. Most cases of epistaxis caused by anti-angiogenics stop spontaneously and require no medical intervention. Regular application of an emollient can be used to prevent the formation of scabs. Copyright © 2011 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Pannus growth regulators as potential targets for biological therapy in rheumatoid arthritis

Directory of Open Access Journals (Sweden)

A. S. Mikhaylova

2018-01-01

Full Text Available The main goal of treatment for rheumatoid arthritis (RA is to suppress inflammation using basic and symptomatic therapies. At the same time, the above strategy does not significantly stop joint  destruction that leads to disability in patients. The review analyzes  publications dealing with a search for intercellular interaction  regulators among the main effector cells in the pannus – fibroblast- like synoviocytes (FLSs. It assesses the influence of FLS aggression  factors on invasive pannus behavior, the possibility of their targeted deactivation during biological therapy, and the preliminary  results of similar treatment by the examples of animal models. It is  shown that the most promising targets for biological therapy may be FLS adhesion molecules, such as transmembrane receptor cadherin  11, integrins α5/β1, and VCAM1, ICAM1, which actively participate in the attachment of FLSs to the cartilage surface and activate their production of cytokines, growth factors and aggression factors.

Adaptive Radiation Therapy for Postprostatectomy Patients Using Real-Time Electromagnetic Target Motion Tracking During External Beam Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Zhu, Mingyao [Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, Missouri (United States); Bharat, Shyam [Philips Research North America, Briarcliff Manor, New York (United States); Michalski, Jeff M.; Gay, Hiram A. [Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, Missouri (United States); Hou, Wei-Hsien [St Louis University School of Medicine, St Louis, Missouri (United States); Parikh, Parag J., E-mail: pparikh@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, Missouri (United States)

2013-03-15

Purpose: Using real-time electromagnetic (EM) transponder tracking data recorded by the Calypso 4D Localization System, we report inter- and intrafractional target motion of the prostate bed, describe a strategy to evaluate treatment adequacy in postprostatectomy patients receiving intensity modulated radiation therapy (IMRT), and propose an adaptive workflow. Methods and Materials: Tracking data recorded by Calypso EM transponders was analyzed for postprostatectomy patients that underwent step-and-shoot IMRT. Rigid target motion parameters during beam delivery were calculated from recorded transponder positions in 16 patients with rigid transponder geometry. The delivered doses to the clinical target volume (CTV) were estimated from the planned dose matrix and the target motion for the first 3, 5, 10, and all fractions. Treatment adequacy was determined by comparing the delivered minimum dose (D{sub min}) with the planned D{sub min} to the CTV. Treatments were considered adequate if the delivered CTV D{sub min} is at least 95% of the planned CTV D{sub min}. Results: Translational target motion was minimal for all 16 patients (mean: 0.02 cm; range: −0.12 cm to 0.07 cm). Rotational motion was patient-specific, and maximum pitch, yaw, and roll were 12.2, 4.1, and 10.5°, respectively. We observed inadequate treatments in 5 patients. In these treatments, we observed greater target rotations along with large distances between the CTV centroid and transponder centroid. The treatment adequacy from the initial 10 fractions successfully predicted the overall adequacy in 4 of 5 inadequate treatments and 10 of 11 adequate treatments. Conclusion: Target rotational motion could cause underdosage to partial volume of the postprostatectomy targets. Our adaptive treatment strategy is applicable to post-prostatectomy patients receiving IMRT to evaluate and improve radiation therapy delivery.

Identifying The Target Market For a New Floatation Therapy Service, Flowtion

OpenAIRE

Varpomaa, Jerry

2016-01-01

The purpose of this thesis was to probe and identify the most potential target market for a new kind of wellness-service for Flowtion, a state-of-the-art floatation therapy center, focusing on floatation tanks. To accomplish the main goal for this thesis, a survey was conducted using “Google Forms”. The survey was spread through social media (Facebook), and as a result 41 people answered. The survey helps Flowtion to define their most potential target segment, their behaviour and profile vari...

Beyond typing and grading: target analysis in individualized therapy as a new challenge for tumour pathology.

Science.gov (United States)

Kreipe, Hans H; von Wasielewski, Reinhard

2007-01-01

In order to bring about its beneficial effects in oncology, targeted therapy depends on accurate target analysis. Whether cells of a tumour will be sensitive to a specific treatment is predicted by the detection of appropriate targets in cancer tissue by immunohistochemistry or molecular methods. In most instances this is performed by histopathologists. Reliability and reproducibility of tissue-based target analysis in histopathology require novel measures of quality assurance by internal and external controls. As a model for external quality assurance in targeted therapy an annual inter-laboratory trial has been set up in Germany applying tissue arrays with up to 60 mammary cancer samples which are tested by participants for expression of HER2/neu and steroid hormone receptors.

The acquisition and retention of ECG interpretation skills after a standardized web-based ECG tutorial

DEFF Research Database (Denmark)

Rolskov Bojsen, Signe; Räder, Sune Bernd Emil Werner; Holst, Anders Gaardsdal

2015-01-01

BACKGROUND: Electrocardiogram (ECG) interpretation is of great importance for patient management. However, medical students frequently lack proficiency in ECG interpretation and rate their ECG training as inadequate. Our aim was to examine the effect of a standalone web-based ECG tutorial...... and to assess the retention of skills using multiple follow-up intervals. METHODS: 203 medical students were included in the study. All participants completed a pre-test, an ECG tutorial, and a post-test. The participants were also randomised to complete a retention-test after short (2-4 weeks), medium (10.......6), respectively). When comparing the pre-test to retention-test delta scores, junior students had learned significantly more than senior students (junior students improved 10.7 points and senior students improved 4.7 points, p = 0.003). CONCLUSION: A standalone web-based ECG tutorial can be an effective means...

Tutorial: Assessment and Analysis of Polysyllables in Young Children

Science.gov (United States)

Masso, Sarah; McLeod, Sharynne; Baker, Elise

2018-01-01

Purpose: Polysyllables, words of 3 or more syllables, represent almost 30% of words used in American English. The purpose of this tutorial is to support speech-language pathologists' (SLPs') assessment and analysis of polysyllables, extending the focus of published assessment tools that focus on sampling and analyzing children's segmental accuracy…

Tumor targeted gene therapy

International Nuclear Information System (INIS)

Kang, Joo Hyun

2006-01-01

Knowledge of molecular mechanisms governing malignant transformation brings new opportunities for therapeutic intervention against cancer using novel approaches. One of them is gene therapy based on the transfer of genetic material to an organism with the aim of correcting a disease. The application of gene therapy to the cancer treatment had led to the development of new experimental approaches such as suicidal gene therapy, inhibition of oncogenes and restoration of tumor-suppressor genes. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a prodrug into a toxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1-tk) and cytosine deaminase (CD). Especially, physicians and scientists of nuclear medicine field take an interest in suicidal gene therapy because they can monitor the location and magnitude, and duration of expression of HSV1-tk and CD by PET scanner

Therapies targeting inflammation after stent implantation.

Science.gov (United States)

Okura, Hiroyuki; Takagi, Tsutomu; Yoshida, Kiyoshi

2013-07-01

Since the introduction of coronary vessel scaffold by metallic stent, percutaneous coronary intervention has become widely performed all over the world. Although drug-eluting stent technology has further decrease the incidence of in-stent restenosis, there still remaining issues related to stent implantation. Vessel inflammation is one of the causes that may be related to stent restenosis as well as stent thrombosis. Therefore, systemic therapies targeting inflammation emerged as adjunctive pharmacological intervention to improve outcome. Statins, corticosteroids, antiplatelets, and immunosuppresive or anti-cancer drugs are reported to favorably impact outcome after bare-metal stent implantation. In type 2 diabetic patients, pioglitazone may be the most promising drug that can lower neointimal proliferation and, as a result, lower incidence of restenosis and target lesion revascularization. On the other hand, several new stent platforms that might decrease inflammatory response after drug-eluting stent implantation have been introduced. Because durable polymer used in the first generation drug-eluting stents are recognized to be responsible for unfavorable vessel response, biocompatible or bioabsorbable polymer has been introduce and already used clinically. Furthermore, polymer-free drug-eluting stent and bioresorbable scaffold are under investigation. Although vessel inflammation may be reduced by using these new drug-eluting stents or scaffold, long-term impact needs to be investigated further.

Use of Neoadjuvant Chemotherapy Plus Molecular Targeted Therapy in Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

Science.gov (United States)

Sabanathan, Dhanusha; Eslick, Guy D; Shannon, Jenny

2016-12-01

Surgery remains the standard of care for patients with colorectal liver metastases (CLMs), with a 5-year survival rate approaching 35%. Perioperative chemotherapy confers a survival benefit in selected patients with CLMs. The use of molecular targeted therapy combined with neoadjuvant chemotherapy for CLMs, however, remains controversial. We reviewed the published data on combination neoadjuvant chemotherapy and molecular targeted therapy for resectable and initially unresectable CLMs. A literature search of the Medline and PubMed databases was conducted to identify studies of neoadjuvant chemotherapy plus molecular targeted therapy in the management of resectable or initially unresectable CLMs. We calculated the pooled proportion and 95% confidence intervals using a random effects model for the relationship of the combination neoadjuvant treatment on the overall response rate and performed a systematic review of all identified studies. The analysis was stratified according to the study design. The data from 11 studies of 908 patients who had undergone systemic chemotherapy plus targeted therapy for CLM were analyzed. The use of combination neoadjuvant therapy was associated with an overall response rate of 68% (95% confidence interval, 63%-73%), with significant heterogeneity observed in the studies (I 2  = 89.35; P chemotherapy plus molecular targeted agents for CLM confers high overall response rates. Combination treatment might also increase the resectability rates in initially unresectable CLM. Further studies are needed to examine the survival outcomes, with a focus on the differential role of molecular targeted therapy in the neoadjuvant versus adjuvant setting. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Characterizing representational learning: A combined simulation and tutorial on perturbation theory

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Antje Kohnle

2017-11-01

Full Text Available Analyzing, constructing, and translating between graphical, pictorial, and mathematical representations of physics ideas and reasoning flexibly through them (“representational competence” is a key characteristic of expertise in physics but is a challenge for learners to develop. Interactive computer simulations and University of Washington style tutorials both have affordances to support representational learning. This article describes work to characterize students’ spontaneous use of representations before and after working with a combined simulation and tutorial on first-order energy corrections in the context of quantum-mechanical time-independent perturbation theory. Data were collected from two institutions using pre-, mid-, and post-tests to assess short- and long-term gains. A representational competence level framework was adapted to devise level descriptors for the assessment items. The results indicate an increase in the number of representations used by students and the consistency between them following the combined simulation tutorial. The distributions of representational competence levels suggest a shift from perceptual to semantic use of representations based on their underlying meaning. In terms of activity design, this study illustrates the need to support students in making sense of the representations shown in a simulation and in learning to choose the most appropriate representation for a given task. In terms of characterizing representational abilities, this study illustrates the usefulness of a framework focusing on perceptual, syntactic, and semantic use of representations.

Characterizing representational learning: A combined simulation and tutorial on perturbation theory

Science.gov (United States)

Kohnle, Antje; Passante, Gina

2017-12-01

Analyzing, constructing, and translating between graphical, pictorial, and mathematical representations of physics ideas and reasoning flexibly through them ("representational competence") is a key characteristic of expertise in physics but is a challenge for learners to develop. Interactive computer simulations and University of Washington style tutorials both have affordances to support representational learning. This article describes work to characterize students' spontaneous use of representations before and after working with a combined simulation and tutorial on first-order energy corrections in the context of quantum-mechanical time-independent perturbation theory. Data were collected from two institutions using pre-, mid-, and post-tests to assess short- and long-term gains. A representational competence level framework was adapted to devise level descriptors for the assessment items. The results indicate an increase in the number of representations used by students and the consistency between them following the combined simulation tutorial. The distributions of representational competence levels suggest a shift from perceptual to semantic use of representations based on their underlying meaning. In terms of activity design, this study illustrates the need to support students in making sense of the representations shown in a simulation and in learning to choose the most appropriate representation for a given task. In terms of characterizing representational abilities, this study illustrates the usefulness of a framework focusing on perceptual, syntactic, and semantic use of representations.

Immune checkpoint inhibitors and targeted therapies for metastatic melanoma: A network meta-analysis.

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Pasquali, Sandro; Chiarion-Sileni, Vanna; Rossi, Carlo Riccardo; Mocellin, Simone

2017-03-01

Immune checkpoint inhibitors and targeted therapies, two new class of drugs for treatment of metastatic melanoma, have not been compared in randomized controlled trials (RCT). We quantitatively summarized the evidence and compared immune and targeted therapies in terms of both efficacy and toxicity. A comprehensive search for RCTs of immune checkpoint inhibitors and targeted therapies was conducted to August 2016. Using a network meta-analysis approach, treatments were compared with each other and ranked based on their effectiveness (as measured by the impact on progression-free survival [PFS]) and acceptability (the inverse of high grade toxicity). Twelve RCTs enrolling 6207 patients were included. Network meta-analysis generated 15 comparisons. Combined BRAF and MEK inhibitors were associated with longer PFS as compared to anti-CTLA4 (HR: 0.22; 95% confidence interval [CI]: 0.12-0.41) and anti-PD1 antibodies alone (HR: 0.38; CI: 0.20-0.72). However, anti-PD1 monoclonal antibodies were less toxic than anti-CTLA4 monoclonal antibodies (RR: 0.65; CI: 0.40-0.78) and their combination significantly increased toxicity compared to either single agent anti-CTLA4 (RR: 2.06; CI: 1.45-2.93) or anti-PD1 monoclonal antibodies (RR: 3.67; CI: 2.27-5.96). Consistently, ranking analysis suggested that the combination of targeted therapies is the most effective strategy, whereas single agent anti-PD1 antibodies have the best acceptability. The GRADE level of evidence quality for these findings was moderate to low. The simultaneous inhibition of BRAF and MEK appears the most effective treatment for melanomas harboring BRAF V600 mutation, although anti-PD1 antibodies appear to be less toxic. Further research is needed to increase the quality of evidence. Copyright © 2017 Elsevier Ltd. All rights reserved.

Patient-derived xenograft models to improve targeted therapy in epithelial ovarian cancer treatment

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Clare eScott

2013-12-01

Full Text Available Despite increasing evidence that precision therapy targeted to the molecular drivers of a cancer has the potential to improve clinical outcomes, high-grade epithelial ovarian cancer patients are currently treated without consideration of molecular phenotype, and predictive biomarkers that could better inform treatment remain unknown. Delivery of precision therapy requires improved integration of laboratory-based models and cutting-edge clinical research, with pre-clinical models predicting patient subsets that will benefit from a particular targeted therapeutic. Patient-derived xenografts (PDX are renewable tumor models engrafted in mice, generated from fresh human tumors without prior in vitro exposure. PDX models allow an invaluable assessment of tumor evolution and adaptive response to therapy.PDX models have been applied to preclinical drug testing and biomarker identification in a number of cancers including ovarian, pancreatic, breast and prostate cancers. These models have been shown to be biologically stable and accurately reflect the patient tumor with regards to histopathology, gene expression, genetic mutations and therapeutic response. However, pre-clinical analyses of molecularly annotated PDX models derived from high-grade serous ovarian cancer (HG-SOC remain limited. In vivo response to conventional and/or targeted therapeutics has only been described for very small numbers of individual HG-SOC PDX in conjunction with sparse molecular annotation and patient outcome data. Recently, two consecutive panels of epithelial ovarian cancer PDX correlate in vivo platinum response with molecular aberrations and source patient clinical outcomes. These studies underpin the value of PDX models to better direct chemotherapy and predict response to targeted therapy. Tumor heterogeneity, before and following treatment, as well as the importance of multiple molecular aberrations per individual tumor underscore some of the important issues

Maintaining Quality While Expanding Our Reach: Using Online Information Literacy Tutorials in the Sciences and Health Sciences

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Talitha Rosa Matlin

2017-09-01

Full Text Available Abstract Objective – This article aims to assess student achievement of higher-order information literacy learning outcomes from online tutorials as compared to in-person instruction in science and health science courses. Methods – Information literacy instruction via online tutorials or an in-person one-shot session was implemented in multiple sections of a biology (n=100 and a kinesiology course (n=54. After instruction, students in both instructional environments completed an identical library assignment to measure the achievement of higher-order learning outcomes and an anonymous student survey to measure the student experience of instruction. Results – The data collected from library assignments revealed no statistically significant differences between the two instructional groups in total assignment scores or scores on specific questions related to higher-order learning outcomes. Student survey results indicated the student experience is comparable between instruction groups in terms of clarity of instruction, student confidence in completing the course assignment after library instruction, and comfort in asking a librarian for help after instruction. Conclusions – This study demonstrates that it is possible to replace one-shot information literacy instruction sessions with asynchronous online tutorials with no significant reduction in student learning in undergraduate science and health science courses. Replacing in-person instruction with online tutorials will allow librarians at this university to reach a greater number of students and maintain contact with certain courses that are transitioning to completely online environments. While the creation of online tutorials is initially time-intensive, over time implementing online instruction could free up librarian time to allow for the strategic integration of information literacy instruction into other courses. Additional time savings could be realized by incorporating auto

A new target concept for proton accelerator driven boron neutron capture therapy applications

International Nuclear Information System (INIS)

Powell, J.R.; Ludewig, H.; Todosow, M.; Reich, M.

1998-01-01

A new target concept termed Discs Incorporating Sector Configured Orbiting Sources (DISCOS), is proposed for spallation applications, including BNCT (Boron Neutron Capture Therapy). In the BNCT application a proton beam impacts a sequence of ultra thin lithium DISCOS targets to generate neutrons by the 7 Li(p,n) 7 Be reaction. The proton beam loses only a few keV of its ∼MeV energy as it passes through a given target, and is re-accelerated to its initial energy, by a DC electric field between the targets

TUTORIAL COACHING AS A STRATEGY OF PROFESSIONAL AND PERSONAL DEVELOPMENT: AN EXPERIENCE-BASED STUDY IN A SECONDARY EDUCATION INSTITUTE

Directory of Open Access Journals (Sweden)

GLADYS IBETH ARIZA ORDÓÑEZ

2005-01-01

Full Text Available Tutorial accompaniment constitutes at present a necessary alternative in the framework of higher education. This workstarts with a general conceptualization of the tutorial, and makes a review of the styles, methods and proceduresrelated to this academic life facet which can effectively contribute to reach the goals the present higher education pursuitwhen it is applied in a coherent and systematic way.Considering the changes that the economy as well as the legislation have generated in education, and mainly in thoseLatin-American university programs, it is necessary to generate changing processes on the curriculum conceptualization,the teaching activities and the academic planning, and also to promote tutorial programs to the students, in order torespond to the difficulties they confront along the different stages of their lives. This research emerges from the onecarried out about the effectiveness of a tutorial program at a Psychology Department. It pretends to highlight theprincipal points of the accompaniment tutorial programs that require to be adjusted and adapted, in order to facilitatean educational service aimed to consider not only the professional training but the personal formation as well.

Medical student perceptions of factors affecting productivity of problem-based learning tutorial groups: does culture influence the outcome?

Science.gov (United States)

Das Carlo, Mandira; Swadi, Harith; Mpofu, Debbie

2003-01-01

The popularization of problem-based learning (PBL) has drawn attention to the motivational and cognitive skills necessary for medical students in group learning. This study identifies the effect of motivational and cognitive factors on group productivity of PBL tutorial groups. A self-administered questionnaire was completed by 115 students at the end of PBL tutorials for 4 themes. The questionnaire explored student perceptions about effect of motivation, cohesion, sponging, withdrawal, interaction, and elaboration on group productivity. We further analyzed (a) differences in perceptions between male and female students, (b) effect of "problems," and (c) effect of student progress over time on group productivity. There were linear relations between a tutorial group's success and the factors studied. Significant differences were noted between male and female student groups. Students and tutors need to recognize symptoms of ineffective PBL groups. Our study emphasizes the need to take into account cultural issues in setting ground rules for PBL tutorials.

Targeting Metabolic Symbiosis to Overcome Resistance to Anti-angiogenic Therapy

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Laura Pisarsky

2016-05-01

Full Text Available Despite the approval of several anti-angiogenic therapies, clinical results remain unsatisfactory, and transient benefits are followed by rapid tumor recurrence. Here, we demonstrate potent anti-angiogenic efficacy of the multi-kinase inhibitors nintedanib and sunitinib in a mouse model of breast cancer. However, after an initial regression, tumors resume growth in the absence of active tumor angiogenesis. Gene expression profiling of tumor cells reveals metabolic reprogramming toward anaerobic glycolysis. Indeed, combinatorial treatment with a glycolysis inhibitor (3PO efficiently inhibits tumor growth. Moreover, tumors establish metabolic symbiosis, illustrated by the differential expression of MCT1 and MCT4, monocarboxylate transporters active in lactate exchange in glycolytic tumors. Accordingly, genetic ablation of MCT4 expression overcomes adaptive resistance against anti-angiogenic therapy. Hence, targeting metabolic symbiosis may be an attractive avenue to avoid resistance development to anti-angiogenic therapy in patients.

Review of the Interaction Between Body Composition and Clinical Outcomes in Metastatic Renal Cell Cancer Treated With Targeted Therapies

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Steven M Yip

2016-03-01

Full Text Available Treatment of metastatic renal cell cancer (mRCC currently focuses on inhibition of the vascular endothelial growth factor pathway and the mammalian target of rapamycin (mTOR pathway. Obesity confers a higher risk of RCC. However, the influence of obesity on clinical outcomes in mRCC in the era of targeted therapy is less clear. This review focuses on the impact of body composition on targeted therapy outcomes in mRCC. The International Metastatic Renal Cell Carcinoma Database Consortium database has the largest series of patients evaluating the impact of body mass index (BMI on outcomes in mRCC patients treated with targeted therapy. Overall survival was significantly improved in overweight patients (BMI ≥ 25 kg/m2, and this observation was externally validated in patients who participated in Pfizer trials. In contrast, sarcopenia is consistently associated with increased toxicity to inhibitors of angiogenesis and mTOR. Strengthening patients with mRCC and sarcopenia, through a structured exercise program and dietary intervention, may improve outcomes in mRCC treated with targeted therapies. At the same time, the paradox of obesity being a risk factor for RCC while offering a better overall survival in response to targeted therapy needs to be further evaluated.

Protein-anchoring therapy to target extracellular matrix proteins to their physiological destinations.

Science.gov (United States)

Ito, Mikako; Ohno, Kinji

2018-02-20

Endplate acetylcholinesterase (AChE) deficiency is a form of congenital myasthenic syndrome (CMS) caused by mutations in COLQ, which encodes collagen Q (ColQ). ColQ is an extracellular matrix (ECM) protein that anchors AChE to the synaptic basal lamina. Biglycan, encoded by BGN, is another ECM protein that binds to the dystrophin-associated protein complex (DAPC) on skeletal muscle, which links the actin cytoskeleton and ECM proteins to stabilize the sarcolemma during repeated muscle contractions. Upregulation of biglycan stabilizes the DPAC. Gene therapy can potentially ameliorate any disease that can be recapitulated in cultured cells. However, the difficulty of tissue-specific and developmental stage-specific regulated expression of transgenes, as well as the difficulty of introducing a transgene into all cells in a specific tissue, prevents us from successfully applying gene therapy to many human diseases. In contrast to intracellular proteins, an ECM protein is anchored to the target tissue via its specific binding affinity for protein(s) expressed on the cell surface within the target tissue. Exploiting this unique feature of ECM proteins, we developed protein-anchoring therapy in which a transgene product expressed even in remote tissues can be delivered and anchored to a target tissue using specific binding signals. We demonstrate the application of protein-anchoring therapy to two disease models. First, intravenous administration of adeno-associated virus (AAV) serotype 8-COLQ to Colq-deficient mice, resulting in specific anchoring of ectopically expressed ColQ-AChE at the NMJ, markedly improved motor functions, synaptic transmission, and the ultrastructure of the neuromuscular junction (NMJ). In the second example, Mdx mice, a model for Duchenne muscular dystrophy, were intravenously injected with AAV8-BGN. The treatment ameliorated motor deficits, mitigated muscle histopathologies, decreased plasma creatine kinase activities, and upregulated expression

LHC@home online tutorial for Mac users - recording

CERN Multimedia

CERN. Geneva

2016-01-01

A step-by-step online tutorial about LHC@home for Mac users by Alexandre Racine. It contains detailed instructions on how-to-join this volunteer computing project.  There are 3 screen capture videos with the real installation process accelerated attached to the event page. This 5' video is linked from http://lhcathome.web.cern.ch/join-us Also from the CDS e-learning category.

Improving the Therapeutic Potential of Human Granzyme B for Targeted Cancer Therapy

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Georg Melmer

2013-01-01

Full Text Available Conventional cancer treatments lack specificity and often cause severe side effects. Targeted therapeutic approaches are therefore preferred, including the use of immunotoxins (ITs that comprise cell-binding and cell death-inducing components to allow the direct and specific delivery of pro-apoptotic agents into malignant cells. The first generation of ITs consisted of toxins derived from bacteria or plants, making them immunogenic in humans. The recent development of human cytolytic fusion proteins (hCFP consisting of human effector enzymes offers the prospect of highly-effective targeted therapies with minimal side effects. One of the most promising candidates is granzyme B (GrB and this enzyme has already demonstrated its potential for targeted cancer therapy. However, the clinical application of GrB may be limited because it is inactivated by the overexpression in tumors of its specific inhibitor serpin B9 (PI-9. It is also highly charged, which means it can bind non-specifically to the surface of non-target cells. Furthermore, human enzymes generally lack an endogenous translocation domain, thus the endosomal release of GrB following receptor-mediated endocytosis can be inefficient. In this review we provide a detailed overview of these challenges and introduce promising solutions to increase the cytotoxic potency of GrB for clinical applications.

Target volume delineation and treatment planning for particle therapy a practical guide

CERN Document Server

Leeman, Jonathan E; Cahlon, Oren; Sine, Kevin; Jiang, Guoliang; Lu, Jiade J; Both, Stefan

2018-01-01

This handbook is designed to enable radiation oncologists to treat patients appropriately and confidently by means of particle therapy. The orientation and purpose are entirely practical, in that the focus is on the physics essentials of delivery and treatment planning , illustration of the clinical target volume (CTV) and associated treatment planning for each major malignancy when using particle therapy, proton therapy in particular. Disease-specific chapters provide guidelines and concise knowledge on CTV selection and delineation and identify aspects that require the exercise of caution during treatment planning. The treatment planning techniques unique to proton therapy for each disease site are clearly described, covering beam orientation, matching/patching field techniques, robustness planning, robustness plan evaluation, etc. The published data on the use of particle therapy for a given disease site are also concisely reported. In addition to fully meeting the needs of radiation oncologists, this "kn...

Effectiveness of Targeted Musical Therapy on Sleep Quality and Overcoming Insomnia in Seniors

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Reza Mottaghi

2016-07-01

Conclusion: The present study showed that targeted music therapy can lead to the improvement in the overall sleep quality, daily functioning, and subjective sleep quality thereby resulting in a sharp decline in the number of sleep drugs in seniors with primary insomnia disorder. Therefore, it is highly recommended by the music therapy and mental health experts for overcoming the sleep problems in older adults.

TUTORIALS AS A STRATEGY TO STRENGTHEN THE UPPER LEVEL

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Francisco Antonio Romero-Leyva

2014-01-01

Full Text Available In the University context tutorials are displayed as a strategy for improving the quality of higher education, therefore the Universidad de Occidente in its educational model has incorporated this program; on the basis of the above it is interesting to perform an analysis and proposal to improve the institutional program of mentoring (PIT of the U de O, El Fuerte unit. The objective of this research was an analysis of the institutional program of tutoring from the Universidad de Occidente, El Fuerte unit and propose suggestions for improvements. The deductive-inductive method was used, non-probability sampling, with a representative sample of 10% of the universe, the techniques applied the questionnaire and the interview. The sources consulted were; personal, institutional, electronic sources and documentary Among the outstanding results include that it is essential that the IES put in place tutorial systems through which students have to throughout their training with the advice and support of a teacher properly prepared, the way how they are implemented is commitment of each institution, in El Fuerte Unit is necessary training quarterly to the body of tutors, have comfortable spaces for the tutorial process, the administrative authorities require compliance with the listing because it allows the tutor to better control and management problems of their tutees, having the program strategies to rescue students who for various reasons leave the classrooms of the University; this program being a tool to comply with Tutoring System, thereby obtaining increased rates and terminal efficiency and comply graduate profile al. As tutors we need to reflect critically on our personal and professional performance when interacting with tutees, to promote change and the process of development of human potential performance.

Investigating Learning with an Interactive Tutorial: A Mixed-Methods Strategy

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de Villiers, M. R.; Becker, Daphne

2017-01-01

From the perspective of parallel mixed-methods research, this paper describes interactivity research that employed usability-testing technology to analyse cognitive learning processes; personal learning styles and times; and errors-and-recovery of learners using an interactive e-learning tutorial called "Relations." "Relations"…

Effect of Tutorial Mode of Computer-Assisted Instruction on Students ...

African Journals Online (AJOL)

This study investigated the effect of Tutorial Mode of Computer- Assisted Instruction (CAI) on students' academic performance in practical geography in Nigeria, However, the sample population of eighty (80) Senior Secondary School Two geography students that were randomly selected from two privately owned secondary ...

Chitosan-based multifunctional nanomedicines and theranostics for targeted therapy of cancer.

Science.gov (United States)

Fathi, Marziyeh; Majidi, Sima; Zangabad, Parham Sahandi; Barar, Jaleh; Erfan-Niya, Hamid; Omidi, Yadollah

2018-05-30

Nanotechnology as an emerging field has established inevitable impacts on nano-biomedicine and treatment of formidable diseases, inflammations, and malignancies. In this regard, substantial advances in the design of systems for delivery of therapeutic agents have emerged magnificent and innovative pathways in biomedical applications. Chitosan (CS) is derived via deacetylation of chitin as the second most abundant polysaccharide. Owing to the unique properties of CS (e.g., biocompatibility, biodegradability, bioactivity, mucoadhesion, cationic nature and functional groups), it is an excellent candidate for diverse biomedical and pharmaceutical applications such as drug/gene delivery, transplantation of encapsulated cells, tissue engineering, wound healing, antimicrobial purposes, etc. In this review, we will document, discuss, and provide some key insights toward design and application of miscellaneous nanoplatforms based on CS. The CS-based nanosystems (NSs) can be employed as advanced drug delivery systems (DDSs) in large part due to their remarkable physicochemical and biological characteristics. The abundant functional groups of CS allow the facile functionalization in order to engineer multifunctional NSs, which can simultaneously incorporate therapeutic agents, molecular targeting, and diagnostic/imaging capabilities in particular against malignancies. These multimodal NSs can be literally translated into clinical applications such as targeted diagnosis and therapy of cancer because they offer minimal systemic toxicity and maximal cytotoxicity against cancer cells and tumors. The recent developments in the CS-based NSs functionalized with targeting and imaging agents prove CS as a versatile polymer in targeted imaging and therapy. © 2018 Wiley Periodicals, Inc.

Tutorial: Calculating Percentile Rank and Percentile Norms Using SPSS

Science.gov (United States)

Baumgartner, Ted A.

2009-01-01

Practitioners can benefit from using norms, but they often have to develop their own percentile rank and percentile norms. This article is a tutorial on how to quickly and easily calculate percentile rank and percentile norms using SPSS, and this information is presented for a data set. Some issues in calculating percentile rank and percentile…

Inhibition of Axl improves the targeted therapy against ALK-mutated neuroblastoma

Energy Technology Data Exchange (ETDEWEB)

Xu, Fei [Department of Neurology, Sichuan Medical Science Institute and Sichuan Provincial Hospital, Chengdu 610072 (China); Li, Hongling [Department of Radiotherapy, Shanghai First People’s Hospital, Shanghai Jiao Tong University, Shanghai 201620 (China); Sun, Yong, E-mail: sunfanqi2010@163.com [Department of Burn and Plastic Surgery, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an 223300 (China)

2014-11-28

Highlights: • First reported Axl is co-expressed with ALK in neuroblastoma tissues and cell lines. • Axl activation promotes cell growth and impairs the efficiency of ALK inhibitor. • Further found silence of Axl leads to increased sensitivity to ALK inhibitors. • Axl inhibitor promotes the efficiency of targeted therapy in vitro and in vivo. • Axl activation should be considered in the clinical application of ALK inhibitors. - Abstract: Neuroblastoma (NB) patients harboring mutated ALK can be expected to potentially benefit from targeted therapy based on ALK tyrosine kinase inhibitor (TKI), such as crizotinib and ceritinib. However, the effect of the treatment varies with different individuals, although with the same genic changes. Axl receptor tyrosine kinase is expressed in a variety of human cancers, but little data are reported in NB, particularly in which carrying mutated ALK. In this study, we focus on the roles of Axl in ALK-mutated NB for investigating rational therapeutic strategy. We found that Axl is expressed in ALK-positive NB tissues and cell lines, and could be effectively activated by its ligand GAS6. Ligand-dependent Axl activation obviously rescued crizotinib-mediated suppression of cell proliferation in ALK-mutated NB cells. Genetic inhibition of Axl with specific small interfering RNA markedly increased the sensitivity of cells to ALK-TKIs. Furthermore, a small-molecule inhibitor of Axl significantly enhanced ALK-targeted therapy, as an increased frequency of apoptosis was observed in NB cells co-expressing ALK and Axl. Taken together, our results demonstrated that activation of Axl could lead to insensitivity to ALK inhibitors, and dual inhibition of ALK and Axl might be a potential therapeutic strategy against ALK-mutated NB.

Redesigning nursing tutorials for ESL students: a pilot study.

Science.gov (United States)

San Miguel, Caroline; Townsend, Lisa; Waters, Cheryl

2013-04-01

Increased enrolments of Bachelor of Nursing (BN) students who speak English as a second language (ESL) can help create a multilingual and culturally diverse workforce that is better prepared to meet the needs of increasingly diverse health populations. However, although ESL enrolments are increasing, attrition rates for ESL students tend to be higher than those of native speakers of English, partly due to academic failure. At the same time, concerns have been expressed in some quarters about the low levels of English language of entering students. As it is unlikely that language entry levels to university will be raised, sustainable programmes that help ESL students better meet the academic challenges they may face need to be developed. So far, models of ESL support have been mostly an adjunct to their degree, voluntary and not well attended. This paper discusses a model using tutorials integrated into the first year nursing curriculum that were specifically designed for ESL students with low levels of English language proficiency. The paper also examines students' perceptions of such tutorials, which they found beneficial to their learning.

Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer

Science.gov (United States)

Matsuda, Naoko; Lim, Bora; Wang, Xiaoping; Ueno, Naoto T.

2018-01-01

Introduction Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted. PMID:28271910

A Design of Computer Aided Instructions (CAI) for Undirected Graphs in the Discrete Math Tutorial (DMT). Part 1.

Science.gov (United States)

1990-06-01

The objective of this thesis research is to create a tutorial for teaching aspects of undirected graphs in discrete math . It is one of the submodules...of the Discrete Math Tutorial (DMT), which is a Computer Aided Instructional (CAI) tool for teaching discrete math to the Naval Academy and the

A Design of Computer Aided Instructions (CAI) for Undirected Graphs in the Discrete Math Tutorial (DMT). Part 2

Science.gov (United States)

1990-06-01

The objective of this thesis research is to create a tutorial for teaching aspects of undirected graphs in discrete math . It is one of the submodules...of the Discrete Math Tutorial (DMT), which is a Computer Aided Instructional (CAI) tool for teaching discrete math to the Naval Academy and the

Low-dose radiation potentiates the therapeutic efficacy of folate receptor-targeted hapten therapy.

Science.gov (United States)

Sega, Emanuela I; Lu, Yingjuan; Ringor, Michael; Leamon, Christopher P; Low, Philip S

2008-06-01

Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm(3) before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapy with low-dose radiotherapy. Mice bearing 300-mm(3) subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon alpha) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm(3). More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice.

Low-Dose Radiation Potentiates the Therapeutic Efficacy of Folate Receptor-Targeted Hapten Therapy

International Nuclear Information System (INIS)

Sega, Emanuela I.; Lu Yingjuan; Ringor, Michael; Leamon, Christopher P.; Low, Philip S.

2008-01-01

Purpose: Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm 3 before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapy with low-dose radiotherapy. Methods and Materials: Mice bearing 300-mm 3 subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon α) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Results: Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm 3 . More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. Conclusions: These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice

The evolutionary landscape of chronic lymphocytic leukemia treated with ibrutinib targeted therapy.

Science.gov (United States)

Landau, Dan A; Sun, Clare; Rosebrock, Daniel; Herman, Sarah E M; Fein, Joshua; Sivina, Mariela; Underbayev, Chingiz; Liu, Delong; Hoellenriegel, Julia; Ravichandran, Sarangan; Farooqui, Mohammed Z H; Zhang, Wandi; Cibulskis, Carrie; Zviran, Asaf; Neuberg, Donna S; Livitz, Dimitri; Bozic, Ivana; Leshchiner, Ignaty; Getz, Gad; Burger, Jan A; Wiestner, Adrian; Wu, Catherine J

2017-12-19

Treatment of chronic lymphocytic leukemia (CLL) has shifted from chemo-immunotherapy to targeted agents. To define the evolutionary dynamics induced by targeted therapy in CLL, we perform serial exome and transcriptome sequencing for 61 ibrutinib-treated CLLs. Here, we report clonal shifts (change >0.1 in clonal cancer cell fraction, Q < 0.1) in 31% of patients during the first year of therapy, associated with adverse outcome. We also observe transcriptional downregulation of pathways mediating energy metabolism, cell cycle, and B cell receptor signaling. Known and previously undescribed mutations in BTK and PLCG2, or uncommonly, other candidate alterations are present in seventeen subjects at the time of progression. Thus, the frequently observed clonal shifts during the early treatment period and its potential association with adverse outcome may reflect greater evolutionary capacity, heralding the emergence of drug-resistant clones.

Molecular mechanisms underlying radio-induced fibro-genic differentiation and fibrosis targeted therapies

International Nuclear Information System (INIS)

Bourgier, C.

2008-01-01

Intestinal complications after radiotherapy are caused by transmural fibrosis (RIF) that impaired the quality of life of cancer patient survivors and considered permanent and irreversible until recently but recent molecular characterization of RIF offered new targeted opportunities for the development of anti-fibrotic therapies. In this thesis work, we identified activation of the Rho/ROCK pathway which is involved in the persistence of fibro-genic signals. In addition, among the new anti-fibrotic targeted therapies, we asked whether specific inhibition of Rho pathway, by Pravastatin could elicit anti-fibrotic action. Therefore, the therapeutic relevance of pravastatin as anti-fibrotic strategy was validated using two different models of intestinal and lung fibrosis. As statins are safe and well tolerated compounds, phase II clinical trial is envisioned within the next months to reverse established fibrosis after radiotherapy. (author)

Interactive video tutorials for enhancing problem solving, reasoning, and meta-cognitive skills of introductory physics students

OpenAIRE

Singh, Chandralekha

2016-01-01

We discuss the development of interactive video tutorial-based problems to help introductory physics students learn effective problem solving heuristics. The video tutorials present problem solving strategies using concrete examples in an interactive environment. They force students to follow a systematic approach to problem solving and students are required to solve sub-problems (research-guided multiple choice questions) to show their level of understanding at every stage of prob lem solvin...

Development of lithium target for accelerator based neutron capture therapy

International Nuclear Information System (INIS)

Taskaev, Sergey; Bayanov, Boris; Belov, Victor; Zhoorov, Eugene

2006-01-01

Pilot innovative accelerator based neutron source for neutron capture therapy of cancer is now of the threshold of its operation at the BINP, Russia. One of the main elements of the facility is lithium target producing neutrons via threshold 7 Li(p,n) 7 Be reaction at 25 kW proton beam with energies 1.915 MeV or 2.5 MeV. The main problems of lithium target were determined to be: 7 Be radioactive isotope activation keeping lithium layer solid, presence of photons due to proton inelastic scattering on lithium nuclei, and radiation blistering. The results of thermal test of target prototype were presented as previous NCT Congress. It becomes clear that water is preferable for cooling the target, and that lithium target 10 cm in diameter is able to run before melting. In the present report, the conception of optimal target is proposed: thin metal disk 10 cm in diameter easy for detaching, with evaporated thin layer of pure lithium from the side of proton beam exposure, its back being intensively cooled with turbulent water flow to maintain lithium layer solid. Design of the target for the neutron source constructed at BINP is shown. The results of investigation of radiation blistering and lithium layer are presented. Target unit of facility is under construction now, and obtaining neutrons is expected in nearest future. (author)

A broadcast engineering tutorial for non-engineers

CERN Document Server

Pizzi, Skip

2014-01-01

A Broadcast Engineering Tutorial for Non-Engineers is the leading publication on the basics of broadcast technology. Whether you are new to the industry or do not have an engineering background, this book will give you a comprehensive primer of television, radio, and digital media relating to broadcast-it is your guide to understanding the technical world of radio and television broadcast engineering. It covers all the important topics such as DTV, IBOC, HD, standards, video servers, editing, electronic newsrooms, and more.

Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly & Cushing Disease Paradigms

Directory of Open Access Journals (Sweden)

Michael Anthony Mooney

2016-07-01

Full Text Available The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment.

Targeted Therapy of Ewing's Sarcoma

Directory of Open Access Journals (Sweden)

Vivek Subbiah

2011-01-01

Full Text Available Refractory and/or recurrent Ewing's sarcoma (EWS remains a clinical challenge because the disease's resistance to therapy makes it difficult to achieve durable results with standard treatments that include chemotherapy, radiation, and surgery. Recently, insulin-like-growth-factor-1-receptor (IGF1R antibodies have been shown to have a modest single-agent activity in EWS. Patient selection using biomarkers and understanding response and resistance mechanisms in relation to IGF1R and mammalian target of rapamycin pathways are areas of active research. Since EWS has a unique tumor-specific EWS-FLI1 t(11;22 translocation and oncogenic fusion protein, inhibition of EWS-FLI1 transcription, translation, and/or protein function may be key to eradicating EWS at the stem-cell level. Recently, a small molecule that blocks the protein-protein interaction of EWS-FLI1 with RNA helicase A has been shown in preclinical models to inhibit EWS growth. The successful application of this first-in-class protein-protein inhibitor in the clinic could become a model system for translocation-associated cancers such as EWS.

A Study of Sustainable Assessment Theory in Higher Education Tutorials

Science.gov (United States)

Beck, Robert J.; Skinner, William F.; Schwabrow, Lynsey A.

2013-01-01

A study of sustainable assessment theory in nine tutorial courses at four colleges demonstrated that three long-term learning outcomes improved: Independence, Intellectual Maturity and Creativity. Eight of 10 traits associated with these outcomes were validated through internal reliability, faculty and student rubrics, and faculty case studies…

Uterine sarcoma part III—Targeted therapy: The Taiwan Association of Gynecology (TAG systematic review

Directory of Open Access Journals (Sweden)

Ming-Shyen Yen

2016-10-01

Full Text Available Uterine sarcoma is a very aggressive and highly lethal disease. Even after a comprehensive staging surgery or en block cytoreduction surgery followed by multimodality therapy (often chemotherapy and/or radiation therapy, many patients relapse or present with distant metastases, and finally die of diseases. The worst outcome of uterine sarcomas is partly because of their rarity, unknown etiology, and highly divergent genetic aberration. Uterine sarcomas are often classified into four distinct subtypes, including uterine leiomyosarcoma, low-grade uterine endometrial stromal sarcoma, high-grade uterine endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Currently, evidence from tumor biology found that these tumors showed alternation and/or mutation of genomes and the intracellular signal pathway. In addition, some preclinical studies showed promising results for targeting receptor tyrosine kinase signaling, phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway, various kinds of growth factor pathways, Wnt/beta-catenin signaling pathway, transforming growth factor β/bone morphogenetic protein signal pathway, aurora kinase A, MDM2 proto-oncogene, histone deacetylases, sex hormone receptors, certain types of oncoproteins, and/or loss of tumor suppressor genes. The current review is attempted to summarize the recurrent advance of targeted therapy for uterine sarcomas.

Patient-Specific Dosimetry and Radiobiological Modeling of Targeted Radionuclide Therapy Grant - final report

Energy Technology Data Exchange (ETDEWEB)

George Sgouros, Ph.D.

2007-03-20

The broad, long-term objectives of this application are to 1. develop easily implementable tools for radionuclide dosimetry that can be used to predict normal organ toxicity and tumor response in targeted radionuclide therapy; and 2. to apply these tools to the analysis of clinical trial data in order to demonstrate dose-response relationships for radionuclide therapy treatment planning. The work is founded on the hypothesis that robust dose-response relationships have not been observed in targeted radionuclide therapy studies because currently available internal dosimetry methodologies are inadequate, failing to adequately account for individual variations in patient anatomy, radionuclide activity distribution/kinetics, absorbed dose-distribution, and absorbed dose-rate. To reduce development time the previously available software package, 3D-ID, one of the first dosimetry software packages to incorporate 3-D radionuclide distribution with individual patient anatomy; and the first to be applied for the comprehensive analysis of patient data, will be used as a platform to build the functionality listed above. The following specific aims are proposed to satisfy the long-term objectives stated above: 1. develop a comprehensive and validated methodology for converting one or more SPECT images of the radionuclide distribution to a 3-D representation of the cumulated activity distribution; 2. account for differences in tissue density and atomic number by incorporating an easily implementable Monte Carlo methodology for the 3-D dosimetry calculations; 3. incorporate the biologically equivalent dose (BED) and equivalent uniform dose (EUD) models to convert the spatial distribution of absorbed dose and dose-rate into equivalent single values that account for differences in dose uniformity and rate and that may be correlated with tumor response and normal organ toxicity; 4. test the hypothesis stated above by applying the resulting package to patient trials of targeted

Novel drugs targeting Toll-like receptors for antiviral therapy.

Science.gov (United States)

Patel, Mira C; Shirey, Kari Ann; Pletneva, Lioubov M; Boukhvalova, Marina S; Garzino-Demo, Alfredo; Vogel, Stefanie N; Blanco, Jorge Cg

2014-09-01

Toll-like receptors (TLRs) are sentinel receptors of the host innate immune system that recognize conserved 'pathogen-associated molecular patterns' of invading microbes, including viruses. The activation of TLRs establishes antiviral innate immune responses and coordinates the development of long-lasting adaptive immunity in order to control viral pathogenesis. However, microbe-induced damage to host tissues may release 'danger-associated molecular patterns' that also activate TLRs, leading to an overexuberant inflammatory response and, ultimately, to tissue damage. Thus, TLRs have proven to be promising targets as therapeutics for the treatment of viral infections that result in inflammatory damage or as adjuvants in order to enhance the efficacy of vaccines. Here, we explore recent advances in TLR biology with a focus on novel drugs that target TLRs (agonists and antagonists) for antiviral therapy.

Biomedical nanotechnology for molecular imaging, diagnostics, and targeted therapy.

Science.gov (United States)

Nie, Shuming

2009-01-01

Biomedical nanotechnology is a cross-disciplinary area of research in science, engineering and medicine with broad applications for molecular imaging, molecular diagnosis, and targeted therapy. The basic rationale is that nanometer-sized particles such as semiconductor quantum dots and iron oxide nanocrystals have optical, magnetic or structural properties that are not available from either molecules or bulk solids. When linked with biotargeting ligands such as monoclonal antibodies, peptides or small molecules, these nanoparticles can be used to target diseased cells and organs (such as malignant tumors and cardiovascular plaques) with high affinity and specificity. In the "mesoscopic" size range of 5-100 nm diameter, nanoparticles also have large surface areas and functional groups for conjugating to multiple diagnostic (e.g., optical, radioisotopic, or magnetic) and therapeutic (e.g., anticancer) agents.

Targeted Therapy Database (TTD: a model to match patient's molecular profile with current knowledge on cancer biology.

Directory of Open Access Journals (Sweden)

Simone Mocellin

Full Text Available BACKGROUND: The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. OBJECTIVE: To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. METHODS: To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. RESULTS AND CONCLUSIONS: We created a manually annotated database (Targeted Therapy Database, TTD where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method

Targeted Therapy Database (TTD): a model to match patient's molecular profile with current knowledge on cancer biology.

Science.gov (United States)

Mocellin, Simone; Shrager, Jeff; Scolyer, Richard; Pasquali, Sandro; Verdi, Daunia; Marincola, Francesco M; Briarava, Marta; Gobbel, Randy; Rossi, Carlo; Nitti, Donato

2010-08-10

The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. We created a manually annotated database (Targeted Therapy Database, TTD) where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method developed to fully exploit the available knowledge on cancer biology with the

La acción tutorial y el clima escolar en los centros de educación secundaria obligatoria

Directory of Open Access Journals (Sweden)

Cristiano Serrano García

2011-02-01

Full Text Available Con el presente estudio se pretende profundizar en cómo incide la Acción Tutorial en el Clima en los centros educativos públicos y concertados de Secundaria y las causas que el profesorado de estos centros señala como determinantes. La implantación de un Plan de Acción Tutorial lleva implícito una serie de dificultades y desafíos que conviene abordar desde una perspectiva realista y de futuro. El Plan de Acción Tutorial debe afrontar la adecuada organización y el buen funcionamiento de los centros, unidos a la participación positiva y a un clima motivador en el trabajo. Es interesante determinar cuáles son los elementos y factores en la Acción Tutorial y el Clima de, así como la relación existente entre ambos. El objetivo de este estudio es comprobar si, desde la Acción Tutorial se mejora la Ecología del Centro, se influye en la Dirección, se mejora la Cultura de Convivencia, se incide sobre el Sistema Social, se mejora el Desarrollo Profesional y se consigue la Satisfacción de los profesionales de ámbitos educativos, se puede mejorar el Clima Escolar como conjunto. Se trata de un estudio evaluativo, para ello se ha aplicado los cuestionarios a 187 profesores de diversos centros públicos y concertados de Secundaria, que conforma la muestra del estudio. Para finalizar es necesario señalar que: «Si desde la Acción Tutorial conseguimos aumentar la comunicación entre la comunidad educativa, aumentaremos la confianza, conseguiremos un alto grado de motivación y esto ayudará a conseguir una participación activa y facilitará la obtención de un mejor clima en el centro educativo».

An innovative pre-targeting strategy for tumor cell specific imaging and therapy.

Science.gov (United States)

Qin, Si-Yong; Peng, Meng-Yun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Cheng, Si-Xue; Feng, Jun; Zhang, Xian-Zheng

2015-09-21

A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the "biotin-avidin" interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments.

Effectiveness of a computer-based tutorial for teaching how to make a blood smear.

Science.gov (United States)

Preast, Vanessa; Danielson, Jared; Bender, Holly; Bousson, Maury

2007-09-01

Computer-aided instruction (CAI) was developed to teach veterinary students how to make blood smears. This instruction was intended to replace the traditional instructional method in order to promote efficient use of faculty resources while maintaining learning outcomes and student satisfaction. The purpose of this study was to evaluate the effect of a computer-aided blood smear tutorial on 1) instructor's teaching time, 2) students' ability to make blood smears, and 3) students' ability to recognize smear quality. Three laboratory sessions for senior veterinary students were taught using traditional methods (control group) and 4 sessions were taught using the CAI tutorial (experimental group). Students in the control group received a short demonstration and lecture by the instructor at the beginning of the laboratory and then practiced making blood smears. Students in the experimental group received their instruction through the self-paced, multimedia tutorial on a laptop computer and then practiced making blood smears. Data was collected from observation, interview, survey questionnaires, and smear evaluation by students and experts using a scoring rubric. Students using the CAI made better smears and were better able to recognize smear quality. The average time the instructor spent in the room was not significantly different between groups, but the quality of the instructor time was improved with the experimental instruction. The tutorial implementation effectively provided students and instructors with a teaching and learning experience superior to the traditional method of instruction. Using CAI is a viable method of teaching students to make blood smears.

Novel epigenetic target therapy for prostate cancer: a preclinical study.

Directory of Open Access Journals (Sweden)

Ilaria Naldi

Full Text Available Epigenetic events are critical contributors to the pathogenesis of cancer, and targeting epigenetic mechanisms represents a novel strategy in anticancer therapy. Classic demethylating agents, such as 5-Aza-2'-deoxycytidine (Decitabine, hold the potential for reprograming somatic cancer cells demonstrating high therapeutic efficacy in haematological malignancies. On the other hand, epigenetic treatment of solid tumours often gives rise to undesired cytotoxic side effects. Appropriate delivery systems able to enrich Decitabine at the site of action and improve its bioavailability would reduce the incidence of toxicity on healthy tissues. In this work we provide preclinical evidences of a safe, versatile and efficient targeted epigenetic therapy to treat hormone sensitive (LNCap and hormone refractory (DU145 prostate cancers. A novel Decitabine formulation, based on the use of engineered erythrocyte (Erythro-Magneto-Hemagglutinin Virosomes, EMHVs drug delivery system (DDS carrying this drug, has been refined. Inside the EMHVs, the drug was shielded from the environment and phosphorylated in its active form. The novel magnetic EMHV DDS, endowed with fusogenic protein, improved the stability of the carried drug and exhibited a high efficiency in confining its delivery at the site of action in vivo by applying an external static magnetic field. Here we show that Decitabine loaded into EMHVs induces a significant tumour mass reduction in prostate cancer xenograft models at a concentration, which is seven hundred times lower than the therapeutic dose, suggesting an improved pharmacokinetics/pharmacodynamics of drug. These results are relevant for and discussed in light of developing personalised autologous therapies and innovative clinical approach for the treatment of solid tumours.

Novel epigenetic target therapy for prostate cancer: a preclinical study.

Science.gov (United States)

Naldi, Ilaria; Taranta, Monia; Gherardini, Lisa; Pelosi, Gualtiero; Viglione, Federica; Grimaldi, Settimio; Pani, Luca; Cinti, Caterina

2014-01-01

Epigenetic events are critical contributors to the pathogenesis of cancer, and targeting epigenetic mechanisms represents a novel strategy in anticancer therapy. Classic demethylating agents, such as 5-Aza-2'-deoxycytidine (Decitabine), hold the potential for reprograming somatic cancer cells demonstrating high therapeutic efficacy in haematological malignancies. On the other hand, epigenetic treatment of solid tumours often gives rise to undesired cytotoxic side effects. Appropriate delivery systems able to enrich Decitabine at the site of action and improve its bioavailability would reduce the incidence of toxicity on healthy tissues. In this work we provide preclinical evidences of a safe, versatile and efficient targeted epigenetic therapy to treat hormone sensitive (LNCap) and hormone refractory (DU145) prostate cancers. A novel Decitabine formulation, based on the use of engineered erythrocyte (Erythro-Magneto-Hemagglutinin Virosomes, EMHVs) drug delivery system (DDS) carrying this drug, has been refined. Inside the EMHVs, the drug was shielded from the environment and phosphorylated in its active form. The novel magnetic EMHV DDS, endowed with fusogenic protein, improved the stability of the carried drug and exhibited a high efficiency in confining its delivery at the site of action in vivo by applying an external static magnetic field. Here we show that Decitabine loaded into EMHVs induces a significant tumour mass reduction in prostate cancer xenograft models at a concentration, which is seven hundred times lower than the therapeutic dose, suggesting an improved pharmacokinetics/pharmacodynamics of drug. These results are relevant for and discussed in light of developing personalised autologous therapies and innovative clinical approach for the treatment of solid tumours.

Target tracking using DMLC for volumetric modulated arc therapy: A simulation study

Energy Technology Data Exchange (ETDEWEB)

Sun Baozhou; Rangaraj, Dharanipathy; Papiez, Lech; Oddiraju, Swetha; Yang Deshan; Li, H. Harold [Department of Radiation Oncology, School of Medicine, Washington University, 4921 Parkview Place, St. Louis, Missouri 63110 (United States); Department of Radiation Oncology, Southwestern Medical Center, University of Texas, Dallas, Texas 75390 (United States); Department of Radiation Oncology, School of Medicine, Washington University, 4921 Parkview Place, St. Louis, Missouri 63110 (United States)

2010-12-15

Purpose: Target tracking using dynamic multileaf collimator (DMLC) is a promising approach for intrafraction motion management in radiation therapy. The purpose of this work is to develop a DMLC tracking algorithm capable of delivering volumetric-modulated arc therapy (VMAT) to the targets that experience two-dimensional (2D) rigid motion in the beam's eye view. Methods: The problem of VMAT delivery to moving targets is formulated as a control problem with constraints. The relationships between gantry speed, gantry acceleration, MLC leaf-velocity, dose rate, and target motion are derived. An iterative search algorithm is developed to find numerical solutions for efficient delivery of a specific VMAT plan to the moving target using 2D DMLC tracking. The delivery of five VMAT lung plans is simulated. The planned and delivered fluence maps in the target-reference frame are calculated and compared. Results: The simulation demonstrates that the 2D tracking algorithm is capable of delivering the VMAT plan to a moving target fast and accurately without violating the machine constraints and the integrity of the treatment plan. The average delivery time is only 29 s longer than that of no-tracking delivery, 101 versus 72 s, respectively. The fluence maps are normalized to 200 MU and the average root-mean-square error between the desired and the delivered fluence is 2.1 MU, compared to 14.8 MU for no-tracking and 3.6 MU for one-dimensional tracking. Conclusions: A locally optimal MLC tracking algorithm for VMAT delivery is proposed, aiming at shortest delivery time while maintaining treatment plan invariant. The inconsequential increase of treatment time due to DMLC tracking is clinically desirable, which makes VMAT with DMLC tracking attractive in treating moving tumors.

uPAR Targeted Radionuclide Therapy with 177Lu-DOTA-AE105 Inhibits Dissemination of Metastatic Prostate Cancer

DEFF Research Database (Denmark)

Persson, Morten; Juhl, Karina; Rasmussen, Palle

2014-01-01

The urokinase-type plasminogen activator receptor (uPAR) is implicated in cancer invasion and metastatic development in prostate cancer and provides therefore an attractive molecular target for both imaging and therapy. In this study, we provide the first in vivo data on an antimetastatic effect...... of uPAR radionuclide targeted therapy in such lesions and show the potential of uPAR positron emission tomography (PET) imaging for identifying small foci of metastatic cells in a mouse model of disseminating human prostate cancer. Two radiolabeled ligands were generated in high purity and specific...... value of 100 nM in a competitive binding experiment. In vivo, uPAR targeted radionuclide therapy significantly reduced the number of metastatic lesions in the disseminated metastatic prostate cancer model, when compared to vehicle and nontargeted 177Lu groups (p

Interleukin-1 beta targeted therapy for type 2 diabetes

DEFF Research Database (Denmark)

Maedler, K.; Dharmadhikari, G.; Schumann, D.M.

2009-01-01

Since having been cloned in 1984, IL-1beta has been the subject of over 22,000 citations in Pubmed, among them over 800 reviews. This is because of its numerous effects. IL-1beta is a regulator of the body's inflammatory response and is produced after infection, injury, and antigenic challenge. I....... We highlight recent clinical studies and experiments in animals and isolated islets using IL-1beta as a potential target for the therapy of type 2 diabetes Udgivelsesdato: 2009/9...

Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer.

Science.gov (United States)

Nagasaka, Misako; Gadgeel, Shirish M

2018-01-01

Adjuvant platinum based chemotherapy is accepted as standard of care in stage II and III non-small cell lung cancer (NSCLC) patients and is often considered in patients with stage IB disease who have tumors ≥ 4 cm. The survival advantage is modest with approximately 5% at 5 years. Areas covered: This review article presents relevant data regarding chemotherapy use in the perioperative setting for early stage NSCLC. A literature search was performed utilizing PubMed as well as clinical trial.gov. Randomized phase III studies in this setting including adjuvant and neoadjuvant use of chemotherapy as well as ongoing trials on targeted therapy and immunotherapy are also discussed. Expert commentary: With increasing utilization of screening computed tomography scans, it is possible that the percentage of early stage NSCLC patients will increase in the coming years. Benefits of adjuvant chemotherapy in early stage NSCLC patients remain modest. There is a need to better define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy. Trials for adjuvant targeted therapy, including adjuvant EGFR-TKI trials and trials of immunotherapy drugs are ongoing and will define the role of these agents as adjuvant therapy.

Targeted therapies for locally advanced or metastatic squamous cell carcinoma of the lung.

Science.gov (United States)

Stinchcombe, Thomas E

2013-12-01

Most patients with squamous cell carcinoma (SCC) present with advanced or metastatic disease at the time of diagnosis. Given the low prevalence of oncogenic driver mutations in SCC, I do not routinely perform molecular testing. The times that I perform molecular testing in SCC are for patients with SCC and a light or never smoking history, adenosquamous histology, or when the histological diagnosis is not definitive. For patients with a good performance status and adequate organ function, a platinum doublet is the standard therapy, and I generally use carboplatin and gemcitabine or carboplatin and paclitaxel. In the second-line setting for patients who are chemotherapy candidates, I will use docetaxel on a weekly or every three week schedule. Erlotinib is a treatment option in the third-line setting. My preference is for patients to participate in clinical trials because the development of novel therapies for patients with SCC has been slow compared with nonsquamous non-small cell lung cancer. Ongoing investigations into the genomics of SCC will hopefully identify driver mutations or alterations in pathways essential for oncogenesis and tumor growth and will lead to the development of targeted therapies. The complexity of the genomics of SCC will make the development of targeted therapies challenging.

Reimbursement of targeted cancer therapies within three different European health care systems

NARCIS (Netherlands)

Mihajlovic, Jovan; Dolk, C.; Postma, Maarten

2014-01-01

Objectives: To identify differences in the recommendations for targeted cancer therapies (TCT) in three distinctive European health care systems: Serbian, Scottish and Dutch, and to examine the role of cost effectiveness analyses (CEA) in such recommendations. Methods: A list of currently approved

Assessing the response to targeted therapies in renal cell carcinoma: technical insights and practical considerations.

Science.gov (United States)

Bex, Axel; Fournier, Laure; Lassau, Nathalie; Mulders, Peter; Nathan, Paul; Oyen, Wim J G; Powles, Thomas

2014-04-01

The introduction of targeted agents for the treatment of renal cell carcinoma (RCC) has resulted in new challenges for assessing response to therapy, and conventional response criteria using computed tomography (CT) are limited. It is widely recognised that targeted therapies may lead to significant necrosis without significant reduction in tumour size. In addition, the vascular effects of antiangiogenic therapy may occur long before there is any reduction in tumour size. To perform a systematic review of conventional and novel imaging methods for the assessment of response to targeted agents in RCC and to discuss their use from a clinical perspective. Relevant databases covering the period January 2006 to April 2013 were searched for studies reporting on the use of anatomic and functional imaging techniques to predict response to targeted therapy in RCC. Inclusion criteria were randomised trials, nonrandomised controlled studies, retrospective case series, and cohort studies. Reviews, animal and preclinical studies, case reports, and commentaries were excluded. A narrative synthesis of the evidence is presented. A total of 331 abstracts and 76 full-text articles were assessed; 34 studies met the inclusion criteria. Current methods of response assessment in RCC include anatomic methods--based on various criteria including Choi, size and attenuation CT, and morphology, attenuation, size, and structure--and functional techniques including dynamic contrast-enhanced (DCE) CT, DCE-magnetic resonance imaging, DCE-ultrasonography, positron emission tomography, and approaches utilising radiolabelled monoclonal antibodies. Functional imaging techniques are promising surrogate biomarkers of response in RCC and may be more appropriate than anatomic CT-based methods. By enabling quantification of tumour vascularisation, functional techniques can directly and rapidly detect the biologic effects of antiangiogenic therapies compared with the indirect detection of belated effects

Difficult incidents and tutor interventions in problem-based learning tutorials.

Science.gov (United States)

Kindler, Pawel; Grant, Christopher; Kulla, Steven; Poole, Gary; Godolphin, William

2009-09-01

Tutors report difficult incidents and distressing conflicts that adversely affect learning in their problem-based learning (PBL) groups. Faculty development (training) and peer support should help them to manage this. Yet our understanding of these problems and how to deal with them often seems inadequate to help tutors. The aim of this study was to categorise difficult incidents and the interventions that skilled tutors used in response, and to determine the effectiveness of those responses. Thirty experienced and highly rated tutors in our Year 1 and 2 medical curriculum took part in semi-structured interviews to: identify and describe difficult incidents; describe how they responded, and assess the success of each response. Recorded and transcribed data were analysed thematically to develop typologies of difficult incidents and interventions and compare reported success or failure. The 94 reported difficult incidents belonged to the broad categories 'individual student' or 'group dynamics'. Tutors described 142 interventions in response to these difficult incidents, categorised as: (i) tutor intervenes during tutorial; (ii) tutor gives feedback outside tutorial, or (iii) student or group intervenes. Incidents in the 'individual student' category were addressed relatively unsuccessfully (effective 75% of the time) by response (iii). None of the interventions worked well when used in response to problems related to 'group dynamics'. Overall, 59% of the difficult incidents were dealt with successfully. Dysfunctional PBL groups can be highly challenging, even for experienced and skilled tutors. Within-tutorial feedback, the treatment that tutors are most frequently advised to apply, was often not effective. Our study suggests that the collective responsibility of the group, rather than of the tutor, to deal with these difficulties should be emphasised.

Targeted therapies in development for non-small cell lung cancer

Directory of Open Access Journals (Sweden)

Thanyanan Reungwetwattana

2013-01-01

Full Text Available The iterative discovery in various malignancies during the past decades that a number of aberrant tumorigenic processes and signal transduction pathways are mediated by "druggable" protein kinases has led to a revolutionary change in drug development. In non-small cell lung cancer (NSCLC, the ErbB family of receptors (e.g., EGFR [epidermal growth factor receptor], HER2 [human epidermal growth factor receptor 2], RAS (rat sarcoma gene, BRAF (v-raf murine sarcoma viral oncogene homolog B1, MAPK (mitogen-activated protein kinase c-MET (c-mesenchymal-epithelial transition, FGFR (fibroblast growth factor receptor, DDR2 (discoidin domain receptor 2, PIK3CA (phosphatidylinositol-4,5-bisphosphate3-kinase, catalytic subunit alpha, PTEN (phosphatase and tensin homolog, AKT (protein kinase B, ALK (anaplastic lym phoma kinase, RET (rearranged during transfection, ROS1 (reactive oxygen species 1 and EPH (erythropoietin-producing hepatoma are key targets of various agents currently in clinical development. These oncogenic targets exert their selective growth advantage through various intercommunicating pathways, such as through RAS/RAF/MEK, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin and SRC-signal transduction and transcription signaling. The recent clinical studies, EGFR tyrosine kinase inhibitors and crizotinib were considered as strongly effective targeted therapies in metastatic NSCLC. Currently, five molecular targeted agents were approved for treatment of advanced NSCLC: Gefitinib, erlotinib and afatinib for positive EGFR mutation, crizotinib for positive echinoderm microtubule-associated protein-like 4 (EML4-ALK translocation and bevacizumab. Moreover, oncogenic mutant proteins are subject to regulation by protein trafficking pathways, specifically through the heat shock protein 90 system. Drug combinations affecting various nodes in these signaling and intracellular processes are predicted and demonstrated to be synergistic and

Implementation of Inquiry-Based Tutorials in AN Introductory Physics Course: the Role of the Graduate Teaching Assistant.

Science.gov (United States)

Thoresen, Carol Wiggins

1994-01-01

This study determined if the training provided physics teaching assistants was sufficient to accomplish the objectives of inquiry-based tutorials for an introductory physics course. Qualitative research methods were used: (1) to determine if the Physics by Inquiry method was modeled; (2) to describe the process from the teaching assistant perspective; (3) to determine TA opinions on training methods; (4) to develop a frame of reference to better understand the role of TA's as instructional support staff. The study determined that the teaching assistants verbalized appropriate instructional actions, but were observed to use a predominantly didactic teaching style. TA's held a variety of perceptions and beliefs about inquiry -based learning and how science is learned. They felt comfortable in the role of tutorial instructor. They were satisfied with the training methods provided and had few suggestions to change or improve training for future tutorial instructors. A concurrent theme of teacher action dependent on teacher beliefs was sustained throughout the study. The TA's actions, as tutorial instructors, reflected their educational beliefs, student background and learning experiences. TA's performance as tutorial instructors depended on what they think and believe about learning science. Practical implications exist for training teaching assistants to be tutorial instructors. Some recommendations may be appropriate for TA's required to use instructional methods that they have not experienced as students. Interview prospective teaching assistants to determine educational experience and beliefs. Employ inexperienced teaching assistants whose perspectives match the proposed instructional role and who might be more receptive to modeling. Incorporate training into staff meetings. Provide time for TA's to experience the instructional model with simulation or role play as students and as instructors, accompanied by conference discussion. Use strategies known to enhance

Tutorial review of spent-fuel degradation mechanisms under dry-storage conditions

International Nuclear Information System (INIS)

Einziger, R.E.

1983-02-01

This tutorial reviews our present understanding of fuel-rod degradation over a range of possible dry-storage environments. Three areas are covered: (1) why study fuel-rod degradation; (2) cladding-degradation mechanisms; and (3) the status of fuel-oxidation studies

Hyperspectral image analysis. A tutorial

DEFF Research Database (Denmark)

Amigo Rubio, Jose Manuel; Babamoradi, Hamid; Elcoroaristizabal Martin, Saioa

2015-01-01

This tutorial aims at providing guidelines and practical tools to assist with the analysis of hyperspectral images. Topics like hyperspectral image acquisition, image pre-processing, multivariate exploratory analysis, hyperspectral image resolution, classification and final digital image processi...... to differentiate between several types of plastics by using Near infrared hyperspectral imaging and Partial Least Squares - Discriminant Analysis. Thus, the reader is guided through every single step and oriented in order to adapt those strategies to the user's case....... will be exposed, and some guidelines given and discussed. Due to the broad character of current applications and the vast number of multivariate methods available, this paper has focused on an industrial chemical framework to explain, in a step-wise manner, how to develop a classification methodology...

Potential efficacy of therapies targeting intrahepatic lesions after sorafenib treatment of patients with hepatocellular carcinoma

International Nuclear Information System (INIS)

Terashima, Takeshi; Yamashita, Tatsuya; Horii, Rika; Arai, Kuniaki; Kawaguchi, Kazunori; Kitamura, Kazuya; Yamashita, Taro; Sakai, Yoshio; Mizukoshi, Eishiro; Honda, Masao; Kaneko, Shuichi

2016-01-01

We investigated the contribution of subsequent therapy for advanced hepatocellular carcinoma refractory or intolerant to sorafenib. Further, we investigated the impact of sorafenib on overall survival using individual data. We reviewed the medical records of patients with advanced hepatocellular carcinoma treated with sorafenib. Survival after sorafenib treatment and overall survival were defined as the time when we discovered that patients were either refractory or intolerant to sorafenib and the period from the start of sorafenib treatment, respectively, until death during the study. We compared patients’ prognoses according to their subsequent treatment as follows: group A, therapies targeting intrahepatic lesions; group B, systemic therapies alone; group C, no subsequent therapy. We used linear regression analysis to determine whether there was an association with survival after sorafenib treatment and with overall survival. Of 79 patients, 63 (79.7 %) received one or more subsequent therapies (44 and 19 patients in groups A and B, respectively). The five patients who survived more than two years after sorafenib treatment was discontinued responded to therapies targeting intrahepatic lesions. The median survival times of groups A, B, and C were 11.9 months, 5.8 months, and 3.6 months, respectively. Multivariate analysis revealed that group A, Child-Pugh score, serum α-fetoprotein level, and cause of failure of sorafenib treatment were independent prognostic factors for survival after sorafenib treatment. Individual survival after sorafenib treatment correlated highly with overall survival. Targeting intrahepatic lesions may be useful for treating patients with advanced hepatocellular carcinoma patients after sorafenib treatment is discontinued. The online version of this article (doi:10.1186/s12885-016-2380-4) contains supplementary material, which is available to authorized users

Aptamer conjugated paclitaxel and magnetic fluid loaded fluorescently tagged PLGA nanoparticles for targeted cancer therapy

Energy Technology Data Exchange (ETDEWEB)

Aravind, Athulya; Nair, Remya; Raveendran, Sreejith; Veeranarayanan, Srivani; Nagaoka, Yutaka; Fukuda, Takahiro; Hasumura, Takahashi; Morimoto, Hisao; Yoshida, Yasuhiko; Maekawa, Toru; Sakthi Kumar, D., E-mail: sakthi@toyo.jp

2013-10-15

Controlled and targeted drug delivery is an essential criterion in cancer therapy to reduce the side effects caused by non-specific drug release and toxicity. Targeted chemotherapy, sustained drug release and optical imaging have been achieved using a multifunctional nanocarrier constructed from poly (D, L-lactide-co-glycolide) nanoparticles (PLGA NPs), an anticancer drug paclitaxel (PTX), a fluorescent dye Nile red (NR), magnetic fluid (MF) and aptamers (Apt, AS1411, anti-nucleolin aptamer). The magnetic fluid and paclitaxel loaded fluorescently labeled PLGA NPs (MF-PTX-NR-PLGA NPs) were synthesized by a single-emulsion technique/solvent evaporation method using a chemical cross linker bis (sulfosuccinimidyl) suberate (BS3) to enable binding of aptamer on to the surface of the nanoparticles. Targeting aptamers were then introduced to the particles through the reaction with the cross linker to target the nucleolin receptors over expressed on the cancer cell surface. Specific binding and uptake of the aptamer conjugated magnetic fluid loaded fluorescently tagged PLGA NPs (Apt-MF-NR-PLGA NPs) to the target cancer cells induced by aptamers was observed using confocal microscopy. Cytotoxicity assay conducted in two cell lines (L929 and MCF-7) confirmed that targeted MCF-7 cancer cells were killed while control cells were unharmed. In addition, aptamer mediated delivery resulting in enhanced binding and uptake to the target cancer cells exhibited increased therapeutic effect of the drug. Moreover, these aptamer conjugated magnetic polymer vehicles apart from actively transporting drugs into specifically targeted tumor regions can also be used to induce hyperthermia or for facilitating magnetic guiding of particles to the tumor regions. - Highlights: • Aptamer escorted, theranostic biodegradable PLGA carriers were developed. • Can target cancer cells, control drug release, image and magnetically guide. • Highly specific to the targeted cancer cells thus delivering

mTOR in squamous cell carcinoma of the oesophagus: a potential target for molecular therapy?

NARCIS (Netherlands)

Boone, J.; ten Kate, F. J. W.; Offerhaus, G. J. A.; van Diest, P. J.; Borel Rinkes, I. H. M.; van Hillegersberg, R.

2008-01-01

AIMS: The mammalian target of rapamycin (mTOR), an important regulator of protein translation and cell proliferation, is activated in various malignancies. In a randomised controlled trial of advanced renal cell carcinoma patients, targeted therapy to mTOR by means of rapamycin analogues has been

A tutorial on machine learning in educational science

OpenAIRE

Kidzinski, Lukasz; Giannakos, Michail; Sampson, Demetrios G.; Dillenbourg, Pierre

2015-01-01

Popularity of massive online open courses (MOOCs) allowed educational researchers to address problems which were not accessible few years ago. Although classical statistical techniques still apply, large datasets allow us to discover deeper patterns and to provide more accu-rate predictions of student’s behaviors and outcomes. The goal of this tutorial is to disseminate knowledge on elementary data analysis tools as well as facilitating simple practical data-analysis activities with the purpo...

Benefits from Taking a Private Tutorial Course for Exam Preparation?

DEFF Research Database (Denmark)

la Cour, Lisbeth; Milhøj, Anders

course in order to perform well at the exam but still more than 50 % of a cohort signs up for the courses. Our data come from the administrative systems at Copenhagen Business School and they are merged with survey data on student satisfaction and tutorial participation. Based on simple regression...

MATS--Management Accounting Tutorial System. Version 1.0. Project Documentation.

Science.gov (United States)

Wardle, Andrew; O'Connor, Rodric

The Management Accounting Tutorial System (MATS) is a management accounting database for a carpet manufacturing company. The system allows the display and output of monthly activities, and is intended to provide a means of illustrating the main topics of the second year management accounting course at Manchester University. The system itself…

MATS--Management Accounting Tutorial System. Version 1.0. User Guide.

Science.gov (United States)

Wardle, Andrew; O'Connor, Rodric

The Management Accounting Tutorial System (MATS) is a management accounting database for a carpet manufacturing company. The system allows the display and output of monthly activities, and is intended to provide a means of illustrating the main topics of the second year management accounting course at Manchester University. The system itself…

Clinical proteomics-driven precision medicine for targeted cancer therapy: current overview and future perspectives.

Science.gov (United States)

Zhou, Li; Wang, Kui; Li, Qifu; Nice, Edouard C; Zhang, Haiyuan; Huang, Canhua

2016-01-01

Cancer is a common disease that is a leading cause of death worldwide. Currently, early detection and novel therapeutic strategies are urgently needed for more effective management of cancer. Importantly, protein profiling using clinical proteomic strategies, with spectacular sensitivity and precision, offer excellent promise for the identification of potential biomarkers that would direct the development of targeted therapeutic anticancer drugs for precision medicine. In particular, clinical sample sources, including tumor tissues and body fluids (blood, feces, urine and saliva), have been widely investigated using modern high-throughput mass spectrometry-based proteomic approaches combined with bioinformatic analysis, to pursue the possibilities of precision medicine for targeted cancer therapy. Discussed in this review are the current advantages and limitations of clinical proteomics, the available strategies of clinical proteomics for the management of precision medicine, as well as the challenges and future perspectives of clinical proteomics-driven precision medicine for targeted cancer therapy.

Targeting Signaling to YAP for the Therapy of NF2

Science.gov (United States)

2015-10-01

which encodes the FERM domain-containing protein Merlin. Children and young adults, who inherit an NF2 mutation, develop Schwannomas, usually of the...targeted therapy in the same way Chronic Myelogenous Leukemia is cured by Gleevec. The prospect of resistance is minimal, as Schwannoma cells do not seem to... treatment with Verteporfin, suggesting that this reporter system is not sensitive enough in physiopathologically relevant cell types. In parallel, it

Conjugate of biotin with silicon(IV) phthalocyanine for tumor-targeting photodynamic therapy.

Science.gov (United States)

Li, Ke; Qiu, Ling; Liu, Qingzhu; Lv, Gaochao; Zhao, Xueyu; Wang, Shanshan; Lin, Jianguo

2017-09-01

In order to improve the efficacy of photodynamic therapy (PDT), biotin was axially conjugated with silicon(IV) phthalocyanine (SiPc) skeleton to develop a new tumor-targeting photosensitizer SiPc-biotin. The target compound SiPc-biotin showed much higher binding affinity toward BR-positive (biotin receptor overexpressed) HeLa human cervical carcinoma cells than its precursor SiPc-pip. However, when the biotin receptors of HeLa cells were blocked by free biotin, >50% uptake of SiPc-biotin was suppressed, demonstrating that SiPc-biotin could selectively accumulate in BR-positive cancer cells via the BR-mediated internalization. The confocal fluorescence images further confirmed the target binding ability of SiPc-biotin. As a consequence of specificity of SiPc-biotin toward BR-positive HeLa cells, the photodynamic effect was also largely dependent on the BR expression level of HeLa cells. The photodynamic activities of SiPc-biotin against HeLa cells were dramatically reduced when the biotin receptors were blocked by the free biotin (IC 50 : 0.18μM vs. 0.46μM). It is concluded that SiPc-biotin can selectively damage BR-positive cancer cells under irradiation. Furthermore, the dark toxicity of SiPc-biotin toward human normal liver cell lines LO2 was much lower than that of its precursor SiPc-pip. The targeting photodynamic activity and low dark toxicity suggest that SiPc-biotin is a promising photosensitizer for tumor-targeting photodynamic therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeted radionuclide therapy

African Journals Online (AJOL)

target for which a speci c treatment/drug is intended (Fig. 1). eranostics .... Using an anti-CD20 antibody as a delivery device to target the follicular ... systems combine diagnostic imaging (Ga-68-DOTATATE PET/CT) .... Intra-articular injected ...

APLIKASI MOBILE LEARNING TUTORIAL PENGKABELAN DALAM MATA KULIAH JARINGAN KOMPUTER II DI STMIK AMIKOM PURWOKERTO

Directory of Open Access Journals (Sweden)

Tri Handoko

2011-02-01

Full Text Available Tujuan penelitian ini adalah membuat aplikasi mobile learning tutorial pengkabelan dalam mata kuliah jaringan komputer II di STMIK AMIKOM Purwokerto. Metode pengumpulan data yang digunakan untuk membuat aplikasi ini adalah metode kepustakaan dan metode observasi secara langsung. Untuk pengembangan sistem dalam penelitian ini menggunakan metode SDLC (System Development Life Cycle, dengan teknik pengembangan sistem waterfall model.Hasil penelitian ini berupa aplikasi mobile learning tutorial pengkabelan dalam mata kuliah jaringan komputer II di STMIK AMIKOM Purwokerto. Aplikasi yang dihasilkan berektensi .swf dan dapat dijalankan menggunakan flashlite player.

Object Oriented Approach for developing of a Tutorial System Work Security and Health in SMEs

Directory of Open Access Journals (Sweden)

2007-01-01

Full Text Available This paper presents the authors' research for developing a tutorial system which enables the delivery of proper training to specialized personnel in Small and Middle Enterprises (SMEs, in order to eliminate or reduce the health and safety risks of these enterprises to an acceptable level, according to the European Union directives. During the analysis phase, the requirements of the tutorial system were described using UML use case diagrams, the activity flow was modeled with an activity diagram, and the relevant classes were identified and described in a class diagram.

ANSYS workbench tutorial release 14 structural & thermal analysis using the ANSYS workbench release 14 environment

CERN Document Server

Lawrence, Kent L

2012-01-01

The exercises in ANSYS Workbench Tutorial Release 14 introduce you to effective engineering problem solving through the use of this powerful modeling, simulation and optimization software suite. Topics that are covered include solid modeling, stress analysis, conduction/convection heat transfer, thermal stress, vibration, elastic buckling and geometric/material nonlinearities. It is designed for practicing and student engineers alike and is suitable for use with an organized course of instruction or for self-study. The compact presentation includes just over 100 end-of-chapter problems covering all aspects of the tutorials.

Potential advantages of DNA methyltransferase 1 (DNMT1)-targeted inhibition for cancer therapy.

Science.gov (United States)

Jung, Yeonjoo; Park, Jinah; Kim, Tai Young; Park, Jung-Hyun; Jong, Hyun-Soon; Im, Seock-Ah; Robertson, Keith D; Bang, Yung-Jue; Kim, Tae-You

2007-10-01

The deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) has been used as a drug in a part of cancer therapy. However, because of its incorporation into DNA during DNA synthesis, 5-aza-dC can cause DNA damage, mutagenesis, and cytotoxicity. In view of the adverse effects of 5-aza-dC, DNMT-targeted inhibition may be a more effective approach than treatment with 5-aza-dC. To address the possibility of DNMT-targeted cancer therapy, we compared the effects of treatment with small interfering ribonucleic acids (siRNAs) specific for DNMT1 or DNMT3b and treatment with 5-aza-dC on transcription, cell growth, and DNA damage in gastric cancer cells. We found that DNMT1-targeted inhibition induced the re-expression and reversed DNA methylation of five (CDKN2A, RASSF1A, HTLF, RUNX3, and AKAP12B) out of seven genes examined, and 5-aza-dC reactivated and demethylated all seven genes. In contrast, DNMT3b siRNAs did not show any effect. Furthermore, the double knockdown of DNMT1 and DNMT3b did not show a synergistic effect on gene re-expression and demethylation. In addition, DNMT1 siRNAs showed an inhibitory effect of cell proliferation in the cancer cells and the induction of cell death without evidence of DNA damage, whereas treatment with 5-aza-dC caused DNA damage as demonstrated by the comet assay. These results provide a rationale for the development of a DNMT1-targeted strategy as an effective epigenetic cancer therapy.

Specific role of targeted molecular therapy in treatment of oral squamous cell carcinoma

Directory of Open Access Journals (Sweden)

Pankaj Gupta

2017-12-01

Full Text Available Oral cancer is a potentially fatal disease that constitutes an important portion of tumors that occur in the head and neck region. Oral cancer can affect overall and mental health, appearance, employment, social life, and family living. The disease can cause serious changes in the functioning of the upper aero digestive tract that affects the quality of life in patients. The use of conventional treatment modalities (surgery, radiation, and/or chemotherapy depends on tumor respectability and location as well as whether an organ preservation approach is feasible. However, their role in oral cancer treatment is nonselective and can cause damage to normal tissue. In particular, chemo radiotherapy is associated with systemic toxicities that often reduce patient compliance and prevent timely completion of therapy. The development of targeted therapies to target select pathways involved in carcinogenesis, potentially decrease systemic toxicities and morbidities associated with cancer burden and hence improve the prognosis in cancer patients. In the present article, the role of various targeted molecules in the treatment of oral cancer is discussed.

Medical image reconstruction. A conceptual tutorial

International Nuclear Information System (INIS)

Zeng, Gengsheng Lawrence

2010-01-01

''Medical Image Reconstruction: A Conceptual Tutorial'' introduces the classical and modern image reconstruction technologies, such as two-dimensional (2D) parallel-beam and fan-beam imaging, three-dimensional (3D) parallel ray, parallel plane, and cone-beam imaging. This book presents both analytical and iterative methods of these technologies and their applications in X-ray CT (computed tomography), SPECT (single photon emission computed tomography), PET (positron emission tomography), and MRI (magnetic resonance imaging). Contemporary research results in exact region-of-interest (ROI) reconstruction with truncated projections, Katsevich's cone-beam filtered backprojection algorithm, and reconstruction with highly undersampled data with l 0 -minimization are also included. (orig.)

Charged particle beam current monitoring tutorial

International Nuclear Information System (INIS)

Webber, R.C.

1994-10-01

A tutorial presentation is made on topics related to the measurement of charged particle beam currents. The fundamental physics of electricity and magnetism pertinent to the problem is reviewed. The physics is presented with a stress on its interpretation from an electrical circuit theory point of view. The operation of devices including video pulse current transformers, direct current transformers, and gigahertz bandwidth wall current style transformers is described. Design examples are given for each of these types of devices. Sensitivity, frequency response, and physical environment are typical parameters which influence the design of these instruments in any particular application. Practical engineering considerations, potential pitfalls, and performance limitations are discussed

Wavelets a tutorial in theory and applications

CERN Document Server

1992-01-01

Wavelets: A Tutorial in Theory and Applications is the second volume in the new series WAVELET ANALYSIS AND ITS APPLICATIONS. As a companion to the first volume in this series, this volume covers several of the most important areas in wavelets, ranging from the development of the basic theory such as construction and analysis of wavelet bases to an introduction of some of the key applications, including Mallat's local wavelet maxima technique in second generation image coding. A fairly extensive bibliography is also included in this volume.Key Features* Covers several of the

Tissue factor is an angiogenic-specific receptor for factor VII-targeted immunotherapy and photodynamic therapy.

Science.gov (United States)

Hu, Zhiwei; Cheng, Jijun; Xu, Jie; Ruf, Wolfram; Lockwood, Charles J

2017-02-01

Identification of target molecules specific for angiogenic vascular endothelial cells (VEC), the inner layer of pathological neovasculature, is critical for discovery and development of neovascular-targeting therapy for angiogenesis-dependent human diseases, notably cancer, macular degeneration and endometriosis, in which vascular endothelial growth factor (VEGF) plays a central pathophysiological role. Using VEGF-stimulated vascular endothelial cells (VECs) isolated from microvessels, venous and arterial blood vessels as in vitro angiogenic models and unstimulated VECs as a quiescent VEC model, we examined the expression of tissue factor (TF), a membrane-bound receptor on the angiogenic VEC models compared with quiescent VEC controls. We found that TF is specifically expressed on angiogenic VECs in a time-dependent manner in microvessels, venous and arterial vessels. TF-targeted therapeutic agents, including factor VII (fVII)-IgG1 Fc and fVII-conjugated photosensitizer, can selectively bind angiogenic VECs, but not the quiescent VECs. Moreover, fVII-targeted photodynamic therapy can selectively and completely eradicate angiogenic VECs. We conclude that TF is an angiogenic-specific receptor and the target molecule for fVII-targeted therapeutics. This study supports clinical trials of TF-targeted therapeutics for the treatment of angiogenesis-dependent diseases such as cancer, macular degeneration and endometriosis.

LOG: Analyzing navigation trough a tutorial of Radiation Protection

International Nuclear Information System (INIS)

Vega, J. M.; Pena, J. J.; Rossell, M. A.; Calvo, J. L.

2003-01-01

Every day, the number of didactic materials presented through Internet, is greater. However, we have not effective tools to obtain the potential academic yield of such a media. The complexity of the Internet protocols, in spite of the easy handling, makes it almost impossible. In this work, a didactic tool to analyse graphically the navigation through a tutorial on radiation protection is presented. For its visualisation, some subjects related with the biogical effects of radiation and with radiological quantities and units have been selected. The graphical representation shows the tour travelled by the user, in our case students of Medicine, and the time employed in eyeing each one of the nodes. The answers to problems about the contents of each node and its graphical representation in the navigation map allow us to follow the learning progress of the students as well as their standard of navigation. The graphical representation analysis of multiple users permits to detect some of the mistakes in the design of the tutorial and to suggest to the author a method for amending these mistakes. The system is developed on LINEX, but it is easily adaptable to other operating systems. (Author) 7 refs

Targeting the NFκB signaling pathways for breast cancer prevention and therapy.

Science.gov (United States)

Wang, Wei; Nag, Subhasree A; Zhang, Ruiwen

2015-01-01

The activation of nuclear factor-kappaB (NFκB), a proinflammatory transcription factor, is a commonly observed phenomenon in breast cancer. It facilitates the development of a hormone-independent, invasive, high-grade, and late-stage tumor phenotype. Moreover, the commonly used cancer chemotherapy and radiotherapy approaches activate NFκB, leading to the development of invasive breast cancers that show resistance to chemotherapy, radiotherapy, and endocrine therapy. Inhibition of NFκB results in an increase in the sensitivity of cancer cells to the apoptotic effects of chemotherapeutic agents and radiation and restoring hormone sensitivity, which is correlated with increased disease-free survival in patients with breast cancer. In this review article, we focus on the role of the NFκB signaling pathways in the development and progression of breast cancer and the validity of NFκB as a potential target for breast cancer prevention and therapy. We also discuss the recent findings that NFκB may have tumor suppressing activity in certain cancer types. Finally, this review also covers the state-of-the-art development of NFκB inhibitors for cancer therapy and prevention, the challenges in targeting validation, and pharmacology and toxicology evaluations of these agents from the bench to the bedside.

Integrating Supplementary Application-Based Tutorials in the Multivariable Calculus Course

Science.gov (United States)

Verner, I. M.; Aroshas, S.; Berman, A.

2008-01-01

This article presents a study in which applications were integrated in the Multivariable Calculus course at the Technion in the framework of supplementary tutorials. The purpose of the study was to test the opportunity of extending the conventional curriculum by optional applied problem-solving activities and get initial evidence on the possible…

Learning Marketing Accounting Skills in the Introductory Marketing Course: The Development, Use, and Acceptance of a Self-Study Tutorial

Science.gov (United States)

Chen, Yi Ju; Greenberg, Barnett; Dickson, Peter; Goodrich, Jonathan

2012-01-01

A self-study tutorial designed to teach, through a learning-by-doing application, how important marketing accounting is to the whole firm, and why every business graduate should have a solid understanding of marketing accounting is tested using an exam and satisfaction survey. Performance on the exam and satisfaction with the tutorial depended…

Targeted magnetic iron oxide nanoparticles for tumor imaging and therapy

Directory of Open Access Journals (Sweden)

Xiang-Hong Peng

2008-10-01

Full Text Available Xiang-Hong Peng1,4, Ximei Qian2,4, Hui Mao3,4, Andrew Y Wang5, Zhuo (Georgia Chen1,4, Shuming Nie2,4, Dong M Shin1,4*1Department of Medical Oncology/Hematology; 2Department of Biomedical Engineering; 3Department of Radiology; 4Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA; 5Ocean Nanotech, LLC, Fayetteville, AR, USAAbstract: Magnetic iron oxide (IO nanoparticles with a long blood retention time, biodegradability and low toxicity have emerged as one of the primary nanomaterials for biomedical applications in vitro and in vivo. IO nanoparticles have a large surface area and can be engineered to provide a large number of functional groups for cross-linking to tumor-targeting ligands such as monoclonal antibodies, peptides, or small molecules for diagnostic imaging or delivery of therapeutic agents. IO nanoparticles possess unique paramagnetic properties, which generate significant susceptibility effects resulting in strong T2 and T*2 contrast, as well as T1 effects at very low concentrations for magnetic resonance imaging (MRI, which is widely used for clinical oncology imaging. We review recent advances in the development of targeted IO nanoparticles for tumor imaging and therapy.Keywords: iron oxide nanoparticles, tumor imaging, MRI, therapy

The multilayer nanoparticles formed by layer by layer approach for cancer-targeting therapy.

Science.gov (United States)

Oh, Keun Sang; Lee, Hwanbum; Kim, Jae Yeon; Koo, Eun Jin; Lee, Eun Hee; Park, Jae Hyung; Kim, Sang Yoon; Kim, Kwangmeyung; Kwon, Ick Chan; Yuk, Soon Hong

2013-01-10

The multilayer nanoparticles (NPs) were prepared for cancer-targeting therapy using the layer by layer approach. When drug-loaded Pluronic NPs were mixed with vesicles (liposomes) in the aqueous medium, Pluronic NPs were incorporated into the vesicles to form the vesicle NPs. Then, the multilayer NPs were formed by freeze-drying the vesicle NPs in a Pluronic aqueous solution. The morphology and size distribution of the multilayer NPs were observed using a TEM and a particle size analyzer. In order to apply the multilayer NPs as a delivery system for docetaxel (DTX), which is a model anticancer drug, the release pattern of the DTX was observed and the tumor growth was monitored by injecting the multilayer NPs into the tail veins of tumor (squamous cell carcinoma)-bearing mice. The cytotoxicity of free DTX (commercial DTX formulation (Taxotere®)) and the multilayer NPs was evaluated using MTT assay. We also evaluated the tumor targeting ability of the multilayer NPs using magnetic resonance imaging. The multilayer NPs showed excellent tumor targetability and antitumor efficacy in tumor-bearing mice, caused by the enhanced permeation and retention (EPR) effect. These results suggest that the multilayer NPs could be a potential drug delivery system for cancer-targeting therapy. Copyright © 2012 Elsevier B.V. All rights reserved.